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981.
982.
Compounds based on the 2,3-distyrylindole scaffold were found to exhibit bactericidal properties upon irradiation with white light. At the concentration of 1?μM, the lead compound 1 completely (ca. 109?CFU/mL) eradicated such Gram-positive organisms as S. aureus (MRSA, MSSA), E. faecalis (VRE), S. pyogenes and S. mutans when irradiated with white light for 2?min. At the concentration of 5?μM and in the presence of polymyxin E at non-bactericidal 1.25?μg/mL concentration, 1 also showed a 7-log to 9-log reductions in bacterial counts of such Gram-negative organisms as multi-drug resistant (MDR) A. baumannii, MDR P. aeruginosa, E. coli and Klebsiella pneumoniae (CRE: KPC and NDM-1), also when irradiated with white light for 2?min. The structure-activity relationship studies revealed that unsubstituted at benzene rings 2,3-distyrylindole 2 was most potent and gave a 5-order of magnitude eradication of a MRSA strain at the concentration of 30?nM upon irradiation with white light. Initial mechanistic experiments revealed the disruption of bacterial cell membrane, but indicated that singlet oxygen production, which is commonly associated with photodynamic therapy, may not play a role in the bactericidal effects of the 2,3-distyrylindoles.  相似文献   
983.
Methionine aminopeptidase (MetAP) is a dinuclear metalloprotease responsible for the cleavage of methionine initiator residues from nascent proteins. MetAP activity is necessary for bacterial proliferation and is therefore a projected novel antibacterial target. A compound library consisting of 294 members containing metal-binding functional groups was screened against Rickettsia prowazekii MetAP to determine potential inhibitory motifs. The compounds were first screened against the target at a concentration of 10?µM and potential hits were determined to be those exhibiting greater than 50% inhibition of enzymatic activity. These hit compounds were then rescreened against the target in 8-point dose–response curves and 11 compounds were found to inhibit enzymatic activity with IC50 values of less than 10?µM. Finally, compounds (1–5) were docked against RpMetAP with AutoDock to determine potential binding mechanisms and the results were compared with crystal structures deposited within the PDB.  相似文献   
984.
Given that phosphate supplies may diminish and become uneconomic to mine after 2020, there is a compelling need to develop alternative industries to support the population on Christmas Island. Former mine sites could be turned into productive agricultural land, however, large-scale commercial agriculture has never been attempted, and, given the uniqueness of the island, the diversity of rhizobia prior to introducing legumes needed evaluation. Therefore, 84 rhizobia isolates were obtained from nine different hosts, both crop and introduced legumes, located at seven sites across the island. Based on 16S rRNA and recA gene sequence analysis, the isolates grouped into 13 clades clustering within the genus Bradyrhizobium, Ensifer, Cupriavidus and Rhizobium. According to the sequences of their symbiosis genes nodC and nifH, the isolates were classified into 12 and 11 clades, respectively, and clustered closest to tropical or crop legume isolates. Moreover, the symbiosis gene phylogeny and Multi Locus Sequence Analysis gene phylogeny suggested vertical transmission in the Alpha-rhizobia but horizontal transmission within the Beta-rhizobia. Furthermore, this study provides evidence of a large diversity of endemic rhizobia associated with both crop and introduced legumes, and highlights the necessity of inoculation for common bean, chickpea and soybean on the Island.  相似文献   
985.
Understanding the mechanisms that produce variation in thermal performance is a key component to investigating climatic effects on evolution and adaptation. However, disentangling the effects of local adaptation and phenotypic plasticity in shaping patterns of geographic variation in natural populations can prove challenging. Additionally, the physiological mechanisms that cause organismal dysfunction at extreme temperatures are still largely under debate. Using the green anole, Anolis carolinensis, we integrate measures of cold tolerance (CTmin), standard metabolic rate, heart size, blood lactate concentration and RNAseq data from liver tissue to investigate geographic variation in cold tolerance and its underlying mechanisms along a latitudinal cline. We found significant effects of thermal acclimation and latitude of origin on variation in cold tolerance. Increased cold tolerance correlates with decreased rates of oxygen consumption and blood lactate concentration (a proxy for oxygen limitation), suggesting elevated performance is associated with improved oxygen economy during cold exposure. Consistent with these results, co‐expression modules associated with blood lactate concentration are enriched for functions associated with blood circulation, coagulation and clotting. Expression of these modules correlates with thermal acclimation and latitude of origin. Our findings support the oxygen and capacity‐limited thermal tolerance hypothesis as a potential contributor to variation in reptilian cold tolerance. Moreover, differences in gene expression suggest regulation of the blood coagulation cascade may play an important role in reptilian cold tolerance and may be the target of natural selection in populations inhabiting colder environments.  相似文献   
986.
