Stress in nurses : stress-related affect and its determinants examined over the nursing day

Peer reviewedPostprin

Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal dominant Parkinson disease (PD), while polymorphic LRRK2 variants are associated with sporadic PD. PD-linked mutations increase LRRK2 kinase activity and induce neurotoxicity in vitro and in vivo. The small GTPase Rab8a is a LRRK2 kinase substrate and is involved in receptor-mediated recycling and endocytic trafficking of transferrin, but the effect of PD-linked LRRK2 mutations on the function of Rab8a is poorly understood. Here, we show that gain-of-function mutations in LRRK2 induce sequestration of endogenous Rab8a to lysosomes in overexpression cell models, while pharmacological inhibition of LRRK2 kinase activity reverses this phenotype. Furthermore, we show that LRRK2 mutations drive association of endocytosed transferrin with Rab8a-positive lysosomes. LRRK2 has been nominated as an integral part of cellular responses downstream of proinflammatory signals and is activated in microglia in postmortem PD tissue. Here, we show that iPSC-derived microglia from patients carrying the most common LRRK2 mutation, G2019S, mistraffic transferrin to lysosomes proximal to the nucleus in proinflammatory conditions. Furthermore, G2019S knock-in mice show a significant increase in iron deposition in microglia following intrastriatal LPS injection compared to wild-type mice, accompanied by striatal accumulation of ferritin. Our data support a role of LRRK2 in modulating iron uptake and storage in response to proinflammatory stimuli in microglia

The Cytosolic Tail of the Golgi Apyrase Ynd1 Mediates E4orf4-Induced Toxicity in Saccharomyces cerevisiae

The adenovirus E4 open reading frame 4 (E4orf4) protein contributes to regulation of the progression of virus infection. When expressed individually, E4orf4 was shown to induce non-classical transformed cell-specific apoptosis in mammalian cells. At least some of the mechanisms underlying E4orf4-induced toxicity are conserved from yeast to mammals, including the requirement for an interaction of E4orf4 with protein phosphatase 2A (PP2A). A genetic screen in yeast revealed that the Golgi apyrase Ynd1 associates with E4orf4 and contributes to E4orf4-induced toxicity, independently of Ynd1 apyrase activity. Ynd1 and PP2A were shown to contribute additively to E4orf4-induced toxicity in yeast, and to interact genetically and physically. A mammalian orthologue of Ynd1 was shown to bind E4orf4 in mammalian cells, confirming the evolutionary conservation of this interaction. Here, we use mutation analysis to identify the cytosolic tail of Ynd1 as the protein domain required for mediation of the E4orf4 toxic signal and for the interaction with E4orf4. We also show that E4orf4 associates with cellular membranes in yeast and is localized at their cytoplasmic face. However, E4orf4 is membrane-associated even in the absence of Ynd1, suggesting that additional membrane proteins may mediate E4orf4 localization. Based on our results and on a previous report describing a collection of Ynd1 protein partners, we propose that the Ynd1 cytoplasmic tail acts as a scaffold, interacting with a multi-protein complex, whose targeting by E4orf4 leads to cell death

The assessment of information technology maturity in emergency response organizations

