Bone mineral density (BMD) is one of the major determinants of risk for osteoporotic fracture. Multiple studies reveal that peak bone mass is under strong genetic influence. One of the major ...susceptibility loci for peak spine BMD has been mapped to chromosome 1q21–q23 in the Caucasian population. We have previously replicated this finding in Southern Chinese pedigrees and detected a maximum multipoint log of odds (LOD) score of 2.36 in this region. To further fine-map this region, 380 single-nucleotide polymorphic (SNP) markers were genotyped in 610 sibpairs from 231 families. Several markers were identified in the association analysis as important candidates underlying BMD variation. Among them, successful replication was demonstrated for SNPs in pre-B-cell leukemia homeobox 1 (PBX1) gene in two other unrelated case–control cohorts. The functional role of PBX1 in bone metabolism was examined in vitro using human bone-derived cells (HBDC) and murine MC3T3-E1 pre-osteoblasts. PBX1 mRNA was constitutively expressed in both HBDC and MC3T3-E1 cells. Immunostaining revealed that PBX1 is localized in the nucleus compartment. Silencing of PBX1 by RNAi in MC3T3-E1 cells decreased the expression of Runx2 and Osterix, the critical transcription factors for osteogenesis, but accelerated cell proliferation and bone nodule formation. Overall, our data suggest a genetic and functional association of PBX1 with BMD.
Lava erupts into cold sea water on the ocean floor at mid-ocean ridges (at depths of 2,500 m and greater), and the resulting flows make up the upper part of the global oceanic crust. Interactions ...between heated sea water and molten basaltic lava could exert significant control on the dynamics of lava flows and on their chemistry. But it has been thought that heating sea water at pressures of several hundred bars cannot produce significant amounts of vapour and that a thick crust of chilled glass on the exterior of lava flows minimizes the interaction of lava with sea water. Here we present evidence to the contrary, and show that bubbles of vaporized sea water often rise through the base of lava flows and collect beneath the chilled upper crust. These bubbles of steam at magmatic temperatures may interact both chemically and physically with flowing lava, which could influence our understanding of deep-sea volcanic processes and oceanic crustal construction more generally. We infer that vapour formation plays an important role in creating the collapse features that characterize much of the upper oceanic crust and may accordingly contribute to the measured low seismic velocities in this layer.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Until recently, mild traumatic brain injury (mTBI) or "concussion" was generally ignored as a major health issue. However, emerging evidence suggests that this injury is by no means mild, considering ...it induces persisting neurocognitive dysfunction in many individuals. Although little is known about the pathophysiological aspects of mTBI, there is growing opinion that diffuse axonal injury (DAI) may play a key role. To explore this possibility, we adapted a model of head rotational acceleration in swine to produce mTBI by scaling the mechanical loading conditions based on available biomechanical data on concussion thresholds in humans. Using these input parameters, head rotational acceleration was induced in either the axial plane (transverse to the brainstem; n=3), causing a 10- to 35-min loss of consciousness, or coronal plane (circumferential to the brainstem; n=2), which did not produce a sustained loss of consciousness. Seven days following injury, immunohistochemical analyses of the brains revealed that both planes of head rotation induced extensive axonal pathology throughout the white matter, characterized as swollen axonal bulbs or varicosities that were immunoreactive for accumulating neurofilament protein. However, the distribution of the axonal pathology was different between planes of head rotation. In particular, more swollen axonal profiles were observed in the brainstems of animals injured in the axial plane, suggesting an anatomic substrate for prolonged loss of consciousness in mTBI. Overall, these data support DAI as an important pathological feature of mTBI, and demonstrate that surprisingly overt axonal pathology may be present, even in cases without a sustained loss of consciousness.
The changes in the redox behavior and nanoscale morphology of poly2,2′-bithiophene deposited onto highly oriented pyrolytic graphite substrates upon repeated doping–undoping were studied. It was ...shown that repeated cycling resulted in very particular changes in the voltammetric response of the polymer films as well as their nanoscale morphology. Specifically, when the cycling was performed to relatively low anodic potentials, the overall doping–undoping charge did not change; however, the shape of voltammograms was consistently changing showing broadening of the voltammograms and reducing of the doping peak height in the anodic scan, as well as broadening and deterioration of the undoping peak in the reverse scan. Furthermore, a remarkable feature was observed that all voltammogram traces intersected at several characteristic potentials producing quasi-isosbestic points. With an increase in the anodic scan potential limit, the overall doping–undoping charge starts to decrease showing irreversible degradation of the polymer; however, the general pattern of the peak broadening could be still observed. Atomic force microscopic (AFM) studies of the polymer films cycled to various anodic limits showed that repeated cycling resulted in a gradual decrease in the degree of crystallinity, as revealed by AFM phase imaging, and an increase in the degree of disorder. Coupled with the changes in the redox behavior, these findings suggested the formation of more flexible and open polymer nanostructure that enables easier penetration of the dopant ions and solvent. However, at the same time, an increase in the degree of disorder reduced the interchain interactions and inhibited the formation of extended electronic states delocalized across neighboring polymer chains. This occurred at first without irreversible degradation of the polymer and a decrease in the overall doping–undoping charge. Cycling to higher anodic potentials resulted in irreversible degradation accompanied by profound changes in the polymer morphology.
