Tetramerization reinforces the dimer interface of MnSOD.

Two yeast manganese superoxide dismutases (MnSOD), one from Saccharomyces cerevisiae mitochondria (ScMnSOD) and the other from Candida albicans cytosol (CaMnSODc), have most biochemical and biophysical properties in common, yet ScMnSOD is a tetramer and CaMnSODc is a dimer or "loose tetramer" in solution. Although CaMnSODc was found to crystallize as a tetramer, there is no indication from the solution properties that the functionality of CaMnSODc in vivo depends upon the formation of the tetrameric structure. To elucidate further the functional significance of MnSOD quaternary structure, wild-type and mutant forms of ScMnSOD (K182R, A183P mutant) and CaMnSODc (K184R, L185P mutant) with the substitutions at dimer interfaces were analyzed with respect to their oligomeric states and resistance to pH, heat, and denaturant. Dimeric CaMnSODc was found to be significantly more subject to thermal or denaturant-induced unfolding than tetrameric ScMnSOD. The residue substitutions at dimer interfaces caused dimeric CaMnSODc but not tetrameric ScMnSOD to dissociate into monomers. We conclude that the tetrameric assembly strongly reinforces the dimer interface, which is critical for MnSOD activity

Exposure of Highway Maintenance Workers to Fine Particulate Matter and Noise

In this study, we assessed the mixed exposure of highway maintenance workers to airborne particles, noise, and gaseous co-pollutants. The aim was to provide a better understanding of the workers' exposure to facilitate the evaluation of short-term effects on cardiovascular health endpoints. To quantify the workers' exposure, we monitored 18 subjects during 50 non-consecutive work shifts. Exposure assessment was based on personal and work site measurements and included fine particulate matter (PM2.5), particle number concentration (PNC), noise (Leq), and the gaseous co-pollutants: carbon monoxide, nitrogen dioxide, and ozone. Mean work shift PM2.5 concentrations (gravimetric measurements) ranged from 20.3 to 321 μg m−3 (mean 62 μg m−3) and PNC were between 1.6×104 and 4.1×105 particles cm−3 (8.9×104 particles cm−3). Noise levels were generally high with Leq over work shifts from 73.3 to 96.0 dB(A); the averaged Leq over all work shifts was 87.2 dB(A). The highest exposure to fine and ultrafine particles was measured during grass mowing and lumbering when motorized brush cutters and chain saws were used. Highest noise levels, caused by pneumatic hammers, were measured during paving and guardrail repair. We found moderate Spearman correlations between PNC and PM2.5 (r = 0.56); PNC, PM2.5, and CO (r = 0.60 and r = 0.50) as well as PNC and noise (r = 0.50). Variability and correlation of parameters were influenced by work activities that included equipment causing combined air pollutant and noise emissions (e.g. brush cutters and chain saws). We conclude that highway maintenance workers are frequently exposed to elevated airborne particle and noise levels compared with the average population. This elevated exposure is a consequence of the permanent proximity to highway traffic with additional peak exposures caused by emissions of the work-related equipmen

Radiation Damage Studies of Silicon Photomultipliers

We report on the measurement of the radiation hardness of silicon photomultipliers (SiPMs) manufactured by Fondazione Bruno Kessler in Italy (1 mm$^2$ and 6.2 mm$^2$), Center of Perspective Technology and Apparatus in Russia (1 mm$^2$ and 4.4 mm$^2$), and Hamamatsu Corporation in Japan (1 mm$^2$). The SiPMs were irradiated using a beam of 212 MeV protons at Massachusetts General Hospital, receiving fluences of up to $3 \times 10^{10}$ protons per cm$^2$ with the SiPMs at operating voltage. Leakage currents were read continuously during the irradiation. The delivery of the protons was paused periodically to record scope traces in response to calibrated light pulses to monitor the gains, photon detection efficiencies, and dark counts of the SiPMs. The leakage current and dark noise are found to increase with fluence. Te leakage current is found to be proportional to the mean square deviation of the noise distribution, indicating the dark counts are due to increased random individual pixel activation, while SiPMs remain fully functional as photon detectors. The SiPMs are found to anneal at room temperature with a reduction in the leakage current by a factor of 2 in about 100 days.Comment: 35 pages, 25 figure

Screening for Latent Tuberculosis Infection among Students of Healthcare Professions and Postgraduates of the Faculty of Medicine of the University of Palermo

Introduction and objective: Italy is a country with a low incidence of tuberculosis and in the last fifty years the annual number of TB cases decreased from 12,247 to 4,418, showing a reduction of approximately 64% in the number of cases and 71% in incidence. Despite of this encouraging trend, in the last years the epidemiology of tuberculosis changed and today it is a re-emerging infectious. The aim of this study is to measure the prevalence of positivity to tuberculosis infection (latent TB) in students, without any obvious manifestation of disease, attending degree courses of the health care professions and postgraduate medical courses of the School of Medicine of the University of Palermo, Italy. Materials and methods: A cross-sectional observational study in students of nursing, midwifery, dentistry degree courses and in resident physicians of postgraduate medical schools was carried out from January 2012 to July 2016. Mantoux test was performed and all positive cases were tested with Interferon-Gamma Release Assay (IGRA). Results: Of the 1,351 subjects evaluated, 25 (1.8%) resulted positive to Mantoux test; in 17 students (1.2%) the diagnosis was confirmed with IGRA. Positive cases were significantly more frequent among students attending Postgraduated Medical School Courses (p<0.001) and were older than negative cases (p<0.001). Conclusion: This study suggests that in our geographic area, latent TB shows a relatively low prevalence among students of medical schools. Despite of this evidence, and considering that several students have been found to be positive for TB, this infectious disease has to be considered a re-emerging biohazard that requires preventive strategies for the containment of the risk in exposed workers as well as in the general population

Mycobacterium tuberculosis Drives Expansion of Low-Density Neutrophils Equipped With Regulatory Activities

In human tuberculosis (TB) neutrophils represent the most commonly infected phagocyte but their role in protection and pathology is highly contradictory. Moreover, a subset of low-density neutrophils (LDNs) has been identified in TB, but their functions remain unclear. Here, we have analyzed total neutrophils and their low-density and normal-density (NDNs) subsets in patients with active TB disease, in terms of frequency, phenotype, functional features, and gene expression signature. Full-blood counts from Healthy Donors (H.D.), Latent TB infected, active TB, and cured TB patients were performed. Frequency, phenotype, burst activity, and suppressor T cell activity of the two different subsets were assessed by flow cytometry while NETosis and phagocytosis were evaluated by confocal microscopy. Expression analysis was performed by using the semi-quantitative RT-PCR array technology. Elevated numbers of total neutrophils and a high neutrophil/lymphocyte ratio distinguished patients with active TB from all the other groups. PBMCs of patients with active TB disease contained elevated percentages of LDNs compared with those of H.D., with an increased expression of CD66b, CD33, CD15, and CD16 compared to NDNs. Transcriptomic analysis of LDNs and NDNs purified from the peripheral blood of TB patients identified 12 genes differentially expressed: CCL5, CCR5, CD4, IL10, LYZ, and STAT4 were upregulated, while CXCL8, IFNAR1, NFKB1A, STAT1, TICAM1, and TNF were downregulated in LDNs, as compared to NDNs. Differently than NDNs, LDNs failed to phagocyte live Mycobacterium tuberculosis (M. tuberculosis) bacilli, to make oxidative burst and NETosis, but caused significant suppression of antigen-specific and polyclonal T cell proliferation which was partially mediated by IL-10. These insights add a little dowel of knowledge in understanding the pathogenesis of human TB

Curcumin affects HSP60 folding activity and levels in neuroblastoma cells

The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial\u2013mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of protein homeostasis and cell survival. High HSP60 levels were correlated, in particular, with cancer development and progression, and for this reason, we investigated the ability of curcumin to affect HSP60 expression, localization, and post-translational modifications using a neuroblastoma cell line. We have also looked at the ability of curcumin to interfere with the HSP60/HSP10 folding machinery. The cells were treated with 6, 12.5, and 25 \ub5M of curcumin for 24 h, and the flow cytometry analysis showed that the compound induced apoptosis in a dose-dependent manner with a higher percentage of apoptotic cells at 25 \ub5M. This dose of curcumin-induced a decrease in HSP60 protein levels and an upregulation of HSP60 mRNA expression. Moreover, 25 \ub5M of curcumin reduced HSP60 ubiquitination and nitration, and the chaperonin levels were higher in the culture media compared with the untreated cells. Furthermore, curcumin at the same dose was able to favor HSP60 folding activity. The reduction of HSP60 levels, together with the increase in its folding activity and the secretion in the media led to the supposition that curcumin might interfere with cancer progression with a protective mechanism involving the chaperonin

Federal Aid and Equality of Educational Opportunity: Evidence from the Introduction of Title I in the South

Title I of the 1965 Elementary and Secondary Education Act substantially increased federal aid for education, with the goal of expanding educational opportunity. Combining the timing of the program’s introduction with variation in its intensity, we find that Title I increased school spending by 46 cents on the dollar in the average school district in the South and increased spending nearly dollar-for-dollar in Southern districts with little scope for local offset. Based on this differential fiscal response, we find that increases in school budgets from Title I decreased high school dropout rates for whites, but not blacks.

