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

Comparison of the action of different proteases on virulence properties related to the staphylococcal surface.

AIMS: The purpose of this study was to evaluate the antimicrobial efficacy of five different proteases belonging to two different families on Staphylococcus aureus and Staphylococcus epidermidis strains. METHODS AND RESULTS: We used three serine proteases and two metalloproteases in single species biofilm formation assays and in human cell invasion processes. Following each protease incubation with bacterial cells, surface protein patterns were analysed by SDS-PAGE and zymography. Some differently expressed proteins were identified by mass spectrometry. CONCLUSIONS: The effect of tested proteases on biofilm formation was not related to the protease category but was strain-dependent and was related to the biofilm formation capacity of each staphylococcal strain. Some proteases showed a nonspecific and indiscriminate effect on surface proteins, while others induced a discrete and reproducible action on protein profiles. SIGNIFICANCE AND IMPACT OF THE STUDY: The inhibition of the surface-related virulence factors is a promising avenue to overcome persistent infections caused by bacterial biofilms. To this end, we show here that proteases, in particular the metalloprotease serratiopeptidase, can interfere with adhesion and invasion of eukaryotic cells and biofilm formation in staphylococci and their use could represent a viable treatment for the development of novel combination therapie

Nanoquasicrystalline Al-Fe-Cr-Ti alloy matrix/γ-Al2O3 nanocomposite powders: The effect of the ball milling process

Quasicrystalline aluminium alloys and aluminium based nanocomposites with the advantage of high strength over commercial aluminium alloys have been studied for many years. In this work a nanoquasicrystalline Al-Fe-Cr-Ti alloy powder and a nanocomposite consisting of a mixture of a nanoquasicrystalline alloy and nanosize γ-Al2O3 powders were produced through mechanical milling with different milling speeds. It has been observed that a higher milling time or milling speed can improve the homogeneity of the γ-Al2O3 distribution. The α-Al crystallite size decreases and the hardness increases with the milling time. The smallest crystallite size (14 nm) and the highest hardness value (638 HV10g) were obtained for the nanocomposite after 30 h of milling at 250 rpm. As the α-Al crystallite size is the main change in the microstructure during the ball milling process, the change in the hardness of the milled powders was found to follow a Hall-Petch type relation with an exponent of 0.25

Describing astronomy identity of upper primary and middle school students through structural equation modeling

We describe how young students situate themselves with respect to astronomy through an identity framework that features four dimensions: interest, utility value, confidence, and conceptual knowledge. Overall, about 900 Italian students, from 5th to 9th grade (9-14 years old), were involved in the study. We tested our model using confirmatory factor analysis and structural equation modeling. Differences between girls and boys and across school levels were also investigated. Results show that interest has both a direct and an indirect effect on astronomy identity. The indirect effect of interest on identity is mediated by utility value. Moreover, confidence mediates the effect of interest on conceptual knowledge. Concerning differences between girls and boys, we found that the effect of interest on identity is greater for girls than for boys and that the utility value mediates the effect of interest on identity for boys but not for girls. Finally, our findings show also that the students' interest in astronomy and confidence in their performance decrease with age, with a potential negative impact on conceptual knowledge and future career choice in astronomy. The astronomy identity framework can be employed to examine the role of affective variables on performance and persistence in astronomy and to improve the design of teaching-learning activities that can potentially stimulate a lasting interest in astronomy

F4-Neuroprostane Effects on Human Sperm

Swim-up selected human sperm were incubated with 7 ng F4-neuroprostanes (F4-NeuroPs) for 2 and 4 h. Sperm motility and membrane mitochondrial potential (MMP) were evaluated. The percentage of reacted acrosome was assessed by pisum sativum agglutinin (PSA). Chromatin integrity was detected using the acridine orange (AO) assay and localization of the ryanodine receptor was performed by immunofluorescence analysis. Sperm progressive motility (p = 0.02) and the percentage of sperm showing a strong MMP signal (p = 0.012) significantly increased after 2 h F4-NeuroP incubation compared to control samples. The AO assay did not show differences in the percentage of sperm with dsDNA between treated or control samples. Meanwhile, a significantly higher number of sperm with reacted acrosomes was highlighted by PSA localization after 4 h F4-NeuroP incubation. Finally, using an anti-ryanodine antibody, the immunofluorescence signal was differentially distributed at 2 and 4 h: a strong signal was evident in the midpiece and postacrosomal sheath (70% of sperm) at 2 h, whereas a dotted one appeared at 4 h (53% of sperm). A defined concentration of F4-NeuroPs in seminal fluid may induce sperm capacitation via channel ions present in sperm cells, representing an aid during in vitro sperm preparation that may increase the positive outcome of assisted fertilization

Strengthening mechanisms in an Al-Fe-Cr-Ti nano-quasicrystalline alloy and composites

We report a study of the structure-processing-property relationships in a high strength AlFeCrTi nano-quasicrystalline alloy and composites containing 10 and 20 vol% ductilising pure Al fibres. The superimposed contributions of several different strengthening mechanisms have been modelled analytically using data obtained from systematic characterisation of the monolithic alloy bar. An observed yield strength of 544 MPa has been substantiated from a combination of solid solution strengthening, work hardening, precipitation hardening and Hall-Petch grain size dependent effects. These materials have been shown by other authors in previous published work to be highly sensitive to the size distribution of particles in the powder from which they are made, and the subsequent thermomechanical processing conditions. The processing condition employed in this study provided micron-sized grains with a strong [111] preferential orientation along the extrusion direction and a bimodal size distribution of the icosahedral nano-quasicrystalline precipitates. Both were deemed to be a significant contributor to the high yield strength observed. The addition of pure Al fibres was found to decrease the yield strength linearly with increasing Al content, and to augment the ductility of the composites.Industrial collaborator ALPOCO Ltd. (and more specifically Steve McArthur) provided the powders. Dr. Karen Kruska and Dr. Alan Xu assisted with sample preparation of FIB lift-out specimens of the atomised powder for TEM analysis. EPSRC Project EP/E040608/1 provided financial support. M. Galano thanks the RAEng for their support by means of a Research Fellowship. F. Audebert and M. Galano thank PICT-Oxford2010/2831. F. Audebert also thanks UBACyT20020130100663 and FONARSEC FS Nano 2010/11 for financial support.Peer Reviewe

The International development of PROQOL-HCV: An instrument to assess the health-related quality of life of patients treated for Hepatitis C virus

Background Hepatitis C virus (HCV) compromises Health-related Quality of Life (HRQL) with detriments to Physical, Mental and Social health domains. Treatment with interferon and ribavirin is associated with side effects which further impair HRQL. New treatments appear potent, effective and tolerable. However, Patient Reported Outcomes instruments that capture the impact on HRQL for people with hepatitis C are largely non-specific and will be needed in the new treatment era. Therefore, we developed a conceptually valid multidimensional model of HCV-specific quality of life and pilot survey instrument, the Patient Reported Outcome Quality of Life survey for HCV (PROQOL-HCV). Methods HCV patients from France (n = 30), Brazil (n = 20) and Australia (n  = 20) were interviewed to investigate HCV-HRQL issues raised in the scientific literature and by treatment specialists. Interviews were recorded, transcribed and translated into English and French. Results Fifteen content dimensions were derived from the qualitative analysis, refined and fitted to four domains: (1) Physical Health included: fatigue, pain, sleep, sexual impairment and physical activity; (2) Mental Health: psychological distress, psychosocial impact, and cognition; (3) Social Health: support, stigma, social activity, substance use; (4) Treatment: management, side effects, and fear of treatment failure. The impact of some dimensions extended beyond their primary domain including: physical activity, cognition, sleep, sexual impairment, and the three treatment dimensions. A bank of 300 items was constructed to reflect patient reports and, following expert review, reduced to a 72-item pilot questionnaire. Conclusion We present a conceptually valid multidimensional model of HCV-specific quality of life and the pilot survey instrument, PROQOL-HCV. The model is widely inclusive of the experience of hepatitis C and the first to include the treatment dimension

Effect of Al addition to Rapidly Solidified Mg-Cu-Rare Earth Alloys

Rapidly solidified Mg based alloys are of interest for industrial applications as a structural material and for hydrogen storage. Mg-Cu-Rare Earth alloys have shown high glass forming ability; full amorphous structure with thickness of mm size can be obtained within these systems. However, their brittle behavior limits their industrial applications. In the present work, the Al effect in substitution of Cu in the Mg65Cu25MM10 (at%, MM: mischmetal) was studied. Samples up to 15at% Al were prepared by splat cooling and their microstructure, stability and mechanical properties were characterised. The crystallization temperature increases with the Al addition; the amorphous phase with different Al content has a Young's modulus of ~55GPa; the microhardness increases with the Al content in the amorphous and crystallized samples and the fracture of the alloy containing 10at% Al showed ductile vein patterns characteristics of ductile metallic glasses. The partial Cu substitution by Al can improve the stability and mechanical properties of the amorphous Mg65Cu25MM10 allo