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The task of preventing suicide in older adults is an important social burden as older adults aged above 65 are exposed to singular psychological aspects that increase suicide risks. Moreover, when an older adult corpse is found, the medico-legal inspection represents a fundamental tool to identify the exact cause of death, classifying or excluding it as suicide. In this scenario, this review aims to explore the neurobiological factors that could be related to suicidal behavior in older adults. A further goal of this review is the exploration of the medico-legal aspects surrounding older adult suicides, clarifying the importance of forensic investigation. Particularly, this review examines issues such as neurotransmitter imbalances, cognitive impairment, neuroinflammation, psychosocial factors related to geriatric suicide, and neurodegenerative diseases. Additionally, medico-legal aspects such as policy considerations, legal frameworks, mental health assessments, ethical implications and forensic investigation were explored. Considering the importance of this phenomenon, especially in western countries, a need has emerged for focused screening tools on suicidal behavior among older adults, in order to contain it. Therefore, this review makes an exhaustive appraisal of the literature giving insights into the delicate interplay between neurobiology as well as mental health in relation to older adult suicide within a medico-legal context. The comprehension of different aspects about this complex phenomenon is fundamental to propose new and more effective interventions, supporting tailored initiatives such as family support and improving healthcare, specifically towards vulnerable ageing societies to reduce older adult suicide risks.

The WHO African Region had 81 million people with chronic hepatitis B in 2019, which remains a silent killer. Hepatitis B virus (HBV), hepatitis delta virus (HDV), and HIV can be transmitted from the mother to child. If the HBV infection is acquired at infancy, it may lead to chronic hepatitis B in 90% of the cases. WHO reports that 6.4 million children under 5 years live with chronic hepatitis B infection worldwide. The prevention of mother-to-child transmission (PMTCT) of HBV is therefore critical in the global elimination strategy of viral hepatitis as we take lessons from PMTCT of HIV programs in Africa. We sought to create a network of multidisciplinary professional and civil society volunteers with the vision to promote cost-effective, country-driven initiatives to prevent the MTCT of HBV in Africa. In 2018, the Mother–Infant Cohort Hepatitis B Network (MICHep B Network) with members from Cameroon, Zimbabwe, and the United Kingdom and later from Chad, Gabon, and Central African Republic was created. The long-term objectives of the network are to organize capacity-building and networking workshops, create awareness among pregnant women, their partners, and the community, promote the operational research on MTCT of HBV, and extend the network activities to other African countries. The Network organized in Cameroon, two “Knowledge, Attitude and Practice” (KAP) surveys, one in-depth interview of 45 health care workers which revealed a high acceptability of the hepatitis B vaccine by families, two in-person workshops in 2018 and 2019, and one virtual in 2021 with over 190 participants, as well as two workshops on grant writing, bioethics, and biostatistics of 30 postgraduate students. Two HBV seroprevalence studies in pregnant women were conducted in Cameroon and Zimbabwe, in which a prevalence of 5.8% and 2.7%, respectively, was reported. The results and recommendations from the MICHep B Network activities could be implemented in countries of the MICHep B Network and beyond, with the goal of providing free birth dose vaccine against hepatitis B in Africa.

Food labeling is increasingly expanding and adding more information to the food package. There is strong evidence about nutrition labeling effectiveness in driving food choice, especially if displayed in the front of package (FoP). Despite the growing attention to nutrition and sustainable diets, few countries have implemented sustainable labels or eco-labels that could address economic, social and/or environmental concerns. Implementing new techniques of eco-labeling emerges as a consumer-focused solution. However, evidence of the effectiveness of eco-labeling in driving consumers’ choices is heterogeneous and not univocal. Thus, this review aims to summarize the evidence about the effectiveness of FoP eco-labeling in driving food choice and provide a reference framework of the eco-labeling initiatives relative to food package labeling. This narrative review addresses both the potential benefits as well as the main concerns that arise from the use of eco-labels. Although eco-labeling seems to provide a series of sustainability benefits for producers and consumers, the implementation of such policies should take into consideration potential trade-offs and inter-sectorial coordination to obtain bigger impacts, assuming that a policy itself cannot transform the whole food system. Eco-labeling could be encouraged and implemented within a set of policies shaping sustainable food systems.

Introduction: The response of the brain to space radiation is an important concern for astronauts during space missions. Therefore, we assessed the response of the brain to 28Si ion irradiation (600 MeV/n), a heavy ion present in the space environment, on cognitive performance and whether the response is associated with altered DNA methylation in the hippocampus, a brain area important for cognitive performance.Methods: We determined the effects of 28Si ion irradiation on object recognition, 6-month-old mice irradiated with 28Si ions (600 MeV/n, 0.3, 0.6, and 0.9 Gy) and cognitively tested two weeks later. In addition, we determined if those effects were associated with alterations in hippocampal networks and/or hippocampal DNA methylation.Results: At 0.3 Gy, but not at 0.6 Gy or 0.9 Gy, 28Si ion irradiation impaired cognition that correlated with altered gene expression and 5 hmC profiles that mapped to specific gene ontology pathways. Comparing hippocampal DNA hydroxymethylation following proton, 56Fe ion, and 28Si ion irradiation revealed a general space radiation synaptic signature with 45 genes that are associated with profound phenotypes. The most significant categories were glutamatergic synapse and postsynaptic density.Discussion: The brain’s response to space irradiation involves novel excitatory synapse and postsynaptic remodeling.

