Does managing a SRI fund cost more? Evidence from the European financial market

open2Our aim is to provide evidence regarding managing costs differences comparing Socially Responsible Investing (SRI) funds with traditional ones, if any, and if these are influenced by the ethical rating of the fund. The methodology is based on a multiple linear regression model in a matched-pair sample of 309 European SRI and non-SRI funds managed by the same managing company and a comprehensive sample of 558 European SRI funds. Our main findings are on size, country, asset class, and ethical rating. Yet, the higher the ethical rating, the lower the TER, especially at the highest level of rating. If investors actively select higher ethically rated SRI funds, he or she will benefit from a lower cost charged by specialised asset managers. In investing in 'good', choose the best!openArrigoni, Stefania; Lanzavecchia, AlbertoArrigoni, Stefania; Lanzavecchia, Albert

Inhibitors of the Cdc34 acidic loop:a computational investigation integrating molecular dynamics, virtual screening and docking approaches

AbstractAmong the different classes of enzymes involved in the ubiquitin pathway, E2 ubiquitin-conjugating enzymes occupy a central role in the ubiquitination cascade. Cdc34-like E2 enzymes are characterized by a 12–14 residue insertion in the proximity of the catalytic site, known as the acidic loop. Cdc34 ubiquitin-charging activity is regulated by CK2-dependent phosphorylation and the regulatory mechanism involves the acidic loop. Indeed, the phosphorylation stabilizes the loop in an open conformation that is competent for ubiquitin charging.Cdc34 is associated with a variety of diseases, such as hepatocellular carcinomas and prostatic adenocarcinomas. In light of its role, the discovery of potential inhibitory compounds would provide the mean to effectively modulate its activity.Here, we carried out a computational study based on molecular dynamics, virtual screening and docking to identify potential inhibitory compounds of Cdc34, modulating the acidic loop conformation. The molecules identified in this study have been designed to act as molecular hinges that can bind the acidic loop in its closed conformation, thus inhibiting the Cdc34-mediated ubiquitination cascade at the ubiquitin-charging step. In particular, we proposed a pharmacophore model featuring two amino groups in the central part of the model and two lateral aromatic chains, which respectively establish electrostatic interactions with the acidic loop (Asp 108 and Glu 109) and a hydrogen bond with Ser 139, which is one of the key residues for Cdc34 activity

A framework for optimizing the acquisition protocol multishell diffusion-weighted imaging for multimodel assessment

Complementary aspects of tissue microstructure can be studied with diffusion-weighted imaging (DWI). However, there is no consensus on how to design a diffusion acquisition protocol for multiple models within a clinically feasible time. The purpose of this study is to provide a flexible framework that is able to optimize the shell acquisition protocol given a set of DWI models. Eleven healthy subjects underwent an extensive DWI acquisition protocol, including 15 candidate shells, ranging from 10 to 3500 s/mm2. The proposed framework aims to determine the optimized acquisition scheme (OAS) with a data-driven procedure minimizing the squared error of model-estimated parameters. We tested the proposed method over five heterogeneous DWI models exploiting both low and high b-values (i.e., diffusion tensor imaging [DTI], free water, intra-voxel incoherent motion [IVIM], diffusion kurtosis imaging [DKI], and neurite orientation dispersion and density imaging [NODDI]). A voxel-level and region of interest (ROI)-level analysis was conducted over the white matter and in 48 fiber bundles, respectively. Results showed that acquiring data for the five abovementioned models via OAS requires 14 min, compared with 35 min for the joint recommended acquisition protocol. The parameters derived from the reference acquisition scheme and the OAS are comparable in terms of estimated values, noise, and tissue contrast. Furthermore, the power analysis showed that the OAS retains the potential sensitivity to group-level differences in the parameters of interest, with the exception of the free water model. Overall, there is a linear correspondence (R2 = 0.91) between OAS and reference-derived parameters. In conclusion, the proposed framework optimizes the shell acquisition scheme for a given set of DWI models (i.e., DTI, free water, IVIM, DKI, and NODDI), combining low and high b-values while saving acquisition time

