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https://www.readbyqxmd.com/read/29145032/intravenous-immunoglobulin-improves-glucose-control-and-%C3%AE-cell-function-in-human-iapp-transgenic-mice-by-attenuating-islet-inflammation-and-reducing-iapp-oligomers
#1
Yue Zhang, Xiao-Lin Yu, Jie Zhu, Shu-Ying Liu, Xiang-Meng Liu, Quan-Xiu Dong, Jia-Qian Chai, Rui-Tian Liu
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by β-cell loss, insulin resistance, islet inflammation and amyloid deposits derived from islet amyloid polypeptide (IAPP). Reducing toxic IAPP oligomers and inhibiting islet inflammation may provide therapeutic benefit in treating T2DM. Intravenous immunoglobulin (IVIg) is an efficient anti-inflammatory and immunomodulatory agent for the treatment of several autoimmune or inflammatory neurological diseases. However, whether IVIg has therapeutic potential on T2DM remains unclear...
November 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29144019/pegylated-precision-segments-based-on-sequence-defined-thiolactone-oligomers
#2
Sensu Celasun, Filip E Du Prez, Hans G Börner
A straightforward access route to multifunctional block copolymers, combining a poly(ethylene glycol) (PEG) block and a monodisperse segment with discrete monomer sequence based on thiolactone chemistry, is described. Exploiting an inverse conjugation strategy on a PEG preloaded poly(styrene) synthesis resin enables the convenient introduction of a predefined PEG-block at the α-terminus of thiolactone-based sequence-defined oligomers. Reaction conditions for the stepwise, submonomer synthesis at polar solid supports are optimized, using sequential synthesis on a model resin that enables to isolate and determine the purity of the oligomer segments by liquid chromatography-electrospray ionization mass spectrometry analysis...
November 16, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/29144013/photocontrolled-synthesis-of-abiotic-sequence-defined-oligo-phosphodiester-s
#3
Niklas Felix König, Sofia Telitel, Salomé Poyer, Laurence Charles, Jean-François Lutz
A photoregulated phosphoramidite iterative process is studied for the synthesis of non-natural, digitally encoded oligo(phosphodiester)s. The oligomers are prepared using two reactive phosphoramidite monomers containing a 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) protected OH group. The stepwise synthesis is performed on an OH-functional soluble polystyrene support, which allows recycling by precipitation in a nonsolvent. Repeating cycles involving phosphoramidite coupling, oxidation of phosphite to phosphate, and NPPOC deprotection by light irradiation at λ = 365 nm are performed in order to prepare oligomers with different lengths and sequences...
November 16, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/29143447/investigation-of-the-interactions-between-aptamer-and-misfolded-proteins-from-monomer-and-oligomer-to-fibril-by-single-molecule-force-spectroscopy
#4
Yan Zheng, Qing Wang, Xiaohai Yang, Zhiping Li, Lei Gao, Hua Zhang, Wenyan Nie, Xiuhua Geng, Kemin Wang
Increasing knowledge on the understanding interactions of aptamer with misfolded proteins (including monomer, oligomer, and amyloid fibril) is crucial for development of aggregation inhibitors and diagnosis of amyloid diseases. Herein, the interactions of lysozyme monomer-, oligomer-, and amyloid fibril-aptamer were investigated using single-molecule force spectroscopy. The results revealed that the aptamer screened against lysozyme monomer could also bind to oligomer and amyloid fibril, in spite of the recognition at a lower binding probability...
