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

The contribution of hyperspectral remote sensing to identify vegetation characteristics necessary to assess the fate of Persistent Organic Pollutants (POPs) in the environment

During recent years hyperspectral remote sensing data were successfully used to characterise the state and properties of vegetation. The information on vegetation cover and status is useful for a range of environmental modelling studies. Recent works devoted to the understanding of the fate of Persistent Organic Pollutants (POPs) in the environment showed that forests and vegetation in general act as a «sponge» for chemicals present in air and the intensity of this «capture» effect depends on some vegetation parameters such as surface area, leaf composition, turnover etc. In the framework of the DARFEM experiment conducted in late June 2001, different airborne hyperspectral images were acquired and analysed to derive some vegetation parameters of relevance for multimedia models, such as the spatial distribution of plant species and their relative foliage biomass. The study area, south west of Milan, encompasses a range of land cover types typical of Northern Italy, including intensive poplar plantations and natural broad-leaf forest. An intensive field campaign was accomplished during the aerial survey to collect vegetation parameters and radiometric measurements. Results obtained from the analysis of hyperspectral images, map of vegetation species, Leaf Area Index (LAI) and foliage biomass are presented and discussed

Diabetic striatopathy: an updated overview of current knowledge and future perspectives

Purpose: Diabetic striatopathy (DS) is a rare complication of poorly controlled diabetes mellitus (DM), characterized by hyperglycemia associated with chorea/ballism and characteristic reversible basal ganglia abnormalities on computed tomography (CT) and/or magnetic resonance imaging (MRI). We propose a narrative review of the literature on this topic, currently unknown to most, and about which physicians should be aware. We intend to summarize, critically review, and take to mean the evidence on this disorder, describing its typical features. Methods: We searched Pubmed for English-language sources using the following keywords in the title and the abstract: diabetic striatopathy, hyperglycemic non-ketotic hemichorea/hemiballism, chorea/hemichorea associated with non-ketotic hyperglycemia, diabetic hemiballism/hemichorea, chorea, hyperglycemia, and basal ganglia syndrome. We collected scientific articles, including case reports, reviews, systematic reviews, and meta-analyses from the years 1975 to 2023. We eliminated duplicate, non-English language or non-related articles. Results: Older Asian women are more frequently affected. Suddenly or insidiously hemichorea/hemiballism, mainly in the limbs, and high blood glucose with elevated HbA1c in the absence of ketone bodies have been observed. Furthermore, CT striatal hyperdensity and T1-weighted MRI hyperintensity have been observed. DS is often a treatable disease following proper hydration and insulin administration. Histopathological findings are variable, and no comprehensive hypothesis explains the atypical cases reported. Conclusion: DS is a rare neurological manifestation of DM. If adequately treated, although treatment guidelines are lacking, the prognosis is good and life-threatening complications may occur occasionally. During chorea/hemiballism, we recommend blood glucose and HbA1c evaluation. Further studies are needed to understand the pathogenesis

Quantization-Aware NN Layers with High-throughput FPGA Implementation for Edge AI

Over the past few years, several applications have been extensively exploiting the advantages of deep learning, in particular when using convolutional neural networks (CNNs). The intrinsic flexibility of such models makes them widely adopted in a variety of practical applications, from medical to industrial. In this latter scenario, however, using consumer Personal Computer (PC) hardware is not always suitable for the potential harsh conditions of the working environment and the strict timing that industrial applications typically have. Therefore, the design of custom FPGA (Field Programmable Gate Array) solutions for network inference is gaining massive attention from researchers and companies as well. In this paper, we propose a family of network architectures composed of three kinds of custom layers working with integer arithmetic with a customizable precision (down to just two bits). Such layers are designed to be effectively trained on classical GPUs (Graphics Processing Units) and then synthesized to FPGA hardware for real-time inference. The idea is to provide a trainable quantization layer, called Requantizer, acting both as a non-linear activation for neurons and a value rescaler to match the desired bit precision. This way, the training is not only quantization-aware, but also capable of estimating the optimal scaling coefficients to accommodate both the non-linear nature of the activations and the constraints imposed by the limited precision. In the experimental section, we test the performance of this kind of model while working both on classical PC hardware and a case-study implementation of a signal peak detection device running on a real FPGA. We employ TensorFlow Lite for training and comparison, and use Xilinx FPGAs and Vivado for synthesis and implementation. The results show an accuracy of the quantized networks close to the floating point version, without the need for representative data for calibration as in other approaches, and performance that is better than dedicated peak detection algorithms. The FPGA implementation is able to run in real time at a rate of four gigapixels per second with moderate hardware resources, while achieving a sustained efficiency of 0.5 TOPS/W (tera operations per second per watt), in line with custom integrated hardware accelerators

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

Understanding the origin and mixing of deep fluids in shallow aquifers and possible implications for crustal deformation studies. San Vittorino plain, Central Apennines

Expanding knowledge about the origin and mixing of deep fluids and the water–rock–gas interactions in aquifer systems can represent an improvement in the comprehension of crustal deformation processes. An analysis of the deep and meteoric fluid contributions to a regional groundwater circulation model in an active seismic area has been carried out. We performed two hydrogeochemical screenings of 15 springs in the San Vittorino Plain (central Italy). Furthermore, we updated the San Vittorino Plain structural setting with a new geological map and cross-sections, highlighting how and where the aquifers are intersected by faults. The application of Na-Li geothermometers, coupled with trace element and gas analyses, agrees in attributing the highest temperatures (>150◦C), the greatest enrichments in Li (124.3 ppb) and Cs (>5 ppb), and traces of mantle-derived He (1–2%) to springs located in correspondence with high-angle faults (i.e., S5, S11, S13, and S15). This evidence points out the role of faults acting as vehicles for deep fluids into regional carbonate aquifers. These results highlight the criteria for identifying the most suitable sites for monitoring variations in groundwater geochemistry due to the uprising of deep fluids modulated by fault activity to be further correlated with crustal deformation and possibly with seismicity

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