An atomic scale comparison of the reaction of Bioglass® in two types of simulated body fluid

A class of melt quenched silicate glasses, containing calcium, phosphorus and alkali metals, and having the ability to promote bone regeneration and to fuse to living bone, is produced commercially as Bioglass. The changes in structure associated with reacting the bioglass with a body fluid simulant (a buffered Tris(hydroxymethyl)aminomethane growth medium solution or a blood plasma-like salt simulated body fluid) at 37°C have been studied using both high energy and grazing incidence x-ray diffraction. This has corroborated the generic conclusions of earlier studies based on the use of calcia–silica sol-gel glasses whilst highlighting the important differences associated with glass composition; the results also reveal the more subtle effects on reaction rates of the choice of body fluid simulant. The results also indicate the presence of tricalcium phosphate crystallites deposited onto the surface of the glass as a precursor to the growth of hydroxyapatite, and indicates that there is some preferred orientation to their growth

Co-culture of mechanically injured cartilage with joint capsule tissue alters chondrocyte expression patterns and increases ADAMTS5 production

We studied changes in chondrocyte gene expression, aggrecan degradation, and aggrecanase production and activity in normal and mechanically injured cartilage co-cultured with joint capsule tissue. Chondrocyte expression of 21 genes was measured at 1, 2, 4, 6, 12, and 24 h after treatment; clustering analysis enabled identification of co-expression profiles. Aggrecan fragments retained in cartilage and released to medium and loss of cartilage sGAG were quantified. Increased expression of MMP-13 and ADAMTS4 clustered with effects of co-culture, while increased expression of ADAMTS5, MMP-3, TGF-β, c-fos, c-jun clustered with cartilage injury. ADAMTS5 protein within cartilage (immunohistochemistry) increased following injury and with co-culture. Cartilage sGAG decreased over 16-days, most severely following injury plus co-culture. Cartilage aggrecan was cleaved at aggrecanase sites in the interglobular and C-terminal domains, resulting in loss of the G3 domain, especially after injury plus co-culture. Together, these results support the hypothesis that interactions between injured cartilage and other joint tissues are important in matrix catabolism after joint injury

A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant staphylococcus aureus pandemic

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens

The Local Bubble and Interstellar Material Near the Sun

The properties of interstellar matter (ISM) at the Sun are regulated by our location with respect to the Local Bubble (LB) void in the ISM. The LB is bounded by associations of massive stars and fossil supernovae that have disrupted natal ISM and driven intermediate velocity ISM into the LB interior void. The Sun is located in such a driven ISM parcel. The Local Fluff has a bulk velocity of 19 km/s in the LSR, and an upwind direction towards the center of the gas and dust ring formed by the Loop I supernova remnant interaction with the LB. When the ram pressure of the LIC is included in the total LIC pressure, and if magnetic thermal and cosmic ray pressures are similar, the LIC appears to be in pressure equilibrium with the local hot bubble plasma.Comment: Proceedings of Symposium on the Composition of Matter, honoring Johannes Geiss on the occasion of his 80th birthday. Space Science Reviews (in press

CYP2B6 Variants and Plasma Efavirenz Concentrations during Antiretroviral Therapy in Port‐au‐Prince, Haiti

Polymorphisms in CYP2B6 are known to predict increased steady-state plasma concentrations of efavirenz. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations among 45 Haitians who initiated antiretroviral therapy in Port-au-Prince

IGF-1 does not moderate the time-dependent transcriptional patterns of key homeostatic genes induced by sustained compression of bovine cartilage

Objective To determine changes in chondrocyte transcription of a range of anabolic, catabolic and signaling genes following simultaneous treatment of cartilage with Insulin-like growth factor-1 (IGF-1) and ramp-and-hold mechanical compression, and compare with effects on biosynthesis. Methods Explant disks of bovine calf cartilage were slowly compressed (unconfined) over 3-min to their 1 mm cut-thickness (0%-compression) or to 50%-compression with or without 300 ng/ml IGF-1. Expression of 24 genes involved in cartilage homeostasis was measured using qPCR at 2, 8, 24, 32, 48 h after compression ±IGF-1. Clustering analysis was used to identify groups of co-expressed genes to further elucidate mechanistic pathways. Results IGF-1 alone stimulated gene expression of aggrecan and collagen II, but simultaneous 24h compression suppressed this effect. Compression alone up-regulated expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 and transforming growth factor (TGF)-β, an effect not reversed by simultaneous IGF-1 treatment. Temporal changes in expression following IGF-1 treatment were generally slower than that following compression. Clustering analysis revealed five distinct groups within which the pairings, tissue inhibitor of metalloproteinase (TIMP)-3 and ADAMTS-5, MMP-1 and IGF-2, and IGF-1 and Collagen II, were all robustly co-expressed, suggesting inherent regulation and feedback in chondrocyte gene expression. While aggrecan synthesis was transcriptionally regulated by IGF-1, inhibition of aggrecan synthesis by sustained compression appeared post-transcriptionally regulated. Conclusion Sustained compression markedly altered the effects of IGF-1 on expression of genes involved in cartilage homeostasis, while IGF-1 was largely unable to moderate the transcriptional effects of compression alone. The demonstrated co-expressed gene pairings suggest a balance of anabolic and catabolic activity following simultaneous mechanical and growth factor stimuli.National Institutes of Health (U.S.) (grant R01-AR33236)National Institutes of Health (U.S.) (grant R01-HG003352)National Institutes of Health (U.S.) (grant P42-ES04699)National Institutes of Health (U.S.) (grant T32-EB006348

Stable isotope food-web analysis and mercury biomagnification in polar bears ( Ursus maritimus )

Mercury (Hg) biomagnification occurs in many ecosystems, resulting in a greater potential for toxicological effects in higher-level trophic feeders. However, Hg transport pathways through different food-web channels are not well known, particularly in high-latitude systems affected by the atmospheric Hg deposition associated with snow and ice. Here, we report on stable carbon and nitrogen isotope ratios, and Hg concentrations, determined for 26, late 19th and early 20th century, polar bear ( Ursus maritimus ) hair specimens, collected from catalogued museum collections. These data elucidate relationships between the high-latitude marine food-web structure and Hg concentrations in polar bears. The carbon isotope compositions of polar bear hairs suggest that polar bears derive nutrition from coupled food-web channels, based in pelagic and sympagic primary producers, whereas the nitrogen isotope compositions indicate that polar bears occupy > fourth-level trophic positions. Our results show a positive correlation between polar bear hair Hg concentrations and δ 15 N. Interpretation of the stable isotope data in combination with Hg concentrations tentatively suggests that polar bears participating in predominantly pelagic food webs exhibit higher mercury concentrations than polar bears participating in predominantly sympagic food webs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73930/1/j.1751-8369.2009.00114.x.pd

Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy