Different cell kinetic changes in rat stomach cancer after treatment with celecoxib or indomethacin: Implications on chemoprevention

Aim: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group. This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg·d)) or indomethacin (3 mg/(kg·d)) to gain more insights into the chemopreventive mechanism. Methods: The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining. Results: Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P<0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P<0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg·d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development. Conclusion: Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Contact behaviour and vibrational response of a high-speed train brake friction block

Brake experiments were conducted on a typical kind of friction blocks of a high-speed train. The friction and wear, interfacial temperature, vibration, and noise generated at or by the brake interface were investigated, and the interrelationship between the vibration response and the contact behaviour of interface was analysed. The results showed the friction coefficient, vibration energy, and noise intensity were lower when the block surface experiences less wear; the friction coefficient and contact angle of the block were important factors affecting the vibration characteristics of the brake system. Moreover, the contact inclination angle increased with the increase in the friction coefficient, and mode coupling of the brake system occurred; as a result, the vibration intensity increased, and squeal occurred

Erratum to : Analysis of the mitochondrial maxicircle of Trypanosoma lewisi, a neglected human pathogen

BACKGROUND The haemoflagellate Trypanosoma lewisi is a kinetoplastid parasite which, as it has been recently reported to cause human disease, deserves increased attention. Characteristic features of all kinetoplastid flagellates are a uniquely structured mitochondrial DNA or kinetoplast, comprised of a network of catenated DNA circles, and RNA editing of mitochondrial transcripts. The aim of this study was to describe the kinetoplast DNA of T. lewisi. METHODS/RESULTS In this study, purified kinetoplast DNA from T. lewisi was sequenced using high-throughput sequencing in combination with sequencing of PCR amplicons. This allowed the assembly of the T. lewisi kinetoplast maxicircle DNA, which is a homologue of the mitochondrial genome in other eukaryotes. The assembly of 23,745 bp comprises the non-coding and coding regions. Comparative analysis of the maxicircle sequence of T. lewisi with Trypanosoma cruzi, Trypanosoma rangeli, Trypanosoma brucei and Leishmania tarentolae revealed that it shares 78 %, 77 %, 74 % and 66 % sequence identity with these parasites, respectively. The high GC content in at least 9 maxicircle genes of T. lewisi (ATPase6; NADH dehydrogenase subunits ND3, ND7, ND8 and ND9; G-rich regions GR3 and GR4; cytochrome oxidase subunit COIII and ribosomal protein RPS12) implies that their products may be extensively edited. A detailed analysis of the non-coding region revealed that it contains numerous repeat motifs and palindromes. CONCLUSIONS We have sequenced and comprehensively annotated the kinetoplast maxicircle of T. lewisi. Our analysis reveals that T. lewisi is closely related to T. cruzi and T. brucei, and may share similar RNA editing patterns with them rather than with L. tarentolae. These findings provide novel insight into the biological features of this emerging human pathogen

A global transition to ferruginous conditions in the early Neoproterozoic oceans

Eukaryotic life expanded during the Proterozoic eon1, 2.5 to 0.542 billion years ago, against a background of fluctuating ocean chemistry2, 3, 4. After about 1.8 billion years ago, the global ocean is thought to have been characterized by oxygenated surface waters, with anoxic and sulphidic waters in middle depths along productive continental margins and anoxic and iron-containing (ferruginous) deeper waters5, 6, 7. The spatial extent of sulphidic waters probably varied through time5, 6, but this surface-to-deep redox structure is suggested to have persisted until the first Neoproterozoic glaciation about 717 million years ago8, 9, 10, 11. Here we report an analysis of ocean redox conditions throughout the Proterozoic using new and existing iron speciation and sulphur isotope data from multiple cores and outcrops. We find a global transition from sulphidic to ferruginous mid-depth waters in the earliest Neoproterozoic, coincident with the amalgamation of the supercontinent Rodinia at low latitudes. We suggest that ferruginous conditions were initiated by an increase in the oceanic influx of highly reactive iron relative to sulphate, driven by a change in weathering regime and the uptake of sulphate by extensive continental evaporites on Rodinia. We propose that this transition essentially detoxified ocean margin settings, allowing for expanded opportunities for eukaryote diversification following a prolonged evolutionary stasis before one billion years ago

SalK/SalR, a Two-Component Signal Transduction System, Is Essential for Full Virulence of Highly Invasive Streptococcus suis Serotype 2

