Designing a Regulatory and Supervisory Framework for Integrated Financial Markets

The financial crisis that started in 2007 casts doubt about the ability of national laws and competent authorities to manage the stability of the financial system and to protect investors. This is due to the relevant evolving features of financial intermediation, like the cross-border strategies in banking, with many M&A undertaken, especially in Europe, and more in general the globalization of finance, also through the many recent operations among exchanges. The associated regulatory and supervisory challenges have proved to be difficult to tackle. An international perspective is needed on single banking regulatory instruments, even if it is impossible at this stage to imagine unique rules and single international authorities managing capital ratios, deposit insurance, reserve requirements and lending of last resort, as well as other tools for providing financial markets stability. However, some common principles on regulation and the structure of supervision may be stated both in US and in Europe: we suggest a “four peak” approach to the matter.The financial crisis that started in 2007 casts doubt about the ability of national laws and competent authorities to manage the stability of the financial system and to protect investors. This is due to the relevant evolving features of financial intermediation, like the cross-border strategies in banking, with many M&A undertaken, especially in Europe, and more in general the globalization of finance, also through the many recent operations among exchanges. The associated regulatory and supervisory challenges have proved to be difficult to tackle. An international perspective is needed on single banking regulatory instruments, even if it is impossible at this stage to imagine unique rules and single international authorities managing capital ratios, deposit insurance, reserve requirements and lending of last resort, as well as other tools for providing financial markets stability. However, some common principles on regulation and the structure of supervision may be stated both in US and in Europe: we suggest a “four peak” approach to the matter.Refereed Working Papers / of international relevanc

A yeast-based screening unravels potential therapeutic molecules for mitochondrial diseases associated with dominant ant1 mutations

Mitochondrial diseases result from inherited or spontaneous mutations in mitochondrial or nuclear DNA, leading to an impairment of the oxidative phosphorylation responsible for the synthesis of ATP. To date, there are no effective pharmacological therapies for these pathologies. We performed a yeast-based screening to search for therapeutic drugs to be used for treating mito-chondrial diseases associated with dominant mutations in the nuclear ANT1 gene, which encodes for the mitochondrial ADP/ATP carrier. Dominant ANT1 mutations are involved in several degen-erative mitochondrial pathologies characterized by the presence of multiple deletions or depletion of mitochondrial DNA in tissues of affected patients. Thanks to the presence in yeast of the AAC2 gene, orthologue of human ANT1, a yeast mutant strain carrying the M114P substitution equivalent to adPEO-associated L98P mutation was created. Five molecules were identified for their ability to suppress the defective respiratory growth phenotype of the haploid aac2M114P . Furthermore, these molecules rescued the mtDNA mutability in the heteroallelic AAC2/aac2M114P strain, which mimics the human heterozygous condition of adPEO patients. The drugs were effective in reducing mtDNA instability also in the heteroallelic strain carrying the R96H mutation equivalent to the more severe de novo dominant missense mutation R80H, suggesting a general therapeutic effect on diseases associated with dominant ANT1 mutations

Adherence and Constancy in LIME-RS Explanations for Recommendation

Explainable Recommendation has attracted a lot of attention due to a renewed interest in explainable artificial intelligence. In particular, post-hoc approaches have proved to be the most easily applicable ones to increasingly complex recommendation models, which are then treated as black boxes. The most recent literature has shown that for post-hoc explanations based on local surrogate models, there are problems related to the robustness of the approach itself. This consideration becomes even more relevant in human-related tasks like recommendation. The explanation also has the arduous task of enhancing increasingly relevant aspects of user experience such as transparency or trustworthiness. This paper aims to show how the characteristics of a classical post-hoc model based on surrogates is strongly model-dependent and does not prove to be accountable for the explanations generatedThe authors acknowledge partial support of PID2019-108965GB-I00, PONARS01_00876BIO-D,CasadelleTecnologie mergenti della Cittàdi Matera, PONARS01_00821FLET4.0, PIAServiziLocali2.0,H2020Passapartout-Grantn. 101016956, PIAERP4.0,andIPZS-PRJ4_IA_NORMATIV

A Trypanosoma cruzi Small Surface Molecule Provides the First Immunological Evidence that Chagas' Disease Is Due to a Single Parasite Lineage

