The relationship between aerosol concentration and atmospheric potential gradient in urban environments.

Urban aerosol is a growing concern for people living within cities; aerosol have been implicated in many ill health conditions, including that of the lung and of the heart. Atmospheric potential gradient is a consequence of charge carried to the ionosphere through thunderstorms, and its value depends on highly electrically mobile ion concentrations, hence local conductivity of the air. Ions attach to aerosol in the atmosphere, reducing their mobility and therefore increasing the potential gradient, and so potential gradient measurements have been suggested as a proxy for aerosol measurements. Particle number count, size distribution and potential gradient were measured for two campaigns in Manchester, U.K., and one campaign in Bristol, U.K. Using a factor based on size distribution to account for preferential attachment at larger sizes provided the best relationship with potential gradient, but particle count alone showed a weaker, but similar relationship. The increase in particle count caused by annual bonfire and fireworks celebrations (November) was evidenced in both potential gradient and particle numbers. Daily regression or correlation did not show a consistent relationship. In the larger Bristol data set, increasing humidity led to a reduction of potential gradient, while increasing particle number led to an increase.

Physical Activity and Exercise Interventions in the Workplace Impacting Work Outcomes: A Stakeholder-Centered Best Evidence Synthesis of Systematic Reviews.

BACKGROUND: The prevention of work disability is beneficial to employees and employers, and mitigates unnecessary societal costs associated with social welfare. Many service providers and employers have initiated workplace interventions designed to reduce unnecessary work disability. OBJECTIVE: To conduct a best-evidence synthesis of systematic reviews on workplace interventions that address physical activities or exercise and their impact on workplace absence, work productivity or financial outcomes. METHODS: Using a participatory research approach, academics and stakeholders identified inclusion and exclusion criteria, built an abstraction table, evaluated systematic review quality and relevance, and interpreted the combined findings. A minimum of two scientists participated in a methodological review of the literature followed by a consensus process. RESULTS: Stakeholders and researchers participated as a collaborative team. 3363 unique records were identified, 115 full text articles and 46 systematic reviews were included, 18 assessed the impact of physical fitness or exercise interventions. 11 focused on general workers rather than workers who were absent from work at baseline; 16 of the reviews assessed work absence, 4 assessed productivity and 6 assessed financial impacts. CONCLUSION: The strongest evidence supports the use of short, simple exercise or fitness programs for both workers at work and those absent from work at baseline. For workers at work, simple exercise programs (1-2 modal components) appear to provide similar benefits to those using more complex multimodal interventions. For workers off-work with subacute low back pain, there is evidence that some complex exercise programs may be more effective than simple exercise interventions, especially if they involve workplace stakeholder engagement, communication and coordination with employers and other stakeholders. The development and utilization of standardized definitions, methods and measures and blinded evaluation would improve research quality and strengthen stakeholder-centered guidance.

Mental Health Interventions in the Workplace and Work Outcomes: A Best-Evidence Synthesis of Systematic Reviews.

BACKGROUND: Mental health issues in the workplace are a growing concern among organizations and policymakers, but it remains unclear what interventions are effective in preventing mental health problems and their associated organizational consequences. This synthesis reports on workplace mental health interventions that impact absenteeism, productivity and financial outcomes. OBJECTIVE: To determine the level of evidence supporting mental health interventions as valuable to work outcomes. METHODS: Databases were searched for systematic reviews between 2000 and 2012: Medline, EMBASE, the Cochrane Database of Systematic Reviews, DARE, CINAHL, PsycINFO and TRIP. Grey literature searches included health-evidence.ca, Rehab+, National Rehabilitation Information Center (NARIC), and Institute for Work and Health. The assessment of articles for inclusion criteria and methodological quality was conducted independently by two or more researchers, with differences resolved through consensus. RESULTS: The search resulted in 3363 titles, of which 3248 were excluded following title/abstract review, with 115 articles retrieved for full-text review. 14 articles finally met the inclusion criteria and are summarized in this synthesis. CONCLUSION: There is moderate evidence for the effectiveness of workplace mental health interventions on improved workplace outcomes. Certain types of programs, such as those incorporating both mental and physical health interventions, multicomponent mental health and/or psychosocial interventions, and exposure in vivo containing interventions for particular anxiety disorders had a greater level of research evidence to support their effectiveness.

Social Support and Supervisory Quality Interventions in the Workplace: A Stakeholder-Centered Best-Evidence Synthesis of Systematic Reviews on Work Outcomes.

BACKGROUND: There is controversy surrounding the impact of workplace interventions aimed at improving social support and supervisory quality on absenteeism, productivity and financial outcomes. OBJECTIVE: To determine the value of social support interventions for work outcomes. METHODS: Databases were searched for systematic reviews between 2000 and 2012 to complete a synthesis of systematic reviews guided by the PRISMA statement and the IOM guidelines for systematic reviews. Assessment of articles for inclusion and methodological quality was conducted independently by at least two researchers, with differences resolved by consensus. RESULTS: The search resulted in 3363 titles of which 3248 were excluded following title/abstract review, leaving 115 articles that were retrieved and underwent full article review. 10 articles met the set inclusion criteria, with 7 focusing on social support, 2 on supervisory quality and 1 on both. We found moderate and limited evidence, respectively, that social support and supervisory quality interventions positively impact workplace outcomes. CONCLUSION: There is moderate evidence that social support and limited evidence that supervisory quality interventions have a positive effect on work outcomes.

Job demand and control interventions: a stakeholder-centered best-evidence synthesis of systematic reviews on workplace disability.

BACKGROUND: Physical and psychological job demands in combination with the degree of control a worker has over task completion, play an important role in reducing stress. Occupational stress is an important, modifiable factor affecting work disability. However, the effectiveness of reducing job demands or increasing job control remains unclear, particularly for outcomes of interest to employers, such as absenteeism or productivity. OBJECTIVE: This systematic review reports on job demand and control interventions that impact absenteeism, productivity and financial outcomes. METHODS: A stakeholder-centered best-evidence synthesis was conducted with researcher and stakeholder collaboration throughout. Databases and grey literature were searched for systematic reviews between 2000 and 2012: Medline, EMBASE, the Cochrane Database of Systematic Reviews, DARE, CINAHL, PsycINFO, TRIP, health-evidence.ca, Rehab+, National Rehabilitation Information Center (NARIC), and Institute for Work and Health. Articles were assessed independently by two researchers for inclusion criteria and methodological quality. Differences were resolved through consensus. RESULTS: The search resulted in 3363 unique titles. After review of abstracts, 115 articles were retained for full-text review. 11 articles finally met the inclusion criteria and are summarized in this synthesis. The best level of evidence we found indicates that multimodal job demand reductions for either at-work or off-work workers will reduce disability-related absenteeism. CONCLUSION: In general, the impacts of interventions that aim to reduce job demands or increase job control can be positive for the organization in terms of reducing absenteeism, increasing productivity and cost-effectiveness. However, more high quality research is needed to further assess the relationships and quantify effect sizes for the interventions and outcomes reviewed in this study.

Learning chronobiology by improving Wikipedia.

Although chronobiology is of growing interest to scientists, physicians, and the general public, access to recent discoveries and historical perspectives is limited. Wikipedia is an online, user-written encyclopedia that could enhance public access to current understanding in chronobiology. However, Wikipedia is lacking important information and is not universally trusted. Here, 46 students in a university course edited Wikipedia to enhance public access to important discoveries in chronobiology. Students worked for an average of 9 h each to evaluate the primary literature and available Wikipedia information, nominated sites for editing, and, after voting, edited the 15 Wikipedia pages they determined to be highest priorities. This assignment (http://www.nslc.wustl.edu/courses/Bio4030/wikipedia_project.html) was easy to implement, required relatively short time commitments from the professor and students, and had measurable impacts on Wikipedia and the students. Students created 3 new Wikipedia sites, edited 12 additional sites, and cited 347 peer-reviewed articles. The targeted sites all became top hits in online search engines. Because their writing was and will be read by a worldwide audience, students found the experience rewarding. Students reported significantly increased comfort with reading, critiquing, and summarizing primary literature and benefited from seeing their work edited by other scientists and editors of Wikipedia. We conclude that, in a short project, students can assist in making chronobiology widely accessible and learn from the editorial process.

Inflammatory mediators hold the key to dendritic cell suppression and tumor progression.

Cancer has long been considered a disease that is associated with immune tolerance. Its connection with inflammation initially appears paradoxical. During the last decade, it has become increasingly clear that immune infiltrates form an integral part of tumor and critically contribute to its development and progression. In the tumor milieu, a variety of inflammatory mediators, such as cytokines (IL- 6, IL-10, VEGF, TGFß, M-CSF and GM-CSF), chemokines (CCL20 and CXCL8), hormones (prostanoids like PGE2), reactive oxygen species and cellular constituents (gangliosides), are continuously produced. These mediators represent a critical interface between immune and neoplastic compartments. Not only do they continuously support tumor survival and expansion, but suppress the function of immune cells, notably, dendritic cells - the powerful antigen presenting cells that are crucial for induction of tumor-specific immune responses. This review summarizes such a dual role of inflammatory factors and discusses the controversies associated with specific mediators including IL-10, GM-CSF and ROS in tumor and immune modulation. Identifying the inflammatory signature of cancer patients hence represents a critical task for individualized immunotherapy in the future.