BackgroundThe consumption of 100% fruit juices has not been associated with substantial detrimental outcomes in population studies and may even contribute to improving the cardiometabolic profile if included in a healthy balanced diet. The main contributors to such potential beneficial effects include vitamins, minerals, and likely the (poly)phenol content. This study aimed to investigate whether the (poly)phenols contained in 100% fruit juices may mediate their effects on cardiometabolic risk factors based on published randomized controlled trials (RCT).MethodsA systematic search in PubMed/MEDLINE and Embase, updated till the end of October 2022, was carried out to identify RCT providing quantitative data on (poly)phenol content in 100% fruit juices and used as an intervention to improve cardiometabolic parameters such as blood lipids, glucose, and blood pressure. Meta-regression analysis was performed to calculate the effect of the intervention [expressed as standardized mean difference and 95% confidence intervals (CI)] using the (poly)phenol content as moderator.ResultsA total of 39 articles on RCT investigating the effects of 100% fruit juices on cardiometabolic risk factors reporting data on total (poly)phenol and anthocyanin content were included in the analysis. Total (poly)phenol content was substantially unrelated to any outcome investigated. In contrast, each 100 mg per day increase in anthocyanins was related to 1.53 mg/dL decrease in total cholesterol (95% CI, −2.83, −0.22, p = 0.022) and 1.94 mg/dL decrease in LDL cholesterol (95% CI, −3.46, −0.42, p = 0.012). No other potential mediating effects of anthocyanins on blood triglycerides, glucose, systolic and diastolic pressure were found, while a lowering effect on HDL cholesterol after excluding one outlier study was observed.DiscussionIn conclusion, the present study showed that anthocyanins may mediate the potential beneficial effects of some 100% fruit juices on some blood lipids. Increasing the content of anthocyanins through specific fruit varieties or plant breeding could enhance the health benefits of 100% fruit juices.

RationaleTherapies that slow idiopathic pulmonary fibrosis (IPF) progression are now available and recent studies suggest that the use of antifibrotic therapy may reduce IPF mortality.ObjectivesThe aim of the study was to evaluate whether, to what extent, and for which factors the survival of IPF in a real-life setting has changed in the last 15 years.MethodsHistorical eye is an observational study of a large cohort of consecutive IPF patients diagnosed and treated in a referral center for ILDs with prospective intention. We recruited all consecutive IPF patients seen at GB Morgagni Hospital, Forlì, Italy between January 2002 and December 2016 (15 years). We used survival analysis methods to describe and model the time to death or lung transplant and Cox regression to model prevalent and incident patient characteristics (time-dependent Cox models were fitted).Measurements and main resultsThe study comprised 634 patients. The year 2012 identifies the time point of mortality shift (HR 0.58, CI 0.46–0.63, p < 0.001). In the more recent cohort, more patients had better preserved lung function, underwent cryobiopsy instead of surgery, and were treated with antifibrotics. Highly significant negative prognostic factors were lung cancer (HR 4.46, 95% CI 3.3–6, p < 0.001), hospitalizations (HR 8.37, 95% CI 6.5–10.7, p < 0.001), and acute exacerbations (HR 8.37, 95% CI 6.52–10.7, p < 0.001). The average antifibrotic treatment effect estimated using propensity score matching showed a significant effect in the reduction of all-cause mortality (ATE coeff −0.23, SE 0.04, p < 0.001), acute exacerbations (ATE coeff −0.15, SE 0.04, p < 0.001), and hospitalizations (ATE coeff −0.15, SE 0.04, p < 0.001) but no effect on lung cancer risk (ATE coeff −0.03, SE 0.03, p = 0.4).ConclusionAntifibrotic drugs significantly impact hospitalizations, acute exacerbations, and IPF survival. After the introduction of cryobiopsy and antifibrotic drugs, the prognosis of IPF patients has significantly improved together with our ability to detect IPF at an earlier stage.

BackgroundDeep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course.MethodsThis study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). 1H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes. ResultsHere, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients.ConclusionThe identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.