Identification of New Peptides from Fermented Milk Showing Antioxidant Properties: Mechanism of Action

Due to their beneficial properties, fermented foods are considered important constituents of the human diet. They also contain bioactive peptides, health-promoting compounds studied for a wide range of effects. In this work, several antioxidant peptides extracted from fermented milk proteins were investigated. First, enriched peptide fractions were purified and analysed for their antioxidant capacity in vitro and in a cellular model. Subsequently, from the most active fractions, 23 peptides were identified by mass spectrometry MS/MS), synthesized and tested. Peptides N-15-M, E-11-F, Q-14-R and A-17-E were selected for their antioxidant effects on Caco-2 cells both in the protection against oxidative stress and inhibition of ROS production. To define their action mechanism, the activation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2(Keap1/Nrf2) pathway was studied evaluating the translocation of Nrf2 from cytosol to nucleus. In cells treated with N-15-M, Q-14-R and A-17-E, a higher amount of Nrf2 was found in the nucleus with respect to the control. In addition, the three active peptides, through the activation of Keap1/Nrf2 pathway, led to overexpression and increased activity of antioxidant enzymes. Molecular docking analysis confirmed the potential ability of N-15-M, Q-14-R and A-17-E to bind Keap1, showing their destabilizing effect on Keap1/Nrf2 interaction

Antifungal activity of essential oils of Myrcia ovata chemotypes and their major compounds on phytopathogenic fungi

This work evaluated the antifungal activity of essential oils of Myrcia ovata chemotypes (MYRO-175, MYRO-156, MYRO-154, MYRO-165, and MYRO-015) and their major compounds (linalool, geraniol, citral, and (E)-nerolidol) on the phytopathogenic fungi Fusarium pallidoroseum (which causes melon postharvest rot) and Colletotrichum musae (which causes anthracnose in banana). The essential oils were obtained by hydrodistillation and analyzed by GCMS/FID. To evaluate the antifungal activity, the essential oils and their major compounds were tested at different concentrations (0.1; 0.3; 0.4; 0.5; 0.7; 1.0; 3.0, and 5.0 mL/L). The major compounds found in the essential oils were nerolic acid, linalool, geraniol, citral, and (E)-nerolidol. The essential oils of the plants MYRO-154, MYRO-165, and MYRO-015 had the minimum inhibitory concentration (MIC) (0.3 mL/L) for F. pallidoroseum and the lowest minimum fungicidal concentration (MFC) (0.7 mL/L), for C. musae. Geraniol and citral had the lowest MFC (0.5 mL / L) for the two fungi tested. For F. pallidoroseum, the essential oils of the chemotypes were more effective than their major compounds. Conversely, the major compounds geraniol of the chemotype MYRO-156 (74.37%) and citral were more effective than their respective essential oils for C. musae. (E)-nerolidol and geraniol of the chemotype MYRO-015 (33.15%) were responsible for the antifungal activity of the essential oils of their respective chemotypes

Functional MRI Studies in Friedreich's Ataxia: A Systematic Review

Friedreich's ataxia (FRDA) is an inherited neurodegenerative movement disorder with early onset, widespread cerebral and cerebellar pathology, and no cure still available. Functional MRI (fMRI) studies, although currently limited in number, have provided a better understanding of brain changes in people with FRDA. This systematic review aimed to provide a critical overview of the findings and methodologies of all fMRI studies conducted in genetically confirmed FRDA so far, and to offer recommendations for future study designs. About 12 cross-sectional and longitudinal fMRI studies, included 198 FRDA children and young adult patients and, 205 healthy controls (HCs), according to the inclusion criteria. Details regarding GAA triplet expansion and demographic and clinical severity measures were widely reported. fMRI designs included motor and cognitive task paradigms, and resting-state studies, with widespread changes in functionally activated areas and extensive variability in study methodologies. These studies highlight a mixed picture of both hypoactivation and hyperactivation in different cerebral and cerebellar brain regions depending on fMRI design and cohort characteristics. Functional changes often correlate with clinical variables. In aggregate, the findings provide support for cerebro-cerebellar loop damage and the compensatory mechanism hypothesis. Current literature indicates that fMRI is a valuable tool for gaining in vivo insights into FRDA pathology, but addressing that its limitations would be a key to improving the design, interpretation, and generalizability of studies in the future

Functional and Structural Brain Damage in Friedreich's Ataxia

Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder caused by a GAA repeat expansion in the FXN gene. There is still no cure or quantitative biomarkers reliaby correlating with the progression rate and disease severity. Investigation of functional and structural alterations characterizing white (WM) and gray matter (GM) in FRDA are needed prerequisite to monitor progression and response to treatment. Here we report the results of a multimodal cross-sectional MRI study of FRDA including Voxel-Based Morphometry (VBM), diffusion-tensor imaging (DTI), functional MRI (fMRI), and a correlation analysis with clinical severity scores. Twenty-one early-onset FRDA patients and 18 age-matched healthy controls (HCs) were imaged at 3T. All patients underwent a complete cognitive and clinical assessment with ataxia scales. VBM analysis showed GM volume reduction in FRDA compared to HCs bilaterally in lobules V, VI, VIII (L>R), as well as in the crus of cerebellum, posterior lobe of the vermis, in the flocculi and in the left tonsil. Voxel-wise DTI analysis showed a diffuse fractional anisotropy reduction and mean, radial, axial (AD) diffusivity increase in both infratentorial and supratentorial WM. ROI-based analysis confirmed the results showing differences of the same DTI metrics in cortico-spinal-tracts, forceps major, corpus callosum, posterior thalamic radiations, cerebellar penduncles. Additionally, we observed increased AD in superior (SCP) and middle cerebellar peduncles. The WM findings correlated with age at onset (AAO), short-allelle GAA, and disease severity. The intragroup analysis of fMRI data from right-handed 14 FRDA and 15 HCs showed similar findings in both groups, including activation in M1, insula and superior cerebellar hemisphere (lobules V–VIII). Significant differences emerged only during the non-dominant hand movement, with HCs showing a stronger activation in the left superior cerebellar hemisphere compared to FRDA. Significant correlations were found between AAO and the fMRI activation in cerebellar anterior and posterior lobes, insula and temporal lobe. Our multimodal neuroimaging protocol suggests that MRI is a useful tool to document the extension of the neurological impairment in FRDA

Reliability of forced internal rotation and active internal rotation to assess lateral instability of the biceps pulley

Purpose: the aim of this study was to investigate the relationship between positive painful forced internal rotation (FIR) and lateral pulley instability in the presence of a pre-diagnosed posterosuperior cuff tear. The same investigation was conducted for painful active internal rotation (AIR). Methods: a multicenter prospective study was conducted in a series of patients scheduled to undergo arthroscopic posterosuperior cuff repair. Pain was assessed using a visual analog scale (VAS) and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) was administered. The VAS score at rest, DASH score, and presence/absence of pain on FIR and AIR were recorded and their relationships with lesions of the lateral pulley, cuff tear patterns and shape of lesions were analyzed. Results: the study population consisted of 115 patients (mean age: 55.1 years) recruited from 12 centers. The dominant arm was affected in 72 cases (62.6%). The average anteroposterior extension of the lesion was 1.61 cm. The mean preoperative VAS and DASH scores were 6.1 and 41.8, respectively. FIR and AIR were positive in 94 (81.7%) and 85 (73.9%) cases, respectively. The lateral pulley was compromised in 50 cases (43.4%). Cuff tears were partial articular in 35 patients (30.4%), complete in 61 (53%), and partial bursal in 19 (16.5%). No statistical correlation between positive FIR or AIR and lateral pulley lesions was detected. Positive FIR and AIR were statistically associated with complete lesions. Negative FIR was associated with the presence of partial articular tears. Conclusions: painful FIR in the presence of a postero-superior cuff tear does not indicate lateral pulley instability. When a cuff tear is suspected, positive FIR and AIR are suggestive of full-thickness tear patterns while a negative FIR suggests a partial articular lesion. Level of evidence: level I, validating cohort study with good reference standards