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51.
Olena V. Nosal Olga P. Lyubanova Valeri G. Naidenov Yaroslav M. Shuba 《Cellular and molecular life sciences : CMLS》2013,70(9):1653-1661
Nickel is considered to be a selective blocker of low-voltage-activated T-type calcium channel. Recently, the Ni2+-binding site with critical histidine-191 (H191) within the extracellular IS3–IS4 domain of the most Ni2+-sensitive Cav3.2 T-channel isoform has been identified. All calcium channels are postulated to also have intrapore-binding site limiting maximal current carried by permeating divalent cations (PDC) and determining the blockade by non-permeating ones. However, the contribution of the two sites to the overall Ni2+ effect and its dependence on PDC remain uncertain. Here we compared Ni2+ action on the wild-type “Ni2+-insensitive” Cav3.1w/t channel and Cav3.1Q172H mutant having glutamine (Q) equivalent to H191 of Cav3.2 replaced by histidine. Each channel was expressed in Xenopus oocytes, and Ni2+ blockade of Ca2+, Sr2+, or Ba2+ currents was assessed by electrophysiology. Inhibition of Cav3.1w/t by Ni2+ conformed to two sites binding. Ni2+ binding with high-affinity site (IC50 = 0.03–3 μM depending on PDC) produced maximal inhibition of 20–30 % and was voltage-dependent, consistent with its location within the channel’s pore. Most of the inhibition (70–80 %) was produced by Ni2+ binding with low-affinity site (IC50 = 240–700 μM). Q172H-mutation mainly affected low-affinity binding (IC50 = 120–160 μM). The IC50 of Ni2+ binding with both sites in the Cav3.1w/t and Cav3.1Q172H was differentially modulated by PDC, suggesting a varying degree of competition of Ca2+, Sr2+, or Ba2+ with Ni2+. We conclude that differential Ni2+-sensitivity of T-channel subtypes is determined only by H-containing external binding sites, which, in the absence of Ni2+, may be occupied by PDC, influencing in turn the channel’s permeation. 相似文献
52.
Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences 总被引:1,自引:1,他引:0
53.
Debora?Baroni Olga?Zegarra-Moran Oscar?MoranEmail author 《Cellular and molecular life sciences : CMLS》2015,72(7):1363-1375
The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is a membrane-integral protein that belongs to the ATP-binding cassette superfamily. Mutations in the CFTR gene cause cystic fibrosis in which salt, water, and protein transports are defective in various tissues. To investigate the conformation of the CFTR in the membrane, we applied the small-angle x-ray scattering (SAXS) technique on microsomal membranes extracted from NIH/3T3 cells permanentely transfected with wild-type (WT) CFTR and with CFTR carrying the ΔF508 mutation. The electronic density profile of the membranes was calculated from the SAXS data, assuming the lipid bilayer electronic density to be composed by a series of Gaussian shells. The data indicate that membranes in the microsome vesicles, that contain mostly endoplasmic reticulum membranes, are oriented in the outside-out conformation. Phosphorylation does not change significantly the electronic density profile, while dephosphorylation produces a significant modification in the inner side of the profile. Thus, we conclude that the CFTR and its associated protein complex in microsomes are mostly phosphorylated. The electronic density profile of the ΔF508-CFTR microsomes is completely different from WT, suggesting a different assemblage of the proteins in the membranes. Low-temperature treatment of cells rescues the ΔF508-CFTR protein, resulting in a conformation that resembles the WT. Differently, treatment with the corrector VX-809 modifies the electronic profile of ΔF508-CFTR membrane, but does not recover completely the WT conformation. To our knowledge, this is the first report of a direct physical measurement of the structure of membranes containing CFTR in its native environment and in different functional and pharmacological conditions. 相似文献
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55.
Olga Moreno-Gonzalo Irene Fernandez-Delgado Francisco Sanchez-Madrid 《Cellular and molecular life sciences : CMLS》2018,75(1):1-19
Extracellular vesicles (EVs) are released by cells to the extracellular environment to mediate inter-cellular communication. Proteins, lipids, nucleic acids and metabolites shuttled in these vesicles modulate specific functions in recipient cells. The enrichment of selected sets of proteins in EVs compared with global cellular levels suggests the existence of specific sorting mechanisms to specify EV loading. Diverse post-translational modifications (PTMs) of proteins participate in the loading of specific elements into EVs. In this review, we offer a perspective on PTMs found in EVs and discuss the specific role of some PTMs, specifically Ubiquitin and Ubiquitin-like modifiers, in exosomal sorting of protein components. The understanding of these mechanisms will provide new strategies for biomedical applications. Examples include the presence of defined PTM marks on EVs as novel biomarkers for the diagnosis and prognosis of certain diseases, or the specific import of immunogenic components into EVs for vaccine generation. 相似文献
56.
