Understanding obesity: new insights from ANKRD26

Mounting evidence sustains the role of DNA methylation in determining obesity as well as the down-stream adverse responses to increased BMI. Thus, identifying new players and mechanisms relevant to obesity and its related endo-phenotypes and understanding whether and how DNA methylation changes may affect these targets is of particular importance. My colleagues and I have recently recognized the Ankyrin repeat domain 26 (Ankrd26) gene as an interesting and proper target to study. This work aims to i. provide clearer evidence in humans of the cause-effect relationship between ANKRD26 gene expression and DNA methylation and investigate the correlation of these changes to obesity-related endo-phenotypes, unhealthy metabolic states and cardio-metabolic risk. Also, I aim to ii. establish in vitro the obesity-induced hypothalamic regulation of Ankrd26 gene in terms of DNA methylation changes, and clarify the role of the Ankrd26 protein on the hypothalamic regulation of anorexigenic signals in vitro. i. Hyper-methylation at three specific CpG sites within the ANKRD26 promoter causes down-regulation of its gene expression and represents a common abnormality in obese patients, particularly if metabolically unhealthy. Furthermore, these mRNA and DNA methylation changes of ANKRD26 gene correlate to increased Body Mass Index (BMI), and raised levels of both pro-inflammatory molecules and cardio-metabolic risk-related factors in humans. ii. Down-regulation of Ankrd26 mRNA and protein expression occur in the hypothalamus of diet-induced obese mice compared to lean control mice. These changes are associated to hyper-methylation of a specific CpG site in the gene promoter. Furthermore, Ankrd26 protein is up-regulated by the treatments with both the hormones, insulin and leptin, and the drug Exendin-4 in murine hypothalamic mHypoE-N46 cells. Also, over-expression of Ankrd26 modulates MAPK signaling and neuropeptide gene expression, by increasing the mRNA of the anorexigenic POMC and CART and decreasing the mRNA of the orexigenic AgRP, in mHypoE-N46-Ankrd26 cells. In conclusion, the results showed in my PhD thesis demonstrated that down-regulation of the ANKRD26 gene and hyper-methylation at specific CpGs of its promoter are common abnormalities in obesity and mark adverse health outcomes. Also, my data demonstrate that Ankrd26 protein might play a pivotal role in the regulation of energy homeostasis in vitro, acting as down-stream effector of anorexigenic signals in hypothalamic neuronal cells

Seismic behaviour of diaphragm arches: case studies from Catalan Gothic churches

The Gothic style spread, starting from the 12th century, from the Ile-de-France to England and other countries of the Mediterranean area, such as Spain and Italy, according to different configurations and construction techniques, influenced by economic, environmental and social factors. The so-called Catalan Gothic style is not exclusive to the architecture of the Principality of Catalonia but extends to the territories of the Crown of Aragon and Southern France. Its most important characteristics, based on the unitary conception of space and horizontality, had the religious architecture as their major reference. Among other structural elements, the large use of diaphragm arches, built transversally to the longitudinal direction of the nave, has been identified as peculiar both in ecclesiastic and civil Catalan Gothic architecture, although this technique is widely diffused also in the rest of the Mediterranean Europe. The present study focuses on the behaviour of this construction system under horizontal loads. After some brief notes on the history, origins and evolution of diaphragm arches, preliminary outcomes obtained by means of seismic analyses are provided in this paper. In particular, the possible collapse mechanisms of such remarkable curved structures have been firstly investigated by implementing FEM Models derived from real Catalan examples. Therefore, seismic analyses by means of analytical models have been carried out on the detected cases in order to demonstrate the capacity of this kind of structural skeleton, the importance of geometric ratios and the influence that specific typical elements may have in modifying the seismic behaviour of the analysed structures.Postprint (published version

Reuse of Wasted Bread as Soil Amendment: Bioprocessing, Effects on Alkaline Soil and Escarole (Cichorium endivia) Production

In an era characterized by land degradation, climate change, and a growing population, ensuring high‐yield productions with limited resources is of utmost importance. In this context, the use of novel soil amendments and the exploitation of plant growth‐promoting microorganisms potential are considered promising tools for developing a more sustainable primary production. This study aimed at investigating the potential of bread, which represents a large portion of the global food waste, to be used as an organic soil amendment. A bioprocessed wasted bread, obtained by an enzymatic treatment coupled with fermentation, together with unprocessed wasted bread were used as amendments in a pot trial. An integrated analytical plan aimed at assessing i) the modification of the physicochemical properties of a typical Mediterranean alkaline agricultural soil, and ii) the plant growth‐promoting effect on escarole (Cichorium endivia var. Cuartana), used as indicator crop, was carried out. Compared to the unamended soils, the use of biomasses raised the soil organic content (up to 37%) and total nitrogen content (up to 40%). Moreover, the lower pH and the higher organic acid content, especially in bioprocessed wasted bread, determined a major availability of Mn, Fe, and Cu in amended soils. The escaroles from pots amended with raw and bioprocessed bread had a number of leaves, 1.7‐ and 1.4‐fold higher than plants cultivated on unamended pots, respectively, showing no apparent phytotoxicity and thus confirming the possible re‐utilization of such residual biomasses as agriculture amendments

