441 research outputs found
Estimating the rate of intersubtype recombination in early HIV-1 group M strains
West Central Africa has been implicated as the epicenter of the HIV-1 epidemic, and almost all group M subtypes can be found there. Previous analysis of early HIV-1 group M sequences from Kinshasa in the Democratic Republic of Congo, formerly Zaire, revealed that isolates from a number of individuals fall in different positions in phylogenetic trees constructed from sequences from opposite ends of the genome as a result of recombination between viruses of different subtypes. Here, we use discrete ancestral trait mapping to develop a procedure for quantifying HIV-1 group M intersubtype recombination across phylogenies, using individuals' gag (p17) and env (gp41) subtypes. The method was applied to previously described HIV-1 group M sequences from samples obtained in Kinshasa early in the global radiation of HIV. Nine different p17 and gp41 intersubtype recombinant combinations were present in the data set. The mean number of excess ancestral subtype transitions (NEST) required to map individuals' p17 subtypes onto the gp14 phylogeny samples, compared to the number required to map them onto the p17 phylogenies, and vice versa, indicated that excess subtype transitions occurred at a rate of approximately 7 × 10(−3) to 8 × 10(−3) per lineage per year as a result of intersubtype recombination. Our results imply that intersubtype recombination may have occurred in approximately 20% of lineages evolving over a period of 30 years and confirm intersubtype recombination as a substantial force in generating HIV-1 group M diversity
Resource use data by patient report or hospital records: Do they agree?
Background: Economic evaluations alongside clinical trials are becoming increasingly common.
Cost data are often collected through the use of postal questionnaires; however, the accuracy of
this method is uncertain. We compared postal questionnaires with hospital records for collecting
data on physiotherapy service use.
Methods: As part of a randomised trial of orthopaedic medicine compared with orthopaedic
surgery we collected physiotherapy use data on a group of patients from retrospective postal
questionnaires and from hospital records.
Results: 315 patients were referred for physiotherapy. Hospital data on attendances was available
for 30% (n = 96), compared with 48% (n = 150) of patients completing questionnaire data (95% Cl
for difference = 10% to 24%); 19% (n = 59) had data available from both sources. The two methods
produced an intraclass correlation coefficient of 0.54 (95% Cl 0.31 to 0.70). However, the two
methods produced significantly different estimates of resource use with patient self report recalling
a mean of 1.3 extra visits (95% Cl 0.4 to 2.2) compared with hospital records.
Conclusions: Using questionnaires in this study produced data on a greater number of patients
compared with examination of hospital records. However, the two data sources did differ in the
quantity of physiotherapy used and this should be taken into account in any analysi
Free fatty acid receptors in GtoPdb v.2023.1
Free fatty acid receptors (FFA, nomenclature as agreed by the NC-IUPHAR Subcommittee on free fatty acid receptors [116, 27]) are activated by free fatty acids. Long-chain saturated and unsaturated fatty acids (including C14.0 (myristic acid), C16:0 (palmitic acid), C18:1 (oleic acid), C18:2 (linoleic acid), C18:3, (α-linolenic acid), C20:4 (arachidonic acid), C20:5,n-3 (EPA) and C22:6,n-3 (docosahexaenoic acid)) activate FFA1 [9, 54, 64] and FFA4 receptors [45, 52, 94], while short chain fatty acids (C2 (acetic acid), C3 (propanoic acid), C4 (butyric acid) and C5 (pentanoic acid)) activate FFA2 [10, 66, 90] and FFA3 [10, 66] receptors. The crystal structure for agonist bound FFA1 has been described [113]
Free fatty acid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Free fatty acid receptors (FFA, nomenclature as agreed by the NC-IUPHAR Subcommittee on free fatty acid receptors [111, 24]) are activated by free fatty acids. Long-chain saturated and unsaturated fatty acids (including C14.0 (myristic acid), C16:0 (palmitic acid), C18:1 (oleic acid), C18:2 (linoleic acid), C18:3, (α-linolenic acid), C20:4 (arachidonic acid), C20:5,n-3 (EPA) and C22:6,n-3 (docosahexaenoic acid)) activate FFA1 [8, 50, 60] and FFA4 receptors [41, 48, 90], while short chain fatty acids (C2 (acetic acid), C3 (propanoic acid), C4 (butyric acid) and C5 (pentanoic acid)) activate FFA2 [9, 62, 86] and FFA3 [9, 62] receptors. The crystal structure for agonist bound FFA1 has been described [108]
Transmission dynamics of Avian Influenza A virus
Influenza A virus (AIV) has an extremely high rate of mutation. Frequent
exchanges of gene segments between different AIV (reassortment) have been
responsible for major pandemics in recent human history. The presence of a wild bird
reservoir maintains the threat of incursion of AIV into domestic birds, humans and
other animals. In this thesis, I addressed unanswered questions of how diverse AIV
subtypes (classified according to antigenicity of the two surface proteins,
haemagglutinin and neuraminidase) evolve and interact among different bird
populations in different parts of the world, using Bayesian phylogenetic methods
with large datasets of full genome sequences.
Firstly, I explored the reassortment patterns of AIV internal segments among
different subtypes by quantifying evolutionary parameters including reassortment
rate, evolutionary rate and selective constraint in time-resolved Bayesian tree
phylogenies. A major conclusion was that reassortment rate is negatively associated
with selective constraint and that infection of wild rather than domestic birds was
associated with a higher reassortment rate. Secondly, I described the spatial
transmission pattern of AIV in China. Clustering of related viruses in particular
geographic areas and economic zones was identified from the viral phylogeographic
diffusion networks. The results indicated that Central China and the Pearl River
Delta are two main sources of viral out flow; while the East Coast, especially the
Yangtze River delta, is the major recipient area. Simultaneously, by applying a
general linear model, the predictors that have the strongest impact on viral spatial
diffusion were identified, including economic (agricultural) activity, climate, and
ecology. Thirdly, I determined the genetic and phylogeographic origin of a recent
H7N3 highly pathogenic avian influenza outbreak in Mexico. Location, subtype,
avian host species and pathogenicity were modelled as discrete traits and jointly
analysed using all eight viral gene segments. The results indicated that the outbreak
AIV is a novel reassortant carried by wild waterfowl from different migration
flyways in North America during the time period studied. Importantly, I concluded
that Mexico, and Central America in general, might be a potential hotspot for AIV
reassortment events, a possibility which to date has not attracted widespread
attention.
Overall, the work carried out in this thesis described the evolutionary dynamics of
AIV from which important conclusions regarding its epidemiological impact in both
Eurasia and North America can be drawn
Taking the LEAP (Learner Engaged Advising Programs): VCCS Advising Practices and Recommendations
The Virginia Community College System (VCCS) administration identified the need for adequate and proactive advising programs to foster student success. This paper presents a review of “best practices” in advising to determine commonalities, provides a comparison with current VCCS advising practices, and offers recommendations that support the goal of ensuring high quality advising programs
Adaptation to Different Human Populations by HIV-1 Revealed by Codon-Based Analyses
Several codon-based methods are available for detecting adaptive evolution in protein-coding sequences, but to date none specifically identify sites that are selected differentially in two populations, although such comparisons between populations have been historically useful in identifying the action of natural selection. We have developed two fixed effects maximum likelihood methods: one for identifying codon positions showing selection patterns that persist in a population and another for detecting whether selection is operating differentially on individual codons of a gene sampled from two different populations. Applying these methods to two HIV populations infecting genetically distinct human hosts, we have found that few of the positively selected amino acid sites persist in the population; the other changes are detected only at the tips of the phylogenetic tree and appear deleterious in the long term. Additionally, we have identified seven amino acid sites in protease and reverse transcriptase that are selected differentially in the two samples, demonstrating specific population-level adaptation of HIV to human populations
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