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Dr. Erick J. Carlson Dr. Rawle Francis Yutong Liu Dr. Ping Li Maximilian Lyon Prof. Celia M. Santi Prof. Derek J. Hook Prof. Jon E. Hawkinson Prof. Gunda I. Georg 《ChemMedChem》2022,17(15):e202000499
The cation channel of sperm (CatSper) is a validated target for nonhormonal male contraception, but it lacks selective blockers, hindering studies to establish its role in both motility and capacitation. Via an innovative calcium uptake assay utilizing human sperm we discovered novel inhibitors of CatSper function from a high-throughput screening campaign of 72,000 compounds. Preliminary SAR was established for seven hit series. HTS hits or their more potent analogs blocked potassium-induced depolarization and noncompetitively inhibited progesterone-induced CatSper activation. CatSper channel blockade was confirmed by patch clamp electrophysiology and these compounds inhibited progesterone- and prostaglandin E1-induced hyperactivated sperm motility. One of the hit compounds is a potent CatSper inhibitor with high selectivity for CatSper over hCav1.2, hNav1.5, moderate selectivity over hSlo3 and hERG, and low cytotoxicity and is therefore the most promising inhibitor identified in this study. These new CatSper blockers serve as useful starting points for chemical probe development and drug discovery efforts. 相似文献
945.
Christoph Ehlers Moritz Schröder Georg Fieg 《American Institute of Chemical Engineers》2015,61(5):1648-1662
The implementation of a vertical dividing wall (DW) into a distillation column is a well‐known concept which can result in considerable energy savings for the separation of multicomponent mixtures. It is commonly known that heat streams across the DW, which are present due to temperature differences between both sides, may either increase or decrease the energy demand for a certain separation task. However, no work has been published so far which explains the maximum influence on energy demand. This article derives the maximum extent to which the minimum energy demand for a given column design can change due to heat transfer across the DW. Additionally, it is illustrated how energy‐efficient column operation can be assured even if the total amount of transferred heat is unknown. These results show that the phenomenon of heat transfer across the DW can be handled very well with a suitable control strategy. © 2015 American Institute of Chemical Engineers AIChE J, 61: 1648–1662, 2015 相似文献
946.
Synthesis of the Human Milk Oligosaccharide Lacto‐N‐Tetraose in Metabolically Engineered,Plasmid‐Free E. coli 下载免费PDF全文
Florian Baumgärtner Dr. Jürgen Conrad Prof. Dr. Georg A. Sprenger Dr. Christoph Albermann 《Chembiochem : a European journal of chemical biology》2014,15(13):1896-1900
Human milk oligosaccharides (HMOs) constitute the third most abundant solid component of human milk. HMOs have been demonstrated to show positive effects on the infant’s well‐being. Despite numerous studies, more physiological analyses of single compounds are needed to fully elucidate these effects. Although being one of the most abundant core structures in human milk, the HMO lacto‐N‐tetraose (LNT) is not available at reasonable prices. In this study, we demonstrate the construction of the first E. coli strain capable of producing LNT in vivo. The strain was constructed by chromosomally integrating the genes lgtA and wbgO, encoding β‐1,3‐N‐acetylglucosaminyltransferase and β‐1,3‐galactosyltransferase. In shake‐flask cultivations, the strain yielded a total concentration of 219.1±3.5 mg L?1 LNT (LNT in culture broth and the cell pellet). After recovery of LNT, structural analysis by NMR spectroscopy confirmed the molecule structure. 相似文献
947.
Inside Cover: Nanosecond Dynamics of Calmodulin and Ribosome‐Bound Nascent Chains Studied by Time‐Resolved Fluorescence Anisotropy (ChemBioChem 7/2014) 下载免费PDF全文
948.
Etya Amsalem Julia Kiefer Stefan Schulz Abraham Hefetz 《Journal of chemical ecology》2014,40(8):900-912
The cephalic labial glands are well developed in many bee species. In bumble bee males, they cover most of the head volume, and their secretion is used in marking reproductive territories and attracting virgin queens. In females, however, they are poorly studied. Here, we present chemical analyses of their secretion in queens and workers of Bombus terrestris under various social conditions. The secretion revealed a context-dependent composition with sterile females possessing large amounts of fatty acid dodecyl esters, ranging from dodecyl hexanoate to dodecyl oleate, compared to small amounts in fertile females. Significant reduction in the dodecyl esters also was found in queens at the competition phase, where worker reproduction, aggression, and gyne differentiation occur. The exclusive production of esters by sterile individuals also is typical of Dufour’s gland secretion in this species, albeit in this case these are octyl rather than dodecyl esters, and the differences between sterile and fertile individuals are qualitative rather than quantitative. We propose that the labial gland esters provide yet another signal of reproductive inactivity. In virgin queens, it may signal that egg laying is deferred to the next season, while in workers it reinforces the message “I am sterile and out of the reproductive competition”. Whether the reduction in dodecyl esters in fertile queens as a function of colony social development is involved in regulating gyne production and the onset of the competition phase is yet to be deciphered. 相似文献
949.
Michael Adam Cekdar Vakifahmetoglu Paolo Colombo Michaela Wilhelm Georg Grathwohl 《Journal of the American Ceramic Society》2014,97(3):959-966
By direct foaming of a Pt‐containing polysiloxane precursor, macroporous ceramics were generated by pyrolysis at 1400°C under nitrogen or argon. The growth of nanowires was induced via a vapor–liquid–solid mechanism in which the Pt particles acted as deposition site for the decomposition gases released upon pyrolyzing the preceramic polymer. SEM, HR‐SEM, TEM/EDX, and XRD investigations revealed that pyrolysis under argon atmosphere leads to short SiC nanowires of only a few micrometers length and under nitrogen atmosphere Si3N4 nanowires evolved, with length of several 10 μm. In both cases the tips of the nanowires mainly consisted of PtSi. In contrast to samples pyrolyzed at 600°C, the components after higher temperature pyrolysis showed moderate‐specific surface areas of 55–67 m2/g. In CO oxidation experiments, a good catalytic activity was found for the Pt silicide particles, suggesting that despite their relatively large size, their location at the tips of the nanowires affords them good reactivity. 相似文献
950.
Controlling the electrical conductivity is a critical issue when processing material systems consisting of an insulating matrix filled with conductive particles. We provide experimental evidence that given shear rates result in specific conductivity levels in such different systems as high-viscosity carbon nanotube/polymer melt or low-viscosity carbon nanotube/epoxy fiber suspensions. The steady-state conductivities are independent of the initial state of the dispersion. The observed behavior is modeled phenomenologically by the competition between build-up and destruction of conductive filler network. A particle-level simulation of flowing fiber suspension also reflects the observed behavior. Our results show that properties of particulate suspensions can be controlled by steady shear. They should be considered to obtain reproducible properties in shear-based processing technologies as injection molding or resin transfer molding. 相似文献