Il Grano di Pietro Gaudenzi. Stato di conservazione e problematiche di intervento

L\u2019opera Il grano (\u201cdipinto murale su intonaco applicato a masonite\u201d, cm 249x434, Pinacoteca del Museo Civico \u201cAla Ponzone\u201d di Cremona) viene realizzata da Pietro Gaudenzi nel 1940 per la seconda edizione del Premio Cremona istituito da Roberto Farinacci nel 1939, a seguito della necessit\ue0 di rafforzare il mercato e le quotazioni d\u2019arte attraverso mostre e premi che richiamassero i valori dell\u2019ideologia fascista in campo artistico. I cartoni preparatori degli affreschi eseguiti da Gaudenzi a Rodi, raccolti nella recente mostra (2015) Pietro Gaudenzi: gli affreschi perduti del Castello dei Cavalieri a Rodi [1], ritenuti l\u2019ultima testimonianza rimasta delle pitture murali che occupavano la Sala del pane e la Sala della famiglia del Castello - ricostruito dagli italiani dal 1936 al 1940 - evocano il trittico che vincer\ue0 il premio Cremona nel 1940. Diversamente dalle tecniche sperimentali che hanno caratterizzato molte delle opere del ritorno alla tradizione decorativa murale, Gaudenzi dipinge il trittico su un intonaco composto da un aggregato silicatico e calce. Il disegno \ue8 stato eseguito tramite incisioni dirette da cartoni preparatori, successivamente ripassate con un tratto bruno, i colori sono stati scelti tra quelli tradizionalmente usati per questo tipo di pittura, unitamente a pigmenti inorganici minerali sintetici in uso a partire dal XIX secolo. L\u2019opera, realizzata su pannelli rigidi (masonite), risulta \u2013 sul fondo \u2013 impermeabile al vapore acqueo che, in situazioni di variazione dei parametri microclimatici ambientali e a causa delle frequenti movimentazioni del dipinto, provoca sollevamenti localizzati di forme tondeggianti (a bolla). La pellicola pittorica, resa leggermente plastica dalla vernice, si rigonfia distaccandosi dal supporto in quantit\ue0 talvolta, estese. I conseguenti necessari interventi di manutenzione, mirati al consolidamento dei sollevamenti, risultano particolarmente complessi per l\u2019impossibilit\ue0 di intervenire dal retro: la necessit\ue0 di attraversare il film protettivo e penetrare la pellicola pittorica in assenza di crettature ha evidenziato l\u2019estrema fragilit\ue0 sia del film pittorico che della materia sottostante. Lo studio presenta alcune metodologie di intervento utilizzate, nel tempo, per consolidare il trittico. La possibilit\ue0 di poter analizzare alcuni microframmenti ha richiesto l\u2019applicazione di una strategia analitica basata sull\u2019uso di microscopi e microsonde. La successione degli strati tecnici \ue8 stata definita in microscopia ottica (OM) ed elettronica a scansione (SEM), su \u201ccross section\u201d. Le tessiture e la composizione chimica dei leganti e dei pigmenti dei singoli strati sono state determinate utilizzando un sistema di microanalisi in dispersione di energia (EDS) e in spettrofotometria FT-IR. Questi dati integrano le informazioni ottenute con le tecniche non invasive d\u2019immagine (luminescenza UV, riflettografia IR e riprese IR in falso colore) e puntuali (XRF) realizzate in situ

In vitro and in vivo characterization of highly purified Human Mesothelioma derived cells

