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There is an increasing trend among food business operators to use natural flavorings in meat preparation to reduce microbial spoilage and extend the shelf life. The objective of this study was to evaluate the prevalence of the use of natural flavoring mixtures in meat preparation, the possible presence of additives in natural flavorings, and the assessment of any transfer of additives contained in natural flavorings into experimentally prepared beef burgers. Based on a preliminary survey conducted as part of the study, approximately 87% of establishments used natural flavoring mixtures in meat preparation. The same natural mixtures used by local industries were added to minced meat in order to produce experimental hamburgers. Citric acid was found in both natural flavoring mixtures ranging from 1760 mg/kg to 92,731 mg/kg and experimental burgers ranging from 57 mg/kg to 2248 mg/kg. Ascorbic acid was present in all natural flavoring mixtures from 260 mg/kg to 98,858 mg/kg but was recovered in three burgers up to 1075 mg/kg. Acetic acid was found in three flavoring mixtures (range 23,539-77,421 mg/kg) and transferred to three treated burgers (range 3063-3202 mg/kg). Nitrite was never found in hamburgers and only once in a natural flavoring mixture at a dose of 26 mg/kg, whereas nitrate was found in some natural flavoring mixtures up to 788 mg/kg but never in hamburgers. The study has raised some critical issues about the appropriate and conscious use of natural flavorings and the possible inadequate meat preparation labeling in the Umbria region.

ObjectiveSexual functioning is a multifaceted aspect of human life that can be profoundly affected in patients with glioma. Most frequent symptoms include reduced sexual desire, difficulties in sexual arousal, or low satisfaction. Such symptoms may cause distress or interpersonal difficulties, inevitably resulting in negative outcomes on different domains of patients’ quality of life. Despite this, sexuality is rarely addressed by medical staff and remains understudied. An important question still unanswered is whether sexual dysfunctions in glioma patients correlate with features of the tumor itself, with its treatment, or with the secondary effects of the tumor on the patient’s psychological status. To answer this question, the present study aims to investigate the incidence of sexual life impairments in a very large population of patients with low- and high-grade gliomas, focusing on demographic, clinical, and treatment factors associated with their occurrence and developments.MethodsA total of 148 patients treated for glioma were evaluated for sexual functioning, i.e., sexual dysfunction (SD), relationship status (RS), intercourse frequency (IF), and sexual satisfaction (SS), by using a specific anonymous questionnaire. Descriptive statistics were utilized to investigate participant characteristics and to evaluate the occurrence of sexual problems. Chi-squared tests were performed to detect the association between “SS” or “IF” and different clinical/demographic factors as well as between “SS” or “IF” and the “subjective–personal skills judgment”.ResultsResults showed no difference between male and female patients, a very low frequency (1.4%) of SD, but a consistent percentage (25%) of subjective deterioration in sexual wellbeing. Notably, 24% of patients reported to have interrupted their relationship after the diagnosis. Chi-squared analyses reveal an association between adjuvant treatments (chemotherapy and radiotherapy) and reduction of IF. Interestingly, “SS” or “IF” was not associated with demographic, clinical, or histomolecular factors.ConclusionOur study showed that sexual problems in glioma patients are not uncommon, and they are especially linked to SS, RS, and IF. Specifically, intercourse frequency reduction is associated with the adjuvant treatments. Results highlight the need for improved assessment strategies and interventions tailored to the unique needs of brain tumor patients.

ObjectiveSafe resection of gliomas involving motor pathways in asleep-anesthesia requires the combination of brain mapping, to identify and spare essential motor sites, and continuous monitoring of motor-evoked potentials (MEPs), to detect possible vascular damage to the corticospinal tract (CST). MEP monitoring, according to intraoperative neurophysiology societies, is generally recommended by transcranial electrodes (TES), and no clear indications of direct cortical stimulation (DCS) or the preferential use of one of the two techniques based on the clinical context is available. The main aim of the study was to identify the best technique(s) based on different clinical conditions, evaluating the efficacy and prognostic value of both methodologies.MethodsA retrospective series of patients with tumors involving the motor pathways who underwent surgical resection with the aid of brain mapping and combined MEP monitoring via TES and DCS was evaluated. Irreversible MEP amplitude reduction (>50% compared to baseline) was used as an intraoperative warning and correlated to the postoperative motor outcome. Selectivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed for both techniques.ResultsFour hundred sixty-two patients were retrospectively analyzed, and only 1.9% showed a long-term motor impairment. Both TES and DCS obtained high specificity and NPV for the acute and 1-month motor deficit. Sensitivity was rather low for the acute deficit but excellent considering the 1-month follow-up for both techniques. DCS was extremely reliable in predicting a postoperative motor decline (PPV of 100% and 90% for acute and long-term deficit, respectively). Conversely, TES produced a high number of false-positive results, especially for long-term deficits (65, 87.8% of all warnings) therefore obtaining poor PPV values (18% and 12% for acute and 1-month deficits, respectively). TES false-positive results were significantly associated with parietal tumors and lateral patient positioning.ConclusionsData support the use of mapping and combined monitoring via TES and DCS. The sole TES monitoring is reliable in most procedures but not in parietal tumors or those requiring lateral positioning. Although no indications are available in international guidelines, DCS should be recommended, particularly for cases approached by a lateral position.

Here, using electrical stimulation on patients undergoing awake brain surgery, the authors show that disruption of the premotor cortex makes patients unconscious of motor arrest. This finding suggests the premotor cortex is crucial for motor awareness.

