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Neonatal Maternal Separation and Alcohol Abuse in C57BL/6J mice: A Study of the Functional Alterations of GABAergic and GLUergic Systems and the Possible Protective Role of Esterogen
No full textStress in early life may play a very important role in neurobiology of addiction developed in adulthood. In this study we investigated the effects of neonatal repeated maternal separation (RMS) on alcohol abuse in adult C57BL/6J mice and potential functional alterations of GABAergic and GLUergic systems in different brain areas. Male animals subjected to RMS consumed significantly higher amount of ethanol when compared to control counterparts. In addition, RMS is markedly associated with severe impairments in both GABAergic and GLUergic transmission that are crucial to the physiologic function of brain areas such as hippocampus and amygdala, involving learning and memory as well as fear and anxiety physiology, respectively. Interestingly females do not shown significant difference in ethanol consumption and impairments in both GABA and GLU neurotransmission, we thus studied the possible protective role showed by estrogen. Animals treated with β-ethinyl estradiol and exposed to RMS showed a similar ethanol preference when compared with controls and some of RMS-induced effect on GABA and GLU neurotransmission impairment are recovered. All together, our behavioral and electrophysiological results suggest that specific stress insult during early stage of life may markedly contribute to the onset of behavioral as well as neuropsychiatric disorders occurring in adulthood
Analisi dei profili di espressione dei microRNA: identificazione di biomarker nel suicidio
Full text linkMicroRNAs (miRNAs) are small non-coding RNAs playing an important role as post-transcriptional regulators of gene expression. A growing body of evidence has shown that alterations in miRNA expression pattern are associated with several pathological processes.
In particular, post-mortem brain studies support miRNA involvement in the pathophysiology of psychiatric disorders but their role as peripheral biomarkers or targets of pharmacological treatments has been scarcely investigated.
Our purpose was to identify potential biological correlates of suicide and to evaluate their role in the pathogenesis and pharmacotherapy of suicide. We conducted a high-throughput profiling of miRNAs in lymphoblastoid cell lines (LCLs), not-treated or treated with lithium in vitro, derived from bipolar suicide completers (S, n=7) and non-suicidal bipolar patients (NS, n=12). Global miRNA expression was measured using nCounter® miRNA expression Assay (NanoString Technologies). In total, 28 miRNAs were differentially expressed or regulated by lithium between the two groups at a false discovery rate of 0.1. Two miRNAs were validated with quantitative Real Time-PCR (qRT-PCR): miR-4286, up-regulated in non-treated LCLs from S versus NS, and miR-186-5p, down-regulated in lithium-treated LCLs from S versus NS. Treatment of human neural progenitor cells with lithium down-regulated both miRNAs. Then, we evaluated the expression of these miRNAs in post-mortem brains from 12 suicidal bipolar subjects (Sbrain) and 13 healthy controls (Cbrain), showing an under-expression of miR-4286 in Sbrain and no differences for miR-186-5p. Finally, we performed a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to clarify the possible role of the identified miRNAs in biological mechanisms involved in suicide. Results from GO analysis indicated that miR-4286 and miR-186-5p regulate the expression of key genes involved in neuronal processes as neurogenesis and synaptic plasticity. Whereas, KEGG pathway analysis showed that both miRNAs are involved in several biological pathways that could be related to suicide, such as TGF-beta signaling pathway and long-term potentiation pathway.
In conclusion, our study suggests that miR-4286 and miR-186-5p could constitute potential biomarkers of suicide and be involved in the mechanism of action of lithium
Applicazione del processo a fanghi aerobici granulari per il trattamento di reflui petrolchimici
Full text linkAerobic granular sludge was successfully cultivated in two lab scale Granular sludge Sequencing Batch Reactors (GSBR, A and B) to remove organic matter and nitrogen from two different petrochemical wastewaters (PWs). The aim of this study was to define the best operating conditions (i.e., shear forces, inoculum source, Ca2+ concentration, pH) to achieve complete granulation and satisfactory long-term process performance. One PW was produced by the Integrated Gasification Combined Cycle (IGCC) and characterized by high concentrations of organic matter, ammonium and toxic substances like cyanides and phenols (IGCC wastewater); the other PW, collected from the equalization tank of the refinery wastewater treatment plant, was a poorly biodegradable mixture of all the refinery discharges which contained, among the others, sulfide, hydrocarbon and low concentrations of COD and ammonium (MS18 wastewater). In order to promote granulation and biomass acclimation during reactors’ start-up, synthetic influents were initially fed to the GSBRs and gradually replaced by real PWs, while a sufficiently high volumetric organic loading rate (vOLR, 3 kgCOD/m3d) was granted by dosing proper amounts of readily degradable organic carbon (sodium acetate, NaAc). Compact and well-settling granules developed into both reactors, which were able to treat 100% MS18 (GSBR-A) and 100% IGCC (GSBR-B) wastewater, showing good process performance in terms of organic matter (TOC) and NH4-N removal efficiencies (GSBR-A, 85% and 75%, respectively; GSBR-B, 94% and 78%, respectively). Mature granules in both GSBRs showed high density (GSBR-A, 58 gTSS/Lgran; GSBR-B, 65 gTSS/Lgran) leading to good solid-liquid separation (GSBR-A, SVI8, 39 mL/gTSS; GSBR-B, SVI8, 10 mL/gTSS) and high biomass retention (GSBR-A, 7,5 gVSS/L; GSBR-B, 4,7 gVSS/L). Although a slight inhibition occurred as the PW fraction in the synthetic influents was progressively increased, granular biomass always showed a quick recovery.
As the synthetic influents were completely replaced by PWs, the supply of NaAc was progressively reduced and finally suspended in order to minimize the operating costs (the corresponding vOLR was reduced to 0,71 kgCOD/m3d and 1,15 kgCOD/m3d in GSBR-A and GSBR-B, respectively). However, both GSBRs maintained satisfactory process performance and their ability to withstand toxic substances contained in PWs.
The results achieved in this study indicate that the aerobic granular sludge technology may be considered as a valid option for the treatment of petrochemical wastewaters, alone (GSBR-A) or in combination (GSBR-B) with conventional systems
Studio di un modello di correlazione tra la fluttuazione del tenore di metalli pesanti e di altri fattori ambientali e la salute umana in Sardegna
Full text linkSince the first half of the 20th century, the incidence of Multiple Sclerosis (MS), Type 1 Diabetes (T1D) and
Autism Spectrum Disorders (ASDs) has increased in Sardinia. T1D results from autoimmune destruction of
insulin, producing beta cells of the pancreas; MS is a chronic disease of the central nervous system, causing
neurological affliction; Autism is defined as a complex developmental disability that generally appears
during the first three years of life. Concerning MS and T1D, Sardinia island has one of the highest incidence
rate in the world. In this island, there is the presence of phenotypes of these diseases, due to the
homogeneous genetic background of the local population. Indeed, Sardinia population is a genetic isolate.
The genetic background by itself does not explain such increasing incidence. T1D and MS increase with
latitude, but Sardinia is an exception. Furthermore, mining exploitation was one of the most important
economic activities in Sardinia during the past centuries and a lot of data are today available for the
researchers. For this reasons Sardinia is an ideal setting to study a possible correlation between
environmental factors and the diseases above, because of sardinian people genetic background and
environmental peculiarities of the island.
A set of environmental data and the frequency data of MS, T1D and ASD were investigated to evaluate the
correlation between environmental factors and the frequency of these diseases. In particular, among the
environmental factors, geochemical data are included in the Geochemical Database of the Department of
Civil, Environmental Engineering and Architecture (DICAAR) of the Cagliari University. This Database is
populated by thousands of data concerning soils, rocks and stream sediments. A stream-sediment-type
sampling, which is widely used for mineral prospecting, has the advantage of effectively representing the
overall geochemical print of a wide portion of territory such as a stream basin. Environmental and diseases
data were analyzed through the statistical methods which were used by mining prospections activities.
