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A rich literature examines the determinants of income inequality. Less is known about the distribution of income composition, or the extent to which different socio-economic groups hold different sources of income. This article explores the drivers of income composition inequality (ICI). Contrary to recent studies, which show that the composition of government has ceased to shape redistribution and income inequality dynamics, this article posits that left-wing parties are associated with lower income composition inequality. We test this expectation with data from thirty European countries between 2003 and 2017. Our results suggest that the polarization between capital and labor income holders declines under left-wing governments. We establish that this is mainly because left-wing parties seek to broaden access to capital income. [ABSTRACT FROM AUTHOR]

Recent studies have highlighted the possibility of using surface electromyographic (EMG) signals to develop human–computer interfaces that are also able to recognize complex motor tasks involving the hand as the handwriting of digits. However, the automatic recognition of words from EMG information has not yet been studied. The aim of this study is to investigate the feasibility of using combined forearm and wrist EMG probes for solving the handwriting recognition problem of 30 words with consolidated machine-learning techniques and aggregating state-of-the-art features extracted in the time and frequency domains. Six healthy subjects, three females and three males aged between 25 and 40 years, were recruited for the study. Two tests in pattern recognition were conducted to assess the possibility of classifying fine hand movements through EMG signals. The first test was designed to assess the feasibility of using consolidated myoelectric control technology with shallow machine-learning methods in the field of handwriting detection. The second test was implemented to assess if specific feature extraction schemes can guarantee high performances with limited complexity of the processing pipeline. Among support vector machine, linear discriminant analysis, and K-nearest neighbours (KNN), the last one showed the best classification performances in the 30-word classification problem, with a mean accuracy of 95% and 85% when using all the features and a specific feature set known as TDAR, respectively. The obtained results confirmed the validity of using combined wrist and forearm EMG data for intelligent handwriting recognition through pattern recognition approaches in real scenarios. [ABSTRACT FROM AUTHOR]

Dystrophin (DMD) gene mutations are associated with skeletal muscle diseases such as Duchenne and Becker Muscular Dystrophy (BMD) and X-linked dilated cardiomyopathy (XL-DCM). To investigate the molecular basis of DCM in a 37-year-old woman. Clinical and genetic investigations were performed. Genetic testing was performed with whole exome sequencing (WES) using the Illumina platform. According to the standard protocol, a variant found by WES was confirmed in all available members of the family by bi-directional capillary Sanger resequencing. The effect of the variant was investigated by using an in silico prediction of pathogenicity. The index case was a 37-year-old woman diagnosed with DCM at the age of 33. A germline heterozygous A>G transversion at nucleotide 10103 in the DMD gene, leading to an aspartic acid–glycine substitution at the amino acid 3368 of the DMD protein (c.10103A>G p.Asp3368Gly), was identified and confirmed by PCR-based Sanger sequencing of the exon 70. In silico prediction suggests that this variant could have a deleterious impact on protein structure and functionality (CADD = 30). The genetic analysis was extended to the first-degree relatives of the proband (mother, father, and sister) and because of the absence of the variant in both parents, the p.Asp3368Gly substitution was considered as occurring de novo. Then, the direct sequencing analysis of her 8-year-old son identified as hemizygous for the same variant. The young patient did not present any signs or symptoms attributable to DCM, but reported asthenia and presented with bilateral calf hypertrophy at clinical examination. Laboratory testing revealed increased levels of creatinine kinase (maximum value of 19,000 IU/L). We report an early presentation of dilated cardiomyopathy in a 33-year-old woman due to a de novo pathogenic variant of the dystrophin (DMD) gene (p.Asp3368Gly). Genetic identification of this variant allowed an early diagnosis of a skeletal muscle disease in her son. [ABSTRACT FROM AUTHOR]

Objective: This study presents the walking abilities of participants fitted with transfemoral bone-anchored prostheses using a total of 14 gait parameters. Design: Two-centre retrospective cross-sectional comparative study. Setting: Research facilities equipped with tridimensional motion capture systems. Participants: Two control arms included eight able-bodied participants arm (54 ± 9 years, 1.75 ± 0.07 m, 76 ± 7 kg) and nine participants fitted with transfemoral socket-suspended prostheses arm (59 ± 9 years, 1.73 ± 0.07 m, 80 ± 16 kg). The intervention arm included nine participants fitted with transfemoral bone-anchored prostheses arm (51 ± 13 years, 1.78 ± 0.09 m, 87.3 ± 16.1 kg). Intervention: Fitting of transfemoral bone-anchored prostheses. Main measures: Comparisons were performed for two spatio-temporal, three spatial and nine temporal gait parameters. Results: The cadence and speed of walking were 107 ± 6 steps/min and 1.23 ± 0.19 m/s for the able-bodied participants arm, 88 ± 7 steps/min and 0.87 ± 0.17 m/s for the socket-suspended prosthesis arm, and 96 ± 6 steps/min and 1.03 ± 0.17 m/s for bone-anchored prosthesis arm, respectively. Able-bodied participants and bone-anchored prosthesis arms were comparable in age, height, and body mass index as well as cadence and speed of walking, but the able-bodied participant arm showed a swing phase 31% shorter. Bone-anchored and socket-suspended prostheses arms were comparable for age, height, mass, and body mass index as well as cadence and speed of walking, but the bone-anchored prosthesis arm showed a step width and duration of double support in seconds 65% and 41% shorter, respectively. Conclusions: Bone-anchored and socket-suspended prostheses restored equally well the gait parameters at a self-selected speed. This benchmark data provides new insights into the walking ability of individuals using transfemoral bionics bone-anchored prostheses. [ABSTRACT FROM AUTHOR]

Online users tend to hide their real identities by adopting different names on the Internet. On Facebook or LinkedIn, for example, people usually appear with their real names. On other standard websites, such as forums, people often use nicknames to protect their real identities. Aliases are used when users are trying to protect their anonymity. This can be a challenge to law enforcement trying to identify users who often change nicknames. In unmonitored contexts, such as the dark web, users expect strong identity protection. Thus, without censorship, these users may create parallel social networks where they can engage in potentially malicious activities that could pose security threats. In this paper, we propose a solution to the need to recognize people who anonymize themselves behind nicknames—the authorship attribution (AA) task—in the challenging context of the dark web: specifically, an English-language Islamic forum dedicated to discussions of issues related to the Islamic world and Islam, in which members of radical Islamic groups are present. We provide extensive analysis by testing models based on transformers, styles, and syntactic features. Downstream of the experiments, we show how models that analyze syntax and style perform better than pre-trained universal language models. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder marked by the death of dopaminergic neurons in the midbrain, the accumulation of α-synuclein aggregates, and motor deficits. A major contributor to dopaminergic neuronal loss is neuroinflammation. The inflammasome is a multiprotein complex that perpetuates neuroinflammation in neurodegenerative disorders including PD. Increases in inflammasome proteins are associated with worsened pathology. Thus, the inhibition of inflammatory mediators has the potential to aid in PD treatment. Here, we investigated inflammasome signaling proteins as potential biomarkers of the inflammatory response in PD. Plasma from PD subjects and healthy age-matched controls were evaluated for levels of the inflammasome protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin (IL)-18. This was carried out using Simple Plex technology to identify changes in inflammasome proteins in the blood of PD subjects. The area under the curve (AUC) was obtained through calculation of the receiver operating characteristics (ROC) to obtain information on biomarker reliability and traits. Additionally, we completed a stepwise regression selected from the lowest Akaike information criterion (AIC) to assess how the inflammasome proteins caspase-1 and ASC contribute to IL-18 levels in people with PD. PD subjects demonstrated elevated caspase-1, ASC, and IL-18 levels when compared to controls; each of these proteins were found to be promising biomarkers of inflammation in PD. Furthermore, inflammasome proteins were determined to significantly contribute to and predict IL-18 levels in subjects with PD. Thus, we demonstrated that inflammasome proteins serve as reliable biomarkers of inflammation in PD and that inflammasome proteins provide significant contributions to IL-18 levels in PD. [ABSTRACT FROM AUTHOR]