In primates, the parietal cortex plays a crucial role in hand-object manipulation. However, its involvement in object manipulation and related hand-muscle control has never been investigated in humans with a direct and focal electrophysiological approach. To this aim, during awake surgery for brain tumors, we studied the impact of direct electrical stimulation (DES) of parietal lobe on hand-muscles during a hand-manipulation task (HMt). Results showed that DES applied to fingers-representation of postcentral gyrus (PCG) and anterior intraparietal cortex (aIPC) impaired HMt execution. Different types of EMG-interference patterns were observed ranging from a partial (task-clumsy) or complete (task-arrest) impairment of muscles activity. Within PCG both patterns coexisted along a medio (arrest)–lateral (clumsy) distribution, while aIPC hosted preferentially the task-arrest. The interference patterns were mainly associated to muscles suppression, more pronounced in aIPC with respect to PCG. Moreover, within PCG were observed patterns with different level of muscle recruitment, not reported in the aIPC. Overall, EMG-interference patterns and their probabilistic distribution suggested the presence of different functional parietal sectors, possibly playing different roles in hand-muscle control during manipulation. We hypothesized that task-arrest, compared to clumsy patterns, might suggest the existence of parietal sectors more closely implicated in shaping the motor output.

Cassiopea andromeda (Forsskål, 1775), commonly found across the Indo-Pacific Ocean, the Red Sea, and now also in the warmest areas of the Mediterranean Sea, is a scyphozoan jellyfish that hosts autotrophic dinoflagellate symbionts (family Symbiodiniaceae). Besides supplying photosynthates to their host, these microalgae are known to produce bioactive compounds as long-chain unsaturated fatty acids, polyphenols, and pigments, including carotenoids, with antioxidant properties and other beneficial biological activities. By the present study, a fractionation method was applied on the hydroalcoholic extract from two main body parts (oral arms and umbrella) of the jellyfish holobiont to obtain an improved biochemical characterization of the obtained fractions from the two body parts. The composition of each fraction (i.e., proteins, phenols, fatty acids, and pigments) as well as the associated antioxidant activity were analyzed. The oral arms proved richer in zooxanthellae and pigments than the umbrella. The applied fractionation method was effective in separating pigments and fatty acids into a lipophilic fraction from proteins and pigment–protein complexes. Therefore, the C. andromeda–dinoflagellate holobiont might be considered as a promising natural source of multiple bioactive compounds produced through mixotrophic metabolism, which are of interest for a wide range of biotechnological applications.

The peripheral nervous system (PNS) has a unique ability for self-repair. Dorsal root ganglion (DRG) neurons regulate the expression of different molecules, such as neurotrophins and their receptors, to promote axon regeneration after injury. However, the molecular players driving axonal regrowth need to be better defined. The membrane glycoprotein GPM6a has been described to contribute to neuronal development and structural plasticity in central-nervous-system neurons. Recent evidence indicates that GPM6a interacts with molecules from the PNS, although its role in DRG neurons remains unknown. Here, we characterized the expression of GPM6a in embryonic and adult DRGs by combining analysis of public RNA-seq datasets with immunochemical approaches utilizing cultures of rat DRG explants and dissociated neuronal cells. M6a was detected on the cell surfaces of DRG neurons throughout development. Moreover, GPM6a was required for DRG neurite elongation in vitro. In summary, we provide evidence on GPM6a being present in DRG neurons for the first time. Data from our functional experiments support the idea that GPM6a could contribute to axon regeneration in the PNS.

This study describes the set-up and optimization of a fermentation strategy applied to a composite raw material containing jellyfish biomass as the principal ingredient. New fermented food was developed by combining fresh jellyfish Rhizostoma pulmo and the sequential solid-state submerged liquid fermentation method used in Asian countries for processing a high-salt-containing raw material. Aspergillus oryzae was used to drive the first fermentation, conducted in solid-state conditions, of a jellyfish-based product, here named Jelly paste. The second fermentation was performed by inoculating the Jelly paste with different selected bacteria and yeasts, leading to a final product named fermented Jellyfish paste. For the first time, a set of safety parameters necessary for monitoring and describing a jellyfish-based fermented food was established. The new fermented products obtained by the use of Debaryomyces hansenii BC T3-23 yeast strain and the Bacillus amyloliquefaciens MS3 bacterial strain revealed desirable nutritional traits in terms of protein, lipids and total phenolic content, as well as valuable total antioxidant activity. The obtained final products also showed a complex enzyme profile rich in amylase, protease and lipase activities, thus making them characterized by unique composite sensory odor descriptors (umami, smoked, dried fruit, spices).

In recent years, the jellyfish (JF) blooms in many coastal areas around the world, due to climate change, have pointed toward its possible exploitation as an alternative seafood product to support the global fishery sector. However, being a novel food in Western countries, there is a gap in knowledge on JF sensory properties. This research aims to develop a sensory lexicon for edible JF through a fast but reliable method, such as RATA. Sensory attributes collected from the literature were selected through RATA applied to five mildly processed JF. The lexicon selected was then validated on three JF samples, through descriptive analysis, to test its applicability and discrimination power. The results showed that RATA could be a reliable tool in the lexicon development of novel foods, such as JF. Moreover, the lexicon developed provides a valuable communication instrument, which will open new sensory research studies focusing on JF palatability.

