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61.
62.
Cristin J. Monaco Corey J. A. Bradshaw David J. Booth Bronwyn M. Gillanders David S. Schoeman Ivan Nagelkerken 《Global Change Biology》2020,26(10):5564-5573
Climate change is redistributing marine and terrestrial species globally. Life‐history traits mediate the ability of species to cope with novel environmental conditions, and can be used to gauge the potential redistribution of taxa facing the challenges of a changing climate. However, it is unclear whether the same traits are important across different stages of range shifts (arrival, population increase, persistence). To test which life‐history traits most mediate the process of range extension, we used a 16‐year dataset of 35 range‐extending coral‐reef fish species and quantified the importance of various traits on the arrival time (earliness) and degree of persistence (prevalence and patchiness) at higher latitudes. We show that traits predisposing species to shift their range more rapidly (large body size, broad latitudinal range, long dispersal duration) did not drive the early stages of redistribution. Instead, we found that as diet breadth increased, the initial arrival and establishment (prevalence and patchiness) of climate migrant species in temperate locations occurred earlier. While the initial incursion of range‐shifting species depends on traits associated with dispersal potential, subsequent establishment hinges more on a species’ ability to exploit novel food resources locally. These results highlight that generalist species that can best adapt to novel food sources might be most successful in a future ocean. 相似文献
63.
Hachemi Kadri Charles S. Matthews Tracey D. Bradshaw Malcolm F. G. Stevens 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):641-647
A new series of fluorinated and non-fluorinated 2-phenylbenzimidazoles bearing oxygenated substituents on the phenyl ring has been synthesized. Synthesis of the new series was based on our previous discovery of 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (PMX 610) as a potent and selective antitumour agent in vitro (sub-nanomolar GI50 in sensitive human cancer cell lines), but with poor aqueous solubility and lack of a definitive cellular target limiting further development. In this study we test the hypothesis that 2-phenylbenzimidazoles with similar substitution patterns to PMX 610 would retain potent antitumour activity but with potentially superior pharmaceutical properties. In general the new compounds were less active than the former benzothiazole series in vitro when tested against the breast cancer cell lines MCF-7 and MDA 468; however the two most active compounds in the present series (3j and 3k) exhibit low micromolar GI50 values in both cell lines and provide the opportunity for further chemical derivatization with a view to target identification. 相似文献
64.
Stefano Bonissone Nitin Gupta Margaret Romine Ralph A. Bradshaw Pavel A. Pevzner 《Molecular & cellular proteomics : MCP》2013,12(1):14-28
N-terminal methionine excision (NME) and N-terminal acetylation (NTA) are two of the most common protein post-translational modifications. NME is a universally conserved activity and a highly specific mechanism across all life forms. NTA is very common in eukaryotes but occurs rarely in prokaryotes. By analyzing data sets from yeast, mammals and bacteria (including 112 million spectra from 57 bacterial species), the largest comparative proteogenomics study to date, it is shown that previous assumptions/perceptions about the specificity and purposes of NME are not entirely correct. Although NME, through the universal enzymatic specificity of the methionine aminopeptidases, results in the removal of the initiator Met in proteins when the second residue is Gly, Ala, Ser, Cys, Thr, Pro, or Val, the comparative genomic analyses suggest that this specificity may vary modestly in some organisms. In addition, the functional role of NME may be primarily to expose Ala and Ser rather than all seven of these residues. Although any of this group provide “stabilizing” N termini in the N-end rule, and de facto leave the remaining 13 amino acid types that are classed as “destabilizing” (in higher eukaryotes) protected by the initiator Met, the conservation of NME-substrate proteins through evolution suggests that the other five are not crucially important for proteins with these residues in the second position. They are apparently merely inconsequential players (their function is not affected by NME) that become exposed because their side chains are smaller or comparable to those of Ala and Ser. The importance of exposing mainly two amino acids at the N terminus, i.e. Ala and Ser, is unclear but may be related to NTA or other post-translational modifications. In this regard, these analyses also reveal that NTA is more prevalent in some prokaryotes than previously appreciated.Although methionine is used to initiate protein synthesis for essentially all proteins, it is subsequently removed in a large percentage of cases, either by cleavage of an N-terminal “signal ” peptide (as part of cellular translocation mechanisms or precursor activations) or by the action of specific methionine aminopeptidases (MetAPs). Approximately two-thirds of the proteins in any proteome are potential substrates for the latter N-terminal methionine excision (NME),1 and MetAPs appear in all organisms from bacteria to eukaryotes (1). The second, or P2, amino acid in protein substrates is crucially important for NME because MetAP specificity mainly depends on the nature of this residue, a selectivity that is conserved across all species (1–5). These enzymes generally excise the N-terminal Met when the second residue is Gly, Ala, Ser, Thr, Cys, Pro, or Val (3, 6, 7), which are the amino acids smallest in size (based on radius of gyration of the side chain (8)). NME is a necessary process for proper cell functioning; it is included in the minimal genome set of eubacteria (9). Eukaryotes contain two MetAPs derived from a version in bacteria (MetAP1), and another found in archea (MetAP2) (11). Just as the deletion of MetAP eubacteria is lethal, the deletion of both MetAPs in yeast is also lethal (10).In 1988, Arfin and Bradshaw (2) observed that the specificity of NME coincided with that of the N-end rule (NER) (12, 13), a ubiquitin-dependent protein degradation process that is based on the recognition of N-terminal residues. The stabilizing residues for the NER include Gly, Ala, Ser, Cys, Thr, Pro, and Val and, with the exception of Met, the destabilizing residues are all found to be in the class of P2-residues that are not substrates for the MetAPs. This suggested that NME acts to release Met from proteins whose stability is unaffected by the NER creating at the same time a second class of proteins, who have the potential for regulated turnover downstream of the cotranslational processing, when, and if, the N-terminal Met is subsequently removed by a mechanism other than the cotranslational action of the MetAPs. However, despite extensive studies, this type of programmed protein turnover (requiring downstream removal of Met) has not been demonstrated to occur. An implication of this correlation is that exposing of the stabilizing residues may also contribute to increasing their lifetime.The stabilizing residues exposed by the action of the MetAPs can be further modified. The most extensive of these reactions is N-terminal acetylation (NTA), which can occur on as much as 70–80% of the mass of the soluble protein in eukaryotes. Although the specificity of the N-acetyltransferase (NAT) responsible is not as rigid as the MetAPs, the principal substrates in the stabilizing class are usually the four smallest residues (Gly, Ala, Ser, and Thr) (6, 14). A second class of NATs can also modify the retained Met when the adjacent residues are Asp, Glu or Asn (15). The functional importance of this modification (in either case) is not known although it has been suggested that it may exert a protective effect against spurious aminopeptidase cleavages. Recently, Hwang et al. (16) have extended the NER to include Nα-acetylated termini as also destabilizing thus providing another possible function for this modification. In contrast, to date, very few instances of Nα-acetylation have been observed in bacteria. Other modifications can also occur in both eukaryotes and prokaryotes although they are generally much more limited in scope.The specificity of the MetAPs suggest an apparent connection between NME and protein degradation. However, this connection has never been examined using high-throughput mass spectrometric data or a comparative genomics approach; thus it remains unclear whether exposing these stabilizing residues contributes to increasing protein half-life and thus represents a primary purpose of NME. (The connection between NME and NER in bacteria, which has an NER with a somewhat different profile (17), is even more obscure.) Recent studies provide some examples where disruption of NME via a single-residue substitution in the P2 position causes protein degradation (18–20); however, some of these experimental results are in conflict with the NER (13). Giglione et al. (20) have shown that NME triggers degradation of D2 protein in Caenorhabditis reinhardtii in the PSII complex after replacing the second (stabilizing) Thr residue by another amino acid to prevent NME. This replacement results in early degradation of D2 and instability of the PSII complex. From this, Giglione et al. (20) postulated that NME determines protein life-span via currently unknown machinery. However, because Bachmair et al. (12) classified Met as a stabilizing residue, it is not entirely clear why substituting one stabilizing residue (Met) by another one (Gly, Ala, Ser, Cys, Thr, Pro, or Val) should affect protein stability and the substitution may have other deleterious effects that are manifested in different ways.The logic for analyzing NME and NER is shown in Fig. 1. NME exposes 7 different residues as new N termini of proteins. The natural conclusion that has become a dogma of NME is that these seven residues are exposed for a functional reason. The broad scope of NME suggests a universal reason that surpasses any particular protein''s role. In turn the comparative genomics postulate (function suggests conservation) leads to the conclusion that the seven residues should be evolutionarily conserved at position P2 of proteins. However, because only two out of the seven residues are conserved, we argue that one of the two assumptions in Fig. 1A must be incorrect and put forth the alternative logic depicted in Fig. 1B, which matches our analysis across dozens of species. According to this logic, NME accomplishes the goal of exposing Ala and Ser by exposing all residues with side chains smaller or comparable in size to Ala and Ser (G, T, V, P, and C). These residues are thus inconsequential players that are not functionally important (and are not evolutionarily conserved) at P2.Open in a separate windowFig. 1.Two alternative cases for NME function.
A, NME exposes seven residues to be new N termini of proteins. Because this is presumably for some functional reason, the conventional assumption is that all seven residues must have functional importance as N termini. By the comparative genomics postulate (as defined in the text), evolutionary conservation of all seven at P2 should be observed. If all of these residues are not conserved, one of the two assumptions must be incorrect; either not all seven residues are important or the comparative genomics postulate is invalid. B, Given that the comparative genomics postulate holds, and only two of the seven residues are of functional importance as N termini, then the other five residues are inconsequential players and only these two residues should be evolutionarily conserved.In this report, we examine the connection between the specificity of NME and stabilizing residues of NER. In doing so, data sets from bacteria (including 112 million mass spectrometric spectra from 57 species), yeast, and mammals, were analyzed for N-terminal peptides both with respect to the excision (or not) of initiator Met residues and the distribution of P2-residues. The results reveal a strong preference of Ala and Ser as P2-residues. However, this process does not appear to be linked to the NER other than being generally compatible with it. These studies also demonstrate a much greater than expected number of Nα-acetylation events in some bacteria. 相似文献
65.
Giuseppe Tortoriello Brandon P. Rhodes Sara M. Takacs Jordyn M. Stuart Arjun Basnet Siham Raboune Theodore S. Widlanski Patrick Doherty Tibor Harkany Heather B. Bradshaw 《PloS one》2013,8(7)
Lipid metabolism is critical to coordinate organ development and physiology in response to tissue-autonomous signals and environmental cues. Changes to the availability and signaling of lipid mediators can limit competitiveness, adaptation to environmental stressors, and augment pathological processes. Two classes of lipids, the N-acyl amides and the 2-acyl glycerols, have emerged as important signaling molecules in a wide range of species with important signaling properties, though most of what is known about their cellular functions is from mammalian models. Therefore, expanding available knowledge on the repertoire of these lipids in invertebrates will provide additional avenues of research aimed at elucidating biosynthetic, metabolic, and signaling properties of these molecules. Drosophila melanogaster is a commonly used organism to study intercellular communication, including the functions of bioactive lipids. However, limited information is available on the molecular identity of lipids with putative biological activities in Drosophila. Here, we used a targeted lipidomics approach to identify putative signaling lipids in third instar Drosophila larvae, possessing particularly large lipid mass in their fat body. We identified 2-linoleoyl glycerol, 2-oleoyl glycerol, and 45 N-acyl amides in larval tissues, and validated our findings by the comparative analysis of Oregon-RS, Canton-S and w1118 strains. Data here suggest that Drosophila represent another model system to use for the study of 2-acyl glycerol and N-acyl amide signaling. 相似文献
66.
