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91.
Glauser DA Chen WC Agin R Macinnis BL Hellman AB Garrity PA Tan MW Goodman MB 《Genetics》2011,188(1):91-103
The ability to avoid noxious extremes of hot and cold is critical for survival and depends on thermal nociception. The TRPV subset of transient receptor potential (TRP) channels is heat activated and proposed to be responsible for heat detection in vertebrates and fruit flies. To gain insight into the genetic and neural basis of thermal nociception, we developed assays that quantify noxious heat avoidance in the nematode Caenorhabditis elegans and used them to investigate the genetic basis of this behavior. First, we screened mutants for 18 TRP channel genes (including all TRPV orthologs) and found only minor defects in heat avoidance in single and selected double and triple mutants, indicating that other genes are involved. Next, we compared two wild isolates of C. elegans that diverge in their threshold for heat avoidance and linked this phenotypic variation to a polymorphism in the neuropeptide receptor gene npr-1. Further analysis revealed that loss of either the NPR-1 receptor or its ligand, FLP-21, increases the threshold for heat avoidance. Cell-specific rescue of npr-1 implicates the interneuron RMG in the circuit regulating heat avoidance. This neuropeptide signaling pathway operates independently of the TRPV genes, osm-9 and ocr-2, since mutants lacking npr-1 and both TRPV channels had more severe defects in heat avoidance than mutants lacking only npr-1 or both osm-9 and ocr-2. Our results show that TRPV channels and the FLP-21/NPR-1 neuropeptide signaling pathway determine the threshold for heat avoidance in C. elegans. 相似文献
92.
93.
An Agrobacterium‐delivered CRISPR/Cas9 system for high‐frequency targeted mutagenesis in maize 下载免费PDF全文
Hartinio Nahampun Bronwyn Frame Marcy Main Martin H. Spalding Philip W. Becraft Blake C. Meyers Virginia Walbot Kan Wang Bing Yang 《Plant biotechnology journal》2017,15(2):257-268
CRISPR/Cas9 is a powerful genome editing tool in many organisms, including a number of monocots and dicots. Although the design and application of CRISPR/Cas9 is simpler compared to other nuclease‐based genome editing tools, optimization requires the consideration of the DNA delivery and tissue regeneration methods for a particular species to achieve accuracy and efficiency. Here, we describe a public sector system, ISU Maize CRISPR, utilizing Agrobacterium‐delivered CRISPR/Cas9 for high‐frequency targeted mutagenesis in maize. This system consists of an Escherichia coli cloning vector and an Agrobacterium binary vector. It can be used to clone up to four guide RNAs for single or multiplex gene targeting. We evaluated this system for its mutagenesis frequency and heritability using four maize genes in two duplicated pairs: Argonaute 18 (ZmAgo18a and ZmAgo18b) and dihydroflavonol 4‐reductase or anthocyaninless genes (a1 and a4). T0 transgenic events carrying mono‐ or diallelic mutations of one locus and various combinations of allelic mutations of two loci occurred at rates over 70% mutants per transgenic events in both Hi‐II and B104 genotypes. Through genetic segregation, null segregants carrying only the desired mutant alleles without the CRISPR transgene could be generated in T1 progeny. Inheritance of an active CRISPR/Cas9 transgene leads to additional target‐specific mutations in subsequent generations. Duplex infection of immature embryos by mixing two individual Agrobacterium strains harbouring different Cas9/gRNA modules can be performed for improved cost efficiency. Together, the findings demonstrate that the ISU Maize CRISPR platform is an effective and robust tool to targeted mutagenesis in maize. 相似文献
94.
SREBP transcription factors: master regulators of lipid homeostasis 总被引:41,自引:0,他引:41
95.
Campbell BE Tarleton M Gordon CP Sakoff JA Gilbert J McCluskey A Gasser RB 《Bioorganic & medicinal chemistry letters》2011,21(11):3277-3281
With the major problems with resistance in parasitic nematodes of livestock to anthelmintic drugs, there is an urgent need to develop new nematocides. In the present study, we employed a targeted approach for the design of a series of norcantharidin analogues (n = 54) for activity testing against the barber’s pole worm (Haemonchus contortus) of small ruminants in a larval development assay (LDA) and also for toxicity testing on nine distinct human cell lines. Although none of the 54 analogues synthesized were toxic to any of these cell lines, three of them (N-octyl-7-oxabicyclo(2.2.1)heptane-2,3-dicarboximide (B2), N-decyl-7-oxabicyclo(2.2.1)heptane-2,3-dicarboximide (B3) and 4-[(4-methyl)-3-ethyl-2-methyl-5-phenylfuran-10-oxa-4-azatricyclo[5.2.1]decane-3,5-dione (B21) reproducibly displayed 99-100% lethality to H. contortus in LDA, with LD50s of 25-40 μM. The high ‘hit rate’ (5.6%) indicates that the approach taken here has advantages over conventional drug screening methods. A major advantage of norcantharidin analogues over some other currently available anthelmintics is that they can be produced in one to two steps in large amounts at low cost and high purity, and do not require any additional steps for the isolation of the active isomer. This positions them well for commercial development. 相似文献
96.
Resource availability is a limiting factor influencing the distribution and composition of faunal communities. Globally, hollow bearing trees are a resource required by wildlife at all trophic levels, and are used for a diverse range of ecological functions. In the northern hemisphere avian species act as primary hollow excavators, whereas the southern hemisphere must rely on complex interactions between stochastic events, and eventual decay. Hollow formation is therefore a slow process in the southern hemisphere. In contrast, hollow loss is quite rapid and influenced greatly by anthropogenic impacts. To identify the ecological characteristics driving hollows over an urban to forest gradient as a resource for the powerful owl (Ninox strenua) and its prey we used presence‐only modelling. The potential for an area to support tree hollows suitable for powerful owls and their prey was linked to the density of ephemeral rivers, land cover, tree cover and distance from riparian vegetation. The potential for large hollows throughout the landscape, suitable for the powerful owl, was also influenced by density of permanent rivers. Potential habitat for tree hollows, capable of supporting powerful owls and their prey was greatest in forested environments, declining with increased urbanization. However the urban region still supported some smaller tree hollows suitable for arboreal marsupials. Managing for urban dwelling species, is not as simple as retaining old hollow producing trees or providing alternate nesting structures. We also need to mitigate increased mortality associated with built environments (e.g. electrocution, collisions). 相似文献
97.
Bronwyn E. Keatley Marianne S. V. Douglas Jules M. Blais Mark L. Mallory John P. Smol 《Hydrobiologia》2009,621(1):191-205
Relationships between key phytoplankton attributes including Chl a-specific light absorption, pigment composition and concentration, photosynthesis, primary production and community structure
were studied in two open shallow nutrient-poor coastal systems receiving similar amounts of sewage water. Both systems were
significantly nitrogen limited. However, differences in wastewater treatment (primary vs secondary) and sewage dilution (50%)
between the two systems caused a greater difference between systems than locally around the outflows. For both systems, water
at the outlet had significantly lower water transparency caused by a 20% higher absorption by coloured dissolved organic matter.
Nutrient concentrations were also elevated, gradually decreasing with distance north (governing current) of the outflows,
causing higher abundance of nano-sized phytoplankton, higher content of carotenoid pigments, 20–50% higher Chl a-specific absorption coefficients and higher photosynthetic capacity. Although maximum rates of Chl a-normalised photosynthesis were strongly related to nitrate availability, no effects were found on the derived areal primary
production or algal biomass suggesting that photosynthetic and optical parameters are more sensitive indicators of nutrient
enrichment than biomass or productivity.
Handling editor: Tasman Peter Crowe 相似文献
98.
Campino S Auburn S Kivinen K Zongo I Ouedraogo JB Mangano V Djimde A Doumbo OK Kiara SM Nzila A Borrmann S Marsh K Michon P Mueller I Siba P Jiang H Su XZ Amaratunga C Socheat D Fairhurst RM Imwong M Anderson T Nosten F White NJ Gwilliam R Deloukas P MacInnis B Newbold CI Rockett K Clark TG Kwiatkowski DP 《PloS one》2011,6(6):e20251
The diversity in the Plasmodium falciparum genome can be used to explore parasite population dynamics, with practical applications to malaria control. The ability to identify the geographic origin and trace the migratory patterns of parasites with clinically important phenotypes such as drug resistance is particularly relevant. With increasing single-nucleotide polymorphism (SNP) discovery from ongoing Plasmodium genome sequencing projects, a demand for high SNP and sample throughput genotyping platforms for large-scale population genetic studies is required. Low parasitaemias and multiple clone infections present a number of challenges to genotyping P. falciparum. We addressed some of these issues using a custom 384-SNP Illumina GoldenGate assay on P. falciparum DNA from laboratory clones (long-term cultured adapted parasite clones), short-term cultured parasite isolates and clinical (non-cultured isolates) samples from East and West Africa, Southeast Asia and Oceania. Eighty percent of the SNPs (n = 306) produced reliable genotype calls on samples containing as little as 2 ng of total genomic DNA and on whole genome amplified DNA. Analysis of artificial mixtures of laboratory clones demonstrated high genotype calling specificity and moderate sensitivity to call minor frequency alleles. Clear resolution of geographically distinct populations was demonstrated using Principal Components Analysis (PCA), and global patterns of population genetic diversity were consistent with previous reports. These results validate the utility of the platform in performing population genetic studies of P. falciparum. 相似文献
99.
David M. de Kretser Jonathan G. Bensley David J. Phillips Bronwyn J. Levvey Greg I. Snell Enjarn Lin Mark P. Hedger Robyn E. O’Hehir 《PloS one》2016,11(1)
Background
Lung transplantation exposes the donated lung to a period of anoxia. Re-establishing the circulation after ischemia stimulates inflammation causing organ damage. Since our published data established that activin A is a key pro-inflammatory cytokine, we assessed the roles of activin A and B, and their binding protein, follistatin, in patients undergoing lung transplantation.Methods
Sera from 46 patients participating in a published study of remote ischemia conditioning in lung transplantation were used. Serum activin A and B, follistatin and 11 other cytokines were measured in samples taken immediately after anaesthesia induction, after remote ischemia conditioning or sham treatment undertaken just prior to allograft reperfusion and during the subsequent 24 hours.Results
Substantial increases in serum activin A, B and follistatin occurred after the baseline sample, taken before anaesthesia induction and peaked immediately after the remote ischemia conditioning/sham treatment. The levels remained elevated 15 minutes after lung transplantation declining thereafter reaching baseline 2 hours post-transplant. Activin B and follistatin concentrations were lower in patients receiving remote ischemia conditioning compared to sham treated patients but the magnitude of the decrease did not correlate with early transplant outcomes.Conclusions
We propose that the increases in the serum activin A, B and follistatin result from a combination of factors; the acute phase response, the reperfusion response and the use of heparin-based anti-coagulants. 相似文献100.