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101.
Carmen Methner Guido Buonincontri Chou-Hui Hu Ana Vujic Axel Kretschmer Stephen Sawiak Adrian Carpenter Johannes-Peter Stasch Thomas Krieg 《PloS one》2013,8(12)
Aim
Stimulation of the nitric oxide (NO) – soluble guanylate (sGC) - protein kinase G (PKG) pathway confers protection against acute ischaemia/reperfusion injury, but more chronic effects in reducing post-myocardial infarction (MI) heart failure are less defined. The aim of this study was to not only determine whether the sGC stimulator riociguat reduces infarct size but also whether it protects against the development of post-MI heart failure.Methods and Results
Mice were subjected to 30 min ischaemia via ligation of the left main coronary artery to induce MI and either placebo or riociguat (1.2 µmol/l) were given as a bolus 5 min before and 5 min after onset of reperfusion. After 24 hours, both, late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) and 18F-FDG-positron emission tomography (PET) were performed to determine infarct size. In the riociguat-treated mice, the resulting infarct size was smaller (8.5±2.5% of total LV mass vs. 21.8%±1.7%. in controls, p = 0.005) and LV systolic function analysed by MRI was better preserved (60.1%±3.4% of preischaemic vs. 44.2%±3.1% in controls, p = 0.005). After 28 days, LV systolic function by echocardiography treated group was still better preserved (63.5%±3.2% vs. 48.2%±2.2% in control, p = 0.004).Conclusion
Taken together, mice treated acutely at the onset of reperfusion with the sGC stimulator riociguat have smaller infarct size and better long-term preservation of LV systolic function. These findings suggest that sGC stimulation during reperfusion therapy may be a powerful therapeutic treatment strategy for preventing post-MI heart failure. 相似文献102.
Satoi Nagasawa Anna S. Sedukhina Yuko Nakagawa Ichiro Maeda Manabu Kubota Shigeko Ohnuma Koichiro Tsugawa Tomohiko Ohta Marta Roche-Molina Juan A. Bernal Ana J. Narváez Anand D. Jeyasekharan Ko Sato 《PloS one》2015,10(2)
LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1. 相似文献
103.
Ana S. Luís Immacolata Venditto Max J. Temple Artur Rogowski Arnaud Baslé Jie Xue J. Paul Knox José A.M. Prates Luís M. A. Ferreira Carlos M. G. A. Fontes Shabir Najmudin Harry J. Gilbert 《The Journal of biological chemistry》2013,288(7):4799-4809
Plant biomass is central to the carbon cycle and to environmentally sustainable industries exemplified by the biofuel sector. Plant cell wall degrading enzymes generally contain noncatalytic carbohydrate binding modules (CBMs) that fulfil a targeting function, which enhances catalysis. CBMs that bind β-glucan chains often display broad specificity recognizing β1,4-glucans (cellulose), β1,3-β1,4-mixed linked glucans and xyloglucan, a β1,4-glucan decorated with α1,6-xylose residues, by targeting structures common to the three polysaccharides. Thus, CBMs that recognize xyloglucan target the β1,4-glucan backbone and only accommodate the xylose decorations. Here we show that two closely related CBMs, CBM65A and CBM65B, derived from EcCel5A, a Eubacterium cellulosolvens endoglucanase, bind to a range of β-glucans but, uniquely, display significant preference for xyloglucan. The structures of the two CBMs reveal a β-sandwich fold. The ligand binding site comprises the β-sheet that forms the concave surface of the proteins. Binding to the backbone chains of β-glucans is mediated primarily by five aromatic residues that also make hydrophobic interactions with the xylose side chains of xyloglucan, conferring the distinctive specificity of the CBMs for the decorated polysaccharide. Significantly, and in contrast to other CBMs that recognize β-glucans, CBM65A utilizes different polar residues to bind cellulose and mixed linked glucans. Thus, Gln106 is central to cellulose recognition, but is not required for binding to mixed linked glucans. This report reveals the mechanism by which β-glucan-specific CBMs can distinguish between linear and mixed linked glucans, and show how these CBMs can exploit an extensive hydrophobic platform to target the side chains of decorated β-glucans. 相似文献
104.
