Association between exposure to second-hand smoke and telomere length: cross-sectional study of 1303 non-smokers

Background: Both active smoking and second-hand smoke (SHS) are important risk factors for many age-related diseases. Active smoking is associated with shortened telomere length. However, whether SHS accelerates telomere attrition with age is uncertain. The aim of this study was to examine the association between SHS exposure and shortening by age of leukocyte telomere length among adult non-smokers. Methods: We undertook a cross-sectional study of the association between self-reported levels of SHS exposure and telomere length shortening per annum on a subgroup of participants from the Scottish Family Health Study. Inclusion was restricted to non-smokers aged ≥ 18 years, who had provided self-reported overall usual SHS exposure (total hours per week) and blood samples for telomere analysis. Linear regression models were used to compare the ratio of telomere repeat copy number to single copy gene number (T/S)by age according to SHS exposure. Results: Of the 1303 eligible participants, 779 (59.8%) reported no SHS exposure, 495 (38.0%) low exposure (1–19 h per week) and 29 (2.2%) high exposure (≥20 h per week). In the univariate linear regression analyses, relative T/S ratio declined with increasing age in all exposure groups. Telomere length decreased more rapidly with increasing age among those with high exposure to SHS [adjusted coefficient −0.019, 95% confidence interval (CI) −0.031- −0.007) when compared with both those with no exposure to SHS (adjusted coefficient −0.006, 95% CI −0.008- −0.004) (high vs no SHS: P = 0.010) and those with low exposure to SHS (adjusted coefficient −0.005, 95% CI −0.007- −0.003) (high vs low SHS: P = 0.005). Conclusions: Our findings suggest that high SHS exposure may accelerate normal biological ageing, and support efforts to protect the public from SHS exposure. Further studies on relevant mechanisms should be conducted

Climate change impact on the feeding habits of Indian mackerel observed along the Kerala coast

While most food and feeding research in fisheries emphasize the feeding habits and diet components of the fish, the aim of the present work was to assess any change in the diet composition of Indian mackerel Rastrelliger kanagurta (Cuvier, 1816) and identify the role of climate change in effecting it. Non-parametric statistical technique, the Generalized Additive Model (GAMs) was used for modeling the causal link of diet changes in relation to climate change using mgcv package of R software. Monthly Index of Relative Importance (IRI) was calculated for 36 months from January 2013 to December 2015 and major prey items in the diet were identified. Climatic variables - Sea Surface Temperature (SST), precipitation (Pr), Chlorophyll a (Chl a), salinity and Ekman transport or coastal upwelling index (CUI)) pertaining to the study area were extracted for the period. Length-wise IRI was compared to check the existing patterns in the feeding habits of the fish. The dominant prey items observed in the gut of Indian mackerel during the study period were diatoms ( Fragillaria sp., Nitzchia sp., Thalassiothrix sp., Thalassiosira sp. and Coscinodiscus sp.), dinoflagellates (Ceratium sp., Ornothocercus sp., Dinophysis sp. and Prorocentrum sp.), copepods (Calanoida, Cyclopoida and Harpacticoida), decapods (Acetes) and tintinnids (Tintinnopsis sp., Codenellopsis sp. and Flavella sp). GAM models were fitted with monthly IRI of the major prey items (copepods, diatoms, dinoflagellates, Acetes and tintinnids) in the gut and climatic variables. Model selection was done in terms of sharpening the relation between the predictors and the response variable using Akaike information criterion, R-squared and F-statistics. GAM model results revealed that occurrence of prey items in the diet of Indian mackerel were influenced by environmental variables. An increase in the relative importance of dinoflagellates, Acetes and tintintids in the diet over the historic period was observed. The study also revealed a shift in the diet composition of younger fishes. The results of the current study provide a more in-depth assessment of the nonlinear relationship between climatic variables and diet composition of Indian mackerel

Macaque anterior cingulate cortex deactivation impairs performance and alters lateral prefrontal oscillatory activities in a rule-switching task

