Some twenty years ago, the search began for B-cell lymphoma (BCL)-10 binding partners that connect via homophilic interaction with its N-terminal caspase recruitment domain (CARD) to induce nuclear factor-kappa B (NF-κB) activation. This effort led first to the identification of the protein CARD9. Soon afterwards, similar searches identified CARD10 (aka CARMA3), CARD11 (aka CARMA1) and CARD14 (aka CARMA2), as further BCL10 interactors. These discoveries paved the way for landmark progress in our understanding of NF-κB activation pathways downstream of several cell surface receptors on multiple cell types, focused particularly on antigen receptors on lymphocytes. An additional binding partner, called Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), was also implicated in the CARD-BCL10 pathway. Since then, the resulting “CBM” complex has been recognized as a key node in signaling cascades leading to NF-κB activation, particularly in immune cells. Mouse models of genetic deficiencies for each CBM component provided the first evidence for their critical role in cell signaling. More recently, studies of human lymphoid malignancies and novel genetic disorders have revealed important new insights. Both gain- and loss-of-function mutations were identified, establishing these CARMA/CARD proteins as key regulators of proliferation and differentiation of immune and non-immune cells, and linking them to human disease. According to the genetic defect involved, dysregulation of CARMA/CARD pathways can lead to a broad spectrum of immune disorders, including severe immune deficiencies, lymphoproliferative disorders, psoriasis and atopy. The aim of this Research Topic is to summarize and update our current understanding of CARMA/CARD protein biology, from initial discoveries to the most recent insights. It focuses on CARD9 and the CARMA proteins CARD10, CARD11 and CARD14, from genetic, signaling and disease perspectives. BCL10 and MALT1 are also reviewed in this context as critical nodes for CBM signal relay and regulation. This Research Topic also aims to delineate the next key questions in the field to guide future research efforts.

Stiehm’s Immune Deficiencies: Inborn Errors in Immunity, Second Edition, is ideal for physicians and other caregivers who specialize in immunology, allergies, infectious diseases and pulmonary medicine. It provides a validated source of information for care delivery to patients, covering approaches to diagnosis that use both new genetic information and emphasize screening strategies. Management has changed dramatically over the past five years, so approaches to infection and autoimmunity are emphasized in an effort to improve outcomes and disseminate new information on the uses of targeted therapy. Covers immune deficiencies that are presented in a practical way, providing helpful information for active clinicians Fills an increasingly deep gap in the information available to clinicians Presents both clinical management and scientific advances for immune deficiencies Provides a primary resource for physicians in the field of immunodeficiencies Includes website access to a range of videos relevant to the topics discussed

The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to phenomenological models of nano- and microscopic events in a corrector scheme of regulated mechanisms when the vessel lumen caliber varies markedly. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning. Volume 4 is devoted to major sets of intracellular mediators that transmit signals upon stimulation of cell-surface receptors. Activation of signaling effectors triggers the release of substances stored in cellular organelles and/or gene transcription and protein synthesis. Complex stages of cell signaling can be studied using proper mathematical models, once the role of each component is carefully handled. Volume 4 also reviews various categories of cytosolic and/or nuclear mediators and illustrates some major signal transduction pathways, such as NFkappaB axis, oxygen sensing, and mechanotransduction.

"Fans of Elizabeth Gilbert's Eat Pray Love will flock to this novel…." —Lori Nelson Spielman, author of The Life List An unexpected journey leads one woman to discover that life after loss is possible, if only you can find the courage to let go... One minute, Tegan Lawson has everything she could hope for: an adoring husband, Gabe, and a baby on the way. The next, a patch of black ice causes a devastating accident that will change her life in ways she never could have imagined. Tegan is consumed by grief--not to mention her anger toward Gabe, who was driving on the night of the crash. But just when she thinks she's hit rock bottom, Gabe reminds her of their Jar of Spontaneity, a collection of their dream destinations and experiences, and so begins an adventure of a lifetime. From the bustling markets of Thailand to the flavors of Italy to the ocean waves in Hawaii, Tegan and Gabe embark on a journey to escape the tragedy and search for forgiveness. But they soon learn that grief follows you no matter how far away you run, and that acceptance comes when you least expect it. Heartbreaking, hopeful and utterly transporting, Come Away with Me is an unforgettable debut and a luminous celebration of the strength of the human spirit. More Praise: "One woman's journey through grief becomes the journey of a lifetime... This emotional love story will stick with you long after you've turned the final page."" —Colleen Oakley, author of Before I Go "[F]ull of lush locations, memorable characters, and a turn of events that is nothing short of jaw-dropping." —Taylor Jenkins Reid, author of Forever, Interrupted and After I Do "[A] beautifully written story of love and loss... Come Away with Me had me smiling through my tears." —Tracey Garvis Graves, New York Times bestselling author of On the Island "[A] heartbreaking yet hopeful tale…Karma Brown is a talented new voice in women's fiction." —Lori Nelson Spielman, author of The Life List

At long last, Sarah Britton, called the “queen bee of the health blogs” by Bon Appétit, reveals 100 gorgeous, all-new plant-based recipes in her debut cookbook, inspired by her wildly popular blog. Every month, half a million readers—vegetarians, vegans, paleo followers, and gluten-free gourmets alike—flock to Sarah’s adaptable and accessible recipes that make powerfully healthy ingredients simply irresistible. My New Roots is the ultimate guide to revitalizing one’s health and palate, one delicious recipe at a time: no fad diets or gimmicks here. Whether readers are newcomers to natural foods or are already devotees, they will discover how easy it is to eat healthfully and happily when whole foods and plants are at the center of every plate.

Parks and Recreation actor and Making It co-host Nick Offerman shares his humorous fulminations on life, manliness, meat, and much more in this New York Times bestseller. Growing a perfect moustache, grilling red meat, wooing a woman—who better to deliver this tutelage than the always charming, always manly Nick Offerman, best known as Parks and Recreation’s Ron Swanson? Combining his trademark comic voice and very real expertise in woodworking—he runs his own woodshop—Paddle Your Own Canoe features tales from Offerman’s childhood in small-town Minooka, Illinois—“I grew up literally in the middle of a cornfield”—to his theater days in Chicago, beginnings as a carpenter/actor and the hilarious and magnificent seduction of his now-wife Megan Mullally. It also offers hard-bitten battle strategies in the arenas of manliness, love, style, religion, woodworking, and outdoor recreation, among many other savory entrees. A mix of amusing anecdotes, opinionated lessons and rants, sprinkled with offbeat gaiety, Paddle Your Own Canoe will not only tickle readers pink but may also rouse them to put down their smart phones, study a few sycamore leaves, and maybe even hand craft (and paddle) their own canoes.

Each human life is the result of a unique set of causes and effects—a condensation, as it were, of past actions, some of which stretch back over many lifetimes. To the student of the esoteric, our bodies—both inner and outer—are receptacles for creative as well as destructive energies and are the product of those cosmic laws of cause and effect known as karma. This book explains the fundamental concept of karma and examines the way karmic consequences manifest in a variety of physical diseases, ranging from arthritis to schizophrenia and alcoholism.