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IntroductionNuclear factor kappa B (NF-κB) is a key regulator of immune and inflammatory responses. Glucocorticoid drugs (GC) act through the glucocorticoid receptor (GR) as immunosuppressant also in pediatric patients inhibiting NF-κB activity. The long non-coding RNA GAS5 interacts with the GR, influencing GC activity. No data on the role of GAS5 on GR-dependent inhibition of NF-κB activity have been published.MethodsThis study investigated the impact of GAS5 on NF-κB activity in HeLa cells overexpressing GAS5, both under basal conditions and during GC treatment. The study used EMSA, RNA-immunoprecipitation (RIP), Western blotting, and bioinformatic analyses to assess NF-κB DNA binding, GAS5-p65 interaction, and NF-κB signaling pathway modulation.ResultsGAS5 overexpression increased NF-κB DNA binding activity in untreated cells. RNA-IP confirmed a direct interaction between GAS5 and the NF-κB subunit p65, suggesting a potential regulatory mechanism. GAS5 overexpression led to downregulation of NF-κB target genes, TNF-α, and NR3C1. GC treatment reduced NF-κB DNA binding activity in GAS5-overexpressing cells, indicating a potential synergistic effect. Furthermore, GAS5 overexpression increased IκB levels and reduced p-p65/pan-p65 levels during GC treatment.DiscussionGAS5 appears to modulate NF-κB activity in a complex manner, influencing both basal and GC-induced signaling. The interaction between GAS5, GCs, and NF-κB is multi-faceted, and further research is needed to fully elucidate the underlying mechanisms. These findings suggest that GAS5 could be a potential target for personalized therapy, particularly in pediatric patients with inflammatory conditions.

Abstract Background The prognostic value of evoked potentials (EPs) in multiple sclerosis (MS) has not been fully established. The correlations between the Expanded Disability Status Scale (EDSS) at First Neurological Evaluation (FNE) and the duration of the disease, as well as between EDSS and EPs, have influenced the outcome of most previous studies. To overcome this confounding relations, we propose to test the prognostic value of EPs within an appropriate patient population which should be based on patients with low EDSS at FNE and short disease duration. Methods We retrospectively selected a sample of 143 early relapsing remitting MS (RRMS) patients with an EDSS < 3.5 from a larger database spanning 20 years. By means of bivariate logistic regressions, the best predictors of worsening were selected among several demographic and clinical variables. The best multivariate logistic model was statistically validated and prospectively applied to 50 patients examined during 2009–2011. Results The Evoked Potentials score (EP score) and the Time to EDSS 2.0 (TT2) were the best predictors of worsening in our sample (Odds Ratio 1.10 and 0.82 respectively, p=0.001). Low EP score (below 15–20 points), short TT2 (lower than 3–5 years) and their interaction resulted to be the most useful for the identification of worsening patterns. Moreover, in patients with an EP score at FNE below 6 points and a TT2 greater than 3 years the probability of worsening was 10% after 4–5 years and rapidly decreased thereafter. Conclusions In an appropriate population of early RRMS patients, the EP score at FNE is a good predictor of disability at low values as well as in combination with a rapid buildup of disability. Interestingly, an EP score at FNE under the median together with a clinical stability lasting more than 3 years turned out to be a protective pattern. This finding may contribute to an early identification of benign patients, well before the term required to diagnose Benign MS (BMS).

A company’s cyber defenses are based on a secure infrastructure and risk-aware behavior by employees. With rising cyber threats and normative training efforts showing limited impact, raising cyber risk awareness is emerging as a challenging effort. The review of the extant literature on awareness diagnosis shows interdisciplinary but mainly theoretical approaches to understanding attitudes and influencing risk behavior. We propose and test a novel methodology to combine and operationalize two tools, deep metaphor interviews and the IDEA risk communication model, to apply them for the first time in the context of behavioral cyber vulnerabilities. The results show a link between diagnosed attitudes and effective risk behavior in a real-life organizational setting, indicating the potential for an expanded diagnostic effort. We propose to develop a broader diagnostic and intervention set to improve cyber awareness and a toolkit to support the business practice of cyber risk management.

