2,304 research outputs found
Comparative transcriptomic assessment of the chemosensory receptor repertoire of Drosophila suzukii adult and larval olfactory organs
The spotted wing Drosophila, Drosophila suzukii, has emerged within the past decade as an invasive species on a global scale, and is one of the most economically important pests in fruit and berry production in Europe and North America. Insect ecology, to a strong degree, depends on the chemosensory modalities of smell and taste. Extensive research on the sensory receptors of the olfactory and gustatory systems in Drosophila melanogaster provide an excellent frame of reference to better understand the fundamentals of the chemosensory systems of D. suzukii. This knowledge may enhance the development of semiochemicals for sustainable management of D. suzukii, which is urgently needed. Here, using a transcriptomic approach we report the chemosensory receptor expression profiles in D. suzukii female and male antennae, and for the first time, in larval heads including the dorsal organ that houses larval olfactory sensory neurons. In D. suzukii adults, we generally observed a lack of sexually dimorphic expression levels in male and female antennae. While there was generally conservation of antennal expression of odorant and ionotropic receptor orthologues for D. melanogaster and D. suzukii, gustatory receptors showed more distinct species-specific profiles. In larval head tissues, for all three receptor gene fam-ilies, there was also a greater degree of species-specific gene expression patterns. Analysis of chemosensory re-ceptor repertoires in the pest species, D. suzukii relative to those of the genetic model D. melanogaster enables comparative studies of the chemosensory, physiology, and ecology of D. suzukii
A frameshift mutation and alternate splicing in human brain generate a functional form of the pseudogene cytochrome P4502D7 that bemethylates codeine to morphine
A frameshift mutation 138delT generates an open reading frame in the pseudogene, cytochrome P4502D7 (CYP2D7), and an alternate spliced functional transcript of CYP2D7 containing partial inclusion of intron 6 was identified in human brain but not in liver or kidney from the same individual. mRNA and protein of the brain variant CYP2D7 were detected in 6 of 12 human autopsy brains. Genotyping revealed the presence of the frameshift mutation 138delT only in those human subjects who expressed the brain variant CYP2D7. Genomic DNA analysis in normal volunteers revealed the presence of functional CYP2D7 in 4 of 8 individuals. In liver, the major organ involved in drug metabolism, a minor metabolic pathway mediated by CYP2D6 metabolizes codeine (pro-drug) to morphine (active drug), whereas norcodeine is the major metabolite. In contrast, when expressed in Neuro2a cells, brain variant CYP2D7 metabolized codeine to morphine with greater efficiency compared with the corresponding activity in cells expressing CYP2D6. Morphine binds to μ-opioid receptors in certain regions of the central nervous system, such as periaqueductal gray, and produces pain relief. The brain variant CYP2D7 and μ-opioid receptor colocalize in neurons of the periaqueductal gray area in human brain, indicating that metabolism of codeine to morphine could occur at the site of opioid action. Histio-specific isoforms of P450 generated by alternate splicing, which mediate selective metabolism of pro-drugs within tissues, particularly the brain, to generate active drugs may play an important role in drug action and provide newer insights into the genetics of metabolism
Taking movement data to new depths : Inferring prey availability and patch profitability from seabird foraging behavior
Funded byNatural Environment Research Council. Grant Number: NE/K007440/1 and Marine Scotland Science and Seabird Tracking and Research (STAR) Project led by the Royal Society for the Protection of Birds (RSPB)Peer reviewedPublisher PD
A randomised controlled trial of succinylated gelatin (4%) fluid on urinary acute kidney injury biomarkers in cardiac surgical patients
Background
Fluid resuscitation is frequently required for cardiac surgical patients admitted to the intensive care unit. The ideal fluid of choice in regard to efficacy and safety remains uncertain. Compared with crystalloid fluid, colloid fluid may result in less positive fluid balance. However, some synthetic colloids are associated with increased risk of acute kidney injury (AKI). This study compared the effects of succinylated gelatin (4%) (GEL) with compound sodium lactate (CSL) on urinary AKI biomarkers in patients after cardiac surgery.
Methods
Cardiac surgical patients who required an intravenous fluid bolus of at least 500 mL postoperatively were randomly allocated to receive GEL or CSL as the resuscitation fluid of choice for the subsequent 24 h. Primary outcomes were serial urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C concentrations measured at baseline, 1 h, 5 h and 24 h after enrolment, with higher concentrations indicating greater kidney injury. Secondary biomarker outcomes included urinary clusterin, α1-microglobulin and F2-isoprostanes concentrations. Differences in change of biomarker concentration between the two groups over time were compared with mixed-effects regression models. Statistical significance was set at P < 0.05.
