A topographic map of recruitment in spinal cord.

Animals move over a range of speeds by using rhythmic networks of neurons located in the spinal cord. Here we use electrophysiology and in vivo imaging in larval zebrafish (Danio rerio) to reveal a systematic relationship between the location of a spinal neuron and the minimal swimming frequency at which the neuron is active. Ventral motor neurons and excitatory interneurons are rhythmically active at the lowest swimming frequencies, with increasingly more dorsal excitatory neurons engaged as swimming frequency rises.

Sample size calculation for the Power Model for dose proportionality studies.

There are several approaches to assess or demonstrate pharmacokinetic dose proportionality. One statistical method is the traditional ANOVA model, where dose proportionality is evaluated using the bioequivalence limits. A more informative method is the mixed effects Power Model, where dose proportionality is assessed using a decision rule for the estimated slope.

Differential effects of exposure to low-light or high-light open-field on anxiety-related behaviors: relationship to c-Fos expression in serotonergic and non-serotonergic neurons in the dorsal raphe nucleus.

Serotonergic systems arising from the mid-rostrocaudal and caudal dorsal raphe nucleus (DR) have been implicated in the facilitation of anxiety-related behavioral responses to anxiogenic drugs or aversive stimuli. In this study we attempted to determine a threshold to engage serotonergic neurons in the DR following exposure to aversive conditions in an anxiety-related behavioral test. We manipulated the intensity of anxiogenic stimuli in studies of male Wistar rats by leaving them undisturbed (CO), briefly handling them (HA), or exposing them to an open-field arena for 15-min under low-light (LL: 8-13 lx) or high-light (HL: 400-500 lx) conditions.

Simple sequence repeats in zebra finch (Taeniopygia guttata) expressed sequence tags: a new resource for evolutionary genetic studies of passerines.

Background: Passerines (perching birds) are widely studied across many biological disciplines including ecology, population biology, neurobiology, behavioural ecology and evolutionary biology. However, understanding the molecular basis of relevant traits is hampered by the paucity of passerine genomics tools. Efforts to address this problem are underway, and the zebra finch (Taeniopygia guttata) will be the first passerine to have its genome sequenced.

Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors.

The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.

Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension.

Clinical and animal studies indicate that intrauterine growth restriction (IUGR) following uteroplacental insufficiency (UPI) reduces nephron number and predisposes toward renal insufficiency early in life and increased risk of adult-onset hypertension. In this study, we hypothesized that the inducible enzyme cyclooxygenase-2 (COX-2), a pivotal protein in nephrogenesis, constitutes a mechanism through which UPI and subsequent glucocorticoid overexposure can decrease nephron number. We further hypothesized that UPI downregulates the key enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which converts corticosterone to inert 11-dehydrocorticosterone, thereby protecting both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) from the actions of corticosterone.

Polyinosinic:polycytidylic acid induces memory processing deficits in the day-old chick.

Anecdotal and experimental evidence has demonstrated that humans and animals exhibit physiological and cognitive alterations in response to sickness and injury. It is now clear that these changes are due to the actions of proinflammatory cytokines. The current study examined the effects of peripheral administration of polyinosinic:polycytidylic acid, a synthetic double-stranded viral RNA, on the memory processes of day-old chicks trained on a single trial passive avoidance task.

Grading movement strength by changes in firing intensity versus recruitment of spinal interneurons.

Animals can produce movements of widely varying speed and strength by changing the recruitment of motoneurons according to the well-known size principle. Much less is known about patterns of recruitment in the spinal interneurons that control motoneurons because of the difficulties of monitoring activity simultaneously in multiple interneurons of an identified class. Here we use electrophysiology in combination with in vivo calcium imaging of groups of identified excitatory spinal interneurons in larval zebrafish to explore how they are recruited during different forms of the escape response that fish use to avoid predators.

Antibodies against six human herpesviruses in relation to seven cancers in black South Africans: a case control study.

Background: Infections with certain human herpesviruses have been established as risk factors for some cancer types. For example, Epstein-Barr Virus is considered a cause of Burkitt's lymphoma and other immunosuppression related lymphomas, Hodgkin lymphoma, and nasopharyngeal cancer. Several other human herpesviruses have been linked to cancers but the totality of evidence is inconclusive.

Efficacy and safety of OPANA ER (oxymorphone extended release) for relief of moderate to severe chronic low back pain in opioid-experienced patients: a 12-week, randomized, double-blind, placebo-controlled study.

Unlabelled: Opioid-experienced (N = 250) patients with chronic, moderate to severe low back pain (LBP) were converted from their prestudy opioid(s) to an approximately equianalgesic dose of OPANA ER (oxymorphone extended release). Patients continued slow titration, with 56% stabilized within 1 month to a dose of OPANA ER that reduced average pain to <40 mm on a visual analog scale with good tolerability. Stabilized patients (n = 143) were randomized to placebo or their stabilized dose of OPANA ER every 12 hours for a 12-week double-blind period.

Combining estimates from multiple early studies to obtain estimates of response: using shrinkage estimates to obtain estimates of response.

Development of anti-cancer therapies usually involve small to moderate size studies to provide initial estimates of response rates before initiating larger studies to better quantify response. These early trials often each contain a single tumor type, possibly using other stratification factors. Response rate for a given tumor type is routinely reported as the percentage of patients meeting a clinical criteria (e.

Exposure to high- and low-light conditions in an open-field test of anxiety increases c-Fos expression in specific subdivisions of the rat basolateral amygdaloid complex.

Anxiety states and anxiety-related behaviors appear to be regulated by a distributed and highly interconnected system of forebrain structures including the basolateral amygdaloid complex (basolateral amygdala). Despite a wealth of research examining the role of the basolateral amygdala in anxiety-related behaviors and anxiety states, the specific subdivisions of the basolateral amygdala that are involved in responses to anxiogenic stimuli have not been examined. In this study, we investigated the effects of exposure to a novel open-field environment, with either low- or high-levels of illumination, on expression of the protein product of the immediate-early gene c-Fos in subdivisions of the rat basolateral amygdala.

Pectoral fin coordination and gait transitions in steadily swimming juvenile reef fishes.

A common feature of animal locomotion is its organization into gaits with distinct patterns of movement and propulsor use for specific speeds. In terrestrial vertebrates, limb gaits have been extensively studied in diverse taxa and gait transitions have been shown to provide efficient locomotion across a wide range of speeds. In contrast, examination of gaits in fishes has focused on axial gaits and the transition between synchronous paired fin locomotion and axial propulsion.

Uteroplacental insufficiency increases p53 phosphorylation without triggering the p53-MDM2 functional circuit response in the IUGR rat kidney.

Uteroplacental insufficiency (UPI) leads to intrauterine growth restriction (IUGR), which predisposes infants toward renal insufficiency early in life and increases the risk of kidney-related adult morbidities, such as hypertension. This compromised in utero environment has been demonstrated to impair nephrogenesis, as evidenced by a reduced nephron endowment in humans and in rats rendered IUGR by UPI. Concordantly, we have observed that IUGR rats have increased kidney p53 protein levels associated with increased apoptosis.

Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race.

Interferon (IFN)-alpha-based therapy for chronic hepatitis C is effective in fewer than 50% of all treated patients, with a substantially lower response rate in black patients. The goal of this study was to investigate the underlying host transcriptional response associated with interferon treatment outcomes. We collected peripheral blood mononuclear cells from chronic hepatitis C patients before initiation of IFN-alpha therapy and incubated the cells with or without IFN-alpha for 6 hours, followed by microarray assay to identify IFN-induced gene transcription.

Comment on "Nature of phosphorus limitation in the ultraoligotrophic eastern Mediterranean".

Thingstad et al. (Reports, 12 August 2005, p. 1068) reported that in situ mesoscale phosphorus enrichment of the eastern Mediterranean Sea altered selected biological parameters and concluded that the added phosphorus was rapidly transferred from bacteria to mesozooplankton.

Phospho-specific flow cytometry: intersection of immunology and biochemistry at the single-cell level.

Striving to achieve greater clinical relevance, researchers in basic science and in drug discovery are transitioning from biochemical investigations using cell lines to technologies that garner mechanistic information from primary patient material. Such studies can be broad in scope, despite limited sample material and cell-type heterogeneity. The development of flow cytometry for following intracellular signaling has met some of these demands and opened new avenues for mechanistic exploration.

A predicted microsatellite map of the passerine genome based on chicken-passerine sequence similarity.

Abstract We present a predicted passerine genome map consisting of 196 microsatellite markers distributed across 25 chromosomes. The map was constructed by assigning chromosomal locations based on the sequence similarity between 550 publicly available passerine microsatellites and the draft chicken genome sequence published by the International Chicken Genome Sequencing Consortium. We compared this passerine microsatellite map with a recently published great reed warbler (Acrocephalus arundinaceus) linkage map derived from the segregation of marker alleles in a pedigree of a natural population.

Correlations between heterozygosity and measures of genetic similarity: implications for understanding mate choice.

There is currently considerable interest in testing the effects of genetic compatibility and heterozygosity on animal mate preferences. Evidence for either effect is rapidly accumulating, although results are not always clear-cut. However, correlations between mating preferences and either genetic similarity or heterozygosity are usually tested independently, and the possibility that similarity and heterozygosity may be confounded has rarely been taken into account.

Pathways of Mycobacterium ulcerans infection: a review.

Buruli ulcer (BU), an often-deforming skin ulceration caused by Mycobacterium ulcerans (MU), is now considered by the World Health Organization to be the third most common mycobacterium infection. However, the reservoir of MU in the environment and the epidemiology of BU are poorly understood. The disease is prevalent in riverine, slow-flowing and swampy areas of several tropical and subtropical regions of the world, especially in West Africa where the disease is rapidly increasing in incidence.

Electrode independent chemoresistive response for cobalt phthalocyanine in the space charge limited conductivity regime.

The electrical properties of 50 nm thick metallophthalocyanine films, prepared by organic molecular beam epitaxy (OMBE) on interdigitated electrodes, were studied with DC current-voltage measurements and impedance spectroscopy. The transition from Ohmic behavior at low voltages to space-charge-limited conductivity (SCLC) at higher voltages depends on the metal electrode (Pt, Pd, and Au), but does not correlate with the work function of the electrode. Impedance spectroscopy studies show the coexistence of low- and high-frequency traps in the thin film devices, and the contribution of low-frequency traps associated with Ohmic behavior diminishes at higher bias.

Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385.

A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385.

Polyarteritis nodosa presenting with a leg mass.

Unlabelled: We report an unusual presentation of polyarteritis nodosa in a 2-y-old child. The child presented with a mass of the left leg adjacent to the calf, and the biopsy showed polyarteritis nodosa. Further investigations confirmed systemic features, and X-rays showed a periosteal reaction.

High degree of conservation of nuclear microsatellite loci in the genus Clusia.

In plants, microsatellites and their flanking DNA are rarely conserved across a whole genus, let alone other genera in the same family. Therefore, the possibility of using microsatellite primers developed for a species across a large number of plant species in the same genus is often limited. Remarkably, dinucleotide nuclear microsatellites developed for Clusia minor and for Clusia nemorosa amplified homologous microsatellites in species across the whole genus Clusia.