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https://www.readbyqxmd.com/read/28930573/molecular-biology-of-amitraz-resistance-in-cattle-ticks-of-the-genus-rhipicephalus
#1
Nicholas N Jonsson, Guilherme Klafke, Sean W Corley, Jason Tidwell, Christina M Berry, Hh Caline Koh-Tan
Amitraz is an important product for the control of cattle ticks around the world. In comparison with other products for the control of ticks, it is quite affordable and it has a rapid knock-down effect. It binds with and activates adrenergic neuro-receptors of animals and it inhibits the action of monoamine oxidases (MAO). Resistance to amitraz has been documented in Rhipicephalus microplus, R. decoloratus and R. appendiculatus. Four mechanisms of resistance have been proposed, each of which is supported by evidence but none of which has been definitively confirmed as the cause of resistance in the field...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28918935/dense-intra-adipose-sympathetic-arborizations-are-essential-for-cold-induced-beiging-of-mouse-white-adipose-tissue
#2
Haochen Jiang, Xiaofan Ding, Ying Cao, Huanhuan Wang, Wenwen Zeng
Efferent signals from the central nervous system represent a key layer of regulation of white adipose tissue (WAT). However, the mechanism by which efferent neural signals control WAT metabolism remains to be better understood. Here, we exploit the volume fluorescence-imaging technique to visualize the neural arborizations in mouse inguinal WAT at single-fiber resolution. The imaging reveals a dense network of sympathetic arborizations that had been previously undetected by conventional methods, with sympathetic fibers being in close apposition to > 90% of adipocytes...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28917508/insulin-dependent-metabolic-and-inotropic-responses-in-the-heart-are-modulated-by-hydrogen-peroxide-from-nadph-oxidase-isoforms-nox2-and-nox4
#3
Benjamin Steinhorn, Juliano L Sartoretto, Andrea Sorrentino, Natalia Romero, Hermann Kalwa, E Dale Abel, Thomas Michel
RATIONALE: Hydrogen peroxide (H2O2) is a stable reactive oxygen species (ROS) that has long been implicated in insulin signal transduction in adipocytes. However, H2O2's role in mediating insulin's effects on the heart are unknown. OBJECTIVE: We investigated the role of H2O2 in activating insulin-dependent changes in cardiac myocyte metabolic and inotropic pathways. The sources of insulin-dependent H2O2 generation were also studied. METHODS AND RESULTS: In addition to the canonical role of insulin in modulating cardiac metabolic pathways, we found that insulin also inhibited beta adrenergic-induced increases in cardiac contractility...
September 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28895001/regulation-of-hypothalamo-pituitary-adrenocortical-responses-to-stressors-by-the-nucleus-of-the-solitary-tract-dorsal-vagal-complex
#4
REVIEW
James P Herman
Hindbrain neurons in the nucleus of the solitary tract (NTS) are critical for regulation of hypothalamo-pituitary-adrenocortical (HPA) responses to stress. It is well known that noradrenergic (as well as adrenergic) neurons in the NTS send direct projections to hypophysiotropic corticotropin-releasing hormone (CRH) neurons and control activation of HPA axis responses to acute systemic (but not psychogenic) stressors. Norepinephrine (NE) signaling via alpha1 receptors is primarily excitatory, working either directly on CRH neurons or through presynaptic activation of glutamate release...
September 11, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28891646/synergic-click-boronate-thiosemicarbazone-system-for-fast-and-irreversible-bioorthogonal-conjugation-in-live-cells
#5
Burcin Akgun, Caishun Li, Yubin Hao, Gareth Lambkin, Ratmir Derda, Dennis G Hall
Fast, high-yielding and selective bioorthogonal 'click' reactions employing non-toxic reagents are in high demand for their great utility in the bioconjugation of biomolecules in live cells. Although a number of click reactions were developed for this purpose, many are associated with drawbacks and limitations that justify the development of alternative systems for both single- or dual-labeling applications. Recent reports highlighted the potential of boronic ester formation as a bioorthogonal click reaction between abiotic boronic acids and diols...
