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1.
Ecol Lett ; 27(6): e14463, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38924275

ABSTRACT

Understanding the interactions among anthropogenic stressors is critical for effective conservation and management of ecosystems. Freshwater scientists have invested considerable resources in conducting factorial experiments to disentangle stressor interactions by testing their individual and combined effects. However, the diversity of stressors and systems studied has hindered previous syntheses of this body of research. To overcome this challenge, we used a novel machine learning framework to identify relevant studies from over 235,000 publications. Our synthesis resulted in a new dataset of 2396 multiple-stressor experiments in freshwater systems. By summarizing the methods used in these studies, quantifying trends in the popularity of the investigated stressors, and performing co-occurrence analysis, we produce the most comprehensive overview of this diverse field of research to date. We provide both a taxonomy grouping the 909 investigated stressors into 31 classes and an open-source and interactive version of the dataset (https://jamesaorr.shinyapps.io/freshwater-multiple-stressors/). Inspired by our results, we provide a framework to help clarify whether statistical interactions detected by factorial experiments align with stressor interactions of interest, and we outline general guidelines for the design of multiple-stressor experiments relevant to any system. We conclude by highlighting the research directions required to better understand freshwater ecosystems facing multiple stressors.


Subject(s)
Ecosystem , Fresh Water , Human Activities , Stress, Physiological
2.
Conserv Physiol ; 11(1): coad043, 2023.
Article in English | MEDLINE | ID: mdl-37346266

ABSTRACT

Climate warming is rapidly altering Arctic ecosystems. Polar bears (Ursus maritimus) need sea ice as a platform from which to hunt seals, but increased sea-ice loss is lengthening periods when bears are without access to primary hunting habitat. During periods of food scarcity, survival depends on the energy that a bear has stored in body reserves, termed storage energy, making this a key metric in predictive models assessing climate change impacts on polar bears. Here, we developed a body composition model for polar bears that estimates storage energy while accounting for changes in storage tissue composition. We used data of dissected polar bears (n = 31) to link routinely collected field measures of total body mass and straight-line body length to the body composition of individual bears, described in terms of structural mass and two storage compartments, adipose and muscle. We then estimated the masses of metabolizable proteins and lipids within these storage compartments, giving total storage energy. We tested this multi-storage model by using it to predict changes in the lipid stores from an independent dataset of wild polar bears (n = 36) that were recaptured 8-200 days later. Using length and mass measurements, our model successfully predicted direct measurements of lipid changes via isotopic dilutions (root mean squared error of 14.5 kg). Separating storage into two compartments, and allowing the molecular composition of storage to vary, provides new avenues for quantifying energy stores of individuals across their life cycle. The multi-storage body composition model thus provides a basis for further exploring energetic costs of physiological processes that contribute to individual survival and reproductive success. Given bioenergetic models are increasingly used as a tool to predict individual fitness and population dynamics, our approach for estimating individual energy stores could be applicable to a wide range of species.

3.
Cult Stud Sci Educ ; 17(2): 405-438, 2022.
Article in English | MEDLINE | ID: mdl-35663843

ABSTRACT

While there are many different frameworks seeking to identify what benefits young people might derive from participation in informal STEM (Science, Technology, Engineering and Mathematics) learning (ISL), this paper argues that the sector would benefit from an approach that foregrounds equity and social justice outcomes. We propose a new model for reflecting on equitable youth outcomes from ISL that identifies five key areas: (1) Grounded fun; (2) STEM capital; (3) STEM trajectories; (4) STEM identity work; and (5) Agency+ . The model is applied to empirical data (interviews, observations and youth portfolios) collected over one year in four UK-based ISL settings with 33 young people (aged 11-14), largely from communities that are traditionally under-represented in STEM. Analysis considers the extent to which participating youth experienced equitable outcomes, or not, in relation to the five areas. The paper concludes with a discussion of implications for ISL and how the model might support ongoing efforts to reimagine ISL as vehicle for social justice.

4.
Sci Educ ; 105(1): 166-203, 2021 Jan.
Article in English | MEDLINE | ID: mdl-34588711

ABSTRACT

Supporting more equitable participation in science, technology, engineering, and mathematics (STEM) remains a key, persistent educational challenge. This paper employs a sociological Bourdieusian lens to explore how equitable youth outcomes might be supported through informal science learning (ISL). Drawing on multimodal, ethnographic data from four case study youth aged 11-14 from two ISL programs, we identify four areas of practice that were enacted to a greater or lesser extent in the programs in support of equitable youth outcomes. We identify how the equitable potential of these practices was realized through a disruption of dominant power relations. It is argued that ISL should focus on changing the field, rather than young people. Affordances and limitations of the Bourdieusian lens are discussed.

5.
Proc Biol Sci ; 288(1958): 20211509, 2021 09 08.
Article in English | MEDLINE | ID: mdl-34521251

ABSTRACT

Metabolism defines the energetic cost of life, yet we still know relatively little about why intraspecific variation in metabolic rate arises and persists. Spatio-temporal variation in selection potentially maintains differences, but relationships between metabolic traits (standard metabolic rate (SMR), maximum metabolic rate (MMR), and aerobic scope) and fitness across contexts are unresolved. We show that associations between SMR, MMR, and growth rate (a key fitness-related trait) vary depending on the thermal regime (a potential selective agent) in offspring of wild-sampled brown trout from two populations reared for approximately 15 months in either a cool or warm (+1.8°C) regime. SMR was positively related to growth in the cool, but negatively related in the warm regime. The opposite patterns were found for MMR and growth associations (positive in warm, negative in the cool regime). Mean SMR, but not MMR, was lower in warm regimes within both populations (i.e. basal metabolic costs were reduced at higher temperatures), consistent with an adaptive acclimation response that optimizes growth. Metabolic phenotypes thus exhibited a thermally sensitive metabolic 'floor' and a less flexible metabolic 'ceiling'. Our findings suggest a role for growth-related fluctuating selection in shaping patterns of metabolic variation that is likely important in adapting to climate change.


Subject(s)
Basal Metabolism , Trout , Acclimatization , Animals , Energy Metabolism , Phenotype
6.
Ecol Evol ; 11(12): 8347-8362, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34188891

ABSTRACT

The occurrence of alternative morphs within populations is common, but the underlying molecular mechanisms remain poorly understood. Many animals, for example, exhibit facultative migration, where two or more alternative migratory tactics (AMTs) coexist within populations. In certain salmonid species, some individuals remain in natal rivers all their lives, while others (in particular, females) migrate to sea for a period of marine growth. Here, we performed transcriptional profiling ("RNA-seq") of the brain and liver of male and female brown trout to understand the genes and processes that differentiate between migratory and residency morphs (AMT-associated genes) and how they may differ in expression between the sexes. We found tissue-specific differences with a greater number of genes expressed differentially in the liver (n = 867 genes) compared with the brain (n = 10) between the morphs. Genes with increased expression in resident livers were enriched for Gene Ontology terms associated with metabolic processes, highlighting key molecular-genetic pathways underlying the energetic requirements associated with divergent migratory tactics. In contrast, smolt-biased genes were enriched for biological processes such as response to cytokines, suggestive of possible immune function differences between smolts and residents. Finally, we identified evidence of sex-biased gene expression for AMT-associated genes in the liver (n = 12) but not the brain. Collectively, our results provide insights into tissue-specific gene expression underlying the production of alternative life histories within and between the sexes, and point toward a key role for metabolic processes in the liver in mediating divergent physiological trajectories of migrants versus residents.

