Night-time shift work and related stress responses: A study on security guards

Work-related stress can induce a break in homeostasis by placing demands on the body that are met by the activation of two different systems, the hypothalamic\u2013pituitary\u2013adrenal axis and the sympathetic nervous system. Night-shift work alters the body\u2019s exposure to the natural light\u2013 dark schedule and disrupts circadian (daily) rhythms. The greatest effect of night-shift work is the disruption of circadian rhythms. The impact that these disruptions may have on the pathogenesis of many diseases, including cancer, is unknown. This study aims to discover the relationship among three different job activities of security guards and their stress-related responses by evaluating salivary cortisol levels and blood pressure. Methods: Ninety security guards, including night-time workers and night-time and daily-shift workers, were recruited for this study. Each security guard provided two saliva samples before and after three scheduled time points: (i) at 22:00, (ii) at 06:30, and (iii) at 14:00. Results: The results of the study showed a significant alteration in cortisol levels. Night-time shift cortisol levels significantly increased before and after the work shifts. A physiological prevalence of the vagal tone on the cardiocirculatory activity was found during night-shift work. Conclusions: This study indicates that cortisol levels and blood pressure are sensitive markers of biological responses to severe work stress. Shift-change consequences may occur at the end of the night shift when there is a significant increase in the cortisol level and a significant variation in cardiovascular parameters

Permeation of β-Lactamase Inhibitors through the General Porins of Gram-Negative Bacteria

Modern medicine relies upon antibiotics, but we have arrived to the point where our inability to come up with new effective molecules against resistant pathogens, together with the declining private investment, is resulting in the number of untreatable infections increasing worldwide at worrying pace. Among other pathogens, widely recognized institutions have indicated Gram-negative bacteria as particularly challenging, due to the presence of the outer membrane. The very first step in the action of every antibiotic or adjuvant is the permeation through this membrane, with small hydrophilic drugs usually crossing through protein channels. Thus, a detailed understanding of their properties at a molecular level is crucial. By making use of Molecular Dynamics simulations, we compared the two main porins of four members of the Enterobacteriaceae family, and, in this paper, we show their shared geometrical and electrostatic characteristics. Then, we used metadynamics simulations to reconstruct the free energy for permeation of selected diazobicyclooctans through OmpF. We demonstrate how porins features are coupled to those of the translocating species, modulating their passive permeation. In particular, we show that the minimal projection area of a molecule is a better descriptor than its molecular mass or the volume. Together with the magnitude and orientation of the electric dipole moment, these are the crucial parameters to gain an efficient compensation between the entropic and enthalpic contributions to the free energy barrier required for permeation. Our results confirm the possibility to predict the permeability of molecules through porins by using a few molecular parameters and bolster the general model according to which the free energy increase is mostly due to the decrease of conformational entropy, and this can be compensated by a favorable alignment of the electric dipole with respect to the channel intrinsic electric field

Molecular Basis of Filtering Carbapenems by Porins from β-Lactam-resistant Clinical Strains of Escherichia coli

Integral membrane proteins known as porins are the major pathway by which hydrophilic antibiotics cross the outer mem- brane of Gram-negative bacteria. Single point mutations in porins can decrease the permeability of an antibiotic, either by reduction of channel size or modification of electrostatics in the channel, and thereby confer clinical resistance. Here, we inves- tigate four mutant OmpC proteins from four different clinical isolates of Escherichia coli obtained sequentially from a single patient during a course of antimicrobial chemotherapy. OmpC porin from the first isolate (OmpC20) undergoes three consec- utive and additive substitutions giving rise to OmpC26, OmpC28, and finally OmpC33. The permeability of two zwitte- rionic carbapenems, imipenem and meropenem, measured using liposome permeation assays and single channel electro- physiology differs significantly between OmpC20 and OmpC33. Molecular dynamic simulations show that the antibiotics must pass through the constriction zone of porins with a specific ori- entation, where the antibiotic dipole is aligned along the electric field inside the porin. We identify that changes in the vector of the electric field in the mutated porin, OmpC33, create an addi- tional barrier by “trapping” the antibiotic in an unfavorable ori- entation in the constriction zone that suffers steric hindrance for the reorientation needed for its onward translocation. Iden- tification and understanding the underlying molecular details of such a barrier to translocation will aid in the design of new anti- biotics with improved permeation properties in Gram-negative bacteria

