Every day, biologists in parkas, raincoats, and rubber boots go into the field to capture and mark a variety of animal species. Back in the office, statisticians create analytical models for the ...field biologists' data. But many times, representatives of the two professions do not fully understand one another's roles. This book bridges this gap by helping biologists understand state-of-the-art statistical methods for analyzing capture-recapture data. In so doing, statisticians will also become more familiar with the design of field studies and with the real-life issues facing biologists.
Reliable outcomes of capture-recapture studies are vital to answering key ecological questions. Is the population increasing or decreasing? Do more or fewer animals have a particular characteristic? In answering these questions, biologists cannot hope to capture and mark entire populations. And frequently, the populations change unpredictably during a study. Thus, increasingly sophisticated models have been employed to convert data into answers to ecological questions. This book, by experts in capture-recapture analysis, introduces the most up-to-date methods for data analysis while explaining the theory behind those methods. Thorough, concise, and portable, it will be immensely useful to biologists, biometricians, and statisticians, students in both fields, and anyone else engaged in the capture-recapture process.
Conventional antiviral memory CD4 T cells typically arise during the first two weeks of acute infection. Unlike most viruses, cytomegalovirus (CMV) exhibits an extended persistent replication phase ...followed by lifelong latency accompanied with some gene expression. We show that during mouse CMV (MCMV) infection, CD4 T cells recognizing an epitope derived from the viral M09 protein only develop after conventional memory T cells have already peaked and contracted. Ablating these CD4 T cells by mutating the M09 genomic epitope in the MCMV Smith strain, or inducing them by introducing the epitope into the K181 strain, resulted in delayed or enhanced control of viral persistence, respectively. These cells were shown to be unique compared to their conventional memory counterparts; producing higher IFNγ and IL-2 and lower IL-10 levels. RNAseq analyses revealed them to express distinct subsets of effector genes as compared to classical CD4 T cells. Additionally, when M09 cells were induced by epitope vaccination they significantly enhanced protection when compared to conventional CD4 T cells alone. These data show that late-rising CD4 T cells are a unique memory subset with excellent protective capacities that display a development program strongly differing from the majority of memory T cells.
Transforming growth factor β (TGFβ) is an important differentiation factor for cytotoxic T lymphocytes (CTLs) and alters the expression levels of several of homing receptors during infection. SMAD4 ...is part of the canonical signaling network used by members of the transforming growth factor family. For this study, genetically modified mice were used to determine how SMAD4 and TGFβ receptor II (TGFβRII) participate in transcriptional programming of pathogen-specific CTLs. We show that these molecules are essential components of opposing signaling mechanisms, and cooperatively regulate a collection of genes that determine whether specialized populations of pathogen-specific CTLs circulate around the body, or settle in peripheral tissues. TGFβ uses a canonical SMAD-dependent signaling pathway to downregulate Eomesodermin (EOMES), KLRG1, and CD62L, while CD103 is induced. Conversely, in vivo and in vitro data show that EOMES, KLRG1, CX
3
CR1, and CD62L are positively regulated via SMAD4, while CD103 and Hobit are downregulated. Intravascular staining also shows that signaling via SMAD4 promotes formation of long-lived terminally differentiated CTLs that localize in the vasculature. Our data show that inflammatory molecules play a key role in lineage determination of pathogen-specific CTLs, and use SMAD-dependent signaling to alter the expression levels of multiple homing receptors and transcription factors with known functions during memory formation.
TNF-related apoptosis inducing ligand (TRAIL) death receptors (DR) regulate apoptosis and inflammation, but their role in antiviral defense is poorly understood. Cytomegaloviruses (CMV) encode many ...immune-modulatory genes that shape host immunity, and they utilize multiple strategies to target the TNF-family cytokines. Here we show that the m166 open reading frame (orf) of mouse CMV (MCMV) is strictly required to inhibit expression of TRAIL-DR in infected cells. An MCMV mutant lacking m166 expression (m166stop) is severely compromised for replication in vivo, most notably in the liver, and depleting natural killer (NK) cells, or infecting TRAIL-DR-/- mice, restored MCMV-m166stop replication completely. These results highlight the critical importance for CMV to have evolved a strategy to inhibit TRAIL-DR signaling to thwart NK-mediated defenses.
Background
Atopic eczema is a common, chronic, inflammatory skin condition with considerable heterogeneity. South Asian people living in the UK frequently have low serum vitamin D3 (25(OH)D3), and ...those with atopic disease can present with severe eczema. The association between vitamin D deficiency and eczema severity, and the role of vitamin D supplementation in atopic eczema is inconsistent, and under‐researched in people with Asian ancestry.
Objectives
This cross‐sectional study investigates the association between serum 25(OH)D3 and eczema severity in a cohort of South Asian children and young adults living in London.
Methods
Eligible participants were Bangladeshi children and young adults aged 0–30 years with eczema, living in London and participating in the Tower Hamlets Eczema Assessment study. Data was collected via parent/patient self‐reporting, clinical history and examination, and hospital databases. 25(OH)D3 levels were documented retrospectively, if available, from hospital databases. Eczema severity was classified by Eczema Area and Severity Index (EASI) score less than or greater than 10 (clear‐mild vs. moderate‐severe). Multivariate logistic regression was used to adjust for confounding factors.
Results
681 participants were included in analyses. 25(OH)D3 results were available for 49.6% (338/681), 84.3% of which had deficient or insufficient lowest 25(OH)D3. Lowest 25(OH)D3 was inversely correlated with EASI score (Spearman's rank R2 = −0.24, p < 0.001). 26.1% (178/681) had EASI >10 and a lower median lowest and nearest 25(OH)D3. After adjustment for confounding EASI > 10 was significantly associated with a lowest 25(OH)D3 < 25 (OR 3.21, 95%CI 1.35, 8.60), use of mild‐moderate potency topical steroid on the face and neck (OR 3.11, 95%CI 1.86, 5.31), calcineurin inhibitor on the face and neck (OR 2.79, 95% CI 1.26, 6.10) and potent – very potent topical steroid on the face and neck (OR2.23, 95%CI 1.02, 4.77) and body (OR 2.11, 95%CI 1.18, 3.87).
Discussion
Vitamin D plays a role in modulation of proteins required for skin barrier function and regulation of the innate immune system, suggesting 25(OH)D3 deficiency contributes to skin inflammation. This study demonstrates a relationship between 25(OH)D3 deficiency and worse eczema severity in a cohort of South Asian children and young adults.
This cross‐sectional study investigates the association between serum vitamin D levels and eczema severity in a cohort of South Asian children and young adults living in London. The results support that vitamin D deficiency is associated with worse eczema severity, after adjustment for confounding factors.
Atopic eczema is a common and complex disease. Missing genetic hereditability and increasing prevalence in industrializing nations point toward an environmental driver. We investigated the temporal ...association of weather and pollution parameters with eczema severity. This cross-sectional clinical study was performed between May 2018 and March 2020 and is part of the Tower Hamlets Eczema Assessment. All participants had a diagnosis of eczema, lived in East London, were of Bangladeshi ethnicity, and were aged <31 years. The primary outcome was the probability of having an Eczema Area and Severity Index score > 10 after previous ambient exposure to commonly studied meteorological variables and pollutants. There were 430 participants in the groups with Eczema Area and Severity Index ≤ 10 and 149 in those with Eczema Area and Severity Index > 10. Using logistic generalized additive models and a model selection process, we found that tropospheric ozone averaged over the preceding 270 days was strongly associated with eczema severity alongside the exposure to fine particles with diameters of 2.5 μm or less (fine particulate matter) averaged over the preceding 120 days. In our models and analyses, fine particulate matter appeared to largely act in a supporting role to ozone. We show that long-term exposure to ground-level ozone at high levels has the strongest association with eczema severity.
In response to infection, T cells adopt a range of differentiation states, creating numerous heterogeneous subsets that exhibit different phenotypes, functions, and migration patterns. This T cell ...heterogeneity is a universal feature of T cell immunity, needed to effectively control pathogens in a context-dependent manner and generate long-lived immunity to those pathogens. Here, we review new insights into differentiation state dynamics and population heterogeneity of CD8+ T cells in acute and chronic viral infections and cancer and highlight the parallels and distinctions between acute and chronic antigen stimulation settings. We focus on transcriptional and epigenetic networks that modulate the plasticity and terminal differentiation of antigen-specific CD8+ T cells and generate functionally diverse T cell subsets with different roles to combat infection and cancer.
Immunological memory is a hallmark of adaptive immunity that confers long-lasting protection from reinfections. Memory CD8
T cells provide protection by actively scanning for their cognate antigen ...and migrating into inflamed tissues. Trafficking patterns of CD8
T cells are also a major determinant of cell fate outcomes during differentiation into effector and memory cell states. CD8
T-cell trafficking must therefore be dynamically and tightly regulated to ensure that CD8
T cells arrive at the correct locations and differentiate to acquire appropriate effector functions. This review aims to discuss the importance of CD8
T-cell trafficking patterns in regulating effector and memory differentiation, maintenance, and reactivation.
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