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https://www.readbyqxmd.com/read/29343286/diagnosis-and-management-of-transthyretin-familial-amyloid-polyneuropathy-in-japan-red-flag-symptom-clusters-and-treatment-algorithm
#1
REVIEW
Yoshiki Sekijima, Mitsuharu Ueda, Haruki Koike, Sonoko Misawa, Tomonori Ishii, Yukio Ando
Hereditary ATTR (ATTRm) amyloidosis (also called transthyretin-type familial amyloid polyneuropathy [ATTR-FAP]) is an autosomal-dominant, adult-onset, rare systemic disorder predominantly characterized by irreversible, progressive, and persistent peripheral nerve damage. TTR gene mutations (e.g. replacement of valine with methionine at position 30 [Val30Met (p.Val50Met)]) lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, which form amyloid fibrils that deposit in peripheral nerves and various organs, giving rise to peripheral and autonomic neuropathy and several non-disease specific symptoms...
January 17, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29339766/the-crystal-structure-of-d-xylonate-dehydratase-reveals-functional-features-of-enzymes-from-the-ilv-ed-dehydratase-family
#2
Mohammad Mubinur Rahman, Martina Andberg, Anu Koivula, Juha Rouvinen, Nina Hakulinen
The Ilv/ED dehydratase protein family includes dihydroxy acid-, gluconate-, 6-phosphogluconate- and pentonate dehydratases. The members of this family are involved in various biosynthetic and carbohydrate metabolic pathways. Here, we describe the first crystal structure of D-xylonate dehydratase from Caulobacter crescentus (CcXyDHT) at 2.7 Å resolution and compare it with other available enzyme structures from the IlvD/EDD protein family. The quaternary structure of CcXyDHT is a tetramer, and each monomer is composed of two domains in which the N-terminal domain forms a binding site for a [2Fe-2S] cluster and a Mg2+ ion...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339296/silent-transmission-of-an-is1294b-deactivated-mcr-1-gene-with-inducible-colistin-resistance
#3
Kai Zhou, Qixia Luo, Qin Wang, Chen Huang, Haifeng Lu, Rossen W A John, Yonghong Xiao, Lanjuan Li
The global dissemination of the mobile colistin resistance mcr-1 is of special concern, as colistin is one of the last-resort antibiotics for the treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria. Here, we characterized an inactive form of mcr-1 in a fluoroquinolone-resistant and colistin-susceptible uropathogenic Escherichia coli isolate (ECO3347). The mcr-1 gene was deactivated by the insertion of a 1.7-Kb IS1294b element flanked by two tetramers (GTTC), and located on a 62-Kb pHNSHP45-like plasmid (p3347-mcr-1)...
January 12, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29337919/functional-impact-of-the-n-terminal-arm-of-proline-dehydrogenase-from-thermus-thermophilus
#4
Mieke M E Huijbers, Ilona van Alen, Jenny W Wu, Arjan Barendregt, Albert J R Heck, Willem J H van Berkel
Proline dehydrogenase (ProDH) is a ubiquitous flavoenzyme that catalyzes the oxidation of proline to Δ¹-pyrroline-5-carboxylate. Thermus thermophilus ProDH (TtProDH) contains in addition to its flavin-binding domain an N-terminal arm, consisting of helices αA, αB, and αC. Here, we report the biochemical properties of the helical arm truncated TtProDH variants ΔA, ΔAB, and ΔABC, produced with maltose-binding protein as solubility tag. All three truncated variants show similar spectral properties as TtProDH, indicative of a conserved flavin-binding pocket...
January 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29336473/usefulness-of-identifying-g-protein-coupled-receptor-dimers-for-diagnosis-and-therapy-of-neurodegenerative-diseases-and-of-gliomas
#5
REVIEW
Irene Reyes-Resina, David Aguinaga, José Luis Labandeira-García, José Luis Lanciego, Gemma Navarro, Rafael Franco
Immunochemical detection of G-protein-coupled receptors (GPCRs) in cells and tissues was a technical challenge for years. After the discovery of formation of GPCR dimers/trimers/tetramers in transfected cells, a most recent challenge has been to confirm receptor-receptor interactions in natural sources. The occurrence of dimers or higher order oligomers is important from a therapeutic point of view, mainly because their physiology/pharmacology is different from those of individual receptors. On the one hand, pathophysiological factors need to count more on GPCR dimers than on individual receptors...
January 16, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29336146/coordination-triggered-hierarchical-folate-zinc-supramolecular-hydrogels-leading-to-printable-biomaterials
#6
Kaerdun Liu, Shihao Zang, Rongrong Xue, Jinghui Yang, Lizhi Wang, Jianbin Huang, Yun Yan
Printable hydrogels desired in bioengineering have extremely high demands on biocompatibility and mechanic strength, which can hardly be achieved in conventional hydrogels made with biopolymers. Here we show that on employment of the strategy of coordination triggered hierarchical self-assembly of naturally occurred small molecule folic acid, supramolecular hydrogels with robust mechanical elastic modulus comparable to synthetic double network (DN) polymer gels can be made at concentrations below 1 %. A sequence of hierarchical steps are involved in the formation of this extraordinary hydrogel: petrin rings on folate form tetramers through hydrogen bonding, tetramers stack into nanofibers by π-π stacking, zinc ions cross-link the nanofibers into larger scale fibrils, and further crosslink the fibril network to gel water...
January 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29334588/molecular-wire-effects-in-phenyleneethynylene-oligomers-surprising-insights
#7
Uwe Heiko Bunz, Marcel Hergert, Markus Bender, Kai Seehafer
We report the synthesis and quenching behavior of a series of water soluble, carboxylate-carrying phenyleneethynylene oligomers - monomer to tetramer - and their polymers and investigate their quenching behavior with different test analytes (paraquat, lead salts, mercury salts, picric acid, methylpyridinium iodide) in water and compare the results to that of the conjugated polymer. We find significant but analyte-dependent enhancement effects. For monovalent quenchers only the molecular wire effect applies but for divalent quenchers multivalency effects are also important...
January 15, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29333638/rapid-profiling-of-polymeric-phenolic-acids-in-salvia-miltiorrhiza-by-hybrid-data-dependent-targeted-multistage-mass-spectrometry-acquisition-based-on-expected-compounds-prediction-and-fragment-ion-searching
#8
Yao Shen, Zijin Feng, Min Yang, Zhe Zhou, Sumei Han, Jinjun Hou, Zhenwei Li, Wanying Wu, De-An Guo
Phenolic acids are the major water-soluble components in Salvia miltiorrhiza (> 5%). According to previous studies, many of them contribute to the cardiovascular effects and antioxidant effects of S. miltiorrhiza. Polymeric phenolic acids can be considered as the tanshinol derived metabolites, e.g., dimmers, trimers and tetramers. A strategy combined with tanshinol-based expected compounds prediction, total ion chromatogram filtering, Fragment Ion Searching and parent list-based multistage mass spectrometry acquisition by Linear Trap Quadropole-orbitrap Velos Mass Spectrometry was proposed to rapid profile polymeric phenolic acids in S...
January 15, 2018: Journal of Separation Science
https://www.readbyqxmd.com/read/29331860/c18-core-shell-column-with-in-series-absorbance-and-fluorescence-detection-for-simultaneous-monitoring-of-changes-in-stilbenoid-and-proanthocyanidin-concentrations-during-grape-cane-storage
#9
Vania Sáez, Camila Gayoso, Sebastián Riquelme, Julie Pérez, Carola Vergara, Claudia Mardones, Dietrich von Baer
Grape canes, the residues from the annual pruning of vines, contain high levels of inducible (E)-resveratrol and also oligomeric stilbenoids and proanthocyanidins. These two families of phenolic compounds are bioactive, but to quantify them in a single chromatographic run using only ultraviolet detection is a difficult task. To overcome this limitation, a chromatographic method was developed using a core shell column for separation, an ultraviolet-visible diode array detector (DAD) and a fluorescence (FL) detector connected in series for quantification, with an electrospray ionization interface (ESI) and a triple quadrupole mass spectrometric detector (MS/MS) added for identification of the analytes...
December 29, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29331225/influence-of-pressure-on-the-retention-of-resorcinarene-based-cavitands
#10
Ibolya Prauda, Endre Bartó, Attila Felinger
The thermodynamics of the retention mechanism of resorcinarene-based cavitands in RPLC as well as the nature of the binding sites have been studied recently. In the present study, the influence of pressure on the retention of the cyclic tetramers on alkylsilyl and polar-embedded C8 and C18 stationary phases is investigated using aqueous methanol mobile phase. The pressure effect for cavity-shaped molecules has been scarcely studied so far. We observed that the retention factors of the analytes increased with the increase of the average column pressure (1-400 bar) when using restricting capillary tubes...
January 9, 2018: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29331224/centrifugal-partition-chromatography-enables-selective-enrichment-of-trimeric-and-tetrameric-proanthocyanidins-for-biomaterial-development
#11
Rasika S Phansalkar, Joo-Won Nam, Shao-Nong Chen, James B McAlpine, Ariene A Leme, Berdan Aydin, Ana-Karina Bedran-Russo, Guido F Pauli
Proanthocyanidins (PACs) find wide applications for human use including food, cosmetics, dietary supplements, and pharmaceuticals. The chemical complexity associated with PACs has triggered the development of various chromatographic techniques, with countercurrent separation (CCS) gaining in popularity. This study applied the recently developed DESIGNER (Depletion and Enrichment of Select Ingredients Generating Normalized Extract Resources) approach for the selective enrichment of trimeric and tetrameric PACs using centrifugal partition chromatography (CPC)...
December 21, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29331201/impact-of-polymer-geometry-on-the-interactions-of-protein-peg-conjugates
#12
Jonathan Zarzar, Whitney Shatz, Nikhil Peer, Rosalynn Taing, Brian McGarry, Yun Liu, Daniel G Greene, Isidro E Zarraga
The conjugation of high molecular weight polyethylene glycol (PEG) to an active pharmaceutical ingredient (API) is an attractive strategy for the modification of biophysical and biodistribution properties of the API. Indeed, several therapeutic proteins conjugated to PEG have been safely administered in the clinic. While there have been studies on the configuration of these conjugates in solution, investigations on the impact of PEG geometry on protein-PEG conjugate interactions is limited. In this study, we use dynamic light scattering (DLS), rheology, and small-angle neutron scattering (SANS) to investigate the biophysical solution and interaction behavior of a 50kDa Fab protein attached to either a linear or tetrameric (branched) 40kDa PEG molecule...
November 8, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/29330472/amyloid-deposition-in-a-mouse-model-humanized-at-the-transthyretin-and-retinol-binding-protein-4-loci
#13
Xiangshun Li, Yanyi Lyu, Jingling Shen, Yanshuang Mu, Lixia Qiang, Li Liu, Kimi Araki, Bruno P Imbimbo, Ken-Ichi Yamamura, Shoude Jin, Zhenghua Li
Familial amyloidotic polyneuropathy is an autosomal dominant disorder caused by a point mutation in the transthyretin (TTR) gene. The process of TTR amyloidogenesis begins with rate-limiting dissociation of the TTR tetramer. Thus, the TTR stabilizers, such as Tafamidis and Diflunisal, are now in clinical trials. Mouse models will be useful to testing the efficacy of these drugs. Although several mouse models have been generated, they all express mouse Rbp4. Thus, human TTR associates with mouse RBP4, resulting in different kinetic and thermodynamic stability profiles of TTR tetramers...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29326162/structural-basis-for-p-ppgpp-synthesis-by-the-staphylococcus-aureus-small-alarmone-synthetase-relp
#14
Melek Cemre Manav, Jelena Beljantseva, Martin Saxtorph Bojer, Tanel Tenson, Hanne Ingmer, Vasili Hauryliuk, Ditlev Egeskov Brodersen
The stringent response is a global reprogramming of bacterial physiology that renders cells more tolerant to antibiotics and induces virulence gene expression in pathogens in response to stress. This process is driven by accumulation of the intracellular alarmone guanosine-5'-di(tri)phosphate-3'-diphosphate ([p]ppGpp), which is produced by enzymes of the RelA SpoT homologue (RSH) family. The Gram-positive Firmicute pathogen, Staphylococcus aureus, encodes three RSH enzymes: a multi-domain RSH (Rel) that senses amino acid starvation on the ribosome and two small alarmone synthetase (SAS) enzymes, RelQ (SAS1) and RelP (SAS2)...
