Long-term effects of neutral proteases on collagen degradation in the rabbit cornea

Includes bibliographical references.I have investigated the effects of neutral proteases on the collagen in the rabbit cornea. Knowing that matrix metalloproteinanse I (MMP I - collagenase) is the primary source of interstial collagen degradation, we asked what the long term affects were of other neutral proteases on collagen degradation. By exposing 3mm rabbit eye corneal punches to various concentrations of endo and exopeptidases, I have shown that leucine aminopeptidase, carboxypeptidase B, carboxypeptidase A, alpha chymotrypsin (bovine), L-tosylamido-2-phenyl ethyl chlorolmethyl ketone- trypsin, plasmin (human), cathepsin G (human), and elastase (human), all have some degradative effect on interstitial collagen ranging from 0.5% to 13% of the total collagen present in corneal punches in 4 days. These findings suggest that these proteases may have very significant effects on overal all collagen metabolism over extended time periods. By heat denaturing the collagen in corneal punches, I have also shown that 63% to 73% of the total collagen in young corneal punches will solubilize out in neutral buffer, while only 22% to 33% of the total collagen in mature corneal punches is liberated. This finding suggest that collagen crosslinking by x j nondisulfide bonds is somewhat effected by aging. Finally, by exposing sections of a 2mm peripheral ring of an 8mm central W corneal punch to neutral buffer, I have shown that 1% to 6.6% of the native interstitial collagen will solubilize out of the medial and lateral sections of the ring, but not in the superior and inferior zones. These findings suggest a regional physiological difference on the surface of the eye, possibly in the area where the eyelids meet during blinking.B.S. (Bachelor of Science

Optical Structure and Proper-Motion Age of the Oxygen-rich Supernova Remnant 1E 0102-7219 in the Small Magellanic Cloud

We present new optical emission-line images of the young SNR 1E 0102-7219 (E0102) in the SMC obtained with the HST Advanced Camera for Surveys (ACS). E0102 is a member of the oxygen-rich class of SNRs showing strong oxygen, neon , and other metal-line emissions in its optical and X-ray spectra, and an absence of H and He. The progenitor of E0102 may have been a Wolf-Rayet star that underwent considerable mass loss prior to exploding as a Type Ib/c or IIL/b SN. The ejecta in this SNR are fast-moving (V > 1000 km/s) and emit as they are compressed and heated in the reverse shock. In 2003, we obtained optical [O III], H-alpha, and continuum images with the ACS Wide Field Camera. The [O III] image captures the full velocity range of the ejecta, and shows considerable high-velocity emission projected in the middle of the SNR that was Doppler-shifted out of the narrow F502N bandpass of a previous Wide Field and Planetary Camera 2 image from 1995. Using these two epochs separated by ~8.5 years, we measure the transverse expansion of the ejecta around the outer rim in this SNR for the first time at visible wavelengths. From proper-motion measurements of 12 ejecta filaments, we estimate a mean expansion velocity for the bright ejecta of ~2000 km/s and an inferred kinematic age for the SNR of \~2050 +/- 600 years. The age we derive from HST data is about twice that inferred by Hughes et al.(2000) from X-ray data, though our 1-sigma error bars overlap. Our proper-motion age is consistent with an independent optical kinematic age derived by Eriksen et al.(2003) using spatially resolved [O III] radial-velocity data. We derive an expansion center that lies very close to X-ray and radio hotspots, which could indicate the presence of a compact remnant (neutron star or black hole).Comment: 28 pages, 8 figures. Accepted to the Astrophysical Journal, to appear in 20 April 2006 issue. Full resolution figures are posted at: http://stevenf.asu.edu/figure

The Cosmic Origins Spectrograph

The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F(sub lambda) approximates 1.0 X 10(exp -14) ergs/s/cm2/Angstrom, COS can achieve comparable signal to noise (when compared to STIS echelle modes) in 1-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (September 2009 - June 2011) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is 9 times that sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of June 2011. COS has measured, for the first time with high reliability, broad Lya absorbers and Ne VIII in the intergalactic medium, and observed the HeII reionization epoch along multiple sightlines. COS has detected the first CO emission and absorption in the UV spectra of low-mass circumstellar disks at the epoch of giant planet formation, and detected multiple ionization states of metals in extra-solar planetary atmospheres. In the coming years, COS will continue its census of intergalactic gas, probe galactic and cosmic structure, and explore physics in our solar system and Galaxy

A Bacterial Cytotoxin Identifies the RhoA Exchange Factor Net1 as a Key Effector in the Response to DNA Damage

Background: Exposure of adherent cells to DNA damaging agents, such as the bacterial cytolethal distending toxin (CDT) or ionizing radiations (IR), activates the small GTPase RhoA, which promotes the formation of actin stress fibers and delays cell death. The signalling intermediates that regulate RhoA activation and promote cell survival are unknown. Principal Findings: We demonstrate that the nuclear RhoA-specific Guanine nucleotide Exchange Factor (GEF) Net1 becomes dephosphorylated at a critical inhibitory site in cells exposed to CDT or IR. Expression of a dominant negative Net1 or Net1 knock down by iRNA prevented RhoA activation, inhibited the formation of stress fibers, and enhanced cell death, indicating that Net1 activation is required for this RhoA-mediated responses to genotoxic stress. The Net1 and RhoAdependent signals involved activation of the Mitogen-Activated Protein Kinase p38 and its downstream target MAPKactivated protein kinase 2. Significance: Our data highlight the importance of Net1 in controlling RhoA and p38 MAPK mediated cell survival in cells exposed to DNA damaging agents and illustrate a molecular pathway whereby chronic exposure to a bacterial toxin ma

