Biomedical subjects

L M Miller

Publications and source records attributed to L M Miller.

At least 19 recordsLinked to original sources

PubMed2005

Rapid establishment of chemical and mechanical properties during lamellar bone formation.

The development of prophylaxes and treatments of bone diseases that can effectively increase the strength of bone as a structure necessitates a better understanding of the time course by which chemical properties define the stiffness of the material during primary and secondary mineralization. It was hypothesized that these processes would be relatively slow in the actively growing skeleton. Seven-week-old Sprague-Dawley female rats (n = 8) were injected with multiple fluorochrome labels over a time span of 3 weeks and killed. Chemical and mechanical properties of the tibial mid-diaphysis were spatially characterized between the endocortical and periosteal surface by in situ infrared microspectroscopy and nanoindentation. The phosphate-to-protein ratio of bone 2-6 days old was 20% smaller at the periosteal surface and 22% smaller at the endocortical surface (P < 0.05 each) compared to older intracortical regions. The ratios of carbonate to protein, crystallinity, type A/type B carbonate, collagen cross-linking, and bone elastic modulus did not differ significantly between bone 2-6, 10-14, and 8-22 days old and intracortical regions. Intracortical properties of 10-week-old rats, except for the carbonate-to-protein ratio which was 23% smaller (P < 0.01), were not significantly different from intracortical matrix properties of young adult rats (5 months, n = 4). Spatially, the phosphate-to-protein ratio (R(2) = 0.33) and the phosphate-to-carbonate ratio (R(2) = 0.55) were significantly correlated with bone material stiffness, while the combination of all chemical parameters raised the R(2) value to 0.83. These data indicate that lamellar bone has the ability to quickly establish its mechanical and chemical tissue properties during primary and secondary mineralization even when the skeleton experiences rapid growth.

Animals↗

PubMed2005

Liver histopathology and liver and serum alanine aminotransferase and alkaline phosphatase activities in epileptic dogs receiving phenobarbital.

Phenobarbital (PB) therapy is frequently associated with elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (AP) activities in dogs without clinical signs of liver disease. The goal of this study was to determine if increased serum ALT and AP activities in clinically healthy PB-treated epileptic dogs are due to hepatic enzyme induction or to subclinical liver injury. Liver biopsies were obtained from 12 PB-treated dogs without clinical signs of liver disease but with elevated serum ALT and/or AP activities or both. Liver biopsies were obtained from eight healthy control dogs not receiving PB. Biopsies were evaluated histopathologically (all dogs) and liver homogenates were assayed for ALT (all dogs) and AP (six treated dogs, all controls) activities. As a positive control, liver cytochrome P4502B, an enzyme known to be induced by PB, was measured by benzyloxyresorufin-O-dealkylase activity and immunoblotting (five treated dogs, all controls). Serum AP isoenzyme analyses were performed. Results showed that ALT and AP activities in liver homogenates were not increased in treated dogs compared with controls, whereas the positive control for induction, CYP2B, was dramatically increased in treated dogs. Histopathological examination of liver biopsies revealed more severe and frequent abnormalities in treated dogs compared to controls, but similar types of abnormalities were found in both groups. Serum AP isoenzyme analyses in treated dogs demonstrated increased corticosteroid-induced and liver isoenzyme activities compared to controls. Results do not support induction of ALT or AP in the liver as the cause of elevated serum activities of these enzymes due to PB.

Alanine Transaminase↗

PubMed2004

Imaging capabilities of synchrotron infrared microspectroscopy.

It has become increasingly clear that synchrotron infrared micro-spectroscopy is an extremely valuable analysis tool when determining the chemical composition of biological and biomedical samples, at the diffraction-limited spatial resolution. Highly resolved infrared micro-spectroscopy, together with the high signal-to-noise level of the recorded spectra, is essential in generating chemical and statistical (multivariate) images. This is illustrated in the case of individual cell and hair section studies. Unprecedented chemical images of lipid distribution and secondary structure relative concentration have been achieved using the synchrotron source. A comparison with a Focal plane Array imaging system, on the same hair section, shows that, despite the fast imaging processing and improved quality achieved with the focal plane array detectors, spectral quality is markedly superior in the case of the synchrotron source. It is clear that the two approaches could be very complementary if combined on the same sample area, in a synchrotron facility.

Algorithms↗

PubMed2004

Lower fitness of hatchery and hybrid rainbow trout compared to naturalized populations in Lake Superior tributaries.

We have documented an early life survival advantage by naturalized populations of anadromous rainbow trout Oncorhynchus mykiss over a more recently introduced hatchery population and outbreeding depression resulting from interbreeding between the two strains. We tested the hypothesis that offspring of naturalized and hatchery trout, and reciprocal hybrid crosses, survive equally from fry to age 1+ in isolated reaches of Lake Superior tributary streams in Minnesota. Over the first summer, offspring of naturalized females had significantly greater survival than offspring of hatchery females in three of four comparisons (two streams and 2 years of stocking). Having an entire naturalized genome, not just a naturalized mother, was important for survival over the first winter. Naturalized offspring outperformed all others in survival to age 1+ and hybrids had reduced, but intermediate, survival relative to the two pure crosses. Averaging over years and streams, survival relative to naturalized offspring was 0.59 for hybrids with naturalized females, 0.37 for the reciprocal hybrids, and 0.21 for hatchery offspring. Our results indicate that naturalized rainbow trout are better adapted to the conditions of Minnesota's tributaries to Lake Superior so that they outperform the hatchery-propagated strain in the same manner that many native populations of salmonids outperform hatchery or transplanted fish. Continued stocking of the hatchery fish may conflict with a management goal of sustaining the naturalized populations.

Animals↗

PubMed2002

Center for Synchrotron Biosciences' U2B beamline: an international resource for biological infrared spectroscopy.

A synchrotron infrared (IR) beamline, U2B, dedicated to the biomedical and biological sciences has been constructed and is in operation at the National Synchrotron Light Source (NSLS) of Brookhaven National Laboratory. The facility is operated by the Center for Synchrotron Biosciences of the Albert Einstein College of Medicine in cooperation with the NSLS. Owing to the broadband nature of the synchrotron beam with brightness 1000 times that of conventional sources, Fourier transform IR spectroscopy experiments are feasible on diffraction-limited sample areas at high signal-to-noise ratios and with relatively short data-acquisition times. A number of synchrotron IR microscopy experiments that have been performed in the mid-IR spectral range (500-5000 cm(-1)) are summarized, including time-resolved protein-folding studies in the microsecond time regime, IR imaging of neurons, bone and other biological tissues, as well as imaging of samples of interest in the chemical and environmental sciences. Owing to the high flux output of this beamline in the far-IR region (50-500 cm(-1)), investigations of hydrogen bonding and dynamic molecular motions of biomolecules have been carried out from 10 to 300 K using a custom-made cryostat and an evacuated box. This facility is intended as an international resource for biological IR spectroscopy fully available to outside users based on competitive proposal.

Bone and Bones↗

PubMed2002

Characterization of bone mineral composition in the proximal tibia of cynomolgus monkeys: effect of ovariectomy and nandrolone decanoate treatment.

