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Colonization by Helicobacter pylori is associated with gastric diseases, ranging from superficial gastritis to more severe pathologies, including intestinal metaplasia and adenocarcinoma. The interplay of the host response and the pathogen affect the outcome of disease. One major component of the mucosal response to H. pylori is the activation of a strong but inefficient immune response that fails to control the infection and frequently causes tissue damage. We have shown that polyamines can regulate H. pylori–induced inflammation. Chemical inhibition of ornithine decarboxylase (ODC), which generates the polyamine putrescine from l-ornithine, reduces gastritis in mice and adenocarcinoma incidence in gerbils infected with H. pylori. However, we have also demonstrated that Odc deletion in myeloid cells enhances M1 macrophage activation and gastritis. Here we used a genetic approach to assess the specific role of gastric epithelial ODC during H. pylori infection. Specific deletion of the gene encoding for ODC in gastric epithelial cells reduces gastritis, attenuates epithelial proliferation, alters the metabolome, and downregulates the expression of immune mediators induced by H. pylori. Inhibition of ODC activity or ODC knockdown in human gastric epithelial cells dampens H. pylori–induced NF-κB activation, CXCL8 mRNA expression, and IL-8 production. Chronic inflammation is a major risk factor for the progression to more severe pathologies associated with H. pylori infection, and we now show that epithelial ODC plays an important role in mediating this inflammatory response.

We evaluated an essential oil (EO) of Tagetes lucida Cav. and the mixture of its main compounds against multi-drug resistant bacteria. We found that EO and the partially reconstituted blend of its main components have antibacterial activity and inhibit antibiotic resistance (ampicillin, chloramphenicol, nalidixic acid, vancomycin and imipenem) in strains of Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa HIM-MR01. The T. lucida EO alone or added to the antibiotics showed antimicrobial activity against S. aureus and P. aeruginosa. The EO main bioactive compounds were methyl eugenol (relative abundance in EO: 46·15%), estragole (32·93%), linalool (2·48%) and geraniol (0·33%). The mixture (PREO) of those compounds at those proportions inhibited the growth of P. aeruginosa in 45% at 683·62 µg ml−1 and that of S. aureus in 51·7% at 39·04 µg ml−1. The PREO had higher antibacterial and modulatory activities than the original EO. In conclusion, we overcame the unpredictability of EO activity (due to their natural variability) by determining which EO components inhibited bacteria and then producing a PREO to generate a reproducible mixture with predictable antibacterial and modulation of resistance activities. Thus, the PREO, and its components, show potential as alternatives to manage multidrug-resistant pathogens.

Colitis-associated colon cancer (CAC) is one of the most common malignant neoplasms and a leading cause of death. The immunologic factors associated with CAC development are not completely understood. Signal transducer and activator of transcription 6 (STAT6) is part of an important signaling pathway for modulating intestinal immune function and homeostasis. However, the role of STAT6 in colon cancer progression is unclear. Following CAC induction in wild-type (WT) and STAT6-deficient mice (STAT6–/–), we found that 70% of STAT6–/– mice were tumor-free after 8 weeks, whereas 100% of WT mice developed tumors. STAT6–/– mice displayed fewer and smaller colorectal tumors than WT mice; this reduced tumorigenicity was associated with decreased proliferation and increased apoptosis in the colonic mucosa in the early steps of tumor progression. STAT6–/– mice also exhibited reduced inflammation, diminished concentrations COX2 and nuclear β-catenin protein in the colon, and decreased mRNA expression of IL17A and TNFα, but increased IL10 expression when compared with WT mice. Impaired mucosal expression of CCL9, CCL25, and CXCR2 was also observed. In addition, the number of circulating CD11b+Ly6ChiCCR2+ monocytes and CD11b+Ly6ClowLy6G+ granulocytes was both decreased in a STAT6-dependent manner. Finally, WT mice receiving a STAT6 inhibitor in vivo confirmed a significant reduction in tumor load as well as less intense signs of CAC. Our results demonstrate that STAT6 is critical in the early steps of CAC development for modulating inflammatory responses and controlling cell recruitment and proliferation. Thus, STAT6 may represent a promising target for CAC treatment. Cancer Immunol Res; 5(5); 385–96. ©2017 AACR.