Results
Forty cardiac surgical patients (n = 20 per group) with similar baseline characteristics were included. There was no significant difference in the median volume of fluid boluses administered over 24 h between the GEL (1250 mL, Q1–Q3 500–1750) and CSL group (1000 mL, Q1–Q3 500–1375) (P = 0.42). There was a significantly greater increase in urinary cystatin C (P < 0.001), clusterin (P < 0.001), α1-microglobulin (P < 0.001) and F2-isoprostanes (P = 0.020) concentrations over time in the GEL group, compared to the CSL group. Change in urinary NGAL concentration (P = 0.68) over time was not significantly different between the groups. The results were not modified by adjustment for either urinary osmolality or EuroSCORE II predicted risk of mortality.
Conclusions
This preliminary randomised controlled trial showed that use of succinylated gelatin (4%) for fluid resuscitation after cardiac surgery was associated with increased biomarker concentrations of renal tubular injury and dysfunction, compared to crystalloid fluid. These results generate concern that use of intravenous gelatin fluid may contribute to clinically relevant postoperative AKI
\u3ci\u3eDe novo\u3c/i\u3e Whole Genome Assembly of the Swede Midge (\u3ci\u3eContarinia nasturtii\u3c/i\u3e), a Specialist of Brassicaceae, Using Linked-Read Sequencing
The swede midge, Contarinia nasturtii, is a cecidomyiid fly that feeds specifically on plants within the Brassicaceae. Plants in this family employ a glucosinolate-myrosinase defense system, which can be highly toxic to non-specialist feeders. Feeding by C. nasturtii larvae induces gall formation, which can cause substantial yield losses thus making it a significant agricultural pest. A lack of genomic resources, in particular a reference genome, has limited deciphering the mechanisms underlying glucosinolate tolerance in C. nasturtii, which is of particular importance for managing this species. Here, we present an annotated, scaffolded reference genome of C. nasturtii using linked-read sequencing from a single individual and explore systems involved in glucosinolate detoxification. The C. nasturtii genome is similar in size and annotation completeness to that of the Hessian fly, Mayetiola destructor, but has greater contiguity. Several genes encoding enzymes involved in glucosinolate detoxification in other insect pests, including myrosinases, sulfatases, and glutathione S-transferases, were found, suggesting that C. nasturtii has developed similar strategies for feeding on Brassicaceae. The C. nasturtii genome will, therefore, be integral to continued research on plant-insect interactions in this system and contribute to effective pest management strategies
Relativistic Landau resonances
The possible interactions between plasma waves and relativistic charged particles are considered. An electromagnetic perturbation in the plasma is formulated as an elliptically polarized wave, and the collisionless plasma is described by a distribution in phase space, which is realized in cylindrical coordinates. The linearized Vlasov equation is solved in the semi-relativistic limit, to obtain the distribution function in the rest frame of the observer. The perturbed currents supported by the ionized medium are then calculated, so that an expression can be written for the total amount of energy available for transfer through the Landau mechanism. It is found that only certain modes of the perturbed current are available for this energy transfer. The final expressions are presented in terms of Stokes parameters, and applied to the special cases of a thermal as well as a nonthermal plasma. The thermal plasma is described by a Maxwellian distribution, while two nonthermal distributions are considered: the kappa distribution and a generalized Weibull distribution
Lattice QCD at finite T and \mu
Recent results of lattice QCD at finite temperature and density are reviewed.
At vanishing density the transition temperature, the equation of state and
hadron properties are discussed both for the pure gauge theory and for
dynamical staggered, Wilson and overlap fermions. The second part deals with
finite density. There are recent results for full QCD at finite temperature and
moderate density, while at larger densities QCD-like models are studied.Comment: 14 pages, 19 figures, lattice2003(plenary). Minor correction
Designed oligomers of cyanovirin-N show enhanced HIV neutralization
Cyanovirin-N (CV-N) is a small, cyanobacterial lectin that neutralizes many enveloped viruses, including human immunodeficiency virus type I (HIV-1). This antiviral activity is attributed to two homologous carbohydrate binding sites that specifically bind high mannose glycosylation present on envelope glycoproteins such as HIV-1 gp120. We created obligate CV-N oligomers to determine whether increasing the number of binding sites has an effect on viral neutralization. A tandem repeat of two CV-N molecules (CVN_2) increased HIV-1 neutralization activity by up to 18-fold compared to wild-type CV-N. In addition, the CVN_2 variants showed extensive cross-clade reactivity and were often more potent than broadly neutralizing anti-HIV antibodies. The improvement in activity and broad cross-strain HIV neutralization exhibited by these molecules holds promise for the future therapeutic utility of these and other engineered CV-N variants
Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin
Background:
Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties.
Methodology/Results:
The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface.
Conclusion:
Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1
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