591 research outputs found
Leveraging Rich Communication Tools: Evidence of Online Trust and Guanxi in China
Driven by the evolution of consumer-to-consumer (C2C) online marketplaces, we examine the role of communication tools (i.e., an instant messenger, internal message box and a feedback system), in facilitating dyadic online transactions in the Chinese C2C marketplace. Integrating the Chinese concept of guanxi with theories of social translucence and social presence, we introduce a structural model that explains how rich communication tools influence a website’s interactivity and presence, subsequently building trust and guanxi among buyers and sellers, and ultimately predicting buyers’ repurchase intentions. The data collected from 185 buyers in TaoBao, China’s leading C2C online marketplace, strongly support the proposed model. We believe that this research is the first formal study to show evidence of guanxi in online C2C marketplaces, and it is attributed to the role of communication tools to enhance a website’s interactivity and presence
Reproductive Failure in UK Harbour Porpoises Phocoena phocoena : Legacy of Pollutant Exposure?
This research was supported by a Marie Curie International Outgoing Fellowship within the Seventh European Community Framework Programme (Project Cetacean-stressors, PIOF-GA-2010-276145 to PDJ and SM). Additional funding was provided through the Agreement on the Conservation of Small Cetaceans of the Baltic, North East Atlantic, Irish and North Seas (ASCOBANS) (Grants SSFA/2008 and SSFA / ASCOBANS / 2010 / 5 to SM). Analysis of Scottish reproductive and teeth samples was funded by the EC-funded BIOCET project (BIOaccumulation of persistent organic pollutants in small CETaceans in European waters: transport pathways and impact on reproduction, grant EVK3-2000-00027 to GJP), and Marine Scotland (GJP). Samples examined in this research were collected under the collaborative Cetacean Strandings Investigation Programme (http://ukstrandings.org/), which is funded by the Department for Environment, Food and Rural Affairs (Defra) and the UK’s Devolved Administrations in Scotland and Wales (http://sciencesearch.defra.gov.uk/Default.aspx?Menu=Menu&Module=More&Location=None&Completed=0&ProjectID=15331) (grants to PDJ, RD). UK Defra also funded the chemical analysis under a service-level agreement with the Centre for Environment, Fisheries and Aquaculture Science (grants to RJL, JB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
Human cytomegalovirus: taking the strain
In celebrating the 60th anniversary of the first isolation of human cytomegalovirus (HCMV), we reflect on the merits and limitations of the viral strains currently being used to develop urgently needed treatments. HCMV research has been dependent for decades on the high-passage strains AD169 and Towne, heavily exploiting their capacity to replicate efficiently in fibroblasts. However, the genetic integrity of these strains is so severely compromised that great caution needs to be exercised when considering their past and future use. It is now evident that wild-type HCMV strains are not readily propagated in vitro. HCMV mutants are rapidly selected during isolation in fibroblasts, reproducibly affecting gene RL13, the UL128 locus (which includes genes UL128, UL130 and UL131A) and often the UL/b′ region. As a result, the virus becomes less cell associated, altered in tropism and less pathogenic. This problem is not restricted to high-passage strains, as even low-passage strains can harbour biologically significant mutations. Cloning and manipulation of the HCMV genome as a bacterial artificial chromosome (BAC) offers a means of working with stable, genetically defined strains. To this end, the low-passage strain Merlin genome was cloned as a BAC and sequentially repaired to match the viral sequence in the original clinical sample from which Merlin was derived. Restoration of UL128L to wild type was detrimental to growth in fibroblasts, whereas restoration of RL13 impaired growth in all cell types tested. Stable propagation of phenotypically wild-type virus could be achieved only by placing both regions under conditional expression. In addition to the development of these tools, the Merlin transcriptome and proteome have been characterized in unparalleled detail. Although Merlin may be representative of the clinical agent, high-throughput whole-genome deep sequencing studies have highlighted the remarkable high level of interstrain variation present in circulating virus. There is a need to develop systems capable of addressing the significance of this diversity, free from the confounding effects of genetic changes associated with in vitro adaptation. The generation of a set of BAC clones, each containing the genome of a different HCMV strain repaired to match the sequence in the clinical sample, would provide a pathway to address the biological and clinical effects of natural variation in wild-type HCMV
Rolofylline, an adenosine A1−receptor antagonist, in acute heart failure
Background:
Worsening renal function, which is associated with adverse outcomes, often develops
in patients with acute heart failure. Experimental and clinical studies suggest that
counterregulatory responses mediated by adenosine may be involved. We tested the
hypothesis that the use of rolofylline, an adenosine A1−receptor antagonist, would
improve dyspnea, reduce the risk of worsening renal function, and lead to a more
favorable clinical course in patients with acute heart failure.