7.
Glob Chang Biol ; 27(16): 3765-3778, 2021 08.
Article in English | MEDLINE | ID: mdl-34009702

ABSTRACT

Global warming over the next century is likely to alter the energy demands of consumers and thus the strengths of their interactions with their resources. The subsequent cascading effects on population biomasses could have profound effects on food web stability. One key mechanism by which organisms can cope with a changing environment is phenotypic plasticity, such as acclimation to warmer conditions through reversible changes in their physiology. Here, we measured metabolic rates and functional responses in laboratory experiments for a widespread predator-prey pair of freshwater invertebrates, sampled from across a natural stream temperature gradient in Iceland (4-18℃). This enabled us to parameterize a Rosenzweig-MacArthur population dynamical model to study the effect of thermal acclimation on the persistence of the predator-prey pairs in response to warming. Acclimation to higher temperatures either had neutral effects or reduced the thermal sensitivity of both metabolic and feeding rates for the predator, increasing its energetic efficiency. This resulted in greater stability of population dynamics, as acclimation to higher temperatures increased the biomass of both predator and prey populations with warming. These findings indicate that phenotypic plasticity can act as a buffer against the impacts of environmental warming. As a consequence, predator-prey interactions between ectotherms may be less sensitive to future warming than previously expected, but this requires further investigation across a broader range of interacting species.


Subject(s)
Food Chain , Predatory Behavior , Acclimatization , Animals , Iceland , Population Dynamics , Temperature
8.
Front Immunol ; 12: 568729, 2021.
Article in English | MEDLINE | ID: mdl-33717060

ABSTRACT

Vertebrates have evolved a complex immune system required for the identification of and coordinated response to harmful pathogens. Migratory species spend periods of their life-cycle in more than one environment, and their immune system consequently faces a greater diversity of pathogens residing in different environments. In facultatively anadromous salmonids, individuals may spend parts of their life-cycle in freshwater and marine environments. For species such as the brown trout Salmo trutta, sexes differ in their life-histories with females more likely to migrate to sea while males are more likely to stay and complete their life-cycle in their natal river. Salmonids have also undergone a lineage-specific whole genome duplication event, which may provide novel immune innovations but our current understanding of the differences in salmonid immune expression between the sexes is limited. We characterized the brown trout immune gene repertoire, identifying a number of canonical immune genes in non-salmonid teleosts to be duplicated in S. trutta, with genes involved in innate and adaptive immunity. Through genome-wide transcriptional profiling ("RNA-seq") of male and female livers to investigate sex differences in gene expression amplitude and alternative splicing, we identified immune genes as being generally male-biased in expression. Our study provides important insights into the evolutionary consequences of whole genome duplication events on the salmonid immune gene repertoire and how the sexes differ in constitutive immune expression.


Subject(s)
Biological Evolution , Gene Expression Regulation , Immune System/immunology , Immune System/metabolism , Salmonidae/genetics , Salmonidae/immunology , Animals , Computational Biology/methods , Evolution, Molecular , Female , Gene Expression Profiling , Genomics/methods , Male , Organ Specificity/genetics , Trout/genetics , Trout/immunology
9.
Int J STEM Educ ; 7(1): 51, 2020.
Article in English | MEDLINE | ID: mdl-33088672

ABSTRACT

BACKGROUND: Identity provides a useful conceptual lens for understanding educational inequalities in science, technology, engineering and mathematics (STEM). In this paper, we examine how paying attention to physical and digital 'materiality' enriches our understanding of identity work, by going beyond the spoken, written and embodied dimensions of identity performances that currently dominate the area of STEM identity scholarship. We draw on a multimodal ethnographic study with 36 young people aged 11-14 carried out over the course of one year at four UK-based informal STEM learning settings. Data collection included a series of interviews, observations and youth-created portfolios focused on STEM experiences. Illustrative case studies of two young men who took part in a community-based digital arts centre are discussed in detail through the theoretical lenses of Judith Butler's identity performativity and Karen Barad's intra-action. RESULTS: We argue that physical and digital materiality mattered for the performances of 'tech identity' in that (i) the focus on the material changed our understanding of tech identity performances; (ii) digital spaces supported identity performances alongside, with and beyond physical bodies, and drew attention to new forms of identity recognition; (iii) identity performances across spaces were unpredictable and contained by the limits of material possibilities; and (iv) particular identity performances associated with technology were aligned with dominant enactments of masculinity and might thus be less accessible to some young people. CONCLUSION: We conclude the paper by suggesting that accounting for materiality in STEM identity research not only guides researchers in going beyond what participants say and are observed doing (and thus engendering richer insights), but also offers more equitable ways of enacting research. Further, we argue that more needs to be done to support the translation of identity resources across spaces, such as between experiences within informal and online spaces, on the one hand, and formal education, on the other.

10.
Conserv Physiol ; 8(1): coaa096, 2020.
Article in English | MEDLINE | ID: mdl-33093959

ABSTRACT

Metabolic rates vary hugely within and between populations, yet we know relatively little about factors causing intraspecific variation. Since metabolic rate determines the energetic cost of life, uncovering these sources of variation is important to understand and forecast responses to environmental change. Moreover, few studies have examined factors causing intraspecific variation in metabolic flexibility. We explore how extrinsic environmental conditions and intrinsic factors contribute to variation in metabolic traits in brown trout, an iconic and polymorphic species that is threatened across much of its native range. We measured metabolic traits in offspring from two wild populations that naturally show life-history variation in migratory tactics (one anadromous, i.e. sea-migratory, one non-anadromous) that we reared under either optimal food or experimental conditions of long-term food restriction (lasting between 7 and 17 months). Both populations showed decreased standard metabolic rates (SMR-baseline energy requirements) under low food conditions. The anadromous population had higher maximum metabolic rate (MMR) than the non-anadromous population, and marginally higher SMR. The MMR difference was greater than SMR and consequently aerobic scope (AS) was higher in the anadromous population. MMR and AS were both higher in males than females. The anadromous population also had higher AS under low food compared to optimal food conditions, consistent with population-specific effects of food restriction on AS. Our results suggest different components of metabolic rate can vary in their response to environmental conditions, and according to intrinsic (population-background/sex) effects. Populations might further differ in their flexibility of metabolic traits, potentially due to intrinsic factors related to life history (e.g. migratory tactics). More comparisons of populations/individuals with divergent life histories will help to reveal this. Overall, our study suggests that incorporating an understanding of metabolic trait variation and flexibility and linking this to life history and demography will improve our ability to conserve populations experiencing global change.

11.
Glob Chang Biol ; 26(5): 2878-2896, 2020 05.
Article in English | MEDLINE | ID: mdl-32103581

ABSTRACT

With rapid global change, organisms in natural systems are exposed to a multitude of stressors that likely co-occur, with uncertain impacts. We explored individual and cumulative effects of co-occurring environmental stressors on the striking, yet poorly understood, phenomenon of facultative migration. We reared offspring of a brown trout population that naturally demonstrates facultative anadromy (sea migration), under different environmental stressor treatments and measured life history responses in terms of migratory tactics and freshwater maturation rates. Juvenile fish were exposed to reduced food availability, temperatures elevated to 1.8°C above natural conditions or both treatments in combination over 18 months of experimental tank rearing. When considered in isolation, reduced food had negative effects on the size, mass and condition of fish across the experiment. We detected variable effects of warm temperatures (negative effects on size and mass, but positive effect on lipids). When combined with food restriction, temperature effects on these traits were less pronounced, implying antagonistic stressor effects on morphological traits. Stressors combined additively, but had opposing effects on life history tactics: migration increased and maturation rates decreased under low food conditions, whereas the opposite occurred in the warm temperature treatment. Not all fish had expressed maturation or migration tactics by the end of the study, and the frequency of these 'unassigned' fish was higher in food deprivation treatments, but lower in warm treatments. Fish showing migration tactics were smaller and in poorer condition than fish showing maturation tactics, but were similar in size to unassigned fish. We further detected effects of food restriction on hypo-osmoregulatory function of migrants that may influence the fitness benefits of the migratory tactic at sea. We also highlight that responses to multiple stressors may vary depending on the response considered. Collectively, our results indicate contrasting effects of environmental stressors on life history trajectories in a facultatively migratory species.


