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Antidiabetic profiling of veramycins,polyketides accessible by biosynthesis,chemical synthesis and precursor-directed modification

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Organic Chemistry frontiers 2022年第6期9卷 1604-1615页

作者： Denis Dardić Nils Böhringer Alberto Plaza florian Zubeil Juliane Pohl Svenja Sommer Leo Padva Jonathan Becker Maria A.Patras Mona-Katharina Bill Michael Kurz Luigi Toti Sven W.Görgens Sören M.M.schuler AndréBillion Oliver schwengers Paulus Wohlfart Alexander Goesmann Norbert Tennagels Andreas Vilcinskas Peter E.Hammann till f.schäberle Armin Bauer fraunhofer Institute for Molecular Biology and Applied Ecology(IME) Branch for Bioresources35392 GießenGermany Justus-Liebig-University Gießen 35392 GießenGermany Sanofi-Aventis Deutschland GmbH R&D Integrated Drug Discovery65926 Frankfurt am MainGermany Sanofi-Aventis Deutschland GmbH R&D German Hub65926 Frankfurt am MainGermany German Center of Infection Research(DZIf) Partner Site Gießen-Marburg-Langen35392 GießenGermany

Seven new polyketides,termed veramycins,were isolated from a Streptomyces *** the Sanofi microbial strain collection along with their known congeners NfAT-133 and *** A,anα-pyrone congener of TM-123 and NfAT-133 showed an increased baseline deoxy-glucose uptake in the absence of insulin in a modified L6 rat skeletal muscle cell line(L6 GLUT4 AS160-like cells).In addition,both compounds slightly increased the sensitivity to insulin in this cell *** syntheses of NfAT-133,TM-123 and veramycin A were accomplished starting from a central building block,which bears the three contiguous stereogenic centers of this polyketide *** approach enables an efficient,selective and flexible access to all possible isomers of the stereotriad for further exploration of this series as a potential anti-diabetic lead structure as exemplified by the synthesis of an NfAT-133 ***,the corresponding biosynthetic gene cluster(BGC)was identified by genome sequencing and gene *** on feeding experiments,a biosynthetic pathway was proposed,which enabled access to new veramycin A analogs by precursor-directed biosynthesis.

关键词： synthesis directed isomers

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Enriching plant diversity in grasslands by large-scale experimental sward disturbance and seed addition along gradients of land-use intensity

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Journal of Plant Ecology 2017年第4期10卷 581-591页

作者： Valentin H.Klaus Deborah schäfer till Kleinebecker Markus f.scher Daniel Prati Norbert Hölzel Institute of Landscape Ecology Münster UniversityHeisenbergstr.248149 MünsterGermany Institute of Plant Sciences University of BernAltenbergrain 213013 BernSwitzerland

Aims The relationship between biodiversity and ecosystem functioning is among the most active areas of ecological ***,enhancing the diversity of degraded ecosystems is a major goal in applied restoration *** grasslands,many species may be locally absent due to dispersal or microsite limitation and may therefore profit from mechanical disturbance of the resident *** established a seed addition and disturbance experiment across several grassland sites of different land use to test whether plant diversity can be increased in these ***,the experiment will allow us testing the consequences of increased plant diversity for ecosystem processes and for the diversity of other taxa in real-world ***,we present details of the experimen-tal design and report results from the first vegetation survey 1 year after disturbance and seed ***,we tested whether the effects of seed addition and disturbance varied among grassland depending on their land use or pre-disturbance plant *** A full-factorial experiment was installed in 73 grasslands in three regions across *** were under regular agricul-tural use,but varied in the type and the intensity of management,thereby representing the range of management typical for large parts of Central *** disturbance treatment consisted of disturbing the top 10 cm of the sward using a rotavator or rotary *** addition consisted of sowing a high-diversity seed mixture of regional plant *** species were all regionally present,but often locally absent,depending on the resident vegetation composi-tion and richness of each *** findings Seven months after sward disturbance,respective plots had significantly increased in bare soil,seedling species richness and number of *** addition had increased plant species richness,but only in combination with sward *** increase in species richness

关键词： grassland restoration germination microsite limitation seed limitation fertilization

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Visualizing mitochondrial dynamics at the nanoscale

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Light(Science & Applications) 2024年第11期13卷 2421-2423页

