Comparative Proteomics of Milk Fat Globule Membrane (MFGM) Proteome across Species and Lactation Stages and the Potentials of MFGM Fractions in Infant Formula Preparation

Milk is a lipid-in-water emulsion with a primary role in the nutrition of newborns. Milk fat globules (MFGs) are a mixture of proteins and lipids with nutraceutical properties related to the milk fat globule membrane (MFGM), which protects them, thus preventing their coalescence. Human and bovine MFGM proteomes have been extensively characterized in terms of their formation, maturation, and composition. Here, we review the most recent comparative proteomic analyses of MFGM proteome, above all from humans and bovines, but also from other species. The major MFGM proteins are found in all the MFGM proteomes of the different species, although there are variations in protein expression levels and molecular functions across species and lactation stages. Given the similarities between the human and bovine MFGM and the bioactive properties of MFGM components, several attempts have been made to supplement infant formulas (IFs), mainly with polar lipid fractions of bovine MFGM and to a lesser extent with protein fractions. The aim is thus to narrow the gap between human breast milk and cow-based IFs. Despite the few attempts made to date, supplementation with MFGM proteins seems promising as MFGM lipid supplementation. A deeper understanding of MFGM proteomes should lead to better results

Shedding light on nocturnal movements in parkinson’s disease: Evidence from wearable technologies

In Parkinson’s disease (PD), abnormal movements consisting of hypokinetic and hyperkinetic manifestations commonly lead to nocturnal distress and sleep impairment, which significantly impact quality of life. In PD patients, these nocturnal disturbances can reflect diseaserelated complications (e.g., nocturnal akinesia), primary sleep disorders (e.g., rapid eye movement behaviour disorder), or both, thus requiring different therapeutic approaches. Wearable technologies based on actigraphy and innovative sensors have been proposed as feasible solutions to identify and monitor the various types of abnormal nocturnal movements in PD. This narrative review addresses the topic of abnormal nocturnal movements in PD and discusses how wearable technologies could help identify and assess these disturbances. We first examine the pathophysiology of abnormal nocturnal movements and the main clinical and instrumental tools for the evaluation of these disturbances in PD. We then report and discuss findings from previous studies assessing nocturnal movements in PD using actigraphy and innovative wearable sensors. Finally, we discuss clinical and technical prospects supporting the use of wearable technologies for the evaluation of nocturnal movements

Determinants of Vitamin D Levels in Italian Children and Adolescents: A Longitudinal Evaluation of Cholecalciferol Supplementation versus the Improvement of Factors Influencing 25(OH)D Status

Objective. This paper aims to assess 25(OH)D levels in Italian children and adolescents identifying risk factors for 25(OH)D deficiency and to evaluate whether a normal 25(OH)D value can be restored in 25(OH)D-deficient patients. Methods. We evaluated 25(OH)D levels in 679 Italian children and adolescents (≤10, 11–20, 21–30, and >30 ng/mL were defined as severe deficiency, deficiency, insufficiency, and sufficiency, resp.). Of these, 365 25(OH)D-deficient were followed up for 1 year; 205 were treated with cholecalciferol (Arm A: 400 I.U.) and 160 by improving the environmental variables influencing 25(OH)D levels (Arm B). Results. At cross-sectional evaluation, 11.3% showed sufficiency, 30.0% insufficiency, and 58.7% 25(OH)D deficiency. Mean 25(OH)D was 19.08±8.44 ng/mL. At the enrollment time (T0), no difference was found between Arms A and B with respect to distribution and 25(OH)D levels. At end time (T1) 26.0% (29.7% in Arm A versus 20.6% in Arm B) showed sufficiency, 38.4% (42.0% versus 34.4%) insufficiency, and 35.6% (28.3% versus 45.0%) 25(OH)D deficiency. Mean 25(OH)D level was 23.71±6.83 ng/mL. Conclusions. Neither changes of lifestyle nor 400 I.U. cholecalciferol supplementation alone appears to be sufficient to restore adequate 25(OH)D levels

The non-anticoagulant heparin-like K5 polysaccharide derivative K5-N,OSepi attenuates myocardial ischaemia/reperfusion injury.

Heparin and low molecular weight heparins have been demonstrated to reduce myocardial ischaemia/reperfusion (I/R) injury, although their use is hampered by the risk of haemorrhagic and thrombotic complications. Chemical and enzymatic modifications of K5 polysaccharide have shown the possibility of producing heparin-like compounds with low anticoagulant activity and strong anti-inflammatory effects. Using a rat model of regional myocardial I/R, we investigated the effects of an epimerized N-,O-sulphated K5 polysaccharide derivative, K5-N,OSepi, on infarct size and histological signs of myocardial injury caused by 30 min. ligature of the left anterior descending coronary artery followed by 1 or 24 h reperfusion. K5-N,OSepi (0.1–1 mg/kg given i.v. 15 min. before reperfusion) significantly reduced the extent of myocardial damage in a dose-dependent manner. Furthermore, we investigated the potential mechanism(s) of the cardioprotective effect(s) afforded by K5-N,OSepi. In left ventricular samples, I/R induced mast cell degranulation and a robust increase in lipid peroxidation, free radical-induced DNA damage and calcium overload. Markers of neutrophil infiltration and activation were also induced by I/R in rat hearts, specifically myeloperoxidase activity, intercellular-adhesion-molecule-1 expression, prostaglandin-E(2) and tumour-necrosis-factor-α production. The robust increase in oxidative stress and inflammatory markers was blunted by K5-N,OSepi, in a dose-dependent manner, with maximum at 1 mg/kg. Furthermore, K5-N,OSepi administration attenuated the increase in caspase 3 activity, Bid and Bax activation and ameliorated the decrease in expression of Bcl-2 within the ischaemic myocardium. In conclusion, we demonstrate that the cardioprotective effect of the non-anticoagulant K5 derivative K5-N,OSepi is secondary to a combination of anti-apoptotic and anti-inflammatory effects

Bone mineral status and metabolism in patients with Williams-Beuren syndrome.

OBJECTIVE: To evaluate bone mineral status and metabolism in a cohort of patients with Williams-Beuren syndrome (WBS). PATIENTS: Thirty-one children (15 females, 16 males; mean age 9.6±2.74 years) and 10 young adults (6 females, 4 males; mean age 21.4±5.11 years) with WBS were cross-sectionally evaluated and compared with two age-, sex-, and body-size-matched paediatric (155 subjects, 75 females and 80 males; mean age 9.7±2.93 years) and adult (50 subjects, 30 females and 20 males; mean age 22.3±5.42 years) healthy controls. MEASUREMENTS: We evaluated ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels, and urinary deoxypyridinoline concentrations. We also calculated the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) z-scores. RESULTS: WBS patients showed a significantly reduced AD-SoS z-score (p <0.001) and BTT z-score (p <0.001) compared with the controls. This finding persisted when we divided the sample into paediatric and adult patients. WBS patients also had significantly higher ionised (p <0.001) and total calcium (p <0.001) levels as well as higher PTH levels (p <0.001) compared with the controls. Furthermore, WBS children and adolescents had significantly lower serum osteocalcin levels (p <0.001) and urinary deoxypyridinoline concentrations (p <0.001) than controls. CONCLUSIONS: WBS subjects exhibit a significant reduction in bone mineral status and impaired bone metabolism. These findings point to the need for close monitoring of WBS patients

CsI(Tl) Pulse Shape Discrimination with the Belle II Electromagnetic Calorimeter as a Novel Method to Improve Particle Identification at Electron-Positron Colliders

This paper describes the implementation and performance of CsI(Tl) pulse shape discrimination for the Belle II electromagnetic calorimeter, representing the first application of CsI(Tl) pulse shape discrimination for particle identification at an electron-positron collider. The pulse shape characterization algorithms applied by the Belle II calorimeter are described. Control samples of $\gamma$, $\mu^+$, $\pi^\pm$, $K^\pm$ and $p/\bar{p}$ are used to demonstrate the significant insight into the secondary particle composition of calorimeter clusters that is provided by CsI(Tl) pulse shape discrimination. Comparisons with simulation are presented and provide further validation for newly developed CsI(Tl) scintillation response simulation techniques, which when incorporated with GEANT4 simulations allow the particle dependent scintillation response of CsI(Tl) to be modelled. Comparisons between data and simulation also demonstrate that pulse shape discrimination can be a new tool to identify sources of improvement in the simulation of hadronic interactions in materials. The $K_L^0$ efficiency and photon-as-hadron fake-rate of a multivariate classifier that is trained to use pulse shape discrimination is presented and comparisons are made to a shower-shape based approach. CsI(Tl) pulse shape discrimination is shown to reduce the photon-as-hadron fake-rate by over a factor of 3 at photon energies of 0.2 GeV and over a factor 10 at photon energies of 1 GeV

Targeting SMYD3 to sensitize homologous recombination-proficient tumors to PARP-mediated synthetic lethality

SMYD3 is frequently overexpressed in a wide variety of cancers. Indeed, its inactivation reduces tumor growth in preclinical in vivo animal models. However, extensive characterization in vitro failed to clarify SMYD3 function in cancer cells, although confirming its importance in carcinogenesis. Taking advantage of a SMYD3 mutant variant identified in a high-risk breast cancer family, here we show that SMYD3 phosphorylation by ATM enables the formation of a multiprotein complex including ATM, SMYD3, CHK2, and BRCA2, which is required for the final loading of RAD51 at DNA double-strand break sites and completion of homologous recombination (HR). Remarkably, SMYD3 pharmacological inhibition sensitizes HR-proficient cancer cells to PARP inhibitors, thereby extending the potential of the synthetic lethality approach in human tumors

Measurement of Branching Fractions and Rate Asymmetries in the Rare Decays B -> K(*) l+ l-

In a sample of 471 million BB events collected with the BABAR detector at the PEP-II e+e- collider we study the rare decays B -> K(*) l+ l-, where l+ l- is either e+e- or mu+mu-. We report results on partial branching fractions and isospin asymmetries in seven bins of di-lepton mass-squared. We further present CP and lepton-flavor asymmetries for di-lepton masses below and above the J/psi resonance. We find no evidence for CP or lepton-flavor violation. The partial branching fractions and isospin asymmetries are consistent with the Standard Model predictions and with results from other experiments.Comment: 16 pages, 14 figures, accepted by Phys. Rev.