Life postmenopausal women, ovariectomized cynomolgus monkeys (Macaca fascicularis) experience accelerated loss of bone mass. Treatment of ovariectomized monkeys with nandrolone decanoate results in an increase in bone mass to levels comparable to those of intact animals. The changes in bone composition that occur with these treatments, however, are less well characterized. In the present study, we used synchrotron Fourier-transform infrared microspectroscopy (FT-IRM) and curve-fitting methods to monitor specific changes at cortical, subchondral, and trabecular bone regions in the proximal tibia. Four groups were studied: (1) sham-operated (sham); (2) ovariectomized and treated with placebo for 2 years (ovx); (3) ovx + nandrolone decanoate for 2 years (NAN); and (4) ovx + nandrolone decanoate beginning 1 year after ovx (dNAN). The results demonstrate that ovariectomy and nandrolone treatment did not affect the degree of mineralization as defined by the phosphate/protein ratio, but acid phosphate content (HPO(4)(2-)) in cortical and subchondral bone was increased by ovariectomy, suggesting this bone to be less mature due to increased remodeling that occurs after ovariectomy. In the subchondral and cortical bone regions, ovariectomized monkeys showed a lower total carbonate content (CO(3)(2-)/matrix ratio) than sham controls, specifically due to the decrease in labile carbonate content. In the trabecular region, no change of carbonate content was observed. Treatment with nandrolone decanoate was found to restore the loss in carbonate, where the resulting mineral had a larger quantity of type B carbonate. Finally, we correlated carbonate content with dual-energy X-ray absorptiometry measurements, and found a positive correlation between bone mineral density and type A carbonate in bone, which is stoichiometrically related to the amount of calcium in bone. Therefore, the results presented herein identify significant differences in bone chemistry after ovariectomy and nandrolone treatment, which may help explain previous findings that, although nandrolone decanoate treatment increased bone mass, it could not reverse the decrease in bone strength due to ovariectomy.

Anabolic Agents↗

PubMed2001

Feature selectivity and interneuronal cooperation in the thalamocortical system.

Action potentials are a universal currency for fast information transfer in the nervous system, yet few studies address how some spikes carry more information than others. We focused on the transformation of sensory representations in the lemniscal (high-fidelity) auditory thalamocortical network. While stimulating with a complex sound, we recorded simultaneously from functionally connected cell pairs in the ventral medial geniculate body and primary auditory cortex. Thalamic action potentials that immediately preceded or potentially caused a cortical spike were more selective than the average thalamic spike for spectrotemporal stimulus features. This net improvement of thalamic signaling indicates that for some thalamic cells, spikes are not propagated through cortex independently but interact with other inputs onto the same target cell. We then developed a method to identify the spectrotemporal nature of these interactions and found that they could be cooperative or antagonistic to the average receptive field of the thalamic cell. The degree of cooperativity with the thalamic cell determined the increase in feature selectivity for potentially causal thalamic spikes. We therefore show how some thalamic spikes carry more receptive field information than average and how other inputs cooperate to constrain the information communicated through a cortical cell.

Acoustic Stimulation↗

PubMed2001

Functional convergence of response properties in the auditory thalamocortical system.

One of the brain's fundamental tasks is to construct and transform representations of an animal's environment, yet few studies describe how individual neurons accomplish this. Our results from correlated pairs in the auditory thalamocortical system show that cortical excitatory receptive field regions can be directly inherited from thalamus, constructed from smaller inputs, and assembled by the cooperative activity of neuronal ensembles. The prevalence of functional thalamocortical connectivity is strictly governed by tonotopy, but connection strength is not. Finally, spectral and temporal modulation preferences in cortex may differ dramatically from the thalamic input. Our observations reveal a radical reconstruction of response properties from auditory thalamus to cortex, and illustrate how some properties are propagated with great fidelity while others are significantly transformed or generated intracortically.

Acoustic Stimulation↗

PubMed2001

A new spectroscopic approach to examining the role of disulfide bonds in the structure and unfolding of soybean trypsin inhibitor.

