CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry.

Hepatitis C virus (HCV) is an enveloped positive-stranded RNA hepatotropic virus. HCV pseudoparticles infect liver-derived cells, supporting a model in which liver-specific molecules define HCV internalization. Three host cell molecules have been reported to be important entry factors or receptors for HCV internalization: scavenger receptor BI, the tetraspanin CD81, and the tight junction protein claudin-1 (CLDN1). None of the receptors are uniquely expressed within the liver, leading us to hypothesize that their organization within hepatocytes may explain receptor activity. Since CD81 and CLDN1 act as coreceptors during late stages in the entry process, we investigated their association in a variety of cell lines and human liver tissue. Imaging techniques that take advantage of fluorescence resonance energy transfer (FRET) to study protein-protein interactions have been developed. Aequorea coerulescens green fluorescent protein- and Discosoma sp. red-monomer fluorescent protein-tagged forms of CD81 and CLDN1 colocalized, and FRET occurred between the tagged coreceptors at comparable frequencies in permissive and nonpermissive cells, consistent with the formation of coreceptor complexes. FRET occurred between antibodies specific for CD81 and CLDN1 bound to human liver tissue, suggesting the presence of coreceptor complexes in liver tissue. HCV infection and treatment of Huh-7.5 cells with recombinant HCV E1-E2 glycoproteins and anti-CD81 monoclonal antibody modulated homotypic (CD81-CD81) and heterotypic (CD81-CLDN1) coreceptor protein association(s) at specific cellular locations, suggesting distinct roles in the viral entry process

Analysis of Rock Varnish from the Mojave Desert by Handheld Laser-Induced Breakdown Spectroscopy

Laser-induced breakdown spectroscopy (LIBS) is a form of optical emission spectroscopy that can be used for the rapid analysis of geological materials in the field under ambient environmental conditions. We describe here the innovative use of handheld LIBS for the in situ analysis of rock varnish. This thinly laminated and compositionally complex veneer forms slowly over time on rock surfaces in dryland regions and is particularly abundant across the Mojave Desert climatic region of east-central California (USA). Following the depth profiling examination of a varnished clast from colluvial gravel in Death Valley in the laboratory, our in situ analysis of rock varnish and visually similar coatings on rock surfaces was undertaken in the Owens and Deep Spring valleys in two contexts, element detection/identification and microchemical mapping. Emission peaks were recognized in the LIBS spectra for the nine elements most abundant in rock varnish—Mn, Fe, Si, Al, Na, Mg, K, Ca and Ba, as well as for H, Li, C, O, Ti, V, Sr and Rb. Focused follow-up laboratory and field studies will help understand rock varnish formation and its utility for weathering and chronological studies

Structural basis of nSH2 regulation and lipid binding in PI3Kα

We report two crystal structures of the wild-type phosphatidylinositol 3-kinase α (PI3Kα) heterodimer refined to 2.9 Å and 3.4 Å resolution: the first as the free enzyme, the second in complex with the lipid substrate, diC4-PIP2, respectively. The first structure shows key interactions of the N-terminal SH2 domain (nSH2) and iSH2 with the activation loop that suggest a mechanism by which the enzyme is inhibited in its basal state. In the second structure, the lipid substrate binds in a positively charged pocket adjacent to the ATP-binding site, bordered by the P-loop, the activation loop and the iSH2 domain. An additional lipid-binding site was identified at the interface of the ABD, iSH2 and kinase domains. The ability of PI3Kα to bind an additional PIP2 molecule was confirmed in vitro by fluorescence quenching experiments. The crystal structures reveal key differences in the way the nSH2 domain interacts with wild-type p110α and with the oncogenic mutant p110αH1047R. Increased buried surface area and two unique salt-bridges observed only in the wild-type structure suggest tighter inhibition in the wild-type PI3Kα than in the oncogenic mutant. These differences may be partially responsible for the increased basal lipid kinase activity and increased membrane binding of the oncogenic mutant

Diffusive gradient thin-films in seawater: time integrated technique for aqueous trace metal monitoring in impacted waterways

