bluuebunny/crossref_metadata_2025 huggingface dataset:
Binding of Fatty Acids to Albumin: A Case Study of Lipid-Protein Interactions
Authors: Hamilton JA
Published: December 2017

13C-nuclear magnetic resonance spectroscopy provides structural and dynamic details of lipid-protein interactions in complexes of fatty acids and serum albumin. With native fatty acids as nonperturbing probes, this determines microscopic properties of fatty acids in individual binding sites of albumin, rather than average properties reflecting multiple binding sites.
Iron-Melanin Interaction and Parkinson's Disease
Authors: Youdim MBH , Ben-Shachar D , Riederer P
Published: December 2017

There now is evidence for oxidative stress in the substantia nigra in brains of patients with Parkinson's disease that may be initiated either by an excessive generation of oxygen free radicals and/or a diminution of scavenging radicals. Evidence for participation of iron and melanin in these processes is described.
Serotonergic Neurons and Neuroendocrine Function
Authors: Van de Kar LD , Brownfield MS
Published: December 2017

The release of serotonin (5-HT) from nerve terminals in the hypothalamus increases secretion of adrenocorticotropic hormone and prolactin from the anterior pituitary, vasopressin and oxytocin from the posterior pituitary gland, and renin secretion from the kidneys. Activation of 5-HT1 and/or 5-HT2 receptors stimulates the secretion of these hormones.
Magnetoencephalography Reveals Functions of the Human Brain
Authors: Hari R
Published: December 2017

Magnetoencephalographic signals, detected noninvasively outside the human head, arise from intracellular currents in the fissural cortex. Localization of these currents gives spatially and temporally accurate information about functional organization of the healthy and diseased human cerebral cortex and about neural basis of cognitive functions.
Velocity of Oxygen Transfer and Erythrocyte Rheology
Authors: Maeda N , Shiga T
Published: December 2017

Rheological properties of erythrocytes relate to the oxygen transfer to tissues in microcirculation. Erythrocytes deform by externally applied physical forces. The deformability modifies the pathway of oxygen diffusion inside the microvessel. The rate of oxygen release from flowing erythrocytes in a single microvessel is determined spectrophotometrically under the microscope.
Myofilament Lattice Spacing Affects Tension in Striated Muscle
Authors: Cecchi G , Bagni MA
Published: December 2017

Myofilament lattice spacing influences the mechanism of force generation in intact muscle fibers. There is an optimum spacing above and below which the force generated by an individual cross bridge is reduced. The cross-bridge force has a radial component that compresses the lattice during activation.
Molecular Mechanisms of Mechanoreceptor Adaptation
Authors: Hamill OP , McBride DW,
Published: December 2017

Mechanoreceptor adaptation to maintained stimulation serves to maximize dynamic sensitivity over a broad stimulus domain. Mechanosensitive channel currents in hair cells and oocytes show similar voltage-dependent adaptation. However, in the hair cell, adaptation appears dependent on Ca2+ influx, whereas in the oocyte, it is intrinsically voltage sensitive.
Macrophages in the Brain: Friends or Enemies?
Authors: Piani D , Constam DB , Frei K , Fontana A
Published: December 2017

Cells of the macrophage lineage are ubiquitously distributed in the body, including the central nervous system. They represent an essential host defense system to protect from infections. However, recent evidence indicates that brain macrophages may also be responsible for tissue destruction, including loss of neurons and demyelination.
Role of Microvessels in Oxygen Supply to Tissue
Authors: Ellsworth ML , Ellis CG , Popel AS , Pittman RN
Published: December 2017

Since the early work of Aug Krogh in 1919, capillaries have been assumed to be the sole supplier of oxygen for tissue. Recent studies provide convincing evidence that other microvessels also contribute to tissue oxygenation and that capillaries play a much more complex role that originally proposed by Krogh.
The Concept of a Cell Membrane: Early Developments
Authors: Kleinzeller Arnost
Published: December 2017

The Concept of a cell membrane is traced back to the now-forgotten study of William Hewson, who in 1773 described osmotic effects on the shape of red blood corpuscles (RBC). The movement of the nucleus in osmotically swollen toad RBC suggested that RBC are vesicles with an elastic structure enveloping a fluid content.
Chromophores in O2 Chemoreception: The Carotid Body Model
Authors: Lahiri S
Published: December 2017

O2 chemoreceptions involving two types of chromophores in the carotid body are proposed. One, elicited by CO in absence of light, can only be explained by its complex formation with, for example, cytochrome a2+3. The other pertains to the inhibition of hypoxic response by CO in bright light.
Why Don't Our Feet Swell in the Upright Position?
Authors: Aukland K
Published: December 2017

Rising to the upright position should a priori increase capillaray pressure in the feet by 100 mmHg and cause excessive filtration. Fortunately, frank edema is automatically prevented by arterial vasoconstriction and reduced capillary surface area, by colloid osmotic hydrostatic counterforces in plasma and interstitium, and by increased lymph drainage.
Mesangial Cells Orchestrate Inflammation in the Renal Glomerulus
Authors: Pfeilschifter J
Published: December 2017

The mesangium is a highly specialized pericapillary tissue that is involved in most pathological processes of the renal glomerulus. Mesangial cells orchestrate inflammatory processes in the renal glomerulus by increased mediator production, increased matrix production, and increased mesangial cell proliferation.
Water Channels in Renal and Nonrenal Tissues
Authors: Sabolic I , Brown D
Published: December 2017

A family of structurally similar channel-forming membrane glycoproteins, termed water channels or aquaporins, accounts for the constitutive as well as vasopressin-regulated water permeability in respective epithelia. Heterogeneity of aquaporins provides a molecular basis for some genetic diseases and treatment of certain diseases with disturbances in water homeostasis.
New Concepts in Hepatocellular Transport and Metabolism of Bilirubin
Authors: Gonzalez-Gallego J
Published: December 2017

Determination of serum bilirubin is a widely used test for evaluation of liver function. Understanding of the bilirubin chemistry, transport, and metabolism is of the greatest importance for correct interpretation of serum bilirubin concentrations and for adequate treatment of those clinical conditions characterized by the presence of jaundice.
Gut Feelings About Hibernation
Authors: Carey HV
Published: December 2017

The winter fast characteristic of mammalian hibernation presents an interesting challenge to the intestine. The absence of feeding reduces energy expenditure and causes atrophy of the mucosa and the potential to compromise absorptive capacity after spring arousal. The preservation of mucosal function in hibernators and ways this might occur despite the dramatic reduction in dietary intake are discussed.
Neural Mechanisms of Hyperalgesia: Peripheral or Central Sensitization?
Authors: Carstens E
Published: December 2017

Everyone has experienced soreness after an injury. What neural processes underlie this increased pain sensitivity (hyperalgesia)? Recent data indicate that injury triggers an increase in the sensitivity of spinal cord pain-signaling neurons. Nonpainful activation of these sensitized neurons evokes an exaggerated signal interpreted as pain.
Scaling of the Mammalian Brain: the Maternal Energy Hypothesis
Authors: Martin RD
Published: December 2017

Mammalian brain sizes have been linked to specific behavioral or physiological features because of simple scaling correlations. Examination of the correlation network for body size, brain size, basal metabolic rate, and gestation period indicates that the primary link is between maternal metabolic capacity and the developing brain of the offspring.
Neuronal Nicotinic Acetylcholine Receptors in the Brain
Authors: Vidal C , Changeux J-P
Published: December 2017

Recent molecular, immunologic, and physiological studies have revealed that wide variety of nicotinic acetylcholine receptors exist in the nervous system of vertebrates. Nicotinic systems in the brain appear to play significant roles in drug addiction and in cognitive functions, as well as in pathologies, such as Alzheimer's disease.
Sleep-Dependent Changes in Regional Circulations
Authors: Franzini C , Zoccoli G , Cianci T , Lenzi P
Published: December 2017

Whereas quiet sleep is characterized by modest quantitative changes in regional circulations, active sleep markedly affects both neural and local controls of the individual vascular beds. The integrated vasomotor patterns controlled by hypothalamic structures are those most perturbed during active sleep.
The Lives and Works of Two Contributors to Medieval Physiology
Authors: Tenney S. Marsh
Published: December 2017

Saint Hildegard of Bingen was a mystic and polymath who was also a medical practitioner who included in some of her works sections that dealt with ideas about physiology that were current in late medieval Europe. Those ideas predated knowledge of Greco-Roman and Arabic learning, which was translated and introduced by Constantine the African.
Transmitter Release at Adrenergic Nerve Endings: Total Exocytosis or Fractional Release?
Authors: Folkow B , Nilsson H
Published: December 2017

Increasing discharge rate in sympathetic neurons elevates transmitter release probability in the neuroeffector junction, with important consequences for neural control and for quantitative estimates of transmitter release. This survey of quantitative data favors the view that the quantum of transmitter released may be only part of the total vesicle contents.
Channelopathies: Their Contribution to Our Knowledge About Voltage-Gated Ion Channels
Authors: Lehmann-Horn F , Rudel R
Published: December 2017

Since 1990, many mutations in genes encoding voltage-dependent sodium, potassium, calcium, and chloride channels have been discovered to cause disorders of heart, skeletal muscle, brain, or kidney. Study of the defective gene products has furthered our knowledge not only of pathology but also of ion-channel function.
Role of Delayed Rectifier Potassium Channels in Cardiac Repolarization and Arrhythmias
Authors: Sanguinetti MC , Keating MT
Published: December 2017

Cardiac action potentials are long because the magnitude of some potassium currents is reduced at depolarized potentials. The slow onset of repolarization is initiated by the opening of delayed rectifier potassium channels. A decrease in function of these channels resulting from gene mutations or pharmacological block increases risk of life-threatening ventricular arrhythmias.
Transport by the Ciliary Epithelium of the Eye
Authors: Civan MM
Published: December 2017

The bilayered ciliary epithelium transfers solute, and secondarily water, from the underlying stroma� to the aqueous humor. Luminal Cl--channel activity probably limits the rate of secretion. Recent informtion suggests that this channel may consist of a protein kinase C-inhibitable conduit regulated by a swelling-activated modulator.
Form and Function: Impulse Propagation in Designer Cultures of Cardiomyocytes
Authors: Rohr S , Kucera JP , Kleber AG
Published: December 2017

The architecture of the cellular network forming the myocardium is an important determinant of the characteristics of impulse propagation. This article describes an experimental approach permitting the systematic study of this structure-function relationship, which is based on optical micromapping of electrical activity in cardiac cell cultures with a defined two-dimensional geometry.
Fish Antifreeze Glycoproteins Protect Cellular Membranes During Lipid-Phase Transitions
Authors: Hays LM , Feeney RE , Tablin F , Oliver AE , Walker NJ , Crowe LM , Crowe JH
Published: December 2017

Antifreeze proteins from Antarctic fish depress solution freezing temperatures, inhibit ice crystal formation, and prevent recrystallization on rewarming. They have been used to enhance survival of some cell types during hypothermic storage. The mechanism of their protection is thought to be important during the transition of lipid bilayers from a liquid crystalline to a gel phase.
Prolactins: Novel Regulators of Angiogenesis
Authors: Clapp C , Martinez de la Escalera G
Published: December 2017

Prolactin, the hormone originally associated with the secretion of milk, is known to represent a family of proteins with a striking variety of actions beyond the scope of reproduction. Current studies have further extended their area of influence by revealing that members of the prolactin family may act as regulators of angiogenesis.
Mitogens and Calcium Channels
Authors: Lovisolo D , Distasi C , Antoniotti S , Munaron L
Published: December 2017

Mitogens and, in particular, growth factors can induce changes in free intracellular Ca2+ concentration by opening voltage-independent cationic channels, with different degrees of Ca2+ selectivity. Recent work has provided preliminary insights into the nature of these channels and their role in the control of cell cycle progression.
The Tuned Cricket
Authors: Michelsen Axel
Published: December 2017

Communication by means of sound is not always easy. Sound suffers much attenuation and degradation close to ground. Crickets have adapted to this by exploiting sharply tuned mechanical systems. A coevolution ensures that the calling song of males and the directional hearing of females are tuned to the same frequency.
Nerves and Intestinal Mast Cells Modulate Responses to Enterotoxins
Authors: Pothoulakis Charalabos , Castagliuolo Ignazio , LaMont J. Thomas
Published: December 2017

Experiments in intact animals exposed to enterotoxins demonstrate that neurons and immune cells of the lamina propria regulate toxin-induced diarrhea and tissue damage. Clostridium difficile toxins cause profound diarrhea and acute inflammation by activating a complex cascade initiated by toxin binding to enterocyte receptors.
The Molecular Physiology of Sodium- and Proton-Coupled Solute Transporters
Authors: Steel Angela , Hediger Matthias A.
Published: December 2017

The expression of cloned Na+- and H+-coupled solute transporters in Xenopus laevis oocytes has permitted detailed molecular and biophysical analysis and illuminated unique mechanistic features. The identification of missense mutations in inherited diseases and site-directed mutagenesis studies have enhanced our understanding of their roles in physiological and pathological processes.
Two Subgroups of Gonadotropin Releasing Hormone Neurons Control Gonadotropin Secretion in Rats
Authors: Kimura Fukuko , Funabashi Toshiya
Published: December 2017

Two distinct subgroups of gonadotropin-releasing hormone (GnRH) neurons are involved in the control of luteinizing hormone secretion, at least in rats: one subgroup located in the mediobasal hypothalamus constitutes the GnRH pulse generator associated with opioid neurons, and the other located in the preoptic area constitutes the GnRH surge generator associated with γ-aminobutyric acid neurons.
Flash Photolysis of Caged Compounds: Casting Light on Physiological Processes
Authors: Giovannardi Stefano , Landò Luca , Peres Antonio
Published: December 2017

Photorelease of bioactive molecules from inactive precursors is a very powerful tool for the study of the molecular mechanisms underlying physiological processes as diverse as ionic channel modulation, exocytosis, phototransduction, ligand-receptor interaction, and cross-bridge activity. A brief account of the methodology, available compounds, and fields of application is presented here.
The Dual Role of Nitric Oxide in Islet β-Cells
Authors: Spinas Giatgen A.
Published: December 2017

In pancreatic islets, nitric oxide (NO) produced on exposure to cytokines mediates β-cell injury leading to diabetes mellitus. On the other hand, l-arginine-derived NO may participate in the signal transduction pathway of physiological insulin secretion. This review focuses on the dual role of NO as a mediator of physiological and pathophysiological processes in pancreatic islets.
Motor Patterns in Walking
Authors: Lacquaniti F. , Grasso R. , Zago M.
Published: December 2017

Despite the fact that locomotion may differ widely in mammals, common principles of kinematic control are at work. These reflect common mechanical and neural constraints. The former are related to the need to maintain balance and to limit energy expenditure. The latter are related to the organization of the central pattern-generating networks.
Sarcomeric Myosin Isoforms: Fine Tuning of a Molecular Motor
Authors: Reggiani Carlo , Bottinelli Roberto , Stienen Ger J. M.
Published: December 2017

Sarcomeric or striated muscle myosins are the molecular motors whose fine tuning is best known. Sarcomeric myosin isoforms convert chemical into mechanical energy at very different rates without losing efficiency. Availability of the amino acid sequences offers for the first time the chance to understand the molecular basis of the versatility of these molecular motors.
Presynaptic Heterogeneity: Vive la difference
Authors: Staple Julie K. , Morgenthaler Florence , Catsicas Stefan
Published: December 2017

Since individual synapses of the same neuron may have different molecular composition, an important question in neurobiology is how the properties of individual synapses are established and maintained. Recent technical advances allow assay of activity at individual synapses and investigation of the relationship between function and molecular composition at the synapse.
The Time Course of Signaling at Central Glutamatergic Synapses
Authors: Jonas Peter
Published: December 2017

Glutamate is the main excitatory transmitter in the mammalian CNS, mediating fast synaptic transmission primarily by activation of AMPA-type glutamate receptor channels. Both synaptic structure and a cell-specific molecular switch in the AMPA receptor subunit expression are involved in the regulation of the synaptic signaling time course.
Molecular Mechanisms in Bile Formation
Authors: Meier Peter J. , Stieger Bruno
Published: December 2017

Active canalicular secretion of bile salts and non-bile salt organic anions represents the major driving force of hepatic bile formation. The most important carriers involved have now been cloned on both the basolateral and canalicular sides of hepatocytes. Elucidation of their structure, transport properties, and regulation is an important step forward in the ultimate understanding of the molecular physiology of bile formation.
Synaptic Transmission at Single Boutons in Sympathetic Ganglia
Authors: Bennett M. R.
Published: December 2017

Synaptic transmission has traditionally been studied at the level of the entire nerve terminal rather than at one of its constituent boutons. Autonomic ganglia provide preparations for recording from individual boutons, as well as for determining the calcium transients necessary for transmitter release at these boutons. The results suggest a new paradigm for synaptic transmission.
Oxygen Radicals as Messengers in Oxygen-Dependent Gene Expression
Authors: Kietzmann Thomas , Fandrey Joachim , Acker Helmut
Published: December 2017

Changes in ambient Po2need to be sensed to allow long-term adaptation of cellular functions via the regulation of gene activity. The generation of OH• from H2O2in an iron-dependent perinuclear Fenton reaction for triggering gene expression could be the key event in the O2signaling pathway.
The Neuroimmune Interface in Prion Diseases
Authors: Klein Michael A. , Aguzzi Adriano
Published: December 2017

Prion diseases are fatal neurodegenerative disorders of animals and humans. Here we address the role of the immune system in the spread of prions from peripheral sites to the central nervous system and its potential relevance to iatrogenic prion disease.
Physiological Properties of Blood Substitutes
Authors: Spahn Donat R. , Pasch Thomas
Published: December 2017

Blood substitutes (modified hemoglobin solutions, perfluorocarbon emulsions) serve as artificial oxygen carriers and are alternatives to blood transfusions. Hemoglobin solutions mimic the sigmoidal oxygen dissociation curve of natural blood. Perflurocarbon emulsions exhibit a linear relation between Po2and dissolved oxygen. The most advanced substances may enter medicine in few years.
Intracellular Ca2+Release Sparks Atrial Pacemaker Activity
Authors: Lipsius Stephen L. , Hüser Jörg , Blatter Lothar A.
Published: December 2017

Electrical excitation of the mammalian heart originates from specialized pacemaker cells in the right atrium. Pacemaker activity depends on multiple ion channels and transport mechanisms that reside primarily within the plasma membrane. However, recent evidence indicates that intracellular Ca2+release from the sarcoplasmic reticulum also contributes importantly to atrial pacemaker function.
ATP-Sensitive Potassium Channels in Dopaminergic Neurons: Transducers of Mitochondrial Dysfunction
Authors: Liss Birgit , Roeper Jochen
Published: December 2017

ATP-sensitive potassium (KATP) channels directly couple the metabolic state of a cell to its electrical activity. Dopaminergic midbrain neurons express alternative types of KATP channels mediating their differential response to mitochondrial complex I inhibition. Because reduced complex I activity is present in Parkinson's Disease, differential KATP channel expression suggests a novel candidate mechanism for selective dopaminergic degeneration.
Brain Images of Pain
Authors: Bromm Burkhart
Published: December 2017

Combined magneto- and encephalography proves the sequential involvement of multiple cortical structures in pain processing. Bilateral activity in secondary somatosensory cortices reflects the sensory-discriminative component and is reduced in states of unconsciousness. Later activity in the posterior cingulum reflects the emotional-aversive component, which is blocked by narcoanalgesics.
Human Myoblast Differentiation: Ca2+ Channels are Activated by K+ Channels
Authors: Bernheim Laurent , Bader Charles R.
Published: December 2017

In a paradigm of cellular differentiation, human myoblast fusion, we investigated how a Ca2+ influx, indispensable for fusion, is triggered. We show how newly expressed Kir2.1 K+ channels, via their hyperpolarizing effect on the membrane potential, generate a window Ca2+ current (mediated by a1H T-type Ca2+ channels), which causes intracellular Ca2+ to rise.
EFFECTS OF OXYGEN AT INCREASED PRESSURE
Authors: Bean John W.
Published: December 2017

Volume 25, 1945. Paper by J. W. Bean: Effects of Oxygen at Increased Pressure. Page 69, 2nd paragraph, line 14, which reads “...137.5 + (3 x 360) + 1226.5 ...” should read “... 137.5 + (3 x 360) + 9 = 1226.5 ...”
Thirst
Authors: Fitzsimons J. T.
Published: December 2017

J. T. Fitzsimons, “Thirst,” vol. 52, no. 2, April 1972, p. 481, line 6, the formula should read:

[See PDF for Equation]
Fluid secretion in the nephron: Relation to renal failure
Authors: Grantham J. J.
Published: December 2017

It had been generally accepted that glomerular filtration and tubular reabsorption were the basic modes of fluid transport in mammalian nephrons. Recently, evidence was obtained to indicate that net fluid secretion may occur in mammalian nephrons as well. In the pars recta portion of proximal tubules of rabbit kidney net fluid secretion was observed in vitro in response to PAH and other aryl acids in the peritubular bathing medium. Net fluid secretion appeared to be coupled to the transcellular transport of aryl acid from bath to lumen. Serum from uremic subjects stimulated net fluid secretion in the pars recta in a manner similar to PAH. The accumulation of high levels of endogenous aryl acids may contribute to the general organ dysfunction that is a part of the uremic syndrome of advanced renal insufficiency. Futhermore, there is evidence to suggest that the fluid-secretion phenomenon in association with aryl acids may significantly affect renal excretion and morphology in slow-flow states, in patients with cystic kidney disease, and in obstructive nephropathy.
Development of neuromuscular synapses
Authors: Bennett M. R.
Published: December 2017

Quantal secretion at nerve terminals in mature muscles depends on the number of terminal branches and the size of release sites (sect. VB4). The physical length of SBL determines the length of terminal branch that can be laid down in a reinnervation experiment (sect. IVA4). A limit is set on the total length of terminal branches formed by a motoneuron; this limit is determined by the amount of TF (sect. IVB) made available from the neuron soma to the peripheral branches of the neuron (sect. VC). As a result of this limit, not all SBL needs to be occupied at a site by terminal branches. The SBL eventually disappears if it is not occupied by terminal branches (sect. IVA2). If a muscle is relatively inactive, it synthesizes and releases at synaptic sites additional amounts of NGF, which stimulates the growth of additional terminal branches. These may secrete sufficient amounts of AF to induce the formation of new SRs with associated SBL. In these circumstances a new synaptic site is formed or an extension of an existing site is created. If the size of a motor unit is decreased, the enhanced release of TF at the remaining terminals ensures that each occupies all the SBL at the synaptic site. Furthermore the enhanced release of AF per terminal induces more SBL, allowing additional terminal branches on the muscle cells to be established. Neither of these changes occurs unless the threshold amount of NGF is available from the muscle to stabilize the terminals. If this condition is met, an increase in quantal release per terminal occurs after reducing the size of a motor unit (sect. VC). An increase in quantal release per terminal also occurs after inactivation of a muscle. Such inactivation leads to an enhanced release of NGF per synaptic site (sect. VA4). Extra terminals may then form if sufficient TF is available; these may innervate existing but empty synaptic sites. In rare circumstances the extra terminal may induce SBL and innervate these new sites if sufficient AF is available. In both cases the quantal release per terminal increases. During development the secretory capacity of the axon terminal depends on the muscle cells with which it synapses. This secretory capacity can be enhanced either by increasing the number of terminal branch pairs or by increasing the secretory capacity of individual release sites. If two terminals innervate a synaptic site, their individual secretory capacity is reduced--in these circumstances the terminal's secretory capacity depends on the amount of NGF available to the terminal; two terminals must share their NGF.
Insulin receptors: binding kinetics and structure-function relationship of insulin
Authors: Gammeltoft S.
Published: December 2017

During the last decade, earlier suggestions that insulin acts at the plasma membrane level via combination with receptors have been amply confirmed in studies of 125I-labeled insulin binding kinetics. Efforts have been devoted to the development of homogeneous, stable, and bioactive tracers, and a preparation of monoiodo[TyrA14]insulin showed 100-125% biological activity. The initially simple model of reversible, bimolecular, and noncooperative interaction between receptor and insulin has been revised to include the existence of at least three affinity states that may be linked to modulation of the biological response induced by the insulin-receptor complex. Thus negative cooperativity seems important in reducing oscillations of insulin action with variations in plasma insulin concentration, and formation of a high-affinity state or positive cooperativity may lead to desensitization of receptors. The kinetic phenomena suggest that receptor-binding affinity and function are actively regulated by insulin itself. At present the receptor model is purely functional and does not imply molecular mechanisms. However, recent advances in the analysis of receptor structure and biochemistry promise that the molecular equivalents of the kinetic phenomena may be elucidated in the near future. Furthermore the reaction between receptor and insulin is irreversible because of degradation of receptor-bound insulin, which may result in termination of the metabolic activation. Morphological and biochemical work suggests that internalization of the receptor-insulin complex from the plasma membrane transfers insulin to intracellular organelles like the lysosomes, the Golgi apparatus, or nucleus, where degradation by insulin protease takes place, whereas the receptor is recycled back to the membrane. Recent advances in the studies of biosynthesis and cellular dynamics of receptors indicate that intracellular processing and redistribution of binding sites may play a role in the mechanism of insulin action. Insulin receptors are widely distributed in all cell types, but evidence has accumulated that receptors show tissue and species variations in their functional properties regarding binding affinity, insulin specificity, cooperativity, and insulin degradation and in structural properties such as antigenic determinants and glycosidic composition. Perhaps these differences reflect cellular adaptations and variations in the physiological role of insulin.(ABSTRACT TRUNCATED AT 400 WORDS)
Mammalian muscle spindle: peripheral mechanisms
Authors: Hunt C. C.
Published: December 2017

The responses of sensory endings of the muscle spindle to stretch are produced by transduction in the sensory terminals and by impulse initiation in the sensory axon, both of which appear to be largely linear and non-time-dependent processes. The marked nonlinearity of spindle responses to length, the processes of gain compression, and the aftereffects of fusimotor activity and of stretch appear to reside mainly in the mechanical properties of the intrafusal fibers. Although the basis of the dynamic sensitivity of the primary ending in the passive spindle is still not well understood, dynamic fusimotor effects have been shown to depend on activation of the bag 1 fiber. Static fusimotor actions result from contraction in the bag 2 and/or chain fibers. Certainly, a great deal is known about the muscle spindle at the level of changes in sensory discharge to variations in muscle length and to fusimotor stimulation, although new insights continue to arise from experiments of this type. However, there is a need for further quantitative information that will lead to greater understanding of transduction mechanisms, impulse initiation, and intrafusal fiber contractile activation.
Synaptic vesicle biogenesis, docking, and fusion: a molecular description
Authors: Calakos N. , Scheller R. H.
Published: December 2017

Secretion of neurotransmitter is the primary means of intercellular communication within the nervous system. This process is regulated by a highly orchestrated cycle of membrane trafficking within the presynaptic nerve terminal. Characterization of proteins localized to the synaptic vesicle and the subsequent studies of their properties have led to a model for the biochemical pathway that underlies vesicle docking, activation, and fusion. The proteins found to function in the synapse are related to those in yeast and other organisms, demonstrating that the mechanisms that mediate vesicle trafficking are conserved in all eukaryotic species.
Molecular and cellular biology of thyrotropin-releasing hormone receptors
Authors: Gershengorn M. C. , Osman R.
Published: December 2017

Thyrotropin-releasing hormone (TRH) receptor (TRH-R) complementary DNAs have been cloned from several species. The deduced amino acid sequences are compatible with TRH-R being a seven-transmembrane-spanning G protein-coupled receptor. These complementary DNAs and reagents derived from them have permitted detailed study of TRH-R biology at the molecular and cellular levels. Studies that have been performed since 1990 are reviewed in this article under the following headings: TRH-R gene, tissue distribution of TRH-R, primary structure of TRH-Rs, three-dimensional structure of the TRH-R binding pocket, TRH-R and G proteins, TRH-R activation, TRH desensitization, TRH-R endocytosis, and regulation of TRH-R number. It is evident that many new insights into the structure, function, and regulation of TRH-Rs have been gained in the last several years but that our understanding of these processes is incomplete. We look forward to even greater progress in the future.
Regulation of protein transport to the nucleus: central role of phosphorylation
Authors: Jans D. A. , Hubner S.
Published: December 2017

Nuclear protein transport is integral to eukaryotic cell processes such as differentiation, transformation, and the control of gene expression. Although the targeting role of nuclear localization signals (NLSs) has been known for some time, more recent results indicate that NLS-dependent nuclear protein import is precisely regulated. Phosphorylation appears to be the main mechanism controlling the nuclear transport of a number of proteins, including transcription factors such as NFkappaB, c-rel, dorsal, and SWI5 from yeast. Cytoplasmic retention factors, intra- and intermolecular NLS masking, and NLS masking by phosphorylation are some of the mechanisms by which phosphorylation specifically regulates nuclear transport. Even nuclear localization of the archetypal NLS-containing simian virus 40 large tumor antigen (T-ag) is regulated, namely by the "CcN motif," which comprises the T-ag NLS ("N") determining ultimate subcellular destination, a casein kinase II site ("C") 13 amino acids NH2-terminal to the NLS modulating the rate of nuclear import, and a cyclin-dependent kinase site ("c") adjacent to the NLS regulating the maximal level of nuclear accumulation. The CcN motif appears to be a special form of phosphorylation-regulated NLS (prNLS), where phosphorylation at site(s) close to the NLS specifically regulates NLS function. The regulation of nuclear transport through phosphorylation and prNLSs appears to be common in eukaryotic cells from yeast and plants to higher mammals.
Genetic and functional changes in mitochondria associated with aging
Authors: Ozawa T.
Published: December 2017

This review is devoted to the molecular genetics and bioenergetics of human mitochondria related to the mechanism of aging. Morphological and functional changes of mitochondria associated with age and age-related disease are overviewed with special reference to the changes in enzymes encoded by mitochondrial-inherent genome. The somatically acquired mutations and oxidative damage of the genome, which lead an individual to the fragmentation of mitochondrial DNA, cellular energy crisis, naturally occurring cell death (apoptosis), and tissue degeneration and atrophy, are reviewed with relation to the inherited point mutational genotypes and the deletion types of mitochondrial DNA. Theories of aging are discussed with disclosed evidence relevant to them. Some trials to prevent age-related damage in mitochondria are introduced for the development of what may be called mitochondrial medicine.
Kinetics of the multidrug transporter (P-glycoprotein) and its reversal
Authors: Stein W. D.
Published: December 2017

Most cancer deaths result from the cancer's either being intrinsically resistant to chemotherapeutic drugs or becoming resistant after being initially sensitive. Often, in cells grown in cell culture, drug resistance correlates with the presence of one or more of the so-called P-glycoproteins or multidrug resistance proteins, products of the mdr family of genes. This review is largely concerned with the transport kinetics of the P-glycoproteins. We first present a brief overview of the P-glycoproteins, their properties, and their clinical significance. Later sections of the review expand on this material with special emphasis on the substrates of P-glycoprotein and how they cross the cell membrane, on the transport kinetics of the P-glycoprotein, on reversers of its action, and on its activity as an ATPase. In a final section, we consider the mechanism of action of P-glycoprotein as an actively transporting membrane pump. The characteristic of P-glycoprotein considered the most difficult to explain is its very broad specificity (or lack of specificity), but there are precedents for this property in well-known proteins such as serum albumin, which binds a range of molecular types, including substrates and reversers of P-glycoprotein, seemingly as broad as does P-glycoprotein. Pointing out this analogy does not provide a molecular explanation for the substrate-binding properties of P-glycoprotein but does make those properties more assimilable.
Retrograde Signaling in the Development and Modification of Synapses
Authors: FITZSIMONDS REIKO MAKI , POO MU-MING
Published: December 2017

Fitzsimonds, Reiko Maki, and Mu-ming Poo. Retrograde Signaling in the Development and Modification of Synapses. Physiol. Rev. 78: 143–170, 1998. — Retrograde signaling from the postsynaptic cell to the presynaptic neuron is essential for the development, maintenance, and activity-dependent modification of synaptic connections. This review covers various forms of retrograde interactions at developing and mature synapses. First, we discuss evidence for early retrograde inductive events during synaptogenesis and how maturation of presynaptic structure and function is affected by signals from the postsynaptic cell. Second, we review the evidence that retrograde interactions are involved in activity-dependent synapse competition and elimination in developing nervous systems and in long-term potentiation and depression at mature synapses. Third, we review evidence for various forms of retrograde signaling via membrane-permeant factors, secreted factors, and membrane-bound factors. Finally, we discuss the evidence and physiological implications of the long-range propagation of retrograde signals to the cell body and other parts of the presynaptic neuron.
Transporters for Cationic Amino Acids in Animal Cells: Discovery, Structure, and Function
Authors: DEVÉS R. , BOYD C. A. R.
Published: December 2017

Devés, R., and C. A. R. Boyd. Transporters for Cationic Amino Acids in Animal Cells: Discovery, Structure, and Function. Physiol. Rev. 78: 487–545, 1998. — The structure and function of the four cationic amino acid transporters identified in animal cells are discussed. The systems differ in specificity, cation dependence, and physiological role. One of them, system y+, is selective for cationic amino acids, whereas the others (B0,+, b0,+, and y+L) also accept neutral amino acids. In recent years, cDNA clones related to these activities have been isolated. Thus two families of proteins have been identified: 1) CAT or cationic amino acid transporters and 2) BAT or broad-scope transport proteins. In the CAT family, three genes encode for four different isoforms [CAT-1, CAT-2A, CAT-2(B) and CAT-3]; these are ∼70-kDa proteins with multiple transmembrane segments ( 12 – 14 ), and despite their structural similarity, they differ in tissue distribution, kinetics, and regulatory properties. System y+is the expression of the activity of CAT transporters. The BAT family includes two isoforms (rBAT and 4F2hc); these are 59- to 78-kDa proteins with one to four membrane-spanning segments, and it has been proposed that these proteins act as transport regulators. The expression of rBAT and 4F2hc induces system b0,+and system y+L activity in Xenopus laevis oocytes, respectively. The roles of these transporters in nutrition, endocrinology, nitric oxide biology, and immunology, as well as in the genetic diseases cystinuria and lysinuric protein intolerance, are reviewed. Experimental strategies, which can be used in the kinetic characterization of coexpressed transporters, are also discussed.
Cellular Mechanisms of Melatonin Action
Authors: VANECEK JIRI
Published: December 2017

Vanecek, Jiri. Cellular Mechanisms of Melatonin Action. Physiol. Rev. 78: 687–721, 1998. — The pineal hormone melatonin is involved in photic regulations of various kinds, including adaptation to light intensity, daily changes of light and darkness, and seasonal changes of photoperiod lengths. The melatonin effects are mediated by the specific high-affinity receptors localized on plasma membrane and coupled to GTP-binding protein. Two different G proteins coupled to the melatonin receptors have been described, one sensitive to pertussis toxin and the other sensitive to cholera toxin. On the basis of the molecular structure, three subtypes of the melatonin receptors have been described: Mel1A, Mel1B, and Mel1C. The first two subtypes are found in mammals and may be distinguished pharmacologically using selective antagonists. Melatonin receptor regulates several second messengers: cAMP, cGMP, diacylglycerol, inositol trisphosphate, arachidonic acid, and intracellular Ca2+concentration ([Ca2+]i). In many cases, its effect is inhibitory and requires previous activation of the cell by a stimulatory agent. Melatonin inhibits cAMP accumulation in most of the cells examined, but the indole effects on other messengers have been often observed only in one type of the cells or tissue, until now. Melatonin also regulates the transcription factors, namely, phosphorylation of cAMP-responsive element binding protein and expression of c-Fos. Molecular mechanisms of the melatonin effects are not clear but may involve at least two parallel transduction pathways, one inhibiting adenylyl cyclase and the other regulating phospholipide metabolism and [Ca2+]i.
Biology of Somatotropin in Growth and Lactation of Domestic Animals
Authors: ETHERTON TERRY D. , BAUMAN DALE E.
Published: December 2017