Jellyfish, marketed and consumed as food in The Far East, are traditionally processed using salt and alum mixtures. In recent years, the interest of Western consumers in jellyfish (JF) as a food source is increasing. In Europe [European Union (EU)], JF-derived food products are regulated by a novel food law, but methods for JF treatment and processing have not been developed yet. In this study, a protocol for the stabilization and processing of JF into semi-finished food products without the use of alum is proposed for the first time. Safety and quality parameters, together with a series of technological and nutritional traits, were used to monitor the proposed process and for the characterization of the JF-derived products. Calcium lactate (E327), calcium citrate (E333), and calcium acetate (E263), which are food thickening/stabilizing agents allowed by EU regulations, were used in order to control the presence of possible microbial pathogens and spoilage species. The use of calcium lactate and citrate led to an increase in texture values (~1.7–1.8-fold higher than in starting raw materials) and in several nutritional traits such as antioxidant activity, and protein and fatty acid content. In particular, the combination of JF treatments with calcium salts and phenolic compounds resulted in an antioxidant activity increase of up to 8-fold, protein concentration increase of up to 2.6-fold, fatty acid composition maintenance, and a ω6/ω3 ratio lower than 1. For the first time, the application of phenolic compounds to improve JF technological and nutritional features was verified. This study proposes a new procedure for JF treatment and stabilization useful for future potential food applications in Western countries.

Abstract Background Protein kinases are enzymes controlling different cellular functions. Genetic alterations often result in kinase dysregulation, making kinases a very attractive class of druggable targets in several human diseases. Existing approved drugs still target a very limited portion of the human ‘kinome’, demanding a broader functional knowledge of individual and co-expressed kinase patterns in physiologic and pathologic settings. The development of novel rapid and cost-effective methods for kinome screening is therefore highly desirable, potentially leading to the identification of novel kinase drug targets. Results In this work, we describe the development of KING-REX (KINase Gene RNA EXpression), a comprehensive kinome RNA targeted custom assay-based panel designed for Next Generation Sequencing analysis, coupled with a dedicated data analysis pipeline. We have conceived KING-REX for the gene expression analysis of 512 human kinases; for 319 kinases, paired assays and custom analysis pipeline features allow the evaluation of 3′- and 5′-end transcript imbalances as readout for the prediction of gene rearrangements. Validation tests on cell line models harboring known gene fusions demonstrated a comparable accuracy of KING-REX gene expression assessment as in whole transcriptome analyses, together with a robust detection of transcript portion imbalances in rearranged kinases, even in complex RNA mixtures or in degraded RNA. Conclusions These results support the use of KING-REX as a rapid and cost effective kinome investigation tool in the field of kinase target identification for applications in cancer biology and other human diseases.

Edible jellyfish are a traditional Southeast Asian food, usually prepared as a rehydrated product using a salt and alum mixture, whereas they are uncommon in Western Countries and considered as a novel food in Europe. Here, a recently developed, new approach for jellyfish processing and stabilization with calcium salt brining was upgraded by modifying the pre-treatment step of freshly caught jellyfish and successfully applied to several edible species. Treated jellyfish obtained by the application of the optimized version of this method respected both quality and safety parameters set by EU law, including no pathogenic microorganisms, absence or negligible levels of histamine and of total volatile basic nitrogen, no heavy metals; and the total bacterial, yeast, and mold counts were either negligible or undetectable. Jellyfish treated by the presented method exhibited unique protein content, amino acid and fatty acid profiles, antioxidant activity, and texture. The optimized method, initially set up on Rhiszostoma pulmo, was also successfully applied to other edible jellyfish species (such as Cotylorhiza tuberculata, Phyllorhiza punctata, and Rhopilema nomadica) present in the Mediterranean Sea. This study discloses an innovative process for the preparation of jellyfish-based food products for potential future distribution in Europe.

ObjectiveAt present, it is not clear whether Mood Disorders (MD) and poor Health Related Quality of Life (HRQoL) in the glioma population correlate with features of the tumor, or rather with secondary symptoms associated with treatment. The aim of this study was to assess the prevalence of MD and decline in HRQoL in glioma patients, and to determine the main factors associated with these two variables.Methods80 patients affected by lower-grade gliomas (LGGs) and 65 affected by high-grade gliomas (HGGs) were evaluated, from admission up to 12 months after surgery, for MD, HRQoL, clinical characteristics, and cognitive functions. Independent factors associated with MD and low HRQoL were identified by using bivariate analysis.ResultsData showed that prevalence of low HRQoL was comparable in both groups during all the time points assessed (pre, 1, 3, 6 and 12 months after surgery). In contrast at 6 months following surgery, HGGs showed a higher prevalence of MD compared to LGGs;. Bivariate analysis revealed that factors associated with MD and HRQoL in LGGs and HGGs were different over the course of the disease. In LGGs, from the pre-operative period to one year post surgery, MD and low HRQOL were associated with the occurrence of cognitive deficits and, from the third month after surgery onward, they were also associated with the effect exerted by adjuvant treatments. In HGGs, MD were associated with cognitive deficits at 3 and 6 months after surgery, along with older age (65-75 years); HRQoL, in its Physical component in particular, was associated with older age only from 6 months after surgery.ConclusionFactors associated with MD and low HRQoL were different in LGGs and HGGs over the course of the disease. In LGGs the effect of adjuvant treatments was prominent in determining the prevalence of both MD and poor HRQoL from the third month after surgery onward. In HGGs, MD and HRQoL were associated with age, at 3 and 6 months after surgery. In both, the occurrence of cognitive deficits was significantly associated with MD.

The cellular and molecular mechanisms underlying neuropsychiatric and neurodevelopmental disorders show that most of them can be categorized as synaptopathies—or damage of synaptic function and plasticity. Synaptic formation and maintenance are orchestrated by protein complexes that are in turn regulated in space and time during neuronal development allowing synaptic plasticity. However, the exact mechanisms by which these processes are managed remain unknown. Large-scale genomic and proteomic projects led to the discovery of new molecules and their associated variants as disease risk factors. Neuronal glycoprotein M6a, encoded by the GPM6A gene is emerging as one of these molecules. M6a has been involved in neuron development and synapse formation and plasticity, and was also recently proposed as a gene-target in various neuropsychiatric disorders where it could also be used as a biomarker. In this review, we provide an overview of the structure and molecular mechanisms by which glycoprotein M6a participates in synapse formation and maintenance. We also review evidence collected from patients carrying mutations in the GPM6A gene; animal models, and in vitro studies that together emphasize the relevance of M6a, particularly in synapses and in neurological conditions.

ObjectiveGiant insular tumors are commonly not amenable to complete resection and are associated with a high postoperative morbidity rate. Transcortical approach and brain mapping techniques allow to identify peri-insular functional networks and, with neurophysiological monitoring, to reduce vascular-associated insults. Cognitive functions to be mapped are still under debate, and the analysis of the functional risk of surgery is currently limited to neurological examination. This work aimed to investigate the neurosurgical outcome (extent of resection, EOR) and functional impact of giant insular gliomas resection, focusing on neuropsychological and Quality of Life (QoL) outcomes.MethodsIn our retrospective analysis, we included all patients admitted in a five-year period with a radiological diagnosis of giant insular glioma. A transcortical approach was adopted in all cases. Resections were pursued up to functional boundaries defined intraoperatively by brain mapping techniques. We examined clinical, radiological, and intra-operative factors possibly affecting EOR and postoperative neurological, neuropsychological, and Quality of Life (QoL) outcomes.ResultsWe finally enrolled 95 patients in the analysis. Mean EOR was 92.3%. A Gross Total Resection (GTR) was obtained in 70 cases (73.7%). Five patients reported permanent morbidity (aphasia in 3, 3.2%, and superior quadrantanopia in 2, 2.1%). Suboptimal EOR associated with poor seizures control postoperatively. Extensive intraoperative mapping (inclusive of cognitive, visual, and haptic functions) decreased long-term neurological, neuropsychological, and QoL morbidity and increased EOR. Tumor infiltration of deep perforators (vessels arising either medial to lenticulostriate arteries through the anterior perforated substance or from the anterior choroidal artery) associated with a higher chance of postoperative ischemia in consonant areas, with the persistence of new-onset motor deficits 1-month post-op, and with minor EOR. Ischemic insults in eloquent sites represented the leading factor for long-term neurological and neuropsychological morbidity.ConclusionIn giant insular gliomas, the use of a transcortical approach with extensive brain mapping under awake anesthesia ensures broad insular exposure and extension of the surgical resection preserving patients’ functional integrity. The relation between tumor mass and deep perforators predicts perioperative ischemic insults, the most relevant risk factor for long-term and permanent postoperative morbidity.

Objective: The intraoperative identification and preservation of optic radiations (OR) during tumor resection requires the patient to be awake. Different tasks are used. However, they do not grant the maintenance of foveal vision during all testing, limiting the ability to constantly monitor the peripheral vision and to inform about the portion of the peripheral field that is encountered. Although hemianopia can be prevented, quadrantanopia cannot be properly avoided. To overcome these limitations, we developed an intra-operative Visual field Task (iVT) to monitor the foveal vision, alerting about the likelihood of injuring the OR during task administration, and to inform about the portion of the peripheral field that is explored. Data on feasibility and efficacy in preventing visual field deficits are reported, comparing the outcome with the standard available task (Double-Picture-Naming-Task, DPNT).Methods: Patients with a temporal and/or parietal lobe tumor in close morphological relationship with the OR, or where the resection can involve the OR at any extent, without pre-operative visual-field deficits (Humphrey) were enrolled. Fifty-four patients were submitted to iVT, 38 to DPNT during awake surgery with brain mapping neurophysiological techniques. Feasibility was assessed as ease of administration, training and mapping time, and ability to alert about the loss of foveal vision. Type and location of evoked interferences were registered. Functional outcome was evaluated by manual and Humphrey test; extent of resection was recorded. Tractography was performed in a sample of patients to compare patient anatomy with intraoperative stimulation site(s).Results: The test was easy to administer and detected the loss of foveal vision in all cases. Stimulation induced visual-field interferences, detected in all patients, classified as detection or discrimination errors. Detection was mostly observed in temporal tumors, discrimination in temporo-parietal ones. Immediate visual disturbances in DPNT group were registered in 84 vs. 24% of iVT group. At 1-month Humphrey evaluation, 26% of iVT vs. 63% of DPNT had quadrantanopia (32% symptomatic); 10% of DPNT had hemianopia. EOR was similar. Detection errors were induced for stimulation of OR; discrimination also for other visual processing tract (ILF).Conclusion: iVT was feasible and sensitive to preserve the functional integrity of the OR.

