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https://www.readbyqxmd.com/read/28806784/structural-analysis-of-p-falciparum-kahrp-and-pfemp1-complexes-with-host-erythrocyte-spectrin-suggests-a-model-for-cytoadherent-knob-protrusions
#1
Erin E Cutts, Niklas Laasch, Dirk M Reiter, Raphael Trenker, Leanne M Slater, Phillip J Stansfeld, Ioannis Vakonakis
Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) and Knob-associated Histidine-rich Protein (KAHRP) are directly linked to malaria pathology. PfEMP1 and KAHRP cluster on protrusions (knobs) on the P. falciparum-infected erythrocyte surface and enable pathogenic cytoadherence of infected erythrocytes to the host microvasculature, leading to restricted blood flow, oxygen deprivation and damage of tissues. Here we characterize the interactions of PfEMP1 and KAHRP with host erythrocyte spectrin using biophysical, structural and computational approaches...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806139/mask-mitigates-mapt-and-fus-induced-degeneration-by-enhancing-autophagy-through-lysosomal-acidification
#2
Mingwei Zhu, Sheng Zhang, Xiaolin Tian, Chunlai Wu
Accumulation of intracellular misfolded or damaged proteins is associated with both normal aging and late-onset degenerative diseases. Two cellular clearance mechanisms, the ubiquitin-proteasome system (UPS) and the macroautophagy/autophagy-lysosomal pathway, work in concert to degrade harmful protein aggregates and maintain protein homeostasis. Here we show that Mask, an Ankyrin-repeat and KH-domain containing protein, plays a key role in promoting autophagy flux and mitigating degeneration caused by protein aggregation or impaired UPS function...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28805980/an-environmental-pollutant-9-10-phenanthrenequinone-activates-human-trpa1-via-critical-cysteines-621-and-665
#3
Katsuhiko Muraki, Takashi Sekine, Yuna Ando, Hiroka Suzuki, Noriyuki Hatano, Tadashi Hirata, Yukiko Muraki
Transient receptor potential ankyrin 1 (TRPA1) is activated by noxious cold, mechanical stimulation, and irritant chemicals. In our recent study, 9, 10-phenanthrenequinone (9,10-PQ) is the most potent irritant for activation of NRF2 among 1395 cigarette smoke components and it may be, therefore, important to find its additional targets. Here, we show that 9,10-PQ functions as an activator of TRPA1 in human embryonic kidney (HEK) cells expressing human wild-type TRPA1 (HEK-wTRPA1) and human alveolar A549 (A549) cells...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28802032/deciphering-critical-amino-acid-residues-to-modify-and-enhance-the-binding-affinity-of-ankyrin-scaffold-specific-to-capsid-protein-of-human-immunodeficiency-virus-type-1
#4
Somphot Saoin, Tanchanok Wisitponchai, Kannaporn Intachai, Koollawat Chupradit, Sutpirat Moonmuang, Sawitree Nangola, Kuntida Kitidee, Kanda Fanhchaksai, Vannajan Sanghiran Lee, Saw-See Hong, Pierre Boulanger, Phimonphan Chuankhayan, Chun-Jung Chen, Chatchai Tayapiwatana
BACKGROUND: AnkGAG1D4 is an artificial ankyrin repeat protein which recognizes the capsid protein (CA) of the human immunodeficiency virus type 1 (HIV-1) and exhibits the intracellular antiviral activity on the viral assembly process. Improving the binding affinity of AnkGAG1D4 would potentially enhance the AnkGAG1D4-mediated antiviral activity. OBJECTIVE: To augment the affinity of AnkGAG1D4 scaffold towards its CA target, through computational predictions and experimental designs...
August 8, 2017: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/28799666/effect-of-resveratrol-on-c-fos-expression-of-rat-trigeminal-spinal-nucleus-caudalis-and-c1-dorsal-horn-neurons-following-mustard-oil-induced-acute-inflammation
#5
Yasuhiro Matsumoto, Kyouhei Komatsu, Yoshihito Shimazu, Shiori Takehana, Yumiko Syouji, Ayumu Kobayashi, Mamoru Takeda
The dietary constituent, resveratrol, was recently identified as a transient receptor potential ankyrin 1 (TRPA1) antagonist, voltage-dependent sodium ion (Na(+) ) channel, and cyclooxygenase-2 (COX-2) inhibitor. The aim of the present study was to investigate whether pretreatment with resveratrol attenuates acute inflammation-induced sensitization of nociceptive processing in rat spinal trigeminal nucleus caudalis (SpVc) and upper cervical (C1) dorsal horn neurons, via c-fos immunoreactivity. Mustard oil (MO), a TRPA1 channel agonist, was injected into the whisker pads of rats to induce inflammation...