Although it is well-known that disulfide bonds stabilize the secondary structure of many proteins, it is difficult to directly probe both disulfide bond formation/breakage and the resulting secondary structural changes during the course of the protein folding/unfolding process. In this work, we have used a new, real-time spectroscopic approach to examine how the reduction of two disulfide bonds affects the secondary structure of soybean trypsin inhibitor (STI). The disulfide bonds are reduced with tris(2-carboxyethyl)phosphine (TCEP) at 40 degrees C, and the reduction process is probed in real-time using sulfur X-ray absorption spectroscopy. Circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopies are used concurrently to determine the structural changes caused by reduction of the disulfide bonds. Results demonstrate a noncooperative reduction of the two disulfide bonds within 5 min, likely because they are located on the surface of the protein. The unfolding of STI lags behind; dramatic changes are not observed until 60-90 min after the reduction was initiated. The CD and FTIR spectra indicate a decrease in the amount of extended (hydrated) coil, suggesting that the STI structure slowly collapses after the disulfide bonds are reduced. Thus, although the disulfide bonds are not located near the active site of STI, they play a crucial role in stabilizing the protein structure, which is necessary to sustain enzymatic activity.

Disulfides↗

PubMed2001

In situ analysis of mineral content and crystallinity in bone using infrared micro-spectroscopy of the nu(4) PO(4)(3-) vibration.

Measurements of bone mineral content and composition in situ provide insight into the chemistry of bone mineral deposition. Infrared (IR) micro-spectroscopy is well suited for this purpose. To date, IR microscopic (including imaging) analyses of bone apatite have centered on the nu(1),nu(3) PO(4)(3-) contour. The nu(4) PO(4)(3-) contour (500-650 cm(-1)), which has been extensively used to monitor the crystallinity of hydroxyapatite in homogenized bone samples, falls in a frequency region below the cutoff of the mercury-cadmium-telluride detectors used in commercial IR microscopes, thereby rendering this vibration inaccessible for imaging studies. The current study reports the first IR micro-spectroscopy spectra of human iliac crest cross sections in the nu(4) PO(4)(3-) spectral regions, obtained with a synchrotron radiation source and a Cu-doped Ge detector coupled to an IR microscope. The acid phosphate (HPO(4)(2-)) content and mineral crystallite perfection (crystallinity) of a human osteon were mapped. To develop spectra-structure correlations, a combination of X-ray powder diffraction data and conventional Fourier transform IR spectra have been obtained from a series of synthetic hydroxyapatite crystals and natural bone powders of various species and ages. X-ray powder diffraction data demonstrate that there is an increase in average crystal size as bone matures, which correlates with an increase in the nu(4) PO(4)(3-) FTIR absorption peak ratio of two peaks (603/563 cm(-1)) within the nu(4) PO(4)(3-) contour. Additionally, the IR results reveal that a band near 540 cm(-1) may be assigned to acid phosphate. This band is present at high concentrations in new bone, and decreases as bone matures. Correlation of the nu(4) PO(4)(3-) contour with the nu(2) CO (3)(2-) contour also reveals that when acid phosphate content is high, type A carbonate content (i.e., carbonate occupying OH(-) sites in the hydroxyapatite lattice) is high. As crystallinity increases and acid phosphate content decreases, carbonate substitution shifts toward occupation of PO(4)(3-) sites in the hydroxyapatite lattice. Thus, IR microscopic analysis of the nu(4) PO(4)(3-) contour provides a straightforward index of both relative mineral crystallinity and acid phosphate concentration that can be applied to in situ IR micro-spectroscopic analysis of bone samples, which are of interest for understanding the chemical mechanisms of bone deposition in normal and pathological states.

Adult↗

PubMed2001

Conformation transition kinetics of regenerated Bombyx mori silk fibroin membrane monitored by time-resolved FTIR spectroscopy.

