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11.
Farahnaz Rashidi Adel Jalili Sasan Babaie Kafaki Khosro Sagheb-Talebi John Hodgson 《Trees - Structure and Function》2012,26(2):363-375
This study investigates responses in the leaf anatomy of Black Locust (Robinia pseudoacacia L.) to the atmospheric pollutants, SO2, NO2 and O3 and climate in Tehran. The anatomical variables studied include thickness of the leaf lamina and of its main constituent
tissues and the length and density of stomata. We present evidence that, in response to urban air pollution, the spongy mesophyll
layer is thinner, the upper cuticle of the leaf thicker and stomatal density and the ratio of palisade parenchyma to spongy
parenchyma are increased. Similar responses were also detected in relation to a climatic gradient. Stomatal density and thickness
of the leaf lamina and of its mesophyll layer were all higher under warmer drier conditions. This overlap in anatomical response
to two very different suites of environmental variables may reflect a functional overlap between mechanisms designed to restrict
water loss in dry climates and those that minimize the uptake of toxic gases in polluted habitats. 相似文献
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Movahedzadeh F Smith DA Norman RA Dinadayala P Murray-Rust J Russell DG Kendall SL Rison SC McAlister MS Bancroft GJ McDonald NQ Daffe M Av-Gay Y Stoker NG 《Molecular microbiology》2004,51(4):1003-1014
Inositol is utilized by Mycobacterium tuberculosis in the production of its major thiol and of essential cell wall lipoglycans. We have constructed a mutant lacking the gene encoding inositol-1-phosphate synthase (ino1), which catalyses the first committed step in inositol synthesis. This mutant is only viable in the presence of extremely high levels of inositol. Mutant bacteria cultured in inositol-free medium for four weeks showed a reduction in levels of mycothiol, but phosphatidylinositol mannoside, lipomannan and lipoarabinomannan levels were not altered. The ino1 mutant was attenuated in resting macrophages and in SCID mice. We used site-directed mutagenesis to alter four putative active site residues; all four alterations resulted in a loss of activity, and we demonstrated that a D310N mutation caused loss of the active site Zn2+ ion and a conformational change in the NAD+ cofactor. 相似文献
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Johan Vande Voorde Suna Sabuncuo?lu Sam Noppen Anders Hofer Farahnaz Ranjbarian Steffen Fieuws Jan Balzarini Sandra Liekens 《The Journal of biological chemistry》2014,289(19):13054-13065
The intracellular metabolism and cytostatic activity of the anticancer drug gemcitabine (2′,2′-difluoro-2′-deoxycytidine; dFdC) was severely compromised in Mycoplasma hyorhinis-infected tumor cell cultures. Pronounced deamination of dFdC to its less cytostatic metabolite 2′,2′-difluoro-2′-deoxyuridine was observed, both in cell extracts and spent culture medium (i.e. tumor cell-free but mycoplasma-containing) of mycoplasma-infected tumor cells. This indicates that the decreased antiproliferative activity of dFdC in such cells is attributed to a mycoplasma cytidine deaminase causing rapid drug catabolism. Indeed, the cytostatic activity of gemcitabine could be restored by the co-administration of tetrahydrouridine (a potent cytidine deaminase inhibitor). Additionally, mycoplasma-derived pyrimidine nucleoside phosphorylase (PyNP) activity indirectly potentiated deamination of dFdC: the natural pyrimidine nucleosides uridine, 2′-deoxyuridine and thymidine inhibited mycoplasma-associated dFdC deamination but were efficiently catabolized (removed) by mycoplasma PyNP. The markedly lower anabolism and related cytostatic activity of dFdC in mycoplasma-infected tumor cells was therefore also (partially) restored by a specific TP/PyNP inhibitor (TPI), or by exogenous thymidine. Consequently, no effect on the cytostatic activity of dFdC was observed in tumor cell cultures infected with a PyNP-deficient Mycoplasma pneumoniae strain. Because it has been reported that some commensal mycoplasma species (including M. hyorhinis) preferentially colonize tumor tissue in cancer patients, our findings suggest that the presence of mycoplasmas in the tumor microenvironment could be a limiting factor for the anticancer efficiency of dFdC-based chemotherapy. Accordingly, a significantly decreased antitumor effect of dFdC was observed in mice bearing M. hyorhinis-infected murine mammary FM3A tumors compared with uninfected tumors. 相似文献
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Roman M Stilling Hendrik Urbanke Vincenzo Capece Susanne Burkhardt Sanaz Bahari‐Javan Jonas Barth Farahnaz Sananbenesi Anna L Schütz Jerzy Dyczkowski Ana Martinez‐Hernandez Cemil Kerimoglu Sharon YR Dent Stefan Bonn Klaus G Reymann Andre Fischer 《The EMBO journal》2014,33(17):1912-1927
Neuronal histone acetylation has been linked to memory consolidation, and targeting histone acetylation has emerged as a promising therapeutic strategy for neuropsychiatric diseases. However, the role of histone‐modifying enzymes in the adult brain is still far from being understood. Here we use RNA sequencing to screen the levels of all known histone acetyltransferases (HATs) in the hippocampal CA1 region and find that K‐acetyltransferase 2a (Kat2a)—a HAT that has not been studied for its role in memory function so far—shows highest expression. Mice that lack Kat2a show impaired hippocampal synaptic plasticity and long‐term memory consolidation. We furthermore show that Kat2a regulates a highly interconnected hippocampal gene expression network linked to neuroactive receptor signaling via a mechanism that involves nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB). In conclusion, our data establish Kat2a as a novel and essential regulator of hippocampal memory consolidation. 相似文献
15.
