Kinetics of radiation- and cytochrome c-induced modifications in liposomes analysed by FT–Raman spectroscopy

AbstractFourier transform Raman spectroscopy on artificial lipid membranes was used to study radiation-induced peroxidation processes as a function of time after radiation exposure. The time dependent intensity changes of the Raman lines of various CC bondings were compared to results obtained by measuring conjugated dienes and by the thiobarbituric acid test for malondialdehydes. The results show that mainly the cis CC bonds of the lipid chains are involved and, therefore, indicate that γ-radiation induces conformational changes in the lipid chain while the mobility of the lipid chains is reduced. New Raman bands can be assigned to aldehyde products induced at the end of the peroxidation process. The immediate decrease of the CH vibration lines was directly correlated with the formation of conjugated CC double bonds suggesting that these vibration lines are in contrast to the CC lines solely Raman active, when isolated CC bonds are present. Cytochrome c (ox.) incorporated into the bilayer of the artificial membranes induced autooxidation processes not influenced by γ-radiation. It was observed that cytochrome c (ox.)-induced changes of the relative intensity of the CC bonds differ from those induced by γ-radiation. These results of cytochrome c together with the inhibitory effects of the antioxidant α-tocopherol suggest that the radical species involved in the cytochrome c induced process might be different from the free radicals involved in the γ-radiation-induced process

Differential behaviour of normal, transformed and Fanconi's anemia lymphoblastoid cells to modeled microgravity

Background: Whether microgravity might influence tumour growth and carcinogenesis is still an open issue. It is not clear also if and how normal and transformed cells are differently solicited by microgravity. The present study was designed to verify this issue.Methods: Two normal, LB and HSC93, and two transformed, Jurkat and 1310, lymphoblast cell lines were used as representative for the two conditions. Two lymphoblast lines from Fanconi's anemia patients group A and C (FA-A and FA-C, respectively), along with their isogenic corrected counterparts (FA-A-cor and FA-C-cor) were also used. Cell lines were evaluated for their proliferative ability, vitality and apoptotic susceptibility upon microgravity exposure in comparison with unexposed cells. Different parameters correlated to energy metabolism, glucose consumption, mitochondrial membrane potential (MMP), intracellular ATP content, red-ox balance and ability of the cells to repair the DNA damage product 8 OHdG induced by the treatment of the cells with 20 mM KBrO3 were also evaluated.Results: Transformed Jurkat and 1310 cells appear resistant to the microgravitational challenge. On the contrary normal LB and HSC93 cells display increased apoptotic susceptibility, shortage of energy storages and reduced ability to cope with oxidative stress. FA-A and FA-C cells appear resistant to microgravity exposure, analogously to transformed cells. FA corrected cells did shown intermediate sensitivity to microgravity exposure suggesting that genetic correction does not completely reverts cellular phenotype.Conclusions: In the light of the reported results microgravity should be regarded as an harmful condition either when considering normal as well as transformed cells. Modeled microgravity and space-based technology are interesting tools in the biomedicine laboratory and offer an original, useful and unique approach in the study of cellular biochemistry and in the regulation of metabolic pathways

Centrosomal and mitotic abnormalities in cell lines derived from papillary thyroid cancer harboring specific gene alterations

<p>Abstract</p> <p>Background</p> <p>Differentiated thyroid carcinoma offers a good model to investigate the possible correlation between specific gene mutations and chromosome instability. Papillary thyroid neoplasms are characterized by different mutually exclusive genetic alterations, some of which are associated with aneuploidy and aggressive phenotype.</p> <p>Results</p> <p>We investigated the centrosome status and mitotic abnormalities in three thyroid carcinoma-derived cell lines, each maintaining the specific, biologically relevant gene alteration harbored by the parental tumors: <it>RET/PTC1 </it>rearrangement in TPC1; heterozygous and homozygous <it>BRAF^V600E</it>mutation in K1 and in B-CPAP, respectively. B-CPAP cells showed a statistically significant (<it>P </it>< 0.01) higher frequency of abnormal mitotic figures compared to TPC1 and K1 cells.</p> <p>Conclusions</p> <p>Our data indicate that <it>RET/PTC1 </it>oncogenic activity is not related to mitotic chromosome impairment and missegregation whereas, based on the consistent difference in types/frequencies of centrosome and spindle abnormalities observed between K1 and B-CPAP cells, the hetero/homozygous allelic status of <it>BRAF^V600E</it>mutation seems to be not irrelevant in respect to chromosomal instability development.</p

How Clusters Create Shared Value in Rural Areas: An Examination of Six Case Studies

The main aim of this paper is to demonstrate that clusters can support the sustainable development of rural areas through the creation of shared value. This is done via the close exam-ination of six different cases of rural clusters in Greece, Italy, Germany, Poland, Denmark, and Sweden. Qualitative as well as quantitative data were taken from the clusters, which demonstrated that their main business approaches naturally coincided with the creation of economic, social, and environmental benefits for the local communities in which they operated. The case clusters were created in a top-down manner, aimed at boosting regional R&D activities and making the local economy more competitive and more sustainable. However, private initiative took over and al-lowed these clusters to flourish because meeting the regions’ economic, social, and environmental needs successfully coincided with the target of the clusters’ own development and profitability. The results show that clusters, with their potential for shared value creation, can constitute a powerful engine for the revitalisation and development of rural areas, addressing the significant challenges which they are currently facing. View Full-TextHorizon 2020 Framework ProgrammePeer Reviewe

