RGD-containing Peptides Inhibit Fibrinogen Binding to Platelet αIIbβ3 by Inducing an Allosteric Change in the Amino-terminal Portion of αIIb

To determine the molecular basis for the insensitivity of rat alpha(IIb)beta(3) to inhibition by RGD-containing peptides, hybrids of human and rat alpha(IIb)beta(3) and chimeras of alpha(IIb)beta(3) in which alpha(IIb) was composed of portions of human and rat alpha(IIb) were expressed in Chinese hamster ovary cells and B lymphocytes, and the ability of the tetrapeptide RGDS to inhibit fibrinogen binding to the various forms of alpha(IIb)beta(3) was measured. These measurements indicated that sequences regulating the sensitivity of alpha(IIb)beta(3) to RGDS are located in the seven amino-terminal repeats of alpha(IIb). Moreover, replacing the first three or four (but not the first two) repeats of rat alpha(IIb) with the corresponding human sequences enhanced sensitivity to RGDS, whereas replacing the first two or three repeats of human alpha(IIb) with the corresponding rat sequences had little or no effect. Nevertheless, RGDS bound to Chinese hamster ovary cells expressing alpha(IIb)beta(3) regardless whether the alpha(IIb) in the heterodimers was human, rat, or a rat-human chimera. These results indicate that the sequences determining the sensitivity of alpha(IIb)beta(3) to RGD-containing peptides are located in the third and fourth amino-terminal repeats of alpha(IIb). Because RGDS binds to both human and rat alpha(IIb)beta(3), the results suggest that differences in RGDS sensitivity result from differences in the allosteric changes induced in these repeats following RGDS binding

Transitions in microbial communities along a 1600 km freshwater trophic gradient

This study examined vertically-resolved patterns in microbial community structure across a freshwater trophic gradient extending 1600 km from the oligotrophic waters of Lake Superior to the eutrophic waters of Lake Erie, the most anthropogenically influenced of the Laurentian Great Lakes system. Planktonic bacterial communities clustered by Principal Coordinates Analysis (PCoA) on UniFrac distance matrices into four groups representing the epilimnion and hypolimnion of the upper Great Lakes (Lakes Superior and Huron), Lake Superior\u27s northern bays (Nipigon and Black bays), and Lake Erie. The microbes within the upper Great Lakes hypolimnion were the most divergent of these groups with elevated abundance of Planctomycetes and Chloroflexi compared to the surface mixed layer. Statistical tests of the correlation between distance matrices identified temperature and sample depth as the most influential community structuring parameters, reflecting the strong UniFrac clustering separating mixed-layer and hypolimnetic samples. Analyzing mixed-layer samples alone showed clustering patterns were correlated with nutrient concentrations. Operational taxonomic units (OTU) which were differentially distributed among these conditions often accounted for a large portion of the reads returned. While limited in coverage of temporal variability, this study contributes a detailed description of community variability that can be related to other large freshwater systems characterized by changing trophic state

Treatment of spasticity in children and adolescents with cerebral palsy in Northern Europe : a CP-North registry study

BackgroundSpasticity is present in more than 80% of the population with cerebral palsy (CP). The aim of this study was to describe and compare the use of three spasticity reducing methods; Botulinum toxin-A therapy (BTX-A), Selective dorsal rhizotomy (SDR) and Intrathecal baclofen therapy (ITB) among children and adolescents with CP in six northern European countries.MethodsThis registry-based study included population-based data in children and adolescents with CP born 2002 to 2017 and recorded in the follow-up programs for CP in Sweden, Norway, Denmark, Iceland and Scotland, and a defined cohort in Finland.ResultsA total of 8,817 individuals were included. The proportion of individuals treated with SDR and ITB was significantly different between the countries. SDR treatment ranged from 0% ( Finland and Iceland) to 3.4% (Scotland) and ITB treatment from 2.2% (Sweden) to 3.7% (Denmark and Scotland). BTX-A treatment in the lower extremities reported 2017-2018 ranged from 8.6% in Denmark to 20% in Norway (pPeer reviewe

Variation in use of procurement biopsies and its implications for discard of deceased donor kidneys recovered for transplantation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150616/1/ajt15325.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150616/2/ajt15325_am.pd

The question-behaviour effect: a theoretical and methodological review and meta-analysis

Research has demonstrated that asking people questions about a behaviour can lead to behaviour change. Despite many, varied studies in different domains, it is only recently that this phenomenon has been studied under the umbrella term of the question-behaviour effect (QBE) and moderators of the effect have been investigated. With a particular focus on our own contributions, this article: (1) provides an overview of QBE research; (2) reviews and offers new evidence concerning three theoretical accounts of the QBE (behavioural simulation and processing fluency; attitude accessibility; cognitive dissonance); (3) reports a new meta-analysis of QBE studies (k = 66, reporting 94 tests) focusing on methodological moderators. The findings of this meta-analysis support a small significant effect of the QBE (g = 0.14, 95% CI = 0.11, 0.18, p < .001) with smaller effect sizes observed in more carefully controlled studies that exhibit less risk of bias and (4) also considers directions for future research on the QBE, especially studies that use designs with low risk of bias and consider desirable and undesirable behaviour separately

