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Tandem pore

Junlan Yao, David McHedlishvili, William E McIntire, Nick A Guagliardo, Alev Erisir, Craig A Coburn, Vincent P Santarelli, Douglas A Bayliss, Paula Q Barrett
Ca(2+) drives aldosterone synthesis in the cytosolic and mitochondrial compartments of the adrenal zona glomerulosa cell. Membrane potential across each of these compartments regulates the amplitude of the Ca(2+) signal; yet, only plasma membrane ion channels and their role in regulating cell membrane potential have garnered investigative attention as pathological causes of human hyperaldosteronism. Previously, we reported that genetic deletion of TASK-3 channels (tandem pore domain acid-sensitive K(+) channels) from mice produces aldosterone excess in the absence of a change in the cell membrane potential of zona glomerulosa cells...
June 19, 2017: Hypertension
Till Siebenmorgen, Martin Zacharias
Telomeric DNA consists of tandem repeats of the sequence d(TTAGGG) that form G-quadruplex structures made of stacked guanines with monovalent cations bound at a central cavity. Although different ions can stabilize a G-quadruplex structure, the preferred bound ions are typically K(+) or Na(+). Several different strand-folding topologies have been reported for Q-quadruplexes formed from telomeric repeats depending on DNA length and ion solution condition. This suggests a possible dependence of the ion selectivity of the central pore on the folding topology of the quadruplex...
June 6, 2017: Biophysical Journal
Nicole Bobak, Sylvain Feliciangeli, Cheng-Chang Chen, Ismail Ben Soussia, Stefan Bittner, Sophie Pagnotta, Tobias Ruck, Martin Biel, Christian Wahl-Schott, Christian Grimm, Sven G Meuth, Florian Lesage
Recombinant TWIK2 channels produce weak basal background K(+) currents. Current amplitudes depend on the animal species the channels have been isolated from and on the heterologous system used for their re-expression. Here we show that this variability is due to a unique cellular trafficking. We identified three different sequence signals responsible for the preferential expression of TWIK2 in the Lamp1-positive lysosomal compartment. Sequential inactivation of tyrosine-based (Y308ASIP) and di-leucine-like (E266LILL and D282EDDQVDIL) trafficking motifs progressively abolishes the targeting of TWIK2 to lysosomes, and promotes its functional relocation at the plasma membrane...
April 5, 2017: Scientific Reports
Wei-Jie Xie, Yong-Ping Zhang, Jian Xu, Xiao-Bo Sun, Fang-Fang Yang
BACKGROUND: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. METHODS: With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Anita Luethy, James D Boghosian, Rithu Srikantha, Joseph F Cotten
The TWIK-related acid-sensitive potassium channel 3 (TASK-3; KCNK9) tandem pore potassium channel function is activated by halogenated anesthetics through binding at a putative anesthetic-binding cavity. To understand the pharmacologic requirements for TASK-3 activation, we studied the concentration-response of TASK-3 to several anesthetics (isoflurane, desflurane, sevoflurane, halothane, α-chloralose, 2,2,2-trichloroethanol [TCE], and chloral hydrate), to ethanol, and to a panel of halogenated methanes and alcohols...
June 2017: Molecular Pharmacology
Kenichi Ishibashi, Yoshiyuki Morishita, Yasuko Tanaka
Aquaporins (AQPs ) are a family of transmembrane proteins present in almost all species including virus. They are grossly divided into three subfamilies based on the sequence around a highly conserved pore-forming NPA motif: (1) classical water -selective AQP (CAQP), (2) glycerol -permeable aquaglyceroporin (AQGP) and (3) AQP super-gene channel, superaquaporin (SAQP). AQP is composed of two tandem repeats of conserved three transmembrane domains and a NPA motif. AQP ancestors probably started in prokaryotes by the duplication of half AQP genes to be diversified into CAQPs or AQGPs by evolving a subfamily-specific carboxyl-terminal NPA motif...
2017: Advances in Experimental Medicine and Biology
Hamed Piri-Moghadam, Sofia Lendor, Janusz Pawliszyn
The aim of the current study is to develop a sensitive solid-phase microextraction (SPME) device for direct and rapid analysis of untreated complex matrixes (i.e., single drop of the samples, V ≤ 2 μL). A thin layer of a biocompatible nanostructured polypyrrole (PPy) was electrochemically deposited inside a medical grade spinal needle, minimizing the matrix effect. Microsampling was facilitated by loading the sample inside the in-tube SPME device (withdraw of sample via plunger), where extraction was performed under static conditions...
December 20, 2016: Analytical Chemistry
Shalene Xue Lin Goh, Hian Kee Lee
A bundled hollow fiber array (BHF)-liquid-phase microextraction (LPME) approach has been developed for the ultra-high performance liquid chromatography tandem mass spectrometric determination of estrone, 17β-estradiol, estriol, and 17α-ethinylestradiol. The BHF was dipped in n-octanol to impregnate only the wall pores of the hollow fibers without deliberate loading of extractant solvent in the lumens, before placing it in the sample for extraction. Parameters influencing extraction efficiency, such as number of bundled hollow fibers, type of extraction and desorption solvent, agitation mode, extraction temperature and duration, and the salting out effect were examined...
March 10, 2017: Journal of Chromatography. A
Xuelin Xia, Jingjing Meng, Hanxin Wu, Tanyu Cheng, Guohua Liu
Facile construction of a multifunctional heterogeneous catalyst through the assembly of Au/carbene and chiral ruthenium/diamine dual complexes in large-pore mesoporous silica was developed. This enables an efficient one-pot hydration-asymmetric transfer hydrogenation enantioselective tandem reaction of haloalkynes, affording chiral halohydrins with up to 99% enantioselectivity. Combined multifunctionalities, such as substrate-promoted silanol-functionality, BF4(-) anion-bonding gold/carbene and covalent-bonding chiral ruthenium/diamine active centers, contributed cooperatively to the catalytic performance...
January 18, 2017: Chemical Communications: Chem Comm
Yufeng Shen, Nikola Tolić, Paul D Piehowski, Anil K Shukla, Sangtae Kim, Rui Zhao, Yi Qu, Errol Robinson, Richard D Smith, Ljiljana Paša-Tolić
Separation of proteoforms for global intact protein analysis (i.e. top-down proteomics) has lagged well behind what is achievable for peptides in traditional bottom-up proteomic approach and is becoming a true bottle neck for top-down proteomics. Herein, we report use of long (≥1M) columns containing short alkyl (C1-C4) bonded phases to achieve high-resolution RPLC for separation of proteoforms. At a specific operation pressure limit (i.e., 96.5MPa or 14Kpsi used in this work), column length was found to be the most important factor for achieving maximal resolution separation of proteins when 1...
January 5, 2017: Journal of Chromatography. A
Mariam Mir, Umar Ansari, Murtaza Najabat Ali
BACKGROUND: Auxetic materials tend to exhibit stretching in the direction of the applied load as well as in the perpendicular direction. This may be an inherent property of the material, or it might be a particular structural characteristic that confers it with auxetic properties. In this study, the auxetic properties of a rotating squares auxetic design were utilized in tandem with a stretching mechanism to manufacture a device that offers the advantages of adjustable pore size and hence tunable drug delivery characteristics...
October 10, 2016: Journal of Applied Biomaterials & Functional Materials
Alissa J Schunter, Xiaoshan Yue, Amanda B Hummon
The contributions of phosphorylation-mediated signaling networks to colon cancer metastasis are poorly defined. To interrogate constitutive signaling alterations in cancer progression, the global phosphoproteomes of patient-matched SW480 (primary colon tumor origin) and SW620 (lymph node metastasis) cell lines were compared with TiO2 and immobilized metal affinity chromatography phosphopeptide enrichment followed by liquid chromatography-tandem mass spectrometry. Network analysis of the significantly altered phosphosites revealed differential regulation in cellular adhesion, mitosis, and messenger RNA translational machinery...
March 2017: Analytical and Bioanalytical Chemistry
Pyung Sun Cho, Han Kyu Lee, Sang Hoon Lee, Jay Zoon Im, Sung Jun Jung
The analgesic mechanism of opioids is known to decrease the excitability of substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary nociceptive afferent fiber by increasing inwardly rectifying K(+) current. In this study, we examined whether a µ-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), affects the two-pore domain K(+) channel (K2P) current in rat SG neurons using a slice whole-cell patch clamp technique. Also we confirmed which subtypes of K2P channels were associated with DAMGO-induced currents, measuring the expression of K2P channel in whole spinal cord and SG region...
September 2016: Korean Journal of Physiology & Pharmacology
Kazuhiro Sakamaki, Takahiro M Ishii, Toshiya Sakata, Kiwamu Takemoto, Chiyo Takagi, Ayako Takeuchi, Ryo Morishita, Hirotaka Takahashi, Akira Nozawa, Hajime Shinoda, Kumiko Chiba, Haruyo Sugimoto, Akiko Saito, Shuhei Tamate, Yutaka Satou, Sang-Kee Jung, Satoshi Matsuoka, Koji Koyamada, Tatsuya Sawasaki, Takeharu Nagai, Naoto Ueno
Activation of caspases is crucial for the execution of apoptosis. Although the caspase cascade associated with activation of the initiator caspase-8 (CASP8) has been investigated in molecular and biochemical detail, the physiological role of CASP8 is not fully understood. Here, we identified a two-pore domain potassium channel, tandem-pore domain halothane-inhibited K(+) channel 1 (THIK-1), as a novel CASP8 substrate. The intracellular region of THIK-1 was cleaved by CASP8 in apoptotic cells. Overexpression of THIK-1, but not its mutant lacking the CASP8-target sequence in the intracellular portion, accelerated cell shrinkage in response to apoptotic stimuli...
November 2016: Biochimica et Biophysica Acta
Bruce A Baggenstoss, Edward N Harris, Jennifer L Washburn, Andria P Medina, Long Nguyen, Paul H Weigel
Hyaluronan synthases (HAS) normally make large (>MDa) hyaluronan (HA) products. Smaller HA fragments (e.g. 100-400 kDa) produced in vivo are associated with inflammation and cell signaling by HA receptors that bind small, but not large, HA. Although HA fragments can arise from breakdown by hyaluronidases, HAS might also be regulated directly to synthesize small HA. Here we examined the Streptococcus equisimilis HAS (SeHAS) C-terminus, which contains a tandem B-X7-B motif (K(398)-X7-R(406)-X7-K(414)), by testing the effects of 27 site-specific scanning mutations and 7 C-terminal truncations on HA synthesis activity and weight-average mass...
January 2017: Glycobiology
Natalia Casado, Sonia Morante-Zarcero, Damián Pérez-Quintanilla, Isabel Sierra
A quick, sensitive and selective analytical reversed-phase multi-residue method using ultra-high performance liquid chromatography coupled to an ion-trap mass spectrometry detector (UHPLC-IT-MS/MS) operating in both positive and negative ion mode was developed for the simultaneous determination of 23 veterinary drug residues (β-blockers, β-agonists and Non-Steroidal Anti-inflammatory Drugs (NSAIDs)) in meat samples. The sample treatment involved a liquid-solid extraction followed by a solid-phase extraction (SPE) procedure...
August 12, 2016: Journal of Chromatography. A
Yi-Bing Hu, Davide Sosso, Xiao-Qing Qu, Li-Qing Chen, Lai Ma, Diane Chermak, De-Chun Zhang, Wolf B Frommer
SWEETs represent a new class of sugar transporters first described in plants and animals/humans and later in prokaryotes. Plant SWEETs play key roles in phloem loading, seed filling, and nectar secretion, whereas the role of archaeal, bacterial, and animal transporters remains elusive. Structural analyses show that eukaryotic SWEETs are composed of 2 triple-helix bundles (THBs) fused via an inversion linker helix, whereas prokaryotic SemiSWEETs contain only a single THB and require homodimerization to form transport pores...
July 13, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Alejandro M Fracaroli, Peter Siman, David A Nagib, Mitsuharu Suzuki, Hiroyasu Furukawa, F Dean Toste, Omar M Yaghi
The design of enzyme-like complexity within metal-organic frameworks (MOFs) requires multiple reactions to be performed on a MOF crystal without losing access to its interior. Here, we show that seven post-synthetic reactions can be successfully achieved within the pores of a multivariate MOF, MTV-IRMOF-74-III, to covalently incorporate tripeptides that resemble the active sites of enzymes in their spatial arrangement and compositional heterogeneity. These reactions build up H2N-Pro-Gly-Ala-CONHL and H2N-Cys-His-Asp-CONHL (where L = organic struts) amino acid sequences by covalently attaching them to the organic struts in the MOFs, without losing porosity or crystallinity...
July 13, 2016: Journal of the American Chemical Society
Joseph J Gillespie, Isabelle Q H Phan, Timothy P Driscoll, Mark L Guillotte, Stephanie S Lehman, Kristen E Rennoll-Bankert, Sandhya Subramanian, Magda Beier-Sexton, Peter J Myler, M Sayeedur Rahman, Abdu F Azad
Many prokaryotes utilize type IV secretion systems (T4SSs) to translocate substrates (e.g. nucleoprotein, DNA, protein) across the cell envelope, and/or to elaborate surface structures (i.e. pili or adhesins). Among eight distinct T4SS classes, P-T4SSs are typified by the Agrobacterium tumefaciens vir T4SS, which is comprised of 12 scaffold components (VirB1-VirB11, VirD4). While most P-T4SSs include all 12 Vir proteins, some differ from the vir archetype by either containing additional scaffold components not analogous to Vir proteins or lacking one or more of the Vir proteins...
August 2016: Pathogens and Disease
Marcel J Tauchert, Clément Hémonnot, Piotr Neumann, Sarah Köster, Ralf Ficner, Achim Dickmanns
In eukaryotic cells, the exchange of macromolecules between the nucleus and cytoplasm is highly selective and requires specialized soluble transport factors. Many of them belong to the importin-β superfamily, the members of which share an overall superhelical structure owing to the tandem arrangement of a specific motif, the HEAT repeat. This structural organization leads to great intrinsic flexibility, which in turn is a prerequisite for the interaction with a variety of proteins and for its transport function...
June 2016: Acta Crystallographica. Section D, Structural Biology
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