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Between 1960 and 1961 a Roman bridge was undercovered in corso Vittorio Emanuele II in Milan, providing a key element for the analysis of the development of the road network in the area. This zone, formerly part of the north-western suburbium, later became a proper urban district within the city walls. The study of the artefacts found in connection with the structure allowed to verify that the place was continuously attended throughout the Roman age.

In 1931, some fragments of stone Roman artifacts were found in the foundation of a modern building in Milan. They were probably originally reused in Late Antiquity during the construction of the walls of Maximian. Some fragments are today preserved in the Civic Archaeological Museum in Milan, while others have been lost. Three fragments were part of a frieze (or more than one) and their original display is unknown. One, today lost, showed a soldier, while the other two show an image of Victory and the lower part of a male figure, with a long mantle and a naked leg and foot, whose skin was completely covered with polychromy. The aim of the paper is a preliminary report about the stone fragments, their context and iconography, with an addendum about the traces of polychromy on the male figure’s skin.

Il volume raccoglie testi relativi a recenti ricerche cercando, attraverso l'analisi di vecchi ritrovamenti e di nuovi scavi, di far emergere e conoscere aspetti inediti dell'antica Mediolanum e del suo territorio.

Il volume raccoglie una serie di contributi dedicate a scoperte recenti o edizioni di vecchi scavi e materiali da Milano e territorio metropolitano

Governments recently adopted new global targets to halt and reverse the loss of biodiversity. It is therefore crucial to understand the outcomes of conservation actions. We conducted a global meta-analysis of 186 studies (including 665 trials) that measured biodiversity over time and compared outcomes under conservation action with a suitable counterfactual of no action. We find that in two-thirds of cases, conservation either improved the state of biodiversity or at least slowed declines. Specifically, we find that interventions targeted at species and ecosystems, such as invasive species control, habitat loss reduction and restoration, protected areas, and sustainable management, are highly effective and have large effect sizes. This provides the strongest evidence to date that conservation actions are successful but require transformational scaling up to meet global targets.

Governments recently adopted new global targets to halt and reverse the loss of biodiversity. It is therefore crucial to understand the outcomes of conservation actions. We conducted a global meta-analysis of 186 studies (including 665 trials) that measured biodiversity over time and compared outcomes under conservation action with a suitable counterfactual of no action. We find that in two-thirds of cases, conservation either improved the state of biodiversity or at least slowed declines. Specifically, we find that interventions targeted at species and ecosystems, such as invasive species control, habitat loss reduction and restoration, protected areas, and sustainable management, are highly effective and have large effect sizes. This provides the strongest evidence to date that conservation actions are successful but require transformational scaling up to meet global targets.

Governments recently adopted new global targets to halt and reverse the loss of biodiversity. It is therefore crucial to understand the outcomes of conservation actions. We conducted a global meta-analysis of 186 studies (including 665 trials) that measured biodiversity over time and compared outcomes under conservation action with a suitable counterfactual of no action. We find that in two-thirds of cases, conservation either improved the state of biodiversity or at least slowed declines. Specifically, we find that interventions targeted at species and ecosystems, such as invasive species control, habitat loss reduction and restoration, protected areas, and sustainable management, are highly effective and have large effect sizes. This provides the strongest evidence to date that conservation actions are successful but require transformational scaling up to meet global targets.

A Milano, nell’area compresa tra corso Vittorio Emanuele II e corso Europa, quando la città divenne capitale dell’Impero Romano di Occidente (286-402 d.C.), fu costruito un esteso complesso termale, la cui pianta richiamava i prestigiosi modelli imperiali di Roma. L’edificio, indagato solo parzialmente dalla seconda metà del XIX secolo, era dotato di una ricca decorazione marmorea, comprendente rivestimenti parietali e pavimentali. L’approvvigionamento idrico del complesso costituisce un tema complesso, ma si può ipotizzare che l’acqua fosse almeno in parte convogliata dall’esterno della città e conservata in appositi serbatoi prima di essere smistata attraverso una apposita rete di canali e tubature.

Since 2005, a Belgian and Italian team has carried out archaeological excavations at the site of the late-antique villa in Aiano (municipality of San Gimignano, Siena, Italy). The settlement was founded between the end of the 3rd and the beginning of the 4th century AD. Between the late 4th century and the 5th century, the entire area underwent a monumental rearrangement. The building was abandoned at the end of the 5th century and, later on, some rooms were reused as productive ateliers, which dismantled and recycled the decorations of the former villa. The entire settlement was eventually abandoned during the 7th century. The presence of marble and stone decoration inside the villa was already well known before the 2015 campaign, but the archaeological excavations conducted from 2015-2021 added some new information. The aim of this paper is to show the new findings of marble and stone fragments in Aiano, which were originally part of wall and floor revetments. The focus will be on a map of the findings, the provenance of the marbles, and the traces of tool marks they show on their surfaces, thus deeping the knowledge about cutting and reuse of marble and stone inside the site of Aiano.

