Linkers as Game-changers in PROTAC Technology: Emphasizing General Trends in PROTAC Pharmacokinetics for their Rational Design.

Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional molecules that act as degraders. They selectively remove disease-associated proteins by hijacking the Ubiquitin-Proteasome System (UPS). Chemically, they consist of three parts: an E3 ligase ligand, a target of interest (TOI) ligand, and a linker, which connects the two moieties.

Assessing the Rheological Properties of Durum Wheat Semolina: A Review.

Empiric rheology is considered a useful tool for assessing the technological quality of wheat. Over the decades, several tests have been adapted from common to durum wheat, and new approaches have been proposed to meet the needs of the players of the durum wheat value chain. Breeders are looking for reliable methods to test the functional quality of wheat lines at early stages, where there are limited amounts of sample; millers need fast and reliable methods for checking wheat quality right at the point of the receiving station; and pasta-makers are looking for suitable methods to predict end product quality.

Supplementation with IMC 510 Modifies Microbiota Composition and Prevents Body Weight Gain Induced by Cafeteria Diet in Rats.

Changes in functionality and composition of gut microbiota (GM) have been associated and may contribute to the development and maintenance of obesity and related diseases. The aim of our study was to investigate for the first time the impact of IMC 510 in a rat model of diet-induced obesity, specifically in the cafeteria (CAF) diet. This diet provides a strong motivation to voluntary overeat, due to the palatability and variety of selected energy-dense foods.

From Conception to Development: Investigating PROTACs Features for Improved Cell Permeability and Successful Protein Degradation.

Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional degraders that specifically eliminate targeted proteins by hijacking the ubiquitin-proteasome system (UPS). This modality has emerged as an orthogonal approach to the use of small-molecule inhibitors for knocking down classic targets and disease-related proteins classified, until now, as "undruggable." In early 2019, the first targeted protein degraders reached the clinic, drawing attention to PROTACs as one of the most appealing technology in the drug discovery landscape.

Migrants as suspects? A participatory consensus conference to promote well-being and inclusion.

One consequence of the securitarian approach against terrorism is the conflictual request both to "spot radicals" and build social cohesion in local communities. As a result, migrants' communities feel discriminated and treated as a "suspect community". The European Project PROVA addressed the prevention of violent radicalization in youth, involving professionals and representatives of local communities, and producing Guidelines in order to contrast the marginalization of suspected communities.

Light Drones for Basic In-Field Phenotyping and Precision Farming Applications: RGB Tools Based on Image Analysis.

Plant phenotyping has garnered major attention in recent years, leading to developing new strategies to measure and assess plant traits of interest. For data acquisition of large fields, devices and sensors are required that deliver detailed and reproducible temporal and spatial information on the cultivated crop. This work proposes the potential use of low-cost light drones for in-field phenotyping applications on cereal crops.

Application of near-infrared handheld spectrometers to predict semolina quality.

Background: Durum wheat semolina is the best raw material for pasta production and its protein content and gluten strength are essential for cooking quality. The need to develop rapid methods to speed up quality control makes near-infrared spectroscopy (NIR) a useful method that is widely accepted in the cereal sector. In this study, two non-destructive and rapid technologies, a low-cost sensor providing a short wavelength NIR range (swNIR: 700-1100 nm) and a handheld NIR spectrometer (NIR: 1600-2400 nm), were employed to evaluate semolina quality.

Exploring the Ubiquitin-Proteasome System (UPS) through PROTAC Technology.

In the context of dysregulated ubiquitylation, the accumulation of oncogenic substrates can lead to tumorigenesis. In particular, mutations in Von Hippel-Lindau (VHL) E3 ubiquitin ligase are related to overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α) which is evolving into renal cell carcinoma (RCC). The classical approach of drug discovery focuses on the development of highly selective small molecules able to bind and to inhibit enzymatic active sites.

Bio-Functional and Structural Properties of Pasta Enriched with a Debranning Fraction from Purple Wheat.