BACKGROUND: Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-component signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant DeltasalKR restored its soaring pathogenicity. Colonization experiments showed that the DeltasalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the DeltasalKR mutant. CONCLUSIONS/SIGNIFICANCE: These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI

C-Terminus Glycans with Critical Functional Role in the Maturation of Secretory Glycoproteins

The N-glycans of membrane glycoproteins are mainly exposed to the extracellular space. Human tyrosinase is a transmembrane glycoprotein with six or seven bulky N-glycans exposed towards the lumen of subcellular organelles. The central active site region of human tyrosinase is modeled here within less than 2.5 Å accuracy starting from Streptomyces castaneoglobisporus tyrosinase. The model accounts for the last five C-terminus glycosylation sites of which four are occupied and indicates that these cluster in two pairs - one in close vicinity to the active site and the other on the opposite side. We have analyzed and compared the roles of all tyrosinase N-glycans during tyrosinase processing with a special focus on the proximal to the active site N-glycans, s6:N337 and s7:N371, versus s3:N161 and s4:N230 which decorate the opposite side of the domain. To this end, we have constructed mutants of human tyrosinase in which its seven N-glycosylation sites were deleted. Ablation of the s6:N337 and s7:N371 sites arrests the post-translational productive folding process resulting in terminally misfolded mutants subjected to degradation through the mannosidase driven ERAD pathway. In contrast, single mutants of the other five N-glycans located either opposite to the active site or into the N-terminus Cys1 extension of tyrosinase are temperature-sensitive mutants and recover enzymatic activity at the permissive temperature of 31°C. Sites s3 and s4 display selective calreticulin binding properties. The C-terminus sites s7 and s6 are critical for the endoplasmic reticulum retention and intracellular disposal. Results herein suggest that individual N-glycan location is critical for the stability, regional folding control and secretion of human tyrosinase and explains some tyrosinase gene missense mutations associated with oculocutaneous albinism type I

Prognostic indices for brain metastases – usefulness and challenges

<p>Abstract</p> <p>Background</p> <p>This review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG) developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA) classes, i.e. between 1997 and 2008. In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed.</p> <p>Methods</p> <p>Based on a systematic literature search, studies with more than 20 patients were included. The methods and results of prognostic factor analyses were extracted and compared. The authors discuss why current data suggest a need for a more refined index than RPA.</p> <p>Results</p> <p>So far, none of the indices has been derived from analyses of all potential prognostic factors. The 3 most recently published indices, including the RTOG's graded prognostic assessment (GPA), all expanded from the primary 3-tiered RPA system to a 4-tiered system. The authors' own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool.</p> <p>Conclusion</p> <p>This review provides a basis for further refinement of the current prognostic indices by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types. Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses.</p

Structural Evolution of Chemically-Driven RuO2 Nanowires and 3-Dimensional Design for Photo-Catalytic Applications

Growth mechanism of chemically-driven RuO2 nanowires is explored and used to fabricate three-dimensional RuO2 branched Au-TiO2 nanowire electrodes for the photostable solar water oxidation. For the real time structural evolution during the nanowire growth, the amorphous RuO2 precursors (Ru(OH)(3)center dot H2O) are heated at 180 degrees C, producing the RuO2 nanoparticles with the tetragonal crystallographic structure and Ru enriched amorphous phases, observed through the in-situ synchrotron x-ray diffraction and the high-resolution transmission electron microscope images. Growth then proceeds by Ru diffusion to the nanoparticles, followed by the diffusion to the growing surface of the nanowire in oxygen ambient, supported by the nucleation theory. The RuO2 branched Au-TiO2 nanowire arrays shows a remarkable enhancement in the photocurrent density by approximately 60% and 200%, in the UV-visible and Visible region, respectively, compared with pristine TiO2 nanowires. Furthermore, there is no significant decrease in the device&apos;s photoconductance with UV-visible illumination during 1 day, making it possible to produce oxygen gas without the loss of the photoactvity.close1

Measurement of the matrix element for the decay η′→ηπ +π -

The Dalitz plot of η⊃′→ηπ⊃+π⊃- decay is studied using (225.2±2.8)×106 J/ψ events collected with the BESIII detector at the BEPCII e⊃+e⊃- collider. With the largest sample of η⊃′ decays to date, the parameters of the Dalitz plot are determined in a generalized and a linear representation. Also, the branching fraction of J/ψ→γη⊃′ is determined to be (4.84±0.03±0.24)×10⊃-3, where the first error is statistical and the second systematic. © 2011 American Physical Society.published_or_final_versio