Autoimmune blistering diseases such as bullous pemphigoid (BP) and pemphigus vulgaris (PV) are complex, multifactorial, and polygenic diseases, whose exact pathogenesis is difficult to pinpoint. Research aimed at elucidating the associated epidemiologic risk factors of these two diseases has been hampered by their rare disease status. Further, a lack of centralization and standardization of available data makes the practical application of this information challenging. In order to collate and clarify the available literature we comprehensively reviewed 61 PV articles from 37 different countries and 35 BP articles from 16 different countries addressing a range of disease relevant clinical parameters including age of onset, sex, incidence, prevalence, and HLA allele association. The reported incidence of PV ranged from 0.098 to 5 patients per 100,000 people, while BP ranged from 0.21 to 7.63 patients per 100,000. Prevalence of PV ranged from 0.38 to 30 per 100,000 people and BP ranged from 1.46 to 47.99 per 100,000. The mean age of onset in patients ranged from 36.5 to 71 years for PV and 64 to 82.6 years for BP. Female-to-male ratios ranged from 0.46 to 4.4 in PV and 1.01 to 5.1 in BP. Our analysis provides support for the reported linkage disequilibrium of HLA DRB1*0402 (an allele previously shown to be associated with PV) and DQB1*0302 alleles in Europe, North America, and South America. Our data also highlight that HLA DQB1*0503 (also known to be associated with PV) appears in linkage disequilibrium with DRB1*1404 and DRB1*1401, mainly in Europe, the Middle East, and Asian countries. The HLA DRB1*0804 allele was only associated with PV in patients of Brazilian and Egyptian descent. Only two HLA alleles were reported as associated with BP more than twice in our review, DQB1*0301 and DQA1*0505. Collectively, our findings provide detailed insights into the variation of disease parameters relevant to PV and BP that can be expected to inform future work aimed at unraveling the complex pathogenesis of these conditions across the globe.

Landslide susceptibility assessment using machine learning models is a popular and consolidated approach worldwide. The main constraint of susceptibility maps is that they are not adequate for temporal assessments: they are generated from static predisposing factors, allowing only a spatial prediction of landslides. Recently, some methodologies have been proposed to provide spatiotemporal landslides prediction starting from machine learning algorithms (e.g., combining susceptibility maps with rainfall thresholds), but the attempt to obtain a dynamic landslide probability map directly by applying machine learning models is still in the preliminary phase. This work provides a contribution to fix this gap, combining in a Random Forest (RF) algorithm a static indicator of the spatial probability of landslide occurrence (i.e., a classical susceptibility index) and a number of dynamic variables (i.e., seasonality and the rainfall amount cumulated over different reference periods). The RF implementation used in this work allows the calculation of the Out-of-Bag Error and depicts Partial Dependence Plots, two indices that were used to quantify the variables’ importance and to comprehend if the model outcomes are consistent with the triggering mechanism observed in the case of study (Metropolitan City of Florence, Italy). The goal of this research is not to set up a landslide probability map, but to 1) understand how to populate training and test datasets with observations sampled over space and time, 2) assess which rainfall variables are statistically more relevant for the identification of the time and location of landslides, and 3) test the dynamic application of RF in a forecasting model for the spatiotemporal prediction of landslides. The proposed dynamic methodology shows encouraging results, consistent with the actual knowledge of the physical mechanism of the triggering of shallow landslides (mainly influenced by short and intense rainfalls) and identifies some benchmark configurations that represents a promising starting point for future regional-scale applications of machine learning models to dynamic landslide probability assessment and early warning.

BackgroundA subgroup of IPF patients can meet IPAF criteria (features suggesting an underlying autoimmune process without fulfilling established criteria for a CTD). This study was aimed to evaluate whether IPAF/IPF patients compared to IPF patients differ in clinical profile, prognosis and disease course.MethodsThis is a retrospective, single center, case–control study. We evaluated 360 consecutive IPF patients (Forlì Hospital, between 1/1/2002 and 28/12/2016) and compared characteristics and outcome of IPAF/IPF to IPF.ResultsTwenty-two (6%) patients met IPAF criteria. IPAF/IPF patients compared to IPF were more frequently females (N = 9/22, 40.9% vs. N = 68/338, 20.1%, p = 0.02), suffered more frequently from gastroesophageal reflux (54.5% vs. 28.4%, p = 0.01), and showed a higher prevalence of arthralgias (86.4% vs. 4.8%, p

Landslides are a worldwide natural hazard that cause more damage and casualties than other hazards. Therefore, social and economic losses can be reduced through a landslide quantitative risk assessment (QRA). In the last two decades, many attempts of quantitative analysis on various scales have been performed; nevertheless, the major difficulty of QRA lies in how precise and reliable the assessment should have to be useful. For this reason, in this paper, we analyzed different freely available datasets and some products of previous research to assess the soundness of the outcomes performed by a recent QRA of slow-moving landslides in the Arno River basin (Central Italy). The validation process was carried out by comparing the abovementioned datasets and two components of the selected QRA (hazard and risk). The obtained results showed a robust correlation between most of the testing dataset and risk components, highlighting the accuracy of the selected QRA.