A colored and fiber-rich fraction from the debranning of purple wheat was incorporated at 25% into semolina- and flour-based pasta produced on a pilot-plant scale, with the aim of increasing anthocyanin and total phenolic content with respect to pasta obtained from whole pigmented grains. The debranning fraction impaired the formation of disulfide-stabilized protein networks in semolina-based systems. Recovery of phenolics was impaired by the pasta making process, and cooking decreased the phenolic content in both enriched samples.

Probiotic characterization of Lactobacillus isolates from canine faeces.

Aims: There is interest in using probiotics such as Lactobacillus species to control canine intestinal infections. The bacterial species should be of canine intestinal origin exhibiting host specificity. Bacterial strains were isolated from dog faecal samples and characterized to select specific probiotics as dietary supplements in feed, promoting health status.

Correction to: Effects of Lactogen 13, a New Probiotic Preparation, on Gut Microbiota and Endocrine Signals Controlling Growth and Appetite of Oreochromis niloticus Juveniles.

The original version of this article unfortunately contained mistakes in Authors First name/Family name order. Please refer to this paper as Gioacchini et al. and not as Giorgia et al.

Effects of Lactogen 13, a New Probiotic Preparation, on Gut Microbiota and Endocrine Signals Controlling Growth and Appetite of Oreochromis niloticus Juveniles.

In the present study, Nile tilapia Oreochromis niloticus was used as experimental model to study the molecular effects of a new probiotic preparation, Lactogen 13 (Lactobacillus rhamnosus IMC 501® encapsulated with vegetable fat matrices by spray chilling and further indicated as probiotic microgranules), on growth and appetite during larval development. Probiotic microgranules were administered for 30 days to tilapia larvae starting from first feeding. Molecular analysis using high-throughput sequencing revealed that the probiotic could populate the gastrointestinal tract and modulate the microbial communities by significantly increasing the proportion of Lactobacillus as well as reducing the proportion of potential pathogens such as members of the Family Microbacteriaceae, Legionellaceae, and Weeksellaceae.

Communicating Effectively in Pediatric Cancer Care: Translating Evidence into Practice.

Effective communication is essential to the practice of pediatric oncology. Clear and empathic delivery of diagnostic and prognostic information positively impacts the ways in which patients and families cope. Honest, compassionate discussions regarding goals of care and hopes for patients approaching end of life can provide healing when other therapies have failed.

Evaluation of the hypocholesterolemic effect and prebiotic activity of a lentil (Lens culinaris Medik) extract.

Scope: The aim of our work was to produce a hydroalcoholic extract of lentils and to examine (a) the hypocholesterolemic action in an animal model, by studying the plasma cholesterol level and the concentration of bile acids in the feces; (b) the potential prebiotic effect, by conducting an in vitro culture fermentation experiment and assessing the level of SCFAs in the feces of rats.

Methods And Results: Lentil extract (LE) was obtained by extracting lentils with a solution of H 0/EtOH (70/30 v/v) for 3 h, and the content of main nutrients was determined. After 71 days of diet-induced hypercholesterolemia in rats, LE reduced the cholesterol level of rats of 16.

Impact of Probiotic SYNBIO(®) Administered by Vaginal Suppositories in Promoting Vaginal Health of Apparently Healthy Women.

The purpose of this study was to investigate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether it promotes normalization and maintenance of pH and Nugent score. A single-arm, open-label controlled towards the baseline (pre-post) study including 35 apparently healthy women was conducted. Each woman was examined three times during the study.

Abusive use of antibiotics in poultry farming in Cameroon and the public health implications.

The types and methods of use of antibiotics in poultry farms in Cameroon, residual levels and potential microbial resistance were determined. A questionnaire-based survey identified the different antibiotics used and high-performance liquid chromatography (HPLC) was used to determine residual levels of antibiotics. Pathogens were isolated, identified by use of commercial API kits and minimum inhibition concentration (MIC) was determined.

