A single cocaine administration alters dendritic spine morphology and impairs glutamate receptor synaptic retention in the medial prefrontal cortex of adolescent rats

The brain is still maturing during adolescence and interfering with such a vulnerable period may lead to structural and functional consequences. We investigated the effect of a single cocaine exposure on dendritic spine structure and glutamate dynamics in the medial prefrontal cortex (mPFC) of adolescent rats 7 days after a single cocaine administration. We found a reduced number of dendritic spines, suggesting that cocaine lowers the density of dendritic spines in the mPFC of adolescent rats. Since dendritic spines are postsynaptic glutamatergic protrusions, we investigated the main determinants of glutamate postsynaptic responsiveness. In the postsynaptic density, cocaine reduced the expression of the NMDA receptor subunits GluN1, GluN2A and GluN2B as well as of the AMPA GluA1 and GluA2 subunits. Cocaine also impaired their synaptic stability since the expression of the scaffolding proteins SAP102 and SAP97, critical for the anchoring of such receptors at the postsynaptic membrane, was reduced as well. The expression of PSD-95 and Arc/Arg3.1, which play structural and functional roles in glutamate neurons, was also similarly reduced. Such changes were not found in the whole homogenate, ruling out a translational effect of cocaine and implying, rather, an impaired synaptic retention at the active zones of the synapse. Notably, neither these critical glutamate determinants nor the density and morphology of the dendritic spines were altered in the mPFC of adult animals, suggesting that a single cocaine exposure selectively impairs the developmental trajectory of the glutamate synapse. These results indicate a dynamic impairment of mPFC glutamate homeostasis during a critical developmental window that persists for at least one week after a single cocaine administration. Our results identify dysfunctional glutamate synapse as a major contributor to the mechanisms that distinguish adolescent vs. adult outcomes of a single cocaine exposure

Practical indications for the prevention and management of SARS-CoV-2 in ambulatory dialysis patients : lessons from the first phase of the epidemics in Lombardy

Confronting the SARS-CoV-2 outbreak has allowed us to appreciate how efficiently highly-resourced settings can respond to crises. However even such settings are not prepared to deal with the situation, and lessons are only slowly being learnt. There is still an urgent need to accelerate protocols that lead to the implementation of rapid point-of-care diagnostic testing and effective antiviral therapies. In some high-risk populations, such as dialysis patients, where several individuals are treated at the same time in a limited space and overcrowded areas, our objective must be to ensure protection to patients, the healthcare team and the dialysis ward. The difficult Italian experience may help other countries to face the challenges. The experience of the Lombardy underlines the need for gathering and sharing our data to increase our knowledge and support common, initially experience-based, and as soon as possible evidence-based position to face this overwhelming crisis

Caveolin-1, breast cancer and ionizing radiation

Breast cancer (BC) recovery has increased in recent years thanks to efforts of Omics-based research in this field. However, despite the important results obtained, BC remains a complex multifactorial pathology that is difficult to treat appropriately. Caveolin-1 (CAV1), the basic constituent protein of specialized plasma membrane invaginations called caveolae, is emerging as a potential therapeutic biomarker in BC. This factor may modulate BC response to chemotherapy and radiation therapy. In addition, recent reports describe the key role of CAV1 during cell response to oxidative stress. The aim of the present review was to describe the biological roles of CAV1 in BC considering its contrasting dual functions as an oncogene and as a tumor suppressor. In addition, we report on how CAV1 may contribute to tumor cell response to ionizing radiation treatment. Finally, new roles of CAV1 in BC both on epithelium and stroma may be useful as prognostic indicators for patient treatment and help clinicians in the selection of the best personalized therapy

The properties, origin and evolution of stellar clusters in galaxy simulations and observations

We investigate the properties and evolution of star particles in two simulations of isolated spiral galaxies, and two galaxies from cosmological simulations. Unlike previous numerical work, where typically each star particle represents one ‘cluster’, for the isolated galaxies we are able to model features we term ‘clusters’ with groups of particles. We compute the spatial distribution of stars with different ages, and cluster mass distributions, comparing our findings with observations including the recent LEGUS survey. We find that spiral structure tends to be present in older (100s Myrs) stars and clusters in the simulations compared to the observations. This likely reflects differences in the numbers of stars or clusters, the strength of spiral arms, and whether the clusters are allowed to evolve. Where we model clusters with multiple particles, we are able to study their evolution. The evolution of simulated clusters tends to follow that of their natal gas clouds. Massive, dense, long-lived clouds host massive clusters, whilst short-lived clouds host smaller clusters which readily disperse. Most clusters appear to disperse fairly quickly, in basic agreement with observational findings. We note that embedded clusters may be less inclined to disperse in simulations in a galactic environment with continuous accretion of gas onto the clouds than isolated clouds and correspondingly, massive young clusters which are no longer associated with gas tend not to occur in the simulations. Caveats of our models include that the cluster densities are lower than realistic clusters, and the simplistic implementation of stellar feedback

Bio-based benzoxazines synthesized in a deep eutectic solvent: A greener approach toward vesicular nanosystems

A green synthesis of benzoxazines, based upon reaction of cardanol with formaldehyde and primary amines, is achieved in high yields using choline chloride-urea mixture as deep eutectic solvent. Then, it is demonstrated how the cardanol-based benxoxazines can be employed as only component for the preparation of a nanovesicular systems

Subcutaneous Adipose Tissue Transcriptome Highlights Specific Expression Profiles in Severe Pediatric Obesity: A Pilot Study

The prevalence of pediatric obesity is rising rapidly worldwide, and "omic" approaches are helpful in investigating the molecular pathophysiology of obesity. This work aims to identify transcriptional differences in the subcutaneous adipose tissue (scAT) of children with overweight (OW), obesity (OB), or severe obesity (SV) compared with those of normal weight (NW). Periumbilical scAT biopsies were collected from 20 male children aged 1-12 years. The children were stratified into the following four groups according to their BMI z-scores: SV, OB, OW, and NW. scAT RNA-Seq analyses were performed, and a differential expression analysis was conducted using the DESeq2 R package. A pathways analysis was performed to gain biological insights into gene expression. Our data highlight the significant deregulation in both coding and non-coding transcripts in the SV group when compared with the NW, OW, and OB groups. A KEGG pathway analysis showed that coding transcripts were mainly involved in lipid metabolism. A GSEA analysis revealed the upregulation of lipid degradation and metabolism in SV vs. OB and SV vs. OW. Bioenergetic processes and the catabolism of branched-chain amino acids were upregulated in SV compared with OB, OW, and NW. In conclusion, we report for the first time that a significant transcriptional deregulation occurs in the periumbilical scAT of children with severe obesity compared with those of normal weight or those with overweight or mild obesity

RNA-seq dataset of subcutaneous adipose tissue: Transcriptional differences between obesity and healthy women

In this data article, we present the dataset from the RNA-Seq analysis of subcutaneous adipose tissue collected from 5 healthy normal weight women (NW, age 37 +/- 6.7 years, BMI 24.3 +/- 0.9 kg/m(2)) and 5 obese women (OBF, age 41 +/- 12.5 years, BMI 38.2 +/- 4.6 kg/m(2)). Raw data obtained from Illumina NextSeq 500 sequencer were processed through BlueBee (R) Genomics Platform while differential expression analysis was performed with the DESeq2 R package and deposited in the GEO public repository with GSE166047 as accession number. Specifically, 20 samples divided between NW (control), OBF (obese women), OBM (obese male) and OBT2D (obese women with diabetes) are deposited in the GSE166047. We hereby describe only 10 samples (5 healthy normal weight women reported as NW and 5 obese women reported as OBF) because we refer to the data published in the article "Transcriptional characterization of Subcutaneous Adipose Tissue in obesity affected women highlights metabolic dysfunction and implications for lncRNAs" (DOI: 10.1016/j.ygeno.2021.09.014). Pathways analyses were performed on g:Profiler, Enrichr, ClueGO and GSEA to gain biological insights on gene expression. Raw data reported in GEO database along with detailed methods description reported in this data article could be reused for comparisons with other datasets on the topic to obtain transcriptional differences in a wider co-hort. Moreover, detailed pathways analysis along with cross-referenced data with other datasets will allow to identify novel dysregulated pathways and genes responsible for this regulation. The biological interpretation of this dataset, along with related in vitro experiments, is reported by Rey et al., in Genomics (DOI: 10.1016/j.ygeno.2021.09.014). (C) 2021 Published by Elsevier Inc

A combined CFD-experimental method for abrasive erosion testing of concrete

Serious damage may occur to concrete hydraulic structures, such as water galleries, spillways, and stilling basins, due to the abrasive erosion caused by the presence of solid particles in the flow. This underlines the importance of being capable in providing characterization of the concrete from the point of view of its vulnerability to abrasive erosion, in order to improve the design of the structure and the material selection. Nevertheless, the existing apparatus for concrete abrasive erosion testing are either far from allowing realistic simulation of the actual environment in which this phenomenon occurs, or show a large degree of complexity and cost. An alternative method has been developed with the aid of Computational Fluid Dynamics (CFD). CFD was first employed to verify the effectiveness of a new laboratory equipment. Afterwards, a parameter has been introduced which, by successful comparison against preliminary experiments, proved suitable to quantify the effect of the fluid dynamic conditions on the concrete abrasive erosion, thereby opening the way to CFD-based customization of the apparatus. In the future, the synergy of numerical and physical modelling will allow developing predictive models for concrete erosion, making it possible to reliably simulate real structures

Redox Imbalance in Neurological Disorders in Adults and Children

Oxygen is a central molecule for numerous metabolic and cytophysiological processes, and, indeed, its imbalance can lead to numerous pathological consequences. In the human body, the brain is an aerobic organ and for this reason, it is very sensitive to oxygen equilibrium. The consequences of oxygen imbalance are especially devastating when occurring in this organ. Indeed, oxygen imbalance can lead to hypoxia, hyperoxia, protein misfolding, mitochondria dysfunction, alterations in heme metabolism and neuroinflammation. Consequently, these dysfunctions can cause numerous neurological alterations, both in the pediatric life and in the adult ages. These disorders share numerous common pathways, most of which are consequent to redox imbalance. In this review, we will focus on the dysfunctions present in neurodegenerative disorders (specifically Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis) and pediatric neurological disorders (X-adrenoleukodystrophies, spinal muscular atrophy, mucopolysaccharidoses and Pelizaeus-Merzbacher Disease), highlighting their underlining dysfunction in redox and identifying potential therapeutic strategies