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Lithiated 2-alkynyl-1,3-dioxanes as fully oxygenated acyl-anion equivalents Synthesis of 1-alkynyl ketones

J.H. Kruithof, K. ; F. Schmitz, R. ; W. Klumpp, G.

Amsterdam : Elsevier

Tetrahedron 39 (1983), S. 3073-3081

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ISSN: 0040-4020

Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Topics: Chemistry and Pharmacology

Type of Medium: Electronic Resource

URL: http://linkinghub.elsevier.com/retrieve/pii/S0040-4020(01)91548-0

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The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants (1997)

K. Scheffzek ; M. R. Ahmadian ; W. Kabsch ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 277(5324): 333-8.

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Publication Date: 1997-07-18

Description: The three-dimensional structure of the complex between human H-Ras bound to guanosine diphosphate and the guanosine triphosphatase (GTPase)-activating domain of the human GTPase-activating protein p120GAP (GAP-334) in the presence of aluminum fluoride was solved at a resolution of 2.5 angstroms. The structure shows the partly hydrophilic and partly hydrophobic nature of the communication between the two molecules, which explains the sensitivity of the interaction toward both salts and lipids. An arginine side chain (arginine-789) of GAP-334 is supplied into the active site of Ras to neutralize developing charges in the transition state. The switch II region of Ras is stabilized by GAP-334, thus allowing glutamine-61 of Ras, mutation of which activates the oncogenic potential, to participate in catalysis. The structural arrangement in the active site is consistent with a mostly associative mechanism of phosphoryl transfer and provides an explanation for the activation of Ras by glycine-12 and glutamine-61 mutations. Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheffzek, K -- Ahmadian, M R -- Kabsch, W -- Wiesmuller, L -- Lautwein, A -- Schmitz, F -- Wittinghofer, A -- New York, N.Y. -- Science. 1997 Jul 18;277(5324):333-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Rheinlanddamm 201, 44139 Dortmund, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9219684" target="_blank"〉PubMed〈/a〉

Keywords: Aluminum Compounds/chemistry/metabolism ; Amino Acid Sequence ; Binding Sites ; Catalysis ; Cell Transformation, Neoplastic ; Crystallography, X-Ray ; Enzyme Activation ; Fluorides/chemistry/metabolism ; GTP Phosphohydrolases/chemistry/*metabolism ; GTP-Binding Proteins/chemistry/metabolism ; GTPase-Activating Proteins ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Humans ; Models, Molecular ; Molecular Sequence Data ; Mutation ; *Protein Conformation ; Protein Structure, Secondary ; Proteins/*chemistry/*metabolism ; Signal Transduction ; ras GTPase-Activating Proteins ; ras Proteins/chemistry/genetics/*metabolism

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses (2012)

V. Litvak ; A. V. Ratushny ; A. E. Lampano ; [et al.]

Nature Publishing Group (NPG)

In: Nature. 490(7420): 421-5. doi: 10.1038/nature11428.

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Publication Date: 2012-09-18

Description: Antiviral responses must be tightly regulated to defend rapidly against infection while minimizing inflammatory damage. Type 1 interferons (IFN-I) are crucial mediators of antiviral responses and their transcription is regulated by a variety of transcription factors; principal among these is the family of interferon regulatory factors (IRFs). The IRF gene regulatory networks are complex and contain multiple feedback loops. The tools of systems biology are well suited to elucidate the complex interactions that give rise to precise coordination of the interferon response. Here we have used an unbiased systems approach to predict that a member of the forkhead family of transcription factors, FOXO3, is a negative regulator of a subset of antiviral genes. This prediction was validated using macrophages isolated from Foxo3-null mice. Genome-wide location analysis combined with gene deletion studies identified the Irf7 gene as a critical target of FOXO3. FOXO3 was identified as a negative regulator of Irf7 transcription and we have further demonstrated that FOXO3, IRF7 and IFN-I form a coherent feed-forward regulatory circuit. Our data suggest that the FOXO3-IRF7 regulatory circuit represents a novel mechanism for establishing the requisite set points in the interferon pathway that balances the beneficial effects and deleterious sequelae of the antiviral response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556990/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Litvak, Vladimir -- Ratushny, Alexander V -- Lampano, Aaron E -- Schmitz, Frank -- Huang, Albert C -- Raman, Ayush -- Rust, Alistair G -- Bergthaler, Andreas -- Aitchison, John D -- Aderem, Alan -- HHSN272200700038C/AI/NIAID NIH HHS/ -- HHSN272200700038C/PHS HHS/ -- HHSN272200800058C/AI/NIAID NIH HHS/ -- HSN272200800058C/PHS HHS/ -- R01 AI025032/AI/NIAID NIH HHS/ -- R01 AI032972/AI/NIAID NIH HHS/ -- R01AI025032/AI/NIAID NIH HHS/ -- R01AI032972/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 GM103511/GM/NIGMS NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- U54GM103511/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Oct 18;490(7420):421-5. doi: 10.1038/nature11428. Epub 2012 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22982991" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Female ; Forkhead Transcription Factors/deficiency/genetics/*metabolism ; Gene Deletion ; Gene Expression Regulation/*immunology ; Inflammation/genetics/*immunology/*pathology ; Interferon Regulatory Factor-7/deficiency/genetics/*metabolism ; Interferon Type I/immunology ; Lung/immunology/pathology/virology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Reproducibility of Results ; Vesiculovirus/*immunology

