In vitro and ex vivo inhibition of canine cyclooxygenase isoforms by robenacoxib: A comparative study

In vitro whole blood canine assays were used to quantify the inhibitory actions of the novel non-steroidal anti-inflammatory drug (NSAID) robenacoxib on the cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, in comparison with other drugs of the NSAID class. COX-1 activity was determined by measuring serum thromboxane (Tx)B₂ synthesis in blood samples allowed to clot at 37 °C for 1 h. COX-2 activity was determined by measuring prostaglandin (PG)E₂ synthesis in blood samples incubated at 37 °C for 24 h in the presence of lipopolysaccharide. The rank order of selectivity for inhibition of COX-2 versus COX-1 (IC₅₀ COX-1:IC₅₀ COX-2) for veterinary drugs was highest with robenacoxib (128.8) compared to deracoxib (48.5), nimesulide (29.2), S+ carprofen (17.6), meloxicam (7.3), etodolac (6.6), R? carprofen (5.8) and ketoprofen (0.88). Selectivity expressed as the clinically relevant ratio IC₂₀ COX-1:IC₈₀ COX-2 was highest for robenacoxib (19.8) compared to deracoxib (2.3), S+ carprofen (2.5), R? carprofen (2.1), nimesulide (1.8), etodolac (0.76), meloxicam (0.46) and ketoprofen (0.21).An in vivo pharmacokinetic ex vivo pharmacodynamic study in the dog established dosage and concentration–effect relationships for single oral doses of robenacoxib over the dosage range 0.5–8.0 mg/kg. Values of C_max and AUC were linearly related to dosage over the tested range. Robenacoxib did not inhibit serum TxB₂ synthesis (COX-1) ex vivo at dosages of 0.5–4.0 mg/kg and produced only transient inhibition (at the 1 h and 2 h sampling times) at the 8 mg/kg dosage. All dosages of robenacoxib (0.5–8 mg/kg) produced marked, significant and dose related inhibition of PGE₂ synthesis (COX-2) ex vivo.The data demonstrate that in the dog robenacoxib is a highly selective inhibitor of the COX-2 isoform of COX, and significantly inhibits COX-2 and spares COX-1 in vivo when administered orally over the dosage range 0.5–4.0 mg/kg.     

Bayesian Methods for Hierarchical Distance Sampling Models

The few distance sampling studies that use Bayesian methods typically consider only line transect sampling with a half-normal detection function. We present a Bayesian approach to analyse distance sampling data applicable to line and point transects, exact and interval distance data and any detection function possibly including covariates affecting detection probabilities. We use an integrated likelihood which combines the detection and density models. For the latter, densities are related to covariates in a log-linear mixed effect Poisson model which accommodates correlated counts. We use a Metropolis-Hastings algorithm for updating parameters and a reversible jump algorithm to include model selection for both the detection function and density models. The approach is applied to a large-scale experimental design study of northern bobwhite coveys where the interest was to assess the effect of establishing herbaceous buffers around agricultural fields in several states in the US on bird densities. Results were compared with those from an existing maximum likelihood approach that analyses the detection and density models in two stages. Both methods revealed an increase of covey densities on buffered fields. Our approach gave estimates with higher precision even though it does not condition on a known detection function for the density model.     

Treatment of dogs with oral melanoma by hypofractionated radiation therapy and platinum-based chemotherapy (1987-1997)

This retrospective study in 39 dogs with incompletely resected oral melanoma examined the efficacy of hypofractionated radiation therapy and platinum-containing chemotherapy. All dogs were completely staged, with the majority of dogs classified as stage 1. Dogs received 6 weekly fractions of 6-gray (Gy) megavoltage irradiation with a cobalt-60 unit or a 4-MeV (megaelectron volts) linear accelerator. Dogs received cisplatin (10-30 mg/m2 IV) or carboplatin (90 mg/m2 IV) chemotherapy 60 minutes before radiation delivery. Durations of local control, metastasis-free survival time, and overall survival time were recorded. By the Kaplan-Meier method, 15% of the dogs had local recurrence within a median time of 139 days. Fifty-one percent of the dogs developed metastatic disease within a median time of 311 days (range, 24-2, 163 days). Median survival time for all 39 dogs was 363 days. The combined use of chemotherapy and radiation therapy in this protocol provided local control consistent with previous studies. Low-dose chemotherapy was used with the intent of enhancing radiation therapy for the local control of an incompletely excised tumor. Survival times were longer than previously reported for dogs with oral malignant melanoma. Additional studies are required to determine whether these results were due to the effects of chemotherapy on microscopic disease or the enhanced local control provided by chemoradiation therapy.     