The characterization of both limbs' behaviour in prosthetic gait is of key importance for improving the prosthetic components and increasing the biomechanical capability of trans-femoral amputees. When characterizing human gait, modular motor control theories have been proven to be powerful in providing a compact description of the gait patterns. In this paper, the planar covariation law of lower limb elevation angles is proposed as a compact, modular description of prosthetic gait; this model is exploited for a comparison between trans-femoral amputees walking with different prosthetic knees and control subjects walking at different speeds. Results show how the planar covariation law is maintained in prostheses users, with a similar spatial organization and few temporal differences. Most of the differences among the different prosthetic knees are found in the kinematic coordination patterns of the sound side. Moreover, different geometrical parameters have been calculated over the common projected plane, and their correlation with classical gait spatiotemporal and stability parameters has been investigated. The results from this latter analysis have highlighted a correlation with several parameters of gait, suggesting that this compact description of kinematics unravels a significant biomechanical meaning. These results can be exploited to guide the control mechanisms of prosthetic devices based purely on the measurement of relevant kinematic quantities. [ABSTRACT FROM AUTHOR]

When analyzing a financial asset, it is essential to study the trend of its time series. It is also necessary to examine its evolution and activity over time to statistically analyze its possible future behavior. Both retail and institutional investors base their trading strategies on these analyses. One of the most used techniques to study financial time series is to analyze its dynamic structure using auto-regressive models, simple moving average models (SMA), and mixed auto-regressive moving average models (ARMA). These techniques, unfortunately, do not always provide appreciable results both at a statistical level and as the Risk-Reward Ratio (RRR); above all, each system has its pros and cons. In this paper, we present CryptoNet; this system is based on the time series extraction exploiting the vast potential of artificial intelligence (AI) and machine learning (ML). Specifically, we focused on time series trends extraction by developing an artificial neural network, trained and tested on two famous crypto-currencies: Bitcoinand Ether. CryptoNet learning algorithm improved the classic linear regression model up to 31% of MAE (mean absolute error). Results from this work should encourage machine learning techniques in sectors classically reluctant to adopt non-standard approaches. [ABSTRACT FROM AUTHOR]

This article studies the global distributions of capital and labor incomes among individuals in 2000 and 2016. By constructing a novel database covering approximately 80% of the global output and 60% of the world population, two major findings stand out. First, the world underwent an important process of capitalization. The share of world individuals with positive capital income rose from 20% to 32%. Second, the global middle class benefited the most, in relative terms, from such a capitalization process, with China being the main driver of this global trend. The findings of this paper are robust to changes in the income definition, top-income and functional income distribution adjustments. The global composition of capital and labor incomes is more equal today than it was twenty years ago. • This paper analyzes the global distributions of capital and labor incomes. • It introduces the "Global Capital and Labor Database" for 2000 and 2016. • The share of world individuals with positive capital income rose from 20% to 32%. • The global middle class benefited the most from such a capitalization process. • The findings of this paper remain robust across a range of adjustments. [ABSTRACT FROM AUTHOR]

The estimation of the sEMG–force relationship is an open problem in the scientific literature; current methods show different limitations and can achieve good performance only on limited scenarios, failing to identify a general solution to the optimization of this kind of analysis. In this work, this relationship has been estimated on two different datasets related to isometric force-tracking experiments by calculating the sEMG amplitude using different fixed-time constant moving-window filters, as well as an adaptive time-varying algorithm. Results show how the adaptive methods might be the most appropriate choice for the estimation of the correlation between the sEMG signal and the force time course. Moreover, the comparison between adaptive and standard filters highlights how the time constants exploited in the estimation strategy is not the only influence factor on this kind of analysis; a time-varying approach is able to constantly capture more information with respect to fixed stationary approaches with comparable window lengths. [ABSTRACT FROM AUTHOR]

Many mobile health (mHealth) application interventions include virtual representations of the self in varying forms, such as agents, or avatars to initiate health behaviour change. This review aimed to determine: (i) which virtual representations are effective in mHealth application interventions, and (ii) whether any studies implemented specific mechanisms (the psychological causes of change) and behaviour change techniques (BCTs) to influence positive behaviour change. Following PRISMA guidelines, a narrative systematic review of empirical studies was conducted from ten different databases (ranging from MEDLINE to Cochrane Library) from inception to December 2021. This included articles reporting a virtual representation of mHealth application intervention, published in English from any time point, which addressed and reported a variety of outcome health behaviours. Information on sample characteristics, study conditions, mechanisms and BCTs, results, and conclusions were extracted. Quality and risk of bias were assessed using the Mixed Methods Appraisal and Cochrane Risk of Bias Tools. Out of the 2,579 original search results, five eligible studies (total participants = 509), with low to moderate quality were included. It was found that customisable virtual representation mHealth interventions were most effective in encouraging behaviour change and app adherence. These interventions included mechanisms such as motivation, feedback, self-image, and BCTs such as goal setting, and self-monitoring. The current evidence suggests that virtual representations in mHealth app interventions may positively influence health behaviour change. However, there is limited evidence available to determine to which these influences are a result of the virtual representations, or the intervention design. [ABSTRACT FROM AUTHOR]

The study examined the glycaemic response to pasta made from three different wheat varieties in individuals with type 2 diabetes. The research found that there were no significant advantages in post-prandial glucose control when using ancient wheat varieties like Khorasan or Senatore Cappelli compared to the modern wheat variety Claudio. The macronutrient composition of the pasta was similar across all three varieties, and the differences in post-prandial glucose response were clinically trivial. The study suggests that individuals with type 2 diabetes can choose pasta based on personal taste preferences without worrying about minor differences in glucose levels. [Extracted from the article]

