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  • Annual Reviews  (20,900)
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  • 1
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    Inherited Autoinflammatory Syndromes (2021)
    Annual Reviews
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    Publication Date: 2021-10-26
    Description: Autoinflammation describes a collection of diverse diseases caused by indiscriminate activation of the immune system in an antigen-independent manner. The rapid advancement of genetic diagnostics has allowed for the identification of a wide array of monogenic causes of autoinflammation. While the clinical picture of these syndromes is diverse, it is possible to thematically group many of these diseases under broad categories that provide insight into the mechanisms of disease and therapeutic possibilities. This review covers archetypical examples of inherited autoinflammatory diseases in five major categories: inflammasomopathy, interferonopathy, unfolded protein/cellular stress response, relopathy, and uncategorized. This framework can suggest where future work is needed to identify other genetic causes of autoinflammation, what types of diagnostics need to be developed to care for this patient population, and which options might be considered for novel therapeutic targeting. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 1553-4006
    Electronic ISSN: 1553-4014
    Topics: Medicine
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  • 2
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    β-Arrestins as Important Regulators of Glucose and Energy Homeostasis (2021)
    Annual Reviews
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    Publication Date: 2021-10-27
    Description: β-Arrestin-1 and -2 (also known as arrestin-2 and -3, respectively) are ubiquitously expressed cytoplasmic proteins that dampen signaling through G protein–coupled receptors. However, β-arrestins can also act as signaling molecules in their own right. To investigate the potential metabolic roles of the two β-arrestins in modulating glucose and energy homeostasis, recent studies analyzed mutant mice that lacked or overexpressed β-arrestin-1 and/or -2 in distinct, metabolically important cell types. Metabolic analysis of these mutant mice clearly demonstrated that both β-arrestins play key roles in regulating the function of most of these cell types, resulting in striking changes in whole-body glucose and/or energy homeostasis. These studies also revealed that β-arrestin-1 and -2, though structurally closely related, clearly differ in their metabolic roles under physiological and pathophysiological conditions. These new findings should guide the development of novel drugs for the treatment of various metabolic disorders, including type 2 diabetes and obesity. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4278
    Electronic ISSN: 1545-1585
    Topics: Biology , Medicine
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  • 3
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    Physiological Functions of CRAC Channels (2021)
    Annual Reviews
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    Publication Date: 2021-10-12
    Description: Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ signaling pathway that is evolutionarily conserved across eukaryotes. SOCE is triggered physiologically when the endoplasmic reticulum (ER) Ca2+ stores are emptied through activation of inositol-1,4,5-trisphosphate receptors. SOCE is mediated by the Ca2+ release-activated Ca2+ (CRAC) channels, which are highly Ca2+ selective. Upon store depletion, the ER Ca2+-sensing STIM proteins aggregate and gain extended conformations spanning the ER-plasma membrane junctional space to bind and activate Orai, the pore-forming proteins of hexameric CRAC channels. In recent years, studies on STIM and Orai tissue-specific knockout mice and gain- and loss-of-function mutations in humans have shed light on the physiological functions of SOCE in various tissues. Here, we describe recent findings on the composition of native CRAC channels and their physiological functions in immune, muscle, secretory, and neuronal systems to draw lessons from transgenic mice and human diseases caused by altered CRAC channel activity. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4278
    Electronic ISSN: 1545-1585
    Topics: Biology , Medicine
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  • 4
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    A Tale of Two Checkpoints: ATR Inhibition and PD-(L)1 Blockade (2021)
    Annual Reviews
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    Publication Date: 2021-10-13
    Description: Innate immunity and the DNA damage response (DDR) pathway are inextricably linked. Within the DDR, ataxia telangiectasia and Rad3-related (ATR) is a key kinase responsible for sensing replication stress and facilitating DNA repair through checkpoint activation, cell cycle arrest, and promotion of fork recovery. Recent studies have shed light on the immunomodulatory role of the ATR-CHK1 pathway in the tumor microenvironment and the specific effects of ATR inhibition in stimulating an innate immune response. With several potent and selective ATR inhibitors in developmental pipelines, the combination of dual ATR and PD-(L)1 blockade has attracted increasing interest in cancer therapy. In this review, we summarize the clinical and preclinical data supporting the combined inhibition of ATR and PD-(L)1, discuss the potential challenges surrounding this approach, and highlight biomarkers relevant for selected patients who are most likely to benefit from the blockade of these two checkpoints. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4219
    Electronic ISSN: 1545-326X
    Topics: Medicine
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  • 5
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    Somatic Mosaicism in Biology and Disease (2021)
    Annual Reviews
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    Publication Date: 2021-10-12
    Description: Contrary to earlier beliefs, every cell in the individual is genetically different due to somatic mutations. Consequently, tissues become a mixture of cells with distinct genomes, a phenomenon termed somatic mosaicism. Recent advances in genome sequencing technology have unveiled possible causes of mutations and how they shape the unique mutational landscape of the tissues. Moreover, the analysis of sequencing data in combination with clinical information has revealed the impacts of somatic mosaicism on disease processes. In this review, we discuss somatic mosaicism in various tissues and its clinical implications for human disease. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4278
    Electronic ISSN: 1545-1585
    Topics: Biology , Medicine
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  • 6
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    The Role of Community Science in Entomology (2021)
    Annual Reviews
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    Publication Date: 2021-10-13
    Description: Community (or citizen) science, the involvement of volunteers in scientific endeavors, has a long history. Over the past few centuries, the contributions of volunteers to our understanding of patterns and processes in entomology has been inspiring. From the collation of large-scale and long-term data sets, which have been instrumental in underpinning our knowledge of the status and trends of many insect groups, to action, including species management, whether for conservation or control, community scientists have played pivotal roles. Contributions, such as pest monitoring by farmers and species discoveries by amateur naturalists, set foundations for the research engaging entomologists today. The next decades will undoubtedly bring new approaches, tools, and technologies to underpin community science. The potential to increase inclusion within community science is providing exciting opportunities within entomology. An increase in the diversity of community scientists, alongside increasing taxonomic and geographic breadth of initiatives, will bring enormous benefits globally for people and nature. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4170
    Electronic ISSN: 1545-4487
    Topics: Biology
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  • 7
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    Mobile Health (mHealth) in Low- and Middle-Income Countries (2021)
    Annual Reviews
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    Publication Date: 2021-10-14
    Description: This article reflects on current trends and proposes new considerations for the future of mobile technologies for health (mHealth). Our focus is predominantly on the value of and concerns with regard to the application of digital health within low- and middle-income countries (LMICs). It is in LMICs and marginalized communities that mHealth (within the wider scope of digital health) could be most useful and valuable. Peer-reviewed literature on mHealth in LMICs provides reassurance of this potential, often reflecting on the ubiquity of mobile phones and ever-increasing connectivity globally, reaching remote or otherwise disengaged populations. Efforts to adapt successful programs for LMIC contexts and populations are only just starting to reap rewards. Private-sector investment in mHealth offers value through enhanced capacity and advances in technology as well as the ability to meet increasing consumer demand for real-time, accessible, convenient, and choice-driven health care options. We examine some of the potential considerations associated with a private-sector investment, questioning whether a core of transparency, local ownership, equity, and safety are likely to be upheld in the current environment of health entrepreneurship. Expected final online publication date for the Annual Review of Public Health, Volume 43 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0163-7525
    Electronic ISSN: 1545-2093
    Topics: Medicine
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  • 8
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    Brain-Protective Mechanisms of Transcription Factor NRF2: Toward a Common Strategy for Neurodegenerative Diseases (2021)
    Annual Reviews
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    Publication Date: 2021-10-12
    Description: Neurodegenerative diseases are characterized by the loss of homeostatic functions that control redox and energy metabolism, neuroinflammation, and proteostasis. The transcription factor nuclear factor erythroid 2–related factor 2 (NRF2) is a master controller of these functions, and its overall activity is compromised during aging and in these diseases. However, NRF2 can be activated pharmacologically and is now being considered a common therapeutic target. Many gaps still exist in our knowledge of the specific role that NRF2 plays in specialized brain cell functions or how these cells respond to the hallmarks of these diseases. This review discusses the relevance of NRF2 to several hallmark features of neurodegenerative diseases and the current status of pharmacological activators that might pass through the blood-brain barrier and provide a disease-modifying effect. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0362-1642
    Electronic ISSN: 1545-4304
    Topics: Chemistry and Pharmacology , Medicine
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  • 9
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    Infection-Related Myelopathies (2021)
    Annual Reviews
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    Publication Date: 2021-10-12
    Description: Recent years have seen growing attention to inflammatory and infectious disorders of the spinal cord, not only due to the discovery of autoantibody-mediated disorders of the spinal cord [e.g., aquaporin-4 immunoglobulin G (IgG) antibodies and myelin oligodendrocyte glycoprotein IgG antibodies], but also due to the emergence of clusters of infection-related myelopathy, now known as acute flaccid myelitis. We review the spectrum of infection-related myelopathies and outline a nosological classification system based on association with infection. We describe the epidemiology and definitions of myelopathies, with a discussion of clinical presentation and neuroimaging features, and then turn to specific discussion of myelopathies due to direct pathogen invasion and those considered to be post- or parainfectious. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 1553-4006
    Electronic ISSN: 1553-4014
    Topics: Medicine
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  • 10
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    Whole Inactivated Virus and Protein-Based COVID-19 Vaccines (2021)
    Annual Reviews
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    Publication Date: 2021-10-12
    Description: The rapid development and deployment of mRNA and adenovirus-vectored vaccines against coronavirus disease 2019 (COVID-19) continue to astound the global scientific community, but these vaccine platforms and production approaches have still not achieved global COVID-19 vaccine equity. Immunizing the billions of people at risk for COVID-19 in the world's low- and middle-income countries (LMICs) still relies on the availability of vaccines produced and scaled through traditional technology approaches. Vaccines based on whole inactivated virus (WIV) and protein-based platforms, as well as protein particle-based vaccines, are the most produced by LMIC vaccine manufacturing strategies. Three major WIV vaccines are beginning to be distributed widely. Several protein-based and protein particle-based vaccines are advancing with promising results. Overall, these vaccines are exhibiting excellent safety profiles and in some instances have shown their potential to induce high levels of virus neutralizing antibodies and T cell responses (and protection) both in nonhuman primates and in early studies in humans. There is an urgent need to continue accelerating these vaccines for LMICs in time to fully vaccinate these populations by the end of 2022 at the latest. Achieving these goals would also serve as an important reminder that we must continue to maintain expertise in producing multiple vaccine technologies, rather than relying on any individual platform. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4219
    Electronic ISSN: 1545-326X
    Topics: Medicine
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  • 11
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    The Diverse Physiological Functions of Mechanically Activated Ion Channels in Mammals (2021)
    Annual Reviews
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    Publication Date: 2021-10-12
    Description: Many aspects of mammalian physiology are mechanically regulated. One set of molecules that can mediate mechanotransduction are the mechanically activated ion channels. These ionotropic force sensors are directly activated by mechanical inputs, resulting in ionic flux across the plasma membrane. While there has been much research focus on the role of mechanically activated ion channels in touch sensation and hearing, recent data have highlighted the broad expression pattern of these molecules in mammalian cells. Disruption of mechanically activated channels has been shown to impact ( a) the development of mechanoresponsive structures, ( b) acute mechanical sensing, and ( c) mechanically driven homeostatic maintenance in multiple tissue types. The diversity of processes impacted by these molecules highlights the importance of mechanically activated ion channels in mammalian physiology. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4278
    Electronic ISSN: 1545-1585
    Topics: Biology , Medicine
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  • 12
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    Organoid Models for Infectious Disease (2021)
    Annual Reviews
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    Publication Date: 2021-10-13
    Description: Infectious diseases affect individual health and have widespread societal impacts. New ex vivo models are critical to understand pathogenesis, host response, and features necessary to develop preventive and therapeutic treatments. Pluripotent and tissue stem cell–derived organoids provide new tools for the study of human infections. Organoid models recapitulate many characteristics of in vivo disease and are providing new insights into human respiratory, gastrointestinal, and neuronal host–microbe interactions. Increasing culture complexity by adding the stroma, interorgan communication, and the microbiome will improve the use of organoids as models for infection. Organoid cultures provide a platform with the capability to improve human health related to infectious diseases. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4219
    Electronic ISSN: 1545-326X
    Topics: Medicine
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  • 13
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    Cardiovascular Effects of Particulate Air Pollution (2021)
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    Publication Date: 2021-10-13
    Description: Inhalation of fine particulate matter (PM2.5), produced by the combustion of fossil fuels, is an important risk factor for cardiovascular disease. Exposure to PM2.5 has been linked to increases in blood pressure, thrombosis, and insulin resistance. It also induces vascular injury and accelerates atherogenesis. Results from animal models corroborate epidemiological evidence and suggest that the cardiovascular effects of PM2.5 may be attributable, in part, to oxidative stress, inflammation, and the activation of the autonomic nervous system. Although the underlying mechanisms remain unclear, there is robust evidence that long-term exposure to PM2.5 is associated with premature mortality due to heart failure, stoke, and ischemic heart disease. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4219
    Electronic ISSN: 1545-326X
    Topics: Medicine
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  • 14
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    Opportunities and Limitations for Reproductive Science in Species Conservation (2021)
    Annual Reviews
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    Publication Date: 2021-10-26
    Description: Reproductive science in the context of conservation biology is often understood solely in terms of breeding threatened species. Although technologies developed primarily for agriculture or biomedicine have a potentially important role in species conservation, their effectiveness is limited if we regard the main objective of animal conservation as helping to support populations rather than to breed a small number of individuals. The global threats facing wild species include the consequences of climate change, population growth, urbanization, atmospheric and water pollution, and the release of chemicals into the environment, to cite but a few. Reproductive sciences provide important and often unexpected windows into many of these consequences, and our aim here is both to demonstrate the breadth of reproductive science and the importance of basic knowledge and to suggest where some of the insights might be useful in mitigating the problems. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 2165-8102
    Electronic ISSN: 2165-8110
    Topics: Biology
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  • 15
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    Paligenosis: Cellular Remodeling During Tissue Repair (2021)
    Annual Reviews
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    Publication Date: 2021-10-27
    Description: Complex multicellular organisms have evolved specific mechanisms to replenish cells in homeostasis and during repair. Here, we discuss how emerging technologies (e.g., single-cell RNA sequencing) challenge the concept that tissue renewal is fueled by unidirectional differentiation from a resident stem cell. We now understand that cell plasticity, i.e., cells adaptively changing differentiation state or identity, is a central tissue renewal mechanism. For example, mature cells can access an evolutionarily conserved program (paligenosis) to reenter the cell cycle and regenerate damaged tissue. Most tissues lack dedicated stem cells and rely on plasticity to regenerate lost cells. Plasticity benefits multicellular organisms, yet it also carries risks. For one, when long-lived cells undergo paligenotic, cyclical proliferation and redifferentiation, they can accumulate and propagate acquired mutations that activate oncogenes and increase the potential for developing cancer. Lastly, we propose a new framework for classifying patterns of cell proliferation in homeostasis and regeneration, with stem cells representing just one of the diverse methods that adult tissues employ. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4278
    Electronic ISSN: 1545-1585
    Topics: Biology , Medicine
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  • 16
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    Salmonella in Swine: Prevalence, Multidrug Resistance, and Vaccination Strategies (2021)
    Annual Reviews
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    Publication Date: 2021-10-26
    Description: An estimated 1.3 million Salmonella infections and 420 deaths occur annually in the United States, with an estimated economic burden of $3.7 billion. More than 50% of US swine operations test positive for Salmonella according to the National Animal Health Monitoring System, and 20% of Salmonella from swine are multidrug resistant (resistant to ≥3 antimicrobial classes) as reported by the National Antimicrobial Resistance Monitoring System. This review on Salmonella in swine addresses the current status of these topics by discussing antimicrobial resistance and metal tolerance in Salmonella and the contribution of horizontal gene transfer. A major challenge in controlling Salmonella is that Salmonella is a foodborne pathogen in humans but is often a commensal in food animals and thereby establishes an asymptomatic reservoir state in such animals, including swine. As food animal production systems continue to expand and antimicrobial usage becomes more limited, the need for Salmonella interventions has intensified. A promising mitigation strategy is vaccination against Salmonella in swine to limit animal, environmental, and food contamination. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 2165-8102
    Electronic ISSN: 2165-8110
    Topics: Biology
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  • 17
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    Dog Models of Aging (2021)
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    Publication Date: 2021-10-26
    Description: As the most phenotypically diverse mammalian species that shares human environments and access to sophisticated healthcare, domestic dogs have unique potential to inform our understanding of the determinants of aging. Here we outline key concepts in the study of aging and illustrate the value of research with dogs, which can improve dog health and support translational discoveries. We consider similarities and differences in aging and age-related diseases in dogs and humans and summarize key advances in our understanding of genetic and environmental risk factors for morbidity and mortality in dogs. We address health outcomes ranging from cancer to cognitive function and highlight emerging research opportunities from large-scale cohort studies in companion dogs. We conclude that studying aging in dogs could overcome many limitations of laboratory models, most notably, the ability to assess how aging-associated pathways influence aging in real-world environments similar to those experienced by humans. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 2165-8102
    Electronic ISSN: 2165-8110
    Topics: Biology
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  • 18
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    Hypoxia Reduction Sensitizes Refractory Cancers to Immunotherapy (2021)
    Annual Reviews
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    Publication Date: 2021-10-26
    Description: In order to fuel their relentless expansion, cancers must expand their vasculature to augment delivery of oxygen and essential nutrients. The disordered web of irregular vessels that results, however, leaves gaps in oxygen delivery that foster tumor hypoxia. At the same time, tumor cells increase their oxidative metabolism to cope with the energetic demands of proliferation, which further worsens hypoxia due to heightened oxygen consumption. In these hypoxic, nutrient-deprived environments, tumors and suppressive stroma evolve to flourish while antitumor immunity collapses due to a combination of energetic deprivation, toxic metabolites, acidification, and other suppressive signals. Reversal of cancer hypoxia thus has the potential to increase the survival and effector function of tumor-infiltrating T cells, as well as to resensitize tumors to immunotherapy. Early clinical trials combining hypoxia reduction with immune checkpoint blockade have shown promising results in treating patients with advanced, metastatic, and therapeutically refractory cancers. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4219
    Electronic ISSN: 1545-326X
    Topics: Medicine
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  • 19
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    Insects as an Alternative Protein Source (2021)
    Annual Reviews
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    Publication Date: 2021-10-26
    Description: The recent COVID-19 pandemic drastically affected food supply chains worldwide, showing the vulnerability of food security. Efforts to develop alternative protein sources that are sustainable and can help alleviate global food shortage problems should be prioritized. Insects have been part of our diet for thousands of years and still are today, and market trends show a global increase in the number of food-grade insect producers. The global market for edible insects has been forecasted to reach US$8 billion by the year 2030. Insects are highly nutritious and have bioactive peptides with potential therapeutic effects. This review provides an overview of the consumption of insects from ancient to modern times, discusses the rationale for using insects as alternative protein sources, and presents a summary of the major insects consumed worldwide as well as a brief description of the traditional and novel technologies currently used to process insects and/or extract their nutritional components. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 13 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 1941-1413
    Electronic ISSN: 1941-1421
    Topics: Process Engineering, Biotechnology, Nutrition Technology
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  • 20
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    Cerebral Vascular Dysfunctions Detected in Human Small Vessel Disease and Implications for Preclinical Studies (2021)
    Annual Reviews
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    Publication Date: 2021-10-26
    Description: Cerebral small vessel disease (SVD) is highly prevalent and a common cause of ischemic and hemorrhagic stroke and dementia, yet the pathophysiology is poorly understood. Its clinical expression is highly varied, and prognostic implications are frequently overlooked in clinics; thus, treatment is currently confined to vascular risk factor management. Traditionally, SVD is considered the small vessel equivalent of large artery stroke (occlusion, rupture), but data emerging from human neuroimaging and genetic studies refute this, instead showing microvessel endothelial dysfunction impacting on cell–cell interactions and leading to brain damage. These dysfunctions reflect defects that appear to be inherited and secondary to environmental exposures, including vascular risk factors. Interrogation in preclinical models shows consistent and converging molecular and cellular interactions across the endothelial-glial-neural unit that increasingly explain the human macroscopic observations and identify common patterns of pathology despite different triggers. Importantly, these insights may offer new targets for therapeutic intervention focused on restoring endothelial-glial physiology. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4278
    Electronic ISSN: 1545-1585
    Topics: Biology , Medicine
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  • 21
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    Mechanisms Underlying Calcium Nephrolithiasis (2021)
    Annual Reviews
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    Publication Date: 2021-10-26
    Description: Nephrolithiasis is a worldwide problem with increasing prevalence, enormous costs, and significant morbidity. Calcium-containing kidney stones are by far the most common kidney stones encountered in clinical practice. Consequently, hypercalciuria is the greatest risk factor for kidney stone formation. Hypercalciuria can result from enhanced intestinal absorption, increased bone resorption, or altered renal tubular transport. Kidney stone formation is complex and driven by high concentrations of calcium-oxalate or calcium-phosphate in the urine. After discussing the mechanism mediating renal calcium salt precipitation, we review recent discoveries in renal tubular calcium transport from the proximal tubule, thick ascending limb, and distal convolution. Furthermore, we address how calcium is absorbed from the intestine and mobilized from bone. The effect of acidosis on bone calcium resorption and urinary calcium excretion is also considered. Although recent discoveries provide insight into these processes, much remains to be understood in order to provide improved therapies for hypercalciuria and prevent kidney stone formation. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Electronic ISSN: 1545-1585
    Topics: Biology , Medicine
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  • 22
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    A Balancing Act: p53 Activity from Tumor Suppression to Pathology and Therapeutic Implications (2021)
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    Publication Date: 2021-10-26
    Description: TP53, encoding the p53 transcription factor, is the most frequently mutated tumor suppressor gene across all human cancer types. While p53 has long been appreciated to induce antiproliferative cell cycle arrest, apoptosis, and senescence programs in response to diverse stress signals, various studies in recent years have revealed additional important functions for p53 that likely also contribute to tumor suppression, including roles in regulating tumor metabolism, ferroptosis, signaling in the tumor microenvironment, and stem cell self-renewal/differentiation. Not only does p53 loss or mutation cause cancer, but hyperactive p53 also drives various pathologies, including developmental phenotypes, premature aging, neurodegeneration, and side effects of cancer therapies. These findings underscore the importance of balanced p53 activity and influence our thinking of how to best develop cancer therapies based on modulating the p53 pathway. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 1553-4006
    Electronic ISSN: 1553-4014
    Topics: Medicine
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  • 23
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    Sepsis-Induced Immunosuppression (2021)
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    Publication Date: 2021-10-27
    Description: Sepsis is expected to have a substantial impact on public health and cost as its prevalence increases. Factors contributing to increased prevalence include a progressively aging population, advances in the use of immunomodulatory agents to treat a rising number of diseases, and immune-suppressing therapies in organ transplant recipients and cancer patients. It is now recognized that sepsis is associated with profound and sustained immunosuppression, which has been implicated as a predisposing factor in the increased susceptibility of patients to secondary infections and mortality. In this review, we discuss mechanisms of sepsis-induced immunosuppression and biomarkers that identify a state of impaired immunity. We also highlight immune-enhancing strategies that have been evaluated in patients with sepsis, as well as therapeutics under current investigation. Finally, we describe future challenges and the need for a new treatment paradigm, integrating predictive enrichment with patient factors that may guide the future selection of tailored immunotherapy. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4278
    Electronic ISSN: 1545-1585
    Topics: Biology , Medicine
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    New Approaches to Glioblastoma (2021)
    Annual Reviews
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    Publication Date: 2021-10-19
    Description: Faced with unique immunobiology and marked heterogeneity, treatment strategies for glioblastoma require therapeutic approaches that diverge from conventional oncological strategies. The selection and prioritization of targeted and immunotherapeutic strategies will need to carefully consider these features and companion biomarkers developed alongside treatment strategies to identify the appropriate patient populations. Novel clinical trial strategies that interrogate the tumor microenvironment for drug penetration and target engagement will inform go/no-go later-stage clinical studies. Innovative trial designs and analyses are needed to move effective agents toward regulatory approvals more rapidly. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4219
    Electronic ISSN: 1545-326X
    Topics: Medicine
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    Repurposing Colchicine for Heart Disease (2021)
    Annual Reviews
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    Publication Date: 2021-09-29
    Description: Colchicine is one of the most ancient medications still prescribed. It is extracted from the Colchicum autumnale plant and is routinely used because of its broad anti-inflammatory properties to treat gout and familial Mediterranean fever. Colchicine has shown efficacy in various clinical settings in which inflammation is a key component, and it has become first-line therapy for acute and recurrent pericarditis. Two landmark clinical trials have recently shown that colchicine significantly improves cardiovascular outcomes on background statin and antiplatelet therapy in patients with coronary artery disease, supporting its role for the prevention of atherothrombotic events. Favorable results have also emerged in atrial fibrillation. We herein briefly review the most recent data related to the multiple cardiovascular conditions for which colchicine has been successfully repurposed. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0362-1642
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    Topics: Chemistry and Pharmacology , Medicine
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  • 26
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    The Role of Cytochrome P450s in Insect Toxicology and Resistance (2021)
    Annual Reviews
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    Publication Date: 2021-09-30
    Description: Insect cytochrome P450 monooxygenases (P450s) perform a variety of important physiological functions, but it is their role in the detoxification of xenobiotics, such as natural and synthetic insecticides, that is the topic of this review. Recent advances in insect genomics and postgenomic functional approaches have provided an unprecedented opportunity to understand the evolution of insect P450s and their role in insect toxicology. These approaches have also been harnessed to provide new insights into the genomic alterations that lead to insecticide resistance, the mechanisms by which P450s are regulated, and the functional determinants of P450-mediated insecticide resistance. In parallel, an emerging body of work on the role of P450s in defining the sensitivity of beneficial insects to insecticides has been developed. The knowledge gained from these studies has applications for the management of P450-mediated resistance in insect pests and can be leveraged to safeguard the health of important beneficial insects. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4170