Chagas' disease is a major health and economic problem caused by the protozoan Trypanosoma cruzi. Multiple independently evolving clones define a complex parasite population that can be arranged into two broad genetic lineages termed T. cruzi I and II. These lineages have different evolutionary origin and display distinct ecological and biological traits. Here we describe a novel molecule termed TSSA for trypomastigote small surface antigen that provides the first immunological marker allowing discrimination between lineages. TSSA is a surface, glycosylphosphatidyl inositol (GPI)-anchored mucin-like protein, highly antigenic during the infection. TSSA sequences from different parasite isolates reveal a population dimorphism that perfectly matches with the two T. cruzi lineages. Interestingly, this dimorphism is restricted to the central region of the molecule, which comprises the immunodominant B cell epitopes. This sequence variability has a major impact on TSSA antigenicity, leading to no immunological cross-reactivity between both isoforms for antibodies present either in immunization or infection sera. Furthermore, the absolute seroprevalence for TSSA in confirmed Chagasic patients is restricted to T. cruzi II isoform, strongly suggesting that human infections are due to this particular subgroup. Even though association of T. cruzi II with Chagas' disease has been proposed based on molecular markers, this is the first immunological evidence supporting this hypothesis. The implications of these results for the future research on Chagas' disease could be envisaged

Mechanisms of base selection by human single-stranded selective monofunctional uracil-DNA glycosylase

hSMUG1 (human single-stranded selective monofunctional uracil-DNA glyscosylase) is one of three glycosylases encoded within a small region of human chromosome 12. Those three glycosylases, UNG (uracil-DNA glycosylase), TDG (thymine-DNA glyscosylase), and hSMUG1, have in common the capacity to remove uracil from DNA. However, these glycosylases also repair other lesions and have distinct substrate preferences, indicating that they have potentially redundant but not overlapping physiological roles. The mechanisms by which these glycosylases locate and selectively remove target lesions are not well understood. In addition to uracil, hSMUG1 has been shown to remove some oxidized pyrimidines, suggesting a role in the repair of DNA oxidation damage. In this paper, we describe experiments in which a series of oligonucleotides containing purine and pyrimidine analogs have been used to probe mechanisms by which hSMUG1 distinguishes potential substrates. Our results indicate that the preference of hSMUG1 for mispaired uracil over uracil paired with adenine is best explained by the reduced stability of a duplex containing a mispair, consistent with previous reports with Escherichia coli mispaired uracil-DNA glycosylase. We have also extended the substrate range of hSMUG1 to include 5-carboxyuracil, the last in the series of damage products from thymine methyl group oxidation. The properties used by hSMUG1 to select damaged pyrimidines include the size and free energy of solvation of the 5-substituent but not electronic inductive properties. The observed distinct mechanisms of base selection demonstrated for members of the uracil glycosylase family help explain how considerable diversity in chemical lesion repair can be achieved

Cross-sectional relationship among different anthropometric parameters and cardiometabolic risk factors in a cohort of patients with overweight or obesity

Background Body fat distribution influences the risk of cardio-metabolic disease in people with overweight. This study was aimed at identifying the anthropometric parameters more strongly associated with the majority of cardio-metabolic risk factors. Methods This study included 1214 subjects (840 women), with a body-mass-index (BMI) = 25 Kg/ m2, aged 39.2 ± 13 years. Fasting blood glucose (FBG), triglycerides (TG), total, HDL- and LDL-cholesterol, uric acid, vitamin D, high-sensitive C-reactive protein (hs-CRP), white blood cells (WBC), platelets, insulin and insulin resistance (HOMA-IR), systolic (SBP) and diastolic blood pressure (DBP), smoking habit and snoring were evaluated as cardio-metabolic risk factors.We also included the Systematic COronary Risk Evaluation (SCORE) to estimate cardiovascular risk in our study population. BMI, waist circumference (WC), waistto- height-ratio (WHtR) and neck circumference (NC) were evaluated as anthropometric parameters. Results All four anthropometric parameters were positively associated to SBP, DBP, TG, FBG, insulin, HOMA-IR, WBC, and snoring (p<0.001), and negatively associated with HDL-cholesterol (p<0.001). NC showed a positive association with LDL-cholesterol (ß = 0.76; p = 0.01; 95% C.I. 0.19 to 1.32), while vitamin D was negatively associated to WC (ß = -0.16; p<0.001; 95% C.I. -0.24 to -0.09), BMI (ß = 0.42); p<0.001; 95% C.I. -0.56 to -0.28) and WHtR (ß = -24.46; p<0.001; 95% C.I. -37 to -11.9). Hs-CRP was positively correlated with WC (ß = 0.003; p = 0.003; 95% C.I. 0.001 to 0.006), BMI (ß = 0.01; p = 0.02; 95% C.I. 0.001 to 0.012) and WHtR (ß = 0.55; p = 0.01; 95% C.I. 0.14 to 0.96). SCORE was associated to NC (ß = 0.15; 95% CI 0.12 to 0.18; p<0.001), BMI (ß = -0.18; 95% CI -0.22 to 0.14; p<0.001) and WHtR (ß = 7.56; 95% CI 5.30 to 9.82; p<0.001). Conclusions NC, combined with BMI and WC or WHtR could represent an essential tool for use in clinical practice to define the cardio-metabolic risk in individuals with excess body weight

Adherence to a mediterranean diet and thyroid function in obesity: A cross-sectional Apulian survey

BackgroundMuch research suggests that Mediterranean eating habits and lifestyle contribute to counteract the risk of chronic diseases while promoting longevity, but little information is available on the effects of the Mediterranean diet (Med-Diet) on thyroid function, particularly among overweight/obese subjects. Nevertheless, consistent data reported a slight increase in serum levels of the thyroid-stimulating hormone (TSH) and a higher rate of conversion of thyroxine (T4) to triiodothyronine (T3) in obesity. This cross-sectional study was aimed at investigating the relationship between adherence to the Med-Diet and circulating thyroid hormones in a cohort of overweight/obese subjects from Apulia (Southern Italy). Methods: We studied 324 consecutive outpatient subjects (228 women and 96 men, age range 14–72 years) taking no drug therapy and showing normal levels of thyroid hormones, but complicated by overweight and obesity (body mass index (BMI) ≥ 25 Kg/m2). The PREDIMED (PREvención con DIeta MEDiterránea) questionnaire was cross-sectionally administered to assess the adherence to the Med-Diet, and hormonal, metabolic, and routine laboratory parameters were collected. Results: Higher adherence to Med-Diet was found to be inversely related to free T3 (p < 0.01) and T4 (p < 0.01) serum levels. Considering each item in the PREDIMED questionnaire, people consuming at least four spoonfuls of extra-virgin olive oil (EVOO) per day, as well as those consuming at least two servings of vegetables per day, had lower free T3 levels (p 0.033 and p 0.021, respectively). Furthermore, consuming at least four spoonfuls of EVOO per day was found to be associated to lower free T4 serum concentrations (p 0.011). Multinomial logistic regression models, performed on tertiles of thyroid hormones to further investigate the relationship with Med-Diet, corroborated the significance only for free T4. Conclusion: Increased adherence to the Med-Diet was independently associated to a slightly reduced thyroid function, but still within the reference range for free T3 and T4 serum levels. This first finding in this field opens up a research line on any underlying biological interplay

TinderBook: Fall in love with culture

More than 2 millions of new books are published every year and choosing a good book among the huge amount of available options can be a challenging endeavor. Recommender systems help in choosing books by providing personalized suggestions based on the user reading history. However, most book recommender systems are based on collaborative filtering, involving a long onboarding process that requires to rate many books before providing good recommendations. Tinderbook provides book recommendations, given a single book that the user likes, through a card-based playful user interface that does not require an account creation. Tinderbook is strongly rooted in semantic technologies, using the DBpedia knowledge graph to enrich book descriptions and extending a hybrid state-of-the-art knowledge graph embeddings algorithm to derive an item relatedness measure for cold start recommendations. Tinderbook is publicly available (http://www.tinderbook.it) and has already generated interest in the public, involving passionate readers, students, librarians, and researchers. The online evaluation shows that Tinderbook achieves almost 50% of precision of the recommendations

Glufosinate constrains synchronous and metachronous metastasis by promoting anti-tumor macrophages

Abstract Glutamine synthetase (GS) generates glutamine from glutamate and controls the release of inflammatory mediators. In macrophages, GS activity, driven by IL10, associates to the acquisition of M2‐like functions. Conditional deletion of GS in macrophages inhibits metastasis by boosting the formation of anti‐tumor, M1‐like, tumor‐associated macrophages (TAMs). From this basis, we evaluated the pharmacological potential of GS inhibitors in targeting metastasis, identifying glufosinate as a specific human GS inhibitor. Glufosinate was tested in both cultured macrophages and on mice bearing metastatic lung, skin and breast cancer. We found that glufosinate rewires macrophages toward an M1‐like phenotype both at the primary tumor and metastatic site, countering immunosuppression and promoting vessel sprouting. This was also accompanied to a reduction in cancer cell intravasation and extravasation, leading to synchronous and metachronous metastasis growth inhibition, but no effects on primary tumor growth. Glufosinate treatment was well‐tolerated, without liver and brain toxicity, nor hematopoietic defects. These results identify GS as a druggable enzyme to rewire macrophage functions and highlight the potential of targeting metabolic checkpoints in macrophages to treat cancer metastasis

Regulation of activation-induced deaminase stability and antibody gene diversification by Hsp90

Hsp90 stabilizes and prevents degradation of cytoplasmic activation-induced deaminase