Nowadays, great efforts are made to gain insight into the molecular mechanisms that underlie structural neuronal plasticity. Moreover, the identification of signaling pathways involved in the development of psychiatric disorders aids the screening of possible therapeutic targets. Genetic variations or alterations in GPM6A expression are linked to neurological disorders such as schizophrenia, depression, and Alzheimer’s disease. GPM6A encodes the neuronal surface glycoprotein M6a that promotes filopodia/spine, dendrite, and synapse formation by unknown mechanisms. A substantial body of evidence suggests that the extracellular loops of M6a command its function. However, the proteins that associate with them and that modulate neuronal plasticity have not been determined yet. To address this question, we generated a chimera protein that only contains the extracellular loops of M6a and performed a co-immunoprecipitation with rat hippocampus samples followed by TMT/MS. Here, we report 72 proteins, which are good candidates to interact with M6a’s extracellular loops and modify its function. Gene ontology (GO) analysis showed that 63% of the potential M6a’s interactor proteins belong to the category “synapse,” at both sides of the synaptic cleft, “neuron projections” (51%) and “presynapse” (49%). In this sense, we showed that endogenous M6a interacts with piccolo, synaptic vesicle protein 2B, and synapsin 1 in mature cultured hippocampal neurons. Interestingly, about 28% of the proteins left were related to the “myelin sheath” annotation, suggesting that M6a could interact with proteins at the surface of oligodendrocytes. Indeed, we demonstrated the (cis and trans) interaction between M6a and proteolipid protein (PLP) in neuroblastoma N2a cells. Finally, the 72 proteins were subjected to disease-associated genes and variants screening by DisGeNET. Apart from the diseases that have already been associated with M6a, most of the proteins are also involved in “autistic disorder,” “epilepsy,” and “seizures” increasing the spectrum of disorders in which M6a could play a role. Data are available viaProteomeXchange with identifier PXD017347.

BackgroundMR Tractography enables non-invasive preoperative depiction of language subcortical tracts, which is crucial for the presurgical work-up of brain tumors; however, it cannot evaluate the exact function of the fibers.PurposeA systematic pipeline was developed to combine tractography reconstruction of language fiber bundles, based on anatomical landmarks (Anatomical-T), with language fMRI cortical activations. A fMRI-targeted Tractography (fMRI-T) was thus obtained, depicting the subsets of the anatomical tracts whose endpoints are located inside a fMRI activation. We hypothesized that fMRI-T could provide additional functional information regarding the subcortical structures, better reflecting the eloquent white matter structures identified intraoperatively.MethodsBoth Anatomical-T and fMRI-T of language fiber tracts were performed on 16 controls and preoperatively on 16 patients with left-hemisphere brain tumors, using a q-ball residual bootstrap algorithm based on High Angular Resolution Diffusion Imaging (HARDI) datasets (b = 3000 s/mm2; 60 directions); fMRI ROIs were obtained using picture naming, verbal fluency, and auditory verb generation tasks. In healthy controls, normalized MNI atlases of fMRI-T and Anatomical-T were obtained. In patients, the surgical resection of the tumor was pursued by identifying eloquent structures with intraoperative direct electrical stimulation mapping and extending surgery to the functional boundaries. Post-surgical MRI allowed to identify Anatomical-T and fMRI-T non-eloquent portions removed during the procedure.ResultsMNI Atlases showed that fMRI-T is a subset of Anatomical-T, and that different task-specific fMRI-T involve both shared subsets and task-specific subsets – e.g., verbal fluency fMRI-T strongly involves dorsal frontal tracts, consistently with the phonogical-articulatory features of this task. A quantitative analysis in patients revealed that Anatomical-T removed portions of AF-SLF and IFOF were significantly greater than verbal fluency fMRI-T ones, suggesting that fMRI-T is a more specific approach. In addition, qualitative analyses showed that fMRI-T AF-SLF and IFOF predict the exact functional limits of resection with increased specificity when compared to Anatomical-T counterparts, especially the superior frontal portion of IFOF, in a subcohort of patients.ConclusionThese results suggest that performing fMRI-T in addition to the ‘classic’ Anatomical-T may be useful in a preoperative setting to identify the ‘high-risk subsets’ that should be spared during the surgical procedure.

Marine invertebrates represent a vast, untapped source of bioactive compounds. Cnidarians are represented by nearly 10,000 species that contain a complex mixture of venoms, collagen, and other bioactive compounds, including enzymes, oligosaccharides, fatty acids, and lipophilic molecules. Due to their high abundance in coastal waters, several jellyfish taxa may be regarded as candidate targets for the discovery of novel lead molecules and biomaterials and as a potential source of food/feed ingredients. The moon jellyfish Aurelia coerulea is one of the most common jellyfish worldwide and is particularly abundant in sheltered coastal lagoons and marinas of the Mediterranean Sea, where it first appeared—as an alien species—in the last century, when Pacific oyster cultivation began. In the present study, the antioxidant and lysozyme antibacterial activities associated with extracts from different medusa compartments—namely the umbrella, oral arms, and secreted mucus—were investigated. Extracts from the oral arms of A. coerulea displayed significant antioxidant activity. Similarly, lysozyme-like activity was the highest in extracts from oral arms. These findings suggest that A. coerulea outbreaks may be used in the search for novel cytolytic and cytotoxic products against marine bacteria. The geographically wide occurrence and the seasonally high abundance of A. coerulea populations in coastal waters envisage and stimulate the search for biotechnological applications of jellyfish biomasses in the pharmaceutical, nutritional, and nutraceutical sectors.

Increasing frequency of native jellyfish proliferations and massive appearance of non-indigenous jellyfish species recently concur to impact Mediterranean coastal ecosystems and human activities at sea. Nonetheless, jellyfish biomass may represent an exploitable novel resource to coastal communities, with reference to its potential use in the pharmaceutical, nutritional, and nutraceutical Blue Growth sectors. The zooxanthellate jellyfish Cassiopea andromeda, Forsskål, 1775 (Cnidaria, Rhizostomeae) entered the Levant Sea through the Suez Canal and spread towards the Western Mediterranean to reach Malta, Tunisia, and recently also the Italian coasts. Here we report on the biochemical characterization and antioxidant activity of C. andromeda specimens with a discussion on their relative biological activities. The biochemical characterization of the aqueous (PBS) and hydroalcoholic (80% ethanol) soluble components of C. andromeda were performed for whole jellyfish, as well as separately for umbrella and oral arms. The insoluble components were hydrolyzed by sequential enzymatic digestion with pepsin and collagenase. The composition and antioxidant activity of the insoluble and enzymatically digestible fractions were not affected by the pre-extraction types, resulting into collagen- and non-collagen-derived peptides with antioxidant activity. Both soluble compounds and hydrolyzed fractions were characterized for the content of proteins, phenolic compounds, and lipids. The presence of compounds coming from the endosymbiont zooxanthellae was also detected. The notable yield and the considerable antioxidant activity detected make this species worthy of further study for its potential biotechnological sustainable exploitation.