The semi-synthetic peptide Lin-SB056-1 in combination with EDTA exerts strong antimicrobial and antibiofilm activity against pseudomonas aeruginosa in conditions mimicking cystic fibrosis sputum

Pseudomonas aeruginosa is a major cause of chronic lung infections in cystic fibrosis (CF) patients. The ability of the bacterium to form biofilms and the presence of a thick and stagnant mucus in the airways of CF patients largely contribute to antibiotic therapy failure and demand for new antimicrobial agents able to act in the CF environment. The present study investigated the anti-P. aeruginosa activity of lin-SB056-1, a recently described semi-synthetic antimicrobial peptide, used alone and in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA). Bactericidal assays were carried out in standard culture conditions and in an artificial sputum medium (ASM) closely resembling the CF environment. Peptideâ\u80\u99s structure and interaction with large unilamellar vesicles in media with different ionic strengths were also investigated through infrared spectroscopy. Lin-SB056-1 demonstrated fast and strong bactericidal activity against both mucoid and non-mucoid strains of P. aeruginosa in planktonic form and, in combination with EDTA, caused significant reduction of the biomass of P. aeruginosa mature biofilms. In ASM, the peptide/EDTA combination exerted a strong bactericidal effect and inhibited the formation of biofilm-like structures of P. aeruginosa. Overall, the results obtained highlight the potential of the lin-SB056-1/EDTA combination for the treatment of P. aeruginosa lung infections in CF patients

Aza- and Mixed Thia/Aza-Macrocyclic Receptors with Quinoline-Bearing Pendant Arms for Optical Discrimination of Zinc(II) or Cadmium(II) Ions

The synthesis and coordination properties of two fluorescent chemosensors, featuring [9]aneN3 (1,4,7-triazacyclononane; L1) and [12]aneNS3 (1-aza-4,7,10-trithiacyclododecane; L2) as receptor units, and a quinoline pendant arm with an amide group as a functional group spacer are described. The optical responses of L1 and L2 in the presence of several metal ions were analysed in MeCN/H2O (1 : 4 v/v) solutions. A selective chelation enhancement of fluorescence (CHEF) effect was observed in the presence of Zn2+ in the case of L1, and in the presence of Cd2+ in the case of L2, following the formation of a 1 : 1 and a 1 : 2 metal/ligand complex, respectively, which was also confirmed by potentiometric measurements. 1H and 13C NMR measurements in CD3CN/CDCl3 in combination with molecular mechanics calculations show that for both complexes of L1 and L2 with Zn2+ and Cd2+, respectively, the coordination of the carbonyl group from the pendant arm could be the origin of the observed optical selectivity

Straining at work and its relationship with personality profiles and individual consequences in healthcare workers (HCWs)

Straining is an attenuated form of mobbing, in which the continuity of vexatious actions is not driven by a discriminatory intent. With the objective of testing the possible moderating role of personality in the relationship between perceptions about straining at work and individual consequences, a correlational design research involved 374 healthcare workers (HCWs) from two Italian hospitals. The following questionnaires were administered: (1) Short Negative Acts Questionnaire (S‐NAQ), to assess discriminative actions at work); (2) the Italian version of the Big Five Inventory (BFI‐10 scale), to assess personality factors; (3) Occupational Stress Indicator (OSI), to measure psychological and physical health. Regression analysis and Structural Equation Models (SEM) were computed in order to test the relationships between variables. Perceived straining showed significant correlations with both psychological and physical health. Conscientiousness was inversely proportional to work‐related bullying (WB), as agreeableness was to personal bullying (PB). Emotional stability was negatively correlated with all the three component scales of S‐NAQ: WB, PB, and social bullying. The results seem to confirm that straining perceptions especially elicit, through emotional stability, psychological consequences. As regards the role of emotional stability in risk perceptions, it seems management has to pay thorough attention to personal factors in organizational perceptions and to straining actions

