Probing inhibitory effects of destruxins from Metarhizium anisopliae using insect cell based impedance spectroscopy : Inhibition vs chemical structure

A noninvasive technique based on electric cell-substrate impedance sensing (ECIS) was demonstrated for on-line probing inhibitory effects of five destruxins on Spodoptera frugiperda Sf9 insect cells. Such chemically structurally similar cyclic hexadepsipeptides, were isolated and purified from the fungus Metarhizium anisopliae. Based on a response function, the inhibitory effect of the destruxins was established from determining the half-inhibition concentration (ECIS50), i.e., the level at which 50% inhibition of the cell response was obtained. Probing by cell based impedance spectroscopy indicated that only a slight change in their chemical structures provoked a significant effect on inhibition. Destruxin B was most inhibitory but replacement of a single methyl group with hydrogen (destruxin B2) or addition of a hydroxylgroup (destruxin C) significantly reduced the inhibition. The removal of one methyl group and one hydrogen (destruxin A) lowered the inhibitory effect even more whereas the formation of an epoxy ring (destruxin E) in the structure nullified the inhibitory effect.NRC publication: Ye

Measurement of αΩ in Ω− → ΛΚ− Decays

The HyperCP experiment (E871) at Fermilab has collected the largest sample of hyperon decays in the world. With a data set of over a million Ω− → ΛΚ− decays we have measured the product of αΩαΛ from which we have extracted αΩ. This preliminary result indicates that αΩ is small, but non‐zero. Prospects for a test of CP symmetry by comparing the α parameters in Ω− and Ω̄+ decays will be discussed. © 2003 American Institute of PhysicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87682/2/251_1.pd

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

Whole Genome PCR Scanning Reveals the Syntenic Genome Structure of Toxigenic Vibrio cholerae Strains in the O1/O139 Population

Vibrio cholerae is commonly found in estuarine water systems. Toxigenic O1 and O139 V. cholerae strains have caused cholera epidemics and pandemics, whereas the nontoxigenic strains within these serogroups only occasionally lead to disease. To understand the differences in the genome and clonality between the toxigenic and nontoxigenic strains of V. cholerae serogroups O1 and O139, we employed a whole genome PCR scanning (WGPScanning) method, an rrn operon-mediated fragment rearrangement analysis and comparative genomic hybridization (CGH) to analyze the genome structure of different strains. WGPScanning in conjunction with CGH revealed that the genomic contents of the toxigenic strains were conservative, except for a few indels located mainly in mobile elements. Minor nucleotide variation in orthologous genes appeared to be the major difference between the toxigenic strains. rrn operon-mediated rearrangements were infrequent in El Tor toxigenic strains tested using I-CeuI digested pulsed-field gel electrophoresis (PFGE) analysis and PCR analysis based on flanking sequence of rrn operons. Using these methods, we found that the genomic structures of toxigenic El Tor and O139 strains were syntenic. The nontoxigenic strains exhibited more extensive sequence variations, but toxin coregulated pilus positive (TCP+) strains had a similar structure. TCP+ nontoxigenic strains could be subdivided into multiple lineages according to the TCP type, suggesting the existence of complex intermediates in the evolution of toxigenic strains. The data indicate that toxigenic O1 El Tor and O139 strains were derived from a single lineage of intermediates from complex clones in the environment. The nontoxigenic strains with non-El Tor type TCP may yet evolve into new epidemic clones after attaining toxigenic attributes

Spontaneous Mirror Parity Violation, Common Origin of Matter and Dark Matter, and the LHC Signatures