The development of awake intraoperative brain-mapping procedures for resection of brain tumors is of growing interest in neuroscience, because it enables direct testing of brain tissue, previously only possible in non-human primates. In a recent study performed in this setting specific effects can be induced by direct electrical stimulation on different sectors of premotor cortex during the execution of a hand manipulation task. Specifically, direct electrical stimulation applied on a dorsal sector of precentral cortex led to an increase in motor unit recruitment in hand muscles during execution of a hand manipulation task (Recruitment sector). The opposite effect was elicited when electrical stimulation was delivered more ventrally on the precentral cortex (Suppression sector). We studied whether the different effects on motor behavior induced by direct electrical stimulation applied on the two sites of the precentral cortex underlie differences in their functional connectivity with other brain areas, measured using resting state fMRI. Using healthy adults scanned as part of the Human Connectome Project, we computed the functional connectivity of each sector used as seeds. The functional connectivity patterns of the two intraoperative seeds was similar but cross-comparison revealed that the left and right Recruitment sectors had stronger functional connections with the hand region of the sensorimotor cortex, while the right Suppression region displayed stronger functional connectivity with a bilateral set of parieto-frontal areas crucial for the integration of perceptual and cognitive hand-related sensorimotor processes required for goal-related hand actions. Our results suggest that analyzing data obtained in the intraoperative setting with resting state functional magnetic resonance imaging in healthy brains can yield useful insight into the roles of different premotor sectors directly involved in hand-object interaction.

A wide variety of polyphenols are reported to have considerable antioxidant and skin photoprotective effects, although the mechanisms of action are not fully known. Environmentally friendly and inexpensive sources of natural bioactive compounds, such as olive mill wastewater (OMWW), the by-product of olive-oil processing, can be considered an economic source of bioactive polyphenols, with a range of biological activities, useful as chemotherapeutic or cosmeceutical agents. Green strategies, such as the process based on membrane technologies, allow to recover active polyphenols from this complex matrix. This study aims to evaluate the antioxidant, pro-oxidant, and photoprotective effects, including the underlying action mechanism(s), of the ultra-filtered (UF) OMWW fractions, in order to substantiate their use as natural cosmeceutical ingredient. Six chemically characterized UF-OMWW fractions, from Italian and Greek olive cultivar processing, were investigated for their antioxidant activities, measured by Trolox Equivalent Antioxidant Capacity (TEAC), LDL oxidation inhibition, and ROS-quenching ability in UVA-irradiated HEKa (Human Epidermal Keratinocytes adult) cultures. The photoprotective properties of UF-OMWW were assayed as a pro-oxidant-mediated pro-apoptotic effect on the UVA-damaged HEKa cells, which can be potentially involved in the carcinogenesis process. All the UF-OMWW fractions exerted an effective antioxidant activity in vitro and in cells when administered together with UV-radiation on HEKa. A pro-oxidative and pro-apoptotic effect on the UVA-damaged HEKa cells were observed, suggesting some protective actions of polyphenol fraction on keratinocyte cell cultures.

Prunus mahaleb L. is a marginal fruit crop producing cherry-like dark purple drupes with a very bitter taste, rich in polyphenolic compounds. A mahaleb fruit concentrated extract (mfce) has been assayed for its biological activities. In this work, we report results on the in vitro effects of mfce including: i) anti-proliferative, gap junction intercellular communication (GJIC) modulation and pro-apoptotic properties in a breast cancer cell line (MCF-7), ii) anti-inflammatory properties in human vascular endothelial cells (HUVEC), iii) anti-mutagenic effect on yeast Saccharomyces cerevisiae strain D7. Mfce exerted a dose-dependent anti-proliferative effect on MCF-7 cells together with a significant time-dependent increase in GJIC and a pro-apoptotic effect. Furthermore, mfce significantly reduced levels of endothelial inflammatory antigens in a concentration-dependent manner. Finally, mfce protected S. cerevisiae cells against H2O2 cytotoxicity by direct radical scavenging activity. This study demonstrated multiple healthful biological effects of mfce, highlighting it as a potential nutraceutical product.

Jellyfish are recorded with increasing frequency and magnitude in many coastal areas and several species display biological features comparable to the most popular Asiatic edible jellyfish. The biochemical and antioxidant properties of wild gelatinous biomasses, in terms of nutritional and nutraceutical values, are still largely unexplored. In this paper, three of the most abundant and commonly recorded jellyfish species (Aurelia sp.1, Cotylorhiza tuberculata and Rhizostoma pulmo) in the Mediterranean Sea were subject to investigation. A sequential enzymatic hydrolysis of jellyfish proteins was set up by pepsin and collagenase treatments of jellyfish samples after aqueous or hydroalcoholic protein extraction. The content and composition of proteins, amino acids, phenolics, and fatty acids of the three species were recorded and compared. Protein content (mainly represented by collagen) up to 40% of jellyfish dry weight were found in two of the three jellyfish species (C. tuberculata and R. pulmo), whereas the presence of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) was significantly higher in the zooxanthellate jellyfish C. tuberculata only. Remarkable antioxidant ability was also recorded from both proteinaceous and non proteinaceous extracts and the hydrolyzed protein fractions in all the three species. The abundance of collagen, peptides and other bioactive molecules make these Mediterranean gelatinous biomasses a largely untapped source of natural compounds of nutraceutical, cosmeceutical and pharmacological interest.