Objective: Research demonstrates that college educated, English language dominant bilinguals underperform relative to English speaking monolinguals on tests of verbal ability. We investigated whether accepting responses in their two languages would reveal improved performance in bilinguals, and whether such improvement would be of sufficient magnitude to demonstrate the same performance level as monolinguals. Method: Participants were college students attending the same university. Spanish-English bilinguals were compared to English speaking monolinguals on the Bilingual Verbal Ability Tests (BVAT), which include Picture Vocabulary, Oral Vocabulary, and Verbal Analogies. Results: When given the opportunity to respond in Spanish to items failed in English, bilinguals obtained significantly higher scores on all three subtests, and their performance matched that of monolinguals on Oral Vocabulary and Verbal Analogies. Conclusion: An "either-language" scoring approach may enable optimal measurement of verbal abilities in bilinguals. We provide normative data for use in applying the either-language scoring approach on subtests of the BVAT. We discuss the findings in the context of clinical assessment. [ABSTRACT FROM AUTHOR]

• Reward-associated stimuli can acquire the ability to activate dopamine cells. • VTA acetylcholine constitutes a primary reward signal. • VTA glutamate constitutes a conditioned stimulus signal. • This article bridges neuroscience with psychology of reward learning. A major goal in psychology is to understand how environmental stimuli associated with primary rewards come to function as conditioned stimuli, acquiring the capacity to elicit similar responses to those elicited by primary rewards. Our neurobiological model is predicated on the Hebbian idea that concurrent synaptic activity on the primary reward neural substrate—proposed to be ventral tegmental area (VTA) dopamine (DA) neurons—strengthens the synapses involved. We propose that VTA DA neurons receive both a strong unconditioned stimulus signal (acetylcholine stimulation of DA cells) from the primary reward capable of unconditionally activating DA cells and a weak stimulus signal (glutamate stimulation of DA cells) from the neutral stimulus. Through joint stimulation the weak signal is potentiated and capable of activating the VTA DA cells, eliciting a conditioned response. The learning occurs when this joint stimulation initiates intracellular second-messenger cascades resulting in enhanced glutamate-DA synapses. In this review we present evidence that led us to propose this model and the most recent evidence supporting it. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is the respiratory disease caused by the novel severe acute respiratory syndrome-coronavirus-2 and is characterized by clinical manifestations ranging from mild, flu-like symptoms to severe respiratory insufficiency and multi-organ failure. Patients with more severe symptoms may require intensive care treatments and face a high mortality risk. Also, thrombotic complications such as pulmonary embolisms and disseminated intravascular coagulation are frequent in these patients. Indeed, COVID-19 is characterized by an abnormal inflammatory response resembling a cytokine storm, which is associated to endothelial dysfunction and microvascular complications. To date, no specific treatments are available for COVID-19 and its life-threatening complication. Immunomodulatory drugs, such as hydroxychloroquine and interleukin-6 inhibitors, as well as antithrombotic drugs such as heparin and low molecular weight heparin, are currently being administered with some benefit. Ozone therapy consists in the administration of a mixture of ozone and oxygen, called medical ozone, which has been used for over a century as an unconventional medicine practice for several diseases. Medical ozone rationale in COVID-19 is the possibility of contrasting endothelial dysfunction, modulating the immune response and acting as a virustatic agent. Thus, medical ozone could help to decrease lung inflammation, slow down viral growth, regulate lung circulation and oxygenation and prevent microvascular thrombosis. Ozone-therapy could be considered a feasible, cost-effective and easy to administer adjuvant therapy while waiting for the synthesis of a therapy or the development of the vaccine. [ABSTRACT FROM AUTHOR]

The purpose of this study is to compare the results obtained using three different systems of osteosynthesis, developed for the surgical treatment of fractures of the trochanteric region of the femur, based on the principle intramedullary nailing: the Gamma nail, the Affixus nail and the ZNN nail. This is a retrospective study: 72 trochanteric fractures treated with the Gamma nail, 68 treated with the Affixus nail and 69 treated with the ZNN nail, between the years 2012 and 2014, with the prerequisite of a minimum follow-up of 18 months. The fractures were classified according to the AO system; the most commonly reported subtype was the A2 fracture. Clinical and radiographic examinations were performed, both at hospital admission and post-operatively, at 1, 3, 6, 12 and 18 months. Of the 209 patients, 171 were women and 38 were men. The average age was 83.12 years old. All three systems guaranteed an early mobilization and ambulation in most of the patients. There were no significant differences in the use of the three nails in terms of recovery of previous functional capacity, or in terms of the time required for the fracture to heal. There were no advantages encountered with the use of one intramedullary nail over another and, in particular, when observing the complications and patient outcome, there were no statistically significant differences detected. [ABSTRACT FROM AUTHOR]

Background: Brugada syndrome (BrS) is an inherited primary channelopathy syndrome associated with the risk of ventricular fibrillation (VF) and sudden cardiac death in a structurally normal heart. Aim of the Study: The aim of this study was to clinically and genetically evaluate a large family with severe autosomal dominant Brugada syndrome. Methods: Clinical and genetic studies were performed. Genetic analysis was conducted with NGS technologies (WES) using the Illumina instrument. According to the standard procedure, variants found by WES were confirmed in all available families by Sanger sequencing. The effect of the variants was studied by using in silico prediction of pathogenicity. Results: The proband was a 52-year-old man who was admitted to the emergency department for syncope at rest. WES of the index case identified a heterozygous VUS CASQ2, c.532T>C, p.(Tyr178His). We studied the segregation of the variation in all pedigree members. All the patients were heterozygous for the variation CASQ2 p.(Tyr178His), whereas the remaining healthy individuals in the family were homozygous for the normal allele. Structural analysis of CASQ2 p.(Tyr178His) was performed and revealed an important effect of the missense variation on monomer stability. The CASQ2 Tyr180 residue is located inside the sarcoplasmic reticulum (SR) junctional face membrane interaction domain and is predicted to disrupt filamentation. Conclusions: Our data suggest that the p.Tyr178His substitution is associated with BrS in the family investigated, affecting the stability of the protein, disrupting filamentation at the interdimer interface, and affecting the subsequent formation of tetramers and polymers that contain calcium-binding sites. [ABSTRACT FROM AUTHOR]

Surface ElectroMyography (sEMG) is widely used as a non-invasive tool for the assessment of motor control strategies. However, the standardization of the methods used for the estimation of sEMG amplitude is a problem yet to be solved; in most cases, sEMG amplitude is estimated through the extraction of the envelope of the signal via different low-pass filtering procedures with fixed cut-off frequencies chosen by the experimenter. In this work, we have shown how it is not possible to find the optimal choice of the cut-off frequency without any a priori knowledge on the signal; considering this, we have proposed an updated version of an iterative adaptive algorithm already present in literature, aiming to completely automatize the sEMG amplitude estimation. We have compared our algorithm to most of the typical solutions (fixed window filters and the previous version of the adaptive algorithm) for the extraction of the sEMG envelope, showing how the proposed adaptive procedure significantly improves the quality of the estimation, with a lower fraction of variance unexplained by the extracted envelope for different simulated modulating waveforms (p < 0.005). The definition of an entropy-based convergence criterion has allowed for a complete automatization of the process. We infer that this algorithm can ensure repeatability of the estimation of the sEMG amplitude, due to its independence from the experimental choices, so allowing for a quantitative interpretation in a clinical environment. [ABSTRACT FROM AUTHOR]

