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https://www.readbyqxmd.com/read/27914061/probing-oligomerized-conformations-of-defensin-in-the-membrane
#1
Wenxun Gan, Dina Schneidman, Ning Zhang, Buyong Ma, Ruth Nussinov
Computational prediction and design of membrane protein-protein interactions facilitate biomedical engineering and biotechnological applications. Due to their antimicrobial activity, human defensins play an important role in the innate immune system. Human defensins are attractive pharmaceutical targets due to their small size, broad activity spectrum, reduced immunogenicity, and resistance to proteolysis. Protein engineering based modification of defensins can improve their pharmaceutical properties. Here we present an approach to computationally probe defensins' oligomerization states in the membrane...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913829/glutamate-fermentation-2-mechanism-of-l-glutamate-overproduction-in-corynebacterium-glutamicum
#2
Takashi Hirasawa, Masaaki Wachi
The nonpathogenic coryneform bacterium, Corynebacterium glutamicum, was isolated as an L-glutamate-overproducing microorganism by Japanese researchers and is currently utilized in various amino acid fermentation processes. L-Glutamate production by C. glutamicum is induced by limitation of biotin and addition of fatty acid ester surfactants and β-lactam antibiotics. These treatments affect the cell surface structures of C. glutamicum. After the discovery of C. glutamicum, many researchers have investigated the underlying mechanism of L-glutamate overproduction with respect to the cell surface structures of this organism...
December 3, 2016: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/27913277/specific-stabilization-of-cftr-by-phosphatidylserine
#3
Ellen Hildebrandt, Netaly Khazanov, John C Kappes, Qun Dai, Hanoch Senderowitz, Ina L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR, ABCC7) is a plasma membrane chloride ion channel in the ABC transporter superfamily. CFTR is a key target for cystic fibrosis drug development, and its structural elucidation would advance those efforts. However, the limited in vivo and in vitro stability of the protein, particularly its nucleotide binding domains, has made structural studies challenging. Here we demonstrate that phosphatidylserine uniquely stimulates and thermally stabilizes the ATP hydrolysis function of purified human CFTR...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27913207/overexpression-of-stim1-in-neurons-in-mouse-brain-improves-contextual-learning-and-impairs-long-term-depression
#4
Łukasz Majewski, Filip Maciąg, Paweł M Boguszewski, Iga Wasilewska, Grzegorz Wiera, Tomasz Wójtowicz, Jerzy Mozrzymas, Jacek Kuznicki
STIM1 is an endoplasmic reticulum calcium sensor that is involved in several processes in neurons, including store-operated calcium entry. STIM1 also inhibits voltage-gated calcium channels, such as Cav1.2 and Cav3.1, and is thus considered a multifunctional protein. The aim of this work was to investigate the ways in which transgenic neuronal overexpression of STIM1 in FVB/NJ mice affects animal behavior and the electrophysiological properties of neurons in acute hippocampal slices. We overexpressed STIM1 from the Thy1...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27911898/bilaterian-giant-ankyrins-have-a-common-evolutionary-origin-and-play-a-conserved-role-in-patterning-the-axon-initial-segment
#5
Timothy Jegla, Michelle M Nguyen, Chengye Feng, Daniel J Goetschius, Esteban Luna, Damian B van Rossum, Bishoy Kamel, Aditya Pisupati, Elliott S Milner, Melissa M Rolls
In vertebrate neurons, the axon initial segment (AIS) is specialized for action potential initiation. It is organized by a giant 480 Kd variant of ankyrin G (AnkG) that serves as an anchor for ion channels and is required for a plasma membrane diffusion barrier that excludes somatodendritic proteins from the axon. An unusually long exon required to encode this 480Kd variant is thought to have been inserted only recently during vertebrate evolution, so the giant ankyrin-based AIS scaffold has been viewed as a vertebrate adaptation for fast, precise signaling...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27911841/high-performance-multiplexed-fluorescence-in-situ-hybridization-in-culture-and-tissue-with-matrix-imprinting-and-clearing
#6
Jeffrey R Moffitt, Junjie Hao, Dhananjay Bambah-Mukku, Tian Lu, Catherine Dulac, Xiaowei Zhuang
Highly multiplexed single-molecule FISH has emerged as a promising approach to spatially resolved single-cell transcriptomics because of its ability to directly image and profile numerous RNA species in their native cellular context. However, background-from off-target binding of FISH probes and cellular autofluorescence-can become limiting in a number of important applications, such as increasing the degree of multiplexing, imaging shorter RNAs, and imaging tissue samples. Here, we developed a sample clearing approach for FISH measurements...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911380/method-for-identifying-small-molecule-inhibitors-of-the-protein-protein-interaction-between-hcn1-and-trip8b
#7
Ye Han, Kyle A Lyman, Matt Clutter, Gary E Schiltz, Quratul-Ain Ismail, Xiangying Cheng, Chi-Hao Luan, Dane M Chetkovich
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed ubiquitously throughout the brain, where they function to regulate the excitability of neurons. The subcellular distribution of these channels in pyramidal neurons of hippocampal area CA1 is regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit. Genetic knockout of HCN pore forming subunits or TRIP8b, both lead to an increase in antidepressant-like behavior, suggesting that limiting the function of HCN channels may be useful as a treatment for Major Depressive Disorder (MDD)...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911331/excitation-contraction-coupling-alterations-in-myopathies
#8
Isabelle Marty, Julien Fauré
During the complex series of events leading to muscle contraction, the initial electric signal coming from motor neurons is transformed into an increase in calcium concentration that triggers sliding of myofibrils. This process, referred to as excitation-contraction coupling, is reliant upon the calcium-release complex, which is restricted spatially to a sub-compartment of muscle cells ("the triad") and regulated precisely. Any dysfunction in the calcium-release complex leads to muscle impairment and myopathy...
November 29, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27910861/paper-based-crp-monitoring-devices
#9
Shang-Chi Lin, Chung-Yuh Tseng, Po-Liang Lai, Min-Yen Hsu, Shueh-Yao Chu, Fan-Gang Tseng, Chao-Min Cheng
Here, we discuss the development of a paper-based diagnostic device that is inexpensive, portable, easy-to-use, robust, and capable of running simultaneous tests to monitor a relevant inflammatory protein for clinical diagnoses i.e. C-reactive protein (CRP). In this study, we first attempted to make a paper-based diagnostic device via the wax printing method, a process that was used in previous studies. This device has two distinct advantages: 1) reduced manufacturing and assay costs and operation duration via using wax printing method to define hydrophobic boundaries (for fluidic devices or general POC devices); and, 2) the hydrophilicity of filter paper, which is used to purify and chromatographically correct interference caused by whole blood components with a tiny amount of blood sample (only 5 μL)...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910058/gene-delivery-for-the-generation-of-bioartificial-pacemaker
#10
Patrick K W Chan, Ronald A Li
Electronic pacemakers have been used in patients with heart rhythm disorders for device-supported pacing. While effective, there are such shortcomings as limited battery life, permanent implantation of catheters, the lack of autonomic neurohumoral responses, and risks of lead dislodging. Here we describe protocols for establishing porcine models of sick sinus syndrome and complete heart block, and the generation of bioartificial pacemaker by delivering a strategically engineered form of hyperpolarization-activated cyclic nucleotide-gated pacemaker channel protein via somatic gene transfer to convert atrial or ventricular muscle cardiomyocytes into nodal-like cells that rhythmically fire action potentials...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909292/crystal-structures-of-the-tric-trimeric-intracellular-cation-channel-orthologues
#11
Go Kasuya, Masahiro Hiraizumi, Andrés D Maturana, Kaoru Kumazaki, Yuichiro Fujiwara, Keihong Liu, Yoshiko Nakada-Nakura, So Iwata, Keisuke Tsukada, Tomotaka Komori, Sotaro Uemura, Yuhei Goto, Takanori Nakane, Mizuki Takemoto, Hideaki E Kato, Keitaro Yamashita, Miki Wada, Koichi Ito, Ryuichiro Ishitani, Motoyuki Hattori, Osamu Nureki
Ca(2+) release from the sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER) is crucial for muscle contraction, cell growth, apoptosis, learning and memory. The trimeric intracellular cation (TRIC) channels were recently identified as cation channels balancing the SR and ER membrane potentials, and are implicated in Ca(2+) signaling and homeostasis. Here we present the crystal structures of prokaryotic TRIC channels in the closed state and structure-based functional analyses of prokaryotic and eukaryotic TRIC channels...
December 2016: Cell Research
https://www.readbyqxmd.com/read/27908768/acute-stress-diminishes-m-current-contributing-to-elevated-activity-of-hypothalamic-pituitary-adrenal-axis
#12
Jing-Jing Zhou, Yonggang Gao, Therese A Kosten, Zongmao Zhao, De-Pei Li
Acute stress stimulates corticotrophin-releasing hormone (CRH)-expressing neurons in the hypothalamic paraventricular nucleus (PVN), which is an essential component of hypothalamic-pituitary-adrenal (HPA) axis. However, the cellular and molecular mechanisms remain unclear. The M-channel is a voltage-dependent K(+) channel involved in stabilizing the neuronal membrane potential and regulating neuronal excitability. In this study, we tested our hypothesis that acute stress suppresses expression of Kv7 channels to stimulate PVN-CRH neurons and the HPA axis...
November 28, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27908670/proteome-of-the-rete-testis-fluid-from-tropically-adapted-morada-nova-rams
#13
Mauricio Fraga van Tilburg, Solange Damasceno Sousa, Révila Bianca Ferreira de Melo, Frederico B Moreno, Ana Cristina Monteiro-Moreira, Renato A Moreira, Arlindo de Alencar Moura
The rete testis has a close relationship with sperm development and may have other functions besides serving as an intercalated channel. The aim of this study was to identify and characterize the proteins of rete testis fluid (RTF) from tropically-adapted Morada Nova rams. Testicles obtained from six Morada Nova rams were dissected and the head of the epididymis was separated to access the efferent ducts. Rete testis fluid was obtained by gentle massage of the testis. The fluid was centrifuged to remove cell debris and sperm...
