Lower expression of inducible nitric oxide synthase and higher expression of arginase in rat alveolar macrophages are linked to their susceptibility to Toxoplasma gondii infection.

Rats are naturally resistant to Toxoplasma gondii infection, particularly the RH strain, while mice are not. Previous studies have demonstrated that inducible nitric oxide synthase (iNOS) and arginase-1 of rodent peritoneal macrophages are linked to the mechanism of resistance. As an increasing number of studies on human and animal infections are showing that pulmonary toxoplasmosis is one of the most severe clinical signs from T. gondii infection, we are interested to know whether T. gondii infection in alveolar macrophages of rats is also linked to the levels of iNOS and arginase-1 activity. Our results demonstrate that T. gondii could grow and proliferate in rat alveolar macrophages, both in vitro and in vivo, at levels higher than resistant rat peritoneal macrophages and at comparable levels to sensitive mouse peritoneal macrophages. Lower activity and expression levels of iNOS and higher activity and expression levels of arginase-1 in rat alveolar macrophages were found to be linked to the susceptibility of T. gondii infection in these cells. These novel findings could aid a better understanding of the pathogenesis of clinical pulmonary toxoplasmosis in humans and domestic animals

Explicit hypoxia targeting with tumor suppression by creating an “obligate” anaerobic Salmonella Typhimurium strain

Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therapeutic use. By placing an essential gene under a hypoxia conditioned promoter, Salmonella Typhimurium strain SL7207 was engineered to survive only in anaerobic conditions (strain YB1) without otherwise affecting its functions. In breast tumor bearing nude mice, YB1 grew within the tumor, retarding its growth, while being rapidly eliminated from normal tissues. YB1 provides a safe bacterial vector for anti-tumor therapies without compromising the other functions or tumor fitness of the bacterium as attenuation methods normally do

Establishment of a New Cell Line from Lepidopteran Epidermis and Hormonal Regulation on the Genes

When an insect molts, old cuticle on the outside of the integument is shed by apolysis and a new cuticle is formed under the old one. This process is completed by the epidermal cells which are controlled by 20-hydroxyecdysone (20E) and juvenile hormone. To understand the molecular mechanisms of integument remolding and hormonal regulation on the gene expression, an epidermal cell line from the 5th instar larval integument of Helicoverpa armigera was established and named HaEpi. The cell line has been cultured continuously for 82 passages beginning on June 30, 2005 until now. Cell doubling time was 64 h. The chromosomes were granular and the chromosome mode was from 70 to 76. Collagenase I was used to detach the cells from the flask bottom. Non-self pathogen AcMNPV induced the cells to apoptosis. The cell line was proved to be an epidermal cell line based on its unique gene expression pattern. It responded to 20E and the non-steroidal ecdysone agonist RH-2485. Its gene expression could be knocked down using RNA interference. Various genes in the cell line were investigated based on their response to 20E. This new cell line represents a platform for investigating the 20E signaling transduction pathway, the immune response mechanism in lepidopteran epidermis and interactions of the genes

Enhanced thermoelectric performance of a chalcopyrite compound CuIn3Se5-xTex (x=0~0.5) through crystal structure engineering

In this work the chalcopyrite CuIn3Se5−xTex (x = 0~0.5) with space group through isoelectronic substitution of Te for Se have been prepared, and the crystal structure dilation has been observed with increasing Te content. This substitution allows the anion position displacement ∆u = 0.25-u to be zero at x ≈ 0.15. However, the material at x = 0.1 (∆u = 0.15 × 10−3), which is the critical Te content, presents the best thermoelectric (TE) performance with dimensionless figure of merit ZT = 0.4 at 930 K. As x value increases from 0.1, the quality factor B, which informs about how large a ZT can be expected for any given material, decreases, and the TE performance degrades gradually due to the reduction in nH and enhancement in κL. Combining with the ZTs from several chalcopyrite compounds, it is believable that the best thermoelectric performance can be achieved at a certain ∆u value (∆u ≠ 0) for a specific space group if their crystal structures can be engineered

A New Cationic Porphyrin Derivative (TMPipEOPP) with Large Side Arm Substituents: A Highly Selective G-Quadruplex Optical Probe

The discovery of uncommon DNA structures and speculation about their potential functions in genes has brought attention to specific DNA structure recognition. G-quadruplexes are four-stranded nucleic acid structures formed by G-rich DNA (or RNA) sequences. G-rich sequences with a high potential to form G-quadruplexes have been found in many important genomic regions. Porphyrin derivatives with cationic side arm substituents are important G-quadruplex-binding ligands. For example, 5,10,15,20-Tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin (TMPyP4), interacts strongly with G-quadruplexes, but has poor selectivity for G-quadruplex versus duplex DNA. To increase the G-quadruplex recognition specificity, a new cationic porphyrin derivative, 5,10,15,20-tetra-{4-[2-(1-methyl-1- piperidinyl)ethoxy]phenyl} porphyrin (TMPipEOPP), with large side arm substituents was synthesized, and the interactions between TMPipEOPP and different DNA structures were compared. The results show that G-quadruplexes cause large changes in the UV-Vis absorption and fluorescence spectra of TMPipEOPP, but duplex and single-stranded DNAs do not, indicating that TMPipEOPP can be developed as a highly specific optical probe for discriminating G-quadruplex from duplex and single-stranded DNA. Visual discrimination is also possible. Job plot and Scatchard analysis suggest that a complicated binding interaction occurs between TMPipEOPP and G-quadruplexes. At a low [G-quadruplex]/[TMPipEOPP] ratio, one G-quadruplex binds two TMPipEOPP molecules by end-stacking and outside binding modes. At a high [G-quadruplex]/[TMPipEOPP] ratio, two G-quadruplexes bind to one TMPipEOPP molecule in a sandwich-like end-stacking mode

The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Plasma Heme Oxygenase-1 Concentration in Relation to Impaired Glucose Regulation in a Non-Diabetic Chinese Population

Background: Our previous study has recently shown that plasma heme oxygenase-1 (HO-1), a stress-responsive protein, is elevated in individuals with type 2 diabetes. The current study aimed to examine the association between plasma HO-1 concentration and impaired glucose regulation (IGR) in non-diabetic individuals. Methods: We conducted a case-control study including a total of 865 subjects (262 IGR individuals and 603 healthy controls) in a Chinese population. Basic characteristics were collected by questionnaire and standardized anthropometric measurements. Plasma HO-1 concentration was determined by ELISA. Results: Plasma HO-1 concentration was significantly increased in IGR individuals compared with healthy controls (1.34 (0.81–2.29) ng/ml vs 0.98 (0.56–1.55) ng/ml, P,0.001). After adjustment for age, sex, and BMI, the ORs for IGR in the highest quartile of plasma HO-1 concentrations, compared with the lowest, was 3.42 (95 % CI 2.11–5.54; P for trend,0.001). The trend remained significant even after additional adjustment for smoking, alcohol drinking, hypertension, family history of diabetes, lipid profiles and C-reactive protein. In the receiver-operating characteristic curve analysis, addition of plasma HO-1 concentration to a model with known risk factors yielded significantly improved discriminative value for IGR (area under the curves 0.75 (95 % CI 0.71–0.78) vs. 0.72 (95 % CI 0.69–0.76); P for difference = 0.026)

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Effects of DAPT and Atoh1 Overexpression on Hair Cell Production and Hair Bundle Orientation in Cultured Organ of Corti from Neonatal Rats

BACKGROUND: In mammals, hair cells do not undergo spontaneous regeneration when they are damaged and result in permanent hearing loss. Previous studies in cultured Organ of Corti dissected from neonatal animals have shown that both DAPT (r-secretase inhibitor in the Notch signal pathway) treatment and Atoh1 overexpression can induce supernumerary hair cells. The effects of simultaneous DAPT treatment and Atoh1 over expression in the cells of cultured Organ of Corti from neonatal rats are still obscure. PRINCIPAL FINDINGS: In this study, we set out to investigate the interaction of DAPT treatment and Atoh1 overexpression as well as culture time and the location of basilar fragment isolated form neonatal rat inner ear. Our results showed that DAPT treatment induced more hair cells in the apical turn, while Atoh1 overexpression induced more extra hair cells in the middle turn of the cultured Organ of Corti. When used together, their effects are additive but not synergistic. In addition, the induction of supernumerary hair cells by both DAPT and Atoh1 overexpression is dependent on the treatment time and the location of the cochlear tissue. Moreover, DAPT treatment causes dramatic changes in the orientation of the stereociliary bundles of hair cells, whereas Atoh1 overexpression didn't induce drastic change of the polarity of stereociliary bundles. CONCLUSIONS/SIGNIFICANCE: Taken together, these results suggest that DAPT treatment are much more potent in inducing supernumerary hair cells than Atoh1 overexpression and that the new hair cells mainly come from the trans-differentiation of supporting cells around hair cells. The orientation change of stereociliary bundle of hair cells may be attributed to the insertion of the newly formed hair cells. The immature hair bundles on the newly formed hair cells may also contribute to the overall chaos of the stereociliary bundle of the sensory epithelia

Chinese Herbal Medicines for the Treatment of Type A H1N1 Influenza: A Systematic Review of Randomized Controlled Trials

Chinese herbs are thought to be effective for type A H1N1 influenza. Series of Chinese herbs have been authorized recommended by the Chinese government, and until now a number of clinical trials of Chinese herbs for H1N1 influenza have been conducted. However, there is no critically appraised evidence such as systematic reviews or metaanalyses on potential benefits and harms of medicinal herbs for H1N1 influenza to justify their clinical use and their recommendation. CENTRAL, MEDLINE, EMBASE, CBM, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites were searched for published and unpublished randomized controlled trials (RCTs) of Chinese herbs for H1N1 influenza till 31 August, 2011. A total of 26 RCTs were identified and reviewed. Most of the RCTs were of high risk of bias with flawed study design and poor methodological quality. The combination of several Chinese herbal medicines with or without oseltamivir demonstrated positive effect on fever resolution, relief of symptoms, and global effectiveness rate compared to oseltamivir alone. However, only one herbal medicine showed positive effect on viral shedding. Most of the trials did not report adverse events, and the safety of herbal medicines is still uncertain. Some Chinese herbal medicines demonstrated potential positive effect for 2009 type A H1N1 influenza; however, due to the lack of placebo controlled trial and lack of repeated test of the intervention, we could not draw confirmative conclusions on the beneficial effect of Chinese herbs for H1N1 influenza. More rigorous trials are warranted to support their clinical use