Background: Dopamine receptors are implicated in cocaine reward and seeking. We hypothesize that (-)-stepholidine, a dopamine D1/D2/D3 multi-receptor agent, would be effective in reducing cocaine reward and seeking in an animal model. We investigated the effects of (-)-stepholidine in cue-induced reinstatement of cocaine seeking and cocaine self-administration (reward).Methods: Cue-induced reinstatement experiment: Rats were trained to press a lever reinforced by cocaine (1 mg/kg/injection) for 15 consecutive daily sessions, after which the response was extinguished by withholding cocaine and cocaine-paired cues (light and pump activation). This was followed by a cue-induced reinstatement test where subjects were exposed to two cocaine cue presentations and presses on the active lever produced cues. Subjects were treated with one of four (-)-stepholidine doses prior to the reinstatement test. Cocaine self-administration (reward) experiment: Rats were trained to self-administer cocaine under a progressive ratio schedule of reinforcement. After stable breakpoints were established, rats were injected with four doses of (-)-stepholidine prior to testing; each dose was injected prior to a separate test session with no-treatment sessions intervening to re-establish break points.Results: (-)-Stepholidine significantly reduced cue-induced reinstatement of cocaine seeking in a dose-related manner. Additionally, (-)-stepholidine significantly reduced break points for cocaine reward. (-)-Stepholidine did not significantly affect locomotor activity.Conclusions: (-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine reward, suggesting that it may be useful in treating relapse in cocaine addiction. [ABSTRACT FROM AUTHOR]

We tested whether (1) the capacity of a reward-associated conditioned stimulus (CS) to cause conditioned activation of ventral tegmental area (VTA) dopamine (DA) neurons is associated with its capacity to elicit conditioned approach responses and (2) whether the acquisition of these capacities by a CS requires N -methyl-D-aspartate (NMDA) and muscarinic acetylcholine (mACh) receptor stimulation. Rats were trained to emit a conditioned approach response to a light CS that was previously paired with food and were treated systemically with scopolamine (a mACh receptor antagonist) or MK-801 (an NMDA receptor antagonist) either prior to each conditioning session (during which animals experienced paired CS and food presentations) or prior to the conditioned approach (CS-only) test. Brains were harvested after the CS-only test and processed for tyrosine hydroxylase (TH) (DA cells) and c-fos in the VTA. When animals received scopolamine or MK-801 treatment prior to conditioning sessions we observed significantly fewer TH-labeled (i.e., DA) cells in the VTA that expressed c-fos and significantly less conditioned approach responding during the CS-only test. Further analysis showed a correlation between the number of VTA DA cells activated and the number of conditioned approach responses. Treatments made prior to the CS-only test did not affect responding. Altogether these results suggest that the degree to which a CS elicits conditioned approach depends partially on the degree to which the CS activates VTA DA cells and that the acquisition of both of these capacities by a CS requires mACh and NMDA receptor stimulation. [ABSTRACT FROM AUTHOR]

In this study, we sought to discover if housing in an enriched environment (EE) is an efficacious intervention for encouraging abstinence from cocaine seeking in an animal “conflict” model of abstinence. Sixteen Long-Evans rats were trained in 3-h daily sessions to self-administer a cocaine solution (1 mg/kg/infusion) until each demonstrated a stable pattern of drug-seeking. Afterward, half were placed in EE cages equipped with toys, obstacles, and a running wheel, while the other half were given clean, standard laboratory housing. All rats then completed daily 30-min sessions during which the 2/3 of flooring closest to the self-administration levers was electrified, causing discomfort should they approach the levers; current strength (mA) was increased after every day of drug seeking until the rat ceased activity on the active lever for 3 consecutive sessions (abstinence). Rats housed in EE abstained after fewer days and at lower current strengths than rats in standard housing. These results support the idea that EE administered after the development of a cocaine-taking habit may be an effective strategy to facilitate abstinence. [ABSTRACT FROM AUTHOR]

• Dopamine D3 receptors play an important role in methamphetamine seeking. • SR 21502 blocks cue-induced reinstatement of methamphetamine seeking in rats. • SR 21502 reduces motivation for methamphetamine. There is as of yet no FDA-approved medication for methamphetamine use disorder. Although dopamine D3 receptor antagonists have been shown to be useful in reducing methamphetamine seeking in animal models their translation to the clinic has been hindered because currently tested compounds can produce dangerously high blood pressure. Thus, it is important to continue to explore other classes of D3 antagonists. We report here the effects of SR 21502, a selective D3 receptor antagonist, on cue-induced reinstatement (i.e., relapse) of methamphetamine-seeking in rats. In Experiment 1, rats were trained to self-administer methamphetamine under a fixed ratio schedule of reinforcement followed by extinction of the response. Then, animals were tested with one of several doses of SR 21502 on cue-induced reinstatement of responding. SR 21502 significantly reduced cue-induced reinstatement of methamphetamine-seeking. In Experiment 2, animals were trained to lever press for food under a PR schedule and tested with the lowest dose of SR 21502 that caused a significant reduction in Experiment 1. These animals responded on average 8 times more than the vehicle-treated rats in Experiment 1, eliminating the possibility that SR 21502-treated rats in Experiment 1 responded less because they were incapacitated. In summary, these data suggest that SR 21502 may selectively inhibit methamphetamine-seeking and may constitute a promising pharmacotherapeutic agent for methamphetamine or other drug use disorders. [ABSTRACT FROM AUTHOR]

This study evaluated the geothermal potential of Caldara di Manziana in central Italy. The chemical composition of gas emissions was used for geothermometric-geobarometric estimations and the total amount of CO 2 released was assessed. The subsurface geology was reconstructed using data from deep exploratory and shallow temperature-gradient wells. The bottom of the superficial volcanic deposits, the thickness of the impervious flysch cover and the top of the geothermal reservoir hosted in fractured Mesozoic limestones were reconstructed by a 3D-GIS modelling. Our results are consistent with a geothermal reservoir (T ∼140 °C) at ∼1000 m depth, with an estimated thermal energy capacity of 46–48 MWt. [ABSTRACT FROM AUTHOR]