    Electronic ISSN: 1545-4487
    Topics: Biology
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    Emerging Therapeutics, Technologies, and Drug Development Strategies to Address Patient Nonadherence and Improve Tuberculosis Treatment (2021)
    Annual Reviews
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    Publication Date: 2021-09-30
    Description: Imperfect medication adherence remains the biggest predictor of treatment failure for patients with tuberculosis. Missed doses during treatment lead to relapse, tuberculosis resistance, and further spread of disease. Understanding individual patient phenotypes, population pharmacokinetics, resistance development, drug distribution to tuberculosis lesions, and pharmacodynamics at the site of infection is necessary to fully measure the impact of adherence on patient outcomes. To decrease the impact of expected variability in drug intake on tuberculosis outcomes, an improvement in patient adherence and new forgiving regimens that protect against missed doses are needed. In this review, we summarize emerging technologies to improve medication adherence in clinical practice and provide suggestions on how digital adherence technologies can be incorporated in clinical trials and practice and the drug development pipeline that will lead to more forgiving regimens and benefit patients suffering from tuberculosis. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0362-1642
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    Topics: Chemistry and Pharmacology , Medicine
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    The Biology of Aging in Insects: From Drosophila to Other Insects and Back (2021)
    Annual Reviews
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    Publication Date: 2021-09-30
    Description: An enormous amount of work has been done on aging in Drosophila melanogaster, a classical genetic and molecular model system, but also in numerous other insects. However, these two extensive bodies of work remain poorly integrated to date. Studies in Drosophila often explore genetic, developmental, physiological, and nutrition-related aspects of aging in the lab, while studies in other insects often explore ecological, social, and somatic aspects of aging in both lab and natural populations. Alongside exciting genomic and molecular research advances in aging in Drosophila, many new studies have also been published on aging in various other insects, including studies on aging in natural populations of diverse species. However, no broad synthesis of these largely separate bodies of work has been attempted. In this review, we endeavor to synthesize these two semi-independent literatures to facilitate collaboration and foster the exchange of ideas and research tools. While lab studies of Drosophila have illuminated many fundamental aspects of senescence, the stunning diversity of aging patterns among insects, especially in the context of their rich ecology, remains vastly understudied. Coupled with field studies and novel, more easily applicable molecular methods, this represents a major opportunity for deepening our understanding of the biology of aging in insects and beyond. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4170
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    Topics: Biology
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    Drosophila sechellia: A Genetic Model for Behavioral Evolution and Neuroecology (2021)
    Annual Reviews
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    Publication Date: 2021-09-16
    Description: Defining the mechanisms by which animals adapt to their ecological niche is an important problem bridging evolution, genetics, and neurobiology. We review the establishment of a powerful genetic model for comparative behavioral analysis and neuroecology, Drosophila sechellia. This island-endemic fly species is closely related to several cosmopolitan generalists, including Drosophila melanogaster, but has evolved extreme specialism, feeding and reproducing exclusively on the noni fruit of the tropical shrub Morinda citrifolia. We first describe the development and use of genetic approaches to facilitate genotype/phenotype associations in these drosophilids. Next, we survey the behavioral, physiological, and morphological adaptations of D. sechellia throughout its life cycle and outline our current understanding of the genetic and cellular basis of these traits. Finally, we discuss the principles this knowledge begins to establish in the context of host specialization, speciation, and the neurobiology of behavioral evolution and consider open questions and challenges in the field. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4197
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    Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology (2021)
    Annual Reviews
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    Publication Date: 2021-09-16
    Description: Chemogenetics refers to experimental systems that dynamically regulate the activity of a recombinant protein by providing or withholding the protein's specific biochemical stimulus. Chemogenetic tools permit precise dynamic control of specific signaling molecules to delineate the roles of those molecules in physiology and disease. Yeast d-amino acid oxidase (DAAO) enables chemogenetic manipulation of intracellular redox balance by generating hydrogen peroxide only in the presence of d-amino acids. Advances in biosensors have allowed the precise quantitation of these signaling molecules. The combination of chemogenetic approaches with biosensor methodologies has opened up new lines of investigation, allowing the analysis of intracellular redox pathways that modulate physiological and pathological cell responses. We anticipate that newly developed transgenic chemogenetic models will permit dynamic modulation of cellular redox balance in diverse cells and tissues and will facilitate the identification and validation of novel therapeutic targets involved in both physiological redox pathways and pathological oxidative stress. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0362-1642
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    Architecture and Dynamics of Meiotic Chromosomes (2021)
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    Publication Date: 2021-09-16
    Description: The specialized two-stage meiotic cell division program halves a cell's chromosome complement in preparation for sexual reproduction. This reduction in ploidy requires that in meiotic prophase, each pair of homologous chromosomes (homologs) identify one another and form physical links through DNA recombination. Here, we review recent advances in understanding the complex morphological changes that chromosomes undergo during meiotic prophase to promote homolog identification and crossing over. We focus on the structural maintenance of chromosomes (SMC) family cohesin complexes and the meiotic chromosome axis, which together organize chromosomes and promote recombination. We then discuss the architecture and dynamics of the conserved synaptonemal complex (SC), which assembles between homologs and mediates local and global feedback to ensure high fidelity in meiotic recombination. Finally, we discuss exciting new advances, including mechanisms for boosting recombination on particular chromosomes or chromosomal domains and the implications of a new liquid crystal model for SC assembly and structure. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4197
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    Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure (2021)
    Annual Reviews
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    Publication Date: 2021-09-13
    Description: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve blood glucose control by blocking renal glucose reabsorption with little subsequent risk of hypoglycemia. Consequently, there are decreases in plasma volume, body weight, and blood pressure. Additional putative benefits include improved cardiovascular energetics, decreased systemic inflammation, and less renal dysfunction. Multiple cardiovascular outcome trials in diabetic patients have demonstrated this drug class reduces the risk of adverse cardiovascular events. Reductions in heart failure (HF) hospitalization suggested that SGLT2 inhibitors might prove useful for the primary treatment of HF. Two large subsequent trials studying SGLT2 inhibitors in heart failure with reduced ejection fraction (HFrEF) demonstrated a reduction in cardiovascular mortality, HF hospitalizations, and renal-specific adverse events. This medication class is now recognized as a new pillar of therapy for patients with HFrEF. The cardiovascular and HF community await the results of ongoing trials of SGLT2 inhibition in patients with HF with preserved ejection fraction. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    HLA Allele–Restricted Immune-Mediated Adverse Drug Reactions: Framework for Genetic Prediction (2021)
    Annual Reviews
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    Publication Date: 2021-09-13
    Description: Human leukocyte antigen (HLA) is a hallmark genetic marker for the prediction of certain immune-mediated adverse drug reactions (ADRs). Numerous basic and clinical research studies have provided the evidence base to push forward the clinical implementation of HLA testing for the prevention of such ADRs in susceptible patients. This review explores current translational progress in using HLA as a key susceptibility factor for immune ADRs and highlights gaps in our knowledge. Furthermore, relevant findings of HLA-mediated drug-specific T cell activation are covered, focusing on cellular approaches to link genetic associations to drug-HLA binding as a complementary approach to understand disease pathogenesis. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Measuring Pharmacogene Variant Function at Scale Using Multiplexed Assays (2021)
    Annual Reviews
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    Publication Date: 2021-09-13
    Description: As costs of next-generation sequencing decrease, identification of genetic variants has far outpaced our ability to understand their functional consequences. This lack of understanding is a central challenge to a key promise of pharmacogenomics: using genetic information to guide drug selection and dosing. Recently developed multiplexed assays of variant effect enable experimental measurement of the function of thousands of variants simultaneously. Here, we describe multiplexed assays that have been performed on nearly 25,000 variants in eight key pharmacogenes ( ADRB2, CYP2C9, CYP2C19, NUDT15, SLCO1B1, TMPT, VKORC1, and the LDLR promoter), discuss advances in experimental design, and explore key challenges that must be overcome to maximize the utility of multiplexed functional data. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    KCNQ Potassium Channels as Targets of Botanical Folk Medicines (2021)
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    Publication Date: 2021-09-13
    Description: Since prehistory, human species have depended on plants for both food and medicine. Even in countries with ready access to modern medicines, alternative treatments are still highly regarded and commonly used. Unlike modern pharmaceuticals, many botanical medicines are in widespread use despite a lack of safety and efficacy data derived from controlled clinical trials and often unclear mechanisms of action. Contributing to this are the complex and undefined composition and likely multifactorial mechanisms of action and multiple targets of many botanical medicines. Here, we review the newfound importance of the ubiquitous KCNQ subfamily of voltage-gated potassium channels as targets for botanical medicines, including basil, capers, cilantro, lavender, fennel, chamomile, ginger, and Camellia, Sophora, and Mallotus species. We discuss the implications for the traditional use of these plants for disorders such as seizures, hypertension, and diabetes and the molecular mechanisms of plant secondary metabolite effects on KCNQ channels. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0362-1642
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    Plant Cell Identity in the Era of Single-Cell Transcriptomics (2021)
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    Publication Date: 2021-09-16
    Description: High-throughput single-cell transcriptomic approaches have revolutionized our view of gene expression at the level of individual cells, providing new insights into their heterogeneity, identities, and functions. Recently, technical challenges to the application of single-cell transcriptomics to plants have been overcome, and many plant organs and tissues have now been subjected to analyses at single-cell resolution. In this review, we describe these studies and their impact on our understanding of the diversity, differentiation, and activities of plant cells. We particularly highlight their impact on plant cell identity, including unprecedented views of cell transitions and definitions of rare and novel cell types. We also point out current challenges and future opportunities for the application and analyses of single-cell transcriptomics in plants. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4197
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  • 37
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    Cold Shock Response in Bacteria (2021)
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    Publication Date: 2021-09-16
    Description: Bacteria often encounter temperature fluctuations in their natural habitats and must adapt to survive. The molecular response of bacteria to sudden temperature upshift or downshift is termed the heat shock response (HSR) or the cold shock response (CSR), respectively. Unlike the HSR, which activates a dedicated transcription factor that predominantly copes with heat-induced protein folding stress, the CSR is mediated by a diverse set of inputs. This review provides a picture of our current understanding of the CSR across bacteria. The fundamental aspects of CSR involved in sensing and adapting to temperature drop, including regulation of membrane fluidity, protein folding, DNA topology, RNA metabolism, and protein translation, are discussed. Special emphasis is placed on recent findings of a CSR circuitry in Escherichia coli mediated by cold shock family proteins and RNase R that monitors and modulates messenger RNA structure to facilitate global translation recovery during acclimation. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    How to Switch from Mitosis to Meiosis: Regulation of Germline Entry in Plants (2021)
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    Publication Date: 2021-09-16
    Description: One of the major cell fate transitions in eukaryotes is entry into meiosis. While in single-celled yeast this decision is triggered by nutrient starvation, in multicellular eukaryotes, such as plants, it is under developmental control. In contrast to animals, plants have only a short germline and instruct cells to become meiocytes in reproductive organs late in development. This situation argues for a fundamentally different mechanism of how plants recruit meiocytes, and consistently, none of the regulators known to control meiotic entry in yeast and animals are present in plants. In recent years, several factors involved in meiotic entry have been identified, especially in the model plant Arabidopsis, and pieces of a regulatory network of germline control in plants are emerging. However, the corresponding studies also show that the mechanisms of meiotic entry control are diversified in flowering plants, calling for further analyses in different plant species. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Methods to Address Confounding and Other Biases in Meta-Analyses: Review and Recommendations (2021)
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    Publication Date: 2021-09-17
    Description: Meta-analyses contribute critically to cumulative science, but they can produce misleading conclusions if their constituent primary studies are biased, for example by unmeasured confounding in nonrandomized studies. We provide practical guidance on how meta-analysts can address confounding and other biases that affect studies’ internal validity, focusing primarily on sensitivity analyses that help quantify how biased the meta-analysis estimates might be. We review a number of sensitivity analysis methods to do so, especially recent developments that are straightforward to implement and interpret and that use somewhat less stringent statistical assumptions than do earlier methods. We give recommendations for how these newer methods could be applied in practice and illustrate using a previously published meta-analysis. Sensitivity analyses can provide informative quantitative summaries of evidence strength, and we suggest reporting them routinely in meta-analyses of potentially biased studies. This recommendation in no way diminishes the importance of defining study eligibility criteria that reduce bias and of characterizing studies’ risks of bias qualitatively. Expected final online publication date for the Annual Review of Public Health, Volume 43 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0163-7525
    Electronic ISSN: 1545-2093
    Topics: Medicine
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    Cellular and Molecular Mechanisms Linking Human Cortical Development and Evolution (2021)
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    Publication Date: 2021-09-17
    Description: The cerebral cortex is at the core of brain functions that are thought to be particularly developed in the human species. Human cortex specificities stem from divergent features of corticogenesis, leading to increased cortical size and complexity. Underlying cellular mechanisms include prolonged patterns of neuronal generation and maturation, as well as the amplification of specific types of stem/progenitor cells. While the gene regulatory networks of corticogenesis appear to be largely conserved among all mammals including humans, they have evolved in primates, particularly in the human species, through the emergence of rapidly divergent transcriptional regulatory elements, as well as recently duplicated novel genes. These human-specific molecular features together control key cellular milestones of human corticogenesis and are often affected in neurodevelopmental disorders, thus linking human neural development, evolution, and diseases. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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  • 41
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    Noncanonical Metabotropic Glutamate Receptor 5 Signaling in Alzheimer's Disease (2021)
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    Publication Date: 2021-09-13
    Description: Metabotropic glutamate receptor 5 (mGluR5) is ubiquitously expressed in brain regions responsible for memory and learning. It plays a key role in modulating rapid changes in synaptic transmission and plasticity. mGluR5 supports long-term changes in synaptic strength by regulating the transcription and translation of essential synaptic proteins. β-Amyloid 42 (Aβ42) oligomers interact with a mGluR5/cellular prion protein (PrPC) complex to disrupt physiological mGluR5 signal transduction. Aberrant mGluR5 signaling and associated synaptic failure are considered an emerging pathophysiological mechanism of Alzheimer's disease (AD). Therefore, mGluR5 represents an attractive therapeutic target for AD, and recent studies continue to validate the efficacy of various mGluR5 allosteric modulators in improving memory deficits and mitigating disease pathology. However, sex-specific differences in the pharmacology of mGluR5 and activation of noncanonical signaling downstream of the receptor suggest that its utility as a therapeutic target in female AD patients needs to be reconsidered. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0362-1642
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  • 42
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    Synthetic Retinoids Beyond Cancer Therapy (2021)
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    Publication Date: 2021-09-13
    Description: While the uses of retinoids for cancer treatment continue to evolve, this review focuses on other therapeutic areas in which retinoids [retinol (vitamin A), all- trans retinoic acid (RA), and synthetic retinoic acid receptor (RAR)α-, β-, and γ-selective agonists] are being used and on promising new research that suggests additional uses for retinoids for the treatment of disorders of the kidneys, skeletal muscles, heart, pancreas, liver, nervous system, skin, and other organs. The most mature area, in terms of US Food and Drug Administration–approved, RAR-selective agonists, is for treatment of various skin diseases. Synthetic retinoid agonists have major advantages over endogenous RAR agonists such as RA. Because they act through a specific RAR, side effects may be minimized, and synthetic retinoids often have better pharmaceutical properties than does RA. Based on our increasing knowledge of the multiple roles of retinoids in development, epigenetic regulation, and tissue repair, other exciting therapeutic areas are emerging. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Endocannabinoid-Based Therapies (2021)
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    Publication Date: 2021-09-13
    Description: The endocannabinoids are lipid-derived messengers that play a diversity of regulatory roles in mammalian physiology. Dysfunctions in their activity have been implicated in various disease conditions, attracting attention to the endocannabinoid system as a possible source of therapeutic drugs. This signaling complex has three components: the endogenous ligands, anandamide and 2-arachidonoyl- sn-glycerol (2-AG); a set of enzymes and transporters that generate, eliminate, or modify such ligands; and selective cell surface receptors that mediate their biological actions. We provide an overview of endocannabinoid formation, deactivation, and biotransformation and outline the properties and therapeutic potential of pharmacological agents that interfere with those processes. We describe small-molecule inhibitors that target endocannabinoid-producing enzymes, carrier proteins that transport the endocannabinoids into cells, and intracellular endocannabinoid-metabolizing enzymes. We briefly discuss selected agents that simultaneously interfere with components of the endocannabinoid system and with other functionally related signaling pathways. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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  • 44
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    Perfecting Targeting in CRISPR (2021)
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    Publication Date: 2021-09-16
    Description: CRISPR-based genome editing holds promise for genome engineering and other applications in diverse organisms. Defining and improving the genome-wide and transcriptome-wide specificities of these editing tools are essential for realizing their full potential in basic research and biomedical therapeutics. This review provides an overview of CRISPR-based DNA- and RNA-editing technologies, methods to quantify their specificities, and key solutions to reduce off-target effects for research and improve therapeutic applications. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    The Recent Rise of Suicide Mortality in the United States (2021)
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    Publication Date: 2021-10-27
