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101.
Herpes simplex virus (HSV) enters cells by means of four essential glycoproteins - gD, gH/gL, gB, activated in a cascade fashion by gD binding to one of its receptors, nectin1 and HVEM. We report that the engineering in gH of a heterologous ligand – a single-chain antibody (scFv) to the cancer-specific HER2 receptor – expands the HSV tropism to cells which express HER2 as the sole receptor. The significance of this finding is twofold. It impacts on our understanding of HSV entry mechanism and the design of retargeted oncolytic-HSVs. Specifically, entry of the recombinant viruses carrying the scFv-HER2–gH chimera into HER2+ cells occurred in the absence of gD receptors, or upon deletion of key residues in gD that constitute the nectin1/HVEM binding sites. In essence, the scFv in gH substituted for gD-mediated activation and rendered a functional gD non-essential for entry via HER2. The activation of the gH moiety in the chimera was carried out by the scFv in cis, not in trans as it occurs with wt-gD. With respect to the design of oncolytic-HSVs, previous retargeting strategies were based exclusively on insertion in gD of ligands to cancer-specific receptors. The current findings show that (i) gH accepts a heterologous ligand. The viruses retargeted via gH (ii) do not require the gD-dependent activation, and (iii) replicate and kill cells at high efficiency. Thus, gH represents an additional tool for the design of fully-virulent oncolytic-HSVs retargeted to cancer receptors and detargeted from gD receptors. 相似文献
102.
Clara?D. van?Karnebeek William?S. Sly Colin?J. Ross Ramona Salvarinova Joy Yaplito-Lee Saikat Santra Casper Shyr Gabriella?A. Horvath Patrice Eydoux Anna?M. Lehman Virginie Bernard Theresa Newlove Henry Ukpeh Anupam Chakrapani Mary?Anne Preece Sarah Ball James Pitt Hilary?D. Vallance Marion Coulter-Mackie Hien Nguyen Lin-Hua Zhang Amit?P. Bhavsar Graham Sinclair Abdul Waheed Wyeth?W. Wasserman Sylvia Stockler-Ipsiroglu 《American journal of human genetics》2014,94(3):453-461
Four children in three unrelated families (one consanguineous) presented with lethargy, hyperlactatemia, and hyperammonemia of unexplained origin during the neonatal period and early childhood. We identified and validated three different CA5A alterations, including a homozygous missense mutation (c.697T>C) in two siblings, a homozygous splice site mutation (c.555G>A) leading to skipping of exon 4, and a homozygous 4 kb deletion of exon 6. The deleterious nature of the homozygous mutation c.697T>C (p.Ser233Pro) was demonstrated by reduced enzymatic activity and increased temperature sensitivity. Carbonic anhydrase VA (CA-VA) was absent in liver in the child with the homozygous exon 6 deletion. The metabolite profiles in the affected individuals fit CA-VA deficiency, showing evidence of impaired provision of bicarbonate to the four enzymes that participate in key pathways in intermediary metabolism: carbamoylphosphate synthetase 1 (urea cycle), pyruvate carboxylase (anaplerosis, gluconeogenesis), propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase (branched chain amino acids catabolism). In the three children who were administered carglumic acid, hyperammonemia resolved. CA-VA deficiency should therefore be added to urea cycle defects, organic acidurias, and pyruvate carboxylase deficiency as a treatable condition in the differential diagnosis of hyperammonemia in the neonate and young child. 相似文献
103.
De Rossi A Zanchetta M Vitone F Antonelli G Bagnarelli P Buonaguro L Capobianchi MR Clementi M Abbate I Canducci F Monachetti A Riva E Rozera G Scagnolari C Tagliamonte M Re MC;SIVIM 《The new microbiologica》2010,33(4):293-302
Despite the widespread use of molecular biology techniques, standardized methods for the measurement of HIV-1 proviral DNA are currently lacking and several discordant results are still present in different studies. To assess the clinical meaning of the proviral DNA load, a study group comprising seven different laboratories was set up to standardize a HIV-1 proviral DNA quantification method able to assess the DNA proviral load of the most relevant circulating HIV-1 subtypes. Reference samples (24 cellular samples infected with HIV-1 clade B, and 40 samples of peripheral blood mononuclear cells containing different concentrations of plasmids expressing different HIV-1 clades) were distributed and tested blindly. All laboratories employed hTERT gene as housekeeping gene and primers within the gag gene to quantify different HIV-1 clades. Inter-laboratory results did not differ statistically but showed only minor variations concerning HIV-1 DNA amounts and different HIV clades, with a good agreement among the laboratories participating in the study. Since test standardization represents a key step for future application in clinical practice, further studies of the patients' samples are in progress to establish the real meaning and utility of the proviral DNA load for clinical management of HIV-1 infected patients. 相似文献
104.
