Cyclic AMP signalling in Dictyostelium : G-proteins activate separate Ras pathways using specific RasGEFs

NARCIS (Netherlands)

Kae, Helmut; Kortholt, Arjan; Rehmann, Holger; Insall, RobertH.; Van Haastert, Peter J. M.; Spiegelman, George B.; Weeks, Gerald

In general, mammalian Ras guanine nucleotide exchange factors (RasGEFs) show little substrate specificity, although they are often thought to regulate specific pathways. Here, we provide in vitro and in vivo evidence that two RasGEFs can each act on specific Ras proteins. During Dictyostelium

A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

Science.gov (United States)

Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

2005-02-22

CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

GEF small grants programme - overview

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-01

This paper describes the GEF small grants program which seeks to enhance the role of households and communities in conserving global biodiversity, mitigating global climate change, and protecting international waters. Grants up to $50k have been granted for projects in 33 countries, with plans for 12 other countries. The author describes the framework that the program works under, and the methodology followed in developing and planning projects. The approach to climate change concerns is to emphasize the development of non-carbon energy development activities to provide energy sources and economic development.

An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

Science.gov (United States)

Kutys, Matthew L; Yamada, Kenneth M

2014-09-01

Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

General Description of Fission Observables - JEFF Report 24. GEF Model

International Nuclear Information System (INIS)

Schmidt, Karl-Heinz; Jurado, Beatriz; Amouroux, Charlotte

2014-06-01

The Joint Evaluated Fission and Fusion (JEFF) Project is a collaborative effort among the member countries of the OECD Nuclear Energy Agency (NEA) Data Bank to develop a reference nuclear data library. The JEFF library contains sets of evaluated nuclear data, mainly for fission and fusion applications; it contains a number of different data types, including neutron and proton interaction data, radioactive decay data, fission yield data and thermal scattering law data. The General fission (GEF) model is based on novel theoretical concepts and ideas developed to model low energy nuclear fission. The GEF code calculates fission-fragment yields and associated quantities (e.g. prompt neutron and gamma) for a large range of nuclei and excitation energy. This opens up the possibility of a qualitative step forward to improve further the JEFF fission yields sub-library. This report describes the GEF model which explains the complex appearance of fission observables by universal principles of theoretical models and considerations on the basis of fundamental laws of physics and mathematics. The approach reveals a high degree of regularity and provides a considerable insight into the physics of the fission process. Fission observables can be calculated with a precision that comply with the needs for applications in nuclear technology. The relevance of the approach for examining the consistency of experimental results and for evaluating nuclear data is demonstrated. (authors)

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

Energy Technology Data Exchange (ETDEWEB)

Park, In Ja [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Kim, Hee Cheol [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Nam Kyu [Section of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Hyeong-Rok [Department of Surgery, Chonnam National University Hwansun Hospital, Gwangju (Korea, Republic of); Kang, Sung-Bum [Department of Surgery, Seoul National University Bungdang Hospital, Bundang (Korea, Republic of); Choi, Gyu-Seog [Division of Colorectal Cancer Center, Kyungpook National University Medical Center, Daegu (Korea, Republic of); Lee, Kang Young [Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seon-Hahn [Department of Surgery, Korea University Anam Hospital, Seoul (Korea, Republic of); Oh, Seung Taek [Department of Surgery, Seoul St. Mary Hospital, Catholic University, Seoul (Korea, Republic of); Lim, Seok-Byung; Kim, Jin Cheon [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Oh, Jae Hwan; Kim, Sun Young [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Lee, Woo Yong [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Jung Bok [Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Yu, Chang Sik, E-mail: csyu@amc.seoul.kr [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of)

2015-07-01

Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

Science.gov (United States)

Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

2015-07-01

To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

International Nuclear Information System (INIS)

Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

2015-01-01

Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits

Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold protein to polarize active Rac1 distribution.

Science.gov (United States)

Kroon, Jeffrey; Heemskerk, Niels; Kalsbeek, Martin J T; de Waard, Vivian; van Rijssel, Jos; van Buul, Jaap D

2017-07-01

Endothelial cells line the lumen of the vessel wall and are exposed to flow. In linear parts of the vessel, the endothelial cells experience laminar flow, resulting in endothelial cell alignment in the direction of flow, thereby protecting the vessel wall from inflammation and permeability. In order for endothelial cells to align, they undergo rapid remodeling of the actin cytoskeleton by local activation of the small GTPase Rac1. However, it is not clear whether sustained and local activation of Rac1 is required for long-term flow-induced cell alignment. Using a FRET-based DORA Rac1 biosensor, we show that local Rac1 activity remains for 12 h upon long-term flow. Silencing studies show that the RhoGEF Trio is crucial for keeping active Rac1 at the downstream side of the cell and, as a result, for long-term flow-induced cell alignment. Surprisingly, Trio appears to be not involved in flow-induced activation of Rac1. Our data show that flow induces Rac1 activity at the downstream side of the cell in a Trio-dependent manner and that Trio functions as a scaffold protein rather than a functional GEF under long-term flow conditions. © 2017 Kroon et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Signaling efficiency of Gαq through its effectors p63RhoGEF and GEFT depends on their subcellular location.

Science.gov (United States)

Goedhart, Joachim; van Unen, Jakobus; Adjobo-Hermans, Merel J W; Gadella, Theodorus W J

2013-01-01

The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Gαq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined to the cytoplasm. Live-cell imaging studies yielded quantitative information on diffusion coefficients, association rates and encounter times of GEFT and p63RhoGEF. Calcium signaling was examined as a measure of the signal transmission, revealing more efficient signaling through the membrane-associated p63RhoGEF. A rapamycin dependent recruitment system was used to dynamically alter the subcellular location and concentration of GEFT, showing efficient signaling through GEFT only upon membrane recruitment. Together, our results show efficient signal transmission through membrane located effectors, and highlight a role for increased concentration rather than increased encounter times due to membrane localization in the Gαq mediated pathways to p63RhoGEF and PLCβ.

A non-typical sequence of phase transitions in (NH4)3GeF7: optical and structural characterization.

Science.gov (United States)

Mel'nikova, S V; Molokeev, M S; Laptash, N M; Misyul, S V

2016-03-28

Single crystals of germanium double salt (NH4)3GeF7 = (NH4)2GeF6·NH4F = (NH4)3[GeF6]F were grown and studied by the methods of polarization optics and X-ray diffraction. The birefringence Δn = (no - ne), the rotation angle of the optical indicatrix ϕ(T) and unit cell parameters were measured in the temperature range 100-400 K. Three structural phase transitions were found at the temperatures: T1↓ = 279.2 K (T1↑ = 279.4 K), T2↑ = 270 K (T2↓ = 268.9 K), T3↓ = 218 K (T3↑ = 227 K). An unusual sequence of symmetry transformations with temperature change was established: P4/mbm (Z = 2) (G1) ↔ Pbam (Z = 4) (G2) ↔ P21/c (Z = 4) (G3) ↔ Pa3[combining macron] (Z = 8) (G4). The crystal structures of different phases were determined. The experimental data were additionally interpreted by a group-theoretical analysis of the complete condensate of order parameters taking into account the critical and noncritical atomic displacements. Strengthening of the N-HF hydrogen bonds can be a driving force of the observed phase transitions.

Robuste Verzweigungserkennung von Gefäßen in CTA-Datensätzen zur modellbasierten Extraktion der Centerline

Science.gov (United States)

Beck, Thomas; Fritz, Dominik; Biermann, Christina; Dillmann, Rüdiger

Bei der Befundung und Visualisierung von Blutgefäßen ist deren Centerline von zentraler Bedeutung. Die Unterscheidung zwischen unverzweigten Abschnitten des Gefäßes und Verzweigungsbereichen ermöglicht den Einsatz spezialisierter und sehr effizienter Algorithmen zur modellbasierten Extraktion der Centerline. In diesem Artikel wird ein robustes Verfahren zur Verzweigungserkennung vorgestellt. Das Verfahren beruht auf einem Front-Propagation-Ansatz mit dynamisch angepassten Schwellwerten und einer anschließenden Clusteranalyse. Die vorgestellte Methode zur Verzweigungserkennung wurde als Komponente einer Architektur zur Extraktion der Centerline auf handannotierten Datensätzen getestet. Erste Ergebnisse sind sehr vielversprechend und ermöglichen auch bei pathologischen Gefäßen eine robuste Detektion von Gefäßverzweigungen.

Coronin-1C and RCC2 guide mesenchymal migration by trafficking Rac1 and controlling GEF exposure

Science.gov (United States)

Williamson, Rosalind C.; Cowell, Christopher A. M.; Hammond, Christina L.; Bergen, Dylan J. M.; Roper, James A.; Feng, Yi; Rendall, Thomas C. S.; Race, Paul R.; Bass, Mark D.

2014-01-01

ABSTRACT Sustained forward migration through a fibrillar extracellular matrix requires localization of protrusive signals. Contact with fibronectin at the tip of a cell protrusion activates Rac1, and for linear migration it is necessary to dampen Rac1 activity in off-axial positions and redistribute Rac1 from non-protrusive membrane to the leading edge. Here, we identify interactions between coronin-1C (Coro1C), RCC2 and Rac1 that focus active Rac1 to a single protrusion. Coro1C mediates release of inactive Rac1 from non-protrusive membrane and is necessary for Rac1 redistribution to a protrusive tip and fibronectin-dependent Rac1 activation. The second component, RCC2, attenuates Rac1 activation outside the protrusive tip by binding to the Rac1 switch regions and competitively inhibiting GEF action, thus preventing off-axial protrusion. Depletion of Coro1C or RCC2 by RNA interference causes loss of cell polarity that results in shunting migration in 1D or 3D culture systems. Furthermore, morpholinos against Coro1C or RCC2, or mutation of any of the binding sites in the Rac1–RCC2–Coro1C complex delays the arrival of neural crest derivatives at the correct location in developing zebrafish, demonstrating the crucial role in migration guidance in vivo. PMID:25074804

Which Way In? The RalF Arf-GEF Orchestrates Rickettsia Host Cell Invasion

Science.gov (United States)

Rennoll-Bankert, Kristen E.; Rahman, M. Sayeedur; Gillespie, Joseph J.; Guillotte, Mark L.; Kaur, Simran J.; Lehman, Stephanie S.; Beier-Sexton, Magda; Azad, Abdu F.

2015-01-01

Bacterial Sec7-domain-containing proteins (RalF) are known only from species of Legionella and Rickettsia, which have facultative and obligate intracellular lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS) effector, is a guanine nucleotide exchange factor (GEF) of ADP-ribosylation factors (Arfs), activating and recruiting host Arf1 to the Legionella-containing vacuole. In contrast, previous in vitro studies showed R. prowazekii (Typhus Group) RalF is a functional Arf-GEF that localizes to the host plasma membrane and interacts with the actin cytoskeleton via a unique C-terminal domain. As RalF is differentially encoded across Rickettsia species (e.g., pseudogenized in all Spotted Fever Group species), it may function in lineage-specific biology and pathogenicity. Herein, we demonstrate RalF of R. typhi (Typhus Group) interacts with the Rickettsia T4SS coupling protein (RvhD4) via its proximal C-terminal sequence. RalF is expressed early during infection, with its inactivation via antibody blocking significantly reducing R. typhi host cell invasion. For R. typhi and R. felis (Transitional Group), RalF ectopic expression revealed subcellular localization with the host plasma membrane and actin cytoskeleton. Remarkably, R. bellii (Ancestral Group) RalF showed perinuclear localization reminiscent of ectopically expressed Legionella RalF, for which it shares several structural features. For R. typhi, RalF co-localization with Arf6 and PI(4,5)P2 at entry foci on the host plasma membrane was determined to be critical for invasion. Thus, we propose recruitment of PI(4,5)P2 at entry foci, mediated by RalF activation of Arf6, initiates actin remodeling and ultimately facilitates bacterial invasion. Collectively, our characterization of RalF as an invasin suggests that, despite carrying a similar Arf-GEF unknown from other bacteria, different intracellular lifestyles across Rickettsia and Legionella species have driven divergent roles for Ral

Signaling efficiency of Galphaq through its effectors p63RhoGEF and GEFT depends on their subcellular location

NARCIS (Netherlands)

Goedhart, J.; Unen, J. van; Adjobo-Hermans, M.J.W.; Gadella, T.W.

2013-01-01

The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Galphaq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined

A computational study of a recreated G protein-GEF reaction intermediate competent for nucleotide exchange: fate of the Mg ion.

Directory of Open Access Journals (Sweden)

Mériam Ben Hamida-Rebaï

Full Text Available Small G-proteins of the superfamily Ras function as molecular switches, interacting with different cellular partners according to their activation state. G-protein activation involves the dissociation of bound GDP and its replacement by GTP, in an exchange reaction that is accelerated and regulated in the cell by guanine-nucleotide exchange factors (GEFs. Large conformational changes accompany the exchange reaction, and our understanding of the mechanism is correspondingly incomplete. However, much knowledge has been derived from structural studies of blocked or inactive mutant GEFs, which presumably closely represent intermediates in the exchange reaction and yet which are by design incompetent for carrying out the nucleotide exchange reaction. In this study we have used comparative modelling to recreate an exchange-competent form of a late, pre-GDP-ejection intermediate species in Arf1, a well-characterized small G-protein. We extensively characterized three distinct models of this intermediate using molecular dynamics simulations, allowing us to address ambiguities related to the mutant structural studies. We observed in particular the unfavorable nature of Mg2+ associated forms of the complex and the establishment of closer Arf1-GEF contacts in its absence. The results of this study shed light on GEF-mediated activation of this small G protein and on predicting the fate of the Mg ion at a critical point in the exchange reaction. The structural models themselves furnish additional targets for interfacial inhibitor design, a promising direction for exploring potentially druggable targets with high biological specificity.

Signaling efficiency of Gαq through its effectors p63RhoGEF and GEFT depends on their subcellular location.

NARCIS (Netherlands)

Goedhart, J.; van Unen, J.; Adjobo-Hermans, M.J.W.; Gadella (jr.), T.W.J.

2013-01-01

The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Galphaq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined

Transforming on-grid renewable energy markets. A review of UNDP-GEF support for feed-in tariffs and related price and market-access instruments

Energy Technology Data Exchange (ETDEWEB)

Glemarec, Yannick; Rickerson, Wilson; Waissbein, Oliver

2012-11-15

As a Global Environment Facility (GEF) founding implementing agency, UNDP has worked on over 230 GEF-supported clean energy projects in close to 100 developing countries since 1992. About 100 of these projects in 80 countries have focused on renewable energy, supported by approximately US $ 293 million in GEF funds and leveraging US $1.48 billion in associated co-financing from national governments, international organizations, the private sector and non-governmental organizations. As part of UNDP efforts to codify and share lessons learnt from these initiatives, this report addresses how scarce public resources can be used to catalyze larger private financial flows for renewable energy. It provides an overview of UNDP-GEF’s extensive work supporting development of national renewable energy policies such as feed-in tariffs. In these activities UNDP-GEF assists developing countries to assess key risks and barriers to technology diffusion and then to identify a mix of policy and financial de-risking measures to remove these barriers and drive investment. This approach is illustrated through three case studies in Uruguay, Mauritius and Kazakhstan. This report is complemented by a companion publication presenting an innovative UNDP financial modeling tool to assist policymakers in appraising different public instruments to promote clean energy.

Raumgefühle – Gefühlsräume. Perspektiven auf die Verschränkung von emotionalen Praktiken und Topografien der Moderne

Directory of Open Access Journals (Sweden)

Benno Gammerl

2015-08-01

Full Text Available Ausgehend von verschiedenen Ansätzen in der Forschung zu Gefühlen und Räumen umreißt der Artikel das theoretische, empirische und politische Potenzial des Spannungsfelds zwischen der affektiven Durchkreuzung geordneter Strukturen und der emotionalen Bearbeitung machtdurchwirkter Raumverhältnisse. Praktiken des urban gardening und Debatten über Gentrifizierung zeigen beispielhaft, wie Analysen der dynamischen Interaktionen zwischen Räumen und Gefühlen für eine kritische Perspektive auf Urbanität fruchtbar werden können. Die Beschäftigung mit der Körperlichkeit von Raumgefühlen und der Materialität von Gefühlsräumen bietet willkommene Gelegenheiten, nach Strategien zu suchen, die weder das beharrliche Wirken des Sozialen noch die widerständige Kraft des Materiellen in deterministischer Manier überbetonen, sondern sich stattdessen auf die ambivalenten Dynamiken und Effekte gefühlsräumlicher Prozesse konzentrieren.

Synthesis and properties of Rb2GeF6:Mn4+ red-emitting phosphors

Science.gov (United States)

Sakurai, Shono; Nakamura, Toshihiro; Adachi, Sadao

2018-02-01

Rb2GeF6:Mn4+ red-emitting phosphors were synthesized by coprecipitation and their structural and optical properties were investigated by laser microscopy observation, X-ray diffraction (XRD) analysis, photoluminescence (PL) analysis, PL excitation (PLE) spectroscopy, and PL decay measurement. Single-crystalline ingots in the form of a hexagonal pyramid were prepared with a basal plane diameter of ˜2 mm. The XRD analysis suggested that Rb2GeF6 crystallizes in the hexagonal structure (C6v4 = P63mc) with a = 0.5955 nm and c = 0.9672 nm. The phosphor exhibited the strong Mn4+-related zero-phonon line (ZPL) emission peak typically observed in host crystals with piezoelectrically active lattices such as a hexagonal lattice. The quantum efficiencies of the bulk ingot and powdered samples were 87 and 74%, respectively, with nearly the same luminescence decay time of ˜6 ms. The exact ZPL energies and related crystal-field and Racah parameters were obtained from the PL and PLE spectra by Franck-Condon analysis. Temperature-dependent PL intensities were analyzed from T = 20 to 500 K using a thermal quenching model by considering Bose-Einstein phonon statistics. A comparative discussion on the phosphor properties of Rb2GeF6:Mn4+ and Rb2MF6:Mn4+ with M = Si and Ti was also given.

Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

Science.gov (United States)

Marcus-Gueret, Nancy; Schmidt, Kristopher L.; Stringham, Eve G.

2012-01-01

The cytoskeleton regulator UNC-53/NAV2 is required for both the anterior and posterior outgrowth of several neurons as well as that of the excretory cell while the kinesin-like motor VAB-8 is essential for most posteriorly directed migrations in Caenorhabditis elegans. Null mutations in either unc-53 or vab-8 result in reduced posterior excretory canal outgrowth, while double null mutants display an enhanced canal extension defect, suggesting the genes act in separate pathways to control this posteriorly directed outgrowth. Genetic analysis of putative interactors of UNC-53 or VAB-8, and cell-specific rescue experiments suggest that VAB-8, SAX-3/ROBO, SLT-1/Slit, and EVA-1 are functioning together in the outgrowth of the excretory canals, while UNC-53 appears to function in a parallel pathway with UNC-71/ADAM. The known VAB-8 interactor, the Rac/Rho GEF UNC-73/TRIO operates in both pathways, as isoform specific alleles exhibit enhancement of the phenotype in double-mutant combination with either unc-53 or vab-8. On the basis of these results, we propose a bipartite model for UNC-73/TRIO activity in excretory canal extension: a cell autonomous function that is mediated by the Rho-specific GEF domain of the UNC-73E isoform in conjunction with UNC-53 and UNC-71 and a cell nonautonomous function that is mediated by the Rac-specific GEF domain of the UNC-73B isoform, through partnering with VAB-8 and the receptors SAX-3 and EVA-1. PMID:21996675

Brief introduction of GEF efficient industrial boiler project in China

Energy Technology Data Exchange (ETDEWEB)

Meijian, T.

1996-12-31

The present situation of installed industrial boilers, their efficiency and environmental impact are assessed. And the factors contribute to the low efficiency and serious pollution are summarized. Based on WB-assisted GEF project, {open_quotes}Efficient Industrial Boiler Project{close_quotes} aimed at CO{sub 2} mitigation in China, a series of effective measures to bring the GHG emission under control are addressed, in technology, system performance, and operation management aspects.

Promoting energy-efficient products: GEF experience and lessons for market transformation in developing countries

International Nuclear Information System (INIS)

Birner, Sabrina; Martinot, Eric

2005-01-01

The Global Environment Facility (GEF) has allocated more than $90 million over the past 10 years to eight projects promoting energy-efficient products in developing and transition countries. We review the early experience from these projects and suggest lessons relevant to market transformation programs. Based on GEF project designs, we also propose a menu of generic supply-side and demand-side interventions useful for designing and analyzing market transformation programs. Experience suggests that institutional and policy changes, leading to sustained price reductions and higher market volumes, are important outcomes for market transformation; that market impacts can appear early in programs due to increased expectations and awareness; and that projects can have a catalytic effect. We recommend eight principles for designers of future projects but caution that no single approach guarantees success

An Assessment of the Subseasonal Forecast Performance in the Extended Global Ensemble Forecast System (GEFS)

Science.gov (United States)

Sinsky, E.; Zhu, Y.; Li, W.; Guan, H.; Melhauser, C.

2017-12-01

Optimal forecast quality is crucial for the preservation of life and property. Improving monthly forecast performance over both the tropics and extra-tropics requires attention to various physical aspects such as the representation of the underlying SST, model physics and the representation of the model physics uncertainty for an ensemble forecast system. This work focuses on the impact of stochastic physics, SST and the convection scheme on forecast performance for the sub-seasonal scale over the tropics and extra-tropics with emphasis on the Madden-Julian Oscillation (MJO). A 2-year period is evaluated using the National Centers for Environmental Prediction (NCEP) Global Ensemble Forecast System (GEFS). Three experiments with different configurations than the operational GEFS were performed to illustrate the impact of the stochastic physics, SST and convection scheme. These experiments are compared against a control experiment (CTL) which consists of the operational GEFS but its integration is extended from 16 to 35 days. The three configurations are: 1) SPs, which uses a Stochastically Perturbed Physics Tendencies (SPPT), Stochastic Perturbed Humidity (SHUM) and Stochastic Kinetic Energy Backscatter (SKEB); 2) SPs+SST_bc, which uses a combination of SPs and a bias-corrected forecast SST from the NCEP Climate Forecast System Version 2 (CFSv2); and 3) SPs+SST_bc+SA_CV, which combines SPs, a bias-corrected forecast SST and a scale aware convection scheme. When comparing to the CTL experiment, SPs shows substantial improvement. The MJO skill has improved by about 4 lead days during the 2-year period. Improvement is also seen over the extra-tropics due to the updated stochastic physics, where there is a 3.1% and a 4.2% improvement during weeks 3 and 4 over the northern hemisphere and southern hemisphere, respectively. Improvement is also seen when the bias-corrected CFSv2 SST is combined with SPs. Additionally, forecast performance enhances when the scale aware

AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

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Matthew J Spindler

Full Text Available A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

Dirac cone and pseudogapped density of states in the topological half-Heusler compound YPtBi

Science.gov (United States)

Kronenberg, A.; Braun, J.; Minár, J.; Elmers, H.-J.; Kutnyakhov, D.; Zaporozhchenko, A. V.; Wallauer, R.; Chernov, S.; Medjanik, K.; Schönhense, G.; Kläui, M.; Chadov, S.; Ebert, H.; Jourdan, M.

2016-10-01

Topological insulators (TIs) are exciting materials, which exhibit unprecedented properties, such as helical spin-momentum locking, which leads to large torques for magnetic switching and highly efficient spin current detection. Here we explore the compound YPtBi, an example from the class of half-Heusler materials, for which the typical band inversion of topological insulators was predicted. We prepared this material as thin films by conventional cosputtering from elementary targets. By in situ time-of-flight momentum microscopy, a Dirac conelike surface state with a Dirac point ≃300 meV below the Fermi energy was observed, in agreement with electronic structure-photoemission calculations. Only little additional spectral weight due to other states was observed at EF, which corroborates the identification of the topologically protected surface state and is highly relevant for spintronics applications.

Photovoltaics in Africa and the GEF: the right path to sustainable development?

International Nuclear Information System (INIS)

Bacon, I.

1998-01-01

This paper explores the relevance of promoting photovoltaic (PV) projects within Africa by focusing on the issues arising from the GEF/Zimbabwe PV project 1992-1997. It questions the utility of such projects and the reasons for the continued promotion of this technology within Africa. It concludes that financial aid for PV technology needs to be thoroughly reviewed and redirected. (author)

La Theorie des Gefühls hegeliana in dialogo con le recenti teorie sulle emozioni

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Caterina Maurer

2017-04-01

Full Text Available Considering the relevance of the interaction between neuroscience, psychology, and philosophy in the contemporary debate on emotions, this paper aims at establishing a fruitful dialogue between Hegel’s Philosophie des subjektiven Geistes and the most important neuroscientific and psychological research on emotions. By means of an analysis of the role of Empfindungen (sensations and Gefühle (feelings in the Enzyklopädie der philosophischen Wissenschaften (1830, we will show that Hegel developed a Theorie des Gefühls. The proposed dialogue between Hegel’s thought and contemporary theories is useful for distinguishing the various types of emotions and their cognitive and affective aspects. In fact, it will emerge that both Hegel and recent studies on emotion consider emotions to be characterized by a cognitive valence which enables a person to orient herself/himself in the world.

Conducting filaments in Pt/ZrCuO{sub y}/Pt resistive switching memory cells

Energy Technology Data Exchange (ETDEWEB)

Tulu, Berhanu [Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan (China); Chu, Jinn P., E-mail: jpchu@mail.ntust.edu.tw [Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan (China); Wang, Sea-Fue [Department of Materials and Minerals Resources Engineering, National Taipei University of Technology, Taipei 10608, Taiwan (China)

2015-11-15

Forming-free unipolar resistive switching with good retention time, low voltage (<1.9 V) and thin thickness (∼11 nm) is obtained in oxygen deficient Pt/ZrCuO{sub y}/Pt devices. Annealing at 150 °C is beneficial to improve the endurance from 286 to >6 × 10{sup 3} and the resistance ratio from ∼13 to ∼25. Nanoscale current path images observed using a conductive atomic force microscope reveal a current density of ∼3.0 × 10{sup 2} nA/μm{sup 2} in the ON state, almost four orders of magnitude higher than ∼3.3 × 10{sup −2} nA/μm{sup 2} in the OFF state. The resistive switching is thought to be dominated by the oxygen vacancies, which serves as the filamentary conduction in the film. - Highlights: • Oxygen deficient Pt/ZrCuOy/Pt device after annealing at 150 °C is studied. • Forming-free resistive switching with good retention time, low voltage is obtained. • Annealing is shown to improve the endurance from 286 to >6 × 10{sup 3}. • The resistive switching is thought to be dominated by the oxygen vacancies.

Purification and crystallization of the catalytic PRONE domain of RopGEF8 and its complex with Rop4 from Arabidopsis thaliana

International Nuclear Information System (INIS)

Thomas, Christoph; Weyand, Michael; Wittinghofer, Alfred; Berken, Antje

2006-01-01

Crystals of the catalytic PRONE domain of the guanine nucleotide exchange factor RopGEF8 and its complex with the Rho-family protein Rop4 from A. thaliana were obtained that diffract to 2.2 and 3.1 Å resolution, respectively. The PRONE domain of the guanine nucleotide exchange factor RopGEF8 (PRONE8) was purified and crystallized free and in complex with the Rho-family protein Rop4 using the hanging-drop vapour-diffusion method. PRONE8 crystals were obtained using NaCl as precipitating agent and belong to the hexagonal space group P6 5 22. Native and anomalous data sets were collected using synchrotron radiation at 100 K to 2.2 and 2.8 Å resolution, respectively. Crystals of the Rop4–PRONE8 complex belonging to space group P6 3 were obtained using Tacsimate and PEG 3350 as precipitating agents and diffracted to 3.1 Å resolution

Purification and crystallization of the catalytic PRONE domain of RopGEF8 and its complex with Rop4 from Arabidopsis thaliana

Energy Technology Data Exchange (ETDEWEB)

Thomas, Christoph; Weyand, Michael; Wittinghofer, Alfred; Berken, Antje, E-mail: antje.berken@mpi-dortmund.mpg.de [Department of Structural Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany)

2006-06-01

Crystals of the catalytic PRONE domain of the guanine nucleotide exchange factor RopGEF8 and its complex with the Rho-family protein Rop4 from A. thaliana were obtained that diffract to 2.2 and 3.1 Å resolution, respectively. The PRONE domain of the guanine nucleotide exchange factor RopGEF8 (PRONE8) was purified and crystallized free and in complex with the Rho-family protein Rop4 using the hanging-drop vapour-diffusion method. PRONE8 crystals were obtained using NaCl as precipitating agent and belong to the hexagonal space group P6{sub 5}22. Native and anomalous data sets were collected using synchrotron radiation at 100 K to 2.2 and 2.8 Å resolution, respectively. Crystals of the Rop4–PRONE8 complex belonging to space group P6{sub 3} were obtained using Tacsimate and PEG 3350 as precipitating agents and diffracted to 3.1 Å resolution.

Closing the Gap GEF Experiences in Global Energy Efficiency

CERN Document Server

Yang, Ming

2013-01-01

Energy efficiency plays and will continue to play an important role in the world to save energy and mitigate greenhouse gas (GHG) emissions. However, little is known on how much additional capital should be invested to ensure using energy efficiently as it should be, and very little is known which sub-areas, technologies, and countries shall achieve maximum greenhouse gas emissions mitigation per dollar of investment in energy efficiency worldwide. Analyzing completed and slowly moving energy efficiency projects by the Global Environment Facility during 1991-2010, Closing the Gap: GEF Experiences in Global Energy Efficiency evaluates impacts of multi-billion-dollar investments in the world energy efficiency. It covers the following areas: 1.       Reviewing the world energy efficiency investment and disclosing the global energy efficiency gap and market barriers that cause the gap; 2.       Leveraging private funds with public funds and other resources in energy efficiency investments; using...

Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction

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Deng Xiaolu

2011-04-01

Full Text Available Abstract Background Tumor necrosis factor-α (TNF-α, a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC barrier dysfunction. Methods Bend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL. RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER. p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability. Results We observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER. Conclusions Taken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF

Geometry and electronic structure of an impurity-trapped exciton in the Cs2GeF6 crystal doped with U4+. The 5f17s1 manifold

International Nuclear Information System (INIS)

Ordejon, B.; Seijo, L.; Barandiaran, Z.

2007-01-01

Complete text of publication follows: Excitons trapped at impurity centres in highly ionic crystals were first described by McClure and Pedrini [Phys. Rev. B 32, 8465 (1985)] as excited states consisting of a bound electron-hole pair with the hole localized on the impurity and the electron on nearby lattice sites, and a very short impurity-ligand bond length. In this work we present a detailed microscopic characterization of an impurity - trapped exciton in Cs 2 GeF 6 doped with U 4+ . Its electronic structure has been studied by means of CASSCF/CASPT2/SOCI relativistic ab initio model potential (AIMP) embedded-cluster calculations on (UF 6 ) 2- and (UF 6 Cs 8 ) 6+ clusters embedded in Cs 2 GeF 6 . The local geometry of the impurity-trapped exciton, the potential energy curves, and the multi electronic wavefunctions, have been obtained as direct, non-empirical results of the methods. The calculated excited states appear to be significantly delocalized outside the UF 6 volume and their U-F bond length turns out to be very short, closer to that of a pentavalent uranium defect than to that of a tetravalent uranium defect. The wavefunctions of these excited states show a dominant U 5f 1 7s 1 configuration character. This result has never been anticipated by simpler models and reveals the unprecedented ability of diffuse orbitals of f-element impurities to act as electron traps in ionic crystals

Investigation of ambient temperature on the performance of GE-F5 gas turbine

International Nuclear Information System (INIS)

Ghazikhani, M.; Taffazoli, D.; Manshori, N.

2002-01-01

The role of ambient temperature in determining the performance of GE-F5 gas turbine is analysed by investigating the Shirvan gas turbine power plant 10 MW , 15 MW and 20 MW power output. These parameters have been brought as a function of ambient temperature. The results show when ambient temperature increases 1 deg C, The compressor pressure decreases about 20 k Pa, compressor outlet temperature increases about 1.13 deg C and exhaust temperature increases about 2.5 deg C. It is revealed that variations are due to decreasing the efficiency of compressor and less due to mass flow rate of air reduction as ambient temperature increases at constant power output. The results shows cycle efficiency reduces 3% with increasing 50 of ambient temperature, also the m increases as ambient temperature increase for constant turbine work. These are also because of reducing the compressor efficiency as ambient temperature increases

The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast

Energy Technology Data Exchange (ETDEWEB)

Tsukamoto, Yuta; Katayama, Chisako [Graduate School of Science, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan); Shinohara, Miki; Shinohara, Akira [Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Maekawa, Shohei [Graduate School of Science, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan); Miyamoto, Masaaki, E-mail: miya@kobe-u.ac.jp [Graduate School of Science, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan); Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan)

2013-11-29

Highlights: •Multiple functions of Rab5 GTPase in fission yeast were found. •Roles of Rab5 in fission yeast were discussed. •Relation between Rab5 and actin cytoskeleton were discussed. -- Abstract: Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our data strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions.

The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast

International Nuclear Information System (INIS)

Tsukamoto, Yuta; Katayama, Chisako; Shinohara, Miki; Shinohara, Akira; Maekawa, Shohei; Miyamoto, Masaaki

2013-01-01

Highlights: •Multiple functions of Rab5 GTPase in fission yeast were found. •Roles of Rab5 in fission yeast were discussed. •Relation between Rab5 and actin cytoskeleton were discussed. -- Abstract: Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our data strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions

Function of the Nucleotide Exchange Activity of Vav1 in T cell Development and Activation*

Science.gov (United States)

Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J.; Rittinger, Katrin; Tybulewicz, Victor L. J.

2012-01-01

The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal–regulated kinase (ERK) and protein kinase D1 (PKD1), and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions. PMID:20009105

Function of the nucleotide exchange activity of vav1 in T cell development and activation.

Science.gov (United States)

Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J; Rittinger, Katrin; Tybulewicz, Victor L J

2009-12-15

The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal-regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.

Remedial Strategies in Structural Proteomics: Expression, Purification, And Crystallization of the Vav1/Rac1 Complex

Energy Technology Data Exchange (ETDEWEB)

Brooun, A.; Foster, S.A.; Chrencik, H.E.; Chien, E.Y.T.; Kolatkar, A.R.; Streiff, M.; Ramage, P.; Widmer, H.; Weckbecker, G.; Kuhn, P.

2007-07-03

The signal transduction pathway involving the Vav1 guanine nucleotide exchange factor (GEF) and the Rac1 GTPase plays several key roles in the immune response mediated by the T cell receptor. Vav1 is also a unique member of the GEF family in that it contains a cysteine-rich domain (CRD) that is critical for Rac1 binding and maximal guanine nucleotide exchange activity, and thus may provide a unique protein-protein interface compared to other GEF/GTPase pairs. Here, we have applied a number of remedial structural proteomics strategies, such as construct and expression optimization, surface mutagenesis, limited proteolysis, and protein formulation to successfully express, purify, and crystallize the Vav1-DH-PH-CRD/Rac1 complex in an active conformation. We have also systematically characterized various Vav1 domains in a GEF assay and Rac1 in vitro binding experiments. In the context of Vav1-DH-PH-CRD, the zinc finger motif of the CRD is required for the expression of stable Vav1, as well as for activity in both a GEF assay and in vitro formation of a Vav1/Rac1 complex suitable for biophysical and structural characterization. Our data also indicate that the isolated CRD maintains a low level of specific binding to Rac1, appears to be folded based on 1D NMR analysis and coordinates two zinc ions based on ICP-MS analysis. The protein reagents generated here are essential tools for the determination of a three dimensional Vav1/Rac1 complex crystal structure and possibly for the identification of inhibitors of the Vav1/Rac1 protein-protein interaction with potential to inhibit lymphocyte activation.

Proteomic analysis of Rac1 signaling regulation by guanine nucleotide exchange factors.

Science.gov (United States)

Marei, Hadir; Carpy, Alejandro; Macek, Boris; Malliri, Angeliki

2016-08-02

The small GTPase Rac1 is implicated in various cellular processes that are essential for normal cell function. Deregulation of Rac1 signaling has also been linked to a number of diseases, including cancer. The diversity of Rac1 functioning in cells is mainly attributed to its ability to bind to a multitude of downstream effectors following activation by Guanine nucleotide Exchange Factors (GEFs). Despite the identification of a large number of Rac1 binding partners, factors influencing downstream specificity are poorly defined, thus hindering the detailed understanding of both Rac1's normal and pathological functions. In a recent study, we demonstrated a role for 2 Rac-specific GEFs, Tiam1 and P-Rex1, in mediating Rac1 anti- versus pro-migratory effects, respectively. Importantly, via conducting a quantitative proteomic screen, we identified distinct changes in the Rac1 interactome following activation by either GEF, indicating that these opposing effects are mediated through GEF modulation of the Rac1 interactome. Here, we present the full list of identified Rac1 interactors together with functional annotation of the differentially regulated Rac1 binding partners. In light of this data, we also provide additional insights into known and novel signaling cascades that might account for the GEF-mediated Rac1-driven cellular effects.

Gef gene therapy enhances the therapeutic efficacy of doxorubicin to combat growth of MCF-7 breast cancer cells

OpenAIRE

2009-01-01

Abstract Purpose The potential use of combined therapy is under intensive study including the association between classical cytotoxic and genes encoding toxic proteins which enhanced the antitumour activity. The main aim of this work was to evaluate whether the gef gene, a suicide gene which has a demonstrated antiproliferative activity in tumour cells, improved the antitumour effect of chemotherapeutic drugs used as first-line treatment in the management...

PH Domain-Arf G Protein Interactions Localize the Arf-GEF Steppke for Cleavage Furrow Regulation in Drosophila.

Directory of Open Access Journals (Sweden)

Donghoon M Lee

Full Text Available The recruitment of GDP/GTP exchange factors (GEFs to specific subcellular sites dictates where they activate small G proteins for the regulation of various cellular processes. Cytohesins are a conserved family of plasma membrane GEFs for Arf small G proteins that regulate endocytosis. Analyses of mammalian cytohesins have identified a number of recruitment mechanisms for these multi-domain proteins, but the conservation and developmental roles for these mechanisms are unclear. Here, we report how the pleckstrin homology (PH domain of the Drosophila cytohesin Steppke affects its localization and activity at cleavage furrows of the early embryo. We found that the PH domain is necessary for Steppke furrow localization, and for it to regulate furrow structure. However, the PH domain was not sufficient for the localization. Next, we examined the role of conserved PH domain amino acid residues that are required for mammalian cytohesins to bind PIP3 or GTP-bound Arf G proteins. We confirmed that the Steppke PH domain preferentially binds PIP3 in vitro through a conserved mechanism. However, disruption of residues for PIP3 binding had no apparent effect on GFP-Steppke localization and effects. Rather, residues for binding to GTP-bound Arf G proteins made major contributions to this Steppke localization and activity. By analyzing GFP-tagged Arf and Arf-like small G proteins, we found that Arf1-GFP, Arf6-GFP and Arl4-GFP, but not Arf4-GFP, localized to furrows. However, analyses of embryos depleted of Arf1, Arf6 or Arl4 revealed either earlier defects than occur in embryos depleted of Steppke, or no detectable furrow defects, possibly because of redundancies, and thus it was difficult to assess how individual Arf small G proteins affect Steppke. Nonetheless, our data show that the Steppke PH domain and its conserved residues for binding to GTP-bound Arf G proteins have substantial effects on Steppke localization and activity in early Drosophila embryos.

Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4.

Science.gov (United States)

Mills, Shirley C; Howell, Lesley; Beekman, Andrew; Stokes, Leanne; Mueller, Anja

2018-01-01

Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling does not regulate cell migration in either suspension or adherent cells. We have confirmed the involvement of Rac1 with the use of a specific Rac1 blocking peptide. We also used a Rac1 inhibitor EHT 1864 and a Rac1-GEF inhibitor NSC23766 to probe the importance of Rac1 in chemotaxis. Both inhibitors did not block CCL3-induced chemotaxis, but they were able to block CXCL12-induced chemotaxis. This confirms that Rac1 activation is not essential for CCL3-induced migration, however NSC23766 might have secondary effects on CXCR4. This small molecule exhibits agonistic features in internalisation and cAMP assays, whereas it acts as an antagonist for CXCR4 in migration and calcium release assays. Our findings strongly suggest that Rac1 activation is not necessary for CCL3 signalling, and reveal that NSC23766 could be a novel CXCR4 receptor ligand. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

Science.gov (United States)

Rice, Thomas W; Ishwaran, Hemant; Kelsen, David P; Hofstetter, Wayne L; Apperson-Hansen, Carolyn; Blackstone, Eugene H

2016-11-01

We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy. © 2016 International Society for Diseases of the Esophagus.

Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer.

Science.gov (United States)

Naiken, Surennaidoo P; Toso, Christian; Rubbia-Brandt, Laura; Thomopoulos, Theodoros; Roth, Arnaud; Mentha, Gilles; Morel, Philippe; Gervaz, Pascal

2014-01-17

Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis. A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence. The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy

Structure-composition sensitivity in 'Metallic' Zintl phases: A study of Eu(Ga1-xTtx)2 (Tt=Si, Ge, 0≤x≤1)

International Nuclear Information System (INIS)

You, Tae-Soo; Zhao Jingtai; Poettgen, Rainer; Schnelle, Walter; Burkhardt, Ulrich; Grin, Yuri; Miller, Gordon J.

2009-01-01

Two isoelectronic series, Eu(Ga 1-x Tt x ) 2 (Tt=Si, Ge, 0≤x≤1), have been synthesized and characterized by powder and single-crystal X-ray diffraction, physical property measurements, and electronic structure calculations. In Eu(Ga 1-x Si x ) 2 , crystal structures vary from the KHg 2 -type to the AlB 2 -type, and, finally, the ThSi 2 -type structure as x increases. The hexagonal AlB 2 -type structure is identified for compositions 0.18(2)≤x 3 nets. As smaller Si atoms replace Ga atoms while the number of valence electrons increases, the lattice parameters, unit cell volumes, and Ga-Si distances in this phase region decrease significantly. Although aspects of X-ray diffraction results suggest puckering of the 6 3 nets for the Si-richest example of the AlB 2 -type Eu(Ga 1-x Si x ) 2 , the complete experimental evidence remains inconclusive. On the other hand, in Eu(Ga 1-x Ge x ) 2 , six different structural types were observed as x varies. In addition to EuGa 2 (KHg 2 -type; space group Imma) and EuGe 2 (own structure type, space group P3-barm1), the ternary phases studied show four different structures: the AlB 2 -type for Ga-rich compositions; the YPtAs-type structure for EuGaGe; and two new structures, which are intergrowths of the YPtAs-type EuGaGe and EuGe 2 , for Ge-rich compositions. These two Ge-rich phases include: (1) Eu(Ga 0.45(2) Ge 0.55(2) ) 2 containing two YPtAs-type motifs of EuGaGe plus one EuGe 2 motif; and (2) Eu(Ga 0.40(2) Ge 0.60(2) ) 2 containing one YPtAs-type motif alternating with a split site at x=2/3 ,y=1/3 and z=0.4798(2) with ca. 50% site occupancy by Ga and Ge along the c-axis. Magnetic susceptibilities of three Eu(Ga 1-x Ge x ) 2 compounds display Curie-Weiss behavior above ca. 100 K, and show effective magnetic moments indicative of divalent Eu with a 4f 7 electronic configuration, consistent with. X-ray absorption spectra (XAS). Density of states (DOS) and crystal orbital Hamilton population (COHP) analyses, based on first

Three-dimensional structures of unligated uridine phosphorylase from Yersinia pseudotuberculosis at 1.4 Å resolution and its complex with an antibacterial drug

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Balaev, V. V.; Lashkov, A. A.; Gabdulkhakov, A. G.; Dontsova, M. V.; Mironov, A. S.; Betzel, C.; Mikhailov, A. M.

2015-07-01

Uridine phosphorylases play an essential role in the cellular metabolism of some antibacterial agents. Acute infectious diseases (bubonic plague, yersiniosis, pseudotuberculosis, etc., caused by bacteria of the genus Yersinia) are treated using both sulfanilamide medicines and antibiotics, including trimethoprim. The action of an antibiotic on a bacterial cell is determined primarily by the character of its interactions with cellular components, including those which are not targets (for example, with pyrimidine phosphorylases). This type of interaction should be taken into account in designing drugs. The three-dimensional structure of uridine phosphorylase from the bacterium Yersinia pseudotuberculosis ( YptUPh) with the free active site was determined for the first time by X-ray crystallography and refined at 1.40 Å resolution (DPI = 0.062 Å; ID PDB: 4OF4). The structure of the complex of YptUPh with the bacteriostatic drug trimethoprim was studied by molecular docking and molecular dynamics methods. The trimethoprim molecule was shown to be buffered by the enzyme YptUPh, resulting in a decrease in the efficiency of the treatment of infectious diseases caused by bacteria of the genus Yersinia with trimethoprim.

GmCLC1 Confers Enhanced Salt Tolerance through Regulating Chloride Accumulation in Soybean

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Peipei Wei

2016-07-01

Full Text Available The family of chloride channel proteins that mediate Cl- transportation play vital roles in plant nutrient supply, cellular action potential and turgor pressure adjustment, stomatal movement, hormone signal recognition and transduction, Cl- homeostasis, and abiotic and biotic stress tolerance. The anionic toxicity, mainly caused by chloride ions (Cl-, on plants under salt stress remains poorly understood. In this work, we investigated the function of soybean Cl-/H+ antiporter GmCLC1 under salt stress in transgenic Arabidopsis thaliana, soybean, and yeast. We found that GmCLC1 enhanced salt tolerance in transgenic A. thaliana by reducing the Cl- accumulation in shoots and hence released the negative impact of salt stress on plant growth. Overexpression of GmCLC1 in the hairy roots of soybean sequestered more Cl- in their roots and transferred less Cl- to their shoots, leading to lower relative electrolyte leakage values in the roots and leaves. When either the soybean GmCLC1 or the yeast chloride transporter gene, GEF1, was transformed into the yeast gef1 mutant, and then treated with different chloride salts (MnCl2, KCl, NaCl, enhanced survival rate was observed. The result indicates that GmCLC1 and GEF1 exerted similar effects on alleviating the stress of diverse chloride salts on the yeast gef1 mutant. Together, this work suggests a protective function of GmCLC1 under Cl- stress.

Electronic excitation to low-lying states of GeF4 molecule by electron impact: A comparative study with CF4 and SiF4 molecules

International Nuclear Information System (INIS)

Ohtomi, S; Matsui, M; Mochizuki, Y; Suga, A; Kato, H; Hoshino, M; Tanaka, H; Duflot, D; Limão-Vieira, P

2015-01-01

We report on the measurements of the electron impact electronic excitation cross sections for XF 4 (X = C, Si and Ge) molecules at 100 eV, 5° scattering angle and 30 eV, 30° in the electron energy loss range 8.0 - 18 eV. For a target of GeF 4 molecule, the optically-forbidden behavior has been observed in the lower electron energy loss range. (paper)

Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration

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Marei, Hadir; Carpy, Alejandro; Woroniuk, Anna; Vennin, Claire; White, Gavin; Timpson, Paul; Macek, Boris; Malliri, Angeliki

2016-01-01

The small GTPase Rac1 has been implicated in the formation and dissemination of tumours. Upon activation by guanine nucleotide exchange factors (GEFs), Rac1 associates with a variety of proteins in the cell thereby regulating various functions, including cell migration. However, activation of Rac1 can lead to opposing migratory phenotypes raising the possibility of exacerbating tumour progression when targeting Rac1 in a clinical setting. This calls for the identification of factors that influence Rac1-driven cell motility. Here we show that Tiam1 and P-Rex1, two Rac GEFs, promote Rac1 anti- and pro-migratory signalling cascades, respectively, through regulating the Rac1 interactome. In particular, we demonstrate that P-Rex1 stimulates migration through enhancing the interaction between Rac1 and the actin-remodelling protein flightless-1 homologue, to modulate cell contraction in a RhoA-ROCK-independent manner. PMID:26887924

In silico analysis of the three-dimensional structures of the homodimer of uridine phosphorylase from Yersinia Pseudotuberculosis in the ligand-free state and in a complex with 5-fluorouracil

Energy Technology Data Exchange (ETDEWEB)

Lashkov, A. A., E-mail: alashkov83@gmail.com; Sotnichenko, S. E.; Mikhailov, A. M. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

2013-03-15

Pseudotuberculosis is an acute infectious disease characterized by a lesion of the gastrointestinal tract. A positive therapeutic effect can be achieved by selectively suppressing the activity of uridine phosphorylase from the causative agent of the disease Yersinia pseudotuberculosis. The synergistic effect of a combination of the chemotherapeutic agent 5-fluorouracil and antimicrobial drugs, which block the synthesis of pyrimidine bases, on the cells of pathogenic protozoa and bacteria is described in the literature. The three-dimensional structures of uridine phosphorylase from Yersinia pseudotuberculosis (YptUPh) both in the ligand-free state and in complexes with pharmacological agents are unknown, which hinders the search for and design of selective inhibitors of YptUPh. The three-dimensional structure of the ligand-free homodimer of YptUPh was determined by homology-based molecular modeling. The three-dimensional structure of the subunit of the YptUPh molecule belongs to {alpha}/{beta} proteins, and its topology is a three-layer {alpha}/{beta}/{alpha} sandwich. The subunit monomer of the YptUPh molecule consists of 38% helices and 24% {beta} strands. A model of the homodimer structure of YptUPh in a complex with 5-FU was obtained by the molecular docking. The position of 5-FU in the active site of the molecule is very consistent with the known data on the X-ray diffraction structures of other bacterial uridine phosphorylases (the complex of uridine phosphorylase from Salmonella typhimurium (StUPh) with 5-FU, ID PDB: 4E1V and the complex of uridine phosphorylase from Escherichia coli (EcUPh) with 5-FU and ribose 1-phosphate, ID PDB: 1RXC).

Viral activation of MK2-hsp27-p115RhoGEF-RhoA signaling axis causes cytoskeletal rearrangements, p-body disruption and ARE-mRNA stabilization.

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Jennifer A Corcoran

2015-01-01

Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the infectious cause of several AIDS-related cancers, including the endothelial cell (EC neoplasm Kaposi's sarcoma (KS. KSHV-infected ECs secrete abundant host-derived pro-inflammatory molecules and angiogenic factors that contribute to tumorigenesis. The precise contributions of viral gene products to this secretory phenotype remain to be elucidated, but there is emerging evidence for post-transcriptional regulation. The Kaposin B (KapB protein is thought to contribute to the secretory phenotype in infected cells by binding and activating the stress-responsive kinase MK2, thereby selectively blocking decay of AU-rich mRNAs (ARE-mRNAs encoding pro-inflammatory cytokines and angiogenic factors. Processing bodies (PBs are cytoplasmic ribonucleoprotein foci in which ARE-mRNAs normally undergo rapid 5' to 3' decay. Here, we demonstrate that PB dispersion is a feature of latent KSHV infection, which is dependent on kaposin protein expression. KapB is sufficient to disperse PBs, and KapB-mediated ARE-mRNA stabilization could be partially reversed by treatments that restore PBs. Using a combination of genetic and chemical approaches we provide evidence that KapB-mediated PB dispersion is dependent on activation of a non-canonical Rho-GTPase signaling axis involving MK2, hsp27, p115RhoGEF and RhoA. PB dispersion in latently infected cells is likewise dependent on p115RhoGEF. In addition to PB dispersion, KapB-mediated RhoA activation in primary ECs caused actin stress fiber formation, increased cell motility and angiogenesis; these effects were dependent on the activity of the RhoA substrate kinases ROCK1/2. By contrast, KapB-mediated PB dispersion occurred in a ROCK1/2-independent manner. Taken together, these observations position KapB as a key contributor to viral reprogramming of ECs, capable of eliciting many of the phenotypes characteristic of KS tumor cells, and strongly contributing to the post

Measurement of Am-242 fission yields at the Lohengrin spectrometer; improvement and Benchmarking of the semi-empirical code GEF

International Nuclear Information System (INIS)

Amouroux, Charlotte

2014-01-01

The study of fission yields has a major impact on the characterization and understanding of the fission process and is mandatory for reactor applications. While the yields are known for the major actinides (U-235, Pu-239) in the thermal neutron-induced fission, only few measurements were performed on Am-242. Moreover, the two main data libraries do not agree among each other on the light peak. Am-241 and Am-242 are nuclei of interest for the MOX-fuel reactors and for the reduction of nuclear waste radiotoxicity using transmutation reactions. Thus, a campaign of precise measurement of the fission mass yields from the reaction Am-241(2n,f) was performed at the Lohengrin mass spectrometer (ILL, France) for both the light and the heavy peak. Forty-one masses were measured. Moreover, the measurement of the isotopic fission yields on the heavy peak by gamma-ray spectrometry led to the extraction of 20 independent isotopic yields. Our measurement was also meant to determine whether there is a difference in fission yields between the Am-242 isomeric state and its ground state as it exists in fission cross sections. The experimental method used to answer this question is based on the measurement a set of fission mass yields as a function of the ratio of Am-242gs to Am-242m fission rate. Results show that the mass yields are independent of the fission rate ratio. A future experimental campaign is proposed to observe a possible influence on the isomeric yields. The theoretical models are nowadays unable to predict the fission yields with enough accuracy and therefore we have to rely on experimental data and phenomenological models. The accuracy of the predictions of the semi empirical GEF fission model predictions makes it a useful tool for evaluation. This thesis also presents the physical content and part of the development of this model. Validation of the kinetic energy distributions, isomeric yields and fission yields predictions was performed. The extension of the GEF

The Drosophila Arf GEF Steppke controls MAPK activation in EGFR signaling.

Science.gov (United States)

Hahn, Ines; Fuss, Bernhard; Peters, Annika; Werner, Tamara; Sieberg, Andrea; Gosejacob, Dominic; Hoch, Michael

2013-06-01

Guanine nucleotide exchange factors (GEFs) of the cytohesin protein family are regulators of GDP/GTP exchange for members of the ADP ribosylation factor (Arf) of small GTPases. They have been identified as modulators of various receptor tyrosine kinase signaling pathways including the insulin, the vascular epidermal growth factor (VEGF) and the epidermal growth factor (EGF) pathways. These pathways control many cellular functions, including cell proliferation and differentiation, and their misregulation is often associated with cancerogenesis. In vivo studies on cytohesins using genetic loss of function alleles are lacking, however, since knockout mouse models are not available yet. We have recently identified mutants for the single cytohesin Steppke (Step) in Drosophila and we could demonstrate an essential role of Step in the insulin signaling cascade. In the present study, we provide in vivo evidence for a role of Step in EGFR signaling during wing and eye development. By analyzing step mutants, transgenic RNA interference (RNAi) and overexpression lines for tissue specific as well as clonal analysis, we found that Step acts downstream of the EGFR and is required for the activation of mitogen-activated protein kinase (MAPK) and the induction of EGFR target genes. We further demonstrate that step transcription is induced by EGFR signaling whereas it is negatively regulated by insulin signaling. Furthermore, genetic studies and biochemical analysis show that Step interacts with the Connector Enhancer of KSR (CNK). We propose that Step may be part of a larger signaling scaffold coordinating receptor tyrosine kinase-dependent MAPK activation.

Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor.

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Croisé, Pauline; Brunaud, Laurent; Tóth, Petra; Gasman, Stéphane; Ory, Stéphane

2017-04-03

Altered Rho GTPase signaling has been linked to many types of cancer. As many small G proteins, Rho GTPases cycle between an active and inactive state thanks to specific regulators that catalyze exchange of GDP into GTP (Rho-GEF) or hydrolysis of GTP into GDP (Rho-GAP). Recent studies have shown that alteration takes place either at the level of Rho proteins themselves (expression levels, point mutations) or at the level of their regulators, mostly RhoGEFs and RhoGAPs. Most reports describe Rho GTPases gain of function that may participate to the tumorigenesis processes. In contrast, we have recently reported that decreased activities of Cdc42 and Rac1 as well as decreased expression of 2 Rho-GEFs, FARP1 and ARHGEF1, correlate with pheochromocytomas, a tumor developing in the medulla of the adrenal gland (Croisé et al., Endocrine Related Cancer, 2016). Here we highlight the major evidence and further study the correlation between Rho GTPases activities and expression levels of ARHGEF1 and FARP1. Finally we also discuss how the decrease of Cdc42 and Rac1 activities may help human pheochromocytomas to develop and comment the possible relationship between FARP1, ARHGEF1 and the 2 Rho GTPases Cdc42 and Rac1 in tumorigenesis.

Auftreten von Falschem Mehltau bei Gartenkresse (Lepidium sativum L. in der Saatgutvermehrung – Evaluierung von Saatgutbehandlung und Wachstumsbedingungen in einem Gefäßversuch

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Zeller, Stefanie

2014-09-01

Full Text Available Die zur Familie der Brassicaceae gehörende Gartenkresse wird in Deutschland überwiegend im biologischen Anbau vermehrt. Seit einigen Jahren werden diese Gartenkressebestände von Erregern des Falschen Mehltaus (Hyaloperonospora parasitica, Perofascia lepidii befallen, was zu einem Totalausfall des Pflanzenbestandes führen kann. Daher ist die biologische Saatgutproduktion von Gartenkresse gefährdet, was eine Beeinträchtigung der Saatgutversorgung für die Keimsprossenerzeugung zur Folge hat. In den laufenden Untersuchungen wird der Einfluss von nicht chemischen Saatgutbehandlungsmaßnahmen (Wasserdampf, Elektronen, sowie Wachstumsbedingungen (Feuchte, Boden auf die Infektion mit Falschem Mehltau untersucht.

A Dilemma in Staging of Esophageal Cancer: How Should We Stage ypT0 N2 M0 Esophageal Cancer after Neoadjuvant Therapy?

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Sebahattin Celik

2015-01-01

Full Text Available Background. Since neoadjuvant treatment in esophageal cancer began to become popular, a complete pathological response at the primary tumour site has been commonly reported. An issue of conflict is whether complete response in the esophageal lumen means that the esophagus is completely tumour-free. Another important issue is whether lymph nodes that are retrieved from pathologically complete response cases are also tumour-free or not. There is a gap in the esophageal cancer staging system for ypT0 N2 M0 tumours that have received neoadjuvant therapy. Here, we will discuss the problem about staging of esophageal cancer associated with neoadjuvant therapy. Case. A female aged 40 years complaining of dysphagia was diagnosed as having locally advanced thoracic esophageal cancer. Neoadjuvant therapy decision was taken by oncology committee. Six weeks after neoadjuvant therapy, with a curative intention, minimal invasive surgery was performed. The pathology report was as follows. “There were no neoplastic cells in the suspected area of the esophageal mucosa upon examination with all staining. There was no cancer at resection margins. Four metastatic lymph nodes were infiltrated with squamous cell cancer.” Conclusion. Despite the growing use of neoadjuvant treatment in locally advanced esophageal cancer in world, we do not have a protocol for the evaluation of these patients’ pathology reports. We believe that new studies and new ideas are needed to resolve this dilemma associated with neoadjuvant therapy.

The Phosphatidylinositol (3,4,5)-Trisphosphate-dependent Rac Exchanger 1·Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1·Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells.

Science.gov (United States)

Lucato, Christina M; Halls, Michelle L; Ooms, Lisa M; Liu, Heng-Jia; Mitchell, Christina A; Whisstock, James C; Ellisdon, Andrew M

2015-08-21

The P-Rex (phosphatidylinositol (3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger) family (P-Rex1 and P-Rex2) of the Rho guanine nucleotide exchange factors (Rho GEFs) activate Rac GTPases to regulate cell migration, invasion, and metastasis in several human cancers. The family is unique among Rho GEFs, as their activity is regulated by the synergistic binding of PIP3 and Gβγ at the plasma membrane. However, the molecular mechanism of this family of multi-domain proteins remains unclear. We report the 1.95 Å crystal structure of the catalytic P-Rex1 DH-PH tandem domain in complex with its cognate GTPase, Rac1 (Ras-related C3 botulinum toxin substrate-1). Mutations in the P-Rex1·Rac1 interface revealed a critical role for this complex in signaling downstream of receptor tyrosine kinases and G protein-coupled receptors. The structural data indicated that the PIP3/Gβγ binding sites are on the opposite surface and markedly removed from the Rac1 interface, supporting a model whereby P-Rex1 binding to PIP3 and/or Gβγ releases inhibitory C-terminal domains to expose the Rac1 binding site. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Five Fractions of Radiation Therapy Followed by 4 Cycles of FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

International Nuclear Information System (INIS)

Myerson, Robert J.; Tan, Benjamin; Hunt, Steven; Olsen, Jeffrey; Birnbaum, Elisa; Fleshman, James; Gao, Feng; Hall, Lannis; Kodner, Ira; Lockhart, A. Craig; Mutch, Matthew; Naughton, Michael; Picus, Joel; Rigden, Caron; Safar, Bashar; Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea; Parikh, Parag

2014-01-01

Background: Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results: 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87

Five Fractions of Radiation Therapy Followed by 4 Cycles of FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

Energy Technology Data Exchange (ETDEWEB)

Myerson, Robert J., E-mail: rmyerson@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Tan, Benjamin [Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Hunt, Steven [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Olsen, Jeffrey [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Birnbaum, Elisa; Fleshman, James [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Gao, Feng [Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri (United States); Hall, Lannis [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Kodner, Ira [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Lockhart, A. Craig [Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Mutch, Matthew [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Naughton, Michael; Picus, Joel; Rigden, Caron [Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Safar, Bashar [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea [Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Parikh, Parag [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

2014-03-15

Background: Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results: 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87

Endoscopic Criteria for Evaluating Tumor Stage after Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer.

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Han, Kyung Su; Sohn, Dae Kyung; Kim, Dae Yong; Kim, Byung Chang; Hong, Chang Won; Chang, Hee Jin; Kim, Sun Young; Baek, Ji Yeon; Park, Sung Chan; Kim, Min Ju; Oh, Jae Hwan

2016-04-01

Local excision may be an another option for selected patients with markedly down-staged rectal cancer after preoperative chemoradiation therapy (CRT), and proper evaluation of post-CRT tumor stage (ypT) is essential prior to local excision of these tumors. This study was designed to determine the correlations between endoscopic findings and ypT of rectal cancer. In this study, 481 patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection between 2004 and 2013 at a single institution were evaluated retrospectively. Pathological good response (p-GR) was defined as ypT ≤ 1, and pathological minimal or no response (p-MR) as ypT ≥ 2. The patients were randomly classified according to two groups, a testing (n=193) and a validation (n=288) group. Endoscopic criteria were determined from endoscopic findings and ypT in the testing group and used in classifying patients in the validation group as achieving or not achieving p-GR. Based on findings in the testing group, the endoscopic criteria for p-GR included scarring, telangiectasia, and erythema, whereas criteria for p-MR included nodules, ulcers, strictures, and remnant tumors. In the validation group, the kappa statistic was 0.965 (p < 0.001), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.362, 0.963, 0.654, and 0.885, respectively. The endoscopic criteria presented are easily applicable for evaluation of ypT after preoperative CRT for rectal cancer. These criteria may be used for selection of patients for local excision of down-staged rectal tumors, because patients with p-MR could be easily ruled out.

Effect of Dioscorea opposita Thunb. (yam) supplementation on physicochemical and sensory characteristics of yogurt.

