Identification and validation of candidate Myb target genes

While a considerable number of candidate Myb target genes have been reported to date, most of these are likely to play little or no role in transformation by myb oncogenes. Here we have used a conditionally myb-transformed myeloid cell line (ERMYB) to further examine Myb regulation of one candidate target gene-c-myc-that has the potential to affect cell proliferation. It was found that the major influence on c-myc expression was the presence of cytokine (GM-CSF) rather than Myb activity. We also describe the application of PCR-based subtractive hybridization and low-density cDNA array screening, in conjunction with the ERMYB line, to the identification of additional Myb target genes. Preliminary identification of a number of candidates is reported; these include myeloperoxidase, which is known to have essential Myb-binding sites in its regulatory region. (C) 2001 Academic Press.

A medial to lateral shift in pre-movement cortical activity in hemi-Parkinson's disease

Objective: Recent evidence suggests that cortical activity associated with voluntary movement is relatively shifted from medial to lateral premotor areas in Parkinson's disease. This shift occurs bilaterally even for unilateral responses. It is not clear whether the shift in processing reflects an overall change in movement strategy, thereby involving alternate cortical areas, or reflects a compensatory change whereby, given the appropriate conditions, less impaired cortical areas are able to provide a similar function in compensation for those areas which are more impaired. This issue was examined in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. Methods: Fourteen patients with hemi-Parkinson's disease and 15 age-matched control subjects performed a Go/NoGo finger movement task and the contingent negative variation (CNV) was recorded from 21 scalp positions. Results and conclusions: Maximal CNV amplitudes were found over central medial regions for control subjects, but were shifted more frontally for Parkinson's disease patients, reduced in amplitude over the midline and lateralized towards the side ipsilateral to the greatest basal ganglia impairment. This shift in cortical activity from medial to lateral areas in Parkinson's disease patients appears to reflect a compensatory mechanism operating predominantly on the side of greatest basal ganglia impairment. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Movement-related potentials in Huntington's disease: movement preparation and execution

Movement-related potentials (MRPs) reflect increasing cortical activity related to the preparation and execution of voluntary movement. Execution and preparatory components may be separated by comparing MRPs recorded from actual and imagined movement. Imagined movement initiates preparatory processes, but not motor execution activity. MRPs are maximal over the supplementary motor area (SMA), an area of the cortex involved in the planning and preparation of movement. The SMA receives input from the basal ganglia, which are affected in Huntington's disease (HD), a hyperkinetic movement disorder. In order to further elucidate the effects of the disorder upon the cortical activity relating to movement, MRPs were recorded from ten HD patients, and ten age-matched controls, whilst they performed and imagined performing a sequential button-pressing task. HD patients produced MRPs of significantly reduced size both for performed and imagined movement. The component relating to movement execution was obtained by subtracting the MRP for imagined movement from the MRP for performed movement, and was found to be normal in HD. The movement preparation component was found by subtracting the MRP found for a control condition of watching the visual cues from the MRP for imagined movement. This preparation component in HD was reduced in early slope, peak amplitude, and post-peak slope. This study therefore reported abnormal MRPs in HD. particularly in terms of the components relating to movement preparation, and this finding may further explain the movement deficits reported in the disease.

Gender differences in bone geometry during the adolescent growth spurt

To investigate whether there are gender differences in the bone geometry of the proximal femur during the adolescent years we used an interactive computer program ?Hip Strength Analysis? developed by Beck and associates (Beck et al., Invest Radiol. 1990,25:6-18.) to derive femoral neck geometry parameters from DXA bone scans (Hologic 2000, array mode). We analyzed a longitudinal data-set collected on 70 boys and 68 girls over a seven year period. Distance and velocity curves for height were fitted for each child utilizing a cubic spline procedure and the age of peak height velocity (PHV) was determined. To control for maturational differences between children of the same chronological age and between boys and girls, section modulus (Z) an index of bending strength, cross sectional area of bone (CSA), sub-periosteal width (SPW), and BMD values at the neck and shaft of the proximal femur were determined for points on each individual?s curve at the age of PHV and one and two years on either side of peak. To control for size differences, height and weight were introduced as co-variates in the two-way analyses of variance looking at gender over time measured at the maturational age points (-2, -1, age of PHV, +1, +2). The following figure presents the results of the analyses on two variables, BMD and Z at neck and shaft regions:After the age of peak linear growth (PHV), independent of body size, there was a gender difference in BMD at the shaft but not at the neck. Section modulus at both sites indicated that male bones became significantly stronger after PHV. Underlying these maturational changes, male bones became wider (SPW) after PHV in both the neck and shaft and enclosed more material (CSA) at all maturational age points at both regions. These results call into question the emphasis on using BMD as a measure of skeletal integrity in growing children

The evolution and star formation of dwarf galaxies in the Fornax Cluster

We present the results of a spectroscopic survey of 675 bright (16.5 < b(J) < 18) galaxies in a 6 degrees field centred on the Fornax cluster with the FLAIR-II spectrograph on the UK Schmidt Telescope. Three galaxy samples were observed: compact galaxies to search for new blue compact dwarfs, candidate M 32-like compact dwarf ellipticals, and a subset of the brightest known cluster members in order to study the cluster dynamics. We measured redshifts for 516 galaxies, of which 108 were members of the Fornax Cluster. Defining dwarf galaxies to be those with b(J) greater than or equal to 15 (M-B greater than or equal to - 16.5), there are a total of 62 dwarf cluster galaxies in our sample. Nine of these are new cluster members previously misidentified as background galaxies. The cluster dynamics show that the dwarf galaxies are still falling into the cluster whereas the giants are virialized. We classified the observed galaxies as late-type if we detected H alpha emission at an equivalent width greater than 1 Angstrom. The spectra were obtained through fixed apertures, so they reflect activity in the galaxy cores, but this does not significantly bias the classifications of the compact dwarfs in our sample. The new classifications reveal a higher rate of star formation among the dwarf galaxies than suggested by morphological classification: 35 per cent have significant H alpha emission indicative of star formations but only 19 per cent were morphologically classified as late-types. The star-forming dwarf galaxies span the full range of physical sizes and we find no evidence in our data for a distinct class of star-forming blue compact dwarf (BCD) galaxy. The distribution of scale sizes is consistent with evolutionary processes which transform late-type dwarfs to early-type dwarfs. The fraction of dwarfs with active star formation drops rapidly towards the cluster centre: this is the usual density-morphology relation confirmed here for dwarf galaxies. The star-forming dwarfs are concentrated in the outer regions of the cluster, the most extreme in an infalling subcluster. We estimate gas depletion time-scales for five dwarfs with detected Hi emission: these are long (of order 10(10) yr), indicating that an active gas removal process must be involved if they are transformed into gas-poor dwarfs as they fall further into the cluster. Finally, in agreement with our previous results, we find no compact dwarf elliptical (M 32-like) galaxies in the Fornax Cluster.

Progress in high field MRI at the University of Florida

In this article we report on progress in high magnetic field MRI at the University of Florida in support of our new 750MHz wide bore and 11.7T/40cm MR instruments. The primary emphasis is on the associated rf technology required, particularly high frequency volume and phased array coils. Preliminary imaging results at 750MHz are presented. Our results imply that the pursuit of even higher fields seems warranted. (C) 2002 Elsevier Science B.V. All rights reserved.

Ecology and behavior of first instar larval Lepidoptera

Neonate Lepidoptera are confronted with the daunting task of establishing themselves on a food plant. The factors relevant to this process need to be considered at spatial and temporal scales relevant to the larva and not the investigator. Neonates have to cope with an array of plant surface characters as well as internal characters once the integument is ruptured. These characters, as well as microclimatic conditions, vary within and between plant modules and interact with larval feeding requirements, strongly affecting movement behavior, which may be extensive even for such small organisms. In addition to these factors, there is an array of predators, pathogens, and parasitoids with which first instars must contend. Not surprisingly, mortality in neonates is high but can vary widely. Experimental and manipulative studies, as well as detailed observations of the animal, are vital if the subtle interaction of factors responsible for this high and variable mortality are to be understood. These studies are essential for an understanding of theories linking female oviposition behavior with larval survival, plant defense theory, and population dynamics, as well as modern crop resistance breeding programs.

Large mitochondrial repeats multiplied during the polymerase chain reaction

The number of repeats in repetitive DNA like micro- and minisatellites is often determined by polymerase chain reaction (PCR). When we counted repeats in an array of mitochondrial repeats in the cattle tick (Boophilus microplus) we found that the number of repeats increased during PCR. Multiplication of the repeats was independent of the primers used to amplify the region, the PCR annealing temperature and the length of the PCR product. The use of PCR to determine the number of repeats in arrays needs to be reassessed. For long repeats, a subset of samples should always be analysed by Southern blot hybridization to confirm the PCR results.

Weight reduction in patients with chronic HCV reduces circulating insulin levels

Steatosis occurs in >50% of patients with chronic HCV. In patients with viral genotype 3, steatosis may be a cytopathic effect of the virus. However in many patients with HCV, the pathogenesis of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease (NAFLD) ie related to increased body mass index (BMI). We studied the effect of a 12 week weight reduction program on metabolic parameters in subjects with chronic HCV genotype 1 (Group 1, n = 16), genotype 3 (Group 2, n = 13) and patients with NAFLD (Group 3, n = 13). A liver biopsy was performed prior to and 3-6 months after the intervention period in 15 patients. The mean (SD) BMI of subjects in groups 1, 2 and 3 was 30.7 (4.0), 29.0 (5.2) and 33.3 (7.7), respectively. There was no significant difference in the amount of weight loss, change in waist circumference, change in ALT or reduction in steatosis between the 3 groups. Mean (SD) weight loss was 5.1 (3.7) kg. In those patients who lost weight, serum insulin (mean (SD) mU/L) changed from 17.8 (7.8) to 11.5 (4.8) (p = 0.003), 12.4 (5.0) to 8.4 (4.3) (p = 0.02), and 16.9 (7.3) to 17.8 (8.1) (p = 0.76) in Groups 1, 2 and 3, respectively. A small amount of weight loss is associated with a reduction in circulating insulin levels in patients with chronic HCV, particularly in genotype 1. In patients with NAFLD, the lack of a significant decrease in circulating insulin with weight reduction may reflect the higher initial BMI or may be due to the pathogenesis of this disorder.

Molecular evolution and phylogeny of elapid snake venom three-finger toxins

Animal venom components are of considerable interest to researchers across a wide variety of disciplines, including molecular biology, biochemistry, medicine, and evolutionary genetics. The three-finger family of snake venom peptides is a particularly interesting and biochemically complex group of venom peptides, because they are encoded by a large multigene family and display a diverse array of functional activities. In addition, understanding how this complex and highly varied multigene family evolved is an interesting question to researchers investigating the biochemical diversity of these peptides and their impact on human health. Therefore, the purpose of our study was to investigate the long-term evolutionary patterns exhibited by these snake venom toxins to understand the mechanisms by which they diversified into a large, biochemically diverse, multigene family. Our results show a much greater diversity of family members than was previously known, including a number of subfamilies that did not fall within any previously identified groups with characterized activities. In addition, we found that the long-term evolutionary processes that gave rise to the diversity of three-finger toxins are consistent with the birth-and-death model of multigene family evolution. It is anticipated that this three-finger toxin toolkit will prove to be useful in providing a clearer picture of the diversity of investigational ligands or potential therapeutics available within this important family.

Phylogeny, evolution and historical zoogeography of ticks: a review of recent progress

There has been much progress in our understanding of the phylogeny and evolution of ticks, particularly hard ticks, in the past 5 years. Indeed, a consensus about the phylogeny of the hard ticks has emerged. Our current working hypothesis for the phylogeny of ticks is quite different to the working hypothesis of 5 years ago. So that the classification reflects our knowledge of ticks, several changes to the nomenclature of ticks are imminent. One subfamily, the Hyalomminae, will probably be sunk, yet another, the Bothriocrotoninae n. subfamily, will be created. Bothriocrotoninae n. subfamily, and Bothriocroton n. genus, are being created to house an early-diverging ('basal') lineage of endemic Australian ticks that used to be in the genus Aponomma (ticks of reptiles). There has been progress in our understanding of the subfamily Rhipicephalinae. The genus Rhipicephalus is almost certainly paraphyletic with respect to the genus Boophilus. Thus, the genus Boophilus will probably become a subgenus of Rhipicephalus. This change to the nomenclature, unlike other options, will keep the name Boophilus in common usage. Rhipicephalus (Boophilus) microplus may still called B. microplus, and Rhipicephalus (Boophilus) annulatus may still be called B. annulatus, but the nomenclature will have been changed to reflect our knowledge of the phylogeny and evolution of these ticks. New insights into the historical zoogeography of ticks will also be presented.

Late Quaternary Milankovitch-scale climatic change and variability and its impact on monsoonal Australasia

Four pollen and charcoal records derived from marine cores around the northern perimeter of Australia are examined to provide a regional picture of patterns, causes and impacts of climate change over the last 100-300 ka. The availability of radiocarbon dates and oxygen isotope records for the cores provides primary chronological control. Spectral analysis of components of these records demonstrates an overall importance of Milankovitch frequencies with clear glacial-interglacial cyclicity dominated by variation in precipitation. In addition, a number of pollen taxa, as well as charcoal particles, exhibit a 30 ka frequency that is considered, from its relationship with biomass burning and with results of past modelling, to reflect changes in the intensity of El Nino-Southern Oscillation (ENSO) variability. Pollen components of all records show a decline, frequently stepwise, in more fire-sensitive vegetation and its replacement with more fire-tolerant vegetation. There is some evidence that this trend is linked to an onset or general increase in ENSO activity and perhaps also to variation in monsoon activity dating from about 300 ka BP that was caused by changes to oceanic circulation within the Indonesian region. The trend may have accelerated within the last 45 ka due to burning by indigenous people. (C) 2003 Elsevier B.V. All rights reserved.

