Synthesis, characterisation and photochemistry of PtIV pyridyl azido acetato complexes

PtII azido complexes [Pt(bpy)(N3)2] (1), [Pt(phen)(N3)2] (2) and trans-[Pt(N3)2(py)2] (3) incorporating the bidentate diimine ligands 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen) or the monodentate pyridine (py) respectively, have been synthesised from their chlorido precursors and characterised by X-ray crystallography; complex 3 shows significant deviation from square-planar geometry (N3–Pt–N3 angle 146.7°) as a result of steric congestion at the Pt centre. The novel PtIV complexes trans, cis-[Pt(bpy)(OAc)2(N3)2] (4), trans, cis-[Pt(phen)(OAc)2(N3)2] (5), trans, trans, trans-[Pt(OAc)2(N3)2(py)2] (6), were obtained from 1–3via oxidation with H2O2 in acetic acid followed by reaction of the intermediate with acetic anhydride. Complexes 4–6 exhibit interesting structural and photochemical properties that were studied by X-ray, NMR and UV-vis spectroscopy and TD-DFT (time-dependent density functional theory). These PtIV complexes exhibit greater absorption at longer wavelengths (ε = 9756 M−1 cm−1 at 315 nm for 4; ε = 796 M−1 cm−1 at 352 nm for 5; ε = 16900 M−1 cm−1 at 307 nm for 6, in aqueous solution) than previously reported PtIV azide complexes, due to the presence of aromatic amines, and 4–6 undergo photoactivation with both UVA (365 nm) and visible green light (514 nm). The UV-vis spectra of complexes 4–6 were calculated using TD-DFT; the nature of the transitions contributing to the UV-vis bands provide insight into the mechanism of production of the observed photoproducts. The UV-vis spectra of 1–3 were also simulated by computational methods and comparison between PtII and PtIV electronic and structural properties allowed further elucidation of the photochemistry of 4–6

S100A6 (Calcyclin) is a prostate basal cell marker absent in prostate cancer and its precursors

S100A6 (Calcyclin) is a calcium-binding protein that has been implicated in a variety of biological functions as well as tumorigenesis. The aim of our study was to investigate the involvement of S100A6 during prostate cancer development and progression. Using immunohistochemistry, the expression of S100A6 was examined in benign (n ¼ 66), premalignant (n ¼ 10), malignant (n ¼ 66) and metastatic prostate (n ¼ 5) tissues arranged in a tissue-microarray or whole sections as well as in prostate cancer cell lines. The S100A6 immunostaining pattern in tissues was compared with that of cytokeratin 5 (a basal cell marker) and 18 (a benign luminal cell marker). In all cases of benign epithelium, intense S100A6 expression was seen in the basal cell layer with absent staining in luminal cells. In all cases of prostatic adenocarcinoma (matched), metastatic lesions and 3/10 high-grade prostatic intraepithelial neoplasia lesions, an absence of S100A6 was seen. Western blotting and RT–PCR analysis of cell lines showed S100A6 expression to be absent in LNCaP, LNCaP-LN3 and LNCaP-Pro5 but present in Du145, PC3, PC-3M and PC-3M-LN4. LNCaP cells treated with 5- Azacytidine, caused re-expression of S100A6 mRNA. Sequencing of bisulphite modified DNA showed CpG methylation within the S100A6 promoter region and exon 1 of LNCaP, LNCaP-LN3 and LNCaP-Pro5 cell lines but not in Du145 cells. Our data suggest that loss of S100A6 protein expression is common in prostate cancer development and may occur at an early stage. The mechanism of loss of expression may involve hypermethylation of CpG sites. The finding of intense S100A6 expression in the basal cells of benign glands but loss of expression in cancer could be useful as a novel diagnostic marker for prostate cancer

Stellar Coronal and Wind Models: Impact on Exoplanets

Surface magnetism is believed to be the main driver of coronal heating and stellar wind acceleration. Coronae are believed to be formed by plasma confined in closed magnetic coronal loops of the stars, with winds mainly originating in open magnetic field line regions. In this Chapter, we review some basic properties of stellar coronae and winds and present some existing models. In the last part of this Chapter, we discuss the effects of coronal winds on exoplanets.Comment: Chapter published in the "Handbook of Exoplanets", Editors in Chief: Juan Antonio Belmonte and Hans Deeg, Section Editor: Nuccio Lanza. Springer Reference Work