A possible role for nitric oxide in modulating the functional cyclosporine toxicity by arginine

A possible role for nitric oxide in modulating the functional cyclosporine toxicity by arginine. The renal damage consequent to cyclosporine A (CsA) administration ranges from hemodynamic alterations to irreversible chronic lesions. The initial vasoconstriction depends upon the imbalance between the various modulators of the renal vascular tone, among which the most powerful are endothelins and nitric oxide (NO). CsA could play a crucial role by inhibiting the Ca++/calmodulin-mediated activation of the constitutive NO synthase (NOS) isoform, which converts L-arginine (L-Arg) into NO and citrulline, with a 1:1 stoichiometry. To investigate the possibility of modulating CsA nephrotoxicity with L-Arg we studied six groups (G) of Lewis rats treated with daily gavage up to eight weeks: G1, CsA 40 mg/kg; G2, G1 plus L-Arg 300 mg/kg; G3, G2 plus the competitive inhibitor of NOS, NG-nitro-L-Arg (L-NNA); G4, L-Arg alone; G5, L-NNA alone; and G6, controls receiving vehicle alone. After eight weeks L-Arg treated rats were protected against the toxic effects of CsA [creatinine (Cr) values, G2, 0.62 ± 0.05 mg/dl vs. G1, 0.99 ± 0.16 mg/dl, P < 0.001; proteinuria (P), G2, 7.2 ± 1.02 mg/day vs. G1, 15.1 ± 1.9 mg/day, P < 0.01]. The administration of L-NNA abolished the protective effect of L-Arg (G3, Cr 1.23 ± 0.16 mg/dl; P 16.9 = 2.3; P < 0.02 and P < 0.005, respectively vs. G2). The levels of Cr in G2 rats were superimposable to control groups. The NOS activity, evaluated by measuring [3H]citrulline formation from [3H]L-Arg in kidney homogenates, was blocked by L-NNA in G5 (0.019 ± 0.009 pmol/min/mg proteins vs. G6 0.047 ± 0.002, P < 0.01). NOS activity was significantly increased versus controls in G1 (0.110 ± 0.032, P < 0.01) and G2 (0.088 ± 0.009, P < 0.02), while L-NNA reversed this phenomenon (G3, 0.052 ± 0.03). The expression of mRNA encoding for cNOS and iNOS was only slightly increased in CsA-treated rats. We suggest that CsA treatment increases NOS activity in the kidney by a mechanism which does not require a de novo synthesis of the enzyme. Such an increase, that may be devoted to counterbalance the vasoconstrictive effects of the drug, is unable to reduce the toxic effect of CsA in the absence of exogenous L-Arg. Administration of L-Arg is likely to reduce CsA nephrotoxicity by accomplishing the higher request of activated NOS for its substrate, thus potentiating NO synthesis in the kidney.

Potential of native and bioprocessed brewers' spent grains as organic soil amendments

IntroductionThe use of novel soil amendments and the exploitation of plant growth-promoting microorganisms are considered promising tools for developing a more sustainable agriculture in times when ensuring high-yield productions with limited resources is essential. MethodsIn this study, the potential of brewers' spent grain (BSG), the major by-product of the brewing industry, as organic soil amendment, was investigated. Bioprocessed BSG, obtained by an enzymatic treatment coupled with fermentation, together with native BSG, were used as amendments in a pot-trial. An integrated analytical approach aimed at assessing the modification of the physicochemical properties of a typical Mediterranean alkaline agricultural soil, and the plant growth-promoting effect on escarole (Cichorium endivia var. Cuartana), was carried out. ResultsThe use of biomasses led to soil organic content and total nitrogen content up to 72 and 42% higher, compared to the unamended soils. Moreover, the lower pH and the higher organic acids content doubled phosphorus availability. Although the number of leaves per plant in escaroles from pots amended with native and bioprocessed BSG did not show any difference compared to plants cultivated on unamended pots, the average fresh weight per escarole head, was higher in pots amended with bioprocessed BSG. DiscussionHence, the results collected so far encourage BSG application for agricultural purpose, while solving the problem of disposing of such abundant side stream.Peer reviewe

Tumor induced osteomalacia: a systematic review and individual patient's data analysis

