Proximity labeling identifies a repertoire of site-specific R-loop modulators

R-loops are three-stranded nucleic acid structures that accumulate on chromatin in neurological diseases and cancers and contribute to genome instability. Using a proximity-dependent labeling system, we identified distinct classes of proteins that regulate R-loops in vivo through different mechanisms. We show that ATRX suppresses R-loops by interacting with RNAs and preventing R-loop formation. Our proteomics screen also discovered an unexpected enrichment for proteins containing zinc fingers and homeodomains. One of the most consistently enriched proteins was activity-dependent neuroprotective protein (ADNP), which is frequently mutated in ASD and causal in ADNP syndrome. We find that ADNP resolves R-loops in vitro and that it is necessary to suppress R-loops in vivo at its genomic targets. Furthermore, deletion of the ADNP homeodomain severely diminishes R-loop resolution activity in vitro, results in R-loop accumulation at ADNP targets, and compromises neuronal differentiation. Notably, patient-derived human induced pluripotent stem cells that contain an ADNP syndrome-causing mutation exhibit R-loop and CTCF accumulation at ADNP targets. Our findings point to a specific role for ADNP-mediated R-loop resolution in physiological and pathological neuronal function and, more broadly, to a role for zinc finger and homeodomain proteins in R-loop regulation, with important implications for developmental disorders and cancers.

Front-of-pack nutrition labels: perceptions and preferences of Brazilian adult consumers

PurposeThis study aimed to examine the perceptions and preferences of Brazilian adult consumers about four different front-of-pack (FOP) food labeling systems proposed by the Brazilian National Health Regulatory Agency.Design/methodology/approachThis is a qualitative study conducted with 33 participants allocated in six focus groups. Four different types of FOP labels were displayed on processed and packaged bread: three interpretive warning labels (black triangle, black octagon and red ellipse) and a hybrid model (nutritional traffic light). Thematic analysis was used to identify the key topics addressed by participants.FindingsThree topics were identified: label design, clarity and precision of information. The results demonstrated an influence of labels on product development and consumers' food choices. Most participants expressed a preference for black warning labels and reported the importance of statements endorsed by the Ministry of Health, which provide credibility and could influence food choices. Furthermore, participants agreed that the traffic light system provides more information but is difficult to interpret when comparing products. Warning labels were reported to have the greatest influence on purchase decisions. However, participants were concerned about how to understand the lack of warning labels on some products.Practical implicationsThe results may help and support the Brazilian Health Regulatory Agency to identify and recommend the most effective FOP labeling system to be adopted in Brazil.Originality/valueFew studies investigating adult consumers' perceptions of different FOP label formats have been conducted in the Brazilian context. Our study contributes to the small pool of evidence on the topic by demonstrating that FOP labels can be helpful for consumers when they are presented in an intuitive, interpretative and trustworthy format.

USE OF THE BMP SYSTEM FOR BLOCKING OF DANGEROUS ENERGIES DURING REALIZATION OF WORKS FROM REPAIR AND MAINTENANCE OF TECHNIQUE

Creating healthy and safe working conditions is the main task of the employer when performing high-risk work. Practice shows that the cause of accidents during the repair and maintenance of equipment are uncoordinated and erroneous actions of staff, resulting in incorrect supply of hazardous energy to the installation where people work. In order to prevent injuries at metallurgical enterprises there is a need to revise and modernize the existing approach to control the supply of hazardous energy during repairs, improve the current labeling system of access to repairs of technological equipment based on the experience of advanced world technologies. Audit). The BMP system is used to perform maintenance and repair of equipment, as well as any other cases where personnel need to enter the danger zone, and includes not only the actual process of blocking and marking, but also all other activities: documentation, organization of storage and issuance of BMP devices, training and testing of personnel knowledge According to the analysis, the current tag system at the metallurgical enterprises of Ukraine is inferior in efficiency to the BMP system, which allows you to almost completely eliminate the risks associated with the human factor in the repair and maintenance of equipment. The foreign experience of using hazardous energy blocking and labeling systems and the existing legal framework on this issue in Ukraine are analyzed. According to the results of research, the basic principles of using the BMP system at the enterprises of the metallurgical industry are established. The sequence of BMP procedure implementation is offered. The information on the basis of which the BMP map is formed is considered in detail. An important stage in the formation of this map is the assessment of industrial risks of exposure to hazardous energies in the process of repair and maintenance of equipment. The direction of further research on the implementation of the BMP system and the legalization of the BMP standard at the state level is substantiated.

