Proteomic characterization of the cytotoxic mechanism of gold (III) porphyrin 1a, a potential anticancer drug

There has been increasing interest in the potential applications of gold (III) complexes as anticancer drugs with higher cytotoxicity and fewer side effects than existing metal anticancer drugs. Our previous findings demonstrated that gold (III) porphyrin la preferentially induced apoptosis in a cancer cell line (SUNE1). In this study, we identified differentially expressed proteins related to the drug's cytotoxic action by comparing the protein alterations induced by gold (III) porphyrin la and cisplatin treatments. Several clusters of altered proteins were identified, including cellular structure and stress-related chaperone proteins, proteins involved in reactive oxygen species and enzyme proteins, translation factors, proteins that mediate cell proliferation or differentiation, and proteins participating in the internal degradation systems. Our results indicated that multiple factors leading to apoptosis were involved in drug cytotoxicity in SUNE1 cells. The balance between pro-apoptotic and anti-apoptotic signals determined the final fate of cancer cells. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.postprin

Preparation and thermal analysis kinetics of the core–nanoshell composite materials doped with Sm

The core–nanoshell composite materials with magnetic fly-ash hollow cenosphere as core and nano SmFeO3 as shell were synthesized by high-energy ball milling method. The magnetic fly-ash hollow cenosphere, samarium nitrate, and iron nitrate were used as raw materials. The synthesis and growth kinetics of the composite materials were investigated using the thermogravimetry and differential thermal analysis (TG–DTA) at different heating rates. The results show that the precursor of the composite materials decomposes in three steps. The apparent activation energy of each stage was calculated using the Doyle–Ozawa and Kissinger methods. The reaction order, frequency factor, and rate equations were also determined. The activation energy of the nano crystallite growth is calculated to be 16.12 kJ mol−1 according to kinetics theory of nano crystallite growth. It can be inferred that the crystallite grows primarily by means of an interfacial reaction during the thermal treatment. The magnetic properties and microwave absorbing properties of samples were analyzed by the vibrating sample magnetometer analysis and vector network analyzer. The results indicated that the exchange coupling interaction happens between ferrite of magnetic fly-ash hollow cenosphere and nanosized ferrite coating, which cause outstanding magnetic properties. In the frequency between 1 MHz and 1 GHz, the absorbing effectiveness of the composite absorbers can achieve −32 dB. The magnetic properties of the composite material are better than those of single phase. So it is consistent with requirements of the microwave absorbing material at the low-frequency absorption.National Natural Science Foundation (China) (No. 20976018)Liaoning Sheng (China) (Science Research Plan Project, Higher Education Department (No. L2013176))China. Ministry of Education (Key Laboratory of Industrial Ecology and Environmental Engineering, KLIEEE-12-03)China. Ministry of Education (National Project of China ‘‘Innovation and Entrepreneurship Training Program of Undergraduate students’’ (201310150002)

Fingerprinting Hysteresis

We test the predictive power of first-oder reversal curve (FORC) diagrams using simulations of random magnets. In particular, we compute a histogram of the switching fields of the underlying microscopic switching units along the major hysteresis loop, and compare to the corresponding FORC diagram. We find qualitative agreement between the switching-field histogram and the FORC diagram, yet differences are noticeable. We discuss possible sources for these differences and present results for frustrated systems where the discrepancies are more pronounced.Comment: 4 pages, 5 figure

Proteomic approach to study the cytotoxicity of dioscin (saponin)

Dioscin, extracted from the root of Polygonatum zanlanscianense pamp, exhibits cytotoxicity towards human myeloblast leukemia HL-60 cells. Proteomic analysis revealed that the expression of mitochondrial associated proteins was substantially altered in HL-60 cells corresponding to the dioscin treatment, suggesting that mitochondria are the major cellular target of dioscin. Mitochondrial functional studies validated that mitochondrial apoptotic pathway was initiated by dioscin treatment. Changes in proteome other than mitochondrial related proteins implicate that other mechanisms were also involved in dioscin-induced apoptosis in HL-60 cells, including the activity impairment in protein synthesis, alterations of phosphatases in cell signaling, and deregulation of oxidative stress and cell proliferation. Current study of protein alterations in dioscin-treated HL-60 cells suggested that dioscin exerts cytotoxicity through multiple apoptosis-inducing pathways. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.postprin

Genetic regulation of mouse liver metabolite levels.

We profiled and analyzed 283 metabolites representing eight major classes of molecules including Lipids, Carbohydrates, Amino Acids, Peptides, Xenobiotics, Vitamins and Cofactors, Energy Metabolism, and Nucleotides in mouse liver of 104 inbred and recombinant inbred strains. We find that metabolites exhibit a wide range of variation, as has been previously observed with metabolites in blood serum. Using genome-wide association analysis, we mapped 40% of the quantified metabolites to at least one locus in the genome and for 75% of the loci mapped we identified at least one candidate gene by local expression QTL analysis of the transcripts. Moreover, we validated 2 of 3 of the significant loci examined by adenoviral overexpression of the genes in mice. In our GWAS results, we find that at significant loci the peak markers explained on average between 20 and 40% of variation in the metabolites. Moreover, 39% of loci found to be regulating liver metabolites in mice were also found in human GWAS results for serum metabolites, providing support for similarity in genetic regulation of metabolites between mice and human. We also integrated the metabolomic data with transcriptomic and clinical phenotypic data to evaluate the extent of co-variation across various biological scales

Selection and environmental adaptation along a path to speciation in the Tibetan frog Nanorana parkeri.

Tibetan frogs, Nanorana parkeri, are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89-95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including DNAJC8 in the brain, TNNC1 and ADORA1 in the heart, and LAMB3 in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation

Exploring interfacial exchange coupling and sublattice effect in heavy metal/ferrimagnetic insulator heterostructures using Hall measurements, x-ray magnetic circular dichroism, and neutron reflectometry

We use temperature-dependent Hall measurements to identify contributions of spin Hall, magnetic proximity, and sublattice effects to the anomalous Hall signal in heavy metal/ferrimagnetic insulator heterostructures with perpendicular magnetic anisotropy. This approach enables detection of both the magnetic proximity effect onset temperature and the magnetization compensation temperature and provides essential information regarding the interfacial exchange coupling. Onset of a magnetic proximity effect yields a local extremum in the temperature-dependent anomalous Hall signal, which occurs at higher temperature as magnetic insulator thickness increases. This magnetic proximity effect onset occurs at much higher temperature in Pt than W. The magnetization compensation point is identified by a sharp anomalous Hall sign change and divergent coercive field. We directly probe the magnetic proximity effect using x-ray magnetic circular dichroism and polarized neutron reflectometry, which reveal an antiferromagnetic coupling between W and the magnetic insulator. Finally, we summarize the exchange-coupling configurations and the anomalous Hall-effect sign of the magnetized heavy metal in various heavy metal/magnetic insulator heterostructures