Olga E. Scaramuzzi C. A. Baile J. Mayer 《Cellular and molecular life sciences : CMLS》1971,27(3):256-257
Zusammenfassung Nachweis der Wirkung verschiedener Prostaglandine auf die Nahrungsaufnahme bei der Ratte.
This work was supported in part by grants-in-aid from the National Institute of Neurological Diseases and Blindness No. NB-01941 and the National Institute of Arthritis and Metabolie Diseases No. AM-02911; and the Fund for Research and Teaching, Department of Nutrition, Harvard School of Public Health. 相似文献
This work was supported in part by grants-in-aid from the National Institute of Neurological Diseases and Blindness No. NB-01941 and the National Institute of Arthritis and Metabolie Diseases No. AM-02911; and the Fund for Research and Teaching, Department of Nutrition, Harvard School of Public Health. 相似文献
57.
Geology and palaeontology of the Upper Miocene Toros-Menalla hominid locality,Chad 总被引:13,自引:0,他引:13
Vignaud P Duringer P Mackaye HT Likius A Blondel C Boisserie JR De Bonis L Eisenmann V Etienne ME Geraads D Guy F Lehmann T Lihoreau F Lopez-Martinez N Mourer-Chauviré C Otero O Rage JC Schuster M Viriot L Zazzo A Brunet M 《Nature》2002,418(6894):152-155
All six known specimens of the early hominid Sahelanthropus tchadensis come from Toros-Menalla site 266 (TM 266), a single locality in the Djurab Desert, northern Chad, central Africa. Here we present a preliminary analysis of the palaeontological and palaeoecological context of these finds. The rich fauna from TM 266 includes a significant aquatic component such as fish, crocodiles and amphibious mammals, alongside animals associated with gallery forest and savannah, such as primates, rodents, elephants, equids and bovids. The fauna suggests a biochronological age between 6 and 7 million years. Taken together with the sedimentological evidence, the fauna suggests that S. tchadensis lived close to a lake, but not far from a sandy desert, perhaps the oldest record of desert conditions in the Neogene of northern central Africa. 相似文献
58.
Sleep affects learning and development in humans and other animals, but the role of sleep in developmental learning has never been examined. Here we show the effects of night-sleep on song development in the zebra finch by recording and analysing the entire song ontogeny. During periods of rapid learning we observed a pronounced deterioration in song structure after night-sleep. The song regained structure after intense morning singing. Daily improvement in similarity to the tutored song occurred during the late phase of this morning recovery; little further improvement occurred thereafter. Furthermore, birds that showed stronger post-sleep deterioration during development achieved a better final imitation. The effect diminished with age. Our experiments showed that these oscillations were not a result of sleep inertia or lack of practice, indicating the possible involvement of an active process, perhaps neural song-replay during sleep. We suggest that these oscillations correspond to competing demands of plasticity and consolidation during learning, creating repeated opportunities to reshape previously learned motor skills. 相似文献
59.
Martin J Han C Gordon LA Terry A Prabhakar S She X Xie G Hellsten U Chan YM Altherr M Couronne O Aerts A Bajorek E Black S Blumer H Branscomb E Brown NC Bruno WJ Buckingham JM Callen DF Campbell CS Campbell ML Campbell EW Caoile C Challacombe JF Chasteen LA Chertkov O Chi HC Christensen M Clark LM Cohn JD Denys M Detter JC Dickson M Dimitrijevic-Bussod M Escobar J Fawcett JJ Flowers D Fotopulos D Glavina T Gomez M Gonzales E Goodstein D Goodwin LA Grady DL Grigoriev I Groza M Hammon N Hawkins T 《Nature》2004,432(7020):988-994
60.
Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation 总被引:2,自引:0,他引:2
How tissues generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Recent work on adult stem cells has highlighted their potential contribution to organ maintenance and repair. However, the extent to which stem cells actually participate in these processes in vivo is not clear. Here we introduce a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest. We focus on pancreatic beta-cells, whose postnatal origins remain controversial. Our analysis shows that pre-existing beta-cells, rather than pluripotent stem cells, are the major source of new beta-cells during adult life and after pancreatectomy in mice. These results suggest that terminally differentiated beta-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in beta-cell replenishment. 相似文献