bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practical Methods for Molecular In Vivo Optical Imaging
Authors: Chen Hannah , Thorne Stephen H. 
Published: January 2012

AbstractTraditional approaches for translating observations of molecular events into the context of a living organism have suffered from the requirements for either sacrificing animals at multiple time points prior to labor‐intensive analyses of multiple tissues, or have relied on subjective observations or measurements of the animals over time. Recently, a plethora of dedicated animal‐imaging modalities and the release of modified clinical imaging devices dedicated for animal imaging have allowed for the design of quantitative real‐time experiments incorporating fewer animals and providing whole‐animal analyses. Of these modalities, optical imaging (bioluminescence and fluorescence) has emerged as a powerful research tool, allowing investigators with limited whole‐animal imaging expertise to rapidly and inexpensively translate models produced in cellular assays into the context of a living animal. Here we will outline the steps necessary for translation of models established in culture systems into rodents. Curr. Protoc. Cytom. 59:12.24.1‐12.24.11. © 2012 by John Wiley & Sons, Inc.
Wnt‐Notch signalling: An integrated mechanism regulating transitions between cell states
Authors: Muñoz‐Descalzo Silvia , de Navascues Joaquin , Arias Alfonso Martinez 
Published: January 2012

AbstractThe activity of Wnt and Notch signalling is central to many cell fate decisions during development and to the maintenance and differentiation of stem cell populations in homeostasis. While classical views refer to these pathways as independent signal transduction devices that co‐operate in different systems, recent work has revealed intricate connections between their components. These observations suggest that rather than operating as two separate pathways, elements of Wnt and Notch signalling configure an integrated molecular device whose main function is to regulate transitions between cell states in development and homeostasis. Here, we propose a general framework for the structure and function of the interactions between these signalling systems that is focused on the notion of ‘transition states’, i.e. intermediates that arise during cell fate decision processes. These intermediates act as checkpoints in cell fate decision processes and are characterised by the mixed molecular identities of the states involved in these processes.Editor's suggested further reading in BioEssays: Notch: Implications of endogenous inhibitors for therapy Abstract
Cytoskeletal Dynamics and Lung Fluid Balance
Authors: Vogel Stephen M. , Malik Asrar B. 
Published: January 2012

AbstractThis article examines the role of the endothelial cytoskeleton in the lung's ability to restrict fluid and protein to vascular space at normal vascular pressures and thereby to protect lung alveoli from lethal flooding. The barrier properties of microvascular endothelium are dependent on endothelial cell contact with other vessel‐wall lining cells and with the underlying extracellular matrix (ECM). Focal adhesion complexes are essential for attachment of endothelium to ECM. In quiescent endothelial cells, the thick cortical actin rim helps determine cell shape and stabilize endothelial adherens junctions and focal adhesions through protein bridges to actin cytoskeleton. Permeability‐increasing agonists signal activation of “small GTPases” of the Rho family to reorganize the actin cytoskeleton, leading to endothelial cell shape change, disassembly of cortical actin rim, and redistribution of actin into cytoplasmic stress fibers. In association with calcium‐ andSrc‐regulated myosin light chain kinase (MLCK), stress fibers become actinomyosin‐mediated contractile units. Permeability‐increasing agonists stimulate calcium entry and induce tyrosine phosphorylation of VE‐cadherin (vascular endothelial cadherin) and β‐catenins to weaken or pull apart endothelial adherens junctions. Some permeability agonists cause latent activation of the small GTPases, Cdc42 and Rac1, which facilitate endothelial barrier recovery and eliminate interendothelial gaps. Under the influence of Cdc42 and Rac1, filopodia and lamellipodia are generated by rearrangements of actin cytoskeleton. These motile evaginations extend endothelial cell borders across interendothelial gaps, and may initiate reannealing of endothelial junctions. Endogenous barrier protective substances, such as sphingosine‐1‐phosphate, play an important role in maintaining a restrictive endothelial barrier and counteracting the effects of permeability‐increasing agonists. © 2012 American Physiological Society.Compr Physiol2:449‐478, 2012.
Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body
Authors: Kumar Prem , Prabhakar Nanduri R. 
Published: January 2012