How Clusters Create Shared Value in Rural Areas: An Examination of Six Case Studies

The main aim of this paper is to demonstrate that clusters can support the sustainable development of rural areas through the creation of shared value. This is done via the close exam-ination of six different cases of rural clusters in Greece, Italy, Germany, Poland, Denmark, and Sweden. Qualitative as well as quantitative data were taken from the clusters, which demonstrated that their main business approaches naturally coincided with the creation of economic, social, and environmental benefits for the local communities in which they operated. The case clusters were created in a top-down manner, aimed at boosting regional R&D activities and making the local economy more competitive and more sustainable. However, private initiative took over and al-lowed these clusters to flourish because meeting the regions’ economic, social, and environmental needs successfully coincided with the target of the clusters’ own development and profitability. The results show that clusters, with their potential for shared value creation, can constitute a powerful engine for the revitalisation and development of rural areas, addressing the significant challenges which they are currently facing. View Full-TextHorizon 2020 Framework ProgrammePeer Reviewe

Secondary Somatic Mutations in G-Protein-Related Pathways and Mutation Signatures in Uveal Melanoma

Background: Uveal melanoma (UM), a rare cancer of the eye, is characterized by initiating mutations in the genes G-protein subunit alpha Q (GNAQ), G-protein subunit alpha 11 (GNA11), cysteinyl leukotriene receptor 2 (CYSLTR2), and phospholipase C beta 4 (PLCB4) and by metastasis-promoting mutations in the genes splicing factor 3B1 (SF3B1), serine and arginine rich splicing factor 2 (SRSF2), and BRCA1-associated protein 1 (BAP1). Here, we tested the hypothesis that additional mutations, though occurring in only a few cases (\u201csecondary drivers\u201d), might influence tumor development. Methods: We analyzed all the 4125 mutations detected in exome sequencing datasets, comprising a total of 139 Ums, and tested the enrichment of secondary drivers in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that also contained the initiating mutations. We searched for additional mutations in the putative secondary driver gene protein tyrosine kinase 2 beta (PTK2B) and we developed new mutational signatures that explain the mutational pattern observed in UM. Results: Secondary drivers were significantly enriched in KEGG pathways that also contained GNAQ and GNA11, such as the calcium-signaling pathway. Many of the secondary drivers were known cancer driver genes and were strongly associated with metastasis and survival. We identified additional mutations in PTK2B. Sparse dictionary learning allowed for the identification of mutational signatures specific for UM. Conclusions: A considerable part of rare mutations that occur in addition to known driver mutations are likely to affect tumor development and progression

Multicenter external validation of the liverpool uveal melanoma prognosticator online: An OOG collaborative study

Uveal melanoma (UM) is fatal in ~50% of patients as a result of disseminated disease. This study aims to externally validate the Liverpool Uveal Melanoma Prognosticator Online V3 (LUMPO3) to determine its reliability in predicting survival after treatment for choroidal melanoma when utilizing external data from other ocular oncology centers. Anonymized data of 1836 UM patients from seven international ocular oncology centers were analyzed with LUMPO3 to predict the 10-year survival for each patient in each external dataset. The analysts were masked to the patient outcomes. Model predictions were sent to an independent statistician to evaluate LUMPO3’s performance using discrimination and calibration methods. LUMPO3’s ability to discriminate between UM patients who died of metastatic UM and those who were still alive was fair-to-good, with C-statistics ranging from 0.64 to 0.85 at year 1. The pooled estimate for all external centers was 0.72 (95% confidence interval: 0.68 to 0.75). Agreement between observed and predicted survival probabilities was generally good given differences in case mix and survival rates between different centers. Despite the differences between the international cohorts of patients with primary UM, LUMPO3 is a valuable tool for predicting all-cause mortality in this disease when using data from external centers

Multicenter External Validation of the Liverpool Uveal Melanoma Prognosticator Online: An OOG Collaborative Study

Uveal melanoma (UM) is fatal in ~50% of patients as a result of disseminated disease. This study aims to externally validate the Liverpool Uveal Melanoma Prognosticator Online V3 (LUMPO3) to determine its reliability in predicting survival after treatment for choroidal melanoma when utilizing external data from other ocular oncology centers. Anonymized data of 1836 UM patients from seven international ocular oncology centers were analyzed with LUMPO3 to predict the 10-year survival for each patient in each external dataset. The analysts were masked to the patient outcomes. Model predictions were sent to an independent statistician to evaluate LUMPO3's performance using discrimination and calibration methods. LUMPO3's ability to discriminate between UM patients who died of metastatic UM and those who were still alive was fair-to-good, with C-statistics ranging from 0.64 to 0.85 at year 1. The pooled estimate for all external centers was 0.72 (95% confidence interval: 0.68 to 0.75). Agreement between observed and predicted survival probabilities was generally good given differences in case mix and survival rates between different centers. Despite the differences between the international cohorts of patients with primary UM, LUMPO3 is a valuable tool for predicting all-cause mortality in this disease when using data from external centers

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice