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41.
A McCluskey C Walkom M C Bowyer S P Ackland E Gardiner J A Sakoff 《Bioorganic & medicinal chemistry letters》2001,11(22):2941-2946
Cantharidin and its analogues have been of considerable interest as potent inhibitors of the serine/threonine protein phosphatases 1 and 2A (PP1 and PP2A). However, limited modifications to the parent compounds is tolerated. As part of an on-going study we have developed a new series of cantharidin analogues, the cantharimides. Inhibition studies indicate that cantharimides possessing a D- or L-histidine, are more potent inhibitors of PP1 and PP2A (PP1 IC(50)=3.22+/-0.7 microM; PP2A IC(50)=0.81+/-0.1 microM and PP1 IC(50)=2.82+/-0.6 microM; PP2A IC(50)=1.35+/-0.3 microM, respectively) than norcantharidin (PP1 IC(50)=5.31+/-0.76 microM; PP2A IC(50)=2.9+/-1.04 microM) and essentially equipotent with cantharidin (PP1 IC(50)=3.6+/-0.42 microM; PP2A IC(50)=0.36+/-0.08 microM). Cantharimides with non-polar or acidic amino acid residues are only poor inhibitors of PP1 and PP2A. 相似文献
42.
Jericho C. Whiting Kelley M. Stewart R. Terry Bowyer Jerran T. Flinders 《European Journal of Wildlife Research》2010,56(3):349-357
Little is known regarding the potential adjustment of maternal care towards late-born young by reintroduced female ungulates, which may be adapted to environments quite different than those at their release site. We compared nursing behaviors of young to investigate whether females would adjust maternal care toward late-born young between two populations of reintroduced bighorn sheep (Ovis canadensis) in Utah, USA. Neonates on Mount Timpanogos were born on average 28 days later in 2002 and 13 days later in 2003 than neonates in Rock Canyon. Suckling and weaning behaviors, however, were similar in 2002 and 2003 between those populations, except for the number of unsuccessful suckles, which was greater for young in Rock Canyon than for young on Mount Timpanogos during the middle of lactation in 2002. Our results provide preliminary evidence that females did not adjust maternal care to compensate for late-born young within the first 3 years following reintroduction, which possibly influenced survivorship of young. 相似文献
43.
Andréia S Lessa Bruno D Paredes Juliana V Dias Adriana B Carvalho Luiz Fernando Quintanilha Christina M Takiya Bernardo R Tura Guilherme FM Rezende Antonio C Campos de Carvalho Célia MC Resende Regina CS Goldenberg 《BMC veterinary research》2010,6(1):1-10
Background
Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries. Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease. However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. The first successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.Results
This study demonstrates that atypical scrapie has distinct clinical, pathological and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.Conclusions
Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage. 相似文献44.
van Beers JJ Raijmakers R Alexander LE Stammen-Vogelzangs J Lokate AM Heck AJ Schasfoort RB Pruijn GJ 《Arthritis research & therapy》2010,12(6):R219
Introduction
Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response to citrullinated fibrinogen in RA, its autoepitopes were systematically mapped using a new methodology. 相似文献45.
Lisa Rizzetto Gloria Giovannini Michael Bromley Paul Bowyer Luigina Romani Duccio Cavalieri 《PloS one》2013,8(2)
For over a century microbiologists and immunologist have categorized microorganisms as pathogenic or non-pathogenic species or genera. This definition, clearly relevant at the strain and species level for most bacteria, where differences in virulence between strains of a particular species are well known, has never been probed at the strain level in fungal species. Here, we tested the immune reactivity and the pathogenic potential of a collection of strains from Aspergillus spp, a fungus that is generally considered pathogenic in immuno-compromised hosts. Our results show a wide strain-dependent variation of the immune response elicited indicating that different isolates possess diverse virulence and infectivity. Thus, the definition of markers of inflammation or pathogenicity cannot be generalized. The profound understanding of the molecular mechanisms subtending the different immune responses will result solely from the comparative study of strains with extremely diverse properties. 相似文献
46.
Claudia T Guimaraes Christiano C Simoes Maria Marta Pastina Lyza G Maron Jurandir V Magalhaes Renato CC Vasconcellos Lauro JM Guimaraes Ubiraci GP Lana Carlos FS Tinoco Roberto W Noda Silvia N Jardim-Belicuas Leon V Kochian Vera MC Alves Sidney N Parentoni 《BMC genomics》2014,15(1)
Background
Aluminum (Al) toxicity is an important limitation to food security in tropical and subtropical regions. High Al saturation on acid soils limits root development, reducing water and nutrient uptake. In addition to naturally occurring acid soils, agricultural practices may decrease soil pH, leading to yield losses due to Al toxicity. Elucidating the genetic and molecular mechanisms underlying maize Al tolerance is expected to accelerate the development of Al-tolerant cultivars.Results
Five genomic regions were significantly associated with Al tolerance, using 54,455 SNP markers in a recombinant inbred line population derived from Cateto Al237. Candidate genes co-localized with Al tolerance QTLs were further investigated. Near-isogenic lines (NILs) developed for ZmMATE2 were as Al-sensitive as the recurrent line, indicating that this candidate gene was not responsible for the Al tolerance QTL on chromosome 5, qALT5. However, ZmNrat1, a maize homolog to OsNrat1, which encodes an Al3+ specific transporter previously implicated in rice Al tolerance, was mapped at ~40 Mbp from qALT5. We demonstrate for the first time that ZmNrat1 is preferentially expressed in maize root tips and is up-regulated by Al, similarly to OsNrat1 in rice, suggesting a role of this gene in maize Al tolerance. The strongest-effect QTL was mapped on chromosome 6 (qALT6), within a 0.5 Mbp region where three copies of the Al tolerance gene, ZmMATE1, were found in tandem configuration. qALT6 was shown to increase Al tolerance in maize; the qALT6-NILs carrying three copies of ZmMATE1 exhibited a two-fold increase in Al tolerance, and higher expression of ZmMATE1 compared to the Al sensitive recurrent parent. Interestingly, a new source of Al tolerance via ZmMATE1 was identified in a Brazilian elite line that showed high expression of ZmMATE1 but carries a single copy of ZmMATE1.Conclusions
High ZmMATE1 expression, controlled either by three copies of the target gene or by an unknown molecular mechanism, is responsible for Al tolerance mediated by qALT6. As Al tolerant alleles at qALT6 are rare in maize, marker-assisted introgression of this QTL is an important strategy to improve maize adaptation to acid soils worldwide.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-153) contains supplementary material, which is available to authorized users. 相似文献47.
48.
Cantharidin analogues: synthesis and evaluation of growth inhibition in a panel of selected tumour cell lines 总被引:7,自引:0,他引:7
McCluskey A Ackland SP Bowyer MC Baldwin ML Garner J Walkom CC Sakoff JA 《Bioorganic chemistry》2003,31(1):68-79
Diels-Alder addition of furans (furan, furfuryl alcohol, and 3-bromofuran) to maelic anhydride yields three distinct 5,6-dehydronorcantharidins. Hydrogenation of (4,10-dioxatricyclo[5.2.1.0]decane-3,5-dione) (4a), in dry ethanol affords the monoester (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic aid monoethyl ester) (6). Subsequent transesterification affords a series of monoesters (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid monomethyl ester (7)), 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid monopropyl ester (8), (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid monohexyl ester (9)) and differentially substituted diesters (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-ethyl ester 3-isopropyl ester) (10), and (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-ethyl ester 3-phenyl ester) (11). Analogues were firstly screened for their ability to inhibit protein phosphatases 1 (PP1) and 2A (PP2A) as the lead compounds cantharidin (1) and norcantharidin (2) are known PP1 and PP2A inhibitors. Only analogues 4a, 6-8 displayed good PP1 and PP2A inhibition (PP1 IC(50)'s=2.0, 2.96, 4.71, and 4.82 microM, respectively; PP2A IC(50)'s=0.2, 0.45, 0.41, and 0.47 microM, respectively). All analogues were also screened for their anti-cancer potential against a panel of tumour cell lines, HL60, L1210, SW480, WiDr, HT29, HCT116, A2780, ADDP, and 143B, producing GI(50) values ranging from 6 microM to >1000 microM. Analogues possessing good PP1 and/or PP2A inhibition also returned moderate to good anti-cancer activity. Analogues with substituents directly attached to the intact bicyclo[2.2.1]heptane skeleton were poor to moderate anti-cancer agents. This correlates well with their lack of PP1 or PP2A activity. Analogues capable of undergoing a facile ring opening of the anhydride or with a single carboxylate were good PP1 and PP2A inhibitors, largely correlating to the observed anti-cancer activity in all cases, except 11. Analogue 11, whist neither a PP1 nor a PP2A inhibitor shows anti-cancer activity comparable to 1 and 2. We believe that intracellular esterases generate the corresponding dicarboxylate, which is a potent PP1 and PP2A inhibitor, and that it is this species which is responsible for the observed anti-cancer activity. 相似文献
49.
We compared histochemical and immunohistochemical staining as well as fluorochrome labeling in murine bone specimens that were fixed with 10% neutral buffered formalin to those fixed with HistoChoice®. We showed that sections from undecalcified tibiae fixed for 4 h in HistoChoice® resulted in enhanced toluidine blue and Von Kossa histochemical staining compared to formalin fixation. HistoChoice® produced comparable or improved staining for alkaline phosphatase. Acid phosphatase localization was better in formalin fixed specimens, but osteoclasts were visuralized more easily in HistoChoice® fixed specimens. As expected, immunohistochemical labeling was antibody dependent; some antibodies labeled better in HistoChoice® fixed specimens while others were better in formalin fixed specimens. Toluidine blue, Von Kossa, and alkaline phosphatase staining of sections fixed for 12 h produced sections that were similar to 4 h fixed sections. Fixation for 12 h preserved acid phosphatase activity better. Increasing fixation to 12 h affected immunolocalization differentially. Bone sialoprotein labeling in HistoChoice® fixed specimens was comparable to formalin fixed samples. On the other hand, after 12 h formalin fixation, osteocalcin labeling was comparable to HistoChoice®. For most histochemical applications, fixing murine bone specimens for 4 h with HistoChoice® yielded superior staining compared to formalin fixation. If immunohistochemical localization is desired, however, individual antibodies must be tested to determine which fixation process retains antigenicity better. In addition, there was no detectable difference in the intensity of fluorochrome labeling using either fixative. Finally, fixation duration did not alter the intensity of labeling. 相似文献
50.
Molecular phylogenetics at the population/species interface in cave spiders of the southern Appalachians (Araneae:Nesticidae:Nesticus) 总被引:5,自引:0,他引:5
This paper focuses on the relationship between population genetic structure
and speciation mechanisms in a monophyletic species group of Appalachian
cave spiders (Nesticus). Using mtDNA sequence data gathered from 256
individuals, I analyzed patterns of genetic variation within and between
populations for three pairs of closely related sister species. Each
sister-pair comparison involves taxa with differing distributional and
ecological attributes; if these ecological attributes are reflected in
basic demographic differences, then speciation might proceed differently
across these sister taxa comparisons. Both frequency-based and gene tree
analyses reveal that the genetic structure of the Nesticus species studied
is characterized by similar and essentially complete population
subdivision, regardless of differences in general ecology. These findings
contrast with results of prior genetic studies of cave-dwelling arthropods
that have typically revealed variation in population structure
corresponding to differences in general ecology. Species fragmentation
through both extrinsic and intrinsic evolutionary forces has resulted in
discrete, perhaps independent, populations within morphologically defined
species. Large sequence divergence values observed between populations
suggest that this independence may extend well into the past. These
patterns of mtDNA genealogical structure and divergence imply that species
as morphological lineages are currently more inclusive than basal
evolutionary or phylogenetic units, a suggestion that has important
implications for the study of speciation mechanisms.
相似文献