作者： till Stephan Peter Ilgen Stefan Jakobs Buchmann Institute for Molecular Life Sciences Goethe University Frankfurt am MainFrankfurt am Main 60438Germany Department of NanoBiophotonics Max Planck Institute for Multidisciplinary Sciences37077 GöttingenGermany Clinic of Neurology University Medical Center GöttingenGöttingen 37075Germany fraunhofer Institute for Translational Medicine and Pharmacology Translational Neuroinflammation and Automated MicroscopyGöttingen 37075Germany

The study of mitochondria is a formidable challenge for super-resolution microscopy due to their dynamic nature and complex membrane *** this issue,Ren et *** HBmito Crimson,a fluorogenic and photostable mitochondrial probe for STED microscopy and investigate how mitochondrial dynamics influence the spatial organization of mitochondrial DNA.

关键词： dynamics Visual dynamic

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The Presence and Localization of Thioredoxins in Diatoms, Unicellular Algae of Secondary Endosymbiotic Origin

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Molecular Plant 2009年第3期2卷 468-477页

作者： till Weber Ansgar Gruber Peter G. Kroth fachbereich Biologie Universitat Konstanz 78457 Konstanz Germany

Diatoms are unicellular algae of great ecological importance. So far, very little is known about the regulation of carbon fixation in these algae; however, there are strong indications that in diatom plastids, the ferredoxin/thioredoxin system might play a minor role in redox regulation of the photosynthetic reactions compared to land plants. Until now, it is unknown whether there are fewer or other target enzymes of thioredoxins in diatoms. Only a single potential target enzyme for thioredoxin, the plastidic fructose-l,6-bisphosphatase, has yet been identified. Nevertheless, during the annotation of the genome of the diatom Phaeodactylum tricornutum, we identified several genes encoding different thioredoxins. Utilizing in vivo expression of GfP：presequence fusion proteins in P. tricornutum, we were able to show that these thioredoxins are targeted either into plastids, mitochondria, or remain in the cytosol. Surprisingly, two of the three usually cytosolic thioredoxin h proteins are apparently plastid associated and, together with a thioredoxin reductase, putatively located in the periplastidic compartment. This is one of the few indications for so far unknown enzymatic reactions in the space between the two pairs of diatom plastid envelope membranes.

关键词： Carbohydrate metabolism enzymology genomics diatoms and phytoplankton

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Are the mechanisms involved in astrocyte and lymphocyte death during HIV infection similar?

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Neural Regeneration Research 2019年第10期14卷 1707-1708页

作者： Diego S. Ojeda Andreas till Jorge Quarleri Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS) Universidad de Buenos Aires-CONICETArgentina Institute of Reconstructive Neurobiology Life & Brain CenterUniversity of BonnBonnGermany

Acquired immune deficiency syndrome is associated with the death of CD4+ T lymphocytes. The entry of the human immunodeficiency virus (HIV) into the central nervous system leads to a broad spectrum of HIV-associated neurocognitive disorders (HAND) ranging from mild to severe dementia. Inside the central nervous system, HIV establishes infection in astrocytes - the predominant cell type in the brain, thus causing neuropathology, but the underlying mechanisms remain unknown.

关键词： Acquired immune broad spectrum remain unknown

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Role of matrix phase and electric field gradient in Na_(1/2)Bi_(1/2)TiO_(3)eBaTiO_(3) :ZnO composites

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Journal of Materiomics 2022年第2期8卷 498-510页

作者： Lalitha Kodumudi Venkataraman till fromling Jurgen Rodel Department of Materials and Earth Sciences Technical University of DarmstadtGermany

Na_(1/2)Bi_(1/2)TiO_(3)-based materials exhibit potential for applications in high-power *** com-posites of Na_(1/2)Bi_(1/2) TiO_(3)-yBaTiO_(3)(NBTyBT;y denotes mole%)with ZnO inclusions were demonstrated to stabilize a ferroelectric equilibrium that led to enhanced thermal depolarization temperature(T_(d))and increased mechanical quality factor(Q_(m)).This work addresses the influence of the matrix NBTyBT phase by investigating two limiting choices based on symmetry(tetragonal/rhombohedral)and polar(relaxor/ferroelectric)*** the composites constituting the tetragonal NBT9BT(non-ergodic relaxor at room temperature)matrix phase exhibit improved T d,the critical temperatures in the composites with rhombohedral NBT3BT(displaying spontaneous ferroelectric order at room temperature)exhibit only marginal ***,NBT3BT composites feature a 45%increase in Q m,while the corresponding increase is roughly three-fold for the NBT9BT composites.A 3-D finite Element Method is used to simulate the electric field gradient at the matrix/inclusion interface,with the effective field distribution estimated to be higher than the applied field for highly conducting ZnO *** electrical properties indicate that,while the deviatoric stress at the matrix/inclusion interface stabilizes the ferroelectric equilibrium for the relaxor matrix phase,the stresses disrupt the long-range order for the ferroelectric matrix *** results establish the volume-limit of the second phase to stabilize a ferroelectric equilibrium,in addition to substantiating the role of residual stress evidenced by changes in the polar ***,a comparison of the composites with different NBTyBT phases is presented,with NBT6BT:ZnO composites demonstrating an optimal increase in both T_(d) and Q_(m).

