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Targeting the FNIP2-SERCA2b axis improves metabolic and mitochondrial defects in Ataxia Telangiectasia
No full textAtaxia telangiectasia (AT) is a rare multisystem disorder caused by the loss of functional ATM protein, leading to immunodeficiency, cancer predisposition, neurodegeneration, diabetes, heart failure, and premature aging. Although ATM's role as a sensor of DNA double-strand breaks (DSBs) is well established, the mechanisms underlying the diverse AT phenotypes remain incompletely understood, with evidence suggesting they extend beyond DSB sensing. Here, we uncover widespread glycogen accumulation as a key feature of AT cells and tissues, driven by dysregulated glucose metabolism and impaired mitochondrial respiration assessed with a multidimensional approach including metabolomics, flux analysis, histopathology, bioenergetic measurements, and electron tomography. These metabolic defects contribute to reduced cellular viability and premature senescence observed in AT patient-derived cells. Strikingly, inactivation of FNIP2, which controls mitochondrial respiration, partially rescues these defects in AT cellular models. We show that FNIP2 interacts with the SERCA2b calcium channel, and its inactivation enhances cytoplasmic calcium availability, stimulating mitochondrial respiration and increasing glucose consumption. This metabolic reprogramming prevents glycogen accumulation and improves survival in AT primary cells. Our findings provide novel insights into AT pathophysiology and indicate the FNIP2-SERCA2b axis as a novel potential target for mitigating the systemic effects of AT and improving outcomes in this complex disease
Convective cold pools and attendant turbulence at the Amazon Tall Tower Observatory (ATTO)
No full textDeep moist convection significantly disturbs the evolution of the planetary boundary layer (PBL) through its convective cold pools (CCPs). This study investigates the statistics of CCPs and their impact on PBL turbulence as observed at the Amazon Tall Tower Observatory (ATTO) site. To obtain a large dataset of CCPs, we adapted an existing CCP-detection algorithm for use in multilevel, micrometeorological data. Application of the algorithm to ATTO observations collected from August 2021 through December 2023 resulted in a dataset consisting of 410 CCPs. CCPs occur nearly every other day at the ATTO site, although they are most common from April through September and are least common from December through March. The occurrence of CCPs is linked to the diurnal cycle of the PBL, with more events around 1800 UTC and the less events around 1100 UTC. The strength of CCP perturbations varies strongly as a function of the distance from the canopy. Above the canopy (approximately 37 m), CCPs exhibit well-defined gust fronts, marked by sharp drops in temperature and humidity, gusting winds, overturning circulations, and pressure rises. During gust front passages, sensible (latent) heat fluxes are briefly enhanced and subsequently invert sign (weaken) in the CCPs, as previously unstable (moister) PBLs become stable (drier). Turbulence is stronger and more anisotropic during gust fronts and just above the canopy due to mechanical drag. Anisotropic turbulence may be transported upward to 200 m by the gust fronts. Below the canopy, CCPs and attendant perturbations are drastically damped, except in high-end cases
Prevalence and clinical outcomes of fibrotic interstitial lung disease in ANCA associated vasculitis: a single-centre, retrospective, cohort study
No full textBackground: antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may affect
multiple organs and interstitial lung disease (ILD) might be the first manifestation.
Limited and discordant data are available on the prevalence of ILD in patients with AAV. Little is
known about prognostic outcomes of these patients.
The primary aim of the study was to determine the prevalence of fibrotic ILD in a cohort of AAV
patients followed-up in a University Hospital in Italy. Clinical and prognostic outcomes of AAV-ILD
were also assessed.
Methods: Data from 71 AAV patients (mean age 60.3 16 years; female 58.9%) were retrospectively
collected and analyzed.
Results: Overall ILD prevalence was 50.7%. Fibrotic ILDs represented 32.4% with a variable
distribution according to diagnosis: microscopic polyangiitis (MPA) 66.7%, eosinophilic granulomatosis
with polyangiitis (EGPA) 41.1%, granulomatosis with polyangiitis (GPA) 31.8%.