The Carnegie Supernova Project: First Near-Infrared Hubble Diagram to z~0.7

The Carnegie Supernova Project (CSP) is designed to measure the luminosity distance for Type Ia supernovae (SNe Ia) as a function of redshift, and to set observational constraints on the dark energy contribution to the total energy content of the Universe. The CSP differs from other projects to date in its goal of providing an I-band {rest-frame} Hubble diagram. Here we present the first results from near-infrared (NIR) observations obtained using the Magellan Baade telescope for SNe Ia with 0.1 < z < 0.7. We combine these results with those from the low-redshift CSP at z <0.1 (Folatelli et al. 2009). We present light curves and an I-band Hubble diagram for this first sample of 35 SNe Ia and we compare these data to 21 new SNe Ia at low redshift. These data support the conclusion that the expansion of the Universe is accelerating. When combined with independent results from baryon acoustic oscillations (Eisenstein et al. 2005), these data yield Omega_m = 0.27 +/- 0.0 (statistical), and Omega_DE = 0.76 +/- 0.13 (statistical) +/- 0.09 (systematic), for the matter and dark energy densities, respectively. If we parameterize the data in terms of an equation of state, w, assume a flat geometry, and combine with baryon acoustic oscillations, we find that w = -1.05 +/- 0.13 (statistical) +/- 0.09 (systematic). The largest source of systematic uncertainty on w arises from uncertainties in the photometric calibration, signaling the importance of securing more accurate photometric calibrations for future supernova cosmology programs. Finally, we conclude that either the dust affecting the luminosities of SNe Ia has a different extinction law (R_V = 1.8) than that in the Milky Way (where R_V = 3.1), or that there is an additional intrinsic color term with luminosity for SNe Ia independent of the decline rate.Comment: 44 pages, 23 figures, 9 tables; Accepted for publication in the Astrophysical Journa

SN 2013ai: a link between Hydrogen-rich and Hydrogen-poor Core-collapse Supernovae

We present a study of the optical and near-infrared (NIR) spectra of SN 2013ai along with its light curves. These data range from discovery until 380 days after explosion. SN 2013ai is a fast declining Type II supernova (SN II) with an unusually long rise time, 18.9 2.7 days in the V-band, and a bright V-band peak absolute magnitude of -18.7 0.06 mag. The spectra are dominated by hydrogen features in the optical and NIR. The spectral features of SN 2013ai are unique in their expansion velocities, which, when compared to large samples of SNe II, are more than 1,000 km s-1 faster at 50 days past explosion. In addition, the long rise time of the light curve more closely resembles SNe IIb rather than SNe II. If SN 2013ai is coeval with a nearby compact cluster, we infer a progenitor zero-age main-sequence mass of ∼17 M o˙. After performing light-curve modeling, we find that SN 2013ai could be the result of the explosion of a star with little hydrogen mass, a large amount of synthesized 56Ni, 0.3-0.4 M o˙, and an explosion energy of 2.5-3.0 1051 erg. The density structure and expansion velocities of SN 2013ai are similar to those of the prototypical SN IIb, SN 1993J. However, SN 2013ai shows no strong helium features in the optical, likely due to the presence of a dense core that prevents the majority of γ-rays from escaping to excite helium. Our analysis suggests that SN 2013ai could be a link between SNe II and stripped-envelope SNe.Fil: Davis, Scott. University of California; Estados UnidosFil: Pessi, Priscila Jael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Fraser, M.. University College Dublin; IrlandaFil: Ertini, Keila Yael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Martinez, Veronica Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Hoeflich, Peter. Florida State University; Estados UnidosFil: Hsiao, Eric. Florida State University; Estados UnidosFil: Folatelli, Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Ashall, Chris. University of Hawaii at Manoa; Estados UnidosFil: Phillips, Mark. Carnegie Observatories. Las Campanas Observatory; ChileFil: Anderson, J. P.. European Southern Observatory Chile; ChileFil: Bersten, Melina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Englert, B.. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Fisher, A.. Florida State University; Estados UnidosFil: Benetti, S.. Osservatorio Astronomico di Padova; ItaliaFil: Simaz Bunzel, Adolfo. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Burns, Christopher R.. Observatories of the Carnegie Institution for Science; Estados UnidosFil: Chen, T. W.. Stockholm University; SueciaFil: Contreras, Carlos. 9Carnegie Observatories. Las Campanas Observatory; ChileFil: Elias Rosa, N.. Osservatorio Astronomico di Padova; ItaliaFil: Falco, E.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Galbany, Lluís. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Kirshner, Robert. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Kumar, S.. Florida State University; Estados UnidosFil: Lu, J.. Florida State University; Estados UnidosFil: Lyman, D.. University of Warwick; Reino UnidoFil: Marion, G. H.. University of Warwick; Reino UnidoFil: Mattila, S.. University of Turku; FinlandiaFil: Maund, J.. University of Sheffield; Reino UnidoFil: Morrell, Nidia Irene. Carnegie Observatories. Las Campanas Observatory; ChileFil: Serón, J.. University of Sheffield; Reino UnidoFil: Stritzinger, Maximilian. Aarhus University; DinamarcaFil: Shahbandeh, Melissa. Florida State University; Estados UnidosFil: Sullivan, Mark. Aarhus University; DinamarcaFil: Suntzeff, N. B.. Texas A&M University; Estados UnidosFil: Young, D. R.. Texas A&M University; Estados Unido

Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol

Abstract Background The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. Methods Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. Discussion SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. Trial registration NCT03331991 . Registered on November 6, 2017.https://deepblue.lib.umich.edu/bitstream/2027.42/146186/1/12879_2018_Article_3444.pd

A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities