Chemical synthesis and folding pathways of large cyclic polypeptide: Studies of the cystine knot polypeptide kalata B1

Kalata B1 is a member of a new family of polypeptides, isolated from. plants, which have a cystine knot structure embedded within an amide-cyclized backbone. This family of molecules are the largest known cyclic peptides, and thus, the mechanism of synthesis and folding is of great interest. To provide information about both these phenomena, we have synthesized kalata B1 using two distinct strategies. In the first, oxidation of the cysteine residues of a linear precursor peptide to form the correct disulfide bonds results in folding of the three-dimensional structure and preorganization of the termini in close proximity for subsequent cyclization. The second approach involved cyclization prior to oxidation. In the first method, the correctly folded peptide was produced only in the presence of partially hydrophobic solvent conditions. These conditions are presumably required to stabilize the surface-exposed hydrophobic residues. However,; in the synthesis,involving cyclization prior to oxidation, the cyclic reduced peptide folded to a significant degree in the absence of hydrophobic solvents and even more efficiently in the presence of hydrophobic solvents. Cyclization clearly has a major effect on the folding pathway and facilitates formation of the correctly disulfide-bonded form in aqueous solution; In addition to facilitating folding to a compact stable structure cyclization has an important effect on biological activity as assessed by hemolytic activity.

A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: The University of Saskatchewan bone mineral accrual study

To investigate the influence of physical activity on bone mineral accrual during the adolescent years, we analyzed 6 years of data from 53 girls and 60 boys. Physical activity, dietary intakes, and anthropometry were measured every 6 months and dual-energy X-ray absorptiometry scans of the total body (TB), lumbar spine (LS), and proximal femur (Hologic 2000, array mode) were collected annually. Distance and velocity curves for height and bone mineral content (BMC) were fitted for each child at several skeletal sites using a cubic spline procedure, from which ages at peak height velocity (PHV) and peak BMC velocity (PBMCV) were identified. A mean age- and gender-specific standardized activity (Z) score was calculated for each subject based on multiple yearly activity assessments collected up until age of PHV. This score was used to identify active (top quartile), average (middle 2 quartiles), or inactive (bottom quartile) groups. Two-way analysis of covariance, with height and weight at PHV controlled for, demonstrated significant physical activity and gender main effects (but no interaction) for PBMCV, for BMC accrued for 2 years around peak velocity, and for BMC at 1 year post-PBMCV for the TB and femoral neck and for physical activity but not gender at the LS (all p < 0.05). Controlling for maturational and size differences between groups, we noted a 9% and 17% greater TB BMC for active boys and girls, respectively, over their inactive peers 1 year after the age of PBMCV. We also estimated that, on average, 26% of adult TB bone mineral was accrued during the 2 years around PBMCV.

A hybrid, inverse approach to the design of magnetic resonance imaging magnets

This paper describes a hybrid numerical method of an inverse approach to the design of compact magnetic resonance imaging magnets. The problem is formulated as a field synthesis and the desired current density on the surface of a cylinder is first calculated by solving a Fredholm equation of the first, kind. Nonlinear optimization methods are then invoked to fit practical magnet coils to the desired current density. The field calculations are performed using a semi-analytical method. The emphasis of this work is on the optimal design of short MRI magnets. Details of the hybrid numerical model are presented, and the model is used to investigate compact, symmetric MRI magnets as well as asymmetric magnets. The results highlight that the method can be used to obtain a compact MRI magnet structure and a very homogeneous magnetic field over the central imaging volume in clinical systems of approximately 1 m in length, significantly shorter than current designs. Viable asymmetric magnet designs, in which the edge of the homogeneous region is very close to one end of the magnet system are also presented. Unshielded designs are the focus of this work. This method is flexible and may be applied to magnets of other geometries. (C) 2000 American Association of Physicists in Medicine. [S0094-2405(00)00303-5].

The Fornax spectroscopic survey I. Survey strategy and preliminary results on the redshift distribution of a complete sample of stars and galaxies

