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Abstract Background MT-ATP6 is a mitochondrial gene which encodes for the intramembrane subunit 6 (or A) of the mitochondrial ATP synthase, also known asl complex V, which is involved in the last step of oxidative phosphorylation to produce cellular ATP through aerobic metabolism. Although classically associated with the NARP syndrome, recent evidence highlights an important role of MT-ATP6 pathogenic variants in complicated adult-onset ataxias. Methods We describe two unrelated patients with adult-onset cerebellar ataxia associated with severe optic atrophy and mild cognitive impairment. Whole mitochondrial DNA sequencing was performed in both patients. We employed patients’ primary fibroblasts and cytoplasmic hybrids (cybrids), generated from patients-derived cells, to assess the activity of respiratory chain complexes, oxygen consumption rate (OCR), ATP production and mitochondrial membrane potential. Results In both patients, we identified the same novel m.8777 T > C variant in MT-ATP6 with variable heteroplasmy level in different tissues. We identifed an additional heteroplasmic novel variant in MT-ATP6, m.8879G > T, in the patients with the most severe phenotype. A significant reduction in complex V activity, OCR and ATP production was observed in cybrid clones homoplasmic for the m.8777 T > C variant, while no functional defect was detected in m.8879G > T homoplasmic clones. In addition, fibroblasts with high heteroplasmic levelsof m.8777 T > C variant showed hyperpolarization of mitochondrial membranes. Conclusions We describe a novel pathogenic mtDNA variant in MT-ATP6 associated with adult-onset ataxia, reinforcing the value of mtDNA screening within the diagnostic workflow of selected patients with late onset ataxias.

Summary: Aiming to shed light on the biology of wild ruminants, we investigated the gut microbiome seasonal dynamics of the Alpine ibex (Capra ibex) from the Central Italian Alps. Feces were collected in spring, summer, and autumn during non-invasive sampling campaigns. Samples were analyzed by 16S rRNA amplicon sequencing, shotgun metagenomics, as well as targeted and untargeted metabolomics. Our findings revealed season-specific compositional and functional profiles of the ibex gut microbiome that may allow the host to adapt to seasonal changes in available forage, by fine-tuning the holobiont catabolic layout to fully exploit the available food. Besides confirming the importance of the host-associated microbiome in providing the phenotypic plasticity needed to buffer dietary changes, we obtained species-level genome bins and identified minimal gut microbiome community modules of 11–14 interacting strains as a possible microbiome-based solution for the bioconversion of lignocellulose to high-value compounds, such as volatile fatty acids.

Abstract The interspecific transmission of pathogens can occur frequently in the environment. Among wild bees, the main spillover cases are caused by pathogens associated with Apis mellifera, whose colonies can act as reservoirs. Due to the limited availability of data in Italy, it is challenging to accurately assess the impact and implications of this phenomenon on the wild bee populations. In this study, a total of 3372 bees were sampled from 11 Italian regions within the BeeNet project, evaluating the prevalence and the abundance of the major honey bee pathogens (DWV, BQCV, ABPV, CBPV, KBV, Nosema ceranae, Ascosphaera apis, Crithidia mellificae, Lotmaria passim, Crithidia bombi). The 68.4% of samples were positive for at least one pathogen. DWV, BQCV, N. ceranae and CBPV showed the highest prevalence and abundance values, confirming them as the most prevalent pathogens spread in the environment. For these pathogens, Andrena, Bombus, Eucera and Seladonia showed the highest mean prevalence and abundance values. Generally, time trends showed a prevalence and abundance decrease from April to July. In order to predict the risk of infection among wild bees, statistical models were developed. A low influence of apiary density on pathogen occurrence was observed, while meteorological conditions and agricultural management showed a greater impact on pathogen persistence in the environment. Social and biological traits of wild bees also contributed to defining a higher risk of infection for bivoltine, communal, mining and oligolectic bees. Out of all the samples tested, 40.5% were co-infected with two or more pathogens. In some cases, individuals were simultaneously infected with up to five different pathogens. It is essential to increase knowledge about the transmission of pathogens among wild bees to understand dynamics, impact and effects on pollinator populations. Implementing concrete plans for the conservation of wild bee species is important to ensure the health of wild and human-managed bees within a One-Health perspective.

Abstract To understand the microbiome composition and interplay among bacterial communities in different compartments of a coupled freshwater aquaponics system growing flathead grey mullet (Mugil cephalus) and lettuces (Lactuca sativa), 16S rRNA gene amplicon sequencing of the V3–V4 region was analysed from each compartment (fish intestine, water from the sedimentation tank, bioballs from the biological filter, water and biofilm from the hydroponic unit, and lettuce roots). The bacterial communities of each sample group showed a stable diversity during all the trial, except for the fish gut microbiota, which displayed lower alpha diversity values. Regarding beta diversity, the structure of bacterial communities belonging to the biofilm adhering to the hydroponic tank walls, bioballs, and lettuce roots resembled each other (weighted and unweighted UniFrac distances), while bacteria from water samples also clustered together. However, both of the above-mentioned bacterial communities did not resemble those of fish gut. We found a low or almost null number of shared Amplicon Sequence Variants (ASVs) among sampled groups which indicated that each compartment worked as an independent microbiome. Regarding fish health and food safety, the microbiome profile did not reveal neither fish pathogens nor bacterial species potentially pathogenic for food health, highlighting the safety of this sustainable food production system.

Abstract Background The Scale for Assessment and Rating of Ataxia (SARA) is widely used in different types of ataxias and has been chosen as the primary outcome measure in the European natural history study for Friedreich ataxia (FA). Methods To assess distribution and longitudinal changes of SARA scores and its single items, we analyzed SARA scores of 502 patients with typical‐onset FA (

Quantitative measurement of physical activity may complement neurological evaluation and provide valuable information on patients’ daily life. We evaluated longitudinal changes of physical activity in patients with Friedreich ataxia (FRDA) using remote monitoring with wearable sensors. We performed an observational study in 26 adult patients with FRDA and 13 age-sex matched healthy controls (CTR). Participants were asked to wear two wearable sensors, at non-dominant wrist and at waist, for 7 days during waking hours. Evaluations were performed at baseline and at 1-year follow-up. We analysed the percentage of time spent in sedentary or physical activities, the Vector Magnitude on the 3 axes (VM3), and average number of steps/min. Study participants were also evaluated with ataxia clinical scales and functional tests for upper limbs dexterity and walking capability. Baseline data showed that patients had an overall reduced level of physical activity as compared to CTR. Accelerometer-based measures were highly correlated with clinical scales and disease duration in FRDA. Significantly changes from baseline to l-year follow-up were observed in patients for the following measures: (i) VM3; (ii) percentage of sedentary and light activity, and (iii) percentage of Moderate-Vigorous Physical Activity (MVPA). Reduction in physical activity corresponded to worsening in gait score of the Scale for Assessment and Rating of Ataxia. Real-life activity monitoring is feasible and well tolerated by patients. Accelerometer-based measures can quantify disease progression in FRDA over 1 year, providing objective information about patient’s motor activities and supporting the usefulness of these data as complementary outcome measure in interventional trials.

Honeybees (Apis mellifera L.) have to face many challenges, including Varroa destructor infestation, associated with viral transmission. Oxalic acid is one of the most common treatments against Varroa. Little is known about the physiological effects of oxalic acid, especially those on honeybees’ immune systems. In this study, the short-term effects (0–96 h) of oxalic acid treatment on the immune system components (i.e., glucose oxidase, phenoloxidase, glutathione S-transferase, catalase activities, and vitellogenin contents) of house bees were preliminarily investigated. Oxalic acid contents of bee bodies and haemolymphs were also measured. The results confirm that oxalic acid is constitutively present in bee haemolymphs and its concentration is not affected by treatment. At 6 h after the treatment, a maximum peak of oxalic acid content was detected on bees’ bodies, which gradually decreased after that until physiological levels were reached at 48 h. In the immune system, the oxalic acid treatment determined a peak in glucose oxidase activity at 48 h, indicating a potential defence response and an increase in vitellogenin content at 24 h. No significant changes were recorded in phenoloxidase, glutathione S-transferase, and catalase activities. These results suggest a time-dependent response to oxalic acid, with potential immune system activation in treated bees.

Following the Water Framework Directive 2000/60/CE (WFD), each member state of the European Union must monitor compliance of its rivers with ecological quality standards through biological quality indicators. The New Italian Index of the Ecological State of Fish Communities (NISECI) was developed in 2017 for the assessment of fish communities, as directed by the WFD in Italian freshwater habitats. According to the WFD, the general reference conditions (GRCs) of NISECI must be refined on a regional scale through new calculation of its metrics and sub-metrics. In the present study we used environmental and ichthyological data from 457 fish samplings distributed among 299 sampling sites within 84 different water bodies collected from 1995 to 2012 to develop: 1) new lists of expected species for six homogeneous zones identified in the Reno basin (Italy) and in the eastern regional basins of the Emilia-Romagna region; and 2) the threshold values for their species-specific abundance. Results were set as refined reference conditions (RRCs) for two of the metrics used in the application of the NISECI index in the study area (i.e. X1, relating to indigenous species and X2,b, for the abundance of expected species). The RRCs were tested by applying NISECI to 24 monitoring sites of the regional surface water monitoring network (i.e., ARPAE) and comparing the results with the application of NISECI using the GRCs. Furthermore, the analytical power of the refined NISECI was evaluated by relating the findings to three expert-based blind assessments of fish community ecological status. The results confirmed an increase in refined NISECI values and its higher consistency with expert-based assessment, supporting the validity of the presented method for RRC development and its potential for application in other regions.

Abstract We explored whether disease severity of Friedreich ataxia can be predicted using data from clinical examinations. From the database of the European Friedreich Ataxia Consortium for Translational Studies (EFACTS) data from up to five examinations of 602 patients with genetically confirmed FRDA was included. Clinical instruments and important symptoms of FRDA were identified as targets for prediction, while variables such as genetics, age of disease onset and first symptom of the disease were used as predictors. We used modelling techniques including generalised linear models, support-vector-machines and decision trees. The scale for rating and assessment of ataxia (SARA) and the activities of daily living (ADL) could be predicted with predictive errors quantified by root-mean-squared-errors (RMSE) of 6.49 and 5.83, respectively. Also, we were able to achieve reasonable performance for loss of ambulation (ROC-AUC score of 0.83). However, predictions for the SCA functional assessment (SCAFI) and presence of cardiological symptoms were difficult. In conclusion, we demonstrate that some clinical features of FRDA can be predicted with reasonable error; being a first step towards future clinical applications of predictive modelling. In contrast, targets where predictions were difficult raise the question whether there are yet unknown variables driving the clinical phenotype of FRDA.

Abstract Because of their recognized global importance, there is now the urgent need to map diversity and distribution patterns of marine microbial communities. Even if available studies provided some advances in the understanding the biogeographical patterns of marine microbiomes at the global scale, their degree of plasticity at the local scale it is still underexplored, and functional implications still need to be dissected. In this scenario here we provide a synoptical study on the microbiomes of the water column and surface sediments from 19 sites in a 130 km2 area located 13.5 km afar from the coast in the North-Western Adriatic Sea (Italy), providing the finest-scale mapping of marine microbiomes in the Mediterranean Sea. Pelagic and benthic microbiomes in the study area showed sector specific-patterns and distinct assemblage structures, corresponding to specific variations in the microbiome network structure. While maintaining a balanced structure in terms of potential ecosystem services (e.g., hydrocarbon degradation and nutrient cycling), sector-specific patterns of over-abundant modules—and taxa—were defined, with the South sector (the closest to the coast) characterized by microbial groups of terrestrial origins, both in the pelagic and the benthic realms. By the granular assessment of the marine microbiome changes at the local scale, we have been able to describe, to our knowledge at the first time, the integration of terrestrial microorganisms in the marine microbiome networks, as a possible natural process characterizing eutrophic coastal area. This raises the question about the biological threshold for terrestrial microorganisms to be admitted in the marine microbiome networks, without altering the ecological balance.