bluuebunny/crossref_metadata_2025 huggingface dataset:
Nerves and Hormones Interact to Control Gallbladder Function
Authors: Mawe Gary M.
Published: December 2017

Ganglia are the target of several regulatory inputs to the gallbladder. Hormonal cholecystokinin and sympathetic nerves can up- or downregulate neurotransmission in the gallbladder, respectively, by altering the rate of acetylcholine release from vagal preganglionic terminals. Peptides released from sensory axons act directly on gallbladder neurons to increase their excitability.
Fluid Shear Stress Modulation of Gene Expression in Endothelial Cells
Authors: Braddock Martin , Schwachtgen Jean-Luc , Houston Parul , Dickson Marion C. , Lee Michael J. , Campbell Callum J.
Published: December 2017

The vascular endothelium, lining the blood vessel wall, is constantly exposed to wall shear stresses generated by flowing blood. Gene regulation, critical for endothelial cell function, depends on complex interactions at the promoter level and utilizes overlapping signal transduction cascades to activate the expression of genes involved in many biological processes.
The Quest for Speed: Muscles Built for High-Frequency Contractions
Authors: Rome Lawrence C. , Lindstedt Stan L.
Published: December 2017

Vertebrate sound-producing muscles can contract at frequencies greater than 100 Hz, a feat impossible in locomotory muscles. This is not accomplished by unique proteins or structures but by qualitative shifts in isoforms and quantitative reapportionment of structures. Speed comes with costs and trade-offs, however, that restrict how a muscle can be used.
Nitric Oxide and Body Temperature Control
Authors: Gerstberger Rüdiger
Published: December 2017

Pharmacological studies of thermoregulatory effector and neuronal responses indicate that nitric oxide (NO) may have differential roles in the control of body temperature and during fever. Histochemical analysis of site-specific changes in NO synthase activity in defined states of thermal stimulation appears a promising approach to unravel the underlying hypothalamic neuronal cytoarchitecture.
Molecular Features of Energy Coupling in the F0F1ATP Synthase
Authors: Nakamoto Robert K.
Published: December 2017

H+translocation is coupled to ATP synthesis in the F0F1ATP synthase via a rotary mechanism. Catalytic turnover, site-site cooperativity, and H+transport obligatorily involve rotation of a set of subunits. The transport domain in the membranous F0and the catalytic domain in the F1are mechanisms designed for generating torque.
Arteriogenesis Versus Angiogenesis: Two Mechanisms of Vessel Growth
Authors: Buschmann I. , Schaper W.
Published: December 2017

After birth, new blood vessel formation proceeds via angiogenesis or arteriogenesis. Angiogenesis (capillary sprouting) results in higher capillary density. Arteriogenesis (rapid proliferation of collateral arteries) is potentially able to significantly alter the outcome of coronary and peripheral artery disease. The processes share some growth features but differ in many aspects.
Epithelial Fluid Transport—A Century of Investigation
Authors: Spring Kenneth R.
Published: December 2017

Our current understanding of the mechanism of fluid transport by epithelia relies upon mathematical models developed 30 years ago to explain the mechanism of solute-solvent coupling and the pathways taken by water across an epithelium. The validity of these models is reconsidered in light of recent findings, and it is concluded that a simple three-compartment model system is adequate to explain fluid absorption and secretion by epithelia.
Aquaporins: Phylogeny, Structure, and Physiology of Water Channels
Authors: Heymann J. Bernard , Engel Andreas
Published: December 2017

How water permeates cellular membranes and what this means for cell functioning and several diseases are now emerging from the study of the aquaporins (AQPs), the water channel family. A combination of sequence analysis, three-dimensional structure determination, and physiology of the AQP family proteins provides a glimpse into the workings of water channels.
Physiology of Receptor-Mediated Lymphocyte Apoptosis
Authors: Lang F. , Szabo I. , Lepple-Wienhues A. , Siemen D. , Gulbins E.
Published: December 2017

Apoptosis (programmed cell death), a physiological mechanism eliminating abundant and potentially harmful cells, is triggered by a variety of stimuli including activation of distinct receptors. The machinery mediating CD95 receptor-induced apoptosis includes caspases, ceramide, kinases, Ras and Rac, formation of O2–, mitochondrial proteins, inhibition of K+ channels, activation of Cl– channels, and osmolyte release.
G Protein Regulation of Inwardly Rectifying K+ Channels
Authors: Karschin Andreas
Published: December 2017

Inwardly rectifying K+ (Kir) channels respond to receptor-stimulated signaling cascades that involve G proteins and other cytosolic messengers. Channel activity is controlled both by direct coupling of G protein subunits and by phosphorylation via protein serine/threonine and tyrosine kinases. The coincidence of both forms of Kir channel signaling may give rise to complex cellular responses.
PTH and PTHrP: Similar Structures but Different Functions
Authors: Schlüter K.-D.
Published: December 2017

Parathyroid hormone and parathyroid hormone-related peptide are two structurally similar peptide hormones that exert mainly identical effects on classical target cells of parathyroid hormone but remarkable differences in their effects on other target cells. This review focuses on their functional differences and the mechanisms underlying these effects.
From Limbs to Lungs: A Newt Perspective on Compensatory Lung Growth
Authors: Gilbert Kirk A. , Rannels D. Eugene
Published: December 2017

Partial lung resection initiates compensatory growth of remaining lobes to restore pulmonary structure and function. Mechanisms underlying this response are not well defined. This article considers molecular pathways involved in control of amphibian limb regeneration and tissue pattern formation for novel insight into the understanding of compensatory lung growth.
Regulation of Mammalian Gene Expression by Glucose
Authors: Rutter Guy A. , Tavaré Jeremy M. , Palmer D. Gail
Published: December 2017

Recent data suggest that cells from species as diverse as yeast and mammals may use similar mechanisms to detect changes in nutrient concentration. Here we review recent advances in understanding how glucose regulates gene transcription in mammals.
Toward Understanding the Role of Methylation in Aldosterone-Sensitive Na+Transport
Authors: Stockand James D. , Edinger Robert S. , Eaton Douglas C. , Johnson John P.
Published: December 2017

Proper endocrine regulation of Na+reabsorption by renal principal cells is the primary means in mammals for maintaining blood pressure. Aldosterone increases Na+reabsorption by activating luminal Na+channels; however, the signal transduction pathway of aldosterone is not fully understood. Cellular methylation is necessary for aldosterone signaling to the luminal Na+channel. We describe the enzymes, regulators, and effectors of aldosterone-mediated methylation relevant to Na+reabsorption.
Marshaling the Anti-Inflammatory Influence of the Neuroimmunomodulator α-MSH
Authors: Lipton J. M. , Catania A. , Ichiyama T.
Published: December 2017

Inflammation in peripheral tissues should benefit from a novel focus on descending neuroimmunomodulatory anti-inflammatory influences stemming from CNS receptors for the peptide α-MSH. Because activation of glial and peripheral cell receptors modulates inflammatory activity, α-MSH peptides may aid treatment of a variety of CNS and peripheral inflammatory disorders. Activation of melanocortin receptors should thus promote control of inflammatory diseases.
Testicular Estrogens and Male Reproduction
Authors: Carreau Serge , Levallet Jérôme
Published: December 2017

Besides somatic cells, aromatase gene expression and its transduction in an active protein in germ cells provides evidence of an additional site for estrogen production within testes of some mammals. Together with the widespread distribution of estrogen receptors in testicular cells, these data illuminate the hormonal regulation of male reproductive function
Stopping Exercise: Role of Pulmonary C Fibers and Inhibition Of Motoneurons
Authors: Gandevia Simon C. , Taylor Janet L. , Butler Jane E.
Published: December 2017

In animals, the J reflex evoked by pulmonary C fibers provides potent inhibition of limb muscles and would act to limit exercise. However, recent work shows that although activation of these fibers causes severe respiratory discomfort, it does not impair the output of limb motoneurons to voluntary, reflex, or locomotor drives in awake humans.
The Role of Dystroglycan and Its Ligands in Physiology and Disease
Authors: Meier Thomas , Ruegg Markus A.
Published: December 2017

Dystroglycan contributes to the formation of basement membrane during embryonic development and enforces cell membrane integrity by bridging cytoskeleton and components of the extracellular matrix. In several forms of muscle disease, dystroglycan is reduced in abundance. Moreover, human viral and bacterial pathogens use dystroglycan as their cellular entry point.
A Novel Pacemaker Mechanism Drives Gastrointestinal Rhythmicity
Authors: Sanders Kenton M. , Ördög Tamás , Koh Sang Don , Ward Sean M.
Published: December 2017

Electric pacemaker activity drives peristaltic and segmental contractions in the gastrointestinal tract. Interstitial cells of Cajal (ICC) are responsible for spontaneous pacemaker activity. ICC remain rhythmic in culture and generate voltage-independent inward currents via a nonselective cation conductance. Ca2+ release from endoplasmic reticulum and uptake by mitochondria initiates pacemaker currents. This novel mechanism provides the basis for electric rhythmicity in gastrointestinal muscles.
Myocardial Reperfusion Injury: Insights Gained from Gene-Targeted Mice
Authors: Jones Steven P. , Lefer David J.
Published: December 2017

Myocardial ischemia-reperfusion injury involves activation of multiple cell types, including leukocytes and endothelial cells. The pursuant inflammation involves diminished nitric oxide production, influx of neutrophils, and myocardial cell injury. Gene-targeted animals provide important clues about the progression of this inflammatory cascade.
Apoptosis in the Heart: About Programmed Cell Death and Survival
Authors: Dispersyn Gerrit D. , Borgers Marcel
Published: December 2017

Substantial evidence has accumulated that apoptosis, sometimes called “programmed cell death,” is important in several cardiac diseases. Although most researchers focus on apoptosis in the hope that by understanding its mechanisms one can block this form of cell death, little attention has been given to programmed cell survival.
Skeletal and Cardiac Muscle Contractile Activation: Tropomyosin “Rocks and Rolls”
Authors: Gordon A. M. , Regnier M. , Homsher E.
Published: December 2017