A platelet tetraspanin superfamily member, CD151, is required for regulation of thrombus growth and stability in vivo.

BACKGROUND: This study was designed to determine the role of CD151 in platelet thrombus formation in vivo and define the contribution of platelet vs. endothelial CD151 in regulating platelet thrombus formation in vivo. METHODS AND RESULTS: Using intravital microscopy and ferric chloride (FeCl(3)) injury of mesenteric arterioles, we found that thrombi formed in CD151(+/-) and CD151(-/-) mice were smaller and less stable, than those formed in CD151(+/+) mice, with a tendency for embolization. Similarly, in Folt's FeCl(3)-induced carotid injury model, both CD151(+/-) and CD151(-/-) mice showed more prolonged times to 95% vessel occlusion than CD151(+/+) mice. In addition, laser-induced injury of cremaster muscle arterioles showed that thrombi formed in CD151(+/-) and CD151(-/-) mice were smaller and less stable than those formed in CD151(+/+) mice. Following platelet depletion/reconstitution with ex vivo-labeled donor platelets, platelet-depleted CD151(+/+) mice that received reconstitution with CD151(-/-) platelets had smaller thrombi that were unstable and embolized. In contrast, platelet-depleted CD151(-/-) mice that received reconstitution with CD151(+/+) platelets had normal thrombi that were stable. CONCLUSIONS: These data provide evidence that platelet CD151 is required for regulating thrombus formation in vivo.

Diffusive sampling of C7-C16 hydrocarbons in workplace air: uptake rates, wall effects and use in oil mist measurements.

The measurement of semi-volatile hydrocarbons in workplace air is complicated by their readiness to condense to form aerosols or adsorb on to surfaces. The diffusive sampling and analysis by thermal desorption of alkanes up to hexadecane was investigated with the aim of quantifying vapour from petroleum distillate fractions and possibly differentiating particles from vapour in oil mist measurements of light mineral oil-based metalworking fluids. Diffusive uptake rates were measured on Perkin Elmer thermal desorption tube samplers packed with Tenax TA, and the potential for deposition within the tubes was examined. Hydrocarbon vapour was found to adsorb on the oxide layer that can develop on the sampler's internal walls. General measurements of mixed hydrocarbon vapours (i.e. petroleum distillate fractions) should not be unduly affected if concentrations are greater than approximately 5 mg m(-3) and the tubes are in good condition. For the purposes of differentiating light mineral oil mist and vapour from a total hydrocarbon measurement, it is unlikely that measuring the vapour separately could be used to calculate mist concentrations <3 mg m(-3) with sufficient accuracy.

Tetraspanin microdomains in immune cell signalling and malignant disease.

A contemporary goal of researchers in leucocyte signalling has been to uncover how cells physically organize and compartmentalize signalling molecules into efficient, regulated signalling networks. This work has revealed important roles of membrane microdomains that are characterized by their distinctive protein and lipid compositions. Recent studies have demonstrated that besides typical cholesterol- and glycosphingolipid-enriched 'rafts', leucocyte membranes are equipped with a different type of microdomain, made up of tetraspanin proteins. Tetraspanin proteins are involved in the organization of tetraspanin-enriched microdomains by virtue of their capacity to specifically associate with key molecules, including integrins, leucocyte receptors and signalling proteins. The aspects of leucocyte function influenced by tetraspanin microdomains include adhesion, proliferation and antigen presentation. However, the mechanisms by which tetraspanin complexes link to intracellular signalling pathways, are still largely unknown. This review discusses how tetraspanin microdomains might function to regulate signalling in lymphoid and myeloid cells, and how they relate to lipid rafts. In addition, we discuss new insights into the role of tetraspanins in malignant disease.

Molecular characterisation of mouse and human TSSC6: evidence that TSSC6 is a genuine member of the tetraspanin superfamily and is expressed specifically in haematopoietic organs.

