Large scale analysis of protein stability in OMIM disease related human protein variants

Modern genomic techniques allow to associate several Mendelian human diseases to single residue variations in different proteins. Molecular mechanisms explaining the relationship among genotype and phenotype are still under debate. Change of protein stability upon variation appears to assume a particular relevance in annotating whether a single residue substitution can or cannot be associated to a given disease. Thermodynamic properties of human proteins and of their disease related variants are lacking. In the present work, we take advantage of the available three dimensional structure of human proteins for predicting the role of disease related variations on the perturbation of protein stability

Dual effects of leptin in perioperative gas exchange of morbidly obese patients

Leptin has shown positive effects on respiratory function in experimental settings. The role of leptin on perioperative respiratory function in morbidly obese patients has not been established. We performed a retrospective analysis of morbidly obese patients undergoing laparoscopic sleeve gastrectomy. Fasting serum leptin and interleukin (IL)-6 were measured preoperatively, and arterial blood gases were obtained pre- and postoperatively. Outcome variables were arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and differences in PaO2 and PaCO2 between pre- and postoperative values (\u394PaO2, \u394PaCO2; postoperative minus preoperative). Patients with lower (<40 \u3bcg/L) and higher ( 6540 \u3bcg/L) leptin levels were compared. Bravais-Pearson's correlation, multiple linear regression, and logistic regression analysis were performed. A total of 112 morbidly obese patients were included. Serum leptin was significantly higher in females than in males (42.86\ub112.89 vs. 30.67\ub113.39 \u3bcg/L, p<0.0001). Leptin was positively correlated with body mass index (r = 0.238; p = 0.011), IL-6 (r = 0.473; p<0.0001), and \u394PaO2 (r = 0.312; p = 0.0008). Leptin was negatively correlated with preoperative PaO2 (r = -0.199; p = 0.035). Preoperative PaO2 was lower, \u394PaCO2 was smaller, and \u394PaO2 was greater in the high leptin group than in the low leptin group. In multiple regression analysis, leptin was negatively associated with preoperative PaO2 (estimate coefficient = -0.147; p = 0.023). In logistic regression analysis, leptin was associated with improved \u394PaO2 (odds ratio [OR] = 1.104; p = 0.0138) and \u394PaCO2 (OR = 0.968; p = 0.0334). Leptin appears to have dual effects related to perioperative gas exchange in obese patients undergoing bariatric surgery. It is associated with worse preoperative oxygenation but improved respiratory function after surgery

Effects of increased space allowance on animal welfare, meat and ham quality of heavy pigs slaughtered at 160Kg

Sixty barrows (Body Weight-BW- range: 23.9-160 kg) were allotted to two experimental groups (6 pens of 5 pigs each): the control group was kept at a space allowance of 1m2/head; the second group was kept at 1.3m2/head. Behaviour, growth parameters, carcass and meat quality were assessed, as well as fat and cured ham quality. Results showed that pigs raised at 1.3m2/head spent more time laying (particularly in lateral recumbency, P&lt;0.01 and P&lt;0.001, respectively) compared to pigs kept at lower space allowance. They also reduced the aimless exploration of the slatted pen floor (P&lt;0.001) and increased overall expression of other, mainly active, behaviors (e.g., drinking, walking and standing, P&lt;0.01). Pigs raised at 1.3m2/head showed higher final BW (P = 0.02), more favourable Average Daily Gain (ADG) and gain-to-Feed ratio (G:F) both during the last period of the trial (P&lt;0.05 for both parameters) and over the entire trial (P = 0.01 for both parameters). No significant difference was observed between groups for carcass traits and the main meat quality attributes. Subcutaneous fat from green hams had higher \u3b1-linolenic acid content (P&lt;0.01) in the group reared at greater space allowance. Green hams from this group lost less weight at trimming (P&lt;0.01) and the resulting cured hams received better sensory evaluations (P&lt;0.05). No difference was observed in fatty acid composition and unsaturation levels of the subcutaneous fat from cured hams. Our data suggest that heavy pigs intended for Parma ham would benefit from the adoption of higher individual floor space allowances, both in terms of animal welfare (increased possibility to rest) and of productive parameters, without having any detrimental effect on the suitability of the thighs for dry-curing or on the quality of the final product