A new class of silica-supported chromo-fluorogenic chemosensors for anion recognition based on a selenourea scaffold

[EN] The first example of a chemosensor (L) containing a selenourea moiety is described here. L is able to colorimetrically sense the presence of CN- and S2- in H2O: MeCN (75 : 25, v/v). Moreover, when L is loaded into functionalised mesoporous silica nanoparticles an increase in the selectivity towards S2- occurs via a selective fluorescence response.The authors thank the financial support from the Fondazione Banco di Sardegna, the Spanish Government, European FEDER funds (project MAT2015-64139-C4-1-R) and the Generalitat Valenciana (project PROMETEOII/2014/047). A. Llopis-Lorente is grateful to the "La Caixa'' Banking Foundation for his PhD fellowship. Dr Tiziana Pivetta is gratefully acknowledged for help with the interpretation of the mass spectra.Casula, A.; Llopis-Lorente, A.; Garau, A.; Isaia, F.; Kubicki, M.; Lippolis, V.; Sancenón Galarza, F.... (2017). A new class of silica-supported chromo-fluorogenic chemosensors for anion recognition based on a selenourea scaffold. Chemical Communications. 53(26):3729-3732. https://doi.org/10.1039/c7cc01214dS372937325326Lee, S., Yuen, K. K. Y., Jolliffe, K. A., & Yoon, J. (2015). Fluorescent and colorimetric chemosensors for pyrophosphate. Chemical Society Reviews, 44(7), 1749-1762. doi:10.1039/c4cs00353eZhang, J. F., Zhou, Y., Yoon, J., & Kim, J. S. (2011). Recent progress in fluorescent and colorimetric chemosensors for detection of precious metal ions (silver, gold and platinum ions). Chemical Society Reviews, 40(7), 3416. doi:10.1039/c1cs15028fZhou, X., Lee, S., Xu, Z., & Yoon, J. (2015). Recent Progress on the Development of Chemosensors for Gases. Chemical Reviews, 115(15), 7944-8000. doi:10.1021/cr500567rZhou, Y., & Yoon, J. (2012). Recent progress in fluorescent and colorimetric chemosensors for detection ofamino acids. Chem. Soc. Rev., 41(1), 52-67. doi:10.1039/c1cs15159bBusschaert, N., Caltagirone, C., Van Rossom, W., & Gale, P. A. (2015). Applications of Supramolecular Anion Recognition. Chemical Reviews, 115(15), 8038-8155. doi:10.1021/acs.chemrev.5b00099Gale, P. A., & Caltagirone, C. (2015). Anion sensing by small molecules and molecular ensembles. Chemical Society Reviews, 44(13), 4212-4227. doi:10.1039/c4cs00179fPanda, S., Panda, A., & Zade, S. S. (2015). Organoselenium compounds as fluorescent probes. Coordination Chemistry Reviews, 300, 86-100. doi:10.1016/j.ccr.2015.04.006Manjare, S. T., Kim, Y., & Churchill, D. G. (2014). Selenium- and Tellurium-Containing Fluorescent Molecular Probes for the Detection of Biologically Important Analytes. Accounts of Chemical Research, 47(10), 2985-2998. doi:10.1021/ar500187vWu, D., Chen, L., Kwon, N., & Yoon, J. (2016). Fluorescent Probes Containing Selenium as a Guest or Host. Chem, 1(5), 674-698. doi:10.1016/j.chempr.2016.10.005Mukherjee, A. J., Zade, S. S., Singh, H. B., & Sunoj, R. B. (2010). Organoselenium Chemistry: Role of Intramolecular Interactions†. Chemical Reviews, 110(7), 4357-4416. doi:10.1021/cr900352jManjare, S. T., Kim, S., Heo, W. D., & Churchill, D. G. (2013). Selective and Sensitive Superoxide Detection with a New Diselenide-Based Molecular Probe in Living Breast Cancer Cells. Organic Letters, 16(2), 410-412. doi:10.1021/ol4033013Kim, Y., Choi, M., Manjare, S. T., Jon, S., & Churchill, D. G. (2016). Diselenide-based probe for the selective imaging of hypochlorite in living cancer cells. RSC Advances, 6(38), 32013-32017. doi:10.1039/c6ra04257kYu, F., Li, P., Li, G., Zhao, G., Chu, T., & Han, K. (2011). A Near-IR Reversible Fluorescent Probe Modulated by Selenium for Monitoring Peroxynitrite and Imaging in Living Cells. Journal of the American Chemical Society, 133(29), 11030-11033. doi:10.1021/ja202582xSaravanan, C., Easwaramoorthi, S., Hsiow, C.-Y., Wang, K., Hayashi, M., & Wang, L. (2013). Benzoselenadiazole Fluorescent Probes – Near-IR Optical and Ratiometric Fluorescence Sensor for Fluoride Ion. Organic Letters, 16(2), 354-357. doi:10.1021/ol403082pGoswami, S., Hazra, A., Chakrabarty, R., & Fun, H.-K. (2009). Recognition of Carboxylate Anions and Carboxylic Acids by Selenium-Based New Chromogenic Fluorescent Sensor: A Remarkable Fluorescence Enhancement of Hindered Carboxylates. Organic Letters, 11(19), 4350-4353. doi:10.1021/ol901737sHussain, R. A., Badshah, A., & Shah, A. (2014). Synthesis and biological applications of selenoureas. Applied Organometallic Chemistry, 28(2), 61-73. doi:10.1002/aoc.3093Hussain, R. A., Badshah, A., Tahir, M. N., Hassan, T.