AbstractThe discovery of thesensorynature of the carotid body dates back to the beginning of the 20th century. Following these seminal discoveries, research into carotid body mechanisms moved forward progressively through the 20th century, with many descriptions of the ultrastructure of the organ and stimulus‐response measurements at the level of the whole organ. The later part of 20th century witnessed the first descriptions of the cellular responses and electrophysiology of isolated and cultured type I and type II cells, and there now exist a number of testable hypotheses of chemotransduction. The goal of this article is to provide a comprehensive review of current concepts on sensory transduction and transmission of the hypoxic stimulus at the carotid body with an emphasis on integrating cellular mechanisms with the whole organ responses and highlighting the gaps or discrepancies in our knowledge. It is increasingly evident that in addition to hypoxia, the carotid body responds to a wide variety of blood‐borne stimuli, including reduced glucose and immune‐related cytokines and we therefore also consider the evidence for a polymodal function of the carotid body and its implications. It is clear that the sensory function of the carotid body exhibits considerable plasticity in response to the chronic perturbations in environmental O2that is associated with many physiological and pathological conditions. The mechanisms and consequences of carotid body plasticity in health and disease are discussed in the final sections of this article. © 2012 American Physiological Society.Compr Physiol2:141‐219, 2012.
Mechanics and Function of the Pulmonary Vasculature: Implications for Pulmonary Vascular Disease and Right Ventricular Function
Authors: Lammers Steven , Scott Devon , Hunter Kendall , Tan Wei , Shandas Robin , Stenmark Kurt R. 
Published: January 2012

AbstractThe relationship between cardiac function and the afterload against which the heart muscle must work to circulate blood throughout the pulmonary circulation is defined by a complex interaction between many coupled system parameters. These parameters range broadly and incorporate system effects originating primarily from three distinct locations: input power from the heart, hydraulic impedance from the large conduit pulmonary arteries, and hydraulic resistance from the more distal microcirculation. These organ systems are not independent, but rather, form a coupled system in which a change to any individual parameter affects all other system parameters. The result is a highly nonlinear system which requires not only detailed study of each specific component and the effect of disease on their specific function, but also requires study of the interconnected relationship between the microcirculation, the conduit arteries, and the heart in response to age and disease. Here, we investigate systems‐level changes associated with pulmonary hypertensive disease progression in an effort to better understand this coupled relationship. © 2012 American Physiological Society.Compr Physiol2:295‐319, 2012.
Phylogenetic Analyses: Comparing Species to Infer Adaptations and Physiological Mechanisms
Authors: Rezende Enrico L. , Diniz‐Filho José Alexandre F. 
Published: January 2012

AbstractComparisons among species have been a standard tool in animal physiology to understand how organisms function and adapt to their surrounding environment. During the last two decades, conceptual and methodological advances from different fields, including evolutionary biology and systematics, have revolutionized the way comparative analyses are performed, resulting in the advent of modern phylogenetic statistical methods. This development stems from the realization that conventional analytical methods assume that observations are statistically independent, which is not the case for comparative data because species often resemble each other due to shared ancestry. By taking evolutionary history explicitly into consideration, phylogenetic statistical methods can account for the confounding effects of shared ancestry in interspecific comparisons, improving the reliability of standard approaches such as regressions or correlations in comparative analyses. Importantly, these methods have also enabled researchers to address entirely new evolutionary questions, such as the historical sequence of events that resulted in current patterns of form and function, which can only be studied with a phylogenetic perspective. Here, we provide an overview of phylogenetic approaches and their importance for studying the evolution of physiological processes and mechanisms. We discuss the conceptual framework underlying these methods, and explain when and how phylogenetic information should be employed. We then outline the difficulties and limitations inherent to comparative approaches and discuss potential problems researchers may encounter when designing a comparative study. These issues are illustrated with examples from the literature in which the incorporation of phylogenetic information has been useful, or even crucial, for inferences on how species evolve and adapt to their surrounding environment. © 2012 American Physiological Society.Compr Physiol2:639‐674, 2012.
Pulmonary Circulation at Exercise
Authors: Naeije Robert , Chesler N. 
Published: January 2012

AbstractThe pulmonary circulation is a high‐flow and low‐pressure circuit, with an average resistance of 1 mmHg/min/L in young adults, increasing to 2.5 mmHg/min/L over four to six decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20 to 25 mmHg threshold associated with interstitial lung edema and altered ventilation/perfusion relationships. Pulmonary artery pressures of 40 to 50 mmHg, which can be achieved at maximal exercise, may correspond to the extreme of tolerable right ventricular afterload. Distension of capillaries that decrease resistance may be of adaptative value during exercise, but this is limited by hypoxemia from altered diffusion/perfusion relationships. Exercise in hypoxia is associated with higher pulmonary vascular pressures and lower maximal cardiac output, with increased likelihood of right ventricular function limitation and altered gas exchange by interstitial lung edema. Pharmacological interventions aimed at the reduction of pulmonary vascular tone have little effect on pulmonary vascular pressure‐flow relationships in normoxia, but may decrease resistance in hypoxia, unloading the right ventricle and thereby improving exercise capacity. Exercise in patients with pulmonary hypertension is associated with sharp increases in pulmonary artery pressure and a right ventricular limitation of aerobic capacity. Exercise stress testing to determine multipoint pulmonary vascular pressures‐flow relationships may uncover early stage pulmonary vascular disease. © 2012 American Physiological Society.Compr Physiol2:711‐741, 2012.
Regulation of Ion Channels by Membrane Lipids
Authors: Rosenhouse‐Dantsker Avia , Mehta Dolly , Levitan Irena 
Published: January 2012