August 11, 2017: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/28796529/designed-ankyrin-repeat-proteins-as-her2-targeting-domains-in-chimeric-antigen-receptor-engineered-t-cells
#6
Elizabeth Siegler, Si Li, Yu Jeong Kim, Pin Wang
Chimeric antigen receptor (CAR) engineering is a branch of cancer immunotherapy that equips immune cells to target tumor antigens expressed on the cell surface using antibody-derived single-chain variable fragments (scFvs). However, other antibody mimetics, such as designed ankyrin repeat proteins (DARPins), can also serve as antigen-binding domains in CARs. This study shows that CAR-engineered T (CAR-T) cells utilizing Her2-targeting DARPins G3 and 929 can target human epidermal growth factor receptor 2 (Her2)-overexpressing cancer cells as effectively as CAR-T cells with the scFv 4D5 in vitro, and G3 CAR-T cells can slow or eliminate tumor growth in vivo as effectively as 4D5 CAR-T cells...
June 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28792844/trpa1-ion-channel-stimulation-enhances-cardiomyocyte-contractile-function-via-a-camkii-dependent-pathway
#7
Spencer R Andrei, Monica Ghosh, Pritam Sinharoy, Souvik Dey, Ian N Bratz, Derek S Damron
RATIONALE: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disc, costamere and intercalated disc. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored. OBJECTIVE: To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action...
August 9, 2017: Channels
https://www.readbyqxmd.com/read/28769868/hydrogen-sulfide-mediating-both-excitatory-and-inhibitory-effects-in-a-rat-model-of-meningeal-nociception-and-headache-generation
#8
Christiane Teicher, Roberto De Col, Karl Messlinger
BACKGROUND/PURPOSE: Hydrogen sulfide (H2S) is a neuromodulator acting through nitroxyl (HNO) when it reacts with nitric oxide (NO). HNO activates transient receptor potential channels of the ankyrin type 1 (TRPA1) causing release of calcitonin gene-related peptide from primary afferents. Activation of meningeal nociceptors projecting to the human spinal trigeminal nucleus (STN) may lead to headaches. In a rat model of meningeal nociception, the activity of spinal trigeminal neurons was used as read-out for the interaction between H2S and NO...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28765088/the-evolving-role-of-ankyrin-b-in-cardiovascular-disease
#9
Sara N Koenig, Peter J Mohler
Over the last decade, ankyrin-B has been identified as a prominent player in cardiac physiology. Ankyrin-B has a multitude of functions, with roles in expression, localization, and regulation of proteins critical for cardiac excitability, cytoskeletal integrity, and signaling. Further, human ANK2 variants that result in ankyrin-B loss-of-function are associated with 'Ankyrin-B syndrome', a complex cardiac phenotype that may include bradycardia and heart rate variability, conduction block, atrial fibrillation, QT interval prolongation, and potentially fatal catecholaminergic polymorphic ventricular tachycardia...
July 29, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28760718/crocodylian-nuclear-factor-kappa-b
#10
Mark Merchant, Vasileios Morkotinis, Amber Hale, Mary White, Chris Moran
We deduced the amino acid (aa) sequence of the nuclear factor kappa B (NFκB) protein from genomic data for the American alligator (Alligator mississippiensis), the estuarine crocodile (Crocodylus porosus), and the Indian gharial (Gavialis gangeticus). A 105kDa protein, NFκB1 exhibits complex post-translational processing, multiple mechanisms of activation, and acts as precursor for a p50, a Rel homology transcription factor which influences the expression of key genes for developmental processes, apoptosis, and immune function...
July 29, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28757145/structural-basis-for-substrate-recognition-by-the-ankyrin-repeat-domain-of-human-dhhc17-palmitoyltransferase
#11
Raffaello Verardi, Jin-Sik Kim, Rodolfo Ghirlando, Anirban Banerjee
DHHC enzymes catalyze palmitoylation, a major post-translational modification that regulates a number of key cellular processes. There are up to 24 DHHCs in mammals and hundreds of substrate proteins that get palmitoylated. However, how DHHC enzymes engage with their substrates is still poorly understood. There is currently no structural information about the interaction between any DHHC enzyme and protein substrates. In this study we have investigated the structural and thermodynamic bases of interaction between the ankyrin repeat domain of human DHHC17 (ANK17) and Snap25b...