November 22, 2016: Animal Reproduction Science
https://www.readbyqxmd.com/read/27907137/voltage-gated-na-channel-isoforms-and-their-mrna-expression-levels-and-protein-abundance-in-three-electric-organs-and-the-skeletal-muscle-of-the-electric-eel-electrophorus-electricus
#14
Biyun Ching, Jia M Woo, Kum C Hiong, Mel V Boo, Wai P Wong, Shit F Chew, Yuen K Ip
This study aimed to obtain the coding cDNA sequences of voltage-gated Na+ channel (scn) α-subunit (scna) and β-subunit (scnb) isoforms from, and to quantify their transcript levels in, the main electric organ (EO), Hunter's EO, Sach's EO and the skeletal muscle (SM) of the electric eel, Electrophorus electricus, which can generate both high and low voltage electric organ discharges (EODs). The full coding sequences of two scna (scn4aa and scn4ab) and three scnb (scn1b, scn2b and scn4b) were identified for the first time (except scn4aa) in E...
2016: PloS One
https://www.readbyqxmd.com/read/27906756/optic-neuritis-the-eye-as-a-window-to-the-brain
#15
Thomas M Jenkins, Ahmed T Toosy
PURPOSE OF REVIEW: Acute optic neuritis is a common clinical problem, requiring a structured assessment to guide management and prevent visual loss. The optic nerve is the most accessible part of the central nervous system, so optic neuritis also represents an important paradigm to help decipher mechanisms of damage and recovery in the central nervous system. Important developments include the advent of optical coherence tomography as a biomarker of central nervous system axonal loss, the discovery of new pathological antibodies, notably against aquaporin-4 and, more recently, myelin oligodendrocyte protein, and emerging evidence for sodium channel blockade as a novel therapeutic approach to address energy failure in neuroinflammatory disease...
November 30, 2016: Current Opinion in Neurology
https://www.readbyqxmd.com/read/27906699/reversal-effects-of-local-anesthetics-on-p-glycoprotein-mediated-cancer-multidrug-resistance
#16
Yong Hu, Xiaobing Qin, Haixia Cao, Shaorong Yu, Jifeng Feng
The existence of multidrug resistance (MDR) is the main reason for failure in cancer chemotherapy. The main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). P-gp, a 170 kDa transmembrane phosphorylated glycoprotein encoded by ABCB1 belonging to a member of the ATP-binding cassette (ABC) super-family of the membrane transporters, is also known as the MDR protein. Local anesthetics (LAs) are a major contributor to medical practice. As a cornerstone of analgesia, LAs provides myriad benefits...
November 30, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#17
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905992/variable-sensitivity-to-complement-dependent-cytotoxicity-in-murine-models-of-neuromyelitis-optica
#18
Yiting Liu, Danielle E Harlow, Katherine S Given, Gregory P Owens, Wendy B Macklin, Jeffrey L Bennett
BACKGROUND: Studies of neuromyelitis optica (NMO), an autoimmune disease of the central nervous system (CNS), have demonstrated that autoantibodies against the water channel aquaporin-4 (AQP4) induce astrocyte damage through complement-dependent cytotoxicity (CDC). In developing experimental models of NMO using cells, tissues or animals from mice, co-administration of AQP4-IgG and normal human serum, which serves as the source of human complement (HC), is required. The sensitivity of mouse CNS cells to HC and CDC in these models is not known...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27905618/mechanism-of-%C3%AE-synuclein-translocation-through-a-vdac-nanopore-revealed-by-energy-landscape-modeling-of-escape-time-distributions
#19
David P Hoogerheide, Philip A Gurnev, Tatiana K Rostovtseva, Sergey M Bezrukov
We probe the energy landscape governing the passage of α-synuclein, a natural "diblock copolymer"-like polypeptide, through a nanoscale pore. α-Synuclein is an intrinsically disordered neuronal protein associated with Parkinson's pathology. The motion of this electrically heterogeneous polymer in the β-barrel voltage-dependent anion channel (VDAC) of the mitochondrial outer membrane strongly depends on the properties of both the charged and uncharged regions of the α-synuclein polymer. We model this motion in two ways...
December 1, 2016: Nanoscale
https://www.readbyqxmd.com/read/27905510/remarkable-alterations-of-nav1-6-in-reactive-astrogliosis-during-epileptogenesis
#20
Hongyan Zhu, Yuxiao Zhao, Hao Wu, Nan Jiang, Ziyi Wang, Weide Lin, Jiahui Jin, Yonghua Ji
Voltage-gated sodium channels (VGSCs) play a vital role in controlling neuronal excitability. Nav1.6 is the most abundantly expressed VGSCs subtype in the adult central nervous system and has been found to contribute to facilitate the hyperexcitability of neurons after electrical induction of status epilepticus (SE). To clarify the exact expression patterns of Nav1.6 during epileptogenesis, we examined the expression of Nav1.6 at protein and mRNA levels in two distinct animal models of temporal lobe epilepsy (TLE) including a post-SE model induced by kainic acid (KA) intrahippocampal injection and a kindling model evoked by pentylenetetrazole (PTZ)...
December 1, 2016: Scientific Reports
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