Soil CO 2 flux and 222 Rn activity measurements may positively contribute to the geochemical monitoring of active volcanoes. The influence of several environmental parameters on the gas signals has been substantially demonstrated. Therefore, the implementation of tools capable of removing (or minimising) the contribution of the atmospheric effects from the acquired time series is a challenge in volcano surveillance. Here, we present 4 years-long continuous monitoring (from April 2007 to September 2011) of radon activity and soil CO 2 flux collected on the NE flank of Stromboli volcano. Both gases record higher emissions during fall–winter (up to 2700 Bq * m − 3 for radon and 750 g m − 2 day − 1 for CO 2 ) than during spring–summer seasons. Short-time variations on 222 Rn activity are modulated by changes in soil humidity (rainfall), and changes in soil CO 2 flux that may be ascribed to variations in wind speed and direction. The spectral analyses reveal diurnal and semi-diurnal cycles on both gases, outlining that atmospheric variations are capable to modify the gas release rate from the soil. The long-term soil CO 2 flux shows a slow decreasing trend, not visible in 222 Rn activity, suggesting a possible difference in the source depth of the of the gases, CO 2 being deeper and likely related to degassing at depth of the magma batch involved in the February–April 2007 effusive eruption. To minimise the effect of the environmental parameters on the 222 Rn concentrations and soil CO 2 fluxes, two different statistical treatments were applied: the Multiple Linear Regression (MLR) and the Principal Component Regression (PCR). These approaches allow to quantify the weight of each environmental factor on the two gas species and show a strong influence of some parameters on the gas transfer processes through soils. The residual values of radon and CO 2 flux, i.e. the values obtained after correction for the environmental influence, were then compared with the eruptive episodes that occurred at Stromboli during the analysed time span (2007–2011) but no clear correlations emerge between soil gas release and volcanic activity. This is probably due to i ) the distal location of the monitoring stations with respect to the active craters and to ii ) the fact that during the investigated period no major eruptive phenomena (paroxysmal explosion, flank eruption) occurred. Comparison of MLR and PCR methods in time-series analysis indicates that MLR can be more easily applied to real time data processing in monitoring of open conduit active volcanoes (like Stromboli) where the transition to an eruptive phase may occur in relatively short times. [ABSTRACT FROM AUTHOR]

Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG). In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9) and effector caspases (caspase 7 and 3) and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins. [ABSTRACT FROM AUTHOR]

The development of analytical devices that can allow an easy, rapid and cost-effective measurement of multiple markers, such as progesterone and β-hCG, could have a role in decreasing the burden associated with pregnancy-related complications, such as ectopic pregnancies. Indeed, ectopic pregnancies are a significant contributor to maternal morbidity and mortality in both high-income and low-income countries. In this work, an effective and highly performing electrochemical strip for a combo determination of progesterone and β-hCG was developed. Two immunosensing approaches were optimized for the determination of these two hormones on the same strip. The immunosensors were realized using cost-effective disposable electrode arrays and reagent-saving procedures. Each working electrode of the array was modified with both the IgG anti-β-hCG and anti-progesterone, respectively. By adding the specific reagents, progesterone or β-hCG can then be determined. Fast quantitative detection was achieved, with the analysis duration being around 1 h. Sensitivity and selectivity were assessed with a limit of detection of 1.5 × 10–2 ng/mL and 2.45 IU/L for progesterone and β-hCG, respectively. The proposed electrochemical combo-strip offers great promise for rapid, simple, cost-effective, and on-site analysis of these hormones and, thus, for the development of a point-of-care diagnostic tool for early detection of pregnancy-related complications. [ABSTRACT FROM AUTHOR]

Torre Alfina is a medium enthalpy (T = 140 °C) geothermal field in Central Italy, hosted in buried fractured Mesozoic limestones, extensively explored in the 1970s and 1980s, but which so far has not been exploited. A detailed diffuse soil CO 2 flux investigation (1336 measurements over a surface of 12.6 km 2 ) and the periodic monitoring of soil CO 2 flux from target areas indicate that in most of the area, even above a pressurized gas cap existing at the reservoir top, the soil CO 2 flux is low and mostly within the background threshold (48 g m − 2 day − 1 ) and is likely generated by biological soil respiration. Anomalous values (up to 30.250 g m − 2 day − 1 ) are found only in the proximity of a small zone with gas vents whose composition is identical to that of the gas produced by the geothermal wells tapping the reservoir. This is the only zone where a fault connecting the deep geothermal reservoir with the surface does exist. These data are compared with those of the near Latera high enthalpy geothermal field (T = 210 °C), where anomalous soil CO 2 flux is recorded above the productive reservoir. The difference of soil CO 2 release in the two fields is attributed to the differences in the impervious cover (allochthonous flysch deposits) above the carbonate reservoir, which is thin and locally lacking at Latera, and continuous and thick (> 400 m) at Torre Alfina. Results demonstrate that soil CO 2 flux investigations are useful in geothermal exploration, but only high flux values likely indicate the presence of a geothermal reservoir at depth, whereas low flux values can indicate either the lack of an active geothermal reservoir at depth or the presence of a very effective impervious cover above the reservoir. [ABSTRACT FROM AUTHOR]

Abstract: The β-amyloid precursor protein undergoes cleavages by β- and γ-secretasses yielding amyloid-β peptides (Aβ) that accumulate in Alzheimer's disease. Subsequently, Aβ peptides are targets of additional truncations or endoproteolytic cleavages explaining the diversity of Aβ-related fragments recovered in cell media or pathologic human fluids. Here, we focused on Aβ1–34 (Aβ34) that has been detected both in vitro and in vivo and that derives from the hydrolysis of Aβ by β-secretase. We have obtained and fully characterized by immunologic and biochemical approaches, a polyclonal antibody that specifically recognizes the C-terminus of Aβx-34. We present immunohistochemical evidence for the presence of Aβx-34 in the brain of 3xTg mice and Alzheimer's disease-affected human brains. Finally, we demonstrate a neprilysin-mediated degradation process of Aβ34 and the ability of synthetic Aβ34 to protect HEK cells overexpressing either wild type or Swedish-mutated β-amyloid precursor protein from apoptosis. [Copyright &y& Elsevier]

Background and rationale: An enormous amount of resources has been devoted to the development of pharmacotherapies for drug addiction, with relatively little or no long-term success reported. The current review argues that a successful drug addiction treatment program will likely be one that focuses on both the neural mechanisms and the environmental contingencies that mediate drug use. Further, because the neural mechanisms and environmental factors that support abstinence in humans are similar in laboratory animals, several animal models of abstinence and relapse have been developed. Thus, this review also compares the similarities in the mechanisms that lead to abstinence between animals and humans. Objective: We evaluate the construct and face validities of the behavioral strategies that help support human drug abstinence. Further, we crucially evaluate animal models by assessing their validity and utility in addressing human behavior that leads to long-term abstinence. Conclusions: We found that the behavioral strategies with the greatest likelihood of supporting long-term abstinence are those that are carried out in drug addicts' natural setting(s) and while drug is readily available. Further, the behavioral strategies that may be most successful in supporting abstinence in humans are those that employ both positive consequences for abstinent related behavior and negative consequences for continued drug seeking or taking. Moreover, the animal models of abstinence and relapse that more closely represent the factors that support long-term abstinence in humans are those that limit their use of extinction or forced abstinence and present negative consequences for drug seeking and taking. [ABSTRACT FROM AUTHOR]

