Application of XeCl308nm excimer laser radiation to mutate industrial microorganisms

EnIn this study, we have investigated the effects of an XeCl308 nm excimer laser radiation on bacterial mutagenesis. Our experiments have revealed that the mutagenesis inducted by the XeCl308 nm excimer laser radiation is independent from RecA protein, the regulator of the SOS response, unlike UV254 nm radiation that is not mutagenic for Escherichia coli mutants lacking the RecA protein. This found suggests that the UV308 nm laser radiation might be mutagenic also in microorganisms naturally lacking the SOS response. To test this hypothesis, we applied our innovative mutagenesis approach on Nonomuraea ATCC 39727, an industrial strain producing an antibiotic, which is relatively refractory to UV254 nm radiation-induced mutagenesis. Our results demonstrated the efficiency of XeCl308 nm excimer laser radiation to induce mutagenesis in Nonomuraea ATCC 39727

DNA damage by a single intense shot of soft X-rays emitted by a laser-produced plasma

EnA suitable plane transmission line was developed and its behaviour analysed at 900 MHz radiofrequency fields to study the DNA mutability and repair of microorganisms. In this work, utilizing such a device, we investigated the behaviour of the DNA mutability and repair of Escherichia coli strains. The transmission line was very simple and versatile in changing its characteristic resistance and field intensity by varying its sizes. In absence of cell samples inside the transmission line, the relative modulation of the electric and/or magnetic field was ±31% with respect to the mean values, allowing the processing of more samples at different exposure fields in a single run. Slight decrease in spontaneous mutability to rifampicin-resistance of the E. Coli JC411 strain, was demonstrated in mismatch-repair proficient samples exposed to the radio-frequency fields during their growth on solid medium

Optimization of 3D ZnO brush-like nanorods for dye-sensitized solar cells

© 2018 The Royal Society of Chemistry This is an Open Access article, distributed under the terms of the Creative Commons Attribution Unported 3.0 license (CC BY 3.0), https://creativecommons.org/licenses/by/3.0/ which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly citedIn a dye-sensitized solar cell (DSSC) the amount of adsorbed dye on the photoanode surface is a key factor that must be maximized in order to obtain enhanced DSSC performance. In this study 3D ZnO nanostructures, named brush-like, are demonstrated as alternative photoanodes. In these structures, long ZnO nanorods are covered with a metal-organic precursor, known as a layered-hydroxide zinc salt (LHZS), which is subsequently converted to crystalline ZnO using two-step annealing. The LHZS is able to easily grow on any surface, such as the ZnO nanorod surface, without needing the assistance of a seed-layer. Brush-like structures synthesized using different citrate concentrations in the growth solutions and different annealing conditions are characterized and tested as DSSC photoanodes. The best-performing structure reported in this study was obtained using the highest citrate concentration (1.808 mM) and the lowest temperature annealing condition in an oxidative environment. Conversion efficiency as high as 1.95% was obtained when these brush-like structures were employed as DSSC photoanodes. These results are extremely promising for the implementation of these innovative structures in enhanced DSSCs, as well as in other applications that require the maximization of surface area exposed by ZnO or similar semiconductors, such as gas- or bio-sensing or photocatalysis.Peer reviewedFinal Published versio

Recommendations for Clinical CYP2C19 Genotyping Allele Selection: A Report of the Association for Molecular Pathology

This document was developed by the Pharmacogenetics (PGx) Working Group of the Association for Molecular Pathology Clinical Practice Committee, whose aim is to recommend variants for inclusion in clinical pharmacogenetic testing panels. The goals of the Association for Molecular Pathology PGx Working Group are to define the key attributes of PGx alleles recommended for clinical testing and to define a minimum set of variants that should be included in clinical PGx genotyping assays. These recommendations include a minimum panel of variant alleles (tier 1) and an extended panel of variant alleles (tier 2) that will aid clinical laboratories when designing PGx assays. The Working Group considered variant allele frequencies in different populations and ethnicities, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. These CYP2C19 genotyping recommendations are the first of a series of recommendations for PGx testing. These recommendations are not to be interpreted as restrictive, but they are meant to provide a helpful guide

