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#33246331   2020/11/27 To Up

Alzheimer's disease brain-derived extracellular vesicles spread tau pathology in interneurons.

Extracellular vesicles are highly transmissible and play critical roles in the propagation of tau pathology, although the underlying mechanism remains elusive. Here, for the first time, we comprehensively characterized the physicochemical structure and pathogenic function of human brain-derived extracellular vesicles isolated from Alzheimer's disease, prodromal Alzheimer's disease, and non-demented control cases. Alzheimer's disease extracellular vesicles were significantly enriched in epitope-specific tau oligomers in comparison to prodromal Alzheimer's disease or control extracellular vesicles as determined by dot blot and atomic force microscopy. Alzheimer's disease extracellular vesicles were more efficiently internalized by murine cortical neurons, as well more efficient in transferring and misfolding tau, than prodromal Alzheimer's disease and control extracellular vesicles in vitro. Strikingly, the inoculation of Alzheimer's disease or prodromal Alzheimer's disease extracellular vesicles containing only 300 pg of tau into the outer molecular layer of the dentate gyrus of 18-month-old C57BL/6 mice resulted in the accumulation of abnormally phosphorylated tau throughout the hippocampus by 4.5 months, whereas inoculation of an equal amount of tau from control extracellular vesicles, isolated tau oligomers, or fibrils from the same Alzheimer's disease donor showed little tau pathology. Furthermore, Alzheimer's disease extracellular vesicles induced misfolding of endogenous tau in both oligomeric and sarkosyl-insoluble forms in the hippocampal region. Unexpectedly, phosphorylated tau was primarily accumulated in glutamic acid decarboxylase 67 (GAD67) GABAergic interneurons and, to a lesser extent, glutamate receptor 2/3-positive excitatory mossy cells, showing preferential extracellular vesicle-mediated GABAergic interneuronal tau propagation. Whole-cell patch clamp recordings of CA1 pyramidal cells showed significant reduction in the amplitude of spontaneous inhibitory post-synaptic currents. This was accompanied by reductions in c-fos+ GAD67+ neurons and GAD67+ neuronal puncta surrounding pyramidal neurons in the CA1 region, confirming reduced GABAergic transmission in this region. Our study posits a novel mechanism for the spread of tau in hippocampal GABAergic interneurons via brain-derived extracellular vesicles and their subsequent neuronal dysfunction.
Zhi Ruan, Dhruba Pathak, Srinidhi Venkatesan Kalavai, Asuka Yoshii-Kitahara, Satoshi Muraoka, Nemil Bhatt, Kayo Takamatsu-Yukawa, Jianqiao Hu, Yuzhi Wang, Samuel Hersh, Maria Ericsson, Santhi Gorantla, Howard E Gendelman, Rakez Kayed, Seiko Ikezu, Jennifer I Luebke, Tsuneya Ikezu

1080 related Products with: Alzheimer's disease brain-derived extracellular vesicles spread tau pathology in interneurons.

96 tests96 tests96 tests96 tests

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#33246328   2020/11/27 To Up

ZC3H4, a novel CCCH-type zinc finger protein, is essential for early embryogenesis in mice.

Zinc finger domains of the Cys-Cys-Cys-His (CCCH) class are evolutionarily conserved proteins that bind nucleic acids and are involved in various biological processes. Nearly 60 CCCH-type zinc finger proteins have been identified in humans and mice, most have not been functionally characterized. Here we provide the first in vivo functional characterization of ZC3H4, a novel CCCH-type zinc finger protein. Our results show that although Zc3h4 mutant embryos exhibit normal morphology at E3.5 blastocyst stage, they cannot be recovered at E7.5 early post-gastrulation stage, suggesting implantation failure. Outgrowth (OG) assays reveal that mutant blastocysts either fail to hatch from the zona pellucida, or can hatch but do not form a typical inner cell mass (ICM) colony, the source of embryonic stem cells (ESCs). While there is no change in levels of reactive oxygen species, Zc3h4 mutants display severe DNA breaks and reduced cell proliferation. Analysis of lineage specification reveals that both epiblast and primitive endoderm lineages are compromised with severe reductions in cell number and/or specification in the mutant blastocysts. In summary, these findings demonstrate the essential role of ZC3H4 during early mammalian embryogenesis.
Jianmin Su, Xiaosu Miao, Danielle Archambault, Jesse Mager, Wei Cui

2300 related Products with: ZC3H4, a novel CCCH-type zinc finger protein, is essential for early embryogenesis in mice.

