121 research outputs found
Reflection and Learning amongst diverse student groups in the workplace: examining the experience
Climate Prosperity: A Greenprint For Southwest Florida
Southwest Florida has been chosen as one of the 8 pilot regions for the Climate Prosperity project. One of the main goals in Southwest Florida is to create and attract jobs to help energize the Southwest Florida economy now as well as future generations. Climate change has edged its way to the top of federal, state, and local agendas. Scientists and leaders across the nation are taking numerous steps to prepare for the positive and negative consequences of a new weather era so that ecosystems, human life, and infrastructure can adapt and survive
The Application of Transformational Leadership Theory to Parenting: Questionnaire Development and Implications for Adolescent Self-Regulatory Efficacy and Life Satisfaction
We draw upon transformational leadership theory to develop an instrument to measure transformational parenting for use with adolescents. First, potential items were generated that were developmentally appropriate and evidence for content validity was provided through the use of focus groups with parents and adolescents. We subsequently provide evidence for several aspects of construct validity of measures derived from the Transformational Parenting Questionnaire (TPQ). Data were collected from 857 adolescents (Mage = 14.70 years), who rated the behaviors of their mothers and fathers. The results provided support for a second-order measurement model of transformational parenting. In addition, positive relationships between mothers’ and fathers’ transformational parenting behaviors, adolescents’ self-regulatory efficacy for physical activity and healthy eating, and life satisfaction were found. The results of this research support the application of transformational leadership theory to parenting behaviors, as well as the construct validity of measures derived from the TPQ. (AUTHORS' ABSTRACT
Genetic Characterization and Role in Virulence of the Ribonucleotide Reductases of Streptococcus sanguinis
Streptococcus sanguinis is a cause of infective endocarditis and has been shown to require a manganese transporter called SsaB for virulence and O2 tolerance. Like certain other pathogens, S. sanguinis possesses aerobic class Ib (NrdEF) and anaerobic class III (NrdDG) ribonucleotide reductases (RNRs) that perform the essential function of reducing ribonucleotides to deoxyribonucleotides. The accompanying paper (Makhlynets, O., Boal, A. K., Rhodes, D. V., Kitten, T., Rosenzweig, A. C., and Stubbe, J. (2014) J. Biol. Chem. 289, 6259–6272) indicates that in the presence of O2, the S. sanguinis class Ib RNR self-assembles an essential diferric-tyrosyl radical (FeIII2-Y•) in vitro, whereas assembly of a dimanganese-tyrosyl radical (MnIII2-Y•) cofactor requires NrdI, and MnIII2-Y• is more active than FeIII2-Y• with the endogenous reducing system of NrdH and thioredoxin reductase (TrxR1). In this study, we have shown that deletion of either nrdHEKF or nrdI completely abolishes virulence in an animal model of endocarditis, whereas nrdD mutation has no effect. The nrdHEKF, nrdI, and trxR1mutants fail to grow aerobically, whereas anaerobic growth requires nrdD. The nrdJgene encoding an O2-independent adenosylcobalamin-cofactored RNR was introduced into the nrdHEKF, nrdI, and trxR1 mutants. Growth of the nrdHEKF and nrdI mutants in the presence of O2 was partially restored. The combined results suggest that MnIII2-Y•-cofactored NrdF is required for growth under aerobic conditions and in animals. This could explain in part why manganese is necessary for virulence and O2 tolerance in many bacterial pathogens possessing a class Ib RNR and suggests NrdF and NrdI may serve as promising new antimicrobial targets
Migratory Flyways May Affect Population Structure in Double‐Crested Cormorants
Double‐crested cormorants (Phalacrocorax auritus) recovered from a demographic bottleneck so well that they are now considered a nuisance species at breeding and wintering grounds across the United States and Canada. Management of this species could be improved by refining genetic population boundaries and assigning individuals to their natal population. Further, recent radio‐telemetry data suggest the existence of Interior and Atlantic migratory flyways, which could reduce gene flow and result in substantial genetic isolation. In this study, we used 1,784 individuals collected across the eastern United States, a large panel of microsatellite markers developed for this species, and individuals banded as chicks and recaptured as adults to explore the effects of migratory flyways on population structure, quantify the genetic effects of demographic bottlenecks, and determine whether individuals could be assigned to their natal population based on genotype. We found evidence for genetic population division only along migratory flyways, no evidence of genetic bottlenecks, and mixed effectiveness of assignment tests. Our population structure findings suggest that gene flow is high across large scales; for example, individuals