Le recenti campagne di scavo dell’Università Cattolica di Milano nel sito di Palazzo Pignano (CR) hanno permesso di individuare poche ma significative tracce di decorazioni musive pertinenti a un complesso rustico databile alla prima età imperiale, sostituito in epoca tardo antica da una grande villa a padiglioni. È stata rinvenuta anche una grande buca piena di tessere mai usate, databile al V secolo per alcuni frammenti ceramici al suo interno, che può esser interpretata come lo scarto dei materiali impiegati dall’officina che si occupò della realizzazione del ciclo musivo nella residenza basso imperiale.

Introduction: Pesticides are artificial or natural chemical substances used for pest control and crop protection, however, they are considered environmental contaminants Objectives: determine populations exposed or potentially exposed to pesticides and the most frequent related symptoms in the Minga Guazú district, Alto Paraná. Methodology: The study is quantitative, cross-sectional, non-randomized, descriptive and analytical. A survey validated and published by the Brazilian Ministry of Health was applied. Results: Nausea, dizziness and vomiting, 4 (15.4%) several times, 2 (7.7%) frequently in children, 1 (3.8%) always and 5 (19.2%) during the fumigation period. Regarding stomach problems, vomiting, pain or diarrhea, 13 (50%) people reported having felt this sometimes 6 (23%), very frequently 1 (3.8%), during the fumigation period 5 (19.2 %) and have never had those symptoms 1 (3.8%). Discussion: In 2021, a study was carried out on the new strategies and tools that are necessary for the control and prevention of harmful effects on human health of the exposed population, which could contribute to reducing the already known effects of prolonged exposure and high doses. harmful to them. Conclusion: The most frequent symptoms reported by the population are tachycardia, gastrointestinal and respiratory and to a lesser extent joint pain, nausea or vomiting and irritation of the skin and mucous membranes. Further studies should be performed to conclusively specify the presence of symptoms, frequency, and time of onset to better determine probable causes., Introducción: Los plaguicidas son sustancias químicas artificiales o naturales utilizadas para el control de plagas y protección de cultivos, sin embargo, son considerados contaminantes ambientales Objetivos: determinar poblaciones expuestas o potencialmente expuestas a plaguicidas y los síntomas relacionados más frecuentes en el distrito de Minga Guazú, Alto Paraná Metodología: El estudio es de tipo cuantitativo, de corte transversal, no aleatorizado, descriptivo y analítico. Se aplicó una encuesta validada y publicada por el Ministerio de la Salud del Brasil Resultados: Náuseas, mareos y vómitos, 4 (15,4%) varias veces, 2 (7,7%) frecuentemente en niños, 1 (3,8%) siempre y 5 (19,2%) durante el periodo de fumigaciones. Relativo a problemas estomacales, vómitos, dolor o diarrea, 13 (50%) personas relataron haber sentido esto algunas veces 6 (23%), con mucha frecuencia 1 (3,8%), durante el periodo de fumigaciones 5 (19,2%) y nunca han tenido esos síntomas 1 (3,8%). Discusión: En 2021, se realizó un estudio sobre las nuevas estrategias y herramientas que son necesarias para el control y prevención de efectos nocivos para la salud humana de población expuesta, que podría contribuir a disminuir los efectos ya conocidos de la exposición prolongada y en dosis nocivas para las mismas. Conclusión: Los síntomas más frecuentes reportados por la población son taquicardia, gastrointestinales y respiratorios y en menor medida dolores articulares, náuseas o vómitos e irritación de la piel y mucosas. Se deben realizar otros estudios para especificar de manera concluyente la presencia de los síntomas, la frecuencia y el tiempo de aparición para determinar mejor las probables causas.

Chitin, the second most abundant biopolymer in the planet after cellulose, represents a renewable carbon and nitrogen source. A thrilling opportunity for the valorization of chitin is focused on the preparation of biomass-derived N-doped carbonaceous materials. In this contribution, chitin-derived N-doped carbons were successfully prepared and functionalized with palladium metal nanoparticles. The physicochemical properties of these nanocomposites were investigated following a multi-technique strategy and their catalytic activity in reductive amination reactions was explored. In particular, a biomass-derived platform molecule, namely furfural, was upgraded to valuable bi-cyclic compounds under continuous flow conditions.

