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  • Articles  (13,627)
  • Annual Reviews
  • Medicine  (12,234)
  • Energy, Environment Protection, Nuclear Power Engineering  (1,393)
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  • 1
    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
    Published by Annual Reviews
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  • 2
    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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  • 3
    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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  • 4
    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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  • 5
    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.
    Print ISSN: 0066-4278
    Electronic ISSN: 1545-1585
    Topics: Biology , Medicine
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  • 6
    Publication Date: 2021-10-21
    Description: The vast majority of the brain's vascular length is composed of capillaries, where our understanding of blood flow control remains incomplete. This review synthesizes current knowledge on the control of blood flow across microvascular zones by addressing issues with nomenclature and drawing on new developments from in vivo optical imaging and single-cell transcriptomics. Recent studies have highlighted important distinctions in mural cell morphology, gene expression, and contractile dynamics, which can explain observed differences in response to vasoactive mediators between arteriole, transitional, and capillary zones. Smooth muscle cells of arterioles and ensheathing pericytes of the arteriole-capillary transitional zone control large-scale, rapid changes in blood flow. In contrast, capillary pericytes downstream of the transitional zone act on slower and smaller scales and are involved in establishing resting capillary tone and flow heterogeneity. Many unresolved issues remain, including the vasoactive mediators that activate the different pericyte types in vivo, the role of pericyte-endothelial communication in conducting signals from capillaries to arterioles, and how neurological disease affects these mechanisms. 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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  • 7
    Publication Date: 2021-10-21
    Description: The body depends on its physical barriers and innate and adaptive immune responses to defend against the constant assault of potentially harmful microbes. In turn, successful pathogens have evolved unique mechanisms to adapt to the host environment and manipulate host defenses. Helicobacter pylori ( Hp), a human gastric pathogen that is acquired in childhood and persists throughout life, is an example of a bacterium that is very successful at remodeling the host-pathogen interface to promote a long-term persistent infection. Using a combination of secreted virulence factors, immune subversion, and manipulation of cellular mechanisms, Hp can colonize and persist in the hostile environment of the human stomach. Here, we review the most recent and relevant information regarding how this successful pathogen overcomes gastric epithelial host defense responses to facilitate its own survival and establish a chronic infection. 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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  • 8
    Publication Date: 2021-10-18
    Description: Climate change threatens core dimensions of human security, including economic prosperity, food availability, and societal stability. In recent years, war-torn regions such as Afghanistan and Yemen have harbored severe humanitarian crises, compounded by climate-related hazards. These cases epitomize the powerful but presently incompletely appreciated links between vulnerability, conflict, and climate-related impacts. In this article, we develop a unified conceptual model of these phenomena by connecting three fields of research that traditionally have had little interaction: ( a) determinants of social vulnerability to climate change, ( b) climatic drivers of armed conflict risk, and ( c) societal impacts of armed conflict. In doing so, we demonstrate how many of the conditions that shape vulnerability to climate change also increase the likelihood of climate–conflict interactions and, furthermore, that impacts from armed conflict aggravate these conditions. The end result may be a vicious circle locking affected societies in a trap of violence, vulnerability, and climate change impacts.
    Print ISSN: 1543-5938
    Electronic ISSN: 1545-2050
    Topics: Energy, Environment Protection, Nuclear Power Engineering
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  • 9
    Publication Date: 2021-10-18
    Description: A series of international initiatives have set ambitious goals for restoring global forests. This review synthesizes natural and social science research on forest restoration (FR), with a focus on restoration on cleared land in low- and middle-income countries. We define restoration more broadly than reestablishing native forests, given that landholders might prefer other forest types. We organize the review loosely around ideas in the forest transition literature. We begin by examining recent trends in FR and forest transition indicators. We then investigate two primary parts of the forest transition explanation for forest recovery: wood scarcity, including its connection to restoration for climate change mitigation, and the dynamic relationships between migration and land use. Next, we review ecological and silvicultural aspects of restoration on cleared land. We conclude by discussing selected interventions to promote restoration and the challenge of scaling up restoration to achieve international initiatives' goals.
    Print ISSN: 1543-5938
    Electronic ISSN: 1545-2050
    Topics: Energy, Environment Protection, Nuclear Power Engineering
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  • 10
    Publication Date: 2021-10-18
    Description: Discounting plays a central role in decisions about global environmental change that affect the well-being of future generations. Discounting the future more heavily tilts decisions toward the present, making it less likely that society will undertake actions to mitigate climate change or other global environmental change. This article reviews the standard economics approach to discounting that emerges from solving for optimal savings and investment through time. Discounting depends on the pure rate of time preference and differences in consumption levels across time, giving rise to different marginal utilities of consumption. Discounting for problems like climate change that impact future generations involves an ethical dimension. This article includes discussions of ethical dimensions of discounting related to intragenerational and intergenerational equity and also covers behavioral economics, ecological economics, and mainstream economics approaches to discounting. The article closes with a review of the debates over discounting in climate change policy.
    Print ISSN: 1543-5938
    Electronic ISSN: 1545-2050
    Topics: Energy, Environment Protection, Nuclear Power Engineering
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