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Charles D Warne, Sophie G Zaloumis, Nadine A Bertalli, Martin B Delatycki, Amanda J Nicoll, Christine E McLaren, John L Hopper, Graham G Giles, Greg J Anderson, John K Olynyk, Lawrie W Powell, Katrina J Allen, Lyle C Gurrin
BACKGROUND AND AIM: Women who are homozygous for the p.C282Y mutation in the HFE gene are at much lower risk of iron overload-related disease than p.C282Y homozygous men, presumably due to the iron-depleting effects of menstruation and pregnancy. We used data from a population cohort study to model the impact of menstruation cessation at menopause on serum ferritin (SF) levels in female p.C282Y homozygotes, with p.C282Y/p.H63D simple or compound heterozygotes and those with neither p...
October 26, 2016: Journal of Gastroenterology and Hepatology
Romain Da Costa, Carsten Röger, Jasmin Segelken, Maya Barben, Christian Grimm, John Neidhardt
Purpose: Gene therapies to treat eye disorders have been extensively studied in the past 20 years. Frequently, adeno-associated viruses were applied to the subretinal or intravitreal space of the eye to transduce retinal cells with nucleotide sequences of therapeutic potential. In this study we describe a novel intravitreal injection procedure that leads to a reproducible adeno-associated virus (AAV)2/8-mediated transduction of more than 70% of the retina. Methods: Prior to a single intravitreal injection of a enhanced green fluorescent protien (GFP)-expressing viral suspension, we performed an aspiration of vitreous tissue from wild-type C57Bl/6J mice...
October 1, 2016: Investigative Ophthalmology & Visual Science
Maruška Budič, Blaž Cigić, Maja Šoštarič, Jerica Sabotič, Vladimir Meglič, Janko Kos, Marjetka Kidrič
Aminopeptidases, together with other proteases, execute and regulate the total and specifically limited protein breakdown involved in plant physiology, raising the possibility of their involvement in response to drought. We have identified, in leaves of Phaseolus vulgaris L., five aminopeptidases (E.C.3.4.11) whose levels of activity changed when three week old plants were subjected to drought. First, second and third trifoliate leaves were investigated separately. The aminopeptidases were first identified then isolated using ion exchange chromatography of leaf extracts...
October 13, 2016: Plant Physiology and Biochemistry: PPB
Isabella Maiellaro, Martin J Lohse, Robert J Kittel, Davide Calebiro
The second messenger cyclic AMP (cAMP) plays an important role in synaptic plasticity. Although there is evidence for local control of synaptic transmission and plasticity, it is less clear whether a similar spatial confinement of cAMP signaling exists. Here, we suggest a possible biophysical basis for the site-specific regulation of synaptic plasticity by cAMP, a highly diffusible small molecule that transforms the physiology of synapses in a local and specific manner. By exploiting the octopaminergic system of Drosophila, which mediates structural synaptic plasticity via a cAMP-dependent pathway, we demonstrate the existence of local cAMP signaling compartments of micrometer dimensions within single motor neurons...
October 25, 2016: Cell Reports
Alexandre Fisette, Stephanie Tobin, Léa Décarie-Spain, Khalil Bouyakdan, Marie-Line Peyot, S R Murthy Madiraju, Marc Prentki, Stephanie Fulton, Thierry Alquier
α/β-Hydrolase domain 6 (ABHD6) is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMH(KO)) have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges...
October 25, 2016: Cell Reports
Karolina A Majorek, Tomasz Osinski, David T Tran, Alina Revilla, Wayne F Anderson, Wladek Minor, Misty L Kuhn
Members of Gcn5-related N-acetyltransferase (GNAT) superfamily catalyze the acetylation of a wide range of small molecule and protein substrates. Due to their abundance in all kingdoms of life and diversity of their functions, they are implicated in many aspects of eukaryotic and prokaryotic physiology. Although numerous GNATs have been identified thus far, many remain structurally and functionally uncharacterized. The elucidation of their structures and functions is critical for broadening our knowledge of this diverse and important superfamily...
October 23, 2016: Biochimica et Biophysica Acta
Carlos Fernandez-Patron, Zamaneh Kassiri, Dickson Leung
Matrix metalloproteinase-2 (MMP-2) is a 72-kDa zinc- and calcium-dependent endopeptidase with intracellular and extracellular functions ranging from the modulation of extracellular matrix remodeling to cell growth and migration, angiogenesis, inflammation, and metabolism. An upregulation of MMP-2 activity has the potential to deregulate lipid metabolism through the cleavage of numerous metabolic mediators including plasma lipoproteins and cell surface receptors of lipoproteins. Paradoxically, MMP-2 deficiency induces inflammation and deregulates metabolism...
September 15, 2016: Comprehensive Physiology
Amy E B Packard, Ann E Egan, Yvonne M Ulrich-Lai
Perhaps the most salient behaviors that individuals engage in involve the avoidance of aversive experiences and the pursuit of pleasurable experiences. Engagement in these behaviors is regulated to a significant extent by an individual's hormonal milieu. For example, glucocorticoid hormones are produced by the hypothalamic-pituitary-adrenocortical (HPA) axis, and influence most aspects of behavior. In turn, many behaviors can influence HPA axis activity. These bidirectional interactions not only coordinate an individual's physiological and behavioral states to each other, but can also tune them to environmental conditions thereby optimizing survival...