Introduction: Nuclear factor kappa B (NF-κB) is a key regulator of immune and inflammatory responses. Glucocorticoid drugs (GC) act through the glucocorticoid receptor (GR) as immunosuppressant also in pediatric patients inhibiting NF-κB activity. The long non-coding RNA GAS5 interacts with the GR, influencing GC activity. No data on the role of GAS5 on GR-dependent inhibition of NF-κB activity have been published. Methods: This study investigated the impact of GAS5 on NF-κB activity in HeLa cells overexpressing GAS5, both under basal conditions and during GC treatment. The study used EMSA, RNA-immunoprecipitation (RIP), Western blotting, and bioinformatic analyses to assess NF-κB DNA binding, GAS5-p65 interaction, and NF-κB signaling pathway modulation. Results: GAS5 overexpression increased NF-κB DNA binding activity in untreated cells. RNA-IP confirmed a direct interaction between GAS5 and the NF-κB subunit p65, suggesting a potential regulatory mechanism. GAS5 overexpression led to downregulation of NF-κB target genes, TNF-a, and NR3C1. GC treatment reduced NF-κB DNA binding activity in GAS5-overexpressing cells, indicating a potential synergistic effect. Furthermore, GAS5 overexpression increased IκB levels and reduced p-p65/pan-p65 levels during GC treatment. Discussion: GAS5 appears to modulate NF-κB activity in a complex manner, influencing both basal and GC-induced signaling. The interaction between GAS5, GCs, and NF-κB is multi-faceted, and further research is needed to fully elucidate the underlying mechanisms. These findings suggest that GAS5 could be a potential target for personalized therapy, particularly in pediatric patients with inflammatory conditions. [ABSTRACT FROM AUTHOR]

Social media usage has grown rapidly in recent years, and with it companies’ interest in interacting with their customers on these platforms. It is, however, not yet clear whether customers welcome more intense relationships on social media and what drives this acceptance in more detail. Our research aims at understanding how age, gender, geography, usage, type of platform, personality, and current insurance provider impact customers’ attitudes towards interacting with insurance companies in the Swiss market. We find that age and frequency of use, in particular, impact acceptance, with younger customers much more open to interactions and insurance presence more welcome on more frequently used tools. This is an encouraging result for insurers, as customers tend to welcome them where customers are already frequently present. In addition, insurers can look forward to increasing interaction as younger individuals, who are more open to social media, age into core customers. Social context, on the other hand, plays only a minor role in customer preferences. The current insurance provider plays no significant role, in spite of insurance companies in the sample following widely different approaches to digital offerings and communication. This may be due to the early stage of development of the industry.

Lockdown measures adopted in Italy to contain the diffusion of Covid-19 altered many variables influencing the anthropogenic pressure on marine ecosystems. Public reactions included surprise at how quickly changes in human activity seemingly improved natural recovery and, at the same time, a generalized anxiety to restart economic activities. In this situation several Institutions from the Italian National Research Council (CNR) made a joint effort to quantify the effects of the unprecedented experimental conditions induced by the reduction of many anthropogenic pressures. The resulting project was conceived with a holistic, interdisciplinary approach, geared to combine scientific, economic and cultural observations to promote collective actions suitable to the governance of socio-ecological systems, reconciling respect for the environment with human activities and wellbeing, and thus grounding an ethical approach to marine resources. Alongside collecting considerable amount of scientific observations, the project is working to complement samplings and analyses with the non-formal knowledge carried by the inhabitants of a set of coastal zones, thus enriching the generated knowledge and widening inclusion and pluralism in defining the challenges at stake; simultaneously it focuses on stimulating a reflection in the research community over the process of knowledge co-construction, its meaning, role and responsibility in the societal context. After a brief contextualization of this activity, we present here the perspective adopted by researchers to build a responsible marine research plan, inclusive on the grounds of both involved actors and knowledge sources. We comment the process- and community-related features, explore limits and opportunities, and propose a set of recommendations, based on a preliminary review of our experience and oriented to promote the development of a shared Ocean ethics.