from New York, Minnesota, and Alabama are all in panmixia. We also found that traditional subspecies ranges may not be valid because \u3e1 subspecies was present in single genetic populations. The lack of evidence for genetic bottlenecks also likely underscores the vagility of this species, suggesting that even during demographic bottlenecks, populations were not isolated from allelic exchange. Finally, the failure of assignment tests to consistently perform is likely due in part to imperfect a priori sampling of Atlantic and Interior chicks and the high vagility of adults. We conclude that the demographic bottleneck is not likely to have reduced genetic diversity, and that assignment tests remain unreliable for this species. We recommend double-crested cormorants be managed by flyway. Further development of genomic resources in this species could improve population subdivision resolution, improve assignment tests, and reveal further information on demographic histories
Expansion of the Knockdown Resistance Frequency Map for Human Head Lice (Phthiraptera: Pediculidae) in the United States Using Quantitative Sequencing
Pediculosis is a prevalent parasitic infestation of humans, which is increasing due, in part, to the selection of lice resistant to either the pyrethrins or pyrethroid insecticides by the knockdown resistance (kdr) mechanism. To determine the extent and magnitude of thekdr-type mutations responsible for this resistance, lice were collected from 138 collection sites in 48 U.S. states from 22 July 2013 to 11 May 2015 and analyzed by quantitative sequencing. Previously published data were used for comparisons of the changes in the frequency of thekdr-type mutations over time. Mean percent resistance allele frequency (mean % RAF) values across the three mutation loci were determined from each collection site. The overall mean % RAF (+/-SD) for all analyzed lice was 98.3 +/- 10%. 132/138 sites (95.6%) had a mean % RAF of 100%, five sites (3.7%) had intermediate values, and only a single site had no mutations (0.0%). Forty-two states (88%) had a mean % RAF of 100%. The frequencies ofkdr-type mutations did not differ regardless of the human population size that the lice were collected from, indicating a uniformly high level of resistant alleles. The loss of efficacy of the Nix formulation (Prestige Brand, Tarrytown, NY) from 1998 to 2013 was correlated to the increase inkdr-type mutations. These data provide a plausible reason for the decrease in the effectiveness of permethrin in the Nix formulation, which is the parallel increase ofkdr-type mutations in lice over time
Early Laser for Burn Scars (ELABS): protocol for a multi-centre randomised, controlled trial of both the effectiveness and cost-effectiveness of the treatment of hypertrophic burn scars with Pulsed Dye Laser and standard care compared to standard care alone [version 1; peer review: 2 approved]
This paper outlines the protocol for a study that is being carried out at multiple centres across the UK in the next three years. It is a Research for Patient Benefit (RfPB) study funded by the National Institute for Healthcare Research (NIHR). The aim is to assess the effectiveness of treating hypertrophic burns scars with pulsed dye laser (PDL) at an early stage of scar formation. The objective is to improve Quality of Life for the patient by improving both the appearance and quality of burn scarring, as well as reducing its psychological impact. This is a parallel-arm randomised, controlled trial to compare PDL and standard care against standard care alone. The difference is measured between baseline and six-month follow-up. Recruits are within three months of healing from a burn injury; with wounds showing a defined potential for hypertrophic scarring. A total of 120 patients are recruited in a multi-centre study; with randomisation in a 1:1 allocation to each arm. The treatment arm receives 3 PDL treatments at six-week intervals in addition to standard care, whereas the control arm receives standard care alone. The primary outcome is the patient-rated part of the Patient and Observer Scar Scale (POSAS). Psychological and psycho-social impact is evaluated using the CARe burn scale (UWE, Bristol) and Quality Adjusted Life Years (QALY) is determined using the Short-Form Health Survey (SF-12). The study evaluates both the cost-effectiveness through an economic analysis and the patient-reported experience of the treatment by phone interviews. Trial registration: ISRCTN14392301 (registered on 14th June 2021) Contact for Public & Scientific Queries: Mark Brewin, [email protected] Public Title: Early Laser for Burn Scars (ELABS): a trial of the effectiveness and cost of the treatment of hypertrophic burn scars with laser Countries of Recruitment: England & Scotland Protocol Version: v11, October 202
Early Laser for Burn Scars (ELABS): protocol for a multi-centre randomised, controlled trial of both the effectiveness and cost-effectiveness of the treatment of hypertrophic burn scars with Pulsed Dye Laser and standard care compared to standard care alone [version 1; peer review: 2 approved].