<p>Abstract</p> <p>Background</p> <p>Malignant pleural mesothelioma is a rare disease known to be resistant to conventional therapies. A better understanding of mesothelioma biology may provide the rationale for new therapeutic strategies. In this regard, tumor cell lines development has been an important tool to study the biological properties of many tumors. However all the cell lines established so far were grown in medium containing at least 10% serum, and it has been shown that primary cell lines cultured under these conditions lose their ability to differentiate, acquire gene expression profiles that differ from that of tissue specific stem cells or the primary tumor they derive from, and in some cases are neither clonogenic nor tumorigenic. Our work was aimed to establish from fresh human pleural mesothelioma samples cell cultures maintaining tumorigenic properties.</p> <p>Methods</p> <p>The primary cell cultures, obtained from four human pleural mesotheliomas, were expanded in vitro in a low serum proliferation-permissive medium and the expression of different markers as well as the tumorigenicity in immunodeficient mice was evaluated.</p> <p>Results</p> <p>The established mesothelioma cell cultures are able to engraft, after pseudo orthotopic intraperitoneal transplantation, in immunodeficient mouse and maintain this ability to after serial transplantation. Our cell cultures were strongly positive for CD46, CD47, CD56 and CD63 and were also strongly positive for some markers never described before in mesothelioma cell lines, including CD55, CD90 and CD99. By real time PCR we found that our cell lines expressed high mRNA levels of typical mesothelioma markers as mesothelin (MSLN) and calretinin (CALB2), and of BMI-1, a stemness marker, and DKK1, a potent Wingless [WNT] inhibitor.</p> <p>Conclusions</p> <p>These cell cultures may provide a valuable in vitro and in vivo model to investigate mesothelioma biology. The identification of new mesothelioma markers may be useful for diagnosis and/or prognosis of this neoplasia as well as for isolation of mesothelioma tumor initiating cells.</p

Pest control and resistance management through release of insects carrying a male-selecting transgene

Development and evaluation of new insect pest management tools is critical for overcoming over-reliance upon, and growing resistance to, synthetic, biological and plant-expressed insecticides. For transgenic crops expressing insecticidal proteins from the bacterium Bacillus thuringiensis (‘Bt crops’) emergence of resistance is slowed by maintaining a proportion of the crop as non-Bt varieties, which produce pest insects unselected for resistance. While this strategy has been largely successful, multiple cases of Bt resistance have now been reported. One new approach to pest management is the use of genetically engineered insects to suppress populations of their own species. Models suggest that released insects carrying male-selecting (MS) transgenes would be effective agents of direct, species-specific pest management by preventing survival of female progeny, and simultaneously provide an alternative insecticide resistance management strategy by introgression of susceptibility alleles into target populations. We developed a MS strain of the diamondback moth, Plutella xylostella, a serious global pest of crucifers. MS-strain larvae are reared as normal with dietary tetracycline, but, when reared without tetracycline or on host plants, only males will survive to adulthood. We used this strain in glasshouse-cages to study the effect of MS male P. xylostella releases on target pest population size and spread of Bt resistance in these populations

Sox2 silencing in glioblastoma tumor initiating cells causes stop of proliferation and loss of tumorigenicity

Glioblastoma, the most aggressive cerebral tumor, is invariably lethal. Glioblastoma cells express several genes typical of normal neural stem cells. One of them, SOX2, is a master gene involved in sustaining self-renewal of several stem cells, in particular neural stem cells. To investigate its role in the aberrant growth of glioblastoma, we silenced SOX2 in freshly derived glioblastoma tumor-initiating cells (TICs). Our results indicate that SOX2 silenced glioblastoma TICs, despite the many mutations they have accumulated, stop proliferating and lose tumorigenicity in immunodeficient mice. SOX2 is then also fundamental for maintenance of the self-renewal capacity of neural stem cells when they have acquired cancer properties. SOX2, or its immediate downstream effectors, would then be an ideal target for glioblastoma therapy