Oral complications of Type 1 diabetes mellitus in a non-smoking population

Type 1 diabetes mellitus (T1DM) is a complex metabolic condition that results in hyperglycemia due to insulin deficiency (Daneman, 2006). Diabetes has a range of effects on almost every system in the body including the kidneys, the eyes, the cardiovascular system, the genito-urinary system, the gastro-intestinal system and the nervous system (Daneman, 2006). The effects of this ondition are widespread and have a significant impact both on life expectancy and the quality of life of individuals suffering from diabetes (Scottish Diabetes Survey Monitoring Group, 2011). The impact of diabetes on oral health has been investigated over many decades, however, the conclusions have been varied and study design has not always been adequate (Mealey et al., 2006; Khader et al., 2006; Chávarray et al., 2009). Research presented in this thesis is largely the result of a cross-sectional clinical study examining the oral cavities of non-smoking T1DM patients, funded by the Chief Scientist Office of the Scottish Government. The clinical part of the study took place between January 2006 and May 2009 in Glasgow Dental Hospital. Chapter one provides an introduction and narrative review on the subject of T1DM, periodontal disease, and the various other reported oral manifestations of diabetes mellitus. The methods for measuring general and oral health related quality of life outcomes are also discussed. Chapter one reveals some of the inadequacies of studies nvestigating the link between T1DM and oral disease to date and ontextualises the studies presented in this thesis. Chapter two presents the main periodontal findings of a large cross-sectional study. 112 non-diabetic subjects and 203 subjects with type 1 diabetes were examined. 203 diabetic patients were divided into well controlled and poorly controlled groups based on their average blood sugar levels over the previous two years. 169 were poorly controlled. (PCD). Those with T1DM, (especially those with poor glycaemic control) had a greater extent and severity of periodontitis than those without diabetes. There was also some evidence that never smoking T1DM patients were more likely to have periodontal disease than non-diabetic subjects. The odds ratio (OR) was 1.43 [0.74 to 2.75] (p = 0.29) for all T1DM patients and 1.58 [0.75 to 3.33] (p = 0.23) for PCD. This difference remained even after the multivariable analysis took into account age, gender and lifestyle including: body mass index of the subject; whether they had smoked in the past; whether they attended a dentist; their level of education and how deprived the area they lived in was. Chapter three presents an analysis of the impact of age, HbA1c, and duration on the expression of periodontal disease in T1DM subjects. Cross-tabulations and multivariable logistic regression analysis was performed on the periodontal data from T1DM subjects and non-diabetic subjects in order to determine the relationship between age, HbA1c and duration, and periodontitis. Diabetic subjects developed periodontitis at a younger age than non-diabetes subjects. This will represent a significant impact on life time dental service provision for subjects affected at a young age. The relationship between HbA1c and severe periodontitis is not a simple one. It is possible that unknown factors confound the relationship between glycaemic control and periodontitis. There was no relationship between duration of diabetes and periodontitis when age was controlled for. Chapter four presents the results of a small study investigating biomarkers of bone turnover in patients with and without T1DM and in patients with and without periodontitis. Patients with T1DM had higher levels of osteoprotegerin an osteoprotective molecule that normally leads to a reduced propensity for bone loss. T1DM patients were also shown to have reduced levels of biomarkers of bone formation (osteocalcin). It is possible that a reduced capacity for bone repair and regeneration may account for the increase levels of periodontitis seen in T1DM. Further prospective studies would be required to confirm this hypothesis. Chapter five investigated the level of caries and oral mucosal abnormalities in T1DM. There was little difference in caries indicators or in oral mucosal lesions between the groups. There was no difference in the bacterial microflora and in the level of resistance to antibiotics found in this cohort. T1DM patients, however, did have an increase in the symptoms of dry mouth, an increased density of candida colonisation and reduced salivary flow rates.Chapter six reports the data derived from the oral health questionnaire, including the Oral Health Impact Profile -14 (OHIP-14) and the Audit of Diabetes Dependent Quality of Life (ADDQOL©). Patients with T1DM, despite having increased levels of periodontal disease, reduced salivary flow rates and increased symptoms of xerostomia did not have higher OHIP scores by any measure. The reasons for this apparently negligible impact of oral disease or oral health related quality of life are discussed. The OHIP-14 was shown to have construct validity in this population although the correlations were relatively weak and the differences were small. It is possible that patients with T1DM do not consider the impact of their oral health to be a significant problem in light of their other on-going medical issues. This finding requires further in-depth investigation of the psychology behind this apparent reduced impact. This is the first study of its kind to examine the oral and dental health of non-smoking type 1 diabetic patients. The conclusions from the clinical data support the view that patients with T1DM should be targeted with oral and dental health advice. Encouragingly the prevalence of periodontitis was lower in well controlled diabetic subjects suggesting that the effect of T1DM on the oral cavity can be ameliorated by good glycaemic control even though logistic regression analysis did not show a linear relationship. It is important that health rofessionals work together in order to prevent and manage the oral complications of T1DM in the same way that there are preventive and screening programmes for other diabetic complications. The pathogenesis behind the increased prevalence and severity of periodontal disease in T1DM requires further study.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Caratterizzazione di Batteri Vibrio harveyi irradiati con luce UV e raggi X