Data about primers used for RT-PCR analysis, including number of cycles and melting temperature

Helicobacter pylori (H. pylori) is the strongest known risk for gastric cancer. The H. pylori cag type IV secretion system is an oncogenic locus that translocates peptidoglycan into host cells, where it is recognized by NOD1, an innate immune receptor. Beyond this, the role of NOD1 in H. pylori–induced cancer remains undefined. To address this knowledge gap, we infected two genetic models of Nod1 deficiency with the H. pylori cag+ strain PMSS1: C57BL/6 mice, which rarely develop cancer, and INS-GAS FVB/N mice, which commonly develop cancer. Infected C57BL/6Nod1–/− and INS-GASNod1−/− mice acutely developed more severe gastritis, and INS-GASNod1−/− mice developed gastric dysplasia more frequently compared with Nod1+/+ mice. Because Nod1 genotype status did not alter microbial phenotypes of in vivo–adapted H. pylori, we investigated host immunologic responses. H. pylori infection of Nod1−/− mice led to significantly increased gastric mucosal levels of Th1, Th17, and Th2 cytokines compared with Nod1 wild-type (WT) mice. To define the role of specific innate immune cells, we quantified cytokine secretion from H. pylori–infected primary gastric organoids generated from WT or Nod1−/− mice that were cocultured with or without WT or Nod1−/− macrophages. Infection increased cytokine production from gastric epithelial cells and macrophages and elevations were significantly increased with Nod1 deficiency. Furthermore, H. pylori infection altered the polarization status of Nod1−/− macrophages compared with Nod1+/+ macrophages. Collectively, these studies demonstrate that loss of Nod1 augments inflammatory and injury responses to H. pylori. Nod1 may exert its restrictive role by altering macrophage polarization, leading to immune evasion and microbial persistence.Significance:These findings suggest that manipulation of NOD1 may represent a novel strategy to prevent or treat pathologic outcomes induced by H. pylori infection.

Primer sequences used for real time RT-PCR quantification.

Background: Development of the intestinal subtype of gastric adenocarcinoma is marked by a progression of histopathologic lesions. Residents of the Andean regions of Colombia are at high risk for gastric cancer.Methods: A cohort of 976 Colombian subjects was followed over 16 years examining effects of Helicobacter pylori eradication and treatment with antioxidants on progression of lesions. We performed methylation analysis of DNA from baseline antral biopsies from 104 subjects for whom follow-up data were available for at least 12 years. Methylation was quantitated for AMPH, CDKN2A, CDH1, EN1, EMX1, NKX6-1, PCDH10, RPRM, RSPO2, SORCS3, ZIC1, and ZNF610 genes, using Pyrosequencing.Results: Levels of DNA methylation were associated with baseline diagnosis for AMPH, EMX1, RPRM, RSPO2, SORCS3, and ZNF610. After adjusting for baseline diagnosis and H. pylori infection, methylation levels of AMPH, PCDH10, RSPO2, and ZNF610 had progression coefficients that increased and P values that decreased over 6, 12, and 16 years. Methylation for SORCS3 was associated with progression at all 3 time points but without the continual strengthening of the effect. Scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes were unrelated to progression.Conclusions: Methylation levels of AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 predict progression of gastric lesions independent of the effect of duration of H. pylori infection, baseline diagnosis, gender of the patient, or scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes.Impact: DNA methylation levels in AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 may contribute to identification of persons with gastric lesions likely to progress. Cancer Epidemiol Biomarkers Prev; 24(10); 1607–13. ©2015 AACR.

RT2 profiler PCR array analysis for NF-kB gene targets in primary gastric epithelial cell organoids induced by strain 7.13

Chemokine and cytokine expression in C57BL/6 mice at 2, 20, and 90 days post-infection with H. pylori PMSS1

Correlation Coefficients for Methylation Levels.

Chemokine and cytokine expression in INS-GAS mice at 2, 20, 40, and 90 days post-infection with H. pylori PMSS1.

Mouse NF-kB RT2 profiler PCR array of gastroids following infection with either H. pylori strain PMSS1 or 7.13.

Map of CpG Sites for Non-commercial Assays

A deep survey of the Large Magellanic Cloud at ~0.1-100TeV photon energies with the Cherenkov Telescope Array is planned. We assess the detection prospects based on a model for the emission of the galaxy, comprising the four known TeV emitters, mock populations of sources, and interstellar emission on galactic scales. We also assess the detectability of 30 Doradus and SN 1987A, and the constraints that can be derived on the nature of dark matter. The survey will allow for fine spectral studies of N157B, N132D, LMC P3, and 30 Doradus C, and half a dozen other sources should be revealed, mainly pulsar-powered objects. The remnant from SN 1987A could be detected if it produces cosmic-ray nuclei with a flat power-law spectrum at high energies, or with a steeper index 2.3-2.4 pending a flux increase by a factor >3-4 over ~2015-2035. Large-scale interstellar emission remains mostly out of reach of the survey if its >10GeV spectrum has a soft photon index ~2.7, but degree-scale 0.1-10TeV pion-decay emission could be detected if the cosmic-ray spectrum hardens above >100GeV. The 30 Doradus star-forming region is detectable if acceleration efficiency is on the order of 1-10% of the mechanical luminosity and diffusion is suppressed by two orders of magnitude within