Changes in thin filament structure induced by Ca2+ binding to troponin and subsequent strong cross-bridge binding regulate additional strong cross-bridge attachment, force development, and dependence of force on sarcomere length in skeletal and cardiac muscle. Variations in activation properties account for functional differences between these muscle types.
Vascular Endothelium: Checkpoint for Inflammation and Immunity
Authors: Biedermann Barbara C.
Published: December 2017

Vascular endothelial cells play a threefold role in the interaction with leukocytes. First, they are gatekeepers in leukocyte recruitment to inflammatory foci and lymphocyte homing to secondary lymphoid organs. Second, they modulate leukocyte activation. Finally, they are targets of leukocyte-derived molecules, resulting either in endothelial cell activation or death.
Molecular Physiology of Renalp-Aminohippurate Secretion
Authors: Burckhardt Gerhard , Bahn Andrew , Wolff Natascha A.
Published: December 2017

Renal proximal tubules secrete various organic anions, including drugs and p-aminohippurate (PAH). Uptake of PAH from blood into tubule cells occurs by exchange with intracellular α-ketoglutarate and is mediated by the organic anion transporter 1. PAH exit into tubule lumen is species specific and may involve ATP-independent and -dependent transporters.
CFTR: Interacting With Everything?
Authors: Kunzelmann Karl
Published: December 2017

More than 1,300 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) are the cause for cystic fibrosis. CFTR is in charge of proper secretion and absorption of electrolytes, and thus the disease is characterized by defective epithelial Cl–secretion and enhanced Na+absorption. Recent studies show that CFTR interacts with other proteins via PDZ domains.
Synaptic Transmission with the Glia
Authors: Vesce Sabino , Bezzi Paola , Volterra Andrea
Published: December 2017

For decades, scientists thought that all of the missing secrets of brain function resided in neurons. However, a wave of new findings indicates that glial cells, formerly considered mere supporters and subordinate to neurons, participate actively in synaptic integration and processing of information in the brain.
Renal Transplantation Studies in Genetic Hypertension
Authors: Grisk Olaf , Rettig Rainer
Published: December 2017

Renal cross-transplantation experiments revealed that the kidney plays a key role in primary hypertension. Advanced animal breeding strategies leading to the generation of congenic and consomic rat strains combined with renal transplantation experiments will allow researchers to quantify the contribution of renal and extrarenal mechanisms to the development of genetic forms of hypertension.
From Funny Current to HCN Channels: 20 Years of Excitation
Authors: Accili E. A. , Proenza C. , Baruscotti M. , DiFrancesco D.
Published: December 2017

The “funny” (pacemaker) current has unusual characteristics, including activation on hyperpolarization, permeability to K+ and Na+, modulation by internal cAMP, and a tiny, single-channel conductance. In cardiac cells and neurons, pacemaker channels control repetitive activity and excitability. The recent cloning of HCN subunits provides new insight into the molecular basis for the funny channel properties.
Chemogenetic Tools for Causal Cellular and Neuronal Biology
Authors: Atasoy Deniz , Sternson Scott M.
Published: December 2017

Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo.
Physiology of Astroglia
Authors: Verkhratsky Alexei , Nedergaard Maiken
Published: December 2017

Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense of the central nervous system (CNS). Astrocytes are highly heterogeneous in morphological appearance; they express a multitude of receptors, channels, and membrane transporters. This complement underlies their remarkable adaptive plasticity that defines the functional maintenance of the CNS in development and aging. Astrocytes are tightly integrated into neural networks and act within the context of neural tissue; astrocytes control homeostasis of the CNS at all levels of organization from molecular to the whole organ.
Antibody Formation
Authors: Haurowitz Felix
Published: December 2017

Felix Haurowitz, “Antibody Formation”

Page 46, volume 45, references 294–296, printer's error, should read:

294. PORTER, R. R. Biochem. J. 46: 473, 1950.

295. PORTER, R. R. Biochem. J. 73: 119, 1959.

296. PORTER, R. R. Brit. Med. Bull. 19: 197, 1963.
Role of rostaglandins in reproduction
Authors: Goldberg V. J. , Ramwell P. W.
Published: December 2017

From the preceding analysis of prostaglandin research in the reproductive field, it is clear that there have been three major discoveries: a) prostaglandins cause contractions of the human uterus during pregnancy; b) prostaglandins are luteolytic in many subprimate species, but not in humans; and c) prostaglandin levels in the blood and amniotic fluid are elevated during labor in many species, including humans. These important findings have led to major advances in clinical medicine and animal husbandry and to a further understanding of some of the events in the reproductive cycle.
Coronary physiology
Authors: Feigl E. O.
Published: December 2017

The major areas of normal coronary physiological research since Berne's 1964 review have been the measurement of ventricular transmural blood flow distribution with microspheres, the adenosine hypothesis of local metabolic control of coronary blood flow, and the autonomic control of coronary blood flow. There is an improved understanding of intramyocardial tissue pressure and extravascular compressive forces on coronary vessels. However, the unexpected finding of zero flow during a prolonged diastole with a coronary artery pressure of 40 mmHg (PZF) is a reminder that the physical forces, including vascular smooth muscle contraction, that determine coronary vascular resistance are incompletely understood. During normal circumstances, the left ventricular subendocardium probably receives more blood flow than the subepicardium does, but the difference is small. When the coronary circulation is compromised by stenosis or aortic valve lesions, the subendocardium is much more vulnerable to underperfusion than is the subepicardium. The coronary vasodilating effect of arterial hypoxia has been confirmed in many studies, but the role of tissue oxygen tension in local metabolic control of coronary blood flow during normoxia is unknown. The coronary vasodilating action of carbon dioxide has received renewed attention, but its role in local control is also unknown. The adenosine hypothesis has passed several critical tests, but despite much research the importance of adenosine in normal coronary regulation is not established. Local metabolic control of coronary blood flow probably involves more than just one factor, but a unified hypothesis has not been put forward. Sympathetic alpha-receptor-mediated coronary vasoconstriction has been demonstrated by nerve stimulation and during a carotid sinus baroreceptor reflex. Sympathetic coronary vasoconstriction is capable of competing with local metabolic control to lower coronary venous oxygen tension under experimental circumstances, but its importance during normal resting conditions is not established. Parasympathetic muscarinic coronary vasodilation has been shown by vagal nerve stimulation, but a role for it during normal blood flow regulation has yet to be demonstrated. There have been elegant descriptive studies of the coronary blood flow response during excitement and exercise, where coronary blood flow increases pari passu with myocardial metabolism; however, there are also data that indicate a concomitant sympathetic vasoconstrictor effect during strenuous exercise. Overall there has been encouraging progress in coronary physiology. Inevitably new knowledge has focused old questions and presented new ones.
Metabolism of 1,25-dihydroxyvitamin D3
Authors: Kumar R.
Published: December 2017

Synthesis of 1,25(OH)2D3 is controlled by numerous factors. The major ones, however, are the circulating amounts of parathyroid hormone (the secretion of which is stimulated by low serum calcium), serum or extracellular fluid phosphorus concentrations, circulating levels of 1,25(OH)2D3 itself, and perhaps serum calcium directly. Many of the other factors noted have effects in vitro only or effects that are observed inconsistently or in one species only. Thus, in low-calcium states, 1,25(OH)2D3 synthesis increases because of increased parathyroid hormone activity. Parathyroid hormone may stimulate 1,25(OH)2D3 synthesis directly or via alterations (a decrease) in serum phosphorus or both. Low serum phosphorus will stimulate 1,25(OH)2D3 synthesis independent of parathyroid hormone levels. Low serum calcium may directly stimulate 25(OH)D3 1 alpha-hydroxylase activity independently of parathyroid hormone. In general terms the vitamin D-endocrine system tends to correct abnormalities in calcium and phosphorus homeostasis. The further metabolism of 1,25(OH)2D3 to other metabolites appears to be mainly a degradative or excretory process. Currently there is no evidence that 1,25(OH)2D3 must itself be altered to other metabolites prior to inducing intestinal calcium transport or bone mobilization. The processes involved in the excretion of 1,25(OH)2D3, such as side-chain oxidation and biliary excretion, are not regulated by serum calcium, phosphorus, or 1,25(OH)2D3 levels. The biliary excretion pathway is also unsaturable over a very wide range and not regulated by calcium, phosphorus, or vitamin D3. Therefore these processes, which account for a large part of the metabolism of 1,25(OH)2D3, are largely unregulated by factors that control the synthesis of 1,25(OH)2D3 and regulate the formation of other calcium-controlling hormones. Other processes involved in the metabolism of 1,25(OH)2D3, such as 24-hydroxylation and 26-hydroxylation, occur in normocalcemic and normophosphatemic states. 24-Hydroxylation is also induced by 1,25(OH)2D3, which benefits the organism, because excessive 1,25(OH)2D3 in various tissues can be altered to a less active metabolite, 1,24,25(OH)3D3. Although there is still no evidence concerning the regulation of C-24 oxidation by dietary calcium and phosphorus levels, the fact that this process is induced by 1,25(OH)2D3 suggests that the metabolic pathway functions in much the same manner as the 24-hydroxylation pathway. The formation of 1,25(OH)2D3-26,23-lactone occurs in normocalcemic states and in situations in which 1,25(OH)2D3 has been administered.
Ionic channels in epithelial cell membranes
Authors: Van Driessche W. , Zeiske W.
Published: December 2017

This review focused on results obtained with methods that allow studies of ionic channels in situ, namely, patch clamping and current-noise analysis. We reported findings for ionic channels in apical and basolateral plasma membranes of various tight and leaky epithelia from a wide range of animal species and tissues. As for ionic channel "species," we restricted ourselves to the discussion of cation-specific (Na+ or K+), hybrid (Na+ and K+), and Cl- channels. For the K+-specific channels it can be said that their properties in conduction (multisite, single file), selectivity (only "K+-like" cations), and blocking behavior (Ba2+, Cs+, TEA) much resemble those observed for K+ channels in excitable membranes. This seems to include also the Ca2+-activated "maxi" K+ channel. Thus, K+ channels in excitable membranes and K+ channels in epithelia appear to be very closely related in their basic structural principles. This is, however, not at all unexpected, because K+ channels provide the dominant permeability characteristics of nearly all plasma membranes from symmetrical and epithelial cells. An exception is, of course, apical membranes of tight epithelia whose duty is Na+ absorption against large electrochemical gradients in a usually anisosmotic environment. Here, Na+ channels dominate, although a minor fraction of membrane permeability comes from K+ channels, as in frog skin, colon, or distal nephron. Epithelial Na+ channels are different from excitable Na+ channels in that they 1) are far more selective and 2) seem to be chemically rather than electrically gated. Furthermore, their specific blockers belong to very different chemical families, although a guanidinium/amidinium moiety is a common feature (TTX vs. amiloride). [For a more detailed summary of Na+ channel properties see sect. IV H.] Most interesting is the occurrence of relatively nonselective cationic (hybrid) channels in apical membranes of tight epithelia, like larval or adult frog skin. Here, not only the weak selectivity is astonishing but also the fact that these channels react with so-called K+-channel-specific (Ba2+, TEA) as well as with Na+-channel-specific (amiloride, BIG) compounds. Moreover, this cross-reactivity does not seem to be inhibitory but, on the contrary, stimulating. Clearly these channels may become a fascinating object with which to assess whether Na+ and K+ channels are not only structurally but also genetically related and whether they can somehow be converted into each other.(ABSTRACT TRUNCATED AT 400 WORDS)
Regulation of hepatic growth
Authors: Alison M. R.
Published: December 2017

The liver is a conditional renewal system, which in the adult organism undergoes minimal cell production and/or cell renewal. However, a reduction in liver cell mass, because of either actual cell loss or cell atrophy, evokes a rapid regenerative response tailored to replace the lost tissue. Synthesis of DNA begins as early as 15 h after a two-thirds hepatectomy, and the fact that all the remaining hepatocytes enter DNA synthesis within the next 48 h does indicate they are all potentially proliferative, and it is unlikely that a distinct stem cell compartment exists. The temporal sequelae of events can be best explained by the semisynchronous passage of cells from G0 into the proliferative cycle (see Fig. 2) where they undergo one or more rounds of cell division before decycling back into the proliferatively quiescent G0 state. The age of the animal and its nutritional and hormonal status are all important modifiers of the response, but none of them is critical to the regenerative process. Experiments involving the administration of sera or the transfer of blood between animals strongly favor the existence of humoral regulatory factors; the liver is apparently capable of producing both inhibitory and stimulatory molecules that act by negative and positive feedback mechanisms, respectively, to control tissue homeostasis, whereas other organs, notably the pancreas, are important sources of facilitatory molecules. A chemical mechanism of self inhibition is a very intellectually appealing hypothesis, but at present there is no consistent message as to the identity of the inhibitory molecule, although most studies suggest the target site for its action is the G1-S transition. Unless the whole field is one of multilateral analysis of an artifact, then endogenous growth inhibitors do exist, but the problem now is one of biochemical isolation and characterization. The field compares rather badly with the many success stories in recent years in which new hormones and peptides have been speedily isolated and purified. A reduction in liver size appears to be associated with a decrease in the concentration of an hepatic growth inhibitor and the production and/or unmasking of a stimulatory factor(s) that is also of hepatic origin. Once again, there is little information about the biochemical nature of the principle and much less on its mode of action. We all assume that such stimulators, and for that matter inhibitors as well, act on "restriction points" or "mitosis operons" and so on.(ABSTRACT TRUNCATED AT 400 WORDS)
Morphology and electrophysiology of the mammalian atrioventricular node
Authors: Meijler F. L. , Janse M. J.
Published: December 2017

The AV node of those mammalian species in which it has been thoroughly investigated (rabbit, ferret, and humans) consists of various cell types: transitional cells, midnodal (or typical nodal cells), lower nodal cells, and cells of the AV bundle. There are at least two inputs to the AV node, a posterior one via the crista terminalis and an anterior one via the interatrial septum, where atrial fibers gradually merge with transitional cells. The role of a possible third input from the left atrium has not been investigated. Since the transition from atrial fibers to nodal fibers is gradual, it is very difficult to define the "beginning" of the AV node, and gross measurements of AV nodal length may be misleading. Histologically, the "end" of the AV node is equally difficult to define. At the site where macroscopically the AV node ends, at the point where the AV bundle penetrates into the membranous septum, typical nodal cells intermingle with His bundle cells. A conspicuous feature, found in all species studied, is the paucity of junctional complexes, most marked in the midnodal area. The functional counterpart of this is an increased coupling resistance between nodal cells. An electrophysiological classification of the AV nodal area, based on transmembrane action potential characteristics during various imposed atrial rhythms (rapid pacing, trains of premature impulses), into AN (including ANCO and ANL), N, and NH zones has been described by various authors for the rabbit heart. In those studies in which activation patterns, transmembrane potential characteristics, and histology have been compared, a good correlation has been found between AN and transitional cells, N cells and the area where transitional cells and cells of the beginning of the AV bundle merge with midnodal cells, and NH cells and cells of the AV bundle. Dead-end pathways correspond to the posterior extension of the bundle of lower nodal cells and to anterior overlay fibers. During propagation of a normal sinus beat, activation of the AN zone accounts for at least 25% of conduction time from atrium to His bundle, the small N zone being the main source of AV nodal delay. Cycle length-dependent conduction delay is localized in the N zone. Conduction block of premature atrial impulses can occur both in the N zone and in the AN zone, depending on the degree of prematurity. Several factors determining AV nodal conduction delay have been identified.(ABSTRACT TRUNCATED AT 400 WORDS)
Energy contributions of volatile fatty acids from the gastrointestinal tract in various species
Authors: Bergman E. N.
Published: December 2017

The VFA, also known as short-chain fatty acids, are produced in the gastrointestinal tract by microbial fermentation of carbohydrates and endogenous substrates, such as mucus. This can be of great advantage to the animal, since no digestive enzymes exist for breaking down cellulose or other complex carbohydrates. The VFA are produced in the largest amounts in herbivorous animal species and especially in the forestomach of ruminants. The VFA, however, also are produced in the lower digestive tract of humans and all animal species, and intestinal fermentation resembles that occurring in the rumen. The principal VFA in either the rumen or large intestine are acetate, propionate, and butyrate and are produced in a ratio varying from approximately 75:15:10 to 40:40:20. Absorption of VFA at their site of production is rapid, and large quantities are metabolized by the ruminal or large intestinal epithelium before reaching the portal blood. Most of the butyrate is converted to ketone bodies or CO2 by the epithelial cells, and nearly all of the remainder is removed by the liver. Propionate is similarly removed by the liver but is largely converted to glucose. Although species differences exist, acetate is used principally by peripheral tissues, especially fat and muscle. Considerable energy is obtained from VFA in herbivorous species, and far more research has been conducted on ruminants than on other species. Significant VFA, however, are now known to be produced in omnivorous species, such as pigs and humans. Current estimates are that VFA contribute approximately 70% to the caloric requirements of ruminants, such as sheep and cattle, approximately 10% for humans, and approximately 20-30% for several other omnivorous or herbivorous animals. The amount of fiber in the diet undoubtedly affects the amount of VFA produced, and thus the contribution of VFA to the energy needs of the body could become considerably greater as the dietary fiber increases. Pigs and some species of monkey most closely resemble humans, and current research should be directed toward examining the fermentation processes and VFA metabolism in those species. In addition to the energetic or nutritional contributions of VFA to the body, the VFA may indirectly influence cholesterol synthesis and even help regulate insulin or glucagon secretion. In addition, VFA production and absorption have a very significant effect on epithelial cell growth, blood flow, and the normal secretory and absorptive functions of the large intestine, cecum, and rumen. The absorption of VFA and sodium, for example, seem to be interdependent, and release of bicarbonate usually occurs during VFA absorption.(ABSTRACT TRUNCATED AT 400 WORDS)
Cardiovascular response to stress
Authors: Herd J. A.
Published: December 2017

The behavioral characteristics of psychological stressors have been operationally defined. A psychological stressor is one that causes a stress response in a predictable percentage of index subjects. However, it may not always produce a stress response, and the probability of producing such a response depends on interactions between the behavioral situation and the individual involved. Thus there is a danger that a psychological stressor will be defined according to the stress response it causes rather than its structural characteristics. The characteristics that enhance the likelihood that a psychological stressor will cause a stress response are its novel, challenging, or threatening aspects that engage a subject in continuous active mental effort. The intensity of the stress response depends on the intensity of mental effort exerted to meet a challenging situation, whether or not that situation is perceived as threatening. The behavioral response to a psychological stressor also has been defined. It includes somatomotor, neuroendocrine, and cardiovascular components. The somatomotor response to stressful psychological events includes purposeful active coping to counter the challenge or threat posed by the stressor. The neuroendocrine response includes a combination of pituitary-adrenal cortical and hypothalamic-sympathetic-adrenal medullary secretions. The cardiovascular response includes a combination of increased rate and force of cardiac contraction, skeletal muscle vasodilation, venoconstriction, splanchnic vasoconstriction, renal vasoconstriction, and decreased renal excretion of sodium. Of all the modifiers that influence the stress response to a psychological stressor, family history is the one most likely to have an effect. A family history of essential hypertension increases the likelihood that a subject will respond to a psychological stressor with a cardiovascular stress response pattern. Other predisposing characteristics that increase the likelihood of a stress response include behavioral patterns of response to challenge or threat but may also include anatomic or biochemical characteristics that increase susceptibility to neurogenic activation of central aminergic mechanisms.
Optical approaches to ontogeny of electrical activity and related functional organization during early heart development
Authors: Kamino K.
Published: December 2017

Direct intracellular measurement of electrical events in the early embryonic heart is impossible because the cells are too small and frail to be impaled with microelectrodes; it is also not possible to apply conventional electrophysiological techniques to the early embryonic heart. For these reasons, complete understanding of the ontogeny of electrical activity and related physiological functions of the heart during early development has been hampered. Optical signals from voltage-sensitive dyes have provided a new powerful tool for monitoring changes in transmembrane voltage in a wide variety of living preparations. With this technique it is possible to make optical recordings from the cells that are inaccessible to microelectrodes. An additional advantage of the optical method for recording membrane potential activity is that electrical activity can be monitored simultaneously from many sites in a preparation. Thus, applying a multiple-site optical recording method with a 100- or 144-element photodiode array and voltage-sensitive dyes, we have been able to monitor, for the first time, spontaneous electrical activity in prefused cardiac primordia in the early chick embryos at the six- and the early seven-somite stages of development. We were able to determine that the time of initiation of the contraction is the middle period of the nine-somite stage. In the rat embryonic heart, the onset of spontaneous electrical activity and contraction occurs at the three-somite stage. In this review, a new view of the ontogenetic sequence of spontaneous electrical activity and related physiological functions such as ionic properties, pacemaker function, conduction, and characteristics of excitation-contraction coupling in the early embryonic heart are discussed.
Mechanical properties of isolated cardiac myocytes
Authors: Brady A. J.
Published: December 2017

A wide variety of techniques have been developed to monitor the mechanical responses of isolated cardiac myocytes. The most successful are those that measure shortening in unattached cells. Because of their relative ease of implementation, edge-detector methods of following cell displacement have become most widespread. Laser diffraction techniques have been applied to the single heart cells, and sophisticated sarcomere imaging systems capable of 2-ms time resolution of shortening responses have also been developed. Active force has been recorded in intact single cells from frog atria; however, the compliance of the force transducers was relatively higher (approximately 5% Lo). (There is an obvious trade-off between transducer sensitivity, which affects noise and drift and compliance.) Some success has been reported with the use of intact rat myocytes supported by suction micropipettes and in guinea pig ventricular myocytes adhering to poly-L-lysine-coated glass beams. With the rat preparation, contractile stress was comparable to that of ventricular muscle, but few cells survived the attachment. In guinea pig myocytes, contractile stress in electrically induced twitches was only approximately 10% of the active stress developed by mammalian trabeculae or papillary muscles at the same temperature (35 degrees C), but, as with the frog atrial transducer, the compliance of the supporting beams was relatively high. Sarcomere uniformity has not been evaluated in these intact preparations. For attachment to the relatively short mammalian cardiac myocytes, the more promising methods that better preserve sarcomere uniformity include double-barreled micropipettes coated with a barnacle adhesive; however, for nonsubmersible transducers, a continuing limitation is the problem of solution surface stability. Unfortunately, the more severe limitation to effective attachment to intact cells is still the extreme sensitivity of the sarcolemma to mechanical stress. The challenge remains to develop an attachment to the intercalated disk such that cell stress can be transferred to the supporting transducers along the normal stress-bearing cellular interface. The ultrastructural and passive mechanical data strongly indicate that although the extracellular collagen limits the extension of cardiac muscle beyond the peak of the active length-tension relation, there is also a substantial cellular component of resistance to extension. Furthermore, this cellular component is related to the cytoskeleton rather than to membranous elements in the cell. The more likely candidates for the longitudinal resting stress-bearing element are titin (connectin) and desmin.(ABSTRACT TRUNCATED AT 400 WORDS)
Long-term control of arterial blood pressure
Authors: Cowley A. W.
Published: December 2017

Two concepts for the long-term regulation of arterial pressure were considered in this review, the neural control hypothesis and the volume regulation hypothesis. The role of the nervous system and fluid volume regulation are intertwined in a way that has made it difficult to experimentally evaluate their separate contributions in the long-term regulation of arterial pressure. Nevertheless, from a substantial body of work related to the neural control of cardiovascular function, it appears that the ability of the nervous system to control arterial pressure is limited to the detection and correction of rapid short-term changes of arterial pressure. A long and exhaustive search has yet yielded no new neural mechanisms beyond the classic sinoaortic baroreceptors that can detect changes of arterial pressure. The baroreceptor mechanisms are of great importance for the moment-to-moment stabilization of arterial pressure, but because they do not possess sufficient strength and because they reset in time to the prevailing level of arterial pressure, they cannot provide a sustained negative feedback signal to provide long-term regulation of arterial pressure in face of sustained stimuli. This is not to say that the nervous system cannot affect the long-term level of arterial pressure. A distinction is made here between the many factors that can influence the long-term level of pressure and those that actually serve to detect changes of pressure and serve to maintain the level of pressure within a narrow range over the period of our adult lifetime. In this sense, there is evidence that in genetically susceptible individuals, environmental stresses can influence the long-term level of arterial pressure via the central and peripheral neural autonomic pathways. It is inappropriate, however, to view the nervous system as a long-term controller of arterial pressure because there is yet no evidence that the CNS can detect changes of arterial pressure nor changes in total body sodium and water content over sustained periods whereby it could provide an adequate long-term normalization of such error signals. In contrast, evidence has grown in support of the renal pressure-diuresis volume regulation hypothesis for the long-term control of arterial pressure over the past decade. An enhanced understanding of the mechanisms of pressure diuresis-natriuresis coupled with studies exploring how changes of vascular volume can influence vascular smooth muscle tone provide a compelling basis for this hypothesis of long-term arterial pressure regulation. This overall concept is represented and summarized in Figure 12.(ABSTRACT TRUNCATED AT 400 WORDS)
Human surfactant protein B: structure, function, regulation, and genetic disease
Authors: Whitsett J. A. , Nogee L. M. , Weaver T. E. , Horowitz A. D.
Published: December 2017

Elucidation of the structure and function of the hydrophobic surfactant protein (SP-B) and the SP-B gene has provided critical insight into surfactant homeostasis and control of respiratory epithelial cell gene expression. Surfactant protein B, in concert with surfactant protein A (SP-A), surfactant protein C (SP-C), and surfactant phospholipids, contributes to the structure and function of surfactant particles, determining surface activities and pathways by which surfactant phospholipids and proteins are processed, routed, packaged, and secreted from lamellar bodies by type II epithelial cells. After secretion, SP-B plays an essential role in determining the structure of tubular myelin, the stability and rapidity of spreading, and the recycling of surfactant phospholipids. The biochemical and structural signals underlying the homeostasis of alveolar surfactant are likely mediated by interactions between the surfactant proteins and phospholipids producing discrete structural forms that vary in size, aproprotein, and phospholipid content. Distinctions in structure, protein, and size are likely to determine the function of surfactant particles, their catabolism, or recycling by alveolar macrophages and airway epithelial cells. Analysis of the genetic controls governing the SP-B gene has led to the definition of DNA-protein interactions that determine respiratory epithelial cell gene expression in general. The important role of SP-B in lung function was defined by the study of a lethal neonatal respiratory disease, hereditary SP-B deficiency, caused by mutations in the human SP-B gene.
Role of microtubule-associated proteins in the control of microtubule assembly
Authors: Maccioni R. B. , Cambiazo V.
Published: December 2017

In eukaryotic cells, microtubules, actin, and intermediate filaments interact to form the cytoskeletal network involved in determination of cell architecture, intracellular transport, modulation of surface receptors, mitosis, cell motility, and differentiation. Cytoskeletal organization and dynamics depend on protein self-associations and interactions with regulatory elements such as microtubule-associated proteins (MAPs). The MAP family includes large proteins like MAP-1A, MAP-1B, MAP-1C, MAP-2, and MAP-4 and smaller components like tau and MAP-2C. This review focuses on relevant aspects of MAP function, with emphasis on their roles in modulating cytoskeletal interactions. In this context, MAP expression mechanisms and posttranslational modifications are also discussed. Microtubule-associated proteins have a rather widespread distribution among cells, but certain MAPs have been identified in specific cell types. Within single neurons, MAP-2 is dendritic while tau is preferentially an axonal protein. Their expression is developmentally regulated. Even though MAPs share a capacity to interact with the COOH-terminal tubulin domain, stabilize microtubules, and link them with other cytoskeletal polymers, they exhibit structural differences. However, MAP-2, MAP-4, and tau have common repetitive microtubule-binding motifs. Microtubule-associated proteins not only control cytoskeletal integrity, but they also appear to interact with highly structural elements of cells. Molecular biological approaches permitted localization of new MAPs in cultured mammalian cells and invertebrate organisms and other microtubule-interacting proteins that exhibit transient interactions with microtubules. The structural/functional aspects of several new MAP-like proteins in centrosomes and the mitotic spindle, functionally implicated in cell cycle events, are also analyzed.
Ion channel regulation by G proteins
Authors: Wickman K. , Clapham D. E.
Published: December 2017

Ion channels are poised uniquely to initiate, mediate, or regulate such distinct cellular activities as action potential propagation, secretion, and gene transcription. In retrospect, it is not surprising that studies of ion channels have revealed considerable diversities in their primary structures, regulation, and expression. From a functional standpoint, the various mechanisms coopted by cells to regulate channel activity are particularly fascinating. Extracellular ligands, membrane potential, phosphorylation, ions themselves, and diffusible second messengers are all well-established regulators of ion channel activity. Heterotrimeric GTP-binding proteins (G proteins) mediate many of these types of ion channel regulation by stimulating or inhibiting phosphorylation pathways, initiating intracellular cascades leading to elevation of cytosolic Ca2+ or adenosine 3',5'-cyclic monophosphate levels, or by generating various lipid-derived compounds. In some cases, it seems that activated G protein subunits can interact directly with ion channels to elicit regulation. Although there is currently little direct biochemical evidence to support such a mechanism, it is the working hypothesis for the most-studied G protein-regulated ion channels.