Search

Weekly glatiramer acetate immunization of transgenic mice modelling Alzheimer's disease resulted in retained cognition (Morris water maze test), decreased amyloid-β plaque burden, and regulation of local inflammation through a mechanism involving enhanced recruitment of monocytes. Ablation of bone marrow-derived myeloid cells exacerbated plaque pathology, whereas weekly administration of glatiramer acetate enhanced cerebral recruitment of innate immune cells, which dampened the pathology. Here, we assessed the therapeutic potential of grafted CD115(+) monocytes, injected once monthly into the peripheral blood of transgenic APPSWE/PS1ΔE9 Alzheimer's disease mouse models, with and without weekly immunization of glatiramer acetate, as compared to glatiramer acetate alone. All immune-modulation treatment groups were compared with age-matched phosphate-buffered saline-injected control transgenic and untreated non-transgenic mouse groups. Two independent cohorts of mice were assessed for behavioural performance (6-8 mice/group); treatments started in 10-month-old symptomatic mice and spanned a total of 2 months. For all three treatments, our data suggest a substantial decrease in cognitive deficit as assessed by the Barnes maze test (P < 0.0001-0.001). Improved cognitive function was associated with synaptic preservation and reduction in cerebral amyloid-β protein levels and astrogliosis (P < 0.001 and P < 0.0001), with no apparent additive effects for the combined treatment. The peripherally grafted, green fluorescent protein-labelled and endogenous monocytes, homed to cerebral amyloid plaques and directly engulfed amyloid-β; their recruitment was further enhanced by glatiramer acetate. In glatiramer acetate-immunized mice and, moreover, in the combined treatment group, monocyte recruitment to the brain was coupled with greater elevation of the regulatory cytokine IL10 surrounding amyloid-β plaques. All treated transgenic mice had increased cerebral levels of MMP9 protein (P < 0.05), an enzyme capable of degrading amyloid-β, which was highly expressed by the infiltrating monocytes. In vitro studies using primary cultures of bone marrow monocyte-derived macrophages, demonstrated that glatiramer acetate enhanced the ability of macrophages to phagocytose preformed fibrillar amyloid-β1-42 (P < 0.0001). These glatiramer acetate-treated macrophages exhibited increased expression of the scavenger receptors CD36 and SCARA1 (encoded by MSR1), which can facilitate amyloid-β phagocytosis, and the amyloid-β-degrading enzyme MMP9 (P < 0.0001-0.001). Overall, our studies indicate that increased cerebral infiltration of monocytes, either by enrichment of their levels in the circulation or by weekly immunization with glatiramer acetate, resulted in substantial attenuation of disease progression in murine Alzheimer's models by mechanisms that involved enhanced cellular uptake and enzymatic degradation of toxic amyloid-β as well as regulation of brain inflammation. [ABSTRACT FROM AUTHOR]

Background: Harmful sulfur-fumigation processing method is abused during Radix Angelicae Dahuricae preparation. However, the analytical technique characterizing Radix Angelicae Dahuricae before and after the sulfur-fumigation process is absent. Materials and Methods: The high performance liquid chromatography (HPLC) technique was adopted to develop methods combining finger-print analysis and multi-ingredients simultaneous determination for quality evaluation of Radix Angelicae Dahuricae before and after the sulfur-fumigation process. The chromatographic fingerprint method was established for qualitative analysis coupled with statistical cluster analysis basing on Euclidean distance. Additionally, a determination method was developed for quantitative analysis, which was able to assay the concentrations of the major coumarins including imperatorin, isoimperatorin, xanthotoxin, xanthotoxol, isoimpinellin, oxypeucedanin, and bergapten in Radix Angelicae Dahuricae simultaneously. The separations of the two methods were both achieved on a Hypersil octadecylsilyl C18 column (250 mm × 4.6 mm, 5 µm) at 35°C under different strategic gradient elution programs. The detection wavelength was set at 254 nm all the time. Method validation data indicated that the methods were both reliable and applicable. They were then used to assay different Radix Angelicae Dahuricae samples collected from good agricultural practice (GAP) bases and local herbal markets. Results: The successful application demonstrated that the combination of HPLC fingerprint and simultaneous quantification of multi-ingredients offers an efficient approach for quality evaluation of Radix Angelicae Dahuricae before and after the sulfur-fumigation process. Conclusion: In order to discriminate Radix Angelicae Dahuricae before and after the sulfur-fumigation process, oxypeucedanin, and xanthotoxol were the most sensitive biomarkers and should be determined. [ABSTRACT FROM AUTHOR]

Background: A new method has been developed for the simultaneous determination of ferulic acid, senkyunolide A, and Z-ligustilide in Angelicae Sinensis Radix before and after sulfur-fumigation using quantitative analysis of multi-components by a single marker (QAMS). Materials and Methods: The feasibility and accuracy of QAMS were checked by the external standard method, and various high-performance liquid chromatographic instruments and chromatographic conditions were investigated to verify its applicability. Using ferulic acid as the internal reference substance, and the contents of senkyunolide A and Z-ligustilide were calculated according to relative correction factors by high-performance liquid chromatography. Meanwhile, the influence of sulfur-fumigation on these chemical components in Angelicae Sinensis Radix were evaluated and discriminated by chromatographic fingerprint and chemometrics. Results: There was no significant difference observed between the QAMS method and the external standard method. Furthermore, sulfur-fumigation reduced the contents of ferulic acid, senkyunolide A, and Z-ligustilide in Angelicae Sinensis Radix by some degree, and the sun-drying and sulfur-fumigation processing could be easily discriminated by chromatographic fingerprint and chemometrics. Conclusion: QAMS is a convenient and accurate approach to analyzing multi-component when reference substances are unavailable, simultaneously, chemometrics is an effective way to discriminate sun-dried and sulfur-fumigated Angelicae Sinensis Radix. [ABSTRACT FROM AUTHOR]

Background: Sulfur-fumigation may induce chemical transformation of traditional Chinese medicines leading to harmful effects following patient ingestion. For quality control, it is urgently needed to develop a reliable and efficient method for sulfur-fumigation identification. Materials and Methods: The spectrochemical identification of non-fumigated and sulfur-fumigated Fritillaria thunbergii Miq. was carried out to evaluate inorganic elements and organic components. The concentrations of 12 elements, including Zn, Mn, Cu, Fe, Li, Mg, Sr, Pb, As, Cd, Hg, and S of samples were determined by microwave digestion - inductively coupled plasma atomic emission spectrometry (ICP-AES). Meanwhile, Fourier transform infrared spectrometry (FTIR) was used for the study of chemical group characteristic reactions after sulfur-fumigation. Results: The concentrations of Fe, Mg, Hg, and S elements showed significant differences between non-fumigated and sulfur-fumigated Fritillaria thunbergii Miq. The characteristic stretching vibrations of some groups in FTIR spectra, such as -OH, -S = O and -S-O, provided the identification basis for the discrimination of non-fumigated and sulfur-fumigated Fritillaria thunbergii Miq. Conclusion: The application of microwave digestion - ICP-AES was successfully used in combination with FTIR to authenticate and evaluate the quality of medicinal Fritillaria thunbergii Miq. Further applications of this technique should be explored. [ABSTRACT FROM AUTHOR]

This paper develops a general equilibrium model with endogenous clusters and an endogenous network of division of labour to formalize and explore the interrelationship and rules of industrial clusters, the network of division of labour, and the economies of specialization and agglomeration in the new era of globalization and regionalization. The model suggests that institutional efficiency and competition among countries and industries will facilitate important circular effects, propelling and shaping the arrangement and allocation of industrial clusters, establishing their position in the value chain, and, consequently, determining the status of economic growth. In particular, the improvements in institutional efficiency of economic and technology systems will expand the demand for transactions and network size, which, in turn, will determine the development of cluster and network scope, as well as the position in the production value chain. [ABSTRACT FROM AUTHOR]

Investigates the bacterial expression, purification and crystallization of different fragments of C-terminal region of DFF45/ICAD proteins. Crystallization by hanging-drop vapor-diffusion method; X-ray crystallography; Protein stability in solution.

Streptococcus pneumoniae hyaluronate lyase (spnHL) is a pathogenic bacterial spreading factor and cleaves hyaluronan, an important constituent of the extra-cellular matrix of connective tissues, through an enzymatic Β-elimination process, different from the hyaluronan degradation by hydrolases in animals. The mechanism of hyaluronan binding and degradation was proposed based on the 1.56 Å resolution crystal structure, substrate modeling and mutugenesis studies on spnHL. Five mutants, R243V, N349A, H399A, Y408F and N580G, were constructed and their activities confirmed our mechanism hypothesis. The important roles of Tyr408, Asn349 and His399 in enzyme catalysis were proposed, explained and confirmed by mutant studies. The remaining weak enzymatic activity of the H399A mutant, the role of the free carboxylate group on the glucuronate residue, the enzymatic behavior on chondroitin and chondroitin sulfate, and the small activity increase in the N580G mutant were explained based on this mechanism. A possible function of the C-terminal Β-sheet domain is to modulate enzyme activity through binding to calcium ions. [ABSTRACT FROM AUTHOR]

For Bi-based cuprate superconductors, increasing its Cu content by heat-treatment is probably a beneficial way to its superconducting transition. In the paper, the corresponding methods and procedures of the experiment were proposed, and the theoretical analysis and explanation of the experimental results were conducted. The method of increasing Cu content by heat-treatment is innovative. [ABSTRACT FROM AUTHOR]

The C-terminal part of tropomodulin protein 1, isoform A, from Caenorhabditis elegans was expressed in Escherichia coli and purified to homogeneity. Optimized from the initial nanoscreen, crystals grew to dimensions of 0.25 × 0.15 × 0.15 mm at 277 K using 28.0%(v/v) PEG 400 as the precipitant by the hanging-drop vapor-diffusion technique. A data set of 94.9% completeness was collected to a resolution of 1.98 Å at 100 K using a synchrotron X-ray source (SER-CAT). The crystals belong to the orthorhombic space group P2[SUB1]2[SUB1]2[SUB1], with unit-cell parameters a = 31.7, b = 50.6, c = 107.1 Å, and contained one molecule per asymmetric unit. [ABSTRACT FROM AUTHOR]

Owing to appealing physical properties such as broad tunability in bandgaps and structural anisotropy, black phosphorus (BP) holds great potential in exploring novel electronic devices. However, it is extremely challenging to use BP to fabricate electronic devices, since it is prone to deteriorate in air. To address this challenge, we demonstrate an in situ fabrication technique which enables us to minimize interfacial degradation and to fabricate vertical Josephson junctions by employing few-layer BP as a barrier between two closely spaced Nb electrodes. The current–voltage characteristics of the junctions are hysteretic at low temperatures and become nonhysteretic when approaching the junction critical temperature. In the resistive state the differential conductance increases with decreasing voltage. Microwave-induced Shapiro steps were observed, confirming the presence of the ac Josephson effect. We present different models to analyze the current–voltage characteristics and conclude that resistive state of the current–voltage characteristics points to a zero bias anomaly, which is presumably caused by Andreev reflections. Our in situ fabrication technique represents a viable way to incorporate air-unstable materials for electronics and offer a chance to explore their unique functionalities. [ABSTRACT FROM AUTHOR]

Graphene transistors were fabricated by a wafer-scale “top-down” process using a graphene sheet formed by the chemical vapor deposition (CVD) method. The devices have a dual-gated structure with an ion-irradiated channel, in which transistor polarity can be electrostatically controlled. We demonstrated, at room temperature, an on/off operation of current and electrostatic control of transistor polarity. By combining two dual-gated transistors, a six-terminal device was fabricated with three top gates and two ion-irradiated channels. In this device, we demonstrated an inverter operation. [ABSTRACT FROM AUTHOR]

In the present article, we tested an optimal vMMN paradigm allowing one to obtain vMMNs for several visual attributes in a short time. vMMN responses to changes in color, duration, orientation, shape, and size were compared between the traditional 'oddball' paradigm (a single type of visual change in each sequence) and the optimal paradigm in which all the 5 types of changes appeared within the same sequence. The vMMNs obtained in the optimal paradigm were equal or larger in amplitude to those in the traditional vMMN paradigm. The optimal paradigm can provide 5 different vMMNs in the same time in which usually only one MMN is obtained. This short objective measure could putatively be used as an index for visual cognition function especially in clinical research. [ABSTRACT FROM AUTHOR]