Thermally-induced lactosylation of whey proteins: Identification and synthesis of lactosylated β-lactoglobulin epitope

The high temperatures used in the production of milk may induce modifications in proteins structure. Due to occurrence of the Maillard reaction, lactose binds lysine residues in proteins, affecting the nutritional value. Milk is also an important source of allergenic proteins (i.e., caseins, β-lactoglobulin and α-lactalbumin). Thus, this modification may also affect the allergenicity of these proteins. Focusing on milk whey proteins, a screening on different Ultra High Temperatures (UHT) and pasteurized milk samples was performed to identify lactosylation sites, in particular in protein known epitopes, and to verify the correlation between lactosylation and the harshness of the treatment. Whey proteins were extracted from milk samples after caseins precipitations at pH 4.6 and, after chymotryptic and tryptic in solution digestion, peptides were analysed by UPLC-MS and LTQ-Orbitrap. Results show the presence of lactosylated lysine residues in several known epitopes. Then, a β-lactoglobulin epitope was selected and synthesized by solid phase synthesis followed by in solution lactosylation, obtaining high reaction yields and purities. The synthesis of lactosylated allergenic epitopes, described here for the first time, is a useful tool for further studies on the technological impacts on food allergenicity

In-depth analysis of the Naming Game dynamics: the homogeneous mixing case

Language emergence and evolution has recently gained growing attention through multi-agent models and mathematical frameworks to study their behavior. Here we investigate further the Naming Game, a model able to account for the emergence of a shared vocabulary of form-meaning associations through social/cultural learning. Due to the simplicity of both the structure of the agents and their interaction rules, the dynamics of this model can be analyzed in great detail using numerical simulations and analytical arguments. This paper first reviews some existing results and then presents a new overall understanding.Comment: 30 pages, 19 figures (few in reduced definition). In press in IJMP

Measurement of Dielectric Suppression of Bremsstrahlung

In 1953, Ter-Mikaelian predicted that the bremsstrahlung of low energy photons in a medium is suppressed because of interactions between the produced photon and the electrons in the medium. This suppression occurs because the emission takes place over on a long distance scale, allowing for destructive interference between different instantaneous photon emission amplitudes. We present here measurements of bremsstrahlung cross sections of 200 keV to 20 MeV photons produced by 8 and 25 GeV electrons in carbon and gold targets. Our data shows that dielectric suppression occurs at the predicted level, reducing the cross section up to 75 percent in our data.Comment: 11 pages, format is postscript file, gzip-ed, uuencode-e

Characterization of defatted products obtained from the Parmigiano–Reggiano manufacturing chain: Determination of peptides and amino acids content and study of the digestibility and bioactive properties

Parmigiano–Reggiano (PR) is a worldwide known Italian, long ripened, hard cheese. Its inclusion in the list of cheeses bearing the protected designation of origin (PDO, EU regulation 510/2006) poses restrictions to its geographic area of production and its technological characteristics. To innovate the Parmigiano–Reggiano (PR) cheese manufacturing chain from the health and nutritional point of view, the output of defatted PR is addressed. Two defatting procedures (Soxhlet, and supercritical CO2 extraction) were tested, and the obtained products were compared in the composition of their nitrogen fraction, responsible for their nutritional, organoleptic, and bioactive functions. Free amino acids were quantified, and other nitrogen compounds (peptides, proteins, and non-proteolytic aminoacyl derivatives) were identified in the extracts and the mixtures obtained after simulated gastrointestinal digestion. Moreover, antioxidant and angiotensin converting enzyme (ACE) inhibition capacities of the digests were tested. Results obtained from the molecular and biofunctional characterization of the nitrogen fraction, show that both the defatted products keep the same nutritional properties of the whole cheese

Evaluation of tip and torque on virtual study models: a validation study

Background: The objectives of this study were to develop and validate a novel analysis protocol to measure linear and angular measurements of tip and torque of each tooth in the dental arches of virtual study models. Methods: Maxillary and mandibular dental casts of 25 subjects with a full permanent dentition were scanned using a three-dimensional model scanner. Sixty points per arch were digitized on each model, five points on each tooth. A custom analysis to measure linear distances and angles of tip and torque was developed using a new reference plane passing as a best-fit among all of the lingual gingival points, with the intermolar lingual distance set as the reference X-axis. The linear distances measured included buccal, lingual, and centroid transverse widths at the level of canines, premolars, and molars as well as arch depth and arch perimeter. Results: There was no systematic error associated with the methodology used. Intraclass correlation coefficient values were higher than 0.70 on every measure. The average random error in the maxilla was 1.5\ub0 \ub1 0.4\ub0 for torque, 1.8\ub0 \ub1 0.5\ub0 for tip, and 0.4 \ub1 0.2 mm for linear measurements. The average random error in the mandible was 1.2\ub0 \ub1 0.3\ub0 for torque, 2.0\ub0 \ub1 0.8\ub0 for tip, and 0.1 \ub1 0.1 mm for the linear measurements. Conclusions: A custom digital analysis protocol to measure traditional linear measurements as well as tip and torque angulation on virtual dental casts was presented. This validation study demonstrated that the digital analysis used in this study has adequate reproducibility, providing additional information and more accurate intra-arch measurements for clinical diagnosis and dentofacial research

