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121.
Giulio Vistoli Alessandro Pedretti Angelica Mazzolari Cristiano Bolchi Bernard Testa 《化学与生物多样性》2009,6(11):2092-2100
Temocapril is a prodrug whose hydrolysis by carboxylesterase 1 (CES1) yields the active ACE inhibitor temocaprilat. This molecular‐dynamics (MD) study uses a resolved structure of the human CES1 (hCES1) to investigate some mechanistic details of temocapril hydrolysis. The ionization constants of temocapril (pK1 and pK3) and temocaprilat (pK1, pK2, and pK3) were determined experimentally and computationally using commercial algorithms. The constants so obtained were in good agreement and revealed that temocapril exists mainly in three ionic forms (a cation, a zwitterion, and an anion), whereas temocaprilat exists in four major ionic forms (a cation, a zwitterion, an anion, and a dianion). All these ionic forms were used as ligands in 5‐ns MS simulations. While the cationic and zwitterionic forms of temocapril were involved in an ion‐pair bond with Glu255 suggestive of an inhibitor behavior, the anionic form remained in a productive interaction with the catalytic center. As for temocaprilat, its cation appeared trapped by Glu255, while its zwitterion and anion made a slow departure from the catalytic site and a partial egress from the protein. Only its dianion was effectively removed from the catalytic site and attracted to the protein surface by Lys residues. A detailed mechanism of product egress emerges from the simulations. 相似文献
122.
Abstract An ultrastructural study has been performed to elucidate the effect of active polypeptide(s) from neo-peptone on heterocyst induction in Anabaena cylindrica [1]. There was an immediate aggregation of A. cylindrica cells and a clumping of filamentous appendages in the mucilaginous sheath on the addition of active polypeptide(s) from neo-peptone. However, there was no change in the cell wall and cell membrane ultrastructure. An increase in cell length, contortion and disintegration of thylakoids, disappearance of polyphosphate bodies and an accumulation of polyglucose bodies were observed after 18 h of treatment. The double heterocysts induced show a normal heterocyst ultrastructure with well-developed polar nodules between the heterocysts and the vegetative cells, as well as between two heterocysts.
It appears that the inductive effect of active polypeptide(s) from neo-peptone is mediated through their specific binding to filamentous appendages in the mucilaginous sheath. 相似文献
It appears that the inductive effect of active polypeptide(s) from neo-peptone is mediated through their specific binding to filamentous appendages in the mucilaginous sheath. 相似文献
123.
Justine M. Toulotte Chrysoula K. Pantazopoulou Maria Angelica Sanclemente Laurentius A. C. J. Voesenek Rashmi Sasidharan 《植物学报(英文版)》2022,64(2):412-430
Cereal crops are significant contributors to global diets. As climate change disrupts weather patterns and wreaks havoc on crops, the need for generating stress-resilient, high-yielding varieties is more urgent than ever. One extremely promising avenue in this regard is to exploit the tremendous genetic diversity expressed by the wild ancestors of current day crop species. These crop wild relatives thrive in a range of environments and accordingly often harbor an array of traits that allow them to do so. The identification and introgression of these traits into our staple cereal crops can lessen yield losses in stressful environments. In the last decades, a surge in extreme drought and flooding events have severely impacted cereal crop production. Climate models predict a persistence of this trend, thus reinforcing the need for research on water stress resilience. Here we review: (i) how water stress (drought and flooding) impacts crop performance; and (ii) how identification of tolerance traits and mechanisms from wild relatives of the main cereal crops, that is, rice, maize, wheat, and barley, can lead to improved survival and sustained yields in these crops under water stress conditions. 相似文献
124.
Bruno Andreoni Antonio Chiappa Emilio Bertani Massimo Bellomi Roberto Orecchia MariaGiulia Zampino Nicola Fazio Marco Venturino Franco Orsi Angelica Sonzogni Ugo Pace Lorenzo Monfardini 《World journal of surgical oncology》2007,5(1):1-10
Background
This study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994–2003.Methods
A consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years ± 11 years, range: 24–88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 ± 24 months; range: 3–108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed.Results
Of the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001).Conclusion
A prospective, uniform follow-up policy used in a single institution over the last decade provides evidence of quality assurance in colorectal cancer surgery with high rates of resection for cure where only stage at presentation functions as an independent variable for cancer-related outcome. 相似文献125.
Stephanie M. Rangel Maureen H. Diaz Claire A. Knoten Angelica Zhang Alan R. Hauser 《PLoS pathogens》2015,11(6)
Hospital-acquired pneumonia is associated with high rates of morbidity and mortality, and dissemination to the bloodstream is a recognized risk factor for particularly poor outcomes. Yet the mechanism by which bacteria in the lungs gain access to the bloodstream remains poorly understood. In this study, we used a mouse model of Pseudomonas aeruginosa pneumonia to examine this mechanism. P. aeruginosa uses a type III secretion system to deliver effector proteins such as ExoS directly into the cytosol of eukaryotic cells. ExoS, a bi-functional GTPase activating protein (GAP) and ADP-ribosyltransferase (ADPRT), inhibits phagocytosis during pneumonia but has also been linked to a higher incidence of dissemination to the bloodstream. We used a novel imaging methodology to identify ExoS intoxicated cells during pneumonia and found that ExoS is injected into not only leukocytes but also epithelial cells. Phagocytic cells, primarily neutrophils, were targeted for injection with ExoS early during infection, but type I pneumocytes became increasingly injected at later time points. Interestingly, injection of these pneumocytes did not occur randomly but rather in discrete regions, which we designate ““fields of cell injection” (FOCI). These FOCI increased in size as the infection progressed and contained dead type I pneumocytes. Both of these phenotypes were attenuated in infections caused by bacteria secreting ADPRT-deficient ExoS, indicating that FOCI growth and type I pneumocyte death were dependent on the ADPRT activity of ExoS. During the course of infection, increased FOCI size was associated with enhanced disruption of the pulmonary-vascular barrier and increased bacterial dissemination into the blood, both of which were also dependent on the ADPRT activity of ExoS. We conclude that the ADPRT activity of ExoS acts upon type I pneumocytes to disrupt the pulmonary-vascular barrier during P. aeruginosa pneumonia, leading to bacterial dissemination. 相似文献
126.