BackgroundThe COVID-19 pandemic prompted the scientific community to share timely evidence, also in the form of pre-printed papers, not peer reviewed yet.PurposeTo develop an artificial intelligence system for the analysis of the scientific literature by leveraging on recent developments in the field of Argument Mining.MethodologyScientific quality criteria were borrowed from two selected Cochrane systematic reviews. Four independent reviewers gave a blind evaluation on a 1–5 scale to 40 papers for each review. These scores were matched with the automatic analysis performed by an AM system named MARGOT, which detected claims and supporting evidence for the cited papers. Outcomes were evaluated with inter-rater indices (Cohen's Kappa, Krippendorff's Alpha, s* statistics).ResultsMARGOT performs differently on the two selected Cochrane reviews: the inter-rater indices show a fair-to-moderate agreement of the most relevant MARGOT metrics both with Cochrane and the skilled interval scores, with larger values for one of the two reviews.Discussion and conclusionsThe noted discrepancy could rely on a limitation of the MARGOT system that can be improved; yet, the level of agreement between human reviewers also suggests a different complexity between the two reviews in debating controversial arguments. These preliminary results encourage to expand and deepen the investigation to other topics and a larger number of highly specialized reviewers, to reduce uncertainty in the evaluation process, thus supporting the retraining of AM systems.

Nowadays, the interest in meat substitutes is increasing, and consumers perceive their nutritional quality better than that of the animal products they intend to resemble. Therefore, this work aimed to investigate the overall nutritional quality of these new products. Regulated information [Regulation (EU) 1169/2011], the presence/absence of nutrition or health claim and organic declarations, the gluten-free indication, and the number of ingredients were collected from the food labels of 269 commercial meat analogues currently sold on the Italian market. Nutritional information of reference animal meat products was used to compare the nutrition profile. As an indicator of the nutritional quality, the Nutri-Score of meat analogues and counterparts was also determined. Plant-based steaks showed significantly higher protein, lower energy, fats and salt contents, and better Nutri-Scores than the other analogues. All the meat analogues showed a higher fibre content than meat products, while plant-based burgers and meatballs had lower protein contents than meat counterparts. Ready-sliced meat analogues showed a lower salt content than cured meats. Overall, all these plant-based products showed a longer list of ingredients than animal meat products. Results from this survey highlighted that plant-based steaks, cutlets, and cured meats have some favourable nutritional aspects compared to animal-based products. However, they cannot be considered a “tout-court” alternative to meat products from a nutritional point of view.

A crucial feature to manage a volcanic crisis is the ability of volcanologists to promptly detect an impending eruption. This is often affected by significant uncertainty, mainly for the difficulty in interpreting the monitoring signals in terms of the exact timing of a possible eruption. Here we contribute to this problem, focusing on the states of active volcanoes with closed conduit, as deduced from monitoring data. Four main states can be identified. In the quiescence state 1) the monitoring data lie on a baseline, suggesting the lack of shallow magma/fluid movement. The unrest state is highlighted by minor 2) to major 3) variations in the intensity and rate of monitoring data; in both cases, radial ground deformation pattern and non-migrating seismicity imply shallow magma and/or fluid accumulation. The state of impending eruption 4) is characterised by non-radial, asymmetric ground deformation pattern and migrating seismicity, which suggest that magma approaches the surface through a propagating dyke. As early recognition of this distinctive state is crucial for timely eruption forecast, monitoring activity should be aimed at its prompt detection. The application of this rationale to two types of active volcanoes in densely inhabited areas, a restless caldera (Campi Flegrei) and a quiescent stratovolcano (Vesuvio), highlights its feasibility and importance in eruption forecasting. This rationale may foster a general reference framework to be adopted in case of unrest, supporting in interpreting the monitoring data, as well as more effective: 1) operationally-oriented, monitoring system; 2) probabilistic forecast; 3) use of volcanic alert levels.

Bacteria possess the ability to adapt to changing environments. To enable this, cells use reversible post-translational modifications on key proteins to modulate their behavior, metabolism, defense mechanisms and adaptation of bacteria to stress. In this review, we focus on bacterial protein switches that are activated during exposure to oxidative stress. Such protein switches are triggered by either exogenous reactive oxygen species (ROS) or endogenous ROS generated as by-products of the aerobic lifestyle. Both thiol switches and metal centers have been shown to be the primary targets of ROS. Cells take advantage of such reactivity to use these reactive sites as redox sensors to detect and combat oxidative stress conditions. This in turn may induce expression of genes involved in antioxidant strategies and thus protect the proteome against stress conditions. We further describe the well-characterized mechanism of selected proteins that are regulated by redox switches. We highlight the diversity of mechanisms and functions (as well as common features) across different switches, while also presenting integrative methodologies used in discovering new members of this family. Finally, we point to future challenges in this field, both in uncovering new types of switches, as well as defining novel additional functions.

Studies on age-related differences in risk perception in a real-world situation, such as the recent COVID-19 outbreak, showed that the risk perception of getting COVID-19 tends to decrease as age increases. This finding raised the question on what factors could explain risk perception in older adults. The present study examined age-related differences in risk perception in the early stages of COVID-19 lockdown, analyzing variables that can explain the differences in perception of risk at different ages. A total of 1,765 adults aged between 18 and 87 years old completed an online survey assessing perceived risk severity and risk vulnerability of getting COVID-19, sociodemographic status, emotional state, experience relating to COVID-19, and physical health status. Results showed that the older the participants, the lower the perceived vulnerability to getting COVID-19, but the higher the perceived severity. Different predictors explain the perception of risk severity and vulnerability at different ages. Overall, self-reported anxiety over the pandemic is a crucial predictor in explaining risk perceptions in all age groups. Theoretical and practical implications of the empirical findings are discussed.

Bacteria in stream biofilms contribute to stream biogeochemical processes and are potentially sensitive to the substantial levels of pollution entering urban streams. To examine the effects of contaminants on stream biofilm bacteria in situ, we exposed growing biofilms to experimental additions of nutrients [nitrogen (N), phosphorus (P), and iron (Fe)], pharmaceuticals (caffeine and diphenhydramine), nutrients plus pharmaceuticals, or no contaminants using contaminant exposure substrates (CES) in three catchments in northern Utah. We performed our study at montane and urban sites to examine the influence of existing pollution on biofilm response. We identified bacterial core communities (core) for each contaminant treatment at each land-use type (e.g., nutrient addition montane bacterial core, nutrient addition urban bacterial core, pharmaceutical addition montane bacterial core) by selecting all taxa found in at least 75% of the samples belonging to each specific grouping. Montane and urban land-use distinguished bacterial cores, while nutrients and pharmaceuticals had subtle, but nonetheless distinct effects. Nutrients enhanced the dominance of already abundant copiotrophs [i.e., Pseudomonadaceae (Gammaproteobacteria) and Comamonadaceae (Betaproteobacteria)] within bacterial cores at montane and urban sites. In contrast, pharmaceuticals fostered species-rich bacterial cores containing unique contaminant-degrading taxa within Pseudomonadaceae and Anaerolineaceae (Chloroflexi). Surprisingly, even at urban sites containing ambient pharmaceutical pollution, pharmaceutical additions increased bacterial core richness, specifically within DR-16 (Betaproteobacteria), WCHB1-32 (Bacteroidetes), and Leptotrichiaceae (Fusobacteria). Nutrients exerted greater selective force than pharmaceuticals in nutrient plus pharmaceutical addition treatments, creating bacterial cores more closely resembling those under nutrient rather than pharmaceutical addition, and promoting unique Oscillatoriales (Cyanobacteria) taxa in urban streams. Our results show that additions of N, P, and Fe intensified the dominance of already abundant copiotrophs, while additions of caffeine and diphenhydramine enabled unique taxa associated with contaminant degradation to participate in bacterial cores. Further, biofilm bacteria at urban sites remained sensitive to pharmaceuticals commonly present in waters, suggesting a dynamic interplay among pharmaceutical pollution, bacterial diversity, and contaminant degradation.

ATP-independent chaperones are widespread across all domains of life and serve as the first line of defense during protein unfolding stresses. One of the known crucial chaperones for bacterial survival in a hostile environment (e.g., heat and oxidative stress) is the highly conserved, redox-regulated ATP-independent bacterial chaperone Hsp33. Using a bioinformatic analysis, we describe novel eukaryotic homologs of Hsp33 identified in eukaryotic pathogens belonging to the kinetoplastids, a family responsible for lethal human diseases such as Chagas disease as caused by Trypanosoma cruzi, African sleeping sickness caused by Trypanosoma brucei spp., and leishmaniasis pathologies delivered by various Leishmania species. During their pathogenic life cycle, kinetoplastids need to cope with elevated temperatures and oxidative stress, the same conditions which convert Hsp33 into a powerful chaperone in bacteria, thus preventing aggregation of a wide range of misfolded proteins. Here, we focused on a functional characterization of the Hsp33 homolog in one of the members of the kinetoplastid family, T. brucei, (Tb927.6.2630), which we have named TrypOx. RNAi silencing of TrypOx led to a significant decrease in the survival of T. brucei under mild oxidative stress conditions, implying a protective role of TrypOx during the Trypanosomes growth. We then adopted a proteomics-driven approach to investigate the role of TrypOx in defining the oxidative stress response. Depletion of TrypOx significantly altered the abundance of proteins mediating redox homeostasis, linking TrypOx with the antioxidant system. Using biochemical approaches, we identified the redox-switch domain of TrypOx, showing its modularity and oxidation-dependent structural plasticity. Kinetoplastid parasites such as T. brucei need to cope with high levels of oxidants produced by the innate immune system, such that parasite-specific antioxidant proteins like TrypOx – which are depleted in mammals – are highly promising candidates for drug targeting.