Changes on fecal microbiota in rats exposed to permethrin during postnatal development.

Alteration of the gut microbiota through diet and environmental contaminants may disturb the mammalian digestive system, leading to various diseases. Because most exposure to environmentally pyrethroid pesticides such as permethrin (PERM) occurs through the diet, the commensal gut microbiota is likely to be exposed to PERM. The study aimed at evaluating the effect of low-dose exposure to PERM in early life on the composition of fecal microbiota in rats.

In vitro evaluation on HeLa cells of protective mechanisms of probiotic lactobacilli against Candida clinical isolates.

Aims: To characterize in vitro the ability of human Lactobacillus strains to inhibit the adhesion, to displace and to compete with clinically isolated Candida strains.

Methods And Results: Three types of assays were performed to determine the inhibitory effect of Lactobacillus plantarum 319, Lactobacillus rhamnosus IMC 501, Lactobacillus paracasei IMC 502 and a specific probiotic combination (SYNBIO) on adhesion of Candida pathogens to HeLa cells: blockage by exclusion (lactobacilli and HeLa followed by pathogens), competition (lactobacilli, HeLa and pathogens together) and displacement (pathogens and HeLa followed by the addition of lactobacilli). Bacterial adhesion to HeLa was quantified by microscopy after May-Grünwald/Giemsa stain.

Exercise and Epstein's TARGET for treatment of depressive symptoms: A randomized study.

This study was designed with a dual goal: (1) to compare the change in the scores of depressive symptoms by means of the implementation of three intervention programs in comparison to a control group: a) based on Epstein's TARGET (ET), b) without TARGET strategies (NET), and c) under conditions of active exercise (AE); and (2) to analyze whether the Self-determination Index (SDI) predicts the reduction of depressive symptoms. The participants ( = 106; 68 females and 38 males), aged between 18-30 years, were randomly assigned to one of the groups. Each treatment lasted 8 weeks (3 hours/week).

Fructan biosynthesis and degradation as part of plant metabolism controlling sugar fluxes during durum wheat kernel maturation.

Wheat kernels contain fructans, fructose based oligosaccharides with prebiotic properties, in levels between 2 and 35 weight % depending on the developmental stage of the kernel. To improve knowledge on the metabolic pathways leading to fructan storage and degradation, carbohydrate fluxes occurring during durum wheat kernel development were analyzed. Kernels were collected at various developmental stages and quali-quantitative analysis of carbohydrates (mono- and di-saccharides, fructans, starch) was performed, alongside analysis of the activities and gene expression of the enzymes involved in their biosynthesis and hydrolysis.

Probiotic-enriched foods and dietary supplement containing SYNBIO positively affects bowel habits in healthy adults: an assessment using standard statistical analysis and Support Vector Machines.

A randomised, double-blind, placebo-controlled, parallel group study assessed in healthy adults how daily consumption of the probiotic combination SYNBIO®, administered in probiotic-enriched foods or in a dietary supplement, affected bowel habits. Primary and secondary outcomes gave the overall assessment of bowel well-being, while a Psychological General Well-Being Index compiled by participants estimated the health-related quality of life as well as the gastrointestinal tolerance determined with the Gastrointestinal Symptom Rating Scale. Support Vector Machine models for classification problems were used to validate the total outcomes on bowel well-being.

Description of Taphrina antarctica f.a. sp. nov., a new anamorphic ascomycetous yeast species associated with Antarctic endolithic microbial communities and transfer of four Lalaria species in the genus Taphrina.

In the framework of a large-scale rock sampling in Continental Antarctica, a number of yeasts have been isolated. Two strains that are unable to grow above 20 °C and that have low ITS sequence similarities with available data in the public domain were found. The D1/D2 LSU molecular phylogeny placed them in an isolated position in the genus Taphrina, supporting their affiliation to a not yet described species.