Sculptural fragments have been found during archaeological excavations in some Late Antique villas of the Western Europe (Germany, France, Italy, Spain) since the xix century. They have constantly been well examined regarding to their iconography, style and chronology, but several doubts still remain about the most common places they were originally set inside the villas. The paper aims to explain archaeology’s contribution in this field. A careful analysis of each sculpture is fundamental: for example, presence of unfinished parts, traces of little hydraulic pipes and data about the place of its discovery can sometimes help to reconstruct which was its original settlement. The study of the villas’ masonry is important too, for example by locating niches along the walls and pedestals. However, it is possible to reconstruct that the sculptures were usually arranged in high visible places such as triclinia, reception rooms and gardens: they contribute to show the power, wealth and education of the dominus, along with other decorations (painting, mosaics...). Sometimes, their exhibition had to be organized during the construction of the villa or during the building’s restoration, because the masonry and the pavements were accommodated in order to host them inside niches and on pedestals.

Fragments of the decorations of the so called Terme Erculee (Herculean Baths), built by emperor Maximianus, were found during the excavations carried out by the 19th century in the area of Corso Europa in Milan. Although these are few remains, they allow to observe similarities with the ornamentations of other Roman Imperial baths and with some monuments of the tetrarchic era. In particular, fragments of mosaics (one depicting the personification of the Seasons) and a colossal marble torso of resting Hercules were found.

Some new elements related to the mosaic decoration of the Late roman villa of Palazzo Pignano (CR) were found during the excavations of 2017 and 2018. In particular, a large pit full of tiles never used was found. It can be interpreted as dump of waste of a workshop specializing in the creation of mosaics in the 5th century.

The finds of intentional deposits of loose mosaic tesserae are rather common during archaeological excavations. They are rich ith informative potential, if correctly assessed and compared to other data. Similar finds can be explained by two hypotheses: they can be dumps of waste or accumulations of materials made within a building or productive site. The essential difference is that in the first case the objects were placed in the dumps without any attention for their future reutilization; in the second, the accumulation was instead an operation planned for the objects’ future use. In each case, the deposits of loose mosaic tesserae allow to obtain considerable data regarding to the history of a building, providing information about its decorations or about the operations of construction or demolition. In some sites, they also attest the manufacture and the commerce of the tesserae.

Some evidences of Roman Age were found in the Vidolasco area; among them there is an acephalous torso of a marble statue datable between the 1st and the 2nd century AD. It represents a naked male figure, whose posture recalls famous Late Classic models. It is quite difficult to identify the subject represented by the statue, due to the small portion conserved and the lack of attributes; some peculiarities of the body allow to consider it a young man. This kind of representations evolved especially from the Hellenistic period and encountered great appreciation during the Imperial Age, especially for the decoration of residential buildings. So we may assume that the torso is the clue of the existence of an important villa decorated with sculptures in the Vidolasco area.

Smoking-related epigenetic changes have been linked to lung cancer, but the contribution of epigenetic alterations unrelated to smoking remains unclear. We sought for a sparse set of CpG sites predicting lung cancer and explored the role of smoking in these associations. We analysed CpGs in relation to lung cancer in participants from two nested case–control studies, using (LASSO)-penalised regression. We accounted for the effects of smoking using known smoking-related CpGs, and through conditional-independence network. We identified 29 CpGs (8 smoking-related, 21 smoking-unrelated) associated with lung cancer. Models additionally adjusted for Comprehensive Smoking Index-(CSI) selected 1 smoking-related and 49 smoking-unrelated CpGs. Selected CpGs yielded excellent discriminatory performances, outperforming information provided by CSI only. Of the 8 selected smoking-related CpGs, two captured lung cancer-relevant effects of smoking that were missed by CSI. Further, the 50 CpGs identified in the CSI-adjusted model complementarily explained lung cancer risk. These markers may provide further insight into lung cancer carcinogenesis and help improving early identification of high-risk patients.

The therapeutic potential of cannabidiol (CBD), a non-psychtropic component of the Cannabis sativa plant, is substantiated more and more. We aimed to determine the pharmacokinetic behavior of CBD after a single dose via intranasal (IN) and intrarectal (IR) administration in six healthy Beagle dogs age 3-8 years old, and compare to the oral administration route (PO). Standardized dosages applied for IN, IR and PO were 20, 100, and 100 mg, respectively. Each dog underwent the same protocol but received CBD through a different administration route. CBD plasma concentrations were determined by ultra-high performance liquid chromatography-tandem mass spectrometry before and at fixed time points after administration. Non-compartmental analysis was performed on the plasma concentration-time profiles. Plasma CBD concentrations after IR administration were below the limit of quantification. The mean area under the curve (AUC) after IN and PO CBD administration was 61 and 1,376 ng/mL*h, respectively. The maximal plasma CBD concentration (C max) after IN and PO CBD administration was 28 and 217 ng/mL reached after 0.5 and 3.5 h (T max), respectively. Significant differences between IN and PO administration were found in the T max ( p = 0.04). Higher AUC and C max were achieved with 100 mg PO compared to 20 mg IN, but no significant differences were found when AUC ( p = 0.09) and C max ( p = 0.44) were normalized to 1 mg dosages. IN administration of CBD resulted in faster absorption when compared to PO administration. However, PO remains the most favorable route for CBD delivery due to its more feasible administration. The IR administration route is not advised for clinical application.