The presence of ILD was significantly different across AAV subgroups. Fibrotic ILD was more
prevalent in MPA (60%) than EGPA (11.8%) and GPA (9.1%) and most frequently associated with
usual interstitial pneumonia (UIP) pattern. The presence of ANCA was significantly associated with
fibrotic ILDs (p=0.01). In univariate analysis only MPA increased the risk of having ILD (OR 2 (CI
95%: 0.96-4.67). Mortality was significantly higher in patients with ILD (p=0.01), with fibrotic forms
influencing this finding and MPA showing the highest mortality.
Conclusions: Fibrotic ILDs are common in patients with AAV and influence clinical and prognostic
outcomes. MPA is the most frequent AAV associated to fibrotic ILD. ILD should be investigated at
diagnosis in all patients with AAV, since early diagnosis might impact the prognosis of these patients
First records of Japanese gall‐forming thrips Ponticulothrips diospyrosi Haga & Okajima, 1983 (Thysanoptera: Phlaeothripidae) in Europe
No full textThe Japanese gall-forming thrips Ponticulothrips diospyrosi Haga & Okajima, 1983 (Thysanoptera: Phlaeothripidae) is a monophagous species associated with persimmon (Diospyros kaki). Until now, P. diospyrosi was limited to the Asian continent (Japan and the Republic of Korea), but in 2023 and 2024, this species was first observed on persimmon trees in private gardens in Italy (Lombardy) and Switzerland (Ticino), respectively. The observed P. diospyrosi induced margin-roll galls on persimmon leaves, and some fruits also showed dotted scars characteristic of thrips on the skin. Insects were collected and identified through morphological and molecular analyses (sequencing). To our knowledge and based on the geographical distribution, this is the first report of the Japanese gall-forming thrips P. diospyrosi in Europe. DNA sequences of both Italian and Swiss specimens obtained in this work represent the first submission on international DNA sequence databases
#ItalianRightGalaxy: investigating the X/Twitter network between radical and extreme-right in Italy
No full textThis article investigates the digital ecosystem of the Italian radical and extreme-right by analyzing shared online audiences on X/Twitter. Employing a bottom-up approach grounded in social network analysis (SNA), the study examines networks of overlapping followers among official party accounts, affiliated youth organizations and non-party actors (such as cultural associations, music labels and newspaper). The main research question asks whether radical-right and extreme-right actors share a common online user base, using follower overlap as a proxy for communicative proximity and symbolic alignment, rather than formal organizational ties. Contrary to expectations of ideological segmentation between radical and extreme-right actors, the findings reveal substantial audience overlap and a highly connected network structure, suggesting that the Italian “far-right” digital sphere is less fragmented at the user level than often assumed. Through Social Newtork Analysis approach (e.g. bipartite projections, community detection and Exponential Random Graph Models), the analysis shows that digital affiliations frequently cut across offline political boundaries. Particular attention is given to cultural and youth-related accounts, which emerge as key intermediaries linking radical and extreme-right audiences and foster cross-sphere visibility, especially for marginalized actors in institutional politics. Despite methodological limitations, the study provides novel insights into the relational structure of the radical and extreme-right digital communities in Italy and contributes to ongoing debates on ideological boundaries, normalization, and audience integration in contemporary digital politics
Fibrosis‐Driven Surgical Risk After Thyroid Nodule Ablation: Quantitative Clinicopathological Determinants of Complications in Post‐Ablative Thyroidectomy—A Retrospective Cohort Study
No full textBackground: Thermal ablation is increasingly used for selected benign and low-risk thyroid nodules, yet some patients still require thyroidectomy for regrowth, persistent symptoms, or new oncologic concern. The surgical and pathological impact of ablation-induced remodeling remains incompletely defined. We aimed to characterize postablation thyroidectomy outcomes and identify histological correlates of perioperative morbidity. Methods: We conducted a single-center retrospective cohort study of patients undergoing thyroidectomy after radiofrequency or ethanol ablation (2021-2025). Clinical and ablation-related variables were collected, and intraoperative neuromonitoring was routinely used. Primary outcomes were recurrent laryngeal nerve (RLN) palsy, reoperative hematoma, and hypoparathyroidism. Surgical specimens underwent blinded dual-pathologist assessment with semiquantitative scoring of sclerosis, necrosis, and residual viability, from which a maturation index was derived. Associations with complications were analyzed using nonparametric methods. Outcomes were descriptively compared with a contemporaneous nonablated cohort for contextual purposes. Results: Thirty-one patients were included. Postoperative complications occurred in 22.6% of ablated cases. Histological analysis demonstrated moderate sclerosis (19.2%), necrosis (14.6%), and high residual viability (66.1%), with frequent pericapsular inflammatory changes and preserved capsule integrity. Sclerosis was the only parameter significantly associated with postoperative complications (30.0% vs. 16.9% and p = 0.008), whereas nodule size, ablation-to-surgery interval, and incidental carcinoma were not predictive. The maturation index increased with time after ablation but did not discriminate complication risk. Exploratory fibrosis-weighted metrics suggested potential risk thresholds, although these findings remain hypothesis-generating given the limited sample size. Conclusions: Thyroidectomy after prior ablation is feasible in experienced centers but may be technically demanding and associated with modestly increased procedural complexity. Mature sclerosis represents the principal histological correlate of perioperative morbidity, linking fibrotic remodeling to operative risk. These findings support centralization of postablation thyroid surgery in high-volume units with routine neuromonitoring and specialized pathology and highlight the need for larger prospective studies to validate fibrosis-based risk stratification tools
Atomic-scale deformation mechanisms at high-pressure in hydroboracite, CaMg[B3O4(OH)3]2·3H2O
No full textThe high-pressure behaviour of hydroboracite [ideally CaMg[B3O4(OH)3]2·3H2O, Sp. Gr. P2/c with a ~ 11.769, b ~ 6.684, c ~ 8.235 Å, and β ~ 102.6° at room conditions] has been studied by two in-situ single-crystal synchrotron X-ray diffraction experiments up to about 15 GPa, using He as pressure-transmitting medium. Between 14.51(5) and 14.72(5) GPa, hydroboracite undergoes a first-order phase transition to its high-pressure polymorph, hydroboracite-II (likely monoclinic with a ~ 11.29, b ~ 6.297, c ~ 7.48 Å, and β ~ 106°, space group unknown). The isothermal bulk modulus (KV0 = β−1P0,T0, where βP0,T0 is the volume compressibility coefficient) of hydroboracite was found to be KV0 = 41.4(6) GPa. The destructive nature of the phase transition prevented any structure resolution of hydroboracite-II or even the continuation of the experiments at pressures higher than 15.45(5) GPa. In the pressure range 0–14.45(5) GPa, the compressional anisotropy of hydroboracite, indicated by the ratio between the principal components of the unit-strain ellipsoid, is ε1:ε2:ε3 = 2.2:1.3:1. The P-induced deformation mechanisms at the atomic scale in hydroboracite are here described
Reducing Early-Life Smoke Exposure as a Preventive Strategy for Pediatric Multiple Sclerosis: Results from the PEDIGREE Study
No full textIntroductionAssessing the environmental impact on multiple sclerosis (MS) is complex because of long disease latency and potential recall bias, especially for perinatal exposures. This study aimed to investigate the association between parental smoking and the development of pediatric MS (PedMS).MethodsAs part of the Italian multicenter PEDIGREE study, the PEQ-IT questionnaire was used for prospective data collection. We enrolled subjects under 18 years with PedMS (2013 Krupp criteria) and disease duration <= 5 years from onset, along with matched controls.ResultsThe study included 114 PedMS cases and 121 controls. Female participants represented 77.2% of cases and 54.4% of controls, with a mean (SD) age of 16.8 (2.7) and 13.5 (4.9) years, respectively. The mean (SD) age at MS onset was 14.2 (2.6) years, and the median EDSS score was 1.0 (range 0-4.0). PedMS risk was higher in subjects with fathers who were current smokers (crude OR 1.94, 95% CI 1.10-3.40) or who smoked 3 months' pre-pregnancy (crude OR 1.79, 95% CI 1.03-3.11). The risk increased when both parents smoked (crude OR 2.03, 95% CI 1.12-3.68) and was highest when both smoked 3 months before pregnancy (crude OR 10.79, 95% CI 1.30-89.54), even after adjustments. No significant association was found with maternal smoking.ConclusionParental smoking, particularly paternal smoking current habit and before pregnancy, may increase the risk of PedMS. Promoting smoke-free behaviors among parents could therefore represent a feasible preventive approach to limit early-life environmental factors involved in disease susceptibility