Indiscriminate discharge of pharmaceutical waste into the aquatic ecosystem may pose serious health challenges to aquatic biota. The effect of acute exposure to ibuprofen was evaluated using changes in behaviour and haematological parameters under static bio-assay method in Clarias gariepinus. Test specimens were exposed to acute concentrations of ibuprofen (0.28, 0.33, 0.38, 0.43 and 0.48 mg l?1) for 24, 48, 72 and 96 h durations respectively. Behavioural and phenotypic changes were observed in surviving fish. There were significant (p < 0.05) concentration and duration-dependent increases in erythrocyte (RBC), haemoglobin (Hb), pack cell volume (PCV) and leukocytes (WBC) in treated fish compared to the control. Insignificant decreases (p > 0.05) in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were observed in treated fish compared to the control. Ibuprofen elicited dose and duration- dependent decrease in neutrophil counts with the decreases being significant (p < 0.05) in the higher doses of 0.43 and 0.48 mg l?1. Ibuprofen did not elicit any significant changes in monocytes, basophils and eosinophils. Changes observed in this study showed that ibuprofen negatively affected the health of the fish and we recommend that discharge of ibuprofen into the aquatic environment should be monitored and controlled.  相似文献   
987.
The Australian Government has sanctioned development of greenhouse gas emissions (GHG) abatement methodologies to meet international emissions reduction obligations. Savanna burning emissions abatement methodologies have been available since 2012, and there are currently 72 registered projects covering approximately 32 million ha. Abatement to date has exceeded 4 million tonnes of carbon dioxide equivalent (CO2‐e) principally through the application of low intensity early dry season fire management to reduce the amount of biomass combusted in higher intensity late dry season (LDS) fires. Savanna burning projects can only be conducted on areas with eligible fire‐prone vegetation fuel types where implementing the improved fire management regime is considered ecologically appropriate. This study assesses the suitability of including tall Acacia shrublands (‘Pindan’) as a new eligible fuel type. These shrublands make up 12% (~2 million ha) of the Kimberley region, Western Australia, where, on average, 32% is fire affected annually, mostly in the LDS. A standard assessment protocol was applied to describe vegetation fuel type structural and pyrolysis characteristics. We show that Pindan (i) can be identified and mapped as a unique tall Acacia shrubland vegetation fuel type, (ii) characterised by a significantly greater shrubby fuel load biomass, and (iii) the conservation status of which would benefit from imposition of strategic prescribed burning programme. Savanna burning projects in the Pindan fuel type could potentially abate up to 24.43 t.CO2e/km2 per year, generating significant income and employment opportunities for predominantly Indigenous land managers in the region.  相似文献   
988.
Tropical rainforests play an important role in the storage and cycling of global terrestrial carbon. In the carbon cycle, net primary productivity of forests is linked to soil respiration through the production and decomposition of forest litter. Climate seasonality appears to influence the production of litter although there is considerable variability within and across forests that makes accurate estimates challenging. We explored the effects of climate seasonality on litterfall dynamics in a lowland humid rainforest over a 7‐year period from 2007 to 2013, including an El Niño/La Niña cycle in 2010/2011. Litterfall was sampled fortnightly in 24 traps of 0.50 m diameter within a 1‐ha forest plot. Total mean litterfall was 10.48 ± 1.32 (±SD, dry weight) Mg ha?1 year?1 and seasonal in distribution. The different components of litterfall were divided into LLeaf (63.5%), LWood (27.7%) and LFF[flowers & fruit] (8.8%), which all demonstrated seasonal dynamics. Peak falls in LLeaf and LWood were highly predictable, coinciding with maximum daily temperatures and 1 and 2 months prior to maximum monthly rainfall. The El Niño/La Niña cycle coincided with elevated local winter temperatures and peak falls of LLeaf and LWood. Importantly, we establish how sampling length and generalized additive models eliminate the requirement for extensive within‐site sampling when the intention is to describe dynamics in litterfall patterns. Further, a greater understanding of seasonal cycles in litterfall allows us to distinguish between endogenous controls and environmental factors, such as El Niño events, which may have significant impacts on biochemical cycles.  相似文献   
989.
Wheat breeders and academics alike use single nucleotide polymorphisms (SNP s) as molecular markers to characterize regions of interest within the hexaploid wheat genome. A number of SNP ‐based genotyping platforms are available, and their utility depends upon factors such as the available technologies, number of data points required, budgets and the technical expertise required. Unfortunately, markers can rarely be exchanged between existing and newly developed platforms, meaning that previously generated data cannot be compared, or combined, with more recently generated data sets. We predict that genotyping by sequencing will become the predominant genotyping technology within the next 5–10 years. With this in mind, to ensure that data generated from current genotyping platforms continues to be of use, we have designed and utilized SNP ‐based capture probes from several thousand existing and publicly available probes from Axiom® and KASP ? genotyping platforms. We have validated our capture probes in a targeted genotyping by sequencing protocol using 31 previously genotyped UK elite hexaploid wheat accessions. Data comparisons between targeted genotyping by sequencing, Axiom® array genotyping and KASP ? genotyping assays, identified a set of 3256 probes which reliably bring together targeted genotyping by sequencing data with the previously available marker data set. As such, these probes are likely to be of considerable value to the wheat community. The probe details, full probe sequences and a custom built analysis pipeline may be freely downloaded from the CerealsDB website (http://www.cerealsdb.uk.net/cerealgenomics/CerealsDB /sequence_capture.php).  相似文献   
990.
Integrin β3 is seen as a key anti‐angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro‐ or anti‐angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3‐dependent adhesome. We show that depletion of β3‐integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3‐integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2‐driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3‐integrin levels are reduced.  相似文献   
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