Ferritin nanovehicle for targeted delivery of cytochrome C to cancer cells

In this work, we have exploited the unique properties of a chimeric archaeal-human ferritin to encapsulate, deliver and release cytochrome c and induce apoptosis in a myeloid leukemia cell line. The chimeric protein combines the versatility in 24-meric assembly and cargo incorporation capability of Archaeglobus fulgidus ferritin with specific binding of human H ferritin to CD71, the “heavy duty” carrier responsible for transferrin-iron uptake. Delivery of ferritin-encapsulated cytochrome C to the Acute Promyelocytic Leukemia (APL) NB4 cell line, highly resistant to transfection by conventional methods, was successfully achieved in vitro. The effective liberation of cytochrome C within the cytosolic environment, demonstrated by double fluorescent labelling, induced apoptosis in the cancer cells

HIV-exposed uninfected children. A systematic review on psychological well-being and association with school performances in Africa

There is a growing number of children affected by HIV in Africa. Research on HIV-exposed uninfected children (HEU) is also growing. This systematic review focuses on the psychological well-being of HEU and its association with school intervention, outcomes, and enrollment in the African context, which is where the rate of HIV reaches its highest levels. Research on public databases was conducted according to PRISMA standards. Only studies on HEU primary school children in Africa, both quantitative and qualitative, were included. Out of 1510 papers retrieved, 50 met the inclusion criteria. These studies demonstrate that HEU children are more likely to perform worse in school compared to their counterparts who were not exposed to HIV and to show poorer concentration in the classroom. Children with parents suffering from AIDS are worried for them and have to take household responsibility, resulting in school dropouts, juvenile work, and risky behaviors. Few interventions have been conducted in the school environment with some of them being successful; therefore, future research should involve schools to create an inclusive environment where HEU children could enhance their potential and improve their psychological health

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy- relevant energies down to stopping

Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25–256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100– 200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments

Probing the statistical decay and alpha-clustering effects in 12c+12c and 14n+10b reactions

An experimental campaign has been undertaken at INFN Laboratori Nazionali di Legnaro, Italy, in order to progress in our understanding of the statistical properties of light nuclei at excitation energies above particle emission threshold, by measuring exclusive data from fusion-evaporation reactions. A first reaction 12C+12C at 7.9 AMeV beam energy has been measured, using the GARFIELD+Ring Counter experimental setup. Fusion-evaporation events have been exclusively selected. The comparison to a dedicated Hauser-Feshbach calculation allows us to give constraints on the nuclear level density at high excitation energy for light systems ranging from C up to Mg. Out-of-equilibrium emission has been evidenced and attributed both to entrance channel effects favoured by the cluster nature of reaction partners and, in more dissipative events, to the persistence of cluster correlations well above the 24Mg threshold for 6 alphas decay. The 24Mg compound nucleus has been studied with a new measurement 14N + 10B at 5.7 AMeV. The comparison between the two datasets would allow us to further constrain the level density of light nuclei. Deviations from a statistical behaviour can be analyzed to get information on nuclear clustering.Comment: 4 pages, 2 figures, Contribution to conference proceedings of the 25th International Nuclear Physics Conference (INPC 2013

GARFIELD + RCo Digital Upgrade: a Modern Set-up for Mass and Charge Identification of Heavy Ion Reaction Products

An upgraded GARFIELD + Ring Counter (RCo) apparatus is presented with improved performances as far as electronics and detectors are concerned. On one side fast sampling digital read out has been extended to all detectors, allowing for an important simplification of the signal processing chain together with an enriched extracted information. On the other side a relevant improvement has been made in the forward part of the setup (RCo): an increased granularity of the CsI(Tl) crystals and a higher homogeneity in the silicon detector resistivity. The renewed performances of the GARFIELD + RCo array make it suitable for nuclear reaction measurements both with stable and with Radioactive Ion Beams (RIB), like the ones foreseen for the SPES facility, where the Physics of Isospin can be studied.Comment: 13 pages, 19 figures - paper submitted to Eur. Phys. J.