Spray-drying as a method for microparticulate controlled release systems preparation: advantages and limits. I. Water soluble drugs

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Microencapsulation of semisolid ketoprofen/polymer microspheres

Ketoprofen controlled release microspheres were prepared, by emulsion/solvent evaporation, at 15 degreesC, in order to avoid the formation of semisolid particles. An identical procedure was carried out at 60 degreesC to speed up the solvent evaporation and the formed semisolid microspheres were directly microencapsulated by complex coacervation and spray-dried in order to recover them as free flowing powder. Microspheres and microcapsules were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray diffractometry, in vitro dissolution studies, and then used for the preparation of tablets. During this step, the compressibility of the prepared powders was measured. Microspheres and microcapsules showed compaction abilities by far better than those of the corresponding physical mixtures. In fact, it was impossible to obtain tablets by direct compressing drug and polymer physical mixtures, but microspheres and microcapsules were easily transformed into tablets. Finally, in vitro dissolution studies were performed and the release control of the tablets was pointed out. Microspheres were able to control ketoprofen release only after their transformation into tablets. Tablets containing eudragit RS were the most effective in slowing down drug release

Update on animal welfare perception by Italian consumers: A descriptive survey

The aim of this study was to evaluate if and how the perception of animal welfare by Italian consumers and their purchasing behavior of animal-friendly foods have evolved in recent years. The research was carried out through a survey on a representative sample of Italian consumers (n=969). Responses showed that 69% of consumers declared to pay attention to animal welfare at time of purchasing, and they mostly acquired information about animal welfare through the mass media. In accordance with previous surveys, the categories perceived as having the highest welfare level were fish and dairy cows, whereas the lowest welfare level was attributed to broilers and pigs. Compared to previous surveys, Italian consumers seem to have improved their knowledge about the legislation on animal protection and increased their interest toward animal welfare issues. However, they still find it difficult to identifyThe aim of this study was to evaluate if and how the perception of animal welfare by Italian consumers and their purchasing behavior of animal-friendly foods have evolved in recent years. The research was carried out through a survey on a representative sample of Italian consumers (n=969). Responses showed that 69% of consumers declared to pay attention to animal welfare at time of purchasing, and they mostly acquired information about animal welfare through the mass media. In accordance with previous surveys, the categories perceived as having the highest welfare level were fish and dairy cows, whereas the lowest welfare level was attributed to broilers and pigs. Compared to previous surveys, Italian consumers seem to have improved their knowledge about the legislation on animal protection and increased their interest toward animal welfare issues. However, they still find it difficult to identify animal-friendly labels, together with a lack of knowledge about non-conventional (e.g. extensive and organic) farming systems, together with a lack of knowledge about non-conventional (e.g. extensive and organic) farming system

Mapping human disease-associated enzymes into Reactome allows characterization of disease groups and their interactions

According to databases such as OMIM, Humsavar, Clinvar and Monarch, 1494 human enzymes are presently associated to 2539 genetic diseases, 75% of which are rare (with an Orphanet code). The Mondo ontology initiative allows a standardization of the disease name into specific codes, making it possible a computational association between genes, variants, diseases, and their effects on biological processes. Here, we tackle the problem of which biological processes enzymes can affect when the protein variant is disease-associated. We adopt Reactome to describe human biological processes, and by mapping disease-associated enzymes in the Reactome pathways, we establish a Reactome-disease association. This allows a novel categorization of human monogenic and polygenic diseases based on Reactome pathways and reactions. Our analysis aims at dissecting the complexity of the human genetic disease universe, highlighting all the possible links within diseases and Reactome pathways. The novel mapping helps understanding the biochemical/molecular biology of the disease and allows a direct glimpse on the present knowledge of other molecules involved. This is useful for a complete overview of the disease molecular mechanism/s and for planning future investigations. Data are collected in DAR, a database that is free for search and available at https://dar.biocomp.unibo.it

3D-printing of porous structures for reproduction of a femoral bone

Background: 3D-printing has shown potential in several medical advances because of its ability to create patient-specific surgical models and instruments. In fact, this technology makes it possible to acquire and study physical models that accurately reproduce patient-specific anatomy. The challenge is to apply 3D-printing to reproduce the porous structure of a bone tissue, consisting of compact bone, spongy bone and bone marrow. Methods: An interesting approach is presented here for reproducing the structure of a bone tissue of a femur by 3D-printing porous structure. Through the process of CT segmentation, the distribution of bone density was analysed. In 3D-printing, the bone density was compared with the density of infill. Results: The zone of compact bone, the zone of spongy bone and the zone of bone marrow can be recognized in the 3D printed model by a porous density additive manufacturing method. Conclusions: The application of 3D-printing to reproduce a porous structure, such as that of a bone, makes it possible to obtain physical anatomical models that likely represent the internal structure of a bone tissue. This process is low cost and easily reproduced

Design and Synthesis of 4-Alkylidene-b-lactams: Benzyland Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity

The emergence of multidrug-resistant bacterial strains is particularly important in chronic pathologies such as cystic fibrosis (CF), in which persistent colonization and selection of resistant strains is favored by the frequent and repeated use of antibacterial agents. Staphylococcus aureus is a common pathogen in CF patients that has an associated increased multidrug resistance. In previous studies we demonstrated that the presence of a 4-alkylidene side chain directly linked to a beta-lactam appeared to strengthen the potency against S. aureus, especially against methicillin-resistant S. aureus (MRSA) strains. In the present study, 21 new 4-alkylidene-beta-lactams were synthesized and evaluated for antibacterial activity. We designed the new compounds to have aryl, benzyl, or phenethyl-carbamate groups on the C3 hydroxyethyl side chain. We found a correlation between biological activity and the nitrogen substituent of the carbamate group, and two phenethyl-carbamate b-lactams were shown to be valuable antibacterial agents against selected linezolid-resistant strains, with a minimum inhibitory concentrations of 2–4 mgL-1

A highly pathogenic porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) strongly modulates cellular innate and adaptive immune subsets upon experimental infection

Highly pathogenic (HP) PRRSV isolates have been discovered within both PRRSV-1 and PRRSV-2 genotypes and investigated in recent years especially for their ability to cause extremely severe disease in conventional pig herds. The exacerbation of general and respiratory clinical signs has been attributed not only to an efficient replication (virulence) but also to the ability to dysregulate viral recognition and induce mechanisms of immune evasion or immune enhancement of humoral and cellular anti-viral responses differently from non-HP PRRSV isolates in terms of intensity and temporal onset. Thus, the understanding of the immunopathogenesis of HP PRRSV is a major concern for the study of virus biology and development of efficacious vaccines. The present study aims at addressing the modulation of relevant immune cell subsets by flow cytometry in the blood of 4- week-old pigs experimentally infected with the recently discovered PR40/2014 HP PRRSV-1.1 strain phenotypically characterized in Canelli et al. (2017) compared to pigs infected with a non-HP PRRSV isolate (PR11/ 2014) and uninfected controls. PR40 infected animals showed an early and marked reduction of pro-inflammatory CD172α+ CD14+CD16+ and CD14+CD163+ monocytes and TCRγδ+CD8α+/CD8α- lymphocytes when pigs were most infected, possibly due to a recruitment sustaining an acute inflammatory response in target tissues. The prolonged increased CD3+CD16+ NKT cell levels may sustain peripheral inflammation and/ or the anti-viral response. The late reduction (potential depletion) of γ/δ T lymphocytes and CD3+CD4+CD8α- naïve Th lymphocytes paralleled with the delayed increase of CD3+CD4+CD8α+ memory and CD3+CD4- CD8α/β+cytotoxic T lymphocytes. In addition, PR40 infection showed an early depletion of activated CD4+CD25+ T lymphocytes and Tregs together with an intense and lasting depletion of CD21+ B lymphocytes. Overall, these features demonstrate that the more severe clinical signs observed upon infection with the HP PR40 strain are sustained by remarkable changes in the peripheral blood distribution of immune cells and provide further insights into the immune regulation/immunopathogenesis induced by PRRSV-1 subtype 1 European isolates