As part of an ambient monitoring program being conducted for the Puget Sound Naval Shipyard & Intermediate Maintenance Facility in Sinclair and Dyes Inlets of the Puget Sound, receiving waters of the Inlets are routinely monitored for trace metals and toxicity to assess water quality status, track progress in achieving water quality goals, and demonstrate protection of aquatic life. Recently, aqueous metal bioavailability using diffusive gradient thin-film (DGT) passive samplers has been incorporated into the monitoring program. The DGT samplers allow for the measurement of trace metal concentrations integrated over time via in situ chelation of labile metals. The DGT samplers are selective for free and weakly complexed metal species, allowing uptake to mimic diffusion limited bioavailability. This provides a monitoring solution by which episodic events are captured that provides a better representation of the potential for biological effects. A combination of laboratory performance tests and field deployed DGTs have been used to assess the reliability of the method to accurately measure labile concentrations Cu, Pb, and Zn under baseline and episodic storm events. Based on the results from DGTs deployed over different intervals spanning continuous deployments of 1-56 days and rainfall events of 0.4 – 3.2 inches/24 hr, reproducibility was affected by the presence of partially labile complexes, mass loading rate (time to equilibrium) which is proportional to free ion concentration, and variation in resin blank values. Best results were obtained for 3-7 day DGT deployments which showed high resolution of labile metal concentrations over varying spatial and temporal scales. The ability to conduct constant surveillance of metal bioavailable for a variety of freshwater and nearshore marine environments under varying environmental conditions greatly improves the assessment of potential ecological effects from exposure to metals

Assessing 21st century contaminants of concern using integrative passive sampling devices to obtain more meaningful and cost effective data on impacts from stormwater runoff

In many cases stormwater compliance monitoring is labor intensive, expensive, and largely unsuccessful in providing the data needed to support stormwater management goals. In addition, data from manual grab sampling and automated composite sampling are rarely collected in a manner that provides the information required to identify sources of contamination, evaluate the effectiveness of Best Management Practices, and inform effective decision making. Furthermore, monitoring is often driven by the need to meet low concentration benchmarks for metals and other constituents that do not take into account loading into the receiving waters, resulting in arbitrary monitoring requirements (monthly or seasonally) that are not tied to the driving forces within the watershed such as hydrology (flow regime), weather (storm events and antecedent dry periods), and upland land use and cover. To help address these issues, passive sampling devices including Diffusive Gradients in Thin films (DGT) for metals and Polar Organic Chemical Integrative Samples (POCIS) for a wide range of household, personal care, pharmaceutical, and endocrine disrupting compounds are being used to monitor stormwater runoff. In the Puget Sound a network of monitoring stations was established in Sinclair and Dyes Inlets to assess runoff from industrial areas of Naval Base Kitsap as well as commercial, residential, and rural areas within the watershed. Passive samplers were co-located with autosamplers to provide a direct comparison with grab and composite sampling. Preliminary results from multiple DGT deployments showed that time-dependent variability in stormwater impacts on ambient metal concentrations could be detected on small time scales, as well as over multiple days of rainfall. The POCIS samplers showed that a wide range of organic compounds could be reliably detected from the surveillance monitoring which should prove very useful for finger printing likely sources of contamination in stormwater runoff in the areas monitored

The Vehicle, Fall 1984

Vol. 26, No. 1 Table of Contents Thoughts on I-57Jim Caldwellpage 3 A Night Between Lonely and BlindJennifer K. Soulepage 4 What is Unnatural is Sometimes MagicAngelique Jenningspage 4 Cutting ClosenessBecky Lawsonpage 5 PhotoBrian Ormistonpage 6 The Sensuality of Corn One Week in AugustMichelle Mitchellpage 7 American MusicJim Caldwellpage 7 Water is WaitingMichael Kuopage 8 WhereJennifer K. Soulepage 8 The Fishing HoleJan Kowalskipage 9 Miller\u27s PondSue Gradypage 9 PhotoCathy Stonerpage 11 Young Man Reading To His LoverMaggie Kennedypage 11 ShellsChristopher R. Albinpage 12 In The ShadeJohn Fehrmannpage 12 FallLynanne Feilenpage 13 IndecisionDave L. Brydenpage 13 Dark Falls SoftlyAngelique Jenningspage 14 Not a Parked \u2757 Chevy in the Summer in the CountryMichelle Mitchellpage 20 BirdAnnie Heisepage 20 Clouds Created Only For Poets And Certain WomenJennifer K. Soulepage 21 SandGraham Lewispage 22 PhotoFred Zwickypage 23 Judgment CallCathy Moepage 23 I was hip that night Dan Hintzpage 24 A Sight Of WindDan Von Holtenpage 25 Tillard Isabel M. Parrottpage 26 The WidowMaggie Kennedypage 27 The SeparationMichelle Mitchellpage 27 The Garden Hose TrialMaggie Kennedypage 28 InterruptionsJennifer K. Soulepage 28 On Happening Across Jesus While Cleaning the BasementMaggie Kennedypage 29 GileonMichelle Mitchellpage 30 If My Father Were A Writer, He Would Still BuildAngelique Jenningspage 36 A Visit to Grandpa Gib\u27s HouseTammy Veachpage 37 For Having SeenAngelique Jenningspage 38 PhotoJudy Klancicpage 39 The Earth in BlueSusan J. Bielskypage 39 Things I Could Have SaidAngelique Jenningspage 40 AcrosticsAnnie Heisepage 40https://thekeep.eiu.edu/vehicle/1044/thumbnail.jp