September 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28874749/structural-and-pharmacological-basis-for-the-induction-of-mitochondrial-biogenesis-by-formoterol-but-not-clenbuterol
#6
Robert B Cameron, Craig C Beeson, Rick G Schnellmann
Mitochondrial dysfunction is associated with numerous acute and chronic degenerative diseases. The beta-2 adrenergic receptor (β2AR) agonist formoterol induces mitochondrial biogenesis (MB), but other β2AR agonists, such as clenbuterol, do not. We sought to identify the MB signaling pathway of formoterol and the differences in signaling between these two ligands that result in the differential induction of MB. While formoterol and clenbuterol increased cAMP, only formoterol increased the phosphorylation of Akt and its downstream target eNOS...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870238/bet-bromodomain-inhibitors-and-agonists-of-the-beta-2-adrenergic-receptor-identified-in-screens-for-compounds-that-inhibit-dux4-expression-in-fshd-muscle-cells
#7
Amy E Campbell, Jonathan Oliva, Matthew P Yates, Jun Wen Zhong, Sean C Shadle, Lauren Snider, Nikita Singh, Shannon Tai, Yosuke Hiramuki, Rabi Tawil, Silvère M van der Maarel, Stephen J Tapscott, Francis M Sverdrup
BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is a progressive muscle disease caused by mutations that lead to epigenetic derepression and inappropriate transcription of the double homeobox 4 (DUX4) gene in skeletal muscle. Drugs that enhance the repression of DUX4 and prevent its expression in skeletal muscle cells therefore represent candidate therapies for FSHD. METHODS: We screened an aggregated chemical library enriched for compounds with epigenetic activities and the Pharmakon 1600 library composed of compounds that have reached clinical testing to identify molecules that decrease DUX4 expression as monitored by the levels of DUX4 target genes in FSHD patient-derived skeletal muscle cell cultures...
September 4, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28854858/history-of-vascular-reactivity-models-and-their-involvement-in-hypertension-pathogenesis
#8
Ana Gabriela Conceição-Vertamatti, Filipy Borghi, Fernando Canova, Dora Maria Grassi-Kassisse
Hypertension is a silent and multifactorial disease. Over two centuries ago, the first device to record blood pressure was developed, making it possible to determine normotension and to establish criteria for hypertension. Since then, several studies have contributed to advance knowledge in this area, promoting significant advances in pharmacological treatments and, as a result, increasing survival of hypertensive people. The main models developed for the study of hypertension and the main findings in the vascular area are included in this review...
August 31, 2017: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/28842436/ca-2-calmodulin-kinase-ii-dependent-regulation-of-atrial-myocyte-late-na-current-ca-2-cycling-and-excitability-a-mathematical-modeling-study
#9
Birce Onal, Daniel Gratz, Thomas J Hund
Atrial fibrillation (AF) affects more than 3 million people per year in the U.S., and is associated with high morbidity and mortality. Both electrical and structural remodeling contribute to AF, but the molecular pathways underlying AF pathogenesis are not well understood. Recently, a role for Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in regulation of persistent "late" sodium current (INa,L) has been identified. While INa,L inhibition is emerging as a potential antiarrhythmic strategy in AF patients, little is known about the mechanism linking INa,L to atrial arrhythmogenesis...
August 25, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28813418/mechanism-of-intracellular-allosteric-%C3%AE-2ar-antagonist-revealed-by-x-ray-crystal-structure
#10
Xiangyu Liu, Seungkirl Ahn, Alem W Kahsai, Kai-Cheng Meng, Naomi R Latorraca, Biswaranjan Pani, A J Venkatakrishnan, Ali Masoudi, William I Weis, Ron O Dror, Xin Chen, Robert J Lefkowitz, Brian K Kobilka
G-protein-coupled receptors (GPCRs) pose challenges for drug discovery efforts because of the high degree of structural homology in the orthosteric pocket, particularly for GPCRs within a single subfamily, such as the nine adrenergic receptors. Allosteric ligands may bind to less-conserved regions of these receptors and therefore are more likely to be selective. Unlike orthosteric ligands, which tonically activate or inhibit signalling, allosteric ligands modulate physiologic responses to hormones and neurotransmitters, and may therefore have fewer adverse effects...
August 24, 2017: Nature
https://www.readbyqxmd.com/read/28780421/antihypertensive-drugs
#11
REVIEW
Stéphane Laurent
Successful treatment of hypertension is possible with limited side effects given the availability of multiple antihypertensive drug classes. This review describes the various pharmacological classes of antihypertensive drugs, under two major aspects: their mechanisms of action and side effects. The mechanism of action is analysed through a pharmacological approach, i.e. the molecular receptor targets, the various sites along the arterial system, and the extra-arterial sites of action, in order to better understand in which type of hypertension a given pharmacological class of antihypertensive drug is most indicated...
October 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28752049/beta-adrenergic-receptors-are-critical-for-weight-loss-but-not-for-other-metabolic-adaptations-to-the-consumption-of-a-ketogenic-diet-in-male-mice
#12
Nicholas Douris, Bhavna N Desai, Ffolliott M Fisher, Theodore Cisu, Alan J Fowler, Eleen Zarebidaki, Ngoc Ly T Nguyen, Donald A Morgan, Timothy J Bartness, Kamal Rahmouni, Jeffrey S Flier, Eleftheria Maratos-Flier
OBJECTIVE: We have previously shown that the consumption of a low-carbohydrate ketogenic diet (KD) by mice leads to a distinct physiologic state associated with weight loss, increased metabolic rate, and improved insulin sensitivity [1]. Furthermore, we identified fibroblast growth factor 21 (FGF21) as a necessary mediator of the changes, as mice lacking FGF21 fed KD gain rather than lose weight [2]. FGF21 activates the sympathetic nervous system (SNS) [3], which is a key regulator of metabolic rate...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28746336/discovery-of-novel-brain-permeable-and-g-protein-biased-beta-1-adrenergic-receptor-partial-agonists-for-the-treatment-of-neurocognitive-disorders
#13
Bitna Yi, Alam Jahangir, Andrew K Evans, Denise Briggs, Kristine Ravina, Jacqueline Ernest, Amir B Farimani, Wenchao Sun, Jayakumar Rajadas, Michael Green, Evan N Feinberg, Vijay S Pande, Mehrdad Shamloo
The beta-1 adrenergic receptor (ADRB1) is a promising therapeutic target intrinsically involved in the cognitive deficits and pathological features associated with Alzheimer's disease (AD). Evidence indicates that ADRB1 plays an important role in regulating neuroinflammatory processes, and activation of ADRB1 may produce neuroprotective effects in neuroinflammatory diseases. Novel small molecule modulators of ADRB1, engineered to be highly brain permeable and functionally selective for the G protein with partial agonistic activity, could have tremendous value both as pharmacological tools and potential lead molecules for further preclinical development...
2017: PloS One
https://www.readbyqxmd.com/read/28744157/the-abc7-regimen-a-new-approach-to-metastatic-breast-cancer-using-seven-common-drugs-to-inhibit-epithelial-to-mesenchymal-transition-and-augment-capecitabine-efficacy
#14
Richard E Kast, Nicolas Skuli, Samuel Cos, Georg Karpel-Massler, Yusuke Shiozawa, Ran Goshen, Marc-Eric Halatsch
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28732063/dopamine-acting-at-d1-like-d2-like-and-%C3%AE-1-adrenergic-receptors-differentially-modulates-theta-and-gamma-oscillatory-activity-in-primary-motor-cortex
#15
Mazhar Özkan, Nicholas W Johnson, Umit S Sehirli, Gavin L Woodhall, Ian M Stanford
The loss of dopamine (DA) in Parkinson's is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology...
2017: PloS One
https://www.readbyqxmd.com/read/28720509/the-neuropeptide-galanin-promotes-an-anti-thrombotic-phenotype-on-endocardial-endothelial-cells-from-heart-failure-patients
#16
Christina Tyrrell, Amanda Toyooka, Faiza Khan, Kent L Thornburg, James O Mudd, Wohaib Hasan
Thromboembolic complications are a significant cause of mortality and re-hospitalization in heart failure (HF) patients. One source of thrombi is the ventricular endocardial surface that becomes increasingly pro-thrombotic as HF progresses. Anticoagulation comes with bleeding risks so identifying therapeutic agents for improving cardiac endothelial health are of critical clinical importance. Endocardial endothelial cells are closely apposed to cardiac sympathetic nerves. In HF, cardiac sympathetic nerves are dysregulated and promote disease progression...