The impact of trained patient educators on musculoskeletal clinical skills attainment in pre-clerkship medical students

<p>Abstract</p> <p>Background</p> <p>Despite the high burden of musculoskeletal (MSK) diseases, few generalists are comfortable teaching MSK physical examination (PE) skills. Patient Partners^®in Arthritis (PP^®IA) is a standardized patient educator program that could potentially supplement current MSK PE teaching. This study aims to determine if differences exist in MSK PE skills between non-MSK specialist physician and PP^®IA taught students.</p> <p>Methods</p> <p>Pre-clerkship medical students attended 2-hour small group MSK PE teaching by either non-MSK specialist physician tutors or by PP^®IA. All students underwent an MSK OSCE and completed retrospective pre-post questionnaires regarding comfort with MSK PE and interest in MSK.</p> <p>Results</p> <p>83 students completed the OSCE (42 PP^®IA, 41 physician taught) and 82 completed the questionnaire (42 PP^®IA, 40 physician taught). There were no significant differences between groups in OSCE scores. For all questionnaire items, post-session ratings were significantly higher than pre-session ratings for both groups. In exploratory analysis PP^®IA students showed significantly greater improvement in 12 of 22 questions including three of five patient-centred learning questions.</p> <p>Conclusions</p> <p>PP^®IA MSK PE teaching is as good as non-MSK specialist physician tutor teaching when measured by a five station OSCE and provide an excellent complementary resource to address current deficits in MSK PE teaching.</p

Weather and Financial Risk-Taking: Is Happiness the Channel?

Weather variables, and sunshine in particular, are found to be strongly correlated with financial variables. I consider self-reported happiness as a channel through which sunshine affects financial variables. I examine the influence of happiness on risk-taking behavior by instrumenting individual happiness with regional sunshine, and I find that happy people appear to be more risk-averse in financial decisions, and accordingly choose safer investments. Happy people take more time for making decisions and have more self-control. Happy people also expect to live longer and accordingly seem more concerned about the future than the present, and expect less inflation

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Abrupt climate change as an important agent of ecological change in the Northeast U.S. throughout the past 15,000 years

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Quaternary Science Reviews 28 (2009): 1693-1709, doi:10.1016/j.quascirev.2009.04.005.We use a series of tests to evaluate two competing hypotheses about the association of climate and vegetation trends in the northeastern United States over the past 15 kyrs. First, that abrupt climate changes on the scale of centuries had little influence on long-term vegetation trends, and second, that abrupt climate changes interacted with slower climate trends to determine the regional sequence of vegetation phases. Our results support the second. Large dissimilarity between temporally-close fossil pollen samples indicates large vegetation changes within 500 years across >4° of latitude at ca. 13.25-12.75, 12.0-11.5, 10.5, 8.25, and 5.25 ka. The evidence of vegetation change coincides with independent isotopic and sedimentary indicators of rapid shifts in temperature and moisture balance. In several cases, abrupt changes reversed long-term vegetation trends, such as when spruce (Picea) and pine (Pinus) pollen percentages rapidly declined to the north and increased to the south at ca. 13.25-12.75 and 8.25 ka respectively. Abrupt events accelerated other long‐term trends, such as a regional increase in beech (Fagus) pollen percentages at 8.5-8.0 ka. The regional hemlock (Tsuga) decline at ca. 5.25 ka is unique among the abrupt events, and may have been induced by high climatic variability (i.e., repeated severe droughts from 5.7-2.0 ka); autoregressive ecological and evolutionary processes could have maintained low hemlock abundance until ca. 2.0 ka. Delayed increases in chestnut (Castanea) pollen abundance after 5.8 and 2.5 ka also illustrate the potential for multi-century climate variability to influence species’ recruitment as well as mortality. Future climate changes will probably also rapidly initiate persistent vegetation change, particularly by acting as broad, regional-scale disturbances.This work was supported by NSF grants to B. Shuman (EAR‐0602408; DEB‐0816731) and J. Donnelly (EAR‐0602380)

The Cosmic Origins Spectrograph

The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F_lambda ~ 1.0E10-14 ergs/s/cm2/Angstrom, COS can achieve comparable signal to noise (when compared to STIS echelle modes) in 1-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (September 2009 - June 2011) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is 9 times that sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of June 2011. COS has measured, for the first time with high reliability, broad Lya absorbers and Ne VIII in the intergalactic medium, and observed the HeII reionization epoch along multiple sightlines. COS has detected the first CO emission and absorption in the UV spectra of low-mass circumstellar disks at the epoch of giant planet formation, and detected multiple ionization states of metals in extra-solar planetary atmospheres. In the coming years, COS will continue its census of intergalactic gas, probe galactic and cosmic structure, and explore physics in our solar system and Galaxy.Comment: 17 pages, 15 figure