    Description: Suicide is a major public health concern in the United States. Between 2000 and 2018, US suicide rates increased by 35%, contributing to the stagnation and subsequent decrease in US life expectancy. During 2019, suicide declined modestly, mostly owing to slight reductions in suicides among Whites. Suicide rates, however, continued to increase or remained stable among all other racial/ethnic groups, and little is known about recent suicide trends among other vulnerable groups. This article ( a) summarizes US suicide mortality trends over the twentieth and early twenty-first centuries, ( b) reviews potential group-level causes of increased suicide risk among subpopulations characterized by markers of vulnerability to suicide, and ( c) advocates for combining recent advances in population-based suicide prevention with a socially conscious perspective that captures the social, economic, and political contexts in which suicide risk unfolds over the life course of vulnerable individuals. Expected final online publication date for the Annual Review of Public Health, Volume 43 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Impact of Stand and Landscape Management on Forest Pest Damage (2021)
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    Publication Date: 2021-10-04
    Description: One promising approach to mitigate the negative impacts of insect pests in forests is to adapt forestry practices to create ecosystems that are more resistant and resilient to biotic disturbances. At the stand scale, local stand management practices often cause idiosyncratic effects on forest pests depending on the environmental context and the focal pest species. However, increasing tree diversity appears to be a general strategy for reducing pest damage across several forest types. At the landscape scale, increasing forest heterogeneity (e.g., intermixing different forest types and/or age classes) represents a promising frontier for improving forest resistance and resilience and for avoiding large-scale outbreaks. In addition to their greater resilience, heterogeneous forest landscapes frequently support a wide range of ecosystem functions and services. A challenge will be to develop cooperation and coordination among multiple actors at spatial scales that transcend historical practices in forest management. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Introduction to the Theme “New Insights, Strategies, and Therapeutics for Common Diseases” (2021)
    Annual Reviews
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    Publication Date: 2021-10-04
    Description: The reviews in Volume 62 of the Annual Review of Pharmacology and Toxicology ( ARPT) cover a diverse range of topics. A theme that encompasses many of these reviews is their relevance to common diseases and disorders, including type 2 diabetes, heart failure, cancer, tuberculosis, Alzheimer's disease, neurodegenerative disorders, and Down syndrome. Other reviews highlight important aspects of therapeutics, including placebos and patient-centric approaches to drug formulation. The reviews with this thematic focus, as well as other reviews in this volume, emphasize new mechanistic insights, experimental and therapeutic strategies, and novel insights regarding topics in the disciplines of pharmacology and toxicology. As the editors of ARPT, we believe that these reviews help advance those disciplines and, even more importantly, have the potential to improve the health care of the world's population. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0362-1642
    Electronic ISSN: 1545-4304
    Topics: Chemistry and Pharmacology , Medicine
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    The Immune Response in Multiple Sclerosis (2021)
    Annual Reviews
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    Publication Date: 2021-10-04
    Description: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative disease that affects the central nervous system (CNS). MS is characterized by immune dysregulation, which results in the infiltration of the CNS by immune cells, triggering demyelination, axonal damage, and neurodegeneration. Although the exact causes of MS are not fully understood, genetic and environmental factors are thought to control MS onset and progression. In this article, we review the main immunological mechanisms involved in MS pathogenesis. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 1553-4006
    Electronic ISSN: 1553-4014
    Topics: Medicine
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    The Molecular Physiology and Toxicology of Inward Rectifier Potassium Channels in Insects (2021)
    Annual Reviews
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    Publication Date: 2021-10-04
    Description: Inward rectifier K+ (Kir) channels have been studied extensively in mammals, where they play critical roles in health and disease. In insects, Kir channels have recently been found to be key regulators of diverse physiological processes in several tissues. The importance of Kir channels in insects has positioned them to serve as emerging targets for the development of insecticides with novel modes of action. In this article, we provide the first comprehensive review of insect Kir channels, highlighting the rapid progress made in understanding their molecular biology, physiological roles, pharmacology, and toxicology. In addition, we highlight key gaps in our knowledge and suggest directions for future research to advance our understanding of Kir channels and their roles in insect physiology. Further knowledge of their functional roles will also facilitate their exploitation as targets for controlling arthropod pests and vectors of economic, medical, and/or veterinary relevance. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    COVID-19 Vaccines: Adenoviral Vectors (2021)
    Annual Reviews
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    Publication Date: 2021-10-05
    Description: The worldwide pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the unprecedented pace of development of multiple vaccines. This review evaluates how adenovirus (Ad) vector platforms have been leveraged in response to this pandemic. Ad vectors have been used in the past for vaccines against other viruses, most notably HIV and Ebola, but they never have been produced, distributed, or administered to humans at such a large scale. Several different serotypes of Ads encoding SARS-CoV-2 Spike have been tested and found to be efficacious against COVID-19. As vaccine rollouts continue and the number of people receiving these vaccines increases, we will continue to learn about this vaccine platform for COVID-19 prevention and control. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4219
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    Topics: Medicine
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    Self-Organization of Cellular Units (2021)
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    Publication Date: 2021-10-06
    Description: The purpose of this review is to explore self-organizing mechanisms that pattern microtubules (MTs) and spatially organize animal cell cytoplasm, inspired by recent experiments in frog egg extract. We start by reviewing conceptual distinctions between self-organizing and templating mechanisms for subcellular organization. We then discuss self-organizing mechanisms that generate radial MT arrays and cell centers in the absence of centrosomes. These include autocatalytic MT nucleation, transport of minus ends, and nucleation from organelles such as melanosomes and Golgi vesicles that are also dynein cargoes. We then discuss mechanisms that partition the cytoplasm in syncytia, in which multiple nuclei share a common cytoplasm, starting with cytokinesis, when all metazoan cells are transiently syncytial. The cytoplasm of frog eggs is partitioned prior to cytokinesis by two self-organizing modules, protein regulator of cytokinesis 1 (PRC1)-kinesin family member 4A (KIF4A) and chromosome passenger complex (CPC)-KIF20A. Similar modules may partition longer-lasting syncytia, such as early Drosophila embryos. We end by discussing shared mechanisms and principles for the MT-based self-organization of cellular units.
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    Promoters and Antagonists of Phagocytosis: A Plastic and Tunable Response (2021)
    Annual Reviews
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    Publication Date: 2021-10-06
    Description: Recent observations indicate that, rather than being an all-or-none response, phagocytosis is finely tuned by a host of developmental and environmental factors. The expression of key phagocytic determinants is regulated via transcriptional and epigenetic means that confer memory on the process. Membrane traffic, the cytoskeleton, and inside-out signaling control the activation of phagocytic receptors and their ability to access their targets. An exquisite extra layer of complexity is introduced by the coexistence of distinct “eat-me” and “don't-eat-me” signals on targets and of corresponding “eat” and “don't-eat” receptors on the phagocyte surface. Moreover, assorted physical barriers constitute “don't-come-close-to-me” hurdles that obstruct the engagement of ligands by receptors. The expression, mobility, and accessibility of all these determinants can be modulated, conferring extreme plasticity on phagocytosis and providing attractive targets for therapeutic intervention in cancer, atherosclerosis, and dementia.
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    Current Advances in Photoactive Agents for Cancer Imaging and Therapy (2021)
    Annual Reviews
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    Publication Date: 2021-07-13
    Description: Photoactive agents are promising complements for both early diagnosis and targeted treatment of cancer. The dual combination of diagnostics and therapeutics is known as theranostics. Photoactive theranostic agents are activated by a specific wavelength of light and emit another wavelength, which can be detected for imaging tumors, used to generate reactive oxygen species for ablating tumors, or both. Photodynamic therapy (PDT) combines photosensitizer (PS) accumulation and site-directed light irradiation for simultaneous imaging diagnostics and spatially targeted therapy. Although utilized since the early 1900s, advances in the fields of cancer biology, materials science, and nanomedicine have expanded photoactive agents to modern medical treatments. In this review we summarize the origins of PDT and the subsequent generations of PSs and analyze seminal research contributions that have provided insight into rational PS design, such as photophysics, modes of cell death, tumor-targeting mechanisms, and light dosing regimens. We highlight optimizable parameters that, with further exploration, can expand clinical applications of photoactive agents to revolutionize cancer diagnostics and treatment.
    Print ISSN: 1523-9829
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    Beyond Casual Resemblance: Rigorous Frameworks for Comparing Regeneration Across Species (2021)
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    Publication Date: 2021-10-06
    Description: The majority of animal phyla have species that can regenerate. Comparing regeneration across animals can reconstruct the molecular and cellular evolutionary history of this process. Recent studies have revealed some similarity in regeneration mechanisms, but rigorous comparative methods are needed to assess whether these resemblances are ancestral pathways (homology) or are the result of convergent evolution (homoplasy). This review aims to provide a framework for comparing regeneration across animals, focusing on gene regulatory networks (GRNs), which are substrates for assessing process homology. The homology of the wound-induced activation of Wnt signaling and of adult stem cells provides examples of ongoing studies of regeneration that enable comparisons in a GRN framework. Expanding the study of regeneration GRNs in currently studied species and broadening taxonomic sampling for these approaches will identify processes that are unifying principles of regeneration biology across animals. These insights are important both for evolutionary studies of regeneration and for human regenerative medicine.