100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized0.1 mg100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized

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#33246314   2020/10/19 To Up

Destabilization of ultrafine bubbles in water using indirect ultrasonic irradiation.

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Shunya Tanaka, Hirona Kobayashi, Seika Ohuchi, Koichi Terasaka, Satoko Fujioka

1373 related Products with: Destabilization of ultrafine bubbles in water using indirect ultrasonic irradiation.

0.1ml0.1ml50μl0.1ml0.1ml0.1ml0.1ml0.1ml0.1ml100 assays100 μg

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#33246307   2020/11/24 To Up

Comparative transcriptome analysis reveals the regulatory effects of acetylcholine on salt tolerance of Nicotiana benthamiana.

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Cheng Qin, Mohammad Abass Ahanger, Bo Lin, Ziguang Huang, Jie Zhou, Nadeem Ahmed, Suilong Ai, Nabil S A Mustafa, Muhammad Ashraf, Lixin Zhang

1137 related Products with: Comparative transcriptome analysis reveals the regulatory effects of acetylcholine on salt tolerance of Nicotiana benthamiana.

5 G10 mg 5 G 2 ml Ready-to-use 100ug1 mg250 mg 5 G 1 G1 15 ml 25 mg

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#33246306   2020/11/24 To Up

Catecholic alkaloid sulfonates and aromatic nitro compounds from Portulaca oleracea and screening of their anti-inflammatory and anti-microbial activities.

Acidic compounds were enriched from a water decoction of Portulaca oleracea using 717 anion exchange resin column chromatography. A total of 22 compounds including 9 catecholamine derivatives, of which six were rare sulfonic acid derivatives, and 9 nitro derivatives, were further isolated through various column chromatographic methods, and their structures were elucidated by interpreting their spectroscopic data and ECD calculations. Among them, 16 compounds were isolated from P. oleracea for the first time, 8 of which were undescribed compounds and four compounds were natural products. Pharmacological screening indicated that cis-3-(3-nitro-4-hydroxyphenyl)-methyl acrylate exhibited anti-inflammatory activity, measured as inhibition of nitric oxide production in LPS-stimulated RAW264.7 macrophage cells, with an EC value of 18.0 μM, The compounds showed only weak anti-microbial activity with (2R)-(+)-2-chloro-3-(3-nitro-4-hydroxyphenyl)-propionic acid methyl ester inhibiting Candida albicans with a MIC of 256 μg/mL, and 3-methoxy-4,5-dinitrophenol inhibiting Shigella sonnei with a MIC of 512 μg/mL.
Shuiyao Hu, Wern Chern Chai, Lintao Xu, Shaoqiang Li, Cuirong Jin, Rongxiu Zhu, Luping Yang, Ranran Zhang, Kaijun Tang, Ping Li, Erlan Yang, Wenqiang Chang, Tao Shen, Susan Semple, Henrietta Venter, Lan Xiang

2326 related Products with: Catecholic alkaloid sulfonates and aromatic nitro compounds from Portulaca oleracea and screening of their anti-inflammatory and anti-microbial activities.

100ul100ul0.1 mg1 ml100.00 ul200 1000 TESTS/0.65ml1000 100 ul100ug50 ug 10 mg

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#33246285   2020/11/17 To Up

Supercritical fluid chromatography - Mass spectrometry in metabolomics: Past, present, and future perspectives.

Metabolomics, which consists of the comprehensive analysis of metabolites within a biological system, has been playing a growing role in the implementation of personalized medicine in modern healthcare. A wide range of analytical approaches are used in metabolomics, notably mass spectrometry (MS) combined to liquid chromatography (LC), gas chromatography (GC), or capillary electrophoresis (CE). However, none of these methods enable a comprehensive analysis of the metabolome, due to its extreme complexity and the large differences in physico-chemical properties between metabolite classes. In this context, supercritical fluid chromatography (SFC) represents a promising alternative approach to improve the metabolome coverage, while further increasing the analysis throughput. SFC, which uses supercritical CO as mobile phase, leads to numerous advantages such as improved kinetic performance and lower environmental impact. This chromatographic technique has gained a significant interest since the introduction of advanced instrumentation, together with the introduction of dedicated interfaces for hyphenating SFC to MS. Moreover, new developments in SFC column chemistry (including sub-2 µm particles), as well as the use of large amounts of organic modifiers and additives in the CO-based mobile phase, significantly extended the application range of SFC, enabling the simultaneous analysis of a large diversity of metabolites. Over the last years, several applications have been reported in metabolomics using SFC-MS - from lipophilic compounds, such as steroids and other lipids, to highly polar compounds, such as carbohydrates, amino acids, or nucleosides. With all these advantages, SFC-MS is promised to a bright future in the field of metabolomics.
Bas van de Velde, Davy Guillarme, Isabelle Kohler

1198 related Products with: Supercritical fluid chromatography - Mass spectrometry in metabolomics: Past, present, and future perspectives.

125 ml 5 mg4 Arrays/Slide100ug Lyophilized100ug100ug Lyophilized 100 UG1 Set

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#33246284   2020/11/17 To Up

Development and validation of samples stabilization strategy and LC-MS/MS method for simultaneous determination of clevidipine and its primary metabolite in human plasma: Application to clinical pharmacokinetic study in Chinese healthy volunteers.

A feasible LC-MS/MS method with reliable stabilizers consisted of sodium fluoride, ascorbic acid and formic acid was developed and validated for the determination of clevidipine and its primary metabolite (H152/81) in human plasma. Sodium fluoride existing in the vacutainer tubes was used to inhibit esterase activity to protect the clevidipine from hydrolysis as soon as blood was collected. Ascorbic acid and formic acid were added to the separated plasma samples to avoid the oxidation and further hydrolysis of clevidipine and H152/81. The further sample preparation was accomplished through a single step liquid-liquid extraction (LLE) by ethyl acetate. The chromatography separation was carried out on an ACE Excel 3 μm SuperC18 (2.1 × 50 mm, id, ACE, United Kingdom) column with gradient elution using 10 mM ammonium acetate water solution and methanol as the mobile phase. Detection was performed in the negative ion electrospray ionization mode using multiple reaction monitoring (clevidipine: m/z 454.1 → 234.0; clevidipine-d7: m/z 461.1 → 240.1; H152/81: m/z 354.0 → 208.0; H152/81-CD: m/z 358.0 → 212.0). The method exhibited good linearity over the concentration ranges of 0.100 to 40.0 ng/mL for clevidipine and 5.00 to 400 ng/mL for H152/81. The intra- and inter-batch precision and accuracy of clevidipine and H152/81 were all within the acceptable criteria. The method was successfully applied to a pharmacokinetic study of clevidipine and H152/81 in healthy Chinese volunteers following 8 mg/h intravenous infusion of clevidipine butyrate injectable emulsion for 0.5 h. The results showed that clevidipine was rapidly eliminated with a short half-life time of 0.244 ± 0.125 h and a maximum concentration of 25.2 ± 7.09 ng/mL. H152/81 was detectable in the plasma samples up to 48.5 h with a half-life time of 10.7 ± 2.30 h and a maximum plasma concentration of 301 ± 38.1 ng/mL.
Yujia Zhang, Shunbo Zhao, Huan Zhou, Li Ding

1355 related Products with: Development and validation of samples stabilization strategy and LC-MS/MS method for simultaneous determination of clevidipine and its primary metabolite in human plasma: Application to clinical pharmacokinetic study in Chinese healthy volunteers.

100 μg 100ul50ul 100ul16 Arrays/Slide100ul 100ul0.05 mg

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#33246283   2020/10/22 To Up

A rapid and highly sensitive UPLC-ESI-MS/MS method for the analysis of the fatty acid profile of edible vegetable oils.

The analysis of the fatty acid profile of triglycerides has long played a central role in the evaluation and classification of edible vegetable oils. However, the range of analytical procedures available to evaluate these profiles remains limited and are typically based on transesterification of the triglyceride fatty acid residues to methyl esters, followed by capillary gas-liquid chromatography (GC) coupled with flame ionization or mass spectrometry detection. Although robust and long-proven, these analytical methods tend to entail long chromatographic runs and are relatively insensitive. In order to expand the range of available techniques for the analysis of the fatty acid profile of triglycerides in vegetable oils, we report herein a novel method based upon a rapid and straightforward transesterification of the triglycerides with dimethylaminoethanol under alkaline conditions, followed by a "dilute-and-shoot" analysis by ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry. The chromatographic analysis is accomplished in 1.5 min, affording a high throughput of samples compared to techniques based upon GC approaches. The method performance was assessed intra- and inter-day with 10 representative saturated and unsaturated fatty acids ranging from C to C and afforded fatty acid profile accuracies of 93-108% and imprecisions of only 0.3-2.0%. The limit of quantification of the method, estimated as the minimum amount of derivatized oil sample capable of affording less than 20% accuracy and precision error was determined to be approximately 0.5 pg on-column, making this new method potentially valuable for fields where high sensitivity, precision, and accuracy may be required, such as in toxicology studies, forensics, archeology, or art analysis.
Suresh K Nagumalli, Cristina C Jacob, Gonçalo Gamboa da Costa

2757 related Products with: A rapid and highly sensitive UPLC-ESI-MS/MS method for the analysis of the fatty acid profile of edible vegetable oils.

100tests100tests100.00 ul50ul1KG 1 G 100ul25 g96 tests

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#33246278   2020/11/17 To Up

Amino acid-based hydrophobic affinity cryogel for protein purification from ora-pro-nobis (Pereskia aculeata Miller) leaves.

The surfaces of the polyacrylamide cryogels were coated with L-tryptophan (cryogel-Trp) or L-phenylalanine (cryogel-Phe) to enhance crude leaf extract-derived ora-pro-nobis (OPN) protein binding via pseudo-specific hydrophobic interactions. Cryogels functionalized with amino acids were prepared and characterized through morphological, hydrodynamic, and thermal analyses. The adsorption capacities of cryogel-Phe and cryogel-Trp were evaluated in terms of type (sodium sulfate or sodium phosphate) and concentration (0.02 or 0.10 mol∙L) of saline solution, pH (4.0, 5.5, or 7.0), and NaCl concentration (0.0 or 0.5 mol∙L). The cryogel-Phe presented a higher adsorptive capacity, achieving its maximum value (q = 92.53 mg∙g) when the crude OPN crude leaf extract was diluted in sodium sulfate 0.02 mol∙L + NaCl 0.50 mol∙L, at pH = 7.0. The dilution rate significantly (p < 0.05) affected the recovered protein amount after the adsorption and elution processes, reaching 94.45% when the feedstock solution was prepared with a crude extract 5 times. The zeta potential for the eluted OPN proteins was 5.76 mV (pH = 3.23) for both dilution rates. The secondary structure composition mainly included β-sheets (46.50%) and α-helices (13.93%). The cryogel-Phe exhibited interconnected pores ranging 20-300 μm in size, with a Young modulus of 1.51 MPa, and thermal degradation started at 230 °C. These results indicate that the cryogel-Phe exhibited satisfactory properties as promising chromatography support for use in high-throughput purification of crude leaf extract-derived OPN proteins.
Isabelle Cristina Oliveira Neves, Adrise Aparecida Rodrigues, Thamires Teixeira Valentim, Ana Cristina Freitas de Oliveira Meira, Sérgio Henrique Silva, Lizzy Ayra Alcântara Veríssimo, Jaime Vilela de Resende

2637 related Products with: Amino acid-based hydrophobic affinity cryogel for protein purification from ora-pro-nobis (Pereskia aculeata Miller) leaves.

50 1 G25 mg 1 G 5 G100 mg10ml50mg10 mg1 mg1 g

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