As the United Nations develops a post-2020 global biodiversity framework for the Convention on Biological Diversity, attention is focusing on how new goals and targets for ecosystem conservation might serve its vision of ‘living in harmony with nature’1,2. Advancing dual imperatives to conserve biodiversity and sustain ecosystem services requires reliable and resilient generalizations and predictions about ecosystem responses to environmental change and management3. Ecosystems vary in their biota4, service provision5 and relative exposure to risks6, yet there is no globally consistent classification of ecosystems that reflects functional responses to change and management. This hampers progress on developing conservation targets and sustainability goals. Here we present the International Union for Conservation of Nature (IUCN) Global Ecosystem Typology, a conceptually robust, scalable, spatially explicit approach for generalizations and predictions about functions, biota, risks and management remedies across the entire biosphere. The outcome of a major cross-disciplinary collaboration, this novel framework places all of Earth’s ecosystems into a unifying theoretical context to guide the transformation of ecosystem policy and management from global to local scales. This new information infrastructure will support knowledge transfer for ecosystem-specific management and restoration, globally standardized ecosystem risk assessments, natural capital accounting and progress on the post-2020 global biodiversity framework.

BACKGROUND: DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer. METHODS: Using data from four prospective case-control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage. RESULTS: None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath 'age acceleration' (AA): OR per SD = 1.02, 95%CI: 0.95-1.10; AA-Hannum: OR = 1.03, 95%CI:0.95-1.12; PhenoAge: OR = 1.01, 95%CI: 0.94-1.09 and GrimAge: OR = 1.03, 95%CI: 0.94-1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01-1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics. CONCLUSION

Smoking-related epigenetic changes have been linked to lung cancer, but the contribution of epigenetic alterations unrelated to smoking remains unclear. We sought for a sparse set of CpG sites predicting lung cancer and explored the role of smoking in these associations. We analysed CpGs in relation to lung cancer in participants from two nested case-control studies, using (LASSO)-penalised regression. We accounted for the effects of smoking using known smoking-related CpGs, and through conditional-independence network. We identified 29 CpGs (8 smoking-related, 21 smoking-unrelated) associated with lung cancer. Models additionally adjusted for Comprehensive Smoking Index-(CSI) selected 1 smoking-related and 49 smoking-unrelated CpGs. Selected CpGs yielded excellent discriminatory performances, outperforming information provided by CSI only. Of the 8 selected smoking-related CpGs, two captured lung cancer-relevant effects of smoking that were missed by CSI. Further, the 50 CpGs identified in the CSI-adjusted model complementarily explained lung cancer risk. These markers may provide further insight into lung cancer carcinogenesis and help improving early identification of high-risk patients.

As the United Nations develops a post-2020 global biodiversity framework for the Convention on Biological Diversity, attention is focusing on how new goals and targets for ecosystem conservation might serve its vision of 'living in harmony with nature'1,2. Advancing dual imperatives to conserve biodiversity and sustain ecosystem services requires reliable and resilient generalizations and predictions about ecosystem responses to environmental change and management3. Ecosystems vary in their biota4, service provision5 and relative exposure to risks6, yet there is no globally consistent classification of ecosystems that reflects functional responses to change and management. This hampers progress on developing conservation targets and sustainability goals. Here we present the International Union for Conservation of Nature (IUCN) Global Ecosystem Typology, a conceptually robust, scalable, spatially explicit approach for generalizations and predictions about functions, biota, risks and management remedies across the entire biosphere. The outcome of a major cross-disciplinary collaboration, this novel framework places all of Earth's ecosystems into a unifying theoretical context to guide the transformation of ecosystem policy and management from global to local scales. This new information infrastructure will support knowledge transfer for ecosystem-specific management and restoration, globally standardized ecosystem risk assessments, natural capital accounting and progress on the post-2020 global biodiversity framework.

As the United Nations develops a post-2020 global biodiversity framework for the Convention on Biological Diversity, attention is focusing on how new goals and targets for ecosystem conservation might serve its vision of 'living in harmony with nature'1,2. Advancing dual imperatives to conserve biodiversity and sustain ecosystem services requires reliable and resilient generalizations and predictions about ecosystem responses to environmental change and management3. Ecosystems vary in their biota4, service provision5 and relative exposure to risks6, yet there is no globally consistent classification of ecosystems that reflects functional responses to change and management. This hampers progress on developing conservation targets and sustainability goals. Here we present the International Union for Conservation of Nature (IUCN) Global Ecosystem Typology, a conceptually robust, scalable, spatially explicit approach for generalizations and predictions about functions, biota, risks and management remedies across the entire biosphere. The outcome of a major cross-disciplinary collaboration, this novel framework places all of Earth's ecosystems into a unifying theoretical context to guide the transformation of ecosystem policy and management from global to local scales. This new information infrastructure will support knowledge transfer for ecosystem-specific management and restoration, globally standardized ecosystem risk assessments, natural capital accounting and progress on the post-2020 global biodiversity framework.