105.
Luis G. García-Montero Paloma Díaz Gabriella Di Massimo Antonio García-Abril 《Mycological Progress》2010,9(3):315-335
Truffles are abundant in some regions of China. Nevertheless, it was not until the 1980s that Tuber species were discovered by Chinese mycologists. In recent years, international truffle markets have shown an increasing interest
in the import of Chinese Tuber. These truffles serve as a complement to European truffles due to their lower prices and their greater availability in a
deficit market. However, Chinese truffles have been the subject of fraudulent commercial practices, and these could have a
negative effect on truffle culture. These concerns have been behind numerous recent studies designed to obtain detailed information
about Chinese Tuber species. Unfortunately, many of these studies are not published in English, and are dispersed throughout the specific local
or national bibliography and proceedings of specialized truffle conferences. In view of the need to expand current knowledge
of Chinese Tuber species, we present a comprehensive summary of the taxonomy, ecology, mycorrhizae, genetics, biochemistry, and cultivation
of Chinese Tuber species. We also provide a synthetic taxonomy and morphological characterization of 16 Chinese Tuber species in order to assist in their verification and monitoring. 相似文献
106.
Edit Kaszab Balázs Kriszt Béla Atzél Gabriella Szabó István Szabó Péter Harkai Sándor Szoboszlay 《Microbial ecology》2010,59(1):37-45
The main aim of this paper was the comprehensive estimation of the occurrence rate and the antibiotic-resistance conditions
of opportunistic pathogen Pseudomonas aeruginosa in hydrocarbon-contaminated environments. From 2002 to 2007, 26 hydrocarbon-contaminated sites of Hungary were screened for
the detection of environmental isolates. Altogether, 156 samples were collected and examined for the determination of appearance, representative cell counts, and
antibiotic-resistance features of P. aeruginosa. The detected levels of minimal inhibitory concentrations of ten different drugs against 36 environmental strains were compared
to the results of a widely used reference strain ATCC 27853 and four other clinical isolates of P. aeruginosa. Based on our long-term experiment, it can be established that species P. aeruginosa was detectable in case of 61.5% of the investigated hydrocarbon-contaminated sites and 35.2% of the examined samples that
shows its widespread occurrence in polluted soil–groundwater systems. In the course of the antibiotic-resistance assay, our
results determined that 11 of the examined 36 environmental strains had multiple drug-resistance against several clinically
effective antimicrobial classes: cephalosporins, wide spectrum penicillins, carbapenems, fluoroquinolones, and aminoglycosides.
The fact that these multiresistant strains were isolated from 8 different hydrocarbon-contaminated sites, mainly from outskirts,
confirms that multiple drug-resistance of P. aeruginosa is widespread not only in clinical, but also in natural surroundings as well. 相似文献
107.
Gabriella Tamasi Agnese Magnani Luisa Chiasserini Chiara Gabbiani Michael A. Jakupec Michael B. Hursthouse 《Journal of inorganic biochemistry》2010,104(8):799-313
The reaction of aqueous cis-[Pt(NH3)2(H2O)2](NO3)2 with Na+HMEL− (H2MEL, meloxicam, 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide), and Na+HISO− (H2ISO, isoxicam, 4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) at pH 7 produced micro-crystalline cis-[Pt(NH3)2(N1′-HMEL)2], 5 and cis-[Pt(NH3)2(N1′-HISO)2], 6. The X-ray diffraction structure of 5 shows two HMEL− anions donating through the thiazole nitrogen atoms and adopting a head-to-tail (HT) conformation. The 1H NMR spectrum for 5 from DMSO-d6 shows inertness of the complex up to at least 24 h. Delivery studies for 5 and 6 from vinyl hydrogel based on l-phenylalanine (pH 6.5, 25 °C) show that concentrations of complexes ranging between 2.5 and 5 μM can be reached after a day. Compounds 5 and 6 show strong anti-proliferative effects on CH1 cells (ovarian carcinoma, human) in vitro, IC50 values being 0.60 and 0.37 μM, respectively (0.16 μM for reference, cis-diamminodichloridoplatinum(II), cisplatin). ESI-MS measurements clearly documented that both 5 and 6 form adducts with the three model proteins ubiquitin (UBI), cytochrome c (CYT C) and superoxide dismutase (SOD), the HISO− complex being significantly more effective than the HMEL− one. Density functional methods help in finding rationale for the easiest dissociation of Pt-H2ISO/HISO bonds when compared to the Pt-N1′-H2MEL/N1′-HMEL linkages. 相似文献
108.
