National smokefree law in New Zealand improves air quality inside bars, pubs and restaurants

<p>Abstract</p> <p>Background:</p> <p>We aimed to: (i) assess compliance with a new smokefree law in a range of hospitality settings; and (ii) to assess the impact of the new law by measuring air quality and making comparisons with air quality in outdoor smoking areas and with international data from hospitality settings.</p> <p>Methods:</p> <p>We included 34 pubs, restaurants and bars, 10 transportation settings, nine other indoor settings, six outdoor smoking areas of bars and restaurants, and six other outdoor settings. These were selected using a mix of random, convenience and purposeful sampling. The number of lit cigarettes among occupants at defined time points in each venue was observed and a portable real-time aerosol monitor was used to measure fine particulate levels (PM_2.5).</p> <p>Results:</p> <p>No smoking was observed during the data collection periods among over 3785 people present in the indoor venues, nor in any of the transportation settings. The levels of fine particulates were relatively low inside the bars, pubs and restaurants in the urban and rural settings (mean 30-minute level = 16 μg/m³for 34 venues; range of mean levels for each category: 13 μg/m³to 22 μg/m³). The results for other smokefree indoor settings (shops, offices etc) and for smokefree transportation settings (eg, buses, trains, etc) were even lower. However, some "outdoor" smoking areas attached to bars/restaurants had high levels of fine particulates, especially those that were partly enclosed (eg, up to a 30-minute mean value of 182 μg/m³and a peak of maximum value of 284 μg/m³). The latter are far above WHO guideline levels for 24-hour exposure (ie, 25μg/m³).</p> <p>Conclusion:</p> <p>There was very high compliance with the new national smokefree law and this was also reflected by the relatively good indoor air quality in hospitality settings (compared to the "outdoor" smoking areas and the comparable settings in countries that permit indoor smoking). Nevertheless, adopting enhanced regulations (as used in various US and Canadian jurisdictions) may be needed to address hazardous air quality in relatively enclosed "outdoor" smoking areas.</p

The Chromatin Remodelling Factor dATRX Is Involved in Heterochromatin Formation

Despite extensive study of heterochromatin, relatively little is known about the mechanisms by which such a structure forms. We show that the Drosophila homologue of the human α-thalassemia and mental retardation X-linked protein (dATRX), is important in the formation or maintenance of heterochromatin through modification of position effect variegation. We further show that there are two isoforms of the dATRX protein, the longer of which interacts directly with heterochromatin protein 1 (dHP-1) through a CxVxL motif both in vitro and in vivo. These two proteins co-localise at heterochromatin in a manner dependent on this motif. Consistent with this observation, the long isoform of the dATRX protein localises primarily to the heterochromatin at the chromocentre on salivary gland polytene chromosomes, whereas the short isoform binds to many sites along the chromosome arms. We suggest that the establishment of a regular nucleosomal organisation may be common to heterochromatin and transcriptionally repressed chromatin in other locations, and may require the action of ATP dependent chromatin remodelling factors

Factors affecting exhaled nitric oxide measurements: the effect of sex

<p>Abstract</p> <p>Background</p> <p>Exhaled nitric oxide (F_ENO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F_ENO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F_ENO in a well characterised adult population.</p> <p>Methods</p> <p>Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on F_ENO were explored by unadjusted and adjusted linear regression analyses.</p> <p>Results</p> <p>The effect of sex on F_ENO was both statistically and clinically significant, with F_ENO levels approximately 25% less in females. Overall, current smoking reduced F_ENO up to 50%, but this effect occurred predominantly in those who smoked on the day of the F_ENO measurement. Atopy increased F_ENO by 60%. The sex-related differences in F_ENO remained significant (p < 0.001) after controlling for all other significant factors affecting F_ENO.</p> <p>Conclusion</p> <p>Even after adjustment, F_ENO values are significantly different in males and females. The derivation of reference values and the interpretation of F_ENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.</p

Induction by transforming growth factor-β1 of epithelial to mesenchymal transition is a rare event in vitro

INTRODUCTION: Transforming growth factor (TGF)-β1 is proposed to inhibit the growth of epithelial cells in early tumorigenesis, and to promote tumor cell motility and invasion in the later stages of carcinogenesis through the induction of an epithelial to mesenchymal transition (EMT). EMT is a multistep process that is characterized by changes in cell morphology and dissociation of cell–cell contacts. Although there is growing interest in TGF-β1-mediated EMT, the phenotype is limited to only a few murine cell lines and mouse models. METHODS: To identify alternative cell systems in which to study TGF-β1-induced EMT, 18 human and mouse established cell lines and cultures of two human primary epithelial cell types were screened for TGF-β1-induced EMT by analysis of cell morphology, and localization of zonula occludens-1, E-cadherin, and F-actin. Sensitivity to TGF-β1 was also determined by [(3)H]thymidine incorporation, flow cytometry, phosphorylation of Smad2, and total levels of Smad2 and Smad3 in these cell lines and in six additional cancer cell lines. RESULTS: TGF-β1 inhibited the growth of most nontransformed cells screened, but many of the cancer cell lines were insensitive to the growth inhibitory effects of TGF-β1. In contrast, TGF-β1 induced Smad2 phosphorylation in the majority of cell lines, including cell lines resistant to TGF-β1-mediated cell cycle arrest. Of the cell lines screened only two underwent TGF-β1-induced EMT. CONCLUSION: The results presented herein show that, although many cancer cell lines have lost sensitivity to the growth inhibitory effect of TGF-β1, most show evidence of TGF-β1 signal transduction, but only a few cell lines undergo TGF-β1-mediated EMT

Evidence for the Contribution of the Hemozoin Synthesis Pathway of the Murine Plasmodium yoelii to the Resistance to Artemisinin-Related Drugs

Plasmodium falciparum malaria is a major global health problem, causing approximately 780,000 deaths each year. In response to the spreading of P. falciparum drug resistance, WHO recommended in 2001 to use artemisinin derivatives in combination with a partner drug (called ACT) as first-line treatment for uncomplicated falciparum malaria, and most malaria-endemic countries have since changed their treatment policies accordingly. Currently, ACT are often the last treatments that can effectively and rapidly cure P. falciparum infections permitting to significantly decrease the mortality and the morbidity due to malaria. However, alarming signs of emerging resistance to artemisinin derivatives along the Thai-Cambodian border are of major concern. Through long-term in vivo pressures, we have been able to select a murine malaria model resistant to artemisinins. We demonstrated that the resistance of Plasmodium to artemisinin-based compounds depends on alterations of heme metabolism and on a loss of hemozoin formation linked to the down-expression of the recently identified Heme Detoxification Protein (HDP). These artemisinins resistant strains could be able to detoxify the free heme by an alternative catabolism pathway involving glutathione (GSH)-mediation. Finally, we confirmed that artemisinins act also like quinolines against Plasmodium via hemozoin production inhibition. The work proposed here described the mechanism of action of this class of molecules and the resistance to artemisinins of this model. These results should help both to reinforce the artemisinins activity and avoid emergence and spread of endoperoxides resistance by focusing in adequate drug partners design. Such considerations appear crucial in the current context of early artemisinin resistance in Asia

An In Vitro Model for Lewy Body-Like Hyaline Inclusion/Astrocytic Hyaline Inclusion: Induction by ER Stress with an ALS-Linked SOD1 Mutation

Neuronal Lewy body-like hyaline inclusions (LBHI) and astrocytic hyaline inclusions (Ast-HI) containing mutant Cu/Zn superoxide dismutase 1 (SOD1) are morphological hallmarks of familial amyotrophic lateral sclerosis (FALS) associated with mutant SOD1. However, the mechanisms by which mutant SOD1 contributes to formation of LBHI/Ast-HI in FALS remain poorly defined. Here, we report induction of LBHI/Ast-HI-like hyaline inclusions (LHIs) in vitro by ER stress in neuroblastoma cells. These LHI closely resemble LBHI/Ast-HI in patients with SOD1-linked FALS. LHI and LBHI/Ast-HI share the following features: 1) eosinophilic staining with a pale core, 2) SOD1, ubiquitin and ER resident protein (KDEL) positivity and 3) the presence of approximately 15–25 nm granule-coated fibrils, which are morphological hallmark of mutant SOD1-linked FALS. Moreover, in spinal cord neurons of L84V SOD1 transgenic mice at presymptomatic stage, we observed aberrant aggregation of ER and numerous free ribosomes associated with abnormal inclusion-like structures, presumably early stage neuronal LBHI. We conclude that the LBHI/Ast-HI seen in human patients with mutant SOD1-linked FALS may arise from ER dysfunction

Type 1 Fimbriae, a Colonization Factor of Uropathogenic Escherichia coli, Are Controlled by the Metabolic Sensor CRP-cAMP

Type 1 fimbriae are a crucial factor for the virulence of uropathogenic Escherichia coli during the first steps of infection by mediating adhesion to epithelial cells. They are also required for the consequent colonization of the tissues and for invasion of the uroepithelium. Here, we studied the role of the specialized signal transduction system CRP-cAMP in the regulation of type 1 fimbriation. Although initially discovered by regulating carbohydrate metabolism, the CRP-cAMP complex controls a major regulatory network in Gram-negative bacteria, including a broad subset of genes spread into different functional categories of the cell. Our results indicate that CRP-cAMP plays a dual role in type 1 fimbriation, affecting both the phase variation process and fimA promoter activity, with an overall repressive outcome on fimbriation. The dissection of the regulatory pathway let us conclude that CRP-cAMP negatively affects FimB-mediated recombination by an indirect mechanism that requires DNA gyrase activity. Moreover, the underlying studies revealed that CRP-cAMP controls the expression of another global regulator in Gram-negative bacteria, the leucine-responsive protein Lrp. CRP-cAMP-mediated repression is limiting the switch from the non-fimbriated to the fimbriated state. Consistently, a drop in the intracellular concentration of cAMP due to altered physiological conditions (e.g. growth in presence of glucose) increases the percentage of fimbriated cells in the bacterial population. We also provide evidence that the repression of type 1 fimbriae by CRP-cAMP occurs during fast growth conditions (logarithmic phase) and is alleviated during slow growth (stationary phase), which is consistent with an involvement of type 1 fimbriae in the adaptation to stress conditions by promoting biofilm growth or entry into host cells. Our work suggests that the metabolic sensor CRP-cAMP plays a role in coupling the expression of type 1 fimbriae to environmental conditions, thereby also affecting subsequent attachment and colonization of host tissues

Transcriptome characterization of the South African abalone Haliotis midae using sequencing-by-synthesis

<p>Abstract</p> <p>Background</p> <p>Worldwide, the genus <it>Haliotis </it>is represented by 56 extant species and several of these are commercially cultured. Among the six abalone species found in South Africa, <it>Haliotis midae </it>is the only aquacultured species. Despite its economic importance, genomic sequence resources for <it>H. midae</it>, and for abalone in general, are still scarce. Next generation sequencing technologies provide a fast and efficient tool to generate large sequence collections that can be used to characterize the transcriptome and identify expressed genes associated with economically important traits like growth and disease resistance.</p> <p>Results</p> <p>More than 25 million short reads generated by the Illumina Genome Analyzer were <it>de novo </it>assembled in 22,761 contigs with an average size of 260 bp. With a stringent <it>E</it>-value threshold of 10^-10, 3,841 contigs (16.8%) had a BLAST homologous match against the Genbank non-redundant (NR) protein database. Most of these sequences were annotated using the gene ontology (GO) and eukaryotic orthologous groups of proteins (KOG) databases and assigned to various functional categories. According to annotation results, many gene families involved in immune response were identified. Thousands of simple sequence repeats (SSR) and single nucleotide polymorphisms (SNP) were detected. Setting stringent parameters to ensure a high probability of amplification, 420 primer pairs in 181 contigs containing SSR loci were designed.</p> <p>Conclusion</p> <p>This data represents the most comprehensive genomic resource for the South African abalone <it>H. midae </it>to date. The amount of assembled sequences demonstrated the utility of the Illumina sequencing technology in the transcriptome characterization of a non-model species. It allowed the development of several markers and the identification of promising candidate genes for future studies on population and functional genomics in <it>H. midae </it>and in other abalone species.</p

Unfolded protein response in cancer: the Physician's perspective

The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials

Regional research priorities in brain and nervous system disorders

The characteristics of neurological, psychiatric, developmental and substance-use disorders in low-and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low-and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities.Fil: Ravindranath, Vijayalakshmi. Indian Institute of Science; IndiaFil: Dang, Hoang Minh. Vietnam National University; VietnamFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Mansour, Hader. University of Pittsburgh; Estados Unidos. Mansoura University; EgiptoFil: Nimgaonkar, Vishwajit L.. University of Pittsburgh; Estados UnidosFil: Russell, Vivienne Ann. University of Cape Town; SudáfricaFil: Xin, Yu. Peking University; Chin