Comparative Evaluation of Anti-Corrosion Coatings for NdFeB-Type Magnets with Respect to Performance and Recyclability via Hydrogen-Assisted Recycling (HPMS)

Various anti-corrosion coatings used on commercially available NdFeB-type magnets were comparatively examined for their durability and suitability for magnet reprocessing by hydrogen-assisted recycling (HPMS). Layer thickness and structure were determined by systematic microstructural analysis, and a standardized corrosion test was used to assess the durability of each layer. Chemical composition of the coatings was analyzed using SEM/EDS and ICP-OES. HPMS behavior was investigated using in situ video monitoring. The results of the presented investigations are an important contribution for the implementation of a sorting and labeling system to support and facilitate a commercially viable recycling of permanent magnets on an industrial scale.

Develop an efficient and specific AAV-based labeling system for Muller glia in mice

Cell degeneration in the retina leads to several ocular diseases and vision loss. Considerable research efforts focus on reprogramming Muller glia (MG) into functional cells to rescue vision as a promising therapeutic strategy, although whether MG can convert into functional amacrine cells, bipolar cells, retinal ganglia cells (RGCs), rods or cones in mammals remains controversial. The broad applicability of tracking MG differentiation thus presents a need for improved labeling efficiency and specificity. Here, we compared AAV-based labeling strategies with conventional lineage-tracking by crossing transgenic mouse lines. We found that reporter expression was weak and not MG-specific in mGFAP-Cre transgenic mice. Different AAV serotypes showed a range of efficiency and specificity in labeling MG, leading us to optimize a human GFAP-Cre reporter system packaged in the AAV9 serotype with the WPRE (WPRE, woodchuck hepatitis virus post-transcriptional regulatory element) removed. The hGFAP-Cre-ΔWPRE reporter could label 20-73.8% MGs, with non-specific RGC labeling rates ranging from 0-0.08% at doses of 1 × 108 to 1010 vector genomes (vg) per eye, an approximate 40-fold reduction compared with the AAV9-hGFAP-Cre-WPRE labeling system. The AAV9-hGFAP-Cre-ΔWPRE system thus represents a highly efficient and specific labeling system for Muller glia, providing a valuable tool for tracking cell fate in vivo.

Are "Clean" Cosmetic Products Really Clean? A Pilot Study on the Validity of Cosmetic Labeling

Background As a result of increased demand for environmental and health-conscious cosmetics, retailers have increasingly marketed their products using terms such as “clean” or "non-toxic". Sephora, a popular beauty retailer, implemented a clean seal system to label and promote their products. This study aims to compare the toxicity concerns of clean vs. non-clean products by using the Environmental Working Group (EWG)'s Skin Deep framework. MethodsEWG’s Skin Deep Framework was used to rank products based on their cancer, allergy and immunotoxicity, developmental and reproductive toxicity, and use-restriction concerns, with lower scores indicating a cleaner product (ranging 0- 10). The distributions of EWG scores among clean and non-clean products were investigated and stratified by different types of products (i.e. fragrance, hair, makeup, or skincare). A multivariable linear regression model was further applied to evaluate the association between EWG scores and clean seals, adjusting by types of products, level of toxicity concerns.Results356 products were screened, including 180 (50.56%) clean products and 176 (49.44%) non-clean products. Clean products yielded a higher percentage of low hazard ingredients compared to non-clean products. EWG scores are positively correlated with the levels of toxicity concern for cancer, allergy and immunotoxicity, respectively. Clean products are also associated with a lower EWG score by 0.71 in the regression model. Fragrance products are most hazardous, with a 2.42 increase in EWG score.ConclusionsProducts under the binary “clean beauty” labeling system at Sephora may not necessarily capture the nuances of EWG’s ten-point scoring system and various dimensions of health concerns. It may be insufficient for consumers to solely rely on the presence of the clean seal when purchasing beauty products. Consulting multiple frameworks and sources to inform decision-making is crucial in addressing knowledge gaps. Further research and increased data availability from EWG’s database are necessary as well as public education on the application of Sephora’s clean seal.

Med-index: a food product labeling system to promote adherence to the mediterranean diet encouraging producers to make healthier and more sustainable food products

Consumers are increasingly demanding transparency in food labeling as they want more and better information about what they are eating and where their food comes from. Several food indexes have been developed in the last decades to promote healthy eating with the aim of reducing certain diseases such as obesity, cancer, and diabetes. The Mediterranean diet is known to be one of the healthiest dietary patterns, and it is associated with a lower incidence of mortality from all-causes, and it is also related to a lower incidence of cardiovascular diseases, type 2 diabetes, certain types of cancer, and neurodegenerative diseases; however, a comprehensive index that quantifies the Mediteraneaness of foods is still missing. The real European challenge is to identify a uniform labeling system for the whole of Europe which promotes a healthy lifestyle. This article describes the development of the Mediterranean Index (MI), which aims to accurately measure the degree of food Mediterraneaness. The MI simultaneously integrates nutritional and sustainability characteristics of foods. The MI may provide an objective basis for the use of the “Mediterraneaness” label on food products, which can ultimately promote adherence to the Mediterranean diet encouraging producers to make healthier and more sustainable food products. Growing consumer concern toward health foods for better health can be a factor useful to promote the applicability of the precision nutrition principles by means of conscious choice.

Policy Implications on Carbon Labeling Scheme Toward Carbon Neutrality in China

Carbon labeling scheme as a quantitative measure on carbon emissions of product or service, can be applied to leading low carbon consumption and production, which is also a powerful tool to achieve carbon neutral. The policy brief reviews the progress of carbon labelling scheme to provide insight into its future perspectives on carbon neutrality in China. The results show that: ① China has not officially fostered as a carbon labeling system, but there is a pilot attempt to electric appliance; ② Publics’ perception towards carbon labeling scheme is in a lower level; ③ There is a room for improvement on the existing carbon labeling scheme, to improve its transparency and comparison.

Identification of genetic diversity of Bali cattle in Bali and Nusa Penida Island with microsatellite DNA

Bali cattle is one of Indonesia’s biodiversity with some superiority. Bali cattle scattered in various region, built centered in Bali Island. Polymorphism is very important to keep a population. Microsatellite is one of easiest methods to identify genetic diversity. The aim of this research was to identify genetic polymorphism loci Bali cattle from SPS115, ETH225, and INRA37 in Bali island and Nusa Penida island with microsatellite DNA labeling system. SPS115, ETH225 and INRA37 had been analyzed from total sample of 48 Bali cattle in Bali Island and 47 in Nusa Penida Island. The results of sequent were analyzed by GenAlEx 6.41. The results of this research showed that SPS115, ETH225 and INRA37 are of higher diversity. The highest heterozygosity was found in loci ETH225 in Bali island. The highest PIC was found in loci INRA37 in Nusa Penida Island. The inbreeding rate of Bali cattle was up to 14.1%. Bali cattle in Bali island and Nusa Penida island were different.

Biological data annotation via a human-augmenting AI-based labeling system

Biology has become a prime area for the deployment of deep learning and artificial intelligence (AI), enabled largely by the massive data sets that the field can generate. Key to most AI tasks is the availability of a sufficiently large, labeled data set with which to train AI models. In the context of microscopy, it is easy to generate image data sets containing millions of cells and structures. However, it is challenging to obtain large-scale high-quality annotations for AI models. Here, we present HALS (Human-Augmenting Labeling System), a human-in-the-loop data labeling AI, which begins uninitialized and learns annotations from a human, in real-time. Using a multi-part AI composed of three deep learning models, HALS learns from just a few examples and immediately decreases the workload of the annotator, while increasing the quality of their annotations. Using a highly repetitive use-case—annotating cell types—and running experiments with seven pathologists—experts at the microscopic analysis of biological specimens—we demonstrate a manual work reduction of 90.60%, and an average data-quality boost of 4.34%, measured across four use-cases and two tissue stain types.