Gli uccelli delle isole circumsiciliane

Gli autori sintetizzano tutte le informazioni bibliografiche e inedite sulle specie che sino al 30 agosto 2015 sono state contattate almeno una volta nelle 14 isole circumsiciliane (Eolie, Ustica, Egadi, Pantelleria e Pelagie), confrontando alla fine la lista complessiva con quella delle isole Maltesi. In totale sono ad oggi note 434 specie (isole Maltesi incluse); molte di esse hanno mostrato nel corso dei secoli una notevole capacità di colonizzazione, fluttuando nel tempo o addirittura estinguendosi e ricolonizzando alcune isole. Questi piccoli territori in mezzo al mare rappresentano ottimi siti di controllo dell’andamento delle migrazioni nel corso dei decenni; alcune specie hanno chiaramente cambiato il loro status rispetto al passato, aumentando o diminuendo. Nel corso di circa 15 anni in alcune di queste isole (Ustica, Marettimo, Lampedusa e Linosa) sono stati condotti dei campi di inanellamento sia primaverili sia autunnali che hanno permesso di inanellare 102.208 uccelli, in gran parte Passeriformes; ciò ha consentito di raccogliere una notevole mole di dati sulle strategie migratorie, che vengono qui brevemente presentati. Le piccole isole sono davvero importanti per gli uccelli migratori transahariani, che devono sostare durante i loro lunghi viaggi per recuperare energie; la disponibilità di risorse sotto forma di frutti selvatici o di insetti (a seconda delle specie) consente a queste masse di migratori di continuare il loro viaggio. La conservazione degli uccelli è dettata dalla Direttiva Uccelli e l’istituzione delle Zone di Protezione Speciale ha proprio lo scopo di salvaguardare alcune specie in determinati territori. Questo è un impegno preso da parte di tutti i Paesi dell’Unione Europea, proprio perché le popolazioni di uccelli non conoscono confini amministrativi e la loro tutela va al di là delle competenze e degli interessi di un singolo Paese. Per quanto riguarda le specie nidificanti, è risultata un’elevata correlazione negativa (r=-0,746), altamente significativa (P=0,002) tra la capacità dispersiva media delle specie e la superficie in km2 delle isole. Le specie con minore capacità dispersiva hanno colonizzato le isole di maggiori dimensioni, ma non quelle più piccole; questo con molta probabilità dipende dalla eterogeneità ambientale, a sua volta legata alla dimensione delle isole ed alla loro posizione geografica. Nel caso delle isole circumsiciliane, sembra che non sia tanto la distanza dalla costa a determinare il numero di specie, quanto le condizioni ambientali e la posizione geografica; indubbiamente la posizione tirrenica delle isole settentrionali rappresenta un vantaggio per la presenza di habitat differenziati e la conseguente colonizzazione di specie ad essi legate, mentre la posizione meridionale, influenzata dall’aridità africana, riduce alcune possibilità colonizzatrici da parte di alcune specie di uccelli e rende altresì problematica la stessa esistenza di habitat diversificati. Il numero delle specie nidificanti in un’isola è variabile nel tempo, essendovi specie che vi nidificano in modo irregolare. La correlazione area/N° specie nelle isole circumsiciliane è pari a 0,58, ma se si esclude l’isola di Pantelleria, sale a 0,86; essa è pari a 0,92 per le sole isole settentrionali (Eolie, Ustica ed Egadi), mentre risulta 0,99 per le sole tre isole meridionali del Canale di Sicilia.Authors summarize all bibliographic and unpublished information on bird species that have been detected at least one time up to 30th August 2015 in the 14 circum-sicilian islands (Eolian, Ustica, Egadi, Pantelleria and Pelagian Is.). The Appendix 1 compares overall lists with that of the Maltese Is., also lying in the Sicilian waters. On the whole, 434 species are known till now (Maltese Is. included); many of them showed a high colonizing capacity along the centuries, fluctuating or even becoming extinct and re-colonising some islands. These small territories in the middle of the Mediterranean sea are very good check-control sites of long-term migration trend; compared to the past, some species changed their status, increasing or declining. Additionally, during the last 15 years in some of these islands (Ustica, Marettimo, Lampedusa and Linosa) bird ringing activity has been carried out, both in spring and in autumn; it allowed to ring 102,208 birds, mainly Passeriformes; this opportunity allowed to collect a remarkable amount of data on migration strategy, here presented. The small islands are very important stop-over sites for transsaharan migratory birds, that must rest during their long journey to recover fuel in the form of fat; the availability of natural resources, such as wild fruits or insects, allows these masses of migrant birds to continue their trip. The conservation of birds has been established by the Bird Directive and the institution of Zones of Special Protection has the aim to safeguard some species in some territories. This agreement was signed by all countries of the EU, because bird populations do not know administrative borders and their conservation lies beyond the interests and authorities of a single country. Concerning breeding birds, a high negative correlation (r=-0.746, P=0.002) has been found between the average dispersal power of species and the area in km2 of islands. Species with minor dispersal power colonized the biggest but not the smallest islands; this, very probably depended on habitat heterogeneity of islands, in turn linked to the size of them and to the geographical position, more than to the distance from the continental land. Tyrrhenian position of northern islands is certainly an advantage for the presence of diversified habitats and birds inhabiting them, whereas southern position of Pantelleria and Pelagian Is., as well as Maltese Is., affected by African dryness, decreases colonizing probabilities of some bird species and the same existence of diversified habitats. The number of breeding species in each island varied along the time and some species bred irregularly. The correlation area/No. species in the islands surrounding Sicily resulted to be 0.58, but if we exclude Pantelleria Is., it grows to 0.86; besides, it grows to 0.92 if we consider only northern islands (Eolian, Ustica and Egadi Is.), and to 0.99 if we consider only southern islands