Measuring variation in potato roots in both field and glasshouse: the search for useful yield predictors and a simple screen for root traits 总被引:1,自引:0,他引:1
Jane Wishart Timothy S. George Lawrie K. Brown Gavin Ramsay John E. Bradshaw Philip J. White Peter J. Gregory 《Plant and Soil》2013,368(1-2):231-249
Aims
Potatoes have an inadequate rooting system for efficient acquisition of water and minerals and use disproportionate amounts of irrigation and fertilizer. This research determines whether significant variation in rooting characteristics of potato exists, which characters correlate with final yield and whether a simple screen for rooting traits could be developed.Methods
Twenty-eight genotypes of Solanum tuberosum groups Tuberosum and Phureja were grown in the field; eight replicate blocks to final harvest, while entire root systems were excavated from four blocks. Root classes were categorised and measured. The same measurements were made on these genotypes in the glasshouse, 2 weeks post emergence.Results
In the field, total root length varied from 40 m to 112 m per plant. Final yield was correlated negatively with basal root specific root length and weakly but positively with total root weight. Solanum tuberosum group Phureja genotypes had more numerous roots and proportionally more basal than stolon roots compared with Solanum tuberosum, group Tuberosum genotypes. There were significant correlations between glasshouse and field measurements.Conclusions
Our data demonstrate that variability in rooting traits amongst commercially available potato genotypes exists and a robust glasshouse screen has been developed. By measuring potato roots as described in this study, it is now possible to assess rooting traits of large populations of potato genotypes. 相似文献67.
The K+/H+ antiporter LeNHX2 increases salt tolerance by improving K+ homeostasis in transgenic tomato 总被引:1,自引:0,他引:1
RAÚL HUERTAS LOURDES RUBIO OLIVIER CAGNAC MARÍA JESÚS GARCÍA‐SÁNCHEZ JUAN DE DIOS ALCHÉ KEES VENEMA JOSÉ ANTONIO FERNÁNDEZ MARÍA PILAR RODRÍGUEZ‐ROSALES 《Plant, cell & environment》2013,36(12):2135-2149
The endosomal LeNHX2 ion transporter exchanges H+ with K+ and, to lesser extent, Na+. Here, we investigated the response to NaCl supply and K+ deprivation in transgenic tomato (Solanum lycopersicum L.) overexpressing LeNHX2 and show that transformed tomato plants grew better in saline conditions than untransformed controls, whereas in the absence of K+ the opposite was found. Analysis of mineral composition showed a higher K+ content in roots, shoots and xylem sap of transgenic plants and no differences in Na+ content between transgenic and untransformed plants grown either in the presence or the absence of 120 mm NaCl. Transgenic plants showed higher Na+/H+ and, above all, K+/H+ transport activity in root intracellular membrane vesicles. Under K+ limiting conditions, transgenic plants enhanced root expression of the high‐affinity K+ uptake system HAK5 compared to untransformed controls. Furthermore, tomato overexpressing LeNHX2 showed twofold higher K+ depletion rates and half cytosolic K+ activity than untransformed controls. Under NaCl stress, transgenic plants showed higher uptake velocity for K+ and lower cytosolic K+ activity than untransformed plants. These results indicate the fundamental role of K+ homeostasis in the better performance of LeNHX2 overexpressing tomato under NaCl stress. 相似文献
68.