Effects of Emx2 inactivation on the gene expression profile of neural precursors

Emx2 plays a crucial role in the development of the diencephalon and dorsal telencephalon. Thus, Emx2-null mutants have abnormal cortical lamination and a reduction in size of the caudal and medial areas of the prosencephalon. Emx2 is expressed in neural precursors of the subventricular zone in vivo and in cultured neurospheres in vitro where it controls the size of the transit-amplifying population, affecting proliferation and clonal efficiency of neural stem cells. To identify the cellular processes mastered by Emx2, and possibly the molecular mechanisms by which the gene exerts its action, we compared the expression profile of cultured neurospheres derived from wild-type and Emx2-null mouse embryos. The differential expression of several genes was also confirmed by semiquantitative RT-PCR, real-time PCR and cytofluorimetric analysis in different preparations of neurospheres, and by in situ hybridization. The gene expression profile suggested a role for Emx2 in regulating the differentiation and migration properties of neural precursor cells. This involvement was confirmed in vitro, where the altered clonogenicity and impaired migration of Emx2-null cells were partially corrected by transduction of the Emx2 gene. Taken together, our results indicate that Emx2 is indeed involved in the transition between resident early progenitors (perhaps stem cells) and more mature precursors capable of migrating out of the ventricular zone, becoming postmitotic and differentiating into the appropriate cell type, and help explain the alterations observed in the brains of knock-out mice

Pharmacokinetics, pharmacodynamics and efficacy on pediatric tumors of the glioma radiosensitizer KU60019

We have recently reported that glioblastoma (GB)-initiating cells (GIC) with low expression and/or mutation of TP53 and high expression of PI3K ("responder" genetic profile) can be effectively and safely radiosensitized by the ATM inhibitor KU60019. We report here on drug's diffusion and elimination from the animal body and brain, its effects on orthotopic GB and efficacy toward pediatric GIC. Healthy mice were infused by convection enhanced delivery (CED) with KU60019 and the drug kinetics followed by high performance liquid chromatography-mass spectrometry. Already at the end of CED, KU60019 had diffused from the injection site to the ipsilateral and, to a lower extent, controlateral hemisphere. After 24 hr, no drug could be detected all over the brain or in other organs, indicating rapid draining and excretion. After intraperitoneal injection, traces only of KU60019 could be detected in the brain, indicating inability to cross the brain-blood barrier. Consistent with the induction of cell cycle progression previously observed in vitro, KU60019 stimulated proliferation of orthotopic GB cells with the highest effect observed 96 hr after drug delivery. Adult GIC with high expression of TP53 and low expression of PI3K could be radiosensitized by KU60019, although less promptly than GIC bearing the "responder" profile. Consistent with the kinetics of proliferation induction, the highest radiosensitizing effect was observed 96 hr after delivery of KU60019 to GIC. Pediatric GIC could be similarly radiosensitized after exposure to KU60019. The results indicate that ATM inhibition may allow to radiosensitize a wide range of adult and pediatric high-grade gliomas

Exploiting Sphingo- and Glycerophospholipid Impairment to Select Effective Drugs and Biomarkers for CMT1A

International audienceIn Charcot-Marie-Tooth type 1A (CMT1A), Schwann cells exhibit a preponderant transcriptional deficiency of genes involved in lipid biosynthesis. This perturbed lipid metabolism affects the peripheral nerve physiology and the structure of peripheral myelin. Nevertheless, the identification and functional characterization of the lipid species mainly responsible for CMT1A myelin impairment currently lack. This is critical in the pathogenesis of the neuropathy since lipids are many and complex molecules which play essential roles in the cell, including the structural components of cellular membranes, cell signaling, and membrane trafficking. Moreover, lipids themselves are able to modify gene transcription, thereby affecting the genotype-phenotype correlation of well-defined inherited diseases, including CMT1A. Here we report for the first time a comprehensive lipid profiling in experimental and human CMT1A, demonstrating a previously unknown specific alteration of sphingolipid (SP) and glycerophospholipid (GP) metabolism. Notably, SP, and GP changes even emerge in biological fluids of CMT1A rat and human patients, implying a systemic metabolic dysfunction for these specific lipid classes. Actually, SP and GP are not merely reduced; their expression is instead aberrant, contributing to the ultrastructural abnormalities that we detailed by X-ray diffraction in rat and human internode myelin. The modulation of SP and GP pathways in myelinating dorsal root ganglia cultures clearly sustains this issue. In fact, just selected molecules interacting with these pathways are able to modify the altered geometric parameters of CMT1A myelinated fibers. Overall, we propose to exploit the present SP and GP metabolism impairment to select effective drugs and validate a set of reliable biomarkers, which remain a challenge in CMT1A neuropathy