September 15, 2016: Comprehensive Physiology
Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
Emma Monte, Manuel Rosa Garrido, Thomas M Vondriska, Jessica Wang
The past two decades have witnessed a rapid evolution in our ability to measure RNA and protein from biological systems. As a result, new principles have arisen regarding how information is processed in cells, how decisions are made, and the role of networks in biology. This essay examines this technological evolution, reviewing (and critiquing) the conceptual framework that has emerged to explain how RNA and protein networks control cellular function. We identify how future investigations into transcriptomes, proteomes, and other cellular networks will enable development of more robust, quantitative models of cellular behavior whilst also providing new avenues to use knowledge of biological networks to improve human health...
September 15, 2016: Comprehensive Physiology
Leszek Kubin
Upper airway muscles subserve many essential for survival orofacial behaviors, including their important role as accessory respiratory muscles. In the face of certain predisposition of craniofacial anatomy, both tonic and phasic inspiratory activation of upper airway muscles is necessary to protect the upper airway against collapse. This protective action is adequate during wakefulness, but fails during sleep which results in recurrent episodes of hypopneas and apneas, a condition known as the obstructive sleep apnea syndrome (OSA)...
September 15, 2016: Comprehensive Physiology
Sharon M Moe
Calcium is an important ion in cell signaling, hormone regulation, and bone health. Its regulation is complex and intimately connected to that of phosphate homeostasis. Both ions are maintained at appropriate levels to maintain the extracellular to intracellular gradients, allow for mineralization of bone, and to prevent extra skeletal and urinary calcification. The homeostasis involves the target organs intestine, parathyroid glands, kidney, and bone. Multiple hormones converge to regulate the extracellular calcium level: parathyroid hormone, vitamin D (principally 25(OH)D or 1,25(OH)2D), fibroblast growth factor 23, and α-klotho...
September 15, 2016: Comprehensive Physiology
Salma Ayoub, Giovanni Ferrari, Robert C Gorman, Joseph H Gorman, Frederick J Schoen, Michael S Sacks
Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical environment of the heart, achieving lifetime durability by processes involving the ongoing remodeling of the extracellular matrix. The focus of this review is on heart valve functional physiology, with insights into the link between disease-induced alterations in valve geometry, tissue stress, and the subsequent cell mechanobiological responses and tissue remodeling...
September 15, 2016: Comprehensive Physiology
Colin H Brown
The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus...
September 15, 2016: Comprehensive Physiology
Heinrich Taegtmeyer, Truong Lam, Giovanni Davogustto
The heart is a biological pump that converts chemical to mechanical energy. This process of energy conversion is highly regulated to the extent that energy substrate metabolism matches energy use for contraction on a beat-to-beat basis. The biochemistry of cardiac metabolism includes the biochemistry of energy transfer, metabolic regulation, and transcriptional, translational as well as posttranslational control of enzymatic activities. Pathways of energy substrate metabolism in the heart are complex and dynamic, but all of them conform to the First Law of Thermodynamics...
September 15, 2016: Comprehensive Physiology
James M Holaska
The nucleus is separated from the cytosol by the nuclear envelope, which is a double lipid bilayer composed of the outer nuclear membrane and the inner nuclear membrane. The intermediate filament proteins lamin A, lamin B, and lamin C form a network underlying the inner nuclear membrane. This proteinaceous network provides the nucleus with its strength, rigidity, and elasticity. Positioned within the inner nuclear membrane are more than 150 inner nuclear membrane proteins, many of which interact directly with lamins and require lamins for their inner nuclear membrane localization...
September 15, 2016: Comprehensive Physiology
Jeffrey L Ardell, John Andrew Armour
Cardiac control is mediated via a series of reflex control networks involving somata in the (i) intrinsic cardiac ganglia (heart), (ii) intrathoracic extracardiac ganglia (stellate, middle cervical), (iii) superior cervical ganglia, (iv) spinal cord, (v) brainstem, and (vi) higher centers. Each of these processing centers contains afferent, efferent, and local circuit neurons, which interact locally and in an interdependent fashion with the other levels to coordinate regional cardiac electrical and mechanical indices on a beat-to-beat basis...
September 15, 2016: Comprehensive Physiology
G F Gebhart, Klaus Bielefeldt
Pain involving thoracic, abdominal, or pelvic organs is a common cause for physician consultations, including one-third of chronic pain patients who report that visceral organs contribute to their suffering. Chronic visceral pain conditions are typically difficult to manage effectively, largely because visceral sensory mechanisms and factors that contribute to the pathogenesis of visceral pain are poorly understood. Mechanistic understanding is particularly problematic in "functional" visceral diseases where there is no apparent pathology and pain typically is the principal complaint...
September 15, 2016: Comprehensive Physiology
Antonia Lanni, Maria Moreno, Fernando Goglia
The hypermetabolic effects of thyroid hormones (THs), the major endocrine regulators of metabolic rate, are widely recognized. Although, the cellular mechanisms underlying these effects have been extensively investigated, much has yet to be learned about how TH regulates diverse cellular functions. THs have a profound impact on mitochondria, the organelles responsible for the majority of cellular energy production, and several studies have been devoted to understand the respective importance of the nuclear and mitochondrial pathways for organelle activity...
September 15, 2016: Comprehensive Physiology
María V Cardo, Alejandra Rubio, Melania Junges, Darío Vezzani, Aníbal E Carbajo
Given their medical and veterinary relevance, the members of the Pipiens Assemblage are a worldwide target of ecological research. The distribution of Culex pipiens s.s. and Cx. quinquefasciatus converge in Buenos Aires, Argentina, where hybrids have been detected. Each member of the assemblage exhibits a distinct eco-physiological behaviour that can affect its efficiency in pathogen transmission. Our aim was to identify the environmental drivers for the spatio-temporal distribution of each member, focusing on latitudinal and urbanisation gradients...
October 24, 2016: Memórias do Instituto Oswaldo Cruz
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