The Fornax Spectroscopic Survey will use the Two degree Field spectrograph (2dF) of the Angle-Australian Telescope to obtain spectra for a complete sample of all 14000 objects with 16.5 less than or equal to b(j) less than or equal to 19.7 in a 12 square degree area centred on the Fornax Cluster. The aims of this project include the study of dwarf galaxies in the cluster (both known low surface brightness objects and putative normal surface brightness dwarfs) and a comparison sample of background field galaxies. We will also measure quasars and other active galaxies, any previously unrecognised compact galaxies and a large sample of Galactic stars. By selecting all objects-both stars and galaxies-independent of morphology, we cover a much larger range of surface brightness and scale size than previous surveys. In this paper we first describe the design of the survey. Our targets are selected from UK Schmidt Telescope sky survey plates digitised by the Automated Plate Measuring (APM) facility. We then describe the photometric and astrometric calibration of these data and show that the APM astrometry is accurate enough for use with the 2dF. We also describe a general approach to object identification using cross-correlations which allows us to identify and classify both stellar and galaxy spectra. We present results from the first 2dF field. Redshift distributions and velocity structures are shown for all observed objects in the direction of Fornax, including Galactic stars? galaxies in and around the Fornax Cluster, and for the background galaxy population. The velocity data for the stars show the contributions from the different Galactic components, plus a small tail to high velocities. We find no galaxies in the foreground to the cluster in our 2dF field. The Fornax Cluster is clearly defined kinematically. The mean velocity from the 26 cluster members having reliable redshifts is 1560 +/- 80 km s(-1). They show a velocity dispersion of 380 +/- 50 km s(-1). Large-scale structure can be traced behind the cluster to a redshift beyond z = 0.3. Background compact galaxies and low surface brightness galaxies are found to follow the general galaxy distribution.

Relationships among climate, latitude and migration: Australian butterflies are not temperate-zone birds

We examined the distribution of butterflies over the mostly arid and semi-arid continent of Australia and analyzed the proportion of migrant species and species diversity with respect to an array of climatic and geographic variables. On a continent-wide scale, latitude explained virtually no variance in either proportion of migrants (r(2) = 0.01) or species diversity (r(2) = 0.03) in Australian butterflies. These results are in marked contrast to those for temperate-zone birds from three continents where latitude explained between 82 and 98% of the variance in frequency of migrants and also accounted for much of the variance in bird species diversity. In eastern Australia where rainfall regimes are similar to those in temperate Europe and North and South America, latitude explains 78% of the variance in frequency of butterfly migrants. In both eastern and central Australia, latitude also accounts for relatively high proportions of the variance in species diversity. Rainfall patterns and especially soil moisture are negatively associated with migration frequency in Australian butterfly faunas, both alone and in combination with other climate variables. Where moisture levels are relatively high, as in eastern Australia, measures of temperature are associated with migration frequency, a result consistent with findings for temperate-zone birds, suggesting latitude is a surrogate for temperature. The ultimate causes of migration in temperate-zone birds and Australian butterflies are the uneven temporal, and in Australia also spatial, distribution of resources. Uneven distribution is brought about primarily by temperature in temperate regions and by erratic rainfall over much of arid Australia. As a key determinant of productivity, especially in the tropics and subtropics, aridity is likely to be an important determinant of the global distributions of migrants.

Calcium accretion in girls and boys during puberty: A longitudinal analysis

The primary purpose of this study was to estimate the magnitude and variability of peak calcium accretion rates in the skeletons of healthy white adolescents. Total-body bone mineral content (BMC) was measured annually on six occasions by dual-energy X-ray absorptiometry (DXA; Hologic 2000, array mode), a BMC velocity curve was generated for each child by a cubic spline fit, and peak accretion rates were determined. Anthropometric measures were collected every 6 months and a 24-h dietary recall was recorded two to three times per year. Of the 113 boys and 115 girls initially enrolled in the study, 60 boys and 53 girls who had peak height velocity (PHV) and peak BMC velocity values were used in this longitudinal analysis. When the individual BR IC velocity curves were aligned on the age of peak bone mineral velocity, the resulting mean peak bone mineral accrual rate was 407 g/year for boys (SD, 92 g/year; range, 226-651 g/year) and 322 g/year for girls (SD, 66 g/year; range, 194-520 g/year). Using 32.2% as the fraction of calcium in bone mineral, as determined by neutron activation analysis (Ellis et al., J Bone Miner Res 1996;11:843-848), these corresponded to peak calcium accretion rates of 359 mg/day for boys (81 mg/day; 199-574 mg/day) and 284 mg/day for girls (58 mg/day; 171-459 mg/day). These longitudinal results are 27-34% higher than our previous cross-sectional analysis in which we reported mean values of 282 mg/day for boys and 212 mg/day for girls (Martin et al., Am J Clin Nutr 1997;66:611-615). Mean age of peak calcium accretion was 14.0 years for the boys (1.0 years; 12.0-15.9 years), and 12.5 years for the girls (0.9 years; 10.5-14.6 years). Dietary calcium intake, determined as the mean of all assessments up to the age of peak accretion was 1140 mg/day (SD, 392 mg/day) for boys and 1113 mg/day (SD, 378 mg/day) for girls. We estimate that 26% of adult calcium is laid down during the 2 adolescent years of peak skeletal growth. This period of rapid growth requires high accretion rates of calcium, achieved in part by increased retention efficiency of dietary calcium.