关键词： Thermal depolarization Na_(1/2)Bi_(1/2)TiO_(3) BaTiO_(3) NBT-Based Lead-free composites Hard-type

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Morphology and morphometry of two hybridizing buntings at their hybrid zone in northern Iran reveal intermediate and transgressive morphotypes

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Avian Research 2023年第4期14卷 523-532页

作者： Ali Gholamhosseini Mansour Aliabadian till Topfer Glenn-Peter Sætre Ornithology Research Laboratory Department of BiologySchool of ScienceShiraz UniversityShirazIran Department of Biology Faculty of SciencesFerdowsi University of MashhadMashhadIran Leibniz Institute for the Analysis of Biodiversity Change Zoological Research Museum Alexander KoenigCentre for Taxonomy and MorphologyBonnGermany Centre for Ecological and Evolutionary Synthesis(CEES) Department of BiosciencesUniversity of OsloNorway

The closely related Black-headed Bunting(Emberiza melanocephala,a western Palearctic lineage)and Red-headed Bunting(Emberiza bruniceps,an eastern Palearctic lineage)hybridize and replace each other south of the Caspian *** parental species have distinct phenotypes and therefore morphology is useful for assessing hybridization in the contact *** the years of 1940 and 1977,quite a few hybrids were collected and studied *** then,the hybrid zone appears to have expanded westwards,but there has been a time gap in the collection of morphological *** we reanalyze bunting specimens morphologically and compare the historical data with recent *** and phenotypic traits from three time periods(1940,1977 and recent)were studied to assess phenotypic variation of hybrids,pattern of hybridization,and transgressive traits in the hybrid *** results show that most of the birds in the hybrid zone exhibit intermediate phenotypes(both colors and morphometric characters),ranging from the pure phenotype of either of the parental ***,hybridization has also produced novel phenotypes not seen in any of the *** a canonical discriminant function analysis,the morphometric characters separated each parental species and the hybrids quite *** results showed morphometric intermediacy of hybrids in accordance with *** observe a time trend in which recent hybrids are more similar to Red-headed Buntings phenotypically compared to historical *** pattern is likely a signature of a westward expansion of the Red-headed Bunting into the breeding range of the Black-headed Bunting.

关键词： Bunting Hybridization Intermediate phenotypes Transgressive traits

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In situ grazing-incidence small-angle X-ray scattering observation of block-copolymer templated formation of magnetic nanodot arrays and their magnetic properties

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Nano Research 2017年第2期10卷 456-471页

作者： Andreas Meyer Norbert franz Hans Peter Oepen Jan Perlich Gerardina Carbone till Hartmut Metzger Institut fiJr Physikalische Chemie Universitat Hamburg Grindelallee 117 20146 Ham burg Germany Institut for Nanostruktur und festkorperphysik Universitat Hamburg Jungiusstr. 11a 20355 Hamburg Germany HASYLAB/Deutsches Elektronen Synchrotron Notkestr. 85 22603 Hamburg Germany European Synchrotron Radiation facility 6 rue Jules Horowitz 38043 Grenoble France