Lo studio dei batteri sottoposti a stimolazioni dovute all'ambiente è di estremo interesse per impli-cazioni strutturali, meccanicistiche ed evolutive. Bat-teri luminescenti evoluti in determinati ambienti han-no sviluppato particolari risposte e il loro comporta-mento può fornire informazioni sulla funzione e sulla produzione dell‟enzima luciferina. Per esaminare l'in-terazione con radiazione UV, in condizioni controlla-te di laboratorio sono stati utilizzati ceppi batterici foto-luminescenti appartenenti alla specie Vibrio har-veyi campionati da una grotta costiera con elevato contenuto di radon che genera radiazioni ionizzanti. La sopravvivenza dei ceppi batterici è stata analizza-ta, alla luce e al buio, a seguito di una varietà di trat-tamenti genotossici tra cui esposizione alle radiazioni UV. I ceppi sono stati irradiati mediante una lampada germicida. I risultati hanno dimostrato che la maggior parte dei ceppi esibiscono un basso tasso di sopravvi-venza dopo l'esposizione ai raggi UV. Tutti i ceppi dopo esposizione a luce visibile e ai raggi UV hanno mostrato una forte capacità di fotoriattivazione. Que-sta capacità era inaspettata, poiché questi batteri sono stati prelevati da un ambiente buio in assenza raggi UV. Questo porta ad ipotizzare che la fotoriattivazio-ne in questi batteri potrebbe essere stata sviluppata dagli stessi per riparare le lesioni del DNA provocate anche da radiazioni diverse dall‟UV (ad esempio, raggi X) e che i batteri luminescenti potrebbero usare la luce da essi emessa per effettuare la fotoriattivazio-ne. L'elevata capacità di fotoriattivazione dei batteri è stata anche confermata dai risultati di deconvoluzio-ne. La deconvoluzione è stata applicata agli spettri di emissione che ha evidenziato la presenza di diversi picchi. La presenza del picco nel visibile è in grado di controllare l'enzima fotoliasi

Therapeutic potential of Mesenchymal Stem Cells for the treatment of type-1 Diabetes

The transplantation of pancreatic islets is an innovative and intriguing therapeutic option for the long term treatment of type-1 diabetes (Remuzzi et al., 2009). Unfortunately, their clinical feasibility is limited by the great number of islets necessary to achieve glycaemic control and their short survival. A possible means to improve the performance of this technique can be represented by Mesenchymal Stem Cells (MSCs), adult stem cells alrady known to support the survival of different cellular populations (Scuteri et al., 2014). In this work the ability of Mesenchymal Stem Cells (MSCs) to improve the feasibility of this approach was verified into an in vivo model represented by Streptozotocin-induced diabetic rats. We compared 5 different groups (8 rats/group): a) healthy controls; b) Diabetic rats; c) Diabetic rats transplanted with pancreatic islets (3000); d) Diabetic rats cotransplanted with pancreatic islets (2000) and MSCs (106); Diabetic rats treated with MSCs (106). Transplantations were performed after the assessment of neuropathic signs, represented by a decreased Nerve Conduction Velocity (NCV) and an impairment of nociceptive thermal and mechanical thresholds. The same parameters were evaluated two months after the transplantation. Diabetic rats transplanted only with pancreatic islets, or co-transplanted with MSCs and a suboptimal number of pancreatic islets, showed a significant glycaemia value reduction, an improvement of thermal and mechanical sensitivity, and an improvement of NCV with respect to diabetic-untreated rats. No differences were observed between diabetic rats and diabetic rats treated with only MSCs. In conclusion, we demonstrated that co-transplantation with MSCs reduces the number of pancreatic islets needed to reach glycaemic control, and induces the regression of painful neuropathy signs, thus ameliorating diabetes complications management. Granted by MIUR – FIRB Futuro in Ricerca 2008 Prot. N° RBFR08VSVI_001

Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats

In spite of the clinical usefulness of cisplatin (CDDP), there are many occasions in which it is difficult to continue the administration of CDDP due to its nephrotoxicity and neurotoxicity. We examined the incorporation of CDDP into polymeric micelles to see if this allowed the resolution of these disadvantages. Cisplatin was incorporated into polymeric micelles through the polymer–metal complex formation between polyethylene glycol poly(glutamic acid) block copolymers and CDDP (NC-6004). The pharmacokinetics, pharmacodynamics, and toxicity studies of CDDP and NC-6004 were conducted in rats or mice. The particle size of NC-6004 was approximately 30 nm, with a narrow size distribution. In rats, the area under the curve and total body clearance values for NC-6004 were 65-fold and one-nineteenth the values for CDDP (P<0.001 and 0.01, respectively). In MKN-45-implanted mice, NC-6004 tended to show antitumour activity, which was comparable to or greater than that of CDDP. Histopathological and biochemical studies revealed that NC-6004 significantly inhibited the nephrotoxicity of CDDP. On the other hand, blood biochemistry revealed transient hepatotoxicity on day 7 after the administration of NC-6004. Furthermore, rats given CDDP showed a significant delay (P<0.05) in sensory nerve conduction velocity in their hind paws as compared with rats given NC-6004. Electron microscopy in rats given CDDP indicated the degeneration of the sciatic nerve, but these findings were not seen in rats given NC-6004. These results were presumably attributable to the significantly reduced accumulation of platinum in nerve tissue when NC-6004 was administered (P<0.05). NC-6004 preserved the antitumour activity of CDDP and reduced its nephrotoxicity and neurotoxicity, which would therefore seem to suggest that NC-6004 could allow the long-term administration of CDDP where caution against hepatic dysfunction must be exercised