Shaping memory consolidation via targeted memory reactivation during sleep

Recent studies have shown that the reactivation of specific memories during sleep can be modulated using external stimulation. Specifically, it has been reported that matching a sensory stimulus (e.g., odor or sound cue) with target information (e.g., pairs of words, pictures, and motor sequences) during wakefulness, and then presenting the cue alone during sleep, facilitates memory of the target information. Thus, presenting learned cues while asleep may reactivate related declarative, procedural, and emotional material, and facilitate the neurophysiological processes underpinning memory consolidation in humans. This paradigm, which has been named targeted memory reactivation, has been successfully used to improve visuospatial and verbal memories, strengthen motor skills, modify implicit social biases, and enhance fear extinction. However, these studies also show that results depend on the type of memory investigated, the task employed, the sensory cue used, and the specific sleep stage of stimulation. Here, we present a review of how memory consolidation may be shaped using noninvasive sensory stimulation during sleep

Proteomic analysis of hydrogen sulfide effect in inflammation. Preliminary study on the effectiveness of sulfureous mineral water inhalation in COPD

Background: Hydrogen sulphide (H2S) is enzymatically generated in various tissues and exerts many physiological effects that suggest its potential role as a regulatory mediator. H2S is involved in the regulation of vascular tone, erectile function, myocardial contractility, inflammation, neurotransmission and insulin secretion. In particular, this gaseous mediator influences the activation of cellular inflammatory processes. On this basis, it is clear the usefulness of molecules able to modulate the plasma and tissue concentration of H2S, especially in the presence of pathologies characterized by the increase in oxidative stress, as occurs in some cardiovascular, metabolic and respiratory diseases. An interesting and certainly innovative approach is the possibility of using molecules capable of slowly releasing H2S in vivo. Taking into account the functional effects of hydrogen sulfide, it is particularly interesting the well-known efficacy of sulfureous inhalation crenotherapy in inflammatory diseases of the respiratory system. Aim: In order to understand the mechanism of the modulatory effect of hydrogen sulfide in inflammation, the proteomic profiling of human neutrophils was performed. The proteome analysis was used to understand the effects of treatments with hydrogen sulfide at the level of protein expression, to study and identify proteins that change the level of expression or undergo post-translational modifications. Furthermore, we investigated the effect of a inhalation crenotherapy cycle with sulfureous waters on a group of patients with COPD evaluating the possible improvement of symptoms and quality of life through the St George’s Respiratory Questionnaire (SGRQ). Materials and Methods: The proteomic analysis on the effects of hydrogen sulfide was carried out on human neutrophils isolated from healthy donors. Extrated cell proteins were resolved by two-dimensional gel electrophoresis and subjected to MALDI mass spectrometry analysis. In the preliminary clinical study, 38 patients with stabilized COPD and 12 healthy smokers and non-smokers were recruited. Patients were treated by one day inhalation with sulfureous bicarbonate calcium water for 12 days. The group was divided into two subgroups, one of which was treated with inhalation by a positive pressure intermittent ventilator and the other subjected to inhalation using conventional aerosol. Results: The proteomic analysis showed in activated neutrophils a high level of expression of the glycolysis enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) compared to the level of the same enzyme in resting neutrophils. In contrast, a decrease in the amount of GAPDH in activated neutrophils was observed in the presence of hydrogen sulfide. The clinical efficacy of sulfureous crenotherapy was assessed by the administration of the validated SGRQ to test the quality of life in patients with COPD. At the end of sulfureous crenotherapy, we observed a significant reduction of the SGRQ score especially in patients treated with positive pressure ventilation. Conclusions: Interestingly, hydrogen sulfide is able to modulate the functional response of neutrophils by influencing the energy metabolism of activated leukocytes. Based on the clinical efficacy of sulfureous crenotherapy in patients with COPD, it will be worth to investigate whether the same functional changes on the leukocytes of the COPD patients can be observed following the sulfureous crenotherapy

Cationic liposomes as efficient nanocarriers for the drug delivery of an anticancer cholesterol-based ruthenium complex

Aiming for novel tools for anticancer therapies, a ruthenium complex, covalently linked to a cholesterol-​contg. nucleolipid and stabilized by co-​aggregation with a biocompatible lipid, is here presented. The amphiphilic ruthenium complex, named ToThyCholRu, is intrinsically neg. charged and has been inserted into liposomes formed by the cationic 1,​2-​dioleyl-​3-​trimethylammoniumpropane chloride (DOTAP) to hinder the degrdn. kinetics typically obsd. for known ruthenium-​based antineoplastic agents. The here described nanovectors contain up to 30​% in moles of the ruthenium complex and are stable for several weeks. This drug delivery system has been characterized using dynamic light scattering (DLS)​, small angle neutron scattering (SANS)​, neutron reflectivity (NR) and ESR techniques. Fluorescence microscopy, following the incorporation of rhodamine-​B within the ruthenium-​loaded liposomes, showed fast cellular uptake in human carcinoma cells, with a strong fluorescence accumulation within the cells. The in vitro bioactivity profile revealed an important antiproliferative activity and, most remarkably, the highest ability in ruthenium vectorization measured so far. Cellular morphol. changes and DNA fragmentation provided evidence of an apoptosis-​inducing activity, in line with several in vitro studies supporting apoptotic events as the main cause for the anticancer properties of ruthenium derivs. Overall, these data highlighted the crucial role played by the cellular uptake properties in detg. the anticancer efficacy of ruthenium-​based drugs, showing DOTAP as a very efficient nanocarrier for their stabilization in aq. media and transport in cells. In vitro bioscreens have shown the high antiproliferative activity of ToThyCholRu-​DOTAP liposomes against specific human adenocarcinoma cell types. Furthermore, these formulations have proved to be over 20-​fold more effective against MCF-​7 and WiDr adenocarcinoma cells with respect to the nude ruthenium complex AziRu we have previously described

Antiproliferative effects of ruthenium-based nucleolipidic nanoaggregates in human models of breast cancer in vitro: insights into their mode of action

Looking for new metal-based anticancer treatments, in recent years many ruthenium complexes have been proposed as effective and safe potential drugs. In this context we have recently developed a novel approach for the in vivo delivery of Ru(III) complexes, preparing stable ruthenium-based nucleolipidic nanoaggregates endowed with significant antiproliferative activity. Herein we describe the cellular response to our ruthenium-containing formulations in selected models of human breast cancer. By in vitro bioscreens in the context of preclinical studies, we have focused on their ability to inhibit breast cancer cell proliferation by the activation of the intrinsic apoptotic pathway, possibly via mitochondrial perturbations involving Bcl-2 family members and predisposing to programmed cell death. In addition, the most efficient ruthenium-containing cationic nanoaggregates we have hitherto developed are able to elicit both extrinsic and intrinsic apoptosis, as well as autophagy. To limit chemoresistance and counteract uncontrolled proliferation, multiple cell death pathways activation by metal-based chemotherapeutics is a challenging, yet very promising strategy for targeted therapy development in aggressive cancer diseases, such as triple-negative breast cancer with limited treatment options. These outcomes provide valuable, original knowledge on ruthenium-based candidate drugs and new insights for future optimized cancer treatment protocols

Data_Sheet_1_Guilt, shame, and embarrassment: similar or different emotions? A comparison between Italians and Americans.PDF

IntroductionGuilt, shame, and embarrassment represent affective experiences with social implications and diverse self-relevant negative affect. While the distinction between these emotion terms has been extensively investigated, little is known about how they diverge and are related to each other and their crosscultural differences.MethodsHere, we used a community sample (N = 163) comprised of Americans and Italians and a scenario-based measure in which we asked participants to report the intensity of emotions that the story’s main character would feel. The elements used to build the scenarios were based on a recent theoretical approach that proposes distinguishing cognitive, somatic, interoceptive, and behavioral ingredients to differentiate between these emotions. We hypothesized that these ingredients might effectively elicit the target emotions and that the main differences across these cultures would be associated with the emotion terms of shame/vergogna.ResultsOur findings suggest that these defining elements are effective in evoking experiences of guilt, shame, and embarrassment. Moreover, we found that shame was equally elicited by the Shame and Guilt Scenarios only in the American sample, thus suggesting a proximity between shame and guilt in the American sample compared to the Italian’s terms of vergogna and colpa.DiscussionThese results suggest important implications for the psychology of moral emotions and highlight the importance of taking into account some cognitive factors, such as the quality of self-evaluation, the discrepancy between the actual self and the ideal self vs. the sense of perceived responsibility, and the different domains related to self-esteem.</p

Mapping the microbial diversity associated with different geochemical regimes in the shallow-water hydrothermal vents of the Aeolian archipelago, Italy

: Shallow-water hydrothermal vents are unique marine environments ubiquitous along the coast of volcanically active regions of the planet. In contrast to their deep-sea counterparts, primary production at shallow-water vents relies on both photoautotrophy and chemoautotrophy. Such processes are supported by a range of geochemical regimes driven by different geological settings. The Aeolian archipelago, located in the southern Tyrrhenian sea, is characterized by intense hydrothermal activity and harbors some of the best sampled shallow-water vents of the Mediterranean Sea. Despite this, the correlation between microbial diversity, geochemical regimes and geological settings of the different volcanic islands of the archipelago is largely unknown. Here, we report the microbial diversity associated with six distinct shallow-water hydrothermal vents of the Aeolian Islands using a combination of 16S rRNA amplicon sequencing along with physicochemical and geochemical measurements. Samples were collected from biofilms, fluids and sediments from shallow vents on the islands of Lipari, Panarea, Salina, and Vulcano. Two new shallow vent locations are described here for the first time. Our results show the presence of diverse microbial communities consistent in their composition with the local geochemical regimes. The shallow water vents of the Aeolian Islands harbor highly diverse microbial community and should be included in future conservation efforts

Current methods to analyze lysosome morphology, positioning, motility and function.

Funder: Maratona da SaúdeFunder: Royal Society WolfsonFunder: Wellcome; Id: http://dx.doi.org/10.13039/100010269Since the discovery of lysosomes more than 70 years ago, much has been learned about the functions of these organelles. Lysosomes were regarded as exclusively degradative organelles, but more recent research has shown that they play essential roles in several other cellular functions, such as nutrient sensing, intracellular signalling and metabolism. Methodological advances played a key part in generating our current knowledge about the biology of this multifaceted organelle. In this review, we cover current methods used to analyze lysosome morphology, positioning, motility and function. We highlight the principles behind these methods, the methodological strategies and their advantages and limitations. To extract accurate information and avoid misinterpretations, we discuss the best strategies to identify lysosomes and assess their characteristics and functions. With this review, we aim to stimulate an increase in the quantity and quality of research on lysosomes and further ground-breaking discoveries on an organelle that continues to surprise and excite cell biologists