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61.
62.
Sarah Zaatreh David Haffner Madlen Strauß Katharina Wegner Mareike Warkentin Claudia Lurtz 《Biofouling》2017,33(4):294-305
Bacterial colonisation and biofilm formation are characteristics of implant-associated infections. In search of candidates for improved prosthetic materials, fast corroding Mg-based coatings on titanium surfaces were examined for their cytotoxic and antimicrobial properties. Human osteoblasts and Staphylococcus epidermidis were each cultured on cylindrical Ti samples coated with a thin layer of Mg/Mg45Zn5Ca, applied via magnetron sputtering. Uncoated titanium samples served as controls. S. epidermidis was quantified by counting colony forming units. The biofilm-bound fraction was isolated via ultrasonic treatment, and the planktonic fraction via centrifugation. Biofilm-bound S. epidermidis was significantly decreased by approximately four to five orders of magnitude in both Mg- and Mg45Zn5Ca-coated samples after seven days compared to the control. The osteoblast viability was within the tolerance threshold of 70% stated in DIN EN ISO 10993-5:2009-10 for Mg (~80%) but not for Mg45Zn5Ca (~25%). Accordingly, Mg-coated titanium was identified as a promising candidate for an implant material with antibacterial properties and low cytotoxicity levels. The approach of exploiting fast corrosion contrasts with existing methods, which have generally focused on reducing corrosion. 相似文献
63.
Katharina Hiebler Zsófia Lengyel Carlos A. Castañeda Olga V. Makhlynets 《Proteins》2017,85(9):1656-1665
AlleyCatE is a de novo designed esterase that can be allosterically regulated by calcium ions. This artificial enzyme has been shown to hydrolyze p‐nitrophenyl acetate (pNPA) and 4‐nitrophenyl‐(2‐phenyl)‐propanoate (pNPP) with high catalytic efficiency. AlleyCatE was created by introducing a single‐histidine residue (His144) into a hydrophobic pocket of calmodulin. In this work, we explore the determinants of catalytic properties of AlleyCatE. We obtained the pKa value of the catalytic histidine using experimental measurements by NMR and pH rate profile and compared these values to those predicted from electrostatics pKa calculations (from both empirical and continuum electrostatics calculations). Surprisingly, the pKa value of the catalytic histidine inside the hydrophobic pocket of calmodulin is elevated as compared to the model compound pKa value of this residue in water. We determined that a short‐range favorable interaction with Glu127 contributes to the elevated pKa of His144. We have rationally modulated local electrostatic potential in AlleyCatE to decrease the pKa of its active nucleophile, His144, by 0.7 units. As a direct result of the decrease in the His144 pKa value, catalytic efficiency of the enzyme increased by 45% at pH 6. This work shows that a series of simple NMR experiments that can be performed using low field spectrometers, combined with straightforward computational analysis, provide rapid and accurate guidance to rationally improve catalytic efficiency of histidine‐promoted catalysis. Proteins 2017; 85:1656–1665. © 2017 Wiley Periodicals, Inc. 相似文献
64.
Guijarro C Rutz S Rothmaier K Turiault M Zhi Q Naumann T Frotscher M Tronche F Jackisch R Kretz O 《Journal of neurochemistry》2006,97(3):747-758
Glucocorticoids have been shown to influence trophic processes in the nervous system. In particular, they seem to be important for the development of cholinergic neurons in various brain regions. Here, we applied a genetic approach to investigate the role of the glucocorticoid receptor (GR) on the maturation and maintenance of cholinergic medial septal neurons between P15 and one year of age by using a mouse model carrying a CNS-specific conditional inactivation of the GR gene (GRNesCre). The number of choline acetyltransferase and p75NTR immuno-positive neurons in the medial septum (MS) was analyzed by stereology in controls versus mutants. In addition, cholinergic fiber density, acetylcholine release and cholinergic key enzyme activity of these neurons were determined in the hippocampus. We found that in GRNesCre animals the number of medial septal cholinergic neurons was significantly reduced during development. In addition, cholinergic cell number further decreased with aging in these mutants. The functional GR gene is therefore required for the proper maturation and maintenance of medial septal cholinergic neurons. However, the loss of cholinergic neurons in the medial septum is not accompanied by a loss of functional cholinergic parameters of these neurons in their target region, the hippocampus. This pinpoints to plasticity of the septo-hippocampal system, that seems to compensate for the septal cell loss by sprouting of the remaining neurons. 相似文献
65.