Environmental factors considered in this study are: geochemical values of each lithology, lithology and
geology, sun exposure and climate. Also spatial analysis distribution of MS, T1D and ASDs was done.
Therefore, a correlation between the environmental factors in reference to the total population and the
frequency of the diseases was evaluated. Moreover, the correlation between the environmental factors in
both male and female population and the frequency of the diseases was investigated. In a first time these
relationships were investigate for each municipalities. Afterwards, 109 Homogeneous Areas (HA) from
lithological point of view were identified. Each Homogeneous Area includes one or more municipalities,
which have the same lithological features. Then, the relationship between the environmental factors and the
frequency of diseases was evaluated for each HA.
About T1D analyses, they revealed negative associations between the incidence of the disease and some
elements, such as Cu (r = -0.349, Pvalue = 2*10-4) and Zn (r = -0.332, Pvalue = 4.20*10-4), while, concerning
MS, a mild correlation was present between Cu (r = -0.460, Pvalue = 1*10-3) and the distribution of the
disease in the male gender. A significant correlations was calculated among Pb (r = 0.478, Pvalue = 3.43*10-
6), Cd (r = 0.412, Pvalue = 8.10*10-5), Zn (r = -0.378, Pvalue = 3.3*10-4) and the presence of ASDs.
In this research was used for the first time a geo-epidemiological approach to identify environmental factors
involved to the geographical distribution of above diseases. Moreover, the elements significantly correlated
with MS, T1D and ASDs could be markers (pathfinders) of other elements not analyzed in this study
(confounding), but they could be potentially involved on the onset of the diseases. Also, our results should be
considered as hypothesis-generating rather than hypothesis testing study. This kind of study is unusual and it
has a deep interdisciplinary approach so the present results must be better confirmed in future studies
Drosophila melanogaster Genetic Model of Parkinson’s Disease: phytotherapy approach for a new and more sustainable pre-clinical investigation
Full text linkDrosophila melanogaster (Dm) is a valuable genetic model for exploring molecular, genetic and cellular aspects of neurodegeneration in Parkinson's disease (PD), for further understanding its etiology and pathogenesis and making valid contributions to drug screening.
This study used two loss-of-function Dm mutants, PINK1B9 and LRRK2WD40 (deletion of WD40 domain), that both express essential phenotypic characteristics of PD in humans, albeit with a different biochemical mechanism and pathways. Since therapeutic treatments to limit the onset of PD are not yet available and the common approach to treating patients is to intervene by relieving symptoms, I sought to investigate the effects of two natural methanolic extracts of Mucuna pruriens (Mpe; a L-Dopa-containing herbal) and Withania somnifera Dunal (Wse). Both plants have been known and used for centuries in Ayurvedic medicine for their anti-oxidant, anti-inflammatory properties and protective features against neurodegeneration.
The two extracts were tested on both male mutants at different concentrations and different physiological states (as adult L-/A+ or as larvae and adult L+/A+). The parameters considered were lifespan, motor activity, olfactory response, synaptic protein expression, mitochondria and synaptic active zone morphology; both in treated and untreated flies. The overall results indicate that Mpe shows a significant effect on PINK1B9 mutants while Wse acts mostly on LRRK2WD40 ones. The two phytochemical extracts tested were able to counteract the motor and non-motor dysfunctions as well as the mitochondrial impairment, although to different extents depending on PD variance (Mpe-PINK1B9 vs Wse-LRRK2WD40). Additional investigations are necessary to further understand the specific characteristics of the different effects in the two types of mutants.
In detail: a) the administration of 0.1% Mpe L+/A+ on PINK1B9 significantly extended lifespan, overcame the olfactory deficit and improved climbing behavior of the PD mutant. Furthermore, TEM analysis of antennal lobes and thoracic ganglia revealed that Mpe administration prevented the loss of synaptic active zones (T-bars) and reduced the number of damaged mitochondria. Lastly, western blot analysis showed restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression, referred to WT control levels. The results highlight multiple sites of action of Mpe and suggest that its effects cannot depend only upon its L-Dopa content; b) the effect of 1% Wse L-/A+ administration on LRRK2WD40 caused a recovery of dysfunctions in locomotor activity, in muscle electrophysiological response to stimuli and in mitochondria degeneration. In contrast, the administration of Wse to Dm LRRK2WD40 as L+/A+, independent of the concentration, worsened lifespan and determined the appearance of increased endosomal activity in the thoracic ganglia.
