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101.
102.
Gerda Oswald Ingo Rombeck B. Song H. Sigel B. Lippert 《Journal of biological inorganic chemistry》1998,3(3):236-245
The synthesis of cis-Pt(NH3)2(dCMP) is reported and by various physico-chemical methods it is demonstrated that it is a macrochelate in which Pt(II) is
bound simultaneously to the N3 site of cytosine in dCMP2– and to a phosphate-oxygen atom. According to the NOESY spectra (cross-peaks between cytosine H6 and H2′ and H3′) the cytosine
ring adopts an anti orientation. Highly unusual is the significant (1 ppm) downfield shift of the sugar proton H5″ in the 1H-NMR spectrum and the sensitivity of the cytosine H6 resonance on the protonation state of the phosphate group. Based on
these three features a geometry for the macrochelate is proposed. The compound is a major product of the reaction of cis-[Pt(NH3)2(H2O)2]2+ with dCMP2– at neutral pH, but it even forms at pH 5. By applying pD-dependent NMR spectroscopy (1H, 31P) and potentiometric pH titration, it is demonstrated that the Pt-coordinated phosphate group can be protonated (pK
a/1=3.21±0.10 and 3.31±0.05, respectively), and 1H- and 31P-NMR spectra also indicate deprotonation (pK
a/2=13.35±0.25) of the exocyclic amino group of the cytosine moiety. The metal ion binding affinity of cis-Pt(NH3)2(dCMP) is very small, as shown for Cu2+ (log K<0.6). The cis-Pt(NH3)2(dCMP) complex reacts with nucleosides and nucleotides (L′) by losing its chelate structure and forming mixed ligand complexes,
cis-Pt(NH3)2(dCMP)(L′); this means that the phosphate group is released from the coordination sphere of Pt(II), indicating that the Pt(II)-O(phosphate)
bond is not very strong.
Received: 23 October 1997 / Accepted: 17 February 1998 相似文献
103.
Ingo Ott Konrad Kowalski Ronald Gust Jörg Maurer Philipp Mücke Rainer F. Winter 《Bioorganic & medicinal chemistry letters》2010,20(3):866-869
Two ethylene linked binuclear mixed ferrocene/ruthenium complexes were biologically investigated in comparison to structurally related mononuclear ferrocene or ruthenium species with styryl substituents or ligands. Results indicated that the electron distribution (but not the redox potential), cellular uptake and (to some minor extent) anti-estrogenic effects were the key contributors to antiproliferative effects observed in tumor cell lines. 相似文献
104.
105.
Roland Frey Alban Gebler Kirk A. Olson Daria Odonkhuu Guido Fritsch Nyamsuren Batsaikhan Ingo W. Stuermer 《Journal of morphology》2008,269(10):1223-1237
This study provides the first evidence of pronounced temporary laryngeal descent in a bovid species. An elaborate acoustic display is prominent in male courtship behavior of polygynous Mongolian gazelle. During rut, rounding up of females is accompanied by continuous head‐up barking by dominant males. Throughout the rut their evolutionarily enlarged larynx descends to a low mid‐neck resting position. In the course of each bark the larynx is additionally retracted toward the sternum by 30% of the resting vocal tract length. A geometric model of active larynx movements was constructed by combining results of video documentation, dissection, skeletonization, and behavioral observation. The considerable distance between resting position and maximal laryngeal descent suggests a backward tilting of the hyoid apparatus and an extension of the thyrohyoid connection during the retraction phase. Return to the resting position is effected by strap muscles and by the elastic recoil of the pharynx and the thyrohyoid connection. An intrapharyngeal inflation of the peculiar palatinal pharyngeal pouch of adult males is inferred from a short‐time expansion of the ventral neck region rostral to the laryngeal prominence. The neck of adult dominant males is accentuated by long gray guard hairs during the rut. The passive swinging of the heavy larynx of adult males during locomotion gives the impression of a handicap imposed on rutting males. Apparently, this disadvantage becomes outweighed by the profits for reproductive success. J. Morphol., 2008. © 2008 Wiley‐Liss, Inc. 相似文献
106.
