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Ann N Y Acad Sci [journal]
- The proper study: preface to The Year in Immunology. [Journal Article]
- Ann N Y Acad Sci 2013 May; 1285(1):v-vii.
- The National Institutes of Health Center for Human Immunology, Autoimmunity, and Inflammation: history and progress. [Journal Article]
- Ann N Y Acad Sci 2013 May; 1285(1):133-47.
The Center for Human Immunology, Autoimmunity, and Inflammation (CHI) is an exciting initiative of the NIH intramural program begun in 2009. It is uniquely trans-NIH in support (multiple institutes) and leadership (senior scientists from several institutes who donate their time). Its goal is an in-depth assessment of the human immune system using high-throughput multiplex technologies for examination of immune cells and their products, the genome, gene expression, and epigenetic modulation obtained from individuals both before and after interventions, adding information from in-depth clinical phenotyping, and then applying advanced biostatistical and computer modeling methods for mining these diverse data. The aim is to develop a comprehensive picture of the human "immunome" in health and disease, elucidate common pathogenic pathways in various diseases, identify and validate biomarkers that predict disease progression and responses to new interventions, and identify potential targets for new therapeutic modalities. Challenges, opportunities, and progress are detailed.
- Human B-1 cells take the stage. [Journal Article]
- Ann N Y Acad Sci 2013 May; 1285(1):97-114.
B-1 cells play critical roles in defending against microbial invasion and in housekeeping removal of cellular debris. B-1 cells secrete natural antibody and manifest functions that influence T cell expansion and differentiation and in these and other ways differ from conventional B-2 cells. B-1 cells were originally studied in mice where they are easily distinguished from B-2 cells, but their identity in the human system remained poorly defined for many years. Recently, functional criteria for human B-1 cells were established on the basis of murine findings, and reverse engineering resulted in identification of the phenotypic profile, CD20(+) CD27(+) CD43(+) CD70(-) , for B-1 cells found in both umbilical cord blood and adult peripheral blood. Human B-1 cells may contribute to multiple disease states through production of autoantibody and stimulation/modulation of T cell activity. Human B-1 cells could be a rich source of antibodies useful in treating diseases present in elderly populations where natural antibody protection may have eroded. Manipulation of human B-1 cell numbers and/or activity may be a new avenue for altering T cell function and treating immune dyscrasias.
- Control of inflammatory heart disease by CD4(+) T cells. [Journal Article]
- Ann N Y Acad Sci 2013 May; 1285(1):80-96.
This review focuses on autoimmune myocarditis and its sequela, inflammatory dilated cardiomyopathy (DCMI), and the inflammatory and immune mechanisms underlying the pathogenesis of these diseases. Several mouse models of myocarditis and DCMI have improved our knowledge of the pathogenesis of these diseases, informing more general problems of cardiac remodeling and heart failure. CD4(+) T cells are critical in driving the pathogenesis of myocarditis. We discuss in detail the role of T helper cell subtypes in the pathogenesis of myocarditis, the biology of T cell-derived effector cytokines, and the participation of other leukocytic effectors in mediating disease pathophysiology. We discuss interactions between these subsets in both suppressive and collaborative fashions. These findings indicate that cardiac inflammatory disease, and autoimmunity in general, may be more diverse in divergent effector mechanisms than has previously been appreciated.
- Anti-β2 -glycoprotein I antibodies. [Journal Article]
- Ann N Y Acad Sci 2013 May; 1285(1):44-58.
Anti-β2 -glycoprotein I (anti-β2 GPI) antibodies are the main antiphospholipid antibodies, along with anticardiolipin and lupus anticoagulant, that characterize the autoimmune disease antiphospholipid syndrome (APS). While the exact physiological functions of β2 GPI are unknown, there is overwhelming evidence that anti-β2 GPI antibodies are pathogenic, contributing to thrombosis, pregnancy morbidity, and accelerated atherosclerosis in APS and systemic lupus erythematosus patients. The revelation that these antibodies play a central role in the pathogenesis and pathophysiology of APS has driven research to characterize the physiology and structure of β2 GPI as well as the pathogenic effects of anti-β2 GPI antibodies. It has also resulted in the development of improved testing methodologies for detecting these antibodies. In this review we discuss the characteristics of β2 GPI; the generation, pathogenic effects, and standardized testing of anti-β2 GPI antibodies; and the potential use of therapies that target the β2 GPI/ anti-β2 GPI interaction in the treatment of APS.
