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https://www.readbyqxmd.com/read/29642692/noncardiac-chest-pain-a-2018-update
#1
Marilena Durazzo, Giuseppe Gargiulo, Rinaldo Pellicano
Noncardiac chest pain (NCCP) is defined as recurring, angina-like, chest pain of noncardiac origin. Studies have estimated that gastroesophageal reflux disease (GERD) is the most common contributing factor for NCCP. In patients with non-GERD related NCCP, esophageal motility disorders, and functional chest pain (FCP) of presumed esophageal origin are the main underlying mechanisms for symptoms. Epidemiologic studies show a high prevalence of panic disorder, anxiety and major depression in NCCP patients. The diagnostic esophageal workup starts only after that cardiac and pulmonary diseases have been ruled out...
April 11, 2018: Minerva Cardioangiologica
https://www.readbyqxmd.com/read/29621672/oyster-transcriptome-response-to-alexandrium-exposure-is-related-to-saxitoxin-load-and-characterized-by-disrupted-digestion-energy-balance-and-calcium-and-sodium-signaling
#2
Audrey M Mat, Christophe Klopp, Laura Payton, Céline Jeziorski, Morgane Chalopin, Zouher Amzil, Damien Tran, Gary H Wikfors, Hélène Hégaret, Philippe Soudant, Arnaud Huvet, Caroline Fabioux
Harmful Algal Blooms are worldwide occurrences that can cause poisoning in human seafood consumers as well as mortality and sublethal effets in wildlife, propagating economic losses. One of the most widespread toxigenic microalgal taxa is the dinoflagellate Genus Alexandrium, that includes species producing neurotoxins referred to as PST (Paralytic Shellfish Toxins). Blooms cause shellfish harvest restrictions to protect human consumers from accumulated toxins. Large inter-individual variability in toxin load within an exposed bivalve population complicates monitoring of shellfish toxicity for ecology and human health regulation...
March 27, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29616558/synthetic-analogs-of-the-snail-toxin-6-bromo-2-mercaptotryptamine-dimer-brmt-reveal-that-lipid-bilayer-perturbation-does-not-underlie-its-modulation-of-voltage-gated-potassium-channels
#3
Christopher Dockendorff, Disha Manoj Gandhi, Ian H Kimball, Kenneth S Eum, Radda Rusinova, Helgi I Ingólfsson, Ruchi Kapoor, Thasin Peyear, Matthew W Dodge, Stephen F Martin, Richard Aldrich, Olaf S Andersen, Jon T Sack
Drugs do not act solely by canonical ligand-receptor binding interactions. Amphiphilic drugs partition into membranes thereby perturbing bulk lipid bilayer properties and possibly altering the function of membrane proteins. Distinguishing membrane perturbation from more direct protein-ligand interactions is an ongoing challenge in chemical biology. Herein, we present one strategy for doing so using dimeric 6-bromo-2-mercaptotryptamine (BrMT) and synthetic analogs. BrMT is a chemically unstable marine snail toxin that has unique effects on voltage-gated K+ channel proteins, making it an attractive medicinal chemistry lead...
April 4, 2018: Biochemistry
https://www.readbyqxmd.com/read/29608274/azide-alkyne-click-conjugation-on-quantum-dots-by-selective-copper-coordination
#4
Victor R Mann, Alexander S Powers, Drew C Tilley, Jon T Sack, Bruce E Cohen
Functionalization of nanocrystals is essential for their practical application, but synthesis on nanocrystal surfaces is limited by incompatibilities with certain key reagents. The copper-catalyzed azide-alkyne cycloaddition is among the most useful methods for ligating molecules to surfaces, but has been largely useless for semiconductor quantum dots (QDs) because Cu+ ions quickly and irreversibly quench QD fluorescence. To discover nonquenching synthetic conditions for Cu-catalyzed click reactions on QD surfaces, we developed a combinatorial fluorescence assay to screen >2000 reaction conditions to maximize cycloaddition efficiency while minimizing QD quenching...
April 4, 2018: ACS Nano
https://www.readbyqxmd.com/read/29605457/arthropod-toxins-and-their-antinociceptive-properties-from-venoms-to-painkillers
#5
REVIEW
Victoria Monge-Fuentes, Claudia Arenas, Priscilla Galante, Jacqueline Coimbra Gonçalves, Márcia Renata Mortari, Elisabeth Ferroni Schwartz
The complex process of pain control commonly involves the use of systemic analgesics; however, in many cases, a more potent and effective polypharmacological approach is needed to promote clinically significant improvement. Additionally, considering side effects caused by current painkillers, drug discovery is once more turning to nature as a source of more efficient therapeutic alternatives. In this context, arthropod venoms contain a vast array of bioactive substances that have evolved to selectively bind to specific pharmacological targets involved in the pain signaling pathway, playing an important role as pain activators or modulators, the latter serving as promising analgesic agents...
March 29, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29604966/anoctamin-9-tmem16j-is-a-cation-channel-activated-by-camp-pka-signal
#6
Hyungsup Kim, Hyesu Kim, Jesun Lee, Byeongjun Lee, Hee-Ryang Kim, Jooyoung Jung, Mi-Ock Lee, Uhtaek Oh
Anoctamins (ANOs) are multifunctional membrane proteins that consist of 10 homologs. ANO1 (TMEM16A) and ANO2 (TMEM16B) are anion channels activated by intracellular calcium that meditate numerous physiological functions. ANO6 is a scramblase that redistributes phospholipids across the cell membrane. The other homologs are not well characterized. We found ANO9/TMEM16J is a cation channel activated by a cAMP-dependent protein kinase A (PKA). Intracellular cAMP-activated robust currents in whole cells expressing ANO9, which were inhibited by a PKA blocker...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29579624/modulating-ion-channel-function-with-antibodies-and-nanobodies
#7
REVIEW
Catelijne Stortelers, Carolina Pinto-Espinoza, Diane Van Hoorick, Friedrich Koch-Nolte
Immune cells express various voltage-gated and ligand-gated ion channels that mediate the influx and efflux of charged ions across the plasma membrane, thereby controlling the membrane potential and mediating intracellular signal transduction pathways. These channels thus present potential targets for experimental modulation of immune responses and for therapeutic interventions in immune disease. Small molecule drugs and natural toxins acting on ion channels have illustrated the potential therapeutic benefit of targeting ion channels on immune cells...
March 23, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29567943/peptide-ion-channel-toxins-from-the-bootlace-worm-the-longest-animal-on-earth
#8
Erik Jacobsson, Håkan S Andersson, Malin Strand, Steve Peigneur, Camilla Eriksson, Henrik Lodén, Mohammadreza Shariatgorji, Per E Andrén, Eline K M Lebbe, K Johan Rosengren, Jan Tytgat, Ulf Göransson
Polypeptides from animal venoms have found important uses as drugs, pharmacological tools, and within biotechnological and agricultural applications. We here report a novel family of cystine knot peptides from nemertean worms, with potent activity on voltage-gated sodium channels. These toxins, named the α-nemertides, were discovered in the epidermal mucus of Lineus longissimus, the 'bootlace worm' known as the longest animal on earth. The most abundant peptide, the 31-residue long α-1, was isolated, synthesized, and its 3D NMR structure determined...
March 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29566083/targeted-deletion-of-the-aquaglyceroporin-aqp9-is-protective-in-a-mouse-model-of-parkinson-s-disease
#9
Katja Stahl, Soulmaz Rahmani, Agnete Prydz, Nadia Skauli, Nanna MacAulay, Maria N Mylonakou, Reidun Torp, Øivind Skare, Torill Berg, Trygve B Leergaard, Ragnhild E Paulsen, Ole P Ottersen, Mahmood Amiry-Moghaddam
More than 90% of the cases of Parkinson's disease have unknown etiology. Gradual loss of dopaminergic neurons of substantia nigra is the main cause of morbidity in this disease. External factors such as environmental toxins are believed to play a role in the cell loss, although the cause of the selective vulnerability of dopaminergic neurons remains unknown. We have previously shown that aquaglyceroporin AQP9 is expressed in dopaminergic neurons and astrocytes of rodent brain. AQP9 is permeable to a broad spectrum of substrates including purines, pyrimidines, and lactate, in addition to water and glycerol...
2018: PloS One
https://www.readbyqxmd.com/read/29565814/bioprinting-perfusion-enabled-liver-equivalents-for-advanced-organ-on-a-chip-applications
#10
Tobias Grix, Alicia Ruppelt, Alexander Thomas, Anna-Klara Amler, Benjamin P Noichl, Roland Lauster, Lutz Kloke
Many tissue models have been developed to mimic liver-specific functions for metabolic and toxin conversion in in vitro assays. Most models represent a 2D environment rather than a complex 3D structure similar to native tissue. To overcome this issue, spheroid cultures have become the gold standard in tissue engineering. Unfortunately, spheroids are limited in size due to diffusion barriers in their dense structures, limiting nutrient and oxygen supply. Recent developments in bioprinting techniques have enabled us to engineer complex 3D structures with perfusion-enabled channel systems to ensure nutritional supply within larger, densely-populated tissue models...