Ceftaroline is a new cephalosporin active against Methicillin-resistant Staphylococcus aureus (MRSA). Based on a representative collection of clinical S. aureus isolates from Germany, supplemented with isolates of clonal lineages ST228 and ST239, we demonstrate the in-vitro susceptibility towards ceftaroline prior to its introduction into clinical use for a total of 219 isolates. Susceptibility testing was performed by broth microdilution, disc diffusion and Etest, respectively. Results were interpreted according to EUCAST guidelines and showed considerable variance in dependence on clonal affiliation of the isolates tested. Among isolates of widespread hospital-associated lineages we found a high proportion of clinical isolates with MICs close to the EUCAST breakpoint (MIC50/90 1.0/1.5 mg/L); currently, interpretation of these “borderline” MICs is complicated by a lack of concordant susceptibility testing methods and reasonable breakpoint determination. Isolates of clonal lineages ST228 and ST239 demonstrated increased MIC50/90 values of 2.5/3.33 mg/L. Sequencing of mecA revealed no association of resistance to a specific mecA polymorphism, but rather reveals two regions in the non-penicillin-binding domain of PbP2a which displayed different combinations of mutations putatively involved in resistance development. This study provides national baseline data to (i) adjust susceptibility testing methods and current breakpoints to clinical and epidemiological requirements, (ii) evaluate current breakpoints with respect to therapeutic outcome and (iii) monitor further resistance evolution. 相似文献
107.
LUMOS - A Sensitive and Reliable Optode System for Measuring Dissolved Oxygen in the Nanomolar Range
Philipp Lehner Christoph Larndorfer Emilio Garcia-Robledo Morten Larsen Sergey M. Borisov Niels-Peter Revsbech Ronnie N. Glud Donald E. Canfield Ingo Klimant 《PloS one》2015,10(6)
Most commercially available optical oxygen sensors target the measuring range of 300 to 2 μmol L-1. However these are not suitable for investigating the nanomolar range which is relevant for many important environmental situations. We therefore developed a miniaturized phase fluorimeter based measurement system called the LUMOS (Luminescence Measuring Oxygen Sensor). It consists of a readout device and specialized “sensing chemistry” that relies on commercially available components. The sensor material is based on palladium(II)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorphenyl)-porphyrin embedded in a Hyflon AD 60 polymer matrix and has a KSV of 6.25 x 10-3 ppmv-1. The applicable measurement range is from 1000 nM down to a detection limit of 0.5 nM. A second sensor material based on the platinum(II) analogue of the porphyrin is spectrally compatible with the readout device and has a measurement range of 20 μM down to 10 nM. The LUMOS device is a dedicated system optimized for a high signal to noise ratio, but in principle any phase flourimeter can be adapted to act as a readout device for the highly sensitive and robust sensing chemistry. Vise versa, the LUMOS fluorimeter can be used for read out of less sensitive optical oxygen sensors based on the same or similar indicator dyes, for example for monitoring oxygen at physiological conditions. The presented sensor system exhibits lower noise, higher resolution and higher sensitivity than the electrochemical STOX sensor previously used to measure nanomolar oxygen concentrations. Oxygen contamination in common sample containers has been investigated and microbial or enzymatic oxygen consumption at nanomolar concentrations is presented. 相似文献
108.
Jorge Esparza-Gordillo Anja Matanovic Ingo Marenholz Anja Bauerfeind Klaus Rohde Katja Nemat Min-Ae Lee-Kirsch Magnus Nordenskj?ld Marten C. G. Winge Thomas Keil Renate Krüger Susanne Lau Kirsten Beyer Birgit Kalb Bodo Niggemann Norbert Hübner Heather J. Cordell Maria Bradley Young-Ae Lee 《PLoS genetics》2015,11(3)
Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental origin, or due to maternal effects reflecting the maternal genome''s influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1meta-analysis = 2.4, P = 1.0 x 10−36), we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10−8). Our data point to two independent and additive effects of FLG mutations: i) carrying a mutation and ii) having a mutation carrier mother. The maternal genotype effect was independent of mutation inheritance and can be seen as a non-genetic transmission of a genetic effect. The FLG maternal effect was observed only when mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels), suggesting that FLG mutation-induced systemic immune responses in the mother may influence AD risk in the child. Notably, the maternal effect reported here was stronger than most common genetic risk factors for AD recently identified through genome-wide association studies (GWAS). Our study highlights the power of family-based studies in the identification of new etiological mechanisms and reveals, for the first time, a direct influence of the maternal genotype on the offspring’s susceptibility to a common human disease. 相似文献
109.
Rita-Eva Varga Mukhran Khundadze Markus Damme Sandor Nietzsche Birgit Hoffmann Tobias Stauber Nicole Koch J. Christopher Hennings Patricia Franzka Antje K. Huebner Michael M. Kessels Christoph Biskup Thomas J. Jentsch Britta Qualmann Thomas Braulke Ingo Kurth Christian Beetz Christian A. Hübner 《PLoS genetics》2015,11(8)
Hereditary spastic paraplegia (HSP) is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs). Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice. 相似文献
110.
Oliver S. Grosser Dennis Kupitz Juri Ruf Damian Czuczwara Ingo G. Steffen Christian Furth Markus Thormann David Loewenthal Jens Ricke Holger Amthauer 《PloS one》2015,10(9)