Edible jellyfish are mainly consumed and marketed in Southeastern Countries, generally produced by a multi-phase drying process, using mixtures of salt and alum. Recently, jellyfish have become very attractive also for Western food markets. They are novel food in Europe and no recognized handling/processing steps have been set up yet. Moreover, no specific food safety and quality parameters are available. In this study, we identified a set of safety and quality parameters for jellyfish, based on standards and process hygiene criteria used in Europe for other products. These assays were tested on three different jellyfish preparations that can be used as raw materials for subsequent food processing. All jellyfish samples revealed the absence of pathogens (Salmonella spp. and Listeria monocytogenes), Enterobacteriaceae and Pseudomonas spp., even if a limited presence of Staphylococci was observed. No biogenic amine histamine was detected and negligible levels of total volatile basic nitrogen (TVB-N) were revealed. Total bacterium, yeast and mold counts were negligible or undetectable by conventional accredited methods, and conversely the results were higher when optimized saline conditions were used. This study, for the first time, established a set of quality and safety parameters necessary for first-operations and subsequent processing of jellyfish as novel food. Highlights: Jellyfish can represent a novel food in Europe. Identification of safety and quality parameters for jellyfish food products. Saline conditions are essential for improving safety and quality assessment of jellyfish as food.

The jellyfish Rhizostoma pulmo, Macrì 1778 (Cnidaria, Rhizostomae) undergoes recurrent outbreaks in the Mediterranean coastal waters, with large biomass populations representing a nuisance or damage for marine and maritime activities. A preliminary overview of the antioxidant activity (AA) of R. pulmo proteinaceous compounds is provided here based on the extraction and characterization of both soluble and insoluble membrane-fractioned proteins, the latter digested by sequential enzymatic hydrolyses with pepsin and collagenases. All jellyfish proteins showed significant AA, with low molecular weight (MW) proteins correlated with greater antioxidant activity. In particular, collagenase-hydrolysed collagen resulted in peptides with MW lower than 3 kDa, ranging 3⁻10 kDa or 10⁻30 kDa, with AA inversely proportional to MW. No cytotoxic effect was detected on cultured human keratinocytes (HEKa) in a range of protein concentration 0.05⁻20 μg/mL for all tested protein fractions except for soluble proteins higher than 30 kDa, likely containing the jellyfish venom compounds. Furthermore, hydrolyzed jellyfish collagen peptides showed a significantly higher AA and provided a greater protective effect against oxidative stress in HEKa than the hydrolyzed collagen peptides from vertebrates. Due to a high reproductive potential, jellyfish may represent a potential socioeconomic opportunity as a source of natural bioactive compounds, with far-reaching beneficial implications. Eventually, improvements in processing technology will promote the use of untapped marine biomasses in nutraceutical, cosmeceutical, and pharmaceutical fields, turning marine management problems into a more positive perspective.

On a global scale, jellyfish populations in coastal marine ecosystems exhibit increasing trends of abundance. High-density outbreaks may directly or indirectly affect human economical and recreational activities, as well as public health. As the interest in biology of marine jellyfish grows, a number of jellyfish metabolites with healthy potential, such as anticancer or antioxidant activities, is increasingly reported. In this study, the Mediterranean “fried egg jellyfish” Cotylorhiza tuberculata (Macri, 1778) has been targeted in the search forputative valuable bioactive compounds. A medusa extract was obtained, fractionated, characterized by HPLC, GC-MS and SDS-PAGE and assayed for its biological activity on breast cancer cells (MCF-7) and human epidermal keratinocytes (HEKa). The composition of the jellyfish extract included photosynthetic pigments, valuable ω-3 and ω-6 fatty acids, and polypeptides derived either from jellyfish tissues and their algal symbionts. Extract fractions showed antioxidant activity and the ability to affect cell viability and intercellular communication mediated by gap junctions (GJIC) differentially in MCF-7and HEKa cells. A significantly higher cytotoxicity and GJIC enhancement in MCF-7 compared to HEKa cells was recorded. A putative action mechanism for the anticancer bioactivity through the modulation of GJIC has been hypothesized and its nutraceutical and pharmaceutical potential was discussed.

Observation of others' actions evokes in primary motor cortex and spinal circuits of observers a subliminal motor resonance response, which reflects the motor program encoding observed actions. We investigated the role of attention in human motor resonance with four experimental conditions, explored in different subject groups: in the first explicit condition, subjects were asked to observe a rhythmic hand flexion-extension movement performed live in front of them. In two other conditions subjects had to monitor the activity of a LED light mounted on the oscillating hand. The hand was clearly visible but it was not the focus of subjects' attention: in the semi-implicit condition hand movement was relevant to task completion, while in the implicit condition it was irrelevant. In a fourth, baseline, condition subjects observed the rhythmic oscillation of a metal platform. Motor resonance was measured with the H-reflex technique as the excitability modulation of cortico-spinal motorneurons driving a hand flexor muscle. As expected, a normal resonant response developed in the explicit condition, and no resonant response in the baseline condition. Resonant responses also developed in both semi-implicit and implicit conditions and, surprisingly, were not different from each other, indicating that viewing an action is, per se, a powerful stimulus for the action observation network, even when it is not the primary focus of subjects' attention and even when irrelevant to the task. However, the amplitude of these responses was much reduced compared to the explicit condition, and the phase-lock between the time courses of observed movement and resonant motor program was lost. In conclusion, different parameters of the response were differently affected by subtraction of attentional resources with respect to the explicit condition: time course and muscle selection were preserved while the activation of motor circuits resulted in much reduced amplitude and lost its kinematic specificity.