Gene Modulation by Peptide Nucleic Acids (PNAs) Targeting microRNAs (miRs)

Since non-viral gene therapy was developed and employed in different in vitro and in vivo experimental systems as an effective way to control and modify gene expression, RNA has been considered as a molecular target of great relevance (Li &Huang, 2008, López-Fraga et al., 2008). In combination with standard chemotherapy, the siRNA therapy can reduce the chemoresistance of certain cancers, demonstrating its potential for treating many malignant diseases. Examples of RNA sequences to be targeted for therapeutic applications are mRNAs coding oncoproteins or RNA coding anti-apoptotic proteins for the development of anti-cancer therapy. In the last years, progresses in molecular biology have allowed to identify many genes Coding for small non coding RNA molecules, microRNA (miRNAs or miRs), able to regulate gene expression at the translation level (Huang et al., 2008, Shrivastava & Shrivastava, 2008, Sahu et al. 2007, Orlacchio et al., 2007, Williams et al., 2008, Papagiannakopoulos & Kosik, 2008). Accordingly, an increasing number of reports associate the changed expression with specific phenotypes and even with pathological conditions (Garzon & Croce, 2008, Mascellani et al., 2008, Sontheimer & Carthew, 2005, Filipowicz et al., 2005, Alvarez-Garcia & Miska, 2005). Interestingly, microRNAs play a double role in cancer, behaving both as oncogenes or tumor suppressor genes. In general, miRs promoting cancer targets mRNA coding for tumor-suppression proteins, while microRNAs exhibiting tumor-suppression properties usually target mRNAs coding oncoproteins. MicroRNAs which have been demonstrated to play a crucial role in the initiation and progression of human cancer are defined as oncogenic miRNAs (oncomiRs) (Cho, 2007). The oncomiR expression profiling of human malignancies has also identified a number of diagnostic and prognostic cancer signals (Cho, 2007, Lowery et al., 2008). Moreover, microRNAs have been firmly demonstrated to be involved in cancer metastasis (metastamiRs). Examples of metastasis-promoting microRNAs are, miR-10b (Calin et al., 2006), miR-373 and - 520c (Woods et al., 2007), miR-21, -143 and -182 (Hayashita et al., 2005; Si et al., 2007; Zhu et al.,2007). Reviews on metastamiR has been recently published Hurst et al. (Hurst et al. 2009, Edmonds et al. 2009). Reviews on metastamiRs has been recently published by Hurst et al

Everolimus and enteric-coated mycophenolate sodium Ab initio after liver transplantation: Midterm results

Background and aim. Everolimus (EVR) use in liver transplantation (OLT) has been prescribed with calcineurin inhibitors (CNIs), steroids, and monoclonal antibodies. The aim of our study was to evaluate the safety, feasibility, and impact on renal function of EVR ab initio, in combination with enteric-coated mycophenolate sodium (EC-MPS) without the use of induction treatment, steroids, or CNIs.Patients and methods. We retrospective analyzed nine consecutive patients who underwent OLT at our institution. The initial dose of EVR (1.5 mg/d) was adjusted to achieve trough levels of 8 to 12 ng/mL. EC-MPS introduced at 1080 mg/d was maintained at the same dose over time.Results. At a mean follow-up of 21.48 (standard deviation [SD] 1.4) months from OLT, 7/9 recipients were alive with stable graft function. The 2-year patient and graft survivals were 77%. One recipient died due to cerebral hemorrhage and one, lung failure. No clinical evidence of an acute rejection episode was observed. Mean estimated glomerular filtration rate value, according to the Modification of Diet in Renal Disease formula increased from 59.5 (SD 9.89) mL/min/1.73 m(2) at OLT to 100.2 (SD 47.5) mL/min/1.73 m(2) (P = .03) after 12 months and 98.71 (SD 33.74) mL/min/1.73 m(2) (P = .03) after 24 months' follow-up.Conclusion. A double immunosuppression therapy with EVR and EC-MPS ab initio seemed to be efficacions and safe, representing a valid alternative to CNIs to prevent renal failure after OLT

Understanding the nature of psychiatric comorbidity in migraine: A systematic review focused on interactions and treatment implications

Background: Migraine is a highly prevalent and disabling neurological disorder which is commonly linked with a broad range of psychiatric comorbidities, especially among subjects with migraine with aura or chronic migraine. Defining the exact nature of the association between migraine and psychiatric disorders and bringing out the pathophysiological mechanisms underlying the comorbidity with psychiatric conditions are relevant issues in the clinical practice. Methods: A systematic review of the most relevant studies about migraine and psychiatric comorbidity was performed using "PubMed", "Scopus", and "ScienceDirect" electronic databases from 1 January 1998 to 15 July 2018. Overall, 178 studies met our inclusion criteria and were included in the current review. Results: According to the most relevant findings of our overview, the associations with psychiatric comorbidities are complex, with a bidirectional association of major depression and panic disorder with migraine. Importantly, optimizing the pharmacological and non-pharmacological treatment of either migraine or its psychiatric comorbidities might help clinicians to attenuate the burden of both these conditions. Conclusions: The available data highlight the need for a comprehensive evaluation of psychiatric disorders in migraine in order to promote an integrated model of care and carefully address the burden and psychosocial impairment related to psychiatric comorbidities in migraine