Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes.

The eukaryotic cell cycle is controlled by a network of interacting regulatory proteins. We used an interaction mating two-hybrid assay to identify connections within the cell cycle regulatory network in Drosophila. We tested interactions between Drosophila cyclins and a panel of hundreds of previously identified proteins. One of the connections we identified was the interaction between cyclin E and a novel Drosophila protein, Cdi4. Because Cdi4 was originally identified by its ability to interact with a Drosophila cyclin-dependent kinase, the finding that it interacts with cyclin E strengthened the notion that it functions in cell cycle regulation. We show that Cdi4 can inhibit cyclin E function both in a yeast assay and in vitro. In light of these results, our sequence analysis revealed that Cdi4 is a unique member of the p21/p27/p57 family of Cdk inhibitors. Our results demonstrate that interaction mating assays using large informative panels of proteins can aid the analysis of regulatory networks by generating and constraining hypotheses that guide further work

Naturally occurring diacetyl and 2,3-pentanedione concentrations associated with roasting and grinding unflavored coffee beans in a commercial setting

AbstractOver the last decade, concerns have been raised about potential respiratory health effects associated with occupational exposure to the flavoring additives diacetyl and 2,3-pentanedione. Both of these diketones are also natural components of many foods and beverages, including roasted coffee. To date, there are no published studies characterizing workplace exposures to these diketones during commercial roasting and grinding of unflavored coffee beans. In this study, we measured naturally occurring diacetyl, 2,3-pentanedione, and respirable dust at a facility that roasts and grinds coffee beans with no added flavoring agents. Sampling was conducted over the course of three roasting batches and three grinding batches at varying distances from a commercial roaster and grinder. The three batches consisted of lightly roasted soft beans, lightly roasted hard beans, and dark roasted hard beans. Roasting occurred for 37 to 41min, and the grinding process took between 8 and 11min. Diacetyl, 2,3-pentanedione, and respirable dust concentrations measured during roasting ranged from less than the limit of detection (<LOD) to 0.0039ppm, <LOD to 0.018ppm, and <LOD to 0.31mg/m3, respectively. During grinding, diacetyl, 2,3-pentanedione, and respirable dust concentrations ranged from 0.018 to 0.39ppm, 0.0089 to 0.21ppm, and <LOD to 1.7mg/m3, respectively. For any given bean/roast combination and sample location, diketone concentrations during grinding were higher than those measured during roasting. During grinding, concentrations decreased with increased distance from the source. Measured concentrations of both diketones were higher during grinding of soft beans than hard beans. The results indicate that airborne concentrations of naturally occurring diacetyl and 2,3-pentanedione associated with unflavored coffee processing: (1) are similar to the concentrations that have been measured in food flavoring facilities; (2) are likely to exceed some recommended short-term occupational exposure limits, but; (3) based on previous analyses of exposure response relationships in animal studies, are far below the concentrations that are expected to cause even minimal responses in the human respiratory tract

Data on the histological and immune cell response in the popliteal lymph node in mice following exposure to metal particles and ions

AbstractHip implants containing cobalt–chromium (CoCr) have been used for over 80 years. In patients with metal-on-metal (MoM) hip implants, it has been suggested that wear debris particles may contribute to metal sensitization in some individuals, leading to adverse reactions. This article presents data from a study in which the popliteal lymph node assay (PLNA) was used to assess immune responses in mice treated with chromium-oxide (Cr2O3) particles, metal salts (CoCl2, CrCl3, and NiCl2) or Cr2O3 particles with metal salts (“A preliminary evaluation of immune stimulation following exposure to metal particles and ions using the mouse popliteal lymph node assay” (B.E. Tvermoes, K.M. Unice, B. Winans, M. Kovochich, E.S. Fung, W.V. Christian, E. Donovan, B.L. Finley, B.L. Kimber, I. Kimber, D.J. Paustenbach, 2016) [1]). Data are presented on (1) the chemical characterization of TiO2 particles (used as a particle control), (2) clinical observations in mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts, (3) PLN weight and weight index (WI) in mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts, (4) histological changes in PLNs of mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts, (5) percentages of immune cells in the PLNs of mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts, and (6) percentages of proliferating cells in the PLNs of mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

An updated evaluation of reported no-observed adverse effect levels for chrysotile asbestos for lung cancer and mesothelioma

<p>Although consumption of chrysotile asbestos has decreased since the 1970s, the latency period of asbestos-related cancers is thought to be at least 20–30 years, and therefore the potential health risks associated with historical exposures is still actively researched. This analysis represents an update to a previous paper in which we evaluated the exposure–response relationships for lung cancer and mesothelioma in chrysotile-exposed cohorts. Here, we review several recently published studies as well as updated information from previous studies. For each of the 14 studies considered, we identified the “no-observed adverse effect level” (NOAEL) for lung cancer and/or mesothelioma. NOAEL values for lung cancer ranged from 1.1 to <20 f/cc-years to 1600–3200 f/cc-years, and for mesothelioma ranged from 100–400 f/cc-years to 800–1599 f/cc-years. The range of “best estimate” NOAELs was estimated to be 89–168 f/cc-years for lung cancer and 208–415 f/cc-years for mesothelioma. None of the six cohorts of cement or friction product manufacturing workers exhibited an increased lung cancer risk at any exposure level, while all of the five studies of textile workers reported an increased risk at one or more exposure levels. This is likely because friction and cement workers were exposed to much shorter chrysotile fibers. Of the seven cases of peritoneal mesothelioma reported in the included studies, none were observed in the analyses of cement or friction product manufacturing workers in the absence of crocidolite exposure. These findings will help characterize potential worker and consumer health risks associated with historical and current chrysotile exposures.</p