Nuclear structure with radioactive muonic atoms

Muonic atoms have been used to extract the most accurate nuclear charge radii based on the detection of X-rays from the muonic cascades. Most stable and a few unstable isotopes have been investigated with muonic atom spectroscopy techniques. A new research project recently started at the Paul Scherrer Institut aims to extend the highresolution muonic atom spectroscopy for the precise determination of nuclear charge radii and other nuclear structure properties of radioactive isotopes. The challenge to combine the high-energy muon beam with small quantity of stopping mass is being addressed by developing the concept of stopping the muon in a high-density, a high-pressure hydrogen cell and subsequent transfer of the muon to the element of interest. Status and perspectives of the project will be presented

High granularity scintillating fiber trackers based on Silicon Photomultiplier

Scintillating fibers coupled to photosensors provide flexible, fast and high granularity detectors which are able to work in high rate environment. We will report about the performances obtained with multi-layer detector prototype based on 250 mm multi-clad square scintillating fibers, 20 cm long, coupled to 1:31:3mm2 active area silicon photomultiplier (SiPMs). Current measurements show results never reached up to now: high detection efficiency for minimum ionizing particles (m.i.p.) already for a single layer (> 90%, mean collected light/fiber 8.5 phe). Also a good spatial resolution can be achieved by keeping the optical cross-talk between fibers at a negligible level (<1%), a level has been achieved by coating the fibers with aluminum.. Finally, the time resolution of the order of 500 ps has been achieved for m.i.p. in a single layer configuration. The resolution improves with increasing the number of detector layers. All measurements have been supported with a Monte Carlo simulation based on Geant4 and a custom code, describing the response of the SiPMs

Recombinant protein expression system in cold loving microorganisms

Soluble and functional proteins are of high demand in modern biotechnology. Although many recombinant proteins have been successfully obtained from common prokaryotic and eukaryotic hosts, these systems result to be often unproductive due to the peculiar properties of the protein to be produced. Incorrect folding of the nascent polypeptide chains is one of the main problems occurring during heterologous protein production in bacteria. Since formation of inclusion bodies often impairs the recombinant production of valuable proteins, many experimental approaches have been explored to minimize this undesirable effect [1, 2]. Expression of "difficult" proteins has also been carried out by lowering the temperature at the physiological limit allowed for the growth of mesophilic host organisms (between 15 and 18°C for Escherichia coli). Lowering the temperature, in fact, has a pleiotropic effect on the folding process, destabilising the hydrophobic interactions needed for intermediates aggregation [3]. On the basis of the above considerations, a rational alternative to mesophilic organisms is the use of naturally cold-adapted bacteria as hosts for protein production at low temperature (even at around 0°C)

Geochemical characterization of bauxite deposits from the Abruzzi Mining district (Italy)

The Abruzzi bauxite district includes the deposits located on the Campo Felice plateau and those of the Monti d'Ocre, which had been mined in the first part of the 20th century. Bauxite is of the karst type, with textures ranging between oolitic and oolitic-conglomeratic, the latter suggesting a partial reworking of evolved lateritic soils. The high contents of Al2O3 and Fe2O3 (average values 53.76 and 21.76 wt %, respectively) are associated with the presence of boehmite, hematite, and minor goethite. SiO2 and TiO2 have average values of 7.79 and 2.75 wt %, corresponding to the presence of kaolinite, anatase and rutile. Among the minor so-called "bauxitophile" elements V, Co, Ni, Cr and Zr, the most enriched is Cr, with an average value of 0.07 wt %. Nickel has an average value of 210.83 ppm. Vanadium shows an average value of 266.57 ppm, whereas the average Co concentration is 35.89 ppm. The total rare earth elements (REE) concentration in the sampled bauxite sites is variable between ca. 700 and 550 ppm. Among REEs, the most abundant element is Ce, with Ce anomalies commonly associated with authigenic REE-fluoro-carbonates, probably produced after the REEs remobilization from primary detrital minerals and their precipitation in neo-formed phases during the bauxitization process. Scandium and Ga occur in small amounts (57 and 60 ppm, respectively), but geochemical proxies of their remobilization and uptake in neo-formed minerals (Feand Al-(hydr) oxides, respectively) have been observed. The mean Eu/Eu* and Al2O3/TiO2 ratios and the Ni-Cr contents of the Abruzzi bauxites suggest that the parent rock of these deposits was a material of acid affinity, likely corresponding to volcanic tephra or eolic loess-type sands

A new anti-infective strategy to reduce the spreading of antibiotic resistance by the action on adhesion-mediated virulence factors in Staphylococcus aureus.

Staphylococcus aureus is a flexible microbial pathogen frequently isolated from community-acquired and nosocomial infections. S. aureus expresses a wide array of secreted and cell surface-associated virulence factors, including proteins that promote adhesion to damaged tissue and to the surface of host cells, and that bind proteins in blood to help evade immune responses. Furthermore, surface proteins have a fundamental role in virulence related properties of S. aureus, including biofilm formation. The present study evaluates the anti-infective capabilities of a secreted protein of Serratia marcescens (serratiopeptidase, SPEP), in impairing some staphylococcal virulence-related properties, such as attachment to inert surfaces and adhesion/invasion on eukaryotic cells. SPEP seems to exert its action by modulating specific proteins. It is not assessed if this action is due to the proteolytic activity of SPEP or to a specific mechanism which triggers an out/inside signal. Proteomic studies performed on surface proteins extracted from SPEP treated S. aureus cultures revealed that a number of proteins are affected by the treatment. Among these we found the adhesin/autolysin Atl, SdrD, Sbi, EF-Tu and EF-G. EF-Tu and EF-G are known to perform a variety of function, depending on their cytoplasmic or surface localization. All these factors can facilitate bacterial colonization, persistence and invasion of host tissues. Our results suggest that SPEP could be developed as a potential "anti-infective agent" capable to hinder the entry of S. aureus into human tissues, and also impairs the ability of this pathogen to adhere to prostheses, catheters and medical device

Serratiopeptidase: a well-known metalloprotease with a new non-proteolytic activity against S. aureus biofilm

Background The use of indwelling medical devices is associated with a significant risk of infections by Staphylococcus aureus (S. aureus) which possesses a variety of virulence factors including many toxins and the ability to invade eukaryotic cells or to form biofilm on biotic and abiotic surfaces. The virulence factors above described are often related to proteins exposed on the bacterial surface. Blocking S. aureus colonization may reduce the incidence of invasive infectious diseases. Previously reports evaluated the anti-infective properties of serratiopeptidase (Spep), an extracellular metalloprotease produced by Serratia marcescens ATCC 21074 (E-15), in impairing virulence-related staphylococcal properties, such as attachment to inert surfaces and adhesion/invasion on eukaryotic cells. However, to date its mechanism of action is unknown. Methods Spep gene was PCR amplified and cloned into expression vector pET28b(+). The mutant EspepA was constructed from plasmid pET28b-Spep applying the one-step overlap extension PCR strategy. There sulting plasmids were costransformed in EcBL21(DE3) cells with the plasmid pRuW4inh1 harboring the Erwinia chrysanthemi secretion system. Bacterial pellets and supernatants were collected and analyzed by SDS-PAGE and zymography. The unambiguous identification and a detailed structure characterization of both the wild type and the mutant Spep were obtained by mass spectrometric analyses. The resultant supernatants sterilized by filtration were separately used to condition biofilm formation of S. aureus. Quantification was based on crystal violet method. Results In this work we constructed Spep mutant by substituting the glutamic acid in the catalytic site with a residue of alanine. In this manner we were able to evaluate the anti-biofilm activity of Spep mutant in absence of proteolytic activity. As expected, this mutant did not display protease activity but it retained its anti-biofilm properties, suggesting that this action is independent by enzymatic activity. Conclusions New knowledge obtained from data reported in this paper calls attention to a novel mechanism of action of Spep. This protein could be developed as a potential “antipathogenic agent” capable to impair the ability of S. aureus to form biofilm on prostheses, catheters and medical devices, exploiting a mechanism different from the proteolytic activity

Routine laboratory tests to risk-stratify patients with chronic coronary artery disease

AbstractBackgroundSeveral biohumoral variables, taken individually, are predictors of prognosis in patients with chronic coronary artery disease (CAD). We hypothesized that taken together, laboratory tests provide prognostic information that is additive to a complete diagnostic work-up.MethodsWe prospectively examined 2370 consecutive patients with chronic CAD, as shown by a >50% coronary stenosis (in 95% of patients), previous coronary revascularization (in 31% of patients), and/or previous myocardial infarction (MI, in 54% of patients). We tested the ability of laboratory and clinical variables to predict future cardiac events (cardiac death and non-fatal MI).ResultsDuring follow-up (median, 46 months), 147 patients (6.2%) died from cardiac causes and 81 (3.4%) experienced a non-fatal MI. Using multivariate analysis, after adjustment for clinical variables (including left ventricular ejection fraction and angiographic extent of coronary stenoses), a high-density lipoprotein cholesterol (HDLc) concentration<35mg/dL (p<0.0001), a neutrophil-to-lymphocyte ratio >2.4 (p=0.0014), and an fT3 serum level<2.1pg/mL with normal thyrotropin (low-T3 syndrome) (p=0.0260) showed an independent and incremental prognostic value, and were associated with an increase in the rate of cardiac events of 86%, 57% and 41%, respectively. When these variables were added to clinical and instrumental variables, the prognostic power of the model increased significantly (global chi-square improvement: from 157.01 to 185.07, p<0.0001).ConclusionLow HDLc, high neutrophil-to-lymphocyte ratio and low-T3 syndrome, both individually and taken together, provide prognostic information that is independent of and incremental to the main clinical and instrumental findings

The role of anaemia in oxidative and genotoxic damage in transfused β-thalassaemic patients.

Redox imbalance and genotoxic damage are commonly observed in β thalassaemic patients. The aim of this study was to assess the role of anaemia in oxidative and genotoxic damage in regularly transfused thalassaemic patients, undergoing iron chelation therapy.We studied the relationships of haematological, biochemical and clinical parameters with oxidative (reactive oxygen species and 8-oxo-7,8-dihydro-2'-deoxyguanosine) and genotoxic biomarkers (Comet assay and cytokinesis-block micronucleus test) in blood samples from 105 patients. To reduce the early effect of redox-active iron, samples were collected when pharmacokinetics of the iron chelators ensured their maximum effectiveness. The transfusion regimen, cardiac and hepatic magnetic resonance imaging T2* were evaluated to characterize the patient cohort. Labile plasma iron (LPI) was also assayed.Haemoglobin level had a significant effect on ROS, %DNA in the tail and micronuclei-micronucleated cell frequency (p  0.05). Higher Hb values reduced redox imbalance. LPI, detectable in 50.5% of patients, was related to the number of apoptotic and necrotic lymphocytes (p = 0.03), demonstrating the cytotoxic effect of iron.The results highlight that an adequate transfusion regimen is essential to limit oxidative and genotoxic damage in β-thalassemic patients undergoing chelation therapy.Owing to the higher risk of cancer in the thalassaemic cohorts, specific genotoxicity/oxidative biomarkers should be monitored in order to ameliorate and formulate more personalized disease management

Effects of 26 weeks of treatment with empagliflozin versus glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes. The randomized, open-label, crossover, active-comparator FIORE trial

Aim To determine whether treatment with empagliflozin was able to affect the myocardial glucose metabolic rate, as assessed by cardiac dynamic F-18-fluorodeoxyglucose-positron emission tomography (F-18-FDG-PET) combined with euglycaemic-hyperinsulinaemic clamp compared with glimepiride in patients with type 2 diabetes. Materials and Methods To further investigate the cardioprotective mechanism of sodium-glucose co-transporter-2 inhibitors, we performed a 26-week, randomized, open-label, crossover, active-comparator study to determine the effects of empagliflozin 10 mg versus glimepiride 2 mg daily on the myocardial glucose metabolic rate assessed by cardiac dynamic F-18-FDG-PET combined with euglycaemic-hyperinsulinaemic clamp in 23 patients with type 2 diabetes. We also measured cardiac geometry and myocardial mechano-energetic efficiency, as well as systolic and diastolic function by echocardiography. Results Compared with glimepiride, treatment with empagliflozin resulted in a greater reduction in the myocardial glucose metabolic rate from baseline to 26 weeks (adjusted difference -6.07 [-8.59, -3.55] mu mol/min/100 g; P &lt; .0001). Moreover, compared with glimepiride, empagliflozin led to significant reductions in left atrial diameter, left ventricular end-systolic and end-diastolic volumes, N-terminal pro b-type natriuretic peptide levels, blood pressure, heart rate, stroke work, and myocardial oxygen consumption estimated by the rate pressure product, and increases in ejection fraction, myocardial mechano-energetic efficiency, red blood cells, and haematocrit and haemoglobin levels. Conclusions The present study provides evidence that empagliflozin treatment in subjects with type 2 diabetes without coronary artery disease leads to a significant reduction in the myocardial glucose metabolic rate