Etherton, Terry D., and Dale E. Bauman. Biology of Somatotropin in Growth and Lactation of Domestic Animals. Physiol. Rev. 78: 745–761, 1998. — Impressive progress has been made during the past 15 years in our understanding of the biology of somatotropin (ST) in domestic animals. In part, this progress was sparked by advances in biotechnology that made feasible the production of large quantities of recombinant bovine ST (bST) and porcine ST (pST). The availability of recombinant bST and pST resulted in an exponential increase in investigations that explored their role in growth and lactation biology, as well as evaluated their potential for commercial use. Collectively, these studies established that administration of bST to lactating dairy cows increased milk yield, and treatment of growing pigs with pST markedly stimulated muscle growth and reduced fat deposition. In addition to these “efficacy” studies, a substantial number of investigations examined the mechanisms by which ST affects lactation and growth of domestic animals. This review summarizes the diverse physiological effects ST has on growth and lactation and discusses the underlying mechanisms that mediate these effects in domestic animals.
Hibernating Myocardium
Authors: HEUSCH GERD
Published: December 2017

Heusch, Gerd. Hibernating Myocardium. Physiol. Rev. 78: 1055–1085, 1998. — Decreased myocardial contraction occurs as a consequence of a reduction in blood flow. The concept of hibernation implies a downregulation of contractile function as an adaptation to a reduction in myocardial blood flow that serves to maintain myocardial integrity and viability during persistent ischemia. Unequivocal evidence for this concept exists in scenarios of myocardial ischemia that lasts for several hours, and sustained perfusion-contraction matching, recovery of energy and substrate metabolism, the potential for recruitment of inotropic reserve at the expense of metabolic recovery, and lack of necrosis are established criteria of short-term hibernation. The mechanisms of short-term hibernation, apart from reduced calcium responsiveness, are not clear at present. Experimental studies with chronic coronary stenosis lasting more than several hours have failed to continuously monitor flow and function. Nevertheless, a number of studies in chronic animal models and patients have demonstrated regional myocardial dysfunction at reduced resting blood flow that recovered upon reperfusion, consistent with chronic hibernation. Further studies are required to distinguish chronic hibernation from cumulative stunning. With a better understanding of the mechanisms underlying short-term hibernation, it is hoped that these adaptive responses can be recruited and reinforced to minimize the consequences of acute myocardial ischemia and delay impending infarction. Patients with chronic hibernation must be identified and undergo adequate reperfusion therapy.
The New Biology of Gastrointestinal Hormones
Authors: REHFELD JENS F.
Published: December 2017

Rehfeld, Jens F. The New Biology of Gastrointestinal Hormones. Physiol. Rev. 78: 1087–1108, 1998. — The classic concept of gastrointestinal endocrinology is that of a few peptides released to the circulation from endocrine cells, which are interspersed among other mucosal cells in the upper gastrointestinal tract. Today more than 30 peptide hormone genes are known to be expressed throughout the digestive tract, which makes the gut the largest endocrine organ in the body. Moreover, development in cell and molecular biology now makes it feasible to describe a new biology for gastrointestinal hormones based on five characteristics. 1) The structural homology groups the hormones into families, each of which is assumed to originate from a common ancestral gene. 2) The individual hormone gene is often expressed in multiple bioactive peptides due to tandem genes encoding different hormonal peptides, alternative splicing of the primary transcript, or differentiated processing of the primary translation product. By these mechanisms, more than 100 different hormonally active peptides are produced in the gastrointestinal tract. 3) In addition, gut hormone genes are widely expressed, also outside the gut. Some are expressed only in neuroendocrine cells, whereas others are expressed in a multitude of different cells, including cancer cells. 4) The different cell types often express different products of the same gene, “cell-specific expression.” 5) Finally, gastrointestinal hormone-producing cells release the peptides in different ways, so the same peptide may act as an acute blood-borne hormone, as a local growth factor, as a neurotransmitter, and as a fertility factor. The new biology suggests that gastrointestinal hormones should be conceived as intercellular messengers of general physiological impact rather than as local regulators of the upper digestive tract.
Microtubule-Dependent Vesicle Transport: Modulation of Channel and Transporter Activity in Liver and Kidney
Authors: HAMM-ALVAREZ SARAH F. , SHEETZ MICHAEL P.
Published: December 2017

Hamm-Alvarez, Sarah F., and Michael P. Sheetz. Microtubule-Dependent Vesicle Transport: Modulation of Channel and Transporter Activity in Liver and Kidney. Physiol. Rev. 78: 1109–1129, 1998. — Microtubule-based vesicle transport driven by kinesin and cytoplasmic dynein motor proteins facilitates several membrane-trafficking steps including elements of endocytosis and exocytosis in many different cell types. Most early studies on the role of microtubule-dependent vesicle transport in membrane trafficking focused either on neurons or on simple cell lines. More recently, other work has considered the role of microtubule-based vesicle transport in other physiological systems, including kidney and liver. Investigation of the role of microtubule-based vesicle transport in membrane trafficking in cells of the kidney and liver suggests a major role for microtubule-based vesicle transport in the rapid and directed movement of ion channels and transporters to and from the apical plasma membranes, events essential for kidney and liver function and homeostasis. This review discusses the evidence supporting a role for microtubule-based vesicle transport and the motor proteins, kinesin and cytoplasmic dynein, in different aspects of membrane trafficking in cells of the kidney and liver, with emphasis on those functions such as maintenance of ion channel and transporter composition in apical membranes that are specialized functions of these organs. Evidence that defects in microtubule-based transport contribute to diseases of the kidney and liver is also discussed.