Large storage dams have widely documented impacts on downstream aquatic environments, but hydroelectric dams with little or no capacity for storage of water inflows (i.e., run-of-river) have received less attention. Two of the world’s largest run-of-river hydropower dams (Jirau and Santo Antônio, Brazil) are located on the Madeira River, the largest tributary to the Amazon River. Here we examine whether the Madeira dams have affected downstream seasonal flood pulses and short-term (daily and sub-daily) flow dynamics. We show that the combined effects of these dams on seasonal flood pulses were modest. However, dam operations significantly increased day-to-day and sub-daily flow variability. The increase in short-term flow variability is largely explained by rapid, short-term variations in river flow caused by fluctuations in energy demand (hydropeaking). Both the magnitude of hydropeaking and the mean absolute day-to-day change in discharge downstream of the dams doubled after dam closure. In addition, the median hourly rate of water level change downstream of the dams was three times higher than upstream. Our findings highlight that even run-of-river dams on very large rivers such as the Madeira—whose average discharge at the dam site is larger than that of the Mississippi River at its mouth—can alter downstream hydrology through hydropeaking. Although little studied in tropical floodplain rivers, hydropeaking by large run-of-river dams may be detrimental to downstream aquatic organisms and human populations that utilize the river for navigation and fisheries.

Headwaters suffer from reduced leaf and wood inputs and retention capacity from historical land actions like watershed logging and agriculture. When in-stream wood is reduced, stream retention capacity declines and subsequent changes in streamwater flow-paths and patterns of deposition alter decomposition and primary production that influence secondary invertebrate production via modified habitat and resources. Wood additions are commonly used as stream restoration tools for habitat improvements that can restore or strengthen food web connections; however, changes in carbon (C) flow through food webs are rarely measured because of time and expense. We quantified allochthonous and autochthonous C flow through aquatic macroinvertebrate communities 1 year before and 2 years after an experimental addition of large wood, compared to macroinvertebrates in an upstream control, in a temperate headwater stream. We predicted wood additions increase macroinvertebrate consumption and assimilation of allochthonous and autochthonous C through retention of leaves and altered flow-paths that expose more gravel and cobble for periphyton colonization. Macroinvertebrate allochthonous C assimilation tended to increase in years with greater organic matter retention and autochthonous C increased with more exposed gravel and cobble across seasons and between reaches. While the effect of wood addition on C flow through the macroinvertebrate community was minimal, it increased by ∼20% relative to the control from an increase in production and C assimilation of common mayfly and caddisfly scrapers, Baetis and Glossossoma. Because the amount of organic matter retained and coarse substrate exposed corresponded with C form and amount consumed, restoration of large wood has the potential to increase organic matter C trophic transfer.

Animal carcasses can provide important resources for a suite of consumers, and bones may provide a largely overlooked component of this resource, as they contain a large proportion of the phosphorus (P) in a carcass and they can persist for decades to millennia. We synthesized several datasets from our research in the Mara River, in which annual mass drownings of wildebeest (Connochaetes taurinus) contribute 2.2 × 105 kg of bones per year, to examine the ecological role that bone could play in this river ecosystem and to prioritize research questions on the role of bones in aquatic ecosystems in general. We measured bone stoichiometry and used in-stream litterbags to measure bone decomposition rate, both of which varied by bone type. Decomposition occurs as a two-stage process, with 15% of the mass being relatively labile and decomposing in 80–120 days and the remaining recalcitrant portion decomposing over > 80 years, leading to an estimated standing stock of 5.1 × 106 kg bones in the river. We used mesocosm experiments to measure leaching rates from bones. Leachate from fresh bones was an order of magnitude higher in inorganic nitrogen (N) than P; however, aged bones from the river leached much more P than N, which stimulated primary production. Biofilms growing on bones had five times greater chlorophyll a and two times greater organic matter than those growing on rocks, although algal composition was not significantly different between the two substrates. Biofilms growing on bones also differed from biofilms on rocks in carbon (C) and N stable isotope signature. Mixing models suggest that biofilms on bones account for 19% of macroinvertebrate and 24% of fish tissues in the Mara River, even months after carcasses were present. In combination, these findings suggest that bones may influence nutrient cycling, ecosystem function, and food webs in the Mara River, potentially on decadal time scales. Bones may also be important in other aquatic ecosystems, and mass extirpations of large land mammals may have led to a loss of this resource. Large animal bones may play a unique role in ecosystems via their slow release of limiting nutrients.

Targeted therapy using monoclonal antibodies conjugated to toxins is gaining space in the treatment of cancer. Here, we report the anti-tumor effect of a new antibody drug conjugate (ADC) delivering a HDAC inhibitor to ErbB2+ solid tumors. Trastuzumab was partially reduced with tris [2-carboxyethyl] phosphine (TCEP) and conjugated to ST7464AA1, the active form of the prodrug HDAC inhibitor ST7612AA1, through a maleimide-thiol linker to obtain the Antibody Drug Conjugate (ADC) ST8176AA1. The average drug/antibody ratio (DAR) was 4.5 as measured by hydrophobic interaction chromatography (HIC). Binding of ST8176AA1 to ErbB2 receptor and internalization in tumor cells were investigated by enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), cytofluorimetry, and High Content Screening (HCS) Imaging. The biological activity of the ADC was evaluated in vitro and in vivo by measuring cell proliferation/cell cycle, apoptosis/DNA damage, tubulin, and histone acetylation and modulation of Epithelial/Mesenchymal Transition (EMT) markers. Receptor binding and internalization of ST8176AA1 were confirmed to be similar to trastuzumab. Higher anti-tumor activity of ST8176AA1 compared to trastuzumab was observed in vitro in tumor cell lines. Such higher activity correlated with increased acetylation of histones and alfa-tubulin as a consequence of HDAC inhibitor-mediated epigenetic modulation that also induced increased expression of ErbB2 and estrogen receptor in triple negative breast cancer cells. Consistently with in vitro data, ST8176AA1 exhibited higher tumor growth inhibition than trastuzumab in xenograft models of ovary and colon carcinoma and in two patient-derived xenograft (PDX) models of pancreatic carcinoma. Immunohistochemistry analysis of tumor masses showed lower expression of the proliferation marker Ki67 and higher expression of cleaved caspase-3 in mice treated with the ADC compared to those treated with trastuzumab and results correlated with increased acetylation of both histones and tubulin. Collectively, present data indicate that ADC ST8176AA1 can target epigenetic modulation to ErbB2+ tumors. Interestingly, the amount of HDACi estimated to be delivered at the ST8176AA1 effective dose would correspond to ~1/1,000 of ST7612AA1 effective dose. Therefore, ST8176AA1 is an attractive new therapeutic candidate because it exhibits increased anti-tumor potency compared to trastuzumab by exerting epigenetic modulation at a much safer dose compared to standard HDACi-based therapeutic protocols.

A photoelectron-photoion-photoion coincidence technique, using an ion imaging detector and tunable synchrotron radiation in the 18.0–37.0 eV photon energy range, inducing the ejection of molecular valence electrons, has been applied to study the double ionization of the propylene oxide, a simple prototype chiral molecule. The experiment performed at the Elettra Synchrotron Facility (Trieste, Italy) allowed to determine angular distributions for ions produced by the two-body dissociation reactions following the Coulomb explosion of the intermediate (C3H6O)2+ molecular dication. The analysis of the coincidence spectra recorded at different photon energies was done in order to determine the dependence of the β anisotropy parameter on the photon energy for the investigated two-body fragmentation channels. In particular, the reaction leading to CH3+ + C2H3O+ appears to be characterized by an increase of β, from β ≈ 0.00 up to β = 0.59, as the photon energy increases from 29.7 to 37.0 eV, respectively. This new observation confirms that the dissociation channel producing CH3+ and C2H3O+ final ions can occur with two different microscopic mechanisms as already indicated by the bimodality obtained in the kinetic energy released (KER) distributions as a function of the photon energy in a recent study. Energetic considerations suggest that experimental data are compatible with the formation of two different stable isomers of C2H3O+: acetyl and oxiranyl cations. These new experimental data are inherently relevant and are mandatory information for further experimental and theoretical investigations involving oriented chiral molecules and linearly or circularly polarized radiation. This work is in progress in our laboratory.

Older adults are assumed to change their affect states in reaction to positive and negative stimuli across the life span. However, little is known about the impact of success and failure events on age-related changes in affect states and, particularly, in self-esteem levels. To fill this gap in the literature, in the present study changes in affect and self-esteem in 100 young (19–30 years) and 102 older adults (65–81 years) were assessed after participants experienced success and failure in a demanding cognitive task. Overall, the success-failure manipulation induced changes on affect states and on state self-esteem, not on trait self-esteem. Regarding age differences, older and young adults were affected to the same extent by experiences of successes and failures. Theoretical considerations of the empirical findings are provided in the general discussion.

We theoretically investigate graphene layers, proposing them as membranes of subnanometer size suitable for CH4/N2 separation and gas uptake. The observed potential energy surfaces, representing the intermolecular interactions within the CH4/N2 gaseous mixtures and between these and the graphene layers, have been formulated by adopting the so-called Improved Lennard-Jones (ILJ) potential, which is far more accurate than the traditional Lennard-Jones potential. Previously derived ILJ force fields are used to perform extensive molecular dynamics simulations on graphene's ability to separate and adsorb the CH4/N2 mixture. Furthermore, the intramolecular interactions within graphene were explicitly considered since they are responsible for its flexibility and the consequent out-of-plane movements of the constituting carbon atoms. The effects on the adsorption capacity of graphene caused by introducing its flexibility in the simulations are assessed via comparison of different intramolecular force fields giving account of flexibility against a simplified less realistic model that considers graphene to be rigid. The accuracy of the potentials guarantees a quantitative description of the interactions and trustable results for the dynamics, as long as the appropriate set of intramolecular and intermolecular force fields is chosen. In particular it is shown that only if the flexibility of graphene is explicitly taken into account, a simple united-atom interaction potential can provide correct predictions. Conversely, when using an atomistic model, neglecting in the simulations the intrinsic flexibility of the graphene sheet has a minor effect. From a practical point of view, the global analysis of the whole set of results proves that these nanostructures are versatile materials competitive with other carbon-based adsorbing membranes suitable to cope with CH4 and N2 adsorption.