The effect of hot days on occupational heat stress in the manufacturing industry: implications for workers' well-being and productivity

Climate change is expected to exacerbate heat stress at the workplace in temperate regions, such as Slovenia. It is therefore of paramount importance to study present and future summer heat conditions and analyze the impact of heat on workers. A set of climate indices based on summer mean (Tmean) and maximum (Tmax) air temperatures, such as the number of hot days (HD: Tmax above 30 °C), and Wet Bulb Globe Temperature (WBGT) were used to account for heat conditions in Slovenia at six locations in the period 1981–2010. Observed trends (1961–2011) of Tmean and Tmax in July were positive, being larger in the eastern part of the country. Climate change projections showed an increase up to 4.5 °C for mean temperature and 35 days for HD by the end of the twenty-first century under the high emission scenario. The increase in WBGT was smaller, although sufficiently high to increase the frequency of days with a high risk of heat stress up to an average of a third of the summer days. A case study performed at a Slovenian automobile parts manufacturing plant revealed non-optimal working conditions during summer 2016 (WBGT mainly between 20 and 25 °C). A survey conducted on 400 workers revealed that 96% perceived the temperature conditions as unsuitable, and 56% experienced headaches and fatigue. Given these conditions and climate change projections, the escalating problem of heat is worrisome. The European Commission initiated a program of research within the Horizon 2020 program to develop a heat warning system for European workers and employers, which will incorporate case-specific solutions to mitigate heat stress.The work was supported by the European Union Horizon 2020 Research and Innovation Action (Project number 668786: HEATSHIELD)

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Job satisfaction and its modeling among township health center employees: a quantitative study in poor rural China

<p>Abstract</p> <p>Background</p> <p>Job satisfaction is important to staff management of township health centers (THCs), as it is associated with organizational performance, quality of care and employee retention. The purpose of this study was to measure job satisfaction level of THC employees in poor rural China and to identify relevant features in order to provide policy advice on human resource development of health service institutions in poor regions.</p> <p>Methods</p> <p>A self-completion questionnaire was used to assess the job satisfaction and relevant features (response rate: 90.5%) among 172 employees (i.e., clinic doctors, medico-technical workers and public health workers) of 17 THCs in Anhui and Xinjiang provinces of China. The study covered a time period of two months in 2007.</p> <p>Results</p> <p>The mean staff job satisfaction scored 83.3, which was in the category of "somewhat satisfied" on a scale ranging from 0 (extremely dissatisfied) to 100 (extremely satisfied) by employing Likert's transformation formula. Exploratory factor analysis (EFA) revealed eight domains involved in modeling of job satisfaction, among which, the caregivers were more satisfied with job significance (88.2), job competency (87.9) and teamwork (87.7), as compared with work reward (72.9) and working conditions (79.7). Mean job satisfaction in Xinjiang (89.7) was higher than that in Anhui (75.5).</p> <p>Conclusions</p> <p>Employees of THCs have moderate job satisfactions in poor areas, which need to be raised further by improving their working conditions and reward.</p

Osteo-Chondroprogenitor–Specific Deletion of the Selenocysteine tRNA Gene, Trsp, Leads to Chondronecrosis and Abnormal Skeletal Development: A Putative Model for Kashin-Beck Disease

Kashin-Beck disease, a syndrome characterized by short stature, skeletal deformities, and arthropathy of multiple joints, is highly prevalent in specific regions of Asia. The disease has been postulated to result from a combination of different environmental factors, including contamination of barley by mold mycotoxins, iodine deficiency, presence of humic substances in drinking water, and, importantly, deficiency of selenium. This multifunctional trace element, in the form of selenocysteine, is essential for normal selenoprotein function, including attenuation of excessive oxidative stress, and for the control of redox-sensitive molecules involved in cell growth and differentiation. To investigate the effects of skeletal selenoprotein deficiency, a Cre recombinase transgenic mouse line was used to trigger Trsp gene deletions in osteo-chondroprogenitors. Trsp encodes selenocysteine tRNA[Ser]Sec, required for the incorporation of selenocysteine residues into selenoproteins. The mutant mice exhibited growth retardation, epiphyseal growth plate abnormalities, and delayed skeletal ossification, as well as marked chondronecrosis of articular, auricular, and tracheal cartilages. Phenotypically, the mice thus replicated a number of the pathological features of Kashin-Beck disease, supporting the notion that selenium deficiency is important to the development of this syndrome

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition