Room for space in agencification reforms: A tale of three Italian museums

The debate on agencification in the public sector has traditionally overlooked the influence of space on how autonomy unfolds in practice. Starting with the contention that organizing and space are interweaved, the study analyses the early stages of the agencification process of three Italian museums and reveals that space is a constraint to, and an enabler of, de facto autonomy for newly created entities. Space is a constraint when spatial changes are temporally misaligned with the agencification process, including directorship cycles. On the other hand, space enables de facto autonomy, as it is purposely modified to accommodate new demands and needs by newly appointed managers. The paper maintains that policy makers and site managers should seriously consider space when dealing with agencification reforms, paying attention to the revenue and cost implications of spatial solutions, and the areas of responsibility concerning buildings and objects

Proteomic profiling of retinoblastoma-derived exosomes reveals potential biomarkers of vitreous seeding

Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remains difficult in the presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes, membrane-derived nanovesicles that are secreted abundantly by aggressive tumor cells and that can be isolated from several biological fluids, represent an interesting alternative for the detection of tumor-associated biomarkers. In this study, we defined the protein signature of exosomes released by RB tumors (RBT) and vitreous seeding (RBVS) primary cell lines by high resolution mass spectrometry. A total of 5666 proteins were identified. Among these, 5223 and 3637 were expressed in exosomes RBT and one RBVS group, respectively. Gene enrichment analysis of exclusively and differentially expressed proteins and network analysis identified in RBVS exosomes upregulated proteins specifically related to invasion and metastasis, such as proteins involved in extracellular matrix (ECM) remodeling and interaction, resistance to anoikis and the metabolism/catabolism of glucose and amino acids

Production of Lipopeptides by Fermentation Processes: Endophytic Bacteria, Fermentation Strategies and Easy Methods for Bacterial Selection

Lipopeptides constitute an important class of microbial secondary metabolites. Some lipopeptides have potent therapeutic activities such as antibacterial, antiviral, antifungal, antitumor and immunomodulator. Surfactin, iturin, fengycin, lichenysin and bacillomycin D from Bacillus species, daptomycin from Streptomyces roseosporus and rhamnolipids from Pseudomonas aeruginosa are among the most studied lipopeptides. These molecules are good candidates to replace those antibiotics and antifungals with no effect on pathogenic microorganisms. Microbial lipopeptides are produced via fermentation processes by bacteria, yeast and actinomycetes either on water miscible and immiscible substrates. However, the major bottlenecks in lipopeptide production are yield increase and cost reduction. Improving the bioindustrial production processes relies on many issues such as selecting hyperproducing strains and the appropriate extraction techniques; purification and identification by Polymerase Chain Reaction(PCR), High Performance Liquid Chromatography-Mass Spectrometry(HPLC-MS), Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometry(MALDI-TOF-MS); the use of cheap raw materials and the optimization of medium-culture conditions. The purpose of this chapter is to orient the reader on the key elements in this field, including the selection of analytical strategies to get a good microbial strain as well as to show some examples of liquid and solid-state low-cost fermentation processes. Last, we introduce endophytic bacteria as lipopeptide-producer candidates

Linear Accelerator Test Facility at LNF Conceptual Design Report

Test beam and irradiation facilities are the key enabling infrastructures for research in high energy physics (HEP) and astro-particles. In the last 11 years the Beam-Test Facility (BTF) of the DA{\Phi}NE accelerator complex in the Frascati laboratory has gained an important role in the European infrastructures devoted to the development and testing of particle detectors. At the same time the BTF operation has been largely shadowed, in terms of resources, by the running of the DA{\Phi}NE electron-positron collider. The present proposal is aimed at improving the present performance of the facility from two different points of view: extending the range of application for the LINAC beam extracted to the BTF lines, in particular in the (in some sense opposite) directions of hosting fundamental physics and providing electron irradiation also for industrial users; extending the life of the LINAC beyond or independently from its use as injector of the DA{\Phi}NE collider, as it is also a key element of the electron/positron beam facility. The main lines of these two developments can be identified as: consolidation of the LINAC infrastructure, in order to guarantee a stable operation in the longer term; upgrade of the LINAC energy, in order to increase the facility capability (especially for the almost unique extracted positron beam); doubling of the BTF beam-lines, in order to cope with the signicant increase of users due to the much wider range of applications.Comment: 71 page

Cytochrome c-promoted cardiolipin oxidation generates singlet molecular oxygen

The interaction of cytochrome c (cyt c) with cardiolipin (CL) induces protein conformational changes that favor peroxidase activity. This process has been correlated with CL oxidation and the induction of cell death. Here we report evidence demonstrating the generation of singlet molecular oxygen [O-2((1)Delta(g))] by a cyt c-CL complex in a model membrane containing CL. The formation of singlet oxygen was directly evidenced by luminescence measurements at 1270 nm and by chemical trapping experiments. Singlet oxygen generation required cyt c-CL binding and occurred at pH values higher than 6, consistent with lipid-protein interactions involving fully deprotonated CL species and positively charged residues in the protein. Moreover, singlet oxygen formation was specifically observed for tetralinoleoyl CL species and was not observed with monounsaturated and saturated CL species. Our results show that there are at least two mechanisms leading to singlet oxygen formation: one with fast kinetics involving the generation of singlet oxygen directly from CL hydroperoxide decomposition and the other involving CL oxidation. The contribution of the first mechanism was clearly evidenced by the detection of labeled singlet oxygen [O-18(2)((1)Delta(g))] from liposomes supplemented with 18-oxygen-labeled CL hydroperoxides. However quantitative analysis showed that singlet oxygen yield from CL hydroperoxides was minor (<5%) and that most of the singlet oxygen is formed from the second mechanism. Based on these data and previous findings we propose a mechanism of singlet oxygen generation through reactions involving peroxyl radicals (Russell mechanism) and excited triplet carbonyl intermediates (energy transfer mechanism).FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico (CNPq)CNPq (Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico)CAPES/PROCAD-NF (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/Programa Nacional de Cooperacao Academica Novas Fronteiras)CAPES/PROCADNF (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/Programa Nacional de Cooperacao Academica Novas Fronteiras)INCT de Processos Redox em Biomedicina - RedoxomaINCT de Processos Redox em Biomedicina RedoxomaNAPRedoxomaNAP-RedoxomaL'OREAL-UNESCO for Women in ScienceLOREALUNESCO for Women in ScienceJohn Simon Guggenheim Memorial FoundationJohn Simon Memorial Guggenheim Foundatio

Neuroblastoma-secreted exosomes carrying miR‐375 promote osteogenic differentiation of bone-marrow mesenchymal stromal cells

Bone marrow (BM) is the major target organ for neuroblastoma (NB) metastasis and its involvement is associated with poor outcome. Yet, the mechanism by which NB cells invade BM is largely unknown. Tumour microenvironment represents a key element in tumour progression and mesenchymal stromal cells (MSCs) have been recognized as a fundamental part of the associated tumour stroma. Here, we show that BM-MSCs isolated from NB patients with BM involvement exhibit a greater osteogenic potential than MSCs from non-infiltrated BM. We show that BM metastasis-derived NB-cell lines secrete higher levels of exosomal miR-375, which promotes osteogenic differentiation in MSCs. Of note, clinical data demonstrate that high level of miR-375 correlates with BM metastasis in NB patients. Our findings suggest, indeed, a potential role for exosomal miR-375 in determining a favourable microenvironment in BM to promote metastatic progression. MiR-375 may, thus, represent a novel biomarker and a potential target for NB patients with BM involvement

Livros e Leituras para Instrução Económica do Povo (1746-1820

Entre 1746 e 1820 surgem diversos textos de marcados pela preocupação de instruir o povo. Entre eles sobressaem os catecismos de agricultura, corolários práticos e almanaques. As pesquisas, no âmbito da história do livro e da leitura, levaram-nos a olhar para este acervo com interesse redobrado e a extrair da sua leitura novos elementos de análise e reflexão. É neste sentido que inscrevemos este trabalho. Com efeito, pretendemos fazer uma sistematização de alguns desses textos populares, e tentaremos responder ás seguintes questões: quais eram os objectivos dos autores? Que leituras eram recomendadas para instrução popular? Eram esses textos lidos pelo povo? Os obstáculos a uma análise deste tipo foram já inventariados por Roger Chartier, a começar pela definição de povo, passando pela grande dificuldade em determinar as práticas de leitura, e são também conhecidos os dilemas de uma história popular, quer porque os textos são, normalmente, produzidos por eclesiásticos, magistrados e outros membros das elites, que tem relativamente ao povo uma atitude de superioridade intelectual e até de distanciamento; quer porque se torna difícil, ou muitas vezes impossível, dada a falta de suporte documental, descrever o impacto dessas obras nas comunidades para que foram dirigidas. Mesmo assim, pensamos que se pode traçar um quadro para nos apercebermos das ideias que animavam os autores que escreviam obras com um nítido objectivo de instruir o povo nas novas técnicas agrícolas e na indústria popular

Sustained kidney biochemical derangement in treated experimental diabetes : a clue to metabolic memory.

The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-? expression, reduced PGC-1? expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA. The sustained decrease of uric acid clearance in treated diabetes may support the prolonged kidney biochemical alterations observed after tight glycemic control, and this regulation is likely mediated by the sustained decrease of AMPK activity and the induction of inflammation. This manuscript proposes the first consideration of the possible role of hyperuricemia and the underlying biochemical changes as part of metabolic memory in diabetic nephropathy development after glycemic control

Enterobacter cloacae, an Endophyte That Establishes a Nutrient-Transfer Symbiosis With Banana Plants and Protects Against the Black Sigatoka Pathogen

Banana (Musa spp.) is an important crop worldwide, but black Sigatoka disease caused by the fungus Pseudocercospora fijiensis threatens fruit production. In this work, we examined the potential of the endophytes of banana plants Enterobacter cloacae and Klebsiella pneumoniae, as antagonists of P. fijiensis and support plant growth in nutrient limited soils by N-transfer. The two bacterial isolates were identified by MALDI-TOF mass spectrometry and corroborated by 16S rRNA sequence analysis. Both bacteria were positive for beneficial traits such as N-fixation, indole acetic acid production, phosphate solubilization, negative for 1-aminocyclopropane 1-carboxylic acid deaminase and were antagonistic to P. fijiensis. To measure the effects on plant growth, the two plant bacteria and an E. coli strain (as non-endophyte), were inoculated weekly for 60 days as active cells (AC) and heat-killed cells (HKC) into plant microcosms without nutrients and compared to a water only treatment, and a mineral nutrients solution (MMN) treatment. Bacterial treatments increased growth parameters and prevented accelerated senescence, which was observed for water and mineral nutrients solution (MMN) treatments used as controls. Plants died after the first 20 days of being irrigated with water; irrigation with MMN enabled plants to develop some new leaves, but plants lost weight (−30%) during the same period. Plants treated with bacteria showed good growth, but E. cloacae AC treated plants had significantly greater biomass than the E. cloacae HKC. After 60 days, plants inoculated with E. cloacae AC showed intracellular bacteria within root cells, suggesting that a stable symbiosis was established. To evaluate the transference of organic N from bacteria into the plants, the 3 bacteria were grown with 15NH4Cl or Na15NO3 as the nitrogen source. The 15N transferred from bacteria to plant tissues was measured by pheophytin isotopomer abundance. The relative abundance of the isotopomers m/z 872.57, 873.57, 874.57, 875.57, 876.57 unequivocally demonstrated that plants acquired 15N atoms directly from bacterial cells, using them as a source of N, to support plant growth in restricted nutrient soils. E. cloacae might be a new alternative to promote growth and health of banana crops