Laval F Haites R Movahedzadeh F Lemassu A Wong CY Stoker N Billman-Jacobe H Daffé M 《The Journal of biological chemistry》2008,283(3):1419-1427
Mycolic acids are major and specific lipid components of the cell envelope of mycobacteria that include the causative agents of tuberculosis and leprosy, Mycobacterium tuberculosis and Mycobacterium leprae, respectively. Subtle structural variations that are known to be crucial for both their virulence and the permeability of their cell envelope occur in mycolic acids. Among these are the introduction of cyclopropyl groups and methyl branches by mycolic acid S-adenosylmethionine-dependent methyltransferases (MA-MTs). While the functions of seven of the M. tuberculosis MA-MTs have been either established or strongly presumed nothing is known of the roles of the remaining umaA gene product and those of M. smegmatis MA-MTs. Mutants of the M. tuberculosis umaA gene and its putative M. smegmatis orthologue, MSMEG0913, were created. The lipid extracts of the resulting mutants were analyzed in detail using a combination of analytical techniques such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and proton nuclear magnetic resonance spectroscopy, and chemical degradation methods. The M. smegmatis mutants no longer synthesized subtypes of mycolates containing a methyl branch adjacent to either trans cyclopropyl group or trans double bond at the "proximal" position of both alpha- and epoxy-mycolates. Complementation with MSMEG0913, but not with umaA, fully restored the wild-type phenotype in M. smegmatis. Consistently, no modification was observed in the structures of mycolic acids produced by the M. tuberculosis umaA mutant. These data proved that despite their synteny and high similarity umaA and MSMEG0913 are not functionally orthologous. 相似文献
16.
ten Bokum AM Movahedzadeh F Frita R Bancroft GJ Stoker NG 《Trends in microbiology》2008,16(9):436-441
Deletion of genes in a pathogen is commonly associated with a reduction in its ability to cause disease. However, some rare cases have been described in the literature whereby deletion of a gene results in an increase in virulence. Recently, there have been several reports of hypervirulence resulting from gene deletion in Mycobacterium tuberculosis. Here, we explore this phenomenon in the context of the interaction between the pathogen and the host response. 相似文献
17.
Roberto Carlos Agís‐Balboa Cemil Kerimoglu Eva Benito Michael Gertig Sanaz Bahari‐Javan Gaurav Jain Susanne Burkhardt Ivana Delalle Alexander Jatzko Markus Dettenhofer Patricia A Zunszain Andrea Schmitt Peter Falkai Julius C Pape Elisabeth B Binder Christophe Mulle Andre Fischer Farahnaz Sananbenesi 《The EMBO journal》2017,36(19):2815-2828
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Several enzymes involved in central carbon metabolism and gluconeogenesisplay a critical role in survival and pathogenesis of Mycobacterium tuberculosis (Mtb). The only known functional fructose 1,6-bisphosphatase (FBPase) in Mtb is encoded by the glpX gene and belongs to the Class II sub-family of FBPase. We describe herein the generation of a ΔglpX strain using homologous recombination. Although the growth profile of ΔglpX is comparable to that of wild type Mtb when grown on the standard enrichment media, its growth is dysgonic with individual gluconeogenic substrates such as oleic acid, glycerol and acetate. In mice lung CFU titers of ΔglpX were 2–3 log10 lower than the wild-type Mtb strain. The results indicate that glpX gene encodes a functional FBPase and is essential for both in vitro and in vivo growth and survival of Mtb. Loss of glpX results in significant reduction of FBPase activity but not complete abolition. These findings verify that the glpX encoded FBPase II in Mtb can be a potential target for drug discovery. 相似文献
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