Science.gov (United States)

Kim, S H; Lee, S Y; Palanivel, G; Kwak, H S

2011-04-01

A study was conducted to examine the physicochemical, microbial, and sensory properties of yogurt made by supplementing powdered yam Dioscorea opposita Thunb. (YPT) at different concentrations (0.2, 0.4, 0.6, and 0.8%, wt/vol) into milk, which was pasteurized and then fermented at 43°C for 6 h and stored for 16 d. The pH values of all samples decreased, whereas viscosity values and mean microbial counts increased during storage. The L* and a* color values (indicators of lightness and redness, respectively) of yogurt samples were not remarkably influenced by adding YPT, whereas the b* values (indicating yellowness) significantly increased with the addition of YPT at all concentrations at 0 d of storage, probably due to the original yellow color of yam powder. In functional component analyses, when the concentration of YPT increased, the amount of allantoin and diosgenin proportionally increased. The content of allantoin was 3.22 and diosgenin 4.69 μg/mL when 0.2% (wt/vol) YPT was supplemented and did not change quantitatively during the storage period (16 d). The sensory test revealed that the overall acceptability scores of YPT-supplemented yogurt samples (0.2 to 0.6%, wt/vol) were quite similar to those of the control throughout the storage period of 16 d. Based on the data obtained from the present study, it was concluded that the concentrations (0.2 to 0.6%, wt/vol) of YPT could be used to produce YPT-supplemented yogurt without significant adverse effects on physicochemical, microbial, and sensory properties, and enhance functional components from the supplementation. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

International Nuclear Information System (INIS)

Yeo, Seung-Gu; Kim, Dae Yong; Kim, Tae Hyun; Jung, Kyung Hae; Hong, Yong Sang; Chang, Hee Jin; Park, Ji Won; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong

2010-01-01

Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. Results: The mean TVRR was 65.0% ± 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p 80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of ≥60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs.

Science.gov (United States)

Levine, Timothy P; Daniels, Rachel D; Gatta, Alberto T; Wong, Louise H; Hayes, Matthew J

2013-02-15

Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS, also called motor neuron disease, MND) are severe neurodegenerative diseases that show considerable overlap at the clinical and cellular level. The most common single mutation in families with FTD or ALS has recently been mapped to a non-coding repeat expansion in the uncharacterized gene C9ORF72. Although a plausible mechanism for disease is that aberrant C9ORF72 mRNA poisons splicing, it is important to determine the cellular function of C9ORF72, about which nothing is known. Sensitive homology searches showed that C9ORF72 is a full-length distant homologue of proteins related to Differentially Expressed in Normal and Neoplasia (DENN), which is a GDP/GTP exchange factor (GEF) that activates Rab-GTPases. Our results suggest that C9ORF72 is likely to regulate membrane traffic in conjunction with Rab-GTPase switches, and we propose to name the gene and its product DENN-like 72 (DENNL72).

Gain-of-function SOS1 mutations cause a distinctive form of noonansyndrome

Energy Technology Data Exchange (ETDEWEB)

Tartaglia, Marco; Pennacchio, Len A.; Zhao, Chen; Yadav, KamleshK.; Fodale, Valentina; Sarkozy, Anna; Pandit, Bhaswati; Oishi, Kimihiko; Martinelli, Simone; Schackwitz, Wendy; Ustaszewska, Anna; Martin, Joes; Bristow, James; Carta, Claudio; Lepri, Francesca; Neri, Cinzia; Vasta,Isabella; Gibson, Kate; Curry, Cynthia J.; Lopez Siguero, Juan Pedro; Digilio, Maria Cristina; Zampino, Giuseppe; Dallapiccola, Bruno; Bar-Sagi, Dafna; Gelb, Brude D.

2006-09-01

Noonan syndrome (NS) is a developmental disordercharacterized by short stature, facial dysmorphia, congenital heartdefects and skeletal anomalies1. Increased RAS-mitogenactivated proteinkinase (MAPK) signaling due to PTPN11 and KRAS mutations cause 50 percentof NS2-6. Here, we report that 22 of 129 NS patients without PTPN11 orKRAS mutation (17 percent) have missense mutations in SOS1, which encodesa RAS-specific guanine nucleotide exchange factor (GEF). SOS1 mutationscluster at residues implicated in the maintenance of SOS1 in itsautoinhibited form and ectopic expression of two NS-associated mutantsinduced enhanced RAS activation. The phenotype associated with SOS1defects is distinctive, although within NS spectrum, with a highprevalence of ectodermal abnormalities but generally normal developmentand linear growth. Our findings implicate for the first timegain-of-function mutations in a RAS GEF in inherited disease and define anew mechanism by which upregulation of the RAS pathway can profoundlychange human development.

Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

Energy Technology Data Exchange (ETDEWEB)

Balaev, V. V.; Lashkov, A. A., E-mail: alashkov83@gmail.com; Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

2015-03-15

Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis (YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability (R{sub work} = 16.2, R{sub free} = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh.

Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

International Nuclear Information System (INIS)

Balaev, V. V.; Lashkov, A. A.; Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M.

2015-01-01

Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis (YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability (R work = 16.2, R free = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh

Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

Science.gov (United States)

Balaev, V. V.; Lashkov, A. A.; Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M.

2015-03-01

Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis ( YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability ( R work = 16.2, R free = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh.

Thiopurine Prodrugs Mediate Immunosuppressive Effects by Interfering with Rac1 Protein Function*

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Shin, Jin-Young; Wey, Michael; Umutesi, Hope G.; Sun, Xiangle; Simecka, Jerry; Heo, Jongyun

2016-01-01

6-Thiopurine (6-TP) prodrugs include 6-thioguanine and azathioprine. Both are widely used to treat autoimmune disorders and certain cancers. This study showed that a 6-thioguanosine triphosphate (6-TGTP), converted in T-cells from 6-TP, targets Rac1 to form a disulfide adduct between 6-TGTP and the redox-sensitive GXXXXGK(S/T)C motif of Rac1. This study also showed that, despite the conservation of the catalytic activity of RhoGAP (Rho-specific GAP) on the 6-TGTP-Rac1 adduct to produce the biologically inactive 6-thioguanosine diphosphate (6-TGDP)-Rac1 adduct, RhoGEF (Rho-specific GEF) cannot exchange the 6-TGDP adducted on Rac1 with free guanine nucleotide. The biologically inactive 6-TGDP-Rac1 adduct accumulates in cells because of the ongoing combined actions of RhoGEF and RhoGAP. Because other Rho GTPases, such as RhoA and Cdc42, also possess the GXXXXGK(S/T)C motif, the proposed mechanism for the inactivation of Rac1 also applies to RhoA and Cdc42. However, previous studies have shown that CD3/CD28-stimulated T-cells contain more activated Rac1 than other Rho GTPases such as RhoA and Cdc42. Accordingly, Rac1 is the main target of 6-TP in activated T-cells. This explains the T-cell-specific Rac1-targeting therapeutic action of 6-TP that suppresses the immune response. This proposed mechanism for the action of 6-TP on Rac1 performs a critical role in demonstrating the capability to design a Rac1-targeting chemotherapeutic agent(s) for autoimmune disorders. Nevertheless, the results also suggest that the targeting action of other Rho GTPases in other organ cells, such as RhoA in vascular cells, may be linked to cytotoxicities because RhoA plays a key role in vasculature functions. PMID:27189938

Vav1: Friend and Foe of Cancer.

Science.gov (United States)

Guo, Fukun; Zheng, Yi

2017-12-01

A recent study shows that the protumorigenic guanine nucleotide exchange factor (GEF) Vav1 functions as a tumor suppressor in T cell acute lymphoblastic leukemia (T-ALL) through its ability to complex with the Cbl-b ubiquitin ligase and the intracellular domain of Notch1 (ICN1) and to promote ICN1 degradation. Vav1can act as a double-edged sword in tumorigenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rezension von: Barbara Holland-Cunz: Gefährdete Freiheit. Über Hannah Arendt und Simone de Beauvoir. Opladen u.a.: Verlag Barbara Budrich 2012.

Directory of Open Access Journals (Sweden)

Mirjam Dierkes

2012-11-01

Full Text Available Von Barbara Holland-Cunz, die sich mit Simone de Beauvoir und Hannah Arendt bereits einzeln beschäftigt hat, liegt nun ein Band vor, in dem sie sich diesen herausragenden Denkerinnen des 20. Jahrhunderts gemeinsam widmet. In einer beinahe synoptisch anmutenden Herangehensweise fokussiert sie dabei auf den Begriff der Freiheit, der bei beiden von eminenter Bedeutung für das jeweilige Theoriegebäude ist. Holland-Cunz zufolge verstehen beide, bei einigen Unterschieden, Freiheit so, dass sie sich vor allem durch eine in sich eingeschriebene Gefährdung auszeichnet: Diese resultiert aus einem heroisch-emphatischen Gestus, der in paradoxer Weise gepaart wird mit einem abgeklärten Realismus. Über weite Strecken liest sich der Weg zu dieser Deutung, v. a. auch wegen einer teilweise sympathisch unkonventionellen und originellen Herangehensweise, sehr anregend und überzeugend.

Tiam1 Regulates the Wnt/Dvl/Rac1 Signaling Pathway and the Differentiation of Midbrain Dopaminergic Neurons

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Čajánek, Lukáš; Ganji, Ranjani Sri; Henriques-Oliveira, Catarina; Theofilopoulos, Spyridon; Koník, Peter

2013-01-01

Understanding the mechanisms that drive the differentiation of dopaminergic (DA) neurons is crucial for successful development of novel therapies for Parkinson's disease, in which DA neurons progressively degenerate. However, the mechanisms underlying the differentiation-promoting effects of Wnt5a on DA precursors are poorly understood. Here, we present the molecular and functional characterization of a signaling pathway downstream of Wnt5a, the Wnt/Dvl/Rac1 pathway. First, we characterize the interaction between Rac1 and Dvl and identify the N-terminal part of Dvl3 as necessary for Rac1 binding. Next, we show that Tiam1, a Rac1 guanosine exchange factor (GEF), is expressed in the ventral midbrain, interacts with Dvl, facilitates Dvl-Rac1 interaction, and is required for Dvl- or Wnt5a-induced activation of Rac1. Moreover, we show that Wnt5a promotes whereas casein kinase 1 (CK1), a negative regulator of the Wnt/Dvl/Rac1 pathway, abolishes the interactions between Dvl and Tiam1. Finally, using ventral midbrain neurosphere cultures, we demonstrate that the generation of DA neurons in culture is impaired after Tiam1 knockdown, indicating that Tiam1 is required for midbrain DA differentiation. In summary, our data identify Tiam1 as a novel regulator of DA neuron development and as a Dvl-associated and Rac1-specific GEF acting in the Wnt/Dvl/Rac1 pathway. PMID:23109420

Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors.

Science.gov (United States)

Yoshimura, Shin-ichiro; Gerondopoulos, Andreas; Linford, Andrea; Rigden, Daniel J; Barr, Francis A

2010-10-18

A key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of the 63 human Rabs have no known GEF. We have performed a systematic characterization of the 17 human DENN domain proteins and demonstrated that they are specific GEFs for 10 Rabs. DENND1A/1B localize to clathrin patches at the plasma membrane and activate Rab35 in an endocytic pathway trafficking Shiga toxin to the trans-Golgi network. DENND2 GEFs target to actin filaments and control Rab9-dependent trafficking of mannose-6-phosphate receptor to lysosomes. DENND4 GEFs target to a tubular membrane compartment adjacent to the Golgi, where they activate Rab10, which suggests a function in basolateral polarized sorting in epithelial cells that compliments the non-DENN GEF Sec2 acting on Rab8 in apical sorting. DENND1C, DENND3, DENND5A/5B, MTMR5/13, and MADD activate Rab13, Rab12, Rab39, Rab28, and Rab27A/27B, respectively. Together, these findings provide a basis for future studies on Rab regulation and function.

Pathologic Nodal Classification Is the Most Discriminating Prognostic Factor for Disease-Free Survival in Rectal Cancer Patients Treated With Preoperative Chemoradiotherapy and Curative Resection

International Nuclear Information System (INIS)

Kim, Tae Hyun; Chang, Hee Jin; Kim, Dae Yong

2010-01-01

Purpose: We retrospectively evaluated the effects of clinical and pathologic factors on disease-free survival (DFS) with the aim of identifying the most discriminating factor predicting DFS in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection. Methods and Materials: The study involved 420 patients who underwent preoperative CRT and curative resection between August 2001 and October 2006. Gender, age, distance from the anal verge, histologic type, histologic grade, pretreatment carcinoembryonic antigen (CEA) level, cT, cN, cStage, circumferential resection margin, type of surgery, preoperative chemotherapy, adjuvant chemotherapy, ypT, ypN, ypStage, and tumor regression grade (TRG) were analyzed to identify prognostic factors associated with DFS. To compare the discriminatory prognostic ability of four tumor response-related pathologic factors (ypT, ypN, ypStage, and TRG), the Akaike information criteria were calculated. Results: The 5-year DFS rate was 75.4%. On univariate analysis, distance from the anal verge, histologic type, histologic grade, pretreatment CEA level, cT, circumferential resection margin, type of surgery, preoperative chemotherapeutic regimen, ypT, ypN, ypStage, and TRG were significantly associated with DFS. Multivariate analysis showed that the four parameters ypT, ypN, ypStage, and TRG were, consistently, significant prognostic factors for DFS. The ypN showed the lowest Akaike information criteria value for DFS, followed by ypStage, ypT, and TRG, in that order. Conclusion: In our study, ypT, ypN, ypStage, and TRG were important prognostic factors for DFS, and ypN was the most discriminating factor.

Clinicopathological outcomes of preoperative chemoradiotherapy using S-1 plus Irinotecan for T4 lower rectal cancer.

Science.gov (United States)

Beppu, Naohito; Yoshie, Hidenori; Kimura, Fumihiko; Aihara, Tsukasa; Doi, Hiroshi; Kamikonya, Norihiko; Matsubara, Nagahide; Tomita, Naohiro; Yanagi, Hidenori; Yamanaka, Naoki

2016-07-01

To investigate the clinicopathological outcomes of patients with T4 lower rectal cancer treated using preoperative chemoradiotherapy with S-1 plus Irinotecan. Between 2005 and 2011, 35 patients with T4M0 lower rectal cancer, diagnosed initially as T4a in 12 and as T4b in 23, were treated with 45 Gy of radiotherapy concomitantly with S-1 plus Irinotecan. The median follow-up period was 50.6 months (range 2-123 months). A total of 32 patients (91.4 %) completed the radiotherapy and 26 (74.3 %) completed the full chemotherapy regimen. Radical surgery was then performed in 33 (94.3 %) of the 35 patients after the exclusion of two patients, who had macroscopic residual disease. The pathological diagnosis was downstaged from T4a to ypT0-3 in all 12 of those patients (100 %) and from T4b to ypT0-4a in 20 of those 23 patients (87.0 %). The tumor regression grade of 1a/1b/2/3 (complete response) was 10/8/15/2, respectively. In terms of long-term survival, the 5-year local relapse-free survival rate was 74.8 % and the recurrence-free survival rate was 52.0 %. This regimen may result in favorable downstaging. Moreover, in this series, pathological evidence of involvement of adjacent organs was rare following preoperative chemoradiotherapy, in the patients with disease diagnosed as T4b at the initial staging.

Role of Gd-DTPA enhanced fat-suppression MR imaging on ovarian tumors

International Nuclear Information System (INIS)

Kang, Heoung Keun; Moon, Woong Jae; Seo, Jeong Jin; Kim, Jae Kyu; Park, Jin Gyoon; Choi, Ho Sun

1995-01-01

To determine the value of Gd-DTPA enhanced fat-suppression (GEFS) MR imaging in the characterization and differentiation of benign from malignant ovarian tumors. MRI findings of thirty-seven patients with surgically proved 44 ovarian tumors (30 benign, 14 malignant) were studied retrospectively. MR imaging with conventional spin echo (CSE; T1-weighted image TR/TE 450/20, T2-weighted image TR/TE 3500/30, 90) and GEFS were performed with a 1.5T GE signa. MRI findings of tumors including cystic or solid, wall and septal thickness, necrosis, invasion to adjacent organ, ascites and lymphadenopathy were assessed separately by using CSE and GEFS images, and then tumors were characterized as benign or malignant. Compared with CSE image, GEFS MR image showed better visualization of solid component in 5 malignant lesions, wall thickness in 5 malignant and 1 benign lesions, septal thickness in 3 malignant and 1 benign lesions, necrosis in 1 malignant lesion, and adjacent soft tissue invasion in 5 malignant lesions. Correct characterization of malignant tumors was increased from 71% on CSE image to 93% on GEFS image. However, correct characterization of benign tumors was 93% on both images. GEFS MR imaging could be useful for characterization of ovarian tumors, especially in malignant cases, and employed for differentiation of benign from malignant tumors

Role of Longwave Cloud-Radiation Feedback in the Simulation of the Madden-Julian Oscillation

Science.gov (United States)

Kim, Daehyun; Ahn, Min-Seop; Kang, In-Sik; Del Genio, Anthony D.

2015-01-01

The role of the cloud-radiation interaction in the simulation of the Madden-Julian oscillation (MJO) is investigated. A special focus is on the enhancement of column-integrated diabatic heating due to the greenhouse effects of clouds and moisture in the region of anomalous convection. The degree of this enhancement, the greenhouse enhancement factor (GEF), is measured at different precipitation anomaly regimes as the negative ratio of anomalous outgoing longwave radiation to anomalous precipitation. Observations show that the GEF varies significantly with precipitation anomaly and with the MJO cycle. The greenhouse enhancement is greater in weak precipitation anomaly regimes and its effectiveness decreases monotonically with increasing precipitation anomaly. The GEF also amplifies locally when convection is strengthened in association with the MJO, especially in the weak precipitation anomaly regime (less than 5 mm day(exp -1)). A robust statistical relationship is found among CMIP5 climate model simulations between the GEF and the MJO simulation fidelity. Models that simulate a stronger MJO also simulate a greater GEF, especially in the weak precipitation anomaly regime (less than 5 mm day(exp -1)). Models with a greater GEF in the strong precipitation anomaly regime (greater than 30 mm day(-1)) represent a slightly slower MJO propagation speed. Many models that lack the MJO underestimate the GEF in general and in particular in the weak precipitation anomaly regime. The results herein highlight that the cloud-radiation interaction is a crucial process for climate models to correctly represent the MJO.

[Subgroup Analysis of the Non-interventional REASON Study: PFS and OS According to Age, Smoking History, Gender, and Histology in NSCLC Patients Treated with Gefitinib or Chemotherapy].

Science.gov (United States)

Schuette, W; Eberhardt, W E E; Waller, C; Schirmacher, P; Dietel, M; Zirrgiebel, U; Radke, S; Thomas, M

2016-09-01

Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis. © Georg Thieme Verlag KG Stuttgart · New York.

BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein regulates neurite development via PI3K-AKT and ERK signaling pathways.

Science.gov (United States)

Zhou, C; Li, C; Li, D; Wang, Y; Shao, W; You, Y; Peng, J; Zhang, X; Lu, L; Shen, X

2013-12-19

The elongation of neuron is highly dependent on membrane trafficking. Brefeldin A (BFA)-inhibited guanine nucleotide-exchange protein 1 (BIG1) functions in the membrane trafficking between the Golgi apparatus and the plasma membrane. BFA, an uncompetitive inhibitor of BIG1 can inhibit neurite outgrowth and polarity development. In this study, we aimed to define the possible role of BIG1 in neurite development and to further investigate the potential mechanism. By immunostaining, we found that BIG1 was extensively colocalized with synaptophysin, a marker for synaptic vesicles in soma and partly in neurites. The amount of both protein and mRNA of BIG1 were up-regulated during rat brain development. BIG1 depletion significantly decreased the neurite length and inhibited the phosphorylation of phosphatidylinositide 3-kinase (PI3K) and protein kinase B (AKT). Inhibition of BIG1 guanine nucleotide-exchange factor (GEF) activity by BFA or overexpression of the dominant-negative BIG1 reduced PI3K and AKT phosphorylation, indicating regulatory effects of BIG1 on PI3K-AKT signaling pathway is dependent on its GEF activity. BIG1 siRNA or BFA treatment also significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation. Overexpression of wild-type BIG1 significantly increased ERK phosphorylation, but the dominant-negative BIG1 had no effect on ERK phosphorylation, indicating the involvement of BIG1 in ERK signaling regulation may not be dependent on its GEF activity. Our result identified a novel function of BIG1 in neurite development. The newly recognized function integrates the function of BIG1 in membrane trafficking with the activation of PI3K-AKT and ERK signaling pathways which are critical in neurite development. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

The Tiam1 PDZ Domain Couples to Syndecan1 and Promotes Cell-Matrix Adhesion

Energy Technology Data Exchange (ETDEWEB)

Shepherd, Tyson R; Klaus, Suzi M; Liu, Xu; Ramaswamy, S; DeMali, Kris A; Fuentes, Ernesto J [Iowa

2010-08-12

The T-cell lymphoma invasion and metastasis gene 1 (Tiam1) is a guanine exchange factor (GEF) for the Rho-family GTPase Rac1 that is crucial for the integrity of adherens junctions, tight junctions, and cell-matrix interactions. This GEF contains several protein-protein interaction domains, including a PDZ domain. Earlier studies identified a consensus PDZ-binding motif and a synthetic peptide capable of binding to the Tiam1 PDZ domain, but little is known about its ligand specificity and physiological role in cells. Here, we investigated the structure, specificity, and function of the Tiam1 PDZ domain. We determined the crystal structures of the Tiam1 PDZ domain free and in complex with a 'model' peptide, which revealed the structural basis for ligand specificity. Protein database searches using the consensus PDZ-binding motif identified two eukaryotic cell adhesion proteins, Syndecan1 and Caspr4, as potential Tiam1 PDZ domain binding proteins. Equilibrium binding experiments confirmed that C-terminal peptides derived from Syndecan1 and Caspr4 bound the Tiam1 PDZ domain. NMR chemical shift perturbation experiments indicated that the Tiam1 PDZ/Syndecan1 and PDZ/Caspr4 complexes were structurally distinct and identified key residues likely to be responsible for ligand selectivity. Moreover, cell biological analysis established that Syndecan1 is a physiological binding partner of Tiam1 and that the PDZ domain has a function in cell-matrix adhesion and cell migration. Collectively, our data provide insight into the structure, specificity, and function of the Tiam1 PDZ domain. Importantly, our data report on a physiological role for the Tiam1 PDZ domain and establish a novel link between two previously unrelated signal transduction pathways, both of which are implicated in cancer.

Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity.

Science.gov (United States)

Katrancha, Sara M; Wu, Yi; Zhu, Minsheng; Eipper, Betty A; Koleske, Anthony J; Mains, Richard E

2017-12-01

Bipolar disorder, schizophrenia, autism and intellectual disability are complex neurodevelopmental disorders, debilitating millions of people. Therapeutic progress is limited by poor understanding of underlying molecular pathways. Using a targeted search, we identified an enrichment of de novo mutations in the gene encoding the 330-kDa triple functional domain (TRIO) protein associated with neurodevelopmental disorders. By generating multiple TRIO antibodies, we show that the smaller TRIO9 isoform is the major brain protein product, and its levels decrease after birth. TRIO9 contains two guanine nucleotide exchange factor (GEF) domains with distinct specificities: GEF1 activates both Rac1 and RhoG; GEF2 activates RhoA. To understand the impact of disease-associated de novo mutations and other rare sequence variants on TRIO function, we utilized two FRET-based biosensors: a Rac1 biosensor to study mutations in TRIO (T)GEF1, and a RhoA biosensor to study mutations in TGEF2. We discovered that one autism-associated de novo mutation in TGEF1 (K1431M), at the TGEF1/Rac1 interface, markedly decreased its overall activity toward Rac1. A schizophrenia-associated rare sequence variant in TGEF1 (F1538Intron) was substantially less active, normalized to protein level and expressed poorly. Overall, mutations in TGEF1 decreased GEF1 activity toward Rac1. One bipolar disorder-associated rare variant (M2145T) in TGEF2 impaired inhibition by the TGEF2 pleckstrin-homology domain, resulting in dramatically increased TGEF2 activity. Overall, genetic damage to both TGEF domains altered TRIO catalytic activity, decreasing TGEF1 activity and increasing TGEF2 activity. Importantly, both GEF changes are expected to decrease neurite outgrowth, perhaps consistent with their association with neurodevelopmental disorders. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dicty_cDB: VSC320 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available factor RasGEF Q (gefQ) gene, complete cds. 597 0.0 3 AB022770 |AB022770.1 Human rotavirus mRNA for NSP2, com...ne, complete cds. 50 0.024 1 X57944 |X57944.1 Human rotavirus segment 7 gp33 gene. 50 0.024 1 AC092543 |AC09

Tiam1/Vav2-Rac1 axis: A tug-of-war between islet function and dysfunction.

Science.gov (United States)

Kowluru, Anjaneyulu

2017-05-15

Glucose-stimulated insulin secretion [GSIS] from the islet β-cell involves a well-orchestrated interplay between metabolic and cationic events. It is well established that intracellular generation of adenine and guanine nucleotide triphosphates [e.g., ATP and GTP] represents one of the requisite signaling steps in GSIS. The small molecular mass GTP-binding proteins [G-proteins; e.g., Rac1 and Cdc42] have been shown to regulate islet β-cell function including actin cytoskeletal remodeling and fusion of insulin granules with the plasma membrane for GSIS to occur. In this context, several regulatory factors for these G-proteins have been identified in the pancreatic β-cell; these include guanine nucleotide exchange factors [GEFs] and guanine nucleotide dissociation inhibitors [GDI]. Recent pharmacological and molecular biological evidence identified Tiam1 and Vav2 as GEFs for Rac1 in promoting physiological insulin secretion. Paradoxically, emerging evidence in multiple cell types, including the islet β-cell, suggests key roles for Rac1 in the onset of cellular dysfunction under conditions of metabolic stress and diabetes. Furthermore, functional inactivation of either Tiam1 or Vav2 appears to attenuate sustained activation of Rac1 and its downstream signaling events [activation of stress kinases] under conditions of metabolic stress. Together, these findings suggest both "friendly" and "non-friendly" roles for Tiam1/Vav2-Rac1 signaling axis in islet β-cell in health and diabetes. Our current understanding of the field and the knowledge gaps that exist in this area of islet biology are heighted herein. Furthermore, potential caveats in the specificity and selectivity of pharmacological inhibitors that are available currently are discussed in this Commentary. Published by Elsevier Inc.

[RS-1 enhanced the efficiency of CRISPR-Cas9 mediated knock-in of human lactoferrin].

Science.gov (United States)

Zhou, Wenjun; Guo, Rihong; Deng, Mingtian; Wang, Feng; Zhang, Yanli

2017-08-25

This study aims to knock out the goat β-lactoglobulin (BLG) gene using CRISPR-Cas9 system and knock in human lactoferrin (hLF) at the BLG locus, and further study the effect of RAD51 stimulatory compound (RS-1) on homologous recombination efficiency. First, we designed an sgRNA targeting the first exon of goat BLG gene and constructed a co-expression vector pCas9-sgBLG. This sgRNA vector was then transfected into goat ear fibroblasts (GEFs), and the target region was examined by T7EN1 assay and sequencing. Second, we constructed a targeting vector pBHA-hLF-NIE including NEO and EGFP genes based on BLG gene locus. This targeting vector together with pCas9-sgBLG expression vector was co-transfected into GEFs. Transfected cells were then treated with 0, 5, 10 and 20 μmol/L RS-1 for 72 h to analyse the EGFP expression efficiency. Next, we used 800 μg/mL G418 to screen G418-resistent cell clones, and studied hLF site-specific knock-in cell clones by PCR and sequencing. The editing efficiency of sgBLG was between 25% and 31%. The EGFP expression efficiency indicated that the gene knock-in efficiency was improved by RS-1 in a dose-dependent manner, which could reach 3.5-fold compared to the control group. The percentage of positive cells with hLF knock-in was increased to 32.61% when 10 μmol/L RS-1 was used. However, when the concentration of RS-1 increased to 20 μmol/L, the percentage of positive cells decreased to 22.22% and resulted in an increase of senescent cell clone number. These results suggested that hLF knock-in and BLG knock-out in GEFs were achieved by using CRISPR/Cas9 system, and optimum concentration of RS-1 could improve knock-in efficiency, which provides a reference for efficiently obtaining gene knock-in cells using CRISPR/Cas9 in the future.

„Gefühlsgemeinschaft“ – Autobiographische Erinnerungen an den BDM und der Erinnerungsdiskurs Community of Feeling—Autobiographical Memories of the BDM and Memory Discourse

Directory of Open Access Journals (Sweden)

Leonie Wagner

2008-11-01

Full Text Available Gisela Miller-Kipp dokumentiert und analysiert 27 Auszüge aus veröffentlichten Erinnerungen ehemaliger BDM-Mitglieder mit dem Ziel, deren Empfindungen und Gefühle zu rekonstruieren. Dabei sind interessante Einblicke möglich, die jedoch die von der Autorin intendierte Repräsentativität nicht einlösen (können. Zudem handelt es sich um Erinnerungen und damit um retrospektiv vorgenommene Konstruktionen, die meist noch mit dem Ziel einer Veröffentlichung aufgeschrieben wurden. Der Band liefert insofern wichtige Anregungen, ist aber in wissenschaftlicher Hinsicht nicht zufriedenstellend.Gisela Miller-Kipp documents and analyzes 27 excerpts from the published memories of former BDM-members with the goal of reconstructing their feelings and perceptions. This approach makes interesting insights possible but it cannot honor the author’s intended representativeness. In addition, because the book is about memories it presents retrospectively collected constructions that were mostly written down after the fact with the goal of publication. The volume therefore provides important perspectives that are not satisfying in a scientific respect.

The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner.

Directory of Open Access Journals (Sweden)

Aniko Keller-Pinter

Full Text Available The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs. Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu mutant of syndecan-4 (SDC4. SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1 to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways.

The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction–dependent manner

Science.gov (United States)

Keller-Pinter, Aniko; Ughy, Bettina; Domoki, Monika; Pettko-Szandtner, Aladar; Letoha, Tamas; Tovari, Jozsef; Timar, Jozsef

2017-01-01

The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1–RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways. PMID:29121646

The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner.

Science.gov (United States)

Keller-Pinter, Aniko; Ughy, Bettina; Domoki, Monika; Pettko-Szandtner, Aladar; Letoha, Tamas; Tovari, Jozsef; Timar, Jozsef; Szilak, Laszlo

2017-01-01

The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways.

Prognostic significance of clinical and pathological stages on locally advanced rectal carcinoma after neoadjuvant chemoradiotherapy

International Nuclear Information System (INIS)

Wen, Bixiu; Zhang, Luning; Wang, Chengtao; Huang, Rong; Peng, Haihua; Zhang, Tian; Dong, Jun; Xiao, Weiwei; Zeng, Zhifan; Liu, Mengzhong; Gao, Yuanhong

2015-01-01

To investigate prognostic significance of clinical and pathological stages in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy (neo-CRT) and total mesorectal excision. 210 patients with locally advanced rectal carcinoma (cT3-4 or cN+) treated with neo-CRT followed by total mesorectal excision. Treatment outcomes were compared according to clinical and pathological stage. Overall survival (OS), disease free survival (DFS) among patients with different clinical stage and pathological stage after neo-CRT. The median follow-up time was 47 months (range, 14–98 months). Clinical T stage was associated with 5 year OS (p = 0.042) and 5 year DFS (p = 0.014) while clinical N stage was not associated with 5 year OS (p = 0.440), 5 year DFS (p = 0.711). Pathological T stage was associate with 5 year OS (p = 0.001) and 5 year DFS (p = 0.046); and N stage was associated with 5 year OS (p = 0.001), 5 year DFS (p = 0.002). The pathological stage was further classified into three groups: ypT0–2N0 in 91 patients (43.3 %), ypT3–4N0 in 69 patients (32.9 %) and ypT0–4N+ in 50 patients (23.8 %). While pathological stage (ypT0–2 vs ypT3–4N0 vs ypT0–4N+) was associated with 5 year OS (87.9 %, 75.5 %, 56.7 %, p = 0.000), 5 year DFS (74.5 %, 77.4 %, 50.5 %, p = 0.003). Multivariate analysis showed that ypN stage was an independent prognostic factor for patients 5 year DFS. Pathological stage is strongly associated with treatment outcomes in patients with locally advanced rectal carcinoma treated with neo-CRT followed by total mesorectal excision, which may be used as guidance for further individualized treatment

Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome–associated Sos1 mutation

Science.gov (United States)

Chen, Peng-Chieh; Wakimoto, Hiroko; Conner, David; Araki, Toshiyuki; Yuan, Tao; Roberts, Amy; Seidman, Christine E.; Bronson, Roderick; Neel, Benjamin G.; Seidman, Jonathan G.; Kucherlapati, Raju

2010-01-01

Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, unique facial features, and congenital heart disease. About 10%–15% of individuals with NS have mutations in son of sevenless 1 (SOS1), which encodes a RAS and RAC guanine nucleotide exchange factor (GEF). To understand the role of SOS1 in the pathogenesis of NS, we generated mice with the NS-associated Sos1E846K gain-of-function mutation. Both heterozygous and homozygous mutant mice showed many NS-associated phenotypes, including growth delay, distinctive facial dysmorphia, hematologic abnormalities, and cardiac defects. We found that the Ras/MAPK pathway as well as Rac and Stat3 were activated in the mutant hearts. These data provide in vivo molecular and cellular evidence that Sos1 is a GEF for Rac under physiological conditions and suggest that Rac and Stat3 activation might contribute to NS phenotypes. Furthermore, prenatal administration of a MEK inhibitor ameliorated the embryonic lethality, cardiac defects, and NS features of the homozygous mutant mice, demonstrating that this signaling pathway might represent a promising therapeutic target for NS. PMID:21041952

"Das unausgesprochene Gefühl der Unzugehörigkeit" : Amerika als Zufluchtsmöglichkeit vor dem Selbst in Max Frischs Romanen Stiller und Homo faber

Directory of Open Access Journals (Sweden)

Vesna Kondrič Horvat

1993-12-01

Full Text Available In seiner Rede Emigranten, die er 1958 anläßlich der Georg-BtichnerPreis- Verleihung hielt und woraus das Titelzitat des vorliegenden Beitrags stammt, äußerte Max Frisch die Meinung, jeder frei gewahlte Wohnsitz solle dem Schriftsteller das unausgesprochene Gefühl der Unzugehörigkeit gestatten. Mit dem Satz: "Ich bin nicht Stiller!" (St 9 beginnt Frisch seinen 1954 veröffentlichten Roman Stiller. Ein Mann - ein Bildhauer -, der viele Versuche unternommen hat, seiner 'eigentlichen ', seelisch-existentiellen Identität zu entgehen, flieht schlieBlich, als alle anderen Versuche (sich im Spanischen Bürgerkrieg als ein mutiger Mann, sich in der Ehe als ein idealer Mann, sich in der Kunst als erfolgreicher Bildhauer zu bewahren scheitern, nach Amerika und läßt seine lungenkranke Frau Julika im Sanatorium in Davos zurück. Nach mehr als sechsjahrigem Fernbleiben kehrt er unter anderem Namen in die Heimat zurück und wird an der Schweizer Grenze - wegen vermeintlicher Verwicklung in eine Spionage-Affäre - verhaftet. An diesem Punkt beginnt der Roman.

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

Energy Technology Data Exchange (ETDEWEB)

Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo; Ema, Akira; Naito, Masanori; Watanabe, Masahiko, E-mail: midoris@med.kitasato-u.ac.jp

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

Large-scale structural alteration of brain in epileptic children with SCN1A mutation

OpenAIRE

Lee, Yun-Jeong; Yum, Mi-Sun; Kim, Min-Jee; Shim, Woo-Hyun; Yoon, Hee Mang; Yoo, Il Han; Lee, Jiwon; Lim, Byung Chan; Kim, Ki Joong; Ko, Tae-Sung

2017-01-01

Objective: Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic chil...

Modulation of B-cell receptor and microenvironment signaling by a guanine exchange factor in B-cell malignancies

International Nuclear Information System (INIS)

Liao, Wei; Sharma, Sanjai

2016-01-01

Objective: Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) cells over-express a guanine exchange factor (GEF), Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods: N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor (BCR) and chemokine signaling pathways were compared in the Rasgrf-1 over-expressing and a control transfected cell line. Results: Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions: This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells

Single crystal studies of platinum alloys for oxygen reduction electrodes

DEFF Research Database (Denmark)

Ulrikkeholm, Elisabeth Therese

/Pt(111) in the following. The prepared alloys were investigate using Low Energy Electron Diffraction (LEED), Xray Photoelectron Spectroscopy (XPS), Ion Scattering Spectroscopy (ISS) and temperature Programmed Desorption (TPD). The LEED pattern indicated that the Y/Pt(111) sample had formed a 1...... peaks with a large shift towards lower temperatures. The change in desorption temperature was ∆T = −180°C for the Y/Pt(111) sample and ∆T = −200°C for the Gd/Pt(111) sample. The ORR activity was measured showing a large enhancement for both alloys. Angle resolved XPS performed on the samples after.......89×1.89 structure, and the Gd/Pt(111) sample has formed a 1.90×1.90 structure compared to pure platinum. From the XPS measurements, it is most likely that alloys with the Pt5Y and Pt5Gd stoichiometry have been formed. The reactivity of the surfaces were probed using TPD. These measurements showed sharp desorption...

Green energy facilitated? The uncertain function of the global environment facility

International Nuclear Information System (INIS)

Young, Z.; Boehmer-Christiansen, S.

1998-01-01

The GEF remains the interim operating entity of the financial mechanism, the aid provider, for the Climate Change Convention (FCCC); It had 1.6 billion dollars to spend between 1994 and 1997 on the 'incremental costs' of implementing UN environmental conventions in eligible countries. The paper describes how this multilateral fund has functioned so far in the energy-environment arena, analyzing its governance and policies, decision-making criteria, project cycle and strategies for monitoring and evaluation. Through the patterns of GEF assistance to climate change related science, technologies and institutions, we explore the origins and wider purposes of the entity and in the process illuminate some assumptions and principles underlying the work of the GEF Secretariat and associated bureaucracies. What can realistically be expected should GEF become a more permanent fund for 'global environmental benefits' after current negotiations for its second replenishment? (author)

Crystal Structure, Spectroscopic Investigations, and Physical Properties of the Ternary Intermetallic REPt2Al3 (RE = Y, Dy–Tm and RE2Pt3Al4 Representatives (RE = Tm, Lu

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Fabian Eustermann

2018-04-01

Full Text Available The REPt2Al3 compounds of the late rare-earth metals (RE = Y, Dy–Tm were found to crystallize isostructural. Single-crystal X-ray investigations of YPt2Al3 revealed an orthorhombic unit cell (a = 1080.73(6, b = 1871.96(9, c = 413.04(2 pm, wR2 = 0.0780, 942 F2 values, 46 variables with space group Cmmm (oC48; q2pji2hedb. A comparison with the Pearson database indicated that YPt2Al3 forms a new structure type, in which the Pt and Al atoms form a [Pt2Al3]δ− polyanion and the Y atoms reside in the cavities within the framework. Via a group-subgroup scheme, the relationship between the PrNi2Al3-type structure and the new YPt2Al3-type structure was illustrated. The compounds with RE = Dy–Tm were characterized by powder X-ray diffraction experiments. While YPt2Al3 is a Pauli-paramagnet, the other REPt2Al3 (RE = Dy–Tm compounds exhibit paramagnetic behavior, which is in line with the rare-earth atoms being in the trivalent oxidation state. DyPt2Al3 and TmPt2Al3 exhibit ferromagnetic ordering at TC = 10.8(1 and 4.7(1 K and HoPt2Al3 antiferromagnetic ordering at TN = 5.5(1 K, respectively. Attempts to synthesize the isostructural lutetium compound resulted in the formation of Lu2Pt3Al4 (Ce2Ir3Sb4-type, Pnma, a = 1343.4(2, b = 416.41(8, c = 1141.1(2 pm, which could also be realized with thulium. The structure was refined from single-crystal data (wR2 = 0.0940, 1605 F2 values, 56 variables. Again, a polyanion with bonding Pt–Al interactions was found, and the two distinct Lu atoms were residing in the cavities of the [Pt3Al4]δ– framework. X-ray photoelectron spectroscopy (XPS measurements were conducted to examine the electron transfer from the rare-earth atoms onto the polyanionic framework.

Epac : effectors and biological functions

NARCIS (Netherlands)

Roscioni, Sara S.; Elzinga, Carolina R. S.; Schmidt, Martina

Epac1 (also known as cAMP-GEF-I) and Epac2 (also known as cAMP-GEF-II) are cyclic AMP-activated guanine nucleotide exchange factors for Ras-like GTPases. Since their discovery about 10 years ago, it is now accepted that Epac proteins are novel cAMP sensors that regulate several pivotal cellular

NtGNL1a ARF-GEF acts in endocytosis in tobacco cells

Czech Academy of Sciences Publication Activity Database

Jelínková, Adriana; Müller, Karel; Pařezová, Markéta; Petrášek, Jan

2015-01-01

Roč. 15, NOV 5 (2015), s. 272 ISSN 1471-2229 R&D Projects: GA ČR GPP305/11/P797 Institutional support: RVO:61389030 Keywords : Endocytosis * PIN1 protein trafficking * Inhibitors of endomembrane trafficking Subject RIV: EA - Cell Biology Impact factor: 3.631, year: 2015

Requirement of the Caenorhabditis elegans RapGEF pxf-1 and rap-1 for epithelial integrity

Czech Academy of Sciences Publication Activity Database

Pellis-van Berkel, W.; Verheijen, M. H. G.; Cuppen, E.; Asahina, Masako; de Rooij, J.; Jansen, G.; Plasterk, R. H. A.; Bos, J. L.; Zwartkruis, F. J. T.

2005-01-01

Roč. 16, č. 1 (2005), s. 106-116 ISSN 1059-1524 R&D Projects: GA AV ČR KJB5022303 Institutional research plan: CEZ:AV0Z60220518 Keywords : Rap signaling pathway * epidermis * Caenorhabditis elegans Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.520, year: 2005

A Trio-Rac1-PAK1 signaling axis drives invadopodia disassembly

Science.gov (United States)

Moshfegh, Yasmin; Bravo-Cordero, Jose Javier; Miskolci, Veronika; Condeelis, John; Hodgson, Louis

2014-01-01

Rho family GTPases control cell migration and participate in the regulation of cancer metastasis. Invadopodia, associated with invasive tumor cells, are crucial for cellular invasion and metastasis. To study Rac1 GTPase in invadopodia dynamics, we developed a genetically-encoded, single-chain Rac1 Fluorescence Resonance Energy Transfer (FRET) biosensor. The biosensor shows Rac1 activity exclusion from the core of invadopodia, and higher activity when invadopodia disappear, suggesting that reduced Rac1 activity is necessary for their stability, and Rac1 activation is involved in disassembly. Photoactivating Rac1 at invadopodia confirmed this previously-unknown Rac1 function. We built an invadopodia disassembly model, where a signaling axis involving TrioGEF, Rac1, PAK1, and phosphorylation of cortactin, causing invadopodia dissolution. This mechanism is critical for the proper turnover of invasive structures during tumor cell invasion, where a balance of proteolytic activity and locomotory protrusions must be carefully coordinated to achieve a maximally invasive phenotype. PMID:24859002

The Arf GTPase-activating protein family is exploited by Salmonella enterica serovar Typhimurium to invade nonphagocytic host cells.

Science.gov (United States)

Davidson, Anthony C; Humphreys, Daniel; Brooks, Andrew B E; Hume, Peter J; Koronakis, Vassilis

2015-02-10

To establish intracellular infections, Salmonella bacteria trigger host cell membrane ruffling and invasion by subverting cellular Arf guanine nucleotide exchange factors (GEFs) that activate Arf1 and Arf6 GTPases by promoting GTP binding. A family of cellular Arf GTPase-activating proteins (GAPs) can downregulate Arf signaling by stimulating GTP hydrolysis, but whether they do this during infection is unknown. Here, we uncovered a remarkable role for distinct Arf GAP family members in Salmonella invasion. The Arf6 GAPs ACAP1 and ADAP1 and the Arf1 GAP ASAP1 localized at Salmonella-induced ruffles, which was not the case for the plasma membrane-localized Arf6 GAPs ARAP3 and GIT1 or the Golgi-associated Arf1 GAP1. Surprisingly, we found that loss of ACAP1, ADAP1, or ASAP1 impaired Salmonella invasion, revealing that GAPs cannot be considered mere terminators of cytoskeleton remodeling. Salmonella invasion was restored in Arf GAP-depleted cells by expressing fast-cycling Arf derivatives, demonstrating that Arf GTP/GDP cycles facilitate Salmonella invasion. Consistent with this view, both constitutively active and dominant-negative Arf derivatives that cannot undergo GTP/GDP cycles inhibited invasion. Furthermore, we demonstrated that Arf GEFs and GAPs colocalize at invading Salmonella and collaborate to drive Arf1-dependent pathogen invasion. This study revealed that Salmonella bacteria exploit a remarkable interplay between Arf GEFs and GAPs to direct cycles of Arf GTPase activation and inactivation. These cycles drive Salmonella cytoskeleton remodeling and enable intracellular infections. To initiate infections, the Salmonella bacterial pathogen remodels the mammalian actin cytoskeleton and invades host cells by subverting host Arf GEFs that activate Arf1 and Arf6 GTPases. Cellular Arf GAPs deactivate Arf GTPases and negatively regulate cell processes, but whether they target Arfs during infection is unknown. Here, we uncovered an important role for the Arf GAP

Prospective, Multicenter Validation Study of Magnetic Resonance Volumetry for Response Assessment After Preoperative Chemoradiation in Rectal Cancer: Can the Results in the Literature be Reproduced?

Energy Technology Data Exchange (ETDEWEB)

Martens, Milou H., E-mail: mh.martens@hotmail.com [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Heeswijk, Miriam M. van [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Broek, Joris J. van den [Department of Surgery, Medical Center Alkmaar, Alkmaar (Netherlands); Rao, Sheng-Xiang [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Radiology, Fudan University, Shanghai (China); Vandecaveye, Vincent [Department of Radiology, University Hospital Leuven, Leuven (Belgium); Vliegen, Roy A. [Department of Radiology, Atrium Medical Center, Heerlen (Netherlands); Schreurs, Wilhelmina H. [Department of Surgery, Medical Center Alkmaar, Alkmaar (Netherlands); Beets, Geerard L. [Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Lambregts, Doenja M.J. [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Beets-Tan, Regina G.H. [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands)

2015-12-01

Purpose: To review the available literature on tumor size/volume measurements on magnetic resonance imaging for response assessment after chemoradiotherapy, and validate these cut-offs in an independent multicenter patient cohort. Methods and Materials: The study included 2 parts. (1) Review of the literature: articles were included that assessed the accuracy of tumor size/volume measurements on magnetic resonance imaging for tumor response assessment. Size/volume cut-offs were extracted; (2) Multicenter validation: extracted cut-offs from the literature were tested in a multicenter cohort (n=146). Accuracies were calculated and compared with reported results from the literature. Results: The review included 14 articles, in which 3 different measurement methods were assessed: (1) tumor length; (2) 3-dimensonial tumor size; and (3) whole volume. Study outcomes consisted of (1) complete response (ypT0) versus residual tumor; (2) tumor regression grade 1 to 2 versus 3 to 5; and (3) T-downstaging (ypTypT0 (accuracy 44%-80%), with the optimal cut-offs being 1.6 cm{sup 3} (after chemoradiation therapy) and a volume reduction of Δ80% to 86.6%. Accuracies for whole-volume measurements to assess tumor regression grade 1 to 2 were 52% to 61%, and for T-downstaging 51% to 57%. Overall accuracies for tumor length ranged between 48% and 53% and for 3D size measurement between 52% and 56%. Conclusions: Magnetic resonance volumetry using whole-tumor volume measurements can be helpful in rectal cancer response assessment with selected cut-off values. Measurements of tumor length or 3-dimensional tumor size are not helpful. Magnetic resonance volumetry is mainly accurate to assess a complete tumor response (ypT0) after chemoradiation therapy (accuracies up to 80%).

A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay.

Science.gov (United States)

Reichman, Melvin; Schabdach, Amanda; Kumar, Meera; Zielinski, Tom; Donover, Preston S; Laury-Kleintop, Lisa D; Lowery, Robert G

2015-12-01

Ras homologous (Rho) family GTPases act as molecular switches controlling cell growth, movement, and gene expression by cycling between inactive guanosine diphosphate (GDP)- and active guanosine triphosphate (GTP)-bound conformations. Guanine nucleotide exchange factors (GEFs) positively regulate Rho GTPases by accelerating GDP dissociation to allow formation of the active, GTP-bound complex. Rho proteins are directly involved in cancer pathways, especially cell migration and invasion, and inhibiting GEFs holds potential as a therapeutic strategy to diminish Rho-dependent oncogenesis. Methods for measuring GEF activity suitable for high-throughput screening (HTS) are limited. We developed a simple, generic biochemical assay method for measuring GEF activity based on the fact that GDP dissociation is generally the rate-limiting step in the Rho GTPase catalytic cycle, and thus addition of a GEF causes an increase in steady-state GTPase activity. We used the Transcreener GDP Assay, which relies on selective immunodetection of GDP, to measure the GEF-dependent stimulation of steady-state GTP hydrolysis by small GTPases using Dbs (Dbl's big sister) as a GEF for Cdc42, RhoA, and RhoB. The assay is well suited for HTS, with a homogenous format and far red fluorescence polarization (FP) readout, and it should be broadly applicable to diverse Rho GEF/GTPase pairs. © 2015 Society for Laboratory Automation and Screening.

GenBank blastx search result: AK060500 [KOME

Lifescience Database Archive (English)

Full Text Available AK060500 001-017-F08 L47838.1 Bacillus subtilis (clone YAC15-6B) ponA gene, yppBCDEFG genes, ypqAE genes..., yprAB genes, cotD gene, ypsABC genes, rnaP gene, yptA gene, ypuA gene, kduDI genes, kdgRKAT genes, ypwA gene, complete cds's.|BCT BCT 1e-18 +1 ...

Dicty_cDB: CHB536 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available xlexggxxliqypkrinsplglqikrwxanxcxnik w*xpsxlklraqxilxnvktxiqxkxrvsxqtnkd*FSAGKQLE...anfcknshw*nhytrs*r**qh*ecknknsrqrr ypt Frame B: ---xrfkkkkvxhqenqgfixxgkxlexggxxliqypkrinsplglqikrwxanxcxnik

Regulation of Ras exchange factors and cellular localization of Ras activation by lipid messengers in T cells

Directory of Open Access Journals (Sweden)

Jesse E. Jun

2013-09-01

Full Text Available The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and SOS-family GEFs.Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood.One large group of biomolecules critically involved in the control of Ras-GEFs´functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells.

Molecular and Clinical Responses in a Pilot Study of Gefitinib With Paclitaxel and Radiation in Locally Advanced Head-and-Neck Cancer

International Nuclear Information System (INIS)

Van Waes, Carter; Allen, Clint T.; Citrin, Deborah; Gius, David; Colevas, A. Dimetrios; Harold, Nancy A.; Rudy, Susan; Nottingham, Liesl; Muir, Christine; Chen, Zhong; Singh, Anurag K.; Dancey, Janet; Morris, John C.

2010-01-01

Purpose: Epidermal growth factor receptor (EGFR) overexpression in head-and-neck squamous cell carcinoma (HNSCC) stimulates tumor cell proliferation, inhibits apoptosis, and increases chemotherapy and radiation resistance. We examined the toxicity, safety and the effects on EGFR signaling in tumor biopsy samples from patients with locally advanced HNSCC treated with the EGFR signaling inhibitor gefitinib (GEF) combined with weekly intravenous paclitaxel (PAC) and radiation therapy (RT). Methods and Materials: This was a pilot Phase I dose-escalation study. Eligibility included Stage III to IVB HNSCC, age ≥18 years, no prior RT or chemotherapy, adequate organ function, and informed consent. Endpoints included determination of maximum tolerated dose (MTD) and analysis of treatment effect on EGFR signaling, tumor cell proliferation, and apoptosis in biopsy samples. Results: Ten patients were treated. The MTD of this combination was GEF 250 mg/d with PAC 36 mg/m 2 intravenously weekly x 6 with concurrent RT. Grade 3/4 toxicities included prolonged (>8 weeks) stomatitis (7 patients), infection (2 patients), and interstitial pneumonitis (1 patient). There were five complete responses (CR) and two partial responses (PR). Of 7 patients undergoing serial biopsies, only 1 patient demonstrated a reduction in phosphorylated EGFR, decreased downstream signaling, and reduced cellular proliferation after initiating GEF. Conclusions: Inhibition of EGFR by GEF was observed in only one of seven tumors studied. The addition of GEF to PAC and RT did not appear to improve the response of locally advanced HNSCC compared with our prior experience with PAC and RT alone. This treatment appeared to delay recovery from stomatitis.

GenBank blastx search result: AK058655 [KOME

Lifescience Database Archive (English)

Full Text Available AK058655 001-018-F07 L47838.1 Bacillus subtilis (clone YAC15-6B) ponA gene, yppBCDEFG genes, ypqAE genes..., yprAB genes, cotD gene, ypsABC genes, rnaP gene, yptA gene, ypuA gene, kduDI genes, kdgRKAT genes, ypwA gene, complete cds's.|BCT BCT 7e-20 +1 ...

GenBank blastx search result: AK062166 [KOME

Lifescience Database Archive (English)

Full Text Available AK062166 001-046-B08 L47838.1 Bacillus subtilis (clone YAC15-6B) ponA gene, yppBCDEFG genes, ypqAE genes..., yprAB genes, cotD gene, ypsABC genes, rnaP gene, yptA gene, ypuA gene, kduDI genes, kdgRKAT genes, ypwA gene, complete cds's.|BCT BCT 2e-12 +1 ...

Two distinct mTORC2-dependent pathways converge on Rac1 to drive breast cancer metastasis.

Science.gov (United States)

Morrison Joly, Meghan; Williams, Michelle M; Hicks, Donna J; Jones, Bayley; Sanchez, Violeta; Young, Christian D; Sarbassov, Dos D; Muller, William J; Brantley-Sieders, Dana; Cook, Rebecca S

2017-06-30

The importance of the mTOR complex 2 (mTORC2) signaling complex in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 signaling to drive tumor formation, tumor cell survival and resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy. Cell motility, a key step in the metastatic process, can be activated by mTORC2 in luminal and triple negative breast cancer cell lines, but its role in promoting metastases from HER2-amplified breast cancers is not yet clear. Because Rictor is an obligate cofactor of mTORC2, we genetically engineered Rictor ablation or overexpression in mouse and human HER2-amplified breast cancer models for modulation of mTORC2 activity. Signaling through mTORC2-dependent pathways was also manipulated using pharmacological inhibitors of mTOR, Akt, and Rac. Signaling was assessed by western analysis and biochemical pull-down assays specific for Rac-GTP and for active Rac guanine nucleotide exchange factors (GEFs). Metastases were assessed from spontaneous tumors and from intravenously delivered tumor cells. Motility and invasion of cells was assessed using Matrigel-coated transwell assays. We found that Rictor ablation potently impaired, while Rictor overexpression increased, metastasis in spontaneous and intravenously seeded models of HER2-overexpressing breast cancers. Additionally, migration and invasion of HER2-amplified human breast cancer cells was diminished in the absence of Rictor, or upon pharmacological mTOR kinase inhibition. Active Rac1 was required for Rictor-dependent invasion and motility, which rescued invasion/motility in Rictor depleted cells. Rictor/mTORC2-dependent dampening of the endogenous Rac1 inhibitor RhoGDI2, a factor that correlated directly with increased overall survival in HER2-amplified breast cancer patients, promoted Rac1 activity and tumor cell invasion/migration. The mTORC2 substrate Akt did not affect RhoGDI2 dampening, but partially

Gradients of Rac1 Nanoclusters Support Spatial Patterns of Rac1 Signaling.

Science.gov (United States)

Remorino, Amanda; De Beco, Simon; Cayrac, Fanny; Di Federico, Fahima; Cornilleau, Gaetan; Gautreau, Alexis; Parrini, Maria Carla; Masson, Jean-Baptiste; Dahan, Maxime; Coppey, Mathieu

2017-11-14

Rac1 is a small RhoGTPase switch that orchestrates actin branching in space and time and protrusion/retraction cycles of the lamellipodia at the cell front during mesenchymal migration. Biosensor imaging has revealed a graded concentration of active GTP-loaded Rac1 in protruding regions of the cell. Here, using single-molecule imaging and super-resolution microscopy, we show an additional supramolecular organization of Rac1. We find that Rac1 partitions and is immobilized into nanoclusters of 50-100 molecules each. These nanoclusters assemble because of the interaction of the polybasic tail of Rac1 with the phosphoinositide lipids PIP2 and PIP3. The additional interactions with GEFs and possibly GAPs, downstream effectors, and other partners are responsible for an enrichment of Rac1 nanoclusters in protruding regions of the cell. Our results show that subcellular patterns of Rac1 activity are supported by gradients of signaling nanodomains of heterogeneous molecular composition, which presumably act as discrete signaling platforms. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

YERSINIA PSEUDOTUBERCULOSIS, SEROGROUP O:1A, INFECTION IN TWO AMAZON PARROTS (AMAZONA AESTIVA AND AMAZONA ORATRIX) WITH HEPATIC HEMOSIDEROSIS.

Science.gov (United States)

Galosi, Livio; Farneti, Silvana; Rossi, Giacomo; Cork, Susan Catherine; Ferraro, Stefano; Magi, Gian Enrico; Petrini, Stefano; Valiani, Andrea; Cuteri, Vincenzo; Attili, Anna-Rita

2015-09-01

Necropsies were conducted on a female blue-fronted Amazon (Amazona aestiva) and a female yellow-headed Amazon (Amazona oratrix) that died after depression, ruffled feathers, diarrhea, and biliverdin in the urine. Gross and microscopic examinations revealed multifocal necrosis in the liver, spleen, lungs, kidneys, intestines, and heart caused by acute bacteremia. Yersinia pseudotuberculosis, serogroup O:1a, was isolated by culturing from the visceral lesions in the liver, intestines, and spleen. Virulence gene analysis showed the presence of the inv gene and the complete pathogenicity island: IS100, psn, yptE, irp1, irp2 ybtP-ybtQ, ybtX-ybtS, and int asnT-Int. Histopathologic findings and chemical analysis also demonstrated hepatic hemosiderosis. As has been demonstrated in other species, hemosiderosis may predispose Amazona spp. to systemic infection with Y. pseudotuberculosis after enteric disease.

Vimar Is a Novel Regulator of Mitochondrial Fission through Miro.

Directory of Open Access Journals (Sweden)

Lianggong Ding

2016-10-01

Full Text Available As fundamental processes in mitochondrial dynamics, mitochondrial fusion, fission and transport are regulated by several core components, including Miro. As an atypical Rho-like small GTPase with high molecular mass, the exchange of GDP/GTP in Miro may require assistance from a guanine nucleotide exchange factor (GEF. However, the GEF for Miro has not been identified. While studying mitochondrial morphology in Drosophila, we incidentally observed that the loss of vimar, a gene encoding an atypical GEF, enhanced mitochondrial fission under normal physiological conditions. Because Vimar could co-immunoprecipitate with Miro in vitro, we speculated that Vimar might be the GEF of Miro. In support of this hypothesis, a loss-of-function (LOF vimar mutant rescued mitochondrial enlargement induced by a gain-of-function (GOF Miro transgene; whereas a GOF vimar transgene enhanced Miro function. In addition, vimar lost its effect under the expression of a constitutively GTP-bound or GDP-bound Miro mutant background. These results indicate a genetic dependence of vimar on Miro. Moreover, we found that mitochondrial fission played a functional role in high-calcium induced necrosis, and a LOF vimar mutant rescued the mitochondrial fission defect and cell death. This result can also be explained by vimar's function through Miro, because Miro's effect on mitochondrial morphology is altered upon binding with calcium. In addition, a PINK1 mutant, which induced mitochondrial enlargement and had been considered as a Drosophila model of Parkinson's disease (PD, caused fly muscle defects, and the loss of vimar could rescue these defects. Furthermore, we found that the mammalian homolog of Vimar, RAP1GDS1, played a similar role in regulating mitochondrial morphology, suggesting a functional conservation of this GEF member. The Miro/Vimar complex may be a promising drug target for diseases in which mitochondrial fission and fusion are dysfunctional.

Value of the prognostic nutritional index in advanced gastric cancer treated with preoperative chemotherapy.

Science.gov (United States)

Sun, Jianyi; Wang, Donghai; Mei, Ying; Jin, Hailong; Zhu, Kankai; Liu, Xiaosun; Zhang, Qing; Yu, Jiren

2017-03-01

The prognostic nutritional index (PNI) is a useful parameter indicating the immune and nutritional status of cancer patients; this study investigated the prognostic value of the PNI in advanced gastric cancer patients treated with preoperative chemotherapy. We retrospectively reviewed 117 advanced gastric cancer patients who met the inclusion criteria for preoperative chemotherapy and underwent surgical resection from July 2004 to December 2011. The patients were divided into PNI-high (PNI ≥ 45) and PNI-low (PNI  0.05). Cox regression analysis indicated that yield pathologic T (ypT), yield pathologic N (ypN) stage, and prechemotherapy PNI were independent prognostic factors (ypT: HR = 2.914, 95% CI = 1.312-6.470, P = 0.009; ypN: HR = 4.909, 95% CI = 1.764-13.660, P = 0.003; prechemotherapy PNI: HR = 1.963, 95% CI = 1.101-3.499, P = 0.022). The prechemotherapy PNI is a useful predictor of the long-term outcome of patients with advanced gastric cancer treated with preoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Epidermal wound repair is regulated by the planar cell polarity signaling pathway.

Science.gov (United States)

Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A; Murdoch, Jennifer N; Humbert, Patrick O; Parekh, Vishwas; Boulos, Nidal; Weber, Thomas; Zuo, Jian; Cunningham, John M; Jane, Stephen M

2010-07-20

The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects, and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3(-)(/-) mice, we identified RhoGEF19, a homolog of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerization, cellular polarity, and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling and broadly implicate this pathway in epidermal repair. (c) 2010 Elsevier Inc. All rights reserved.

Disease: H00783 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H00783 Febrile seizures, including: Febrile convulsions; Generalized epilepsy with... febrile seizure plus (GEFS+); Dravet syndrome/ Severe myoclonic epilepsy in infancy [DS:H01818] Febrile sei... represent the most common form of childhood seizures. Generalized epilepsy with ...febrile seizures plus (GEFS+) is a familial epilepsy syndrome with a spectrum of phenotypes including FS. Severe epilepsy...Weber YG, Lerche H ... TITLE ... Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy

RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation.