Ammar Jabali Anne Hoffrichter Ana Uzquiano Fabio Marsoner Ruven Wilkens Marco Siekmann Bettina Bohl Andrea C Rossetti Sandra Horschitz Philipp Koch Fiona Francis Julia Ladewig 《EMBO reports》2022,23(5)
Malformations of human cortical development (MCD) can cause severe disabilities. The lack of human‐specific models hampers our understanding of the molecular underpinnings of the intricate processes leading to MCD. Here, we use cerebral organoids derived from patients and genome edited‐induced pluripotent stem cells to address pathophysiological changes associated with a complex MCD caused by mutations in the echinoderm microtubule‐associated protein‐like 1 (EML1) gene. EML1‐deficient organoids display ectopic neural rosettes at the basal side of the ventricular zone areas and clusters of heterotopic neurons. Single‐cell RNA sequencing shows an upregulation of basal radial glial (RG) markers and human‐specific extracellular matrix components in the ectopic cell population. Gene ontology and molecular analyses suggest that ectopic progenitor cells originate from perturbed apical RG cell behavior and yes‐associated protein 1 (YAP1)‐triggered expansion. Our data highlight a progenitor origin of EML1 mutation‐induced MCD and provide new mechanistic insight into the human disease pathology. 相似文献
105.
Mar Masiá Sergio Padilla Marta Fernández Carmen Rodríguez Ana Moreno Jose A. Oteo Antonio Antela Santiago Moreno Julia del Amo Félix Gutiérrez CoRIS Biobanco 《PloS one》2016,11(4)
ObjectiveWe aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients.MethodsWe conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F2-IsoPs) and malondialdehyde (MDA) plasma levels in the first blood sample obtained after cohort engagement.Results54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP), the association of F2-IsoPs with mortality remained significant (adjusted OR per 1 log10 increase, 2.34 [1.23–4.47], P = 0.009). The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI) per 1 log10 increase, 2.05 [0.91–4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI) per 1 log10 increase, 1.39 (1.01–1.91), P = 0.043; and OR (95% CI) per 1 log10 increase, 1.46 (1.07–1.99), P = 0.014, respectively, when adjustment included F2-IsoPs and MDA.ConclusionOxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2-IsoPs, this association is independent of HIV-related factors and subclinical inflammation. 相似文献
106.
Álvaro Rodríguez-Peña Ana C. Gonzalez-Franco Jared Hernández-Huerta Nora A. Salas-Salazar Dámaris L. Ojeda-Barrios Esteban Sánchez Loreto Robles-Hernández 《Phyton》2022,91(7):1341-1351
Antibiotics are widely used in fire blight management programs, yet there are no studies that demonstrate the evaluation of their efficacy in Mexico. Therefore, the present study was conducted to investigate the effects of the active ingredients in five commercial products (Kasumin® 2L, Agrygent Plus®, Agricultural Terramycin®, Agrimicin® 100, and Actigard®) on fire blight suppression, and fruit yield and quality of apple (Malus domestica Borkh.) cv. Golden Glory. The experiment was conducted in a commercial orchard using a completely randomized block design, with six treatments: (1) Oxytetracycline [Ox], 110 mg L−1; (2) Kasugamycin [Kas], 4.7 mL L−1; (3) Oxytetracycline + Gentamicin [Ox + Gen], 48 mg L−1 + 12 mg L−1; (4) Streptomycin + Oxytetracycline [Str + Ox], 90 mg L−1 + 9 mg L−1; (5) Acibenzolar-S-methyl [ASM], 70 mg L−1; and (6) Control, only water, with four replications, and three 11-year-old trees as an experimental unit. Variables of infection including flowers, shoots and fruits, yield and fruit quality were evaluated. All treatments suppressed infection in flowers, shoots, and fruits. ASM provided the highest levels of reduction of flower and shoot infection, while Kas had the least effect on the reduction of infection in these variables. The Ox + Gen treatment had the greatest suppression of fruit infection, and the best results on fruit yield and quality, followed by Ox and ASM. This is the first study conducted to evaluate the efficacy of the active ingredients of five commercial products used for the management of fire blight in apple trees in Mexico. 相似文献
107.
108.
Richard P. Shefferson Tiiu Kull Michael J. Hutchings Marc‐André Selosse Hans Jacquemyn Kimberly M. Kellett Eric S. Menges Richard B. Primack Juha Tuomi Kirsi Alahuhta Sonja Hurskainen Helen M. Alexander Derek S. Anderson Rein Brys Emilia Brzosko Slavomir Dostálik Katharine Gregg Zdeněk Ipser Anne Jäkäläniemi Jana Jersáková W. Dean Kettle Melissa K. McCormick Ana Mendoza Michael T. Miller Asbjørn Moen Dag‐Inge Øien Ülle Püttsepp Mélanie Roy Nancy Sather Nina Sletvold Zuzana Štípková Kadri Tali Robert J. Warren II Dennis F. Whigham 《Ecology letters》2018,21(5):724-733
Vegetative dormancy, that is the temporary absence of aboveground growth for ≥ 1 year, is paradoxical, because plants cannot photosynthesise or flower during dormant periods. We test ecological and evolutionary hypotheses for its widespread persistence. We show that dormancy has evolved numerous times. Most species displaying dormancy exhibit life‐history costs of sprouting, and of dormancy. Short‐lived and mycoheterotrophic species have higher proportions of dormant plants than long‐lived species and species with other nutritional modes. Foliage loss is associated with higher future dormancy levels, suggesting that carbon limitation promotes dormancy. Maximum dormancy duration is shorter under higher precipitation and at higher latitudes, the latter suggesting an important role for competition or herbivory. Study length affects estimates of some demographic parameters. Our results identify life historical and environmental drivers of dormancy. We also highlight the evolutionary importance of the little understood costs of sprouting and growth, latitudinal stress gradients and mixed nutritional modes. 相似文献
109.
The effect of operation regime and culture system on carotenoid productivity by the halotolerant alga Dunaliella salina has been analyzed. Operation strategies tested included batch and semi continuous regime, as well as a two-stage approach run simultaneously in both, open tanks and closed reactor. The best results were obtained with the closed tubular photobioreactor. The highest carotenoid production (328.8 mg carotenoid l−1 culture per month) was achieved with this culture system operated following the two-stage strategy. Also, closed tubular photobioreactor provided the highest carotenoid contents (10% of dry weight) in Dunaliella biomass and β-carotene abundance (90% of total carotenoids) as well as the highest 9-cis to all-trans β-carotene isomer ratio (1.5 at sunrise). 相似文献
110.
The toxic dinoflagellate Alexandrium tamarense and other dinoflagellatespecies were studied, along with water temperature and nutrientconcentrations, from September 1995 to December 1998 in theGolfo Nuevo, Chubut, Argentina. Nutrient concentrations werelow, showing a peak of high concentration in winter and a phaseof depletion in late spring and summer. Dinoflagellates tendedto be abundant during spring and summer, when Prorocentrum micanswas the most important species. Other dinoflagellates were Pyrophacushorologium and Dinophysis acuminata. Ceratium tripos, C. fususand C. horridum were present during the autumn, and a C. tripospeak up to 5.9 x 103 cell l1 was observed in May 1997.Alexandrium tamarense showed strong interannual variation, thehighest concentration being found in spring (SeptemberOctober)1995, with densities up to 15 x 103 cells l1. The secondA.tamarense peak was observed during OctoberNovember1998 with maximal densities up to 5 x 103 cells l1. Moderatelyhigh A. tamarense cyst densities, up to 300 cysts cm3of sediment, were found in the deep zone of the Golfo Nuevobasin. Among meteorolog-ical variables, increased late winterrain and higher solar radiation during spring may have influencedA. tamarense blooms. 相似文献