March 22, 2018: Genes
https://www.readbyqxmd.com/read/29564531/shaker-related-voltage-gated-potassium-channels-kv1-in-human-hippocampus
#11
Michael Willis, Irmgard Leitner, Klaus Seppi, Maria Trieb, Georg Wietzorrek, Josef Marksteiner, Hans-Günther Knaus
In this study, we investigated the tissue expression levels, alpha subunit composition and distribution of Shaker-related voltage-dependent potassium Kv1 channels in human hippocampus by combining western blotting experiments, toxin autoradiography, in vivo radioligand binding studies, immunoprecipitation and immunohistochemistry. Tissue expression of Kv1.1 and Kv1.2 α-subunits in human post-mortem brain tissue was confirmed in immunoblot analysis using a panel of specific monoclonal and polyclonal antibodies...
March 21, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29561852/proteomic-endorsed-transcriptomic-profiles-of-venom-glands-from-tityus-obscurus-and-t-serrulatus-scorpions
#12
Ursula Castro de Oliveira, Milton Yutaka Nishiyama, Maria Beatriz Viana Dos Santos, Andria de Paula Santos-da-Silva, Hipócrates de Menezes Chalkidis, Andreia Souza-Imberg, Denise Maria Candido, Norma Yamanouye, Valquíria Abrão Coronado Dorce, Inácio de Loiola Meirelles Junqueira-de-Azevedo
BACKGROUND: Except for the northern region, where the Amazonian black scorpion, T. obscurus, represents the predominant and most medically relevant scorpion species, Tityus serrulatus, the Brazilian yellow scorpion, is widely distributed throughout Brazil, causing most envenoming and fatalities due to scorpion sting. In order to evaluate and compare the diversity of venom components of Tityus obscurus and T. serrulatus, we performed a transcriptomic investigation of the telsons (venom glands) corroborated by a shotgun proteomic analysis of the venom from the two species...
2018: PloS One
https://www.readbyqxmd.com/read/29558726/detection-of-salivary-protein-biomarkers-of-saliva-secretion-disorder-in-a-primary-sj%C3%A3-gren-syndrome-murine-model
#13
Peisheng Liang, Wangyong Zhu, Tianjun Lan, Qian Tao
Saliva secretion disorder is one of the most common symptoms in primary Sjögren syndrome (pSS). Salivary biomarkers related to saliva secretion disorder were identified in a pSS murine model, NOD/ShiLtJ mouse, using differential proteomic analysis. Candidate biomarkers were screened with Kyoto Encyclopedia of Genes and Genomes pathway analysis and validated in saliva and salivary glands by western blotting and immunohistochemistry (IHC). Biological functions were detected using ingenuity pathway analysis (IPA)...
March 12, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29556761/recent-advances-of-animal-model-of-focal-segmental-glomerulosclerosis
#14
REVIEW
Jae Won Yang, Anne Katrin Dettmar, Andreas Kronbichler, Heon Yung Gee, Moin Saleem, Seong Heon Kim, Jae Il Shin
In the last decade, great advances have been made in understanding the genetic basis for focal segmental glomerulosclerosis (FSGS). Animal models using specific gene disruption of the slit diaphragm and cytoskeleton of the foot process mirror the etiology of the human disease. Many animal models have been developed to understand the complex pathophysiology of FSGS. Therefore, we need to know the usefulness and exact methodology of creating animal models. Here, we review classic animal models and newly developed genetic animal models...
March 20, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29550876/refining-protein-penetration-into-the-lipid-bilayer-using-fluorescence-quenching-and-molecular-dynamics-simulations-the-case-of-diphtheria-toxin-translocation-domain
#15
Alexander Kyrychenko, Nathan M Lim, Victor Vasquez-Montes, Mykola V Rodnin, J Alfredo Freites, Linh P Nguyen, Douglas J Tobias, David L Mobley, Alexey S Ladokhin
Dynamic disorder of the lipid bilayer presents a challenge for establishing structure-function relationships in membranous systems. The resulting structural heterogeneity is especially evident for peripheral and spontaneously inserting membrane proteins, which are not constrained by the well-defined transmembrane topology and exert their action in the context of intimate interaction with lipids. Here, we propose a concerted approach combining depth-dependent fluorescence quenching with Molecular Dynamics simulation to decipher dynamic interactions of membrane proteins with the lipid bilayers...
March 17, 2018: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29545539/solution-structure-of-extracellular-loop-of-human-%C3%AE-4-subunit-of-bk-channel-and-its-biological-implication-on-chtx-sensitivity
#16
Yanting Wang, Wenxian Lan, Zhenzhen Yan, Jing Gao, Xinlian Liu, Sheng Wang, Xiying Guo, Chunxi Wang, Hu Zhou, Jiuping Ding, Chunyang Cao
Large-conductance Ca2+ - and voltage-dependent K+ (BK) channels display diverse biological functions while their pore-forming α subunit is coded by a single Slo1 gene. The variety of BK channels is correlated with the effects of BKα coexpression with auxiliary β (β1-β4) subunits, as well as newly defined γ subunits. Charybdotoxin (ChTX) blocks BK channel through physically occluding the K+ -conduction pore. Human brain enriched β4 subunit (hβ4) alters the conductance-voltage curve, slows activation and deactivation time courses of BK channels...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29540506/insights-into-toxic-prymnesium-parvum-blooms-the-role-of-sugars-and-algal-viruses
#17
REVIEW
Ben A Wagstaff, Edward S Hems, Martin Rejzek, Jennifer Pratscher, Elliot Brooks, Sakonwan Kuhaudomlarp, Ellis C O'Neill, Matthew I Donaldson, Steven Lane, John Currie, Andrew M Hindes, Gill Malin, J Colin Murrell, Robert A Field
Prymnesium parvum is a toxin-producing microalga that causes harmful algal blooms globally, which often result in large-scale fish kills that have severe ecological and economic implications. Although many toxins have previously been isolated from P. parvum , ambiguity still surrounds the responsible ichthyotoxins in P. parvum blooms and the biotic and abiotic factors that promote bloom toxicity. A major fish kill attributed to P. parvum occurred in Spring 2015 on the Norfolk Broads, a low-lying set of channels and lakes (Broads) found on the East of England...
March 14, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29534110/sodium-ion-channel-alkaloid-resistance-does-not-vary-with-toxicity-in-aposematic-dendrobates-poison-frogs-an-examination-of-correlated-trait-evolution
#18
Michael L Yuan, Ian J Wang
Spatial heterogeneity in the strength or agents of selection can lead to geographic variation in ecologically important phenotypes. Many dendrobatid frogs sequester alkaloid toxins from their diets and often exhibit fixed mutations at NaV1.4, a voltage-gated sodium ion channel associated with alkaloid toxin resistance. Yet previous studies have noted an absence of resistance mutations in individuals from several species known to sequester alkaloid toxins, suggesting possible intraspecific variation for alkaloid resistance in these species...
2018: PloS One
https://www.readbyqxmd.com/read/29532737/the-venom-of-ornithoctonus-huwena-affect-the-electrophysiological-stability-of-neonatal-rat-ventricular-myocytes-by-inhibiting-sodium-potassium-and-calcium-current
#19
Sha Yan, Pengfei Huang, Ying Wang, Xiongzhi Zeng, Yiya Zhang
Spider venoms are known to contain various toxins that are used as an effective means to capture their prey or to defend themselves against predators. An investigation of the properties of Ornithoctonus huwena (O.huwena) crude venom found that the venom can block neuromuscular transmission of isolated mouse phrenic nerve-diaphragm and sciatic nerve-sartorius preparations. However, little is known about its electrophysiological effects on cardiac myocytes. In this study, electrophysiological activities of ventricular myocytes were detected by 100 μg/mL venom of O...
March 13, 2018: Channels
https://www.readbyqxmd.com/read/29531133/determinants-of-raft-partitioning-of-the-helicobacter-pylori-pore-forming-toxin-vaca
#20
Krishnan Raghunathan, Nora J Foegeding, Anne M Campbell, Timothy L Cover, Melanie D Ohi, Anne K Kenworthy
Helicobacter pylori , a Gram-negative bacterium, is a well-known risk factor for gastric cancer. H. pylori vacuolating cytotoxin A (VacA) is a secreted pore-forming toxin that induces a wide range of cellular responses. Like many other bacterial toxins, VacA has been hypothesized to utilize lipid rafts to gain entry into host cells. Here, we use Giant Plasma Membrane Vesicles (GPMVs) as a model system to understand the preferential partitioning of VacA into lipid rafts. We show that a wild-type toxin predominantly associates with the raft phase...
March 12, 2018: Infection and Immunity
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