Science.gov (United States)

Wu, Nan; Ren, Dong; Li, Su; Ma, Wenli; Hu, Shaoyan; Jin, Yan; Xiao, Sheng

2018-01-10

Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds the switch regions of Rac1 to prevent access from GEFs. Three cancer cell lines with up- or down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1 signaling and sensitivity to a group of nine chemotherapeutic drugs. RCC2 expression in lung cancer and ovarian cancer were studied using immunochemistry stain of tumor tissue arrays. Forced RCC2 expression in tumor cells blocked spontaneous- or Staurosporine (STS)-induced apoptosis. In contrast, RCC2 knock down in these cells resulted in increased apoptosis to STS treatment. The protective activity of RCC2 on apoptosis was revoked by a constitutively activated Rac1, confirming a role of RCC2 in apoptosis by regulating Rac1. In an immunohistochemistry evaluation of tissue microarray, RCC2 was over-expressed in 88.3% of primary lung cancer and 65.2% of ovarian cancer as compared to non-neoplastic lung and ovarian tissues, respectively. Because chemotherapeutic drugs can kill tumor cells by activating Rac1/JNK pathway, we suspect that tumors with RCC2 overexpression would be more resistant to these drugs. Tumor cells with forced RCC2 expression indeed had significant difference in drug sensitivity compared to parental cells using a panel of common chemotherapeutic drugs. RCC2 regulates apoptosis by blocking Rac1 signaling. RCC2 expression in tumor can be a useful marker for predicting chemotherapeutic response.

[Exon-dependent Subgroup-analysis of the Non-interventional REASON-Study: PFS and OS in EGFR-mutated NSCLC Patients Treated with Gefitinib or Chemotherapy].

Science.gov (United States)

Schuette, W; Dietel, M; Thomas, M; Eberhardt, W; Griesinger, F; Zirrgiebel, U; Radke, S; Schirmacher, P

2016-08-01

To analyze the influence of the localization of mutations in the epidermal growth factor receptor (EGFR) gene on progression-free (PFS) and overall survival (OS) in patients (pts) with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with gefitinib (gef) or chemotherapy (CT) under real world conditions within the REASON study. Subgroups of pts with mutations in exon 19 (n = 141), 18/20 (n = 43), and 21 (n = 104) were analyzed for PFS and OS according to gef or CT treatment and compared using the log-rank test. Pts with mutations in exon 19 and 18/20 treated with gef as first line therapy showed increased PFS and OS compared to CT. This increase was statistically significant in pts with exon 19 mutation (11.3 vs. 6.5 months), but was not found in pts with exon 21 mutation (9.1 vs. 9.3 months). Also, OS was significantly increased in patients with mutation in exon 19 treated with gef ever over all treatment lines compared to CT (21.8 vs. 10.6 months), whereas this was not found in pts with mutation in exon 21 (14.1 vs. 13.9 months). Localization and nature of EGFR mutations influences gefitinib treatment outcomes under routine conditions and should therefore be analyzed in detail. © Georg Thieme Verlag KG Stuttgart · New York.

Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline.

Science.gov (United States)

Yang, Long; Bashaw, Greg J

2006-11-22

Son of sevenless (Sos) is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases and thus is uniquely poised to integrate signals that affect both gene expression and cytoskeletal reorganization. Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand. Intriguingly, the Ras and Rac-GEF activities of Sos can be uncoupled during Robo-mediated axon repulsion; Sos axon guidance function depends on its Rac-GEF activity, but not its Ras-GEF activity. These results provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules and support a model in which Robo recruits Sos to the membrane via Dock to activate Rac during midline repulsion.

The Emerging Role of Guanine Exchange Factors in ALS and other neurodegenerative diseases

Directory of Open Access Journals (Sweden)

Cristian eDroppelmann

2014-09-01

Full Text Available Small GTPases participate in a broad range of cellular processes such as proliferation, differentiation and migration. The exchange of GDP for GTP resulting in the activation of these GTPases is catalyzed by a group of enzymes called guanine nucleotide exchange factors (GEFs, of which two classes: Dbl-related exchange factors and the more recently described Dock family exchange factors. Increasingly, deregulation of normal GEF activity or function has been associated with a broad range of disease states, including neurodegeneration and neurodevelopmental disorders. In this review, we examine this evidence with special emphasis on the novel role of Rho guanine nucleotide exchange factor (RGNEF/p190RhoGEF in the pathogenesis of amyotrophic lateral sclerosis (ALS. RGNEF is the first neurodegeneration-linked GEF that regulates not only RhoA GTPase activation but also functions as an RNA binding protein that directly acts with low molecular weight neurofilament (NEFL mRNA 3’UTR to regulate its stability. This dual role for RGNEF, coupled with the increasing understanding of the key role for GEFs in modulating the GTPase function in cell survival suggests a prominent role for GEFs in mediating a critical balance between cytotoxicity and neuroprotection which, when disturbed, contributes to neuronal loss.

RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin.

Directory of Open Access Journals (Sweden)

Hiroaki Kajiho

Full Text Available The Rab family of small guanosine triphosphatases (GTPases plays a vital role in membrane trafficking. Its active GTP-bound state is driven by guanine nucleotide-exchange factors (GEFs. Ras and Rab interactor (or Ras interaction/interference-like (RINL, which contains a conserved VPS9 domain critical for GEF action, was recently identified as a new Rab5 subfamily GEF in vitro. However, its detailed function and interacting molecules have not yet been fully elucidated. Here we found that RINL has GEF activity for the Rab5 subfamily proteins by measuring their GTP-bound forms in cultured cells. We also found that RINL interacts with odin, a member of the ankyrin-repeat and sterile-alpha motif (SAM domain-containing (Anks protein family. In addition, the Eph tyrosine kinase receptor EphA8 formed a ternary complex with both RINL and odin. Interestingly, RINL expression in cultured cells reduced EphA8 levels in a manner dependent on both its GEF activity and interaction with odin. In addition, knockdown of RINL increased EphA8 level in HeLa cells. Our findings suggest that RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin.

Hypoxia and Nutrient Reduction in the Coastal Zone: Advice for Prevention, Remediation and Research.

Digital Repository Service at National Institute of Oceanography (India)

Meryl Williams, M.; Harper, N.; Chaitovitz, C.; Dansie, A.; Diaz, R.; Harper, N.; Heidemeier, J.; Jiang, Y.; Kemp, M.; Naqvi, S.W.A.; Neretin, L.; Ross, A.; Susan, C.; Schuster-Wallace, C.; Zavadksy, I.

the issue, beyond current actions. This STAP Advisory Document is based on a review of the scien- tific evidence, and scientific and management expert consultations. It has been reviewed by subject matter experts, the GEF Secretariat, the GEF International... limited impact. Intervention areas should be selected based on their expected potential for preven- tion or remediation and progress should be monitored. GEF should establish principles for supporting priority systems in which to test management responses...

Graduated clinical manifestations according to mutation type in patients with severe myoclonic epilepsy in infancy

DEFF Research Database (Denmark)

Brusgaard, Klaus; Møller, Rikke Steensbjerre; Dahl, Hans Atli

. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development stagnates around the second year of life. SME is considered to be the most severe phenotype within the spectrum of GEFS+. SME is a malignant epileptic...... and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end Patients and methods 87 infants representing GEFS+ were analyzed by bidirectional sequencing of all exons of the SCN1A, SCN2A, GABRG2 or SCN1B genes. Additionally, MLPA analysis of SCN1A was performed. Results...... to the SMEI phenotype represent de novo incidences....

MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

Energy Technology Data Exchange (ETDEWEB)

Franklin, J.M., E-mail: jamiemfranklin@hotmail.com [Churchill Hospital, Headington, Oxford (United Kingdom); Anderson, E.M.; Gleeson, F.V. [Churchill Hospital, Headington, Oxford (United Kingdom)

2012-06-15

Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having {>=}80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.

MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

International Nuclear Information System (INIS)

Franklin, J.M.; Anderson, E.M.; Gleeson, F.V.

2012-01-01

Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having ≥80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.

APLIKASI PENGOLAHAN DATA PELANGGARAN SISWA PADA SMK YAYASAN PENDIDIKAN TEKNOLOGI 1 PURBALINGGA TERINTEGRASI DENGAN SMS GATEWAY

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Rizki Wahyudi

2017-08-01

Full Text Available Penelitian ini bertujuan untuk mempermudah penanganan ketidakdisiplinan siswa dalam lingkungan sekolah dengan membangun aplikasi yang mempermudah perhitungan point pelanggaran tata tertib siswa sehingga pihak sekolah dapat melakukan tindakan dan kebijakan-kebijakan yang berkaitan dengan peningkatan kepribadian siswa serta dengan di integrasikannya aplikasi dengan sms gateway yang secara otomatis mengirimkan laporan tentang ketidakdisiplinan siswa langsung kepada wali murid. Data poin pelanggaran siswa di ambil dari SMK YPT 1 Purbalingga. Jumlah point kesalahan yang dihitung kemudian ditindak lanjuti dalam berbagai tingkatan, mulai dari peringatan, panggilan disertai membuat surat perjanjian, sampai pada tingkat yang paling tinggi dengan bobot /jumlah point kesalahan paling besar dikembalikan kepada wali murid. Metode pengembangan sistem yang digunakan adalah metode waterfall. Perancangan sistem menggunakan Data Flow Diagram (DFD, implementasi program menggunakan bahasa Visual Studio 2012 dan database MySQL dan pengujian dilakukan menggunakan metode black-box yang hasilnya fungsional sistem bekerja menghasilkan output yang diharapkan.

Rasfonin, a novel 2-pyrone derivative, induces ras-mutated Panc-1 pancreatic tumor cell death in nude mice.

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Xiao, Z; Li, L; Li, Y; Zhou, W; Cheng, J; Liu, F; Zheng, P; Zhang, Y; Che, Y

2014-05-22

Rasfonin is a novel 2-pyrone derivative reported to induce apoptosis in ras-dependent cells. In this study, its effects on ras-mutated pancreatic cancer cells were investigated in vitro and in vivo. Two human pancreatic cancer cell lines Panc-1 (mutated K-ras) and BxPC-3 (wild-type K-ras) were selected to test the effects of rasfonin on cell proliferation, clone formation, migration and invasion in vitro. Immunoblotting was used to detect the expressions of EGFR-Ras-Raf-MEK-ERK signaling pathway proteins. Ras activity was measured using a pull-down ELISA kit and guanine exchange factor (GEF)/GTPase-activating proteins (GAP) activity was measured by [(3)H]-GDP radiometric ligand binding. For an in vivo study, CD1 nude mice bearing Panc-1 cells were treated with rasfonin or Salirasib (FTS). We found that rasfonin suppressed proliferation more strongly in Panc-1 cells (IC50=5.5 μM) than BxPC-3 cells (IC50=10 μM) in vitro. Clone formation, migration and invasion by Panc-1 cells were also reduced by rasfonin. Rasfonin had little effect on the farnesylation of Ras, but it strongly downregulated Ras activity and consequently phosphorylation of c-Raf/MEK/ERK. Further experiments indicated that rasfonin reduced Son of sevenless (Sos1) expression but did not alter GEF and GAP activities. The in vivo experiments also revealed that rasfonin (30 mg/kg) delayed the growth of xenograft tumors originating from Panc-1 cells. Tumor weight was ultimately decreased after 20 days of treatment of rasfonin. Rasfonin is a robust inhibitor of pancreatic cancers with the K-ras mutation. The reduction of Sos1 expression and the consequently depressed Ras-MAPK activity could be important in its anticancer activity.

Methane recovery from landfill in China

Energy Technology Data Exchange (ETDEWEB)

Gaolai, L.

1996-12-31

GEF has approved a special project for a demonstration project for Methane Recovery from the Urban Refuse Land Fill. This paper will introduce the possibility of GHG reduction from the landfill in China, describe the activities of the GEF project, and the priorities for international cooperation in this field. The Global Environment Facility (GEF) approved the project, China Promoting Methane Recovery and Unlization from Mixed Municipal Refuse, at its Council meeting in last April. This project is the first one supported by international organization in this field.

Biofuel consumption, biodiversity, and the environmental Kuznets curve: trivariate analysis in a panel of biofuel consuming countries.

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Zaman, Khalid

2017-11-01

This study examined the relationship between biofuel consumption, forest biodiversity, and a set of national scale indicators of per capita income, foreign direct investment (FDI) inflows, trade openness, and population density with a panel data of 12 biofuels consuming countries for a period of 2000 to 2013. The study used Global Environmental Facility (GEF) biodiversity benefits index and forest biodiversity index in an environmental Kuznets curve (EKC) framework. The results confirmed an inverted U-shaped relationship between GEF biodiversity index and per capita income, while there is flat/no relationship between carbon emissions and economic growth, and between forest biodiversity and economic growth models. FDI inflows and trade openness both reduce carbon emissions while population density and biofuel consumption increase carbon emissions and decrease GEF biodiversity index. Trade openness supports to increases GEF biodiversity index while it decreases forest biodiversity index and biofuel consumption in a region.

Structural diversities induced by cation sizes in a series of fluorogermanophosphates: A2[GeF2(HPO4)2] (A = Na, K, Rb, NH4, and Cs).

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Chen, Zhang-Gai; Huang, Xia; Zhuang, Rong-Chuan; Zhang, Yu; Liu, Xin; Shi, Tao; Wang, Shuai-Hua; Wu, Shao-Fan; Mi, Jin-Xiao; Huang, Ya-Xi

2017-09-12

Germanophosphates, in comparison with other metal phosphates, have been less studied but potentially exhibit more diverse structural chemistry with wide applications. Herein we applied a hydro-/solvo-fluorothermal route to make use of both the "tailor effect" of fluoride for the formation of low dimensional anionic clusters and the presence of alkali cations of different sizes to align the anionic clusters to control the overall crystal symmetries of germanophosphates. The synergetic effects of fluoride and alkali cations led to structural changes from chain-like structures to layered structures in a series of five novel fluorogermanophosphates: A 2 [GeF 2 (HPO 4 ) 2 ] (A = Na, K, Rb, NH 4 , and Cs, denoted as Na, K, Rb, NH4, and Cs). Although these fluorogermanophosphates have stoichiometrically equivalent formulas, they feature different anionic clusters, diverse structural dimensionalities, and contrasting crystal symmetries. Chain-like structures were observed for the compounds with the smaller sized alkali ions (Na + , K + , and Rb + ), whereas layered structures were found for those containing the larger sized cations ((NH 4 ) + and Cs + ). Specifically, monoclinic space groups were observed for the Na, K, Rb, and NH4 compounds, whereas a tetragonal space group P4/mbm was found for the Cs compound. These compounds provide new insights into the effects of cation sizes on the anionic clusters built from GeO 4 F 2 octahedra and HPO 4 tetrahedra as well as their influences on the overall structural symmetries in germanophosphates. Further characterization including IR spectroscopy and thermal analyses for all five compounds is also presented.

Solo/Trio8, a membrane-associated short isoform of Trio, modulates endosome dynamics and neurite elongation.

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Sun, Ying-Jie; Nishikawa, Kaori; Yuda, Hideki; Wang, Yu-Lai; Osaka, Hitoshi; Fukazawa, Nobuna; Naito, Akira; Kudo, Yoshihisa; Wada, Keiji; Aoki, Shunsuke

2006-09-01

With DNA microarrays, we identified a gene, termed Solo, that is downregulated in the cerebellum of Purkinje cell degeneration mutant mice. Solo is a mouse homologue of rat Trio8-one of multiple Trio isoforms recently identified in rat brain. Solo/Trio8 contains N-terminal sec14-like and spectrin-like repeat domains followed by a single guanine nucleotide exchange factor 1 (GEF1) domain, but it lacks the C-terminal GEF2, immunoglobulin-like, and kinase domains that are typical of Trio. Solo/Trio8 is predominantly expressed in Purkinje neurons of the mouse brain, and expression begins following birth and increases during Purkinje neuron maturation. We identified a novel C-terminal membrane-anchoring domain in Solo/Trio8 that is required for enhanced green fluorescent protein-Solo/Trio8 localization to early endosomes (positive for both early-endosome antigen 1 [EEA1] and Rab5) in COS-7 cells and primary cultured neurons. Solo/Trio8 overexpression in COS-7 cells augmented the EEA1-positive early-endosome pool, and this effect was abolished via mutation and inactivation of the GEF domain or deletion of the C-terminal membrane-anchoring domain. Moreover, primary cultured neurons transfected with Solo/Trio8 showed increased neurite elongation that was dependent on these domains. These results suggest that Solo/Trio8 acts as an early-endosome-specific upstream activator of Rho family GTPases for neurite elongation of developing Purkinje neurons.

PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways.

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Dunn, Henry A; Ferguson, Stephen S G

2015-10-01

G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na(+)/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Gα-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and

Mesothelioma With a Large Prevascular Lymph Node: N1 Involvement or Something Different?

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Berzenji, Lawek; Van Schil, Paul E; Snoeckx, Annemie; Hertoghs, Marjan; Carp, Laurens

2018-05-01

A 64-year-old man presented with a large amount of right-sided pleural fluid on imaging, together with calcified pleural plaques and an enlarged nodular structure in the prevascular mediastinum, presumably an enlarged lymph node. Pleural biopsies were obtained during video-assisted thoracoscopic surgery to exclude malignancy. Histopathology showed an epithelial malignant pleural mesothelioma. Induction chemotherapy with cisplatin and pemetrexed was administered followed by an extended pleurectomy and decortication with systematic nodal dissection. Histopathology confirmed the diagnosis of a ypT3N0M0 (stage IB) mesothelioma, and an unexpected thymoma type B2 (stage II) was discovered in the prevascular nodule. Simultaneous occurrence of a mesothelioma and thymoma is extremely rare. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Assessing public health policy approaches to level-up the gradient in health inequalities: the Gradient Evaluation Framework.

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Davies, J K; Sherriff, N S

2014-03-01

This paper seeks to introduce and analyse the development of the Gradient Evaluation Framework (GEF) to facilitate evaluation of policy actions for their current or future use in terms of their 'gradient friendliness'. In particular, this means their potential to level-up the gradient in health inequalities by addressing the social determinants of health and thereby reducing decision-makers' chances of error when developing such policy actions. A qualitative developmental study to produce a policy-based evaluation framework. The scientific basis of GEF was developed using a comprehensive consensus-building process. This process followed an initial narrative review, based on realist review principles, which highlighted the need for production of a dedicated evaluation framework. The consensus-building process included expert workshops, a pretesting phase, and external peer review, together with support from the Gradient project Scientific Advisory Group and all Gradient project partners, including its Project Steering Committee. GEF is presented as a flexible policy tool resulting from a consensus-building process involving experts from 13 European countries. The theoretical foundations which underpin GEF are discussed, together with a range of practical challenges. The importance of systematic evaluation at each stage of the policy development and implementation cycle is highlighted, as well as the socio-political context in which policy actions are located. GEF offers potentially a major contribution to the public health field in the form of a practical, policy-relevant and common frame of reference for the evaluation of public health interventions that aim to level-up the social gradient in health inequalities. Further research, including the need for practical field testing of GEF and the exploration of alternative presentational formats, is recommended. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Energizing change

International Nuclear Information System (INIS)

El-Ashry, M.T.

1998-01-01

Since its creation in 1991, the Global Environment Facility (GEF) has committed over US D 725 million to nearly 200 projects in 49 nations in concrete action to combat climate changes. Its activities are implemented by the United Nations Environmental Programme, the United Nations Development Programme and the World Bank. This paper describes the GEF's work to combat climatic changes

Bioinformatic and Comparative Localization of Rab Proteins Reveals Functional Insights into the Uncharacterized GTPases Ypt10p and Ypt11p†

OpenAIRE

Buvelot Frei, Stéphanie; Rahl, Peter B.; Nussbaum, Maria; Briggs, Benjamin J.; Calero, Monica; Janeczko, Stephanie; Regan, Andrew D.; Chen, Catherine Z.; Barral, Yves; Whittaker, Gary R.; Collins, Ruth N.

2006-01-01

A striking characteristic of a Rab protein is its steady-state localization to the cytosolic surface of a particular subcellular membrane. In this study, we have undertaken a combined bioinformatic and experimental approach to examine the evolutionary conservation of Rab protein localization. A comprehensive primary sequence classification shows that 10 out of the 11 Rab proteins identified in the yeast (Saccharomyces cerevisiae) genome can be grouped within a major subclass, each comprising ...

Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3 and KIT driven Leukemogenesis

Science.gov (United States)

Chatterjee, Anindya; Ghosh, Joydeep; Ramdas, Baskar; Mali, Raghuveer Singh; Martin, Holly; Kobayashi, Michihiro; Vemula, Sasidhar; Canela, Victor H.; Waskow, Emily R.; Visconte, Valeria; Tiu, Ramon V.; Smith, Catherine C.; Shah, Neil; Bunting, Kevin D.; Boswell, H. Scott; Liu, Yan; Chan, Rebecca J.; Kapur, Reuben

2015-01-01

SUMMARY Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN) and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK), whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis. PMID:25456130

Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis

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Anindya Chatterjee

2014-11-01

Full Text Available Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML and myeloproliferative neoplasms (MPNs, and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis.

Neuronal adaptor FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating ELMO1.

Science.gov (United States)

Li, Wen; Tam, Ka Ming Vincent; Chan, Wai Wan Ray; Koon, Alex Chun; Ngo, Jacky Chi Ki; Chan, Ho Yin Edwin; Lau, Kwok-Fai

2018-04-03

Neurite outgrowth is a crucial process in developing neurons for neural network formation. Understanding the regulatory mechanisms of neurite outgrowth is essential for developing strategies to stimulate neurite regeneration after nerve injury and in neurodegenerative disorders. FE65 is a brain-enriched adaptor that stimulates Rac1-mediated neurite elongation. However, the precise mechanism by which FE65 promotes the process remains elusive. Here, we show that ELMO1, a subunit of ELMO1-DOCK180 bipartite Rac1 GEF, interacts with the FE65 N-terminal region. Overexpression of FE65 and/or ELMO1 enhances whereas knockdown of FE65 or ELMO1 inhibits neurite outgrowth and Rac1 activation. The effect of FE65 alone or together with ELMO1 is attenuated by an FE65 double mutation that disrupts FE65-ELMO1 interaction. Notably, FE65 is found to activate ELMO1 by diminishing ELMO1 intramolecular autoinhibitory interaction and to promote the targeting of ELMO1 to the plasma membrane where Rac1 is activated. We also show that FE65, ELMO1 and DOCK180 form a tripartite complex. Knockdown of DOCK180 reduces the stimulatory effect of FE65-ELMO1 on Rac1 activation and neurite outgrowth. Thus, we identify a novel mechanism that FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating of ELMO1. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

β1-C121W Is Down But Not Out: Epilepsy-Associated Scn1b-C121W Results in a Deleterious Gain-of-Function

Science.gov (United States)

Kruger, Larisa C.; O'Malley, Heather A.; Hull, Jacob M.; Kleeman, Amanda; Patino, Gustavo A.

2016-01-01

Voltage-gated sodium channel (VGSC) β subunits signal through multiple pathways on multiple time scales. In addition to modulating sodium and potassium currents, β subunits play nonconducting roles as cell adhesion molecules, which allow them to function in cell–cell communication, neuronal migration, neurite outgrowth, neuronal pathfinding, and axonal fasciculation. Mutations in SCN1B, encoding VGSC β1 and β1B, are associated with epilepsy. Autosomal-dominant SCN1B-C121W, the first epilepsy-associated VGSC mutation identified, results in genetic epilepsy with febrile seizures plus (GEFS+). This mutation has been shown to disrupt both the sodium-current-modulatory and cell-adhesive functions of β1 subunits expressed in heterologous systems. The goal of this study was to compare mice heterozygous for Scn1b-C121W (Scn1b+/W) with mice heterozygous for the Scn1b-null allele (Scn1b+/−) to determine whether the C121W mutation results in loss-of-function in vivo. We found that Scn1b+/W mice were more susceptible than Scn1b+/− and Scn1b+/+ mice to hyperthermia-induced convulsions, a model of pediatric febrile seizures. β1-C121W subunits are expressed at the neuronal cell surface in vivo. However, despite this, β1-C121W polypeptides are incompletely glycosylated and do not associate with VGSC α subunits in the brain. β1-C121W subcellular localization is restricted to neuronal cell bodies and is not detected at axon initial segments in the cortex or cerebellum or at optic nerve nodes of Ranvier of Scn1bW/W mice. These data, together with our previous results showing that β1-C121W cannot participate in trans-homophilic cell adhesion, lead to the hypothesis that SCN1B-C121W confers a deleterious gain-of-function in human GEFS+ patients. SIGNIFICANCE STATEMENT The mechanisms underlying genetic epilepsy syndromes are poorly understood. Closing this gap in knowledge is essential to the development of new medicines to treat epilepsy. We have used mouse models to

Knochen, Herz und Gefäße – „Bone-Vascular Axis“: Eine systematische Übersicht prospektiver Beobachtungsstudien // The Bone-Cardiovascular Axis: A Systematic Review of Prospective Studies

Directory of Open Access Journals (Sweden)

Tomaschitz A

2016-01-01

bone diseases the current evidence however indicates a potential benefit in screening for cardiovascular diseases and osteoporosis in respective risk groups. p bKurzfassung/b: Osteoporose und atherosklerotische Erkrankungen sind mit massiv erhöhter Morbidität, Mortalität und Gesundheitskosten verbunden. Mit der „bone-vascular axis“ entstand in den letzten Jahren ein intensiv beforschtes, klinisch hoch relevantes Gebiet. Mechanistische Studien identifizierten komplexe wechselseitige Beziehungen zwischen der vaskulären Physiologie, der Knochenneubildung und der Knochenmineralisation. Herz und Gefäße spielen eine relevante Rolle für die muskuloskelettale Funktion und umgekehrt beeinflusst das Knochengewebe u. a. über endo- und parakrine Signalwege das Herz-Kreislaufsystem. Epidemiologische Studien wiesen auch nach Berücksichtigung gemeinsamer Risikofaktoren auf unabhängige, wechselseitige Interaktionen zwischen Herz, Gefäßen und Knochengewebe hin.brIm Rahmen einer systematischen Literaturrecherche (Medline, Pubmed wurden insgesamt 49 prospektive Studien, die den Zusammenhang zwischen Osteoporose, Knochenmineraldichte und Auftreten von Frakturen mit atherosklerotischen Erkrankungen beschreiben, selektiert. Dabei konnten diese Untersuchungen mehrheitlich eine erhöhte kardiovaskuläre Morbidität und Mortalität bei Frauen und Männern mit verminderter Knochenmineraldichte an verschiedenen Lokalisationen sowie nach osteoporotischen Frakturen nachweisen. Umgekehrt konnten zahlreiche Studien ein erhöhtes Risiko für die Entstehung einer Osteoporose sowie von osteoporotischen Frakturen bei Patienten mit atherosklerotischen Erkrankungen nachweisen. Schließlich konnten konsistente Assoziationen zwischen Herzinsuffizienz (7 Studien, Schlaganfall (16 Studien, peripherer arterieller Verschlusskrankheit (3 Studien und Knochenmineraldichte sowie Frakturrisiko detektiert werden.brGrundsätzlich lassen Beobachtungsstudien keine Rückschlüsse auf die Kausalität der

Global Environment Facility |

Science.gov (United States)

environment Countries pledge US$4.1 billion to the Global Environment Facility Ringtail lemur mom with two of paradise Nations rally to protect global environment Countries pledge US$4.1 billion to the Global Environment Facility Stockholm, Sweden birds-eye view Events GEF-7 Replenishment Trung Truong Son Landscapes

Airfield Damage Recovery Techniques of 18th Engineer Brigade in Europe

Science.gov (United States)

1980-12-01

have to be observed. Comparable German regulations are published in "Verordnung uber gefAbrliche Arbeitsstoffe", issue May 1, 1976. Ŗ.1. Most important...rules: Rubber boots, acid-prove protective gloves, protective facial masks, water spray bottles for eyes 2.2. No smoking, no eating at jobside 3

Role for cER and Mmr1p in anchorage of mitochondria at sites of polarized surface growth in budding yeast.

Science.gov (United States)

Swayne, Theresa C; Zhou, Chun; Boldogh, Istvan R; Charalel, Joseph K; McFaline-Figueroa, José Ricardo; Thoms, Sven; Yang, Christine; Leung, Galen; McInnes, Joseph; Erdmann, Ralf; Pon, Liza A

2011-12-06

Mitochondria accumulate at neuronal and immunological synapses and yeast bud tips and associate with the ER during phospholipid biosynthesis, calcium homeostasis, and mitochondrial fission. Here we show that mitochondria are associated with cortical ER (cER) sheets underlying the plasma membrane in the bud tip and confirm that a deletion in YPT11, which inhibits cER accumulation in the bud tip, also inhibits bud tip anchorage of mitochondria. Time-lapse imaging reveals that mitochondria are anchored at specific sites in the bud tip. Mmr1p, a member of the DSL1 family of tethering proteins, localizes to punctate structures on opposing surfaces of mitochondria and cER sheets underlying the bud tip and is recovered with isolated mitochondria and ER. Deletion of MMR1 impairs bud tip anchorage of mitochondria without affecting mitochondrial velocity or cER distribution. Deletion of the phosphatase PTC1 results in increased Mmr1p phosphorylation, mislocalization of Mmr1p, defects in association of Mmr1p with mitochondria and ER, and defects in bud tip anchorage of mitochondria. These findings indicate that Mmr1p contributes to mitochondrial inheritance as a mediator of anchorage of mitochondria to cER sheets in the yeast bud tip and that Ptc1p regulates Mmr1p phosphorylation, localization, and function. Copyright © 2011 Elsevier Ltd. All rights reserved.

Study of multiplet structures of Mn4+ activated in fluoride crystals

International Nuclear Information System (INIS)

Novita, Mega; Honma, Tetsuo; Hong, Byungchul; Ohishi, Atsushi; Ogasawara, Kazuyoshi

2016-01-01

We investigated the optical properties of Mn 4+ in some fluoride crystals such as Cs 2 MnF 6 , Cs 2 GeF 6 , Rb 2 GeF 6 , Cs 2 SiF 6 , K 2 SiF 6 , Rb 2 MnF 6 , Rb 2 SiF 6 , K 2 GeF 6 , K 2 TiF 6 , Li 2 MnF 6 , Na 2 GeF 6 , Na 2 SiF 6 , and Na 2 TiF 6 based on the first-principle calculation using the discrete-variational multi-electron method. In order to estimate the lattice relaxation, we performed EXAFS measurement of Mn 4+ doped in K 2 SiF 6 , K 2 TiF 6 , and K 2 GeF 6 . The relaxation rates of A 2 BF 6 :Mn 4+ were fixed to be the above estimated values, 102.24%, 107.37% or 96.80% for crystal having Si, Ge, or Ti at the B cation site, respectively. In this work, we also considered some corrections such as configuration dependent correction and correlation correction to improve the theoretical energies. It has been shown that to reproduce multiplet energy levels quantitatively, the lattice relaxation is very important. On the other hand, for a qualitative prediction of the tendencies of the multiplet energies, the combination of lattice relaxation effect, configuration dependent correction, and correlation correction is effective. - Highlights: • Multiplet structures of A 2 BF 6 :Mn 4+ were calculated from first-principles. • Lattice relaxation was estimated based on EXAFS experiment. • Lattice relaxation is important to reproduce multiplet energies quantitatively. • CDC and CC are important to reproduce tendencies of multiplet energies.

The domain architecture of large guanine nucleotide exchange factors for the small GTP-binding protein Arf

Directory of Open Access Journals (Sweden)

Geldner Niko

2005-02-01

Full Text Available Abstract Background Small G proteins, which are essential regulators of multiple cellular functions, are activated by guanine nucleotide exchange factors (GEFs that stimulate the exchange of the tightly bound GDP nucleotide by GTP. The catalytic domain responsible for nucleotide exchange is in general associated with non-catalytic domains that define the spatio-temporal conditions of activation. In the case of small G proteins of the Arf subfamily, which are major regulators of membrane trafficking, GEFs form a heterogeneous family whose only common characteristic is the well-characterized Sec7 catalytic domain. In contrast, the function of non-catalytic domains and how they regulate/cooperate with the catalytic domain is essentially unknown. Results Based on Sec7-containing sequences from fully-annotated eukaryotic genomes, including our annotation of these sequences from Paramecium, we have investigated the domain architecture of large ArfGEFs of the BIG and GBF subfamilies, which are involved in Golgi traffic. Multiple sequence alignments combined with the analysis of predicted secondary structures, non-structured regions and splicing patterns, identifies five novel non-catalytic structural domains which are common to both subfamilies, revealing that they share a conserved modular organization. We also report a novel ArfGEF subfamily with a domain organization so far unique to alveolates, which we name TBS (TBC-Sec7. Conclusion Our analysis unifies the BIG and GBF subfamilies into a higher order subfamily, which, together with their being the only subfamilies common to all eukaryotes, suggests that they descend from a common ancestor from which species-specific ArfGEFs have subsequently evolved. Our identification of a conserved modular architecture provides a background for future functional investigation of non-catalytic domains.

Ion chemistry in germane/fluorocompounds gaseous mixtures: a mass spectrometric and theoretical study.

Science.gov (United States)

Antoniotti, Paola; Rabezzana, Roberto; Turco, Francesca; Borocci, Stefano; Giordani, Maria; Grandinetti, Felice

2008-10-01

The ion-molecule reactions occurring in GeH(4)/NF(3), GeH(4)/SF(6), and GeH(4)/SiF(4) gaseous mixtures have been investigated by ion trap mass spectrometry and ab initio calculations. While the NF(x)(+) (x=1-3) react with GeH(4) mainly by the exothermic charge transfer, the open-shell Ge(+) and GeH(2)(+) undergo the efficient F-atom abstraction from NF(3) and form GeF(+) and F-GeH(2)(+) as the only ionic products. The mechanisms of these two processes are quite similar and involve the formation of the fluorine-coordinated complexes Ge-F-NF(2)(+) and H(2)Ge-F-NF(2)(+), their subsequent crossing to the significantly more stable isomers FGe-NF(2)(+) and F-GeH(2)-NF(2)(+), and the eventual dissociation of these ions into GeF(+) (or F-GeH(2)(+)) and NF(2). The closed-shell GeH(+) and GeH(3)(+) are instead much less reactive towards NF(3), and the only observed process is the less efficient formation of GeF(+) from GeH(+). The theoretical investigation of this unusual H/F exchange reaction suggests the involvement of vibrationally-hot GeH(+). Passing from NF(3) to SF(6) and SiF(4), the average strength of the M-F bond increases from 70 to 79 and 142 kcal mol(-1), and in fact the only process observed by reacting GeH(n)(+) (n=0-3) with SF(6) and SiF(4) is the little efficient F-atom abstraction from SF(6) by Ge(+). Irrespective of the experimental conditions, we did not observe any ionic product of Ge-N, Ge-S, or Ge-Si connectivity. This is in line with the previously observed exclusive formation of GeF(+) from the reaction between Ge(+) and C-F compounds such as CH(3)F. Additionally observed processes include in particular the conceivable formation of the elusive thiohypofluorous acid FSH from the reaction between SF(+) and GeH(4).

Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion

DEFF Research Database (Denmark)

Peters, C; Bayer, M J; Bühler, S

2001-01-01

-complex formation occurs downstream from trans-SNARE pairing, and depends on both the Rab-GTPase Ypt7 and calmodulin. The maintenance of existing complexes and completion of fusion are independent of trans-SNARE pairs. Reconstituted proteolipids form sealed channels, which can expand to form aqueous pores in a Ca2...

Characterization of the human GARP (Golgi associated retrograde protein) complex

International Nuclear Information System (INIS)

Liewen, Heike; Meinhold-Heerlein, Ivo; Oliveira, Vasco; Schwarzenbacher, Robert; Luo Guorong; Wadle, Andreas; Jung, Martin; Pfreundschuh, Michael; Stenner-Liewen, Frank

2005-01-01

The Golgi associated retrograde protein complex (GARP) or Vps fifty-three (VFT) complex is part of cellular inter-compartmental transport systems. Here we report the identification of the VFT tethering factor complex and its interactions in mammalian cells. Subcellular fractionation shows that human Vps proteins are found in the smooth membrane/Golgi fraction but not in the cytosol. Immunostaining of human Vps proteins displays a vesicular distribution most concentrated at the perinuclear envelope. Co-staining experiments with endosomal markers imply an endosomal origin of these vesicles. Significant accumulation of VFT complex positive endosomes is found in the vicinity of the Trans Golgi Network area. This is in accordance with a putative role in Golgi associated transport processes. In Saccharomyces cerevisiae, GARP is the main effector of the small GTPase Ypt6p and interacts with the SNARE Tlg1p to facilitate membrane fusion. Accordingly, the human homologue of Ypt6p, Rab6, specifically binds hVps52. In human cells, the 'orphan' SNARE Syntaxin 10 is the genuine binding partner of GARP mediated by hVps52. This reveals a previously unknown function of human Syntaxin 10 in membrane docking and fusion events at the Golgi. Taken together, GARP shows significant conservation between various species but diversification and specialization result in important differences in human cells

Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis.

Science.gov (United States)

Chatterjee, Anindya; Ghosh, Joydeep; Ramdas, Baskar; Mali, Raghuveer Singh; Martin, Holly; Kobayashi, Michihiro; Vemula, Sasidhar; Canela, Victor H; Waskow, Emily R; Visconte, Valeria; Tiu, Ramon V; Smith, Catherine C; Shah, Neil; Bunting, Kevin D; Boswell, H Scott; Liu, Yan; Chan, Rebecca J; Kapur, Reuben

2014-11-20

Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs), and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK) whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Guanine nucleotide exchange factor αPIX leads to activation of the Rac 1 GTPase/glycogen phosphorylase pathway in interleukin (IL)-2-stimulated T cells

DEFF Research Database (Denmark)

Llavero, Francisco; Urzelai, Bakarne; Osinalde, Nerea

2015-01-01

Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation. In the lymphoid system, Rac 1 and in general other small GTPases of the Rho family participate...... in the signaling cascades that are activated after engagement of the T cell antigen receptor. However, little is known about the IL-2-dependent Rac 1 activator molecules. For the first time, a signaling pathway leading to the activation of Rac 1/PYGM in response to IL-2-stimulated T cell proliferation is described....... More specifically, αPIX, a known guanine nucleotide exchange factor for the small GTPases of the Rho family, preferentially Rac 1, mediates PYGM activation in Kit 225 T cells stimulated with IL-2. Using directed mutagenesis, phosphorylation of αPIX Rho-GEF serines 225 and 488 is required for activation...

Sectoral assessments

Energy Technology Data Exchange (ETDEWEB)

Callaway, J M; Fenhann, J; Gorham, R; Makundi, W; Sathaye, J

1999-09-01

This publication contains five papers that were written as a part of the GEF project, The Economics of Greenhouse Gas Limitations. The main goal of the project was to assess the greenhouse gas reductions and incremental costs of mitigation option sin Ecuador, Argentina, Senegal, Mauritius, Vietnam, Indonesia, Estonia and Hungary. In addition, regional studies were conducted for the Andean Pact nations and Southern Africa to assess various aspects of regional co-operation in reducing greenhouse gas emissions. The GEF study also involved the development of a methodological framework for climate change assessment, with a special emphasis on developing countries. These guidelines have been published in a separate document, Economics of Greenhouse Gas Limitations: Methodological Guidelines. The papers in this publication focus on various methodological and policy aspects of greenhouse gas mitigation at the sectoral level, and are outgrowth of work performed on other parts of the GEF project. (au)

The Impact of Conflict on Forests in South Sudan

Science.gov (United States)

Gorsevski, V.; Kasischke, E. S.; Dempewolf, J.; Loboda, T. V.; Geores, M.

2014-12-01

The impacts of armed conflict on ecosystems are complex and difficult to assess due to restricted access to affected areas making satellite remote sensing a useful tool for studying direct and indirect effects of conflict on the landscape. The Imatong Central Forest Reserve (ICFR) in South Sudan together with the nearby Dongotana Hills and the Agoro-Agu Forest Reserve (AFR) in Northern Uganda share a boundary and encompass a biologically diverse montane ecosystem. This study used satellite data combined with general human population trends to examine the impact of armed conflict and its outcome on similar forest ecosystems both during and after hostilities. A Disturbance Index (DI) was used to investigate the location and extent of forest cover loss and gain in three areas for two key time periods. Results indicate that the rate of forest recovery was significantly higher than the rate of disturbance both during and after wartime in and around the ICFR. In contrast, the nearby Dongotana Hills experienced relatively high rates of disturbance during both periods; however, post war period losses were largely offset by some gains in forest cover. Discussions with local inhabitants confirmed these findings and provided further insights into the underlying causes impacting forest cover and wildlife. South Sudan is the latest nation to join the Global Environment Facility (GEF). While the GEF does not explicitly address conflict, many of the projects it supports occur in conflict and post-conflict zones with wide-ranging repercussions for both people and the environment. In an effort to assess best practices for working in conflict and post-conflict areas, the GEF Scientific and Technical Advisory Panel (STAP) will undertake an analysis of GEF-funded projects over the last two decades to identify where the GEF has promoted cooperation between groups and states, and/or made a positive contribution toward conflict avoidance resulting in shared environmental benefits.

Modificarea gradului de exercitare a funcțiilor ecoprotective: o analiză comparativă în păduri de stat și private [ Changes in the degree of ecoprotective functions effectiveness: a comparative study in state and private forests

Directory of Open Access Journals (Sweden)

Barbu Cătălina

2015-12-01

Full Text Available The article uses the ecoprotective function effectiveness index (GEF to identify how far the changes in the management practices in the last 20 years had an impact on the capacity of forest ecosystem to provide optimal functions. The study was carried out in Forest District Vama (Production Unit I Deia, Suceava County and employs an integrated methodology based on forest management plans, remote sensing tools and field inventory. The structural patterns of state and private forests have been compared in two periods (1990, 2014. The private forests integrated in the analysis have been restituted according to the law 18/1991 and have been for more than 20 years managed by the new forest owners. For the state forests, GEF was computed using structural characteristics of the stands obtained from the management plans. In the restituted forests, due to the lack of management plans, all the characteristics were obtained from field inventory. The study successfully identifies how the components of the index have changed and how this influenced the overall effectiveness of the ecoprotective functions. The changes in GEF index values in the state forests were influenced by natural evolution of the stands while in private forests by the anthropic and natural disturbances. For the state forests, the GEF index values showed a slight increase in 2014 comparatively to 1990. In the private forests the GEF index value for 2014 decreased with more than 5 points for more than one half of the area compared to 1990 (prior to forest restitution. The study argues the possibility to adapt the index as an efficient tool to assess such changes at a broader scale, as a decisional support in forest policy processes.

Timing of surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer - A comparison of magnetic resonance imaging at two time points and histopathological responses.

Science.gov (United States)

West, M A; Dimitrov, B D; Moyses, H E; Kemp, G J; Loughney, L; White, D; Grocott, M P W; Jack, S; Brown, G

2016-09-01

There is wide inter-institutional variation in the interval between neoadjuvant chemoradiotherapy (NACRT) and surgery for locally advanced rectal cancer. We aimed to assess the association of magnetic resonance imaging (MRI) at 9 and 14 weeks post-NACRT; T-staging (ymrT) and post-NACRT tumour regression grading (ymrTRG) with histopathological outcomes; histopathological T-stage (ypT) and histopathological tumour regression grading (ypTRG) in order to inform decision-making about timing of surgery. We prospectively studied 35 consecutive patients (26 males) with MRI-defined resection margin threatened rectal cancer who had completed standardized NACRT. Patients underwent a MRI at Weeks 9 and 14 post-NACRT, and surgery at Week 15. Two readers independently assessed MRIs for ymrT, ymrTRG and volume change. ymrT and ymrTRG were analysed against histopathological ypT and ypTRG as predictors by logistic regression modelling and receiver operating characteristic (ROC) curve analyses. Thirty-five patients were recruited. Inter-observer agreement was good for all MR variables (Kappa > 0.61). Considering ypT as an outcome variable, a stronger association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.064 vs. p = 0.010; Volume change - p = 0.062 vs. p = 0.007). Similarly, considering ypTRG as an outcome variable, a greater association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.005 vs. p = 0.042; Volume change - p = 0.004 vs. 0.055). Following NACRT, greater tumour down-staging and volume reduction was observed at Week 14. Timing of surgery, in relation to NACRT, merits further investigation. NCT01325909. Copyright © 2016 Elsevier Ltd. All rights reserved.

VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells

Directory of Open Access Journals (Sweden)

Ayumi Yoshida

2015-09-01

Full Text Available Neuropilin-1 (NRP1 has been identified as a VEGF-A receptor. DJM-1, a human skin cancer cell line, expresses endogenous VEGF-A and NRP1. In the present study, the RNA interference of VEGF-A or NRP1 suppressed DJM-1 cell proliferation. Furthermore, the overexpression of the NRP1 wild type restored shNRP1-treated DJM-1 cell proliferation, whereas NRP1 cytoplasmic deletion mutants did not. A co-immunoprecipitation analysis revealed that VEGF-A induced interactions between NRP1 and GIPC1, a scaffold protein, and complex formation between GIPC1 and Syx, a RhoGEF. The knockdown of GIPC1 or Syx reduced active RhoA and DJM-1 cell proliferation without affecting the MAPK or Akt pathway. C3 exoenzyme or Y27632 inhibited the VEGF-A-induced proliferation of DJM-1 cells. Conversely, the overexpression of the constitutively active form of RhoA restored the proliferation of siVEGF-A-treated DJM-1 cells. Furthermore, the inhibition of VEGF-A/NRP1 signaling upregulated p27, a CDK inhibitor. A cell-penetrating oligopeptide that targeted GIPC1/Syx complex formation inhibited the VEGF-A-induced activation of RhoA and suppressed DJM-1 cell proliferation. In conclusion, this new signaling pathway of VEGF-A/NRP1 induced cancer cell proliferation by forming a GIPC1/Syx complex that activated RhoA to degrade the p27 protein.

PI3-kinase γ promotes Rap1a-mediated activation of myeloid cell integrin α4β1, leading to tumor inflammation and growth.

Directory of Open Access Journals (Sweden)

Michael C Schmid

Full Text Available Tumor inflammation, the recruitment of myeloid lineage cells into the tumor microenvironment, promotes angiogenesis, immunosuppression and metastasis. CD11b+Gr1lo monocytic lineage cells and CD11b+Gr1hi granulocytic lineage cells are recruited from the circulation by tumor-derived chemoattractants, which stimulate PI3-kinase γ (PI3Kγ-mediated integrin α4 activation and extravasation. We show here that PI3Kγ activates PLCγ, leading to RasGrp/CalDAG-GEF-I&II mediated, Rap1a-dependent activation of integrin α4β1, extravasation of monocytes and granulocytes, and inflammation-associated tumor progression. Genetic depletion of PLCγ, CalDAG-GEFI or II, Rap1a, or the Rap1 effector RIAM was sufficient to prevent integrin α4 activation by chemoattractants or activated PI3Kγ (p110γCAAX, while activated Rap (RapV12 promoted constitutive integrin activation and cell adhesion that could only be blocked by inhibition of RIAM or integrin α4β1. Similar to blockade of PI3Kγ or integrin α4β1, blockade of Rap1a suppressed both the recruitment of monocytes and granulocytes to tumors and tumor progression. These results demonstrate critical roles for a PI3Kγ-Rap1a-dependent pathway in integrin activation during tumor inflammation and suggest novel avenues for cancer therapy.

Evaluation of the economic and financial management in Mexican microenterprises

Directory of Open Access Journals (Sweden)

Malena Portal Boza

2016-10-01

Full Text Available The exhibit features Mexican microenterprises today give evidence of the problems that they face in terms of managing their activities, where the role of economic-financial elements is perceived. Although the issue has been addressed in previous studies the contribution of this study is to evaluate in an integrated manner the level of economic and financial management (GEF in micro and impact on business results. To do an index is constructed from indicators synthetic methodology using the principal components factor analysis, accompanied by linear regression exercises. The results confirm the presence of elements of GEF in micro studied. Moreover, it was found that the extent to which GEF elements are incorporated in its activities, the impact on their business results will be positive. These observations constitute the prelude to the creation of public policies seeking to establish improvement strategies for such companies, besides that fosters future research for analysis but by sectors of economic activity.

The clinicopathologic relevance and prognostic value of tumor deposits and the applicability of N1c category in rectal cancer with preoperative radiotherapy.

Science.gov (United States)

Wei, Xiao-Li; Qiu, Miao-Zhen; Zhou, Yi-Xin; He, Ming-Ming; Luo, Hui-Yan; Wang, Feng-Hua; Zhang, Dong-Sheng; Li, Yu-Hong; Xu, Rui-Hua

2016-11-15

The clinicopathologic relevance and prognostic value of tumor deposits in colorectal cancer has been widely demonstrated. However, there are still debates in the prognostic value of tumor deposits and the applicability of N1c category in rectal cancer with preoperative radiotherapy. In this study, rectal cancer with preoperative radiotherapy followed by resection of primary tumors registered in Surveillance, Epidemiology and End Results (SEER) database from 2010-2012 were analyzed. There were 4,813 cases eligible for this study, and tumor deposits were found in 514 (10.7%) cases. The presence of tumor deposits was significantly associated with some aggressive characteristics, including poorer tumor differentiation, more advanced ypT category, ypN category and ypTNM stage, distant metastasis, elevated carcinoembryonic antigen, higher positive rates of circumferential resection margin and perineural invasion (all P < = 0.001). Tumor deposit was also an independent negative prognostic factor for cancer-specific survival in rectal cancer with preoperative radiotherapy (adjusted HR and 95% CI: 2.25 (1.51 - 3.35)). N1c category had significant worse survival compared with N0 category (adjusted HR and 95% CI: 2.41 (1.24 - 4.69)). In conclusion, tumor deposit was a significant and independent prognostic factor, and the N1c category by the 7th edition of AJCC/TNM staging system was applicable in rectal cancer with preoperative radiotherapy.

Mixed valent noble metal perovskites Ba/sub 3/B/sup 3 +/Pt/sub x/Ru/sub 2-x//sup 4. 5+/O/sub 9/

Energy Technology Data Exchange (ETDEWEB)

Moessner, B; Kemmler-Sack, S; Ehmann, A [Tuebingen Univ. (Germany, F.R.). Lehrstuhl fuer Anorganische Chemie 2

1982-04-01

In perovskites of type Ba/sub 3/B/sup 3 +/Pt/sub x/Ru/sub 2-x//sup 4.5+/O/sub 9/ the ruthenium can be substituted by platinum up to x = 1. The compounds crystallize in a 1:2 ordered hexagonal BaTiO/sub 3/ structure (sequence (hcc)/sub 2/) with face connected Pt/sub x/Ru/sub 2-x/O/sub 9/ double octahedra. Intensity calculations on powder data of Ba/sub 3/YPt/sub 1/2/Ru/sub 3/2/O/sub 9/ (space group P6/sub 3//mmc) gave a refined, intensity related R' value of 8.6%. The vibrational spectroscopic and catalytic properties are reported.

[Effects of recruitment maneuver in prone position on hemodynamics in patients with severe pulmonary infection].

Science.gov (United States)

Fan, Yuan-hua; Liu, Yuan-fei; Zhu, Hua-yong; Zhang, Min

2012-02-01

To evaluate effects of recruitment maneuver in prone position on hemodynamics in patients with severe pulmonary infection, based on the protective pulmonary ventilation strategy. Ninety-seven cases with severe pulmonary infection admitted to intensive care unit (ICU) of Ganzhou City People's Hospital undergoing mechanical ventilation were involved. Volume controlled ventilation mode with small tidal volume (8 ml/kg) and positive end-expiratory pressure (PEEP) of 6 cm H(2)O [1 cm H(2)O = 0.098 kPa] was conducted. Each patient underwent recruitment maneuver in supine position and then in prone position [PEEP 20 cm H(2)O+pressure control (PC) 20 cm H(2)O]. Heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation [SpO(2)] and blood gas analysis data were recorded before and after recruitment maneuver in either position. A double-lumen venous catheter was inserted into internal jugular vein or subclavian vein, and a pulse index contour cardiac output (PiCCO) catheter was introduced into femoral artery. Cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index (SVRI), intra-thoracic blood volume index (ITBVI), extra vascular lung water index (EVLWI), global end-diastolic volume index (GEDVI), global ejection fraction (GEF), stroke volume variation (SVV) and central vein pressure (CVP) were monitored. (1) Compared with data before recruitment maneuver, there were no significant differences in HR and MAP after supine position and prone position recruitment maneuver, but significant differences in SpO(2) were found between before and after recruitment maneuver when patients' position was changed (supine position: 0.954 ± 0.032 vs. 0.917 ± 0.025, P recruitment maneuver (P recruitment maneuver, CI [L×min(-1)×m(-2)], SVI (ml/m(2)), GEDVI (ml/m(2)) and GEF were decreased significantly during recruitment maneuver (supine position: CI 3.2 ± 0.4 vs. 3.8 ± 0.6, SVI 32.4 ± 5.6 vs. 38.8 ± 6.5, GEDVI 689 ± 44 vs. 766 ± 32, GEF 0.267 ± 0

E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor

International Nuclear Information System (INIS)

Jenei, Veronika; Andersson, Tommy; Jakus, Judit; Dib, Karim

2005-01-01

E3B1, a human homologue of the mouse gene product Abi-1, has been implicated in growth-factor-mediated regulation of the small GTPases p21 Ras and Rac. E3b1 is a regulator of Rac because it can form a complex with Sos-1 and eps8, and such a Sos-1-e3B1-eps8 complex serves as a guanine nucleotide exchange factor for Rac. In the present study, we found that overexpression of e3B1 in NIH3T3/EGFR cells sensitized EGF-induced activation of Rac1, whereas it had no impact on EGF-induced activation of p21 Ras . Remarkably, we found that EGF-induced activation of the p21 Ras -related GTPase Rap1 was also sensitized in NIH3T3/EGFR-e3B1 cells. Thus, in NIH3T3/EGFR-e3B1 cells, maximal EGF-induced activation of Rap1 occurs with a dose of EGF much lower than in NIH3T3/EGFR cells. We also report that overexpression of e3B1 in NIH3T3/EGFR cells renders EGF-induced activation of Rap1 completely dependent on Src tyrosine kinases but not on c-Abl. However, EGF-induced tyrosine phosphorylation of the Rap GEF C3G occurred regardless of whether e3B1 was overexpressed or not, and this did not involve Src tyrosine kinases. Accordingly, we propose that overexpression of e3B1 in NIH3T3/EGFR cells leads to mobilization of Src tyrosine kinases that participate in EGF-induced activation of Rap1 and inhibition of cell proliferation

Hochaufgelöste Magnetresonanz-Bildgebung der Mäuseaorta zur Bestimmung der Dynamik funktioneller Parameter durch Laufrad-Training bei ApoE-Knock-Out-Mäusen

OpenAIRE

Offenberger, Wolfgang

2009-01-01

Einführung: Atherosklerose ist eine führende Ursache von Morbidität und Mortalität weltweit. Die ApoE-Knock-Out-Maus (ApoE-/-) ist das wichtigste Tiermodell für das Studium der Atherosklerose und von Interventionen auf diese Erkrankung. Mittels hochaufgelöster Magnet-Resonanz-Bildgebung ist es möglich, eine nicht-invasive in-vivo Gefäß-Charakterisierung bei Mäusen durchzuführen. In dieser Arbeit wurden die Auswirkungen von Sport auf die Gefäßfunktion der Aorta ascendens und abdominalis bei Ap...

In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains.

Science.gov (United States)

Côté, Jean-François; Vuori, Kristiina

2006-01-01

Rho family GTPases regulate a large variety of biological processes, including the reorganization of the actin cytoskeleton. Like other members of the Ras superfamily of small GTP-binding proteins, Rho GTPases cycle between a GDP-bound (inactive) and a GTP-bound (active) state, and, when active, the GTPases relay extracellular signals to a large number of downstream effectors. Guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP on Rho GTPases, thereby activating them. Most Rho-GEFs mediate their effects through their signature domain known as the Dbl Homology-Pleckstrin Homology (DH-PH) module. Recently, we and others identified a family of evolutionarily conserved, DOCK180-related proteins that also display GEF activity toward Rho GTPases. The DOCK180-family of proteins lacks the canonical DH-PH module. Instead, they rely on a novel domain, termed DHR-2, DOCKER, or CZH2, to exchange GDP for GTP on Rho targets. In this chapter, the experimental approach that we used to uncover the exchange activity of the DHR-2 domain of DOCK180-related proteins will be described.

GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5·Vps9 system.

Science.gov (United States)

Uejima, Tamami; Ihara, Kentaro; Goh, Tatsuaki; Ito, Emi; Sunada, Mariko; Ueda, Takashi; Nakano, Akihiko; Wakatsuki, Soichi

2010-11-19

Many GTPases regulate intracellular transport and signaling in eukaryotes. Guanine nucleotide exchange factors (GEFs) activate GTPases by catalyzing the exchange of their GDP for GTP. Here we present crystallographic and biochemical studies of a GEF reaction with four crystal structures of Arabidopsis thaliana ARA7, a plant homolog of Rab5 GTPase, in complex with its GEF, VPS9a, in the nucleotide-free and GDP-bound forms, as well as a complex with aminophosphonic acid-guanylate ester and ARA7·VPS9a(D185N) with GDP. Upon complex formation with ARA7, VPS9 wedges into the interswitch region of ARA7, inhibiting the coordination of Mg(2+) and decreasing the stability of GDP binding. The aspartate finger of VPS9a recognizes GDP β-phosphate directly and pulls the P-loop lysine of ARA7 away from GDP β-phosphate toward switch II to further destabilize GDP for its release during the transition from the GDP-bound to nucleotide-free intermediates in the nucleotide exchange reaction.

T1R3 homomeric sweet taste receptor regulates adipogenesis through Gαs-mediated microtubules disassembly and Rho activation in 3T3-L1 cells.

Directory of Open Access Journals (Sweden)

Yosuke Masubuchi

Full Text Available We previously reported that 3T3-L1 cells express a functional sweet taste receptor possibly as a T1R3 homomer that is coupled to Gs and negatively regulates adipogenesis by a Gαs-mediated but cAMP-independent mechanism. Here, we show that stimulation of this receptor with sucralose or saccharin induced disassembly of the microtubules in 3T3-L1 preadipocytes, which was attenuated by overexpression of the dominant-negative mutant of Gαs (Gαs-G226A. In contrast, overexpression of the constitutively active mutant of Gαs (Gαs-Q227L as well as treatment with cholera toxin or isoproterenol but not with forskolin caused disassembly of the microtubules. Sweetener-induced microtubule disassembly was accompanied by activation of RhoA and Rho-associated kinase (ROCK. This was attenuated with by knockdown of GEF-H1, a microtubule-localized guanine nucleotide exchange factor for Rho GTPase. Furthermore, overexpression of the dominant-negative mutant of RhoA (RhoA-T19N blocked sweetener-induced dephosphorylation of Akt and repression of PPARγ and C/EBPα in the early phase of adipogenic differentiation. These results suggest that the T1R3 homomeric sweet taste receptor negatively regulates adipogenesis through Gαs-mediated microtubule disassembly and consequent activation of the Rho/ROCK pathway.

The UNDP/GEF Baltic wind atlas

DEFF Research Database (Denmark)

Rathmann, O.

2003-01-01

based on 7 stations in the coastal area: the 3 Lithuanian sites Kretinga, Vilkyciai and Taurage; the Latvian site Särnate; and the 3 Estonian sites Prangli, Virtsu and Uulu. In addition, private data measured at theEstonian site Türisalu was made available to the project. Although the campaign...... was running for about two years it was only possible to get one full one-year data series for each site with start time ranging from primo May 2001 to primo October 2001. Themeasured data have been analysed according to the “Wind Atlas Method”, implying cleansing the wind data for nearby terrain effects......-institute stations with long-term records as well as datafor the short-term measurement period of the present campaign. Similarly, inter-comparison techniques were used to adjust for data fall-out for longer unbroken periods. The data from this project have been supplemented by in-land data from measuringstations...

Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors

Energy Technology Data Exchange (ETDEWEB)

Malaby, Andrew W.; Das, Sanchaita; Chakravarthy, Srinivas; Irving, Thomas C.; Bilsel, Osman; Lambright, David G.

2018-01-01

Membrane dynamic processes including vesicle biogenesis depend on Arf guanosine triphosphatase (GTPase) activation by guanine nucleotide exchange factors (GEFs) containing a catalytic Sec7 domain and a membrane-targeting module such as a pleckstrin homology (PH) domain. The catalytic output of cytohesin family Arf GEFs is controlled by autoinhibitory interactions that impede accessibility of the exchange site in the Sec7 domain. These restraints can be relieved through activator Arf-GTP binding to an allosteric site comprising the PH domain and proximal autoinhibitory elements (Sec7-PH linker and C-terminal helix). Small-angle X-ray scattering and negative-stain electron microscopy were used to investigate the structural organization and conformational dynamics of cytohesin-3 (Grp1) in autoinhibited and active states. The results support a model in which hinge dynamics in the autoinhibited state expose the activator site for Arf-GTP binding, while subsequent C-terminal helix unlatching and repositioning unleash conformational entropy in the Sec7-PH linker to drive exposure of the exchange site.

Identification of a negative regulatory region for the exchange activity and characterization of T332I mutant of Rho guanine nucleotide exchange factor 10 (ARHGEF10).

Science.gov (United States)

Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu

2011-08-26

The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1-332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant.

