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Neurotransmitters are rapidly removed from the extracellular space primarily through the actions of plasma membrane transporters. This uptake process is not only essential in the termination of neurotransmission but also serves to replenish intracellular levels of transmitter for further release. Neurotransmitter transporters couple the inward movement of substrate to the movement of Na(+) down a concentration gradient and, in addition to their transport function, some carriers also display channel-like activities. Five Na(+)/K(+)-dependent glutamate transporter subtypes belong to the solute carrier 1 (SLC1) family and a second family, SLC6, encompasses the Na(+)/Cl(-)-dependent transporters for dopamine, 5-hydroxytryptamine (serotonin), noradrenaline, GABA and glycine. Recent advances, including high-resolution structures from both families, are now providing new insights into the molecular determinants that contribute to substrate translocation and ion channel activities. Other influential studies have explored how cellular regulatory mechanisms modulate transporter function, and how the different functions of the carrier shape the patterns of neurotransmitter signaling. This review focuses on recent studies of glutamate and monoamine transporters as prototypes of the two carrier families. 相似文献
64.
Manuel Valmaseda Gonzalo Almendros Angel T. Martínez 《Applied microbiology and biotechnology》1990,33(4):481-484
Summary The ability of 45 fungal strains to degrade wheat straw and beech wood was studied. Degradation patterns were defined in terms of chemical evolution of substrates and changes in lignin and polysaccharides. Trametes versicolor produced an important degradation of lignin and increased substrate digestibility, but it caused high weight losses and gave rise to similar decay patterns on both substrates. A preferential degradation of lignin was produced during straw transformation by Pleurotus eryngii. The increase of soluble lignin and decreases of lignin content and H/C ratio defined the degradation tendency after principal component analysis. The cation exchange capacity and water and alkali solubility presented the highest loading factors for the characterization of fungal transformation of beech wood.
Offprint requests to: A. T. Martínez 相似文献
65.
Labarrere CA Woods JR Hardin JW Campana GL Ortiz MA Jaeger BR Baldridge LA Pitts DE Kirlin PC 《PloS one》2012,7(4):e36100
Background
Cardiac allograft vasculopathy (CAV) is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluated the prognostic value of the first heart biopsy (median: 9 days post-transplant) versus all biopsies obtained within the first three months for the prediction of CAV and graft failure due to CAV.Methods and Findings
In a prospective cohort study, we developed multivariate regression models evaluating markers of atherothrombosis (fibrin, antithrombin and tissue plasminogen activator [tPA]) and endothelial activation (intercellular adhesion molecule-1) in serial biopsies obtained during the first three months post-transplantation from 172 patients (median follow-up = 6.3 years; min = 0.37 years, max = 16.3 years). Presence of fibrin was the dominant predictor in first-biopsy models (Odds Ratio [OR] for one- and 10-year graft failure due to CAV = 38.70, p = 0.002, 95% CI = 4.00–374.77; and 3.99, p = 0.005, 95% CI = 1.53–10.40) and loss of tPA was predominant in three-month models (OR for one- and 10-year graft failure due to CAV = 1.81, p = 0.025, 95% CI = 1.08–3.03; and 1.31, p = 0.001, 95% CI = 1.12–1.55). First-biopsy and three-month models had similar predictive and discriminative accuracy and were comparable in their capacities to correctly classify patient outcomes, with the exception of 10-year graft failure due to CAV in which the three-month model was more predictive. Both models had particularly high negative predictive values (e.g., First-biopsy vs. three-month models: 99% vs. 100% at 1-year and 96% vs. 95% at 10-years).Conclusions
Patients with absence of fibrin in the first biopsy and persistence of normal tPA in subsequent biopsies rarely develop CAV or graft failure during the next 10 years and potentially could be monitored less invasively. Presence of early risk markers in the transplanted heart may be secondary to ischemia/reperfusion injury, a potentially modifiable factor. 相似文献66.
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Miguel de Mulder Gonzalo Yebra Adriana Navas María Isabel de José María Dolores Gurbindo María Isabel González-Tomé María José Mellado Jesús Saavedra-Lozano María ángeles Mu?oz-Fernández Santiago Jiménez de Ory José Tomás Ramos áfrica Holguín Madrid Cohort of HIV-Infected Children 《PloS one》2012,7(12)
68.
