Assembly and Alignment of Fibronectin-Coated Gold Beads into Fibrils by Human Skin Fibroblasts

The assembly of fibronectin into fibrils was monitored by high voltage electron microscopy using 18 nm colloidal gold beads bound to fibronectin (Au18-fibronectin) or an amino terminal 70 kd fragment of fibronectin (Au18-70 kd) that blocks the incorporation of fibronectin into disulfide bonded fibrils. Subconfluent cultures of human skin fibroblasts were incubated with the colloidal gold complexes for 0.25, 0.5, 1.5 and 5 h. In fibroblast cultures incubated with Au18-fibronectin and Au18-70 kd fragments for 0.25 and 0.5 h, the complexes of Au18-fibronectin and Au18-70 kd fragment were observed bound to the cell surface in clusters near bundles of intracellular microfilaments, usually along the lateral edges of the fibroblasts. Fibroblast cultures incubated with Au18-fibronectin and Au18-70 kd fragment for 1.5 and 5 h showed a more linear arrangement of the Au18-fibronectin and Au18-70 kd fragment along the lateral and retracting edges and on filopodia. This alignment of Au18-fibronectin into linear arrangements on the fibroblast cell surface suggests that the assembly of fibronectin fibrils occurs on specific regions of the fibroblast

Activated avb3 Integrin Regulates avb5 Integrin-Mediated Phagocytosis in Trabecular Meshwork Cells

PURPOSE. To investigate the roles of avb3 and avb5 integrins in phagocytosis in human trabecular meshwork (HTM) cells. METHODS. Immunofluorescence microscopy and FACS analysis were used to determine levels of avb3 and avb5 integrins in TM tissue and cultures of normal and immortalized TM cells. Phagocytosis was measured using pHrodo-labeled S. aureus bioparticles followed by FACS analysis. The role of avb5 integrin in phagocytosis was evaluated by knocking down avb5 integrin expression with siRNA against the human b5 gene. Signaling from focal adhesion kinase (FAK) was blocked using FAK inhibitor 14. The role of avb3 integrins in phagocytosis was determined by treating HTM cells with dexamethasone (DEX) or ethanol (EtOH) and by generating stable cell lines that overexpressed either wild type (WT) or constitutively active (CA) b3 integrin subunit. RESULTS. Both TM tissue and cell lines expressed avb3 and avb5 integrins. Knockdown of avb5 integrin reduced phagocytosis by~60% and FAK inhibition significantly reduced phagocytosis up to 84%, in a dose-dependent manner. DEX treatment increased avb3 integrin expression in HTM cells but reduced phagocytosis by~50% compared with untreated and EtOH-treated cells. The CA b3 integrin-expressing cell line showed increased avb3 integrin levels and decreased phagocytosis by~50% compared with the control. CONCLUSIONS. The avb5 integrin-FAK-mediated pathway regulates phagocytosis in TM cells and this pathway is inhibited by activation of avb3 integrins. This suggests that changes in integrin expression and activity may be responsible for alterations in phagocytosis observed in steroid induced glaucoma

Annual Summary of Vital Statistics-1997

Many positive trends in the health of Americans continued into 1997. In 1997, the preliminary birth rate declined slightly to 14.6 births per 1000 population, and the fertility rate, births per 1000 women 15 to 44 years of age, was unchanged from the previous year (65.3). These indicators suggest that the downward trend in births observed since the early 1990s may have abated. Fertility rates for white, black, and Native American women were essentially unchanged between 1996 and 1997. Fertility among Hispanic women declined 2% in 1997 to 103.1, the lowest level reported since national data for this group have been available. For the sixth consecutive year, birth rates dropped for teens. Birth rates for women 30 years or older continued to increase. The proportion of births to unmarried women (32.4%) was unchanged in 1997. The trend toward earlier utilization of prenatal care continued for 1997; 82.5% of women began prenatal care in the first trimester. There was no change in the percentage with late (third trimester) or no care in 1997. The cesarean delivery rate rose slightly to 20.8% in 1997, a reversal of the downward trend observed since 1989. The percentage of low birth weight (LBW) infants rose again in 1997 to 7.5%. The percentage of very low birth weight was up only slightly to 1.41%. Among births to white mothers, LBW increased for the fifth consecutive year, to 6.5%, whereas the rate for black mothers remained unchanged at 13%. Much, but not all, of the rise in LBW for white mothers during the 1990s can be attributed to an increase in multiple births. In 1996, the multiple birth rate rose again by 5%, and the higher-order multiple birth rate climbed by 20%. Infant mortality reached an all time low level of 7.1 deaths per 1000 births, based on preliminary 1997 data. Both neonatal and postneonatal mortality rates declined. In 1996, 64% of all infant deaths occurred to the 7.4% of infants born at LBW. Infant mortality rates continue to be more than two times greater for black than for white infants. Among all the states in 1996, Maine, Massachusetts, and New Hampshire had the lowest infant mortality rates. Despite declines in infant mortality, the United States continues to rank poorly in international comparisons of infant mortality. Expectation of life at birth reached a new high in 1997 of 76.5 years for all gender and race groups combined. Age-adjusted death rates declined in 1997 for diseases of the heart, accidents and adverse affects (unintentional injuries), homicide, suicide, malignant neoplasms, cerebrovascular disease, chronic liver disease and cirrhosis, and diabetes. In 1997, mortality due to HIV infection declined by 47%. Death rates for children from all major causes declined again in 1997. Motor vehicle traffic injuries and firearm injuries were the two major causes of traumatic death. A large proportion of childhood deaths continue to occur as a result of preventable injuries

Transportation Energy Pathways LDRD.