A deep survey of the Large Magellanic Cloud at ~0.1-100TeV photon energies with the Cherenkov Telescope Array is planned. We assess the detection prospects based on a model for the emission of the galaxy, comprising the four known TeV emitters, mock populations of sources, and interstellar emission on galactic scales. We also assess the detectability of 30 Doradus and SN 1987A, and the constraints that can be derived on the nature of dark matter. The survey will allow for fine spectral studies of N157B, N132D, LMC P3, and 30 Doradus C, and half a dozen other sources should be revealed, mainly pulsar-powered objects. The remnant from SN 1987A could be detected if it produces cosmic-ray nuclei with a flat power-law spectrum at high energies, or with a steeper index 2.3-2.4 pending a flux increase by a factor >3-4 over ~2015-2035. Large-scale interstellar emission remains mostly out of reach of the survey if its >10GeV spectrum has a soft photon index ~2.7, but degree-scale 0.1-10TeV pion-decay emission could be detected if the cosmic-ray spectrum hardens above >100GeV. The 30 Doradus star-forming region is detectable if acceleration efficiency is on the order of 1-10% of the mechanical luminosity and diffusion is suppressed by two orders of magnitude within, Accepted for publication in MNRAS. Corresponding authors: Pierrick Martin, Maria Isabel Bernardos Martin, Fabio Iocco

Existe escasa literatura sobre las asimetrías en el pádel, un deporte de naturaleza asimétrica. Para estudiar el desarrollo de asimetrías en este deporte se evaluó, con bioimpedancia, la masa magra de ambos miembros superiores de 96 jugadores de pádel jóvenes y de 76 esquiadores (grupo control) y se calculó el índice de simetría. Los jugadores de pádel tuvieron una asimetría entre ambos miembros superiores mayor que los esquiadores, cuando se consideró toda la muestra (7.2 ± 5 % vs. 1.4 ± 3.2 %; p < 0.001), en jugadores con un estado de madurez negativo (5,7 ± 3,2 % vs. 1,5 ± 3,8 %; p < 0,001) y en aquellos con un estado de madurez positivo (8,3 ± 5,8 % vs. 1,3 ± 2,4 %; p < 0,001). Este estudio revela que el pádel genera asimetrías de masa magra en los miembros superiores, incluso antes de la edad de crecimiento pico., There is little literature on asymmetries in paddle tennis, a sport of an asymmetrical nature. To study the development of upper limb asymmetries, 96 young paddle players and 76 skiers (control group) were evaluated via bioimpedance. The lean mass symmetry index was then compared, considering the sport (paddle tennis players and skiers) and the maturity offset (positive or negative). Paddle-tennis players had a systematically greater upper limbs asymmetry than skiers (7.2 ± 5 % vs. 1.4 ± 3.2 %; p < 0.001). This also occurs when comparing only the subsamples with a negative maturity offset (5.7 ± 3.2 % vs. 1.5 ± 3.8 %; p < 0.001) or with a positive maturity offset (8.3 ± 5.8 % vs. 1.3 ± 2.4 %; p < 0.001). The study reveals that paddle tennis generates asymmetries of lean mass in upper limbs, even before growth spurt., Spanish Government FPU15/02949

Summary The formation/precipitation and deposition of pipeline solids, such as gas hydrates, asphaltenes, and waxes have long plagued production fields. Given the vast differences in chemistries of these solids, any current prevention or mitigation strategy, particularly for cases in which multiple issues are a concern, is likely to involve an extensive assortment of chemical additives that are both costly and add complexity to the system. Surface treatments (coatings), on the other hand, present a relatively viable option for management strategies. A chemically and physically robust surface treatment with the ability to address deposition issues for multiple pipeline solids could not only decrease the operating expenditures for a field through material cost savings and obviation of downstream separation, but could also simplify produced fluids by eliminating additional chemicals from the mixture. The purpose of this study was to explore the feasibility of a particular surface treatment as part of a solids management strategy. This work used an omniphobic surface treatment to probe its effects on gas hydrate, asphaltene, and wax deposition. Specifically, an interfacial tensiometer (IFT) collected contact angle measurements for wettability studies. High-pressure rocking cells studied gas hydrate nucleation and deposition. A bench-scale flow loop quantified the deposition of oil and asphaltenes after a set time period. Finally, a mechanical shear device measured the adhesion force of wax deposits on untreated/treated surfaces. Static contact angle results showed that the omniphobic surface treatment had reduced surface interaction with water droplets in air, altering from the complete wetting on corroded surfaces to slightly hydrophobic conditions of greater than 100°. In addition, rocking-cell tests indicated that these omniphobic surface treatments may prevent gas hydrate deposition for up to 72 hours. The gas hydrate rocking-cell tests also demonstrated possible increases in induction time and occasional elimination of hydrate nucleation with the surface treatment. Finally, the surface treatment application, which also decreased surface roughness, showed that crude oil and asphaltene particles deposition, as well as the shear required to remove solidified wax deposits, could be reduced by a large factor. Overall, promising results were recorded for all major flow-assurance solids in the presence of the surface treatment.