Jones B Su H Bhat A Lei H Bajko J Hevi S Baltus GA Kadam S Zhai H Valdez R Gonzalo S Zhang Y Li E Chen T 《PLoS genetics》2008,4(9):e1000190
Dot1 is an evolutionarily conserved histone methyltransferase specific for lysine 79 of histone H3 (H3K79). In Saccharomyces cerevisiae, Dot1-mediated H3K79 methylation is associated with telomere silencing, meiotic checkpoint control, and DNA damage response. The biological function of H3K79 methylation in mammals, however, remains poorly understood. Using gene targeting, we generated mice deficient for Dot1L, the murine Dot1 homologue. Dot1L-deficient embryos show multiple developmental abnormalities, including growth impairment, angiogenesis defects in the yolk sac, and cardiac dilation, and die between 9.5 and 10.5 days post coitum. To gain insights into the cellular function of Dot1L, we derived embryonic stem (ES) cells from Dot1L mutant blastocysts. Dot1L-deficient ES cells show global loss of H3K79 methylation as well as reduced levels of heterochromatic marks (H3K9 di-methylation and H4K20 tri-methylation) at centromeres and telomeres. These changes are accompanied by aneuploidy, telomere elongation, and proliferation defects. Taken together, these results indicate that Dot1L and H3K79 methylation play important roles in heterochromatin formation and in embryonic development. 相似文献
69.
Gonzalo P Reboud JP 《Biology of the cell / under the auspices of the European Cell Biology Organization》2003,95(3-4):179-193
The lateral flexible stalk of the large ribosomal subunit is made of several interacting proteins anchored to a conserved region of the 28S (26S) rRNA termed the GTPase-associated domain or thiostrepton loop. This structure is demonstrated to adopt puzzling changes of conformation following the different steps of the elongation cycle. Some of these proteins termed the P-proteins in eukaryotes and L10 and L7/L12 in bacteria, present little structural similarities between Eubacteria on one side and Archae and Eukaryotes on the other side. However, up to now, these proteins seem to present a similar macromolecular organisation and they have been involved in the same functions. Convincing evidence attests that these proteins participate in elongation factor binding to the ribosome, and it has been suggested that these proteins might be evolved in a GTP hydrolysis activating protein activity. Involvement of these proteins in the translational mechanism is discussed. Moreover, in eukaryotes, small P-proteins are also found as isolated proteins in a cytoplasmic pool that exchanges with the ribosome-associated P-proteins. Moreover, a part of the ribosomal proteins is phosphorylated (hence their P-protein names). The biological signification of these particularities is discussed. 相似文献
70.
Gonzalo Izaguirre Lixin Qi Mary Lima Steven T. Olson 《The Journal of biological chemistry》2013,288(30):21802-21814
α1-Protease inhibitor Portland (α1PDX) is an engineered serpin family inhibitor of the proprotein convertase (PC), furin, that exhibits high specificity but limited selectivity for inhibiting furin over other PC family proteases. Here, we characterize serpin B8, a natural inhibitor of furin, together with α1PDX-serpin B8 and furin-PC chimeras to identify determinants of serpin specificity and selectivity for furin inhibition. Replacing reactive center loop (RCL) sequences of α1PDX with those of serpin B8 demonstrated that both the P4–P1 RXXR recognition sequence as well as the P1′–P5′ sequence are critical determinants of serpin specificity for furin. Alignments of PC catalytic domains revealed four variable active-site loops whose role in furin reactivity with serpin B8 was tested by engineering furin-PC loop chimeras. The furin(298–300) loop but not the other loops differentially affected furin reactivity with serpin B8 and α1PDX in a manner that depended on the serpin RCL-primed sequence. Modeling of the serpin B8-furin Michaelis complex identified serpin exosites in strand 3C close to the 298–300 loop whose substitution in α1PDX differentially affected furin reactivity depending on the furin loop and serpin RCL-primed sequences. These studies demonstrate that RCL-primed residues, strand 3C exosites, and the furin(298–300) loop are critical determinants of serpin reactivity with furin, which may be exploited in the design of specific and selective α1PDX inhibitors of PCs. 相似文献