September 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28699713/-potential-role-of-norepinephrine-in-the-immune-dysfunction-associated-with-sepsis
#17
Anna Bauer-Dörries, Sarah De Cupis, Lucas Liaudet
Septic shock may be complicated by a state of immune suppression, with ominous prognosis significance. Although the underlying pathophysiological mechanisms are poorly understood, it is possible that norepinephrine, used to treat circulatory failure during septic shock, plays a significant contributing role. Indeed, besides its hemodynamic effects, norepinephrine exerts multiple immunosuppressive actions, which are primarily mediated by beta-2 adrenergic receptors expressed by immune cells. Furthermore, norepinephrine has the ability to promote the growth of numerous bacteria, and could thereby foster the development of nosocomial infections...
July 12, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28670631/cardiac-directed-expression-of-adenylyl-cyclase-catalytic-domain-reverses-cardiac-dysfunction-caused-by-sustained-beta-adrenergic-receptor-stimulation
#18
Mei Hua Gao, N Chin Lai, Dimosthenis Giamouridis, Young Chul Kim, Zhen Tan, Tracy Guo, Wolfgang H Dillmann, Jorge Suarez, H Kirk Hammond
OBJECTIVE: To test the hypothesis that cardiac-directed expression of the cytoplasmic domains of adenylyl cyclase-6 (AC6) would have beneficial effects on the heart. BACKGROUND: Eliminating the two transmembrane domains of AC6 yields a protein with an intact catalytic domain that is disengaged from membrane-associated β-adrenergic receptor stimulation, but with enhanced propensity for intracellular interactions. METHODS: We constructed a peptide of the C1 and C2 segments of AC6 (C1C2), expressed C1C2 in an adenovirus vector and generated transgenic lines with cardiac-directed C1C2 expression, which underwent sustained isoproterenol (Iso) infusion...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28664928/co-activation-of-metabotropic-glutamate-receptor-3-and-beta-adrenergic-receptors-modulates-cyclic-amp-long-term-potentiation-and-disrupts-memory-reconsolidation
#19
Adam G Walker, Douglas J Sheffler, Andrew S Lewis, Jonathan W Dickerson, Daniel J Foster, Rebecca K Senter, Mark S Moehle, Xiaohui Lv, Branden J Stansley, Zixiu Xiang, Jerri M Rook, Kyle A Emmitte, Craig W Lindsley, P Jeffrey Conn
Activation of β-adrenergic receptors (βARs) enhances both the induction of long-term potentiation (LTP) in hippocampal CA1 pyramidal cells and hippocampal-dependent cognitive function. Interestingly, previous studies reveal that coincident activation of group II metabotropic glutamate (mGlu) receptors with βARs in the hippocampal astrocytes induces a large increase in cyclic-AMP (cAMP) accumulation and release of adenosine. Adenosine then acts on A1 adenosine receptors at neighboring excitatory Schaffer collateral terminals, which could counteract effects of activation of neuronal βARs on excitatory transmission...
June 30, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28641581/thyrotoxic-and-pheochromocytoma-multisystem-crisis-a-case-report
#20
Kodai Suzuki, Takahito Miyake, Hideshi Okada, Fuminori Yamaji, Yuichiro Kitagawa, Tetsuya Fukuta, Ryu Yasuda, Yoshihito Tanaka, Haruka Okamoto, Sho Nachi, Tomoaki Doi, Takahiro Yoshida, Keisuke Kumada, Shozo Yoshida, Hiroaki Ushikoshi, Izumi Toyoda, Shinji Ogura
BACKGROUND: Thyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management. CASE PRESENTATION: A 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming...
June 23, 2017: Journal of Medical Case Reports
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