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101.
Rosalind J. Dodd David R. Chadwick Ian M. Harris Adrian Hines Dan Hollis Theodoros Economou Dylan Gwynn‐Jones John Scullion David A. Robinson David L. Jones 《Ecology letters》2021,24(1):60-72
Extreme weather events have become a dominant feature of the narrative surrounding changes in global climate with large impacts on ecosystem stability, functioning and resilience; however, understanding of their risk of co‐occurrence at the regional scale is lacking. Based on the UK Met Office’s long‐term temperature and rainfall records, we present the first evidence demonstrating significant increases in the magnitude, direction of change and spatial co‐localisation of extreme weather events since 1961. Combining this new understanding with land‐use data sets allowed us to assess the likely consequences on future agricultural production and conservation priority areas. All land‐uses are impacted by the increasing risk of at least one extreme event and conservation areas were identified as the hotspots of risk for the co‐occurrence of multiple event types. Our findings provide a basis to regionally guide land‐use optimisation, land management practices and regulatory actions preserving ecosystem services against multiple climate threats. 相似文献
102.
Steven A. Harris Bhumit A. Patel Adrian Gospodarek Jayesh Desai Alejandro de Janon Gutiérrez Edita Botonjic-Sehic Mark Brower Nuno D. S. Pinto 《Biotechnology progress》2021,37(5):e3187
Protein concentration determination is a necessary in-process control for the downstream operations within biomanufacturing. As production transitions from batch mode to an integrated continuous bioprocess paradigm, there is a growing need to move protein concentration quantitation from off-line to in-line analysis. One solution to fulfill this process analytical technology need is an in-line index of refraction (IoR) sensor to measure protein concentration in real time. Here the performance of an IoR sensor is evaluated through a series of experiments to assess linear response, buffer matrix effects, dynamic range, sensor-to-sensor variability, and the limits of detection and quantitation. The performance of the sensor was also tested in two bioprocessing scenarios, ultrafiltration and capture chromatography. The implementation of this in-line IoR sensor for real-time protein concentration analysis and monitoring has the potential to improve continuous bioprocess manufacturing. 相似文献
103.
Perry A. Frey Adrian D. Hegeman Frank J. Ruzicka 《Critical reviews in biochemistry and molecular biology》2013,48(1):63-88
ABSTRACTThe radical S-adenosylmethionine (SAM) superfamily currently comprises more than 2800 proteins with the amino acid sequence motif CxxxCxxC unaccompanied by a fourth conserved cysteine. The charcteristic three-cysteine motif nucleates a [4Fe–4S] cluster, which binds SAM as a ligand to the unique Fe not ligated to a cysteine residue. The members participate in more than 40 distinct biochemical transformations, and most members have not been biochemically characterized. A handful of the members of this superfamily have been purified and at least partially characterized. Significant mechanistic and structural information is available for lysine 2,3-aminomutase, pyruvate formate-lyase, coproporphyrinogen III oxidase, and MoaA required for molybdopterin biosynthesis. Biochemical information is available for spore photoproduct lyase, anaerobic ribonucleotide reductase activation subunit, lipoyl synthase, and MiaB involved in methylthiolation of isopentenyladenine-37 in tRNA. The radical SAM enzymes biochemically characterized to date have in common the cleavage of the [4Fe–4S]1 + –SAM complex to [4Fe–4S]2 +–Met and the 5′ -deoxyadenosyl radical, which abstracts a hydrogen atom from the substrate to initiate a radical mechanism. 相似文献
104.
Magdalena Świderska Anna Zalewska Joanna Pogorzelska Robert Flisiak Adrian Chabowski 《Free radical research》2013,47(8):841-850
The objective of this study is to determine if treatment with the angiogenesis inhibitor TNP-470 results in impairment of oxidative stress, inhibition of nuclear factor kappa B (NF-κB) activation and decrease of nitric oxide production in an experimental model of rat hepatocarcinogenesis. Tumour was induced by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out at 28 weeks after initiating the treatment. TNP-470 was administered at 30 mg/kg, three times per week from 20 to 28 weeks. Carcinomatous tissue growing outside dysplastic nodules and a marked expression of placental glutathione S-transferase were detected in rats with induced carcinogenesis. Liver concentrations of thiobarbituric acid reactive substances, reduced glutathione (GSH) and glutathione disulfide (GSSG) were significantly higher than those of controls and there was a significant increase in the GSSG/GSH ratio. Tumour growth was accompanied by augmented expression of inducible nitric oxide synthase, activation of (NF-κB) and proteolysis of IkappaB. All these effects were absent in animals receiving TNP-470. Our results indicate that TNP-470 inhibits oxidative stress, nitric oxide production and NF-κB activation induced by experimental hepatocarcinogenesis. These changes would contribute to the beneficial effects of TNP-470 in cancer treatment. 相似文献
105.