Plants can frequently experience low oxygen concentrations due to environmental factors such as flooding or waterlogging. It has been reported that both anoxia and the transition from anoxia to re-oxygenation determine a strong imbalance in the cellular redox state involving the production of reactive oxygen species (ROS) and nitric oxide (NO). Plant cell cultures can be a suitable system to study the response to oxygen deprivation stress since a close control of physicochemical parameters is available when using bioreactors. For this purpose, Arabidopsis cell suspension cultures grown in a stirred bioreactor were subjected to a severe anoxic stress and analyzed during anoxia and re-oxygenation for alteration in ROS and NO as well as in antioxidant enzymes and metabolites. The results obtained by confocal microscopy showed the dramatic increase of ROS, H2O2 and NO during the anoxic shock. All the ascorbate-glutathione related parameters were altered during anoxia but restored during re-oxygenation. Anoxia also induced a slight but significant increase of α-tocopherol levels measured at the end of the treatment. Overall, the evaluation of cell defenses during anoxia and re-oxygenation in Arabidopsis cell cultures revealed that the immediate response involving the overproduction of reactive species activated the antioxidant machinery including ascorbate-glutathione system, α-tocopherol and the ROS-scavenging enzymes ascorbate peroxidase, catalase and peroxidase making cells able to counteract the stress towards cell survival.

During the rubber hand illusion (RHI), subjects experience an artificial hand as part of their own body, while the real hand is subject to a sort of 'disembodiment'. Can this altered belief about the body also affect physiological mechanisms involved in body-ownership, such as motor control? Here we ask whether the excitability of the motor pathways to the real (disembodied) hand are affected by the illusion. Our results show that the amplitude of the motor-evoked potentials recorded from the real hand is significantly reduced, with respect to baseline, when subjects in the synchronous (but not in the asynchronous) condition experience the fake hand as their own. This finding contributes to the theoretical understanding of the relationship between body-ownership and motor system, and provides the first physiological evidence that a significant drop in motor excitability in M1 hand circuits accompanies the disembodiment of the real hand during the RHI experience.

Besides its function in normal cellular growth, the molecular chaperone heat shock protein 90 (Hsp90) binds to a large number of client proteins required for promoting cancer cell growth and/or survival. In an effort to discover new small molecules able to inhibit the Hsp90 ATPase and chaperoning activities, we screened, by a surface plasmon resonance assay, a small library including different plant polyphenols. The ellagitannin geraniin, was identified as the most promising molecule, showing a binding affinity to Hsp90α similar to that of 17-(allylamino)-17-demethoxygeldanamycin (17AGG). Geraniin was able to inhibit in vitro the Hsp90α ATPase activity in a dose-dependent manner, with an inhibitory efficiency comparable to that measured for 17-AAG. In addition, this compound compromised the chaperone activity of Hsp90α, monitored by the citrate synthase thermal induced aggregation assay. Geraniin decreased the viability of HeLa and Jurkat cell lines and caused an arrest in G2/M phase. We also proved that following exposure to different concentrations of geraniin, the level of expression of the client proteins c-Raf, pAkt, and EGFR was strongly down-regulated in both the cell lines. These results, along with the finding that geraniin did not exert any appreciable cytotoxicity on normal cells, encourage further studies on this compound as a promising chemical scaffold for the design of new Hsp90 inhibitors.

Plant productivity is severely affected by unfavourable environmental conditions (biotic and abiotic stresses). Among others, water deficit is the plant stress condition which mostly limits the quality and the quantity of plant products. Tolerance to water deficit is a polygenic trait strictly dependent on the coordinated expression of a large set of genes coding for proteins directly involved in stress-induced protection/repair mechanisms (dehydrins, chaperonins, enzymes for the synthesis of osmoprotectants and detoxifying compounds, and others) as well as genes involved in transducing the stress signal and regulating gene expression (transcription factors, kinases, phosphatases). Recently, research activities in the field evolved from the study of single genes directly involved in cellular stress tolerance (functional genes) to the identification and characterization of key regulatory genes involved in stress perception and transduction and able to rapidly and efficiently activate the complex gene network involved in the response to stress. The complexity of the events occurring in response to stress have been recently approached by genomics tools; in fact the analysis of transcriptome, proteome and metabolome of a plant tissue/cell in response to stress already allowed to have a global view of the cellular and molecular events occurring in response to water deficit, by the identification of genes activated and co-regulated by the stress conditions and the characterization of new signalling pathways. Moreover the recent application of forward and reverse genetic approaches, trough mutant collection development, screening and characterization, is giving a tremendous impulse to the identification of gene functions with key role in stress tolerance. The integration of data obtained by high-throughput genomic approaches, by means of powerful informatic tools, is allowing nowadays to rapidly identify of major genes/QTLs involved in stress tolerance, and to develop appropriate strategies to obtain, through genetic engineering or Marker Assisted Breeding (MAS) water stress tolerant plants. In the present review we reported the most recent results obtained, in both model and crop species, in the field of the plant genetics of water stress tolerance with special attention to new insights into the complex gene networks activated in response to water deficit (ABA-dependent and -indipendent pathways), the innovative genetic approaches to determine key gene functions (forward-reverse genetics), and the application of new genetic strategies to obtain tolerant genotypes (genetic engineering, QTL-based MAS).