Generation of two human iPSC lines, FINCBi002-A and FINCBi003-A, carrying heteroplasmic macrodeletion of mitochondrial DNA causing Pearson's syndrome

Pearson marrow pancreas syndrome (PMPS) is a sporadic mitochondrial disease, resulting from the clonal expansion of a mutated mitochondrial DNA (mtDNA) molecule bearing a macro-deletion, and therefore missing essential genetic information. PMPS is characterized by the presence of deleted (Δ) mtDNA that co-exist with the presence of a variable amount of wild-type mtDNA, a condition termed heteroplasmy. All tissues of the affected individual, including the haemopoietic system and the post-mitotic, highly specialized tissues (brain, skeletal muscle, and heart) contain the large-scale mtDNA deletion in variable amount. We generated human induced pluripotent stem cells (hiPSCs) from two PMPS patients, carrying different type of large-scale deletion

Short-term physiological and biometrical responses of Lepidium sativum seedlings exposed to PET-made microplastics and acid rain.

Abstract Plastics enter in terrestrial natural system primarily by agricultural purposes, while acid rain is the result of anthropogenic activities. The synergistic effects of microplastics and acid rain on plant growth are not known. In this study, different sizes of polyethylene terephthalate (PET) and acid rain are tested on Lepidium sativum, in two separate experimental sets. In the first one we treated plants only with PET, in the second one we used PET and acid rain together. In both experimentations we analyzed: i) plant biometrical parameters (shoot height, leaf number, percentage inhibition of seed germination, fresh biomass), and ii) oxidative stress responses (hydrogen peroxide; ascorbic acid and glutathione). Results carried out from our experiments highlighted that different sizes of polyethylene terephthalate are able to affect plant growth and physiological responses, with or without acid rain supplied during acute toxicity (6 days). Short description This study showed that different sizes of PET microplastics affect physiological and biometrical responses of Lepidum sativum seedlings, with or without acid rain; roots and leaves responded differently

Litter in alien species of possible commercial interest: The blue crab (Callinectes sapidus Rathbun, 1896) as case study

Marine litter levels were measured in the stomach contents, hepatopancreas, and gonad tissues of crustacea decapod (Callinectes sapidus Rathbun, 1896; n\ua0=\ua06), a widespread alien species affecting the Lesina lagoon. Results highlight a mean of 2.5 (SD\ua0=\ua01.6) items/animal and indicate the presence of metals fragments (13%) and plastics (13% PE; 6.7% PET) in the stomach contents of collected individuals. No microplastic particles were detected in the hepatopancreas or in muscle tissue, while microplastic fibres (nylon, rayon, polyester) were found present in female specimen gonads. The presence of synthetic fibres in the investigated species reflects the relative contamination level in this habitat type and suggests that the blue crab could be considered a model organism for evaluating the contamination status of the study area

Pathological mitophagy disrupts mitochondrial homeostasis in Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON), a disease associated with a mitochondrial DNA mutation, is characterized by blindness due to degeneration of retinal ganglion cells (RGCs) and their axons, which form the optic nerve. We show that a sustained pathological autophagy and compartment-specific mitophagy activity affects LHON patient-derived cells and cybrids, as well as induced pluripotent-stem-cell-derived neurons. This is variably counterbalanced by compensatory mitobiogenesis. The aberrant quality control disrupts mitochondrial homeostasis as reflected by defective bioenergetics and excessive reactive oxygen species production, a stress phenotype that ultimately challenges cell viability by increasing the rate of apoptosis. We counteract this pathological mechanism by using autophagy regulators (clozapine and chloroquine) and redox modulators (idebenone), as well as genetically activating mitochondrial biogenesis (PGC1-α overexpression). This study substantially advances our understanding of LHON pathophysiology, providing an integrated paradigm for pathogenesis of mitochondrial diseases and druggable targets for therapy

Collapse of the North American ice saddle 14,500 years ago caused widespread cooling and reduced ocean overturning circulation

Collapse of ice sheets can cause significant sea level rise and widespread climate change. We examine the climatic response to meltwater generated by the collapse of the Cordilleran-Laurentide ice saddle (North America) ~14.5 thousand years ago (ka) using a high-resolution drainage model coupled to an ocean-atmosphere-vegetation general circulation model. Equivalent to 7.26 m global mean sea level rise in 340 years, the meltwater caused a 6 sverdrup weakening of Atlantic Meridional Overturning Circulation (AMOC) and widespread Northern Hemisphere cooling of 1–5°C. The greatest cooling is in the Atlantic sector high latitudes during Boreal winter (by 5–10°C), but there is also strong summer warming of 1–3°C over eastern North America. Following recent suggestions that the saddle collapse was triggered by the Bølling warming event at ~14.7–14.5 ka, we conclude that this robust submillennial mechanism may have initiated the end of the warming and/or the Older Dryas cooling through a forced AMOC weakening

Mowat-Wilson syndrome : growth charts

Background Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of theZEB2gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children. Results In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7 years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7 years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build. Conclusions These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS.Peer reviewe

Impact of different exposure models and spatial resolution on the long-term effects of air pollution.