As the United Nations develops a post-2020 global biodiversity framework for the Convention on Biological Diversity, attention is focusing on how new goals and targets for ecosystem conservation might serve its vision of ‘living in harmony with nature’1,2. Advancing dual imperatives to conserve biodiversity and sustain ecosystem services requires reliable and resilient generalizations and predictions about ecosystem responses to environmental change and management3. Ecosystems vary in their biota4, service provision5 and relative exposure to risks6, yet there is no globally consistent classification of ecosystems that reflects functional responses to change and management. This hampers progress on developing conservation targets and sustainability goals. Here we present the International Union for Conservation of Nature (IUCN) Global Ecosystem Typology, a conceptually robust, scalable, spatially explicit approach for generalizations and predictions about functions, biota, risks and management remedies across the entire biosphere. The outcome of a major cross-disciplinary collaboration, this novel framework places all of Earth’s ecosystems into a unifying theoretical context to guide the transformation of ecosystem policy and management from global to local scales. This new information infrastructure will support knowledge transfer for ecosystem-specific management and restoration, globally standardized ecosystem risk assessments, natural capital accounting and progress on the post-2020 global biodiversity framework.

Marine species and ecosystems are widely affected by anthropogenic stressors, ranging from pollution and fishing to climate change. Comprehensive assessments of how species and ecosystems are impacted by anthropogenic stressors are critical for guiding conservation and management investments. Previous global risk or vulnerability assessments have focused on marine habitats, or on limited taxa or specific regions. However, information about the susceptibility of marine species across a range of taxa to different stressors everywhere is required to predict how marine biodiversity will respond to human pressures. We present a novel framework that uses life-history traits to assess species' vulnerability to a stressor, which we compare across more than 44,000 species from 12 taxonomic groups (classes). Using expert elicitation and literature review, we assessed every combination of each of 42 traits and 22 anthropogenic stressors to calculate each species' or representative species group's sensitivity and adaptive capacity to stressors, and then used these assessments to derive their overall relative vulnerability. The stressors with the greatest potential impact were related to biomass removal (e.g., fisheries), pollution, and climate change. The taxa with the highest vulnerabilities across the range of stressors were mollusks, corals, and echinoderms, while elasmobranchs had the highest vulnerability to fishing-related stressors. Traits likely to confer vulnerability to climate change stressors were related to the presence of calcium carbonate structures, and whether a species exists across the interface of marine, terrestrial, and atmospheric realms. Traits likely to confer vulnerability to pollution stressors were related to planktonic state, organism size, and respiration. Such a replicable, broadly applicable method is useful for informing ocean conservation and management decisions at a range of scales, and the framework is amenable to further testing and improve

BackgroundBiological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.ResultsLeveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.ConclusionThis study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10−7), which annotated to the AHRR, F2RL3, FLJ43663

Glioblastoma multiforme (GBM) has a mean survival of only 15 months. Tumour heterogeneity and blood‐brain barrier (BBB) mainly hinder the transport of active agents, leading to late diagnosis, ineffective therapy and inaccurate follow‐up. The use of hydrogel nanoparticles, particularly hyaluronic acid as naturally occurring polymer of the extracellular matrix (ECM), has great potential in improving the transport of drug molecules and, furthermore, in facilitatating the early diagnosis by the effect of hydrodenticity enabling the T1 boosting of Gadolinium chelates for MRI. Here, crosslinked hyaluronic acid nanoparticles encapsulating gadolinium-diethylenetriamine pentaacetic acid (Gd‐DTPA) and the chemotherapeutic agent irinotecan (Thera-cHANPs) are proposed as theranostic nanovectors, with improved MRI capacities. Irinotecan was selected since currently repurposed as an alternative compound to the poorly effective temozolomide (TMZ), generally approved as the gold standard in GBM clinical care. Also, active crossing and targeting are achieved by theranostic cHANPs decorated with angiopep‐2 (Thera‐ ANG‐cHANPs), a dual‐targeting peptide interacting with low density lipoprotein receptor related protein‐1(LRP‐1) receptors overexpressed by both endothelial cells of the BBB and glioma cells. Results showed preserving the hydrodenticity effect in the advanced formulation and internalization by the active peptide‐mediated uptake of Thera‐cHANPs in U87 and GS‐102 cells. Moreover, Thera‐ANG‐cHANPs proved to reduce ironotecan time response, showing a significant cytotoxic effect in 24 h instead of 48 h.

Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Result(s): Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion(s): This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Copyright © 2021, The Author(s).

Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Result(s): Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion(s): This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Copyright © 2021, The Author(s).

Background: Age-related epigenetic dysregulations are associated with several diseases, including cancer. The number of stochastic epigenetic mutations (SEM) has been suggested as a biomarker of life-course accumulation of exposure-related DNA damage; however, the predictive role of SEMs in cancer has seldom been investigated. Method(s): A SEM, at a given CpG site, was defined as an extreme outlier of DNA methylation value distribution across individuals. We investigated the association of the total number of SEMs with the risk of eight cancers in 4,497 case-control pairs nested in three prospective cohorts. Furthermore, we investigated whether SEMs were randomly distributed across the genome or enriched in functional genomic regions. Result(s): In the three-study meta-analysis, the estimated ORs per one-unit increase in log(SEM) from logistic regression models adjusted for age and cancer risk factors were 1.25; 95% confidence interval (CI), 1.11-1.41 for breast cancer, and 1.23; 95% CI, 1.07-1.42 for lung cancer. In the Melbourne Collaborative Cohort Study, the OR for mature B-cell neoplasm was 1.46; 95% CI, 1.25-1.71. Enrichment analyses indicated that SEMs frequently occur in silenced genomic regions and in transcription factor binding sites regulated by EZH2 and SUZ12 (P < 0.0001 and P 1/4 0.0005, respectively): two components of the polycomb repressive complex 2 (PCR2). Finally, we showed that PCR2-specific SEMs are generally more stable over time compared with SEMs occurring in the whole genome. Conclusion(s): The number of SEMs is associated with a higher risk of different cancers in prediagnostic blood samples. Impact: We identified a candidate biomarker for cancer early detection, and we described a carcinogenesis mechanism involving PCR2 complex proteins worthy of further investigations. The authors are very thankful to Dr. Akram Ghantous (IARC, Lyon, France) for the methylation analyses of PEM-Turin study, produced within the Exposomics EC FP7 grant (gran

The heterozygous Phospholamban p.Arg14del mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. This mutation triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca2+ dynamics. Little is known about the physiological processes preceding induced cardiomyopathy, which is characterized by sub-epicardial accumulation of fibrofatty tissue, and a specific drug treatment is currently lacking. Here, we address these issues using a knock-in Phospholamban p.Arg14del zebrafish model. Hearts from adult zebrafish with this mutation display age-related remodeling with sub-epicardial inflammation and fibrosis. Echocardiography reveals contractile variations before overt structural changes occur, which correlates at the cellular level with action potential duration alternans. These functional alterations are preceded by diminished Ca2+ transient amplitudes in embryonic hearts as well as an increase in diastolic Ca2+ level, slower Ca2+ transient decay and longer Ca2+ transients in cells of adult hearts. We find that istaroxime treatment ameliorates the in vivo Ca2+ dysregulation, rescues the cellular action potential duration alternans, while it improves cardiac relaxation. Thus, we present insight into the pathophysiology of Phospholamban p.Arg14del cardiomyopathy.

BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

BackgroundBiological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.ResultsLeveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.ConclusionThis study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

This dataset includes the current version of the indicative distribution maps and profiles for Ecosystem Functional Groups - Level 3 of IUCN Global Ecosystem Typology (v2.1). Please refer to Keith et al. (2020) and Keith et al. (2022). The descriptive profiles provide brief summaries of key ecological traits and processes for each functional group of ecosystems to enable any ecosystem type to be assigned to a group. Maps are indicative of global distribution patterns and are not intended to represent fine-scale patterns. The maps show areas of the world containing major (value of 1, coloured red) or minor occurrences (value of 2, coloured yellow) of each ecosystem functional group. Minor occurrences are areas where an ecosystem functional group is scattered in patches within matrices of other ecosystem functional groups or where they occur in substantial areas, but only within a segment of a larger region. Most maps were prepared using a coarse-scale template (e.g. ecoregions), but some were compiled from higher resolution spatial data where available (see details in profiles). Higher resolution mapping is planned in future publications. We emphasise that spatial representation of Ecosystem Functional Groups does not follow higher-order groupings described in respective ecoregion classifications. Consequently, when Ecosystem Functional Groups are aggregated into functional biomes (Level 2 of the Global Ecosystem Typology), spatial patterns may differ from those of biogeographic biomes. Differences reflect the distinctions between functional and biogeographic interpretations of the term, “biome”., This dataset includes the current version of the indicative distribution maps and profiles for Ecosystem Functional Groups - Level 3 of IUCN Global Ecosystem Typology (v2.1). Please refer to Keith et al. (2020) and Keith et al. (2022). The descriptive profiles provide brief summaries of key ecological traits and processes for each functional group of ecosystems to enable any ecosystem type to be assigned to a group. Maps are indicative of global distribution patterns and are not intended to represent fine-scale patterns. The maps show areas of the world containing major (value of 1, coloured red) or minor occurrences (value of 2, coloured yellow) of each ecosystem functional group. Minor occurrences are areas where an ecosystem functional group is scattered in patches within matrices of other ecosystem functional groups or where they occur in substantial areas, but only within a segment of a larger region. Most maps were prepared using a coarse-scale template (e.g. ecoregions), but some were compiled from higher resolution spatial data where available (see details in profiles). Higher resolution mapping is planned in future publications. We emphasise that spatial representation of Ecosystem Functional Groups does not follow higher-order groupings described in respective ecoregion classifications. Consequently, when Ecosystem Functional Groups are aggregated into functional biomes (Level 2 of the Global Ecosystem Typology), spatial patterns may differ from those of biogeographic biomes. Differences reflect the distinctions between functional and biogeographic interpretations of the term, “biome”.

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from eight prospective population-based cohort studies, representing 13,021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had an excess mortality from all causes of 57 deaths per 10,000 person-years (95% confidence interval (CI): 38, 76) compared to their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10,000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the WHO risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

This study intended to provide preliminary normative data for the short version of the Wisconsin Card Sorting Test (WCST-64) for elderly in the South of Brazil. 310 cognitively preserved elderly were divided into five age groups and into five groups according to schooling. The applied instruments were: sociodemographic data questionnaire, MEEM, GDS-15 and WCST-64. Age was associated with a large majority of WCST-64 scores, while the years of schooling were not related to any scores. Based on these, it is possible to present preliminary normative data for this population and identify the influence of age on the participant’s performance. It is important to consider sociodemographic characteristics while assessing the performance of the elderly, also enlarging other regions of the country, Este estudo visou fornecer dados normativos preliminares da versão reduzida do Teste Wisconsin de Classificação de Cartas (WCST-64) para adultos idosos do Sul do Brasil. 310 adultos idosos cognitivamente preservados foram divididos em cinco faixas etárias e em cinco grupos por escolaridade. Os instrumentos utilizados foram: ficha de dados sociodemográficos, MEEM, GDS-15 e WCST-64. A idade associou-se à maioria dos escores do WCST-64, enquanto os anos de escolaridade não se relacionaram com nenhuma das pontuações. A partir disso, é possível apresentar dados normativos preliminares do WCST-64 para esta população e identificar a influência da idade no desempenho dos participantes. Ressalta-se a importância de considerar as características sociodemográficas ao avaliar o desempenho de adultos idosos, contemplando ainda demais regiões do país., Este estudio tuvo como objetivo proporcionar datos normativos preliminares de la versión reducida del Wisconsin Card Sorting Test (WCST-64) para adultos mayores del sur de Brasil. 310 adultos mayores cognitivamente conservados fueron divididos en cinco grupos de edad y en cinco grupos por niveles de educación. Los instrumentos utilizados fueron: formulario de datos sociodemográficos, MMSE, GDS-15 y WCST-64. La edad estaba asociada a la mayoría de las puntuaciones del WCST64, mientras que los años de educación no estaban relacionados con ninguna de las puntuaciones. A partir de esto, es posible presentar datos normativos preliminares del WCST-64 para esta población e identificar la influencia de la edad en el rendimiento de los participantes. Es importante considerar las características sociodemográficas a la hora de evaluar el desempeño de los adultos mayores, considerando también otras regiones del país

The heterozygous Phospholamban p.Arg14del mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. This mutation triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca2+ dynamics. Little is known about the physiological processes preceding induced cardiomyopathy, which is characterized by sub-epicardial accumulation of fibrofatty tissue, and a specific drug treatment is currently lacking. Here, we address these issues using a knock-in Phospholamban p.Arg14del zebrafish model. Hearts from adult zebrafish with this mutation display age-related remodeling with sub-epicardial inflammation and fibrosis. Echocardiography reveals contractile variations before overt structural changes occur, which correlates at the cellular level with action potential duration alternans. These functional alterations are preceded by diminished Ca2+ transient amplitudes in embryonic hearts as well as an increase in diastolic Ca2+ level, slower Ca2+ transient decay and longer Ca2+ transients in cells of adult hearts. We find that istaroxime treatment ameliorates the in vivo Ca2+ dysregulation, rescues the cellular action potential duration alternans, while it improves cardiac relaxation. Thus, we present insight into the pathophysiology of Phospholamban p.Arg14del cardiomyopathy.

The Convention on Biological Diversity’s post-2020 Global Biodiversity Framework will probably include a goal to stabilize and restore the status of species. Its delivery would be facilitated by making the actions required to halt and reverse species loss spatially explicit. Here, we develop a species threat abatement and restoration (STAR) metric that is scalable across species, threats and geographies. STAR quantifies the contributions that abating threats and restoring habitats in specific places offer towards reducing extinction risk. While every nation can contribute towards halting biodiversity loss, Indonesia, Colombia, Mexico, Madagascar and Brazil combined have stewardship over 31% of total STAR values for terrestrial amphibians, birds and mammals. Among actions, sustainable crop production and forestry dominate, contributing 41% of total STAR values for these taxonomic groups. Key Biodiversity Areas cover 9% of the terrestrial surface but capture 47% of STAR values. STAR could support governmental and non-state actors in quantifying their contributions to meeting science-based species targets within the framework.

The Convention on Biological Diversity’s post-2020 Global Biodiversity Framework will probably include a goal to stabilize and restore the status of species. Its delivery would be facilitated by making the actions required to halt and reverse species loss spatially explicit. Here, we develop a species threat abatement and restoration (STAR) metric that is scalable across species, threats and geographies. STAR quantifies the contributions that abating threats and restoring habitats in specific places offer towards reducing extinction risk. While every nation can contribute towards halting biodiversity loss, Indonesia, Colombia, Mexico, Madagascar and Brazil combined have stewardship over 31% of total STAR values for terrestrial amphibians, birds and mammals. Among actions, sustainable crop production and forestry dominate, contributing 41% of total STAR values for these taxonomic groups. Key Biodiversity Areas cover 9% of the terrestrial surface but capture 47% of STAR values. STAR could support governmental and non-state actors in quantifying their contributions to meeting science-based species targets within the framework.

Glioblastoma multiforme (GBM) has a mean survival of only 15 months. Tumour heterogeneity and blood‐brain barrier (BBB) mainly hinder the transport of active agents, leading to late diagnosis, ineffective therapy and inaccurate follow‐up. The use of hydrogel nanoparticles, particularly hyaluronic acid as naturally occurring polymer of the extracellular matrix (ECM), has great potential in improving the transport of drug molecules and, furthermore, in facilitatating the early diagnosis by the effect of hydrodenticity enabling the T1 boosting of Gadolinium chelates for MRI. Here, crosslinked hyaluronic acid nanoparticles encapsulating gadolinium-diethylenetriamine pentaacetic acid (Gd‐DTPA) and the chemotherapeutic agent irinotecan (Thera-cHANPs) are proposed as theranostic nanovectors, with improved MRI capacities. Irinotecan was selected since currently repurposed as an alternative compound to the poorly effective temozolomide (TMZ), generally approved as the gold standard in GBM clinical care. Also, active crossing and targeting are achieved by theranostic cHANPs decorated with angiopep‐2 (Thera‐ ANG‐cHANPs), a dual‐targeting peptide interacting with low density lipoprotein receptor related protein‐1(LRP‐1) receptors overexpressed by both endothelial cells of the BBB and glioma cells. Results showed preserving the hydrodenticity effect in the advanced formulation and internalization by the active peptide‐mediated uptake of Thera‐cHANPs in U87 and GS‐102 cells. Moreover, Thera‐ANG‐cHANPs proved to reduce ironotecan time response, showing a significant cytotoxic effect in 24 h instead of 48 h.

The White-winged Dog-like Bat (Peropteryx leucoptera) and the Pale-winged Dog-like Bat (Peropteryx pallidoptera) are distinguished from the other emballonurid bats because they have white or translucent wings. Their distribution and biology are poorly known due to they are no captured in traditional bat inventories using mist nets. In this contribution, we extend the known distribution of P. leucoptera 260 km NE and P. pallidoptera 290 km NE. Our records are from three specimens collected in a mammal assessment at the riparian corridor of the river Meta in the Vichada department. This locality is the northern limit of the distributional range of both species. We highlight the need to continue the fieldwork on mammals inventories with specimen collections through the Colombian Llanos. We call attention to the importance of horizontal rotten logs as roost of P. leucoptera and other little known neotropical bats., El murciélago cara de perro de alas blancas (Peropteryx leucoptera) y el murciélago cara de perro de alas pálidas (Peropteryx pallidoptera) se diferencian de otros murciélagos embalonúridos porque tienen las alas blancas o translucidas. Su distribución y biología son poco conocidas porque no son capturados usanso redes de niebla en inventarios tradicionales. En esta contribución, ampliamos la distribución conocida de P. leucoptera 260 km al noreste y la de P. pallidopera 290 km al noroeste. Nuestros registros son de tres especímenes recolectados en un inventario en el corredor ripario del río Meta en el departamento del Vichada. Esta localidad, es el límite norte de la distribución de ambas especies. Es necesario continuar el trabajo de campo e inventarios de mamíferos con recolección de especímenes a lo largo de la región de los Llanos. llamamos la atención sobre la importancia de los troncos caidos como refugio de P. leucoptera y otras especies poco conocidas de murciélagos neotropicales.