The Vehicle, Fall 1984

Vol. 26, No. 1 Table of Contents Thoughts on I-57Jim Caldwellpage 3 A Night Between Lonely and BlindJennifer K. Soulepage 4 What is Unnatural is Sometimes MagicAngelique Jenningspage 4 Cutting ClosenessBecky Lawsonpage 5 PhotoBrian Ormistonpage 6 The Sensuality of Corn One Week in AugustMichelle Mitchellpage 7 American MusicJim Caldwellpage 7 Water is WaitingMichael Kuopage 8 WhereJennifer K. Soulepage 8 The Fishing HoleJan Kowalskipage 9 Miller\u27s PondSue Gradypage 9 PhotoCathy Stonerpage 11 Young Man Reading To His LoverMaggie Kennedypage 11 ShellsChristopher R. Albinpage 12 In The ShadeJohn Fehrmannpage 12 FallLynanne Feilenpage 13 IndecisionDave L. Brydenpage 13 Dark Falls SoftlyAngelique Jenningspage 14 Not a Parked \u2757 Chevy in the Summer in the CountryMichelle Mitchellpage 20 BirdAnnie Heisepage 20 Clouds Created Only For Poets And Certain WomenJennifer K. Soulepage 21 SandGraham Lewispage 22 PhotoFred Zwickypage 23 Judgment CallCathy Moepage 23 I was hip that night Dan Hintzpage 24 A Sight Of WindDan Von Holtenpage 25 Tillard Isabel M. Parrottpage 26 The WidowMaggie Kennedypage 27 The SeparationMichelle Mitchellpage 27 The Garden Hose TrialMaggie Kennedypage 28 InterruptionsJennifer K. Soulepage 28 On Happening Across Jesus While Cleaning the BasementMaggie Kennedypage 29 GileonMichelle Mitchellpage 30 If My Father Were A Writer, He Would Still BuildAngelique Jenningspage 36 A Visit to Grandpa Gib\u27s HouseTammy Veachpage 37 For Having SeenAngelique Jenningspage 38 PhotoJudy Klancicpage 39 The Earth in BlueSusan J. Bielskypage 39 Things I Could Have SaidAngelique Jenningspage 40 AcrosticsAnnie Heisepage 40https://thekeep.eiu.edu/vehicle/1044/thumbnail.jp

Is adolescent body mass index and waist circumference associated with the food environments surrounding schools and homes? A longitudinal analysis

Background: There has been considerable interest in the role of access to unhealthy food options as a determinant of weight status. There is conflict across the literature as to the existence of such an association, partly due to the dominance of cross-sectional study designs and inconsistent definitions of the food environment. The aim of our study is to use longitudinal data to examine if features of the food environment are associated to measures of adolescent weight status. Methods: Data were collected from secondary schools in Leeds (UK) and included measurements at school years 7 (ages 11/12), 9 (13/14), and 11 (15/16). Outcome variables, for weight status, were standardised body mass index and standardised waist circumference. Explanatory variables included the number of fast food outlets, supermarkets and ‘other retail outlets’ located within a 1 km radius of an individual’s home or school, and estimated travel route between these locations (with a 500 m buffer). Multi-level models were fit to analyse the association (adjusted for confounders) between the explanatory and outcome variables. We also examined changes in our outcome variables between each time period. Results: We found few associations between the food environment and measures of adolescent weight status. Where significant associations were detected, they mainly demonstrated a positive association between the number of amenities and weight status (although effect sizes were small). Examining changes in weight status between time periods produced mainly non-significant or inconsistent associations. Conclusions: Our study found little consistent evidence of an association between features of the food environment and adolescent weight status. It suggests that policy efforts focusing on the food environment may have a limited effect at tackling the high prevalence of obesity if not supported by additional strategies

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