[EN] In emergency response organizations, information technologies are not adequately explored. Sometimes, the mere adoption of new information technologies is not productive, as their efficient use depends on other interrelated technologies and the environment where they are installed. This work describes a model to help organizations understand their capability in respect to the adoption of these technologies. The model also helps the performing of the evaluation from different perspectives, making it suitable to collaborative evaluation. Using the proposed model, an organization can measure its maturity level in different aspects of the evaluation and guide the investment on its capabilities. Part of the model has been developed for emergency response organizations and the information technology dimension of the model has been applied to two fire department installations.Marcos R. S. Borges was partially supported by grants No. 560223/2010-2 and 480461/2009-0 from CNPq (Brazil). Work of José H. Canós is partially funded by the Spanish Ministerio. de Educación y Ciencia (MEC) under grant TIPEX (TIN2010–19859-C03-03). The cooperation between the Brazilian and the Spanish research groups was partially sponsored by the CAPES/MECD Cooperation Program, Project #169/ PHB2007-0064-PC.Santos, RS.; Borges, MRS.; Canos Cerda, JH.; Gomes, JO. (2011). The assessment of information technology maturity in emergency response organizations. Group Decision and Negotiation. 20(5):593-613. doi:10.1007/s10726-011-9232-zS593613205Bigley G, Roberts KH (2001) The incident command system: high reliability organizing for complex and volatile task environments. Acad Manag J 44(6): 1281–1299Chinowsky P, Molenaar K, Realph A (2007) Learning organizations in construction. J Manag Eng 23(1): 27–34Diniz VB, Borges MRS, Gomes JO, Canós JH (2008) Decision making support in emergency response. In: Encyclopedia of decision making, Information Science Reference (an imprint of IGI Global), New York, pp 184–191Dörner R, Grimm P, Seiler C (2001) ETOILE—an environment for team, organizational and individual learning. CG Top 13(3): 5–6Dykstra E (2003) Concept paper: toward an international system model in emergency management. In: Proceedings of toward an international system model in emergency management, Public Entity Risk InstituteFederal Emergency Management Agency (FEMA) (1998) Emergency management guide for business and industry: a step-by-step approach to emergency planning, response and recovery for companies of all sizesGu Q, Mendonça D (2005) Patterns of group information seeking in a simulated emergency response environment. In: Proceedings of the 2nd international ISCRAM conference, Brussels, BelgiumHale J (1997) A layered communication architecture for the support of crisis response. J Manag Inf Syst 14(1): 235–255King W, Teo T (1997) Integration between business planning and information systems planning: validating a stage hypothesis. Decis Sci 28(2): 279–307Lachner J, Hellwagner H (2008) Information and communication systems for mobile emergency response. Lecture notes in business information processing, vol 5. pp 213–224Lavoie D, Culbert A (1978) Stages in organization and development. Human Relat 31(5): 417–438Lindel MK, Prater C, Perry RW (2007) Emergency management. Wiley, New YorkLlavador M, Letelier P, Penadés MC, Borges MRS, Solís C (2006) Precise yet flexible specification of emergency resolution procedures. In: Proceedings of the information systems for crisis response and management (ISCRAM), pp 110–120Meissner A, Wang Z, Putz W, Grimmer J (2006) MIKoBOS: a mobile information and communication system for emergency response. In: Proceedings of the 3rd international ISCRAM conference, Newark, New JerseyNonaka I, Takeuchi H (1995) The knowledge creating company: how Japanese companies create the dynamics of innovation. Oxford University Press, OxfordOchoa S, Neyem A, Pino JA, Borges MRS (2007) Supporting group decision making and coordination in urban disasters relief efforts. J Decis Syst 16(2): 143–172Paton D, Flin R (1999) Disaster stress: an emergency management perspective. Disaster Prev Manag 8(4): 261–267Paulk MC, Weber C, Curtis B, Chrissis M (1995) The capability maturity model: guidelines for improving the software process. Addison-Wesley, ReadingQuarantelli EL (1997) Problematical aspects of the information/communication revolution for disaster planning and research: ten non-technical issues and questions. Disaster Prev Manag 6(2): 94–106Santos RS, Borges MRS, Gomes JO, Canós JH (2008) Maturity levels of information technologies in emergency response organizations. In: Proceedings of the international workshop on groupware, Omaha, Nebraska, USA. Groupware: design, implementation and use. Lecture notes in computer science, vol 5411. Springer, Berlin, pp 135–150Schoenharl T, Szabo G, Madey G, Barabasi AL (2006) WIPER: a multi-agent system for emergency response. In: Proceedings of the 3rd international ISCRAM conference, Newark, New JerseyTuroff M (2002) Past and future emergency response information systems. Commun ACM 45(4): 29–33Turoff M, Chumer M, Hiltz R, Clasher R, Alles M, Vasarhelyi M, Kogan A (2004a) Assuring homeland security: continuous monitoring, control and assurance of emergency preparedness. J Inf Technol Theor Appl (JITTA) 6(3): 1–24Turoff M, Chumer M, Vande Walle B, Yao X (2004b) The design of a dynamic emergency response management information system (DERMIS). J Inf Technol Theor Appl (JITTA) 5(4): 1–35Van der Lee MDE, Van Vugt M (2004) IMI—An information system for effective multidisciplinary incident management. In: Proceedings of the 1st international ISCRAM conference, Brussels, BelgiumYuan Y, Deltor B (2005) Intelligent mobile crisis response systems. Commun ACM 28(2): 95–98Zimmerman R, Restrepo CE (2006) Information technology (IT) and critical infrastructure interdependencies for emergency response. In: Proceedings of the 3rd international ISCRAM conference, Newark, New Jerse