Previous analyses of the murine and human TSSC6 (also known as Phemx) proteins were not carried out using the full length sequence. Using 5'-RACE and cDNA library screening, we identified an additional 5' sequence for both the murine Tssc6 cDNA and its human homologue TSSC6. This novel sequence encodes a 5' exon encoding an in frame, upstream start codon, an N-terminal cytoplasmic domain and a transmembrane domain. The deduced, and now full length, murine and human TSSC6 proteins contained four hydrophobic regions together with other features characteristic of the tetraspanin superfamily. Computational analyses of the full length sequences show that TSSC6 is a genuine, albeit relatively divergent member of this superfamily. Using RNA from a number of mouse tissues, we identified seven splice variants of Tssc6. Splice variants of the human gene were also detected. Tssc6 expression was detected early in embryogenesis in primitive blood cells and was confined to haematopoietic organs in the adult mouse. Tssc6 expression was detected in many haematopoietic cell lines and was highest in cell lines of the erythroid lineage.

Molecular cloning of a C-type lectin superfamily protein differentially expressed by CD8alpha(-) splenic dendritic cells.

Dendritic cells (DC) are potent antigen presenting cells that activate naive T cells. It is becoming increasingly clear that DC are not a homogeneous cell population, but comprise different subpopulations that differ in ontogeny and function. To further the molecular characterisation of DC, we screened for genes that were differentially expressed amongst DC subsets and could therefore give insight into their varying biological functions. Using Representational Difference Analysis (RDA) we identified a gene (CIRE) that is expressed at higher levels in the myeloid-related CD8alpha(-) DC than in the lymphoid-related CD8alpha(+) DC. CIRE is a 238 amino acid type II membrane protein, of approximately 33 kDa in size, whose extracellular region contains a C-type lectin domain. Northern blot analysis revealed that CIRE is almost exclusively expressed in DC and was not detected in organs such as heart, brain, kidney, liver, and thymus. T cells failed to express message for CIRE, whilst B cells expressed very low levels. These data here further substantiated by Northern blot analysis of 18 cell lines of various origins (myeloid, macrophage, B and T cell) where only one cell line, which was of myeloid origin and could give rise to DC, expressed mRNA for CIRE. Semi-quantitative RT-PCR suggested that CIRE is down-regulated upon activation. CIRE shares 57% identity with human DC-SIGN, a molecule that has been shown to be the ligand of ICAM-3 and that is also a receptor that binds HIV and facilitates trans-infection of T cells.

Molecular cloning of F4/80-like-receptor, a seven-span membrane protein expressed differentially by dendritic cell and monocyte-macrophage subpopulations.

A novel dendritic cell (DC) surface molecule termed F4/80-like-receptor (FIRE) has been selected based on its differential expression between DC subsets. The gene encoding FIRE has been cloned and sequenced, and mAbs specific for FIRE have been produced. FIRE is a seven-transmembrane-spanning molecule with two epidermal growth factor-like domains in the extracellular region. It is a novel member of the epidermal growth factor/transmembrane-7 protein subfamily and shows similarity to the macrophage marker F4/80. FIRE is expressed by CD8- DC, but not by CD8+ DC, and it is down-regulated on DC activation. It is expressed by blood monocytes and by some tissue macrophages, but not by most macrophage cell lines or by lymphoid cells. FIRE is a useful marker of myeloid cells with a DC developmental potential.

A proficiency testing scheme for aromatic hydrocarbons in air by the manual thermal desorption-GC method: a comparison of laboratory performance with the uncertainty requirements of the European Union Ambient Air Directive.

The Workplace Analysis Scheme for Proficiency (WASP) is a proficiency testing scheme for the analysis of occupational hygiene and environmental air samples and is operated in the UK by the Health and Safety Laboratory. Since 1997, WASP has offered samples of benzene, toluene and m-xylene, at environmental levels on Tenax, and has about 35 laboratories participating, mostly from industry, local government and consultancy organisations in the UK. The results reported cover the first 10 rounds of the environmental analytes (1997-1999) and demonstrate the important role of proficiency testing in assessing the quality of laboratory performance. Estimates are obtained for within-laboratory precision and the total variability at each analyte level. The estimates of within-laboratory precision suggest that laboratories have more difficulty analysing toluene and m-xylene than benzene. Linear relationships for the reproducibility relative standard deviation (RSDT) with loading level are evident for the analytes at occupational levels. At environmental levels, the relationship between loading level and reproducibility is much less well defined. The standard deviation for the proficiency testing assessment for all three analytes at the environmental level is 14%, as derived from the benzene data. Expanded uncertainty estimates (k = 1.96), for the analysis of samples since the scheme started, are obtained from the average total variance, and are 27% for benzene, 39% for toluene and 36% for m-xylene. Although the linear trend of performance against round number was not significant at the 95% level of confidence (p = 0.23 for benzene, p = 0.3 for toluene and p = 0.32 for m-xylene), there was a general improvement in RSDT from 26-34% to about 8-13% 10 rounds later. Currently, for a laboratory to meet one of the data quality objectives in the Ambient Air Directive (indicative measurement of benzene, expanded uncertainty +/- 30% or less), it would have to achieve a level of analytical performance to satisfy the category 1 (best performance) limit of better than +/- 8.8%. In the last proficiency testing round, discussed in this paper, only 58% of laboratories obtained performance scores that indicated that they were able to consistently achieve this level of performance.

