Long Term Aggresome Accumulation Leads to DNA Damage, p53-dependent Cell Cycle Arrest, and Steric Interference in Mitosis.

Juxtanuclear aggresomes form in cells when levels of aggregation-prone proteins exceed the capacity of the proteasome to degrade them. It is widely believed that aggresomes have a protective function, sequestering potentially damaging aggregates until these can be removed by autophagy. However, most in-cell studies have been carried out over a few days at most, and there is little information on the long term effects of aggresomes. To examine these long term effects, we created inducible, single-copy cell lines that expressed aggregation-prone polyglutamine proteins over several months. We present evidence that, as perinuclear aggresomes accumulate, they are associated with abnormal nuclear morphology and DNA double-strand breaks, resulting in cell cycle arrest via the phosphorylated p53 (Ser-15)-dependent pathway. Further analysis reveals that aggresomes can have a detrimental effect on mitosis by steric interference with chromosome alignment, centrosome positioning, and spindle formation. The incidence of apoptosis also increased in aggresome-containing cells. These severe defects developed gradually after juxtanuclear aggresome formation and were not associated with small cytoplasmic aggregates alone. Thus, our findings demonstrate that, in dividing cells, aggresomes are detrimental over the long term, rather than protective. This suggests a novel mechanism for polyglutamine-associated developmental and cell biological abnormalities, particularly those with early onset and non-neuronal pathologies

Contenidos de fósforo total en suelos con características vérticas de la Provincia de Entre Ríos

p.53-58En Entre Ríos, los suelos con características vérticas ocupan el 69 por ciento del total de la superficie provincial, sin contar el D elta del río Paraná (Proyecto PN U D-FA O -INTA, 1980), generalmente estos suelos son deficientes en fósforo. El objetivo de este trabajo fue evaluar el contenido de fósforo total y su distribución en las fracciones orgánicas e inorgánicas en perfiles de suelos con características vérticas de Entre Ríos. Se tomaron muestras de suelo provenientes de cuatro Vertisoles, tres Alfisoles y un Molisol con características vérticas. En superficie los contenidos de fósforo total (Pt) de los suelos de los tres ordenes estudiados fueron de 200 a 300 mg kg. Del P total superficial de estos suelos predomina la fracción de P orgánico (Po) en relación a las formas inorgánicas (Pi). La distribución del P orgánico total en el perfil sigue un patrón general de disminución con el aumento de la profundidad, mientras que el Pi tiene una tendencia opuesta. Los horizontes C mostraron valores de P inorgánico de 150 a 200 mg de P kg `1 de suelo, reduciéndose aproximadamente a la mitad en los horizontes superficiales. Como resultado de este estudio, se puede concluir que los suelos del centro norte de la provincia de Entre Ríos presentan valores bajos de Pt. En estos suelos son im portantes las proporciones de Po en superficie, las cuales oscilan entre el 60 por ciento el 70 por ciento del Pt

APPLICATION OF HEATING MICROSCOPY ON SINTERING AND MELTING BEHAVIOUR OF NATURAL SANDS OF ARCHAEOLOGICAL INTEREST

In antiquity, beach sand was one of the main raw materials for glass-making and for the production of other vitreous materials, like Egyptian blue and faience. During the 1st century AD, glass and pigments manufacturing industry was active along the Gulf of Naples, Italy, where we sampled four littoral sands. Samples were analyzed with different techniques: chemical analysis was performed by means of X-Ray Fluorescence (XRF) and mineralogical analyses with X-Ray Powder Diffraction (XRPD) and Raman Spectroscopy. The complete sintering to melting thermal behaviour of the four sands was studied by heating microscopy or hot-stage microscope (HSM) equipped with an high resolution camera capable to collect sample profile during heating. The effect of the grain size on the sintering curves, which were automatically elaborated by specimen profile transformation, was also investigated. Finally, some deductions about the granulometry effect and the presence of alkaline and alkaline-earth oxides on sintering and melting behaviour were drawn. All the four sands were found suitable for highly sintered manufacts rather than glasses, to reach complete amorphous materials the addition of fluxes was necessary

SURGERY IN PATIENTS WITH TESTICULAR MALIGNANT GERM CELL TUMORS: COMPLIANCE TO SURGICAL GUIDELINES AND RESULTS IN THE ITALIAN COOPERATIVE STUDY