A company's cyber defenses are based on a secure infrastructure and risk-aware behavior by employees. With rising cyber threats and normative training efforts showing limited impact, raising cyber risk awareness is emerging as a challenging effort. The review of the extant literature on awareness diagnosis shows interdisciplinary but mainly theoretical approaches to understanding attitudes and influencing risk behavior. We propose and test a novel methodology to combine and operationalize two tools, deep metaphor interviews and the IDEA risk communication model, to apply them for the first time in the context of behavioral cyber vulnerabilities. The results show a link between diagnosed attitudes and effective risk behavior in a real-life organizational setting, indicating the potential for an expanded diagnostic effort. We propose to develop a broader diagnostic and intervention set to improve cyber awareness and a toolkit to support the business practice of cyber risk management. [ABSTRACT FROM AUTHOR]

The conceptual framework of Essential Biodiversity Variables (EBVs) aims to capture the major dimensions of biodiversity change by structuring biodiversity monitoring and by ruling data collection amongst different providers. Amongst the research infrastructures adopting and implementing the EBV framework, LTER-Europe - the European node of ILTER (International Long-Term Ecological Research) - follows the approach to compare site-based biodiversity observations within and across its networks. However, a synoptic overview of their contributions with EBVs-relevant data is still missing, since data are not made available for several reasons. In this paper, we assess the capacity of LTER-Italy, one of the richest and heterogeneous networks of LTER sites in Europe, to provide data to “Species Distribution” and “Species Abundance” EBVs without inspecting and downloading their contents. To this aim, we mine the EBVs information which is publicly structured and shared by LTER site managers through DEIMS-SDR, the LTER-Europe online metadata repository. We classify the sites according to two types of contributions: (i) the actual contribution, based on metadata of datasets and (ii) the potential contribution, based on metadata of sites. Through these assessments, we investigate if LTER-Italy monitoring activities can provide EBVs measures and which sites currently provide datasets. By comparing the two contributions, we pinpoint the factors hampering the accessibility of LTER-Italy data and suggest solutions to increase the discoverability and reusability of LTER-Italy EBVs measurements. The research provides the first overview of EBVs monitored in LTER-Italy and the corresponding data management practices, as well as an evaluation of the interoperability of this network with respect to other research organisations for legal and technical aspects.

The design and establishment of Marine Ecological Observatories (MEOs) are fostered at the European level. MEOs should adopt a holistic view, integrating and harmonizing long-term oceanographic and ecological research and monitoring, and increasing conservation strategies effectiveness according to the ecological connectivity concept. The data and knowledge collected and made available through MEOs should inform policies dealing with conservation and management of the marine environment. We present and discuss these issues in the Adriatic Sea context, where the transnational ecological observatory “ECOAdS” is under development in the framework of the Interreg Italy-Croatia project ECOSS (Observing System in the Adriatic Sea: oceanographic observations for biodiversity), which aims to support Natura 2000 network implementation and cross-border coordination of multiple monitoring initiatives. We analyse the main EU directives that deal with marine conservation, notably the Habitats and Birds directives, the Water Framework Directive, and the Marine Strategy Framework Directive, as they are the primary instruments that can guide the development of the observatory while strengthening cooperation at the basin scale. We bring out the synergies and discrepancies among these legal instruments, and build on them ECOAdS as a monitoring platform that may respond and contribute to their requirements, boosting the synergies and overcoming the weaknesses. Finally, we provide some hints for the further development of this transnational MEO as a collector of the existing monitoring efforts aimed at harmonizing their approaches and incorporating the ecological connectivity to foster an ecosystem-based approach to conservation management.

This work presents a practical case study of the Open Science principles applied to the valorization of a long-term marine dataset collected in the Northern Adriatic Sea, one of the Long-Term Ecological Research (LTER) sites of the LTER-Italy network. The dataset covers a temporal range of 50 years (1965–2015), and it is composed of abiotic, and phyto- and zooplankton data, for a total of 21 parameters. The case study involved many actions, which will be described here, distinguishing between the ones affecting the whole research project workflow and those acting more specifically on the dataset. We evaluate strengths, weaknesses, and possible improvements for each action. The present study pointed out that, despite the initial and still some remaining mistrust, opening research projects is more than a best practice. It is (i) important because it improves research transparency (increasing researchers’ credibility, replicability of science, and products reuse), (ii) required by many international initiatives and regulations, and (iii) enriching because it encourages cooperation between scientists across different fields and laboratories.

