Selective vulnerability of neurons to acute toxicity after proteasome inhibitor treatment: Implications for oxidative stress and insolubility of newly synthesized proteins

Maintaining protein homeostasis is vital to cell viability, with numerous studies demonstrating a role for proteasome inhibition occurring during the aging of a variety of tissues and, presumably, contributing to the disruption of cellular homeostasis during aging. In this study we sought to elucidate the differences between neurons and astrocytes in regard to basal levels of protein synthesis, proteasome-mediated protein degradation, and sensitivity to cytotoxicity after proteasome inhibitor treatment. In these studies we demonstrate that neurons have an increased vulnerability, compared to astrocyte cultures, to proteasome-inhibitor-induced cytotoxicity. No significant difference was observed between these two cell types in regard to the basal rates of protein synthesis, or basal rates of protein degradation, in the pool of short-lived proteins. After proteasome inhibitor treatment neuronal crude lysates were observed to undergo greater increases in the levels of ubiquitinated and oxidized proteins and selectively exhibited increased levels of newly synthesized proteins accumulating within the insoluble protein pool, compared to astrocytes. Together, these data suggest a role for increased oxidized proteins and sequestration of newly synthesized proteins in the insoluble protein pool, as potential mediators of the selective neurotoxicity after proteasome inhibitor treatment. The implications for neurons exhibiting increased sensitivity to acute proteasome inhibitor exposure, and the corresponding changes in protein homeostasis observed after proteasome inhibition, are discussed in the context of both aging and age-related disorders of the nervous system.Fil: Dasuri, Kalavathi. State University of Louisiana; Estados UnidosFil: Ebenezer, Philip J.. State University of Louisiana; Estados UnidosFil: Zhang, Le. State University of Louisiana; Estados UnidosFil: Fernandez Kim, Sun Ok. State University of Louisiana; Estados UnidosFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Gavilán, Elena. State University of Louisiana; Estados UnidosFil: Di Blasio, Alessia. State University of Louisiana; Estados UnidosFil: Keller, Jeffrey N.. State University of Louisiana; Estados Unido

A Review of Model Predictive Controls Applied to Advanced Driver-Assistance Systems

Advanced Driver-Assistance Systems (ADASs) are currently gaining particular attention in the automotive field, as enablers for vehicle energy consumption, safety, and comfort enhancement. Compelling evidence is in fact provided by the variety of related studies that are to be found in the literature. Moreover, considering the actual technology readiness, larger opportunities might stem from the combination of ADASs and vehicle connectivity. Nevertheless, the definition of a suitable control system is not often trivial, especially when dealing with multiple-objective problems and dynamics complexity. In this scenario, even though diverse strategies are possible (e.g., Equivalent Consumption Minimization Strategy, Rule-based strategy, etc.), the Model Predictive Control (MPC) turned out to be among the most effective ones in fulfilling the aforementioned tasks. Hence, the proposed study is meant to produce a comprehensive review of MPCs applied to scenarios where ADASs are exploited and aims at providing the guidelines to select the appropriate strategy. More precisely, particular attention is paid to the prediction phase, the objective function formulation and the constraints. Subsequently, the interest is shifted to the combination of ADASs and vehicle connectivity to assess for how such information is handled by the MPC. The main results from the literature are presented and discussed, along with the integration of MPC in the optimal management of higher level connection and automation. Current gaps and challenges are addressed to, so as to possibly provide hints on future developments

Microplastics Occurrence in the European Common Frog (Rana temporaria) from Cottian Alps (Northwest Italy)

Microplastics (MPs) pollution is arousing growing attention, yet knowledge about its occurrence in amphibians is scant to date. With this study, we aimed to determine whether plastic (>5000 μm) and MPs (10–5000 μm) could be detected in adult Rana temporaria from a high-mountain ecosystem (the Cottian Alps, northwest Italy). To do this, aquatic compartments and the digestive tract of adult R. temporaria were analyzed. Water, sediment, periphyton, aquatic macroinvertebrates, and tadpoles tested negative for plastic and MPs. Microplastics were detected in all the adult frogs (n = 5); all the identified items (one per specimen) were fibers (size range: 550.91–2355.51 µm). A statistically significant positive correlation between the particle length and frog size was recorded. The predominant fiber color was blue. The chemical composition was polyamide (60%), polyethylene (20%), and polyethylene terephthalate (20%). Since both the biotic and the abiotic freshwater compartments (tadpoles included) revealed the absence of MPs, it can be assumed that adult frogs ingest MPs from the surrounding terrestrial environment.This research was partially funded by Fondazione CRT, the ALPLA II project, grant number 21D03.Peer reviewe

CHIRURGIA PROFILATTICA DELLA MAMMELLA NELLE PAZIENTI PORTATRICI DI MUTAZIONE DEL GENE BRCA 1/2. PERCORSO DIAGNOSTICO-TERAPEUTICO.

Le donne portatrici di una mutazione del gene BRCA1 o BRCA2 presentano un alto rischio di sviluppare un carcinoma mammario ed ovarico nel corso della vita. Le opzioni per controllare o ridurre questo rischio sono una sorveglianza clinico-strumentale regolare, la chemioprevenzione, la chirurgia \u201crisk reducing\u201d (mastectomia bilaterale o controlaterale) e la salpingo-ooforectomia. La Chirurgia presenta una riduzione del rischio di insorgenza del carcinoma mammario ed ovarico fino al 90-95%, ma \ue8 una procedura irreversibile con implicazioni fisiche e psicologiche importanti per le donne interessate. Gli Autori riportano l\u2019esperienza in tema di tumori ereditari della mammella sottolineando l\u2019importanza di allestire un team multidisciplinare dedicato nel cui ambito sia disponibile un \u201ccounseling onco-genetico\u201d specifico e la necessit\ue0 di allestire un consenso informato adeguato a questa problematica

Micrometastasi al linfonodo sentinella in pazienti con carcinoma della mammella: quando \ue8 possibile evitare la dissezione del cavo ascellare?

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Isolation of Arcobacter species and other neglected opportunistic agents from aborted bovine and caprine fetuses

Background: Infectious abortion in ruminants is a problem in animal husbandry worldwide. It is important to obtain a diagnosis, to make sure that proper control measures can be instituted, but most abortion cases remain without an etiologic diagnosis. This report describes the presence of Arcobacter species and several neglected opportunistic abortifacient agents in ruminant abortion cases showing or not co-infections among at least one of the major recognized protozoal, fungal, bacterial and viral abortifacient agents. Results: A total of 67 fetuses (55 cattle and 12 goats) and just one placenta (cattle) were considered. Among the most common abortive agents, Neospora caninum (19,4%), followed by Chlamydophila abortus (4,5%), Listeria monocytogenes 1/2a (2,98%), Bovine Viral Diarrhea Virus type 1b (2,98%), Bovine herpesvirus 4 (2,98%), and Aspergillus spp. (2,98%) were detected. The isolated neglected opportunistic bacteria include Escherichia coli, Acinetobacter lwoffii, Staphylococcus spp., Streptococcus spp., Streptococcus uberis, Streptococcus suis, Trueperella pyogenes, Mannheimia haemolytica, Bacillus cereus and Nocardia spp. Other bacterial species, not associated with abortion by literature, but described as causes of diseases occurring sporadically both in humans and animals, were also detected. Three Arcobacter strains, namely two A. skirrowii and one A. cryaerophilus, were isolated from 3 bovine aborted fetuses, and A. butzleri was isolated from the placenta. Conclusions: A not negligible isolation of Arcobacter species and other neglected abortifacient agents has to be mentioned, with prevalences that seem to be emerging and replacing or co-placing the major infectious players in bovine and caprine reproductive failure due to abortion disease, even if further studies investigating the aetiological power and transmission routes are needed in order to define the role of these microrganisms in ruminant abortion