Quantitative trait locus mapping and functional genomics of an organophosphate resistance trait in the western corn rootworm, Diabrotica virgifera virgifera.

The western corn rootworm, Diabrotica virgifera virgifera, is an insect pest of corn and population suppression with chemical insecticides is an important management tool. Traits conferring organophosphate insecticide resistance have increased in frequency amongst D. v. virgifera populations, resulting in the reduced efficacy in many corn-growing regions of the USA. We used comparative functional genomic and quantitative trait locus (QTL) mapping approaches to investigate the genetic basis of D. v. virgifera resistance to the organophosphate methyl-parathion. RNA from adult methyl-parathion resistant and susceptible adults was hybridized to 8331 microarray probes. The results predicted that 11 transcripts were significantly up-regulated in resistant phenotypes, with the most significant (fold increases ≥ 2.43) being an α-esterase-like transcript. Differential expression was validated only for the α-esterase (ST020027A20C03), with 11- to 13-fold greater expression in methyl-parathion resistant adults (P < 0.05). Progeny with a segregating methyl-parathion resistance trait were obtained from a reciprocal backcross design. QTL analyses of high-throughput single nucleotide polymorphism genotype data predicted involvement of a single genome interval. These data suggest that a specific carboyxesterase may function in field-evolved corn rootworm resistance to organophosphates, even though direct linkage between the QTL and this locus could not be established.

Novel time-temperature and 'consume-within' indicator based on gas-diffusion.

The novel time-temperature indicator label comprises an ammonia sensitive indicator layer film pressed onto a second film, comprising an ammonia-generating, adhesive layer. When separated the blue-coloured indicator film reverts back to its original (ammonia free) yellow form at a controllable, temperature dependant rate. The labels are easily made and stored.

AFLP-based genetic linkage map of the Colorado potato beetle Leptinotarsa decemlineata: sex chromosomes and a pyrethroid-resistance candidate gene.

A genetic linkage map was constructed from an intraspecific cross of the Colorado potato beetle, Leptinotarsa decemlineata. This is an initial step toward mapping the loci that underlie important phenotypes associated with insect adaptation to an agroecosystem. The map was made with 172 AFLP and 10 anonymous codominant markers segregating among 74 backcross (BC(1)) individuals. Markers were mapped to 18 linkage groups and a subset of the markers with a mean intermarker distance of 11.1 cM is presented. A pyrethroid-resistance candidate gene, LdVssc1, was placed onto the map as well. The sex chromosome was identified by exploiting the XO nature of sex determination in this species using patterns of variation at LdVssc1 and the codominant markers.

Genetic Mapping in Saccharomyces IV. Mapping of Temperature-Sensitive Genes and Use of Disomic Strains in Localizing Genes.

Through use of tetrad, random spore, trisomic, and mitotic analysis procedures a large number of genes, including 48 new genetic markers, were studied for their locations on the genetic maps of the yeast Saccharomyces cerevisiae. Eighteen new centromere linked genes were discovered and all but one was located on various ones of the 16 previously-established chromosomes. Five fragments of linked genes were also assigned to chromosomes; four were located on known chromosomes while the fifth determined one arm of a new chromosome. The experiments indicate that seventeen is likely to be the haploid chromosome number in this yeast. Most chromosomes have been established by genetic means to be metacentric and their genetic lengths vary from 5 cM to approximately 400 cM. Functionally-related sets of genes generally were found to be dispersed over the genome.

UGA mutations and UGA suppressors in yeast.

Eight UGA alleles have been obtained in S. cerevisiae. Two UGA alleles, ade5,7-143 and gal10-1, were isolated as forward mutations from wildtype. Six UGA alleles, arg4-2' (UGA), his5-2' (UGA), ilv3-1' (UGA), leu2'1' (UGA), lys1-1' (UGA), and asp5-1' (UGA), were derived from UAA alleles by selecting from revertants in the presence of UGA suppressors. With these 8 UGA alleles, two classes of UGA-specific suppressors can be distinguished. Suppressors in one class act upon all 8 allelqs ; while suppressors in the second class act upon all but 3 alleles : ade5,7-143, arg4-2' (UGA), and gal10-1.

Electromyographic study of the anterior cruciate ligament-hamstrings synergy during isometric knee extension.

The purpose of this investigation was to determine the role the hamstrings group may play in augmenting passive articular mechanisms during activity in which anterior drawer force may detrimentally affect the anterior cruciate ligament (ACL). Nine male subjects performed non-weight-bearing isometric knee extension at 10% increments of maximum voluntary contraction (MVC). Electromyographic (EMG) signals were detected and recorded from the vastus lateralis, vastus medialis oblique, vastus medialis longus, and the long head of the biceps femoris. The EMG signals were rectified and integrated over 1000 ms and normalized to subject-specific values. The data were subjected to a repeated-measures analysis of variance. The results demonstrated that expected significant increases in quadriceps excitation accompanied increases in knee extensor torque. Hamstrings excitation was not found to change significantly (total change = 3.4%). It was concluded that functionally adequate knees do not require posterior drawer force in excess of that provided passively by articular structures.

Conditions of isokinetic knee flexion that enhance isokinetic knee extension.

The results of two experiments are reported. The purpose of the initial investigation was to determine the effect of isokinetic knee flexion contraction intensity on subsequent knee extension contraction. Seven subjects performed ten isokinetic knee flexion-extension cycles at six isokinetic velocities under two antagonist contraction conditions. In the first condition, isokinetic knee flexion and extension were speed-matched, and, in the second condition, the high-speed condition, knee flexion was 7.85 rad.s-1 irrespective of knee extension velocity, which ranged from 0.52 to 7.85 rad.s-1. Significantly greater isokinetic knee extension measures were observed at low isokinetic velocities and were associated with the high-speed contraction condition. Enhancement of the knee extension contraction was in the initial work phase of the isokinetic contraction. The second experiment was conducted to determine whether the enhancement of the initial work phase could be associated, in part, with passive elastic qualities of the involved musculature. In this study the range of motion for the knee involved musculature. In this study the range of motion for the knee extension-flexion cycles was reduced from the previous 2.01 rad to 1.57 rad. Two isokinetic knee extension velocities were studied (1.57 and 7.85 rad.s-1) under five conditions: initiated from rest, initiated from isometric knee flexion MVC, and with preceding isokinetic knee flexion at 0.52, 4.19, and 7.85 rad.s-1. The hypothesis that knee extension contraction measures would not increase was supported. Based upon the results of the two experiments, it is suggested that the increases in knee extension contraction measures observed in the first experiment are at least partially mediated by the contribution to net torque by passive elastic musculotendinous elements. Further study of this phenomenon with the inclusion of electromyographic measures will allow determination of the presence and contribution of increased neural drive.

Determination of BMS-186318 in dog, rat and monkey plasma by liquid chromatography-ionspray mass spectrometry.

BMS-186318 is a member of the recently discovered "aminodiol" class of HIV protease inhibitors. A simple but sensitive method was developed for the determination of BMS-186318 in dog plasma and then applied to monkey and rat plasma. The compound was extracted from dog plasma with methyl tert-butyl ether at basic pH. The dried extract was reconstituted in mobile phase and injected into a 150 x 2.1 mm i.d. Zorbax Rx-C18 HPLC column. A portion of the effluent was directed into the LC-ionspray MS system, where the [M+H]+ ion of the secondary amine compound was monitored. The HPLC conditions were chosen in order to achieve a short run time and large sample throughput, with both analyte and internal standard eluting within 1.5 min. The liquid-liquid extraction procedure provided very clean extracts so that sufficient signal-to-noise ratio was obtained with single-stage mass spectrometry instead of the more costly tandem mass spectrometry. The required lower limit of quantitation of 2.5 ng ml-1 was easily achieved. The method has also been validated for BMS-186318 in monkey plasma without modification. The method has been modified for rat plasma. Owing to irreproducibility observed when applying the liquid-liquid extraction method to rat plasma, a solid-phase extraction method was developed. The addition of phenylmethylsulfonyl fluoride was necessary to stabilize BMS-186318 in rat blood and plasma.

Are science and caring compatible?

Scientific progress has led us to believe we are masters of our destiny and in control of our world. But, science and technology can destroy our humanity if they serve no higher power than their own advancement. We can be overwhelmed by a surplus of information that clouds our thoughts and hinders us as we try to find true meaning and purpose in our lives.

Leadership 99. Interview by Terese Hudson.

Cost control, customer service and collaboration among health care sectors rank as top concerns with panelists in H&HN's annual Leadership Report. Efforts to improve community health are a priority, too, but are often frustrated by financial and other constraints. The 16 panelists represent managed care, physicians, and hospitals and health systems.

Randomized, placebo-controlled single-ascending-dose study to evaluate the safety, tolerability and pharmacokinetics of the HIV nucleoside reverse transcriptase inhibitor, BMS-986001, in healthy subjects.

The objectives of this study were to evaluate the safety, tolerability and pharmacokinetics (PK) of BMS-986001 as a single oral dose in healthy male subjects. Sixty-four healthy male subjects were randomized to receive a single dose of BMS-986001 or placebo in this single-blind, placebo-controlled, sequential ascending-dose study. There were eight treatment groups (10, 30, 100, 300, 600, and 900 mg fed; and 100 and 300 mg fasted) of eight subjects each (BMS-986001 n = 6/placebo n = 2). BMS-986001 was well tolerated, with no serious adverse events (AEs), deaths, or discontinuations due to AEs reported. AEs were experienced by 14.6% of subjects receiving BMS-986001; however, these did not appear to be dose related and were not considered to be related to study drug. BMS-986001 was rapidly absorbed and exhibited a linear dose-exposure relationship across the dose range studied. PK appeared similar whether administered with or without food. Administration of BMS-986001 as a single dose was generally safe and well tolerated. A linear dose-exposure relationship was seen across all doses studied, with no apparent food effect. Further clinical development is warranted.

Feeding mode and prey detectability half-lives in molecular gut-content analysis: an example with two predators of the Colorado potato beetle.

The time during which prey remains are detectable in the gut of a predator is an important consideration in the interpretation of molecular gut-content data, because predators with longer detectability times may appear on the basis of unweighted data to be disproportionately important agents of prey population suppression. The rate of decay in detectability, typically expressed as the half-life, depends on many variables; one that has not been explicitly examined is the manner in which the predator processes prey items. The influence of differences in feeding mode and digestive physiology on the half-life of DNA for a single prey species, the Colorado potato beetle Leptinotarsa decemlineata (Say), is examined in two predators that differ dramatically in these attributes: the pink ladybeetle, Coleomegilla maculata (DeGeer), which feeds by chewing and then ingesting the macerated material into the gut for digestion; and the spined soldier bug, Podisus maculiventris (Say), which physically and enzymatically processes the prey extra-orally before ingestion and further digestion in the gut. In order to standardize the amount of DNA consumed per predator, a single L. decemlineata egg was used as the prey item; all predators were third instars. The PCR assay yields estimated prey DNA half-lives, for animals maintained under field temperatures, of 7.0 h in C. maculata and 50.9 h in P. maculiventris. The difference in the prey DNA half-lives from these two predators underscores the need to determine detectabilities from assemblages of predators differing in feeding mode and digestive physiology, in order to weight positives properly, and hence determine the predators' relative impacts on prey population suppression.

Does nursing theory adequately prepare psychiatric nurses to work with delusional patients?

The theory and practice of psychiatric nursing has been subjected to little serious research; consequently some nursing interventions recommended by nursing texts lack formal evaluation. This study examined one aspect of practice: the way in which nurses work with delusional patients. Registered psychiatric nurses were asked to describe the way in which they deal with patients whose delusions are a major clinical problem. The findings highlight a disparity between practice and theory.