© 2019 Ma et al. In primates, both the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (dlPFC) are key regions of the frontoparietal cognitive control network. To study the role of the dACC and its communication with the dlPFC in cognitive control, we recorded local field potentials (LFPs) from the dlPFC before and during the reversible deactivation of the dACC, in macaque monkeys engaging in uncued switches between 2 stimulus-response rules, namely prosaccade and antisaccade. Cryogenic dACC deactivation impaired response accuracy during maintenance of—but not the initial switching to—the cognitively demanding antisaccade rule, which coincided with a reduction in task-related theta activity and the correct-error (C-E) difference in dlPFC beta-band power. During both rule switching and maintenance, dACC deactivation prolonged the animals’ reaction time and reduced task-related alpha power in the dlPFC. Our findings support a role of the dACC in prefrontal oscillatory activities that are involved the maintenance of a new, challenging task rule

PBRM1 acts as a p53 lysine-acetylation reader to suppress renal tumor growth.

p53 acetylation is indispensable for its transcriptional activity and tumor suppressive function. However, the identity of reader protein(s) for p53 acetylation remains elusive. PBRM1, the second most highly mutated tumor suppressor gene in kidney cancer, encodes PBRM1. Here, we identify PBRM1 as a reader for p53 acetylation on lysine 382 (K382Ac) through its bromodomain 4 (BD4). Notably, mutations on key residues of BD4 disrupt recognition of p53 K382Ac. The mutation in BD4 also reduces p53 binding to promoters of target genes such as CDKN1A (p21). Consequently, the PBRM1 BD4 mutant fails to fully support p53 transcriptional activity and is defective as a tumor suppressor. We also find that expressions of PBRM1 and p21 correlate with each other in human kidney cancer samples. Our findings uncover a tumor suppressive mechanism of PBRM1 in kidney cancer and provide a mechanistic insight into the crosstalk between p53 and SWI/SNF complexes

Influenza A virus NS1 gene mutations F103L and M106I increase replication and virulence

<p>Abstract</p> <p>Background</p> <p>To understand the evolutionary steps required for a virus to become virulent in a new host, a human influenza A virus (IAV), A/Hong Kong/1/68(H3N2) (HK-wt), was adapted to increased virulence in the mouse. Among eleven mutations selected in the NS1 gene, two mutations F103L and M106I had been previously detected in the highly virulent human H5N1 isolate, A/HK/156/97, suggesting a role for these mutations in virulence in mice and humans.</p> <p>Results</p> <p>To determine the selective advantage of these mutations, reverse genetics was used to rescue viruses containing each of the NS1 mouse adapted mutations into viruses possessing the HK-wt NS1 gene on the A/PR/8/34 genetic backbone. Both F103L and M106I NS1 mutations significantly enhanced growth <it>in vitro </it>(mouse and canine cells) and <it>in vivo </it>(BALB/c mouse lungs) as well as enhanced virulence in the mouse. Only the M106I NS1 mutation enhanced growth in human cells. Furthermore, these NS1 mutations enhanced early viral protein synthesis in MDCK cells and showed an increased ability to replicate in mouse interferon β (IFN-β) pre-treated mouse cells relative to rPR8-HK-NS-wt NS1. The double mutant, rPR8-HK-NS-F103L + M106I, demonstrated growth attenuation late in infection due to increased IFN-β induction in mouse cells. We then generated a rPR8 virus possessing the A/HK/156/97 NS gene that possesses 103L + 106I, and then rescued the L103F + I106M mutant. The 103L + 106I mutations increased virulence by >10 fold in BALB/c mice. We also inserted the avian A/Ck/Beijing/1/95 NS1 gene (the source lineage of the A/HK/156/97 NS1 gene) that possesses 103L + 106I, onto the A/WSN/33 backbone and then generated the L103F + I106M mutant. None of the H5N1 and H9N2 NS containing viruses resulted in increased IFN-β induction. The rWSN-A/Ck/Beijing/1/95-NS1 gene possessing 103L and 106I demonstrated 100 fold enhanced growth and >10 fold enhanced virulence that was associated with increased tropism for lung alveolar and bronchiolar tissues relative to the corresponding L103F and I106M mutant.</p> <p>Conclusions</p> <p>The F103L and M106I NS1 mutations were adaptive genetic determinants of growth and virulence in both human and avian NS1 genes in the mouse model.</p

