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991.
Andrea Fantuzzi Friederike Allgwer Holly Baker Gemma McGuire Wee Kii Teh Ana P. Gamiz-Hernandez Ville R. I. Kaila A. William Rutherford 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(6)
Photosystem II (PSII), the water/plastoquinone photo-oxidoreductase, plays a key energy input role in the biosphere. , the reduced semiquinone form of the nonexchangeable quinone, is often considered capable of a side reaction with O2, forming superoxide, but this reaction has not yet been demonstrated experimentally. Here, using chlorophyll fluorescence in plant PSII membranes, we show that O2 does oxidize at physiological O2 concentrations with a t1/2 of 10 s. Superoxide is formed stoichiometrically, and the reaction kinetics are controlled by the accessibility of O2 to a binding site near , with an apparent dissociation constant of 70 ± 20 µM. Unexpectedly, could only reduce O2 when bicarbonate was absent from its binding site on the nonheme iron (Fe2+) and the addition of bicarbonate or formate blocked the O2-dependant decay of . These results, together with molecular dynamics simulations and hybrid quantum mechanics/molecular mechanics calculations, indicate that electron transfer from to O2 occurs when the O2 is bound to the empty bicarbonate site on Fe2+. A protective role for bicarbonate in PSII was recently reported, involving long-lived triggering bicarbonate dissociation from Fe2+ [Brinkert et al., Proc. Natl. Acad. Sci. U.S.A. 113, 12144–12149 (2016)]. The present findings extend this mechanism by showing that bicarbonate release allows O2 to bind to Fe2+ and to oxidize . This could be beneficial by oxidizing and by producing superoxide, a chemical signal for the overreduced state of the electron transfer chain.Photosystem II (PSII) is the water/plastoquinone photo-oxidoreductase that uses the energy of red light to drive the oxidation of water and the reduction of plastoquinone (PQ). This process leads to the formation of a radical pair on the chlorophyll PD1•+ and pheophytin PheoD1•−. The electron hole is transferred from the chlorophyll cation radical, PD1•+, via a redox-active tyrosine (TyrZ) to the Mn4O5Ca cluster, where, after four sequential photochemical turnovers, two water molecules are oxidized on the luminal side of the membrane. The electron is transferred from the pheophytin anion radical (PheoD1•−) via a nonexchangeable plastoquinone (QA), which acts as a one-electron relay, to an exchangeable plastoquinone (QB), the terminal electron acceptor (1–3). QB accepts two electrons and takes up two protons from the aqueous phase to form QBH2 before it is released as a PQH2 into the PQ/PQH2 pool in the membrane (4). From here, the PQH2 delivers electrons to cytochrome b6f complex, the subsequent enzyme of the photosynthetic electron transfer chain.As photochemical charge separation is intrinsically a one-photon-per-electron process, two photochemical turnovers are required to form PQH2, with the one-electron reduced semiquinone, , formed as an intermediate. Semiquinones can be very reactive, but is rendered thermodynamically stable by the environment provided by its binding site on the D1 protein (4). The electron on is still able to back-react via with the S2 and S3 states, the two semistable intermediates of the water oxidizing enzyme (5). This back-reaction occurs by thermal repopulation of the intermediate radical pairs between and . can either repopulate P*, which can decay radiatively (5, 6), or it undergoes direct charge recombination, forming the chlorophyll triplet state, 3P680 (7–9). As expected for a long-lived chlorophyll triplet state, it reacts with dioxygen to form a highly reactive singlet oxygen species, 1O2, which causes photodamage (10, 11).On the electron acceptor-side of PSII (Fig. 1), the reduced forms of the electron transfer cofactors can potentially reduce oxygen, forming superoxide radical () by a one-electron transfer to O2. This would be a wasteful leak of electrons, and the formed could be damaging and act as redox signal within the cell. During forward electron transfer, has a half-time of ∼1 ms (1) and is unlikely to react with O2. However, when, for example, QB and the PQ pool are reduced, is longer lived, and it is then more likely to reduce oxygen. Oxygen reduction by is often discussed in the literature (12–16), but clear experimental evidence for this reaction has not been reported. Here, using PSII membranes, we have directly tested for electron transfer from to O2 and for formation of superoxide. We show the reaction does occur, and we characterized the reaction in terms of the O2 binding site using biochemical and computational approaches. The results indicate the reaction constitutes an unexpected regulatory mechanism involving bicarbonate.Open in a separate windowFig. 1.The quinone-iron complex in PSII. The nonheme iron shown as a red sphere and the bicarbonate in pink. The amino acid side chains involved in the hydrogen-bonding network are shown, green if belonging to D1 and cyan if belonging to D2. Data from the 1.9-Å crystal structure (PDB ID: 3WU2) (41). 相似文献
992.
Andrea N. Mazzarello Eva Gentner-Gbel Marcus Dühren-von Minden Tatyana N. Tarasenko Antonella Nicol Gerardo Ferrer Stefano Vergani Yun Liu Davide Bagnara Kanti R. Rai Jan A. Burger Peter J. McGuire Palash C. Maity Hassan Jumaa Nicholas Chiorazzi 《The Journal of clinical investigation》2022,132(2)
In chronic lymphocytic leukemia (CLL), the B cell receptor (BCR) plays a critical role in disease development and progression, as indicated by the therapeutic efficacy of drugs blocking BCR signaling. However, the mechanism(s) underlying BCR responsiveness are not completely defined. Selective engagement of membrane IgM or IgD on CLL cells, each coexpressed by more than 90% of cases, leads to distinct signaling events. Since both IgM and IgD carry the same antigen-binding domains, the divergent actions of the receptors are attributed to differences in immunoglobulin (Ig) structure or the outcome of signal transduction. We showed that IgM, not IgD, level and organization associated with CLL-cell birth rate and the type and consequences of BCR signaling in humans and mice. The latter IgM-driven effects were abrogated when BCR signaling was inhibited. Collectively, these studies demonstrated a critical, selective role for IgM in BCR signaling and B cell fate decisions, possibly opening new avenues for CLL therapy. 相似文献
993.
The Older Americans Act is the most comprehensive legislation concerning the aged and provides programs, services, and administration of elderly services nationwide. It is important that nurses understand the role this act plays in the health and well-being of elders as we deal with the everchanging health care delivery and payment system. 相似文献
994.
995.
996.
A Prospective,Case‐Controlled Study Evaluating the Use of Enamel Matrix Derivative on Human Buccal Recession Defects: A Human Histologic Examination
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Background: Connective tissue grafts (CTGs) and coronally advanced flaps (CAFs) do not regenerate periodontal attachment apparatus when used to treat gingival recessions (GRs). Instead of generating new bone, cementum, and inserting periodontal ligament fibers, CTG+CAF repairs through a long epithelial junction and connective tissue attachment. Enamel matrix derivatives (EMDs) have demonstrated proof‐of‐principle that periodontal regeneration can be achieved, although data are limited. Methods: Three patients, each requiring extraction of four premolars before orthodontic treatment, were enrolled in a randomized, open‐label study. Two months after induction of Miller Class I and II GR, each patient received EMD+CAF for three teeth and CTG+CAF for one tooth for root coverage. Nine months after root coverage, all four premolars from each of the three patients were surgically extracted en bloc for histologic and microcomputed tomography (micro‐CT) analysis, looking for evidence of periodontal regeneration. Standard clinical measurements, radiographs, and intraoral photographs were taken over prescribed time points. Results: Seven of the nine teeth treated with EMD+CAF demonstrated varying degrees of periodontal regeneration, detailed through histology with new bone, cementum, and inserting fibers. Micro‐CT corroborated these findings. None of the three teeth treated with CTG+CAF showed periodontal regeneration. Clinical measurements were comparable for both treatments. One instance of root resorption and ankylosis was noted with EMD+CAF. Conclusions: EMD+CAF continues to show histologic evidence of periodontal regeneration via human histology, this being the largest study (nine teeth) examining its effect when treating GR. The mechanism of action, ideal patient profile, and criteria leading to predictable regeneration are in need of further exploration. 相似文献
997.
The cotton-top tamarin (CTT) (Sagiunus oedipus) has been used as an animal model to investigate the etiology and pathophysiology of several human diseases, including ulcerative colitis and its associated colorectal carcinoma (CRC). Little is known, however, about genetic synteny between CTT and humans, and about chromosome aberrations in CTT CRC. To address these issues, we have analyzed CTT lymphoblastoid and CRC cell lines using cytogenetics, fluorescence in situ hybridization (Zoo-FISH), and direct sequencing. The CTT lymphocytes had pseudodiploid chromosomes of 46. The CTT CRC cells showed near-diploid chromosomes of 45. Several clonal structural aberrations were observed, including der(1), a marker chromosome, and double minutes. Zoo-FISH using human chromosome 2, 3, 5, 6, 9, 11, 13, 15, 16, 17, 19, 22, and X paints identified homologous chromosomes and subchromosomal regions in the CTT genome. Fluorescence in situ hybridization with human telomeric probe also detected a homologous sequence in CTT genome. Direct sequencing of CTT genomic DNA using primers amplifying exons 4 and 15 of the human APC gene identified DNA sequences in CTT genome with 99% and 95% homology, respectively. These results provide a basis for further comparative studies of CTT and human genome. 相似文献
998.
The highly prevalent, prediabetic condition of impaired glucose tolerance (IGT) confers a high risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). There is an emerging body of cost-effectiveness literature in the management of IGT. For acarbose, an alpha-glucosidase inhibitor, economic analyses have been conducted for Spain, Germany, Sweden and Canada. In Spain, acarbose was more effective and less costly (dominant) compared with placebo. In Germany, the cost per patient free of diabetes was under Pounds 800; acarbose was dominant for those at high risk for T2DM, CVD or both, and a similar outcome in the Swedish study. In Canada, acarbose was dominant compared with no intervention and very cost-effective compared with metformin [C Dollars 1798/life years gained (LYG)]. The particularly cost-effective outcomes or cost savings delivered by acarbose for IGT subjects at high risk for T2DM and/or CVD render an IGT-intervention program prioritised to such high-risk individuals an economically attractive strategy. 相似文献
999.
MacSweeney M Campbell R Woll B Giampietro V David AS McGuire PK Calvert GA Brammer MJ 《NeuroImage》2004,22(4):1605-1618
Gestures of the face, arms, and hands are components of signed languages used by Deaf people. Signaling codes, such as the racecourse betting code known as Tic Tac, are also made up of such gestures. Tic Tac lacks the phonological structure of British Sign Language (BSL) but is similar in terms of its visual and articulatory components. Using fMRI, we compared the neural correlates of viewing a gestural language (BSL) and a manual-brachial code (Tic Tac) relative to a low-level baseline task. We compared three groups: Deaf native signers, hearing native signers, and hearing nonsigners. None of the participants had any knowledge of Tic Tac. All three groups activated an extensive frontal-posterior network in response to both types of stimuli. Superior temporal cortex, including the planum temporale, was activated bilaterally in response to both types of gesture in all groups, irrespective of hearing status. The engagement of these traditionally auditory processing regions was greater in Deaf than hearing participants. These data suggest that the planum temporale may be responsive to visual movement in both deaf and hearing people, yet when hearing is absent early in development, the visual processing role of this region is enhanced. Greater activation for BSL than Tic Tac was observed in signers, but not in nonsigners, in the left posterior superior temporal sulcus and gyrus, extending into the supramarginal gyrus. This suggests that the left posterior perisylvian cortex is of fundamental importance to language processing, regardless of the modality in which it is conveyed. 相似文献
1000.