Subject(s)
Animal Migration , Trout , Animals , Fresh Water , Temperature
12.
J Anim Ecol ; 88(11): 1670-1683, 2019 11.
Article in English | MEDLINE | ID: mdl-31283002

ABSTRACT

Global warming is one of the greatest threats to the persistence of populations: increased metabolic demands should strengthen pairwise species interactions, which could destabilize food webs at the higher organizational levels. Quantifying the temperature dependence of consumer-resource interactions is thus essential for predicting ecological responses to warming. We explored feeding interactions between different predator-prey pairs in controlled-temperature chambers and in a system of naturally heated streams. We found consistent temperature dependence of attack rates across experimental settings, though the magnitude and activation energy of attack rate were specific to each predator, which varied in mobility and foraging mode. We used these parameters along with metabolic rate measurements to estimate energetic efficiency and population abundance with warming. Energetic efficiency accurately estimated field abundance of a mobile predator that struggled to meet its metabolic demands, but was a poor predictor for a sedentary predator that operated well below its energetic limits. Temperature effects on population abundance may thus be strongly dependent on whether organisms are regulated by their own energy intake or interspecific interactions. Given the widespread use of functional response parameters in ecological modelling, reconciling outcomes from laboratory and field studies increases the confidence and precision with which we can predict warming impacts on natural systems.


Subject(s)
Food Chain , Predatory Behavior , Animals , Global Warming , Temperature
13.
Eur J Med Genet ; 62(5): 368-375, 2019 May.
Article in English | MEDLINE | ID: mdl-30590173

ABSTRACT

While many people enjoy popular culture, these transactional experiences may not translate into formal or academic learning about a subject. In education and science communication settings popular culture is often presented as a source of inaccurate information about science. Different publics are often positioned as, at best, undiscriminating consumers and at worst victims of distorted scientific information. We explore how people use their own knowledge and interests to engage with genetics. Here, data from family interviews are used to illustrate how participants draw on popular culture as a resource to engage with and articulate their beliefs about genetics. Using qualitative data from family interviews we describe two perspectives: first, popular culture represents a source of narratives and metaphors used for rhetorical purposes. Second participants used fictional narratives in more depth - as sense-making devices - allowing people to explore the moral and ethical implications of genetics. We argue that by utilising patients' interests - such as popular culture - we can potentially enrich communication in a genetic counselling context.


Subject(s)
Attitude , Genetic Counseling/psychology , Genetics , Popular Culture , Adult , Aged , Female , Genetic Counseling/methods , Humans , Information Literacy , Male , Middle Aged , Public Opinion
14.
Sex Roles ; 76(3): 156-174, 2017.
Article in English | MEDLINE | ID: mdl-28133410

ABSTRACT

The present article investigates explanations for gendered trends in Physics and Engineering access, reporting findings from a large-scale study funded by the UK Economic and Social Research Council and drawing primarily on data from interviews with 132 15-16 year-old adolescents and their parents. Survey results in our study and elsewhere show strong gender disparities in anticipated pursuit of Physics after completion of compulsory education. In order to explore the constructions of gender and Physics underlying these trends, we focus on qualitative interview data, applying Foucaultian analysis of discourse to investigate gendered narratives underpinning adolescents' and their parents' articulations. This analysis reveals three key discourses at work on the topic of women's access to Physics: (a) equality of opportunity, (b) continued gender discrimination in and around Physics, and (c) Physics as quintessentially masculine. We additionally identify five distinct narratives supporting the discourse of physics as masculine. These various discourses and narratives are interrogated, and their implications explored. We conclude that it is only by disrupting prevalent constructions of the Physical sciences as a masculine and "hard" domain will we increase the presence of women in the sector. Working with young people to analyse and deconstruct the discursive assumptions made in relation to gender and Physics, as well as further work to increase accessibility and broaden representation in Physics, may be fruitful ways to challenge these longstanding associations between Physics and masculinity.