Identification of a Negative Regulatory Region for the Exchange Activity and Characterization of T332I Mutant of Rho Guanine Nucleotide Exchange Factor 10 (ARHGEF10)*

Science.gov (United States)

Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu

2011-01-01

The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1–332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant. PMID:21719701

Saccharomyces cerevisiae GTPase complex: Gtr1p-Gtr2p regulates cell-proliferation through Saccharomyces cerevisiae Ran-binding protein, Yrb2p

International Nuclear Information System (INIS)

Wang Yonggang; Nakashima, Nobutaka; Sekiguchi, Takeshi; Nishimoto, Takeharu

2005-01-01

A Gtr1p GTPase, the GDP mutant of which suppresses both temperature-sensitive mutants of Saccharomyces cerevisiae RanGEF/Prp20p and RanGAP/Rna1p, was presently found to interact with Yrb2p, the S. cerevisiae homologue of mammalian Ran-binding protein 3. Gtr1p bound the Ran-binding domain of Yrb2p. In contrast, Gtr2p, a partner of Gtr1p, did not bind Yrb2p, although it bound Gtr1p. A triple mutant: yrb2Δ gtr1Δ gtr2Δ was lethal, while a double mutant: gtr1Δ gtr2Δ survived well, indicating that Yrb2p protected cells from the killing effect of gtr1Δ gtr2Δ. Recombinant Gtr1p and Gtr2p were purified as a complex from Escherichia coli. The resulting Gtr1p-Gtr2p complex was comprised of an equal amount of Gtr1p and Gtr2p, which inhibited the Rna1p/Yrb2 dependent RanGAP activity. Thus, the Gtr1p-Gtr2p cycle was suggested to regulate the Ran cycle through Yrb2p

Phosphorylation of Rac1 T108 by Extracellular Signal-Regulated Kinase in Response to Epidermal Growth Factor: a Novel Mechanism To Regulate Rac1 Function

Science.gov (United States)

Tong, Junfeng; Li, Laiji; Ballermann, Barbara

2013-01-01

Accumulating evidence has implicated Rho GTPases, including Rac1, in many aspects of cancer development. Recent findings suggest that phosphorylation might further contribute to the tight regulation of Rho GTPases. Interestingly, sequence analysis of Rac1 shows that Rac1 T108 within the 106PNTP109 motif is likely an extracellular signal-regulated kinase (ERK) phosphorylation site and that Rac1 also has an ERK docking site, 183KKRKRKCLLL192 (D site), at the C terminus. Indeed, we show here that both transfected and endogenous Rac1 interacts with ERK and that this interaction is mediated by its D site. Green fluorescent protein (GFP)-Rac1 is threonine (T) phosphorylated in response to epidermal growth factor (EGF), and EGF-induced Rac1 threonine phosphorylation is dependent on the activation of ERK. Moreover, mutant Rac1 with the mutation of T108 to alanine (A) is not threonine phosphorylated in response to EGF. In vitro ERK kinase assay further shows that pure active ERK phosphorylates purified Rac1 but not mutant Rac1 T108A. We also show that Rac1 T108 phosphorylation decreases Rac1 activity, partially due to inhibiting its interaction with phospholipase C-γ1 (PLC-γ1). T108 phosphorylation targets Rac1 to the nucleus, which isolates Rac1 from other guanine nucleotide exchange factors (GEFs) and hinders Rac1's role in cell migration. We conclude that Rac1 T108 is phosphorylated by ERK in response to EGF, which plays an important role in regulating Rac1. PMID:24043306

Thermoelectrical properties of the compounds ScM{sup VIII}Sb and YM{sup VIII}Sb (M{sup VIII} = Ni, Pd, Pt)

Energy Technology Data Exchange (ETDEWEB)

Oestreich, J; Probst, U; Richardt, F; Bucher, E [University of Konstanz, PO Box X916, D-78457 Konstanz (Germany)

2003-02-05

The research into new materials with good thermoelectric properties has revealed new compounds consisting of metallic elements (Bando Y, Suemitsu T, Takagi K, Tokushima H, Echizen Y, Katoh K, Umeo K, Maeda Y and Takabatake T 2000 J. Alloys Compounds 313 1-6, Ghelani N, Loo S, Chung D, Sportouch S, Nardi S, Kanatzidis M, Hogan T and Nolas G 2000 Mater. Res. Soc. 626 Z8.6.1). The half-Heusler compound ZrNiSn, in particular, shows promising thermoelectric properties and has been studied by many scientists during recent years (Uher C, Hu S, Yang J, Meisner G P and Morelli D T 1997 Proc. ICT'97: 16th Int. Conf. on Thermoelectrics pp 485-8, Romaka L P, Stadnyk Yu V, Goryn A M, Gorelenko Yu K and Skolozdra R V 1997 Proc. ICT'97: 16th Int. Conf. on Thermoelectrics pp 516-19, Hohl H, Ramirez A P, Goldmann C, Ernst G, Woelfing B and Bucher E 1998 J. Phys.: Condens. Matter 11 1697-709, Oestreich J, Kaefer W, Richardt F, Probst U and Bucher E 1999 Proc. 5th European Workshop on Thermoelectrics pp 192-5). In an effort to find new thermoelectric materials, the half-Heusler compounds of the groups ScM{sup VIII}Sb and YM{sup VIII}Sb (M{sup VIII} = Ni, Pd, Pt) were synthesized by arc melting and the thermoelectric properties were examined by standard characterization methods. Doping experiments showed that it is possible to change the electrical properties of the compounds while retaining the half-Heusler structure. Within the two groups, YPtSb showed the best thermoelectrical properties. At a temperature of 400 K the electrical conductivity of YPtSb is 748{omega}{sup -1} cm{sup -1} and the Seebeck coefficient is 116.3{mu}V K{sup -1}. The thermal conductivity at 400 K extrapolated using the Wiedemann-Franz law is 2.87 W K{sup -1} m{sup -1}. This leads to a dimensionless figure of merit of 0.14.

Sensorik für Fahrzeugrundumsicht

Science.gov (United States)

Knoll, Peter

Mit einer elektronischen Rundumsicht lassen sich zahlreiche Fahrerassistenzsysteme realisieren. Das "sehende“ Auto nimmt mithilfe von Sensoren das Fahrzeugumfeld wahr, interpretiert es, erkennt frühzeitig gefährliche Situationen, unterstützt den Fahrer und greift zukünftig immer heftiger selbsttätig in Fahrmanöver ein. Je nach Aufgabe und Anforderungen kommen verschiedene Sensoren zum Einsatz (Bild 1).

Comparative studies on the human serum albumin binding of the clinically approved EGFR inhibitors gefitinib, erlotinib, afatinib, osimertinib and the investigational inhibitor KP2187.

Science.gov (United States)

Dömötör, Orsolya; Pelivan, Karla; Borics, Attila; Keppler, Bernhard K; Kowol, Christian R; Enyedy, Éva A

2018-05-30

Binding interactions between human serum albumin (HSA) and four approved epidermal growth factor receptor (EGFR) inhibitors gefitinib (GEF), erlotinib (ERL), afatinib (AFA), osimertinib (OSI), as well as the experimental drug KP2187, were investigated by means of spectrofluorometric and molecular modelling methods. Steady-state and time resolved spectrofluorometric techniques were carried out, including direct quenching of protein fluorescence and site marker displacement measurements. Proton dissociation processes and solvent dependent fluorescence properties were investigated as well. The EGFR inhibitors were predominantly presented in their single protonated form (HL + ) at physiological pH except ERL, which is charge-neutral. Significant solvent dependent fluorescence properties were found for GEF, ERL and KP2187, namely their emission spectra show strong dependence on the polarity and the hydrogen bonding ability of the solvents. The inhibitors proved to be bound at site I of HSA (in subdomain IIA) in a weak-to-moderate fashion (logK' 3.9-4.9) using spectrofluorometry. OSI (logK' 4.3) and KP2187 can additionally bind in site II (in subdomain IIIA), while GEF, ERL and AFA clearly show no interaction here. Docking methods qualitatively confirmed binding site preferences of compounds GEF and KP2187, and indicated that they probably bind to HSA in their neutral forms. Binding constants calculated on the basis of the various experimental data indicate a weak-to-moderate binding on HSA, only OSI exhibits somewhat higher affinity towards this protein. However, model calculations performed at physiological blood concentrations of HSA resulted in high (ca. 90%) bound fractions for the inhibitors, highlighting the importance of plasma protein binding. Copyright © 2018 Elsevier B.V. All rights reserved.

Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13.

Science.gov (United States)

Scherer, Stephanie L; Cain, Matthew D; Kanai, Stanley M; Kaltenbronn, Kevin M; Blumer, Kendall J

2017-06-16

The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ 5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G i/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G i/o signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα 13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα 13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα 13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα 13 ·R7-RGS complexes. Because Gα 13 /R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ 5 with or without R7BP. We found that neurite retraction evoked by Gα 12/13 -dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα 12/13 but not Gα i/o These findings provide the first evidence that R7-RGS heterotrimers interact with Gα 13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by

Single-molecule tracking of small GTPase Rac1 uncovers spatial regulation of membrane translocation and mechanism for polarized signaling

Science.gov (United States)

Das, Sulagna; Yin, Taofei; Yang, Qingfen; Zhang, Jingqiao; Wu, Yi I.; Yu, Ji

2015-01-01

Polarized Rac1 signaling is a hallmark of many cellular functions, including cell adhesion, motility, and cell division. The two steps of Rac1 activation are its translocation to the plasma membrane and the exchange of nucleotide from GDP to GTP. It is, however, unclear whether these two processes are regulated independent of each other and what their respective roles are in polarization of Rac1 signaling. We designed a single-particle tracking (SPT) method to quantitatively analyze the kinetics of Rac1 membrane translocation in living cells. We found that the rate of Rac1 translocation was significantly elevated in protrusions during cell spreading on collagen. Furthermore, combining FRET sensor imaging with SPT measurements in the same cell, the recruitment of Rac1 was found to be polarized to an extent similar to that of the nucleotide exchange process. Statistical analysis of single-molecule trajectories and optogenetic manipulation of membrane lipids revealed that Rac1 membrane translocation precedes nucleotide exchange, and is governed primarily by interactions with phospholipids, particularly PI(3,4,5)P3, instead of protein factors. Overall, the study highlights the significance of membrane translocation in spatial Rac1 signaling, which is in addition to the traditional view focusing primarily on GEF distribution and exchange reaction. PMID:25561548

ARF6 Activated by the LHCG Receptor through the Cytohesin Family of Guanine Nucleotide Exchange Factors Mediates the Receptor Internalization and Signaling*

Science.gov (United States)

Kanamarlapudi, Venkateswarlu; Thompson, Aiysha; Kelly, Eamonn; López Bernal, Andrés

2012-01-01

The luteinizing hormone chorionic gonadotropin receptor (LHCGR) is a Gs-coupled GPCR that is essential for the maturation and function of the ovary and testis. LHCGR is internalized following its activation, which regulates the biological responsiveness of the receptor. Previous studies indicated that ADP-ribosylation factor (ARF)6 and its GTP-exchange factor (GEF) cytohesin 2 regulate LHCGR internalization in follicular membranes. However, the mechanisms by which ARF6 and cytohesin 2 regulate LHCGR internalization remain incompletely understood. Here we investigated the role of the ARF6 signaling pathway in the internalization of heterologously expressed human LHCGR (HLHCGR) in intact cells using a combination of pharmacological inhibitors, siRNA and the expression of mutant proteins. We found that human CG (HCG)-induced HLHCGR internalization, cAMP accumulation and ARF6 activation were inhibited by Gallein (βγ inhibitor), Wortmannin (PI 3-kinase inhibitor), SecinH3 (cytohesin ARF GEF inhibitor), QS11 (an ARF GAP inhibitor), an ARF6 inhibitory peptide and ARF6 siRNA. However, Dynasore (dynamin inhibitor), the dominant negative mutants of NM23-H1 (dynamin activator) and clathrin, and PBP10 (PtdIns 4,5-P2-binding peptide) inhibited agonist-induced HLHCGR and cAMP accumulation but not ARF6 activation. These results indicate that heterotrimeric G-protein, phosphatidylinositol (PI) 3-kinase (PI3K), cytohesin ARF GEF and ARF GAP function upstream of ARF6 whereas dynamin and clathrin act downstream of ARF6 in the regulation of HCG-induced HLHCGR internalization and signaling. In conclusion, we have identified the components and molecular details of the ARF6 signaling pathway required for agonist-induced HLHCGR internalization. PMID:22523074

GHG emissions from primary aluminum production in China: Regional disparity and policy implications

International Nuclear Information System (INIS)

Hao, Han; Geng, Yong; Hang, Wen

2016-01-01

Highlights: • GHG emissions from primary aluminum production in China were accounted. • The impact of regional disparity of power generation was considered for this study. • GHG emissions factor of China’s primary aluminum production was 16.5 t CO_2e/t Al ingot in 2013. • Total GHG emissions from China’s primary aluminum production were 421 mt CO_2e in 2013. - Abstract: China is the world-leading primary aluminum production country, which contributed to over half of global production in 2014. Primary aluminum production is power-intensive, for which power generation has substantial impact on overall Greenhouse Gas (GHG) emissions. In this study, we explore the impact of regional disparity of China’s power generation system on GHG emissions for the sector of primary aluminum production. Our analysis reveals that the national GHG emissions factor (GEF) of China’s primary aluminum production was 16.5 t CO_2e/t Al ingot in 2013, with province-level GEFs ranging from 8.2 to 21.7 t CO_2e/t Al ingot. There is a high coincidence of provinces with high aluminum productions and high GEFs. Total GHG emissions from China’s primary aluminum production were 421 mt CO_2e in 2013, approximately accounting for 4% of China’s total GHG emissions. Under the 2020 scenario, GEF shows a 13.2% reduction compared to the 2013 level, but total GHG emissions will increase to 551 mt CO_2e. Based on our analysis, we recommend that the government should further promote energy efficiency improvement, facilitate aluminum industry redistribution with low-carbon consideration, promote secondary aluminum production, and improve aluminum industry data reporting and disclosure.

Science of Integrated Approaches to Natural Resources Management

Science.gov (United States)

Tengberg, Anna; Valencia, Sandra

2017-04-01

To meet multiple environmental objectives, integrated programming is becoming increasingly important for the Global Environmental Facility (GEF), the financial mechanism of the multilateral environmental agreements, including the United Nations Convention to Combat Desertification (UNCCD). Integration of multiple environmental, social and economic objectives also contributes to the achievement of the Sustainable Development Goals (SDGs) in a timely and cost-effective way. However, integration is often not well defined. This paper therefore focuses on identifying key aspects of integration and assessing their implementation in natural resources management (NRM) projects. To that end, we draw on systems thinking literature, and carry out an analysis of a random sample of GEF integrated projects and in-depth case studies demonstrating lessons learned and good practices in addressing land degradation and other NRM challenges. We identify numerous challenges and opportunities of integrated approaches that need to be addressed in order to maximise the catalytic impact of the GEF during problem diagnosis, project design, implementation and governance. We highlight the need for projects to identify clearer system boundaries and main feedback mechanisms within those boundaries, in order to effectively address drivers of environmental change. We propose a theory of change for Integrated Natural Resources Management (INRM) projects, where short-term environmental and socio-economic benefits will first accrue at the local level. Implementation of improved INRM technologies and practices at the local level can be extended through spatial planning, strengthening of innovation systems, and financing and incentive mechanisms at the watershed and/or landscape/seascape level to sustain and enhance ecosystem services at larger scales and longer time spans. We conclude that the evolving scientific understanding of factors influencing social, technical and institutional innovations and

Climate change and the World Bank: opportunity for global governance?

International Nuclear Information System (INIS)

Boehmer-Christiansen, S.A.

1999-01-01

The direct and indirect efforts of the World Bank and its off-spring, the Global Environment Facility (GEF), to become leading international agents of global environmental 'governance' and 'sustainable development' are described and analysed politically with reference to the development of an implementation regime of the Framework Convention on Climate Change (FCCC). The Bank/GEF are seen as engaging in a potentially dangerous experiment of 'global ecological modernisation', or industrial transformation, in 'emerging economies', an experiment legitimised by reference to the catastrophic threat of man-made 'global warming'. This threat is already being translated into political, commercial and bureaucratic benefits accruing to a small global elite. How was this achieved and what are the likely political implications? (author)

Interplay between Solo and keratin filaments is crucial for mechanical force–induced stress fiber reinforcement

Science.gov (United States)

Fujiwara, Sachiko; Ohashi, Kazumasa; Mashiko, Toshiya; Kondo, Hiroshi; Mizuno, Kensaku

2016-01-01

Mechanical force–induced cytoskeletal reorganization is essential for cell and tissue remodeling and homeostasis; however, the underlying cellular mechanisms remain elusive. Solo (ARHGEF40) is a RhoA-targeting guanine nucleotide exchange factor (GEF) involved in cyclical stretch–induced human endothelial cell reorientation and convergent extension cell movement in zebrafish gastrula. In this study, we show that Solo binds to keratin-8/keratin-18 (K8/K18) intermediate filaments through multiple sites. Solo overexpression promotes the formation of thick actin stress fibers and keratin bundles, whereas knockdown of Solo, expression of a GEF-inactive mutant of Solo, or inhibition of ROCK suppresses stress fiber formation and leads to disorganized keratin networks, indicating that the Solo-RhoA-ROCK pathway serves to precisely organize keratin networks, as well as to promote stress fibers. Of importance, knockdown of Solo or K18 or overexpression of GEF-inactive or deletion mutants of Solo suppresses tensile force–induced stress fiber reinforcement. Furthermore, knockdown of Solo or K18 suppresses tensile force-induced RhoA activation. These results strongly suggest that the interplay between Solo and K8/K18 filaments plays a crucial role in tensile force–induced RhoA activation and consequent actin cytoskeletal reinforcement. PMID:26823019

Leapfrogging over development? Promoting rural renewables for climate change mitigation

Energy Technology Data Exchange (ETDEWEB)

Zerriffi, Hisham [Liu Institute for Global Issues, 6476 NW Marine Dr., University of British Columbia, Vancouver BC (Canada); Wilson, Elizabeth [Hubert Humphrey Institute of Public Affairs, University of Minnesota, Minneapolis MN (United States)

2010-04-15

Renewable energy technologies have the potential to help solve two pressing problems. On one hand, carbon-free energy sources must play a role in climate change mitigation. On the other hand, renewables might help meet needs of rural people without access to modern energy services. However, if renewables are deployed to combat climate change (primarily resulting from emissions in the developed economies) then providing basic energy services in the developing world may be compromised. The tendency to conflate the two drivers by installing renewables in rural areas for carbon mitigation reasons rather than for development reasons could compromise both goals. The danger is supporting sub-optimal policies for mitigating carbon and for rural energy. This is problematic given the limited funds available for energy development and reducing greenhouse gases. This paper analyzes how these goals have been balanced by the Global Environment Facility (GEF). Project documents are used to determine whether incremental costs of installing renewables were covered by GEF funds and whether the costs are comparable with other carbon mitigation options. The results raise concerns about the effectiveness and appropriateness of GEF funding of such projects and highlight the importance of post-Kyoto framework design to reduce emissions and promote development. (author)

Impact of Clipping versus Coiling on Postoperative Hemodynamics and Pulmonary Edema after Subarachnoid Hemorrhage

Directory of Open Access Journals (Sweden)

Nobutaka Horie

2014-01-01

Full Text Available Volume management is critical for assessment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH. This multicenter prospective cohort study compared the impact of surgical clipping versus endovascular coiling on postoperative hemodynamics and pulmonary edema in patients with SAH. Hemodynamic parameters were measured for 14 days using a transpulmonary thermodilution system. The study included 202 patients, including 160 who underwent clipping and 42 who underwent coiling. There were no differences in global ejection fraction (GEF, cardiac index, systemic vascular resistance index, or global end-diastolic volume index between the clipping and coiling groups in the early period. However, extravascular lung water index (EVLWI and pulmonary vascular permeability index (PVPI were significantly higher in the clipping group in the vasospasm period. Postoperative C-reactive protein (CRP level was higher in the clipping group and was significantly correlated with postoperative brain natriuretic peptide level. Multivariate analysis found that PVPI and GEF were independently associated with high EVLWI in the early period, suggesting cardiogenic edema, and that CRP and PVPI, but not GEF, were independently associated with high EVLWI in the vasospasm period, suggesting noncardiogenic edema. In conclusion, clipping affects postoperative CRP level and may thereby increase noncardiogenic pulmonary edema in the vasospasm period. His trial is registered with University Hospital Medical Information Network UMIN000003794.

Leapfrogging over development? Promoting rural renewables for climate change mitigation

International Nuclear Information System (INIS)

Zerriffi, Hisham; Wilson, Elizabeth

2010-01-01

Renewable energy technologies have the potential to help solve two pressing problems. On one hand, carbon-free energy sources must play a role in climate change mitigation. On the other hand, renewables might help meet needs of rural people without access to modern energy services. However, if renewables are deployed to combat climate change (primarily resulting from emissions in the developed economies) then providing basic energy services in the developing world may be compromised. The tendency to conflate the two drivers by installing renewables in rural areas for carbon mitigation reasons rather than for development reasons could compromise both goals. The danger is supporting sub-optimal policies for mitigating carbon and for rural energy. This is problematic given the limited funds available for energy development and reducing greenhouse gases. This paper analyzes how these goals have been balanced by the Global Environment Facility (GEF). Project documents are used to determine whether incremental costs of installing renewables were covered by GEF funds and whether the costs are comparable with other carbon mitigation options. The results raise concerns about the effectiveness and appropriateness of GEF funding of such projects and highlight the importance of post-Kyoto framework design to reduce emissions and promote development.

e-Infrastructures Austria 2016: Bericht über das dritte Jahr des Hochschulraumstrukturmittelprojekts für den koordinierten Aufbau und die kooperative Weiterentwicklung von Repositorieninfrastrukturen

Directory of Open Access Journals (Sweden)

Bruno Bauer

2017-05-01

Full Text Available Im letzten Jahr des vom Bundesministerium für Wissenschaft, Forschung und Wirtschaft auf drei Jahre geförderten HRSM-Projektes e-Infrastructures Austria konnten die drei Teilprojekte erfolgreich zu Ende geführt werden. An 25 Partnereinrichtungen wurden als In-Kind-Leistungen Repositorien aufgebaut bzw. sind derzeit in Planung. 2016 wurde von einer ExperInnengruppe eine Muster-Policy für Forschungsdatenmanagement; an einzelnen der Partnereinrichtungen wurden Forschungsdatenmanagementpläne erprobt. Das Ziel, Fortbildung und Vernetzung für Forschungsdatenmanagement zu ermöglichen, wurde im Berichtsjahr in Form von Workshops zu den Themen Metadaten und Langzeitarchivierung und insbesondere durch ein viertätiges Seminar für den professionellen Umgang mit Forschungsdaten erfolgreich umgesetzt. Es ist sehr erfreulich, dass mit dem Projektende von e-Infrastructures Austria das Thema Forschungsdatenmanagement nicht wieder aus dem Blickfeld der Universitäten und Forschungseinrichtungen geraten wird, sondern vielmehr – in mehreren Projekten – dieses Thema ab 2017 weiterentwickelt wird. Neben dem Folgeprojekt e-Infrastructures Austria Plus, an dem sich neun Institutionen beteiligen werden, widmen sich noch acht weitere öffentlich geförderte Projekte dem Thema Open Science. Gemeinsam bilden sie den Use Case Austria im Rahmen der European Open Science Cloud.

Biochemical characterization of a heterotrimeric G(i)-protein activator peptide designed from the junction between the intracellular third loop and sixth transmembrane helix in the m4 muscarinic acetylcholine receptor.

Science.gov (United States)

Terawaki, Shin-ichi; Matsubayashi, Rina; Hara, Kanako; Onozuka, Tatsuki; Kohno, Toshiyuki; Wakamatsu, Kaori

Muscarinic acetylcholine receptors (mAChRs) are G-protein coupled receptors (GPCRs) that are activated by acetylcholine released from parasympathetic nerves. The mAChR family comprises 5 subtypes, m1-m5, each of which has a different coupling selectivity for heterotrimeric GTP-binding proteins (G-proteins). m4 mAChR specifically activates the Gi/o family by enhancing the guanine nucleotide exchange factor (GEF) reaction with the Gα subunit through an interaction that occurs via intracellular segments. Here, we report that the m4 mAChR mimetic peptide m4i3c(14)Gly, comprising 14 residues in the junction between the intracellular third loop (i3c) and transmembrane helix VI (TM-VI) extended with a C-terminal glycine residue, presents GEF activity toward the Gi1 α subunit (Gαi1). The m4i3c(14)Gly forms a stable complex with guanine nucleotide-free Gαi1 via three residues in the VTI(L/F) motif, which is conserved within the m2/4 mAChRs. These results suggest that this m4 mAChR mimetic peptide, which comprises the amino acid of the mAChR intracellular segments, is a useful tool for understanding the interaction between GPCRs and G-proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

GEF climate change operational strategy: Whither UNDP?

Energy Technology Data Exchange (ETDEWEB)

Hosier, R.

1996-12-31

The paper discusses aspects of the implementation of the program for climatic change which has been come about as part of the U.N. Framework Convention on Climate Change. Initial effort has focused on providing strategic information and help to countries, on achieving offsets in greenhouse gas emissions by energy conservation or carbon sinking, and an emphasis on development of renewable energy supplies. The U.N. Development Agency has limited funding to help support startup on projects submitted. Specific examples are discussed in the areas of energy conservation and energy efficiency, adoption of renewable energy sources, and reducing the long-term costs of low greenhouse gas-emitting energy technologies.

A bacterial cytotoxin identifies the RhoA exchange factor Net1 as a key effector in the response to DNA damage.

Directory of Open Access Journals (Sweden)

Lina Guerra

Full Text Available BACKGROUND: Exposure of adherent cells to DNA damaging agents, such as the bacterial cytolethal distending toxin (CDT or ionizing radiations (IR, activates the small GTPase RhoA, which promotes the formation of actin stress fibers and delays cell death. The signalling intermediates that regulate RhoA activation and promote cell survival are unknown. PRINCIPAL FINDINGS: We demonstrate that the nuclear RhoA-specific Guanine nucleotide Exchange Factor (GEF Net1 becomes dephosphorylated at a critical inhibitory site in cells exposed to CDT or IR. Expression of a dominant negative Net1 or Net1 knock down by iRNA prevented RhoA activation, inhibited the formation of stress fibers, and enhanced cell death, indicating that Net1 activation is required for this RhoA-mediated responses to genotoxic stress. The Net1 and RhoA-dependent signals involved activation of the Mitogen-Activated Protein Kinase p38 and its downstream target MAPK-activated protein kinase 2. SIGNIFICANCE: Our data highlight the importance of Net1 in controlling RhoA and p38 MAPK mediated cell survival in cells exposed to DNA damaging agents and illustrate a molecular pathway whereby chronic exposure to a bacterial toxin may promote genomic instability.

Apical accumulation of the Sevenless receptor tyrosine kinase during Drosophila eye development is promoted by the small GTPase Rap1.

Science.gov (United States)

Baril, Caroline; Lefrançois, Martin; Sahmi, Malha; Knævelsrud, Helene; Therrien, Marc

2014-08-01

The Ras/MAPK-signaling pathway plays pivotal roles during development of metazoans by controlling cell proliferation and cell differentiation elicited, in several instances, by receptor tyrosine kinases (RTKs). While the internal mechanism of RTK-driven Ras/MAPK signaling is well understood, far less is known regarding its interplay with other co-required signaling events involved in developmental decisions. In a genetic screen designed to identify new regulators of RTK/Ras/MAPK signaling during Drosophila eye development, we identified the small GTPase Rap1, PDZ-GEF, and Canoe as components contributing to Ras/MAPK-mediated R7 cell differentiation. Rap1 signaling has recently been found to participate in assembling cadherin-based adherens junctions in various fly epithelial tissues. Here, we show that Rap1 activity is required for the integrity of the apical domains of developing photoreceptor cells and that reduced Rap1 signaling hampers the apical accumulation of the Sevenless RTK in presumptive R7 cells. It thus appears that, in addition to its role in cell-cell adhesion, Rap1 signaling controls the partitioning of the epithelial cell membrane, which in turn influences signaling events that rely on apico-basal cell polarity. Copyright © 2014 by the Genetics Society of America.

Analytische Geometrie

Science.gov (United States)

Kemnitz, Arnfried

Der Grundgedanke der Analytischen Geometrie besteht darin, dass geometrische Untersuchungen mit rechnerischen Mitteln geführt werden. Geometrische Objekte werden dabei durch Gleichungen beschrieben und mit algebraischen Methoden untersucht.

Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

Science.gov (United States)

Patel, Uday B; Taylor, Fiona; Blomqvist, Lennart; George, Christopher; Evans, Hywel; Tekkis, Paris; Quirke, Philip; Sebag-Montefiore, David; Moran, Brendan; Heald, Richard; Guthrie, Ashley; Bees, Nicola; Swift, Ian; Pennert, Kjell; Brown, Gina

2011-10-01

To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

Investing in efficient industrial boiler systems in China and Vietnam

International Nuclear Information System (INIS)

Yang Ming; Dixon, Robert K.

2012-01-01

Energy efficiency in industrial boiler steam systems can be very low due to old technologies, improper design and non-optimal operation of the steam systems. Solutions include efficiency assessments and investments in steam system optimizations, education and training for operators of the systems. This paper presents case studies on assessing and investing in boiler steam systems in China and Vietnam. Methodologies and approaches for data collection and analyses were designed specifically for each of the two countries. This paper concludes: (1) investing in energy efficiency in industrial boiler steam system in China and Vietnam are cost effective; (2) government should not sent national energy efficiency standards lower than that of energy companies or energy equipment manufactures. - Highlights: ► GEF successfully catalyzed investment in industrial energy efficiency boilers in China in 1990s. ► With about $100 million of investment by the GEF/World Bank/Chinese government, the project will mitigate 40 million tons of CO 2 by 2019. ► This generated lowest unit cost of carbon reduction in the world: about $2.5 per ton of CO 2 mitigation. ► Investing in energy efficiency in industrial boiler steam system today in Vietnam will be the same cost effective as in China: $2.1 per ton of CO 2 mitigation.

Protein Kinase A (PKA) Type I Interacts with P-Rex1, a Rac Guanine Nucleotide Exchange Factor: EFFECT ON PKA LOCALIZATION AND P-Rex1 SIGNALING.

Science.gov (United States)

Chávez-Vargas, Lydia; Adame-García, Sendi Rafael; Cervantes-Villagrana, Rodolfo Daniel; Castillo-Kauil, Alejandro; Bruystens, Jessica G H; Fukuhara, Shigetomo; Taylor, Susan S; Mochizuki, Naoki; Reyes-Cruz, Guadalupe; Vázquez-Prado, José

2016-03-18

Morphology of migrating cells is regulated by Rho GTPases and fine-tuned by protein interactions and phosphorylation. PKA affects cell migration potentially through spatiotemporal interactions with regulators of Rho GTPases. Here we show that the endogenous regulatory (R) subunit of type I PKA interacts with P-Rex1, a Rac guanine nucleotide exchange factor that integrates chemotactic signals. Type I PKA holoenzyme interacts with P-Rex1 PDZ domains via the CNB B domain of RIα, which when expressed by itself facilitates endothelial cell migration. P-Rex1 activation localizes PKA to the cell periphery, whereas stimulation of PKA phosphorylates P-Rex1 and prevents its activation in cells responding to SDF-1 (stromal cell-derived factor 1). The P-Rex1 DEP1 domain is phosphorylated at Ser-436, which inhibits the DH-PH catalytic cassette by direct interaction. In addition, the P-Rex1 C terminus is indirectly targeted by PKA, promoting inhibitory interactions independently of the DEP1-PDZ2 region. A P-Rex1 S436A mutant construct shows increased RacGEF activity and prevents the inhibitory effect of forskolin on sphingosine 1-phosphate-dependent endothelial cell migration. Altogether, these results support the idea that P-Rex1 contributes to the spatiotemporal localization of type I PKA, which tightly regulates this guanine exchange factor by a multistep mechanism, initiated by interaction with the PDZ domains of P-Rex1 followed by direct phosphorylation at the first DEP domain and putatively indirect regulation of the C terminus, thus promoting inhibitory intramolecular interactions. This reciprocal regulation between PKA and P-Rex1 might represent a key node of integration by which chemotactic signaling is fine-tuned by PKA. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor.

Science.gov (United States)

Gerondopoulos, Andreas; Langemeyer, Lars; Liang, Jin-Rui; Linford, Andrea; Barr, Francis A

2012-11-20

Hermansky-Pudlak syndrome (HPS) is a human disease characterized by partial loss of pigmentation and impaired blood clotting. These symptoms are caused by defects in the biogenesis of melanosomes and platelet dense granules, often referred to as lysosome-related organelles. Genes mutated in HPS encode subunits of the biogenesis of lysosome-related organelles complexes (BLOCs). BLOC-1 and BLOC-2, together with the AP-3 clathrin adaptor complex, act at early endosomes to sort components required for melanin formation and melanosome biogenesis away from the degradative lysosomal pathway toward early stage melanosomes. However the molecular functions of the Hps1-Hps4 complex BLOC-3 remain mysterious. Like other trafficking pathways, melanosome biogenesis and transport of enzymes involved in pigmentation involves specific Rab GTPases, in this instance Rab32 and Rab38. We now demonstrate that BLOC-3 is a Rab32 and Rab38 guanine nucleotide exchange factor (GEF). Silencing of the BLOC-3 subunits Hps1 and Hps4 results in the mislocalization of Rab32 and Rab38 and reduction in pigmentation. In addition, we show that BLOC-3 can promote specific membrane recruitment of Rab32/38. BLOC-3 therefore defines a novel Rab GEF family with a specific function in the biogenesis of lysosome-related organelles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chlamydial entry involves TARP binding of guanine nucleotide exchange factors.

Directory of Open Access Journals (Sweden)

B Josh Lane

2008-03-01

Full Text Available Chlamydia trachomatis attachment to cells induces the secretion of the elementary body-associated protein TARP (Translocated Actin Recruiting Protein. TARP crosses the plasma membrane where it is immediately phosphorylated at tyrosine residues by unknown host kinases. The Rac GTPase is also activated, resulting in WAVE2 and Arp2/3-dependent recruitment of actin to the sites of chlamydia attachment. We show that TARP participates directly in chlamydial invasion activating the Rac-dependent signaling cascade to recruit actin. TARP functions by binding two distinct Rac guanine nucleotide exchange factors (GEFs, Sos1 and Vav2, in a phosphotyrosine-dependent manner. The tyrosine phosphorylation profile of the sequence YEPISTENIYESI within TARP, as well as the transient activation of the phosphatidylinositol 3-kinase (PI3-K, appears to determine which GEF is utilized to activate Rac. The first and second tyrosine residues, when phosphorylated, are utilized by the Sos1/Abi1/Eps8 and Vav2, respectively, with the latter requiring the lipid phosphatidylinositol 3,4,5-triphosphate. Depletion of these critical signaling molecules by siRNA resulted in inhibition of chlamydial invasion to varying degrees, owing to a possible functional redundancy of the two pathways. Collectively, these data implicate TARP in signaling to the actin cytoskeleton remodeling machinery, demonstrating a mechanism by which C.trachomatis invades non-phagocytic cells.

Interaction of LRRK2 with kinase and GTPase signaling cascades

Directory of Open Access Journals (Sweden)

Joon Y Boon

2014-07-01

Full Text Available LRRK2 is a protein that interacts with a plethora of signaling molecules, but the complexity of LRRK2 function presents a challenge for understanding the role of LRRK2 in the pathophysiology of Parkinson’s disease. Studies of LRRK2 using over-expression in transgenic mice have been disappointing, however studies using invertebrate systems have yielded a much clearer picture, with clear effects of LRRK2 expression, knockdown or deletion in C. elegans and Drosophila on modulation of survival of dopaminergic neurons. Recent studies have begun to focus attention on particular signaling cascades that are a target of LRRK2 function. LRRK2 interacts with members of the MAPK pathway and might regulate the pathway action by acting as a scaffold that directs the location of MAPK pathway activity, without strongly affecting the amount of MAPK pathway activity. Binding to GTPases, GAPs and GEFs are another strong theme in LRRK2 biology, with LRRK2 binding to Rac1, cdc42, rab5, rab7L1, endoA, RGS2, ArfGAP1 and ArhGEF7. All of these molecules appear to feed into a function output for LRRK2 that modulates cytoskeletal outgrowth and vesicular dynamics, including autophagy. These functions likely impact modulation of α-synuclein aggregation and associated toxicity eliciting the disease processes that we term Parkinson’s disease.

Deals and Dealings: Inconclusive Peace and Treacherous Trade along the South Sudan–Uganda Border Geschäfte und Deals: Gefährdeter Frieden und riskante Handelsbeziehungen entlang der südsudanesisch-ugandischen Grenze

Directory of Open Access Journals (Sweden)

Mareike Schomerus

2012-01-01

Full Text Available Since Sudan’s Comprehensive Peace Agreement (CPA was signed, its border with Uganda has become a hub of activity. Contrasting developments on the Ugandan side of the border with those on the South Sudanese side, the paper draws on empirical fieldwork to argue that the CPA has created new centres of power in the margins of both states. However, in day-to-day dealings on either side of the border, South Sudanese military actors have become dominant. In the particular case of Arua and the South Sudan–Uganda border, past wartime authority structures determine access to opportunities in a tightly regulated, inconclusive peace. This means that small-scale Ugandan traders – although vital to South Sudan – have become more vulnerable to South Sudan’s assertions of state authority. The experience of Ugandan traders calls into question the broad consensus that trade across the border is always beneficial for peace-building. The paper concludes that trade is not unconditionally helpful to the establishment of a peaceful environment for everyone.Seit Unterzeichnung des Comprehensive Peace Agreement (CPA im Sudan hat sich die Grenze zwischen Südsudan und Uganda zu einem lebendigen Drehkreuz entwickelt. Gestützt auf eigene Feldforschungen stellen die Autoren die Entwicklungen in den Grenzregionen beider Länder dar, wo seit Abschluss des CPA neue Machtzentren entstanden sind. In den alltäglichen Geschäftsbeziehungen entlang der Grenze dominieren allerdings militärische Akteure. Im konkreten Fall von Arua und der südsudanesisch-ugandischen Grenze bestimmen Machtstrukturen aus Kriegszeiten den Zugang zu Handelsgelegenheiten, die in der Nachkriegsphase noch starken Regulierungen unterliegen. Ugandische Kleinhändler – für die Versorgung des Südsudan von zentraler Bedeutung – sind in dieser Situation zunehmend durch Eingriffe der neuen südsudanesischen Staatsmacht gefährdet. Die Erfahrungen der Händler aus Arua stellen den breiten Konsens

Evaluations of Extended-Range tropical Cyclone Forecasts in the Western North Pacific by using the Ensemble Reforecasts: Preliminary Results

Science.gov (United States)

Tsai, Hsiao-Chung; Chen, Pang-Cheng; Elsberry, Russell L.

2017-04-01

The objective of this study is to evaluate the predictability of the extended-range forecasts of tropical cyclone (TC) in the western North Pacific using reforecasts from National Centers for Environmental Prediction (NCEP) Global Ensemble Forecast System (GEFS) during 1996-2015, and from the Climate Forecast System (CFS) during 1999-2010. Tsai and Elsberry have demonstrated that an opportunity exists to support hydrological operations by using the extended-range TC formation and track forecasts in the western North Pacific from the ECMWF 32-day ensemble. To demonstrate this potential for the decision-making processes regarding water resource management and hydrological operation in Taiwan reservoir watershed areas, special attention is given to the skill of the NCEP GEFS and CFS models in predicting the TCs affecting the Taiwan area. The first objective of this study is to analyze the skill of NCEP GEFS and CFS TC forecasts and quantify the forecast uncertainties via verifications of categorical binary forecasts and probabilistic forecasts. The second objective is to investigate the relationships among the large-scale environmental factors [e.g., El Niño Southern Oscillation (ENSO), Madden-Julian Oscillation (MJO), etc.] and the model forecast errors by using the reforecasts. Preliminary results are indicating that the skill of the TC activity forecasts based on the raw forecasts can be further improved if the model biases are minimized by utilizing these reforecasts.

Activation of Extracellular Signal-Regulated Kinase but Not of p38 Mitogen-Activated Protein Kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS

Science.gov (United States)

Jun, Jesse E.; Yang, Ming; Chen, Hang; Chakraborty, Arup K.

2013-01-01

Thymocytes convert graded T cell receptor (TCR) signals into positive selection or deletion, and activation of extracellular signal-related kinase (ERK), p38, and Jun N-terminal protein kinase (JNK) mitogen-activated protein kinases (MAPKs) has been postulated to play a discriminatory role. Two families of Ras guanine nucleotide exchange factors (RasGEFs), SOS and RasGRP, activate Ras and the downstream RAF-MEK-ERK pathway. The pathways leading to lymphocyte p38 and JNK activation are less well defined. We previously described how RasGRP alone induces analog Ras-ERK activation while SOS and RasGRP cooperate to establish bimodal ERK activation. Here we employed computational modeling and biochemical experiments with model cell lines and thymocytes to show that TCR-induced ERK activation grows exponentially in thymocytes and that a W729E allosteric pocket mutant, SOS1, can only reconstitute analog ERK signaling. In agreement with RasGRP allosterically priming SOS, exponential ERK activation is severely decreased by pharmacological or genetic perturbation of the phospholipase Cγ (PLCγ)-diacylglycerol-RasGRP1 pathway. In contrast, p38 activation is not sharply thresholded and requires high-level TCR signal input. Rac and p38 activation depends on SOS1 expression but not allosteric activation. Based on computational predictions and experiments exploring whether SOS functions as a RacGEF or adaptor in Rac-p38 activation, we established that the presence of SOS1, but not its enzymatic activity, is critical for p38 activation. PMID:23589333

tripleC-Interview mit Kerem Schamberger über Berufsverbote, linke Kommunikationswissenschaft und Kritik an der deutschen Wissenschaftslandschaft

Directory of Open Access Journals (Sweden)

Kerem Schamberger

2017-01-01

Full Text Available Kerem Schamberger ist ein Doktorand am Institut für Kommunikationswissenschaft und Medienforschung der Ludwig-Maximilians-Universität München. Er ist auch ein linker Aktivist und Mitglied der Deutschen Kommunistischen Partei (DKP. Im Zuge seiner Anstellung wurde auf Basis der bayrischen Gesetzeslage vom Bayrischen Verfassungsschutz geprüft, ob Kerem als verfassungsfeindlich gilt und ihm daher die Anstellung verweigert werden sollte. In der deutschen Mediensoziologie gab es mit Horst Holzer in den 1970er-Jahren einen ähnlichen Fall eines Berufsverbots, das damals durchgesetzt wurde. tripleC hat ein Interview mit Kerem geführt und ihn gebeten, die Hintergründe genauer zu erläutern. Das Interview wurde von Christian Fuchs und Thomas Allmer auf Deutsch geführt und ins Englische übersetzt.

Ein Beitrag zur Blutzellmorphologie ausgewählter karnivorer Zootierarten

OpenAIRE

Güth, Henrike

2004-01-01

Henrike Güth Ein Beitrag zur Blutzellmorphologie ausgewählter karnivorer Zootierarten Zoo Leipzig Januar 2003 156 Seiten, 222 Abbildungen, 67 Tabellen, 1 Graphik, 151 Literaturangaben, Anhang mit 25 Abbildungen und 6 Tabellen Zur Beurteilung des Blutbildes ist es nötig, neben der quantitativen Betrachtung der Blutzellen auch ihre Morphologie in die Untersuchungen einzubeziehen. In der Praxis werden dazu häufig nach May-Grünwald-Giemsa-gefärbte Ausstriche verwendet. Referenzwerte zur physiolog...

Проектная деятельность школьников в рамках преемственности начального и основного общего образования

OpenAIRE

Григорьева, Е.; Клементьева, Н.

2014-01-01

The article raises the problem of continuity of project activities in primary and basic school, explores the history of «project method» and the mod- ern requirements of the GEF to the project activity

Understanding the Oxygen Reduction Reaction on a Y/Pt(111) Single Crystal

DEFF Research Database (Denmark)

Ulrikkeholm, Elisabeth Therese; Johansson, Tobias Peter; Malacrida, Paolo

2014-01-01

Polymer electrolyte membrane fuel cells (PEMFC) hold promise as a zero-emission source of power, particularly suitable for automotive vehicles. However, the high loading of Pt required to catalyse the oxygen reduction reaction (ORR) at the PEMFC cathode, prevents the commercialisation of this tec......Polymer electrolyte membrane fuel cells (PEMFC) hold promise as a zero-emission source of power, particularly suitable for automotive vehicles. However, the high loading of Pt required to catalyse the oxygen reduction reaction (ORR) at the PEMFC cathode, prevents the commercialisation...... using electrochemical measurements, low energy electron diffraction, ion scattering spectroscopy, angle resolved X-ray photoelectron spectroscopy, temperature programmed desorption of CO, and synchrotron based X-ray absorption spectroscopy and surface sensitive X-ray diffraction. These measurements were...

Lck/PLCγ control migration and proliferation of interleukin (IL)-2-stimulated T cells via the Rac1 GTPase/glycogen phosphorylase pathway.

Science.gov (United States)

Llavero, Francisco; Artaso, Alain; Lacerda, Hadriano M; Parada, Luis A; Zugaza, José L

2016-11-01

Recently, we have reported that the IL-2-stimulated T cells activate PKCθ in order to phosphorylate the serine residues of αPIX-RhoGEF, and to switch on the Rac1/PYGM pathway resulting in T cell migration and proliferation. However, the molecular mechanism connecting the activated IL-2-R with the PKCθ/αPIX/Rac1/PYGM pathway is still unknown. In this study, the use of a combined pharmacological and genetic approach identified Lck, a Src family member, as the tyrosine kinase phosphorylating PLCγ leading to Rac1 and PYGM activation in the IL-2-stimulated Kit 225 T cells via the PKCθ/αPIX pathway. The PLCγ tyrosine phosphorylation was required to activate first PKCθ, and then αPIX and Rac1/PYGM. The results presented here delineate a novel signalling pathway ranking equally in importance to the three major pathways controlled by the IL-2-R, i.e. PI3K, Ras/MAPK and JAK/STAT pathways. The overall evidence strongly indicates that the central biological role of the novel IL-2-R/Lck/PLCγ/PKCθ/αPIX/Rac1/PYGM signalling pathway is directly related to the control of fundamental cellular processes such as T cell migration and proliferation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A brief method for preparation of gintonin-enriched fraction from ginseng

Directory of Open Access Journals (Sweden)

Sun-Hye Choi

2015-10-01

Conclusion: Because GEF can be prepared through water precipitation of ginseng ethanol extract and is easily reproducible with high yield, it could be commercially utilized for the development of gintonin-derived functional health food and natural medicine.

Journal of Earth System Science | Indian Academy of Sciences

Indian Academy of Sciences (India)

NCMRWF Global ForecastSystem) with ETR (Ensemble Transform with Rescaling) based Global Ensemble Forecast (GEFS) ofresolution T-190L28 is investigated. The experiment is conducted for a period of one week in June 2013and forecast ...

Baseline neutrophil-lymphocyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation

International Nuclear Information System (INIS)

Shen, Lijun; Zhang, Hui; Liang, Liping; Li, Guichao; Fan, Ming; Wu, Yongxin; Zhu, Ji; Zhang, Zhen

2014-01-01

The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may predict the clinical outcome in some cancers, such as head and neck cancer and gastric cancer. However, the value of this ratio is variable in different cancers. Studies of the relationship between NLR and both survival and response to chemoradiation have been limited with respect to locally advanced rectal cancer. From 2006 to 2011, 199 consecutive locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiation in the Shanghai Cancer Center were enrolled and analysed retrospectively. Tumor response was evaluated by pathological findings. The baseline total white blood cell count (WBC) and the neutrophil, lymphocyte, platelet counts were recorded. The neutrophil-lymphocyte ratio (NLR) and the relationship with clinical outcomes such as overall survival (OS) and disease-free survival (DFS) was analyzed. With ROC analysis, the baseline NLR value was found to significantly predict prognosis in terms of OS well in locally advanced rectal cancer patients. A multivariate analysis identified that a cut-off value of NLR ≥ 2.8 could be used as an independent factor to indicate decreased OS (HR, 2.123; 95% CI, 1.140-3.954; P = 0.018). NLR ≥ 2.8 was also associated with worse DFS in univariate analysis (HR, 1.662; 95% CI, 1.037-2.664; P = 0.035), though it was not significant in the multivariate analysis (HR, 1.363; 95% CI, 0.840-2.214; P = 0.210). There was no observed significant correlation of mean value of NLR to the response to neoadjuvant chemoradiation. The mean NLR in the ypT0-2 N0 group was 2.68 ± 1.38, and it was 2.77 ± 1.38 in the ypT3-4/N+ group, with no statistical significance (P = 0.703). The mean NLR in the TRG 0–1 group was 2.68 ± 1.42, and it was 2.82 ± 1.33 in the TRG 2–3 group with no statistical significance (P = 0.873). An elevated baseline NLR is a valuable and easily available prognostic factor for OS in

Modelling the widths of fission observables in GEF

Directory of Open Access Journals (Sweden)

Schmidt K.-H.

2013-03-01

Full Text Available The widths of the mass distributions of the different fission channels are traced back to the probability distributions of the corresponding quantum oscillators that are coupled to the heat bath, which is formed by the intrinsic degrees of freedom of the fissioning system under the influence of pairing correlations and shell effects. Following conclusion from stochastic calculations of Adeev and Pashkevich, an early freezing due to dynamical effects is assumed. It is shown that the mass width of the fission channels in low-energy fission is strongly influenced by the zero-point motion of the corresponding quantum oscillator. The observed variation of the mass widths of the asymmetric fission channels with excitation energy is attributed to the energy-dependent properties of the heat bath and not to the population of excited states of the corresponding quantum oscillator.

Programa de Cooperacion sur - sur Convenio de Cooperacion Tecnica y Cientifica a Mexico-Panama. Proyecto: Producción de Semilla de Moluscos y Cultivos en el Mar

OpenAIRE

Mazón Suástegui, J.M.,; Guerra-Lima, Z.I.,

2012-01-01

Este documento presenta 4 aspectos importantes 1. Generación de nuevo conocimiento: Estudios básicos sobre crecimiento, supervivencia, reproducción, nutrición, cultivo larvario de moluscos bivalvos y evaluación de dietas para juveniles. 2. Aplicación del conocimiento: Diseño de instalaciones y equipos para el cultivo de moluscos bivalvos. Asesoría internacional para el cultivo de moluscos nativos, financiados por PNUD, SENACYT-CCP (Ciencia Contra Pobreza), GEF-PNUD. Participan producto...

The Dictyostelium Bcr/Abr-related protein DRG regulates both Rac- and Rab-dependent pathways

OpenAIRE

Knetsch, Menno L.W.; Schäfers, Nicole; Horstmann, Heinz; Manstein, Dietmar J.

2001-01-01

Dictyostelium discoideum DdRacGap1 (DRG) contains both Rho-GEF and Rho-GAP domains, a feature it shares with mammalian Bcr and Abr. To elucidate the physiological role of this multifunctional protein, we characterized the enzymatic activity of recombinant DRG fragments in vitro, created DRG-null cells, and studied the function of the protein in vivo by analysing the phenotypic changes displayed by DRG-depleted cells and DRG-null cells complemented with DRG or DRG fragments. Our results show t...

The World Bank and the environment, fiscal 1992, exercise 92. Annual report

International Nuclear Information System (INIS)

1992-09-01

The report describes the Bank's activities in assisting countries with environmental management, such as programs to reduce poverty without exhausting natural resources. Included are assessments of the environmental impacts of projects supported by World Bank loans, and accounts of efforts to meet global environmental challenges with coordinated international action through the Global Environment Facility (GEF). Among the events in the period covered by the report are the affirmation of the World Bank's participation with United Nations organizations in the GEF and the Bank's administration of pilot programs aimed at finding solutions to such global environmental problems as pollution of international waters, global warming, depletion of the Earth's ozone layer, and dwindling biological diversity; the United Nations Conference on Environment and Development; and the publication of the World Development Report 1992, with its theme of development and the environment

The world bank and the environment, exercise 1992. Annual report

International Nuclear Information System (INIS)

1992-01-01

The report describes the Bank's activities in assisting countries with environmental management, such as programs to reduce poverty without exhausting natural resources. Included are assessments of the environmental impacts of projects supported by World Bank loans, and accounts of efforts to meet global environmental challenges with coordinated international action through the Global Environment Facility (GEF). Among the events in the period covered by the report are the affirmation of the World Bank's participation with United Nations organizations in the GEF and the Bank's administration of pilot programs aimed at finding solutions to such global environmental problems as pollution of international waters, global warming, depletion of the Earth's ozone layer, and dwindling biological diversity; the United Nations Conference on Environment and Development; and the publication of the World Development Report 1992, with its theme of development and the environment

WB to Lend $441m for Energy Efficiency in China

Institute of Scientific and Technical Information of China (English)

无

2008-01-01

@@ The World Bank (WB) has approved loans of $441 million to improve energy efficiency and reduce emissions from power plants in China. The loans, which account for almost one third of planned loans for China in fiscal 2008, would go to three projects, according to the lender.The energy efficiency project, co-financed by the WB and the Global Environment Facility (GEF), would get a loan of $200 million. The project, which would also receive a grant of 13.5 million U.S. dollars from the GEF, aims to boost large-scale loans for energy efficiency programs in China. China's commercial banks are also reported to participate in the project, such as the Export-Import Bank of China and Huaxia Bank, to offer loans ranging from 5 million to 10 million U. S. dollars for energy conservation projects, especially in heavy industries.

Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

International Nuclear Information System (INIS)

Mendoza-Catalán, Miguel A; Castañeda-Saucedo, Eduardo; Cristóbal-Mondragón, Gema R; Adame-Gómez, Jesús; Valle-Flores, Heidi N del; Coppe, José Fco; Sierra-López, Laura; Romero-Hernández, Mirna A; Carmen Alarcón-Romero, Luz del; Illades-Aguiar, Berenice

2012-01-01

Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766). Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression

pix-1 controls early elongation in parallel with mel-11 and let-502 in Caenorhabditis elegans.

Science.gov (United States)

Martin, Emmanuel; Harel, Sharon; Nkengfac, Bernard; Hamiche, Karim; Neault, Mathieu; Jenna, Sarah

2014-01-01

Cell shape changes are crucial for metazoan development. During Caenorhabditis elegans embryogenesis, epidermal cell shape changes transform ovoid embryos into vermiform larvae. This process is divided into two phases: early and late elongation. Early elongation involves the contraction of filamentous actin bundles by phosphorylated non-muscle myosin in a subset of epidermal (hypodermal) cells. The genes controlling early elongation are associated with two parallel pathways. The first one involves the rho-1/RHOA-specific effector let-502/Rho-kinase and mel-11/myosin phosphatase regulatory subunit. The second pathway involves the CDC42/RAC-specific effector pak-1. Late elongation is driven by mechanotransduction in ventral and dorsal hypodermal cells in response to body-wall muscle contractions, and involves the CDC42/RAC-specific Guanine-nucleotide Exchange Factor (GEF) pix-1, the GTPase ced-10/RAC and pak-1. In this study, pix-1 is shown to control early elongation in parallel with let-502/mel-11, as previously shown for pak-1. We show that pix-1, pak-1 and let-502 control the rate of elongation, and the antero-posterior morphology of the embryos. In particular, pix-1 and pak-1 are shown to control head, but not tail width, while let-502 controls both head and tail width. This suggests that let-502 function is required throughout the antero-posterior axis of the embryo during early elongation, while pix-1/pak-1 function may be mostly required in the anterior part of the embryo. Supporting this hypothesis we show that low pix-1 expression level in the dorsal-posterior hypodermal cells is required to ensure high elongation rate during early elongation.

Genetic evidence of 'genuine' empty follicle syndrome: a novel effective mutation in the LHCGR gene and review of the literature.

Science.gov (United States)

Yuan, Ping; He, Zuyong; Zheng, Lingyan; Wang, Wenjun; Li, Yu; Zhao, Haijing; Zhang, Victor Wei; Zhang, Qingxue; Yang, Dongzi

2017-04-01

Empty follicle syndrome (EFS) is a reproductive disorder in which no oocytes are retrieved during IVF. The existence of genuine EFS (GEFS) is still controversial, and to date, only one missense mutation of Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR) has been reported to be associated with this disease. Here, we describe a GEFS patient in a non-consanguineous family from China. A 27-year-old woman presented with a 5-year history of primary infertility and LH resistance-like ovaries of unequal sizes, but with normal levels of circulating LH. In spite of a satisfactory ovarian reserve and response, no oocytes were retrieved after two cycles of IVF. Her condition did not appear to be failure of the hCG injection. It is more likely to be a genetic cause. A novel homozygous mutation in LHCGR gene, c.1345G>A (p.Ala449Thr), was detected in this patient. Each of her parents is heterozygous for this change, and the change was absent from 407 control subjects. Alanine at this amino acid position was highly conserved and replacement of threonine was predicted to disrupt the third transmembrane helix of the rhodopsin-like G protein-coupled receptor domain. Protein localization studies revealed that a portion of the mutant LHCGR protein molecules was retained intracellularly. Signalling studies demonstrated that this mutation had differing effects on the response of LHCGR to hCG or LH at different concentrations. Specifically, at a concentration 1 IU/ml), the mutant was activated by both hCG and LH. These data suggest that screening for mutations in the LHCGR gene may assist in the diagnosis of patients with GEFS. The literature describing the relationship between phenotype and genotypes in females is reviewed, and possible aetiologies and treatment options for this disease are proposed based on our and other studies. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved

Haploinsufficiency of the Sec7 guanine nucleotide exchange factor gea1 impairs septation in fission yeast.

Directory of Open Access Journals (Sweden)

Alan M Eckler

Full Text Available Membrane trafficking is essential to eukaryotic life and is controlled by a complex network of proteins that regulate movement of proteins and lipids between organelles. The GBF1/GEA family of Guanine nucleotide Exchange Factors (GEFs regulates trafficking between the endoplasmic reticulum and Golgi by catalyzing the exchange of GDP for GTP on ADP Ribosylation Factors (Arfs. Activated Arfs recruit coat protein complex 1 (COP-I to form vesicles that ferry cargo between these organelles. To further explore the function of the GBF1/GEA family, we have characterized a fission yeast mutant lacking one copy of the essential gene gea1 (gea1+/-, the Schizosaccharomyces pombe ortholog of GBF1. The haploinsufficient gea1+/- strain was shown to be sensitive to the GBF1 inhibitor brefeldin A (BFA and was rescued from BFA sensitivity by gea1p overexpression. No overt defects in localization of arf1p or arf6p were observed in gea1+/- cells, but the fission yeast homolog of the COP-I cargo sac1 was mislocalized, consistent with impaired COP-I trafficking. Although Golgi morphology appeared normal, a slight increase in vacuolar size was observed in the gea1+/- mutant strain. Importantly, gea1+/- cells exhibited dramatic cytokinesis-related defects, including disorganized contractile rings, an increased septation index, and alterations in septum morphology. Septation defects appear to result from altered secretion of enzymes required for septum dynamics, as decreased secretion of eng1p, a β-glucanase required for septum breakdown, was observed in gea1+/- cells, and overexpression of eng1p suppressed the increased septation phenotype. These observations implicate gea1 in regulation of septum breakdown and establish S. pombe as a model system to explore GBF1/GEA function in cytokinesis.

Changes in Ect2 Localization Couple Actomyosin-Dependent Cell Shape Changes to Mitotic Progression

OpenAIRE

Matthews, Helen K.; Delabre, Ulysse; Rohn, Jennifer L.; Guck, Jochen; Kunda, Patricia; Baum, Buzz

2012-01-01

Summary As they enter mitosis, animal cells undergo profound actin-dependent changes in shape to become round. Here we identify the Cdk1 substrate, Ect2, as a central regulator of mitotic rounding, thus uncovering a link between the cell-cycle machinery that drives mitotic entry and its accompanying actin remodeling. Ect2 is a RhoGEF that plays a well-established role in formation of the actomyosin contractile ring at mitotic exit, through the local activation of RhoA. We find that Ect2 first...

The Juxtamembrane and carboxy-terminal domains of Arabidopsis PRK2 are critical for ROP-induced growth in pollen tubes

Science.gov (United States)

Polarized growth of pollen tubes is a critical step for successful reproduction in angiosperms and is controlled by ROP GTPases. Spatiotemporal activation of ROP (Rho GTPases of plants) necessitates a complex and sophisticated regulatory system, in which guanine nucleotide exchange factors (RopGEFs)...

The Reorientation of Cell Nucleus Promotes the Establishment of Front-Rear Polarity in Migrating Fibroblasts

Czech Academy of Sciences Publication Activity Database

Maninová, Miloslava; Klímová, Zuzana; Parsons, J. T.; Weber, M. J.; Iwanicki, M. P.; Vomastek, Tomáš

2013-01-01

Roč. 425, č. 11 (2013), s. 2039-2055 ISSN 0022-2836 R&D Projects: GA ČR GA204/09/0614 Institutional support: RVO:61388971 Keywords : FAK * RhoGAP * RhoGEF Subject RIV: CE - Biochemistry Impact factor: 3.959, year: 2013

Interplay between Solo and keratin filaments is crucial for mechanical force-induced stress fiber reinforcement.

Science.gov (United States)

Fujiwara, Sachiko; Ohashi, Kazumasa; Mashiko, Toshiya; Kondo, Hiroshi; Mizuno, Kensaku

2016-03-15

Mechanical force-induced cytoskeletal reorganization is essential for cell and tissue remodeling and homeostasis; however, the underlying cellular mechanisms remain elusive. Solo (ARHGEF40) is a RhoA-targeting guanine nucleotide exchange factor (GEF) involved in cyclical stretch-induced human endothelial cell reorientation and convergent extension cell movement in zebrafish gastrula. In this study, we show that Solo binds to keratin-8/keratin-18 (K8/K18) intermediate filaments through multiple sites. Solo overexpression promotes the formation of thick actin stress fibers and keratin bundles, whereas knockdown of Solo, expression of a GEF-inactive mutant of Solo, or inhibition of ROCK suppresses stress fiber formation and leads to disorganized keratin networks, indicating that the Solo-RhoA-ROCK pathway serves to precisely organize keratin networks, as well as to promote stress fibers. Of importance, knockdown of Solo or K18 or overexpression of GEF-inactive or deletion mutants of Solo suppresses tensile force-induced stress fiber reinforcement. Furthermore, knockdown of Solo or K18 suppresses tensile force-induced RhoA activation. These results strongly suggest that the interplay between Solo and K8/K18 filaments plays a crucial role in tensile force-induced RhoA activation and consequent actin cytoskeletal reinforcement. © 2016 Fujiwara et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Spatiotemporal dynamics of membrane remodeling and fusion proteins during endocytic transport.

Science.gov (United States)

Arlt, Henning; Auffarth, Kathrin; Kurre, Rainer; Lisse, Dominik; Piehler, Jacob; Ungermann, Christian

2015-04-01

Organelles of the endolysosomal system undergo multiple fission and fusion events to combine sorting of selected proteins to the vacuole with endosomal recycling. This sorting requires a consecutive remodeling of the organelle surface in the course of endosomal maturation. Here we dissect the remodeling and fusion machinery on endosomes during the process of endocytosis. We traced selected GFP-tagged endosomal proteins relative to exogenously added fluorescently labeled α-factor on its way from the plasma membrane to the vacuole. Our data reveal that the machinery of endosomal fusion and ESCRT proteins has similar temporal localization on endosomes, whereas they precede the retromer cargo recognition complex. Neither deletion of retromer nor the fusion machinery with the vacuole affects this maturation process, although the kinetics seems to be delayed due to ESCRT deletion. Of importance, in strains lacking the active Rab7-like Ypt7 or the vacuolar SNARE fusion machinery, α-factor still proceeds to late endosomes with the same kinetics. This indicates that endosomal maturation is mainly controlled by the early endosomal fusion and remodeling machinery but not the downstream Rab Ypt7 or the SNARE machinery. Our data thus provide important further understanding of endosomal biogenesis in the context of cargo sorting. © 2015 Arlt et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Die Reformdiskussion in der senegalesischen Sprachplanungs- politik

African Journals Online (AJOL)

Die Reformdiskussion in der senegalesischen Sprachplanungspolitik 13 hatten afrikanische Bildungspolitiker und Kulturtheoretiker (Senghor, Nkrumah, Kenyatta, etc.) sehr früh die Rolle der Sprache und Bildung in einem zukünftigen souveränen afrikanischen Staat anerkannt. Die damals geführten staatsrechtlichen ...

Relevance of soil and terrain information in studies of major global issues

NARCIS (Netherlands)

Bindraban, P.S.; Batjes, N.H.; Leenaars, J.G.B.; Bai, Z.G.

2010-01-01

The Carbon Benefits Project (CBP) is working to produce a standardized system for Global Environmental Facility (GEF) and other sustainable land management (SLM) projects to measure, monitor and model carbon stock changes and greenhouse gas (GHG) emissions. The project builds on existing C-inventory

Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow.

Science.gov (United States)

Lee, Dooyoung; Kim, Jiyeon; Beste, Michael T; Koretzky, Gary A; Hammer, Daniel A

2012-06-01

T lymphocyte arrest within microvasculature is an essential process in immune surveillance and the adaptive immune response. Integrins and chemokines coordinately regulate when and where T cells stop under flow via chemokine-triggered inside-out activation of integrins. Diacylglycerol kinases (DGKs) regulate the levels of diacylglycerol (DAG) which in turn determine the activation of guanine nucleotide exchange factors (GEFs) and Ras proximity 1 (Rap1) molecules crucial to the activation of integrin lymphocyte function-associated antigen 1 (LFA-1). However, how the level of DGK regulates chemokine-stimulated LFA-1-mediated T cell arrest under flow is unknown. Using a combination of experiment and computational modeling, we demonstrate that DGKζ is a crucial regulator of CXCL12-triggered T cell arrest on surfaces presenting inter-cellular adhesion molecule 1 (ICAM-1). Using flow chamber assays, we found that the deficiency of DGKζ in T cells significantly increased firm arrest to ICAM-1-coated substrates and shortened the time to stop without altering the rolling velocity. These results suggest that DGKζ levels affect LFA-1-mediated T cell firm arrest, but not P-selectin-mediated rolling during CXCL12 stimulation. We accurately simulated the role of DGKζ in firm arrest of T cells computationally using an Integrated-Signaling Adhesive Dynamics (ISAD). In the absence of DGK catalytic reaction, the model cells rolled for a significantly shorter time before arrest, compared to when DGK molecules were present. Predictions of our model for T cell arrest quantitatively match experimental results. Overall these results demonstrate that DGKζ is a negative regulator of CXCL12-triggered inside-out activation of LFA-1 and firm adhesion of T cells under shear flow.

Protein Kinase A (PKA) Type I Interacts with P-Rex1, a Rac Guanine Nucleotide Exchange Factor

Science.gov (United States)

Chávez-Vargas, Lydia; Adame-García, Sendi Rafael; Cervantes-Villagrana, Rodolfo Daniel; Castillo-Kauil, Alejandro; Bruystens, Jessica G. H.; Fukuhara, Shigetomo; Taylor, Susan S.; Mochizuki, Naoki; Reyes-Cruz, Guadalupe; Vázquez-Prado, José

2016-01-01

Morphology of migrating cells is regulated by Rho GTPases and fine-tuned by protein interactions and phosphorylation. PKA affects cell migration potentially through spatiotemporal interactions with regulators of Rho GTPases. Here we show that the endogenous regulatory (R) subunit of type I PKA interacts with P-Rex1, a Rac guanine nucleotide exchange factor that integrates chemotactic signals. Type I PKA holoenzyme interacts with P-Rex1 PDZ domains via the CNB B domain of RIα, which when expressed by itself facilitates endothelial cell migration. P-Rex1 activation localizes PKA to the cell periphery, whereas stimulation of PKA phosphorylates P-Rex1 and prevents its activation in cells responding to SDF-1 (stromal cell-derived factor 1). The P-Rex1 DEP1 domain is phosphorylated at Ser-436, which inhibits the DH-PH catalytic cassette by direct interaction. In addition, the P-Rex1 C terminus is indirectly targeted by PKA, promoting inhibitory interactions independently of the DEP1-PDZ2 region. A P-Rex1 S436A mutant construct shows increased RacGEF activity and prevents the inhibitory effect of forskolin on sphingosine 1-phosphate-dependent endothelial cell migration. Altogether, these results support the idea that P-Rex1 contributes to the spatiotemporal localization of type I PKA, which tightly regulates this guanine exchange factor by a multistep mechanism, initiated by interaction with the PDZ domains of P-Rex1 followed by direct phosphorylation at the first DEP domain and putatively indirect regulation of the C terminus, thus promoting inhibitory intramolecular interactions. This reciprocal regulation between PKA and P-Rex1 might represent a key node of integration by which chemotactic signaling is fine-tuned by PKA. PMID:26797121

Ausbreitung des parasitischen Unkrauts Phelipanche ramosa in der deutschen Landwirtschaft

DEFF Research Database (Denmark)

Kohlschmid, Eva; Müller-Stöver, Dorette Sophie; Sauerborn, J.

2011-01-01

Petersilie auf ihren Flächen anzubauen. Dies hatte zur Folge, dass diese nun mit P. ramosa befallen wurde. Noch vor 10 Jahren als Fallenpflanze eingesetzt, hatte die Petersilie eine eher geringe Wirkung auf die verzweigte Sommerwurz. Dieses Gefährdungspotential vor allem durch weitere potentielle...

Introduction

African Journals Online (AJOL)

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(Kiunsi and Meadows 2006). According to ... were chosen to represent three habitat/landscape types in the area: a flat, .... African Journal of Ecology. Volume 30 no.4 pp 335-345. Global Environmental Facility (2009) Investing in Land Stewardship. GEFs efforts to combat land degradation and desertification globally.

Inter-American Biodiversity Information Network (IABIN)

Science.gov (United States)

site. IABIN Inter-American Biodiversity Information Network (IABIN) OAS » SEDI » DSD » IABIN IABIN GEF Logo inbio natserve usgs polpar wcm The Inter-American Biodiversity Information Network (IABIN , and use of biodiversity information relevant to policy and decision-making on natural resources

Nach dem Deutschstudium in Afrika wird man – was? Eine ...

African Journals Online (AJOL)

Eva Hamann. 196. 2. Die Legitimierungsdebatte. Die Debatte um die Legitimierung und Relevanz des Studienfachs Deutsch in Afrika, geführt von afrikanischen Auslandsgermanisten, spiegelt sich ab den 80er Jahren in afrikanischen. Periodika wie Études Germano-Africaines und in deutschen Periodika wie Jahrbuch DaF.

Rsr1 Focuses Cdc42 Activity at Hyphal Tips and Promotes Maintenance of Hyphal Development in Candida albicans

Science.gov (United States)

Pulver, Rebecca; Heisel, Timothy; Gonia, Sara; Robins, Robert; Norton, Jennifer; Haynes, Paula

2013-01-01

The extremely elongated morphology of fungal hyphae is dependent on the cell's ability to assemble and maintain polarized growth machinery over multiple cell cycles. The different morphologies of the fungus Candida albicans make it an excellent model organism in which to study the spatiotemporal requirements for constitutive polarized growth and the generation of different cell shapes. In C. albicans, deletion of the landmark protein Rsr1 causes defects in morphogenesis that are not predicted from study of the orthologous protein in the related yeast Saccharomyces cerevisiae, thus suggesting that Rsr1 has expanded functions during polarized growth in C. albicans. Here, we show that Rsr1 activity localizes to hyphal tips by the differential localization of the Rsr1 GTPase-activating protein (GAP), Bud2, and guanine nucleotide exchange factor (GEF), Bud5. In addition, we find that Rsr1 is needed to maintain the focused localization of hyphal polarity structures and proteins, including Bem1, a marker of the active GTP-bound form of the Rho GTPase, Cdc42. Further, our results indicate that tip-localized Cdc42 clusters are associated with the cell's ability to express a hyphal transcriptional program and that the ability to generate a focused Cdc42 cluster in early hyphae (germ tubes) is needed to maintain hyphal morphogenesis over time. We propose that in C. albicans, Rsr1 “fine-tunes” the distribution of Cdc42 activity and that self-organizing (Rsr1-independent) mechanisms of polarized growth are not sufficient to generate narrow cell shapes or to provide feedback to the transcriptional program during hyphal morphogenesis. PMID:23223038

Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate.

Science.gov (United States)

Lee, Young Kwang; Low-Nam, Shalini T; Chung, Jean K; Hansen, Scott D; Lam, Hiu Yue Monatrice; Alvarez, Steven; Groves, Jay T

2017-04-28

The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition. This inhibitory role of the PR domain limits Grb2-independent recruitment of SOS to the membrane through binding of Ras·GTP in the SOS allosteric binding site. More generally, this assay strategy enables characterization of the functional behaviour of GEFs with single-molecule precision but without the need for purification.

Gridded Calibration of Ensemble Wind Vector Forecasts Using Ensemble Model Output Statistics

Science.gov (United States)

Lazarus, S. M.; Holman, B. P.; Splitt, M. E.

2017-12-01

A computationally efficient method is developed that performs gridded post processing of ensemble wind vector forecasts. An expansive set of idealized WRF model simulations are generated to provide physically consistent high resolution winds over a coastal domain characterized by an intricate land / water mask. Ensemble model output statistics (EMOS) is used to calibrate the ensemble wind vector forecasts at observation locations. The local EMOS predictive parameters (mean and variance) are then spread throughout the grid utilizing flow-dependent statistical relationships extracted from the downscaled WRF winds. Using data withdrawal and 28 east central Florida stations, the method is applied to one year of 24 h wind forecasts from the Global Ensemble Forecast System (GEFS). Compared to the raw GEFS, the approach improves both the deterministic and probabilistic forecast skill. Analysis of multivariate rank histograms indicate the post processed forecasts are calibrated. Two downscaling case studies are presented, a quiescent easterly flow event and a frontal passage. Strengths and weaknesses of the approach are presented and discussed.

Role of βPix in the kidney

Directory of Open Access Journals (Sweden)

Alexander eStaruschenko

2012-05-01

Full Text Available Small GTPases function as molecular switches in cell signaling, alternating between an inactive, GDP-bound state, and active GTP-bound state. βPix is one of guanine nucleotide exchange factors (GEFs that catalyze the exchange of bound GDP for ambient GTP. The central goal of this review article is to summarize recent findings on βPix and the role it plays in kidney pathology and physiology. Recent studies shed new light on several key questions concerning the signaling mechanisms mediated by βPix. This manuscript provides a review of the various mechanisms whereby βPix has been shown to function within the kidney through a wide range of actions. Both canonical GEF activity and non-canonical signaling pathways mediated by βPix are discussed. Distribution patterns of βPix in the kidney will be also covered. Much has yet to be discerned, but it is clear that βPix plays a significant role in the kidney.

Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

Energy Technology Data Exchange (ETDEWEB)

Lin, Chi-Chen [Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan (China); Institute of Biomedical Science, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan (China); Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan (China); Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan (China); Chen, Jing-Ting [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Lin, Meng-Wei [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); Chan, Chia-Hao [Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan (China); Wen, Yueh-Feng [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan (China); Wu, Shin-Bei [Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); Chung, Ting-Wen [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Lyu, Kevin W. [Lutheran Medical Center, Brooklyn, NY (United States); Global Scholars Program, St. George' s University/Northumbria University, Newcastle upon Tyne (United Kingdom); Chou, Hsiu-Chuan, E-mail: chouhc@mail.nhcue.edu.tw [Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); and others

2015-11-01

Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC. - Highlights: • 164 proteins associated with gefitinib resistance were identified through proteomic analysis. • In this study, a lung adenocarcinoma and its gefitinib resistant partner were established. • mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.

Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

International Nuclear Information System (INIS)

Lin, Chi-Chen; Chen, Jing-Ting; Lin, Meng-Wei; Chan, Chia-Hao; Wen, Yueh-Feng; Wu, Shin-Bei; Chung, Ting-Wen; Lyu, Kevin W.; Chou, Hsiu-Chuan

2015-01-01

Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC. - Highlights: • 164 proteins associated with gefitinib resistance were identified through proteomic analysis. • In this study, a lung adenocarcinoma and its gefitinib resistant partner were established. • mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.

Die Brustflosse des Grönlandswales (Balaena mysticetus L.)

NARCIS (Netherlands)

Kükenthal, W.

1922-01-01

Das Studium der Brustflosse des Grönlandswales hat zu Fragen von allgemeinerem Interesse geführt. Ihre kurze und breite Form sowie ihre anscheinende Fünffingerigkeit, die ausserdem nur noch beim südlichen Glattwal (Balaena australis) vorkommt, liess sie ursprünglicher erscheinen als die schlankere

Construction of an efficient biologically contained Pseudomonas putida strain and its survival in outdoor assays

DEFF Research Database (Denmark)

Molina, Lazaro; Rodriguez, Cayo Juan Ramos; Ronchel, Maria C.

1998-01-01

Active biological containment systems consist of two components, a killing element designed to induce cell death and a control element which modulates the expression of the killing function. We constructed a mini-Tn5 transposon bearing a fusion of the P(lac) promoter to the gef killing gene...

RAF and Protection Warfighting Function

Science.gov (United States)

2015-02-01

countries and challenges (including both the Asian Pacific and the Middle East).10 To execute this strategy in an increasingly complex world, the...of the Force (GEF) to prepare and review theatre campaign plans (TCP).27 The TCP is the CCDR’s vehicle for operationalizing the theater strategy. The

Extracellular adenosine-induced Rac1 activation in pulmonary endothelium: Molecular mechanisms and barrier-protective role.

Science.gov (United States)

Kovacs-Kasa, Anita; Kim, Kyung Mi; Cherian-Shaw, Mary; Black, Stephen M; Fulton, David J; Verin, Alexander D

2018-08-01

We have previously shown that Gs-coupled adenosine receptors (A2a) are primarily involved in adenosine-induced human pulmonary artery endothelial cell (HPAEC) barrier enhancement. However, the downstream events that mediate the strengthening of the endothelial cell (EC) barrier via adenosine signaling are largely unknown. In the current study, we tested the overall hypothesis that adenosine-induced Rac1 activation and EC barrier enhancement is mediated by Gs-dependent stimulation of cAMP-dependent Epac1-mediated signaling cascades. Adenoviral transduction of HPAEC with constitutively-active (C/A) Rac1 (V12Rac1) significantly increases transendothelial electrical resistance (TER) reflecting an enhancement of the EC barrier. Conversely, expression of an inactive Rac1 mutant (N17Rac1) decreases TER reflecting a compromised EC barrier. The adenosine-induced increase in TER was accompanied by activation of Rac1, decrease in contractility (MLC dephosphorylation), but not Rho inhibition. Conversely, inhibition of Rac1 activity attenuates adenosine-induced increase in TER. We next examined the role of cAMP-activated Epac1 and its putative downstream targets Rac1, Vav2, Rap1, and Tiam1. Depletion of Epac1 attenuated the adenosine-induced Rac1 activation and the increase in TER. Furthermore, silencing of Rac1 specific guanine nucleotide exchange factors (GEFs), Vav2 and Rap1a expression significantly attenuated adenosine-induced increases in TER and activation of Rac1. Depletion of Rap1b only modestly impacted adenosine-induced increases in TER and Tiam1 depletion had no effect on adenosine-induced Rac1 activation and TER. Together these data strongly suggest that Rac1 activity is required for adenosine-induced EC barrier enhancement and that the activation of Rac1 and ability to strengthen the EC barrier depends, at least in part, on cAMP-dependent Epac1/Vav2/Rap1-mediated signaling. © 2017 Wiley Periodicals, Inc.

Fission yields data generation and benchmarks of decay heat estimation of a nuclear fuel

Science.gov (United States)

Gil, Choong-Sup; Kim, Do Heon; Yoo, Jae Kwon; Lee, Jounghwa

2017-09-01

Fission yields data with the ENDF-6 format of 235U, 239Pu, and several actinides dependent on incident neutron energies have been generated using the GEF code. In addition, fission yields data libraries of ORIGEN-S, -ARP modules in the SCALE code, have been generated with the new data. The decay heats by ORIGEN-S using the new fission yields data have been calculated and compared with the measured data for validation in this study. The fission yields data ORIGEN-S libraries based on ENDF/B-VII.1, JEFF-3.1.1, and JENDL/FPY-2011 have also been generated, and decay heats were calculated using the ORIGEN-S libraries for analyses and comparisons.

De beteekenis der persoonsnamen voor onze kennis van het leven en denken der oude babyloniërs en assyriërs

NARCIS (Netherlands)

Gemser, Berend

1924-01-01

a. Antiek Naamsbegrip. Als GOETHE in de Faust den hoofdpersoon, sprekende met Margarete in Marthe's tuin over God, zeggen laat: "Nenn es dann, wie du willst,.... Gefühl ist alles; Name is Schall und Rauch, umnebelnd Himmelsglut", dan is dit modern en niet antiek gevoeld. Voor den mensch van de

Rational Design of Rho Protein Inhibitors

National Research Council Canada - National Science Library

Rojas, Rafael J

2006-01-01

... nucleotide exchange factors (RhoGEFs). We have developed a high throughput screening strategy identify novel inhibitors of Rho activation are currently following up on several compounds which appear to selectively inhibit Rho activation. These compounds may form the basis of future drug development strategies for the treatment of metastatic breast cancer.

Rational Design of Rho Protein Inhibitors

National Research Council Canada - National Science Library

Rojas, Rafael J

2005-01-01

... nucleotide exchange factors (RhoGEFs). We have developed a high throughput screening strategy identify novel inhibitors of Rho activation are currently following up on several compounds which appear to selectively inhibit Rho activation. These compounds may form the basis of future drug development strategies for the treatment of metastatic breast cancer.

Developing Financial Mechanisms for Long-Term Funding of Biodiversity Conservation

OpenAIRE

Jeri Larsen

1993-01-01

On March 12, 1992, the Regional Environment Divisions and the Global Environment Facility Administration in the Environment Department sponsored a one-day workshop. Conservation professionals, financial and legal specialists, and Bank operational staff involved with biodiversity, particularly Global Environment Facility (GEF) projects, gathered to discuss trust funds, endowments, and found...

Financial news

NARCIS (Netherlands)

NN,

1996-01-01

The Government of Indonesia had received a grant of US$7.2 dollars from GEF through the World Bank and this grant was supplemented by US$4.2 million from the Indonesian Government for the biodiversity collections project at Puslitbang Biologi. A similar proposal will be submitted to the World

Die Kunst des Scheiterns

DEFF Research Database (Denmark)

Juul, Jesper

2014-01-01

Menschen haben von Kindesbeinen an das Verlangen, Erfolge zu erzielen und Kompetenz zu erreichen. Computerspieler entscheiden sich jedoch fortlaufend für eine Aktivität, die oft und wiederholt zum Verlieren führen muss und ein taubes Gefühl der Unfähigkeit erzeugt. Im Kino, im Theatersaal und bei...

Why are SiX5(-) and GeX5(-) (X = F, Cl) stable but not CF5(-) and CCl5(-)?

Science.gov (United States)

Marchaj, Marzena; Freza, Sylwia; Skurski, Piotr

2012-03-01

The possible existence of the CF(5)(-), CCl(5)(-), SiF(5)(-), SiCl(5)(-), GeF(5)(-), and GeCl(5)(-) anions has been investigated using ab initio methods. The species containing Si and Ge as central atoms were found to adopt the D(3h)-symmetry trigonal bipyramidal equilibrium structures whose thermodynamic stabilities were confirmed by examining the most probable fragmentation channels. The ab initio re-examination of the electronic stabilities of the SiF(5)(-), SiCl(5)(-), GeF(5)(-), and GeCl(5)(-) anions [using the OVGF(full) method with the 6-311+G(3df) basis set] led to the very large vertical electron detachment (VDE) energies of 9.316 eV (SiF(5)(-)) and 9.742 eV (GeF(5)(-)), whereas smaller VDEs of 6.196 and 6.452 eV were predicted for the SiCl(5)(-) and GeCl(5)(-) species, respectively. By contrast, the high-symmetry and structurally compact anionic CF(5)(-) and CCl(5)(-) systems cannot exist due to the strongly repulsive potential predicted for the X(-) (F(-) or Cl(-)) approaching the CX(4) (CF(4) or CCl(4)). The formation of weakly bound CX(4)···X(-) (CF(4)···F(-) and CCl(4)···Cl(-)) anionic complexes (consisting of pseudotetrahedral neutral CX(4) with the weakly tethered X(-)) might be expected at low temperatures (approaching 0 K), whereas neither CX(5)(-) (CF(5)(-), CCl(5)(-)) systems nor CX(4)···X(-) (CF(4)···F(-) and CCl(4)···Cl(-)) complexes can exist in the elevated temperatures (above 0K) due to their susceptibility to the fragmentation (leading to the X(-) loss). © 2012 American Chemical Society

MJO simulation in CMIP5 climate models: MJO skill metrics and process-oriented diagnosis

Science.gov (United States)

Ahn, Min-Seop; Kim, Daehyun; Sperber, Kenneth R.; Kang, In-Sik; Maloney, Eric; Waliser, Duane; Hendon, Harry

2017-12-01

The Madden-Julian Oscillation (MJO) simulation diagnostics developed by MJO Working Group and the process-oriented MJO simulation diagnostics developed by MJO Task Force are applied to 37 Coupled Model Intercomparison Project phase 5 (CMIP5) models in order to assess model skill in representing amplitude, period, and coherent eastward propagation of the MJO, and to establish a link between MJO simulation skill and parameterized physical processes. Process-oriented diagnostics include the Relative Humidity Composite based on Precipitation (RHCP), Normalized Gross Moist Stability (NGMS), and the Greenhouse Enhancement Factor (GEF). Numerous scalar metrics are developed to quantify the results. Most CMIP5 models underestimate MJO amplitude, especially when outgoing longwave radiation (OLR) is used in the evaluation, and exhibit too fast phase speed while lacking coherence between eastward propagation of precipitation/convection and the wind field. The RHCP-metric, indicative of the sensitivity of simulated convection to low-level environmental moisture, and the NGMS-metric, indicative of the efficiency of a convective atmosphere for exporting moist static energy out of the column, show robust correlations with a large number of MJO skill metrics. The GEF-metric, indicative of the strength of the column-integrated longwave radiative heating due to cloud-radiation interaction, is also correlated with the MJO skill metrics, but shows relatively lower correlations compared to the RHCP- and NGMS-metrics. Our results suggest that modifications to processes associated with moisture-convection coupling and the gross moist stability might be the most fruitful for improving simulations of the MJO. Though the GEF-metric exhibits lower correlations with the MJO skill metrics, the longwave radiation feedback is highly relevant for simulating the weak precipitation anomaly regime that may be important for the establishment of shallow convection and the transition to deep convection.

Recurrent De Novo Mutations Disturbing the GTP/GDP Binding Pocket of RAB11B Cause Intellectual Disability and a Distinctive Brain Phenotype.

Science.gov (United States)

Lamers, Ideke J C; Reijnders, Margot R F; Venselaar, Hanka; Kraus, Alison; Jansen, Sandra; de Vries, Bert B A; Houge, Gunnar; Gradek, Gyri Aasland; Seo, Jieun; Choi, Murim; Chae, Jong-Hee; van der Burgt, Ineke; Pfundt, Rolph; Letteboer, Stef J F; van Beersum, Sylvia E C; Dusseljee, Simone; Brunner, Han G; Doherty, Dan; Kleefstra, Tjitske; Roepman, Ronald

2017-11-02

The Rab GTPase family comprises ∼70 GTP-binding proteins, functioning in vesicle formation, transport and fusion. They are activated by a conformational change induced by GTP-binding, allowing interactions with downstream effectors. Here, we report five individuals with two recurrent de novo missense mutations in RAB11B; c.64G>A; p.Val22Met in three individuals and c.202G>A; p.Ala68Thr in two individuals. An overlapping neurodevelopmental phenotype, including severe intellectual disability with absent speech, epilepsy, and hypotonia was observed in all affected individuals. Additionally, visual problems, musculoskeletal abnormalities, and microcephaly were present in the majority of cases. Re-evaluation of brain MRI images of four individuals showed a shared distinct brain phenotype, consisting of abnormal white matter (severely decreased volume and abnormal signal), thin corpus callosum, cerebellar vermis hypoplasia, optic nerve hypoplasia and mild ventriculomegaly. To compare the effects of both variants with known inactive GDP- and active GTP-bound RAB11B mutants, we modeled the variants on the three-dimensional protein structure and performed subcellular localization studies. We predicted that both variants alter the GTP/GDP binding pocket and show that they both have localization patterns similar to inactive RAB11B. Evaluation of their influence on the affinity of RAB11B to a series of binary interactors, both effectors and guanine nucleotide exchange factors (GEFs), showed induction of RAB11B binding to the GEF SH3BP5, again similar to inactive RAB11B. In conclusion, we report two recurrent dominant mutations in RAB11B leading to a neurodevelopmental syndrome, likely caused by altered GDP/GTP binding that inactivate the protein and induce GEF binding and protein mislocalization. Copyright © 2017 American Society of Human Genetics. All rights reserved.

Digitale Antidiskriminierungsarbeit

Directory of Open Access Journals (Sweden)

Simone Rafael

2017-12-01

Full Text Available Rechtsextreme und andere Menschenfeind_innen nutzen das Internet intensiv, um Abwertung von Gruppen zu normalisieren und Bedrohung und Hass zu verbreiten. Wie tritt die digitale demokratische Zivilgesellschaft dem entgegen? – Mit Fakten und Argumentationsstrategien, der Stärkung von Gegenrede durch NGOs und Privatpersonen und digitaler Streetwork mit gefährdeten Jugendlichen.

Evaluation of ensemble precipitation forecasts generated through post-processing in a Canadian catchment

Science.gov (United States)

Jha, Sanjeev K.; Shrestha, Durga L.; Stadnyk, Tricia A.; Coulibaly, Paulin

2018-03-01

Flooding in Canada is often caused by heavy rainfall during the snowmelt period. Hydrologic forecast centers rely on precipitation forecasts obtained from numerical weather prediction (NWP) models to enforce hydrological models for streamflow forecasting. The uncertainties in raw quantitative precipitation forecasts (QPFs) are enhanced by physiography and orography effects over a diverse landscape, particularly in the western catchments of Canada. A Bayesian post-processing approach called rainfall post-processing (RPP), developed in Australia (Robertson et al., 2013; Shrestha et al., 2015), has been applied to assess its forecast performance in a Canadian catchment. Raw QPFs obtained from two sources, Global Ensemble Forecasting System (GEFS) Reforecast 2 project, from the National Centers for Environmental Prediction, and Global Deterministic Forecast System (GDPS), from Environment and Climate Change Canada, are used in this study. The study period from January 2013 to December 2015 covered a major flood event in Calgary, Alberta, Canada. Post-processed results show that the RPP is able to remove the bias and reduce the errors of both GEFS and GDPS forecasts. Ensembles generated from the RPP reliably quantify the forecast uncertainty.

Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer.

Science.gov (United States)

Myerson, Robert J; Tan, Benjamin; Hunt, Steven; Olsen, Jeffrey; Birnbaum, Elisa; Fleshman, James; Gao, Feng; Hall, Lannis; Kodner, Ira; Lockhart, A Craig; Mutch, Matthew; Naughton, Michael; Picus, Joel; Rigden, Caron; Safar, Bashar; Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea; Parikh, Parag

2014-03-15

Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT chemotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

DIDACTIC ASPECTS OF USING WEB 2.0 TECHNOLOGY IN TRAINING EXPERTS IN PHYSICAL CULTURE AND SPORTS

Directory of Open Access Journals (Sweden)

А А Азевич

2016-12-01

Full Text Available This article discusses techniques for using Web 2.0 technologies in modern education. Based on practical experience suggests approaches to the formation of didactic means of implementing the requirements of the GEF training in the field of physical culture and sports with the use of information and communication technologies, in particular Internet services.

Steinzeitliche Kochexperimente

DEFF Research Database (Denmark)

Philippsen, Bente; Glykou, Aikaterini; Piezonka, Henny

dem Kohlenstoff aus den Krusten können die Gefäße 14C-datiert werden. In den letzten Jahren wurde allerdings immer deutlicher, dass 14C-Daten durch einen Süßwasser-Reservoireffekt verzerrt werden können. Proben, die aus einem Süßwassersystem stammen, erscheinen dadurch bei der 14C-Datierung einige...

Immer schlanker und kranker? Models in der Werbung

NARCIS (Netherlands)

Koch, T.; Hofer, L.; Holtz-Bacha, C.

2011-01-01

Es gibt eine mit Regelmäßigkeit und Vehemenz in den Massenmedien geführte Diskussion darüber, ob die mediale Darstellung so genannter „Magermodels" insbesondere für junge Frauen als eine Art Vorbild dienen könnte und spezifische Wirkungen nach sich zöge, etwa negative Körperbilder, Magersucht oder

Mixed-valent perovskites of the type Ba/sub 3/Bsup(III)PtRuO/sub 9/

Energy Technology Data Exchange (ETDEWEB)

Kemmler-Sack, S; Ehmann, A; Herrmann, M [Tuebingen Univ. (Germany, F.R.). Lehrstuhl fuer Anorganische Chemie 2

1981-08-01

Compounds of type Ba/sub 3/Bsup(III)PtRuO/sub 9/ - with a mean oxydation state of the noble metals of +4.5 - crystallize with Bsup(III) = Gd-Lu, Y in a variant of hexagonal BaTiO/sub 3/ type with ordered cationic distribution. Intensity calculations on powder data of Ba/sub 3/YPtRuO/sub 9/ (a = 5.88/sub 8/; c = 14.7/sub 0/ A) gave in the space group P6/sub 3//mmc (sequence (hcc)/sub 2/) a refined, intensity related R' value of 5.9%. With Bsup(III) = Eu the lattice is monoclinic and for Bsup(III) = Sm, Nd, La triclinic distorted.

Letzte Welt Die Wissenschaft gefährdet unser Überleben

CERN Multimedia

Rees, Martin J

2003-01-01

The mathematician and mystic Blaise Pascal had a famous argument about religious behavior: Even if you consider it extraordinarily improbable that an eagerness God exists, it would be careful and reasonable to behave as if he had existed

Das „neue“ Private. Familie als intime Gefühlsgemeinschaft

Directory of Open Access Journals (Sweden)

Regina Harzer

2006-11-01

Full Text Available Methodisch versteht sich die Habilitationsschrift als Beitrag zur Rekonstruktion moderner politischer Philosophie. Als zentraler Ansatzpunkt dient das Familienkonzept von Rousseau, seine Schriften werden auf Geschlechterkonstruktionen und bürgerliche Geschlechterordnungen hin untersucht. Grundanliegen der Studie ist es, Bürgerlichkeit unter ihrem zentralen Aspekt des Privaten zu betrachten und in den Kontext moderner kontraktualistischer Philosophie zu stellen. Die Autorin vertritt die Ausgangsthese, Rousseau müsse eine „Schlüsselstellung“ (S. 9 in der Geschichte der bürgerlichen Geschlechter- und Familienordnung zugesprochen werden. Durch ihn sei die Trennung des Privaten vom Öffentlichen eingeleitet und festgeschrieben worden.

Simultaneous detection and quantification of Phytophthora nicotianae and P. cactorum, and distribution analyses in strawberry greenhouses by duplex real-time PCR.

Science.gov (United States)

Li, Mingzhu; Inada, Minoru; Watanabe, Hideki; Suga, Haruhisa; Kageyama, Koji

2013-01-01

Phytophthora nicotianae and P. cactorum cause Phytophthora rot of strawberry. A duplex real-time PCR technique for simultaneous detection and quantification of the two pathogens was developed. Species-specific primers for P. nicotianae and P. cactorum were designed based on the internal transcribed spacer regions (ITS) of rDNA and the ras-related protein gene Ypt1, respectively. TaqMan probes were labeled with FAM for P. nicotianae and HEX for P. cactorum. Specificities were demonstrated using 52 isolates, including various soil-borne pathogens. Sensitivities for P. nicotianae and P. cactorum DNAs were 10 fg and 1 pg, respectively. The technique was applied to naturally infested soil and root samples; the two pathogens were detected and the target DNA concentrations were quantified. Significant correlations of DNA quantities in roots and the surrounding soils were found. The minimum soil DNA concentration predicting the development of disease symptoms was estimated as 20 pg (g soil)(-1). In three strawberry greenhouses examined, the target DNA concentrations ranged from 1 to 1,655 pg (g soil)(-1) for P. nicotianae and from 13 to 233 pg (g soil)(-1) for P. cactorum. The method proved fast and reliable, and provides a useful tool to monitor P. nicotianae and P. cactorum in plants or soils.

Alexandria electricity distribution company (AEDC) experience in energy conservation

International Nuclear Information System (INIS)

Youssef, K.; Soliman, O.; Nabil, A.

2005-01-01

Alexandria is the second capital of Egypt and represents forty percent of Egypt's industrial activities. There are about 350 big industrial firms and more than 2 thousands small and medium enterprises. This industries produces significant greenhouse gas emission. Good efforts are exerted in the field of energy saving and environment conservation by AEDC in order to reduce and limit greenhouse gas emission. AEDC participated in many projects sponsored by different foreign counterparts. These projects are: 1 - Energy and urban environment in Mediterranean countries: Phases 1, 2(1995-1996). 2 - Demand side management (DSM) 1996 - 1997. 3 - Energy and urban environment in Mediterranean countries: Phases 3 (2002-2003). 4 - Global environment facility ( GEF ) 1999 - 2003. The results of these pilot projects are presented in details in this paper

C3G knock-down enhances migration and invasion by increasing Rap1-mediated p38α activation, while it impairs tumor growth through p38α-independent mechanisms

Science.gov (United States)

Priego, Neibla; Arechederra, María; Sequera, Celia; Bragado, Paloma; Vázquez-Carballo, Ana; Gutiérrez-Uzquiza, Álvaro; Martín-Granado, Víctor; Ventura, Juan José; Kazanietz, Marcelo G.; Guerrero, Carmen; Porras, Almudena

2016-01-01

C3G, a Guanine nucleotide Exchange Factor (GEF) for Rap1 and R-Ras, has been shown to play important roles in development and cancer. Previous studies determined that C3G regulates cell death through down-regulation of p38α MAPK activity. Here, we found that C3G knock-down in MEFs and HCT116 cells promotes migration and invasion through Rap1-mediated p38α hyper-activation. These effects of C3G were inhibited by Rap1 knock-down or inactivation. The enhanced migration observed in C3G depleted HCT116 cells was associated with reduction in E-cadherin expression, internalization of ZO-1, actin cytoskeleton reorganization and decreased adhesion. We also found that matrix metalloproteases MMP2 and MMP9 are involved in the pro-invasive effect of C3G down-regulation. Additionally, our studies revealed that both C3G and p38α collaborate to promote growth of HCT116 cells in vitro and in vivo, possibly by enhancing cell survival. In fact, knocking-down C3G or p38α individually or together promoted cell death in vitro, although only the double C3G-p38α silencing was able to increase cell death within tumors. Notably, we found that the pro-tumorigenic function of C3G does not depend on p38α or Rap1 activation. Altogether, our studies uncover novel mechanisms by which C3G controls key aspects of tumorigenesis. PMID:27286263

Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold protein to polarize active Rac1 distribution

NARCIS (Netherlands)

Kroon, Jeffrey; Heemskerk, Niels; Kalsbeek, Martin J. T.; de Waard, Vivian; van Rijssel, Jos; van Buul, Jaap D.

2017-01-01

Endothelial cells line the lumen of the vessel wall and are exposed to flow. In linear parts of the vessel, the endothelial cells experience laminar flow, resulting in endothelial cell alignment in the direction of flow, thereby protecting the vessel wall from inflammation and permeability. In order

Rab14 and its exchange factor FAM116 link endocytic recycling and adherens junction stability in migrating cells.

Science.gov (United States)

Linford, Andrea; Yoshimura, Shin-ichiro; Nunes Bastos, Ricardo; Langemeyer, Lars; Gerondopoulos, Andreas; Rigden, Daniel J; Barr, Francis A

2012-05-15

Rab GTPases define the vesicle trafficking pathways underpinning cell polarization and migration. Here, we find that Rab4, Rab11, and Rab14 and the candidate Rab GDP-GTP exchange factors (GEFs) FAM116A and AVL9 are required for cell migration. Rab14 and its GEF FAM116A localize to and act on an intermediate compartment of the transferrin-recycling pathway prior to Rab11 and after Rab5 and Rab4. This Rab14 intermediate recycling compartment has specific functions in migrating cells discrete from early and recycling endosomes. Rab14-depleted cells show increased N-cadherin levels at junctional complexes and cannot resolve cell-cell junctions. This is due to decreased shedding of cell-surface N-cadherin by the ADAM family protease ADAM10/Kuzbanian. In FAM116A- and Rab14-depleted cells, ADAM10 accumulates in a transferrin-positive endocytic compartment, and the cell-surface level of ADAM10 is correspondingly reduced. FAM116 and Rab14 therefore define an endocytic recycling pathway needed for ADAM protease trafficking and regulation of cell-cell junctions. Copyright © 2012 Elsevier Inc. All rights reserved.

Evaluation of ensemble precipitation forecasts generated through post-processing in a Canadian catchment

Directory of Open Access Journals (Sweden)

S. K. Jha

2018-03-01

Full Text Available Flooding in Canada is often caused by heavy rainfall during the snowmelt period. Hydrologic forecast centers rely on precipitation forecasts obtained from numerical weather prediction (NWP models to enforce hydrological models for streamflow forecasting. The uncertainties in raw quantitative precipitation forecasts (QPFs are enhanced by physiography and orography effects over a diverse landscape, particularly in the western catchments of Canada. A Bayesian post-processing approach called rainfall post-processing (RPP, developed in Australia (Robertson et al., 2013; Shrestha et al., 2015, has been applied to assess its forecast performance in a Canadian catchment. Raw QPFs obtained from two sources, Global Ensemble Forecasting System (GEFS Reforecast 2 project, from the National Centers for Environmental Prediction, and Global Deterministic Forecast System (GDPS, from Environment and Climate Change Canada, are used in this study. The study period from January 2013 to December 2015 covered a major flood event in Calgary, Alberta, Canada. Post-processed results show that the RPP is able to remove the bias and reduce the errors of both GEFS and GDPS forecasts. Ensembles generated from the RPP reliably quantify the forecast uncertainty.

World Bank support for renewable energy - the ASTAE experience

International Nuclear Information System (INIS)

Schaeffer, L.

1999-01-01

Historically, the World Bank has helped finance the generation, transmission and distribution of electricity as well as improvements in supply-side energy efficiency. The World Bank's ability to mainstream renewable energy technologies in developing countries is enhanced by the Global Energy Facility (GEF), the World Bank Solar Initiative (and the nascent Solar Development Corporation), the International Finance Corporation and the Asia Alternative Energy Unit (ASTAE). (orig./RHM)

Pädagogik als Kulturwissenschaft. Programmatische Überlegungen zum Status der Allgemeinen Erziehungswissenschaft

OpenAIRE

Wimmer, Michael

2002-01-01

Ausgehend von einer schlaglichtartigen Charakterisierung gegenwärtiger Transformationsprozesse, die nicht nur zu grundlegenden Wandlungen in den gesellschaftlichen Verhältnissen und im kulturellen Selbstverständnis geführt haben, sondern auch die Prämissen ihrer begrifflichen Identifizierbarkeit und einer reflexiven Selbstvergewisserung erschüttern, wird die interne Situation der Erziehungswissenschaft skizziert, die sich ebenfalls dilemmatisch darstellt. Denn zum einen haben neuere Theorieen...

THE ROLE OF UNIVERSITIES IN THE DEVELOPMENT OF ENTREPRENEURIAL SKILLS OF STUDENTS

Directory of Open Access Journals (Sweden)

Evgeniy A. Deviatkin

2014-01-01

Full Text Available The article discusses the conceptual issues of formation of the competence approach, foreign experience of study competencies, the introduction of competence-based approach in the Russian universities in the transition to the GEF, presented requirements of the labor market to a graduates , found the place and role of entrepreneurial competencies of students in the recruitment process, shown teaching methods forming entrepreneurial skills.

Leben im emotionalen Kapitalismus

Directory of Open Access Journals (Sweden)

Martin Spetsmann-Kunkel

2007-07-01

Full Text Available Die israelische Soziologin Eva Illouz geht in ihrem Buch Gefühle in Zeiten des Kapitalismus von der These aus, dass der Kapitalismus eine emotionale Kultur ausgebildet hat, die sich sowohl am Arbeitsplatz als auch in intimen Beziehungen finden lässt. Die vermehrte Rationalisierung des emotionalen Lebens und die gleichzeitige Emotionalisierung von Arbeitsabläufen charakterisieren den „emotionalen Kapitalismus”.

The Shock and Vibration Digest. Volume 16, Number 12

Science.gov (United States)

1984-12-01

Rades, M. Beards, G.EF. Ibrahim, R.A. Ramamurti, V. Beltzer, A. gnaczak, J. Rao, D. K. *BenzlIey, S. E. lwatsubo, T. Rao, J.S. Bernard , J.E. Jennings...Baskar, S .................. 2733 Bernante, R .......... 2152, 2200 Bojarskl, N.N ......... 743, 1818 Bass, H.E ................... 713 Bernard , R.D...2004 Chung, A.W ................. 1077 Cornwell , R.E ............... 396 Dalmotas, D.J .............. 1966 Chung, H ................... 2400

M&A-Transaktionen - Fluch oder Segen der Realoptionstheorie?

OpenAIRE

Franke, Günter; Hopp, Christian

2005-01-01

Technologische und politische Veränderungen sowie komplexere Wertschöpfungsketten haben in den letzten Jahrzehnten zu einer verstärkten Unternehmensexpansion mittels Mergers and Acquisitions geführt. Unter dem Sammelbegriff "Mergers and Acquisitions" werden strategische Entscheidungen eines Unternehmens subsumiert, ein anderes Unternehmen oder einen Geschäftsbereich eines anderen Unternehmens durch Aktientausch oder Barentschädigung zu erwerben oder sich mit einem anderen Unternehmen zusammen...

Transnationale Städtenetzwerke als Instrument interkommunaler Kooperation im Zeitalter globaler Vernetzung : Das europäisch-lateinamerikanische Städtenetzwerk URB-AL

OpenAIRE

Rothfuß, Rainer

2006-01-01

Netzwerke spielen eine immer wichtigere Rolle als räumliche Struktur wirtschaftlicher Entwicklungsprozesse und auch als Form der Steuerung und Organisation politischer, unternehmerischer und sozialer Verflechtungen. Der Bedeutungszuwachs transnationaler Netzwerkstrukturen wurde erst durch die technologische Revolution im Bereich der Kommunikation und des Transportwesens ermöglicht. Im Hinblick auf die räumlichen Wirtschaftsstrukturen wurde er aber auch gefördert durch die Neudefinierung grund...

Outcomes of patients with abdominoperineal resection (APR) and low anterior resection (LAR) who had very low rectal cancer.

Science.gov (United States)

Yeom, Seung-Seop; Park, In Ja; Jung, Sung Woo; Oh, Se Heon; Lee, Jong Lyul; Yoon, Yong Sik; Kim, Chan Wook; Lim, Seok-Byung; Kim, Nayoung; Yu, Chang Sik; Kim, Jin Cheon

2017-10-01

We compared the oncological outcomes of sphincter-saving resection (SSR) and abdominoperineal resection (APR) in 409 consecutive patients with very low rectal cancer (i.e., tumors within 3 cm from the anal verge); 335 (81.9%) patients underwent APR and 74 (18.1%) underwent SSR. The APR group comprised higher proportions of men (67.5% vs 55.4%, P = .049) and advanced-stage patients (P cancer stages. RFS was associated with ypT and ypN stages in patients who received PCRT, while pN stage, lymphovascular invasion (LVI), and circumferential resection margin (CRM) involvement were risk factors for RFS in those who did not receive PCRT. Notably, SSR was not found to be a risk factor for RFS in either subgroup. Patients who were stratified according to cancer stage and PCRT also showed no differences in RFS according to the mode of surgery. Our results demonstrate that, regardless of PCRT administration, SSR is an effective treatment for very low rectal cancer, while CRM is an important prognostic factor for patients who did not receive PCRT.

Majorana surface modes of nodal topological pairings in spin-3/2 semimetals

Science.gov (United States)

Yang, Wang; Xiang, Tao; Wu, Congjun

2017-10-01

When solid state systems possess active orbital-band structures subject to spin-orbit coupling, their multicomponent electronic structures are often described in terms of effective large-spin fermion models. Their topological structures of superconductivity are beyond the framework of spin singlet and triplet Cooper pairings for spin-1/2 systems. Examples include the half-Heusler compound series of RPtBi, where R stands for a rare-earth element. Their spin-orbit coupled electronic structures are described by the Luttinger-Kohn model with effective spin-3/2 fermions and are characterized by band inversion. Recent experiments provide evidence to unconventional superconductivity in the YPtBi material with nodal spin-septet pairing. We systematically study topological pairing structures in spin-3/2 systems with the cubic group symmetries and calculate the surface Majorana spectra, which exhibit zero energy flat bands, or, cubic dispersion depending on the specific symmetry of the superconducting gap functions. The signatures of these surface states in the quasiparticle interference patterns of tunneling spectroscopy are studied, which can be tested in future experiments.

Dravet syndrome

Directory of Open Access Journals (Sweden)

Incorpora Gemma

2009-09-01

Full Text Available Abstract "Dravet syndrome" (DS previously named severe myoclonic epilepsy of infancy (SMEI, or epilepsy with polymorphic seizures, is a rare disorder characterized by an early, severe, generalized, epileptic encephalopathy. DS is characterized by febrile and afebrile seizures beginning in the 1st year of life followed by different types of seizures (either focal or generalized, which are typically resistant to antiepileptic drugs. A developmental delay from the 2nd to 3rd year of life becomes evident, together with motor disturbances and personality disorders. Beside the classic syndrome, there are milder cases which have been called severe myoclonic epilepsy borderline (SMEB. DS is caused by a mutation in the neuronal sodium channel gene, SCN1A , that is also mutated in generalized epilepsy with FS+ (GEFS+.

Cell polarity and patterning by PIN trafficking through early endosomal compartments in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Hirokazu Tanaka

2013-05-01

Full Text Available PIN-FORMED (PIN proteins localize asymmetrically at the plasma membrane and mediate intercellular polar transport of the plant hormone auxin that is crucial for a multitude of developmental processes in plants. PIN localization is under extensive control by environmental or developmental cues, but mechanisms regulating PIN localization are not fully understood. Here we show that early endosomal components ARF GEF BEN1 and newly identified Sec1/Munc18 family protein BEN2 are involved in distinct steps of early endosomal trafficking. BEN1 and BEN2 are collectively required for polar PIN localization, for their dynamic repolarization, and consequently for auxin activity gradient formation and auxin-related developmental processes including embryonic patterning, organogenesis, and vasculature venation patterning. These results show that early endosomal trafficking is crucial for cell polarity and auxin-dependent regulation of plant architecture.

Die Zukunft des Sozialstaates Deutschland: Elemente einer Reformstrategie

OpenAIRE

Lampert, Heinz

1998-01-01

Die Notwendigkeit einer Reform des Sozialstaates Deutschland ist nach Auffassung des Autors evident, weil eine zu hohe Staats- und Sozialabgabenquote zu Steuervermeidung, Verringerung der Leistungsbereitschaft, Schwarzarbeit, Steuerhinterziehung, Korruption und Betrug führen und die Wettbewerbsfähigkeit der Wirtschaft gefährden. Der Sozialstaat, den der Verfasser als eine der großen Errungenschaften der Neuzeit interpretiert, kann nach seiner Überzeugung aber so reformiert werden, daß soziale...

„Aber es gibt keine Antisemiten mehr“: Eine experimentelle Studie zur Kommunikationslatenz antisemitischer Einstellungen

OpenAIRE

Beyer, Heiko; Krumpal, Ivar

2010-01-01

Die öffentliche Sanktionierung des Antisemitismus nach 1945 hat dazu geführt, dass antisemitische Einstellungen in der bundesdeutschen Öffentlichkeit selten offen geäußert werden, teilweise jedoch im privaten Raum überdauern. Diese Entwicklung wurde von der Antisemitismusforschung zwar theoretisch mit dem Konzept der „Kommunikationslatenz“ aufgearbeitet, methodisch blieben diese Überlegungen jedoch weitgehend folgenlos. Aufgrund des heiklen Charakters antisemitischer Einstellungen ist davon a...

MicroRNAs and vascular remodeling in pulmonary hypertension

OpenAIRE

Brock, Matthias

2012-01-01

Die pulmonale Hypertonie (PH) ist der Überbegriff für verschiedene Krankheitsbilder, welche in einer signifikanten Erhöhung des Blutdrucks im Lungenkreislauf resultieren und auf Grund des vermehrten rechtsventrikulären Afterloads letztendlich zum Rechtsherzversagen führt. Die chronisch Drucksteigerung in der Lungenblutbahn wird im Wesentlichen durch drei pathogenetische Ereignisse verursacht: eine Mikrothrombosierung der Gefässbahn, eine übermässige Vasokonstriktion, sowie durch einen fibroti...

Paradigmenwechsel in der politischen Ökologie? Zur deutschen Diskussion über die Lokale Agenda 21

OpenAIRE

Pettenkofer, Andreas

2001-01-01

Der Text berichtet über die in Deutschland geführte sozialwissenschaftliche Diskussion über das umweltpolitische Programm Lokale Agenda 21; er versucht eine vorläufige Rekonstruktion der spezifischen Gestalt der Agenda-Prozesse und ihrer Abweichungen von der westdeutschen Tradition der Politischen Ökologie, und diskutiert die theoretischen Fragen, die sich angesichts dieser neuartigen Phänomene stellen. Dabei geht es vor allem um die Angemessenheit der modernisierungstheoretischen Perspektive...

Übergewicht und Adipositas, Gesundheit und Krankheit : Diskussionsbeiträge aus philosophischer Sicht

OpenAIRE

Gottschalk-Mazouz, Niels; Ertelt, Susanne; Radinkovic, Zeljko

2010-01-01

Der vorliegende Band vereint Studien, die im Rahmen des Philosophie-Teilprojekts des Forschungsverbunds "Übergewicht und Adipositas bei Kindern, Jugendlichen und jungen Erwachsenen als systemisches Risiko" entstanden sind. Dieser Verbund wurde vom BMBF von 2006-2009 im Rahmen der sozial-ökologischen Forschung im Themenbereich: Strategien zum Umgang mit systemischen Risiken gefördert. In diesem Verbund wurden unter der Leitung des Risikosoziologen Ortwin Renn die Perspektiven von Epidemiologie...

Mädchenschule und Geschlecht: Eine fallrekonstruktive Untersuchung der kollektiven Orientierungen und Weiblichkeitskonstruktionen von Schülerinnen monoedukativer Schulen

OpenAIRE

Waburg, Wiebke

2010-01-01

Die Dissertation ist im Rahmen des Projektes "Schulkultur, Geschlechtersegregation und Mädchensozialisation – DIAM" (Projektleitung L. Herwartz-Emden; gefördert von der DFG) entstandenen. In der Arbeit erfolgt die Rekonstruktion der Geschlechtskonstruktionen von Schülerinnen aus Mädchenschulen. Untersucht werden die kollektiven (geschlechtsbezogenen) Orientierungen von Mädchen und jungen Frauen im Alter von 13-19 Jahren. Die Schülerinnen befinden sich in der kulturell definierten Altersphase ...

Vorhersagbarkeit einer koronaren Herzkrankheit im Rahmen einer arbeitsmedizinischen Vorsorgeuntersuchung

OpenAIRE

Berghoff, Bent Elger

2004-01-01

Angesichts der hohen Prävalenz der koronaren Herzkrankheit in der Bundesrepublik Deutschland sollte deren frühe Erkennung wesentlicher Bestandteil einer arbeitsmedizinischen Vorsorgeuntersuchung sein. Dies sollte nicht nur zum Schutz des betroffenen Arbeitnehmers geschehen, sondern auch zum Schutz Dritter, die als Folge einer unerwarteten Manifestation gefährdet werden könnten. Mehrere Gesetze und Verordnungen schreiben daher verschiedene Anlässe vor, die eine spezielle arbeitsmedizinisch...

World Bank support for renewable energy - the ASTAE experience

Energy Technology Data Exchange (ETDEWEB)

Schaeffer, L. [World Bank, Washington, DC (United States). Asia Alternative Energy Unit

1999-07-01

Historically, the World Bank has helped finance the generation, transmission and distribution of electricity as well as improvements in supply-side energy efficiency. The World Bank's ability to mainstream renewable energy technologies in developing countries is enhanced by the Global Energy Facility (GEF), the World Bank Solar Initiative (and the nascent Solar Development Corporation), the International Finance Corporation and the Asia Alternative Energy Unit (ASTAE). (orig./RHM)

Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

KAUST Repository

Lissanu Deribe, Yonathan

2016-03-01

PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.

Science.gov (United States)

Lissanu Deribe, Yonathan; Shi, Yanxia; Rai, Kunal; Nezi, Luigi; Amin, Samir B; Wu, Chia-Chin; Akdemir, Kadir C; Mahdavi, Mozhdeh; Peng, Qian; Chang, Qing Edward; Hornigold, Kirsti; Arold, Stefan T; Welch, Heidi C E; Garraway, Levi A; Chin, Lynda

2016-03-01

PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2(E824)*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57(KIP2)). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

KAUST Repository

Lissanu Deribe, Yonathan; Shi, Yanxia; Rai, Kunal; Nezi, Luigi; Amin, Samir B.; Wu, Chia-Chin; Akdemir, Kadir C.; Mahdavi, Mozhdeh; Peng, Qian; Chang, Qing Edward; Hornigold, Kirsti; Arold, Stefan T.; Welch, Heidi C. E.; Garraway, Levi A.; Chin, Lynda

2016-01-01

PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

Prognostic Role of Carcinoembryonic Antigen Level after Preoperative Chemoradiotherapy in Patients with Rectal Cancer.

Science.gov (United States)

Huh, Jung Wook; Yun, Seong Hyeon; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Kim, Hee Cheol; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

2018-05-29

The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT. We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (level was 1.7 ng/mL (range, 0.1-207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4-176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival. The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer.

Generalized Energy Flow Analysis Considering Electricity Gas and Heat Subsystems in Local-Area Energy Systems Integration

Directory of Open Access Journals (Sweden)

Jiaqi Shi

2017-04-01

Full Text Available To alleviate environmental pollution and improve the efficient use of energy, energy systems integration (ESI—covering electric power systems, heat systems and natural gas systems—has become an important trend in energy utilization. The traditional power flow calculation method, with the object as the power system, will prove difficult in meeting the requirements of the coupled energy flow analysis. This paper proposes a generalized energy flow (GEF analysis method which is suitable for an ESI containing electricity, heat and gas subsystems. First, the models of electricity, heat, and natural gas networks in the ESI are established. In view of the complexity of the conventional method to solve the gas network including the compressor, an improved practical equivalent method was adopted based on different control modes. On this basis, a hybrid method combining homotopy and the Newton-Raphson algorithm was executed to compute the nonlinear equations of GEF, and the Jacobi matrix reflecting the coupling relationship of multi-energy was derived considering the grid connected mode and island modes of the power system in the ESI. Finally, the validity of the proposed method in multi-energy flow calculation and the analysis of interacting characteristics was verified using practical cases.

Mutation-Specific Mechanisms of Hyperactivation of Noonan Syndrome SOS Molecules Detected with Single-molecule Imaging in Living Cells.

Science.gov (United States)

Nakamura, Yuki; Umeki, Nobuhisa; Abe, Mitsuhiro; Sako, Yasushi

2017-10-26

Noonan syndrome (NS) is a congenital hereditary disorder associated with developmental and cardiac defects. Some patients with NS carry mutations in SOS, a guanine nucleotide exchange factor (GEF) for the small GTPase RAS. NS mutations have been identified not only in the GEF domain, but also in various domains of SOS, suggesting that multiple mechanisms disrupt SOS function. In this study, we examined three NS mutations in different domains of SOS to clarify the abnormality in its translocation to the plasma membrane, where SOS activates RAS. The association and dissociation kinetics between SOS tagged with a fluorescent protein and the living cell surface were observed in single molecules. All three mutants showed increased affinity for the plasma membrane, inducing excessive RAS signalling. However, the mechanisms by which their affinity was increased were specific to each mutant. Conformational disorder in the resting state, increased probability of a conformational change on the plasma membrane, and an increased association rate constant with the membrane receptor are the suggested mechanisms. These different properties cause the specific phenotypes of the mutants, which should be rescuable with different therapeutic strategies. Therefore, single-molecule kinetic analyses of living cells are useful for the pathological analysis of genetic diseases.

Potent and Selective Peptide-based Inhibition of the G Protein Gαq*

Science.gov (United States)

Charpentier, Thomas H.; Waldo, Gary L.; Lowery-Gionta, Emily G.; Krajewski, Krzysztof; Strahl, Brian D.; Kash, Thomas L.; Harden, T. Kendall; Sondek, John

2016-01-01

In contrast to G protein-coupled receptors, for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gαq binds its two major classes of effectors, the phospholipase C (PLC)-β isozymes and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gαq within its canonical binding site consisting of a groove formed between switch II and helix α3. This information was exploited to synthesize peptides that bound active Gαq in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gαq. A representative peptide was specific for active Gαq because it did not bind inactive Gαq or other classes of active Gα subunits and did not inhibit the activation of PLC-β3 by Gβ1γ2. In contrast, the peptide robustly prevented activation of PLC-β3 or p63RhoGEF by Gαq; it also prevented G protein-coupled receptor-promoted neuronal depolarization downstream of Gαq in the mouse prefrontal cortex. Moreover, a genetically encoded form of this peptide flanked by fluorescent proteins inhibited Gαq-dependent activation of PLC-β3 at least as effectively as a dominant-negative form of full-length PLC-β3. These attributes suggest that related, cell-penetrating peptides should effectively inhibit active Gαq in cells and that these and genetically encoded sequences may find application as molecular probes, drug leads, and biosensors to monitor the spatiotemporal activation of Gαq in cells. PMID:27742837

A multicentric randomized controlled trial on the impact of lengthening the interval between neoadjuvant radiochemotherapy and surgery on complete pathological response in rectal cancer (GRECCAR-6 trial): rationale and design

International Nuclear Information System (INIS)

Lefevre, Jérémie H; Rousseau, Alexandra; Svrcek, Magali; Parc, Yann; Simon, Tabassome; Tiret, Emmanuel

2013-01-01

Neoadjuvant radiochemotherapy (RCT) is now part of the armamentarium of cancer of the lower and middle rectum. It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+. Histological complete response, defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival. Surgical excision is usually performed between 6 and 8 weeks after completion of CRT and pathological complete response rate ranges around 12%. In retrospective studies, a lengthening of the interval after RCT beyond 10 weeks was found as an independent factor increasing the rate of pathological complete response (between 26% and 31%), with a longer disease-free survival and without increasing the operative morbidity. The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery. The current study is a multicenter randomized trial in two parallel groups comparing 7 and 11 weeks of delay between the end of RCT and cancer surgery of rectal tumors. At the end of the RCT, surgery is planified and randomization is performed after patient’s written consent for participation. The histological complete response (ypT0N0) will be determined with analysis of the complete residual tumor and double reading by two pathologists blinded of the group of inclusion. Patients will be followed in clinics for 5 years after surgery. Participation in this trial does not change patient’s management in terms of treatment, investigations or visits. Secondary endpoints will include overall and disease free survival, rate of sphincter conservation and quality of mesorectal excision. The number of patients needed is 264. ClinicalTrial.gov: http://www.clinicaltrials.gov/NCT01648894

Correlating Structure and Oxygen Reduction Activity on Y/Pt(111) and Gd/Pt(111) Single Crystals

DEFF Research Database (Denmark)

Ulrikkeholm, Elisabeth Therese; Pedersen, Anders Filsøe; Johansson, Tobias Peter

2015-01-01

Polymer Electrolyte Membrane Fuel Cells (PEMFC) hold promise as a zero-emission source of power, particularly suitable for automotive vehicles. However, the high loading of Pt required to catalyse the Oxygen Reduction Reaction (ORR) at the PEMFC cathode prevents the commercialisation of this tech......Polymer Electrolyte Membrane Fuel Cells (PEMFC) hold promise as a zero-emission source of power, particularly suitable for automotive vehicles. However, the high loading of Pt required to catalyse the Oxygen Reduction Reaction (ORR) at the PEMFC cathode prevents the commercialisation...... of this technology. Improving the activity of Pt by alloying it with other metals could decrease the loading of Pt at the cathode to a level comparable to Pt-group metal loading in internal combustion engines. PtxY and PtxGd exhibit exceptionally high activity for oxygen reduction, both in the polycrystalline form...

Anforderungen an ein System zur Evaluierung potentieller Langzeitschäden durch den Einsatz gentechnischer Methoden in der Nahrungsmittelherstellung und -verarbeitung

OpenAIRE

Katzek, Jens

2000-01-01

Der Einsatz der gentechnischer Methoden bei der Synthese und Veränderung von Lebensmittelbestandteilen unterliegt strengen gesetzlichen Regeln, die eine umfangreiche Risikoabschätzung vor dem Inverkehrbringen gewährleisten sollen. Erfahrungen aus anderen Technikbereichen – insbesondere der Pharmazie – zeigen jedoch, daß Risikoabschätzungen vor dem Inverkehrbringen eines Produktes nicht in der Lage sind, alle möglichen Rahmenbedingungen für die Evaluierung des Gefährdungspotentials bereits im ...

Technologies for adaptation. Perspectives and practical experiences; Climate change

Energy Technology Data Exchange (ETDEWEB)

Christiansen, Lars; Olhoff, A; Traerup, S

2011-11-15

The present report is the second volume of the UNEP Risoe Centre Technology Transfer Perspectives Series. The report is related to the global Technology Needs Assessment (TNA) project, financed by the Global Environment Facility (GEF) and implemented by UNEP Risoe Centre. The nine articles in this volume discuss issues like: a) the concepts and context of technologies for adaptation; b) assessments of adaptation technology needs; c) practical experiences from working with technologies for adaptation. (LN)

Wildnisbildung als Möglichkeit zur Professionalisierung zukünftiger Geographielehrer/innen – ein neuer Ansatz zur Bildung für nachhaltige Entwicklung?. GW-Unterricht|GW-Unterricht 142/143|

OpenAIRE

Lindau, Anne-Kathrin; Hottenroth, Daniela; Lindner, Martin

2016-01-01

Der in den deutschen Nationalparken seit mehreren Jahren thematisierte und praktizierte Ansatz der Wildnisbildung stellt möglicherweise einen neuen Zugang zur Bildung für nachhaltige Entwicklung (BNE) in der universitären Lehrer/innenbildung im Fach Geographie dar. Am Beispiel des DBU-geförderten Projektes „Wildnis macht stark“ wird eine Konzeption für die Umsetzung von Wildnisbildung im Rahmen des Geographie-Lehramtsstudiums vorgestellt und mit ersten Forschungsergebnissen zur Wirksamkeit in...

A Balanced Chromosomal Translocation Disrupting ARHGEF9 Is Associated With Epilepsy, Anxiety, Aggression, and Mental Retardation

OpenAIRE

Kalscheuer, Vera M.; Musante, Luciana; Fang, Cheng; Hoffmann, Kirsten; Fuchs, Celine; Carta, Eloisa; Deas, Emma; Venkateswarlu, Kanamarlapudi; Menzel, Corinna; Ullmann, Reinhard; Tommerup, Niels; Dalprà, Leda; Tzschach, Andreas; Selicorni, Angelo; Lüscher, Bernhard

2009-01-01

Clustering of inhibitory γ-aminobutyric acidA (GABAA) and glycine receptors at synapses is thought to involve key interactions between the receptors, a “scaffolding” protein known as gephyrin and the RhoGEF collybistin. We report the identification of a balanced chromosomal translocation in a female patient presenting with a disturbed sleep-wake cycle, late-onset epileptic seizures, increased anxiety, aggressive behavior, and mental retardation, but not hyperekplexia. Fine mapping of the brea...

Relating Operational Art to the National Guard State Partnership Program

Science.gov (United States)

2014-05-15

Program Coordinator GEF Global Employment of the Force DSCA Defense Support of Civil Authorities BCA Budget Control Act NATO North Atlantic Treaty...between Florida and the U.S. Virgin Islands are referred to as the Regional Security System (RSS). Florida and the U.S. Virgin Islands partner with... Atlantic Treaty Organization (NATO) in 2004 due, in part, to the mentorship from the Maryland National Guard.54 Not only did the Maryland National Guard

Panama: 100 Jahre Unabhängigkeit, Handlungsspielräume und Transformationsprozesse einer Kanalrepublik

OpenAIRE

Zoller, Rüdiger

2015-01-01

Während der 1990er Jahre standen die interamerikanischen Beziehungen auf Initiative des Amerikanisten Prof. Dr. Helmbrecht Breinig im Brennpunkt einer Reihe interdisziplinärer, von der DFG geförderter Forschungsvorhaben an der Universität Erlangen-Nürnberg. Den gemeinsamen konzeptionellen Rahmen für diese Teilprojekte entwickelte Prof. Dr. Friedrich von Krosigk mit seinen Überlegungen zu "Macht und Gegenmacht im Wandel interamerikanischer Beziehungen". Er selbst beteiligte sich mit einem Teil...

Diagnosis-Related Groups for Stroke in Europe: Patient Classification and Hospital Reimbursement in 11 Countries

OpenAIRE

Peltola, Mikko; Quentin, Wilm

2013-01-01

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich. This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. Background: Diagnosis-related groups (DRGs) are increasingly being used for various purposes in many countries. However, there are no studies comparing different DRG systems...

Sprache als Schlüssel zur Welt: Bibliotheken und Sprach-Kitas in guter Partnerschaft

OpenAIRE

Susanne Brandt

2017-01-01

Von 2016 bis voraussichtlich 2020 wird durch das Bundesministerium für Familie, Senioren, Frauen und Jugend das Bundesprogramm „Sprach-Kitas. Weil Sprache der Schlüssel zur Welt ist“ gefördert. Es richtet sich an Kindertageseinrichtungen, die von einem überdurchschnittlich hohen Anteil von Kindern mit besonderem Bedarf an sprachlicher Bildung und Förderung besucht werden. Dabei stehen besonders die folgenden drei Zielbereiche im Fokus: alltagsintegrierte sprachliche Bildung, inklusive Bildung...

Kulturmorphologie als Zivilisationskritik

DEFF Research Database (Denmark)

Peters, Rikke Alberg

2010-01-01

Der Untergang des Abendlandes wird oft als dasjenige Werk betrachtet, das am tiefsten die national gefärbte Gegenüberstellung von Kultur und Zivilisation in der Zwischenkriegszeit geprägt und propagiert hat. Wie auch bei anderen Autoren der Konservativen Revolution, vor allem bei Thomas Mann und...... Arthur Moeller van den Bruck, tritt der Begriff ‚Kultur’ bei Spengler als normativer Wertbegriff auf, der im Kontrast zu einer degenerierten und seelenlosen Zivilisation steht....

Hexagonal perovskites with cationic vacancies. 2. Ba/sub 8/Re/sub 2/W/sub 3/vacant/sub 3/O/sub 24/ - a novel hexagonal perovskite (24 L-type)

Energy Technology Data Exchange (ETDEWEB)

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

1978-07-01

The yellow Ba/sub 8/Re/sub 2/W/sub 3/vacant/sub 3/O/sub 24/ crystallizes in a rhombohedral layer structure of 24 L-type with a = 5.81/sub 3/ A; c = 55.52/sub 5/ A for the unit cell in trigonal setting and 3 formula units in the cell (rhosub(gef.) = 7.2/sub 6/ g/cm/sup 3/; rhosub(ber.) = 7.37/sub 8/ g/cm/sup 3/).

Horizontal cooperations between logistics service providers:motives, structure, performance

OpenAIRE

Schmoltzi, Christina; Wallenburg, Carl Marcus

2011-01-01

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich. This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. Purpose – This paper aims to provide a comprehensive overview of the motives, structure and performance attributes of horizontal cooperations between logistics service provi...

Steueroptimierte Alters- und Berufsunfähigkeitsvorsorge nach dem Alterseinkünftegesetz

OpenAIRE

Eberhardt, Michael G.

2007-01-01

Eine höhere Lebenserwartung bei gleichzeitiger Überalterung der deutschen Gesellschaft sind maßgebliche Gründe eines heute bereits festzustellenden Defizits der gesetzlichen Rentenversicherung. Die jüngste Rentenreform mit dem Altersvermögens- und Alterseinkünftegesetz setzte deshalb maßgebliche Anreize, die Alterssicherung eigenverantwortlich um eine private, staatlich geförderte Vorsorge zu ergänzen. Jedoch mangelt es derzeit vorwiegend an einer fachkundigen Informations- und Beratungsleist...

Produkteinführung im Umfeld des Niedergangs: Die Blu-ray Disk

OpenAIRE

Oestreicher, Klaus; Walton, Nigel; Newnham, M.

2014-01-01

Dieses Kapitel diskutiert die Problematik existenzieller Bedrohung durch radikale Innovationen. Virtuelle Marktangebote verändern Märkte im Home Entertainment und das Konsumverhalten grund¬legend. Zunehmend gefährden dematerialisierte Produkte, welche zu Services werden und Folge der Information Communication Tech¬nologies (ICT) sind, die Lebensfähigkeit physischer Produkte. Deren Märkte sind im Niedergang und das bedroht nicht nur die Hersteller optischer Disks (CD und DVD), sondern beeinflu...

Abfallentsorgung zu Lasten der Bürger? : Probleme der Kreislaufwirtschaft und Lösungsansätze für eine Entlastung der Haushalte

OpenAIRE

Kaimer, Martin; Schade, Diethard

2000-01-01

Das heutige Abfallentsorgungssystem und die ihm zugrunde liegenden gesetzlichen Regelungen haben eine lange Vorgeschichte und beruhen auf unterschiedlichen Zielsetzungen. Im Ergebnis haben die daraus folgenden Anforderungen zu teilweise fragwürdigen Entsorgungspfaden, zu einem komplizierten Nebeneinander privater und öffentlichrechtlicher Entsorger und vor allem zu höheren Müllgebühren für die Bürger geführt. Ausgehend von den Wirkungen, die mit der Umsetzung der gesetzlichen Regelungen errei...

International Advocacy against DDT and Other Public Health Insecticides for Malaria Control

Science.gov (United States)

2011-01-19

2010 Nov 15. 17. Betlem J. Importancia mundial de los resultados del proyecto : Programa Mundial sobre demonstracion y aumento de alterna- tivas...Demonstration of Sustainable Alternatives for Malaria Vector Control without the Use of DDT in Mexico and Central America”], Proyecto DDT/PNUMA/GEF/OPS [DDT...epidemiológico de la malaria en las comunidades de los proyectos demostrativos en Meso América. Presented at V Reunion del Comite Directivo “Programa

Inhibitors of plant hormone transport

Czech Academy of Sciences Publication Activity Database

Klíma, Petr; Laňková, Martina; Zažímalová, Eva

2016-01-01

Roč. 253, č. 6 (2016), s. 1391-1404 ISSN 0033-183X R&D Projects: GA MŠk(CZ) LD15088 Institutional support: RVO:61389030 Keywords : polar auxin transport * acid-binding protein * gnom arf-gef * equilibrative nucleoside transporter * efflux carrier polarity * plasma-membrane-protein * cultured tobacco cells * arabidopsis-thaliana * gravitropic response * brefeldin-a * Plant hormones * Transport * Inhibitors * Auxin * Cytokinins * Strigolactones * Abscisic acid * Cell biology Subject RIV: ED - Physiology Impact factor: 2.870, year: 2016

Rückstandsanalytische Untersuchungen für eine aktualisierte Bewertung des Einsatzes hormonal wirksamer Leistungsförderer in der Tiermast

OpenAIRE

Lange, Iris Gudrun

2005-01-01

Bei der Anwendung hormonal wirksamer Leistungsförderer in der Tiermast in Form von Implantationspräparaten ist die Einhaltung der "Guten Veterinärpraxis" unabdingbar. Gelangen Implantationsstellen in die Nahrungskette, können ganze Chargen von Fleischprodukten kontaminiert werden. Das höchste Gefährdungspotential geht dabei von Trenbolonacetatpräparaten aus, gefolgt von Östradiol bzw. Östradiolbenzoat, Testosteronpropionat und Progesteron. Eine Evaluierung von Zeranol war diesbezüglich im Rah...

WBSCR16 Is a Guanine Nucleotide Exchange Factor Important for Mitochondrial Fusion

Directory of Open Access Journals (Sweden)

Guorui Huang

2017-07-01

Full Text Available Regulated inter-mitochondrial fusion/fission is essential for maintaining optimal mitochondrial respiration and control of apoptosis and autophagy. In mammals, mitochondrial fusion is controlled by outer membrane GTPases MFN1 and MFN2 and by inner membrane (IM GTPase OPA1. Disordered mitochondrial fusion/fission contributes to various pathologies, and MFN2 or OPA1 mutations underlie neurodegenerative diseases. Here, we show that the WBSCR16 protein is primarily associated with the outer face of the inner mitochondrial membrane and is important for mitochondrial fusion. We provide evidence of a WBSCR16/OPA1 physical interaction in the intact cell and of a WBSCR16 function as an OPA1-specific guanine nucleotide exchange factor (GEF. Homozygosity for a Wbscr16 mutation causes early embryonic lethality, whereas neurons of mice heterozygous for the mutation have mitochondria with reduced membrane potential and increased susceptibility to fragmentation upon exposure to stress, suggesting roles for WBSCR16 deficits in neuronal pathologies.

MURC deficiency in smooth muscle attenuates pulmonary hypertension.

Science.gov (United States)

Nakanishi, Naohiko; Ogata, Takehiro; Naito, Daisuke; Miyagawa, Kotaro; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Kasahara, Takeru; Nishi, Masahiro; Matoba, Satoaki; Ueyama, Tomomi

2016-08-22

Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increased Murc mRNA expression in the mouse lung, and that Murc-null mice exhibited attenuation of hypoxia-induced pulmonary hypertension (PH) accompanied by reduced ROCK activity in the lung. Conditional knockout mice lacking Murc in smooth muscle also resist hypoxia-induced PH. MURC regulates the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through Rho/ROCK signalling. Cav1 suppresses RhoA activity in PASMCs, which is reversed by MURC. MURC binds to Cav1 and inhibits the association of Cav1 with the active form of Gα13, resulting in the facilitated association of the active form of Gα13 with p115RhoGEF. These results reveal that MURC has a function in the development of PH through modulating Rho/ROCK signalling.

Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model.

Science.gov (United States)

Casey, F P; Baird, D; Feng, Q; Gutenkunst, R N; Waterfall, J J; Myers, C R; Brown, K S; Cerione, R A; Sethna, J P

2007-05-01

We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor signalling, trafficking and down-regulation. The model incorporates the role of a recently discovered protein complex made up of the E3 ubiquitin ligase, Cbl, the guanine exchange factor (GEF), Cool-1 (beta -Pix) and the Rho family G protein Cdc42. The complex has been suggested to be important in disrupting receptor down-regulation. We demonstrate that the model interactions can accurately reproduce the experimental observations, that they can be used to make predictions with accompanying uncertainties, and that we can apply ideas of optimal experimental design to suggest new experiments that reduce the uncertainty on unmeasurable components of the system.

Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase

LENUS (Irish Health Repository)

McSherry, Elaine A

2011-03-23

and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. Conclusions Our findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and β1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis.

Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase.

LENUS (Irish Health Repository)

McSherry, Elaine A

2011-03-23

-6 and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. CONCLUSIONS: Our findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and β1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis.

Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase.

LENUS (Irish Health Repository)

McSherry, Elaine A

2012-02-01

JAM-A, AF-6 and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. CONCLUSIONS: Our findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and beta1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis.

Combined evaluation of first-pass radionuclide angiography and epuilibrium radionuclide ventriculography in the diagnosis of coronary artery disease. Pt. 1

International Nuclear Information System (INIS)

Knesewitsch, P.; Kleinhans, E.; Buell, U.

1986-01-01

The results of 203 patients who underwent first-pass radionuclide angiography (FP), as well as quantitative equilibrium radionuclide ventriculography (qERNV), were stored in a data base system and evaluated statistically. In patients with coronary artery disease (CAD) without previous myocardial infarction (MI), evaluation of global and regional ejection fraction (gEF, rEF) at rest revealed a poor sensitivity of 64% (Rest-qERNV) and 69% (Rest-FP), respectively. In patients with a history of one previous MI, the sensitivity of both methods was equivalent: FP 87% and qERNV 84%. In patients with several MIs, sensitivity was higher than 90%. Concerning localization of MI, remarkable differences between FP and qERNV were found. In posterior wall infarction, the FP sensitivity was 87% and qERNV only 67%, whereas in anterior wall infarction, the results were similar for both methods.: 93% (FP) and 96% (qERNV), respectively. Since 30 0 RAO camera position achieves the best visualization of the anterior and posterior wall, FP is superior to qERNV in the evaluation of posterior wall asynergies. In addition, qERNV often fails to discriminate anterior and posterior wall motion abnormalities. (orig.)

Global programme to demonstrate the viability and removal of barriers that impede adoption and successful implementation of available, non-combustion technologies for destroying persistent organic pollutants (POPs)

International Nuclear Information System (INIS)

2005-01-01

Council: 1. Inconsistencies in the document with regard to the size of PCB waste and PCB containing equipment to be destroyed during both the GEF project time frame and the post-project operational phase; 2. The specific capital and operating costs of the likely candidate technologies; 3. The typical costs paid by European and Slovak industries for PCB waste destruction using traditional incineration technologies; 4. Questions regarding the stated very high PCB content of soils and sediments in the major PCB hot spot located in the Kosice region of Eastern Slovakia; 5. The roles and responsibilities of the different private sector partners; 6. Proposals to identify and pre-select the specific non-combustion technology prior to the initiation of project implementation; and lastly, 7. Clarifications regarding the absence of specific vendor names in the final project document

Incorporating Medium-Range Weather Forecasts in Seasonal Crop Scenarios over the Greater Horn of Africa to Support National/Regional/Local Decision Makers

Science.gov (United States)

Shukla, S.; Husak, G. J.; Funk, C. C.; Verdin, J. P.

2015-12-01

The USAID's Famine Early Warning Systems Network (FEWS NET) provides seasonal assessments of crop conditions over the Greater Horn of Africa (GHA) and other food insecure regions. These assessments and current livelihood, nutrition, market conditions and conflicts are used to generate food security scenarios that help national, regional and local decision makers target their resources and mitigate socio-economic losses. Among the various tools that FEWS NET uses is the FAO's Water Requirement Satisfaction Index (WRSI). The WRSI is a simple yet powerful crop assessment model that incorporates current moisture conditions (at the time of the issuance of forecast), precipitation scenarios, potential evapotranspiration and crop parameters to categorize crop conditions into different classes ranging from "failure" to "very good". The WRSI tool has been shown to have a good agreement with local crop yields in the GHA region. At present, the precipitation scenarios used to drive the WRSI are based on either a climatological forecast (that assigns equal chances of occurrence to all possible scenarios and has no skill over the forecast period) or a sea-surface temperature anomaly based scenario (which at best have skill at the seasonal scale). In both cases, the scenarios fail to capture the skill that can be attained by initial atmospheric conditions (i.e., medium-range weather forecasts). During the middle of a cropping season, when a week or two of poor rains can have a devastating effect, two weeks worth of skillful precipitation forecasts could improve the skill of the crop scenarios. With this working hypothesis, we examine the value of incorporating medium-range weather forecasts in improving the skill of crop scenarios in the GHA region. We use the NCEP's Global Ensemble Forecast system (GEFS) weather forecasts and examine the skill of crop scenarios generated using the GEFS weather forecasts with respect to the scenarios based solely on the climatological forecast

Kongress Die Zukunft des Menschen : Dokumentation ; 10 Jahre Akademie für Technikfolgenabschätzung ; 8./9. Juli 2002, Stuttgart

OpenAIRE

2003-01-01

Die Lebenswissenschaften haben einen Forschungsstand erreicht, der es ihnen erstmals erlaubt, an den Grundfesten des Menschseins zu rühren. Erwartungshaltung und Wirklichkeit klaffen jedoch weit auseinander. Zudem ist es oft schwierig, das Machbare von der Fiktion zu unterscheiden, angesichts der häufig emotional geführten Diskussion und dem ungehemmten Drang zur Selbstdarstellung bei manchen Beteiligten. Die „Durchbrüche“ auf diesem Gebiet sind außerdem noch wenig belastbar, wie man an dem f...

Fusion Culture : Fashion beyond Orientalism and Occidentalism

OpenAIRE

Lehnert, Gertrud; Mentges, Gabriele

2017-01-01

Tagungsbericht zu 'Fusion Culture: Fashion beyond Orientalism and Occidentalism', Universität Potsdam, 5. bis 7. November 2009 Die von Gabriele Mentges (Dortmund) und Gertrud Lehnert (Potsdam) veranstaltete und von der Volkswagen Stiftung geförderte Tagung befasste sich mit dem Thema 'Orientalismus und Mode' zum einen unter historischen Aspekten, zum anderen unter gegenwärtigen Bedingungen, in denen von 'Orientalismus' kaum noch die Rede sein kann. Denn längst haben wechselseitige Bezüge ...

Linking Risk Management Practices and Strategies to Performance

OpenAIRE

Wieland, Andreas; Wallenburg, Carl Marcus

2014-01-01

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich. This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. Purpose – The effects of supply chain risk management (SCRM) on the performance of a supply chain remain unexplored. It is assumed that SCRM helps supply chains to cope with...

Topology of silica supported vanadium–titanium oxide catalysts for oxidative dehydrogenation of propane

OpenAIRE

Hamilton, N.; Wolfram, T.; Tzolova-Müller, G.; Hävecker, M.; Kröhnert, J.; Carrero, C.; Schomäcker, R.; Trunschke, A.; Schlögl, R.

2012-01-01

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich. This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. Two-dimensional vanadia and titania surface clusters were hosted on the walls of the hierarchical pore system of mesoporous silica SBA-15. The topology of the catalyst surfa...

The tumor suppressor adenomatous polyposis coli controls the direction in which a cell extrudes from an epithelium

OpenAIRE

Marshall, Thomas W.; Lloyd, Isaac E.; Delalande, Jean Marie; N?thke, Inke; Rosenblatt, Jody

2011-01-01

Despite high rates of cell death, epithelia maintain intact barriers by squeezing dying cells out using a process termed cell extrusion. Cells can extrude apically into the lumen or basally into the tissue the epithelium encases, depending on whether actin and myosin contract at the cell base or apex, respectively. We previously found that microtubules in cells surrounding a dying cell target p115 RhoGEF to the actin cortex to control where contraction occurs. However, what controls microtubu...

Entwicklung eines Summenparameters für potenziell bioakkumulierbare Stoffe (PBS) im Abwasser

OpenAIRE

Stenz, Georg

2001-01-01

Es wurde ein Summenparameter für potenziell bioakkumulierbare Stoffe (PBS) im Abwasser entwickelt. Der Summenparameter soll als Instrumentarium zur Überwachung von Einleitungen, Emissionen und Verlusten an anreicherungsfähigen Stoffen eingesetzt werden, da die Bioakkumulation besonders für marine Ökosysteme ein Gefährdungskriterium darstellt. Stoffe werden nach dem „Technical Guidance Document (TGD)“ als potenziell bioakkumulierbar bertrachtet, wenn deren log POW-Wert größer als drei ist. Der...

Lean-Prinzipien für verbesserte Kosteneffizienz: Instandhaltungseffizienz durch Lean Maintenance

OpenAIRE

Bandow, G.; Schmidt, A.

2008-01-01

Die Bedeutung der Instandhaltung nimmt weiter zu. In einem Lean Umfeld mit einer immer verschwendungsärmeren Produktion stehen nicht nur die Kosteneffizienz und Verfügbarkeit der Produktionsmittel im Fokus. Unplanmäßige Stillstände kosten Geld und gefährden häufig auch Personal und Produkt. Lean Maintenance vermeidet Verschwendung und optimiert so die Effektivität und Effizienz der Instandhaltung. Das zielgerichtete Zusammenspiel von Menschen, Prozessen und Technik garantiert dabei den Erfolg...

Biodiversity information system of the national parks administration of Argentina

Directory of Open Access Journals (Sweden)

Leonidas Lizarraga

2014-06-01

Full Text Available Introduction The Biodiversity Information System (BIS of the National Parks Administration of Argentina (NPA was launched in 2002, with the support of the Global Environmental Fund (GEF through the Biodiversity Conservation Project in Argentina. The BIS consists of a set of thematic databases and Geographic Information System (GIS set to support management decisions, and to provide information to the general public on the national protected areas of Argentina. Currently, the BIS-NPA progr...

Towards the elucidation of the high oxygen electroreduction activity of Pt_xY: surface science and electrochemical studies of Y/Pt(111)

DEFF Research Database (Denmark)

Johansson, Tobias Peter; Ulrikkeholm, Elisabeth Therese; Hernandez-Fernandez, Patricia

2014-01-01

programmed desorption of CO. When depositing a large amount of yttrium at 1173 K, a (1.88 × 1.88)R30° structure relative to Pt(111) was observed by low energy electron diffraction. Such an electron diffraction pattern could correspond to a (2 × 2)R30° structure under 6% compressive strain. This structure...... is in agreement with the structure of the vacancies in a Pt Kagomé layer in Pt5Y rotated 30° with respect to the bulk of the Pt(111). The Pt overlayer is relatively stable in air; however, after performing oxygen reduction activity measurements in an electrochemical cell, a thick Pt overlayer was measured...

The activation of RhoC in vascular endothelial cells is required for the S1P receptor type 2-induced inhibition of angiogenesis.

Science.gov (United States)

Del Galdo, Sabrina; Vettel, Christiane; Heringdorf, Dagmar Meyer Zu; Wieland, Thomas

2013-12-01

Sphingosine-1-phosphate (S1P) is a multifunctional phospholipid inducing a variety of cellular responses in endothelial cells (EC). S1P responses are mediated by five G protein coupled receptors of which three types (S1P1R-S1P3R) have been described to be of importance in vascular endothelial cells (EC). Whereas the S1P1R regulates endothelial barrier function by coupling to Gαi and the monomeric GTPase Rac1, the signaling pathways involved in the S1P-induced regulation of angiogenesis are ill defined. We therefore studied the sprouting of human umbilical vein EC (HUVEC) in vitro and analyzed the activation of the RhoGTPases RhoA and RhoC. Physiological relevant concentrations of S1P (100-300nM) induce a moderate activation of RhoA and RhoC. Inhibition or siRNA-mediated depletion of the S1P2R preferentially decreased the activation of RhoC. Both manipulations caused an increase of sprouting in a spheroid based in vitro sprouting assay. Interestingly, a similar increase in sprouting was detected after effective siRNA-mediated knockdown of RhoC. In contrast, the depletion of RhoA had no influence on sprouting. Furthermore, suppression of the activity of G proteins of the Gα12/13 subfamily by adenoviral overexpression of the regulator of G protein signaling domain of LSC as well as siRNA-mediated knockdown of the Rho specific guanine nucleotide exchange factor leukemia associated RhoGEF (LARG) inhibited the S1P-induced activation of RhoC and concomitantly increased sprouting of HUVEC with similar efficacy. We conclude that the angiogenic sprouting of EC is suppressed via the S1P2R subtype. Thus, the increase in basal sprouting can be attributed to blocking of the inhibitory action of autocrine S1P stimulating the S1P2R. This inhibitory pathway involves the activation of RhoC via Gα12/13 and LARG, while the simultaneously occurring activation of RhoA is apparently dispensable here. © 2013.

[Anti-EGFR Antibody Combination Chemotherapy Was Effective against Locally Advanced Ascending Colon Cancer as Well as a Recurrent Lesion - A Case Report].

Science.gov (United States)

Yamada, Yasufumi; Yokomizo, Hajime; Yano, Yuki; Okayama, Sachiyo; Satake, Masaya; Ida, Arika; Usui, Takebumi; Yamaguchi, Kentaro; Shiozawa, Shunichi; Yoshimatsu, Kazuhiko; Shimakawa, Takeshi; Katsube, Takao; Naritaka, Yoshihiko; Kato, Hiroyuki

2017-10-01

Here we report a case in which a locally advanced ascending colon cancer was successfully treated with anti-EGFR immunotherapy combined with chemotherapy and curative resection, and recurrent cancer was treated with the same chemotherapy. A 71-year-old man was diagnosed with ascending colon cancer in our department. No distant metastasis was observed, but curative resection was considered impossible because of extensive local cancer invasion. Because a genetic analysis revealed the presence of the wild-type KRAS gene, 6 courses of mFOLFOX6 plus cetuximab were administered. A cPR was obtained and curative resection was performed. The final diagnosis was ypT3N1M0, ypStage III a colon cancer, and chemotherapy improved the cancer stage to Grade 1b. Six courses of FOLFOX6 were then administered, followed by observation. After 2 years 6 months, a tumor of approximately 5 cm in size was noted in the right buttock using surveillance CT and was diagnosed as recurrent colon cancer. We considered further curative resection difficult and therefore 6 courses of mFOLFOX6 plus panitumumab were administered, a cPR was obtained, and right hip tumor extirpation surgery was performed. These results suggest that chemotherapy combined with anti-EGFR antibody immunotherapy is effective in treating recurrent colon cancer.

Cooperation of distinct Rac-dependent pathways to stabilise E-cadherin adhesion.

Science.gov (United States)

Erasmus, Jennifer C; Welsh, Natalie J; Braga, Vania M M

2015-09-01

The precise mechanisms via which Rac1 is activated by cadherin junctions are not fully known. In keratinocytes Rac1 activation by cadherin junctions requires EGFR signalling, but how EGFR does so is unclear. To address which activator could mediate E-cadherin signalling to Rac1, we investigated EGFR and two Rac1 GEFs, SOS1 and DOCK180. EGFR RNAi prevented junction-induced Rac1 activation and led to fragmented localization of E-cadherin at cadherin contacts. In contrast, depletion of another EGFR family member, ErbB3, did not interfere with either process. DOCK180 RNAi, but not SOS1, prevented E-cadherin-induced Rac1 activation. However, in a strong divergence from EGFR RNAi phenotype, DOCK180 depletion did not perturb actin recruitment or cadherin localisation at junctions. Rather, reduced DOCK180 levels impaired the resistance to mechanical stress of pre-formed cell aggregates. Thus, within the same cell type, EGFR and DOCK180 regulate Rac1 activation by newly-formed contacts, but control separate cellular events that cooperate to stabilise junctions. Copyright © 2015. Published by Elsevier Inc.

SU-E-J-164: Estimation of DVH Variation for PTV Due to Interfraction Organ Motion in Prostate VMAT Using Gaussian Error Function

International Nuclear Information System (INIS)

Lewis, C; Jiang, R; Chow, J

2015-01-01

Purpose: We developed a method to predict the change of DVH for PTV due to interfraction organ motion in prostate VMAT without repeating the CT scan and treatment planning. The method is based on a pre-calculated patient database with DVH curves of PTV modelled by the Gaussian error function (GEF). Methods: For a group of 30 patients with different prostate sizes, their VMAT plans were recalculated by shifting their PTVs 1 cm with 10 increments in the anterior-posterior, left-right and superior-inferior directions. The DVH curve of PTV in each replan was then fitted by the GEF to determine parameters describing the shape of curve. Information of parameters, varying with the DVH change due to prostate motion for different prostate sizes, was analyzed and stored in a database of a program written by MATLAB. Results: To predict a new DVH for PTV due to prostate interfraction motion, prostate size and shift distance with direction were input to the program. Parameters modelling the DVH for PTV were determined based on the pre-calculated patient dataset. From the new parameters, DVH curves of PTVs with and without considering the prostate motion were plotted for comparison. The program was verified with different prostate cases involving interfraction prostate shifts and replans. Conclusion: Variation of DVH for PTV in prostate VMAT can be predicted using a pre-calculated patient database with DVH curve fitting. The computing time is fast because CT rescan and replan are not required. This quick DVH estimation can help radiation staff to determine if the changed PTV coverage due to prostate shift is tolerable in the treatment. However, it should be noted that the program can only consider prostate interfraction motions along three axes, and is restricted to prostate VMAT plan using the same plan script in the treatment planning system

Potent and Selective Peptide-based Inhibition of the G Protein Gαq.

Science.gov (United States)

Charpentier, Thomas H; Waldo, Gary L; Lowery-Gionta, Emily G; Krajewski, Krzysztof; Strahl, Brian D; Kash, Thomas L; Harden, T Kendall; Sondek, John

2016-12-02

In contrast to G protein-coupled receptors, for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gα q binds its two major classes of effectors, the phospholipase C (PLC)-β isozymes and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gα q within its canonical binding site consisting of a groove formed between switch II and helix α3. This information was exploited to synthesize peptides that bound active Gα q in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gα q A representative peptide was specific for active Gα q because it did not bind inactive Gα q or other classes of active Gα subunits and did not inhibit the activation of PLC-β3 by Gβ 1 γ 2 In contrast, the peptide robustly prevented activation of PLC-β3 or p63RhoGEF by Gα q ; it also prevented G protein-coupled receptor-promoted neuronal depolarization downstream of Gα q in the mouse prefrontal cortex. Moreover, a genetically encoded form of this peptide flanked by fluorescent proteins inhibited Gα q -dependent activation of PLC-β3 at least as effectively as a dominant-negative form of full-length PLC-β3. These attributes suggest that related, cell-penetrating peptides should effectively inhibit active Gα q in cells and that these and genetically encoded sequences may find application as molecular probes, drug leads, and biosensors to monitor the spatiotemporal activation of Gα q in cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of mechanical feedback on the stability of cardiac scroll waves: A bidomain electro-mechanical simulation study.

Science.gov (United States)

Colli Franzone, P; Pavarino, L F; Scacchi, S

2017-09-01

In this work, we investigate the influence of cardiac tissue deformation on re-entrant wave dynamics. We have developed a 3D strongly coupled electro-mechanical Bidomain model posed on an ideal monoventricular geometry, including fiber direction anisotropy and stretch-activated currents (SACs). The cardiac mechanical deformation influences the bioelectrical activity with two main mechanical feedback: (a) the geometric feedback (GEF) due to the presence of the deformation gradient in the diffusion coefficients and in a convective term depending on the deformation rate and (b) the mechano-electric feedback (MEF) due to SACs. Here, we investigate the relative contribution of these two factors with respect to scroll wave stability. We extend the previous works [Keldermann et al., Am. J. Physiol. Heart Circ. Physiol. 299, H134-H143 (2010) and Hu et al., PLoS One 8(4), e60287 (2013)] that were based on the Monodomain model and a simple non-selective linear SAC, while here we consider the full Bidomain model and both selective and non-selective components of SACs. Our simulation results show that the stability of cardiac scroll waves is influenced by MEF, which in case of low reversal potential of non-selective SACs might be responsible for the onset of ventricular fibrillation; GEF increases the scroll wave meandering but does not determine the scroll wave stability.

Comprehensive Binary Interaction Mapping of SH2 Domains via Fluorescence Polarization Reveals Novel Functional Diversification of ErbB Receptors

Science.gov (United States)

Ciaccio, Mark F.; Chuu, Chih-pin; Jones, Richard B.

2012-01-01

First-generation interaction maps of Src homology 2 (SH2) domains with receptor tyrosine kinase (RTK) phosphosites have previously been generated using protein microarray (PM) technologies. Here, we developed a large-scale fluorescence polarization (FP) methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB) domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry procedures. This

Comprehensive binary interaction mapping of SH2 domains via fluorescence polarization reveals novel functional diversification of ErbB receptors.

Directory of Open Access Journals (Sweden)

Ronald J Hause

Full Text Available First-generation interaction maps of Src homology 2 (SH2 domains with receptor tyrosine kinase (RTK phosphosites have previously been generated using protein microarray (PM technologies. Here, we developed a large-scale fluorescence polarization (FP methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry

Results of the Accord 12/0405- prodige 2 randomized test in the rectum cancers of stage T(2) 3-4 NX M0; Resultat de l'essai randomise Accord 12/0405-prodige 2 dans les cancers du rectum de stade T(2) 3-4 NX M0

Energy Technology Data Exchange (ETDEWEB)

Gerard, J.P.; Benezery, K. [Centre Antoine-Lacassagne, 06 - Nice (France); Azria, D.; Gourgou-Bourgade, S. [CRLCC Val d' Aurelle-Paul-Lamarque, 34 - Montpellier (France); Martel-Laffay, I. [Centre Leon-Berard, 69 - Lyon (France); Hennequin, C. [Hopital St-Louis, 75 - Paris (France); Etienne, P.L. [Clinique Armoricaine de Radiologie, 22 - Saint-Brieuc (France); Vendrely, V. [CHU, 33 - Bordeaux (France); Peiffert, D. [Centre Alexis-Vautrin, 54 - Nancy (France); Montoto-Grillot, C. [FNCLCC-BECT, 75 - Paris (France)

2009-10-15

The Capox 50 protocol increase the early toxicity without reducing the possibilities of surgery. It does not increase neither the sphincter conservation rate nor the surgery complications. It improves noticeably the histological tumor response (ypT) and the negative circumferential margin rate. The Star Italian protocol randomized for similar patients exclusively oxaliplatin, without increasing the histological tumor response rate and with 25% of grade 3 or 4 early toxicity. In comparison between the tests Accord 12 and Star it is possible to propose as neoadjuvant treatment of these rectum cancers (stage T3-4 Mo) a Cape 50 protocol associating a 50 Gy radiotherapy in 25 fractions and five weeks and a concomitant chemotherapy (capecitabine: 1600 mg/M{sup 2}/d). The oxaliplatin can be proposed out of radiotherapy to eradicate the infra clinical metastases. (N.C.)

An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress.

Science.gov (United States)

West, Junior J; Zulueta-Coarasa, Teresa; Maier, Janna A; Lee, Donghoon M; Bruce, Ashley E E; Fernandez-Gonzalez, Rodrigo; Harris, Tony J C

2017-08-07

In response to a pulling force, a material can elongate, hold fast, or fracture. During animal development, multi-cellular contraction of one region often stretches neighboring tissue. Such local contraction occurs by induced actomyosin activity, but molecular mechanisms are unknown for regulating the physical properties of connected tissue for elongation under stress. We show that cytohesins, and their Arf small G protein guanine nucleotide exchange activity, are required for tissues to elongate under stress during both Drosophila dorsal closure (DC) and zebrafish epiboly. In Drosophila, protein localization, laser ablation, and genetic interaction studies indicate that the cytohesin Steppke reduces tissue tension by inhibiting actomyosin activity at adherens junctions. Without Steppke, embryogenesis fails, with epidermal distortions and tears resulting from myosin misregulation. Remarkably, actomyosin network assembly is necessary and sufficient for local Steppke accumulation, where live imaging shows Steppke recruitment within minutes. This rapid negative feedback loop provides a molecular mechanism for attenuating the main tension generator of animal tissues. Such attenuation relaxes tissues and allows orderly elongation under stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Scham im Kino : Kleine Phänomenologie eines peinlichen Gefühls

NARCIS (Netherlands)

Hanich, Julian

Wer ans Kino denkt, denkt nicht an Scham. Die Emotionsmaschine „Kino“ rührt das Publikum zu Tränen, versetzt es in Angst und Schrecken oder zwingt es zum Lachen. Zuschauer reagieren wütend, erfreut, angeekelt, sie staunen und bewundern. Vielleicht sind sie sogar heimlich in Cary Grant oder Claudia

On-site detection of Phytophthora spp.—single-stranded target DNA as the limiting factor to improve on-chip hybridization

International Nuclear Information System (INIS)

Schwenkbier, Lydia; Pollok, Sibyll; Popp, Jürgen; Weber, Karina; König, Stephan; Wagner, Stefan; Werres, Sabine; Weber, Jörg; Hentschel, Martin

2014-01-01

We report on a lab-on-a-chip approach for on-site detection of Phytophthora species that allows visual signal readout. The results demonstrate the significance of single-stranded DNA (ssDNA) generation in terms of improving the intensity of the hybridization signal and to improve the reliability of the method. Conventional PCR with subsequent heat denaturation, sodium hydroxide-based denaturation, lambda exonuclease digestion and two asymmetric PCR methods were investigated for the species P. fragariae, P. kernoviae, and P. ramorum. The positioning of the capture probe within the amplified yeast GTP-binding protein (YPT1) target DNA was also of interest because it significantly influences the intensity of the signal. Statistical tests were used to validate the impact of the ssDNA generation methods and the capture-target probe position. The single-stranded target DNA generated by Linear-After-The-Exponential PCR (LATE-PCR) was found to produce signal intensities comparable to post-PCR exonuclease treatment. The LATE-PCR is the best method for the on-site detection of Phytophthora because the enzymatic digestion after PCR is more laborious and time-consuming. (author)

Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the reverse of the Will Rogers phenomenon?

Science.gov (United States)

Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Hess, Clemens; Becker, Heinz; Sauer, Rolf; Wittekind, Christian; Rödel, Claus

2015-06-01

Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes. © 2015 American Cancer Society.

Different metastasis promotive potency of small G-proteins RalA and RalB in in vivo hamster tumor model

Directory of Open Access Journals (Sweden)

Trukhanova Lyubov S

2011-06-01

Full Text Available Abstract Background Previously we have shown that oncogenic Ha-Ras stimulated in vivo metastasis through RalGEF-Ral signaling. RalA and RalB are highly homologous small G proteins belonging to Ras superfamily. They can be activated by Ras-RalGEF signaling pathway and influence cellular growth and survival, motility, vesicular transport and tumor progression in humans and in animal models. Here we first time compared the influence of RalA and RalB on tumorigenic, invasive and metastatic properties of RSV transformed hamster fibroblasts. Methods Retroviral vectors encoding activated forms or effector mutants of RalA or RalB proteins were introduced into the low metastatic HET-SR cell line. Tumor growth and spontaneous metastatic activity (SMA were evaluated on immunocompetent hamsters after subcutaneous injection of cells. The biological properties of cells, including proliferation, clonogenicity, migration and invasion were determined using MTT, wound healing, colony formation and Boyden chamber assays respectively. Protein expression and phosphorylation was detected by Westen blot analysis. Extracellular proteinases activity was assessed by substrate-specific zymography. Results We have showed that although both Ral proteins stimulated SMA, RalB was more effective in metastasis stimulation in vivo as well as in potentiating of directed movement and invasion in vitro. Simultaneous expression of active RalA and RalB didn't give synergetic effect on metastasis formation. RalB activity decreased expression of Caveolin-1, while active RalA stimulated MMP-1 and uPA proteolytic activity, as well as CD24 expression. Both Ral proteins were capable of Cyclin D1 upregulation, JNK1 kinase activation, and stimulation of colony growth and motility. Among three main RalB effectors (RalBP1, exocyst complex and PLD1, PLD1 was essential for RalB-dependent metastasis stimulation. Conclusions Presented results are the first data on direct comparison of RalA and Ral

Experimentelle, analytische und numerische Untersuchungen des Rührreibschweißprozesses

OpenAIRE

Hoßfeld, Max

2016-01-01

Mit dem Rührreibschweißverfahren steht seit einigen Jahren eine Fügetechnologie zur Verfügung, mit der viele fügetechnische Problemstellungen speziell beim Fügen von Aluminiumlegierungen gelöst oder vermieden werden können. Mittels Rührreibschweißen können sämtliche Aluminiumlegierungen zuverlässig, hocheffizient und mit einem sehr hohen Verbindungswirkungsgrad gefügt werden. Dabei weisen rührreibgeschweißte Verbindungen bereits ohne Nachbehandlung sehr gute statische und zyklische Festigkeit...

The potential for the production of bioenergy for lighting and cooking using Jatropha (Jatropha curcas L. Euphorbiaceae) by small scale farmers on the Kenyan coast

OpenAIRE

Boerstler, Fritjof

2010-01-01

The overall objective of this study is to examine the potential of introducing renewable biomass for a decentralized household energy provision in rural areas at the Kenyan South Coast. The main question posed in this research is whether the renewable products of an oil tree and related energy end-use appliances could potentially be a cheap, widely available and socially accepted substitute for kerosene and traditional biomass. The research data and results are based on a UNDP GEF SGP funded...

Membrane association of the Arabidopsis ARF exchange factor GNOM involves interaction of conserved domains

DEFF Research Database (Denmark)

Anders, Nadine; Nielsen, Michael M.; Keicher, Jutta

2008-01-01

vesicle formation by activating ARF GTPases on specific membranes in animals, plants, and fungi. However, apart from the catalytic exchange activity of the SEC7 domain, the functional significance of other conserved domains is virtually unknown. Here, we show that a distinct N-terminal domain of GNOM......The GNOM protein plays a fundamental role in Arabidopsis thaliana development by regulating endosome-to-plasma membrane trafficking required for polar localization of the auxin efflux carrier PIN1. GNOM is a family member of large ARF guanine nucleotide exchange factors (ARF-GEFs), which regulate...... mediates dimerization and in addition interacts heterotypically with two other conserved domains in vivo. In contrast with N-terminal dimerization, the heterotypic interaction is essential for GNOM function, as mutations abolishing this interaction inactivate the GNOM protein and compromise its membrane...

Features micro plastic deformation auxetic beryllium irradiated with high-energy electrons

International Nuclear Information System (INIS)

Rarans'kij, M.D.; Olyijnich-Lisyuk, A.V.; Tashchuk, O.Yu.

2016-01-01

By low-frequency internal friction (LFIF) (1...3 Hz) method, the study of the behavior of the dynamic modulus of torsion (Gef) and by mathematical modeling of dislocation motion studied micro plastic deformation in naturally aged and irradiated with high-energy (18 MeV) electrons auxetic beryllium. With increasing doses of radiation found an increase in IF and speed of movement of dislocations in 2-3 times. Installed stage character micro strain auxetic Be. By mathematical modeling showed that in the irradiated material the deformation occurs due to the accelerated movement of the twin dislocations in the early stages, and anomalous dynamic deceleration of complete dislocations with an increase in the degree of deformation in the second stage. It is shown that theoretically estimated values are in good agreement with the experimentally determined.

Der antiskeptische Boden unter dem Gehirn im Tank

OpenAIRE

Müller, Olaf L.

2001-01-01

Crispin Wright hat die bislang beste Rekonstruktion von Putnams Beweis gegen die skeptische Hypothese vom Gehirn im Tank vorgelegt. Aber selbst in Wrights Fassung hat der Beweis einen Mangel: Er wird mithilfe eines Prädikates wie z.B. "Tiger" geführt und funktioniert nur, wenn man sich darauf verlassen kann, dass es Tiger wirklich gibt. Aber die Skeptikerin bestreitet, über die Existenz von Tigern bescheid zu wissen. Das Problem lässt sich dadurch beheben, dass man den Beweis – statt mit dem ...

Entweder/Und, Wiederkunft/Erlösung

OpenAIRE

Löschenkohl, Birte

2016-01-01

Mit merklicher Begeisterung verfasst Walter Benjamin am 6. Januar 1938 einen Brief an Max Horkheimer, in dem er ihm von einem "seltnen Fund" von höchster Bedeutsamkeit berichtet, der seine Arbeit "entscheidend beeinflussen" werde (GB VI, 9). Bei dem Fund handelte es sich um Louis Auguste Blanquis (1805–1881) kosmologische Schrift 'L’Éternité par les astres', verfasst 1871 im Kerker einer Gefängnisburg vor der Küste der Bretagne. Der Autor, einer der umtriebigsten Revolutionäre Frankreichs im ...

Detection methods for atoms and radicals in the gas phase

Science.gov (United States)

Hack, W.

This report lists atoms and free radicals in the gas phase which are of interest for environmental and flame chemistry and have been detected directly. The detection methods which have been used are discussed with respect to their range of application, specificity and sensitivity. In table 1, detection methods for the five atoms of group IV (C, Si, Ge, Sn, Pb) and about 60 radicals containing at least one atom of group IV are summarized (CH, Cd, Cf, CC1, CBr, Cn, Cs, CSe, CH2, CD2, Chf, Cdf, CHC1, CHBr, CF2, CC12, CBr2, CFC1, CFBr, CH3, CD3, CF3, CH2F, CH2C1, CH2Br, CHF2, CHC12, CHBr2, Hco, Fco, CH30, CD30, CH2OH, CH3S, Nco, CH4N, CH302, CF302; C2, C2N, C2H, C20, C2HO, C2H3, C2F3, C2H5, C2HsO, C2H4OH, CH3CO, CD3CO, C2H3O, C2H502, CH3COO2, C2H4N, C2H6N, C3; Si, SiF, SiF2, SiO, SiC, Si2; Ge, GeC, GeO, GeF, GeF2, GeCl2, Sn, SnF, SnO, SnF2, Pb, PbF, PbF2, PbO, PbS). In table 2 detection methods for about 25 other atoms and 60 radicals are listed: (H, D, O, O2, Oh, Od, HO2, DO2, F, Ci, Br, I, Fo, Cio, BrO, Io, FO2, C1O2, Li, Na, K, Rb, Cs, N, N3, Nh, Nd, Nf, Nci, NBr, NH2, ND2, Nhd, Nhf, NF2, NC12, N2H3, No, NO2, NO3, Hno, Dno, P, Ph, Pd, Pf, Pci, PH2, PD2, PF2, Po, As, AsO, AsS, Sb, Bi, S, S2, Sh, Sd, Sf, SF2, So, Hso, Dso, Sn, Se, Te, Se2, SeH, SeD, SeF, SeO, SeS, SeN, TeH, TeO, Bh, BH2, Bo, Bn, B02, Cd, Hg, UF5). The tables also cite some recent kinetic applications of the various methods.

Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.

Directory of Open Access Journals (Sweden)

Masao Terasawa

Full Text Available The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain the Dbl homology domain typically found in guanine nucleotide exchange factors (GEFs, DOCK2 mediates the GTP-GDP exchange reaction for Rac via its DOCK homology region (DHR-2 (also known as CZH2 or Docker domain. DOCK2 DHR-2 domain is composed of three lobes, and Rac binding site and catalytic center are generated entirely from lobes B and C. On the other hand, lobe A has been implicated in dimer formation, yet its physiological significance remains unknown. Here, we report that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration. We found that unlike wild-type DOCK2, DOCK2 mutant lacking lobe A failed to restore motility and polarity when expressed in thymoma cells and primary T cells lacking endogenous expression of DOCK2. Similar results were obtained with the DOCK2 point mutant having a defect in dimerization. Deletion of lobe A from the DHR-2 domain did not affect Rac GEF activity in vitro. However, fluorescence resonance energy transfer analyses revealed that lobe A is required for DOCK2 to activate Rac effectively during cell migration. Our results thus indicate that DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and Rac are localized to the plasma membrane.

Ric-8A, a Gα protein guanine nucleotide exchange factor potentiates taste receptor signaling

Directory of Open Access Journals (Sweden)

Claire J Fenech

2009-10-01

Full Text Available Taste receptors for sweet, bitter and umami tastants are G-protein coupled receptors (GPCRs. While much effort has been devoted to understanding G-protein-receptor interactions and identifying the components of the signalling cascade downstream of these receptors, at the level of the G-protein the modulation of receptor signal transduction remains relatively unexplored. In this regard a taste-specific regulator of G-protein signaling (RGS, RGS21, has recently been identified. To study whether guanine nucleotide exchange factors (GEFs are involved in the transduction of the signal downstream of the taste GPCRs we investigated the expression of Ric-8A and Ric-8B in mouse taste cells and their interaction with G-protein subunits found in taste buds. Mammalian Ric-8 proteins were initially identified as potent GEFs for a range of Gα subunits and Ric-8B has recently been shown to amplify olfactory signal transduction. We find that both Ric-8A and Ric-8B are expressed in a large portion of taste bud cells and that most of these cells contain IP3R-3 a marker for sweet, umami and bitter taste receptor cells. Ric-8A interacts with Gα-gustducin and Gαi2 through which it amplifies the signal transduction of hTas2R16, a receptor for bitter compounds. Overall, these findings are consistent with a role for Ric-8 in mammalian taste signal transduction.

Phased Array Noise Source Localization Measurements of an F404 Nozzle Plume at Both Full and Model Scale

Science.gov (United States)

Podboy, Gary G.; Bridges, James E.; Henderson, Brenda S.

2010-01-01

A 48-microphone planar phased array system was used to acquire jet noise source localization data on both a full-scale F404-GE-F400 engine and on a 1/4th scale model of a F400 series nozzle. The full-scale engine test data show the location of the dominant noise sources in the jet plume as a function of frequency for the engine in both baseline (no chevron) and chevron configurations. Data are presented for the engine operating both with and without afterburners. Based on lessons learned during this test, a set of recommendations are provided regarding how the phased array measurement system could be modified in order to obtain more useful acoustic source localization data on high-performance military engines in the future. The data obtained on the 1/4th scale F400 series nozzle provide useful insights regarding the full-scale engine jet noise source mechanisms, and document some of the differences associated with testing at model-scale versus fullscale.

Changes in Ect2 Localization Couple Actomyosin-Dependent Cell Shape Changes to Mitotic Progression

Science.gov (United States)

Matthews, Helen K.; Delabre, Ulysse; Rohn, Jennifer L.; Guck, Jochen; Kunda, Patricia; Baum, Buzz

2012-01-01

Summary As they enter mitosis, animal cells undergo profound actin-dependent changes in shape to become round. Here we identify the Cdk1 substrate, Ect2, as a central regulator of mitotic rounding, thus uncovering a link between the cell-cycle machinery that drives mitotic entry and its accompanying actin remodeling. Ect2 is a RhoGEF that plays a well-established role in formation of the actomyosin contractile ring at mitotic exit, through the local activation of RhoA. We find that Ect2 first becomes active in prophase, when it is exported from the nucleus into the cytoplasm, activating RhoA to induce the formation of a mechanically stiff and rounded metaphase cortex. Then, at anaphase, binding to RacGAP1 at the spindle midzone repositions Ect2 to induce local actomyosin ring formation. Ect2 localization therefore defines the stage-specific changes in actin cortex organization critical for accurate cell division. PMID:22898780

The dynamic interplay of plasma membrane domains and cortical microtubules in secondary cell wall patterning

Directory of Open Access Journals (Sweden)

Yoshihisa eOda

2013-12-01

Full Text Available Patterning of the cellulosic cell wall underlies the shape and function of plant cells. The cortical microtubule array plays a central role in the regulation of cell wall patterns. However, the regulatory mechanisms by which secondary cell wall patterns are established through cortical microtubules remain to be fully determined. Our recent study in xylem vessel cells revealed that a mutual inhibitory interaction between cortical microtubules and distinct plasma membrane domains leads to distinctive patterning in secondary cell walls. Our research revealed that the recycling of active and inactive ROP proteins by a specific GAP and GEF pair establishes distinct de novo plasma membrane domains. Active ROP recruits a plant-specific microtubule-associated protein, MIDD1, which mediates the mutual interaction between cortical microtubules and plasma membrane domains. In this mini review, we summarize recent research regarding secondary wall patterning, with a focus on the emerging interplay between plasma membrane domains and cortical microtubules through MIDD1 and ROP.

Konzepte und Methoden zur Qualitätssicherung bei der Produktion von hypertextuellen Online-Lernumgebungen

Directory of Open Access Journals (Sweden)

Christian Swertz

2002-04-01

Full Text Available Die didaktische Ontologie der Webdidaktik ermöglicht die Qualitätssicherung von Prozessen und Ergebnissen bei der Produktion von Online- Lernumgebungen. Die Qualität wird durch die am pädagogischen Prozess beteiligten Menschen bestimmt. Der Qualitätssicherungsprozess kann durch Software unterstützt werden. Für diese Prozesse der Qualitätssicherung bringt der Autor Beispiele aus dem Lerndorf (www.lerndorf.de und der Lernumgebung des von der Deutschen Bundesstiftung Umwelt geförderten Forschungs- und Entwicklungsprojekt «Zentrum für Umweltwissen und Bildung» (ZUB.

Análisis de la Cooperación Multilateral para la Gestión de biodiversidad en Instituciones Subregionales. Caso de Estudio: Estrategia regional para la conservación y uso Sostenible de recursos en el Amazonas (TCA) y Proyecto Facilitación de financiamiento para negocios de biodiversidad y apoyo al desarrollo de actividades del mercado en la Región Andina (CAN) 2000-2009

OpenAIRE

Martín Hilarión, Jorge Luis

2012-01-01

Este trabajo de investigación analiza la importancia de la cooperación internacional para la gestión de biodiversidad entregada por el Global Environmental Facilty-GEF, para la conservación y uso sostenible de la biodiversidad en la cuenca Andino-amazónica. Esto a través del estudio de los proyectos de alcance regional financiados a dos instituciones subregionales, el primero, “Estrategia Regional para la Conservación y Uso Sostenible de Recursos en el Amazonas” perteneciente al Tratado de Co...

Der Einfluss des mikrovaskulären Systems auf das Überleben eines Hauttransplantats

OpenAIRE

Motsch, Benjamin

2017-01-01

Transplantierte Organe benötigen eine zuverlässige Versorgung über das Gefäßsystem. Daher richtet diese Studie ihr Augenmerk darauf, ob eine Hemmung von Thrombozyten, sowohl allein als auch in Kombination mit einem mTOR-Hemmer, einen positiven Effekt auf die Ausprägung der mikrovaskulären Struktur in Hauttransplantaten bei einem allogenen Mausmodell hat. Für die Hauttransplantation wurde die Haut von C57BL6 (H-2b) als Spendertiere auf CBA/J(H-2k) Mäuse übertragen. Auf diese Weise wurde eine v...

Kurz zum Klima: Zu viel Salz verdirbt den Boden

OpenAIRE

Zimmer, Markus; Lippelt, Jana; Frank, Jonas

2012-01-01

Der zunehmende Einsatz von Anlagen zur Bewässerung sowie mangelnde Erfahrungswerte und Unkenntnis über den richtigen Einsatz der künstlichen Bewässerung haben in den letzten Jahrzehnten zu einer massiven Zunahme der Versalzung des Bodens geführt. Durch diese Bodenversalzung werden weite Flächen für die Landwirtschaft unbrauchbar. Sie sind nur durch hohen Aufwand und Kosten wieder renaturierbar. Der Beitrag in der Reihe »Kurz zum Klima« gibt einen Überblick über die Versalzung in Anbaugebiet...

Databases on Demand (DBoD)

OpenAIRE

Poley, Christoph

2009-01-01

In einer der letzten Ausgaben haben wir ausführlich über das Projekt DBoD berichtet. Darin wurde detailliert auf den Inhalt von DBoD, die Benutzergruppen an den Hochschulen, auf technische Details und die Verknüpfung it dem Datenbank-Informationssystem (DBIS) eingegangen. DBoD wird von der Europäischen Union im Rahmen des Europäischen Fonds für regionale Entwicklung (EFRE) gefördert. Seitdem ist ein halbes Jahr vergangen. Zeit, in der sich DBoD von einem Projekt in den Startlöchern hin zu ein...

Die «ASEAN-Wirtschaftsgemeinschaft»

DEFF Research Database (Denmark)

Juego, Bonn

2014-01-01

Seit dem Ende der 1990er-Jahre verfolgt die ASEAN die Vision einer politischen, wirtschaftlichen und sozialen Gemeinschaft. Doch wie realistisch ist die Umsetzung eines solch ambitionierten Vorhabens vor dem Hintergrund der enormen Heterogenität der Region? ASEAN vereint Staaten auf...... Entwicklungsstufen, wie sie unterschiedlicher kaum sein können. Der Autor, Bonn Juego, nimmt die ASEAN Vision 2020 sowie die Debatten, die diesbezüglich in den einzelnen Ländern geführt werden, unter die Lupe. Er geht dem Potenzial des ASEANAnsatzes zu sozialer Teilhabe und wirtschaftlicher Verteilungsgerechtigkeit...

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders

International Nuclear Information System (INIS)

Bujko, Krzysztof; Richter, Piotr; Kolodziejczyk, Milena; Nowacki, Marek P.; Kulig, Jan; Popiela, Tadeusz; Gach, Tomasz; Oledzki, Janusz; Sopylo, Rafal; Meissner, Wiktor; Wierzbicki, Ryszard; Polkowski, Wojciech; Kowalska, Teresa; Stryczynska, Grazyna; Paprota, Krzysztof

2009-01-01

Background and purpose: To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer. Materials and methods: Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5 x 5 Gy + 4 Gy boost (N = 31) or chemoradiation (50.4 Gy + 5.4 Gy boost, 1.8 Gy per fraction + 5-fluorouracyl and leucovorin; N = 13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin. Results: The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure. Conclusion: Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.

Über die Gefügeausbildung technischer Magnesiumlegierungen in industriellen Gießprozessen

OpenAIRE

Klaus, Gerald

2011-01-01

The demand for lightweight constructions and light weight materials is probably as old as the transportation of people and goods. The aspiration in gaining even better light weight materials with increased mechanical properties is an old, but still actual topic. At this point magnesium alloys can be applied to fullfill this demand. Actually available commercial alloys have to be improved regarding their mechanical properties, especially for increased temperatures. This work aims to gain a bet...

BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

Science.gov (United States)

Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

2018-05-03

BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

List of hazardous substances for 1995. Hazardous substances at the working place; Gefahrstoffliste 1995. Gefahrstoffe am Arbeitsplatz

Energy Technology Data Exchange (ETDEWEB)

Pflaumbaum, W. [Berufsgenossenschaftliches Inst. fuer Arbeitssicherheit, St. Augustin (Germany); Blome, H. [Berufsgenossenschaftliches Inst. fuer Arbeitssicherheit, St. Augustin (Germany); Kleine, H. [Berufsgenossenschaftliches Inst. fuer Arbeitssicherheit, St. Augustin (Germany); Stamm, R. [Berufsgenossenschaftliches Inst. fuer Arbeitssicherheit, St. Augustin (Germany)

1995-04-01

The List of Hazardous Substances for 1995 contains a summarizing table of the most important regulations concerning safety and health at the working place together with supplementary information. The present version, compiled by the Berufsgenossenschaftliche Institut fuer Arbeitssicherheit (Trade Associations` Institute for Working Safety), is an update of the List of Hazardous Substances for 1994. The List contains the prescribed classifications and designations of substances and preparations pursuant to the EC Directive 67/548/EEC (including the 20th amendment); the substances contained in the ``List of carcinogenic, mutagenic and reproduction-endangering substances`` (TRGS 905); the air pollution limit values of MAK and TRK (``Air pollution limit values at the working place``, TRGS 900); and the Biological Tolerance Values (BAT, TRGS 903). At the end it provides information, amongst other things, on measuring methods (DFG, ZH1/120, BIA desk folder, HSE, NIOSH, OSHA), industrial medicine, substance-specific regulations of the Ordinance On Hazardous Substances (GefStoffV), Ordinance of Prohibitions Concerning Chemicals (ChemVerbotsV), and Hazardous Substances Technical Code (TRGS), and on regulations of the trade associations. The amendments to the Technical Code (e.g. TRGS 900 and 905) published in early 1995 have also been incorporated. (orig./SR) [Deutsch] Das Berufsgenossenschaftliche Institut fuer Arbeitssicherheit - BIA hat in der Gefahrstoffliste 1995 die wichtigsten Regelungen fuer die Sicherheit und Gesundheit am Arbeitsplatz sowie ergaenzende Hinweise in einer Tabelle zusammengefasst. Die vorliegende Version aktualisiert die Gefahrstoffliste aus dem Jahr 1994. Die Liste enthaelt die vorgeschriebenen Einstufungen und Kennzeichnungen von Stoffen und Zubereitungen gemaess der EU-Richtlinie 67/548/EWG (einschliesslich 20. Anpassung) sowie die in der TRGS 905 ``Verzeichnis krebserzeugender, erbgutveraendernder und fortpflanzungsgefaehrdender Stoffe

阴道毛滴虫Rac1蛋白的cDNA克隆和序列分析%Molecular Cloning and Characterization of a Rac1 Homologue cDNA from Trichomonas vaginalis

Institute of Scientific and Technical Information of China (English)

傅玉才; 章家新; 郑晓虹; 刘红

2004-01-01

Objective To clone and characterize a Racl homologue from Trichomonas vaginalis for studying cell cycle of the organism. Methods A cDNA library derived from T. vaginalis mRNA was constructed into λ TriplEx2 phage vector. An expression sequence tag program was launched. Sequences of cDNA clones were analyzed using NCBI BLAST algorithms, and ClustalW and Treeview programs. Results A cDNA clone with a length of 714 base pairs was isolated. The sequence analysis showed that the cDNA clone has an open reading frame with 600 bp. The deduced amino acid sequence from the open reading frame contains 200 residuals and is most homologous to Rac1 subfamily of Rho GTPases with ＞ 60% identity. The conserved sequence elements of Rho GTPases, such as GTP-binding sites, GTPase-activating protein (GAP) interaction motifs, GTP-dissociation inhibitors (GDI) interaction motifs, guanine nucleotide exchange factor (GEF) interaction elements, etc, were detected in the amino acid sequence. The phylogenetic analysis showed that the cDNA clone is grouped in the Rac subfamily and is more closely related to Rac1 proteins of protozoa. Conclusion The cDNA clone isolated belongs to Rac subfamily of Rho GTPases and is probably a Rac1 protein of T. vaginalis.%目的获得阴道毛滴虫Rac1蛋白的cDNA克隆,研究其在细胞周期中的调解作用.方法提取阴道毛滴虫总RNA,构建cDNA表达文库,随机分离cDNA克隆并测序.用在线生物分析软件NCBI BLAST、ClustalW以及Treeview等程序进行序列分析.结果获得一株有714 bp的cDNA克隆.序列分析表明,该克隆开放阅读框具600 bp,推测肽链具200个氨基酸.该肽链与Rho家族中Rac1鸟苷三磷酸(GTP)酶同源性最高(＞60%),并具多种Rho GTP酶的保守基序,如GTP结合部位、GTP酶激活蛋白作用基序、GTP分离抑制因子作用基序、鸟嘌呤核苷酸交换因子作用基序等.进化树分析显示该克隆属于Rac亚家族GTP酶,与原虫Rac1蛋白最接近.结论该克隆�

Emoción, Sentimiento y Pasión en Kant

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Ana Marta González

2015-12-01

Full Text Available RESUMEN:En este trabajo se analiza el modo en que Kant distingue entre sentimiento y emoción, por un lado, y emoción y pasión, por otro, para mostrar: 1 que bajo el término “emoción” (Affekt Kant entiende principalmente la afección orgánica privada de contenido cognitivo, aunque precedida y seguida de representaciones; 2 que la emoción constituye un elemento integral de lo que Kant denomina “sentimiento” (Gefühl, término del que se sirve para designar la dimensión subjetiva de la experiencia en sentido amplio, no limitado a la afección empírica; 3 que su concepción negativa de la pasión justifica la posterior distinción entre emoción y pasión introducida en los estudios científicos.

WBP: The wood Brazilian BIG-GT demonstration project

Energy Technology Data Exchange (ETDEWEB)

Carpentieri, E. [Companhia Hidro Eletrica do Sao Francisco, Recife (Brazil)

1993-12-31

Brazil is one of the leading countries in the use of renewable energy. Most of its electricity comes from hydro power, about 200,000 barrels a day of ethanol from sugar cane is used as fuel, around 38% of the pig iron, and 20% of the steel production, uses charcoal as a reducing medium. Located in the tropics, with the sun shining all year round, and with its vast territory, the Country may be regarded as having all the basic conditions to develop a modern Biomass for Electricity industry. The conjunction of those characteristics with, the necessity of developing new energy resources for electricity production in the Northeast of the Country, the results of the studies made by Princeton University, Shell and Chesf, the progress achieved by the BIG-GT (Biomass Integrated Gasification Gas Turbine) technology in Europe, and the organization of the Global Environment Facility (GEF), provided the unique opportunity for the implementation of a commercial demonstration in Brazil. This paper describes the idea, the scope, the technical challenges, and actual status of development of the WBP, a project which aims to demonstrate the commercial viability of the BIG-GT technology. It also highlights, the project management structure, the role of the GEF, World Bank and of the United Nations Development Program (UNDP), and the participation of the Brazilian Federal Government, through the Ministry of Science and Technology (MCT). Finally it describes the Participants (ELETROBRAS, CVRD, CIENTEC, SHELL, and CHESF), their role in the project, and how the group was formed and operates.

Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin

Science.gov (United States)

Lin, Changsheng; Ear, Jason; Midde, Krishna; Lopez-Sanchez, Inmaculada; Aznar, Nicolas; Garcia-Marcos, Mikel; Kufareva, Irina; Abagyan, Ruben; Ghosh, Pradipta

2014-01-01

A long-standing issue in the field of signal transduction is to understand the cross-talk between receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major and distinct signaling hubs that control eukaryotic cell behavior. Although stimulation of many RTKs leads to activation of trimeric G proteins, the molecular mechanisms behind this phenomenon remain elusive. We discovered a unifying mechanism that allows GIV/Girdin, a bona fide metastasis-related protein and a guanine-nucleotide exchange factor (GEF) for Gαi, to serve as a direct platform for multiple RTKs to activate Gαi proteins. Using a combination of homology modeling, protein–protein interaction, and kinase assays, we demonstrate that a stretch of ∼110 amino acids within GIV C-terminus displays structural plasticity that allows folding into a SH2-like domain in the presence of phosphotyrosine ligands. Using protein–protein interaction assays, we demonstrated that both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Gαi, and growth factor receptors and for activation of Gαi after growth factor stimulation. Expression of a SH2-deficient GIV mutant (Arg 1745→Leu) that cannot bind RTKs impaired all previously demonstrated functions of GIV—Akt enhancement, actin remodeling, and cell migration. The mechanistic and structural insights gained here shed light on the long-standing questions surrounding RTK/G protein cross-talk, set a novel paradigm, and characterize a unique pharmacological target for uncoupling GIV-dependent signaling downstream of multiple oncogenic RTKs. PMID:25187647

Anticholinerge Therapie der OAB

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Hampel C

2007-01-01

Full Text Available Kenntnisse über Differentialdiagnostik und Pathophysiologie des Blasenüberaktivitäts-Syndroms sind essentiell für eine erfolgreiche Therapie. Obwohl Verhaltenstraining und Elektrostimulation ihre Wirksamkeit bei OAB bewiesen haben, ist die Therapie der ersten Wahl nach wie vor die anticholinerge Behandlung. Dessen ungeachtet ist die Einnahmetreue der Patienten unbefriedigend, was in der letzten Zeit zu verschiedenen Medikamentenneuentwicklungen mit verbesserter Verträglichkeit bei gleichbleibend hoher Effektivität geführt hat. Retard-Formulierungen, extraenterale Applikationswege und Rezeptor-Subselektivität sind hierbei die Prinzipien, welche die Behandlungsakzeptanz und Patientenzufriedenheit steigern sollen.

Bibliothekarische Berufsethik in der Praxis – Ergebnisse eines Studienprojekts aus Deutschland und Großbritannien

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Jens Boye

2011-10-01

Full Text Available Sowohl in Deutschland als auch in Großbritannien existieren seit einigen Jahren Grundsatzpapiere zur Berufsethik im Informations- und Bibliotheksbereich. Neben der bloßen Existenz derartiger Kodizes stellt sich die Frage, welche Relevanz diese Dokumente in der beruflichen Praxis haben. Dieser Frage wurde im Rahmen einer Team-Projektarbeit an der FH Köln nachgegangen. Mithilfe eines standardisierten Fragebogens wurden deutsche Bibliotheksleitungen zu der Thematik befragt. In Großbritannien wurde ein Interview mit Paul Sturges geführt, darüber hinaus erfolgte eine Analyse der Online-Angebote von CILIP, insbesondere des Information Ethics Blog.

Delinking environmental concerns from energy production and use

International Nuclear Information System (INIS)

Anderson, D.

1994-01-01

The author identifies six key elements to a successful energy policy. These are: efficiency in energy pricing and taxation, pollution taxes and regulations; investment increases (such as the Global Environment Facility); national energy R ampersand D programs; international R ampersand D; and work in the field of renewable energy. Good progress is being made on the first two, which well summarizes the major activities of the international development banks. The GEF represents a small but good beginning to the third. However, there is still much work needed on the last three elements of policy. 2 refs

A stochastic killing system for biological containment of Escherichia coli

DEFF Research Database (Denmark)

Klemm, P.; Jensen, Lars Bogø; Molin, Søren

1995-01-01

Bacteria with a stochastic conditional lethal containment system have been constructed. The invertible switch promoter located upstream of the fimA gene from Escherichia coli was inserted as expression cassette in front of the Lethal gef gene deleted of its own natural promoter. The resulting...... fusion was placed on a plasmid and transformed to E. coli. The phenotype connected with the presence of such a plasmid was to reduce the population growth rate with increasing significance as the cell growth rate was reduced. In very fast growing cells, there was no measurable effect on growth rate. When...

Rezension von: Jutta Allmendinger: Verschenkte Potenziale? Lebensverläufe nicht erwerbstätiger Frauen. Frankfurt am Main u.a.: Campus Verlag 2010.

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Stefanie Maria Ernst

2011-01-01

Full Text Available Allmendiger berichtet über zwei durch das Bundesministerium für Familie, Senioren, Frauen und Jugend geförderte Projekte zu Frauen, die aus verschiedenen Gründen ihre Erwerbskarriere unterbrochen haben und in den Beruf zurückkehren wollen, aber auf erhebliche strukturelle Probleme im konservativen Wohlfahrtsstaat mit seinen ambivalenten Geschlechter- und Arbeitsordnungen stoßen. Umfassend und materialreich wird ein Sozialprofil dieser sogenannten „Schattenfrauen“ sichtbar, die allein im Begriff der traditionellen Hausfrau nicht mehr adäquat zu erfassen sind und die neuartige Herausforderungen an eine geschlechtergerechtere Arbeitsmarkt- und Gesellschaftspolitik stellen.

Transgender und „Transsexualität“ als Frage der Menschenrechte. Eine Einführung anhand von Rechtsfällen

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Arne Duncker

2006-07-01

Full Text Available Als deutschsprachige Monographie zum neueren Transgender-Recht ist die vorliegende Dissertation Greifs über weite Strecken eine Pionierarbeit. Die Autorin untersucht in einer sehr schönen fallorientierten Übersicht die aktuelle Rechtsprechung oberster europäischer Gerichte (EuGH, EGMR. Ergänzend stellt sie die österreichische Rechtslage dar und schildert als Hintergrund der juristischen Entscheidungsprozesse die Entwicklung der außerjuristischen, namentlich medizinischen Diskurse. Die Arbeit stellt einen wichtigen Schritt zur rechtswissenschaftlichen Verarbeitung der bisher vorwiegend auf kulturwissenschaftlichem und medizinischem Gebiet geführten Transgender-Diskurse dar. Ihr ist eine weite Verbreitung zu wünschen.

Multimedia und Lernstiltyp. Unterstützt Online-Distance-Learning unterschiedliche Lernstiltypen und führt zu mehr Lernerfolg?

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Petra Lindemann-Matthies

2006-09-01

Full Text Available In der vorliegenden Studie haben wir uns mit der Frage beschäftigt, ob Lernerfolg, Multimedianutzung und der Lernstiltyp nach Kolb (1984 im Distance- Learning-Kurs VIRT.UM, der online angeboten wird, zusammenhängen. Dabei stellte sich heraus, dass Studierende beim Arbeiten mit VIRT.UM zwar selektiv unter den ihnen angebotenen Multimediatypen auswählten, die Auswahl aber nicht von ihrem jeweiligen Lernstiltyp abhing. Der Lernerfolg der Studierenden wurde durch die Nutzung bestimmter Multimediatypen gefördert, hing aber ebenfalls nicht vom Lernstiltyp ab. Hierfür gibt es verschiedene, sich nicht ausschliessende Erklärungen.

Risikobasiertes Supply-Chain-Management

DEFF Research Database (Denmark)

Wieland, Andreas; Schinz, Philipp

2015-01-01

Das Management erlebt seit einigen Jahren dahingehend einen Paradigmenwechsel, dass nicht mehr Unternehmen als einzelne autonome Einheiten im Wettbewerb zueinander stehen, sondern die Supply Chains, in denen diese Unternehmen eingebunden sind. Ursachen hierfür sind beispielsweise die Auslagerung...... von Nicht-Kernprozessen auf vorgelagerte Stufen der Supply Chain oder auf Supply-Chain-Dienstleister sowie die Internationalisierung der Beschaffung. Dieser Paradigmenwechsel hat traditionelles Denken in den Schranken des Systems „Unternehmen“ abgelöst und zum Supply- Chain-Denken geführt, das vor......- und nachgelagerte Stufen des Systems „End-to-End-Supply-Chain“ einbezieht, etwa auch die Lieferanten von Lieferanten....

Reconstructive phase transition in (NH4)3TiF7 accompanied by the ordering of TiF6 octahedra.

Science.gov (United States)

Molokeev, Maxim; Misjul, S V; Flerov, I N; Laptash, N M

2014-12-01

An unusual phase transition P4/mnc → Pa\\bar 3 has been detected after cooling the (NH4)3TiF7 compound. Some TiF6 octahedra, which are disordered in the room-temperature tetragonal structure, become ordered in the low-temperature cubic phase due to the disappearance of the fourfold axis. Other TiF6 octahedra undergo large rotations resulting in huge displacements of the F atoms by 1.5-1.8 Å that implies a reconstructive phase transition. It was supposed that phases P4/mbm and Pm\\bar 3m could be a high-temperature phase and a parent phase, respectively, in (NH4)3TiF7. Therefore, the sequence of phase transitions can be written as Pm\\bar 3m → P4/mbm → P4/mnc → Pa\\bar 3. The interrelation between (NH4)3TiF7, (NH4)3GeF7 and (NH4)3PbF7 is found, which allows us to suppose phase transitions in relative compounds.

C9orf72’s interaction with Rab GTPases - modulation of membrane traffic and autophagy

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Bor Luen Tang

2016-10-01

Full Text Available Hexanucleotide repeat expansion in an intron of Chromosome 9 open reading frame 72 (C9orf72 is the most common genetic cause of Amyotrophic Lateral Sclerosis (ALS and Frontotemporal Dementia (FTD. While functional haploinsufficiency of C9orf72 resulting from the mutation may play a role in ALS/FTD, the actual cellular role of the protein has been unclear. Recent findings have now shown that C9orf72 physically and functionally interacts with multiple members of the Rab small GTPases family, consequently exerting important influences on cellular membrane traffic and the process of autophagy. Loss of C9orf72 impairs endocytosis in neuronal cell lines, and attenuated autophagosome formation. Interestingly, C9orf72 could influence autophagy both as part of a Guanine nucleotide exchange factor (GEF complex, or as a Rab effector that facilitates transport of the Unc-51-like Autophagy Activating Kinase 1 (Ulk1 autophagy initiation complex. The cellular function of C9orf72 is discussed in the light of these recent findings

Ist der Euro gefährdet? Is the European currency euro put at risk?

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Armin Rohde

2012-01-01

Full Text Available Due to high national debt in several member states of the Euro-Currency-Area which led to huge relief programmes the single European currency Euro seems to be at risk. Bur neither inflation rates nor exchange rate movements of the Euro since 1999 up to 2011 give reasons to believe that an up to now success story of the Euro will come to a sudden end in shortness. On the other hand it often had been argued that increasing national debt will inevitably lead to higher inflation rates and will endanger a currency by permanent devaluation. But the institutional and legal framework of the European monetary policy, if used correctly, will give sufficient protection against inflation pressure due to increasing national debt. The most danger for the European currency or for the European-Currency-Area can be seen in drifting apart of national competiveness between the member states of the Euro- Area, especially due to an existing lack of coordination in wage policy. Different wage policies in the member states of the Euro-Area in the past had led to different national inflation rates and had caused calculated real exchange rate movements which had lasting influence on national competiveness, which hamper international trade in the case of real appreciation or which promote international trade in the case of real depreciation..

Pretreatment Evaluation of Microcirculation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Survival in Primary Rectal Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

DeVries, Alexander Friedrich [Department of Radio-Oncology, Academic Teaching Hospital Feldkirch, Feldkirch (Austria); Piringer, Gudrun, E-mail: gudrun.piringer@hotmail.com [Department of Oncology, Wels-Grieskirchen Medical Hospital, Wels (Austria); Kremser, Christian; Judmaier, Werner [Department of Radiology, Innsbruck Medical University, Innsbruck (Austria); Saely, Christoph Hubert [Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch (Austria); Lukas, Peter [Department of Radio-Oncology, Innsbruck Medical University, Innsbruck (Austria); Öfner, Dietmar [Department of Surgery, Paracelsus Medical University, Salzburg (Austria)

2014-12-01

Purpose: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. Methods and Materials: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T{sub 1} mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration–time curve divided by the maximum of the arterial input function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. Results: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). Conclusions: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.

cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP).

Science.gov (United States)

Roberts, Owain Llŷr; Dart, Caroline

2014-02-01

The second messenger cAMP plays a central role in mediating vascular smooth muscle relaxation in response to vasoactive transmitters and in strengthening endothelial cell-cell junctions that regulate the movement of solutes, cells and macromolecules between the blood and the surrounding tissue. The vasculature expresses three cAMP effector proteins: PKA (protein kinase A), CNG (cyclic-nucleotide-gated) ion channels, and the most recently discovered Epacs (exchange proteins directly activated by cAMP). Epacs are a family of GEFs (guanine-nucleotide-exchange factors) for the small Ras-related GTPases Rap1 and Rap2, and are being increasingly implicated as important mediators of cAMP signalling, both in their own right and in parallel with the prototypical cAMP target PKA. In the present paper, we review what is currently known about the role of Epac within blood vessels, particularly with regard to the regulation of vascular tone, endothelial barrier function and inflammation.

Steroid markers to assess sewage and other sources of organic contaminants in surface sediments of Cienfuegos Bay, Cuba.

Science.gov (United States)

Tolosa, I; Mesa, M; Alonso-Hernandez, C M

2014-09-15

Analyses of faecal steroids in coastal sediments from Cienfuegos Bay Cuba indicate chronic sewage contamination at the main outfalls from the city, where concentrations of coprostanol up to 5400ngg(-)(1) (dry wt) were measured. In contrast, steroid concentrations and compositions from sites from the south part of the Bay are characteristic of uncontaminated sewage environments. The levels of coprostanol in the Cienfuegos sediments compares to the lower to mid-range of concentrations reported for coastal sediments on a world-wide basis, with sedimentary levels markedly below those previously reported for heavily impacted sites. This study delivers baseline data for further investigation of the effectiveness of the proposed sewerage plan promoted by the GEF project in Cienfuegos. Investigations on the correlations between faecal steroids and other organic contaminants confirmed that the major source of petroleum hydrocarbons within the bay was associated with the sewage effluents from the Cienfuegos city. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton

DEFF Research Database (Denmark)

Ly, Donald L.; Waheed, Faiza; Lodyga, Monika

2013-01-01

Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactiv......Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin......-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus...... in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF...

Grundlagen der ultraschallgezielten transurethralen Stammzelltherapie der Harn-Inkontinenz

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Strasser H

2005-01-01

Full Text Available In präklinischen Studien wurden Sicherheit und Durchführbarkeit von durch transurethralen Ultraschall geführten Injektionen von autologen Myo- und Fibroblasten zur Behandlung der Stressinkontinenz untersucht. Zwischen 2002 und März 2005 wurden 129 inkontinente Patienten (Alter 36–85 Jahre, 92 Frauen, 37 Männer in eine klinische Studie aufgenommen, um zu untersuchen, ob die Stressinkontinenz effektiv mittels durch transurethralen Ultraschall geführte Injektionen von autologen Myo- und Fibroblasten behandelt werden kann. Die Patienten litten an Stress- oder gemischter Harninkontinenz. Vor und nach der Therapie wurden ein definierter Inkontinenz-Score, Veränderungen der Lebensqualität sowie Morphologie und Funktion von Urethra und Rhabdosphinkter bewertet. Der transurethrale Ultraschall wurde zur Untersuchung und Visualisierung des unteren Harntraktes verwendet. Zusätzlich wurden vor und nach der Behandlung urodynamische und Labortests durchgeführt. Es wurden kleine Muskelbiopsien am Oberarm unter Lokalanästhesie entnommen und die Zellen in einem GMP-Labor zum Wachstum gebracht. Die Fibroblasten wurden fallweise mit einer kleinen Menge an Kollagen als Trägermaterial (ca. 2,5 ml gemischt. Mittels transurethralem Ultraschall und einer speziell entwickelten Injektionsvorrichtung wurden die Fibroblasten in die urethrale Mukosa zur Atrophiebehandlung injiziert. Die Myoblasten wurden direkt in den Rabdosphinkter zur Muskelrekonstruktion injiziert. Bei 108 Patienten konnte die Harninkontinenz nach der Injektion geheilt werden. Die postoperative Lebensqualität sowie die Dicke von Urethra und Rhabdosphinkter und die Aktivität und Kontraktilität des Rhabdosphinkter waren nach der Behandlung wesentlich verbessert. Bei 21 Patienten kam es zu einer Verbesserung der Harninkontinenz. Es traten keine Nebenwirkungen oder Komplikationen auf.

Die emotionale Dimension während der Sprechproduktion im Fremdsprachenlernprozess

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Bahar İŞİGÜZEL

2017-12-01

Full Text Available Die Gefühle bzw. Emotionen der Lernenden beim Fremdsprachenlehr- und Lernprozess spielen eine wichtige Rolle. Mit der Verknüpfung der Emotion und Kognition beim Lernprozess, haben die positiven Gefühle eine große Bedeutung für den Lernerfolg. Als eine produktive Fertigkeit hat das Sprechen eine wesentlich intensive Beziehung mit den Emotionen, weil es in der realen Zeit fließend laufen muss. Der Lernende soll bei der Sprechproduktion spontan die richtigen Wörter auf die richtige Art und Weise anwenden und sie auch noch verständlich aussprechen. Leider erreicht die Sprechfertigkeit meistens eine niedrigere Niveaustufe als die anderen drei (Schreiben, Lesen und Hören Fertigkeiten im Fremdsprachenunterrichtprozess. Diese qualitative Untersuchung konzentriert sich auf die Daten (Tonaufnahme, die anhand eines Interviews während einer Sprechproduktionsübung im universitären Fremdsprachenunterricht gesammelt wurden. Um die emotionale Dimension der Lernenden während der Sprechproduktion zu identifizieren, wurden im Einzelinterview die Frage „Wie fühlst du dich während du eine Fremdsprache (Englisch sprichst?“ gestellt. Die Teilnehmer dieser Untersuchung waren 29 Studenten, die im WS 2016 - 2017 an Universität Nevşehir Hacı Bektaş Veli (Türkei immatrikuliert waren. Die Auswertung des Interviews folgte mit einer Transkription und einer Interpretation der Tonaufnahmen. Die Meinungen zu der emotionalen Dimension während der Sprechproduktion der Studenten wurden kategorisiert. Die Resultate dieser qualitativen Untersuchung zeigen, dass die emotionale Dimension der Lernenden im universitären Kontext sich in drei Kategorien (positiv, negativ und frühere Ausbildung verteilen.

Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons.

Science.gov (United States)

Audebert, M; Zeman, F; Beaudoin, R; Péry, A; Cravedi, J-P

2012-04-01

Polycyclic Aromatic Hydrocarbons (PAHs) constitute a family of over one hundred compounds and can generally be found in complex mixtures. PAHs metabolites cause DNA damage which can lead to the development of carcinogenesis. Toxicity assessment of PAH complex mixtures is currently expressed in terms of toxic equivalents, based on Toxicity Equivalent Factors (TEFs). However, the definition of new TEFs for a large number of PAH could overcome some limitations of the current method and improve cancer risk assessment. The current investigation aimed at deriving the relative potency factors of PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a new genotoxic assay (γH2AX) with two human cell lines (HepG2 and LS-174T) to analyze the genotoxic properties of 13 selected PAHs at low doses after 24h treatment. The dose-response for genotoxic effects was modeled with a Hill model; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. In the two cell lines tested, we observed a clear dose-response for genotoxic effects for 11 tested compounds. LS-174T was on average ten times more sensitive than HepG2 towards PAHs regarding genotoxicity. We developed new TEFs, which we named Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were generally higher than the TEF usually used. Our study proposed a new in vitro based method for the establishment of relevant TEFs for PAHs to improve cancer risk assessment. Copyright © 2012 Elsevier Inc. All rights reserved.

eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control.

Science.gov (United States)

Jennings, Martin D; Kershaw, Christopher J; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P; Costello, Joseph L; Donaldson, Ian J; Zhou, Yu; Pavitt, Graham D

2016-11-16

In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Environmental Land Management in Tajikistan

Science.gov (United States)

Makhmudov, Zafar; Ergashev, Murod

2015-04-01

Associations (WUAs) to introduce sustainable on-farm water management practices. The Project comprises three components to be implemented in five years: 1. Rural Production and Land Resource Management Investments; 2. Knowledge Management and Institutional Support, and 3. Project Management and Coordination. These components include a set of grants from the PPCR and GEF that betrays the particular importance of the grant sources for the Project funding. This innovative combination of the PPCR and GEF grant funding will help in scheduling a scope of work under the Project and enable to implement certain activities on a pilot basis that otherwise could not be implemented at this level. Key partners are the Committee for Environmental Protection (Implementing Agency), the Ministry of Finance, the PPCR Secretariat in Tajikistan, Farkhor, Kulyab, Khovaling, Baljuvan, Tavildara and Jirgatal districts, the German Agency for International Development (GIZ) with its GREAT program which provides additional support to the community-based Project planning and institutional development, as well as technical agricultural advisory services. Currently the project has Project Implementation Group and most of its Facilitating Organizations in place that will carry out financial management, disbursements, procurement process, environmental management, social development, monitoring and evaluation. Workshops on coordinating the Project were held in the districts, as well as a series of Trainings of trainings and meetings were conducted for specialists and technical personnel. Next step is to initiate supporting local initiatives for climate adaptive land management and improved livelihoods based on Community Action Plans.

PERSEPSI MASYARAKAT DESA PENYANGGA TERHADAP KAWASAN TAMAN NASIONAL KERINCI SEBLAT PASCA PELAKSANAAN KEGIATAN KONSERVASI TERPADU : Studi Kasus di Desa Napal Licin dan Desa Pulau Kidak, Kecamatan Ulu Rawas, Kabupaten Musi Rawas, Propinsi Sumatera Selatan

Directory of Open Access Journals (Sweden)

Mamat Rahmat

2017-01-01

Full Text Available Selama tahun 1998-2002, Bank Dunia melalui Global Environment Facility (GEF bekerja sama dengan Departemen Kehutanan dan Departemen Dalam Negeri dan Otonomi Daerah melakukan kegiatan  Program Konservasi dan Pembangunan Terpadu (Integrated Conservation and Development Program/ICDP di Taman Nasional Kerinci Seblat. Penelitian ini dilakukan untuk mengetahui dampak pelaksanaan program tersebut terhadap persepsi masyarakat di 2 desa mengenai keberadaan TNKS. Penelitian dilakukan di desa Napal Licin dan Desa Pulau Kidak, Kecamatan Ulu Rawas, Kabupaten Rawas Ulu, Provinsi Sumatera Selatan. Metodologi penelitian yang digunakan adalah metode survey rumah tangga dengan menggunakan kuisioner. Hasil penelitian ini menunjukkan bahwa program ICDP belum mampu merubah persepsi masyarakat terhadap keberadaan kawasan TNKS.

Ethik, Recht und Theologie. Reproduktionstechnologien in Polen

Directory of Open Access Journals (Sweden)

Susanne Lettow

2006-03-01

Full Text Available Die bisherigen Debatten um Stammzellforschung, Klonen und Reproduktionstechnologien wurden in Deutschland weitgehend im nationalstaatlichen Rahmen und mit Blick auf Entwicklungen im angelsächsischen Raum geführt. Dabei sind diese Forschungsrichtungen und Technologien kein genuin „westliches“ Phänomen – immerhin wurde das erste Retortenkind in Polen bereits 1987 geboren. Heidi Hofmann lässt in ihrem Band polnische Philosoph/-innen, Jurist/-innen und Politikerinnen zu Wort kommen und öffnet den Blick dafür, dass die Art und Weise, in der Reproduktionstechnologien gesellschaftlich problematisiert werden, in Polen durch ganz andere politische, kulturelle und historische Konstellationen geprägt ist als in Deutschland.

Summary guidelines

Energy Technology Data Exchange (ETDEWEB)

Halsnaes, K.; Painuly, J.P.; Turkson, J.; Meyer, H.J.; Markandya, A.

1999-09-01

This document is a summary version of the methodological guidelines for climate change mitigation assessment developed as part of the Global Environment Facility (GEF) project Economics of Greenhouse Gas Limitations; Methodological Guidelines. The objectives of this project have been to develop a methodology, an implementing framework and a reporting system which countries can use in the construction of national climate change mitigation policies and in meeting their future reporting obligations under the FCCC. The methodological framework developed in the Methodological Guidelines covers key economic concepts, scenario building, modelling tools and common assumptions. It was used by several country studies included in the project. (au) 13 refs.

Peniskarzinom mit exulzerierten Lymphknotenmetastasen links inguinal

Directory of Open Access Journals (Sweden)

Presich K

2003-01-01

Full Text Available Im Oktober 2001 wurde ein 53jähriger Patient mit ausgedehnten exulzerierten Lymphknotenmetastasen rechts inguinal an einer auswärtigen chirurgischen Abteilung vorgestellt. Im Rahmen der Durchuntersuchung fand sich eine verhärtete, von einem nicht retrahierbaren Präputium verdeckte Glans als mögliches Primum. Eine Circumcision sowie Biopsie aus der Glans ergaben das histologische Ergebnis eines invasiven, schwach verhornenden Plattenepithelkarzinoms mittleren Differenzierungsgrades (G2-G3. In einer Unterbauch-Computertomographie wurde rechts inguinal ein ausgedehnter, ca. 10 cm messender, teils solider, teils nekrotischer Prozeß, bis an die großen Gefäße heranreichend, beschrieben. Die linke Leiste war unauffällig.

[Leben im Eismeer - Tauchuntersuchungen zur Biologie arktischer Meerespflanzen und Meerestiere

Science.gov (United States)

Lippert; Karsten; Wiencke

2000-01-01

Die Maske wird nochmals auf Dichtigkeit überprüft, der Knoten der Sicherungsleine mit zwei halben Schlägen fixiert, dann rutscht die Taucherin von der Eiskante in das kalte Wasser. Eine halbe Stunde vergeht, bevor ihr Kopf wieder aus dem Eisloch auftaucht und sie ein großes Sammelnetz nach oben reicht, gefüllt mit verschiedenen Arten von Makroalgen. Obwohl noch große Flächen des Kongsfjordes im arktischen Spitzbergen zugefroren sind und das Festland von einer dicken Schneedecke bedeckt ist, hat unter Wasser in den Algenwäldern bereits der Sommer und damit die Saison der Meeresbiologen begonnen.

Multilateral financing sources for photovoltaic projects in the rural areas of developing countries; Fuentes multilaterales de financiacion de proyectos con tecnologia fotovoltaica en el medio rural de los paises en desarrollo

Energy Technology Data Exchange (ETDEWEB)

Vazquez, I.; Vazquez, M.

2004-07-01

The massive introduction of the photovoltaic energy in the rural areas of the developing countries can only be achieved with wide and generous aid programmes. The multilateral financing sources are leaded and supported by the World Bank. These are: the Global Environment Facility (GEF); the Multilateral Development Banks (MDB); the International Development Association (IDA) and the International Finance Corporation (IFC). This last has created the specific funds: Photovoltaic Market Transformation Initiative (PVMTI), Small and Medium-Scale Enterprise (SME) and Solar Development Group (SDG). In addition, there are two specialized programmes on energy of the World Bank: Energy Sector Management Assistance Program (ESMAP) and Asia Alternative Energy Program (ASTAE). (Author)

Le système d’information sur la biodiversité de l’administration des parcs nationaux argentins

Directory of Open Access Journals (Sweden)

Leonidas Lizarraga

2014-06-01

Full Text Available Introduction Le système d’information sur la biodiversité (SIB, Sistema de Información de Biodiversidad de l’administration des parcs nationaux argentins (APN, Administración de Parques Nacionales a été lancé en 2002, avec le soutien du Global Environment Fund (GEF dans le cadre du Projet de préservation de la biodiversité mené par l’État argentin. Le dispositif, abrégé en SIB-APN, est composé d’un ensemble de bases de données thématiques et d’un système d’information géographique : son ob...

Summary of the technical guidelines used in the project: The economics of greenhouse gas limitations

International Nuclear Information System (INIS)

Halsnaes, Kirsten

1998-01-01

This document is a summary version of the technical guidelines for climate change mitigation assessment developed as a part of the Global Environment Facility (GEF) project The Economics of Greenhouse Gas Limitations; Technical guidelines (UNEP 1998). The objectives of this project have been to support the development of a methodology, an implementing framework and a reporting system which countries can use in the construction of national climate change policies and in meeting their future reporting obligations under the FCCC. The methodological framework developed in the guidelines covers key economic concepts, scenario building, modelling tools and common assumptions. It was used by several country studies included in the project. (au)

Roles of the TRAPP-II Complex and the Exocyst in Membrane Deposition during Fission Yeast Cytokinesis.

Directory of Open Access Journals (Sweden)

Ning Wang

2016-04-01

Full Text Available The cleavage-furrow tip adjacent to the actomyosin contractile ring is believed to be the predominant site for plasma-membrane insertion through exocyst-tethered vesicles during cytokinesis. Here we found that most secretory vesicles are delivered by myosin-V on linear actin cables in fission yeast cytokinesis. Surprisingly, by tracking individual exocytic and endocytic events, we found that vesicles with new membrane are deposited to the cleavage furrow relatively evenly during contractile-ring constriction, but the rim of the cleavage furrow is the main site for endocytosis. Fusion of vesicles with the plasma membrane requires vesicle tethers. Our data suggest that the transport particle protein II (TRAPP-II complex and Rab11 GTPase Ypt3 help to tether secretory vesicles or tubulovesicular structures along the cleavage furrow while the exocyst tethers vesicles at the rim of the division plane. We conclude that the exocyst and TRAPP-II complex have distinct localizations at the division site, but both are important for membrane expansion and exocytosis during cytokinesis.

The Resilience Assessment Framework: a common indicator for land management?

Science.gov (United States)

Cowie, Annette; Metternicht, Graciela; O'Connell, Deborah

2015-04-01

At the Rio+20 conference in June 2013, the United Nations Convention to Combat Desertification (UNCCD), the Convention on Biological Diversity (CBD), and the United Nations Framework Convention on Climate Change (UNFCCC) reinforced their mutual interests in building linkages between biodiversity conservation, sustainable land management, and climate change mitigation and adaptation. The UNCCD sees building resilience of agro-ecosystems as a common interest that could strengthen linkages between the conventions and deliver synergies in progressing goals of each of the conventions. Furthermore, enhancing resilience of productive agro-ecosystems is fundamental to food security and sustainable development, and thus aligns with the Sustainable Development Goals (SDGs). The Global Environment Facility (GEF) shares the interest of the conventions in building resilience in agro-ecosystems. Indicators of resilience are required for monitoring progress in these endeavors, application of a common indicator between the UNCCD, UNFCCC and CBD as a measure of both land-based adaptation and ecosystem resilience, could strengthen links between the conventions and increase attention to the broad benefits of improved land management. Consequently, the Scientific and Technical Advisory Panel (STAP) to the GEF commissioned the Commonwealth Scientific and Industrial Research Organisation (CSIRO) to produce a report reviewing the conceptual basis for resilience, and proposing an indicator approach that could meet the needs of the Conventions and the GEF for an indicator of agro-ecosystem resilience and land-based adaption. The paper presents a synthesis of scientific understanding of resilience in agro-ecosystems, reviews indicators that have been proposed, and, having concluded that none of the extant indicator approaches adequately assesses resilience of agro-ecosystems, proposes a new approach to the assessment of resilience. Recognizing that no single indicator of resilience is

Two Decades after the Rio Earth Summit: Sustainable Development Quo Vadis?

Directory of Open Access Journals (Sweden)

Korinna Horta

2011-01-01

Full Text Available The world’s most influential development agency, the World Bank Group (WBG, is the leading actor in development finance and plays a central role in global efforts to protect the environment. Following the Rio Earth Summit in 1992, the institution was responsible for all investment projects of the Global Environment Facility (GEF, which was then newly established to serve as the interim financial mechanism for the United Nations Conventions on Climate Change and Biodiversity. The promise that the GEF would lead to the “greening” of development finance remains largely unfulfilled.More recently the United Nations Framework Convention on Climate Change appointed the WBG as the interim trustee of the new Green Climate Fund which plans to mobilize an estimated US$ 100 billion per year by 2020.While the World Bank Group plays this critical role in global environmental efforts, its main business continues to be lending for development. This includes the financing of large-scale infrastructure projects, agribusiness, large dams as well as investments in gas, oil and mining. This regular lending portfolio for development is often at odds with environmental sustainability. For example, despite the growing area of climate finance, support for fossil fuel projects continues to be dominant in the institution’s lending for the energy sector. Another climate-related area is the World Bank’s pioneering role in advancing REDD+, an initiative designed to reduce the emission of global green house gases by integrating efforts to protect forest areas into global carbon markets. Ultimately, its success will depend on addressing sensitive questions such as land ownership, forest governance and the equitable sharing of benefits.In conclusion the paper considers the underlying corporate culture and the difficulties in reconciling environmental and social sustainability with the institution’s supply-side driven focus on meeting lending targets.

Der Körper als Gefäß. Eine Studie zur visuellen Anthropologie des Alten Orients

OpenAIRE

Schroer Silvia/Kipfer Sara

2015-01-01

The perception of the human body as container is widespread in cognitive linguistics psychology and anthropology and is estimated to be universal. But what can we say about the specific context of the Hebrew Bible as well as Ancient Near Eastern texts and material culture and more especially about anthropomorphic vessels in the Levant? Biblical Egyptian and Mesopotamian texts compare the human body with pottery in order to emphasize its status of having been created (Geschöpflichkeit) on the ...

Gefährlicher Trend : Smartphone im Strassenverkehr : auch zu Fuss ist das Ablenkungspotenzial sehr gross.

NARCIS (Netherlands)

2016-01-01

Viele Menschen, die sich zu Fuß im Straßenverkehr bewegen, nutzen dabei das Smartphone. Dies ist das Ergebnis einer Erhebung von DEKRA in sechs europäischen Hauptstädten. Von den rund 14.000 erfassten Personen nutzten fast 17 Prozent ihr Handy — für Textnachrichten, zum Telefonieren oder Musikhören.

Fahrstuhlfahrten und Einstiegsschwierigkeiten. Erschließungstechniken in Georges Perecs »La Vie mode d’emploi«

Directory of Open Access Journals (Sweden)

Johanne Mohs

2014-05-01

Full Text Available Der Artikel ist eine produktionsästhetische Untersuchung zu Einstiegsschwierigkeiten in literarische Schreibprozesse und ihre Auflösung mithilfe räumlicher und sprachspielerischer Erschließungstechniken. Als Beispiel dient mir die Poetik des OuLiPo (»Ouvroir de littérature potentielle« und hier insbesondere (die Genese von Georges Perecs Roman »La vie mode d’emploi«. Genauer wird daran gezeigt, wie Perec eine blockierte Fahrstuhlfahrt als metaphorische Referenz auf seine anfängliche Schreibhemmung in den Roman einfügt und wie diese Referenz als Kommentar zur Erzählbarkeit komplexer Raum-Zeit-Gefüge im Gesellschaftsroman des 20. Jahrhunderts, insbesondere zu Marcel Prousts »Recherche«, verstanden werden kann.

Steueroasen und Regulierungsoasen – Auswirkungen auf die Stabilität des Finanzmarkts und politische Implikationen

Directory of Open Access Journals (Sweden)

Michaela Schmidt

2012-12-01

Full Text Available In diesem Beitrag wird dargelegt, dass Steuer- und Regulierungsoasen nicht nur Steuerausfälle und Kapitalflucht ermöglichen, sondern auch eine Hauptursache für die Finanzkrise 2007/2008 waren und weiterhin die Stabilität des Finanzmarkts gefährden. Sie haben den Boden bereitet für das Aufkommen nicht regulierter Finanzinstitutionen, sogenannter Schattenbanken. Regulierungsoasen ermöglichen Finanzmarktakteuren eine Umgehung von Regulierungs- und Aufsichtsvorschriften und heizen den Wettbewerb um niedrige Regulierungsvorschriften maßgeblich an. Jeder Schritt zu einer finanzpolitischen Re-Regulierung von Steuer- und Regulierungsoasen sowie Schattenbanken ist ein aktiver Schritt zur Krisenvorbeugung und damit zum Schutz der ArbeitnehmerInnen vor den gewaltigen volkswirtschaftlichen Kosten von Finanzkrisen.

Emotionalisierung der Nachhaltigkeitskommunikation

DEFF Research Database (Denmark)

Pedersen, Anne Grethe Julius

Nachhaltigkeitskommunikation (Brugger 2010: 3f). Untersucht wird das Potenzial kommunikativer Handlungen über soziales und ökologisches Engagement, bestimmte Gefühle bei den Empfängern hervorzurufen und eine emotionale Bindung zum Unternehmen herzustellen, u.a. durch emotive Ausdrücke und Bilder, Intensivierungen und...... emotional (mehr als rational) angesprochen - Welche Emotionalisierungsstrategien werden benutzt - Inwieweit unterscheidet sich die deutschsprachige Nachhaltigkeitskommunikation von der dänischsprachigen. Das Textkorpus umfasst online verfügbare Nachhaltigkeitskommunikation auf Websites und in neuen Medien......Die Nachhaltigkeitskommunikation gewinnt an Umfang und Bedeutung und immer öfter werden bei der Bewertung von Unternehmen durch z.B. Investoren und Kunden auch nicht-finanzielle Aspekte herangezogen. Im Fokus des vorliegenden Beitrags steht die emotionale Dimension der unternehmerischen...

Host Adaptation and Speciation through Hybridization and Polyploidy in Phytophthora

Science.gov (United States)

Bertier, Lien; Leus, Leen; D’hondt, Liesbet; de Cock, Arthur W. A. M.; Höfte, Monica

2013-01-01

It is becoming increasingly evident that interspecific hybridization is a common event in phytophthora evolution. Yet, the fundamental processes underlying interspecific hybridization and the consequences for its ecological fitness and distribution are not well understood. We studied hybridization events in phytophthora clade 8b. This is a cold-tolerant group of plant pathogenic oomycetes in which six host-specific species have been described that mostly attack winter-grown vegetables. Hybrid characterization was done by sequencing and cloning of two nuclear (ITS and Ypt1) and two mitochondrial loci (Cox1 and Nadh1) combined with DNA content estimation using flow cytometry. Three different mtDNA haplotypes were recovered among the presumed hybrid isolates, dividing the hybrids into three types, with different parental species involved. In the nuclear genes, additivity, i.e. the presence of two alleles coming from different parents, was detected. Hybrid isolates showed large variations in DNA content, which was positively correlated with the additivity in nuclear loci, indicating allopolyploid hybridization followed by a process of diploidization. Moreover, indications of homeologous recombination were found in the hybrids by cloning ITS products. The hybrid isolates have been isolated from a range of hosts that have not been reported previously for clade 8b species, indicating that they have novel pathogenic potential. Next to this, DNA content measurements of the non-hybrid clade 8b species suggest that polyploidy is a common feature of this clade. We hypothesize that interspecific hybridization and polyploidy are two linked phenomena in phytophthora, and that these processes might play an important and ongoing role in the evolution of this genus. PMID:24386473

Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration*

Science.gov (United States)

Ou, Young; Chan, Gordon; Zuo, Jeremy; Rattner, Jerome B.; van der Hoorn, Frans A.

2016-01-01

The tight, relative positioning of the nucleus and centrosome in mammalian cells is important for the regulation of cell migration. Under pathophysiological conditions, the purinergic A2b receptor can regulate cell motility, but the underlying mechanism remains unknown. Expression of A2b, normally low, is increased in tissues experiencing adverse physiological conditions, including hypoxia and inflammation. ATP is released from such cells. We investigated whether extracellular cues can regulate centrosome-nucleus positioning and cell migration. We discovered that hypoxia as well as extracellular ATP cause a reversible increase in the distance between the centrosome and nucleus and reduced cell motility. We uncovered the underlying pathway: both treatments act through the A2b receptor and specifically activate the Epac1/RapGef3 pathway. We show that cells lacking A2b do not respond in this manner to hypoxia or ATP but transfection of A2b restores this response, that Epac1 is critically involved, and that Rap1B is important for the relative positioning of the centrosome and nucleus. Our results represent, to our knowledge, the first report demonstrating that pathophysiological conditions can impact the distance between the centrosome and nucleus. Furthermore, we identify the A2b receptor as a central player in this process. PMID:27226580

Studies of fission fragment yields via high-resolution γ-ray spectroscopy

Science.gov (United States)

Wilson, J. N.; Lebois, M.; Qi, L.; Amador-Celdran, P.; Bleuel, D.; Briz, J. A.; Carroll, R.; Catford, W.; Witte, H. De; Doherty, D. T.; Eloirdi, R.; Georgiev, G.; Gottardo, A.; Goasduff, A.; Hadyñska-Klek, K.; Hauschild, K.; Hess, H.; Ingeberg, V.; Konstantinopoulos, T.; Ljungvall, J.; Lopez-Martens, A.; Lorusso, G.; Lozeva, R.; Lutter, R.; Marini, P.; Matea, I.; Materna, T.; Mathieu, L.; Oberstedt, A.; Oberstedt, S.; Panebianco, S.; Podolyak, Zs.; Porta, A.; Regan, P. H.; Reiter, P.; Rezynkina, K.; Rose, S. J.; Sahin, E.; Seidlitz, M.; Serot, O.; Shearman, R.; Siebeck, B.; Siem, S.; Smith, A. G.; Tveten, G. M.; Verney, D.; Warr, N.; Zeiser, F.; Zielinska, M.

2018-03-01

Precise spectroscopic information on the fast neutron induced fission of the 238U(n,f) reaction was recently gained using a new technique which involved coupling of the Miniball high resolution y-ray spectrometer and the LICORNE directional neutron source. The experiment allowed measurement of the isotopic fission yields for around 40 even-even nuclei at an incident neutron energy of around 2 MeV where yield data are very sparse. In addition spectroscopic information on very neutron-rich fission products was obtained. Results were compared to models, both the JEFF-3.1.1 data base and the GEF code, and large discrepancies for the S1 fission mode in the Sn/Mo isotope pair were discovered. This suggests that current models are overestimating the role played by spherical shell effects in fast neutron induced fission. In late 2017 and 2018 the nu-ball hybrid spectrometer will be constructed at the IPN Orsay to perform further experimental investigations with directional neutrons coupled to a powerful hybrid Ge/LaBr3 detector array. This will open up new possibilities for measurements of fission yields for fast-neutron-induced fission using the spectroscopic technique and will be complimentary to other methods being developed.

Studies of fission fragment yields via high-resolution γ-ray spectroscopy

Directory of Open Access Journals (Sweden)

Wilson J.N.

2018-01-01

Full Text Available Precise spectroscopic information on the fast neutron induced fission of the 238U(n,f reaction was recently gained using a new technique which involved coupling of the Miniball high resolution y-ray spectrometer and the LICORNE directional neutron source. The experiment allowed measurement of the isotopic fission yields for around 40 even-even nuclei at an incident neutron energy of around 2 MeV where yield data are very sparse. In addition spectroscopic information on very neutron-rich fission products was obtained. Results were compared to models, both the JEFF-3.1.1 data base and the GEF code, and large discrepancies for the S1 fission mode in the Sn/Mo isotope pair were discovered. This suggests that current models are overestimating the role played by spherical shell effects in fast neutron induced fission. In late 2017 and 2018 the nu-ball hybrid spectrometer will be constructed at the IPN Orsay to perform further experimental investigations with directional neutrons coupled to a powerful hybrid Ge/LaBr3 detector array. This will open up new possibilities for measurements of fission yields for fast-neutron-induced fission using the spectroscopic technique and will be complimentary to other methods being developed.

Aktuelle Entwicklungen - Orthopädische Implantate

Science.gov (United States)

Riner, Marc A.

Die guten Resultate und langen Standzeiten von bis zu 15 und 20 Jahren von implantierten Hüftendoprothesen führen dazu, immer jüngere Patienten mit einem Hüftgelenkersatz zu behandeln. Die Versorgung von jungen aktiven Patienten mit einer Hüftendoprothese stellt jedoch eine besondere Herausforderung dar [1]. Trotz umfangreicher Materialentwicklungen, Designoptimierungen und Verbesserungen der Operationstechnik, haben sich die Standzeiten der Prothesen zwar wesentlich verbessert, ist jedoch bei jungen Patienten verglichen mit denen von älteren Patienten deutlich verkürzt [2, 3]. Zudem kann die Hüftprothesenverankerung durch Knochenresektion im Rahmen der Erstimplantation, Adaptionsvorgängen im Knochen (stress shielding) aufgrund unphysiologischer Krafteinleitung, abriebbedingte Osteolyse und während der Implantat- bzw. Knochenzemententfernung auftretende knöcherne Defekte zu unbefriedigende Reimplantationsbedingungen im Fall einer Revision führen [4]. Dies hat in jüngerer Zeit zur Entwicklung von verschiedenen Endoprothesensystemen mit einem möglichst geringen Knochenverlust und damit einhergehenden verbesserten Rückzugsmöglichkeit im Revisionsfall geführt. Bei den knochensparend verankerten Hüftprothesen werden allgemein zwei Typen, die Schenkelhalsprothese und der Oberflächenersatz, unterschieden.

Four African Nations Agree to Water Management Programme

International Nuclear Information System (INIS)

2013-01-01

Full text: Seeking to improve their management of water resources, four northeast African nations today agreed at the International Atomic Energy Agency (IAEA) to establish a long-term framework for utlizing a key underground water system. Chad, Egypt, Libya and Sudan signed a Strategic Action Programme (SAP) that aims to optimize the equitable use of the Nubian Sandstone Aquifer System, a huge water resource that lies beneath the four nations. The SAP also commits the countries to strengthen and build upon a previously existing regional coordination mechanism, in part by establishing a new Joint Authority for the Nubian Aquifer System. The Programme lays the groundwork for improving cooperation among the four arid nations and for strengthening their capacity to monitor and manage the aquifer effectively. With growing populations and decreasing water availability from other sources in the region, the aquifer is under mounting pressure. Removing water without a clear understanding of transboundary and other implications threatens water quality and has the potential to harm biodiversity and accelerate land degradation. The agreement resulted from a joint Technical Cooperation project of the United Nations Development Programme (UNDP) and the Global Environment Facility (GEF), the United Nations Educational, Scientific and Cultural Organization (UNESCO) and the IAEA. ''I congratulate all involved on this significant achievement,'' said IAEA Director General Yukiya Amano. ''Water is a key resource, and effective management and use of such water resources is essential for the future. The agreement of the Strategic Action Programme is the result of real cooperation between the four States, the Agency and UNDP-GEF. I am confident that this Programme will be a success and will benefit the people of the region. This positive project experience benefits strengthened and expanded cooperation between the IAEA and the UNDP-GEF.'' ''UNDP would like to congratulate the

Boden

Science.gov (United States)

Pfeiffer, Eva-Maria; Eschenbach, Annette; Munch, Jean Charles

Auch wenn die Risiken bisher kaum quantifizierbar sind, ist davon auszugehen, dass aufgrund der Einbindung des Bodens in die Energie-, Wasser- und Stoffkreisläufe die zu erwartenden Temperatur- und Niederschlagsänderungen die Funktionen dieser zentralen Lebensgrundlage auch in Deutschland gefährden. Nach einer Darstellung der Vielfältigkeit von Böden geht es in diesem Kapitel um mögliche Änderungen der Standortfunktion von Böden und der Leistungen im Ökosystem sowie um den Bodenwasserhaushalt. An herausgehobener Stelle diskutieren die Autoren die Klimafunktion von Böden und stellen mögliche Strategien zu ihrem Schutz vor. Eine große Rolle spielt die Verschränkung mit den anderen Themenbereichen von Teil III, etwa Landwirtschaft, Forstwirtschaft und Wasser.

Leben im emotionalen Kapitalismus Life in Emotional Capitalism

Directory of Open Access Journals (Sweden)

Martin Spetsmann-Kunkel

2007-07-01

Full Text Available Die israelische Soziologin Eva Illouz geht in ihrem Buch Gefühle in Zeiten des Kapitalismus von der These aus, dass der Kapitalismus eine emotionale Kultur ausgebildet hat, die sich sowohl am Arbeitsplatz als auch in intimen Beziehungen finden lässt. Die vermehrte Rationalisierung des emotionalen Lebens und die gleichzeitige Emotionalisierung von Arbeitsabläufen charakterisieren den „emotionalen Kapitalismus”.In her book Cold Intimacies: Emotions and Late Capitalism, the Israeli sociologist Eva Illouz begins with the thesis that capitalism has created an emotional culture, which is found in both the work place as well as intimate relationships. The increasing rationalization of emotional life and the concurrent emotionalizing of work processes characterize this “emotional capitalism.”

Rezension zu: Christina Holtz-Bacha (Hg.: Frauen, Politik und Medien. Wiesbaden: VS Verlag für Sozialwissenschaften 2008

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Tanja Maier

2009-03-01

Full Text Available In dem von Christina Holtz-Bacha herausgegebenen Sammelband wird aus einer kommunikationswissenschaftlichen Perspektive untersucht, wie Politikerinnen in höchsten politischen Ämtern medial repräsentiert werden. In den einzelnen Beiträgen wird der Frage nachgegangen, ob die zunehmende Sichtbarkeit von Politikerinnen wie Angela Merkel, Christina Kirchner oder Ségolène Royal auch zu einer veränderten medialen Berichterstattung geführt habe. Analysiert werden nicht nur die mediale Präsenz von Politikerinnen im Vergleich zu ihren männlichen Kollegen, sondern auch die Gemeinsamkeiten und Unterschiede in den textuellen und bildlichen Darstellungsweisen. Der Band liefert aus der Perspektive der politischen Kommunikationsforschung einige interessante empirische Einzelanalysen. Die theoretische Auseinandersetzung mit Konzepten der Geschlechterforschung spielt nur am Rande eine Rolle.

Zur Rekonstruktion einer Typologie jugendlichen Medienhandelns gemäß dem Leitbild der Triangulation

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Klaus Peter Treumann

2017-09-01

Full Text Available Die im Folgenden dargestellten Ergebnisse sind im Rahmen des von der DFG geförderten Forschungsprojekts „Eine Untersuchung zum Mediennutzungsverhalten 12- bis 20-Jähriger und zur Entwicklung von Medienkompetenz im Jugendalter“ entstanden, das gemeinsam von Klaus Peter Treumann, Uwe Sander und Dorothee Meister geleitet wird. Das Forschungsprojekt untersucht das Medienhandeln Jugendlicher sowohl hinsichtlich Neuer als auch alter Medien. Zum einen fragen wir dabei nach den Ausprägungen von Medienkompetenz in verschiedenen Dimensionen und zum anderen konzentrieren wir uns auf die Entwicklung einer empirisch fundierten Typologie jugendlichen Medienhandelns. Methodologisch ist die Untersuchung an dem Leitbild der Triangulation orientiert und kombiniert qualitative und quantitative Zugänge zum Forschungsfeld in Form von Gruppendiskussionen, leitfadengestützten Einzelinterviews und einer Repräsentativerhebung.

Das ovarielle Überstimulationssyndrom (OHSS

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Sander T

2011-01-01

Full Text Available Das ovarielle Überstimulationssyndrom (OHSS ist eine relativ häufige Komplikation bei der künstlichen Befruchtung bzw. bei einer ovariellen Stimulationsbehandlung. Es wird über die Pathophysiologie berichtet, die durch eine erhöhte Gefäßpermeabilität mit einer Flüssigkeitsverschiebung in den extravasalen Raum bedingt ist, vermutlich getriggert durch den vaskulären endothelialen Wachstumsfaktor (VEGF. Junge Frauen mit hyperandrogenämischen Zyklusstörungen und polyzystischem Ovarsyndrom (PCOS haben ein erhöhtes Risiko und eine Ovulationsinduktion mit HCG (humanem Choriongonadotropin sollte vermieden werden. Erscheinungsbild, Präventionsmaßnahmen und Therapie werden mit dem Ziel erläutert, die Komplikationsrate niedrig und die Schwangerschaftsrate so hoch wie möglich zu halten.

Climate change studies in Estonia

International Nuclear Information System (INIS)

Kallaste, Tiit; Kuldna, Piret

1998-01-01

The present collection of papers was compiled on the basis of research papers written by Estonian scientists during the United Nations Environment Programme and Global Environment Facility initiated climate change programme Country Case Study on Climate Change Impacts and Adaptations Assessments. The Estonian country case study was finally approved by UNEP/GEF in February 1996, practical work started in September. The priorities for Estonia in the study of global climate change impacts and adaptation have been in the following areas of interest: agriculture, water resources, forestry, the Baltic Sea and Estonian coast, also historical climate and socioeconomic background together with the biggest producer of greenhouse gases, the energy sector. Those areas have been studied more carefully during the one and half year period of the project

The N-terminal domains of Vps3 and Vps8 are critical for localization and function of the CORVET tethering complex on endosomes.

Directory of Open Access Journals (Sweden)

Nadine Epp

Full Text Available Endosomal biogenesis depends on multiple fusion and fission events. For fusion, the heterohexameric CORVET complex as an effector of the endosomal Rab5/Vps21 GTPase has a central function in the initial tethering event. Here, we show that the CORVET-specific Vps3 and Vps8 subunits, which interact with Rab5/Vps21, require their N-terminal domains for localization and function. Surprisingly, CORVET may lack either one of the two N-terminal domains, but not both, to promote protein sorting via the endosome. The dually truncated complex mislocalizes to the cytosol and is impaired in endocytic protein sorting, but not in assembly. Furthermore, the endosomal localization can be rescued by overexpression of Vps21 or one of the truncated CORVET subunits, even though CORVET assembly is not impaired by loss of the N-terminal domains or in strains lacking all endosomal Rab5s and Ypt7. We thus conclude that CORVET requires only its C-terminal domains for assembly and has beyond its putative β-propeller domains additional binding sites for endosomes, which could be important to bind Vps21 and other endosome-specific factors for efficient endosome tethering.

Diffusive-like effects and possible non trivial local topology on the half-Heusler YPdBi compound

Science.gov (United States)

Souza, J. C.; Lesseux, G. G.; Urbano, R. R.; Rettori, C.; Pagliuso, P. G.

2018-05-01

The non-ambiguous experimental identification of topological states of matter is one of the main interesting problems regarding this new quantum state of matter. In particular, the half-Heusler family RMT (R = rare-earth, T = Pd, Pt or Au and T = Bi, Sb, Pb or Sn) could be a useful platform to explore these states due to their cubic symmetry and the topological properties tunable via their unit cell volume and/or the nuclear charges of the M and T atoms. In this work, we report electron spin resonance (ESR) and complementary macroscopic measurements in the Nd3 + -doped putative topologically trivial semimetal YPdBi. Following the Nd3 + ESR lineshape as a function of microwave power, size of the particle and temperature, we have been able to observe an evolution from a Dysonian lineshape to a diffusive-like lineshape. Furthermore, the Nd3 + ESR intensity saturation is concentration dependent, which could be due to a phonon-bottleneck process. Comparing these results with the Nd3 + -doped YPtBi, we discuss a possible scenario in which the Nd3 + ions could locally tune the topological properties of the system.

Gefässpflanzen auf der Jütischen Halbinsel, Muster der Phytodiversität und aktuelle Naturschutzprobleme

DEFF Research Database (Denmark)

Hobohm, Carsten; Wind, Peter

2014-01-01

The paper deals with the composition and patterns of vascular plants at the Jutland (or Cimbric) Peninsula. Species diversity is not obviously increasing from North to South as in many regions and coutries in Europe. Species numbers represent higher values to the East than to the West...... or abandonment of agriculture and forestry. Thus, the populations of many vascular plant taxa de-creased, are threatend with extinction or already became extinct. The most affected habitat types are those embeded or connected to farmland. While some positive trends can be recognized we can not see a reversal...

Molecular cloning, functional expression and subcellular localization of two putative vacuolar voltage-gated chloride channels in rice (Oryza sativa L.).

Science.gov (United States)

Nakamura, Atsuko; Fukuda, Atsunori; Sakai, Shingo; Tanaka, Yoshiyuki

2006-01-01

We isolated two cDNA clones (OsCLC-1 and OsCLC-2) homologous to tobacco CLC-Nt1, which encodes a voltage-gated chloride channel, from rice (Oryza sativa L. ssp. japonica, cv. Nipponbare). The deduced amino acid sequences were highly conserved (87.9% identity with each other). Southern blot analysis of the rice genomic DNA revealed that OsCLC-1 and OsCLC-2 were single-copy genes on chromosomes 4 and 2, respectively. OsCLC-1 was expressed in most tissues, whereas OsCLC-2 was expressed only in the roots, nodes, internodes and leaf sheaths. The level of expression of OsCLC-1, but not of OsCLC-2, was increased by treatment with NaCl. Both genes could partly substitute for GEF1, which encodes the sole chloride channel in yeast, by restoring growth under ionic stress. These results indicate that both genes are chloride channel genes. The proteins from both genes were immunochemically detected in the tonoplast fraction. Tagged synthetic green fluorescent protein which was fused to OsCLC-1 or OsCLC-2 localized in the vacuolar membranes. These results indicate that the proteins may play a role in the transport of chloride ions across the vacuolar membrane. We isolated loss-of-function mutants of both genes from a panel of rice mutants produced by the insertion of a retrotransposon, Tos17, in the exon region, and found inhibition of growth at all life stages.

Use of reporter-gene based bacteria to quantify phenanthrene biodegradation and toxicity in soil

Energy Technology Data Exchange (ETDEWEB)

Shin, Doyun [Department of Civil and Environmental Engineering, Seoul National University, Gwanakno 599, Seoul 151-742 (Korea, Republic of); Moon, Hee Sun [School of Earth and Environmental Science, Seoul National University, Gwanakno 599, Seoul 151-742 (Korea, Republic of); Lin, Chu-Ching; Barkay, Tamar [Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901 (United States); Nam, Kyoungphile, E-mail: kpnam@snu.ac.k [Department of Civil and Environmental Engineering, Seoul National University, Gwanakno 599, Seoul 151-742 (Korea, Republic of)

2011-02-15

A phenanthrene-degrading bacterium, Sphingomonas paucimobilis EPA505 was used to construct two fluorescence-based reporter strains. Strain D harboring gfp gene was constructed to generate green fluorescence when the strain started to biodegrade phenanthrene. Strain S possessing gef gene was designed to die once phenanthrene biodegradation was initiated and thus to lose green fluorescence when visualized by a live/dead cell staining. Confocal laser scanning microscopic observation followed by image analysis demonstrates that the fluorescence intensity generated by strain D increased and the intensity by strain S decreased linearly at the phenanthrene concentration of up to 200 mg/L. Such quantitative increase and decrease of fluorescence intensity in strain D (i.e., from 1 to 11.90 {+-} 0.72) and strain S (from 1 to 0.40 {+-} 0.07) were also evident in the presence of Ottawa sand spiked with the phenanthrene up to 1000 mg/kg. The potential use of the reporter strains in quantitatively determining biodegradable or toxic phenanthrene was discussed. - Research highlights: A novel reporter bacterial strain has been developed. The bacterium can quantitatively determine the change in fluorescence intensity. The intensity can represent the bioavailable phenanthrene in solid matrix. - A cell-killing gene harboring reporter bacterium shows phenanthrene toxicity.

Suppression of chemotaxis by SSeCKS via scaffolding of phosphoinositol phosphates and the recruitment of the Cdc42 GEF, Frabin, to the leading edge.

Science.gov (United States)

Ko, Hyun-Kyung; Guo, Li-wu; Su, Bing; Gao, Lingqiu; Gelman, Irwin H

2014-01-01

Chemotaxis is controlled by interactions between receptors, Rho-family GTPases, phosphatidylinositol 3-kinases, and cytoskeleton remodeling proteins. We investigated how the metastasis suppressor, SSeCKS, attenuates chemotaxis. Chemotaxis activity inversely correlated with SSeCKS levels in mouse embryo fibroblasts (MEF), DU145 and MDA-MB-231 cancer cells. SSeCKS loss induced chemotactic velocity and linear directionality, correlating with replacement of leading edge lamellipodia with fascin-enriched filopodia-like extensions, the formation of thickened longitudinal F-actin stress fibers reaching to filopodial tips, relative enrichments at the leading edge of phosphatidylinositol (3,4,5)P3 (PIP3), Akt, PKC-ζ, Cdc42-GTP and active Src (SrcpoY416), and a loss of Rac1. Leading edge lamellipodia and chemotaxis inhibition in SSeCKS-null MEF could be restored by full-length SSeCKS or SSeCKS deleted of its Src-binding domain (ΔSrc), but not by SSeCKS deleted of its three MARCKS (myristylated alanine-rich C kinase substrate) polybasic domains (ΔPBD), which bind PIP2 and PIP3. The enrichment of activated Cdc42 in SSeCKS-null leading edge filopodia correlated with recruitment of the Cdc42-specific guanine nucleotide exchange factor, Frabin, likely recruited via multiple PIP2/3-binding domains. Frabin knockdown in SSeCKS-null MEF restores leading edge lamellipodia and chemotaxis inhibition. However, SSeCKS failed to co-immunoprecipitate with Rac1, Cdc42 or Frabin. Consistent with the notion that chemotaxis is controlled by SSeCKS-PIP (vs. -Src) scaffolding activity, constitutively-active phosphatidylinositol 3-kinase could override the ability of the Src inhibitor, SKI-606, to suppress chemotaxis and filopodial enrichment of Frabin in SSeCKS-null MEF. Our data suggest a role for SSeCKS in controlling Rac1 vs. Cdc42-induced cellular dynamics at the leading chemotactic edge through the scaffolding of phospholipids and signal mediators, and through the reorganization of the

The Large Marine Ecosystem Approach for 21st Century Ocean Health and International Sustainable Development

Science.gov (United States)

Honey, K. T.

2014-12-01

The global coastal ocean and watersheds are divided into 66 Large Marine Ecosystems (LMEs), which encompass regions from river basins, estuaries, and coasts to the seaward boundaries of continental shelves and margins of major currents. Approximately 80% of global fisheries catch comes from LME waters. Ecosystem goods and services from LMEs contribute an estimated US 18-25 trillion dollars annually to the global economy in market and non-market value. The critical importance of these large-scale systems, however, is threatened by human populations and pressures, including climate change. Fortunately, there is pragmatic reason for optimism. Interdisciplinary frameworks exist, such as the Large Marine Ecosystem (LME) approach for adaptive management that can integrate both nature-centric and human-centric views into ecosystem monitoring, assessment, and adaptive management practices for long-term sustainability. Originally proposed almost 30 years ago, the LME approach rests on five modules are: (i) productivity, (ii) fish and fisheries, (iii) pollution and ecosystem health, (iv) socioeconomics, and (v) governance for iterative adaptive management at a large, international scale of 200,000 km2 or greater. The Global Environment Facility (GEF), World Bank, and United Nations agencies recognize and support the LME approach—as evidenced by over 3.15 billion in financial assistance to date for LME projects. This year of 2014 is an exciting milestone in LME history, after 20 years of the United Nations and GEF organizations adopting LMEs as a unit for ecosystem-based approaches to management. The LME approach, however, is not perfect. Nor is it immutable. Similar to the adaptive management framework it propones, the LME approach itself must adapt to new and emerging 21st Century technologies, science, and realities. The LME approach must further consider socioeconomics and governance. Within the socioeconomics module alone, several trillion-dollar opportunities exist

Potential options to reduce GHG emissions in Venezuela

Energy Technology Data Exchange (ETDEWEB)

Pereira, N.; Bonduki, Y.; Perdomo, M.