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    Mechanisms of Selective Autophagy (2021)
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    Publication Date: 2021-10-06
    Description: Selective autophagy is the lysosomal degradation of specific intracellular components sequestered into autophagosomes, late endosomes, or lysosomes through the activity of selective autophagy receptors (SARs). SARs interact with autophagy-related (ATG)8 family proteins via sequence motifs called LC3-interacting region (LIR) motifs in vertebrates and Atg8-interacting motifs (AIMs) in yeast and plants. SARs can be divided into two broad groups: soluble or membrane bound. Cargo or substrate selection may be independent or dependent of ubiquitin labeling of the cargo. In this review, we discuss mechanisms of mammalian selective autophagy with a focus on the unifying principles employed in substrate recognition, interaction with the forming autophagosome via LIR-ATG8 interactions, and the recruitment of core autophagy components for efficient autophagosome formation on the substrate.
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    Vascular Mechanobiology: Homeostasis, Adaptation, and Disease (2021)
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    Publication Date: 2021-07-13
    Description: Cells of the vascular wall are exquisitely sensitive to changes in their mechanical environment. In healthy vessels, mechanical forces regulate signaling and gene expression to direct the remodeling needed for the vessel wall to maintain optimal function. Major diseases of arteries involve maladaptive remodeling with compromised or lost homeostatic mechanisms. Whereas homeostasis invokes negative feedback loops at multiple scales to mediate mechanobiological stability, disease progression often occurs via positive feedback that generates mechanobiological instabilities. In this review, we focus on the cell biology, wall mechanics, and regulatory pathways associated with arterial health and how changes in these processes lead to disease. We discuss how positive feedback loops arise via biomechanical and biochemical means. We conclude that inflammation plays a central role in overriding homeostatic pathways and suggest future directions for addressing therapeutic needs.
    Print ISSN: 1523-9829
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    The Fertilization Enigma: How Sperm and Egg Fuse (2021)
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    Publication Date: 2021-10-06
    Description: Fertilization is a multistep process that culminates in the fusion of sperm and egg, thus marking the beginning of a new organism in sexually reproducing species. Despite its importance for reproduction, the molecular mechanisms that regulate this singular event, particularly sperm–egg fusion, have remained mysterious for many decades. Here, we summarize our current molecular understanding of sperm–egg interaction, focusing mainly on mammalian fertilization. Given the fundamental importance of sperm–egg fusion yet the lack of knowledge of this process in vertebrates, we discuss hallmarks and emerging themes of cell fusion by drawing from well-studied examples such as viral entry, placenta formation, and muscle development. We conclude by identifying open questions and exciting avenues for future studies in gamete fusion.
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    Bottom-Up Forces in Agroecosystems and Their Potential Impact on Arthropod Pest Management (2021)
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    Publication Date: 2021-10-04
    Description: Bottom-up effects are major ecological forces in crop–arthropod pest–natural enemy multitrophic interactions. Over the past two decades, bottom-up effects have been considered key levers for optimizing integrated pest management (IPM). Irrigation, fertilization, crop resistance, habitat manipulation, organic management practices, and landscape characteristics have all been shown to trigger marked bottom-up effects and thus impact pest management. In this review, we summarize current knowledge on the role of bottom-up effects in pest management and the associated mechanisms and discuss several key study cases showing how bottom-up effects practically promote natural pest control. Bottom-up effects on IPM also contribute to sustainable intensification of agriculture in the context of agricultural transition and climate change. Finally, we highlight new research priorities in this important area. Together with top-down forces (biological control), future advances in understanding ecological mechanisms underlying key bottom-up forces could pave the way for developing novel pest management strategies and new optimized IPM programs. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4170
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    Wax, Wings, and Swarms: Insects and Their Products as Art Media (2021)
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    Publication Date: 2021-10-05
    Description: Every facet of human culture is in some way affected by our abundant, diverse insect neighbors. Our relationship with insects has been on display throughout the history of art, sometimes explicitly but frequently in inconspicuous ways. This is because artists can depict insects overtly, but they can also allude to insects conceptually or use insect products in a purely utilitarian manner. Insects themselves can serve as art media, and artists have explored or exploited insects for their products (silk, wax, honey, propolis, carmine, shellac, nest material), body parts (e.g., wings), and whole bodies (dead, alive, individually, or as collectives). This review surveys insects and their products used as media in the visual arts and considers the untapped potential for artistic exploration of media derived from insects. The history, value, and ethics of insect media art are relevant topics at a time when the natural world is at unprecedented risk. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Molecular Mechanisms of Sexually Dimorphic Nervous System Patterning in Flies and Worms (2021)
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    Publication Date: 2021-10-06
    Description: Male and female brains display anatomical and functional differences. Such differences are observed in species across the animal kingdom, including humans, but have been particularly well-studied in two classic animal model systems, the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans. Here we summarize recent advances in understanding how the worm and fly brain acquire sexually dimorphic features during development. We highlight the advantages of each system, illustrating how the precise anatomical delineation of sexual dimorphisms in worms has enabled recent analysis into how these dimorphisms become specified during development, and how focusing on sexually dimorphic neurons in the fly has enabled an increasingly detailed understanding of sex-specific behaviors.
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    A Pandemic Year: Perils and Possibilities (2021)
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    Publication Date: 2021-10-06
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    Defensive Symbionts and the Evolution of Parasitoid Host Specialization (2021)
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    Publication Date: 2021-10-06
    Description: Insect host–parasitoid interactions abound in nature and are characterized by a high degree of host specialization. In addition to their behavioral and immune defenses, many host species rely on heritable bacterial endosymbionts for defense against parasitoids. Studies on aphids and flies show that resistance conferred by symbionts can be very strong and highly specific, possibly as a result of variation in symbiont-produced toxins. I argue that defensive symbionts are therefore an important source of diversifying selection, promoting the evolution of host specialization by parasitoids. This is likely to affect the structure of host–parasitoid food webs. I consider potential changes in terms of food web complexity, although the nature of these effects will also be influenced by whether maternally transmitted symbionts have some capacity for lateral transfer. This is discussed in the light of available evidence for horizontal transmission routes. Finally, I propose that defensive mutualisms other than microbial endosymbionts may also exert diversifying selection on insect parasitoids. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Biomedical Applications of Metal 3D Printing (2021)
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    Publication Date: 2021-07-13
    Description: Additive manufacturing's attributes include print customization, low per-unit cost for small- to mid-batch production, seamless interfacing with mainstream medical 3D imaging techniques, and feasibility to create free-form objects in materials that are biocompatible and biodegradable. Consequently, additive manufacturing is apposite for a wide range of biomedical applications including custom biocompatible implants that mimic the mechanical response of bone, biodegradable scaffolds with engineered degradation rate, medical surgical tools, and biomedical instrumentation. This review surveys the materials, 3D printing methods and technologies, and biomedical applications of metal 3D printing, providing a historical perspective while focusing on the state of the art. It then identifies a number of exciting directions of future growth: ( a) the improvement of mainstream additive manufacturing methods and associated feedstock; ( b) the exploration of mature, less utilized metal 3D printing techniques; ( c) the optimization of additively manufactured load-bearing structures via artificial intelligence; and ( d) the creation of monolithic, multimaterial, finely featured, multifunctional implants.
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    Components and Mechanisms of Nuclear Mechanotransduction (2021)
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    Publication Date: 2021-10-06
    Description: The cell nucleus is best known as the container of the genome. Its envelope provides a barrier for passive macromolecule diffusion, which enhances the control of gene expression. As its largest and stiffest organelle, the nucleus also defines the minimal space requirements of a cell. Internal or external pressures that deform a cell to its physical limits cause a corresponding nuclear deformation. Evidence is consolidating that the nucleus, in addition to its genetic functions, serves as a physical sensing device for critical cell body deformation. Nuclear mechanotransduction allows cells to adapt their acute behaviors, mechanical stability, paracrine signaling, and fate to their physical surroundings. This review summarizes the basic chemical and mechanical properties of nuclear components, and how these properties are thought to be utilized for mechanosensing.
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    Mechanobiology of T Cell Activation: To Catch a Bond (2021)
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    Publication Date: 2021-10-06
    Description: T cell activation is a critical event in the adaptive immune response, indispensable for cell-mediated and humoral immunity as well as for immune regulation. Recent years have witnessed an emerging trend emphasizing the essential role that physical force and mechanical properties play at the T cell interface. In this review, we integrate current knowledge of T cell antigen recognition and the different models of T cell activation from the perspective of mechanobiology, focusing on the interaction between the T cell receptor (TCR) and the peptide–major histocompatibility complex (pMHC) antigen. We address the shortcomings of TCR affinity alone in explaining T cell functional outcomes and the rising status of force-regulated TCR bond lifetimes, most notably the TCR catch bond. Ultimately, T cell activation and the ensuing physiological responses result from mechanical interaction between TCRs and the pMHC.