Print ISSN: 0028-0836

Electronic ISSN: 1476-4687

Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics

Published by Nature Publishing Group (NPG)

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High temperature and dynamic testing of AHSS for an analytical description of the adiabatic cutting process (2017)

S Winter, F Schmitz, T Clausmeyer, A E Tekkaya and M F-X Wagner

Institute of Physics (IOP)

In: IOP Conference Series: Materials Science and Engineering

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Publication Date: 2017-03-18

Description: In the automotive industry, advanced high strength steels (AHSS) are widely used as sheet part components to reduce weight, even though this leads to several challenges. The demand for high-quality shear cutting surfaces that do not require reworking can be fulfilled by adiabatic shear cutting: High strain rates and local temperatures lead to the formation of adiabatic shear bands (ASB). While this process is well suited to produce AHSS parts with excellent cutting surface quality, a fundamental understanding of the process is still missing today. In this study, compression tests in a Split-Hopkinson Pressure Bar with an initial strain rate of 1000 s -1 were performed in a temperature range between 200 °C and 1000 °C. The experimental results show that high strength steels with nearly the same mechanical properties at RT may possess a considerably different behavior at higher temperatures. The resulting microstructures after testing at different temperatures were analy...

Print ISSN: 1757-8981

Electronic ISSN: 1757-899X

Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics

Published by Institute of Physics (IOP)

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First crystal-structure determination of chromites from an acapulcoite and ordinary chondrites (2015)

Lenaz, D., Princivalle, F., Schmitz, B., Grew, E.

Mineralogical Society of Great Britain and Ireland

In: Mineralogical Magazine

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Publication Date: 2015-08-22

Description: We report the first crystal-structure determinations of chromites from an acapulcoite and from ordinary chondrites. Cell edges range from 8.3212 (3) to 8.3501 (1) Å, while the oxygen positional parameters are in the range 0.2624 (3) to 0.26298 (9). Their compositions show they are very close to the chromite end-member FeCr 2 O 4 with limited Al and Mg content. Titanium oxide content exceeds 1 wt.%, whereas the amount of Fe 3+ is negligible. Extraterrestrial chromite is distinguished readily from terrestrial analogues on the basis of the cell edge and oxygen positional parameter. These distinctions will facilitate ongoing attempts to reconstruct the palaeoflux of meteorites to Earth from resistant extraterrestrial spinel grains recovered from ancient sediments.

Print ISSN: 0026-461X

Electronic ISSN: 1471-8022

Topics: Geosciences

Published by Mineralogical Society of Great Britain and Ireland

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Sustainability, Vol. 11, Pages 2871: Designing Protected Areas for Social–Ecological Sustainability: Effectiveness of Management Guidelines for Preserving Cultural Landscapes (2019)

Patricio Sarmiento-Mateos, Cecilia Arnaiz-Schmitz, Cristina Herrero-Jáuregui, Francisco D. Pineda, María F. Schmitz

MDPI

In: Sustainability

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Publication Date: 2019

Description: Rural cultural landscapes are social–ecological systems that have been shaped by traditional human land uses in a co-evolution process between nature and culture. Protected areas should be an effective way to protect cultural landscapes and support the way of life and the economy of the local population. However, nature conservation policymaking processes and management guidelines frequently do not take culturalness into account. Through a new quantitative approach, this paper analyzes the regulatory framework of two protected areas under different management categories, located in an ancient cultural landscape of the Madrid Region (Central Spain), to identify the similarities in their conservation commitments and the effectiveness of their zoning schemes. The results show some arbitrariness in the design and management of these parks, highlighting the importance of prohibited measures in their zoning schemes that encourage uses and activities more related to naturalness than to culturalness. The recognition of protected areas as cultural landscapes and their management considering both naturalness and culturalness issues are important methods of better achieving sustainable management objectives from a social–ecological approach. This methodological approach has proven useful to unravel various legislative content, and its application on a larger scale could reveal important information for the sound management of protected areas (PAs) in cultural landscapes.

Electronic ISSN: 2071-1050

Topics: Energy, Environment Protection, Nuclear Power Engineering

Published by MDPI

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