1996-12-31

The Government of Venezuela ratified the United Nations Framework Convention on Climate Change (UNFCCC) in December, 1994. The Convention requires all parties to develop and publish national inventories of anthropogenic greenhouse gas emissions (GHG) as well as national plans to reduce or control emissions, taking into account their common but differentiated responsibilities and their specific national and regional development priorities, objectives, and circumstances. Within this context, the Ministry of Environment and Renewable Natural Resources and the Ministry of Energy and Mines developed the `Venezuelan Case-Study to Address Climate Change`. The study was initiated in October 1993, with the financial and technical assistance of the Government of United States, through the U.S. Country Studies Program (USCSP), and the Global Environment Facility (GEF), through the United Nations Environment Programme (UNEP).

Analysis of Grid Emission Factors for the Electricity Sector in Caribbean Countries

DEFF Research Database (Denmark)

Hinostroza, Miriam L.; Desgain, Denis DR; Perez Martín, David

by undertaking a study to calculate standardized grid emissionfactors (GEF) for sixteen independent nations or groups of countries in the Caribbean region as a basis to the further identification of mitigation activities such as CDM PoAs or any other market-related instrument to be approved by the UNFCCC......As part of their capacity development efforts to promote mitigation actions, the UNEP DTU Partnership, together with the UNFCCC Regional Collaborating Centre in the Caribbean, UNDP and OLADE, agreed to collaborate with Caribbean countries willing to update or establish their grid emission factors...... emission factor for countries with generation units with similar characteristics. Data on the power systems of the different countries have been collected from several centres and institutions, including the UNEP DTU Partnership, the Latin American Energy Organization (OLADE), the Caribbean Community...

Spatially restricted actin-regulatory signaling contributes to synapse morphology

Science.gov (United States)

Nicholson, Daniel A.; Cahill, Michael E.; Tulisiak, Christopher T.; Geinisman, Yuri; Penzes, Peter

2012-01-01

The actin cytoskeleton in dendritic spines is organized into microdomains, but how signaling molecules that regulate actin are spatially governed is incompletely understood. Here we examine how the localization of the RacGEF kalirin-7, a well-characterized regulator of actin in spines, varies as a function of postsynaptic density (PSD) area and spine volume. Using serial section electron microscopy (EM), we find that extrasynaptic, but not synaptic, expression of kalirin-7 varies directly with synapse size and spine volume. Moreover, we find that overall expression levels of kalirin-7 differ in spines bearing perforated and non-perforated synapses, due primarily to extrasynaptic pools of kalirin-7 expression in the former. Overall, our findings indicate that kalirin-7 is differentially compartmentalized in spines as a function of both synapse morphology and spine size. PMID:22458534

National action to mitigate global climate change

International Nuclear Information System (INIS)

1995-06-01

Over 170 participants from 60 countries met for three days in Copenhagen from 7 to 9 June 1994 to discuss howe the aims of the United Nations Framework convention on Climate Change can be translated into practical action. The Conference was organised by the UNEP collaborating Centre on Energy and Environment (UCCEE), with financial support from the Danish International Development Agency (Danida), the Global Environment Facility (GEF), the United Nations Environment Programme (UNEP) and Risoe National Laboratory, Denmark. The main objective of the conference was to identify common approaches to national mitigation analysis for countries to use in meeting their commitments under the FCCC, and in setting priorities for national actions. Although addressing a broader theme, the conference marked the completion and publication of the second phase on UNEP Greenhouse Gas Abatement Costing Study. (au)

Superconductivity in three-dimensional spin-orbit coupled semimetals

Science.gov (United States)

Savary, Lucile; Ruhman, Jonathan; Venderbos, Jörn W. F.; Fu, Liang; Lee, Patrick A.

2017-12-01

Motivated by the experimental detection of superconductivity in the low-carrier density half-Heusler compound YPtBi, we study the pairing instabilities of three-dimensional strongly spin-orbit coupled semimetals with a quadratic band touching point. In these semimetals the electronic structure at the Fermi energy is described by spin j =3/2 quasiparticles, which are fundamentally different from those in ordinary metals with spin j =1/2 . For both local and nonlocal pairing channels in j =3/2 materials we develop a general approach to analyzing pairing instabilities, thereby providing the computational tools needed to investigate the physics of these systems beyond phenomenological considerations. Furthermore, applying our method to a generic density-density interaction, we establish that: (i) The pairing strengths in the different symmetry channels uniquely encode the j =3/2 nature of the Fermi surface band structure—a manifestation of the fundamental difference with ordinary metals. (ii) The leading odd-parity pairing instabilities are different for electron doping and hole doping. Finally, we argue that polar phonons, i.e., Coulomb interactions mediated by the long-ranged electric polarization of the optical phonon modes, provide a coupling strength large enough to account for a Kelvin-range transition temperature in the s -wave channel, and are likely to play an important role in the overall attraction in non-s -wave channels. Moreover, the explicit calculation of the coupling strengths allows us to conclude that the two largest non-s -wave contributions occur in nonlocal channels, in contrast with what has been commonly assumed.

Paget's disease of bone resembling bone metastasis from gastric cancer.

Science.gov (United States)

Shimoyama, Yasuyuki; Kusano, Motoyasu; Shimoda, Yoko; Ishihara, Shingo; Toyomasu, Yoshitaka; Ohno, Tetsuro; Mochiki, Erito; Sano, Takaaki; Hirato, Junko; Mori, Masatomo

2011-08-01

A 74-year-old man had an endoscopic type 0'-IIc tumor in the upper gastric body on the greater curvature and biopsy showed the tumor to be a well-differentiated adenocarcinoma (Group 5). He was referred to us for endoscopic submucosal dissection (ESD). Endoscopy revealed fold convergency, fold swelling, and fusion of the fold, indicating tumor invasion into the submucosa, which was outside the indications for ESD. In addition, there was an increase of serum bone-type alkaline phosphatase (ALP-III and ALP-IV) and urinary cross-linked N-terminal telopeptide of type I collagen (a bone metabolism marker), while (18)F-fluorodeoxyglucose positron emission tomography showed increased uptake in the left pelvis and Th10, suggesting bone metastases. We first diagnosed gastric cancer with bone metastases; however, the symptoms suggested pathological bone fracture and no bone pain. Therefore, a computed tomography-guided aspiration bone biopsy was performed to exclude the possibility of Paget's disease of bone. Biopsy specimens revealed no tumor and a mosaic pattern. No increased uptake of (18)F-FAMT (L-[3-(18)F] α-methyltyrosine) supported a diagnosis of no bone metastases from gastric cancer. We finally diagnosed gastric cancer accompanied by Paget's disease of bone and performed a laparoscopy-assisted proximal gastrectomy. The pathological diagnosis was U less 0-IIb, and U post 0-IIc ypT1a (M) N0H0P0M0 yp stage IA. In gastric cancer patients with suspected bone metastasis, we also need to consider Paget's disease of bone.

Outcome and histopathologic regression in oral squamous cell carcinoma after preoperative radiochemotherapy

International Nuclear Information System (INIS)

Driemel, Oliver; Ettl, Tobias; Reichert, Torsten E.; Koelbl, Oliver; Dresp, Bernd V.; Reuther, Juergen; Pistner, Hans

2009-01-01

Background and purpose: preoperative radiochemotherapy has been reported to enhance tumor response and to improve long-term survival in advanced squamous cell carcinoma of the head and neck. This retrospective study evaluates regression rate and long-term survival in 228 patients with primary oral squamous cell carcinoma treated by neoadjuvant radiochemotherapy and radical surgery. Patients and methods: all patients with biopsy-proven, resectable oral squamous cell carcinoma - TNM stages II-IV without distant metastasis - received preoperative treatment consisting of fractioned irradiation of the primary and the regional lymph nodes with a total dose of 40 Gy and additional cisplatin (n = 160) or carboplatin (n = 68) during the 1st week of treatment. Radical surgery and neck dissection followed after a delay of 10-14 days. The study only included cases with histologically negative resection margins. Results: after a median follow-up of 5.2 years, 53 patients (23.2%) had experienced local-regional recurrence. The median 2-year disease-specific survival (DSS) rate was 86.2%. 5-year DSS and 10-year DSS were 76.3% and 66.7%, respectively. Complete histological local tumor regression after surgery (ypTO) was observed in 50 patients (21.9%) and was independent of pretreatment tumor classification. Uni- and multivariate survival analysis revealed that ypT- and ypN-stage were the most decisive predictors for DSS. Conclusion: preoperative radiochemotherapy with cisplatin/carboplatin followed by radical surgery attains favorable long-term survival rates. This applies especially to cases with complete histological tumor regression after radiochemotherapy, which can be assumed for one of five patients. (orig.)

Genome-Wide Identification of circRNAs in Pathogenic Basidiomycetous Yeast Cryptococcus neoformans Suggests Conserved circRNA Host Genes over Kingdoms

Directory of Open Access Journals (Sweden)

Liang Huo

2018-02-01

Full Text Available Circular RNAs (circRNAs, a novel class of ubiquitous and intriguing noncoding RNA, have been found in a number of eukaryotes but not yet basidiomycetes. In this study, we identified 73 circRNAs from 39.28 million filtered RNA reads from the basidiomycete Cryptococcus neoformans JEC21 using next-generation sequencing (NGS and the bioinformatics tool circular RNA identification (CIRI. Furthermore, mapping of newly found circRNAs to the genome showed that 73.97% of the circRNAs originated from exonic regions, whereas 20.55% were from intergenic regions and 5.48% were from intronic regions. Enrichment analysis of circRNA host genes was conducted based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases. The results reveal that host genes are mainly responsible for primary metabolism and, interestingly, ribosomal protein production. Furthermore, we uncovered a high-level circRNA that was a transcript from the guanosine triphosphate (GTPase gene CNM01190 (gene ID: 3255052 in our yeast. Coincidentally, YPT5, CNM01190′s ortholog of the GTPase in Schizosaccharomyces pombe, protists, and humans, has already been proven to generate circRNAs. Additionally, overexpression of RNA debranching enzyme DBR1 had varied influence on the expression of circRNAs, indicating that multiple circRNA biosynthesis pathways exist in C. neoformans. Our study provides evidence for the existence of stable circRNAs in the opportunistic human pathogen C. neoformans and raises a question regarding their role related to pathogenesis in this yeast.

PCBs and PCDD/Fs distribution in tissues and organs of marine animals in Russian Arctic

Energy Technology Data Exchange (ETDEWEB)

Amirova, Z.; Kruglov, E.; Loshkina, E.; Khalilov, R. [Environmental Research and Protection Centre, Ufa (Russian Federation); Melnikov, S.; Vlasov, S. [Regional Centre Monitoring of the Arctic, St. Petersburg (Russian Federation)

2004-09-15

Studies of persistent organic pollutants (POPs) in the Russian Arctic were conducted recently by a Arctic Monitoring and Assessment Program (AMAP) project. This project developed new data on the POPs pollution levels in the environment and biosphere, including PCBs and PCDD/Fs, in arctic regions of Russia. Transboundary transport and biomagnification within food chains in arctic regions result in POPs accumulation in tissues of fish and marine animals. The aim of this study was to determine the concentration of indicator PCBs, co-planar PCBs and PCDD/Fs in different tissues and organs of seals, walruses and whales caught near the seashore of Chukotski Peninsula (settlement of Lavrenty), Russia, to determine the background level of arctic biota pollution and to study distribution of toxicants in organisms of marine animals. Sampling was made in the course of the 1{sup st} and the 2{sup nd} stages of the 4{sup th} phase of Raipon/AMAP/GEF project ''Persistent Toxic Substances (PTS), Food Security and Indigenous Peoples of the Russian North'' in 2002 by researchers of the Regional Center for Monitoring of the Arctic (RCMA), St. Petersburg, Russia.

Narrative Discourse, Memory and the Experience of Travel in W. G. Sebald’s Vertigo

Directory of Open Access Journals (Sweden)

Pieldner Judit

2016-12-01

Full Text Available Sebald’s first prose work, entitled Vertigo (Schwindel. Gefühle, 1990 is perhaps the most intriguing in terms of the absence of clear-cut links between the four narrative segments: “Beyle; or Love is a Madness Most Discrete,” “All’estero,” “Dr. K Takes the Waters at Riva” and “Il ritorno in patria.” Beyle, i.e. Stendhal, Dr. K, i.e. Kafka, and the first-person narrator of the two quasi-autobiographical parts, are three subjects living in distinct times and places, whose journeys and experiences coalesce into a Sebaldian puzzle to solve, challenging the most varied interpretive terms and discourses, from the Freudian uncanny, through intertextuality (Kristeva and the indexicality of photography (Barthes, Sontag, to the working of cultural memory (Assmann and the non-places of what Marc Augé calls hypermodernity. By trying to disclose the discursive strategies of a profoundly elusive and highly complex narrative, the article is aimed at pointing out the rhetorical and textual connections lying at the heart of Sebald’s floating way of writing, heralding a vertiginous oeuvre, an unsettling literary journey.1

Ein gefährdetes Kulturgut : Neue Perspektiven für die Konservierung von Goldleder in den Niederlanden

NARCIS (Netherlands)

Groves, R.M.; Koldeweij, E.; Posthuma de Boer, M.

2016-01-01

Das 17. und 18. Jahrhundert gilt als „Goldenes Zeitalter“ des Goldleders in den Nord- und Südniederlanden. Obwohl dieses Material einst ähnlich berühmt war wie die Delfter Keramik, ist unglücklicherweise viel davon verloren gegangen. Gründe dafür sind Renovierungen, Materialzersetzungen und

Understanding cAMP-dependent allostery by NMR spectroscopy: comparative analysis of the EPAC1 cAMP-binding domain in its apo and cAMP-bound states.

Science.gov (United States)

Mazhab-Jafari, Mohammad T; Das, Rahul; Fotheringham, Steven A; SilDas, Soumita; Chowdhury, Somenath; Melacini, Giuseppe

2007-11-21

cAMP (adenosine 3',5'-cyclic monophosphate) is a ubiquitous second messenger that activates a multitude of essential cellular responses. Two key receptors for cAMP in eukaryotes are protein kinase A (PKA) and the exchange protein directly activated by cAMP (EPAC), which is a recently discovered guanine nucleotide exchange factor (GEF) for the small GTPases Rap1 and Rap2. Previous attempts to investigate the mechanism of allosteric activation of eukaryotic cAMP-binding domains (CBDs) at atomic or residue resolution have been hampered by the instability of the apo form, which requires the use of mixed apo/holo systems, that have provided only a partial picture of the CBD apo state and of the allosteric networks controlled by cAMP. Here, we show that, unlike other eukaryotic CBDs, both apo and cAMP-bound states of the EPAC1 CBD are stable under our experimental conditions, providing a unique opportunity to define at an unprecedented level of detail the allosteric interactions linking two critical functional sites of this CBD. These are the phosphate binding cassette (PBC), where cAMP binds, and the N-terminal helical bundle (NTHB), which is the site of the inhibitory interactions between the regulatory and catalytic regions of EPAC. Specifically, the combined analysis of the cAMP-dependent changes in chemical shifts, 2 degrees structure probabilities, hydrogen/hydrogen exchange (H/H) and hydrogen/deuterium exchange (H/D) protection factors reveals that the long-range communication between the PBC and the NTHB is implemented by two distinct intramolecular cAMP-signaling pathways, respectively, mediated by the beta2-beta3 loop and the alpha6 helix. Docking of cAMP into the PBC perturbs the NTHB inner core packing and the helical probabilities of selected NTHB residues. The proposed model is consistent with the allosteric role previously hypothesized for L273 and F300 based on site-directed mutagenesis; however, our data show that such a contact is part of a

Effect of preoperative treatment strategies on the outcome of patients with clinical T3, non-metastasized rectal cancer: A comparison between Dutch and Canadian expert centers.

Science.gov (United States)

Breugom, A J; Vermeer, T A; van den Broek, C B M; Vuong, T; Bastiaannet, E; Azoulay, L; Dekkers, O M; Niazi, T; van den Berg, H A; Rutten, H J T; van de Velde, C J H

2015-08-01

High-dose-rate brachytherapy (HDRBT) appears to be associated with less treatment-related toxicity compared with external beam radiotherapy in patients with rectal cancer. The present study compared the effect of preoperative treatment strategies on overall survival, cancer-specific deaths, and local recurrences between a Dutch and Canadian expert center with different preoperative treatment strategies. We included 145 Dutch and 141 Canadian patients with cT3, non-metastasized rectal cancer. All patients from Canada were preoperatively treated with HDRBT. The preoperative treatment strategy for Dutch patients consisted of either no preoperative treatment, short-course radiotherapy, or chemoradiotherapy. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) comparing overall survival. We adjusted for age, cN stage, (y)pT stage, comorbidity, and type of surgery. Primary endpoint was overall survival. Secondary endpoints were cancer-specific deaths and local recurrences. Five-year overall survival was 70.9% (95% CI 62.6%-77.7%) in Dutch patients compared with 86.9% (80.1%-91.6%) in Canadian patients, resulting in an adjusted HR of 0.70 (95% CI 0.39-1.26; p = 0.233). Of 145 Dutch patients, 6.9% (95% CI 2.8%-11.0%) had a local recurrence and 17.9% (95% CI 11.7%-24.2%) patients died of rectal cancer, compared with 4.3% (95% CI 0.9%-7.5%) local recurrences and 10.6% (95% CI 5.5%-15.7%) rectal cancer deaths out of 141 Canadian patients. We did not detect statistically significant differences in overall survival between a Dutch and Canadian expert center with different treatment strategies. This finding needs to be further investigated in a randomized controlled trial. Copyright © 2015 Elsevier Ltd. All rights reserved.

Proteomic and Transcriptomic Analysis of Aspergillus fumigatus on Exposure to Amphotericin B▿ †

Science.gov (United States)

Gautam, Poonam; Shankar, Jata; Madan, Taruna; Sirdeshmukh, Ravi; Sundaram, Curam Sreenivasacharlu; Gade, Wasudev Namdeo; Basir, Seemi Farhat; Sarma, Puranam Usha

2008-01-01

Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections, including invasive aspergillosis. It has been our aim to understand the molecular targets of AMB in Aspergillus fumigatus by genomic and proteomic approaches. In transcriptomic analysis, a total of 295 genes were found to be differentially expressed (165 upregulated and 130 downregulated), including many involving the ergosterol pathway, cell stress proteins, cell wall proteins, transport proteins, and hypothetical proteins. Proteomic profiles of A. fumigatus alone or A. fumigatus treated with AMB showed differential expression levels for 85 proteins (76 upregulated and 9 downregulated). Forty-eight of them were identified with high confidence and belonged to the above-mentioned categories. Differential expression levels for Rho-GDP dissociation inhibitor (Rho-GDI), secretory-pathway GDI, clathrin, Sec 31 (a subunit of the exocyst complex), and RAB GTPase Ypt51 in response to an antifungal drug are reported here for the first time and may represent a specific response of A. fumigatus to AMB. The expression of some of these genes was validated by real-time reverse transcription-PCR. The AMB responsive genes/proteins observed to be differentially expressed in A. fumigatus may be further explored for novel drug development. PMID:18838595

Proteomic and transcriptomic analysis of Aspergillus fumigatus on exposure to amphotericin B.

Science.gov (United States)

Gautam, Poonam; Shankar, Jata; Madan, Taruna; Sirdeshmukh, Ravi; Sundaram, Curam Sreenivasacharlu; Gade, Wasudev Namdeo; Basir, Seemi Farhat; Sarma, Puranam Usha

2008-12-01

Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections, including invasive aspergillosis. It has been our aim to understand the molecular targets of AMB in Aspergillus fumigatus by genomic and proteomic approaches. In transcriptomic analysis, a total of 295 genes were found to be differentially expressed (165 upregulated and 130 downregulated), including many involving the ergosterol pathway, cell stress proteins, cell wall proteins, transport proteins, and hypothetical proteins. Proteomic profiles of A. fumigatus alone or A. fumigatus treated with AMB showed differential expression levels for 85 proteins (76 upregulated and 9 downregulated). Forty-eight of them were identified with high confidence and belonged to the above-mentioned categories. Differential expression levels for Rho-GDP dissociation inhibitor (Rho-GDI), secretory-pathway GDI, clathrin, Sec 31 (a subunit of the exocyst complex), and RAB GTPase Ypt51 in response to an antifungal drug are reported here for the first time and may represent a specific response of A. fumigatus to AMB. The expression of some of these genes was validated by real-time reverse transcription-PCR. The AMB responsive genes/proteins observed to be differentially expressed in A. fumigatus may be further explored for novel drug development.

Botswana country study

Energy Technology Data Exchange (ETDEWEB)

1999-09-01

This study was carried out in Botswana, Tanzania and Zambia as part of the project `Climate Change Mitigation in Southern Africa` funded by the Danish International Development Agency (Danida). The project was conducted parallel to the UNEP/GEF project `Economics of Greenhouse Gas Limitations` which involved 8 other developing countries and 2 regional projects in Latin America and the SADC region. The limitation of greenhouse gas (GHG) emissions is a complex issue, intimately connected with economic development at local, national, regional and global levels. Key economic sectors such as energy, agriculture, industry and forestry all produce GHGs, and are likely to be affected directly and indirectly by any mitigation policy. The UNEP Greenhouse Gas Abatement Costing Studies, initiated in 1991, attempted to address these complex issues, developing a methodological framework and testing it through practical application in ten countries. (EHS) 28 refs.

Chronische Polyarthritis (Früharthritis

Directory of Open Access Journals (Sweden)

Machold K

2005-01-01

Full Text Available Die Akkumulation von Knorpel- und Knochenschäden, wie sie für chronisch-destruktive Arthritisformen typisch ist, kann durch frühzeitige Intervention mit wirksamen Medikamenten verzögert oder verhindert werden. Voraussetzung ist die rechtzeitige Übernahme der Betreuung gefährdeter Patienten durch einen in der speziellen rheumatologischen Diagnostik und Therapie bewanderten Arzt. Dieser muß das gesamte Repertoire der Arthritistherapie (Medikamente, ergotherapeutische und physiotherapeutische Maßnahmen, Patientenaufklärung etc. entsprechend dem „State of the Art“ beherrschen. In den letzten Jahren erfolgte in vielen Ländern die Etablierung von Spezialeinrichtungen für Patienten mit früher Arthritis. Die an diesen Patienten gewonnenen Erkenntnisse deuten darauf hin, daß die „kritische Periode“, innerhalb derer eine chronische Arthritis möglicherweise reversibel ist, bei 6 bis 12 Wochen liegt.

International organizations as orchestrators

CERN Document Server

Abbott, Kenneth W

2015-01-01

International Organizations as Orchestrators reveals how IOs leverage their limited authority and resources to increase their effectiveness, power, and autonomy from states. By 'orchestrating' intermediaries - including NGOs - IOs can shape and steer global governance without engaging in hard, direct regulation. This volume is organized around a theoretical model that emphasizes voluntary collaboration and support. An outstanding group of scholars investigate the significance of orchestration across key issue areas, including trade, finance, environment and labor, and in leading organizations, including the GEF, G20, WTO, EU, Kimberley Process, UNEP and ILO. The empirical studies find that orchestration is pervasive. They broadly confirm the theoretical hypotheses while providing important new insights, especially that states often welcome IO orchestration as achieving governance without creating strong institutions. This volume changes our understanding of the relationships among IOs, nonstate actors and sta...

Methodological guidelines

Energy Technology Data Exchange (ETDEWEB)

Halsnaes, K.; Callaway, J.M.; Meyer, H.J.

1999-04-01

The guideline document establishes a general overview of the main components of climate change mitigation assessment. This includes an outline of key economic concepts, scenario structure, common assumptions, modelling tools and country study assumptions. The guidelines are supported by Handbook Reports that contain more detailed specifications of calculation standards, input assumptions and available tools. The major objectives of the project have been provided a methodology, an implementing framework and a reporting system which countries can follow in meeting their future reporting obligations under the FCCC and for GEF enabling activities. The project builds upon the methodology development and application in the UNEP National Abatement Coasting Studies (UNEP, 1994a). The various elements provide countries with a road map for conducting climate change mitigation studies and submitting national reports as required by the FCCC. (au) 121 refs.

Nicht förderungswürdig. Weshalb die Evaluation der Exzellenzinitiative gegen deren Fortsetzung spricht

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Tilman Reitz

2016-11-01

Full Text Available Die deutsche Hochschulpolitik hat eine Verstetigung der Exzellenzinitiative auf den Weg gebracht. In Zukunft sollen nach einem Antragswettbewerb ca. fünfzig Exzellenzcluster und acht bis elf Exzellenz-Universitäten für jeweils sieben Jahre vom Bund gefördert werden. Grundlage der politischen Entscheidung ist die Evaluation der Exzellenzinitiative durch eine Expert_innenkommission(Imboden-Bericht. Der Beitrag kommentiert diesen Bericht kritisch und reflektiert problematische Folgen des Wettbewerbs um Fördermittel und ‚Exzellenz‘. Hohe Arbeitslasten, schlechte Betreuungsverhältnisse und die prekäre Lage im wissenschaftlichen Mittelbau an deutschen Hochschulen werden unterstrichen, die angestrebte vertikale Differenzierung des deutschen Hochschulsystems und die Forderung nach starken Hochschulleitungen kritisiert sowie die Verstärkung sozialer Ungleichheiten durch Elitehochschulen angesprochen. Schließlich wird die Grundsatzfrage gestellt, wieso es überhaupt Antrags- und Statuswettbewerbe geben muss.

Influence of Z-phase on Long-term Creep Stability of Martensitic 9 to 12 % Cr Steels

DEFF Research Database (Denmark)

Danielsen, Hilmar Kjartansson; Hald, John

2009-01-01

Die langfristige Kriechstabilität der neuesten Generation martensitischer 9 bis 12 % kriechfester Stähle basiert auf dem bekannten Grade 91, d. h. auf der Stärkung durch die feinen MNNitride (V und Nb). Langzeit-Hochtemperaturtests zeigen den Ersatz der MN-Nitride durch die thermodynamisch...... stabileren Z-Phasen (Cr(V,Nb)N) mit einem Verlust an Kriechfestigkeit. Cr-Gehalte >10,5 % beschleunigen die Ausscheidung der Z-Phasen. Dies beschränkte Bemühungen, einen martensitischen, kriechfesten Stahl mit hohem Cr-Gehalt zum Schutz vor Oxidation zu entwickeln. 9-%-Cr-Stähle werden offensichtlich nicht...... durch die Z-Phase negativ beeinflusst. Die Untersuchung der Z-Phasen-Ausscheidung hat zur Entwicklung eines 12-%-Cr-martensitischen Versuchsstahls geführt, dessen Kriechfestigkeit durch die Z-Phase gewährleistet wird. Derartige Stähle erlauben die ombination hoher Festigkeit bei gleichzeitig guter...

Methodological guidelines

International Nuclear Information System (INIS)

Halsnaes, K.; Callaway, J.M.; Meyer, H.J.

1999-01-01

The guideline document establishes a general overview of the main components of climate change mitigation assessment. This includes an outline of key economic concepts, scenario structure, common assumptions, modelling tools and country study assumptions. The guidelines are supported by Handbook Reports that contain more detailed specifications of calculation standards, input assumptions and available tools. The major objectives of the project have been provided a methodology, an implementing framework and a reporting system which countries can follow in meeting their future reporting obligations under the FCCC and for GEF enabling activities. The project builds upon the methodology development and application in the UNEP National Abatement Coasting Studies (UNEP, 1994a). The various elements provide countries with a road map for conducting climate change mitigation studies and submitting national reports as required by the FCCC. (au) 121 refs

Staat und Welt als Bezugssysteme des Handelns im Prozess der Globalisierung

Directory of Open Access Journals (Sweden)

Lutz Zündorf

2002-07-01

Full Text Available In diesem Beitrag wird Globalisierung als Prozess der Umstellung von Bezugssystemen des Denkens und Handelns von "Staat" auf "Welt" konzipiert. Von der klassischen Definition des Nationalstaates ausgehend, werden zuerst drei staatszentrierte Bezugssysteme (Rechtsstaat, Sozialstaat, Territorialstaat skizziert. Im zweiten Schritt werden globale Bezugssysteme (Welt als einheitlicher Markt, als Gefüge von Herrschaftsgebilden, als Konglomerat von Kulturen umrissen. Die Argumentation läuft darauf hinaus, zu zeigen, dass es sich bei diesen Konzeptionen keineswegs um geschlossene und harmonische Gesellschafts- und Weltbilder handelt; vielmehr enthält jedes der sechs Bezugsysteme spezifische Spannungs- und Konfliktlinien, aus denen sich ihre jeweilige Dynamik speist. Im dritten Schritt werden Prozesse der Umstellung der Bezugssysteme in Richtung Globalität auf drei Ebenen analysiert: auf der Ebene umfassender historischer Prozesse, auf der Ebene staatlichen Handelns und auf der Ebene individueller Akteure.

MODULAR TRAINING IN THE FRAMEWORK OF REALIZATION OF INTERSUBJECT LINKS OF MATHEMATICS WITH OTHER SCHOOL SUBJECTS

Directory of Open Access Journals (Sweden)

О Г Игнатова

2016-12-01

Full Text Available The article deals inter-subject relations with other subjects of algebra curriculum. As part of the GEF activities from the teacher required the formation of a coherent picture of the world, which means that the results of a meta-subject teaching to be achieved. As an example, deals with the topic of non- uniform motion in physics and quadratic functions in algebra. The analysis of the requirements for learning outcomes, the study objectives and data integration capabilities in the process of the study. Just a list of tasks and issues for study in each of the lessons in both integrated classes, and the framework of the modular study. The question of the use and visualization tools as well as the combination of this material and other items (we considered the example of computer science lessons.

Feministische Rechtswissenschaft am Beispiel des Völkerrechts

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Regina Harzer

2007-07-01

Full Text Available Insbesondere das zwischenstaatliche, durch Diplomatie und Außenpolitik geprägte Völkerrecht, war früher – und das liegt nicht sehr lange zurück – reine „Männersache”. Bereits mit dem Titel des Buches möchte Beate Rudolf auf insofern deutlich veränderte Verhältnisse hinweisen. Frauen sind nicht nur potentielle Opfer und damit Gegenstand völkerrechtlichen Schutzes, wenn es um politische Konflikte oder kriegerische Auseinandersetzungen geht. Frauen haben bedeutsame Rechtspositionen erlangt, die national, inter- und transnational Geltung haben und zumindest theoretisch Anerkennung gefunden haben. Frauen verändern Völkerrecht aktiv. Sie wirken mit als Beteiligte staatlicher Delegationen, als Mitglieder von Kontrollgremien und internationalen Organisationen, und Frauen sind wesentlich beteiligt in Nichtregierungsorganisationen. Der Band weist aber auch auf Gefährdungen der erreichten Positionen hin.

Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies

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Tasnuva Sarowar

2016-01-01

Full Text Available Shank proteins (Shank1, Shank2, and Shank3 act as scaffolding molecules in the postsynaptic density of many excitatory neurons. Mutations in SHANK genes, in particular SHANK2 and SHANK3, lead to autism spectrum disorders (ASD in both human and mouse models. Shank3 proteins are made of several domains—the Shank/ProSAP N-terminal (SPN domain, ankyrin repeats, SH3 domain, PDZ domain, a proline-rich region, and the sterile alpha motif (SAM domain. Via various binding partners of these domains, Shank3 is able to bind and interact with a wide range of proteins including modulators of small GTPases such as RICH2, a RhoGAP protein, and βPIX, a RhoGEF protein for Rac1 and Cdc42, actin binding proteins and actin modulators. Dysregulation of all isoforms of Shank proteins, but especially Shank3, leads to alterations in spine morphogenesis, shape, and activity of the synapse via altering actin dynamics. Therefore, here, we highlight the role of Shank proteins as modulators of small GTPases and, ultimately, actin dynamics, as found in multiple in vitro and in vivo models. The failure to mediate this regulatory role might present a shared mechanism in the pathophysiology of autism-associated mutations, which leads to dysregulation of spine morphogenesis and synaptic signaling.

Planning, budgeting and performance management at Swiss hospitals – Are Swiss hospitals at a crossroads – Will these medical specialist organisations in future develop into institutions with a business orientation? [Die Krankenhäuser der Schweiz am Wendepunkt von der medizinischen Expertenorganisation hin zu betriebswirtschaftlich geführten Institutionen? – Untersuchung zu deren Performance-Management-System

Directory of Open Access Journals (Sweden)

Walser, Konrad

2013-11-01

äuser leistungsorientiert geführt werden.

Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

Science.gov (United States)

Perez, Kimberly; Safran, Howard; Sikov, William; Vrees, Matthew; Klipfel, Adam; Shah, Nishit; Schechter, Steven; Oldenburg, Nicklas; Pricolo, Victor; Rosati, Kayla; Dipetrillo, Thomas

2017-06-01

Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery. Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation. Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%). CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

BRCAness and Prognosis in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

Directory of Open Access Journals (Sweden)

Hirokazu Tanino

Full Text Available BRCAness is defined as the set of traits in which BRCA1 dysfunction, arising from gene mutation, methylation or deletion, results in DNA repair deficiency. In the present study, we addressed BRCAness, therapeutic efficacy, recurrence, and survival in patients with triple negative breast cancer (TNBC who were treated with neoadjuvant chemotherapy at Kitasato University Hospital, Japan, between April 2006 and October 2012. BRCAness was determined by preoperative core needle biopsy (CNB specimens and surgical specimens. Assay was performed using Multiplex Ligation-dependent Probe Amplification (MLPA with P376-B2 BRCA1ness probemix (MRC-Holland, Amsterdam, The Netherlands. The relative copy number ratio of each sample was compared to Human Genomic DNA (Promega, Madison, WI, USA as reference samples was calculated with Coffalyser.NET default settings. The BRCAness score was calculated with the relative copy number ratio of various DNA sequences. Values of 0.5 or more were determined as the BRCA1-like Type (BRCAness and those of less than 0.5 as the Sporadic Type to analyze pathological complete response (pCR rate, recurrence, and survival. pCR (ypT0/Tis/N0 was observed in 15 patients (pCR rate: 37.5%. These patients had no recurrence. Twelve patients recurred, 8 died from breast cancer. The BRCA1-like Type were 22 and Sporadic Type were 18 in CNB specimens. No major differences were observed between the BRCA1-like Type and Sporadic Type with pCR rate, recurrence rate and survival. Twenty four surgical specimens of non-pCR patients were available and 9 were BRCA1-like Type, who had more recurrences (7/9 vs. 5/15, and their relapse-free survival was also lower (p<0.05 than that of Sporadic Type. Seven BRCA1-like Type patients remained BRCA1-like Type in surgical specimens, were worse in recurrence (p<0.01 and survival (p<0.05 compared with 6 patients whose BRCA status in surgical specimens turned to Sporadic Type. New clinical trials assessing the true

KRISENZUSTÄNDE UND ANWENDUNG VON ZWANGSMASSNAHMEN IN DER PSYCHIATRIE

Directory of Open Access Journals (Sweden)

Vesna Šendula Jengić

2017-01-01

Full Text Available In der Arbeit wird über die Phänomene der Aggressivität und Gewalt bei Menschen diskutiert, wobei man besonderen Wert auf die Personen mit seelischen Störungen legt. Krisenzustände und Gewaltverhalten gibt es nicht nur in der Psychiatrie. Es kann immer zu einem solchem Zustand und Verhalten kommen und jeder kann unter bestimmten Umständen sowohl Opfer als auch Täter sein. Multikausalität und Komplexität sowie auch individuelle Umstände und situationsbezogene Faktoren, welche zum Gewaltverhalten führen können, haben nur geringen Prognosekraft. Statistische Indikatoren andererseits können falsch positive und falsch negative Ergebnisse verbergen, wobei ein Fehler in der Einschätzung das Risiko zum Erscheinen eines Verhaltens drastisch erhöhen oder zum unrechtfertigten Entziehung der Freiheit führen kann. Zwangsmaβnahmen in der Psychiatrie sind nur ausnahmsweise anzuwenden, und zwar, wenn ein gefährliches Verhalten direkt das Leben und die Gesundheit einer Person oder einer Umgebung gefährdet. Darüber hinaus ist die Dauer von Zwangsmaβnahmen auch beschränkt. Die Gesetzesregulative, insbesondere das Gesetz über den Schutz von Personen mit seelischen Störungen (Amtsblatt der Republik Kroatien Nr. 76/2014 und die Ordnung über die Arten und die Weise der Anwendung von Zwangsmaβnahmen gegenüber den Personen mit schwierigen seelischen Störungen (Amtsblatt der Republik Kroatien Nr. 16/2015, dient als zusätzlicher Schutz der Rechte dieser Patientengruppe und schreibt die Arten und die Weise der Anwendung von Zwangsmaβnahmen sowie auch die Vorgehensweise. Zusätzliche Richtlinien und Vorgehensstrategien wurden auch von den Gesellschaften für Psychiatrie gegeben. In der Arbeit wird betont, dass bessere Bedingungen, Infrastruktur und Arbeitskräfte sowie auch ständige Entwicklung und Bewertung der Arbeitsqualität in der Psychiatrie erforderlich sind. Abschlieβend werden Standards und ethische Fragen in Betracht gezogen, wie

Cathodoluminescence investigation of Ge-point defects in silica-based optical fibers

Energy Technology Data Exchange (ETDEWEB)

Reghioua, I., E-mail: imene.reghioua@univ-st-etienne.fr [Univ-Lyon, Laboratoire H. Curien, UMR CNRS 5516, 18 rue du Pr. Benoît Lauras, 42000 Saint-Etienne (France); Girard, S.; Alessi, A.; Di Francesca, D. [Univ-Lyon, Laboratoire H. Curien, UMR CNRS 5516, 18 rue du Pr. Benoît Lauras, 42000 Saint-Etienne (France); Martin-Samos, L.; Fanetti, M. [Materials Research Laboratory, University of Nova Gorica, Vipavska 11c 5270-Ajdovscina (Slovenia); Richard, N.; Raine, M. [CEA, DAM, DIF, F91297, Arpajon (France); Valant, M. [Materials Research Laboratory, University of Nova Gorica, Vipavska 11c 5270-Ajdovscina (Slovenia); Boukenter, A.; Ouerdane, Y. [Univ-Lyon, Laboratoire H. Curien, UMR CNRS 5516, 18 rue du Pr. Benoît Lauras, 42000 Saint-Etienne (France)

2016-11-15

Cathodoluminescence (CL) measurements have been performed on Ge doped and Ge/F co-doped optical fibers, in the aim of studying the spatial distributions of the emitting precursor defects present in the as-drawn optical fiber as well as those of the radiation induced centers generated by the 10 keV electron exposure. Using the CL instrument, we recorded different emission bands located in the visible spectral domain (300–750 nm) as well as CL imaging of associated defects, with a spatial resolution of about 1 µm, along the fiber transverse cross sections. In the pristine fiber, Germanium Lone Pair Centers (GLPCs) emitting at 400 nm are the main precursor sites observed in both fibers. Whereas during electron exposure, these centers are converted into other Ge-related defects. In this paper, we studied in situ their bleaching kinetic using CL monochromatic imaging. As expected, our results show that the GLPC signal decreases with the electron fluence, confirming its precursor role. Thanks to the CL abilities, we also demonstrate that the GLPC conversion into radiation induced defects (and then its bleaching kinetic) depends on the germanium concentration, opening the way to a better control of the radiation sensitivity of germanosilicate glass.

Vietnam

Energy Technology Data Exchange (ETDEWEB)

1999-09-01

As a Party to the United Nations Framework Convention on Climate Change (UNFCCC) Viet Nam will make its strong effort to implement the UNFCCC through effective activities in order to reduce GHG emissions as well as enhance carbon sinks in the country. The UNEP/GEF Project `Economics of GHG Limitation - Phase 1: Establishment of a Methodological Framework for Climate Change Mitigation Assessment` developed by the UNEP Collaborating Centre on Energy and Environment (UCCEE) in cooperation with Lawrence Berkeley Laboratory has been deployed in Viet Nam since 1996. The project deals with GHG mitigation analysis and options, focusing on the main issues: a) Associated macro-economics, b) Energy, c) Land use and forestry. For this study, a number of different data related to energy, industry, forestry and agriculture sectors as well as Viet Nam socio-economic development up to the year 2030, are collected. Besides, several models such as MEDEE-S, EFOM-ENV, COMAP are applied for development and assessment of GHG mitigation options in the next decades. The MEDEE-S and EFOM-ENV models are used as a tool for determining the cost-effective strategies to abate GHG emissions for energy sector while COMAP model is applied for forestry sector. (au) 39 refs.

Paxillin: a crossroad in pathological cell migration

Directory of Open Access Journals (Sweden)

Ana María López-Colomé

2017-02-01

Full Text Available Abstract Paxilllin is a multifunctional and multidomain focal adhesion adapter protein which serves an important scaffolding role at focal adhesions by recruiting structural and signaling molecules involved in cell movement and migration, when phosphorylated on specific Tyr and Ser residues. Upon integrin engagement with extracellular matrix, paxillin is phosphorylated at Tyr31, Tyr118, Ser188, and Ser190, activating numerous signaling cascades which promote cell migration, indicating that the regulation of adhesion dynamics is under the control of a complex display of signaling mechanisms. Among them, paxillin disassembly from focal adhesions induced by extracellular regulated kinase (ERK-mediated phosphorylation of serines 106, 231, and 290 as well as the binding of the phosphatase PEST to paxillin have been shown to play a key role in cell migration. Paxillin also coordinates the spatiotemporal activation of signaling molecules, including Cdc42, Rac1, and RhoA GTPases, by recruiting GEFs, GAPs, and GITs to focal adhesions. As a major participant in the regulation of cell movement, paxillin plays distinct roles in specific tissues and developmental stages and is involved in immune response, epithelial morphogenesis, and embryonic development. Importantly, paxillin is also an essential player in pathological conditions including oxidative stress, inflammation, endothelial cell barrier dysfunction, and cancer development and metastasis.

Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

International Nuclear Information System (INIS)

Kita, Ayako; Higa, Mari; Doi, Akira; Satoh, Ryosuke; Sugiura, Reiko

2015-01-01

Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2 + gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2 + gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking

Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

Energy Technology Data Exchange (ETDEWEB)

Kita, Ayako; Higa, Mari [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Doi, Akira [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Satoh, Ryosuke [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Sugiura, Reiko, E-mail: sugiurar@phar.kindai.ac.jp [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan)

2015-02-13

Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2{sup +} gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2{sup +} gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking.

The Use of Ecological Indicators as a Basis for Operationalizing a PES Scheme on Forest Conservation in Northern Argentina

Science.gov (United States)

Gobbi, José; Deguillon, Marie

2017-04-01

Payments for ecosystem services (PES) aim to improve the supply of ecosystem services (ES) by making payments to service providers, which are conditional on the provision of those services. Payments cannot be conditional unless the service can be effectively monitored. Direct monitoring of ES to assess conditionality could be methodologically complex and operatively expensive. To overcome such constraints, the pilot "GEF-PES Project" of Northern Argentina has developed a set of five indicators on forest conservation status (CS) as a basis for estimating the amount of ES provided -considering a positive correlation between the CS of a forest and its level of provision of ecosystem services -and for operationalizing the PES. Field data indicate that selected indicators: (i) exhibit strong correlation with the amount of carbon and biodiversity provided by forests according to their CS, ii) are cost-effective to monitor ES conditionality and (iii) allow easy application of payment levels.

WBP/SIGAME the Brazilian BIG-GT demonstration project actual status and perspectives

International Nuclear Information System (INIS)

Carpentier, E.; Silva, A.

1998-01-01

Located in the tropics, with the sun shining all year round, and with its vast territory, Brazil may be regarded as having all the basic conditions to develop a modern Biomass for Electricity industry. Those characteristics together with: (a) the necessity of developing new energy resources for electricity production, in the northeast of the country; (b) the results of studies made by various entities, including CHESF; (c) the progress achieved by the BIG-GT technology; (d) the organisation of the Global Environment Facility (GEF); (e) and the support of the Brazilian government, through the Ministry of Science and Technology (MCT), provided the unique opportunity for the implementation of a commercial demonstration of that technology in Brazil. This paper describes the idea, scope, challenges, lessons, and actual status of development of the WBP/SIGAME project. It also highlights some institutional issues, budget figures, and energy prices. (author)

Frege – The Unintentional Linguist. On Frege’s Views of Language in the Context of 19th Century German Linguistics

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Karsten Hvidtfelt Nielsen

2008-05-01

Full Text Available Sein ganzes berufliches Leben hindurch betrachtete Frege die Sprache als eine gefährliche Bedrohung des wissenschaftlichen Erkennens, der mit allen Mitteln der Logik zu begegnen war. Im ersten Teil des Aufsatzes wird aufgezeigt, wie Frege diese Auffassung in oft unbewusster und ungewollter Übereinstimmung mit gleichzeitigen Tendenzen sowohl in der deutschen Linguistik (Becker, Steinthal, Paul, Wundt als auch in der deutschen Sprachkritik (Gruppe, Nietzsche, Mauthner entwickelte und wie sein epistemologischer ‚Kampf gegen die Sprache’ mit einer bitteren persönlichen und professionellen Niederlage endete. Der zweite Teil des Aufsatzes enthält eine Rekonstruktion von Freges logischer Grammatik sowie eine Darstellung des linguistischen Argumentes, das für Freges endgültiges (und tragisches Akzept vom Sprachskeptizismus entscheidend wurde (das sogenannte Fregesche Paradox. Der Aufsatz schließt mit einer Evaluierung der Relevanz des Fregeschen Paradoxes für die heutige Linguistik.

Frege – The Unintentional Linguist. On Frege’s Views of Language in the Context of 19th Century German Linguistics

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Karsten Hvidtfelt Nielsen

2008-06-01

Full Text Available Sein ganzes berufliches Leben hindurch betrachtete Frege die Sprache als eine gefährliche Bedrohung des wissenschaftlichen Erkennens, der mit allen Mitteln der Logik zu begegnen war. Im ersten Teil des Aufsatzes wird aufgezeigt, wie Frege diese Auffassung in oft unbewusster und ungewollter Übereinstimmung mit gleichzeitigen Tendenzen sowohl in der deutschen Linguistik (Becker, Steinthal, Paul, Wundt als auch in der deutschen Sprachkritik (Gruppe, Nietzsche, Mauthner entwickelte und wie sein epistemologischer ‚Kampf gegen die Sprache’ mit einer bitteren persönlichen und professionellen Niederlage endete. Der zweite Teil des Aufsatzes enthält eine Rekonstruktion von Freges logischer Grammatik sowie eine Darstellung des linguistischen Argumentes, das für Freges endgültiges (und tragisches Akzept vom Sprachskeptizismus entscheidend wurde (das sogenannte Fregesche Paradox. Der Aufsatz schließt mit einer Evaluierung der Relevanz des Fregeschen Paradoxes für die heutige Linguistik.

Gestaltung einer netzbasierten Lernumgebung für einen Fernstudiengang zu „Medien und Informationstechnologien in Erziehung, Unterricht und Bildung“

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Gerhard Tulodziecki

2017-07-01

Full Text Available In diesem Beitrag stelle ich dar, wie wir in einem kooperativen Verbund eine netzbasierte Lernumgebung für einen Fernstudiengang zu „Medien und Informationstechnologien in Erziehung, Unterricht und Bildung“ gestalten. Das Projekt wird von zwei Arbeitsgruppen an der Universität Paderborn (Allgemeine Didaktik und Medienpädagogik, Didaktik der Informatik und einer Arbeitsgruppe an der Fernuniversität Hagen (Theorie der Schule und des Unterrichts getragen. Die Projektleitung teile ich mit Horst Dichanz, Bardo Herzig und Johannes Magenheim. Der Fernstudiengang basiert auf Entwicklungen zur Lehrerausbildung im Bereich neuer Medien, wie sie im Rahmen der Initiative „Bildungswege in der Informationsgesellschaft (BIG“ erarbeitet wurden (vgl. u.a. Tulodziecki/Moll/Gallasch 2001. Die – 1995 begonnene – BIG-Initiative geht auf die Bertelsmann Stiftung und Heinz Nixdorf Stiftung zurück. Die jetzige Projektarbeit wird von der ,,e-nitiative.nrw.Netzwerk für Bildung“ gefördert.

Förderung beruflicher Handlungskompetenz durch reflektiertes Erfahrungslernen mit digitalen Medien

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Jan Hellriegel

2017-02-01

Full Text Available Eine gelingende Entwicklung beruflicher Handlungsfähigkeit in der dualen Berufsausbildung ist auf eine Kooperation von Lehrenden, Ausbildenden und Auszubildenden angewiesen. Häufig scheitert diese Zusammenarbeit jedoch an den spezifischen Lernkulturen und der räumlichen Trennung der verschiedenen Lernorte. Das BMBF-geförderte Forschungsprojekt KOLA: «Kompetenzorientiertes Lernen im Arbeitsprozess mit digitalen Medien» greift diese Problematik auf und verfolgt das Ziel, mithilfe digitaler Medien eine Lernortkooperation zu befördern. Erprobt wird das entwickelte System, bestehend aus einer App und einer Browser-basierten Plattform, in saarländischen Ausbildungsstätten des Elektrohandwerks im Untersuchungszeitraum von Oktober 2014 bis September 2017. Im Rahmen dieses Projektes wird ein lerntheoretischer Ansatz verfolgt, der sich im Kontext von Konstruktivismus und Pragmatismus verorten lässt. Der vorliegende Beitrag fokussiert dabei das didaktische Konzept des Projektes, welches einerseits die didaktischen Grundannahmen und andererseits das hieraus abgeleitete Nutzungsszenario darstellt.

Rezension von: Thomas Martinec, Claudia Nitschke (Hg.: Familie und Identität in der deutschen Literatur. Frankfurt am Main u.a.: Peter Lang Verlag 2009. — Ariane Eichenberg: Familie – Ich – Nation. Göttingen: V&R unipress 2009.

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Christine Kanz

2010-06-01

Full Text Available Die Themen Generation und Familie gehören zu den wichtigsten Sujets literarischer Texte, insbesondere wenn diese die Herausbildung oder die Zerstörung von Identität problematisieren. Ein neuer, von Claudia Nitschke und Thomas Martinec herausgegebener Tagungsband ist der literatur- und kulturwissenschaftlichen Auseinandersetzung mit diesen Themen gewidmet. Sechs Jahrzehnte nach dem Ende des Zweiten Weltkrieges hat vor allem das Genre des Generationenromans Hochkonjunktur, insbesondere Texte der dritten Generation zum Umgang der Großeltern-Generation mit dem Nationalsozialismus. Den Verfasser/-innen dieses neuen, in sich heterogenen Genres wird in der Studie von Ariane Eichenberg allerdings keine allzu große Wirkmächtigkeit bescheinigt. Im Gegenteil nährten die modischen Texte mit den Funden aus der Vergangenheit vor allem das Ich der Erzähler/-innen, deren eigene Gefühle und Selbstvergewisserung in einer von Unsicherheiten geprägten Gegenwart.

Wäre es Dir lieber, ich würde zu Recht verurteilt? - Sokrates Bund und die Frage der Kontrolle

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Katharina Kaiser-Müller

2014-09-01

Full Text Available Die Ablösung von zweifelhafter menschlicher Kontrolle durch eine zuverlässige Software bietet eindrucksvolle Möglichkeiten. Mit der flächendeckenden Einführung von Sokrates Bund zum Schuljahr 2014/2015 wird endlich die Identifzierung von Pisadurchschnittsverderbern möglich. Die AutorInnen diskutieren die Lage ... Die Situation war dramatisch: Ungerecht angeklagt wegen Verführung der Jugend und Gottlosigkeit, sieht Sokrates dem Tod durch den Schierlingsbecher entgegen und antwortet auf die ob des Fehlurteils durchaus verständliche Klage von Xanthippe mit der titelgebenden Frage. Anschließend verweigert er die Flucht und zieht es vor, sich dem formal korrekt gefällten falschen Urteil zu beugen. Eine legendäre Entscheidung, in der Sokrates die Gesetzestreue mit der Begründung, man müsse schlechte Gesetze ändern, dürfe sie aber nicht übertreten, über das eigene Wohl stellt.

Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection.

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Eva Rothmeier

2013-09-01

Full Text Available The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS to form in phagocytes a distinct "Legionella-containing vacuole" (LCV, which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila.

Activation of Ran GTPase by a Legionella Effector Promotes Microtubule Polymerization, Pathogen Vacuole Motility and Infection

Science.gov (United States)

Rothmeier, Eva; Pfaffinger, Gudrun; Hoffmann, Christine; Harrison, Christopher F.; Grabmayr, Heinrich; Repnik, Urska; Hannemann, Mandy; Wölke, Stefan; Bausch, Andreas; Griffiths, Gareth; Müller-Taubenberger, Annette; Itzen, Aymelt; Hilbi, Hubert

2013-01-01

The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS) to form in phagocytes a distinct “Legionella-containing vacuole” (LCV), which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF) domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP) in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED) fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila. PMID:24068924

Sequential analysis of trans-SNARE formation in intracellular membrane fusion.

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Kannan Alpadi

2012-01-01

Full Text Available SNARE complexes are required for membrane fusion in the endomembrane system. They contain coiled-coil bundles of four helices, three (Q(a, Q(b, and Q(c from target (t-SNAREs and one (R from the vesicular (v-SNARE. NSF/Sec18 disrupts these cis-SNARE complexes, allowing reassembly of their subunits into trans-SNARE complexes and subsequent fusion. Studying these reactions in native yeast vacuoles, we found that NSF/Sec18 activates the vacuolar cis-SNARE complex by selectively displacing the vacuolar Q(a SNARE, leaving behind a Q(bcR subcomplex. This subcomplex serves as an acceptor for a Q(a SNARE from the opposite membrane, leading to Q(a-Q(bcR trans-complexes. Activity tests of vacuoles with diagnostic distributions of inactivating mutations over the two fusion partners confirm that this distribution accounts for a major share of the fusion activity. The persistence of the Q(bcR cis-complex and the formation of the Q(a-Q(bcR trans-complex are both sensitive to the Rab-GTPase inhibitor, GDI, and to mutations in the vacuolar tether complex, HOPS (HOmotypic fusion and vacuolar Protein Sorting complex. This suggests that the vacuolar Rab-GTPase, Ypt7, and HOPS restrict cis-SNARE disassembly and thereby bias trans-SNARE assembly into a preferred topology.

The adaptor molecule Nck localizes the WAVE complex to promote actin polymerization during CEACAM3-mediated phagocytosis of bacteria.

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Stefan Pils

Full Text Available BACKGROUND: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. PRINCIPAL FINDINGS: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. CONCLUSIONS: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment.

De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor-Positive Phase II Randomized Trial-Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET.

Science.gov (United States)

Harbeck, Nadia; Gluz, Oleg; Christgen, Matthias; Kates, Ronald Ernest; Braun, Michael; Küemmel, Sherko; Schumacher, Claudia; Potenberg, Jochem; Kraemer, Stefan; Kleine-Tebbe, Anke; Augustin, Doris; Aktas, Bahriye; Forstbauer, Helmut; Tio, Joke; von Schumann, Raquel; Liedtke, Cornelia; Grischke, Eva-Maria; Schumacher, Johannes; Wuerstlein, Rachel; Kreipe, Hans Heinrich; Nitz, Ulrike Anneliese

2017-09-10

Purpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen

Efficacy of Early Intervention with Liskantin or Primidone to Decrease Developmental Delay in Children with Drowet and GEFS+ Syndrome

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Mohammad Reza Koushesh

2014-03-01

Full Text Available Objective: Febrile seizure (FS occurs between 6 months and 6 years of age. Febrile seizure is a common disease in pediatrics. Some patients are retarded with recurrent febrile seizure. For example Drawet syndrome was started with febrile seizure and progress into the intractable seizure and finally are retarded. Materials & Methods: This article is the clinical trial study. Population in this study are 86 children whit febrile seizure refer to pediatrics’ medical central. This study was carried out in 2013. In this study evaluated patients with febrile seizure’s criteria and included in the population. Children statistics with febrile seizure refer to pediatrics’ medical center registered and compared with other statistics. Data enter the SPSS program 18 version (SPSS Inc, Chicago, USA and used analysis statistical tests and also T-test, Chi Square tests. Finally evaluated total parameters by MIN+SD and reported significant difference (P-value<0.05. Numbers of patients determined according to previous study. Results: In this study 46 patients with complex febrile seizure and early initiation of treatment were not retarded and haven’t any complications. Conclusion: Early initiation of treatment in the patient whit febrile seizure very important to prophylaxis of developmental delay and developmental regression.

Digital Medien im Naturwissenschaftlichen Unterricht

CERN Document Server

Meßinger-Koppelt, Jenny

2014-01-01

„Morgens, 8 Uhr: Kurz vor der Schultür werden noch die neuesten Posts auf Facebook geliked, ein Selfie in die Whats-App-Gruppe hochgeladen oder auf YouTube noch ein #LOL-Video gestreamed. Dann klingelt es und die Digital Natives greifen wieder zu Stift, Papier und werden frontal mit Fakten gefüttert“ (A. Spang). Für Schüler sind Internet, Smartphone und Tablet-PC heute selbstverständlicher Teil ihrer Lernwelt. Und auch die Alltags- und Berufswelt ist ohne Informationstechnologien nicht mehr vorstellbar. Doch was bedeutet das für den Schulunterricht, insbesondere für die techniknahen Naturwissenschaften? Wie gelingt im Schulalltag die Balance zwischen Kreidezeit und interaktivem Whiteboard nach mittlerweile 30 Jahren Erfahrung mit Schulcomputern? Der vorliegende Sammelband präsentiert zahlreiche Praxisbeispiele aus dem Schulalltag zum sinnvollen Einsatz digitaler Medien im Biologie-, Chemie- und Physik-Unterricht sowie den aktuellen Stand der fachdidaktischen Forschung. Zu Wort kommen Hochschullehr...

World bank and the environment. Progress report

International Nuclear Information System (INIS)

1991-01-01

The second annual report describes specific environmental strategies and environmental lending in the Bank's four operational regions: Africa; Asia; Europe, Middle East, and North Africa; and Latin America and the Caribbean. It details the Bank's progress in eight environmental categories: energy and the environment, pollution, urban environment, water resources management, forest and land management, social and cultural, environmental economics, and the global environment. One chapter is devoted exclusively to tropical forests, studying ways in which the Bank is dealing with deforestation as a part of the constant review of its forest policies. Suggestions are made for decreasing the degradation of tropical forests while meeting demands for forest products. This chapter reflects a shift in Bank emphasis from commercial ventures to conservation measures. The publication reports on other initiatives by the Bank during fiscal 1991, including the launching of the Global Environment Facility (GEF)--a pilot program to oversee reduction of global warming, preservation of biological diversity, protection of international waters, and prevention of ozone depletion

And the winner is … Von Rankings und Ökonomen-Hitparaden: einige provokante Überlegungen

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Kathrin Deumelandt

2014-03-01

Full Text Available Der Versuch, wissenschaftliche Qualität von Universitäten, Fachbereichen und einzelnen WissenschaftlerInnen zu messen und vergleichbar zu machen, nimmt nicht nur in der Wirtschaftswissenschaft in Form von Rankings einen immer breiteren Raum ein. Solche Rankings befriedigen aber nicht nur den vielleicht verständlichen Wunsch nach Komparabilität, sondern entscheiden immer stärker über Ressourcenallokation, Forschungsausrichtungen und, noch grundsätzlicher, über Karrierechancen von WissenschaftlerInnen. Auch die vielfach hervorgebrachte Kritik an den verschiedenen Methodiken der Ranking-Erstellung hat nicht dazu geführt, die Ranking-Aktivitäten zu reduzieren oder auch nur deren Wirkungsmacht zu begrenzen. Neben der grundsätzlichen Kritik an dem Versuch, das Unmessbare messbar zu machen, wird in diesem Artikel insbesondere auf das Diskriminierungspotenzial von Rankings verwiesen, deren Erstellungsmethodik plurale und heterodoxe Forschung systematisch benachteiligen. Zur Illustration dieses Umstands wird mittels alternativer Kriterien ein Robustheitstest des einschlägigsten Rankings durchgeführt.

Review: Eine Replik auf: Schmitt, Rudolf (2011. Review Essay: Rekonstruktive und andere Metaphernanalysen

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Jan Kruse

2012-03-01

Full Text Available udolf SCHMITT ist unbestreitbar ein fundierter Experte im deutschsprachigen Raum im Hinblick auf eine umfassende und fokussierte Metaphernanalyse als ein spezifisches Verfahren der Analyse qualitativer Daten. Mit seiner in FQS erschienenen Rezension zu unserem Buch "Metaphernanalyse. Ein rekonstruktiver Ansatz" wird dies abermals deutlich. SCHMITT ordnet unser Verfahren zur rekonstruktiven Metaphernanalyse in andere sozialwissenschaftliche Metaphernanalysen ein und versucht auf dieser Grundlage, Vor- und Nachteile unseres metaphernanalytischen Zugangs hervorzuheben. Ausgehend von diesem Vergleichshorizont gelingt ihm die Besprechung eines grundlegenden Buches zur Einführung in die sozialwissenschaftliche Metaphernanalyse – welches unser Buch aber weder ist noch vorgibt zu sein. Wir begrüßen seine breit gefächerte Auswahl sozialwissenschaftlicher metaphernanalytischer Zugänge, glauben aber, dass die Zielsetzungen unseres Ansatzes (und unseres Buches in seinem Review-Essay zu sehr in den Hintergrund treten. Wir haben uns daher zu dieser Replik entschlossen, um die "sozialwissenschaftliche Metaphernanalyse" weiter in einem diskursiven Prozess zu halten. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1202102

Climate change mitigation in Africa

Energy Technology Data Exchange (ETDEWEB)

Mackenzie, G A; Turkson, J K; Davidson, O R [eds.

1998-10-01

The UNEP Collaborating Centre on Energy and Environment (UCCEE) in conjunction with the Southern Centre for Energy and Environment (SCEE) hosted a conference on `Climate Change Mitigation in Africa` between 18 and 20 May. The Conference set out to address the following main objectives: to present to a wider audience the results of UNEP/GEF and related country studies; to present results of regional mitigation analysis; exchange of information with similar projects in the region; to expose countries to conceptual and methodological issues related to climate change mitigation; to provide input to national development using climate change related objectives. This volume contains reports of the presentations and discussions, which took place at the conference at Victoria Falls between 18 and 20 May 1998. Representatives of 11 country teams made presentations and in addition two sub-regions were discussed: the Maghreb region and SADC. The conference was attended by a total of 63 people, representing 22 African countries as well as international organisations. (EG)