Ulrich Dobramysl Iris Katharina Jarsch Yoshiko Inoue Hanae Shimo Benjamin Richier Jonathan R. Gadsby Julia Mason Alicja Szaapak Pantelis Savvas Ioannou Guilherme Pereira Correia Astrid Walrant Richard Butler Edouard Hannezo Benjamin D. Simons Jennifer L. Gallop 《The Journal of cell biology》2021,220(4)
Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways. 相似文献
66.
67.
Polyploidy, the duplication of entire genomes, plays a major role in plant evolution. In allopolyploids, genome duplication is associated with hybridization between two or more divergent genomes. Successive hybridization and polyploidization events can build up species complexes of allopolyploids with complicated network-like histories, and the evolutionary history of many plant groups cannot be adequately represented by phylogenetic trees because of such reticulate events. The history of complex genome mergings within a high-polyploid species complex in the genus Cerastium (Caryophyllaceae) is here untangled by the use of a network algorithm and noncoding sequences of a low-copy number gene. The resulting network illustrates how hybridization and polyploidization have acted as key evolutionary processes in creating a plant group where high-level allopolyploids clearly outnumber extant parental genomes. 相似文献
68.
Blm10 is bound to the yeast proteasome core particle, a crucial protease of eukaryotic cells [corrected]. Two gates, at both ends of the CP, control the access of protein substrates to the catalytic cavity of the CP. Normally, substrate access is auto-inhibited by a closed gate conformation unless regulatory complexes are bound to the CP and translocate protein substrates in an ATP-dependent manner. Here, we provide evidence that Blm10 recognizes pre-activated open gate CPs, which are assumed to exist in an equilibrium with inactive closed gate CP. Consequently, single-capped Blm10-CP shows peptide hydrolysis activity. Under conditions of disturbed CP assembly, as well as in open gate mutants, pre-activated CP or constitutively active CP, respectively, prevail. Then, Blm10 sequesters disordered and open gate CP by forming double-capped Blm10(2)-CP in which peptide hydrolysis activity is repressed. We conclude that Blm10 distinguishes between gate conformations and regulates the activation of CP. 相似文献
69.
Krysko DV Diez-Fraile A Criel G Svistunov AA Vandenabeele P D'Herde K 《Apoptosis : an international journal on programmed cell death》2008,13(9):1065-1087
The vertebrate ovary is an extremely dynamic organ in which excessive or defective follicles are rapidly and effectively eliminated
early in ontogeny and thereafter continuously throughout reproductive life. More than 99% of follicles disappear, primarily
due to apoptosis of granulosa cells, and only a minute fraction of the surviving follicles successfully complete the path
to ovulation. The balance between signals for cell death and survival determines the destiny of the follicles. An abnormally
high rate of cell death followed by atresia can negatively affect fertility and eventually lead irreversibly to premature
ovarian failure. In this review we provide a short overview of the role of programmed cell death in prenatal differentiation
of the primordial germ cells and in postnatal folliculogenesis. We also discuss the issue of neo-oogenesis. Next, we highlight
molecules involved in regulation of granulosa cell apoptosis. We further discuss the potential use of scores for apoptosis
in granulosa cells and characteristics of follicular fluid as prognostic markers for predicting the outcome of assisted reproduction.
Potential therapeutic strategies for combating premature ovarian failure are also addressed. 相似文献
70.