156 research outputs found
Mathematical modelling of T cell homeostasis
No full textT cell homeostasis describes the process through which the immune system
regulates cell survival, proliferation, differentiation and death to maintain T
cell numbers and diversity in a range of different conditions. The aim of this
thesis is to better understand how this process leads to the development of the
naive CD4+ T cell compartment during childhood. Mathematical modelling is
used in combination with experimental observations to estimate naive T cell
kinetics over the lifetime of an individual. The analysis described here shows
that post-thymic proliferation contributes more than double the number of cells
entering the pool each day from the thymus. This ratio is preserved from birth
to age 20 years; as the thymus involutes, the average time between naive T-cell
divisions in the periphery lengthens with age and the naive population is maintained
by improved naive cell survival. Thymic output is quantified from birth
to age 60 years by combining models to interpret naive T cell TRECs and Ki67
expression data. Three distinct phases of thymic T cell output are identified: (i)
increasing production from birth to age 1 year; (ii) steep decline to age 8 years;
(iii) slow decline from age 8 years onwards. Finally, the role of inter-cellular
variation in T cell residency times is explored. It is able to explain the persistence
of PTK7+ naive CD4+ T cells in thymectomised individuals. Importantly,
the model predicts the accumulation of veteran PTK7+ T cells in older individuals
and suggests that the residual population in thymectomised individuals
will also consist predominantly of veteran PTK7+ T cells. The model has implications
for the use of PTK7 as a marker of recent thymic emigration and also
naturally explains improved T cell survival in older individuals
Deficits in growth, muscle mass, and body composition following placental insufficiency-induced intrauterine growth restriction persisted in lambs at 60 d of age but were improved by daily clenbuterol supplementation
No full textLow birthweight in livestock results from stress-induced intrauterine growth restriction (IUGR; Yates et al., 2018). IUGR fetuses exhibit diminished muscle growth that persists in the neonatal stage, leading to asymmetric body composition and decreased weight gain (Cadaret et al., 2019). Ultimately, low birthweight diminishes yield and carcass merit at harvest (Greenwood et al., 2000), making effective postnatal treatment strategies to improve IUGR growth outcomes necessary. In this study, we examined the benefits of injecting the β2 agonist clenbuterol daily to target adrenergic adaptations that we previously observed in IUGR muscle (Posont et al., 2018; Yates et al., 2018). We hypothesized that IUGRinduced growth deficits would persist at the juvenile stage, manifesting in inferior body composition and carcass traits. We also postulated that clenbuterol would at least partially recover growth and body symmetry. Our objective was to test this hypothesis by assessing growth metrics and body composition in IUGR-born lambs hand-reared to 60 d of age and supplemented daily with injectable clenbuterol
The relationship between depression and chronotype: A longitudinal assessment during childhood and adolescence
No full textBackground/Objective
During adolescence, chronotype shifts towards “eveningness.” “Eveningness” is related to negative physical and mental health outcomes. Little is known about what influences the shift in chronotype beyond pubertal status. The current study examined the influence of earlier depression predicting later individual differences in adolescent chronotype, accounting for pubertal status, and the prospective prediction of later increases in depression from earlier chronotype.
Methods
Youth (age M=12.06, SD=2.35; 56.5% girls) from the community completed repeated assessments of depression, including both self-reports (14 assessments) and diagnostic interviews (8 assessments), over a 48-month period. At the 36-month time-point, participants completed chronotype and pubertal development measures. Regression and ANOVA analyses examined: (1) the influence of earlier depression levels (baseline to 36-months) upon chronotype, and (2) chronotype (at 36 months) upon later depression (48 months).
Results
Youth with higher earlier depression symptoms (β=-.347, p<.001) and history of depression diagnosis (β=-.13, p=.045) showed a greater eveningness preference controlling for pubertal status, age and gender. Further, depression diagnosis history interacted with pubertal status to predict chronotype: (F(1,243)=4.171, p=.045) such that the influence of depression on chronotype was greatest among postpubertal youth (t=3.271, p=.002). Chronotype (greater eveningness preference) predicted prospective increases in depression symptoms (β=-.16, p=.03) and onset of depressive episode (b=-.085, OR=.92, p=.03) one year later.
Conclusion
Depression, experienced earlier in life, predicts greater preference for eveningness, especially among postpubertal youth. In turn, later depression is predicted by evening preference. These findings suggest the reciprocal interplay between mood and biological rhythms, especially depression and chronotype, during adolescence.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-12-01The student, Dustin Haraden, accepted the attached license on 2017-12-12 at 16:34.The student, Dustin Haraden, submitted this Thesis for approval on 2017-12-12 at 16:40.This Thesis was approved for publication on 2017-12-13 at 08:22.DSpace SAF Submission Ingestion Package generated from Vireo submission #11961 on 2018-03-13 at 10:38:25Made available in DSpace on 2018-03-13T17:35:57Z (GMT). No. of bitstreams: 2
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Previous issue date: 2017-12-13Embargo set by: Seth Robbins for item 105503
Lift date: 2020-03-13T17:36:05Z
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Dousing the flame: reviewing the mechanisms of inflammatory programming during stress-induced intrauterine growth restriction and the potential for ω-3 polyunsaturated fatty acid intervention
No full textIntrauterine growth restriction (IUGR) arises when maternal stressors coincide with peak placental development, leading to placental insufficiency. When the expanding nutrient demands of the growing fetus subsequently exceed the capacity of the stunted placenta, fetal hypoxemia and hypoglycemia result. Poor fetal nutrient status stimulates greater release of inflammatory cytokines and catecholamines, which in turn lead to thrifty growth and metabolic programming that benefits fetal survival but is maladaptive after birth. Specifically, some IUGR fetal tissues develop enriched expression of inflammatory cytokine receptors and other signaling cascade components, which increases inflammatory sensitivity even when circulating inflammatory cytokines are no longer elevated after birth. Recent evidence indicates that greater inflammatory tone contributes to deficits in skeletal muscle growth and metabolism that are characteristic of IUGR offspring. These deficits underlie the metabolic dysfunction that markedly increases risk for metabolic diseases in IUGR-born individuals. The same programming mechanisms yield reduced metabolic efficiency, poor body composition, and inferior carcass quality in IUGR-born livestock. The ω-3 polyunsaturated fatty acids (PUFA) are diet-derived nutraceuticals with anti-inflammatory effects that have been used to improve conditions of chronic systemic inflammation, including intrauterine stress. In this review, we highlight the role of sustained systemic inflammation in the development of IUGR pathologies. We then discuss the potential for ω-3 PUFA supplementation to improve inflammation-mediated growth and metabolic deficits in IUGR offspring, along with potential barriers that must be considered when developing a supplementation strategy
Going Up Inflame: Reviewing the Underexplored Role of Inflammatory Programming in Stress-Induced Intrauterine Growth Restricted Livestock
No full textThe impact of intrauterine growth restriction (IUGR) on health in humans is well-recognized. It is the second leading cause of perinatal mortality worldwide, and it is associated with deficits in metabolism and muscle growth that increase lifelong risk for hypertension, obesity, hyperlipidemia, and type 2 diabetes. Comparatively, the barrier that IUGR imposes on livestock production is less recognized by the industry. Meat animals born with low birthweight due to IUGR are beset with greater early death loss, inefficient growth, and reduced carcass merit. These animals exhibit poor feed-to-gain ratios, less lean mass, and greater fat deposition, which increase production costs and decrease value. Ultimately, this reduces the amount of meat produced by each animal and threatens the economic sustainability of livestock industries. Intrauterine growth restriction is most commonly the result of fetal programming responses to placental insufficiency, but the exact mechanisms by which this occurs are not well-understood. In uncompromised pregnancies, inflammatory cytokines are produced at modest rates by placental and fetal tissues and play an important role in fetal development. However, unfavorable intrauterine conditions can cause cytokine activity to be excessive during critical windows of fetal development. Our recent evidence indicates that this impacts developmental programming of muscle growth and metabolism and contributes to the IUGR phenotype. In this review, we outline the role of inflammatory cytokine activity in the development of normal and IUGR phenotypes. We also highlight the contributions of sheep and other animal models in identifying mechanisms for IUGR pathologies
Inflammatory Mediation of Heat Stress-Induced Growth Deficits in Livestock and Its Potential Role as a Target for Nutritional Interventions: A Review