Stephen L. Pinkosky Sergey Filippov Rai Ajit K. Srivastava Jeffrey C. Hanselman Cheryl D. Bradshaw Timothy R. Hurley Clay T. Cramer Mark A. Spahr Ashley F. Brant Jacob L. Houghton Chris Baker Mark Naples Khosrow Adeli Roger S. Newton 《Journal of lipid research》2013,54(1):134-151
ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel investigational drug being developed for the treatment of dyslipidemia and other cardio-metabolic risk factors. The hypolipidemic, anti-atherosclerotic, anti-obesity, and glucose-lowering properties of ETC-1002, characterized in preclinical disease models, are believed to be due to dual inhibition of sterol and fatty acid synthesis and enhanced mitochondrial long-chain fatty acid β-oxidation. However, the molecular mechanism(s) mediating these activities remained undefined. Studies described here show that ETC-1002 free acid activates AMP-activated protein kinase in a Ca2+/calmodulin-dependent kinase β-independent and liver kinase β 1-dependent manner, without detectable changes in adenylate energy charge. Furthermore, ETC-1002 is shown to rapidly form a CoA thioester in liver, which directly inhibits ATP-citrate lyase. These distinct molecular mechanisms are complementary in their beneficial effects on lipid and carbohydrate metabolism in vitro and in vivo. Consistent with these mechanisms, ETC-1002 treatment reduced circulating proatherogenic lipoproteins, hepatic lipids, and body weight in a hamster model of hyperlipidemia, and it reduced body weight and improved glycemic control in a mouse model of diet-induced obesity. ETC-1002 offers promise as a novel therapeutic approach to improve multiple risk factors associated with metabolic syndrome and benefit patients with cardiovascular disease. 相似文献
69.
A.D. Bradshaw 《Plant Ecology & Diversity》2013,6(4):303-311
Summary In the light of all that has been discovered about the mechanism of evolution it has become tempting to follow Darwin's lead and to “see no limit to this power“. Yet a careful examination of situations in which evolution is known to be occurring in some species, shows complete absence of evolution in others. This not because these species have not had the opportunity; in many situations there may even be uncolonised bare space. The explanation must lie in the supply of appropriate variation. A tacit assumption of evolution by natural selection is that the necessary variation is always available. Yet there is no a priori justification for this. Evidence from populations in nature, particularly of species which are potential colonists of old metal mine workings and similar metal contaminated habitats, shows that the species that successfully colonise these habitats, by the evolution of metal tolerant populations, possess within their normal populations the necessary variation. But those species which fail to colonise these habitats, despite the opportunity, do not possess this variation. This applies also at the level of the population, in the replicated evolutionary situations occurring under electricity pylons. Such evidence, together with arguments from theory, suggests that the failures of evolution have been as important as its successes in moulding the living world as we see it today, and that the reasons for failure must be sought at the molecular level in limitations to the origin of new variation. 相似文献
70.
James D. Johnston Steven C. Tuttle Morgan C. Nelson Rebecca K. Bradshaw Taylor G. Hoybjerg Julene B. Johnson Bryce A. Kruman Taylor S. Orton Ryan B. Cook Dennis L. Eggett K. Scott Weber 《PloS one》2016,11(1)
Concerns about energy consumption and climate change make residential evaporative coolers a popular alternative to central air conditioning in arid and semi-arid climates. However, evaporative coolers have been shown to significantly increase indoor relative humidity and dust mite allergen levels in some studies, while showing no association in other studies. Improved measurement of temporal fluctuations in indoor relative humidity may help identify factors that promote mite growth in homes in dry climates. Dust samples and continuous indoor relative humidity measurements were collected from homes with central air conditioning and homes with evaporative coolers in Utah. Samples were collected over two seasons, winter/spring (Jan–Apr) and summer (July–Sept), 2014. Dust samples were analyzed for Der p 1 and Der f 1 using a two-site monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) analysis. Housing characteristics including age of home, occupant density, and age of mattresses, furniture, and carpeting were also measured. Positive Der p 1 or Der f 1 samples were found in 25.0% of the homes and there was no difference in mean allergen levels by type of air conditioning. Indoor relative humidity was significantly higher in homes with evaporative coolers compared to those with central air conditioning during the summer. Homes with evaporative coolers also spent significantly more time during summer above 55.0% and 65.0% relative humidity compared to central air homes, but not above 75.0%. Findings from this study suggest that increased humidity from evaporative coolers may not be sufficient to exceed the critical equilibrium humidity or maintain humidity excursions for sufficient duration in relatively larger single-family homes in semi-arid climates to support mite growth and reproduction. 相似文献