The ethanol-induced conformation transition of regenerated Bombyx mori silk fibroin membrane from a poorly defined to the well ordered state was monitored by time-resolved Fourier transform infrared spectroscopy (FTIR) for the first time. From the analysis of FTIR difference spectra, taken on time scales as short as 6 s and up to 1 h after addition of ethanol, intensity vs. time plots of an increasing band at 1618 cm(-1) were observed indicating formation of a beta-sheet coincident with the loss of intensity of a band at 1668 cm(-1) indicating decreases of random coil and/or silk I structure. Both infrared markers were fitted with identical biphasic exponential decay functions, however, there was a clear burst phase occurring prior to the onset of the observed transitions. The conformation transition process is indicated to either proceed sequentially through (at least) two intermediate states that contain different levels of beta-sheet structure or to have parallel pathways of initial beta-sheet formation followed by a slower 'perfection' phase. The first observed process forms in a burst phase a few seconds after mixing (or even faster), prior to the collection of the first spectrum at 6 s. The second observed process occurs with a time constant of approximately 0.5 min, the intermediate present at this stage then continues with a time constant of 5.5 min completing the observed formation of the beta-sheet. The conformation transition of this slower intermediate is not only indicated by an analysis of the kinetics of the random coil and beta-sheet-specific bands discussed above, it roughly coincides with the appearance of an additional infrared marker at 1695 cm(-1), which may be a marker for beta-sheet structure specific to the formation of the perfected structure. The conformation transition of this protein analyzed by infrared spectroscopy provides insight into a part of the fascinating process of cocoon formation in B. mori.

Animals↗

PubMed2001

Informatics and multiplexing of intact protein identification in bacteria and the archaea.

Although direct fragmentation of protein ions in a mass spectrometer is far more efficient than exhaustive mapping of 1-3 kDa peptides for complete characterization of primary structures predicted from sequenced genomes, the development of this approach is still in its infancy. Here we describe a statistical model (good to within approximately 5%) that shows that the database search specificity of this method requires only three of four fragment ions to match (at +/-0.1 Da) for a 99.8% probability of being correct in a database of 5,000 protein forms. Software developed for automated processing of protein ion fragmentation data and for probability-based retrieval of whole proteins is illustrated by identification of 18 archaeal and bacterial proteins with simultaneous mass-spectrometric (MS) mapping of their entire primary structures. Dissociation of two or three proteins at once for such identifications in parallel is also demonstrated, along with retention and exact localization of a phosphorylated serine residue through the fragmentation process. These conceptual and technical advances should assist future processing of whole proteins in a higher throughput format for more robust detection of co- and post-translational modifications.

Algorithms↗

PubMed2001

Interval mapping of carcass and meat quality traits in a divergent swine cross.

An autosomal scan of the swine genome with 119 polymorphic microsatellite (ms) markers and data from 116 F2 barrows of the University of Illinois Meishan x Yorkshire Swine Resource Families identified genomic regions with effects on variance in carcass composition and meat quality at nominal significance (p-value <0.05). Marker intervals on chromosomes 1, 6, 7, 8 and 12 (SSC1, SSC6, SSC7, SSC8, SSC12) with phenotypic effects on carcass length, 10th rib backfat thickness, average backfat thickness, leaf fat, loin eye area and intramuscular fat content confirm QTL effects identified previously based on genome wide significance (p-value <0.05). Several marker intervals included nominally significant (p-value <0.05) dominance effects on leaf fat, 10th rib backfat thickness, loin eye area, muscle pH and intramuscular fat content.

Adipose Tissue↗

PubMed2001

Methodology for the measurement of mucociliary function in the mouse by scintigraphy.