Based on the last decade of activities at the Italian Long Term Ecological Research network (LTER-Italy), I describe and highlight here some major outcomes and challenges, by picturing different voices, which we are listening to and we are talking with. Organisms, ecosystems, methodologies, data, researchers, stakeholders and citizens: their “voices” - which we receive, interpret and express - create our experience and knowledge, which we share with and convey to our contemporaries and future generations. One of the main narrator’s voices will be that of plankton: how we “listen” to them, describe and share long-term data and researches, also with the wide public. Through the “voices from the water” I will report and discuss experiences, which have been relevant also to open up the views on the role that science is challenged to play in a world of rapid change, characterized by complexity and contradictions. In particular I will consider: (i) the voices coming from various LTER aquatic sites, mainly addressing the comparison among them, (ii) how to make the voices most harmonized and audible through the open science approach, and (iii) how to put the LTER voices in an effective dialogue with society. Finally I will share some thoughts about the necessity and the possibility to open the purely scientific cognitive approach to other forms of knowledge.

Transitional waters are subject to a high degree of variability in space and time. In this study, protist plankton communities of the Lagoon of Venice were compared among four sites characterised by different environmental conditions with a metabarcoding approach. High throughput sequencing (HTS) of the V4-18S rDNA fragment in 32 samples collected on four dates, from April 2016 to February 2017, produced 1,137,113 reads, which were grouped into 4,058 OTUs at 97% similarity. Bacillariophyta and Ciliophora were the most abundant groups in the entire dataset in terms of read number (27.6% and 16.6%, respectively), followed by Dinophyta (10.9%), Cryptophyceae (9.7%), and Syndiniales (6.1%). The contribution of protist groups markedly varied across the seasons, but spatial differences were also recorded in the lagoon. In April, a higher contribution of Bacillariophyta characterized St1 and 5 (68.0% and 61.1%), whereas Sts2 and 3 showed a higher percentage of Ciliophora (18.6 and 23.4%, respectively) and dinoflagellates (10.3 and 7.7%). In July, diatom blooms occurred at Sts1, 2 and 3, with some differences in the dominant species. At St2 Dinophyta reached the highest contribution of the whole sampling period in the area (30.6%), while St5 was quite distinct, with a low contribution of diatoms and a dominance of Ciliophora (34.0%) and Trebouxiophyceae (36.4%). All the stations in November were characterized by relatively high abundance of Ciliophora (21.4-51.9%). In February, diatom contribution was relevant only at St5 (29.3%), Teleaulax acuta peaked at St3 (ca. 36%), Syndiniales at St2 (38.8%) and Dictyochophyceae at St1 (24.2%). The α-diversity indexes (observed OTUs, Shannon and Pielou evenness) showed a high variability over space and time. Overall, diversity and community composition were rather similar between the intermediate and deeper Sts2 and 3 on all sampling dates whereas they at time differed between the landward and shallow Sts1 and 5. While the most marked differences occurred over the temporal scale, the depth of the station and the relatedness with the external marine coastal environment appear to play a major role in the spatial distribution of protist communities within the lagoon.