- Evolutionary dynamics and information hierarchies in biological systems. [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2013 May 20.
The study of evolution has entered a revolutionary new era, where quantitative and predictive methods are transforming the traditionally qualitative and retrospective approaches of the past. Genomic sequencing and modern computational techniques are permitting quantitative comparisons between variation in the natural world and predictions rooted in neo-Darwinian theory, revealing the shortcomings of current evolutionary theory, particularly with regard to large-scale phenomena like macroevolution. Current research spanning and uniting diverse fields and exploring the physical and chemical nature of organisms across temporal, spatial, and organizational scales is replacing the model of evolution as a passive filter selecting for random changes at the nucleotide level with a paradigm in which evolution is a dynamic process both constrained and driven by the informational architecture of organisms across scales, from DNA and chromatin regulation to interactions within and between species and the environment.
- What can stimulated emission do for bioimaging? [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2013 May 21.
Advances in bioimaging have revolutionized our ability to study life phenomena at a microscopic scale. In particular, the stimulated emission process, a universal mechanism that competes with spontaneous emission, has emerged as a powerful driving force for advancing light microscopy. The present review summarizes and compares three related techniques that each measure a different physical quantity involved in the stimulated emission process in order to tackle various challenges in light microscopy. Stimulated emission depletion microscopy, which detects the residual fluorescence after quenching, can break the diffraction-limited resolution barrier in fluorescence microscopy. Stimulated emission microscopy is capable of imaging nonfluorescent but absorbing chromophores by detecting the intensity gain of the stimulated emission beam. Very recently, stimulated emission reduced fluorescence microscopy has been proposed, in which the reduced fluorescence due to focal stimulation is measured to extend the fundamental imaging-depth limit of two-photon microscopy. Thus, through ingenious spectroscopy design in distinct microscopy contexts, stimulated emission has opened up several new territories for bioimaging, allowing examination of biological structures that are ever smaller, darker, and deeper.
- The paradox of overnutrition in aging and cognition. [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2013 May 17.
Populations of many countries are becoming increasingly overweight and obese, driven largely by excessive calorie intake and reduced physical activity; greater body mass is accompanied by epidemic levels of comorbid metabolic diseases. At the same time, individuals are living longer. The combination of aging and the increased prevalence of metabolic disease is associated with increases in aging-related comorbid diseases such as Alzheimer's disease, cerebrovascular dementia, and sarcopenia. Here, correlative and causal links between diseases of overnutrition and diseases of aging and cognition are explored.
- Vitamin D: beyond bone. [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2013 May 17.
In recent years, vitamin D has been received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries and the identification of extraskeletal effects of vitamin D, suggesting unexpected benefits of vitamin D in health and disease, beyond bone health. The possibility of extraskeletal effects of vitamin D was first noted with the discovery of the vitamin D receptor (VDR) in tissues and cells that are not involved in maintaining mineral homeostasis and bone health, including skin, placenta, pancreas, breast, prostate and colon cancer cells, and activated T cells. However, the biological significance of the expression of the VDR in different tissues is not fully understood, and the role of vitamin D in extraskeletal health has been a matter of debate. This report summarizes recent research on the roles for vitamin D in cancer, immunity and autoimmune diseases, cardiovascular and respiratory health, pregnancy, obesity, erythropoiesis, diabetes, muscle function, and aging.
- Specific-gene studies of evolutionary mechanisms in an age of genome-wide surveying. [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2013 May 16.
The molecular tools of genomics have great power to reveal patterns of genetic difference within or among species, but must be complemented by the mechanistic study of the genetic variants found if these variants' evolutionary meaning is to be well understood. Central to this purpose is knowledge of the organisms' genotype-phenotype-environment interactions, which embody biological adaptation and constraint and thus drive natural selection. The history of this approach is briefly reviewed. Strategies embracing the complementarity of genomics and specific-gene studies in evolution are considered. Implementation of these strategies, and examples showing their feasibility and power, are discussed. Initial generalizations emphasize: (1) reproducibility of adaptive mechanisms; (2) evolutionary co-importance of variation in protein sequences and expression; (3) refinement of rudimentary molecular functions as an origin of evolutionary innovations; (4) identification of specific-gene mechanisms as underpinnings of genomic or quantitative genetic variation; and (5) multiple forms of adaptive or constraining epistasis among genes. Progress along these lines will advance understanding of evolution and support its use in addressing urgent medical and environmental applications.