-, & Bano, A. (2013). Synthesis, Chemical Characterization, DNA Binding, Antioxidant, Antibacterial, and Antifungal Activities of Ferrocence Incorporated Selenoureas. Journal of Biochemical and Molecular Toxicology, 28(2), 60-68. doi:10.1002/jbt.21536Hussain, R. A., Badshah, A., Tahir, M. N., Lal, B., & Khan, I. A. (2013). Synthesis, Chemical Characterisation, and DNA Binding Studies of Ferrocene-Incorporated Selenoureas. Australian Journal of Chemistry, 66(6), 626. doi:10.1071/ch12570Hussain, R. A., Badshash, A., Sohail, M., Lal, B., & Altaf, A. A. (2013). Synthesis, chemical characterization, DNA interaction and antioxidant studies of ortho, meta and para fluoro substituted ferrocene incorporated selenoureas. Inorganica Chimica Acta, 402, 133-139. doi:10.1016/j.ica.2013.04.003Takahashi, H., Nishina, A., Fukumoto, R., Kimura, H., Koketsu, M., & Ishihara, H. (2005). Selenoureas and thioureas are effective superoxide radical scavengers in vitro. Life Sciences, 76(19), 2185-2192. doi:10.1016/j.lfs.2004.08.037Caltagirone, C., Bazzicalupi, C., Bencini, A., Isaia, F., Garau, A., & Lippolis, V. (2012). Anion recognition properties of pyridine-2,6-dicarboxamide and isophthalamide derivatives containingl-tryptophan moieties. Supramolecular Chemistry, 24(2), 95-100. doi:10.1080/10610278.2011.628391Caltagirone, C., Bazzicalupi, C., Isaia, F., Light, M. E., Lippolis, V., Montis, R., … Picci, G. (2013). A new family of bis-ureidic receptors for pyrophosphate optical sensing. Organic & Biomolecular Chemistry, 11(15), 2445. doi:10.1039/c3ob27244cCasula, A., Bazzicalupi, C., Bettoschi, A., Cadoni, E., Coles, S. J., Horton, P. N., … Caltagirone, C. (2016). Fluorescent asymmetric bis-ureas for pyrophosphate recognition in pure water. Dalton Transactions, 45(7), 3078-3085. doi:10.1039/c5dt04497aOlivari, M., Montis, R., Karagiannidis, L. E., Horton, P. N., Mapp, L. K., Coles, S. J., … Caltagirone, C. (2015). Anion complexation, transport and structural studies of a series of bis-methylurea compounds. Dalton Transactions, 44(5), 2138-2149. doi:10.1039/c4dt02893gTetilla, M. A., Aragoni, M. C., Arca, M., Caltagirone, C., Bazzicalupi, C., Bencini, A., … Meli, V. (2011). Colorimetric response to anions by a «robust» copper(ii) complex of a [9]aneN3 pendant arm derivative: CN− and I− selective sensing. Chemical Communications, 47(13), 3805. doi:10.1039/c0cc04500dFernández-Bolaños, J. G., López, Ó., Ulgar, V., Maya, I., & Fuentes, J. (2004). Synthesis of O -unprotected glycosyl selenoureas. A new access to bicyclic sugar isoureas. Tetrahedron Letters, 45(21), 4081-4084. doi:10.1016/j.tetlet.2004.03.143GANS, P., SABATINI, A., & VACCA, A. (1996). Investigation of equilibria in solution. Determination of equilibrium constants with the HYPERQUAD suite of programs. Talanta, 43(10), 1739-1753. doi:10.1016/0039-9140(96)01958-3H. Deddek , Progress in NMR Spectroscopy, Pergamon, Oxford, 1995, vol. 27, pp. 1–323Bigoli, F., Demartin, F., Deplano, P., Devillanova, F. A., Isaia, F., Lippolis, V., … Trogu, E. F. (1996). Synthesis, Characterization, and Crystal Structures of New Dications Bearing the −Se−Se− Bridge. Inorganic Chemistry, 35(11), 3194-3201. doi:10.1021/ic9510019Isaia, F., Aragoni, M. C., Arca, M., Demartin, F., Devillanova, F. A., Floris, G., … Verani, G. (2008). Interaction of Methimazole with I2: X-ray Crystal Structure of the Charge Transfer Complex Methimazole−I2. Implications for the Mechanism of Action of Methimazole-Based Antithyroid Drugs. Journal of Medicinal Chemistry, 51(13), 4050-4053. doi:10.1021/jm8001857Roy, G., Bhabak, K. P., & Mugesh, G. (2011). Interactions of Antithyroid Drugs and Their Analogues with Halogens and their Biological Implications. Crystal Growth & Design, 11(6), 2279-2286. doi:10.1021/cg101688vCliment, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 49(40), 7281-7283. doi:10.1002/anie.201001847Santos-Figueroa, L. E., Giménez, C., Agostini, A., Aznar, E., Marcos, M. D., Sancenón, F., … Amorós, P. (2013). Selective and Sensitive Chromofluorogenic Detection of the Sulfite Anion in Water Using Hydrophobic Hybrid Organic-Inorganic Silica Nanoparticles. Angewandte Chemie International Edition, 52(51), 13712-13716. doi:10.1002/anie.20130668