This paper outlines the protocol for a study that is being carried out at multiple centres across the UK in the next three years. It is a Research for Patient Benefit (RfPB) study funded by the National Institute for Healthcare Research (NIHR). The aim is to assess the effectiveness of treating hypertrophic burns scars with pulsed dye laser (PDL) at an early stage of scar formation. The objective is to improve Quality of Life for the patient by improving both the appearance and quality of burn scarring, as well as reducing its psychological impact. This is a parallel-arm randomised, controlled trial to compare PDL and standard care against standard care alone. The difference is measured between baseline and six-month follow-up. Recruits are within three months of healing from a burn injury; with wounds showing a defined potential for hypertrophic scarring. A total of 120 patients are recruited in a multi-centre study; with randomisation in a 1:1 allocation to each arm. The treatment arm receives 3 PDL treatments at six-week intervals in addition to standard care, whereas the control arm receives standard care alone. The primary outcome is the patient-rated part of the Patient and Observer Scar Scale (POSAS). Psychological and psycho-social impact is evaluated using the CARe burn scale (UWE, Bristol) and Quality Adjusted Life Years (QALY) is determined using the Short-Form Health Survey (SF-12). The study evaluates both the cost-effectiveness through an economic analysis and the patient-reported experience of the treatment by phone interviews
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Functional dynamic genetic effects on gene regulation are specific to particular cell types and environmental conditions
Genetic effects on gene expression and splicing can be modulated by cellular and environmental factors; yet interactions between genotypes, cell type and treatment have not been comprehensively studied together. We used an induced pluripotent stem cell system to study multiple cell types derived from the same individuals and exposed them to a large panel of treatments. Cellular responses involved different genes and pathways for gene expression and splicing, and were highly variable across contexts. For thousands of genes, we identified variable allelic expression across contexts and characterized different types of gene-environment interactions, many of which are associated with complex traits. Promoter functional and evolutionary features distinguished genes with elevated allelic imbalance mean and variance. On average half of the genes with dynamic regulatory interactions were missed by large eQTL mapping studies, indicating the importance of exploring multiple treatments to reveal previously unrecognized regulatory loci that may be important for disease
Unequal distribution of genetically-intact HIV-1 proviruses in cells expressing the immune checkpoint markers PD-1 and/or CTLA-4
IntroductionHIV-1 persists in resting CD4+ T-cells despite antiretroviral therapy (ART). Determining the cell surface markers that enrich for genetically-intact HIV-1 genomes is vital in developing targeted curative strategies. Previous studies have found that HIV-1 proviral DNA is enriched in CD4+ T-cells expressing the immune checkpoint markers programmed cell death protein-1 (PD-1) or cytotoxic T-lymphocyte associated protein-4 (CTLA-4). There has also been some success in blocking these markers in an effort to reverse HIV-1 latency. However, it remains unclear whether cells expressing PD-1 and/or CTLA-4 are enriched for genetically-intact, and potentially replication-competent, HIV-1 genomes. MethodsWe obtained peripheral blood from 16 HIV-1-infected participants, and paired lymph node from four of these participants, during effective ART. Memory CD4+ T-cells from either site were sorted into four populations: PD-1-CTLA-4- (double negative, DN), PD-1+CTLA-4- (PD-1+), PD-1-CTLA-4+ (CTLA-4+) and PD-1+CTLA-4+ (double positive, DP). We performed an exploratory study using the full-length individual proviral sequencing (FLIPS) assay to identify genetically-intact and defective genomes from each subset, as well as HIV-1 genomes with specific intact open reading frames (ORFs). Results and DiscussionIn peripheral blood, we observed that proviruses found within PD-1+ cells are more likely to have intact ORFs for genes such as tat, rev and nef compared to DN, CTLA-4+ and DP cells, all of which may contribute to HIV-1 persistence. Conversely, we observed that CTLA-4 expression is a marker for cells harbouring HIV-1 provirus that is more likely to be defective, containing low levels of these intact ORFs. In the lymph node, we found evidence that CTLA-4+ cells contain lower levels of HIV-1 provirus compared to the other cell subsets. Importantly, however, we observed significant participant variation in the enrichment of HIV-1 proviruses with intact genomes or specific intact ORFs across these memory CD4+ T-cell subsets, and therefore consideration of additional cellular markers will likely be needed to consistently identify cells harbouring latent, and potentially replication-competent, HIV-1
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