The development of phototrophic biofilms deteriorating stone cultural heritage is a well-known phenomenon that causes not only discoloration but also micro-decohesion of substrates. Recently, essential oils (EOs) have resulted as successful natural biocides to be used for the restoration of cultural heritage as an alternative to chemicals. In a first experiment EOs of Lavandula angustifolia Mill. and Thymus vulgaris L. at 5% concentration were tested against cyanobacterial biofilms. Moreover, to develop a suitable protocol for in situ application, diverse concentrations (0.5% - 0.25% - 0.1%) of T. vulgaris EO were encapsulated within an alginate hydrogel and applied for different times on cyanobacterial biofilms. Chemical profiles of the two EOs were investigated via GC-MS, to identify the main plant compounds underlying the biocidal effects. Results showed that T. vulgaris EO, rich in thymol, had the greatest inhibitory effect of photosynthetic efficiency compared to essential oil of L. angustifolia , especially if suspended into hydrogel. The development of such innovative protocol allowed the concentration of the tested essential oil to be 0.1% (v/v), maintaining antimicrobial efficacy against cyanobacteria and reducing the volatility of the terpene components. This innovative method will facilitate the application also on vertical surfaces and the removal of the biofilm. • Phototrophic biofilms deteriorating stone monuments. • Essential oils (EOs) resulted as promising safe biocides against biodeterioration. • To be more effective essential oils has been encapsulated in a hydrogel (HG) matrix. • Biocide activity has been evaluated with measurement of photosynthetic yield. • Low concentration EOs in HG and time of application protocol has been developed. [ABSTRACT FROM AUTHOR]

Abstract: The essential micronutrient zinc has long been known to be a functional component of diverse structural proteins and enzymes. More recently, important roles for free or loosely bound intracellular zinc as a signaling factor have been reported. Insufficient zinc intake was shown to exacerbate symptoms in mouse models of inflammation such as experimental colitis, while zinc supplementation was found to improve intestinal barrier function. Herein, we provide evidence that intracellular zinc is essential for maintaining intestinal epithelial integrity when cells are exposed to the inflammatory cytokine Tumor Necrosis Factor (TNF)α. Using the human intestinal Caco-2/TC7 cell line as an in vitro model, we demonstrate that depletion of intracellular zinc affects TNFα-triggered signaling by shifting intestinal cell fate from survival to death. The mechanism underlying this effect was investigated. We show that TNFα promotes a zinc-dependent survival pathway that includes modulation of gene expression of transcription factors and signaling proteins. We have identified multiple regulatory steps regulated by zinc availability which include the induction of cellular Inhibitor of APoptosis (cIAP2) mRNA, possibly through activation of Nuclear Factor-Kappa B (NF-κB), as both nuclear translocation of the p65 subunit of NF-κB and up-regulation of cIAP2 mRNA were impaired following zinc depletion. Moreover, X-linked inhibitor of apoptosis protein level was profoundly reduced by zinc depletion. Our results provide a possible molecular explanation for the clinical observation that zinc supplements ameliorate Crohn''s disease symptoms and decrease intestinal permeability in experimental colitis. [Copyright &y& Elsevier]

The mechanisms underlying obesity-related kidney disease are not well understood. Growing evidence suggests that free fatty acids, a cause of oxidative stress, play an important role in obesity and its related complications. So, we decided to investigate, in a human-conditioned immortalized podocyte cell line, the capacity of physiopathological concentrations of 27nM of nonconjugated palmitate to induce intracellular reactive oxygen species (ROS) production, podocytes endoplasmic reticulum stress, podocytes inflammation, and mitochondrial dysfunction. A conditionally immortalized human podocyte cell line was exposed to different percentages of palmitate conjugated to bovine serum albumin for 24h. We observed that palmitate, at the same concentrations seen in obese patients, caused overproduction of ROS in human podocytes and this oxidative stress induces dysfunctions in podocytes like inflammation and changes in profibrotic and lipotoxic markers. Highmobility group box 1 is likely known to be a major mediator of ROS damaging effects, as its pharmacological inhibition prevents all ROS effects on podocytes. Our study shows how, in podocytes, an unbounded fraction of 27nM of palmitate can induce dysfunctions similar to that observed in obesity-related glomerulopathy (ORG). These results could contribute to elucidating underlying mechanisms contributing to the ORG pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies have highlighted the potential physiopathological and diagnostic role of N- and C-terminally truncated amyloid-β (Aβ) peptides in Alzheimer''s disease. However, our knowledge about their production remains incomplete, in part due to the lack of very specific and sensitive tools for their detection. We thus developed specific monoclonal antibodies that target either Aβ11-x or Aβ17-x species, which result from the combined cleavages by β/γ- or α/γ-secretases, respectively. The presence of Aβ peptides truncated at residue 11 and 17 peptides was qualitatively and quantitatively assessed, using surface enhanced laser desorption ionization-time of flight mass spectrometry and xMAP (Multi-Analyte Profiling) immunoassays, in the supernatant of HEK293 cells that overexpress wild type or mutant Aβ protein precursor or in which α- and β-secretase activities had been modulated. Our results show a differential secretion of Aβ11–40 and Aβ17–40 species by these HEK293 cell lines. Finally, Aβ11–40 concentration in human cerebrospinal fluid (measured with the new xMAP immunoassays) from a first pilot study was higher in cerebrospinal fluid samples from patients with Alzheimer''s disease than in samples from patients with other types of dementia. [Copyright &y& Elsevier]

Abstract: The early pronucleus stage of the mouse zygote has been characterised in vitro as radiosensitive, due to a high rate of induction of chromosome-type chromosome abnormalities (CA). We have investigated the repair of irradiation induced double strand DNA breaks in vivo by γH2AX foci and first cleavage metaphase analysis. Breaks were induced in sperm and in the early zygote stages comprising sperm chromatin remodelling and early pronucleus expansion. Moreover, the role of PARP1 in the formation and repair of spontaneous and radiation-induced double strand breaks in the zygote was evaluated by comparing observations in C57BL/6J and PARP1 genetically ablated females. The results confirmed in vivo that the rate of chromosome aberration induction by X-rays was approximately 3-fold higher in the zygote than in mouse lymphocytes. This finding was related to a diminished efficiency of double strand break signalling, as shown by a lower rate of γH2AX radiation-induced foci compared to that measured in most other somatic cell types. The spontaneous frequency of CA in PARP1 depleted zygotes was slightly but significantly higher than in wild type zygotes. Also, these zygotes showed some impairment of the radiation-induced DNA Damage Response when exposed closer to the start of S-phase, revealed by a higher number of γH2AX foci and a longer cell cycle delay. The rate of chromosome aberrations, however, was not elevated over that of wild type zygotes, possibly thanks to backup repair pathways and/or selection mechanisms against damaged cells. When comparing with the literature data on irradiation induced CA in mouse zygotes in vitro, the levels of induction were strikingly similar as was the frequency of misrepair of double strand breaks (γH2AX foci). This result can be reassuring for in vitro human gamete and embryo handling, because it shows that culture conditions do not significantly affect double strand DNA break repair. [Copyright &y& Elsevier]