November 16, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29142509/using-an-nmr-metabolomics-approach-to-investigate-the-pathogenicity-of-amyloid-beta-and-alpha-synuclein
#5
M M Phelan, E Caamaño-Gutiérrez, M S Gant, R X Grosman, J Madine
Introduction: The pathogenicity at differing points along the aggregation pathway of many fibril-forming proteins associated with neurodegenerative diseases is unclear. Understanding the effect of different aggregation states of these proteins on cellular processes is essential to enhance understanding of diseases and provide future options for diagnosis and therapeutic intervention. Objectives: To establish a robust method to probe the metabolic changes of neuronal cells and use it to monitor cellular response to challenge with three amyloidogenic proteins associated with neurodegenerative diseases in different aggregation states...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/29139533/at-the-very-beginning-of-life-on-earth-the-thiol-rich-peptide-trp-world-hypothesis
#6
Yannick Vallee, Ibrahim Shalayel, Kieu-Dung Ly, K V Raghavendra Rao, Gael De Paëpe, Katharina Märker, Anne Milet
Life developed on Earth probably about 3.8 billion years ago, on a planet that was already largely covered by oceans and where the atmosphere was very humid. The reactions, which may have led to the formation of the first polymers, particularly to the first peptides and nucleic acids, must have been compatible with these conditions. This is the case of the reaction of nitriles with aminothiols, such as cysteine and homocysteine. Since aminonitriles are the probable precursors of amino acids, this condensation reaction has been able to rapidly yield dipeptides, tripeptides, oligomers and even true polymers, each containing thiol functions...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/29139289/tetraaza-14-and-octaaza-18-paracyclophane-synthesis-and-characterization-of-their-neutral-and-cationic-states
#7
Daisuke Sakamaki, Akihiro Ito, Yusuke Tsutsui, Shu Seki
Two kinds of aza[1n]paracyclophanes, tetraaza[14]paracyclophane (P4) and octaaza[18]paracyclophane (P8), were synthesized as the smallest and the largest monodisperse macrocyclic oligomers of polyaniline ever made. Herein we reports the electronic nature of the cationic species of these two macrocycles with different ring-size. By combining ESR spectroscopy and DFT calculations, it was suggested that P4·+ was classified into delocalized class III or poised on the class II/III borderline, while P8·+ was regarded as localized class II mixed-valence system...
November 15, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29138762/identifying-cu-ii-amyloid-peptide-binding-intermediates-in-the-early-stages-of-aggregation-by-resonance-raman-spectroscopy-a-simulation-study
#8
Hao Ren, Yu Zhang, Sibei Guo, Na Lin, Li Deng, Tongtao Yue, Fang Huang
The aggregation of amyloid beta (Aβ) peptides plays a crucial role in the pathology and etiology of Alzheimer's disease. Experimental evidence shows that copper ion is an aggregation-prone species with the ability to coordinately bind to Aβ and further induce the formation of neurotoxic Aβ oligomers. However, the detailed structures of Cu(ii)-Aβ complexes have not been illustrated, and the kinetics and dynamics of the Cu(ii) binding are not well understood. Two Cu(ii)-Aβ complexes have been proposed to exist under physiological conditions, and another two might exist at higher pH values...
November 15, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29138001/pdz-ligand-binding-induced-conformational-coupling-of-the-pdz-sh3-gk-tandems-in-psd-95-family-maguks
#9
Menglong Zeng, Fei Ye, Jia Xu, Mingjie Zhang
DLG MAGUKs are abundantly expressed in glutamatergic synapses, crucial for synaptic transmission and plasticity by anchoring various postsynaptic components including glutamate receptors, downstream scaffold proteins and signaling enzymes. Different DLG members have shared structures and functions, but also contain unique features. How DLG family proteins function individually and cooperatively are largely unknown. Here, we report that PSD-95 PDZ3 directly couples with SH3-GK tandem in a PDZ ligand binding-dependent manner, and the coupling can promote PSD-95 dimerization and multimerization...
November 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29137975/microarray-analysis-of-an-synthetic-%C3%AE-synuclein-induced-cellular-model-reveals-the-expression-profile-of-long-non-coding-rna-in-parkinson-s-disease
#10
D Lin, Y Liang, X Jing, Y Chen, M Lei, Z Zeng, T Zhou, X Wu, S Peng, D Zheng, K Huang, L Yang, S Xiao, J Liu, E Tao
Long non-coding RNAs (lncRNAs) are a new research focus that are reported to influence the pathogenetic process of neurodegenerative disorders. To uncover new disease-associated genes and their relevant mechanisms, we carried out a gene microarray analysis based on a Parkinson's disease (PD) in vitro model induced by α-synuclein oligomers. This cellular model induced by 25 μmol/L α-synuclein oligomers has been confirmed to show the stable, transmissible neurotoxicity of α-synuclein, a typical PD pathological marker...
November 11, 2017: Brain Research
https://www.readbyqxmd.com/read/29137651/abnormal-dendritic-calcium-activity-and-synaptic-depotentiation-occur-early-in-a-mouse-model-of-alzheimer-s-disease
#11
Yang Bai, Miao Li, Yanmei Zhou, Lei Ma, Qian Qiao, Wanling Hu, Wei Li, Zachary Patrick Wills, Wen-Biao Gan
BACKGROUND: Alzheimer's disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention and treatment of AD. METHODS: We performed in vivo two-photon calcium imaging to examine the activities of somas, dendrites and dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex in the APPswe/PS1dE9 mouse model of AD and age-matched wild type control mice...
November 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29137322/the-c-jun-n-terminal-kinase-plays-a-key-role-in-ocular-degenerative-changes-in-a-mouse-model-of-alzheimer-disease-suggesting-a-correlation-between-ocular-and-brain-pathologies
#12
Lucia Buccarello, Alessandra Sclip, Matteo Sacchi, Anna Maria Castaldo, Ilaria Bertani, Andrea ReCecconi, Silvia Maestroni, Gianpaolo Zerbini, Paolo Nucci, Tiziana Borsello
Recently a range of ocular manifestations such as retinal and lens amyloid-beta accumulation and retinal nerve fiber layer loss have been proposed as potential biomarkers in Alzheimer disease (AD). The TgCRND8 mouse model of AD exhibits age-dependent amyloid β (Aβ) oligomers accumulation and cognitive defects, amyloid plaques and hyperphosphorylated Tau deposition and inflammation. We proved the correlation between ocular pathologies and AD, observing increased levels of p-APP and p-Tau, accumulation of Aβ oligomers in the retina, eye, and optic nerve...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135234/evaluating-the-effect-of-phosphorylation-on-the-structure-and-dynamics-of-hsp27-dimers-by-means-of-ion-mobility-mass-spectrometry
#13
Blagojce Jovcevski, Megan A Kelly, J Andrew Aquilina, Justin L P Benesch, Heath Ecroyd
The quaternary structure and dynamics of the human small heat-shock protein Hsp27 is linked to its molecular chaperone function and influenced by post-translational modifications, including phosphorylation. Phosphorylation of Hsp27 promotes oligomer dissociation and can enhance chaperone activity. This study explored the impact of phosphorylation on the quaternary structure and dynamics of Hsp27. Using mutations that mimic phosphorylation and ion mobility mass spectrometry we show that successive substitutions result in an increase in the conformational heterogeneity of Hsp27 dimers...
November 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29135003/elucidating-electrolyte-decomposition-under-electron-rich-environments-at-the-lithium-metal-anode
#14
Luis E Camacho-Forero, Perla B Balbuena
The lithium metal anode is one of the key components of the lithium-sulfur (Li-S) batteries, which are considered one of the most promising candidates for the next generation of battery systems. However, one of the main challenges that have prevented Li-metal anodes from becoming feasible to be used in commercial batteries is the continuous decomposition of the electrolyte due to its high reactivity, which leads to the formation of solid-electrolyte interphase (SEI) layers. The properties of the SEI can dramatically affect the performance of the batteries...
November 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29134806/acid-catalyzed-skeletal-rearrangements-in-arenes-aryl-vs-alkyl-ring-pirouettes-in-anthracene-and-phenanthrene
#15
Sarah L Skraba-Joiner, Jeffrey W Brulet, Min K Song, Richard P Johnson
In 1 M triflic acid/dichloroethane, anthracene is completely protonated at C9 and the resulting 9-anthracenium ion is easily observed at ambient temperature. When heated at > 84 °C as a dilute (10-3 M) solution in 1 M triflic acid/dichloroethane (DCE), anthracene undergoes conversion to phenanthrene as the major volatile product. Minor dihydro and tetrahydro products are also observed. MALDI analysis supports the simultaneous formation of oligomers, primarily dimeric, which represent 10 - 60% of the product mixture...
November 14, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29134248/the-ancient-claudin-dni2-facilitates-yeast-cell-fusion-by-compartmentalizing-dni1-into-a-membrane-subdomain
#16
M-Ángeles Curto, Sandra Moro, Francisco Yanguas, Carmen Gutiérrez-González, M-Henar Valdivieso
Dni1 and Dni2 facilitate cell fusion during mating. Here, we show that these proteins are interdependent for their localization in a plasma membrane subdomain, which we have termed the mating fusion domain. Dni1 compartmentation in the domain is required for cell fusion. The contribution of actin, sterol-dependent membrane organization, and Dni2 to this compartmentation was analysed, and the results showed that Dni2 plays the most relevant role in the process. In turn, the Dni2 exit from the endoplasmic reticulum depends on Dni1...
November 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29133893/two-step-process-for-disassembly-mechanism-of-proteasome-%C3%AE-7-homo-tetradecamer-by-%C3%AE-6-revealed-by-high-speed-atomic-force-microscopy
#17
Toshiya Kozai, Taichiro Sekiguchi, Tadashi Satoh, Hirokazu Yagi, Koichi Kato, Takayuki Uchihashi
The 20S proteasome is a core particle of the eukaryotic proteasome responsible for proteolysis and is composed of layered α and β hetero-heptameric rings. The α7 subunit, which is one of components of the α ring, is known to self-assemble into a double-ringed homo-tetradecamer composed of two layers of the α7 heptameric ring. The α7 tetradecamer is known to disassemble upon the addition of α6 subunit, producing a 1:7 hetero-octameric α6-α7 complex. However, the detailed disassembly mechanism remains unclear...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133832/jmjd8-is-a-novel-endoplasmic-reticulum-protein-with-a-jmjc-domain
#18
Kok Siong Yeo, Ming Cheang Tan, Yat-Yuen Lim, Chee-Kwee Ea
Jumonji C (JmjC) domain-containing proteins have been shown to regulate cellular processes by hydroxylating or demethylating histone and non-histone targets. JMJD8 belongs to the JmjC domain-only family that was recently shown to be involved in angiogenesis and TNF-induced NF-κB signaling. Here, we employed bioinformatic analysis and immunofluorescence microscopy to examine the physiological properties of JMJD8. We demonstrated that JMJD8 localizes to the lumen of endoplasmic reticulum and that JMJD8 forms dimers or oligomers in vivo...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29132139/study-of-hspb6-insights-into-the-properties-of-the-multifunctional-protective-agent
#19
Fazhao Li, Han Xiao, Fangfang Zhou, Zhiping Hu, Binbin Yang
HSPB6(Heat shock protein B6), is also referred to as P20/HSP20. Unlike other many other members of sHSP(small Heat shock protein) family, which tend to form high-molecular-mass oligomers, in solution, human HSPB6 only forms dimers. However, it still exhibits chaperon-like activity comparable with that of HSPB5. It is expressed ubiquitously, with high and constitutive expression in muscular tissues. sHSPs characteristically function as molecular chaperones and HSPB6 also has a molecular chaperone activity. HSPB6 is up-regulated in response to diverse cellular stress or damage and protect cells from otherwise lethal conditions...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29131216/detection-of-the-electronic-structure-of-iron-iii-oxo-oligomers-forming-in-aqueous-solutions
#20
Robert Seidel, Katrin Kraffert, Anke Kabelitz, Marvin N Pohl, Ralph Kraehnert, Franziska Emmerling, Bernd Winter
The nature of the small iron-oxo oligomers in iron-(iii) aqueous solutions has a determining effect on the chemical processes that govern the formation of nanoparticles in aqueous phase. Here we report on a liquid-jet photoelectron-spectroscopy experiment for the investigation of the electronic structure of the occurring iron-oxo oligomers in FeCl3 aqueous solutions. The only iron species in the as-prepared 0.75 M solution are Fe(3+) monomers. Addition of NaOH initiates Fe(3+) hydrolysis which is followed by the formation of iron-oxo oligomers...
November 13, 2017: Physical Chemistry Chemical Physics: PCCP
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