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Protein kinase C iota is required for various cell biological processes including epithelial tissue polarity and organ morphogenesis. To gain mechanistic insight into different roles of this kinase, it is essential to identify specific substrate proteins i

The retention of superparamagnetic nanoparticles under the influence of a high-gradient magnetic field was investigated. A simulation algorithm for prediction of the particle's trajectories and, therefore, the total amount of adhered particles in an artificial vessel was developed. Comparisons between in vitro experiments and simulations showed that the required experimental magnetic moments were greater than the theoretically estimated magnetic moments. This paper presents a method for investigating magnetic fields and for determining the magnetic moment of particles by simulation of their trajectories. The detailed function of magnetic drug targeting is of great importance in animal studies and in human therapies [ABSTRACT FROM PUBLISHER]

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of mixtures of 1,9-nonanediamine (NMDA) and 2-methyl-1,8-octanediamine (MODA) when used to produce polyamide food contact materials for contact with all food types for long-term storage at room temperature and below, including heating up to 121°C for up to 2 h. The polyamide material is also intended to be used for repeated use up to 121°C with short contact (up to 30 min). The polymer typically contains ■■■■■ of a low molecular weight fraction (LMWF, < 1000 Da). The specific migration was measured with polyamide samples in a set of migration tests with 3% acetic acid and 10% ethanol. NMDA and MODA were not detected at ■■■■■, respectively. The specific migration of the LMWF consisting of NMDA/MODA-related species was up to ■■■■■. The overall migration in olive oil was below the detection limit (3 mg/dm 2 ). The most abundant migrating LMWF oligomers were identified. Toxicological studies were performed with NMDA, MODA and with polyamide formulations enriched in the LMWF. The results of genotoxicity assays did not raise a concern. From a repeated-dose oral 90-day toxicity study in rats, the Panel identified a no observed adverse effect level (NOAEL) of 1000 mg/kg body weight per day for the migrating LMWF. The CEP Panel concluded that NMDA/MODA mixtures do not raise a safety concern for the consumer when used as comonomer with terephthalic acid to manufacture polyamide articles intended for contact with all food types, except for infant formula and human milk, if the migration of NMDA and MODA does not exceed 0.05 mg/kg food (as a sum of the two substances) and if the migration of the LMWF consisting of NMDA/MODA-related species does not exceed 5 mg/kg food., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Despite the importance of pollinators to ecosystem functioning and human food production, comprehensive pollinator monitoring data are still lacking across most regions of the world. Policy-makers have recently prioritised the development of large-scale monitoring programmes for pollinators to better understand how populations respond to land use, environmental change and restoration measures in the long term. Designing such a monitoring programme is challenging, partly because it requires both ecological knowledge and advanced knowledge in sampling design. This study aims to develop a conceptual framework to facilitate the spatial sampling design of large-scale surveillance monitoring. The system is designed to detect changes in pollinator species abundances and richness, focusing on temperate agroecosystems. The sampling design needs to be scientifically robust to address questions of agri-environmental policy at the scales of interest. To this end, we followed a six-step procedure as follows: (1) defining the spatial sampling units, (2) defining and delimiting the monitoring area, (3) deciding on the general sampling strategy, (4) determining the sample size, (5) specifying the sampling units per sampling interval, and (6) specifying the pollinator survey plots within each sampling unit. As a case study, we apply this framework to the "Wild bee monitoring in agricultural landscapes of Germany" programme. We suggest this six-step procedure as a conceptual guideline for the spatial sampling design of future large-scale pollinator monitoring initiatives., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background: This study aims to explore the association between exposure to neighborhood violence and the presence of common mental disorders (CMDs) among Brazilian adolescents aged 12 to 17 years. Additionally, we aim to analyze whether sex, age and race are modifiers of the effect of this association., Methods: The study comprised 1,686 adolescents residing in the municipality of Rio de Janeiro, situated in the Southeast region of Brazil. To measure exposure to community violence, we constructed three crime indicators using data from Civil Police of the State of Rio de Janeiro: crimes against property, nonlethal crimes, and lethal crimes. Employing geospatial analysis based on the adolescents' residence location, logistic regression modeling was performed to measure the association between violence and CMDs., Results: Adolescents living in regions with higher rates of the three types of violence studied herein were more likely to have CMDs, with odds ratios (ORs) ranging from 2.33 to 2.99. When stratified by sex, age and race, girls, older adolescents and blacks have a greater magnitude of effect on the measure of association, indicating a heightened risk for CMDs., Conclusion: This study provides important contributions to the public health field, as it reveals new information on the influence of community violence on the mental health of adolescents. Given the elevated rates of violence globally, knowing the effects of such violence on adolescents becomes crucial for the prevention and treatment of CMDs within this population., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of poly(2-hydroxypropanoic acid), n-octyl/n-decyl esters (OLA8), which is intended to be used as a plasticiser into polylactic acid (PLA) in contact with non-fatty foods. OLA8 is intended to be used at up to 5% and 15% w/w with or without starch, respectively (or with other additives with similar function). The migration for 10 days at 40°C from the film without starch was 0.16 mg/kg in 10% ethanol and 0.01 mg/kg in 3% acetic acid, while from the film with the starch it was well above 0.05 mg/kg food in all simulants. Some of the testing conditions were inconsistently reported. The substance did not induce gene mutations in bacterial cells and did not induce structural chromosomal aberrations or polyploidy in mammalian cells, thus, does not raise concern for genotoxicity. Instead of providing a 90-day oral toxicity study, a hydrolysis study in ■■■■■ was submitted to read-across from the authorised starting substances, ■■■■■ and the ■■■■■. However, the data provided did not allow to perform the read-across, thus no appropriate toxicological data were provided to support migration above 0.05 mg/kg food (including for contact with 10% ethanol and use in combination with starch). The Panel concluded that OLA8 does not raise a safety concern for the consumer if it is used as an additive at up to 15% w/w in the manufacture of PLA articles that do not contain starch (and other additives with similar function), that are intended to be in contact for 10 days at 40°C with foods simulated by 3% acetic acid and from which the migration does not exceed 0.05 mg/kg food., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) assessed the safety of the 'waxes, paraffinic, refined, derived from petroleum-based or synthetic hydrocarbon feedstock, low viscosity' (FCM No. 93), for which the uses were requested to be extended for articles in contact with fatty foods. Migration from low-density polyethylene samples containing 1% w/w of a representative wax was tested in food simulants. In fatty food simulants, the migration of mineral oil saturated hydrocarbons (MOSH) ≤ C35 was 142 mg/kg food, exceeding the overall migration limit for plastic FCM. Mineral oil aromatic hydrocarbons (MOAH) with at least two rings are largely removed during the manufacturing process. Based on various lines of evidence, the Panel concluded that any concern for the potential presence of MOAH with two or more conjugated aromatic rings can be ruled out. Based on the genotoxicity studies and on the content of polycyclic aromatic hydrocarbons (PAHs), the substance does not raise a concern for genotoxicity. Available toxicokinetic data showed a limited accumulation of MOSH. No adverse effects were observed up to the highest tested dose of 9 g/kg body weight per day in a 90-day repeated oral toxicity study in Sprague-Dawley rats. The available results showed that FCM No. 93 is devoid of endocrine activity. The provided information on chronic toxicity and carcinogenicity was limited and inadequate to reach conclusions on these endpoints. Therefore, the CEP Panel concluded that under the intended and tested conditions of uses, the substance does not raise safety concern for the consumer if used to a level ensuring that its migration into food is no more than 5 mg/kg., (© 2023 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