The fabrication of bit-patterned media （BPM） is crucial for new types of hard disk drives. The development of methods for the production of BPM is progressing rapidly. Conventional lithography reaches the limit regarding lateral resolution, and new routes are needed. In this study, we mainly focus on the dependence of the size and shape of magnetic nanodots on the Ar＋-ion etching duration, using silica dots as masks. Two-dimensional （2D） arrays of magnetic nanostructures are created using silica-filled diblock-copolymer micelles as templates. After the self-assembly of the micelles into 2D hexagonal arrays, the polymer shell is removed, and the SiO2 cores are utilized to transform the morphology into a （Co/Pt）2-multilayer via ion etching under normal incidence. The number of preparation steps is kept as low as possible to simplify the formation of the nanostructure arrays. High-resolution in situ grazing-incidence small-angle X-ray scattering （GISAXS） investigations are performed during the Ar＋-ion etching to monitor and control the fabrication process. The in situ investigation provides information on how the etching conditions can be improved for further ex situ experiments. The GISAXS patterns are compared with simulations. We observe that the dots change in shape from cylindrical to conical during the etching process. The magnetic behavior is studied by utilizing the magneto-optic Kerr effect. The Co/Pt dots exhibit different magnetic behaviors depending on their size, interparticle distance, and etching time. They show ferromagnetism with an easy axis of magnetization perpendicular to the film. A systematic dependence of the coercivitv on the dot size is observed.

关键词： poly(styrene)-b-poly(vinyl pyridine) argon ion etching self-assembly grazing-incidence small-angle X-ray scattering(GISAXS) simulation magnetic nanodot coercivity

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tillING and Associated Technologies

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Journal of Integrative Plant Biology 2010年第11期52卷 1027-1028页

作者： Trevor Wang Cristobal Uauy Brad till Chun-Ming Liu John Innes Centre Norwich UK International Atomic Energy Agency/food and Agriculture Organisation Vienna Austria Institute of Botany The Chinese Academy of Sciences Beijing China

As part of a collaboration between the John Innes Centre （JIC）,Norwich,UK and the Centre for Signal Transduction and Metabolomics （C-STM） at the Institute of Botany （IOB）,

关键词： tillING and Associated Technologies IOB

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functional Cooperativity of Enzymes of Phosphoinositide Conversion According to Synergistic Effects on Pectin Secretion in Tobacco Pollen Tubes

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Molecular Plant 2010年第5期3卷 870-881页

作者： till Ischebeck Linh Hai Vu Xu Jin Irene Stenzel Christian Lofke Ingo Heilmann Department of Plant Biochemistry Albrecht-von-Haller-lnstitute for Plant Sciences Georg-August-University Gottingen Justus-von-Liebig-Weg 11 37077 Guttingen Germany Present address: Center for Biochemistry Cologne University Joseph-Stelzmann-Straβe 52 50931 Cologne Germany Present address: Department of forest Botany Georg-August-University Gottingen Busgenweg 2 37077 Gottingen Germany Present address: Department of Plant Cell Biology Albrecht-von-Haller-lnstitute for Plant Sciences Georg-August-University Gottingen Untere Karspule 2 37073 Gottingen Germany

The Arabidopsis phosphoinositide kinases PI4Kβ1 and PIP5K5 have been implicated in the control of directional vesicle trafficking underlying polar tip growth in pollen tubes. PI4Kβ1 and PIP5K5 catalyze key consecutive steps of phosphoinositide conversion, and it appears obvious that phosphatidylinositol-4-phosphate formed by PI4Kβ1 might act as a substrate for phosphatidylinositol-4,5-bisphosphate formation by PIP5K5. However, this hypothesis has not been experimentally addressed and distinct localization patterns of PI4Kβ1, PIP5K5, and also PI-synthases （PIS） generating phosphatidylinositol suggest additional complexity. Here, the synergistic functionality of enzymes of phosphoinositide conversion was assessed. In tobacco and Arabidopsis pollen tubes, phosphoinositides influence the apical secretion of pectin, and increased pectin deposition results in characteristic morphological alterations. Catalytically active and dominant negative variants of PI4Kβ1 and PIP5K5 were systematically co-expressed in tobacco pollen tubes and the incidence of morphologies related to enhanced pectin secretion was evaluated. The data support a proposed functional interplay of PI4Kβ1 and PIP5K5 at the trans-Golgi network, mediating directional vesicle trafficking. Co-expression experiments additionally including PIS isoforms, PIS1 or PIS2, indicate that pectin secretion is synergistically mediated by PI4Kβ1 and PIPSK5 acting on Ptdlns formed by PIS2 rather than PIS1. Possible ramifications for the preferential channeling of phosphoinositide intermediates between particular isoforms of PI pathway enzymes are discussed.

关键词： Phosphatidylinositol synthase phosphatidylinositol 4-kinase phosphatidylinositol-4-phosphate 5-kinase cooperativity pectin secretion pollen tubes.

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