15.
Transplantation ; 99(5): 1078-83, 2015 May.
Article in English | MEDLINE | ID: mdl-25757211

ABSTRACT

BACKGROUND: Lung transplantation is limited by a scarcity of suitable donors resulting in high waiting list mortality. Ex vivo lung perfusion (EVLP) allows the evaluation and reconditioning of marginal donor lungs for use in transplantation. This study aimed to compare clinical outcome of patients transplanted with marginal organs by means of EVLP with a standard lung transplant cohort through a multicenter open trial. METHODS: Group 1 (n = 9) included patients transplanted using EVLP reconditioned marginal lungs. Group 2 (n = 46) consisted of date-matched patients transplanted using standard transplantation of acceptable lungs. The primary composite endpoint included acute rejection and infection at 12 months after transplantation. RESULTS: There was no significant difference in the overall incidence of acute rejection (P = 0.754) and the number of treated infection episodes (proven/probable pneumonia; P = 0.857/0.368 and proven/probable tracheobronchitis; P = 0.226/0.529) up to 12 months after transplantation, between group 1 and group 2. Additionally, there was no significant difference in early clinical outcome, including intensive care unit stay, hospital stay, and 1 year mortality between the two groups (P = 0.338, P = 0.112 and P = 0.372, respectively). DISCUSSION: This multicenter study demonstrates that EVLP is associated with no adverse effect on clinical outcome, including the incidence of acute rejection and infection after lung transplantation.


Subject(s)
Lung Transplantation/methods , Lung/blood supply , Tissue Donors , Adult , Aged , Female , Graft Rejection/epidemiology , Humans , Lung Transplantation/adverse effects , Male , Middle Aged , Perfusion
16.
Sci Educ ; 99(2): 199-237, 2015 03.
Article in English | MEDLINE | ID: mdl-28579645

ABSTRACT

There are widespread policy concerns to improve (widen and increase) science, technology, engineering, and mathematics participation, which remains stratified by ethnicity, gender, and social class. Despite being interested in and highly valuing science, Black students tend to express limited aspirations to careers in science and remain underrepresented in post-16 science courses and careers, a pattern which is not solely explained by attainment. This paper draws on survey data from nationally representative student cohorts and longitudinal interview data collected over 4 years from 10 Black African/Caribbean students and their parents, who were tracked from age 10-14 (Y6-Y9), as part of a larger study on children's science and career aspirations. The paper uses an intersectional analysis of the qualitative data to examine why science careers are less "thinkable" for Black students. A case study is also presented of two young Black women who "bucked the trend" and aspired to science careers. The paper concludes with implications for science education policy and practice.

17.
J Inherit Metab Dis ; 37(1): 1-12, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23653226

ABSTRACT

Mucopolysaccharide (MPS) diseases are lysosomal storage disorders (LSDs) caused by deficiencies in enzymes required for glycosaminoglycan (GAG) catabolism. Mucopolysaccharidosis I (MPS I), MPS IIIA, MPS IIIB and MPS VII are deficient in the enzymes α-L-Iduronidase, Heparan-N-Sulphatase, N-Acetylglucosaminidase and Beta-Glucuronidase, respectively. Enzyme deficiency leads to the progressive multi-systemic build-up of heparan sulphate (HS) and dermatan sulphate (DS) within cellular lysosomes, followed by cell, tissue and organ damage and in particular neurodegeneration. Clinical manifestations of MPS are well established; however as lysosomes represent vital components of immune cells, it follows that lysosomal accumulation of GAGs could affect diverse immune functions and therefore influence disease pathogenesis. Theoretically, MPS neurodegeneration and GAGs could be substantiating a threat of danger and damage to alert the immune system for cellular clearance, which due to the progressive nature of MPS storage would propagate disease pathogenesis. Innate immunity appears to have a key role in MPS; however the extent of adaptive immune involvement remains to be elucidated. The current literature suggests a complex interplay between neuroinflammation, microglial activation and adaptive immunity in MPS disease.


Subject(s)
Inflammation/pathology , Microglia/pathology , Mucopolysaccharidoses/diagnosis , Mucopolysaccharidoses/immunology , Neurons/pathology , Adaptive Immunity , Autophagy , B-Lymphocytes/cytology , Dendritic Cells/cytology , Enzymes/deficiency , Humans , Lysosomes/metabolism , Mucopolysaccharidoses/pathology , Neurodegenerative Diseases/immunology , Oxidative Stress , Peptides/immunology , T-Lymphocytes/immunology , Toll-Like Receptors/metabolism
18.
J Inherit Metab Dis ; 36(2): 257-62, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22773246