July 18, 2017: Structure
https://www.readbyqxmd.com/read/28754924/dynamic-scaffolds-for-neuronal-signaling-in-silico-analysis-of-the-tanc-protein-family
#12
Alessandra Gasparini, Silvio C E Tosatto, Alessandra Murgia, Emanuela Leonardi
The emergence of genes implicated across multiple comorbid neurologic disorders allows to identify shared underlying molecular pathways. Recently, investigation of patients with diverse neurologic disorders found TANC1 and TANC2 as possible candidate disease genes. While the TANC proteins have been reported as postsynaptic scaffolds influencing synaptic spines and excitatory synapse strength, their molecular functions remain unknown. Here, we conducted a comprehensive in silico analysis of the TANC protein family to characterize their molecular role and understand possible neurobiological consequences of their disruption...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28754591/camkii-inhibition-mitigates-ischemia-reperfusion-elicited-calpain-activation-and-the-damage-to-membrane-skeleton-proteins-in-isolated-rat-hearts
#13
Ling-Heng Kong, Xiao-Ming Gu, Feng Wu, Zhen-Xiao Jin, Jing-Jun Zhou
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in myocardial ischemia/reperfusion (IR) injury. The aim of this study was to determine the effect of CaMKII on the damage to membrane skeleton proteins, which is an important cause of IR injury. Isolated rat hearts were subjected to 45-min global ischemia/2-h reperfusion. Both KN-62 and KN-93 were used to inhibit CaMKII. Compared with controls, the hearts in the IR group exhibited remarkable myocardial injury area, LDH release, cell apoptosis and contractile dysfunction, along with an increase in the phosphorylation of CaMKII and its substrate phospholamban...
July 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28751503/ankyrin-1-gene-exhibits-allelic-heterogeneity-in-conferring-protection-against-malaria
#14
Hong Ming Huang, Denis C Bauer, Patrick M Lelliott, Matthew Wa Dixon, Leann Tilley, Brendan J McMorran, Simon J Foote, Gaetan Burgio
Allelic heterogeneity is a common phenomenon where a gene exhibit different phenotype depending on the nature of its genetic mutations. In the context of genes affecting malaria susceptibility, it allowed us to explore and understand the intricate host-parasite interactions during malaria infections. In this study, we described a gene encoding erythrocytic ankyrin-1 (Ank-1) which exhibits allelic-dependent heterogeneous phenotypes during malaria infections. We conducted an ENU mutagenesis screen on mice and identified two Ank-1 mutations, one resulted in an amino acid substitution (MRI95845), and the other a truncated Ank-1 protein (MRI96570)...
July 27, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28747176/comparative-rna-seq-based-transcriptome-profiling-of-waterlogging-response-in-cucumber-hypocotyls-reveals-novel-insights-into-the-de-novo-adventitious-root-primordia-initiation
#15
Xuewen Xu, Minyang Chen, Jing Ji, Qiang Xu, Xiaohua Qi, Xuehao Chen
BACKGROUND: Waterlogging is a serious abiotic stress to plant growth because it results in the decline in the supplement of oxygen to submerged tissues. Although cucumber (Cucumis sativus L.) is sensitive to waterlogging, its ability to generate adventitious roots (ARs) facilitates gas diffusion and increases plant survival when the oxygen concentration is decreased. To gain a better understanding of the molecular mechanisms that enable de novo AR primordia emergence upon waterlogging, the RNA sequencing-based transcriptomic responses of two contrasting cucumber genotypes, Zaoer-N (waterlogging tolerant) and Pepino (waterlogging sensitive), which differed in their abilities to form AR were compared...