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The Lagoon of Venice (LoV) and the Gulf of Venice (GoV), two adjacent coastal Long Term Ecological Research (LTER) sites in the northern Adriatic Sea, represent a transitional/marine coupled ecosystem under the influence of regional and local factors. In this study, these sites were sampled on four dates from April 2016 to February 2017 for environmental DNA and relevant abiotic variables, aiming to assess the relative importance of habitat heterogeneity and connectivity in structuring the protist community. High Throughput Sequencing of V4-18S rRNA gene from 56 samples collected at seven stations produced ca 6 million reads, grouped into 7,336 Operational Taxonomic Units (OTUs) at 97% similarity, which were affiliated to protists belonging to 34 taxonomic groups. The whole community was dominated by Bacillariophyta, especially in spring-summer in the LoV, and by Dinophyta, mainly in the GoV. Ciliophora, Syndiniales, and Cryptophyceae were the next more abundant groups. The community structure varied across the seasons and was different in the two ecosystems, which shared 96% of the reads but showed a high proportion of OTUs distributed preferentially in one of the two sites (specialists) and a different partitioning of trophic categories. GoV specialists were mainly Dinophyceae (>56%), followed by Syndiniales and Bacillariophyta, while the LoV specialists were distributed among several groups, including Bacillariophyta, Syndiniales, Ciliophora, Cryptophyceae, and Trebouxiophyceae. The main abiotic drivers of the differences between protist communities were salinity and temperature, which however explained a minor part of the variance (17%), pointing at a higher relevance of biotic factors and inter-taxa relationships. This was more evident in the LoV, where the network analysis highlighted a higher number of OTUs’ connections than in the GoV. Overall, the metabarcoding approach allowed to depict the composition of the whole protist community in the lagoon and adjacent coastal waters with high resolution, revealing many taxa so far not reported in the area. In addition, despite no clear barrier to dispersal processes, differences in the relative abundance and temporal variability of local protist communities indicate that environmental heterogeneity, in these adjacent and connected ecosystems, can be strong enough to allow for ecological segregation.

Understanding the threats to global biodiversity and ecosystem services posed by human impacts on coastal and marine environments requires the establishment and maintenance of ecological observatories that integrate the biological, physical, geological, and biogeochemical aspects of ecosystems. This is crucial to provide scientists and stakeholders with the support and knowledge necessary to quantify environmental change and its impact on the sustainable use of the seas and coasts. In this paper, we explore the potential for the coastal and marine components of the International Long-Term Ecological Research Network (ILTER) to fill this need for integrated global observation, and highlight how ecological observations are necessary to address the challenges posed by climate change and evolving human needs and stressors within the coastal zone. The ILTER is a global network encompassing 44 countries and 700 research sites in a variety of ecosystems across the planet, more than 100 of which are located in coastal and marine environments (ILTER-CMS). While most of the ILTER-CMS were established after the year 2000, in some cases they date back to the early 1900s. At ILTER sites, a broad variety of abiotic and biotic variables are measured, which may feed into other global initiatives. The ILTER community has produced tools to harmonize and compare measurements and methods, allowing for data integration workflows and analyses between and within individual ILTER sites. After a brief historical overview of ILTER, with emphasis on the marine component, we analyze the potential contribution of the ILTER-CMS to global coastal and ocean observation, adopting the “Strength, Weakness, Opportunity and Threats (SWOT)” approach. We also identify ways in which the in situ parameters collected at ILTER sites currently fit within the Essential Ocean Variables framework (as proposed by the Framework for Ocean Observation recommendations) and provide insights on the use of new technology in long-term studies. Final recommendations point at the need to further develop observational activities at LTER sites and improve coordination among them and with external related initiatives in order to maximize their exploitation and address present and future challenges in ocean observations.

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This study investigates the role of Information and Communication Technologies (ICT) investment and diffusion on Pakistan’s economic growth by proposing the threshold level of ICT investment. At our proposed level, the ICT imports significantly enhance the intermediate inputs to capital goods, ultimately enhancing economic growth. For this empirical investigation, we use the maximum available data on technological innovation and investment, ranging from 2003 to 2018. Incorporating the structural breaks, the results of regression analysis reveal that Pakistan’s economic growth is unaffected by ICT development. However, we observe the mixed shreds of evidence on the ICT investment. Following existing literature, we use ICT goods exports and imports as a proxy for ICT investment. Interestingly, the economic growth of Pakistan is again unaffected by the ICT goods exports. However, we observe that a one percent increase in ICT goods imports enhances economic growth by 1.73 percent. Then, we extend this analysis to the threshold approach, which reveals that ICT imports affect the overall economic growth when the ICT goods imports reach the level of 4.13 percent of the total imports. At this threshold, the ICT goods import significantly enhances the intermediate input to the capital goods, leading to higher economic growth. Therefore, the policymakers should ensure that the ICT goods import must be greater than the 4.13 percent of Pakistani imports.