Search

This paper aimed at investigating the relationship between HEXACO personality traits and academic performance in two samples of Italian 10-14 years old middle-school adolescents (N = 714 and N = 1093) using Multilevel Mixed Models. The main results show that: 1) Conscientiousness and Openness to Experience were the most important predictors of school performance, followed by Honesty-Humility; 2) a modest effect was present also for eXtraversion and Emotionality; 3) these influences occurred net of the influence of gender and class and could be generalized to male and female adolescents across 6 th , 7 th and 8 th grade; 5) Perfectionism, Diligence and Prudence within Conscientiousness, Inquisitiveness within Openness, and Sincerity within Honesty-Humility were the facets more correlated with school performance; 6) results were replicated in two studies. Results are discussed and conclusions are drawn., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The Russian invasion of Ukraine on February 24, 2022, has had devastating effects on the Ukrainian population and the global economy, environment, and political order. However, little is known about the psychological states surrounding the outbreak of war, particularly the mental well-being of individuals outside Ukraine. Here, we present a longitudinal experience-sampling study of a convenience sample from 17 European countries (total participants = 1,341, total assessments = 44,894, countries with >100 participants = 5) that allows us to track well-being levels across countries during the weeks surrounding the outbreak of war. Our data show a significant decline in well-being on the day of the Russian invasion. Recovery over the following weeks was associated with an individual's personality but was not statistically significantly associated with their age, gender, subjective social status, and political orientation. In general, well-being was lower on days when the war was more salient on social media. Our results demonstrate the need to consider the psychological implications of the Russo-Ukrainian war next to its humanitarian, economic, and ecological consequences., (© 2024. The Author(s).)

In this cross-sectional study we aimed at: 1) validating the observer (Obs) version of HEXACO Medium School Inventory Extended (MSI-E); 2) establishing convergent and divergent construct validity of the HEXACO-MSI-E; 3) establishing criterion validity of HEXACO-MSI-E. We administered the HEXACO-MSI-E, the Big Five Questionnaire-Children (BFQ-C), the Internalizing and Externalizing scales of Youth Self Report (YSR), some items of the 2019 Middle School Youth Risk Behavior Survey (YRB) and some items about adolescents' values, beliefs, behaviors, and desired features of a possible future job to 1175 adolescents (Mage = 12.03, SD = 0.89) and the observer version of these measures (except for BFQ-C) to 854 parents or legal guardians. The factorial structure and the reliability of the Observer Report of HEXACO-MSI-E were confirmed. Convergent and divergent validity were successfully established with a version of the inventory filled out by parents. Convergent and divergent validity were also established with BFQ-C notwithstanding some only apparent anomalies. Criterion validity was established with respect to four specific groups of criteria collected in both self-report and observer form. HEXACO-MSI-E traits were more predictive with respect to self-report than to observer criteria and the majority were common. Together with the positive results of this study, implications and issues for future studies are discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mottola et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Smart wearable devices enable personalized at-home healthcare by unobtrusively collecting patient health data and facilitating the development of intelligent platforms to support patient care and management. The accurate analysis of data obtained from wearable devices is crucial for interpreting and contextualizing health data and facilitating the reliable diagnosis and management of critical and chronic diseases. The combination of edge computing and artificial intelligence has provided real-time, time-critical, and privacy-preserving data analysis solutions. However, based on the envisioned service, evaluating the additive value of edge intelligence to the overall architecture is essential before implementation. This article aims to comprehensively analyze the current state of the art on smart health infrastructures implementing wearable and AI technologies at the far edge to support patients with chronic heart failure (CHF). In particular, we highlight the contribution of edge intelligence in supporting the integration of wearable devices into IoT-aware technology infrastructures that provide services for patient diagnosis and management. We also offer an in-depth analysis of open challenges and provide potential solutions to facilitate the integration of wearable devices with edge AI solutions to provide innovative technological infrastructures and interactive services for patients and doctors.

Objective: The aim of the present study was to explore whether there was an interaction effect between such personal aspects and veracity on realism, clarity, and reconstructability of the story., Methods: A total of 158 participants took part in the experiment and were asked to tell a truth and a lie during an interview (veracity condition). They filled in a questionnaire measuring their metamemory performance and their level of functional and dysfunctional impulsivity. A k-means cluster analysis on metamemory and impulsivity was conducted, and three clusters were obtained: controlled-memory inefficient, controlled-memory efficient, and impulsive-average memory., Results: The results showed that participants scored higher on all three reality monitoring criteria when telling the truth than when lying. Further, a cluster membership by veracity interaction for realism was also significant, but when telling the truth, there was no difference between clusters in terms of realism used in the explanation. Follow-up analyses showed that, when lying, the level of realism in the story was significantly higher for people belonging to the cluster "impulsive-average memory" than for people belonging to the cluster "controlled-memory efficient", a result that seems to indicate that people with good memory and can control dysfunctional impulsivity have more difficulties when lying., Conclusions: Research has shown that realism, clarity, and reconstructability of the story, all part of reality monitoring, can be useful to assess veracity. Generally, truth tellers obtain higher scores on all three variables than liars, but there is some variability across individuals owing to their personal characteristics. Metamemory and impulsivity also play a role in deception. From the implications of the results, the limitations of the study and suggestions for future research are also provided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sergi, Mottola, Gnisci, Caso and Palena.)

Objective: This contribution aimed at investigating the moderating role of risk (e.g., the negative influence of COVID-19 on mental health) and protective (e.g., post-traumatic growth) factors on the relationship between the concern for war and stress and anxiety/depression levels among Italian people., Methods: A questionnaire that included sociodemographic characteristics, the Perceived Stress Scale (PSS-4), the Patient Health Questionnaire (PHQ-4), the Brief Resilience Scale (BRS), the Post-Traumatic Growth Inventory (PTGI), and questions formulated ad hoc about concern for war was administered online. A sample of 755 participants (65.4% females, mean age = 32.39, SD = 12.64, range = 18-75) was recruited by convenience and snowball sampling. The researchers spread the link to the questionnaire to their acquaintances asking them to fill it out and to recruit other people., Results: Results showed that concern for war significantly augmented the levels of stress and anxiety/depression in Italian people. Being a healthcare professional or having a chronic illness negatively moderated the effect of concern for war on stress and anxiety/depression. Instead, the negative influence of COVID-19 on mental health positively moderated the effect of concern for war on stress. Moreover, the overall positive changes after trauma and four of its five scales (i.e., Relating to Others, New Possibilities, Personal Strength, and Spiritual Change), negatively moderated the effect of concern for war on anxiety/depression., Conclusions: In conclusion, concern about the Russian-Ukrainian war affects the mental health of the Italian population even if they are not directly involved in the conflict., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mottola, Gnisci, Kalaitzaki, Vintilă and Sergi.)

In this paper, we aimed at developing and validating a novel instrument to evaluate personality in 10-14 years old adolescents with six basic traits, with two dedicated studies. In Study 1, we generated a large pool of items (384 items) from three basic items sources, which we administered to 714 Italian adolescents. Using principal component analysis (PCA) and extension factor analysis, we selected the best eight items for each facet, and so the best 32 items for each factor, except for the Unconventionality facet of Openness to Experience (O) for which we selected the best six items. This resulted in a total of 190 items. The 190-item HEXACO-MSI had very good levels of dimensional validity and reliability, but it fell short in containing 8 items for each facet (i.e., for Unconventionality) and in balancing normal and reversed items within each facet. Therefore, in a second study we added items to the scale and verified again the dimensionality and reliability with the goal of developing a final version of the scale. In Study 2, we administered a version of the HEXACO-MSI consisting of 219 items to 1175 Italian adolescents. Using principal component analysis (PCA), we selected the best eight items for each facet equally balanced between normal and reversed items within each facet and factor. Confirmatory factor analysis (CFA) confirmed the six-factor structure and its invariance. The results showed that the HEXACO-MSI-E had a clear six-factor structure in adolescents, that was invariant across gender and across the three middle school classes, and was reliable. Finally, we established temporal stability of each factor in two measurements after one year. Together with the positive results of this contribution, we discussed some aspects for future studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gnisci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Personalised healthcare has seen significant improvements due to the introduction of health monitoring technologies that allow wearable devices to unintrusively monitor physiological parameters such as heart health, blood pressure, sleep patterns, and blood glucose levels, among others. Additionally, utilising advanced sensing technologies based on flexible and innovative biocompatible materials in wearable devices allows high accuracy and precision measurement of biological signals. Furthermore, applying real-time Machine Learning algorithms to highly accurate physiological parameters allows precise identification of unusual patterns in the data to provide health event predictions and warnings for timely intervention. However, in the predominantly adopted architectures, health event predictions based on Machine Learning are typically obtained by leveraging Cloud infrastructures characterised by shortcomings such as delayed response times and privacy issues. Fortunately, recent works highlight that a new paradigm based on Edge Computing technologies and on-device Artificial Intelligence significantly improve the latency and privacy issues. Applying this new paradigm to personalised healthcare architectures can significantly improve their efficiency and efficacy. Therefore, this paper reviews existing IoT healthcare architectures that utilise wearable devices and subsequently presents a scalable and modular system architecture to leverage emerging technologies to solve identified shortcomings. The defined architecture includes ultrathin, skin-compatible, flexible, high precision piezoelectric sensors, low-cost communication technologies, on-device intelligence, Edge Intelligence, and Edge Computing technologies. To provide development guidelines and define a consistent reference architecture for improved scalable wearable IoT-based critical healthcare architectures, this manuscript outlines the essential functional and non-functional requirements based on deductions from existing architectures and emerging technology trends. The presented system architecture can be applied to many scenarios, including ambient assisted living, where continuous surveillance and issuance of timely warnings can afford independence to the elderly and chronically ill. We conclude that the distribution and modularity of architecture layers, local AI-based elaboration, and data packaging consistency are the more essential functional requirements for critical healthcare application use cases. We also identify fast response time, utility, comfort, and low cost as the essential non-functional requirements for the defined system architecture.

One of the main concerns of the last century is regarding the air pollution and its effects caused on human health. Its impact is particularly evident in cities and urban areas where governments are trying to mitigate its effects. Although different solutions have been already proposed, citizens continue to report bad conditions in the areas in which they live. This paper proposes a solution to support governments in monitoring the city pollution through the combination of user feedbacks/reports and real-time data acquired through dedicated mobile IoT sensors dynamically re-located by government officials to verify the reported conditions of specific areas. The mobile devices leverage on dedicated sensors to monitor the air quality and capture main roads traffic conditions through machine learning techniques. The system exposes a mobile application and a website to support the collection of citizens' reports and show gathered data to both institutions and end-users. A proof-of-concept of the proposed solution has been prototyped in a medium-sized university campus. Both the performance and functional validation have demonstrated the feasibility and the effectiveness of the system and allowed the definition of some lessons learned, as well as future works.

In this work we performed a comparison between two different approaches to track a person in indoor environments using a locating system based on BLE technology with a smartphone and a smartwatch as monitoring devices. To do so, we provide the system architecture we designed and describe how the different elements of the proposed system interact with each other. Moreover, we have evaluated the system's performance by computing the mean percentage error in the detection of the indoor position. Finally, we present a novel location prediction system based on neural embeddings, and a soft-attention mechanism, which is able to predict user's next location with 67% accuracy.

In recent literature, many researchers have highlighted that the feeling of loneliness can be considered a sign of relevant distress with short- and long-term consequences on the health of people who needs to be appropriately monitored and treated. In this view, the Interpersonal Acceptance-Rejection Loneliness Scale (IPARLS) has been developed to evaluate the subjective feelings and distress related to interpersonal loneliness and to overcome the limits of the previous scales; however, its psychometric characteristics have not yet been fully investigated. Starting from these considerations, two studies have been conducted. The first study, involving 688 adults (19-69 years; 51% females), assessed dimensionality, reliability, and validity of and tested the measurement invariance (MI) of the Italian version of the IPARLS. The second study, involving 205 adults (20-69 years; 51% females), investigated the relationship between loneliness and psychological adjustment. Results confirmed the unidimensionality of the scale and showed that it is reliable, valid, and fully invariant as a function of age and gender. Moreover, data showed a strong association between perceived loneliness and psychological adjustment. The IPARLS is confirmed to be a valid and reliable measure to investigate loneliness in the life cycle from clinical and research perspectives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Senese, Nasti, Mottola, Sergi, Massaro and Gnisci.)

Recently, one of the hottest topics in the logistics sector has been the traceability of goods and the monitoring of their condition during transportation. Perishable goods, such as fresh goods, have specifically attracted attention of the researchers that have already proposed different solutions to guarantee quality and freshness of food through the whole cold chain. In this regard, the use of Internet of Things (IoT)-enabling technologies and its specific branch called edge computing is bringing different enhancements thereby achieving easy remote and real-time monitoring of transported goods. Due to the fast changes of the requirements and the difficulties that researchers can encounter in proposing new solutions, the fast prototype approach could contribute to rapidly enhance both the research and the commercial sector. In order to make easy the fast prototyping of solutions, different platforms and tools have been proposed in the last years, however it is difficult to guarantee end-to-end security at all the levels through such platforms. For this reason, based on the experiments reported in literature and aiming at providing support for fast-prototyping, end-to-end security in the logistics sector, the current work presents a solution that demonstrates how the advantages offered by the Azure Sphere platform, a dedicated hardware (i.e., microcontroller unit, the MT3620) device and Azure Sphere Security Service can be used to realize a fast prototype to trace fresh food conditions through its transportation. The proposed solution guarantees end-to-end security and can be exploited by future similar works also in other sectors.

The HEXACO Personality Inventory-Revised (HEXACO-PI-R) has become one of the most heavily applied measurement tools for the assessment of basic personality traits. Correspondingly, the inventory has been translated to many languages for use in cross-cultural research. However, formal tests examining whether the different language versions of the HEXACO-PI-R provide equivalent measures of the 6 personality dimensions are missing. We provide a large-scale test of measurement invariance of the 100-item version of the HEXACO-PI-R across 16 languages spoken in European and Asian countries ( N  = 30,484). Multigroup exploratory structural equation modeling and confirmatory factor analyses revealed consistent support for configural and metric invariance, thus implying that the factor structure of the HEXACO dimensions as well as the meaning of the latent HEXACO factors is comparable across languages. However, analyses did not show overall support for scalar invariance; that is, equivalence of facet intercepts. A complementary alignment analysis supported this pattern, but also revealed substantial heterogeneity in the level of (non)invariance across facets and factors. Overall, results imply that the HEXACO-PI-R provides largely comparable measurement of the HEXACO dimensions, although the lack of scalar invariance highlights the necessity for future research clarifying the interpretation of mean-level trait differences across countries.

Impulsivity is a multifaceted construct particularly relevant for understanding a wide variety of behaviors, especially risky behaviors. A recent conceptualization of impulsivity identifies three impulsivity factors-pervasive influence of feelings, feelings trigger action, and lack of follow-through-that have been shown to predict different behaviors. In this contribution, we examine the psychometric properties of an Italian version of such a three-factor model on a relatively large sample ( N  = 845). Moreover, on a subsample ( n  = 766) we determined whether specific dimensions of impulsivity are related to a series of risky behaviors, assessed 3 weeks later, by testing the predictive validity of the multidimensional inventory also in comparison with a standard measure of personality (HEXACO). An exploratory structural equation model confirmed the original 3-dimension structure and showed that the Italian adaptation has satisfactory psychometric properties. Convergent validity with the HEXACO dimensions was established. Furthermore, only the factors feelings trigger action and lack of follow-through, not pervasive influence of feelings, predicted risky behaviors. Findings provide a clear support to the 3-factor model of impulsivity and demonstrate its usefulness for a better comprehension of risky behaviors.

Sarcopenia is a highly prevalent, age-related muscle disorder associated with adverse outcomes. It is very important from a medical point of view to periodically monitor patients at risk of developing sarcopenia in order to early detect its onset or progression through objective and specific indicators. Today, the emerging Internet of Things (IoT)-enabling technologies allow us to create innovative, wearable, and non-invasive systems that can offer useful clinical support in this area. This work is focused on the use of combined hardware and software technologies, enabling the IoT, in order to monitor people suffering from sarcopenia by offering a high value-added service in the field of the Ambient Assisted Living (AAL). In addition to the description of the proposed system architecture, a validation of the entire system is also included, from both a performance and a functional point of view. Test beds have been carried out by using the independent replications method, and all measurements related to the identified sarcopenia parameters are characterized by a 95% confidence interval with a 5% maximum relative error. The implementation of these technologies as a supporting clinical tool used in a specific setting could significantly impact the life and independence of the sarcopenic frail elderly population.

Objectives: The nine-item Problematic Internet Use Questionnaire (PIUQ-9) is a brief self-report screening instrument for problematic internet use. The main objective of the present study was to explore the psychometric properties of the PIUQ-9 among nine different language-based samples of European internet users (Italian, German, French, Polish, Turkish, Hungarian, English, and Greek). Methods: The total sample comprised 5,593 internet users (38.1% men), aged between 18 and 87 years ( M = 25.81; SD = 8.61). Via online recruitment, participants completed the PIUQ-9, the Brief Symptom Inventory (BSI) and items about time spent online. Results: Confirmatory factor analysis demonstrated that the bifactor model with one general factor (i.e., general problem) and two-specific factors (i.e., obsession and neglect + control disorder) yielded acceptable or good fit indices in all subsamples except for one. The common variance index in the bifactor model indicated that the general problem factor explained from 57.0 to 76.5% of common variance, which supports the presence of a strong global factor. According to the multiple indicators multiple causes (MIMIC) model, psychiatric symptoms had a moderate-to-strong direct effect on the general problem factor in all subsamples, ranging from β = 0.28 to β = 0.52 supporting the construct validity of the scale. Furthermore, in a majority of the subsamples, time spent online during the weekend had considerably higher effect sizes on the general problem factor than time spent online during weekdays. Conclusion: The present study highlights the appropriate psychometric properties of the PIUQ-9 across a number of European languages and cultures.

Although research on facial emotion recognition abounds, there has been little attention on the nature of the underlying mechanisms. In this article, using a "reverse engineering" approach, we suggest that emotion inference from facial expression mirrors the expression process. As a strong case can be made for an appraisal theory account of emotional expression, which holds that appraisal results directly determine the nature of facial muscle actions, we claim that observers first detect specific appraisals from different facial muscle actions and then use implicit inference rules to categorize and name specific emotions. We report three experiments in which, guided by theoretical predictions and past empirical evidence, we systematically manipulated specific facial action units individually and in different configurations via synthesized avatar expressions. Large, diverse groups of participants judged the resulting videos for the underlying appraisals and/or the ensuing emotions. The results confirm that participants can infer targeted appraisals and emotions from synthesized facial actions based on appraisal predictions. We also report evidence that the ability to correctly interpret the synthesized stimuli is highly correlated with emotion recognition ability as part of emotional competence. We conclude by highlighting the importance of adopting a theory-based experimental approach in future research, focusing on the dynamic unfolding of facial expressions of emotion. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

The behavioral analysis of laboratory mice plays a key role in several medical and scientific research areas, such as biology, toxicology, pharmacology, and so on. Important information on mice behavior and their reaction to a particular stimulus is deduced from a careful analysis of their movements. Moreover, behavioral analysis of genetically modified mice allows obtaining important information about particular genes, phenotypes or drug effects. The techniques commonly adopted to support such analysis have many limitations, which make the related systems particularly ineffective. Currently, the engineering community is working to explore innovative identification and sensing technologies to develop new tracking systems able to guarantee benefits to animals' behavior analysis. This work presents a tracking solution based on passive Radio Frequency Identification Technology (RFID) in Ultra High Frequency (UHF) band. Much emphasis is given to the software component of the system, based on a Web-oriented solution, able to process the raw tracking data coming from a hardware system, and offer 2D and 3D tracking information as well as reports and dashboards about mice behavior. The system has been widely tested using laboratory mice and compared with an automated video-tracking software (i.e., EthoVision). The obtained results have demonstrated the effectiveness and reliability of the proposed solution, which is able to correctly detect the events occurring in the animals' cage, and to offer a complete and user-friendly tool to support researchers in behavioral analysis of laboratory mice.

Evaluating the behavior of mice and rats has substantially contributed to the progress of research in many scientific fields. Researchers commonly observe recorded video of animal behavior and manually record their observations for later analysis, but this approach has several limitations. The authors developed an automated system for tracking and analyzing the behavior of rodents that is based on radio frequency identification (RFID) in an ultra-high-frequency bandwidth. They provide an overview of the system's hardware and software components as well as describe their technique for surgically implanting passive RFID tags in mice. Finally, the authors present the findings of two validation studies to compare the accuracy of the RFID system versus commonly used approaches for evaluating the locomotor activity and object exploration of mice.

The aim of the present study was to compare the activation levels of true and false memories in the Deese-Roediger-McDermott (DRM) paradigm. For this purpose, we used a lexical decision task (LDT) that can be considered a relative pure measure of activation. Participants had to study a list of words that were semantically associated to a critical non-presented word (CI), and afterwards had to classify the actually studied words, the CI and new words in the LDT. Results indicated that the classification latency of the CI was the same as actually studied words and shorter than new words. The results might be interpreted as evidence that the false and true memory items have the same activation level and that the false memory effect can be based on the indirect activation of the CI at the encoding.

The abilities of males and females to make spatial inferences were compared. Spatial inference is concerned with the ability to work out new spatial information from memory. In two experiments, participants had to study line drawings depicting shapes linked either by straight or meandering lines. Afterwards, they had to remember the straight-line distances or to infer the straight-line distances. Several spatial abilities were also assessed: perceptual discrimination, mental rotation, and visuo-spatial working memory span. The results showed that males outperformed females in spatial inference and mental rotation. Experiment 2 extended the study to old people. The results replicated and clarified those obtained in Experiment 1. Spatial inference and mental rotation showed age-related and gender-related differences; in addition, age reduced the visuo-spatial memory span. Overall, the findings suggest that gender differences favouring males are maximised with tasks requiring active processing and strategic control of metric information.

In this preliminary study we investigate gender differences in object location memory. Our purpose is to extend the results about object location memory obtained in laboratory settings to a real 3-D environment and to further distinguish the specific components involved in this kind of memory by considering the strategies adopted to perform the task. To do this, we join the three-level model of spatial representations (landmark, route, and survey) proposed by Siegel and White (1975) with the three subcomponents of spatial memory (what, where, and what + where) identified by Postma and De Haan (1996). We adopted the object relocation task devised by Postma and De Haan (1996), adapted to a real environment. Seven common objects were placed on the floor of a cylindrical room. Sixty-four males and 64 females were asked to memorize the spatial layout. Next, the experimenter moved the objects to a different position along with seven new objects and the participants had to relocate the original objects to their initial positions. In line with Postma, Izendoorn, and De Haan (1998), we found no gender difference in object recognition, and in recalling absolute distance and categorical spatial relations; however males were better than females in recalling the distance between objects and the size of the layout. Overall, the data show a male advantage in some components of spatial cognition closely linked to the encoding of the metric structure of the spatial relationships at both route and survey level.

This study investigated the extent to which the type of task influences children's prospective memory performance. 80 subjects, aged 7 to 11 yr. participated in an experiment in which the type of task (time-based vs event-based) and the retention interval (5 min. vs 10 min.) varied. The prospective memory task was embedded in a principal task lasting about 15 min. and required subjects perform an action at a given time or in response to a specific cue. Analysis indicated that the delay was associated with prospective memory performance only on a time-based task in which the intention has to be performed after 10 min. but not age. Analysis indicated also that time monitoring was associated with shorter latency between the target time and the execution of the intention on the time-based task. Implications were discussed.

The makers have examined 455 fingerprint cards of accidents at biologic risk needed in a sanitary structure from the month of november 1995 to the month of december 1998. After they have described the protocol of the sanitary supervision applied, the procedure of the accidents, the qualifications, and the departments mainly interested by the subject of study event, they have pointed out the need of a greater vaccinable covering against the virus B, parvying attention to the "non responders" subjects, thinking also it's necessary bigger resources for the personnel, training and information.

Alkaline (pI 8.6-7.5) and neutral (pI 7.0-6.0) isoforms of human TSH have been isolated from a highly purified intrapituitary preparation by isoelectric focusing and compared for their respective actions on thyroid cell proliferation. Both TSH isoforms displayed the same ability to bind to porcine thyroid membranes as the original hormone preparation, indicating a similar recognition at the receptor sites. Alkaline forms showed a higher potency in inducing either cyclic AMP (cAMP) production or [3H]thymidine incorporation in FRTL-5 cells (half-maximal effective doses (ED50 values) = 0.25 and 0.29 nM respectively) compared with their neutral counterparts (ED50 values = 0.66 and 0.70 nM respectively). Increasing the concentration of alkaline forms in the presence of a half-maximal concentration of neutral TSH resulted in a profound inhibition of cell growth without a significant change in cAMP. Conversely, increasing the amount of neutral forms in the presence of a half-maximal dose of alkaline TSH resulted in an additive response for cAMP production but not in cell proliferation. To assess whether glycosylation might be responsible for the variation in hormone action, both alkaline and neutral TSH isoforms were tested for recognition of their carbohydrate chains by concanavalin A (Con A) and ricin. No major difference was found in binding to Con A, indicating that the contribution of carbohydrates to changes in hormone pI was not related to core branching. Very few galactose residues were accessible in either hormone fraction since little binding to ricin was observed. Isoelectric focusing of TSH forms before and after neuraminidase treatment revealed that neutral forms had a higher sialic acid content than alkaline TSH. In conclusion, the current findings show that TSH isoforms differentially affect cAMP production and cell growth. TSH fractions with a high sialic acid content and a low mitogenic activity behave as antagonists to the more active forms for cell proliferation. It is suggested that physiological control of TSH action at the thyroid gland may reside in the respective amounts of various TSH forms which, once bound to their receptor, can induce variable activation of post-receptor events while controlling cell proliferation.

To understand better why patients with TSH-secreting pituitary tumors exhibit variable degree of hyperthyroidism, we analyzed the various isoforms of TSH and alpha-subunit secreted by 4 TSH-secreting adenomas in primary culture. All patients had macrodenomas clinically associated with hyperthyroidism with normal to elevated TSH plasma levels. The in vivo molar alpha/TSH ratio ranged from 18.4 to 3.8. The hormone material secreted over 4 to 48 h in culture was separated by gel isoelectrofocusing, eluted and estimated by immunoassays. The release of free alpha-subunit was noticeably different among adenomas. Three tumors were found to release an homogeneous and acidic (pI = 5.4-4.5) species totally unrelated to the alpha-subunit dissociated from intrapituitary TSH (5 isoforms, pI = 8.8-5.8) while another was more heterogeneous (pI = 8.8, 8.4, 7.6, 6.8, 5.8, 5.4-4.5). Tumoral TSH exhibited at least six detectable isoforms (pI = 8.6, 8.3-8.0, 7.5, 7.0, 6.5, 6.0) very similar to those present in a purified intrapituitary hormone preparation. While intrapituitary TSH was composed of 70% of alkaline (pI = 8.6-7.5), 25% of neutral (pI = 7.0-6.0) and 5% (pI = 5.8-4.5) of acidic forms, these species were found to be more evenly distributed in adenomatous secretion (43%/42%/15%). The TSH-secreting tumors thus appeared to relase preferentially neutral and acidic forms of TSH than alkaline components but for one tumor, this ratio could be modified by chronic incubation with TRH. When assayed for their capacity to stimulate 3H-thymidine incorporation in FRTL-5 cells, neutral TSH appeared definitely less potent than the alkaline and acidic isohormones. Altogether, these data show that pituitary adenomas synthesize normal forms of TSH but release them in variable amount in the medium. When circulating in the blood, the ratio between active and inactive isoforms of TSH may thus be responsible for the variable stimulation of the thyroid gland observed in the patients.

