368 research outputs found

    Spectrophotometric Determination of Formation Constants of Molecular Complexes

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    Drug-efflux and target-site gene expression patterns in Haemonchus contortus larvae able to survive increasing concentrations of levamisole in vitro

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    While there is some evidence that changes in nicotinic acetylcholine receptor (nAChR) subunits confer resistance to levamisole in gastrointestinal helminth parasites, the exact nature of the resistance mechanism(s) is unclear. We utilised the presence of a resistant fraction within the Wallangra 2003 isolate of Haemonchus contortus larvae in order to subdivide the population into three subpopulations of larvae able to survive increasing concentrations of the drug. We then measured gene expression levels in the subpopulations and the larval population as a whole, focusing on genes encoding the subunit components of levamisole-sensitive receptors, genes encoding ancillary proteins involved in receptor assembly, and P-glycoprotein (P-gp) genes. The subpopulation surviving the lowest levamisole concentration showed increases of 1.5- to 3-fold in a number of P-gp genes (Hco-pgp-3, -4, -10, and -14) alongside unchanged receptor genes, compared to the whole Wallangra larval population. On the other hand, the subpopulation surviving the intermediate levamisole concentration showed an increase in only a single P-gp (Hco-pgp-14), alongside decreases in some receptor subunit (Hco-unc-63a) and ancillary protein genes (Hco-unc-50, Hco-ric-3.1 and 3.1). The subpopulation surviving the highest levamisole concentration showed further decreases in receptor subunit genes (Hco-unc-63a and Hco-unc-29 paralogs) as well as genes involved in receptor assembly (Hco-unc-74, Hco-unc-50, Hco-ric-3.1 and 3.1), alongside no increased P-gp gene levels. This suggests a biphasic pattern of drug resistance in the larvae of this worm isolate, in which a non-specific P-gp-mediated mechanism confers low levels of resistance, while higher level resistance is due to altered receptor subunit composition as a result of changes in both subunit composition and in the levels of proteins involved in receptor assembly

    Stability of Executive Functioning of Moderately-Late Preterm and Full-Term Born Children at Ages 11 and 19:The TRAILS Cohort Study

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    Moderately-late preterm-born children (MLPs, 32-36 weeks gestational age, GA) have poorer executive functioning (EF) at primary school age than full-term children (FTs). Evidence is lacking on their EF in adolescence, but for early preterm-born children, this has been shown to be much poorer. We, therefore, compared EF of MLPs and FTs at ages 11 and 19 and assessed development between these ages. We obtained data from TRAILS, a community-based prospective cohort study in the northern Netherlands, on 98 MLPs and 1832 FTs. We assessed EF by the Amsterdam Neuropsychological Tasks (ANT) at ages 11 and 19 years and computed gender-specific z-scores on reaction time and accuracy. We compared baseline speed, pattern search, working memory, sustained attention, inhibition, and attentional flexibility of MLPs and FTs crude, and adjusted for small-for-GA status, socioeconomic status, and estimated intelligence. MLPs and FTs performed similarly on all EF components at ages 11 and 19, except for the speed, but not the accuracy measure of attentional flexibility. This was slightly poorer for MLPs than FTs at age 19 (adjusted B 0.25; 95% confidence interval: 0.00 to 0.50; p = 0.047), but not at age 11 (adjusted B -0.02; -0.19 to 0.22; p = 0.87). Differences in EF between MLPs and FTs did not change significantly from age 11 to 19. MLPs had comparable EF on most components as FTs, with only attentional flexibility at age 19 developing slightly poorer for MLPs than for FTs. These findings suggest the effects of MLP birth on long-term EF to be small

    Assessment of beetle diversity, community composition and potential threats to forestry using kairomone-baited traps

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    Traps designed to capture insects during normal movement/dispersal, or via attraction to non-specific (plant) volatile lures, yield by-catch that carries valuable information about patterns of community diversity and composition. In order to identify potential native/introduced pests and detect predictors of colonization of non-native pines, we examined beetle assemblages captured in intercept panel traps baited with kairomone lures used during a national monitoring of the woodwasp, Sirex noctilio, in Southern Africa. We identified 50 families and 436 morphospecies of beetles from nine sites sampled in both 2008 and 2009 and six areas in 2007 (trap catch pooled by region) across a latitudinal and elevational gradient. The most diverse groups were mainly those strongly associated with trees, known to include damaging pests. While native species dominated the samples in terms of richness, the dominant species was the introduced bark beetle Orthotomicus erosus (Curculionidae: Scolytinae) (22 ± 34 individuals/site). Four Scolytinae species without previous records in South Africa, namely Coccotrypes niger, Hypocryphalus robustus (formerly Hypocryphalus mangiferae), Hypothenemus birmanus and Xyleborus perforans, were captured in low abundances. Communities showed temporal stability within sites and strong biogeographic patterns across the landscape. The strongest single predictors of community composition were potential evaporation, latitude and maximum relative humidity, while the strongest multifactor model contained elevation, potential evaporation and maximum relative humidity. Temperature, land use variables and distance to natural areas did not significantly correlate with community composition. Non-phytophagous beetles were also captured and were highly diverse (32 families) perhaps representing important beneficial insects.The DST-NRF Centre of Excellence in Tree Health Biotechnology and the Tree Protection Cooperative Programme.http://journals.cambridge.org/action/displayJournal?jid=BER2017-08-31hb2017Forestry and Agricultural Biotechnology Institute (FABI)Zoology and Entomolog

    From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions

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    ©2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNA–protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA–protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA–protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA–protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA–protein interaction modes exhibit some similarity to specific DNA–protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Å from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA–protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein

    The Diamond STING Server.

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    Diamond STING is a new version of the STING suite of programs for a comprehensive analysis of a relationship between protein sequence, structure, function and stability. We have added a number of new functionalities by both providing more structure parameters to the STING Database and by improving/expanding the interface for enhanced data handling. The integration among the STING components has also been improved. A new key feature is the ability of the STING server to handle local files containing protein structures (either modeled or not yet deposited to the Protein Data Bank) so that they can be used by the principal STING components: JavaProtein Dossier (JPD) and STING Report. The current capabilities of the new STING version and a couple of biologically relevant applications are described here. We have provided an example where Diamond STING identifies the active site amino acids and folding essential amino acids (both previously determined by experiments) by filtering out all but those residues by selecting the numerical values/ranges for a set of corresponding parameters. This is the fundamental step toward a more interesting endeavor?the prediction of such residues. Diamond STING is freely accessible at http://sms.cbi.cnptia.embrapa.br and http://trantor.bioc.columbia.edu/SMS.Supplement

    Photometry of very bright stars with Kepler and K2 smear data

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    High-precision time series photometry with the Kepler satellite has been crucial to our understanding both of exoplanets, and via asteroseismology, of stellar physics. After the failure of two reaction wheels, the Kepler satellite has been repurposed as Kepler-2 (K2), observing fields close to the ecliptic plane. As these fields contain many more bright stars than the original Kepler field, K2 provides an unprecedented opportunity to study nearby objects amenable to detailed follow-up with ground-based instruments. Due to bandwidth constraints, only a small fraction of pixels can be downloaded, with the result that most bright stars which saturate the detector are not observed. We show that engineering data acquired for photometric calibration, consisting of collateral ‘smear’ measurements, can be used to reconstruct light curves for bright targets not otherwise observable with Kepler/K2. Here we present some examples from Kepler Quarter 6 and K2 Campaign 3, including the δ Scuti variables HD 178875 and 70 Aqr, and the red giant HR 8500 displaying solar-like oscillations. We compare aperture and smear photometry where possible, and also study targets not previously observed. These encouraging results suggest this new method can be applied to most Kepler and K2 fields

    Haunted Landscapes: Nature, Supernature and the Environment

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    The Haunted Landscapes Symposium was organised as a literary event by staff from the writing course at Falmouth University. The symposium included an exhibition of paintings, prints and photographs, curated and selected by Laurence North and Neil Mcleod. Artists selected to exhibit also presented papers within the symposium's academic panels

    The Diamond STING server

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    Diamond STING is a new version of the STING suite of programs for a comprehensive analysis of a relationship between protein sequence, structure, function and stability. We have added a number of new functionalities by both providing more structure parameters to the STING Database and by improving/expanding the interface for enhanced data handling. The integration among the STING components has also been improved. A new key feature is the ability of the STING server to handle local files containing protein structures (either modeled or not yet deposited to the Protein Data Bank) so that they can be used by the principal STING components: (Java)Protein Dossier ((J)PD) and STING Report. The current capabilities of the new STING version and a couple of biologically relevant applications are described here. We have provided an example where Diamond STING identifies the active site amino acids and folding essential amino acids (both previously determined by experiments) by filtering out all but those residues by selecting the numerical values/ranges for a set of corresponding parameters. This is the fundamental step toward a more interesting endeavor—the prediction of such residues. Diamond STING is freely accessible at and
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