Anticancer Activity and Biophysical Reactivity of Copper Complexes of 2-(benzo[d][1,3]dioxol-5-ylmethylene)-N-Alkylhydrazinecarbothioamides

A series of copper complexes were synthesized from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) thiosemicarbazones (RHpTSC where R = H, CH3, C2H5 or C6H5 (Ph)). The complexes show interesting variations in geometry depending on the thiosemicarbazone; a dinuclear complex [Cu(HpTSC)Cl]2, a mononuclear complex [Cu(RHpTSC)2Cl2] (R = CH3 or C2H5) and another mononuclear complex [Cu(PhHpTSC)(PhpTSC)Cl] was generated. The complexes bind in a moderately strong fashion to DNA with binding constants on the order of 104 M− 1. They are also strong binders of human serum albumin with binding constants near 104 M− 1. The complexes show good in vitro cytotoxic profiles against two human colon cancer cell lines (HCT-116 and HT29) and two human breast cancer cell lines (MCF-7 and MDA-MB-231) with IC50 values in the low millimolar concentration range

Marine climate and fisheries scenario of Kerala Climcard-3

Marine climate and fisheries scenario of Kerala Climcard-

Exposure to secondhand smoke and risk of peripheral arterial disease in southern Chinese non-smokers: the Guangzhou Biobank Cohort Study-Cardiovascular Disease Sub-cohort

Objectives: We studied the association between secondhand smoke (SHS) exposure and peripheral arterial disease (PAD) in Chinese non-smokers. Methods: We conducted a cross-sectional study using baseline data from the Guangzhou Biobank Cohort Study: Cardiovascular Disease Sub-cohort Study (GBCS-CVD). Guangzhou residents aged ≥ 50 years were recruited between 2003 and 2008. Baseline data included measurement of ankle brachial pressure index (ABPI) and self-reported smoking status and SHS exposure. Univariate and multivariate logistic regression analyses were used to analyze the association between SHS and PAD (defined as ABPI &lt; 0.9). Results: Of the 1507 non-smokers, 24 (1.6%) had PAD. Of these, 12 were men and 12 were women. Exposure to SHS at home of ≥25 h per week was reported by 16.7% of PAD cases compared with 3.8% of those without PAD (χ2 test, p = 0.003). After adjustment for potential confounders, exposure to ≥25 h per week at home was still associated with PAD (adjusted OR 7.86, 95% CI 2.00–30.95, p = 0.003), with suggestion of a dose-response relationship. Conclusions: Our results extend the US Surgeon General’s 2006 report that SHS exposure is an independent risk factor for PAD. National smoke-free legislation is needed to protect all people from exposure

Pilot testing of enhanced sorbents for calcium looping with cement production

One of the main challenges for commercialising calcium looping (CaL) as a CO2 capture technology is maintaining a high level of sorbent reactivity during long-term cycling. In order to mitigate the decay in carrying capacity, research has moved towards producing enhanced sorbents. However, this creates potential problems related to ease of scaling up production techniques and production costs, and raises the question as to whether such approaches can be used at large scale. On the other hand, a key advantage of CaL over other carbon capture technologies is synergy with the cement industry, i.e., use of spent sorbent as a feedstock for clinker production. In this work two enhanced materials: (i) limestone doped with HBr through a particle surface impregnation technique; and (ii) pellets prepared from limestone and calcium aluminate cement, were tested in a 25 kWth dual fluidised bed pilot-scale reactor in order to investigate their capture performance and mechanical stability under realistic CaL conditions. Moreover, the spent sorbent was then used as a raw material to make cement, which was characterised for phase and chemical composition as well as compressive strength. The HBr-doped limestone showed better performance in terms of both mechanical strength and stability of the CO2 uptake when compared to that of pellets. Furthermore, it was shown that the cement produced has similar characteristics and performance as those of commercial CEM 1 cement. This indicates the advantages of using the spent sorbent as feedstock for cement manufacture and shows the benefits of synthetic sorbents in CaL and suitability of end-use of spent sorbents for the cement industry, validating their synergy at pilot scale. Finally, this study demonstrates the possibility of using several practical techniques to improve the performance of CaL at the pilot scale, and more importantly demonstrates that commercial-grade cement can be made from the lime product from this technology