We present 8–13 μm spectropolarimetry of 55 sources and 16–22 μm spectropolarimetry of six of these. This represents a substantial fraction of star formation regions that can be observed in this way ...with current technology on 4-m class telescopes (i.e. brighter than about 20 Jy at 10 μm in a 4-arcsec beam). Most of the sources are embedded young stellar objects (YSOs), H ii regions containing sites of star formation or bipolar protoplanetary nebulae (PPN), although a few other sources (e.g. NGC 1068, MWC 349) are also included. The majority have oxygen-rich chemistry but there are three carbon-rich sources. Many of the oxygen-rich sources show deep silicate absorption overlying featureless or optically thin silicate emission. Absorptive polarization with polarization per optical depth (paτ)≃1–3 per cent is common, and many also show evidence for an emissive polarization component as well, although pure polarization in emission is rare. The observed ranges of paτ and pe are very similar, rather surprising in view of their origin from very different environments. Typically the absorptive polarization profiles are similar to the archetypal silicate polarization found in OMC1 BN, but an exception is AFGL 2591, which displays an additional narrow polarization feature at 11.2 μm, which has been attributed to annealed silicates. Many of the intensity absorption spectra also show an inflection near 11.2 μm, which might also be attributable to annealed silicates. The carbon-rich sources have nearly featureless polarizations in the 0.5–1 per cent range, which we ascribe to dichroism in carbon-based grains; this is the first evidence that such grains can be aligned. In two of these sources the polarization appears to be caused by absorption by SiC. A few of the polarization spectra have no straightforward interpretation.
Effects of breed type and sex on the fatty acid composition of subcutaneous neutral lipid and intramuscular neutral and phospholipids of longissimus lumborum muscle were investigated using 145 steers ...and 82 heifers that consisted of pure Japanese Black and Holstein and crossbreds among Japanese Black, Holstein, Japanese Brown, and Charolais. Steers and heifers were reared on a high plane of nutrition and were fed the same concentrate diet and rice straw. All animals were slaughtered serially and carcass composition was determined by dissection of the left side of the carcass. Breed type and sex differences of fatty acid percentages of carcass lipids were compared by adjusting the percentages to mean carcass fat percentages. Heifers had higher contents of 18:1 and total monounsaturated fatty acids in subcutaneous and intramuscular neutral lipids than steers (P < .05). The fatty acid composition of intramuscular phospholipids differed between sexes for 16:0, 20:1, and 20:5, but the differences were small. Breed differences were significant (P < .05) in steers for 16:0, 16:1, 18:1, and total saturated and monounsaturated fatty acids in both subcutaneous and intramuscular neutral lipids, and iso-16:0, 16:0, and total saturated fatty acids in phospholipids, respectively. However, in heifers, fewer fatty acids differed (P < .05) among breed types in the neutral lipids. It is suggested that the Japanese Black has a genetic predisposition for producing carcass lipids containing higher concentrations of monounsaturated fatty acids than Holstein, Japanese Brown, or Charolais.
Transcriptional noise is known to play a crucial role in heterogeneity in bacteria and yeast. Mammalian macrophages are known to exhibit cell-to-cell variation in their responses to pathogens, but ...the source of this heterogeneity is not known. We have developed a detailed stochastic model of gene expression that takes into account scaling effects due to cell size and genome complexity. We report the results of applying this model to simulating gene expression variability in mammalian macrophages, demonstrating a possible molecular basis for heterogeneity in macrophage signalling responses. We note that the nature of predicted transcriptional noise in macrophages is different from that in yeast and bacteria. Some molecular interactions in yeast and bacteria are thought to have evolved to minimize the effects of the high-frequency noise observed in these species. Transcriptional noise in macrophages results in slow changes to gene expression levels and would not require the type of spike-filtering circuits observed in yeast and bacteria.