In conclusion, this study strengthens the relevance of using PINK1B9 Dm and LRRK2WD40 Dm as a translational model in studying the properties of both Mucuna pruriens and Withania somnifera for PD treatment
On Inflationary cosmological models
Full text linkThe most common mechanisms leading to in
ation are based on models of gravity minimally
coupled to a scalar field rolling on a suitable potential V. We discuss such a
model defined by the action I = ∫√-g p [R -2 (ϕ)2 )] d4x, in order to find exact
general isotropic and homogeneous cosmological solutions displaying an in
ationary behavior
at early times and a power-law expansion at late times.
We also study the effect of the inclusion of matter (in the form of a perfect
uid): in this case,
we do not find exact solutions because of the non-integrability of the field equations, but we
can investigate their global properties (and hence their stability) by means of methods of
the theory of dynamical systems
Il precondizionamento ischemico e la regolazione dell'apparato cardiovascolare: ruolo delle terminazioni nervose libere III e IV
Full text linkBackground: Ischemic preconditioning (IP) is the exposure to brief periods of
circulatory occlusion and reperfusion in order to protect local or systemic organs
against subsequent bouts of ischemia. IP has been shown to improve exercise
performance and to delay fatigue. It has been hypothesized that IP lowers the
sensation of fatigue by reducing the discharge of group III and IV nerve endings,
which also regulate hemodynamics during the metaboreflex. We hypothesized that if
the preconditioning reduces the discharge of group III and IV nerve endings then can
reduce also the blood pressure response during the metaboreflex.
Objective: The purpose of this study is to verify if IP reduces the blood pressure
response during the metaboreflex and if improves exercise performance.
Methods: Fourteen healthy males (age between 25-48 years) participated in this
study. They underwent the following randomly assigned protocol: control exercise
recovery session (CER) test, post-exercise muscle ischemia (PEMI) test, PEMI after
IP (IP-PEMI) test. The exercises was performed with dynamic handgrip.
Hemodynamics were evaluated by echocardiography and impedance cardiography.
Results: We found that after IP the mean arterial pressure response was reduced in
comparison with the PEMI test (+3.37±6.41 vs. +9.16±7.09 mmHg; P < 0.05). It was
reduced because of a lower stroke volume during the IP-PEMI in comparison with
the PEMI test (-1.43±15.35 vs. +10.28±10.479 ml; P < 0.05).
Conclusions: The main result of the present investigation was that IP was able to
reduce the blood pressure response during the metaboreflex activation. The IP seems
to change hemodynamics mainly because it impairs the capacity to augment venous
return and to recruit the cardiac pre-load reserve. It was hypothesized that this is the
consequence of an increased nitric oxide production which reduces the possibility to
constrict venous capacity vessels
La risposta cardiocircolatoria all’attivazione dei metaboriflessi muscolari nella sclerosi multipla
Full text linkThe muscle metaboreflex activation has been shown essential to reach normal hemodynamic response during exercise. It has been demonstrated in numerous studies that patients with multiple sclerosis (MS) have impaired autonomic functions and cardiovascular regulation during exercise. However, to the best of our knowledge, no previous research to date has studied the metaboreflex in MS patients. The purpose of this study was to investigate the hemodynamic response to metaboreflex activation in patients with MS (n= 43) compared to an age-matched, control group (CTL, n= 21). Cardiovascular response during the metaboreflex activation was evaluated using the post-exercise muscle ischemia (PEMI) method and during a control exercise recovery (CER) test. The difference in hemodynamic parameters between the PEMI and the CER test was calculated and this procedure allowed for the assessment of the metaboreflex response. Hemodynamics was estimated by impedance cardiography. The MS group showed a normal mean blood pressure (MBP) response as compared to the CTL group (+6.5±6.9 vs. +8±6.8 mmHg respectively), but this response was achieved with an increase in systemic vascular resistance (SVR), that was higher in the MS with respect to the CTL group (+137.6±300.5 vs. -14.3±240 dyne·s-1·cm-5 respectively). This was the main consequence of the MS group’s incapacity to raise the stroke volume (-0.65±10.6 vs. +6.2±12.8 ml respectively). It was concluded that MS patients have an impaired capacity to increase stroke volume (SV) in response to metaboreflex activation, even if they could sustain the MBP response by vasoconstriction. This was probably a consequence of their chronic physical de-conditioning
Il contratto di assicurazione sulla vita a favore di terzo: alternativa al testamento?