Context: Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is characterized by renal phosphate leak, causing hypophosphatemia and osteomalacia. This review was performed to assess the clinical characteristics of TIO patients described worldwide so far. Evidence acquisition: On 06/26/2021, a systematic search was performed in Medline, Google Scholar, Google book, and Cochrane Library using the terms: "tumor induced osteomalacia", "oncogenic osteomalacia", "hypophosphatemia". There were no language restrictions. This review was performed according to PRISMA criteria. Evidence results: Overall, 1725 TIO cases were collected. TIO was more frequent in adult men, who showed a higher incidence of fractures compared to TIO women. The TIO causing neoplasms were identified in 1493 patients. The somatostatin receptor-based imaging modalities have the highest sensitivity for the identification of TIO-causing neoplasms. TIO causing neoplasms were equally located in bone and soft tissues; these latter showed a higher prevalence of fractures and deformities. The surgery is the preferred TIO definitive treatment (successful in &gt;90% of patients). Promising non-surgical therapies are treatments with burosumab in TIO patients with elevated Fibroblast Growth Factor-23 levels, and with radiolabeled somatostatin analogs in patients with TIO-causing neoplasm identified by somatostatin receptor-based imaging techniques. Conclusion: TIO occurs preferentially in adult men. The TIO clinical expressiveness is more severe in men as well as in patients with TIO-causing neoplasms located to soft tissues. Treatments with burosumab and with radiolabeled somatostatin analogs are the most promising non-surgical therapies

Natural treatments for erectile dysfunction: A focus on mobile health applications

To the Editor, Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain penile erection sufficient for satisfactory sexual performance. ED represents one of the most important male sexual dysfunctions with a prevalence of 52% and affecting more than 150 million men worldwide (estimated to be 322 million worldwide for 2025) [...

Nonprehensile Manipulation of Deformable Objects: Achievements and Perspectives from the RobDyMan Project

International audienceThe goal of this work is to disseminate the results achieved so far within the RODYMAN project related to planning and control strategies for robotic nonprehensile manipulation. The project aims at advancing the state of the art of nonprehensile dynamic manipulation of rigid and deformable objects to future enhance the possibility of employing robots in anthropic environments. The final demonstrator of the RODYMAN project will be an autonomous pizza maker. This article is a milestone to highlight the lessons learned so far and pave the way towards future research directions and critical discussions

Dissection of reverse gyrase activities: insight into the evolution of a thermostable molecular machine†

Reverse gyrase is a peculiar DNA topoisomerase, specific of thermophilic microorganisms, which induces positive supercoiling into DNA molecules in an ATP-dependent reaction. It is a modular enzyme and comprises an N-terminal helicase-like module fused to a C-terminal topoisomerase IA-like domain. The exact molecular mechanism of this unique reaction is not understood, and a fundamental mechanistic question is how its distinct steps are coordinated. We studied the cross-talk between the components of this molecular motor and probed communication between the DNA-binding sites and the different activities (DNA relaxation, ATP hydrolysis and positive supercoiling). We show that the isolated ATPase and topoisomerase domains of reverse gyrase form specific physical interactions, retain their own DNA binding and enzymatic activities, and when combined cooperate to achieve the unique ATP-dependent positive supercoiling activity. Our results indicate a mutual effect of both domains on all individual steps of the reaction. The C-terminal domain shows ATP-independent topoisomerase activity, which is repressed by the N-terminal domain in the full-length enzyme; experiments with the isolated domains showed that the C-terminal domain has stimulatory influence on the ATPase activity of the N-terminal domain. In addition, the two domains showed a striking reciprocal thermostabilization effect

Perceptions and attitudes toward the use of telemedicine for the postoperative outpatient urological care during the COVID-19 pandemic in an Academic Hospital in Southern Italy

Introduction: Telemedicine is a most used tools in various medical and surgical scenarios. The aim of the present study was to explore attitudes and perceptions by urologic patients toward the use of telemedicine in the context of patient-physicians communication during the post-operative follow-up in a large academic tertiary urology referral department in Italy. Materials and methods: An anonymous questionnaire consisting of 15 multiple choice questions was designed including three sections: respondents' demographics, attitudes, and perceptions towards the use of telemedicine. Invitations to participate to this anonymous questionnaire was given to outpatients attended at Urology Department, University of Naples Federico II. Results: In total 697 responses were received (participation rate 73%). The frequency of telemedicine use was described as frequently, occasional, rarely, and never by 41.6%, 30.4%, 15.1%, and 12.6% of respondents, respectively. WhatsApp messenger used by 59.5% of respondents and telephone call (34.3%) were the most common type of tools. Satisfaction in using telemedicine was reported as very satisfied, satisfied, neutral, dissatisfied, and very dissatisfied by 39.6%,41.4%,10%,7% and 2% of respondents respectively. Overall, 43.7%% of participants individuated limited interaction and risk of misdiagnosis as the major limit of telemedicine. Conclusions: Telemedicine represents the future of medical practice due to several benefits as well as convenience, increased access to care and decreased healthcare costs