Abstract Long-term exposure to air pollution has been related to mortality in several epidemiological studies. The investigations have assessed exposure using various methods achieving different accuracy in predicting air pollutants concentrations. The comparison of the health effects estimates are therefore challenging. This paper aims to compare the effect estimates of the long-term effects of air pollutants (particulate matter with aerodynamic diameter less than 10 μm, PM10, and nitrogen dioxide, NO2) on cause-specific mortality in the Rome Longitudinal Study, using exposure estimates obtained with different models and spatial resolutions. Annual averages of NO2 and PM10 were estimated for the year 2015 in a large portion of the Rome urban area (12 × 12 km2) applying three modelling techniques available at increasing spatial resolution: 1) a chemical transport model (CTM) at 1km resolution; 2) a land-use random forest (LURF) approach at 200m resolution; 3) a micro-scale Lagrangian particle dispersion model (PMSS) taking into account the effect of buildings structure at 4 m resolution with results post processed at different buffer sizes (12, 24, 52, 100 and 200 m). All the exposures were assigned at the residential addresses of 482,259 citizens of Rome 30+ years of age who were enrolled on 2001 and followed-up till 2015. The association between annual exposures and natural-cause, cardiovascular (CVD) and respiratory (RESP) mortality were estimated using Cox proportional hazards models adjusted for individual and area-level confounders. We found different distributions of both NO2 and PM10 concentrations, across models and spatial resolutions. Natural cause and CVD mortality outcomes were all positively associated with NO2 and PM10 regardless of the model and spatial resolution when using a relative scale of the exposure such as the interquartile range (IQR): adjusted Hazard Ratios (HR), and 95% confidence intervals (CI), of natural cause mortality, per IQR increments in the two pollutants, ranged between 1.012 (1.004, 1.021) and 1.018 (1.007, 1.028) for the different NO2 estimates, and between 1.010 (1.000, 1.020) and 1.020 (1.008, 1.031) for PM10, with a tendency of larger effect for lower resolution exposures. The latter was even stronger when a fixed value of 10 μg/m3 is used to calculate HRs. Long-term effects of air pollution on mortality in Rome were consistent across different models for exposure assessment, and different spatial resolutions

The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/ 27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality

A Multidisciplinary Approach to Evaluate the Effects of Contaminants of Emerging Concern on Natural Freshwater and Brackish Water Phytoplankton Communities

7noEcotoxicological assays on monospecific phytoplankton have limited application for detecting the effects of environmental pollutants on multiple species communities. With this study, we took an ecotoxicological, ecological, and biochemical approach to evaluate the effects of two contaminants of emerging concern (zinc oxide nanoparticles, ZnO NPs, and potassium dichromate, K2Cr2O7) at different concentrations (K2Cr2O7 5.6–18–50 mg/L; ZnO NPs 10–100–300 mg/L) on natural freshwater and brackish water phytoplankton communities. Cell density and absorbance values decreased in freshwater and brackish water phytoplankton communities after exposure to ZnO NPs (100 mg/L and 300 mg/L only for freshwater), whereas growth rate was increased in both freshwater and brackish water phytoplankton communities after exposure to ZnO NPs 10 mg/L. Differently, there was no clear relationship between concentration and inhibition growth after exposure to K2Cr2O7: the lowest cell density was recorded after exposure to 18 mg/L. Moreover, the evenness index value was lower compared to the other concentrations, indicating the growth of a few, albeit resistant species to higher K2Cr2O7 concentrations. Generally, Bacillariophyceae and Dinoficee were prevalent in phytoplankton cultures after exposure to ZnO NPs and K2Cr2O7. The Shannon-Wiener index was slightly higher in the negative than the positive controls, but diversity was low after all treatments in both ecotoxicological assays. The evenness index was always very close to zero, indicating the numerical predominance of one or very few species. Finally, the decrease in chlorophyll-a and pheophytin-a in both ecotoxicological assays indicated a change in photosynthetic activity. Our findings provide evidence for alterations in natural phytoplankton after exposure to emerging contaminants that can disrupt an entire ecosystem’s integrity.openopenPastorino, Paolo; Broccoli, Andrea; Bagolin, Elisa; Anselmi, Serena; Cavallo, Andrea; Prearo, Marino; Renzi, MoniaPastorino, Paolo; Broccoli, Andrea; Bagolin, Elisa; Anselmi, Serena; Cavallo, Andrea; Prearo, Marino; Renzi, Moni

Influence of Salinity on Copper Toxicity in <i>Paracentrotus lividus</i> and <i>Arbacia lixula</i> Embryos

The sea urchins Paracentrotus lividus and Arbacia lixula have a key role in benthic dynamics and they are often used to assess the toxicity of environmental contaminants. The aim of this research was to investigate the influence of salinity on copper toxicity on P. lividus and A. lixula embryos, evaluating the impact of future ocean salinity variations and estimating an optimum range for embryos. For this purpose, sea urchin embryos were exposed to different copper concentrations under varying salinity regimes, estimating the toxic effects with the percentage of abnormal embryos and the Integrative Toxicity Index (ITI). Results revealed acceptable levels of anomalies in a salinity range of 33–36‰ for A. lixula and 33–39‰ for P. lividus. The effect concentrations (EC50) of copper reveals increasing toxicity at increasing salinity for both sea urchin species, but between 33–36‰ (A. lixula) and 36–39‰ (P. lividus) the toxicity appear inversely related with salinity. This study illustrates the difficulty in relating a biological response to bioavailability, because the uptake and the sensitivity to copper across salinities is influenced by differences in osmoregulation, enhancing our knowledge about optimal salinity ranges and the potential impact of climate change on sea urchin embryo development