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Wildfires can negatively impact the health and well-being of wildland firefighters through a variety of exposure pathways. Many studies have measured acute health effects from occupational exposure to pollutants in wildfire smoke; however, research specifically examining cancer risks from exposure to carcinogens is limited. This review aimed to better understand cancer risk in this occupation by assessing the existing evidence of exposures and summarizing measured concentrations of carcinogens among wildland firefighters. A systematic search was conducted to identify scientific papers using the following databases: Medline(OVID), Embase(OVID), PsycINFO(OVID), Cochrane Library, CINAHL(EBSCOHost), EconLit(EBSCOHost), Scopus, Agricultural and Environmental Science Collect(ProQuest), and NIOSHTIC-2. Forty-nine papers were identified that met eligibility criteria. Across the papers, 31 carcinogens were identified and quantified using a variety of assessment methods. Papers measured particulate matter (N = 26), polycyclic aromatic hydrocarbons (N = 12), volatile organic compounds (N = 14), crystalline silica (N = 5), black carbon (N = 4), asbestos (N = 3), radionuclides (N = 7), and metals (N = 2). Most papers measured inhalation exposures through traditional air sampling methods, but a subset of exposures to polycyclic aromatic hydrocarbons (N = 8), as well as heavy metals (N = 1), were measured through urinary biomarkers and naphthalene was measured using dermal wipe samples (N = 2). Although the heterogeneity of exposure assessment methods made direct comparison of concentrations difficult, the papers provide consistent evidence that wildland firefighters are regularly exposed to carcinogens. All wildland fire personnel should continue to implement recommended mitigation strategies and support new mitigations to reduce exposure to carcinogens on the job. [ABSTRACT FROM AUTHOR]

Single-molecule fluorescence spectroscopy is used to study dye diffusion within organically modified silicate (ORMOSIL) films. ORMOSIL films are prepared from sols containing tetraethoxysilane and isobutyltrimethoxysilane in 2:1 and 1:9 molar ratios. Nile red and a new silanized form of nile red that can be covalently attached to the silicate matrix are used as fluorescent probe molecules. The number and rate of single molecules diffusing through these films increases dramatically with increasing film organic content. Autocorrelation of the fluorescence images yields a quantitative measure of the relative populations of fixed and diffusing species. Surprisingly, both 'free' and silicate-bound nile red exhibit relatively facile translational motions. Single-molecule/single-point fluorescence correlation spectroscopy (FCS) is used to measure the dye diffusion coefficients in submicrometer-scale film regions. The most common diffusion coefficients for 'free' and silicate-bound nile red molecules in the 1:9 films are 3.9 x [10.sup.-10] and 1.6 x [10.sup.-10] [cm.sup.2]/s, respectively. The unexpectedly rapid diffusion of silicate-bound nile red is attributed to the presence of liquidlike silicate oligomers in the films. A lower bound for the molecular weight of the oligomers is estimated at 2900. Bulk solution-phase FCS experiments performed on 'free' and silicate-bound nile red species extracted into chloroform solutions provide valuable support for these conclusions. Comparison of the results derived from experimental and simulated time transients indicates film heterogeneity occurs on sub-100-nm-length scales and likely results from the presence of inorganic- and organic-rich domains.

The development of multidimensional chromatography coupled to tandem mass spectrometry for shotgun proteomic analyses which are frequently performed to obtain information ranging from simple protein identification to more complex post-translational modification studies are reviewed.

Proteomic analyses have contributed substantially to our understanding of diverse cellular processes. Improvements in the sensitivity of mass spectrometry approaches are enabling more in-depth analyses of protein-protein networks and, in some cases, are providing surprising new insights into well established, longstanding problems. Here, we describe such a proteomic analysis that exploits MudPIT mass spectrometry and has led to the discovery of a physical and functional link between the orphan nuclear receptor hepatocyte nuclear factor 4α (HNF4α) and transcription factor lID (TFIID). A systematic characterization of the HNF4α-TFIID link revealed that the HNF4α DNA-binding domain binds directly to the TATA boxbinding protein (TBP) and, through this interaction, can target TBP or TFIID to promoters containing HNF4α-binding sites in vitro. Supporting the functional significance of this interaction, an HNF4α mutation that blocks binding of TBP to HNF4α interferes with HNF4α transactivation activity in cells. These findings identify an unexpected role for the HNF4α DNA-binding domain in mediating key regulatory interactions and provide new insights into the roles of HNF4α and TFIID in RNA polymerase II transcription. [ABSTRACT FROM AUTHOR]

The ability of actin filaments to function in cell morphogenesis and motility is closely coupled to their dynamic properties. Yeast cells contain two prominent actin structures, cables and patches, both of which are rapidly assembled and disassembled. Although genetic studies have shown that rapid actin turnover in patches and cables depends on cofilin, how cofilin might control cable disassembly remains unclear, because tropomyosin, a component of actin cables, is thought to protect actin filaments against the depolymerizing activity of ADF/cofilin. We have identified cofilin as a yeast tropomyosin (Tpm1) binding protein through Tpm1 affinity column and mass spectrometry. Using a variety of assays, we show that yeast cofilin can efficiently depolymerize and sever yeast actin filaments decorated with either Tpm1 or mouse tropomyosins TM1 and TM4. Our results suggest that yeast cofilin has the intrinsic ability to promote actin cable turnover, and that the severing activity may rely on its ability to bind Tpm1. [ABSTRACT FROM AUTHOR]

In yeast, the macromolecular complex Set1/COMPASS is capable of methylating H3K4, a posttranslational modification associated with actively transcribed genes. There is only one Set1 in yeast; yet in mammalian cells there are multiple H3K4 methylases, including Set1A/B, forming human COMPASS complexes, and MLL1-4, forming human COMPASS-like complexes. We have shown that Wdr82, which associates with chromatin in a histone H2B ubiquitination-dependent manner, is a specific component of Set1 complexes but not that of MLL1-4 complexes. RNA interference-mediated knockdown of Wdr82 results in a reduction in the H3K4 trimethylation levels, although these cells still possess active MLL complexes. Comprehensive in vitro enzymatic studies with Set1 and MLL complexes demonstrated that the Set1 complex is a more robust H3K4 trimethylase in vitro than the MLL complexes. Given our in vivo and in vitro observations, it appears that the human Set1 complex plays a more widespread role in H3K4 trimethylation than do the MLL complexes in mammalian cells. [ABSTRACT FROM AUTHOR]