Bioalcohols are a promising family of biofuels. Among them, 1-butanol has a strong potential as a substitute for petrol. In this manuscript, we report on a theoretical and experimental characterization of 1-butanol thermal decomposition, a very important process in the 1-butanol combustion at high temperatures. Advantage has been taken of a flash pyrolysis experimental set-up with mass spectrometric detection, in which the brief residence time of the pyrolyzing mixture inside a short, resistively heated SiC tube allows the identification of the primary products of the decomposing species, limiting secondary processes. Dedicated electronic structure calculations of the relevant potential energy surface have also been performed and RRKM estimates of the rate coefficients and product branching ratios up to 2,000 K are provided. Both electronic structure and RRKM calculations are in line with previous determinations. According to the present study, the H2O elimination channel leading to 1-butene is more important than previously believed. In addition to that, we provide experimental evidence that butanal formation by H2 elimination is not a primary decomposition route. Finally, we have experimental evidence of a small yield of the CH3 elimination channel.

Synthetic Aperture Radar Interferometry (InSAR) techniques have been long exploited for detecting and mapping slow-moving ground surface displacements due to their millimeter accuracy, non-invasiveness and wide area coverage. A review on different applications of Persistent Scatterers InSAR approaches, proposed and applied over Tuscany region (Italy) across time, is here presented. The study area is characterized by both subsidence of alluvial plains and landslides on hilly and mountainous reliefs. Tuscany has a leading role in Italy in the field of interferometric applications: the first InSAR analyses, which date back to 2003, were performed at local basin scale, by exploiting various PSI-based approaches for risk mapping. The first InSAR applications at regional scale date back to 2009, relying on historical SAR archives of ERS and ENVISAT satellites for updating subsidence and landslide inventory maps at a certain temporal date. Nowadays, the availability of Sentinel-1 SAR data with a regular and systematic 6-days acquisitions plan, allows near-real time monitoring of deformative scenario at regional scale rather than solely mapping of geo-hydrological phenomena. Most recent innovative InSAR applications over Tuscany region scan the territory, exploiting the regular repeat pass of Sentinel-1, and promptly highlight the sites affected by the highest ground movements with high temporal frequency. Such approaches permit us to pass from a static ‘picture’ of regional slope instability to a weekly updated ‘movie’ with improved detail, useful for civil protection practices. These last ongoing works significantly enhance the value of multi-temporal InSAR approaches for investigating and managing geo-hazards over the Region.

We propose a methodology to couple rainfall thresholds and susceptibility maps for dynamic landslide hazard assessment at regional scale. Both inputs are combined in a purposely-built hazard matrix to get a spatially and temporally variable definition of landslide hazard: while statistical rainfall thresholds are used to accomplish a temporal forecasting with very coarse spatial resolution, landslide susceptibility maps provide static spatial information about the probability of landslide occurrence at fine spatial resolution. The test site is the Northern part of Tuscany (Italy), where a recent landslide susceptibility map and a set of recently updated rainfall thresholds are available. These products were modified and updated to meet the requirements of the proposed procedure: the susceptibility map was reclassified and the threshold set was expanded defining additional thresholds. The hazard matrix combines three susceptibility classes (S1, low susceptibility; S2 medium susceptibility; S3 high susceptibility) and three rainfall rate classes (R1, R2, R3), defining five hazard classes, from H0 (null hazard) to H4 (high hazard). A key passage of the procedure is the appropriate calibration and validation of the matrix, letting the hazard classes have a precise meaning in terms of expected consequences and hazard management. The employ of the proposed procedure in a regional warning system brings two main advantages: (i) it is possible to better hypothesize when and where landslide are expected and with which hazard degree, thus fostering a more effective hazard and risk management (e.g., setting priorities of intervention); (ii) the spatial resolution of the regional scale warning system is markedly refined because from time to time the areas where landslides are expected represent only a fraction of the alert zone.

This study presents a new method for producing long-term hazard maps for pyroclastic density currents (PDC) originating at Campi Flegrei caldera. Such method is based on a doubly stochastic approach and is able to combine the uncertainty assessments on the spatial location of the volcanic vent, the size of the flow and the expected time of such an event. The results are obtained by using a Monte Carlo approach and adopting a simplified invasion model based on the box model integral approximation. Temporal assessments are modeled through a Cox-type process including self-excitement effects, based on the eruptive record of the last 15 kyr. Mean and percentile maps of PDC invasion probability are produced, exploring their sensitivity to some sources of uncertainty and to the effects of the dependence between PDC scales and the caldera sector where they originated. Conditional maps representative of PDC originating inside limited zones of the caldera, or of PDC with a limited range of scales are also produced. Finally, the effect of assuming different time windows for the hazard estimates is explored, also including the potential occurrence of a sequence of multiple events. Assuming that the last eruption of Monte Nuovo (A.D. 1538) marked the beginning of a new epoch of activity similar to the previous ones, results of the statistical analysis indicate a mean probability of PDC invasion above 5% in the next 50 years on almost the entire caldera (with a probability peak of ~25% in the central part of the caldera). In contrast, probability values reduce by a factor of about 3 if the entire eruptive record is considered over the last 15 kyr, i.e., including both eruptive epochs and quiescent periods.