Patrick Gérardin Adrian Fianu Alain Michault Corinne Mussard Karim Boussa?d Olivier Rollot Philippe Grivard Somar Kassab Eric Bouquillard Gianandrea Borgherini Bernard-Alex Gaüzère Denis Malvy Gérard Bréart Fran?ois Favier 《Arthritis research & therapy》2013,15(1):R9
Introduction
Long-lasting relapsing or lingering rheumatic musculoskeletal pain (RMSP) is the hallmark of Chikungunya virus (CHIKV) rheumatism (CHIK-R). Little is known on their prognostic factors. The aim of this prognostic study was to search the determinants of lingering or relapsing RMSP indicative of CHIK-R.Methods
Three hundred and forty-six infected adults (age ≥ 15 years) having declared RMSP at disease onset were extracted from the TELECHIK cohort study, Reunion island, and analyzed using a multinomial logistic regression model. We also searched for the predictors of CHIKV-specific IgG titres, assessed at the time of a serosurvey, using multiple linear regression analysis.Results
Of these, 111 (32.1%) reported relapsing RMSP, 150 (43.3%) lingering RMSP, and 85 (24.6%) had fully recovered (reference group) on average two years after acute infection. In the final model controlling for gender, the determinants of relapsing RMSP were the age 45-59 years (adjusted OR: 2.9, 95% CI: 1.0, 8.6) or greater or equal than 60 years (adjusted OR: 10.4, 95% CI: 3.5, 31.1), severe rheumatic involvement (fever, at least six joints plus four other symptoms) at presentation (adjusted OR: 3.6, 95% CI: 1.5, 8.2), and CHIKV-specific IgG titres (adjusted OR: 3.2, 95% CI: 1.8, 5.5, per one unit increase). Prognostic factors for lingering RMSP were age 45-59 years (adjusted OR: 6.4, 95% CI: 1.8, 22.1) or greater or equal than 60 years (adjusted OR: 22.3, 95% CI: 6.3, 78.1), severe initial rheumatic involvement (adjusted OR: 5.5, 95% CI: 2.2, 13.8) and CHIKV-specific IgG titres (adjusted OR: 6.2, 95% CI: 2.8, 13.2, per one unit increase). CHIKV specific IgG titres were positively correlated with age, female gender and the severity of initial rheumatic symptoms.Conclusions
Our data support the roles of age, severity at presentation and CHIKV specific IgG titres for predicting CHIK-R. By identifying the prognostic value of the humoral immune response of the host, this work also suggest a significant contribution of the adaptive immune response to the physiopathology of CHIK-R and should help to reconsider the paradigm of this chronic infection primarily shifted towards the involvement of the innate immune response. 相似文献106.
Astrid?Adrian Kathrin?Schoppmann Juri?Sromicki Sonja?Brungs Melanie?von der Wiesche Bertold?Hock Waldemar?Kolanus Ruth?Hemmersbach Oliver?Ullrich
Gravity has been a constant force throughout the Earth’s evolutionary history. Thus, one of the fundamental biological questions is if and how complex cellular and molecular functions of life on Earth require gravity. In this study, we investigated the influence of gravity on the oxidative burst reaction in macrophages, one of the key elements in innate immune response and cellular signaling. An important step is the production of superoxide by the NADPH oxidase, which is rapidly converted to H2O2 by spontaneous and enzymatic dismutation. The phagozytosis-mediated oxidative burst under altered gravity conditions was studied in NR8383 rat alveolar macrophages by means of a luminol assay. Ground-based experiments in “functional weightlessness” were performed using a 2 D clinostat combined with a photomultiplier (PMT clinostat). The same technical set-up was used during the 13th DLR and 51st ESA parabolic flight campaign. Furthermore, hypergravity conditions were provided by using the Multi-Sample Incubation Centrifuge (MuSIC) and the Short Arm Human Centrifuge (SAHC). The results demonstrate that release of reactive oxygen species (ROS) during the oxidative burst reaction depends greatly on gravity conditions. ROS release is 1.) reduced in microgravity, 2.) enhanced in hypergravity and 3.) responds rapidly and reversible to altered gravity within seconds. We substantiated the effect of altered gravity on oxidative burst reaction in two independent experimental systems, parabolic flights and 2D clinostat / centrifuge experiments. Furthermore, the results obtained in simulated microgravity (2D clinorotation experiments) were proven by experiments in real microgravity as in both cases a pronounced reduction in ROS was observed. Our experiments indicate that gravity-sensitive steps are located both in the initial activation pathways and in the final oxidative burst reaction itself, which could be explained by the role of cytoskeletal dynamics in the assembly and function of the NADPH oxidase complex. 相似文献
107.
Diversity in the fertilization envelopes of echinoderms 总被引:1,自引:0,他引:1
108.
Anna Maria Aviñó Adrian Mayordomo Ruth Espuny Montse Bach Ramon Eritja 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1613-1617
Abstract The preparation of N2, N2-dimethylguanosine is described. The use of the 2-(p-nitrophenyl)ethyl group instead of the benzyl protecting group for the O6 position of the guanine ring resulted in better yields and shorter protocols. 相似文献
109.
The copper(II) complexes with ciprofloxacin (CFLH), levofloxacin (LFLH), norfloxacin (NFLH), and neutral bidentate ligands have been synthesized and characterized. The complexes have been evaluated for their antibacterial activity against selective species. Complexes have been also checked for their interacting behavior with DNA, and were found to have two different modes of interaction, classical and partial intercalation. Tested complexes were found to be better antioxidants with their IC50 values ranging from 0.51 to 0.97 μM. 相似文献
110.
Alicia L. Richards Catherine E. Vincent Adrian Guthals Christopher M. Rose Michael S. Westphall Nuno Bandeira Joshua J. Coon 《Molecular & cellular proteomics : MCP》2013,12(12):3812-3823
We report the use of neutron-encoded (NeuCode) stable isotope labeling of amino acids in cell culture for the purpose of C-terminal product ion annotation. Two NeuCode labeling isotopologues of lysine, 13C615N2 and 2H8, which differ by 36 mDa, were metabolically embedded in a sample proteome, and the resultant labeled proteins were combined, digested, and analyzed via liquid chromatography and mass spectrometry. With MS/MS scan resolving powers of ∼50,000 or higher, product ions containing the C terminus (i.e. lysine) appear as a doublet spaced by exactly 36 mDa, whereas N-terminal fragments exist as a single m/z peak. Through theory and experiment, we demonstrate that over 90% of all y-type product ions have detectable doublets. We report on an algorithm that can extract these neutron signatures with high sensitivity and specificity. In other words, of 15,503 y-type product ion peaks, the y-type ion identification algorithm correctly identified 14,552 (93.2%) based on detection of the NeuCode doublet; 6.8% were misclassified (i.e. other ion types that were assigned as y-type products). Searching NeuCode labeled yeast with PepNovo+ resulted in a 34% increase in correct de novo identifications relative to searching through MS/MS only. We use this tool to simplify spectra prior to database searching, to sort unmatched tandem mass spectra for spectral richness, for correlation of co-fragmented ions to their parent precursor, and for de novo sequence identification.The ability to make de novo sequence identifications directly from tandem mass spectra has long been a holy grail of the proteomic community. Such a capability would wean the field from its reliance upon sequenced genome databases. Even for organisms with fully annotated genomes, events such as single nucleotide polymorphisms, alternative splicing, gene fusion, and a host of other genomic transformations can result in altered proteomes. These alterations can vary from cell to cell and individual to individual. Thus, one could argue that the most valuable proteomic information, the individual and cellular proteome variation from the genome, remains elusive (1). This problem has received considerable attention; that said, it is not easy to de novo correlate spectrum to sequence in a large-scale, automated fashion (2–6). Improvements in mass accuracy have helped, but routine, reliable de novo sequencing without database assistance is not standard (7–10).A primary means to facilitate de novo spectral interpretation is the simple annotation of m/z peaks in tandem mass spectra as either N- or C-terminal. We and others have investigated this seemingly simple first step. Real-world spectra, however, are complex. Difficulties often arise in determining the charge state of the fragment or in differentiating between fragment ions and peaks arising from neutral loss, internal fragmentation, or spectral noise, both electronic and chemical. Several strategies have focused on product ion annotation. These approaches have included manipulation of the N-terminus basicity combined with electron transfer dissociation (ETD)1 (11–13). This approach can yield mostly N-terminal fragments for peptides having only two charges. However, it requires both ETD and the protease LysN. Other methods have used differential labeling of N- and C-terminal peptides to shift either one or the other product ion series, by either metabolic or chemical means (14–18). Metabolic incorporation of amino acids is an efficient method of introducing distinctive labels that eliminates in vitro labeling, but this method requires that the sample be amenable to cell culture (19, 20). Additionally, it may be difficult to achieve complete labeling in complex systems. Several other approaches used to introduce heavy isotopes onto one terminus have been investigated, including trypsin digestion in 18O water (21–23), differential isotopic esterification (24, 25), derivatization of the C-terminal carboxylate by p-bromophenethylamine (8, 26), N-terminal derivatization with sulfonic acid groups (27, 28), and formaldehyde labeling via reductive amination (29–31). These chemical modifications are introduced after cell lysis, often immediately prior to analysis. Although chemical labeling strategies can be used with a variety of samples, difficulties can arise from differences in labeling efficiency between samples, and often a clean-up step is required following labeling, which may lead to sample loss. No matter the labeling method, in this regime, the two precursors must be separately isolated, fragmented, and analyzed either together or separately. The recognition and selection of the broadly spaced doublet in real time also are necessary. These requirements have limited the utility of these approaches. Our own laboratory discovered that the c- and ●z-type product ions generated from either electron capture dissociation or ETD have distinct chemical formulae and therefore can always be distinguished based on accurate mass alone (32). The problem with this approach is that extremely high mass accuracy (<500 ppb) is required in order to distinguish these product ion types above ∼600 Da in mass. Thus, the majority of the product ions within a spectrum cannot be readily mapped to either terminus with high confidence.Despite these difficulties, we assert that robust de novo sequencing methodology would benefit greatly from a simple method that could be used to distinguish N- and C-terminal product ions with high accuracy and precision. Ideally, the approach would work regardless of the choice of proteolytic enzyme or dissociation method. Recently, we described a new technology for protein quantification called neutron encoding (NeuCode) (33). NeuCode embeds millidalton mass differences into peptides and proteins by exploiting the mass defect induced by differences in the nuclear binding energies of the various stable isotopes of common elements such as C, N, H, and O. For example, consider the amino acid lysine, which has eight additional neutrons (+8 Da). One way to synthesize this amino acid is to add six 13C atoms and two 15N atoms (+8.0142 Da). Another isotopologue could be constructed by adding eight 2H atoms (+8.0502). These two isotopologues differ by only 36 mDa; peptide precursors containing both of these amino acids would appear as a single, unresolved precursor m/z peak at a mass resolving power of less than ∼100,000. However, under high resolving powers (i.e. greater than ∼100,000 at m/z 400), this doublet is resolved. We first developed this NeuCode concept in the context of metabolic labeling, akin to stable isotope labeling with amino acids in cell culture (SILAC), except that instead of the precursor partners being separated by 4 to 8 Da, they are separated by only 6 to 40 mDa. For quantitative purposes, NeuCode promises to deliver ultraplexed SILAC (>12) without increasing spectral complexity.We reasoned that the isotopologues of Lys that permit NeuCode SILAC would generate a distinct fingerprint on C-terminal product ions. Specifically, peptides that have been labeled with NeuCode SILAC and digested with LysC uniformly contain Lys at the C terminus. Upon MS/MS, all C-terminal product ions should present as doublets (with duplex NeuCode), whereas N-terminal products will be detected as a single m/z peak. The very close m/z spacing of the NeuCode SILAC partners will ensure that each partner is always co-isolated and that the signatures are visible only upon high-resolving-power mass analysis. Here we investigate the combination of NeuCode SILAC and high-resolving-power MS/MS analysis to allow the straightforward identification of C-terminal product ions.