Total synthesis, isolation, surfactant properties, and biological evaluation of ananatosides and related macrodilactone-containing rhamnolipids

Rhamnolipids are a specific class of microbial surfactants, which hold great biotechnological and therapeutic potential. However, their exploitation at the industrial level is hampered because they are mainly produced by the opportunistic pathogenPseudomonas aeruginosa. The non-human pathogenic bacteriumPantoea ananatisis an alternative producer of rhamnolipid-like metabolites containing glucose instead of rhamnose residues. Herein, we present the isolation, structural characterization, and total synthesis of ananatoside A, a 15-membered macrodilactone-containing glucolipid, and ananatoside B, its open-chain congener, from organic extracts ofP. ananatis. Ananatoside A was synthesized through three alternative pathways involving either an intramolecular glycosylation, a chemical macrolactonization or a direct enzymatic transformation from ananatoside B. A series of diasteroisomerically pure (1→2), (1→3), and (1→4)-macrolactonized rhamnolipids were also synthesized through intramolecular glycosylation and their anomeric configurations as well as ring conformations were solved using molecular modeling in tandem with NMR studies. We show that ananatoside B is a more potent surfactant than its macrolide counterpart. We present evidence that macrolactonization of rhamnolipids enhances their cytotoxic and hemolytic potential, pointing towards a mechanism involving the formation of pores into the lipidic cell membrane. Lastly, we demonstrate that ananatoside A and ananatoside B as well as synthetic macrolactonized rhamnolipids can be perceived by the plant immune system, and that this sensing is more pronounced for a macrolide featuring a rhamnose moiety in its native1C4conformation. Altogether our results suggest that macrolactonization of glycolipids can dramatically interfere with their surfactant properties and biological activity

Transport of Explosive Residue Surrogates in Saturated Porous Media

Department of Defense operational ranges may become contaminated by particles of explosives residues (ER) as a result of low-order detonations of munitions. The goal of this study was to determine the extent to which particles of ER could migrate through columns of sandy sediment, representing model aquifer materials. Transport experiments were conducted in saturated columns (2 × 20 cm) packed with different grain sizes of clean sand or glass beads. Fine particles (approximately 2 to 50 μm) of 2,6-dinitrotoluene (DNT) were used as a surrogate for ER. DNT particles were applied to the top 1 cm of sand or beads in the columns, and the columns were subsequently leached with artificial groundwater solutions. DNT migration occurred as both dissolved and particulate phases. Concentration differences between unfiltered and filtered samples indicate that particulate DNT accounted for up to 41% of the mass recovered in effluent samples. Proportionally, more particulate than dissolved DNT was recovered in effluent solutions from columns with larger grain sizes, while total concentrations of DNT in effluent were inversely related to grain size. Of the total DNT mass applied to the uppermost layer of the column, <3% was recovered in the effluent with the bulk remaining in the top 2 cm of the column. Our results suggest there is some potential for subsurface migration of ER particles and that most of the particles will be retained over relatively short transport distances

Topology of molecular machines of the endoplasmic reticulum: a compilation of proteomics and cytological data

The endoplasmic reticulum (ER) is a key organelle of the secretion pathway involved in the synthesis of both proteins and lipids destined for multiple sites within and without the cell. The ER functions to both co- and post-translationally modify newly synthesized proteins and lipids and sort them for housekeeping within the ER and for transport to their sites of function away from the ER. In addition, the ER is involved in the metabolism and degradation of specific xenobiotics and endogenous biosynthetic products. A variety of proteomics studies have been reported on different subcompartments of the ER providing an ER protein dictionary with new data being made available on many protein complexes of relevance to the biology of the ER including the ribosome, the translocon, coatomer proteins, cytoskeletal proteins, folding proteins, the antigen-processing machinery, signaling proteins and proteins involved in membrane traffic. This review examines proteomics and cytological data in support of the presence of specific molecular machines at specific sites or subcompartments of the ER

Influence of the calcium concentration in the presence of organic phosphorus on the physicochemical compatibility and stability of all-in-one admixtures for neonatal use

<p>Abstract</p> <p>Background</p> <p>Preterm infants need high amounts of calcium and phosphorus for bone mineralization, which is difficult to obtain with parenteral feeding due to the low solubility of these salts. The objective of this study was to evaluate the physicochemical compatibility of high concentrations of calcium associated with organic phosphate and its influence on the stability of AIO admixtures for neonatal use.</p> <p>Methods</p> <p>Three TPN admixture formulas were prepared in multilayered bags. The calcium content of the admixtures was adjusted to 0, 46.5 or 93 mg/100 ml in the presence of a fixed organic phosphate concentration as well as lipids, amino acids, inorganic salts, glucose, vitamins and oligoelements at pH 5.5. Each admixture was stored at 4°C, 25°C or 37°C and evaluated over a period of 7 days. The physicochemical stability parameters evaluated were visual aspect, pH, sterility, osmolality, peroxide formation, precipitation, and the size of lipid globules.</p> <p>Results</p> <p>Color alterations occurred from the first day on, and reversible lipid film formation from the third day of study for the admixtures stored at 25°C and 37°C. According to the parameters evaluated, the admixtures were stable at 4°C; and none of them presented precipitated particles due to calcium/phosphate incompatibility or lipid globules larger than 5 μm, which is the main parameter currently used to evaluate lipid emulsion stability. The admixtures maintained low peroxide levels and osmolarity was appropriate for parenteral administration.</p> <p>Conclusion</p> <p>The total calcium and calcium/phosphorus ratios studied appeared not to influence the physicochemical compatibility and stability of AIO admixtures.</p

The bZIP Transcription Factor Rca1p Is a Central Regulator of a Novel CO2 Sensing Pathway in Yeast

Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO2 concentration. This response involves two major proteins: adenylyl cyclase and carbonic anhydrase (CA). Here, we demonstrate that CA expression is tightly controlled by the availability of CO2 and identify the bZIP transcription factor Rca1p as the first CO2 regulator of CA expression in yeast. We show that Rca1p upregulates CA expression during contact with mammalian phagocytes and demonstrate that serine 124 is critical for Rca1p signaling, which occurs independently of adenylyl cyclase. ChIP-chip analysis and the identification of Rca1p orthologs in the model yeast Saccharomyces cerevisiae (Cst6p) point to the broad significance of this novel pathway in fungi. By using advanced microscopy we visualize for the first time the impact of CO2 build-up on gene expression in entire fungal populations with an exceptional level of detail. Our results present the bZIP protein Rca1p as the first fungal regulator of carbonic anhydrase, and reveal the existence of an adenylyl cyclase independent CO2 sensing pathway in yeast. Rca1p appears to regulate cellular metabolism in response to CO2 availability in environments as diverse as the phagosome, yeast communities or liquid culture

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012