Heat flow for Yang-Mills-Higgs fields, part I

The Yang-Mills-Higgs field generalizes the Yang-Mills field. The authors establish the local existence and uniqueness of the weak solution to the heat flow for the Yang-Mills-Higgs field in a vector bundle over a compact Riemannian 4-manifold, and show that the weak solution is gauge-equivalent to a smooth solution and there are at most finite singularities at the maximum existing time.

Marine bioprospecting - Trawling for treasure and pleasure

This Microreview seeks to highlight the molecular diversity present in marine organisms, and illustrate by example some of the challenges encountered in exploring this resource. Marine natural products exhibit an impressive array of structural motifs, many of which are derived from biosynthetic pathways that are uniquely marine, Most importantly some marine metabolites possess noteworthy biological activities, activities that have potential application outside marine ecosystems, such as antibiotics, antiparasitics, anticancer agents etc... The isolation, spectroscopic characterisation and assignment of stereostructures to these unusual metabolites is both challenging and rewarding. Examples featured in this Microreview follow a common theme in that they are all recent accounts of the isolation of natural products from Australian marine sponges, carried out in the laboratories of the author. In addition to presenting brief comments on specific structure elucidation strategies, an effort is made to emphasize techniques for solving stereochemical issues, as well as to speculate on the biosynthetic origins of some of these exotic marine natural products.

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.

Galaxy threshing and the formation of ultracompact dwarf galaxies

Recent spectroscopic and morphological observational studies of galaxies around NGC 1399 in the Fornax Cluster have discovered several ultracompact dwarf galaxies with intrinsic sizes of similar to 100 pc and absolute B-band magnitudes ranging from -13 to -11 mag. In order to elucidate the origin of these enigmatic objects, we perform numerical simulations on the dynamical evolution of nucleated dwarf galaxies orbiting NGC 1399 and suffering from its strong tidal gravitational field. Adopting a plausible scaling relation for dwarf galaxies, we find that the outer stellar components of a nucleated dwarf are totally removed. This is due to them being tidally stripped over the course of several passages past the central region of NGC 1399. The nucleus, however, manages to survive. We also find that the size and luminosity of the remnant are similar to those observed for ultracompact dwarf galaxies, if the simulated precursor nucleated dwarf has a mass of similar to 10(8) M.. These results suggest that ultracompact dwarf galaxies could have previously been more luminous dwarf spheroidal or elliptical galaxies with rather compact nuclei.

A new formation model for M32: a threshed early-type spiral galaxy?

The origin of M32, the closest compact elliptical galaxy (cE), is a long-standing puzzle of galaxy fort-nation in the Local Group. Our N-body/smoothed particle hydrodynamics simulations suggest a new scenario in which the strong tidal field of M31 can transform a spiral galaxy into a compact elliptical galaxy. As a low-luminosity spiral galaxy plunges into the central region of M31, most of the outer stellar and gaseous components of its disk are dramatically stripped as a result of M31's tidal field. The central bulge component, on the other hand, is just weakly influenced by the tidal field, owing to its compact configuration, and retains its morphology. M31's strong tidal field also induces rapid gas transfer to the central region, triggers a nuclear starburst, and consequently forms the central high-density and more metal-rich stellar populations with relatively young ages. Thus, in this scenario, M32 was previously the bulge of a spiral galaxy tidally interacting with M31 several gigayears ago. Furthermore, we suggest that cE's like M32 are rare, the result of both the rather narrow parameter space for tidal interactions that morphologically transform spiral galaxies into cE's and the very short timescale (less than a few times 10(9) yr) for cE's to be swallowed by their giant host galaxies (via dynamical friction) after their formation.

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.

Ultracompact dwarf galaxies in the Fornax Cluster

By utilizing the large multiplexing advantage of the Two-degree Field spectrograph on the Anglo-Australian Telescope, we have been able to obtain a complete spectroscopic sample of all objects in a predefined magnitude range, 16.5 < b(j) < 19.7 regardless of morphology, in an area toward the center of the Fornax Cluster of galaxies. Among the unresolved or marginally resolved targets, we have found five objects that are actually at the redshift of the Fornax Cluster; i.e., they are extremely compact dwarf galaxies or extremely large star clusters. All five have absorption-line spectra. With intrinsic sizes of less than 1.1 HWHM (corresponding to approximately 100 pc at the distance of the cluster), they are more compact and significantly less luminous than other known compact dwarf galaxies, yet much brighter than any globular cluster. In this paper we present new ground-based optical observations of these enigmatic objects. In addition to having extremely high central surface brightnesses, these objects show no evidence of any surrounding low surface brightness envelopes down to much fainter limits than is the case for, e.g., nucleated dwarf elliptical galaxies. Thus, if they are not merely the stripped remains of some other type of galaxy, then they appear to have properties unlike any previously known type of stellar system.

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.