The interaction of Leucine-enkephalin (Leu-enkephalin) with reactive nitrogen species has been investigated. Reactive nitrogen species are capable of nitrating and oxidizing Leu-enkephalin. HPLC analysis shows the formation of two major enkephalin derivatives by peroxynitrite. The tyrosine amino-terminal residue of Leu-enkephalin is converted either to 3-nitrotyrosine thus producing nitroenkephalin and to dityrosine by dimerization with the production of an enkephalin dimer. The evidence of the formation of the nitroenkephalin and of the enkephalin dimer—dienkephalin—was achieved by electrospray ionisation mass spectrometry. In addition to peroxynitrite, the methylene blue photosensitized oxidation of enkephalin in the presence of nitrite leads to the formation of the nitrated peptide. Moreover, the nitropeptide can be also obtained by peroxidase-generated nitrogen reactive species. 相似文献
109.
Dávid Kurszán Jász Ágnes Lilla Szilágyi Eszter Tuboly Bálint Baráth Anett Roxána Márton Petra Varga Gabriella Varga Dániel Érces Árpád Mohácsi Anna Szabó Renáta Bozó Kamilla Gömöri Anikó Görbe Mihály Boros Petra Hartmann 《Journal of cellular and molecular medicine》2021,25(11):5113-5123
Albeit previous experiments suggest potential anti-inflammatory effect of exogenous methane (CH4) in various organs, the mechanism of its bioactivity is not entirely understood. We aimed to investigate the potential mitochondrial effects and the underlying mechanisms of CH4 in rat cardiomyocytes and mitochondria under simulated ischaemia/reperfusion (sI/R) conditions. Three-day-old cultured cardiomyocytes were treated with 2.2% CH4-artificial air mixture during 2-hour-long reoxygenation following 4-hour-long anoxia (sI/R and sI/R + CH4, n = 6-6), with normoxic groups serving as controls (SH and SH + CH4; n = 6-6). Mitochondrial functions were investigated with high-resolution respirometry, and mitochondrial membrane injury was detected by cytochrome c release and apoptotic characteristics by using TUNEL staining. CH4 admixture had no effect on complex II (CII)-linked respiration under normoxia but significantly decreased the complex I (CI)-linked oxygen consumption. Nevertheless, addition of CH4 in the sI/R + CH4 group significantly reduced the respiratory activity of CII in contrast to CI and the CH4 treatment diminished mitochondrial H2O2 production. Substrate-induced changes to membrane potential were partially preserved by CH4, and additionally, cytochrome c release and apoptosis of cardiomyocytes were reduced in the CH4-treated group. In conclusion, the addition of CH4 decreases mitochondrial ROS generation via blockade of electron transport at CI and reduces anoxia-reoxygenation-induced mitochondrial dysfunction and cardiomyocyte injury in vitro. 相似文献
110.
Emelia Zukowski Marco Sannella Jack Donato Rockhold Gabriella H. Kalantar Jingting Yu Sara SantaCruz-Calvo Madison K. Kuhn Nasun Hah Ling Ouyang Tzu-Wen Wang Lyanne Murphy Heather Marszalkowski Kaleigh Gibney Micah J. Drummond Elizabeth A. Proctor Hatice Hasturk Barbara S. Nikolajczyk Leena P. Bharath 《Aging cell》2023,22(11):e13996
Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and function in T cells from older adults and partially recapitulated aging-related cytokine profiles. Our data show the mechanistic link among mitoSTAT3, mitochondrial dynamics, function, and T-cell cytokine production. 相似文献