Objective The previous Pexelizumab for Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery I (PRIMO-CABG I) trial (n = 3099) indicated that C5 complement inhibition with ...pexelizumab might reduce myocardial infarction (MI) and postoperative mortality. PRIMO-CABG II was designed to investigate the safety and efficacy of terminal complement inhibition in reducing perioperative MI and mortality in patients undergoing CABG surgery who have 2 or more predefined preoperative risk factors. Methods PRIMO-CABG II, a randomized, double-blind, placebo-controlled trial, enrolled 4254 patients undergoing CABG with or without valve surgery at 249 hospitals in North America and Western Europe from June 2004 to July 2005. The patients were randomly assigned to receive intravenous pexelizumab or placebo. The primary composite endpoint was the incidence of death or MI within 30 days of randomization. Results The PRIMO-CABG II trial did not meet its prespecified primary endpoint of death or MI at 30 days, the secondary endpoints of death at 30 days, or the development of new or worsening congestive heart failure (relative risk 0.91, 0.82, and 1.01, respectively; P > .05). However, in a combined analysis of both pivotal trials, PRIMO-CABG I and II (n = 7353), death at 30 days was significantly reduced for the greatest risk subset (n = 2156, pexelizumab 5.7% vs placebo 8.1%, P = .024). Furthermore, this mortality reduction persisted throughout the 180-day follow-up period (pexelizumab 11.1% vs placebo 14.4%, P = .036). Conclusions Pexelizumab was associated with a nonsignificant 6.7% reduction in the primary composite endpoint of death or MI at postoperative day 30 in CABG patients enrolled in the PRIMO-CABG II trial, despite the suggestion of a more favorable treatment effect in the previous PRIMO-CABG I trial. However, an exploratory analysis of the combined PRIMO I and II data set using an established predictive risk model showed a mortality benefit for high-risk surgical patients.
We present an analysis of the dust and gas in Andromeda, using Herschel images sampling the entire far-infrared peak. We fit a modified-blackbody model to ~4000 quasi-independent pixels with spatial ...resolution of ~ 140 pc and find that a variable dust-emissivity index (beta) is required to fit the data. We find no significant long-wavelength excess above this model, suggesting there is no cold dust component. We show that the gas-to-dust ratio varies radially, increasing from ~20 in the center to ~70 in the star-forming ring at 10 kpc, consistent with the metallicity gradient. In the 10 kpc ring the average beta is ~1.9, in good agreement with values determined for the Milky Way (MW). However, in contrast to the MW, we find significant radial variations in beta, which increases from 1.9 at 10 kpc to ~2.5 at a radius of 3.1 kpc and then decreases to 1.7 in the center. The dust temperature is fairly constant in the 10 kpc ring (ranging from 17 to 20 K), but increases strongly in the bulge to ~30 K. Within 3.1 kpc we find the dust temperature is highly correlated with the 3.6 mum flux, suggesting the general stellar population in the bulge is the dominant source of dust heating there. At larger radii, there is a weak correlation between the star formation rate and dust temperature. We find no evidence for "dark gas" in M31 in contrast to recent results for the MW. Finally, we obtained an estimate of the CO X-factor by minimizing the dispersion in the gas-to-dust ratio, obtaining a value of (1.9 + or - 0.4) x 10 super(20) cm super(-2) K km s super(-1) super(-1).
Three treatments designed to initiate the process of restoring the surface fire regime and open forest structure of a southwestern ponderosa pine forest were compared on the Kaibab National Forest ...along the Grand Canyon’s South Rim. The treatments were: (1)
full restoration (FULL)—thinning trees to emulate stand structure prior to fire regime disruption ca. 1887, forest floor fuel treatment, and prescribed burning, (2)
minimal thinning (MIN)—removing young trees only around living old-growth (pre-1887) trees, fuel treatment, and prescribed burning, (3)
burn-only (BURN)—representing the current management policy in Grand Canyon National Park (GCNP), and (4) CONTROL. Each treatment was applied to a 12
ha unit. Compared to reconstructed 1887 conditions, all study sites were much more dense prior to treatment (94–176
trees/ha in 1887, compared to 783–3693
trees/ha in 1997). However, basal area increases were less striking (12.6–20.3 in 1887, 17.5–27.0
m
2/ha in 1997), reflecting past harvest and dwarf mistletoe reduction treatments that removed many large pines. In 2000, 1 year after treatment, tree densities were reduced to 11, 23, and 37 of pre-treatment levels in the FULL, MIN, and BURN treatments, respectively. Understory plant communities showed significant declines in richness and plant frequency across years, probably due to a severe drought in 2000 (60% of average precipitation). No differences in plant communities were observed across treatments, despite the mechanized disturbance associated with tree removal in the FULL treatment. Prescribed fire behavior (flame length, flaming zone depth) and effects (bole char, crown scorch) were similar across all three burned treatments. Simulated fire behavior under dry, windy conditions was reduced in all three treatments compared to the control. The FULL treatment was much less susceptible to crownfire due to reduced crown bulk density and crown fuel load and increased crown base height. Crownfire susceptibility of the BURN treatment was only slightly reduced, while the MIN treatment was intermediate. Compared to the reference conditions of forest structure, the FULL treatment represented the most rapid and comprehensive restoration treatment, although the residual stand was at the low end of historical density. The BURN treatment thinned many small trees but had minor effects on crownfire susceptibility. Effects of the MIN treatment fell between FULL and BURN. The experimental treatments may be useful for the creation of defensible firebreaks near developments, roads, and boundaries with the FULL treatment, supplemented by MIN and BURN treatments over larger areas.
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