The evolution of redirecting resources from plant defense to growth or reproduction may explain why some exotic species are successful invaders in new environments. For example, the evolution of increased competitive ability hypothesis posits that escape from herbivores by invasive plants results in the selection of more vigorous genotypes that reduce their allocation of resources to defense. In addition, understanding the defense strategy of an invasive plant may help forecast the likely impact of herbivory. We tested the prediction of reduced defense (i.e., resistance) in Genista monspessulana, measured indirectly as the performance of a specialist psyllid herbivore, by comparing five native and introduced plant populations. We also examined the ability of G. monspessulana to compensate for herbivory in the presence and the absence of psyllids for a single plant population from the native and introduced regions. Plant origin (native or introduced) did not influence the psyllid’s abundance and population growth rate, suggesting no change in resistance to herbivory for introduced plants. Similarly, we found no overall difference in plant performance between individuals in the presence and the absence of psyllid herbivory, suggesting that G. monspessulana was able to fully compensate for herbivory. Damaged plants compensated by changing the pattern of branching, which also resulted in greater dry leaf biomass. We conclude that evolution of reduced defenses does not explain the success of G. monspessulana as an invader and that compensation for herbivory may limit the efficacy of the psyllid as a biological control agent. 相似文献
127.
Coutinho LB Gomes AO Araújo EC Barenco PV Santos JL Caixeta DR Silva DA Cunha-Júnior JP Ferro EA Silva NM 《International journal for parasitology》2012,42(4):341-352
Congenital toxoplasmosis is associated with adverse pregnancy outcome. Despite the type 1 immune response, C57BL/6 mice are more susceptible than BALB/c mice to Toxoplasma gondii infection. Additionally, successful pregnancy appears to be correlated with type 2 T helper maternal immunity and regulatory T cells. In order to investigate the mechanisms of susceptibility/resistance to congenital toxoplasmosis in mice with different genetic backgrounds and the influence of inducible nitric oxide synthase in pregnancy outcome, groups of C57BL/6, BALB/c and C57BL/6 iNOS(-/-) females were orally infected with T. gondii ME-49 strain on day 1 of pregnancy and were sacrificed on day 8 p.i. and day 19 p.i. The uterus and placenta were evaluated for the foetal resorption rate, parasite load, immunological and histological changes. C57BL/6 mice presented inflammatory foci in the decidua (endometrium) of the uterus at a higher frequency than BALB/c mice on day 8 p.i., and a large number of pregnant C57BL/6 mice presented necrotic implantation sites. The parasite was seldom found in the uterus or placenta of either lineage of mice. Interestingly, there was no observed difference in inducible nitric oxide synthase expression in the uterus and placenta of infected mice. In addition, higher levels of TNF-α were detected in serum samples from C57BL/6 mice compared with BALB/c mice. Accordingly, C57BL/6 mice presented with levels of 90% abortion compared with 50% in BALB/c mice on day 19 p.i. C57BL/6 iNOS(-/-) mice showed low placental parasite counts and high absorption rates, similar to wild type mice. The data suggest that the impaired pregnancy outcome due to T. gondii infection in C57BL/6 mice could be associated with a higher inflammatory response leading to cell apoptosis and necrosis of implantation sites compared with BALB/c mice, and this phenomenon was not due to inducible nitric oxide synthase expression in the decidua. 相似文献
128.
Nitrosamine water disinfection byproducts (DBPs) are an emerging class of non-halogenated, nitrogen-containing water contaminants. Five nitrosamine DBPs were analyzed for genotoxicity (N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR) and N-nitrosodiphenylamine (NDPhA). Using Salmonella typhimurium strain YG7108 the descending rank order of mutagenicity was NDMA>NPIP>NMOR>NPYR; NDPhA was not mutagenic. We developed and calibrated an exogenous S9 mix that was highly effective in activating NDMA in Chinese hamster ovary (CHO) cells using the SCGE (Comet) assay. The descending rank order for genotoxicity was NDMA>NPIP>NMOR. NDPhA was genotoxic only at one concentration and NPYR was not genotoxic. The genotoxic potencies in S. typhimurium and CHO cells were highly correlated. Based on their comparative genotoxicity attention should be focused on the generation and occurrence of NDMA, NPIP and NMOR. Current drinking water disinfection processes may need to be modified such that the generation of nitrosamine DBPs is effectively limited in order to protect the environment and the public health. 相似文献
129.
Guo C Kephart S Ornelas M Gonzalez J Linton A Pairish M Nagata A Greasley S Elleraas J Hosea N Engebretsen J Fanjul AN 《Bioorganic & medicinal chemistry letters》2012,22(2):1230-1236
High throughput cell-based screening led to the identification of 3-aryloxy lactams as potent androgen receptor (AR) antagonists. Refinement of these leads to improve the ADME profile and remove residual agonism led to the discovery of 12, a potent full antagonist with greater oral bioavailability. Improvements in the ADME profile were realized by designing more ligand-efficient molecules with reduced molecular weights and lower lipophilicities. 相似文献
130.
Julio Castro-Guerrero Angelica Romero José J. Aguilar Ma. Luisa Xiqui Jesús O. Sandoval Beatriz E. Baca 《Plant and Soil》2012,356(1-2):139-150