Methods:
We conducted a multicenter, double-blind, placebo-controlled trial involving patients
hospitalized for acute heart failure with impaired renal function. Within 24 hours
after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive
daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end
point was treatment success, treatment failure, or no change in the patient’s clinical
condition; this end point was defined according to survival, heart-failure status,
and changes in renal function. Secondary end points were the post-treatment development
of persistent renal impairment and the 60-day rate of death or readmission
for cardiovascular or renal causes.
Results:
Rolofylline, as compared with placebo, did not provide a benefit with respect to the
primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35).
Persistent renal impairment developed in 15.0% of patients in the rolofylline group
and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission
for cardiovascular or renal causes had occurred in similar proportions of patients
assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86).
Adverse-event rates were similar overall; however, only patients in the rolofylline
group had seizures, a known potential adverse effect of A1-receptor antagonists.
Conclusions:
Rolofylline did not have a favorable effect with respect to the primary clinical composite
end point, nor did it improve renal function or 60-day outcomes. It does not
show promise in the treatment of acute heart failure with renal dysfunction. (Funded
by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692
and NCT00354458.
Porphyrin Binding to Gun4 protein, Facilitated by a Flexible Loop, Controls Metabolite Flow through the Chlorophyll Biosynthetic Pathway
In oxygenic phototrophs, chlorophylls, hemes and bilins are synthesized by a common branched pathway. Given the phototoxic nature of tetrapyrroles, this pathway must be tightly regulated and an important regulatory role is attributed to Mgchelatase enzyme at the branching between the heme and chlorophyll pathway. Gun4 is a porphyrin-binding protein known to stimulate in vitro the Mg-chelatase activity but how the Gun4-porphyrin complex acts in the cell was
unknown. To address this issue we first performed simulations to determine the porphyrin-docking mechanism to the
cyanobacterial Gun4 structure. After correcting crystallographic loop contacts, we determined the binding site for Mgprotoporphyrin IX. It revealed that the orientation of 6/7 loop is critical for the binding and the magnesium ion held within the porphyrin is coordinated by Asn211 residue. We also identified the basis for stronger binding in the Gun4-1 variant and for weaker binding in the W192A mutant. The W192A-Gun4 was further characterized in Mg-chelatase assay showing that tight porphyrin-binding in Gun4 facilitates its interaction with the Mg-chelatase ChlH
subunit. Finally, we introduced the W192A mutation into Synechocystis 6803 cells and show that the Gun4-porphyrin complex is important for the accumulation of ChlH and for channeling metabolites into the chlorophyll biosynthetic pathway.This work was supported by project P501/12/G055 of the Czech Science Foundation, and by the National Programme of Sustainability I (LO1416) and by ERC 2009-Adg25027-PELE (to V.G). J.K. was supported by project Algain (EE2.3.30.0059). N.B.P.A., P.A.D., A.A.B. and C.N.H. thank
the Biotechnology and Biological Sciences Research Council (BBSRC) U.K. for funding, under award numbers BB/G021546/1 and BB/M000265/1. CNH was also supported by an Advanced Award 338895 from the European Research Council.Peer ReviewedPostprint (author's final draft
Structural and functional consequences of removing the N-terminal domain from the magnesium chelatase ChlH subunit of Thermosynechococcus elongatus
Magnesium chelatase (MgCH) initiates chlorophyll biosynthesis by catalysing the ATP-dependent insertion of Mg2+ into protoporphyrin. This large enzyme complex comprises ChlH, I and D subunits, with I and D involved in ATP hydrolysis, and H the protein that handles the substrate and product. The 148 kDa ChlH subunit has a globular N-terminal domain attached by a narrow linker to a hollow cage-like structure. Following deletion of this ~18 kDa domain from the Thermosynechoccus elongatus ChlH, we used single particle reconstruction to show that the apo- and porphyrin-bound forms of the mutant subunit consist of a hollow globular protein with three connected lobes; superposition of the mutant and native ChlH structures shows that, despite the clear absence of the N-terminal ‘head’ region, the rest of the protein appears to be correctly folded. Analyses of dissociation constants shows that the ΔN159ChlH mutant retains the ability to bind protoporphyrin and the Gun4 enhancer protein, although the addition of I and D subunits yields an extremely impaired active enzyme complex. Addition of the Gun4 enhancer protein, which stimulates MgCH activity significantly especially at low Mg2+ concentrations, partially reactivates the ΔN159ChlH–I–D mutant enzyme complex, suggesting that the binding site or sites for Gun4 on H do not wholly depend on the N-terminal domain
Biography of Leann L Birch, PhD, 25 June 1946 – 26 May 2019
On 26 May, 2019, the nutrition community lost a visionary ambassador, trusted advisor, and cherished mentor. Leann Birch was a pioneer in bringing a developmental psychology perspective to the study of children\u27s nutrition as a means to respond to real-world questions raised by parents. Leann Elsie Traub was born in Owosso, Michigan 25 June, 1946. She grew up primarily in Southern California and received a bachelor\u27s degree in psychology from California State University, Long Beach, in 1971. She completed her graduate studies at the University of Michigan where she received a master\u27s degree in 1973 and a doctorate in 1975, both in psychology. She subsequently held faculty appointments reflecting affiliations with nutrition as well as human development at the University of Illinois, Urbana-Champaign (1976–1992), the Pennsylvania State University (1992–2014), and the University of Georgia (2014–2019).
Over this time, Leann was a prolific scientist, publishing \u3e250 publications (with \u3e51,000 citations) and receiving \u3e$30 million in federal research funding. The public health impact and reach of Leann\u27s work is profound. References to her work can be found everywhere: federal dietary guidance, position statements from leading professional organizations, early-childhood education policies, anticipatory guidance given in the pediatrician\u27s office, and popular books on feeding children
Spatio-Temporal Variability of Harbor Porpoise Life History Parameters in the North-East Atlantic
Harbor porpoises exhibit early maturation, relatively short gestation/lactation periods and a faster rate of reproduction as compared to other cetacean species. Intrinsic and extrinsic factors can influence both population vital rates and population structure, which ultimately cause changes in dynamics within and between populations. Here, we undertook a retrospective analysis of mortality data collected over a 24-year period for assessing life history traits of the North-east Atlantic harbor porpoise population. We use time-period specific models for key life history relationships that considered cause of death of individuals (as a proxy for health status), sex and management unit (MU). Sexual variation in asymptotic length, asymptotic age, average length at 50% maturity (L50) and average age at 50% maturity (A50) were observed, with females attaining a larger asymptotic length, larger L50, and delaying attainment of both sexual and physical maturity, compared to males. While females are constrained in their minimum body size due to giving birth to proportionally larger offspring, males exhibited more plasticity in size at sexual maturity, enabling re-allocation of available energy resources toward reproduction. Data were then used to compare biological parameters among two porpoise MUs in United Kingdom waters, both of which in the current study exhibited reduced reproductive rates compared to other geographic regions. In both MUs, females significantly increased their A50 and males significantly declined in their L50. An increase in the age at asymptotic length was also observed in both sexes, along with a significant decline in the Gompertz growth rate parameter that was more apparent in the female data. While availability of suitable prey resources may be a limiting factor, a combination of other factors cannot be ruled out. Porpoises in the Celtic and Irish Seas MU were significantly larger in their maximum length, asymptotic length and L50 compared to porpoises in the North Sea MU throughout the study period, suggesting limited gene flow between these two MUs. These results justify the maintenance of these harbor porpoise MUs or assessment units, as two separate units, within the range of the North-east Atlantic population, and for indicator assessments under the EU’s Marine Strategy Framework Directive
Metal artifact reduction in patients with dental implants using multispectral three-dimensional data acquisition for hybrid PET/MRI
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