Existence of a mirror world in the universe is a fundamental way to restore the observed parity violation in weak interactions and provides the lightest mirror nucleon as a unique GeV-scale dark matter particle candidate. The visible and mirror worlds share the same spacetime of the universe and are connected by a unique space-inversion symmetry -- the mirror parity (P). We conjecture that the mirror parity is respected by the fundamental interaction Lagrangian, and study its spontaneous breaking from minimizing the Higgs vacuum potential. The domain wall problem is resolved by a unique soft breaking linear-term from the P-odd weak-singlet Higgs field. We also derive constraint from the Big-Bang nucleosynthesis. We then analyze the neutrino seesaw for both visible and mirror worlds, and demonstrate that the desired amounts of visible matter and mirror dark matter in the universe arise from a common origin of CP violation in the neutrino sector via leptogenesis. We derive the Higgs mass-spectrum and Higgs couplings with gauge bosons and fermions. We show their consistency with the direct Higgs searches and the indirect precision constraints. We further study the distinctive signatures of the predicted non-standard Higgs bosons at the LHC. Finally, we analyze the direct detections of GeV-scale mirror dark matter by TEXONO and CDEX experiments.Comment: 55pp. PRD final version. Only minor refinements (including to comment on the latest LHC Higgs searches in Sec.5 and estimate abundances of mirror dark matter particles in Sec.6); more references adde

CP Violation in Hyperon and Charged Kaon Decays

The primary purpose of the HyperCP experiment at Fermilab is to test CP in hyperon decays by comparing the decay distributions for Ξ− (“cascade”) decays in the decay sequence: Ξ− → π− + Λ0, Λ0 → π− + p, with those for the antiparticle Ξ̄+. In addition, we can test CP in charged kaon decays by comparing the slopes of the Dalitz plot for Κ+ and Κ− decays. We are also looking at rare decay modes of charged kaons and hyperons, particularly those involving muons. In two runs in 1997 and 1999, we collected approx. 500 millon charged kaon decays, 2.5 billion Ξ− and Ξ̄+ decays, and 19 million Ω− and Ω̄+ decays. This is the largest sample of fully reconstructed particle decays ever collected. © 2002 American Institute of PhysicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87464/2/298_1.pd

Genetic Variants in MARCO Are Associated with the Susceptibility to Pulmonary Tuberculosis in Chinese Han Population

BACKGROUND: Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk. PRINCIPAL FINDINGS: To specifically investigated whether single nucleotide polymorphisms (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control subjects using a hospital based case-control association study. Single-point and haplotype analysis revealed an association in intron and exon region of MARCO gene. One SNP (rs17009726) was associated with susceptibility to pulmonary tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI = 1.32-2.05, p(corrected) = 9.27E-5) increased risk of pulmonary tuberculosis. Haplotype analysis revealed that haplotype GC containing G allele of 17009726 and haplotype TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also associated with susceptibility to pulmonary tuberculosis (p(corrected) = 0.0001 and 0.029, respectively). CONCLUSIONS: Our study suggested that genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population, and the findings emphasize the importance of MARCO mediated immune responses in the pathogenesis of tuberculosis

Socio-demographic and health-related factors associated with cognitive impairment in the elderly in Taiwan

<p>Abstract</p> <p>Background</p> <p>Cognitive impairment is an age-related condition as the rate of cognitive decline rapidly increases with aging. It is especially important to better understand factors involving in cognitive decline for the countries where the older population is growing rapidly. The aim of this study was to examine the association between socio-demographic and health-related factors and cognitive impairment in the elderly in Taiwan.</p> <p>Methods</p> <p>We analysed data from 2119 persons aged 65 years and over who participated in the 2005 National Health Interview Survey. Cognitive impairment was defined as having the score of the Mini Mental State Examination lower than 24. The χ²test and multiple logistic regression models were used to evaluate the association between cognitive impairment and variables of socio-demography, chronic diseases, geriatric conditions, lifestyle, and dietary factors.</p> <p>Results</p> <p>The prevalence of cognitive impairment was 22.2%. Results of multivariate analysis indicated that low education, being single, low social support, lower lipid level, history of stroke, physical inactivity, non-coffee drinking and poor physical function were associated with a higher risk of cognitive impairment.</p> <p>Conclusion</p> <p>Most of the characteristics in relation to cognitive impairment identified in our analysis are potentially modifiable. These results suggest that improving lifestyle behaviours such as regular exercise and increased social participation could help prevent or decrease the risk of cognitive impairment. Further investigations using longitudinal data are needed to clarify our findings.</p