The molecular characterisation of mouse tspan-3.

The Tetraspanin/Transmembrane-4 Superfamily of cell surface molecules is defined by their four highly conserved transmembrane domains and is found in a wide variety of species and cell types. A common function for these molecules has yet to be discovered, however their broad expression patterns and conservation over evolution suggests that they will have an important general function relevant to many cell lineages. Here we describe the cloning and characterisation of the murine homologue of a recently described member of this superfamily, tspan-3. Murine tspan-3 was remarkably similar to the human molecule showing 88% identity at the nucleic acid level and 98% homology on the amino acid level. Northern blot analyses of mouse tspan-3 show a very broad pattern of expression, with expression readily detected in most organs including neural and bone marrow derived tissues.

The L6 membrane proteins--a new four-transmembrane superfamily.

L6, IL-TMP, and TM4SF5 are cell surface proteins predicted to have four transmembrane domains. Previous sequence analysis led to their assignment as members of the tetraspanin superfamily. In this paper, we identify a new sequence (L6D) that is strikingly similar to L6, IL-TMP, and TM4SF5. Analyses of these four sequences indicate that they are not significantly related to genuine tetraspanins, but instead constitute their own L6 superfamily.

Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions.

CD37 is a membrane protein of the tetraspanin superfamily, which includes CD9, CD53, CD63, CD81, and CD82. Many of these molecules are expressed on leukocytes and have been implicated in signal transduction, cell-cell interactions, and cellular activation and development. We generated and analyzed mice deficient for CD37. Despite the high expression of CD37 on cells of the immune system, no changes in development and cellular composition of lymphoid organs were observed in mice lacking CD37. Analyses of humoral immune responses revealed a reduced level of immunoglobulin G1 (IgG1) in the sera of nonimmunized mice and an alteration of responses to T-cell-dependent antigens. Antibody responses to model antigen administered in the absence of adjuvant and to viral infections were generally poor in CD37-deficient mice. These poor antibody responses could be overcome by the immunization of antigen together with adjuvant. These results suggest a role for CD37 in T-cell-B-cell interactions which manifests itself under suboptimal costimulatory conditions.

The molecular characterisation of a novel tetraspanin protein, TM4-B(1).

TM4-B is a novel member of the Tetraspanin superfamily and displays characteristics typical of the superfamily. It bears significant homology to other superfamily members and is most similar to Tspan-1. This molecule is broadly expressed in most human tissues and cell lines including neural and bone marrow derived tissues. TM4-B was mapped to the q34 region on human chromosome 9.

The schizosaccharomyces pombe dim1(+) gene interacts with the anaphase-promoting complex or cyclosome (APC/C) component lid1(+) and is required for APC/C function.

The Schizosaccharomyces pombe dim1(+) gene is required for entry into mitosis and for chromosome segregation during mitosis. To further understand dim1p function, we undertook a synthetic lethal screen with the temperature-sensitive dim1-35 mutant and isolated lid (for lethal in dim1-35) mutants. Here, we describe the temperature-sensitive lid1-6 mutant. At the restrictive temperature of 36 degrees C, lid1-6 mutant cells arrest with a "cut" phenotype similar to that of cut4 and cut9 mutants. An epitope-tagged version of lid1p is a component of a multiprotein approximately 20S complex; the presence of lid1p in this complex depends upon functional cut9(+). lid1p-myc coimmunoprecipitates with several other proteins, including cut9p and nuc2p, and the presence of cut9p in a 20S complex depends upon the activity of lid1(+). Further, lid1(+) function is required for the multiubiquitination of cut2p, an anaphase-promoting complex or cyclosome (APC/C) target. Thus, lid1p is a component of the S. pombe APC/C. In dim1 mutants, the abundances of lid1p and the APC/C complex decline significantly, and the ubiquitination of an APC/C target is abolished. These data suggest that at least one role of dim1p is to maintain or establish the steady-state level of the APC/C.