July 26, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28740174/plakophilin-2-is-required-for-transcription-of-genes-that-control-calcium-cycling-and-cardiac-rhythm
#16
Marina Cerrone, Jerome Montnach, Xianming Lin, Yan-Ting Zhao, Mingliang Zhang, Esperanza Agullo-Pascual, Alejandra Leo-Macias, Francisco J Alvarado, Igor Dolgalev, Thomas V Karathanos, Kabir Malkani, Chantal J M Van Opbergen, Joanne J A van Bavel, Hua-Qian Yang, Carolina Vasquez, David Tester, Steven Fowler, Fengxia Liang, Eli Rothenberg, Adriana Heguy, Gregory E Morley, William A Coetzee, Natalia A Trayanova, Michael J Ackerman, Toon A B van Veen, Hector H Valdivia, Mario Delmar
Plakophilin-2 (PKP2) is a component of the desmosome and known for its role in cell-cell adhesion. Mutations in human PKP2 associate with a life-threatening arrhythmogenic cardiomyopathy, often of right ventricular predominance. Here, we use a range of state-of-the-art methods and a cardiomyocyte-specific, tamoxifen-activated, PKP2 knockout mouse to demonstrate that in addition to its role in cell adhesion, PKP2 is necessary to maintain transcription of genes that control intracellular calcium cycling. Lack of PKP2 reduces expression of Ryr2 (coding for Ryanodine Receptor 2), Ank2 (coding for Ankyrin-B), Cacna1c (coding for CaV1...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28734032/characterization-of-the-axon-initial-segment-of-mice-substantia-nigra-dopaminergic-neurons
#17
Cristian González-Cabrera, Rodrigo Meza, Lorena Ulloa, Paulina Merino-Sepúlveda, Valentina Luco, Ana Sanhueza, Alejandro Oñate-Ponce, J Paul Bolam, Pablo Henny
The axon initial segment (AIS) is the site of initiation of action potentials and also influences action potential waveform, firing pattern and rate. In view of the fundamental aspects of motor function and behavior that depend on the firing of substantia nigra pars compacta (SNc) dopaminergic neurons, we identified and characterized their AIS in the mouse. Immunostaining for tyrosine hydroxylase (TH), sodium channels (Nav ) and ankyrin-G (Ank-G) was used to visualize the AIS of dopaminergic neurons. Reconstructions of sampled AIS of dopaminergic neurons revealed variable lengths (12 - 60 μm) and diameters (0...
July 22, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28726540/mechanisms-of-the-analgesic-effect-of-calcitonin-on-chronic-pain-by-alteration-of-receptor-or-channel-expression
#18
Akitoshi Ito, Megumu Yoshimura
The polypeptide hormone calcitonin is well known clinically for its ability to relieve osteoporotic back pain and neuropathic pain such as spinal canal stenosis, diabetic neuropathy, chemotherapy-induced neuropathy, and complex regional pain syndrome. Because the analgesic effects of calcitonin have a broad range, the underlying mechanisms of pain relief by calcitonin are largely unknown. However, recent studies using several types of chronic pain models combined with various methods have been gradually clarifying the mechanism...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28716263/exogenous-acrolein-intensifies-sensory-hypersensitivity-after-spinal-cord-injury-in-rat
#19
Breanne Butler, Glen Acosta, Riyi Shi
Acrolein, an α,β-unsaturated aldehyde associated with oxidative stress, is also a major toxic component of tobacco cigarette smoke, which has been reported in the clinic to coincide with the exacerbation of neuropathic pain after SCI. Previous reports have shown that acrolein involvement in spinal cord injury (SCI) is crucial to the development and persistence of neuropathic pain. Through the activation and upregulation of the transient receptor protein ankyrin-1 (TRPA1) cation channel, acrolein is capable of sensitizing the central nervous system in the acute and chronic stages of SCI...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28713955/altered-axon-initial-segment-in-hippocampal-newborn-neurons-associated-with-recurrence-of-temporal-lobe-epilepsy-in-rats
#20
Tian-Tian Liu, Li Feng, Heng-Fang Liu, Yi Shu, Bo Xiao
Hippocampal neurogenesis in temporal lobe epilepsy (TLE) may result in alteration of the excitability of neurons, which contributes to spontaneous recurrent seizures. Axon initial segment (AIS) structural and functional plasticity is important in the control of neuronal excitability. It remains to be elucidated whether the plasticity of AIS occurs in hippocampal newly‑generated neurons that are involved in recurrent seizures following pilocarpine‑induced status epilepticus (SE). The present study first established a pilocarpine‑induced TLE rat model to assess the features of newborn neurons and AIS plasticity alterations using double immunofluorescence staining of Ankyrin G and doublecortin (DCX)...
September 2017: Molecular Medicine Reports
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