Effects of restricted cochlear lesions in adult cats on the frequency organization of the inferior colliculus

Restricted cochlear lesions in adult animals result in plastic changes in the representation of the lesioned cochlea, and thus in the frequency map, in the contralateral auditory cortex and thalamus. To examine the contribution of subthalamic changes to this reorganization, the effects of unilateral mechanical cochlear lesions on the frequency organization of the central nucleus of the inferior colliculus (ICC) were examined in adult cats. Lesions typically resulted in a broad high-frequency hearing loss extending from a frequency in the range 15-22 kHz. After recovery periods of 2.5-18 months, the frequency organization of ICC contralateral to the lesioned cochlea was determined separately for the onset and late components of multiunit responses to tone-burst stimuli. For the late response component in all but one penetration through the ICC, and for the onset response component in more than half of the penetrations, changes in frequency organization in the lesion projection zone were explicable as the residue of prelesion responses. In half of the penetrations exhibiting nonresidue type changes in onset-response frequency organization, the changes appeared to reflect the unmasking of normally inhibited inputs. In the other half it was unclear whether the changes reflected unmasking or a dynamic process of reorganization. Thus, most of the observed changes were explicable as passive consequences of the lesion, and there was limited evidence for plasticity in the ICC. The implications of the data with respect to the primary locus of the changes and to the manner in which they contribute to thalamocortical reorganization are considered. (C) 2003 Wiley-Liss, Inc.

Patterns of variation within self-incompatibility loci

Diverse self-incompatibility (SI) mechanisms permit flowering plants to inhibit fertilization by pollen that express specificities in common with the pistil. Characteristic of at least two model systems is greatly reduced recombination across large genomic tracts surrounding the S-locus, which regulates SI. In three angiosperm families, including the Solanaceae, the gene that controls the expression of gametophytic SI in the pistil encodes a ribonuclease (S-RNase). The gene that controls pollen SI expression is currently unknown, although several candidates have recently been proposed. Although each candidate shows a high level of polymorphism and complete allelic disequilibrium with the S-RNase gene, such properties may merely reflect tight linkage to the S-locus, irrespective of any functional role in SI. We analyzed the magnitude and nature of nucleotide variation, with the objective of distinguishing likely candidates for regulators of SI from other genes embedded in the S-locus region. We studied the S-RNase gene of the Solanaceae and 48A, a candidate for the pollen gene in this system, and we also conducted a parallel analysis of the regulators of sporophytic SI in Brassica, a system in which both the pistil and pollen genes are known. Although the pattern of variation shown by the pollen gene of the Brassica system is consistent with its role as a determinant of pollen specificity, that of 48A departs from expectation. Our analysis further suggests that recombination between 48A and S-RNase may have occurred during the interval spanned by the gene genealogy, another indication that 48A may not regulate SI expression in pollen.

Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gamma delta T cells

Few studies have demonstrated that innate lymphocytes play a major role in preventing spontaneous tumor formation. We evaluated the development of spontaneous tumors in mice lacking beta-2 microglobulin (beta2m; and thus MHC class I, CD1d, and CD16) and/or perform, since these tumor cells would be expected to activate innate effector cells. Approximately half the cohort of perform gene-targeted mice succumbed to spontaneous disseminated B cell lymphomas and in mice that also lacked beta2m, the lymphomas developed earlier (by more than 100 d) and with greater incidence (84%). B cell lymphomas from perforin/beta2m gene-targeted mice effectively primed cell-mediated cytotoxicity and perform, but not IFN-gamma, IL-12, or IL-18, was absolutely essential for tumor rejection. Activated NK1.1(+) and gammadeltaTCR(+) T cells were abundant at the tumor site, and transplanted tumors were strongly rejected by either, or both, of these cell types. Blockade of a number of different known costimulatory pathways failed to prevent tumor rejection. These results reflect a critical role for NK cells and gammadeltaTCP(+) T cells in innate immune surveillance of B cell lymphomas, mediated by as yet undetermined pathway(s) of tumor recognition.