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    A New Infectious Unit: Extracellular Vesicles Carrying Virus Populations (2021)
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    Publication Date: 2021-10-06
    Description: Viral egress and transmission have long been described to take place through single free virus particles. However, viruses can also shed into the environment and transmit as populations clustered inside extracellular vesicles (EVs), a process we had first called vesicle-mediated en bloc transmission. These membrane-cloaked virus clusters can originate from a variety of cellular organelles including autophagosomes, plasma membrane, and multivesicular bodies. Their viral cargo can be multiples of nonenveloped or enveloped virus particles or even naked infectious genomes, but egress is always nonlytic, with the cell remaining intact. Here we put forth the thesis that EV-cloaked viral clusters are a distinct form of infectious unit as compared to free single viruses (nonenveloped or enveloped) or even free virus aggregates. We discuss how efficient and prevalent these infectious EVs are in the context of virus-associated diseases and highlight the importance of their proper detection and disinfection for public health.
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    Tribolium castaneum: A Model Insect for Fundamental and Applied Research (2021)
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    Publication Date: 2021-10-06
    Description: Tribolium castaneum has a long history as a model species in many distinct subject areas, but improved connections among the genetics, genomics, behavioral, ecological, and pest management fields are needed to fully realize this species’ potential as a model. Tribolium castaneum was the first beetle whose genome was sequenced, and a new genome assembly and enhanced annotation, combined with readily available genomic research tools, have facilitated its increased use in a wide range of functional genomics research. Research into T. castaneum’s sensory systems, response to pheromones and kairomones, and patterns of movement and landscape utilization has improved our understanding of behavioral and ecological processes. Tribolium castaneum has also been a model in the development of pest monitoring and management tactics, including evaluation of insecticide resistance mechanisms. Application of functional genomics approaches to behavioral, ecological, and pest management research is in its infancy but offers a powerful tool that can link mechanism with function and facilitate exploitation of these relationships to better manage this important food pest. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Biology and Models of the Blood–Brain Barrier (2021)
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    Publication Date: 2021-07-13
    Description: The blood–brain barrier (BBB) is one of the most selective endothelial barriers. An understanding of its cellular, morphological, and biological properties in health and disease is necessary to develop therapeutics that can be transported from blood to brain. In vivo models have provided some insight into these features and transport mechanisms adopted at the brain, yet they have failed as a robust platform for the translation of results into clinical outcomes. In this article, we provide a general overview of major BBB features and describe various models that have been designed to replicate this barrier and neurological pathologies linked with the BBB. We propose several key parameters and design characteristics that can be employed to engineer physiologically relevant models of the blood–brain interface and highlight the need for a consensus in the measurement of fundamental properties of this barrier.
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    Mitochondria and Inflammatory Bowel Diseases: Toward a Stratified Therapeutic Intervention (2021)
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    Publication Date: 2021-10-06
    Description: Mitochondria serve numerous critical cellular functions, rapidly responding to extracellular stimuli and cellular demands while dynamically communicating with other organelles. Mitochondrial function in the gastrointestinal epithelium plays a critical role in maintaining intestinal health. Emerging studies implicate the involvement of mitochondrial dysfunction in inflammatory bowel disease (IBD). This review presents mitochondrial metabolism, function, and quality control that converge in intestinal epithelial stemness, differentiation programs, barrier integrity, and innate immunity to influence intestinal inflammation. Intestinal and disease characteristics that set the stage for mitochondrial dysfunction being a key factor in IBD, and in turn, pathogenic mitochondrial mechanisms influencing and potentiating the development of IBD, are discussed. These findings establish the basis for potential mitochondrial-targeted interventions for IBD therapy. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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    Trypanosome Signaling—Quorum Sensing (2021)
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    Publication Date: 2021-10-08
    Description: African trypanosomes are responsible for important diseases of humans and animals in sub-Saharan Africa. The best-studied species is Trypanosoma brucei, which is characterized by development in the mammalian host between morphologically slender and stumpy forms. The latter are adapted for transmission by the parasite's vector, the tsetse fly. The development of stumpy forms is driven by density-dependent quorum sensing (QS), the molecular basis for which is now coming to light. In this review, I discuss the historical context and biological features of trypanosome QS and how it contributes to the parasite's infection dynamics within its mammalian host. Also, I discuss how QS can be lost in different trypanosome species, such as T. brucei evansi and T. brucei equiperdum, or modulated when parasites find themselves competing with others of different genotypes or of different trypanosome species in the same host. Finally, I consider the potential to exploit trypanosome QS therapeutically.
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    Hostile Takeover: How Viruses Reprogram Prokaryotic Metabolism (2021)
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    Publication Date: 2021-10-08
    Description: To reproduce, prokaryotic viruses must hijack the cellular machinery of their hosts and redirect it toward the production of viral particles. While takeover of the host replication and protein synthesis apparatus has long been considered an essential feature of infection, recent studies indicate that extensive reprogramming of host primary metabolism is a widespread phenomenon among prokaryotic viruses that is required to fulfill the biosynthetic needs of virion production. In this review we provide an overview of the most significant recent findings regarding virus-induced reprogramming of prokaryotic metabolism and suggest how quantitative systems biology approaches may be used to provide a holistic understanding of metabolic remodeling during lytic viral infection.
    Print ISSN: 0066-4227
    Electronic ISSN: 1545-3251
    Topics: Biology
    Published by Annual Reviews
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    Advances in the Evolution and Ecology of 13- and 17-Year Periodical Cicadas (2021)
    Annual Reviews
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    Publication Date: 2021-10-08
    Description: Apart from model organisms, 13- and 17-year periodical cicadas (Hemiptera: Cicadidae: Magicicada) are among the most studied insects in evolution and ecology. They are attractive subjects because they predictably emerge in large numbers; have a complex biogeography shaped by both spatial and temporal isolation; and include three largely sympatric, parallel species groups that are, in a sense, evolutionary replicates. Magicicada are also relatively easy to capture and manipulate, and their spectacular, synchronized mass emergences facilitate outreach and citizen science opportunities. Since the last major review, studies of Magicicada have revealed insights into reproductive character displacement and the nature of species boundaries, provided additional examples of allochronic speciation, found evidence for repeated and parallel (but noncontemporaneous) evolution of 13- and 17-year life cycles, quantified the amount and direction of gene flow through time, revealed phylogeographic patterning resulting from paleoclimate change, studied the timing of juvenile development, and created hypotheses for the evolution of life-cycle control and the future effects of climate change on Magicicada life cycles. New ecological studies have supported and questioned the role of prime numbers in Magicicada ecology and evolution, found bidirectional shifts in population size over generations, quantified the contribution of Magicicada to nutrient flow in forest ecosystems, and examined behavioral and biochemical interactions between Magicicada and their fungal parasites and bacterial endosymbionts. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4170
    Electronic ISSN: 1545-4487
    Topics: Biology
    Published by Annual Reviews
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    The Ecology of Hyperparasitoids (2021)
    Annual Reviews
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    Publication Date: 2021-10-04
    Description: Hyperparasitoids are some of the most diverse members of insect food webs. True hyperparasitoids parasitize the larvae of other parasitoids, reaching these larvae with their ovipositor through the herbivore that hosts the parasitoid larva. During pupation, primary parasitoids also may be attacked by pseudohyperparasitoids that lay their eggs on the parasitoid (pre)pupae. By attacking primary parasitoids, hyperparasitoids may affect herbivore population dynamics, and they have been identified as a major challenge in biological control. Over the past decades, research, especially on aphid- and caterpillar-associated hyperparasitoids, has revealed that hyperparasitoids challenge rules on nutrient use efficiency in trophic chains, account for herbivore outbreaks, or stabilize competitive interactions in lower trophic levels, and they may use cues derived from complex interaction networks to locate their hosts. This review focuses on the fascinating ecology of hyperparasitoids related to how they exploit and locate their often inconspicuous hosts and the insect community processes in which hyperparasitoids are prominent players. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    Print ISSN: 0066-4170
    Electronic ISSN: 1545-4487
    Topics: Biology
    Published by Annual Reviews
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    A Tale of Three Systems: Toward a Neuroimmunoendocrine Model of Obesity (2021)
    Annual Reviews
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    Publication Date: 2021-10-06
    Description: The prevalence of obesity is on the rise. What was once considered a simple disease of energy imbalance is now recognized as a complex condition perpetuated by neuro- and immunopathologies. In this review, we summarize the current knowledge of the neuroimmunoendocrine mechanisms underlying obesity. We examine the pleiotropic effects of leptin action in addition to its established role in the modulation of appetite, and we discuss the neural circuitry mediating leptin action and how this is altered with obesity, both centrally (leptin resistance) and in adipose tissues (sympathetic neuropathy). Finally, we dissect the numerous causal and consequential roles of adipose tissue macrophages in obesity and highlight recent key studies demonstrating their direct role in organismal energy homeostasis.
    Print ISSN: 1081-0706
    Electronic ISSN: 1530-8995