LGBT+ Training needs for health and social care professionals: a cross-cultural comparison among seven European countries

Introduction Research suggests that specific training on LGBT+ issues may improve the competencies and skills of health and social care (HSC) professionals, which reduces the negative attitudes toward LGBT+ people. Despite this, there seems to be a lack of coverage of LGBT+ needs in HSC education. The present study aims to explore the specific LGBT+ training needs of HSC professionals and to examine the relationship between these training needs and the four dimensions of the Papadopoulos model, i.e. cultural awareness, cultural knowledge, cultural sensitivity, and cultural competence. Methods The research used data from a cross-cultural project, “Intercultural Education for Nurses in Europe (IENE9),” which was administered to 412 HSC academics and workers (62% females; Mage=46.06, SDage=10.48) between February 2020 and July 2020, in seven European countries: UK (coordinator), Denmark, Spain, Germany, Cyprus, Italy, and Romania. Results Hierarchical multiple regression showed that higher training needs were associated with cultural awareness, cultural knowledge, and cultural competence. The need for training on LGBT+ issues was higher for Cyprus, Romania, Spain, Italy, and the UK, compared with Denmark (no differences between Germany and Denmark were found). Conclusions We believe that there has been a lack of focus on the LGBT+ training needs of HSC professionals: Greater efforts are required to develop a culturally competent and compassionate LGBT+ curriculum. Social Policy Implications Findings from the present study will inform the development of a free, Massive Open Online Course (MOOC), for culturally competent and compassionate HSC professionals in Europe to improve the quality of their car

Charged particle decay of hot and rotating 88^{88}Mo nuclei in fusion-evaporation reactions

A study of fusion-evaporation and (partly) fusion-fission channels for the $^{88}$Mo compound nucleus, produced at different excitation energies in the reaction $^{48}$Ti + $^{40}$Ca at 300, 450 and 600 MeV beam energies, is presented. Fusion-evaporation and fusion-fission cross sections have been extracted and compared with the existing systematics. Experimental data concerning light charged particles have been compared with the prediction of the statistical model in its implementation in the Gemini++ code, well suited even for high spin systems, in order to tune the main model parameters in a mass region not abundantly covered by exclusive experimental data. Multiplicities for light charged particles emitted in fusion evaporation events are also presented. Some discrepancies with respect to the prediction of the statistical model have been found for forward emitted $\alpha$-particles; they may be due both to pre-equilibrium emission and to reaction channels (such as Deep Inelastic Collisions, QuasiFission/QuasiFusion) different from the compound nucleus formation.Comment: 14 pages, 14 figure

A gold-containing drug against parasitic polyamine metabolism: the X-ray structure of trypanothione reductase from Leishmania infantum in complex with auranofin reveals a dual mechanism of enzyme inhibition

Auranofin is a gold(I)-containing drug in clinical use as an antiarthritic agent. Recent studies showed that auranofin manifests interesting antiparasitic actions very likely arising from inhibition of parasitic enzymes involved in the control of the redox metabolism. Trypanothione reductase is a key enzyme of Leishmania infantum polyamine-dependent redox metabolism, and a validated target for antileishmanial drugs. As trypanothione reductase contains a dithiol motif at its active site and gold(I) compounds are known to be highly thiophilic, we explored whether auranofin might behave as an effective enzyme inhibitor and as a potential antileishmanial agent. Notably, enzymatic assays revealed that auranofin causes indeed a pronounced enzyme inhibition. To gain a deeper insight into the molecular basis of enzyme inhibition, crystals of the auranofin-bound enzyme, in the presence of NADPH, were prepared, and the X-ray crystal structure of the auranofin–trypanothione reductase–NADPH complex was solved at 3.5 Å resolution. In spite of the rather low resolution, these data were of sufficient quality as to identify the presence of the gold center and of the thiosugar of auranofin, and to locate them within the overall protein structure. Gold binds to the two active site cysteine residues of TR, i.e. Cys52 and Cys57, while the thiosugar moiety of auranofin binds to the trypanothione binding site; thus auranofin appears to inhibit TR through a dual mechanism. Auranofin kills the promastigote stage of L. infantum at micromolar concentration; these findings will contribute to the design of new drugs against leishmaniasis

A water-filled garment to protect astronauts during interplanetary missions tested on board the ISS

Abstract As manned spaceflights beyond low Earth orbit are in the agenda of Space Agencies, the concerns related to space radiation exposure of the crew are still without conclusive solutions. The risk of long-term detrimental health effects needs to be kept below acceptable limits, and emergency countermeasures must be planned to avoid the short-term consequences of exposure to high particle fluxes during hardly predictable solar events. Space habitat shielding cannot be the ultimate solution: the increasing complexity of future missions will require astronauts to protect themselves in low-shielded areas, e.g. during emergency operations. Personal radiation shielding is promising, particularly if using available resources for multi-functional shielding devices. In this work we report on all steps from the conception, design, manufacturing, to the final test on board the International Space Station (ISS) of the first prototype of a water-filled garment for emergency radiation shielding against solar particle events. The garment has a good shielding potential and comfort level. On-board water is used for filling and then recycled without waste. The successful outcome of this experiment represents an important breakthrough in space radiation shielding, opening to the development of similarly conceived devices and their use in interplanetary missions as the one to Mars