Purpose: Surgery represents a main and often the only treatment in patients with testicular Malignant Germ Cell Tumors (MGCT). We analyzed the compliance to surgical guidelines and the results in a series of patients with testicular MGCT -/+ retroperitoneal node involvement, without distant metastases. Method: 42 patients, observed in 15 Centers were enrolled in the Italian Cooperative Study on MGCT (January2004–December2010). 14/42 were younger than 2 y. of age, 28/42 between 13–18 y. Treatment was delivered according to COG-Staging-System: St.I patients (complete excision with inguinal orchifunicolectomy+decrease of markers, +hemiscrotectomy if scrotal involvement) did not receive further treatment; St.II patients (scrotal involvement after hemiscrotectomy and/or retroperitoneal node (RPN) enlargement:2 cm) had RPN Dissection if residuals were suspected after PEBx3or4. Results: St.I: 26 patients. 3/26 had a scrotal approach due to suspected testicular torsion: 1/3 underwent hemiscrotectomy, 2 did not receive further therapy after decrease of alphaFP, due to patient’s or physician’s decision respectively. 3/26 were successfully treated for RPN relapse, occurred at 3,6,9 months after adequate surgery (2 adolescents, 1 infant). St.II: in 4 patients CTwas delivered due to slight enlargement of RPN (+persistent alphaFP in 1). St.III: 12 patients received CT and RPND (bilateral in 1). Histology was negative in 11/12. All patients are alive without disease, 39 in 1stCR, 3 in 2ndCR (f.u 9–86 m.:med.48). 1 St.1 patient suffered from postoperative scrotal hematoma. Among patients younger than 2 y, 10/14 had a pure YST, 12/14 had St.I disease; among those between 13–18 y, 27/28 had a mixed histology, 14/28 were St.II or St.III. In 3 adolescents a testicular prosthesis was positioned during primary operation. Conclusion: Outcome was excellent. Regional relapses, observed only in St.I patients, were cured. Surgical guidelines were followed in 40/42 cases. Scrotal approach did not worsen the outcome of patients who did not receive further treatment

Prediction of Displacements in Unstable Areas Using a Neural Model

In pipeline management the accurate prediction of weak displacements is a crucial factor in drawing up a prevention policy since the accumulation of these displacements over a period of several years can lead to situations of high risk. This work addresses the specific problem related to the prediction of displacements induced by rainfall in unstable areas, of known geology, and crossed by underground pipelines. A neural model has been configured which learns of displacements from instrumented sites (where inclinometric measurements are available) and is able to generalise to other sites not equipped with inclinometers

Identification of mobile lipids in human cancer tissues by ex vivo diffusion edited HR-MAS MRS

Magnetic Resonance Spectroscopy visible mobilelipids are considered important markers in the diagnosis ofhuman cancer and are thought to be closely involved in variousaspects of tumour transformation, such as cell proliferation,necrosis, apoptosis, hypoxia and drug resistance. A methodallowing the straightforward identification of the lipid classescontributing to the mobile lipids in human malignant tissuesis highly advisable. Ex vivo High Resolution Magic AngleSpinning Magnetic Resonance Spectroscopy was done directlyon human cerebral, renal and colorectal malignant tissuespecimens. A diffusion edited sequence, based on stimulatedecho and bipolar gradient pulses, was used to characterizemolecules with low diffusion rates, arising from mobile lipidcomponents. Cholesterol, triglycerides and phosphatidylcholineare simultaneously detected and all contribute to the mobilelipid resonances present in malignant glioma and clear cellrenal carcinoma tissue specimens spectra. On the contrary,papillary cell renal carcinoma spectrum is predominated byphosphatidylcholine resonances and that of colorectal adenocarcinoma is characterized by signals arising from triglycerides. Ex vivo diffusion edited High Resolution Magic AngleSpinning Magnetic Resonance Spectroscopy, done on intacttissue, is a powerful analytical tool to obtain a simple andimmediate identification of mobile lipid components. This can offer a significant contribution to better understanding their involvement in cancer tissues. Furthermore, ex vivo high resolution spectroscopic measurements allow to improve the interpretation of in vivo Magnetic Resonance spectra, increasing its clinical potentiality

Louis-Ferdinand Céline, literary genius or national pariah? Defining moral parameters for influential cultural figures, post- Charlie Hebdo

In January 2011 the French Minister of Culture, Frédéric Mitterrand, withdrew Louis-Ferdinand Céline from a list of famous French authors specifically selected for a national celebration of culture. This bold decision polarized opinion: while many welcomed Mitterrand’s intervention, a number of prominent writers, some of them Jewish, opposed it on the grounds that Céline’s abhorrent political beliefs – expressed in three anti-Semitic pamphlets and his flirtation with Nazism- should in no way detract from his literary genius. In the light of this controversy, and of the rise in anti-Semitism following the Charlie Hebdo attacks of January 2015, this paper proposes Céline as a vital case study of the moral parameters a democratic nation should apply to a culturally important figure whose political views are deemed unacceptably reactionary