The objective of the study was to develop a scintigraphic method for measurement of airway mucociliary clearance in small laboratory rodents such as the mouse. Previous investigations have characterized the secretory cell types present in the mouse airway, but analysis of the mucus transport system has been limited to in vitro examination of tissue explants or invasive in vivo measures of a single airway, the trachea. Three methods were used to deposit insoluble, radioisotopic colloidal particles: oropharyngeal aspiration, intratracheal instillation, and nose-only aerosol inhalation. The initial distribution of particles within the lower respiratory tract was visualized by gamma-camera, and clearance of particles was followed intermittently over 6 h and at the conclusion, 24 h postdelivery. Subsets of mice underwent lavage for evidence of tissue inflammation, and others were restudied for reproducibility of the methods. The aspiration and instillation methods of delivery led to greater distributions of deposited activity within the lungs, i.e., approximately 60--80% of the total respiratory tract radioactivity, whereas the nose-only aerosol technique attained a distribution of 32% to the lungs. However, the aerosol technique maximized the fraction of particles that cleared the airway over a 24-h period, i.e, deposited onto airway epithelial surfaces and cleared by mucociliary function such that lung retention at 24 h averaged 57% for delivery by aerosol inhalation and > or =80% for the aspiration or intratracheal instillation techniques. Particle delivery methods did not cause lung inflammation/injury with use of inflammatory cells and chemoattractant cytokines as criteria. Scintigraphy can discern particle deposition and clearance from the lower respiratory tract in the mouse, is noninvasive and reproducible, and includes the capability for restudy and lung lavage when time course or chronic treatments are being considered.

Animals↗

PubMed2001

Early alteration in glomerular reserve in humans at genetic risk of essential hypertension: mechanisms and consequences.

Essential hypertension has a familial predisposition, but the phenotype of elevated blood pressure has delayed penetrance. Because the kidney is a crucial determinant of blood pressure homeostasis, we studied early glomerular alterations in still-normotensive young subjects at genetic risk of hypertension. Thirty-nine normotensive adults (mean age 29 to 31 years), stratified by genetic risk (parental family history [FH]) of hypertension (26 with positive FH [FH+], 13 with negative FH [FH-]), underwent intravenous infusion of mixed amino acids. Before and during amino acid administration, we measured glomerular filtration rate (GFR), putative second messengers of amino acids (nitric oxide [NO.] metabolites and cGMP), serum insulin and amino acid concentrations, and the FE(Li)+ as an index of renal proximal tubular reabsorption. The FH+ group had a blunted GFR rise in response to amino acids (2.43+/-8.16% versus 31.0+/-13.4% rise, P:=0.0126). The amino acid-induced change in GFR correlated (r=0.786, P:<0.01) with the change in urinary NO. metabolite excretion; a diminished rise in urinary NO. metabolite excretion in the FH+ group (P:=0.0105) suggested a biochemical mechanism for the different GFR responses between FH groups: a relative inability to convert arginine to NO. The FH+ group had a far lower initial cGMP excretion at baseline (261+/-21.1 versus 579+/-84.9 nmol. h(-1)/1.73 m(2), P:=0.001), although cGMP did not change during the amino acid infusion (P:=0.703). FH status, baseline GFR, and baseline serum insulin jointly predicted GFR response to amino acids (P:=0.0013), accounting for approximately 45% of the variance in GFR response. Decline in FE(Li)+, an inverse index of proximal tubular reabsorption, paralleled increase in GFR (r=-0.506, P:=0.01), suggesting differences in proximal tubular reabsorption during amino acids between the FH groups. GFR response to amino acid infusion was blunted in the FH+ group despite significantly higher serum concentrations of 6 amino acids (arginine, isoleucine, leucine, methionine, phenylalanine, and valine) in the FH+ group, suggesting a novel form of insulin resistance (to the amino acid-translocating action of insulin) in FH+ subjects. We conclude that blunted glomerular filtration reserve in response to amino acids is an early-penetrance phenotype seen even in still-normotensive subjects at genetic risk of hypertension and is linked to impaired formation of NO. in the kidney. Corresponding changes in GFR and fractional excretion of Li(+) suggest that altered proximal tubular reabsorption after amino acids is an early pathophysiologic mechanism. Resistance to the amino acid-translocating actions of insulin may play a role in the biological response to amino acids in this setting. This glomerular reserve phenotype may be useful in genetic studies of renal traits preceding or predisposing to hypertension.

Adult↗

PubMed2000

Stimulus-based state control in the thalamocortical system.