Full text linkLife insurance contract is a well-fitted instrument to ensure wealth transmission as an
alternative to last will and testament. The possibility to state or revoke the beneficiary
indication by will and its effectiveness since the death of the insured, gives the opportunity to
avoid the ban of succession agreements or necessary succession. In addition, the social
security aim, which characterizes this kind of contract, allows guaranteeing the insured
amount of money and a favourable tax application. These reasons are suitable to make it a
reasonable choice to optimize wealth distribution despite of or in accordance to last will and
testament. The synergic adoption of these two options, which show to compensate the
respective disadvantages, allows guaranteeing an optimal wealth distribution, in the case that
the judicial system would continue to recognize the reserved share of an estate, assigned by
law, to a specific relative regardless of the content of the will
Reti complesse e analisi del segnale elettroencefalografico
Full text linkThe identification of subject-specific traits extracted from patterns of brain activity still represents an important challenge. The need to detect distinctive brain features, which is relevant for biometric and brain computer interface systems, has been also emphasized in monitoring the effect of clinical treatments and in evaluating the progression of brain disorders. Graph theory and network science tools have revealed fundamental mechanisms of functional brain organization in resting-state M/EEG analysis. Nevertheless, it is still not clearly understood how several methodological aspects may bias the topology of the reconstructed functional networks. In this context, the literature shows inconsistency in the chosen length of the selected epochs, impeding a meaningful comparison between results from different studies.
In this study we propose an approach which aims to investigate the existence of a distinctive functional core (sub-network) using an unbiased reconstruction of network topology. Brain signals from a public and freely available EEG dataset were analyzed using a phase synchronization based measure, minimum spanning tree and k-core decomposition. The analysis was performed for each classical brain rhythm separately. Furthermore, we aim to provide a network approach insensitive to the effects that epoch length has on functional connectivity (FC) and network reconstruction. Two different measures, the phase lag index (PLI) and the Amplitude Envelope Correlation (AEC), were applied to EEG resting-state recordings for a group of eighteen healthy volunteers. Weighted clustering coefficient (CCw), weighted characteristic path length (Lw) and minimum spanning tree (MST) parameters were computed to evaluate the network topology. The analysis was performed on both scalp and source-space data.
Results about distinctive functional core, show highest classification rates from k-core decomposition in gamma (EER=0.130, AUC=0.943) and high beta (EER=0.172, AUC=0.905) frequency bands.
Results from scalp analysis concerning the influence of epoch length, show a decrease in both mean PLI and AEC values with an increase in epoch length, with a tendency to stabilize at a length of 12 seconds for PLI and 6 seconds for AEC. Moreover, CCw and Lw show very similar behaviour, with metrics based on AEC more reliable in terms of stability. In general, MST parameters stabilize at short epoch lengths, particularly for MSTs based on PLI (1-6 seconds versus 4-8 seconds for AEC). At the source-level the results were even more reliable, with stability already at 1 second duration for PLI-based MSTs.
Our results confirm that EEG analysis may represent an effective tool to identify subject-specific characteristics that may be of great impact for several bioengineering applications. Regarding epoch length, the present work suggests that both PLI and AEC depend on epoch length and that this has
an impact on the reconstructed network topology, particularly at the scalp-level. Source-level MST topology is less sensitive to differences in epoch length, therefore enabling the comparison of brain network topology between different studies