Optimisation of larval culture of the mussel <Emphasis Type="Italic">Mytilus</Emphasis><Emphasis Type="Italic">edulis</Emphasis> (L.)

The blue mussel Mytilus edulis is a commercially important species whose fishery and culture generally relies on natural spat collection. Hatchery-production could provide an alternative source of seed, enabling reliable expansion of the industry. Mussel spawning and larval rearing trials were carried out to optimise elements of hatchery production. Culturing fertilised eggs at low density (20–200 eggs cm⁻²) rather than high density (400–720 eggs cm⁻²) significantly improved the quality of first veliger larvae and differences in this improvement were evident between the eggs from different females (maternal effects). Veliger larval growth at 17 or 21°C was significantly faster than growth at 14°C. Feeding veliger larvae an identical total ration either daily or at 2–3 day intervals did not significantly affect their growth. Different microalgal diets (1: Isochrysis sp. (clone T-ISO), 2: Chaetoceros calcitrans forma pumilus, 3: C. muelleri, 4: mixed Isochrysis sp. (clone T-ISO) and C. calcitrans f. pumilus, and 5: mixed Isochrysis sp. (clone T-ISO) and C. muelleri) were tested on veliger larval growth and mixed diets outperformed single-species diets.     

Two-dimensional nanosheets produced by liquid exfoliation of layered materials

If they could be easily exfoliated, layered materials would become a diverse source of two-dimensional crystals whose properties would be useful in applications ranging from electronics to energy storage. We show that layered compounds such as MoS(2), WS(2), MoSe(2), MoTe(2), TaSe(2), NbSe(2), NiTe(2), BN, and Bi(2)Te(3) can be efficiently dispersed in common solvents and can be deposited as individual flakes or formed into films. Electron microscopy strongly suggests that the material is exfoliated into individual layers. By blending this material with suspensions of other nanomaterials or polymer solutions, we can prepare hybrid dispersions or composites, which can be cast into films. We show that WS(2) and MoS(2) effectively reinforce polymers, whereas WS(2)/carbon nanotube hybrid films have high conductivity, leading to promising thermoelectric properties.     

Cross-species identification of Mendel's I locus

A key gene involved in plant senescence, mutations of which partially disable chlorophyll catabolism and confer stay-green leaf and cotyledon phenotypes, has been identified in Pisum sativum, Arabidopsis thaliana, and Festuca pratensis by using classical and molecular genetics and comparative genomics. A stay-green locus in F. pratensis is syntenically equivalent to a similar stay-green locus on rice chromosome 9. Functional testing in Arabidopsis of a homolog of the rice candidate gene revealed (i) senescence-associated gene expression and (ii) a stay-green phenotype after RNA interference silencing. Genetic mapping in pea demonstrated cosegregation with the yellow/green cotyledon polymorphism (I/i) first reported by Gregor Mendel in 1866.     

Reselection of a Pearl Millet Cultivar Utilizing Residual Variability for Downy Mildew Reaction*

‘BJ 104’ was the most widely grown pearl millet hybrid in India until it became susceptible to downy mildew (DM) in 1984—85. Residual variability for resistance was found in both parental lines, 5141 B (maintainer of 5141 A) and J 104, and through four generations of pedigree selection under intense disease pressure in the DM nursery, two lines, IC-MA841 (from 5141 B) and ICMP 84814 (from J 104), were selected resulting in a reconstituted DM resistant hybrid (‘ICMH 84814’) which was equal in yield to the original ‘BJ 104’. The reconstituted hybrid, though phenotypically similar, can be distinguished from “BJ 104” being slightly taller, flowers later, has heavier heads, and 1000-seed weight, but tillers less. A similar exercise was attempted on Tifton 23 B, the female parent of the first widely grown hybrid (‘HB 3’— the male parent was also J 104), but no variability for resistance to DM was found.     

Evaluation of the hemagglutination-inhibition test for measuring the response of chickens to avian infectious bronchitis virus vaccination

An infectious bronchitis virus (IBV) hemagglutination-inhibition (HI) test was used to assay serum-antibody titers after IBV vaccination of IBV-susceptible specific-pathogen-free broilers and commercial layers. Three-week-old broilers were vaccinated via eye-drop with IBV strains that represent the antigenic spectrum of commercial vaccines--Holland, Massachusetts 41 (41 Ms), Connecticut 46, Florida 18288, or JMK strain--and revaccinated 3 weeks later with either the same or a heterologous strain. Weekly serum samples were tested by IBV HI with homologous and heterologous antigens. Vaccinates, except for those vaccinated with the Holland strain, were HI-positive with homologous but not heterologous antigens by 1 to 2 weeks postvaccination. Sixteen-week-old IBV-vaccinated commercial layers were revaccinated with IBV Holland 52 (H 52) strain and subsequently infected with Arkansas 99 (Ark 99) and SE 17 strains. In contrast to the limited HI cross-reactivity of serum from IBV-vaccinated broilers, there were extensive cross-reactions in HI tests with 41 Ms, H 52, Ark 99, and SE 17 antigens of revaccinated layers. These results demonstrate that the IBV HI test is more strain-specific than previous reports indicate, especially when the test samples are from early postvaccination.     

Evaluation of maternal parent and puroindoline allele on kernel texture in a reciprocal cross between two hard spring wheat cultivars

Kernel texture is an important characteristic for both the milling and the end-use quality of wheat (Triticum aestivum L.). Gene sequence variation and mutations to the two puroindoline genes (Pina and Pinb), located at the Ha locus on chromosome 5DS, account for the majority of variation in wheat kernel texture. Other factors also influence kernel texture, including effects associated with different maternal parent backgrounds. To investigate the effect of two hard puroindoline alleles in different maternal backgrounds, a population of 228 recombinant inbred lines (RILs) derived from a reciprocal cross between two wheat cultivars ID377s (Pina-D1b/Pinb-D1a) and Klasic (Pina-D1a/Pinb-D1b) were examined in two succeeding generations (F₇ & F₈). Kernel texture was determined using the Single Kernel Characterization System (SKCS) and the RIL puroindoline haplotype was identified by the sequence-specific PCR amplification of each gene. Analysis of variance identified a significant (P 0.001) effect of the maternal parent and puroindoline mutation on kernel texture. RILs containing the Pina-D1b mutation were significantly harder than lines containing the Pinb-D1b mutation. RILs which had Klasic as the maternal parent were significantly harder than those which had ID377s as the maternal parent. When the maternal parent and puroindoline allele were analyzed in combination, RILs derived from Klasic as the maternal parent and the Pina-D1b allele were significantly harder (P 0.001) than those containing the same allele but ID377s as the maternal parent. The same occurred for RILs containing the Pinb-D1b allele, lines with Klasic as the maternal parent were harder than lines with ID377s as the maternal parent. These results corroborate the harder phenotype of the Pina-D1b allele and indicate a significant maternally-inherited contribution to kernel texture variation.     

Double haploids,markers and QTL analysis in vegetable brassicas

Double haploid (DH) plants of Brassica spp. can be produced via anther culture or culture of microspores. This paper reviews the uses of double haploids in crop improvement research in vegetable brassicas (B. oleracea). Applications of DH lines are described for breeding; construction of linkage maps; genetic analysis of quantitative traits and capturing genetic variation. The advantages and disadvantages of DH lines are discussed