Neural systems operate in various dynamic states that determine how they process information (Livingstone and Hubel, 1981; Funke and Eysel, 1992; Morrow and Casey, 1992; Abeles et al., 1995; Guido et al., 1995; Mukherjee and Kaplan, 1995; Kenmochi and Eggermont, 1997; Wörgötter et al., 1998; Kisley and Gerstein, 1999). To investigate the function of a brain area, it is therefore crucial to determine the state of that system. One grave difficulty is that even under well controlled conditions, the thalamocortical network may undergo random dynamic state fluctuations which alter the most basic spatial and temporal response properties of the neurons. These uncontrolled state changes hinder the evaluation of state-specific properties of neural processing and, consequently, the interpretation of thalamocortical function. Simultaneous extracellular recordings were made in the auditory thalamus and cortex of the ketamine-anesthetized cat under several stimulus conditions. By considering the cellular and network mechanisms that govern state changes, we develop a complex stimulus that controls the dynamic state of the thalamocortical network. Traditional auditory stimuli have ambivalent effects on thalamocortical state, sometimes eliciting an oscillatory state prevalent in sleeping animals and other times suppressing it. By contrast, our complex stimulus clamps the network in a dynamic state resembling that observed in the alert animal. It thus allows evaluation of neural information processing not confounded by uncontrolled variations. Stimulus-based state control illustrates a general and direct mechanism whereby the functional modes of the brain are influenced by structural features of the external world.

Acoustic Stimulation↗

PubMed2000

Null mutations in the lin-31 gene indicate two functions during Caenorhabditis elegans vulval development.

The lin-31 gene is required for the proper specification of vulval cell fates in the nematode Caenorhabditis elegans and encodes a member of the winged-helix family of transcription factors. Members of this important family have been identified in many organisms and are known to bind specific DNA targets involved in a variety of developmental processes. DNA sequencing of 13 lin-31 alleles revealed six nonsense mutations and two missense mutations within the DNA-binding domain, plus three deletions, one transposon insertion, and one frameshift mutation that all cause large-scale disruptions in the gene. The missense mutations are amino acid substitutions in the DNA-binding domain and probably disrupt interactions of the LIN-31 transcription factor with its DNA target. In addition, detailed phenotypic analysis of all 19 alleles showed similar penetrance for several characteristics examined. From our analysis we conclude: (1) the null phenotype of lin-31 is the phenotype displayed by almost all of the existing alleles, (2) the DNA-binding domain plays a critical role in LIN-31 function, and (3) direct screens for multivulva and vulvaless mutants will probably yield only null (or strong) alleles of lin-31.

Alleles↗

PubMed2000

Examination of bone chemical composition in osteoporosis using fluorescence-assisted synchrotron infrared microspectroscopy.

Although it is clear that osteoporosis is associated with a reduction in bone mass and a fragile skeleton, it is not understood whether the chemical composition of osteoporotic bone is different from normal bone. In this study, cynomolgus monkeys (Macaca fascicularis) were administered fluorochrome labels at one and two years after ovariectomy (Ovx) or Sham ovariectomy (intact), that were taken up into newly remodeled bone. Using fluorescence-assisted synchrotron infrared microspectroscopy, the chemical composition of bone from intact versus Ovx monkeys has been compared. Results from overall composition distributions (labeled + non-labeled bone) reveal similar carbonate/protein and phosphate/protein ratios, but increased acid phosphate content and different collagen structure in the Ovx animals. Analysis of the fluorochrome-labeled bone indicates similar degrees of mineralization in bone remodeled after one year, but decreased mineralization in Ovx bone remodeled two years after surgery. Thus, bone from monkeys with osteoporosis can be characterized as having abnormal collagen structure and reduced rates of mineralization. Coupled with factors such as trabecular architecture and bone shape and size, these ultrastructural factors may play a contributing role in the increased bone fragility in osteoporosis.

Animals↗