Purpose: Increasing cellular phone service and nonresponse are causing random digit dial (RDD) users to search for alternative ways of sampling geographically large populations. This study evaluated the feasibility and utility in using a modified version of respondent-driven sampling (RDS) as an alternative method. Methods: Using RDS, 469 residents of Albany County, New York were enrolled into a telephone-based health survey. Participants answered health and RDS feasibility questions. Results were compared to a previously collected RDD sample and census data. Results: Participation was high (81.4%) and participants referred at least one peer 65.9% of the time. The RDS method produced a more ethnically diverse sample, otherwise respondent demographics were similar to the RDD sample. The most common reason for participating (51.9%) was because a peer told them about the study; 44.9% would not have participated in an RDD study. Persons not willing to participate in a RDD study reported being less healthy and less likely to participate in healthy activities (e.g., have a physical exam in the past 24 months). Conclusions: Although more research is needed, RDS methods may be developed into a viable alternative for collecting health data from large general populations. [ABSTRACT FROM AUTHOR]

Abstract: Toscana virus (TOSV) infection is a frequent cause of meningitis in central Italy during summer. The disease generally has a benign course. Rarely, the infection produces a severe disease, with encephalitis and signs of systemic involvement, including lymphadenopathy. Since there is no clinical necessity of performing lymph node biopsy in such cases, the histopathological feature of TOSV-related lymphadenitis is not known. We herein present a case in which lymphadenopathy preceded the onset of meningitis. The excised lymph node showed a non-specific mixed-type lymphoid hyperplasia, with follicular hyperplasia, sinusal expansion and paracortical involvement. We also demonstrated the presence of viral protein and viral RNA in the lymph node tissue. [Copyright &y& Elsevier]

Abstract: The mechanisms whereby reward-associated stimuli come to function as conditioned stimuli and acquire the capacity to activate the same neural regions activated by primary rewards (i.e., dopamine terminal regions) is not fully understood. We hypothesized that NMDA receptor stimulation in the VTA is necessary for the acquisition by a CS to both produce conditioned approach and activate dopamine terminal regions. Rats were tested in a conditioned approach protocol that consisted of light stimulus-food conditioning sessions (30 randomly presented light stimulus-food pellet pairings), a session with no stimuli or food and 1 session with only light stimulus (CS-only) presentations. Food trough head entries during the CS and just prior to the CS were recorded and a CS/pre-CS ratio indicating the conditioned approach response was calculated. Brain tissue was harvested after the CS-only session and processed for c-fos expression in prefrontal cortex area 2, nucleus accumbens core and shell and medial and lateral caudate. When bilateral intra-VTA microinjections of AP-5 (0, 0.25 or 0.5μg) were made prior to each of the conditioning sessions the 0.5μg AP-5 dose prevented the acquisition of conditioned approach; when 0.5μg AP-5 injections were made prior to the CS-only test they failed to affect expression of the response. Also, 0.5μg AP-5 prior to conditioning significantly reduced c-fos expression in response to the CS in nucleus accumbens core. These results suggest that VTA NMDA receptor stimulation is necessary for both the acquisition of reward-related learning and acquisition by the CS to activate dopamine terminal regions. [Copyright &y& Elsevier]

Abstract: N-terminal pro-B-type natriuretic peptide (Nt-proBNP) is a peptide released from myocardium in response to ventricular wall stress and dysfunction. Nt-proBNP plasma levels are elevated in a variety of cardiovascular disorders and are largely used for diagnosis and treatment of cardiac diseases. The cardiac cycle efficiency (CCE) is a haemodynamic variable that represents the left ventricle wall stress and the heart''s effort to maintain an adequate blood flow to tissues. We investigated the relationship between Nt-proBNP and CCE values in patients undergoing cardiac surgery. Twenty-five patients undergoing aortic valve replacement were studied. Plasma Nt-proBNP concentrations were performed by electroluminescence immunoassay before starting surgery (t0), at the end of extracorporeal circulation (t1) and 3hours after surgery (t2). CCE measurements were acquired at the same intervals and correlations with Nt-proBNP levels were calculated. Nt-proBNP plasma concentration was 1430±341pg/ml at t0, peaked significantly at t1 (2129±561pg/ml, p <0.001) and moderately decreased at t2 (1924±477pg/ml, p <0.05). A direct correlation between Nt-proBNP measured at t0 and t1 was found (r =0.91, p <0.001). Overall, a negative correlation between CCE and proBNP values was found (r =−0.89, p <0.01). Correlations between CCE and Nt-proBNP were −0.91, −0.83 and −0.88, at t0, t1 and t2, respectively (p <0.01). Nt-proBNP levels reflect the severity of left ventricle dysfunction in patients undergoing cardiac surgery. CCE correlated well with serum Nt-proBNP levels and seems to be a useful variable to monitor the left ventricular stress and recovery during the various phases of surgery. [Copyright &y& Elsevier]

Abstract: Otolith metal concentrations may be related to the environmental exposure history of fish to contamination. Otoliths of pink snapper (Pagrus auratus) collected from the marine basin of Cockburn Sound and offshore near Rottnest Island were analysed by laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS) to measure the concentrations of 11 trace metals. The following metals were investigated using their respective isotopes: aluminum (27Al), calcium (44Ca), manganese (55Mn), iron (57Fe), copper (65Cu), zinc (66Zn), strontium (88Sr), cadmium (111Cd), barium (138Ba), mercury (202Hg) and lead (208Pb). Significant differences in otolith metal concentrations were found between the sampling locations for Zn, Cd and Pb. These metals were significantly higher in the otolith edges of the pink snapper captured from the extensive industrial area bordering Cockburn Sound. Life history transects of Zn, Cd and Pb within otoliths of pink snapper sampled from Cockburn Sound typically showed temporal trends that may correspond to the movement of this fish species in and out of this contaminated area during the yearly spawning season. [Copyright &y& Elsevier]

Abstract: The ability to learn about conditioned stimuli (CS) associated with rewards is a crucial adaptive mechanism. Activity in the mesocorticolimbic dopamine (DA) system, as well as in the ventral tegmental area (VTA), is correlated with responding to and learning about CSs. The mechanism by which VTA neurons become activated by signals associated with conditioned stimuli is not fully understood. Our model suggests that NMDA receptor stimulation in the VTA allows originally weak glutamate signals carrying information about environmental stimuli, coincident with strong excitation correlated with primary rewards, to be strengthened and thereby acquire the ability to activate VTA neurons in themselves, producing approach. Furthermore, once synaptic strengthening occurs, the model suggests that NMDA receptor stimulation in VTA is not necessary for the expression of reward-related learning. In this review we survey evidence that VTA cells respond to cues associated with primary rewards, that this responding is acquired, and that the VTA possesses the attributes to function as a site of integration of signals of primary and conditioned stimuli. [Copyright &y& Elsevier]