AbstractThe major membrane lipid regulators of ion channel function includecholesterol, one of the main lipid components of the plasma membranes,phosphoinositides, a group of regulatory phospholipids that constitute a minor component of the membrane lipids but are known to play key roles in regulation of multiple proteins andsphingolipids, particularlysphingosine‐1‐phosphate, a signaling biolipid that is generated from ceramide and is known to regulate multiple cellular functions. Furthermore, specific effects of all the lipid modulators are highly heterogeneous varying significantly between different types of ion channels, as well as between different cell types. In terms of the mechanisms, three general mechanisms have been shown to underlie lipid regulation of ion channels: specific lipid‐protein interactions, changes in the physical properties of the membrane, and facilitating the association of the channel proteins with other regulatory proteins within multiproteins signaling complexes termed membrane rafts. In this article, we present comprehensive analysis of the roles of several lipid modulators, including cholesterol, bile acids, phosphoinositides, and sphingolipids on ion channel function. © 2012 American Physiological Society.Compr Physiol2:31‐68, 2012.
Bioenergetics of Exercising Humans
Authors: Brooks George A. 
Published: January 2012

AbstractHuman muscles, limbs and supporting ventilatory, cardiovascular, and metabolic systems are well adapted for walking, and there is reasonable transfer of efficiency of movement to bicycling. Our efficiency and economy of movement of bipedal walking (≈30%) are far superior to those of apes. This overall body efficiency during walking and bicycling represents the multiplicative interaction of a phosphorylative coupling efficiency of ≈60%, and a mechanical coupling efficiency of ≈50%. These coupling efficiencies compare well with those of other species adapted for locomotion. We are capable runners, but our speed and power are inferior to carnivorous and omnivorous terrestrial mammalian quadrupeds because of biomechanical and physiological constraints. But, because of our metabolic plasticity (i.e., the ability to switch among carbohydrate (CHO)‐ and lipid‐derived energy sources) our endurance capacity is very good by comparison to most mammals, but inferior to highly adapted species such as wolves and migratory birds. Our ancestral ability for hunting and gathering depends on strategy and capabilities in the areas of thermoregulation, and metabolic plasticity. Clearly, our competitive advantage of survival in the biosphere depends in intelligence and behavior. Today, those abilities that served early hunter‐gatherers make for interesting athletic competitions due to wide variations in human phenotypes. In contemporary society, the stresses of regular physical exercise serve to minimize morbidities and mortality associated with physical inactivity, overnutrition, and aging. © 2012 American Physiological Society.Compr Physiol2:537‐562, 2012.
Motility, Survival, and Proliferation
Authors: Gerthoffer William T. , Schaafsma Dedmer , Sharma Pawan , Ghavami Saeid , Halayko Andrew J. 
Published: January 2012

AbstractAirway smooth muscle has classically been of interest for its contractile response linked to bronchoconstriction. However, terminally differentiated smooth muscle cells are phenotypically plastic and have multifunctional capacity for proliferation, cellular hypertrophy, migration, and the synthesis of extracellular matrix and inflammatory mediators. These latter properties of airway smooth muscle are important in airway remodeling which is a structural alteration that compounds the impact of contractile responses on limiting airway conductance. In this overview, we describe the important signaling components and the functional evidence supporting a view of smooth muscle cells at the core of fibroproliferative remodeling of hollow organs. Signal transduction components and events are summarized that control the basic cellular processes of proliferation, cell survival, apoptosis, and cellular migration. We delineate known intracellular control mechanisms and suggest future areas of interest to pursue to more fully understand factors that regulate normal myocyte function and airway remodeling in obstructive lung diseases. © 2012 American Physiological Society.Compr Physiol2:255‐281, 2012.
Neural Control of the Upper Airway: Integrative Physiological Mechanisms and Relevance for Sleep Disordered Breathing
Authors: Horner Richard L. 
Published: January 2012

AbstractThe various neural mechanisms affecting the control of the upper airway muscles are discussed in this review, with particular emphasis on structure‐function relationships and integrative physiological motor‐control processes. Particular foci of attention include the respiratory function of the upper airway muscles, and the various reflex mechanisms underlying their control, specifically the reflex responses to changes in airway pressure, reflexes from pulmonary receptors, chemoreceptor and baroreceptor reflexes, and postural effects on upper airway motor control. This article also addresses the determinants of upper airway collapsibility and the influence of neural drive to the upper airway muscles, and the influence of common drugs such as ethanol, sedative hypnotics, and opioids on upper airway motor control. In addition to an examination of these basic physiological mechanisms, consideration is given throughout this review as to how these mechanisms relate to integrative function in the intact normal upper airway in wakefulness and sleep, and how they may be involved in the pathogenesis of clinical problems such obstructive sleep apnea hypopnea. © 2012 American Physiological Society.Compr Physiol2:479‐535, 2012.
TRPChannels
Authors: Gees Maarten , Owsianik Grzegorz , Nilius Bernd , Voets Thomas 
Published: January 2012

AbstractTRP channels constitute a large superfamily of cation channel forming proteins, all related to the gene product of the transient receptor potential (trp) locus inDrosophila. In mammals, 28 different TRP channel genes have been identified, which exhibit a large variety of functional properties and play diverse cellular and physiological roles. In this article, we provide a brief and systematic summary of expression, function, and (patho)physiological role of the mammalian TRP channels. © 2012 American Physiological Society.Compr Physiol2:563‐608, 2012.
Cryo‐EM in the Study of Membrane Transport Proteins
Authors: Kim Laura Yaunhee , Johnson Matthew C. , Schmidt‐Krey Ingeborg 
Published: January 2012

AbstractElectron cryomicroscopy (cryo‐EM) has evolved as a widely used approach to understand a range of structure‐function questions, particularly of membrane proteins. Studies by both electron crystallography and single particle analysis have provided a wealth of information on membrane transport proteins. Cryo‐EM methods with an emphasis on electron crystallography, which has yielded the most membrane transport protein structural information of any of the cryo‐EM techniques, are described here. Two‐dimensional crystallization approaches are outlined, as well as advances in cryo‐EM specimen preparation, data collection, and image processing. Examples of membrane transport protein structure described serve to illustrate some of the advances in both structural understanding and methods. Further examples outline impressive results that were obtained by a combination of electron crystallography and X‐ray crystallography as well as additional complementary methods. © 2012 American Physiological Society.Compr Physiol2:283‐293, 2012.
Micropuncture of the Kidney: A Primer on Techniques
Authors: Lorenz John N. 
Published: January 2012

AbstractTechniques to evaluate renal function at the single nephron level have been instrumental and indispensible in furthering our understanding of the mammalian kidney. Techniques that were first introduce in the 1920s, and later refined in the 1950s and 1960s, permit sophisticated interrogation of glomerular filtration and hemodynamics, and tubular epithelial transport activity. Much of what we know about the physiology and pathophysiology of the kidney has been produced or, to some degree, confirmed by renal micropuncture. While micropuncture is perhaps not as widely employed as before, it remains an essential tool for comprehensive evaluation of kidney function, particularly in this age of genetically pliable experimental models. This review aims to provide a introduction to common methodologies and approaches used to conduct micropuncture experiments. Topics covered include instrumentation and equipment, pipet fabrication techniques, animal preparation, and experimental procedures for evaluating single nephron hemodynamics and tubular function. © 2012 American Physiological Society.Compr Physiol2:621‐637, 2012.
Weight loss/maintenance as an effective tool for controlling type 2 diabetes: novel methodology to sustain weight reduction
Authors: Gage Dennis 
Published: January 2012

SummaryThe type 2 diabetes epidemic closely parallels the obesity epidemic. Although weight loss is frequently initiated successfully, most patients regain substantial amounts of weight within the first year after completing a weight loss programme. Several studies have shown success over time with weight loss and type 2 diabetes prevention and/or remission. These include the Diabetes Prevention Program and the Look AHEAD study. Novel approaches to weight management have recently found their way onto the internet.With advances in medicine, there has been more patient success in the weight maintenance field. We review the Weight Management System that permits daily counselling to patients who have been losing or maintaining weight. The Weight Management System is a method that combines four fundamental elements: (1) remote daily weight monitoring by the system and the health professional; (2) daily feedback from the system and, when necessary, the health professional; (3) customized information for the needs and desires of the particular patient; and (4) a proprietary algorithm to detect early signs of weight regain. Recent beta testing of this system has confirmed Dr Rena Wing's statistics and has opened up a novel approach to long‐term weight management and diabetes prevention. Copyright © 2012 John Wiley & Sons, Ltd.