Concurrent Proinflammatory and Apoptotic Activity of a Helicobacter pylori Protein (HP986) Points to Its Role in Chronic Persistence

Helicobacter pylori induces cytokine mediated changes in gastroduodenal pathophysiology, wherein, the activated macrophages at the sub-mucosal space play a central role in mounting innate immune response against the antigens. The bacterium gains niche through persistent inflammation and local immune-suppression causing peptic ulcer disease or chronic gastritis; the latter being a significant risk factor for the development of gastric adenocarcinoma. What favors persistence of H. pylori in the gastric niches is not clearly understood. We report detailed characterization of a functionally unknown gene (HP986), which was detected in patient isolates associated with peptic ulcer and gastric carcinoma. Expression and purification of recombinant HP986 (rHP986) revealed a novel, ∼29 kDa protein in biologically active form which associates with significant levels of humoral immune responses in diseased individuals (p<0.001). Also, it induced significant levels of TNF-α and Interleukin-8 in cultured human macrophages concurrent to the translocation of nuclear transcription factor-κB (NF-κB). Further, the rHP986 induced apoptosis of cultured macrophages through a Fas mediated pathway. Dissection of the underlying signaling mechanism revealed that rHP986 induces both TNFR1 and Fas expression to lead to apoptosis. We further demonstrated interaction of HP986 with TNFR1 through computational and experimental approaches. Independent proinflammatory and apoptotic responses triggered by rHP986 as shown in this study point to its role, possibly as a survival strategy to gain niche through inflammation and to counter the activated macrophages to avoid clearance

Role of TNF-α in lung tight junction alteration in mouse model of acute lung inflammation

In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO) to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1) TNF-α production in pleural exudates and in the lung tissues, (2) the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity), (3) the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry) and (4) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction

Factors affecting commencement and cessation of smoking behaviour in Malaysian adults

<p>Abstract</p> <p>Background</p> <p>Tobacco consumption peak in developed countries has passed, however, it is on the increase in many developing countries. Apart from cigarettes, consumption of local hand-rolled cigarettes such as <it>bidi </it>and <it>rokok daun </it>are prevalent in specific communities. Although factors associated with smoking initiation and cessation has been investigated elsewhere, the only available data for Malaysia is on prevalence. This study aims to investigate factors associated with smoking initiation and cessation which is imperative in designing intervention programs.</p> <p>Methods</p> <p>Data were collected from 11,697 adults by trained recording clerks on sociodemographic characteristics, practice of other risk habit and details of smoking such as type, duration and frequency. Smoking commencement and cessation were analyzed using the Kaplan-Meier estimates and log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to calculate the hazard rate ratios.</p> <p>Results</p> <p>Males had a much higher prevalence of the habit (61.7%) as compared to females (5.8%). Cessation was found to be most common among the Chinese and those regularly consuming alcoholic beverages. Kaplan-Meier plot shows that although males are more likely to start smoking, females are found to be less likely to stop. History of betel quid chewing and alcohol consumption significantly increase the likelihood of commencement (p < 0.0001), while cessation was least likely among Indians, current quid chewers and kretek users (p < 0.01).</p> <p>Conclusions</p> <p>Gender, ethnicity, history of quid chewing and alcohol consumption have been found to be important factors in smoking commencement; while ethnicity, betel quid chewing and type of tobacco smoked influences cessation.</p

Bright Extragalactic ALMA Redshift Survey (BEARS) III: Detailed study of emission lines from 71 Herschel targets

We analyse the molecular and atomic emission lines of 71 bright Herschel-selected galaxies between redshifts 1.4 to 4.6 detected by the Atacama Large Millimetre/submillimetre Array. These lines include a total of 156 CO, [C I], and H2O emission lines. For 46 galaxies, we detect two transitions of CO lines, and for these galaxies we find gas properties similar to those of other dusty star-forming galaxy (DSFG) samples. A comparison to photo-dissociation models suggests that most of Herschel-selected galaxies have similar interstellar medium conditions as local infrared-luminous galaxies and high-redshift DSFGs, although with denser gas and more intense far-ultraviolet radiation fields than normal star-forming galaxies. The line luminosities agree with the luminosity scaling relations across five orders of magnitude, although the star-formation and gas surface density distributions (i.e., Schmidt-Kennicutt relation) suggest a different star-formation phase in our galaxies (and other DSFGs) compared to local and low-redshift gas-rich, normal star-forming systems. The gas-to-dust ratios of these galaxies are similar to Milky Way values, with no apparent redshift evolution. Four of 46 sources appear to have CO line ratios in excess of the expected maximum (thermalized) profile, suggesting a rare phase in the evolution of DSFGs. Finally, we create a deep stacked spectrum over a wide rest-frame frequency (220-890 GHz) that reveals faint transitions from HCN and CH, in line with previous stacking experiments.Comment: 30 pages, 17 figures, accepted for publication in Monthly Notices of the Royal Astronomical Society Main Journal. Comments are warmly welcome

A dusty proto-cluster surrounding the binary galaxy HerBS-70 at z = 2.3

We report on deep SCUBA-2 observations at 850 μm and NOEMA spectroscopic measurements at 2 mm of the environment surrounding the luminous, massive (M* ≈ 2 × 1011 M⊙) Herschel-selected source HerBS-70. This source was revealed by previous NOEMA observations to be a binary system of dusty star-forming galaxies at z = 2.3, with the East component (HerBS-70E) hosting an Active Galactic Nucleus (AGN). The SCUBA-2 observations detected, in addition to the binary system, twenty-one sources at >3.5σ over an area of ∼25 square comoving Mpc with a sensitivity of 1σ850 = 0.75 mJy. The surface density of continuum sources around HerBS-70 is three times higher than for field galaxies. The NOEMA spectroscopic measurements confirm the protocluster membership of three of the nine brightest sources through their CO(4–3) line emission, yielding a volume density 36 times higher than for field galaxies. All five confirmed sub-mm galaxies in the HerBS-70 system have relatively short gas depletion times (80 − 500 Myr), indicating the onset of quenching for this protocluster core due to the depletion of gas. The dark matter halo mass of the HerBS-70 system is estimated around 5 × 1013 M⊙, with a projected current-day mass of 1015 M⊙, similar to the local Virgo and Coma clusters. These observations support the claim that DSFGs, in particular the ones with observed multiplicity, can trace cosmic overdensities

The bright extragalactic ALMA redshift survey (BEARS) I: redshifts of bright gravitationally-lensed galaxies from the <i>Herschel</i> ATLAS

We present spectroscopic measurements for 71 galaxies associated with 62 of the brightest high-redshift submillimeter sources from the Southern fields of the Herschel Astrophysical Terahertz Large Area Survey (H-ATLAS), while targeting 85 sources which resolved into 142. We have obtained robust redshift measurements for all sources using the 12-m Array and an efficient tuning of ALMA to optimise its use as a redshift hunter, with 73 per cent of the sources having a robust redshift identification. Nine of these redshift identifications also rely on observations from the Atacama Compact Array. The spectroscopic redshifts span a range 1.41 z −1 −1 with a mean value of ∼500 km s−1, in line with other high-z samples. The derived CO(1-0) luminosity is significantly elevated relative to line-width to CO(1-0) luminosity scaling relation, which is suggestive of lensing magnification across our sources. In fact, the distribution of magnification factors inferred from the CO equivalent widths is consistent with expectations from galaxy-galaxy lensing models, though there is a hint of an excess at large magnifications that may be attributable to the additional lensing optical depth from galaxy groups or clusters