The opening of the lid that controls the access to the active site of human pancreatic lipase (HPL) was measured from the magnetic interaction between two spin labels grafted on this enzyme. One spin label was introduced at a rigid position in HPL where an accessible cysteine residue (C181) naturally occurs. A second spin label was covalently bound to the mobile lid after introducing a cysteine residue at position 249 by site-directed mutagenesis. Double electron-electron resonance (DEER) experiments allowed the estimation of a distance of 19 ± 2 Å between the spin labels when bilabeled HPL was alone in a frozen solution, i.e., with the lid in the closed conformation. A magnetic interaction was however detected by continuous wave EPR experiments, suggesting that a fraction of bilabeled HPL contained spin labels separated by a shorter distance. These results could be interpreted by the presence of two conformational subensembles for the spin label lateral chain at position 249 when the lid was closed. The existence of these conformational subensembles was revealed by molecular dynamics experiments and confirmed by the simulation of the EPR spectrum. When the lid opening was induced by the addition of bile salts and colipase, a larger distance of 43 ± 2 A between the two spin labels was estimated from DEER experiments. The distances measured between the spin labels grafted at positions 181 and 249 were in good agreement with those estimated from the known X-ray structures of HPL in the closed and open conformations, but for the first time, the amplitude of the lid opening was measured in solution or in a frozen solution in the presence of amphiphiles. [ABSTRACT FROM AUTHOR]

In adult tissue the quiescent state of a single cell is maintained by the steady state conditions of its own microenvironment for what concern both cell-cell as well as cell-ECM interaction and soluble factors concentration. Physiological or pathological conditions can alter this quiescent state through an imbalance of both soluble and insoluble factors that can trigger a cellular phenotypic response. The kind of cellular response depends by many factors but one of the most important is the concentration of soluble cytokines sensed by the target cell. In addition, due to the intrinsic plasticity of many cellular types, every single cell is able, in response to the same stimulus, to rapidly switch phenotype supporting minimal changes of microenviromental cytokines concentration. Wound healing is a typical condition in which epithelial, endothelial as well as mesenchymal cells are firstly subjected to activation of their motility in order to repopulate the damaged region and then they show a strong proliferative response in order to successfully complete the wound repair process. This schema constitute the leitmotif of many other physiological or pathological conditions such as development vasculogenesis/angiogenesis as well as cancer outgrowth and metastasis. Our review focuses on the molecular mechanisms that control the starting and, eventually, the switching of cellular phenotypic outcome in response to changes in the symmetry of the extracellular environment. [ABSTRACT FROM AUTHOR]

A non-menopausal women underwent gynecological evaluation for spotting and menstrual irregularities. After first line gynecological assessments, the patient underwent office hysteroscopy. By using an in-office technique, two isthmic endometrial polyps and one cervical polyp were removed. One endometrial polyp was found to harbor a B-cell high-grade lymphoma just on the apex (found to be necrotic). The following staging examinations and the pathological assessment of the endometrium, the uterus, the adnexa, and the lymphatic regional nodes did not find any localization of the lymphoma. No additional treatments were done. The patient is alive and disease-free at 18 months follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Ochratoxin A (OTA) is a harmful mycotoxin frequently contaminating foods, feeds and beverages. OTA was reported to be nephrotoxic, immunotoxic, hepatotoxic and a potential carcinogen, with yet poorly characterized mechanisms. Although intestinal cells are relatively resistant to high concentrations of OTA, interaction with other dietary factors or specific nutritional conditions may increase OTA toxicity to the intestinal mucosa. The role of intracellular zinc stores in protecting the integrity of intestinal mucosa has been investigated in human Caco-2/TC7 cells challenged with OTA. Zinc depletion of cells incubated with TPEN, a specific zinc chelator, caused an increase of tight junction permeability in OTA treated cells, accompanied by increased apoptosis. These effects were fully reverted by zinc supplementation during TPEN treatment, showing a specific role for this micronutrient in enterocyte defence mechanisms from OTA toxicity. A complex perturbation of zinc homeostasis was also demonstrated by analyzing the expression of genes coding for proteins involved in cellular zinc. In particular, zinc-dependent up-regulation of the metallothionein gene MT2A upon OTA treatment may indicate that the mycotoxin acts through generation of redox imbalance and that zinc deprivation reduces the intracellular defence mechanisms against noxious insults. [Copyright &y& Elsevier]

Abstract: Laboratory experiments were conducted to examine if incorporation of Cd into the otoliths of juvenile pink snapper (Pagrus auratus Forster) was related to levels in the food or water. In the first experiment, fish were fed a regular diet (control group) or a Cd-contaminated diet (500mgCdkg−1 or 1500mgCdkg−1) for 35days. In the second experiment, fish were exposed to waterborne Cd concentrations of <0.002µgL−1 (control), 50µgL−1, 100µgL−1 and 150µgL−1 for 35days. The sagittal otoliths were analysed using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Juvenile fish exposed to higher concentrations of waterborne or dietary Cd showed increased Cd levels in their otoliths. This study clearly demonstrated that both aqueous and dietary Cd exposures can result in Cd incorporation into the otoliths of pink snapper. [Copyright &y& Elsevier]

The structural changes induced in human pancreatic lipase (HPL) by lowering the pH were investigated using a combined approach involving the use of site-directed spin labeling coupled to electron paramagnetic resonance (SDSL-EPR) and Fourier transform infrared (ATR-FTIR) spectroscopy. The secondary structure of HPL observed with ATR-FTIR spectroscopy was found to be stable in the pH range of 3.0-6.5, where HPL remained active. Using a spin-label introduced into the lid of HPL at position 249, a reversible opening of the lid controlling the access to the active site was observed by EPR spectroscopy in the pH range of 3.0-5.0. In the same pH range, some structural changes were also found to occur outside the lid in a peptide stretch located near catalytic aspartate 176, using a spin-label introduced at position 181. Below pH 3.0, ATR-FTIR measurements indicated that HPL had lost most of its secondary structure. At these pH levels, the loss of enzyme activity was irreversible and the ability of HPL to bind to lipid emulsions was abolished. The EPR spectrum of the spin-label introduced at position 181, which was typical of a spin-label having a high mobility, confirmed the drastic structural change undergone by HPL in this particular region. The EPR spectrum of the spin-label at position 249 indicated, however, that the environment of this residue within the lid was not affected at pH 3.0 in comparison with that observed in the pH range of 3.0-5.0. This finding suggests that the disulfide bridge between the hinges of the lid kept the secondary structure of the lid intact, whereas the HPL was completely unfolded. [ABSTRACT FROM AUTHOR]

Abstract: We tested the hypothesis that sensitization to heroin enhances appetitive motivational processes involving food reward. In Experiment 1, sixteen rats were exposed to positive pairings of a light stimulus and food for 4 consecutive daily sessions. Then, the rats received either saline or heroin (2 mg/kg) injections before placement in activity monitors for 9 consecutive daily sessions. Rats were then tested in operant conditioning chambers where one lever produced the light stimulus previously paired with food and another lever produced a tone stimulus not paired with anything. Heroin produced both significant progressive increases in locomotor activity (sensitization) and significantly enhanced conditioned reinforcement of instrumental lever pressing by the food-associated stimulus. In Experiment 2, thirty-two rats were given Pavlovian discrimination training in a conditioned magazine approach task where one stimulus was associated with food and a second unpaired with food. Rats then received repeated saline or heroin injections as in Experiment 1, before being tested under extinction conditions with the two stimuli without the drug. Chronic heroin had no effect on performance in this test, but it facilitated learning of the reversed discrimination in a subsequent phase. These data suggest that sensitization to heroin enhances appetitive motivational processes involving food reward. [Copyright &y& Elsevier]