Analysis of metabolomic data: tools, current strategies and future challenges for omics data integration

Metabolomics is a rapidly growing field consisting of the analysis of a large number of metabolites at a system scale. The two major goals of metabolomics are the identification of the metabolites characterizing each organism state and the measurement of their dynamics under different situations (e.g. pathological conditions, environmental factors). Knowledge about metabolites is crucial for the understanding of most cellular phenomena, but this information alone is not sufficient to gain a comprehensive view of all the biological processes involved. Integrated approaches combining metabolomics with transcriptomics and proteomics are thus required to obtain much deeper insights than any of these techniques alone. Although this information is available, multilevel integration of different 'omics' data is still a challenge. The handling, processing, analysis and integration of these data require specialized mathematical, statistical and bioinformatics tools, and several technical problems hampering a rapid progress in the field exist. Here, we review four main tools for number of users or provided features (MetaCore(TM), MetaboAnalyst, InCroMAP and 3Omics) out of the several available for metabolomic data analysis and integration with other 'omics' data, highlighting their strong and weak aspects; a number of related issues affecting data analysis and integration are also identified and discussed. Overall, we provide an objective description of how some of the main currently available software packages work, which may help the experimental practitioner in the choice of a robust pipeline for metabolomic data analysis and integration

Advances toward precision therapeutics for developmental and epileptic encephalopathies

Developmental and epileptic encephalopathies are childhood syndromes of severe epilepsy associated with cognitive and behavioral disorders. Of note, epileptic seizures represent only a part, although substantial, of the clinical spectrum. Whether the epileptiform activity per se accounts for developmental and intellectual disabilities is still unclear. In a few cases, seizures can be alleviated by antiseizure medication (ASM). However, the major comorbid features associated remain unsolved, including psychiatric disorders such as autism-like and attention deficit hyperactivity disorder-like behavior. Not surprisingly, the number of genes known to be involved is continuously growing, and genetically engineered rodent models are valuable tools for investigating the impact of gene mutations on local and distributed brain circuits. Despite the inconsistencies and problems arising in the generation and validation of the different preclinical models, those are unique and precious tools to identify new molecular targets, and essential to provide prospects for effective therapeutics

Differential Recruitment of Auditory Cortices in the Consolidation of Recent Auditory Fearful Memories.

Memories of frightening events require a protracted consolidation process. Sensory cortex, such as the auditory cortex, is involved in the formation of fearful memories with a more complex sensory stimulus pattern. It remains controversial, however, whether the auditory cortex is also required for fearful memories related to simple sensory stimuli. In the present study, we found that, 1 d after training, the temporary inactivation of either the most anterior region of the auditory cortex, including the primary (Te1) cortex, or the most posterior region, which included the secondary (Te2) component, did not affect the retention of recent memories, which is consistent with the current literature. However, at this time point, the inactivation of the entire auditory cortices completely prevented the formation of new memories. Amnesia was site specific and was not due to auditory stimuli perception or processing and strictly related to the interference with memory consolidation processes. Strikingly, at a late time interval 4 d after training, blocking the posterior part (encompassing the Te2) alone impaired memory retention, whereas the inactivation of the anterior part (encompassing the Te1) left memory unaffected. Together, these data show that the auditory cortex is necessary for the consolidation of auditory fearful memories related to simple tones in rats. Moreover, these results suggest that, at early time intervals, memory information is processed in a distributed network composed of both the anterior and the posterior auditory cortical regions, whereas, at late time intervals, memory processing is concentrated in the most posterior part containing the Te2 region

Early application of ipsilateral cathodal-tDCS in a mouse model of brain ischemia results in functional improvement and perilesional microglia modulation

Early stroke therapeutic approaches rely on limited options, further characterized by a narrow therapeutic time window. In this context, the application of transcranial direct current stimulation (tDCS) in the acute phases after brain ischemia is emerging as a promising non-invasive tool. Despite the wide clinical application of tDCS, the cellular mechanisms underlying its positive effects are still poorly understood. Here, we explored the effects of cathodal tDCS (C-tDCS) 6 h after focal forelimb M1 ischemia in Cx3CR1GFP/+ mice. C-tDCS improved motor functionality of the affected forelimb, as assessed by the cylinder and foot-fault tests at 48 h, though not changing the ischemic volume. In parallel, histological analysis showed that motor recovery is associated with decreased microglial cell density in the area surrounding the ischemic core, while astrocytes were not affected. Deeper analysis of microglia morphology within the perilesional area revealed a shift toward a more ramified healthier state, with increased processes' complexity and a less phagocytic anti-inflammatory activity. Taken together, our findings suggest a positive role for early C-tDCS after ischemia, which is able to modulate microglia phenotype and morphology in parallel to motor recovery

Marco Praga e Tatiana Pavlova : due mondi teatrali a confronto

In the twenties the playwright and stage director Marco Praga became a dramatic critic on the \u201cIllustrazione italiana\u201d. In his incisive production an interesting section is devoted to Tatiana Pavlova, a Russian actress who started performing in Italy in 1923, and gradually introduced a new concept of acting and show.Referring to reviews and pictures, this article investigates two different points of view about theatre, the relationship between text and stage, performance and further components of the show

Intraoperative electrically auditory brainstem responses to monitor auditory functionality preservation during auditory brainstem implant application.

Background: Perceptual outcomes of individuals with neurofibromatosis type II implanted with auditory brainstem implant are poor, and many factors seem to be involved. Undoubtedly, the preservation of neural functionality is the crucial aspect. The aim of this study is to verify that the use of intraoperative electrically auditory brainstem responses can help to understand if there is neural damage related to the tumor, and / or surgery. Material and Methods: A retrospective case series analysis was performed to review data from 6 adult patients affected by neurofibromatosis type 2 who received an auditory brainstem implant. A correlation was sought between intraoperative electrophysiological data, auditory performance at 1 and 2.5 years of follow-up, and auditory brainstem implant stimulation levels. Results: Patients with a better perceptual outcomes were those with more intraoperative peaks and peaks with wider amplitudes in the electrically auditory brainstem response recordings. Conclusions: Electrically auditory brainstem responses used for auditory brainstem implant placement can be a valuable tool for monitoring the preservation of neural acoustic functionality

Tra Lettura e Teatro: Il caso di Libri da Ardere di Amélie Nothomb

Les combustibles (translated into Italian as Libri da ardere) is the third Amélie Nothomb work and her unique theatrical text. However, it can’t be considered as a canonical play, for its strong relationship with the page and the reader. The paper focuses on two theatrical versions produced by Teatro dell’Elfo in Milan in 2006 and 2018, adapted and directed by Cristina Crippa. The show maintains the link with the book through the declamation of stage directions by the three characters, in an experiment between reading and theatre.   Combustibles, Nothomb, Cristina Crippa, Teatro dell’Elfo