ABSTRACT

BACKGROUND: Mucopolysaccharidosis I (MPS I) is a metabolic disorder caused by α-L-Iduronidase (IDUA) deficiency, resulting in lysosomal accumulation of heparan (HS) and dermatan sulphate (DS). This has been reported in microglia, yet currently the effect of IDUA deficiency on T cells and dendritic cells (DC) and their functionality in disease pathogenesis remains unclear. METHODS: Peripheral blood was collected from 3 month old C57BL/6 MPS I (n = 11) and wildtype (WT) (n = 6) mice. T cell and DC phenotype and functional characteristics were identified by flow cytometry. RESULTS: MPS I mice exhibited a reduction in DC (p = <0.001) along with CD8+ cytotoxic (p = 0.01) and CD4+ T helper (p = 0.032) cells, compared to WT controls. MPS I DC displayed a significant decrease in cell surface CD123 (p = 0.02) and CD86 (p = 0.006) expression. Furthermore, CD45RB expression was significantly reduced on T helper cells in the MPS I population (p = 0.019). CONCLUSION: We report a reduction in circulating DC and T cells in the MPS I mouse; indicative of adaptive immune dysfunction. DC reduction may occur in response to down-regulation of the IL-3 receptor (CD123), necessary for DC survival. We also report down-regulation of cell surface CD86, a molecule required for T cell co-stimulation. T helper cell down-regulation of CD45RB is redolent of an anti-inflammatory phenotype with poor proliferative capacity. The definitive causes of our findings and the consequences and role that these findings play in the pathogenesis of MPS are unclear, but may be in response to lysosomal storage of unmetabolized HS and DS.


Subject(s)
Dendritic Cells/immunology , Mucopolysaccharidosis I/immunology , T-Lymphocytes, Helper-Inducer/immunology , Animals , Down-Regulation/immunology , Leukocyte Common Antigens/immunology , Mice , Mice, Inbred C57BL , Receptors, Interleukin-3/immunology
20.
Cardiovasc Ther ; 27(3): 181-6, 2009.
Article in English | MEDLINE | ID: mdl-19689617

ABSTRACT

It remains possible that the benefit from beta-blockers (BBs) in chronic heart failure (CHF) may not entirely be derived from a class-specific effect. Several experimental reports have alluded to the capability of immunomodulation by individual BBs. Given the increasingly recognized importance of the immune system in the pathogenesis of CHF, we studied the effects of BBs on the circulating immune system of these patients. Blood samples from CHF outpatients were prospectively analyzed using flow cytometry and gating software. Results were analyzed against comprehensive clinical details that were recorded during sample donation, including the type of BB administered. 273 blood samples were analyzed from 141 CHF patients, with an average ejection fraction of 31.9% and a mean age of 69.1 years. Patients taking carvedilol had a significantly lower expression of CD107a on cytotoxic T cells compared to bisoprolol (P= 0.001) and nebivolol (P= 0.008). They also had a significantly lower expression of HLA-DR on lymphocytes (P < 0.001 and P= 0.009 for bisoprolol and nebivolol, respectively). Cytotoxic T cells and lymphocytes expressing HLA-DR have been implicated in the pathogenesis of CHF. The fact that carvedilol, but not other commonly used beta-blockers, appears to modulate these important parameters, supports the concept that important differences exist between these agents, which may affect outcomes in CHF.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Adrenergic beta-Antagonists/therapeutic use , Carbazoles/pharmacology , Heart Failure/drug therapy , Heart Failure/immunology , Immune System/drug effects , Propanolamines/pharmacology , Aged , Benzopyrans/pharmacology , Benzopyrans/therapeutic use , Bisoprolol/pharmacology , Bisoprolol/therapeutic use , Carbazoles/therapeutic use , Carvedilol , Chronic Disease , Cohort Studies , Edetic Acid , Ethanolamines/pharmacology , Ethanolamines/therapeutic use , Female , Flow Cytometry , HLA-DR Antigens/metabolism , Humans , Male , Middle Aged , Nebivolol , Propanolamines/therapeutic use , Prospective Studies , Stroke Volume/drug effects , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/immunology
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