To compare the structural topology of the human TSH to that of the structurally related gonadotropins, 10 peptides covering the entire primary sequence of the alpha- and beta-subunits of TSH were synthesized and used as antigens for the preparation of polyclonal antibodies. The alpha-subunit was synthesized as 4 nonoverlapping peptides (1-25, 26-51, 49-73, 72-92) while the beta-subunit was segmented in 6 overlapping sequences (2-18, 10-38, 31-51, 53-76, 77-96, 92-112). Most of the peptide sequences were predicted to contain a putative antigenic determinant. All antipeptide antisera were found to bind to the corresponding synthetic sequence in an enzyme-linked immunosorbent assay as well as to denatured TSH subunits after Western blotting. The N-terminal half of the alpha-subunit was found differentially accessible in TSH and gonadotropins compared to the free subunit: antipeptide-alpha 1-25 antibodies exhibited variable affinity for the four glycoprotein hormones whereas anti-alpha 26-51 displayed a remarkable recognition of free alpha-subunit. Four peptides proved to be accessible in the TSH beta-subunit: the N-terminal peptide (beta 2-18) elicited antibodies that bound to free TSH-beta and poorly to the dimer while antibodies against the C-terminal sequence (beta 92-112) recognized equally well free beta-subunit and TSH. Antipeptide-beta 31-51 antibodies proved to be specific for TSH while the beta 53-76 contiguous peptide appeared accessible in both TSH and gonadotropins. The current findings therefore demonstrate that most of the sequences predicted to contain antigenic sites in the alpha- or the beta-subunits are indeed accessible at the surface of these proteins. Additionally, both subunits appear to contain amino acid sequences that are differentially expressed in TSH and gonadotropins as well as in free and combined subunits.

Enzymatic deglycosylation of human thyroid-stimulating hormone (hTSH) was shown to result in a mixture of partially and fully deglycosylated forms of the hormone by gel electrophoresis, silver staining and immunoblotting. Radioiodination of the enzymatic digest, followed by gel filtration and concanavalin A-Sepharose chromatography allowed to separate two different forms of partially deglycosylated [125I]hTSH and a fully deglycosylated hormone. The final recovery was of approx. 60% for [125I]hTSH deglycosylated in its beta-subunit, of 30% for [125I]hTSH missing the oligosaccharide in beta and one in alpha but only of 10% for [125I]hTSH deglycosylated in both the alpha- and beta-subunits. Gel electrophoresis under non-denaturing conditions showed that each form migrated distinctly from free subunits and reverse-phase high performance liquid chromatography after reduction and carboxymethylation identified the presence of the two subunits. Mapping of [125I]hTSH derivatives with polyclonal, monoclonal and anti-peptide antibodies allowed to identify two novel glycosylation-independent epitopes preserved in deglycosylated hTSH while the main immunogenic determinant was lost. When assayed in a bioassay with FRTL-5 cells, the hormone deprived of its beta-linked carbohydrate chain was found to be as effective as the native hormone on cAMP production and cell growth. In contrast, the fully deglycosylated derivative proved to stimulate cAMP release but appeared to be definitely less potent on thyroid cell growth. Our findings thus demonstrate that glycosylation of the alpha-subunit but not that of the beta-subunit is essential to express the domains involved in hTSH immunoreactivity as well as those controlling the post-receptor biological activity of the hormone.

Isoforms of intrapituitary human TSH were separated by gel isoelectrofocusing, and their immunoreactivity analyzed by subsequent immunoblotting using polyclonal and monoclonal antibodies. Under these conditions, TSH polymorphism could be resolved as seven major isoforms (pI 8.6, 8.3, 8.0, 7.5, 7.0, 6.5, and 6.0) by both silver staining of the gels and binding to anti-TSH polyclonal antibodies. The distribution pattern of these forms appeared totally distinct from that of individual TSH alpha (pI 8.8, 8.4, 8.2, 7.6, 7.4, 6.8, 6.6, 5.8, and 5.4) and TSH beta (pI 8.7, 8.1, 7.2, 6.8, 6.2, and 5.8) subunits. While most anti-TSH polyclonal antibodies recognized neutral and alkaline isoforms of TSH (pI 8.6, 8.3, 8.0, 7.5, 7.0, 6.5, and 6.0) through beta determinants, they displayed a variable potency to bind acidic forms of the hormone (pI 5.8, 5.5, 4.8, and 4.5), in contrast to anti-TSH alpha antisera, which enlighted the broadest spectrum of isoforms. Monoclonal antibodies of various specificities largely reproduced this distribution, indicating that at least five distinct epitopes are coexpressed in the neutral and alkaline forms of TSH, but only two are expressed in the acidic ones. All of the forms were found to induce cAMP production and stimulate growth of FRTL-5 rat thyroid cells, although neutral forms proved to be definitely less potent than the others. We therefore, conclude that TSH isoforms differ in the expression of both their immunoreactive and bioactive domains and that the bioactive/immunoreactive ratio is not an accurate index for the biopotency of the hormone.

When wheat-germ RNA polymerase II is subjected to mild proteolytic attack in the presence of trypsin, the resulting form of the enzyme migrates as a single species on electrophoresis in native polyacrylamide gels, with an apparent Mr significantly smaller than that of the native enzyme. Analysis by denaturing gel electrophoresis of the truncated eukaryotic polymerase revealed that the two largest subunits of the native enzyme, i.e. the 220,000-Mr and 140,000-Mr subunits, were cleaved, giving rise to shorter polypeptide chains of Mr 172,800, 155,000, 143,000, 133,800, 125,000 and 115,000. The use of affinity-purified antibodies directed against each of the two large subunits of the native enzyme allowed us to probe for possible precursor/product relationships between the 220,000-Mr and 140,000-Mr subunits of wheat-germ RNA polymerase II and their breakdown products generated in the presence of trypsin. None of the smaller subunits of the plant RNA polymerase II appeared to be sensitive to trypsin attack. The results indicate that the truncated RNA polymerase retained a multimeric structure, and therefore that the proteolyzed largest subunits of the enzyme remained associated with the smaller ones. Furthermore, in transcription of a poly[d(A-T)] template, the catalytic activity of the proteolyzed form of wheat-germ RNA polymerase II was identical to that of the native enzyme. Therefore, the protein domains that can be deleted by the action of trypsin from the two large subunits of the plant transcriptase are not involved in DNA binding and/or nucleotide binding, and do not play an important role in template-directed catalysis of phosphodiester bond formation.

To probe possible effects of carbohydrate chains in the conformation of pituitary glycoprotein hormones, two radiolabeled derivatives of human thyroid-stimulating hormone (hTSH), either partially deglycosylated in the beta-subunit or fully deglycosylated in both the alpha- and beta-subunits, were compared to the native hormone for binding to monoclonal as well as polyclonal antibodies. Monoclonal antibodies were screened for their ability to bind the intact hormone (anti-hTSH), hTSH and its free alpha-subunit (anti-alpha) or its free beta-subunit (anti-beta). A panel of 14 monoclonal antibodies directed against at least eight out of the 12 epitopes known to be present in the hormone was tested in solid-phase assays for their capacity to bind intact and deglycosylated forms of hTSH. All of them displayed identical recognition of native and partially deglycosylated 125I-hTSH. In contrast, binding of fully deglycosylated 125I-hTSH to anti-hTSH and anti-beta antibodies was dramatically lost while that of anti-alpha was preserved. This clearly indicates that most of the epitopes specific for subunit association as well as those present on the beta-subunit are glycosylation dependent. No alteration was found in antibody recognition following deglycosylation of free individual subunits, indicating that the carbohydrate effect can only occur in the combined dimer. Using polyclonal antisera raised against the International Reference Preparations, we found that the deglycosylated hormone could be bound by the anti-beta antiserum although at a much lower dilution than the native antigen, suggesting the presence of at least one glycosylation-independent epitope in the beta-subunit. Competitive binding assays revealed that deglycosylated hTSH is 5 times less immunoreactive toward the anti-beta compared to the anti-alpha antiserum. The current data thus demonstrate the presence of the glycosylation-independent epitopes in the alpha-subunit of hTSH and the localization of most of the glycosylation-dependent domains in the beta-subunit.