This report presents a system dynamics based model of the supply-demand interactions between the USlight-duty vehicle (LDV) fleet, its fuels, and the corresponding primary energy sources through the year2050. An important capability of our model is the ability to conduct parametric analyses. Others have reliedupon scenario-based analysis, where one discrete set of values is assigned to the input variables and used togenerate one possible realization of the future. While these scenarios can be illustrative of dominant trendsand tradeoffs under certain circumstances, changes in input values or assumptions can have a significantimpact on results, especially when output metrics are associated with projections far into the future. Thistype of uncertainty can be addressed by using a parametric study to examine a range of values for the inputvariables, offering a richer source of data to an analyst.The parametric analysis featured here focuses on a trade space exploration, with emphasis on factors thatinfluence the adoption rates of electric vehicles (EVs), the reduction of GHG emissions, and the reduction ofpetroleum consumption within the US LDV fleet. The underlying model emphasizes competition between13 different types of powertrains, including conventional internal combustion engine (ICE) vehicles, flex-fuel vehicles (FFVs), conventional hybrids(HEVs), plug-in hybrids (PHEVs), and battery electric vehicles(BEVs).We find that many factors contribute to the adoption rates of EVs. These include the pace of technologicaldevelopment for the electric powertrain, battery performance, as well as the efficiency improvements inconventional vehicles. Policy initiatives can also have a dramatic impact on the degree of EV adoption. Theconsumer effective payback period, in particular, can significantly increase the market penetration rates ifextended towards the vehicle lifetime.Widespread EV adoption can have noticeable impact on petroleum consumption and greenhouse gas(GHG) emission by the LDV fleet. However, EVs alone cannot drive compliance with the most aggressiveGHG emission reduction targets, even as the current electricity source mix shifts away from coal and towardsnatural gas. Since ICEs will comprise the majority of the LDV fleet for up to forty years, conventional vehicleefficiency improvements have the greatest potential for reductions in LDV GHG emissions over this time.These findings seem robust even if global oil prices rise to two to three times current projections. Thus,investment in improving the internal combustion engine might be the cheapest, lowest risk avenue towardsmeeting ambitious GHG emission and petroleum consumption reduction targets out to 2050.3 AcknowledgmentThe authors would like to thank Dr. Andrew Lutz, Dr. Benjamin Wu, Prof. Joan Ogden and Dr. ChristopherYang for their suggestions over the course of this project. This work was funded by the Laboratory DirectedResearch and Development program at Sandia National Laboratories.

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Photometric and Spectroscopic Observations of SN 1990E in NGC 1035: Observational Constraints for Models of Type II Supernovae

We present 126 photometric and 30 spectral observation of SN 1990E spanning from 12 days before B maximum to 600 days past discovery. These observations show that SN 1990E was of type II-P, displaying hydrogen in its spectrum, and the characteristic plateau in its light curve. SN 1990E is one of the few SNe II which has been well observed before maximum light, and we present evidence that this SN was discovered very soon after its explosion. In the earliest spectra we identify, for the first time, several N II lines. We present a new technique for measuring extinction to SNe II based on the evolution of absorption lines, and use this method to estimate the extinction to SN 1990E, Av=1.5+/-0.3 mag. From our photometric data we have constructed a bolometric light curve for SN 1990E and show that, even at the earliest times, the bolometric luminosity was falling rapidly. We use the late-time bolometric light curve to show that SN 1990E trapped a majority of the gamma rays produced by the radioactive decay of 56Co, and estimate that SN 1990E ejected 0.073 Mo of 56Ni, an amount virtually identical to that of SN 1987A. [excerpt

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

A systematic review evaluating the psychometric properties of measures of social inclusion

Introduction: Improving social inclusion opportunities for population health has been identified as a priority area for international policy. There is a need to comprehensively examine and evaluate the quality of psychometric properties of measures of social inclusion that are used to guide social policy and outcomes. Objective: To conduct a systematic review of the literature on all current measures of social inclusion for any population group, to evaluate the quality of the psychometric properties of identified measures, and to evaluate if they capture the construct of social inclusion. Methods: A systematic search was performed using five electronic databases: CINAHL, PsycINFO, Embase, ERIC and Pubmed and grey literature were sourced to identify measures of social inclusion. The psychometric properties of the social inclusion measures were evaluated against the COSMIN taxonomy of measurement properties using pre-set psychometric criteria. Results: Of the 109 measures identified, twenty-five measures, involving twenty-five studies and one manual met the inclusion criteria. The overall quality of the reviewed measures was variable, with the Social and Community Opportunities Profile-Short, Social Connectedness Scale and the Social Inclusion Scale demonstrating the strongest evidence for sound psychometric quality. The most common domain included in the measures was connectedness (21), followed by participation (19); the domain of citizenship was covered by the least number of measures (10). No single instrument measured all aspects within the three domains of social inclusion. Of the measures with sound psychometric evidence, the Social and Community Opportunities Profile-Short captured the construct of social inclusion best. Conclusions: The overall quality of the psychometric properties demonstrate that the current suite of available instruments for the measurement of social inclusion are promising but need further refinement. There is a need for a universal working definition of social inclusion as an overarching construct for ongoing research in the area of the psychometric properties of social inclusion instruments