January 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29322425/production-of-recombinant-killer-immunoglobulin-like-receptors-for-crystallography-and-luminex-based-assays
#15
Phillip Pymm, Julian P Vivian
The killer immunoglobulin-like receptors (KIR) are a highly diverse family of cell-surface receptors that are of importance to the effector function of Natural Killer cells. KIR have been implicated in the detection and clearance of malignantly transformed cells and in the immune-control of viruses including HIV, HCV and CMV. Recently, the mismatching of donor and recipient KIR has been demonstrated to improve success of hematopoietic stem cell transplantation treatments of leukemias. Due to the high degree of diversity amongst the KIR, a number of strategies are required for the production of recombinant protein for medical, biochemical and structural applications...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321329/a-cyclin-binding-motif-in-human-samhd1-is-required-for-its-hiv-1-restriction-dntpase-activity-tetramer-formation-and-efficient-phosphorylation
#16
Corine St Gelais, Sun Hee Kim, Victoria V Maksimova, Olga Buzovetsky, Kirsten Knecht, Caitlin Shepard, Baek Kim, Yong Xiong, Li Wu
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) regulates intracellular deoxynucleoside triphosphate (dNTP) levels and functions as a retroviral restriction factor through its dNTP triphosphohydrolase (dNTPase) activity. Human SAMHD1 interacts with cell cycle regulatory proteins cyclin A2, cyclin-dependent kinase 1 (CDK1), and CDK2. This interaction mediates phosphorylation of SAMHD1 at threonine 592 (T592), which negatively regulates HIV-1 restriction. We previously reported that the interaction is mediated, at least in part, through a cyclin-binding motif (RXL, aa...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29318657/crystal-structure-of-tetrameric-human-rabin8-gef-domain
#17
Melanie Vetter, Niels Boegholm, Anni Christensen, Sagar Bhogaraju, Marie B Andersen, Anna Lorentzen, Esben Lorentzen
Rab GTPases and their effectors, activators and guanine nucleotide exchange factors (GEFs) are essential for vesicular transport. Rab8 and its GEF Rabin8 function in formation of the cilium organelle important for developmental signaling and sensory reception. Here we show by size exclusion chromatography and analytical ultracentrifugation that Rabin8 exists in equilibrium between dimers and tetramers. The crystal structure of tetrameric Rabin8 GEF domain reveals an occluded Rab8 binding site suggesting that this oligomer is enzymatically inactive, a notion we verify experimentally using Rabin8/Rab8 GEF assays...
January 10, 2018: Proteins
https://www.readbyqxmd.com/read/29316124/analysis-of-quaternary-structure-of-hb-beckman-variant-and-molecular-interpretation-of-its-functional-abnormality-a-mass-spectrometry-based-approach
#18
Monita Muralidharan, Rajdeep Das, Vijay Bhat, Amit Kumar Mandal
Electrostatic attraction between α and β globin chains hold the subunits together in tetrameric human hemoglobin molecule (α₂β₂). Compared to normal globin chains, the affinity of a mutant chain to its partner globin in genetic variants of hemoglobin might be different. This leads to an unequal abundance of normal and variant hemoglobin in heterozygous sample, even though the rates of synthesis of both normal and variant chains are same. The aforementioned affinities across various globin chains might be assessed by the quantification of different forms of tetramers present in a variant hemoglobin sample...
January 8, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29315587/comparisons-of-electron-transfer-reactions-in-a-cyanobacterial-tetrameric-and-trimeric-photosystem-i-complexes
#19
Ivan V Shelaev, Mahir D Mamedov, Fedor E Gostev, Arseny V Aybush, Meng Li, Jonathan Nguyen, Barry D Bruce, Victor A Nadtochenko
Photosystem I (PSI) is a Type-I reaction center and the largest photosynthetic complex to be characterized. In cyanobacteria, PSI is organized as a trimer with a three-fold axis of symmetry. Recently, a tetrameric form of PSI has been identified in cyanobacteria. Plastids in plants and algae only contain monomeric PSI, suggesting that tetrameric PSI may be key in the transition from ancestral cyanobacterial trimeric PSI to plant/algal monomeric PSI. We have investigated the kinetics of e- transfer to the initial acceptor in PSI tetramer isolated from Chroococcidiopsis TS-821...
January 8, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29315406/snapshots-of-a-molecular-swivel-in-action
#20
Caitlin S Trejo, Ronald S Rock, W Marshall Stark, Martin R Boocock, Phoebe A Rice
Members of the serine family of site-specific recombinases exchange DNA strands via 180° rotation about a central protein-protein interface. Modeling of this process has been hampered by the lack of structures in more than one rotational state for any individual serine recombinase. Here we report crystal structures of the catalytic domains of four constitutively active mutants of the serine recombinase Sin, providing snapshots of rotational states not previously visualized for Sin, including two seen in the same crystal...
January 5, 2018: Nucleic Acids Research
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