No full textHeat stress is detrimental to well-being and growth performance in livestock, and systemic inflammation arising during chronic heat stress contributes to these poor outcomes. Sustained exposure of muscle and other tissues to inflammation can impair the cellular processes that facilitate muscle growth and intramuscular fat deposition, thus reducing carcass quality and yield. Climate change is expected to produce more frequent extreme heat events, increasing the potential impact of heat stress on sustainable livestock production. Feedlot animals are at particularly high risk for heat stress, as confinement limits their ability to seek cooling from the shade, water, or breeze. Economically practical options to circumvent heat stress in feedlot animals are limited, but understanding the mechanistic role of inflammation in heat stress outcomes may provide the basis for treatment strategies to improve well-being and performance. Feedlot animals receive formulated diets daily, which provides an opportunity to administer oral nutraceuticals and other bioactive products to mitigate heat stress-induced inflammation. In this review, we examine the complex associations between heat stress, systemic inflammation, and dysregulated muscle growth in meat animals. We also present evidence for potential nutraceutical and dietary moderators of inflammation and how they might improve the unique pathophysiology of heat stress
Supplemental material2 - Supplemental material for Building and Maintaining a Citizen Science Network With Fishermen and Fishing Communities Post Deepwater Horizon Oil Disaster Using a CBPR Approach
No full textSupplemental material, Supplemental material2 for Building and Maintaining a Citizen Science Network With Fishermen and Fishing Communities Post Deepwater Horizon Oil Disaster Using a CBPR Approach by Academic Authors: John Sullivan, Sharon Croisant, Marilyn Howarth, Gilbert T. Rowe, Harshica Fernando, Amanda Phillips-Savoy, Dan Jackson, John Prochaska, Ghulam A. S. Ansari, Trevor M. Penning, Cornelis Elferink and Community Partner Authors: Louisiana Environmental Action Network, United Houma Nation, Bayou Interfaith Shared Community Organizing, Dustin Nguyen-Vietnamese Community Partner, Center for Environmental & Economic Justice, and Alabama Fisheries CooperativeProject Community Scientist Author: Wlima Subra in NEW SOLUTIONS: A Journal of Environmental and Occupational Health Policy</p
Supplemental material1 - Supplemental material for Building and Maintaining a Citizen Science Network With Fishermen and Fishing Communities Post Deepwater Horizon Oil Disaster Using a CBPR Approach
No full textSupplemental material, Supplemental material1 for Building and Maintaining a Citizen Science Network With Fishermen and Fishing Communities Post Deepwater Horizon Oil Disaster Using a CBPR Approach by Academic Authors: John Sullivan, Sharon Croisant, Marilyn Howarth, Gilbert T. Rowe, Harshica Fernando, Amanda Phillips-Savoy, Dan Jackson, John Prochaska, Ghulam A. S. Ansari, Trevor M. Penning, Cornelis Elferink and Community Partner Authors: Louisiana Environmental Action Network, United Houma Nation, Bayou Interfaith Shared Community Organizing, Dustin Nguyen-Vietnamese Community Partner, Center for Environmental & Economic Justice, and Alabama Fisheries CooperativeProject Community Scientist Author: Wlima Subra in NEW SOLUTIONS: A Journal of Environmental and Occupational Health Policy</p
Supplemental material4 - Supplemental material for Building and Maintaining a Citizen Science Network With Fishermen and Fishing Communities Post Deepwater Horizon Oil Disaster Using a CBPR Approach
No full textSupplemental material, Supplemental material4 for Building and Maintaining a Citizen Science Network With Fishermen and Fishing Communities Post Deepwater Horizon Oil Disaster Using a CBPR Approach by Academic Authors: John Sullivan, Sharon Croisant, Marilyn Howarth, Gilbert T. Rowe, Harshica Fernando, Amanda Phillips-Savoy, Dan Jackson, John Prochaska, Ghulam A. S. Ansari, Trevor M. Penning, Cornelis Elferink and Community Partner Authors: Louisiana Environmental Action Network, United Houma Nation, Bayou Interfaith Shared Community Organizing, Dustin Nguyen-Vietnamese Community Partner, Center for Environmental & Economic Justice, and Alabama Fisheries CooperativeProject Community Scientist Author: Wlima Subra in NEW SOLUTIONS: A Journal of Environmental and Occupational Health Policy</p
Supplemental material3 - Supplemental material for Building and Maintaining a Citizen Science Network With Fishermen and Fishing Communities Post Deepwater Horizon Oil Disaster Using a CBPR Approach
No full textSupplemental material, Supplemental material3 for Building and Maintaining a Citizen Science Network With Fishermen and Fishing Communities Post Deepwater Horizon Oil Disaster Using a CBPR Approach by Academic Authors: John Sullivan, Sharon Croisant, Marilyn Howarth, Gilbert T. Rowe, Harshica Fernando, Amanda Phillips-Savoy, Dan Jackson, John Prochaska, Ghulam A. S. Ansari, Trevor M. Penning, Cornelis Elferink and Community Partner Authors: Louisiana Environmental Action Network, United Houma Nation, Bayou Interfaith Shared Community Organizing, Dustin Nguyen-Vietnamese Community Partner, Center for Environmental & Economic Justice, and Alabama Fisheries CooperativeProject Community Scientist Author: Wlima Subra in NEW SOLUTIONS: A Journal of Environmental and Occupational Health Policy</p
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