VDAC3 as a sensor of oxidative state of the intermembrane space of mitochondria: the putative role of cysteine residue modifications

Voltage-Dependent Anion selective Channels (VDAC) are pore-forming mitochondrial outer membrane proteins. In mammals VDAC3, the least characterized isoform, presents a set of cysteines predicted to be exposed toward the intermembrane space. We find that cysteines in VDAC3 can stay in different oxidation states. This was preliminary observed when, in our experimental conditions, completely lacking any reducing agent, VDAC3 presented a pattern of slightly different electrophoretic mobilities. This observation holds true both for rat liver mitochondrial VDAC3 and for recombinant and refolded human VDAC3. Mass spectroscopy revealed that cysteines 2 and 8 can form a disulfide bridge in native VDAC3. Single or combined site-directed mutagenesis of cysteines 2, 8 and 122 showed that the protein mobility in SDS-PAGE is influenced by the presence of cysteine and by the redox status. In addition, cysteines 2, 8 and 122 are involved in the stability control of the pore as shown by electrophysiology, complementation assays and chemico-physical characterization. Furthermore, a positive correlation between the pore conductance of the mutants and their ability to complement the growth of porin-less yeast mutant cells was found. Our work provides evidence for a complex oxidation pattern of a mitochondrial protein not directly involved in electron transport. The most likely biological meaning of this behavior is to buffer the ROS load and keep track of the redox level in the intermembrane space, eventually signaling it through conformational change