Structural Biology has moved beyond the aim of simply identifying the components of a cellular subsystem towards analysing the dynamics and interactions of multiple players within a cell. This focal shift comes with additional requirements for the analytical tools used to investigate these systems of increased size and complexity, such as Native Mass Spectrometry, which has always been an important tool for structural biology. Scientific advance and recent developments, such as new ways to mimic a cell membrane for a membrane protein, have caused established methods to struggle to keep up with the increased demands. In this review, we summarize the possibilities, which Laser Induced Liquid Bead Ion Desorption (LILBID) mass spectrometry offers with regard to the challenges of modern structural biology, like increasingly complex sample composition, novel membrane mimics and advanced structural analysis, including next neighbor relations and the dynamics of complex formation., (© 2022 The Author(s).)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the combined use of cyclooctene homopolymer (PCOE) and cobalt stearate (CoS) intended as a oxygen scavenger in the packaging of all kinds of food stored at room temperature or below for up to 6 months. The CoS is the oxidation catalyst and the PCOE is intentionally oxidised for the oxygen scavenging function. They are incorporated into a plastic layer that is intended to be either in direct or indirect contact with the food. The potential migration of cobalt and cyclooctene monomer were below their respective specific migration limit (SML). The potential migration of PCOE non-oxidised oligomeric low molecular weight fraction (LMWF) < 1,000 Da was estimated to be up to ■■■■■ The Panel concluded that this fraction does not raise concern for genotoxicity potential and that the no observed adverse effect level (NOAEL) derived from a subchronic toxicity study would ensure a margin of exposure large enough to not raise a safety concern. However, the Panel considered the analysis of the oxidised PCOE LMWF not sufficiently comprehensive, i.e. that additional oxidation products of different nature may be formed, and that the limit of detection corresponding to ca. ■■■■■ for individual substances is too high. The oxidised PCOE LMWF was not covered by the genotoxicity tests or the 90-day study on the PCOE oligomers. The assessment of the identified potential oxidised migrants was considered conclusive, but not that of the migrants having remained undetected. Therefore, the CEP Panel was not able to conclude on the safety of the proposed use of cyclooctene homopolymer and cobalt stearate together as active substances in a layer for scavenging oxygen, either in direct contact with the food or separated from the food by a passive layer of polymer., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

The recently identified proteobacterial antimicrobial compound efflux (PACE) transporters are multidrug transporters energized by the electrochemical gradient of protons. Here, we present the results of phylogenetic and functional studies on the PACE family transporter PA2880 from Pseudomonas aeruginosa. A phylogenetic analysis of the PACE family revealed that PA2880 and AceI from Acinetobacter baumannii are classified into evolutionarily distinct clades, although they both transport chlorhexidine. We demonstrate that PA2880 mainly exists as a dimer in solution, which is independent of pH, and its dimeric state is essential for its proper function. Electrogenicity studies revealed that the chlorhexidine/H + antiport process is electrogenic. The function of several highly conserved residues was investigated. These findings provide further insights into the functional features of PACE family transporters, facilitating studies on their transport mechanisms. IMPORTANCE Pseudomonas aeruginosa is a pathogen that causes hospital-acquired (nosocomial) infections, such as ventilator-associated pneumonia and sepsis syndromes. Chlorhexidine diacetate is a disinfectant used for bacterial control in various environments potentially harboring P. aeruginosa. Therefore, investigation of the mechanism of the efflux of chlorhexidine mediated by PA2880, a PACE family transporter from P. aeruginosa, is of significance to combat bacterial infections. This study improves our understanding of the transport mechanism of PACE family transporters and will facilitate the effective utilization of chlorhexidine for P. aeruginosa control.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids assessed the safety of the substance bleached cellulose pulp, consisting of cellulose fibres (70-92%) and hemicellulose (8-30%) obtained from pine and spruce wood. The substance is intended to be used ■■■■■ in polyethylene and polypropylene food contact materials. The final articles are intended to be used for all food types and for long-term storage at room temperature, with or without a short time at higher temperature, including hot-fill. Low-density polyethylene samples containing ■■■■■ of the substance were subjected to a broad set of migration tests with food simulants and extraction tests with dichloromethane. The limits of detection ranged from ■■■■■ (when specified). The Panel noted that they do not ensure the detection of genotoxic substances at a concentration leading to a human exposure above the Threshold of Toxicological Concern. Moreover, not all possibly migrating substances were identified or amenable to the analytical methods applied. No toxicological data were provided for the substance itself, as its migration into food is not expected. The safety of the potentially migrating substances of low molecular mass detected was addressed individually and was considered adequate. However, the Panel considered this approach insufficient owing to a substantial fraction of unidentified components. The Panel concluded that the information provided by the applicant does not allow the safety assessment of the substances below 1,000 Da from bleached cellulose pulp from pine and spruce wood used in plastic food contact materials potentially migrating into food. Therefore, the Panel could not conclude on the safety of the use of bleached cellulose pulp from pine and spruce wood as a plastic additive., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the substance diethyl[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl] phosphonate, FCM substance No. 1007, which is intended to be used in the polymerisation reaction to make poly(ethylene 2,5-furandicarboxylate) (PEF) plastic. The substance is intended to become a component of the backbone of the polymer and has an antioxidant function that provides thermal stability to the polyester during heat processing. The resulting plastic is intended to be used in contact with all types of food under any condition of time and temperature. A PEF sample made using 0.1% w/w of the substance (which is the maximum intended use) was used in a comprehensive set of migration tests with food simulants. The migration of the substance was below the quantification limits estimated around 10 µg/kg. Solvent extraction tests showed no presence of impurities or breakdown products of the substance. The toxicological data provided are the same as those submitted by the same applicant and previously evaluated. The resulting assessment and conclusions are considered still valid by the CEP Panel. Therefore, the CEP Panel concluded that the substance diethyl[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate does not raise a safety concern for the consumer if used at up to 0.1% w/w (based on the weight of the polymer) in the polymerisation to make PEF intended for contact with all types of foods under any contact conditions., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the substance 'nano precipitated calcium carbonate', FCM substance No. 1087, the particles size of which is in the range of ■■■■■, with a median of ■■■■■. The substance is intended to be used as a filler in all plastics at up to 5% w/w for contact with acidic food and at up to 40% w/w for contact with all other types of food. Articles made with the substance are intended for long-term storage at room temperature or below. The particulate form of the calcium carbonate dissolved rapidly under simulated gastric conditions and, therefore, in accordance with the EFSA Guidance on Particle - Technical Requirements (2021), an assessment of the particles in nanoform is not required and a conventional risk assessment is sufficient. Calcium carbonate, not in nanoform, is authorised for use in plastic FCM without specific migration limit (FCM No. 21) and for use as a food additive (E 170). Migration, from low-density polyethylene (LDPE) containing 40% of the substance, was below 0.03 mg/kg in isooctane and 95% ethanol, and 5.4 mg/kg in 10% ethanol. For LDPE containing 5% of the substance, corresponding to the maximum intended amount for contact with acidic foods, the migration was 17 mg/kg. Therefore, the CEP Panel concluded that the substance nano precipitated calcium carbonate is not of safety concern for consumers when used as a filler in all types of polymer for all types of food, except for infant food formulae. The Panel noted, however, that for acidic foods, the overall migration limit may be exceeded., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the substance identified by the applicant as 'fatty acid-coated nano precipitated calcium carbonate'. It is intended to be used as a filler in all plastics at up to 5% for contact with acidic food and at up to 40% for contact with all other types of food. Articles made with the substance are intended for long-term storage over 6 months at room temperature and below. No information was provided on the mechanism of coating as to whether there is chemical modification of the surface and/or physical adsorption. The substance was not properly characterised, either as pristine material or when incorporated into plastic. Contrary to the non-coated material, data show that the coated material does not dissolve fully and quickly under pH conditions simulating gastrointestinal tract. Surface analysis with electron microscopy of low-density polyethylene (LDPE) samples before and after migration experiments showed major differences that indicate release of the substance from the surface after the tests with 3% acetic acid and to a lesser extent with 10% ethanol. This is consistent with measurable migrations that were up to 39 mg CaCO 3 /kg when using an LDPE sample made with 5% of the substance in contact with acetic acid for 64 days at 40°C. The required data on the release of nanoparticles and on the potential toxicity of the substance in nanoform were not provided. Therefore, the Panel could not conclude on the safe use of the substance., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of chopped carbon fibres, from carbonised polyacrylonitrile, as food contact material (FCM) substance No 1086, which is intended to be used as a filler for polyether ether ketone (PEEK) polymer at up to 40% w/w. The plastic is intended for repeated use in contact with all types of foods under all conditions of use. The chopped carbon fibres have a length of ■■■■■ and a diameter of ■■■■■, with no fragments lower than ■■■■■ in any dimension. They do not include a fraction of particles at the nanoscale and are fully embedded in the PEEK matrix, and therefore the fibres and any fragments are not expected to migrate. Based on the results of a battery of three genotoxicity tests, the Panel concluded that the substance does not raise a concern for genotoxicity. Therefore, the CEP Panel concluded that the substance chopped carbon fibres, from carbonised polyacrylonitrile, with a minimum carbon content of 95% (at sizes not at the nanoscale) does not raise a safety concern for the consumer if the substance is used as a filler at up to 40% w/w for PEEK plastic in contact with all food types and under all conditions of use., (© 2022 Wiley‐VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the additive silver nanoparticles intended to be used in plastics. All the silver particles are in the size range of 1-100 nm, with about 15 nm mean diameter and 99% by number of particles below 20 nm. The additive is intended to be used as a surface biocide at up to 0.025% w/w in non-polar plastics for contact with a wide variety of foods, times, temperatures and food contact surface/mass of food ratios. The particulate form is maintained when the additive is incorporated into plastics, albeit with some aggregation/agglomeration observed. The data and information on theoretical considerations, on specific migration and abrasion tests show that, under the intended and tested conditions of uses, the silver nanoparticles stay embedded in the polymer, do not migrate and resist release by abrasion, thus, do not give rise to exposure via food and to toxicological concern. There is migration of silver in soluble ionic form up to 6 μg/kg food from the surface of the additive particles. This is below the group restriction of 50 μg silver/kg food proposed by the AFC Panel in 2004 and would lead to a maximum exposure from FCM that would be below the acceptable daily intake (ADI) of 0.9 μg silver ions/kg body weight (bw) per day established by ECHA. Therefore, the Panel concluded that the substance does not raise safety concern for the consumer if used as an additive at up to 0.025% w/w in polymers, such as polyolefins, polyesters and styrenics, that do not swell in contact with aqueous foods and food simulants. The Panel noted, however, that exposure to silver from other sources of dietary exposure may exceed the ADI set by ECHA., (© 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) assessed the safety of the substance 'phosphorous acid, triphenyl ester, polymer with alpha-hydro-omega-hydroxypoly[oxy(methyl-1,2-ethanediyl)], C10-16 alkyl esters' obtained by reaction of ■■■■■ This food contact material (FCM) substance No 1076 was evaluated by the CEP Panel in 2019 for its use in high impact polystyrene. This opinion deals with the safety assessment of the substance when used as an additive at up to 0.025% w/w in acrylonitrile-butadiene-styrene (ABS) copolymers. The plastic is intended for repeated use in contact with aqueous, acidic, alcoholic and oil-in-water emulsion foods, for long-term storage at room temperature and below. Migration from ABS formulated with the substance at 0.02% w/w was up to 0.002 mg/kg in 10% ethanol, 0.005 mg/kg in 3% acetic acid and 0.027 mg/kg in 50% ethanol. Migration levels into 50% ethanol declined under repeated-use test conditions and this decline was considered to also cover repeated contacts with 10% ethanol and 3% acetic acid simulants. The toxicological data are the same as those submitted by the same applicant in a previous dossier (EFSA-Q-2018-00411). They were reported in the scientific opinion of the CEP Panel in 2019 and the conclusions on toxicity are still valid. Overall, the CEP Panel concluded that the substance phosphorous acid, triphenyl esters, polymer with alpha-hydro-omega-hydroxypoly[oxy(methyl-1,2-ethanediyl)], C10-16 alkyl esters, does not raise a safety concern for the consumer if it is used as an additive at up to 0.025% w/w in ABS materials and articles for single and repeated use in contact with aqueous, acidic, alcoholic and oil-in-water emulsion foods, for long-term storage at room temperature and below, and if its migration does not exceed 0.05 mg/kg food., (© 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Protein kinases are important regulators in cellular signal transduction. As one major type of Hsp90 client, protein kinases rely on the ATP-dependent molecular chaperone Hsp90, which maintains their structure and supports their activation. Depending on client type, Hsp90 interacts with different cofactors. Here we report that besides the kinase-specific cofactor Cdc37 large PPIases of the Fkbp-type strongly bind to kinase•Hsp90•Cdc37 complexes. We evaluate the nucleotide regulation of these assemblies and identify prominent interaction sites in this quaternary complex. The synergistic interaction between the participating proteins and the conserved nature of the interaction suggests functions of the large PPIases Fkbp51/Fkbp52 and their nematode homolog FKB-6 as contributing factors to the kinase cycle of the Hsp90 machinery.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) was requested by the European Commission to re-evaluate the safety of styrene (FCM No 193) for use in plastic food contact materials (FCM) following the classification by the International Agency for Research on Cancer (IARC) as 'probably carcinogenic to humans'. The IARC Monograph pertains to hazard identification, based on studies on high-dose occupational exposures by inhalation and animal studies, also mainly by inhalation. The Panel considered that the IARC conclusions cannot be directly applied to the evaluation of risks for consumers from the oral exposure to styrene, but also concluded that, based on the data provided in the IARC Monograph and by the industry, a concern for genotoxicity associated with oral exposure to styrene cannot be excluded. The migration of styrene into foods packed in styrenic plastics is below 10 μg/kg for the majority of the foods, but up to 230 μg/kg was reported. Migration tends to be high for contact with fatty foods, and/or with high surface to volume ratios of the FCM. Dietary exposure of the consumers to styrene migrating from styrenic plastics was estimated in the order of 0.1 μg/kg body weight (bw) per day. It is in the same range as exposure from styrene present in foods as such. The dietary exposure (food component plus migration from styrenic plastics) is similar or lower than that by inhalation in the general population. Taking the human exposure data into account, the Panel concluded that a systematic review of genotoxicity and mechanistic data, comparative toxicokinetics and analysis of species differences is required for assessing the safety of styrene for its use in FCM., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of benzophenone-3,3',4,4'-tetracarboxylic dianhydride (BTDA), FCM substance No 1083, as co-monomer for the production of polyimides used in repeated use materials and articles that are in contact with acidic and fatty foods at temperatures up to 250°C. Migration of BTDA from a polyimide containing 43% BTDA, ■■■■■ into olive oil was below the limit of quantification of about 3 μg/kg food, and in 3% acetic acid it decreased from 30.3 μg/kg in the first test to 22.1 μg/kg in the third test (2 h/100°C). In a semi-quantitative screening using acetonitrile and acetonitrile/water to extract the polymer powder, linear and cyclic oligomers were detected at levels below 1 mg/kg material. In thermal desorption of the polymer powder at 250°C, phenol, tentatively identified ■■■■■ were found, but the modelled migrations of these were far below a level of potential concern. ■■■■■. The substance did not induce gene mutations in bacterial and mammalian cells. In an in vitro chromosomal aberration test, the substance was found to be directly clastogenic in the absence of metabolic activation. In an in vivo follow-up, the substance did not induce the formation of micronuclei in experimental conditions associated with evidence of systemic exposure and therefore the Panel considered that the substance does not raise concern for genotoxicity. The CEP Panel concluded that the use of the substance BTDA is not of safety concern for the consumer if it is applied at up to 43% as a co-monomer in the production of polyimides for repeated use contact with acidic or fatty foods at temperatures up to 250°C. In addition, the migration of BTDA should not exceed 50 μg/kg., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) was requested by the European Commission to review the substances for which a Specific Migration Limit (SML) is not assigned in Regulation (EU) No 10/2011. These substances had been covered by the Generic SML of 60 mg/kg food, but with Regulation (EU) 2016/1416 it was removed, necessitating their re-examination. EFSA was requested to identify those substances requiring an SML to ensure the authorisation is sufficiently protective to health, grouping them in high, medium and low priority to serve as the basis for future re-evaluations of individual substances. The CEP Panel established a stepwise procedure. This took into account existing hazard assessments for each substance on carcinogenicity/mutagenicity/reprotoxicity (CMR), bioaccumulation and endocrine disruptor (ED) properties along with the use of in silico generated predictions on genotoxicity. Molecular weights and boiling points were considered with regard to their effect on potential consumer exposure. This prioritisation procedure was applied to a total of 451 substances, from which 78 substances were eliminated at the outset, as they had previously been evaluated by EFSA as food contact substances. For 89 substances, the Panel concluded that a migration limit should not be needed. These are in the lists 0 and 1 of the Scientific Committee for Food (SCF), defined as substances for which an Acceptable Daily Intake (ADI) does not need to be established, along with substances that are controlled by existing restrictions and/or generic limits. Of the remaining 284 substances, 179 were placed into the low priority group, 102 were placed into the medium priority group and 3 were placed into the high priority group, i.e. salicylic acid (FCM No 121), styrene (FCM No 193) and lauric acid, vinyl ester (FCM No 436)., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the substance phosphoric acid, mixed esters with 2-hydroxyethyl methacrylate, FCM substance No 1082, which is intended to be used at up to ■■■■■% w/w ■■■■■ for the production of kitchen countertops and sinks. These composite articles are intended for repeated contact with all food types. The contact time is not expected to exceed several hours at room temperature or a short time at high temperature (1 h at 70°C). The substance is thermally stable under the manufacturing conditions. Under conservative conditions of testing, the specific migration into 10% ethanol, 95% ethanol and 3% acetic acid was up to 24.8 μg/6 dm 2 . Screening tests for migrating oligomers and reaction products resulting from the use of the substance ■■■■■. Based on the negative results observed in the Ames and in vitro micronucleus tests, the Panel concluded that the substance does not raise concern for genotoxicity. The CEP Panel concluded that the substance phosphoric acid, mixed esters with 2-hydroxyethyl methacrylate, is not of safety concern for the consumer if used as a co-monomer at up to ■■■■■% to manufacture ■■■■■ food preparation surfaces, such as countertops or sinks, intended for repeated contact with all food types. Additionally, the migration of phosphoric acid, mixed esters with 2-hydroxyethyl methacrylate should not exceed 0.05 mg/kg food expressed as the sum of the mono-, di- and triesters of phosphoric acid and the mono-, di-, tri- and tetraesters of diphosphoric acid., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the substance (triethanolamine-perchlorate, sodium salt) dimer, FCM substance No 1080, intended to be used as a thermal stabiliser at up to 0.15% w/w in rigid poly(vinyl chloride) (PVC) for repeated use bottles in contact with water. No thermal degradation of the substance is expected during the manufacture of the PVC articles. In water, the substance fully dissociates into triethanolamine, sodium (cations) and perchlorate. Therefore, migration would lead to exposure to triethanolamine and perchlorate and not to the substance itself. Specific migration of perchlorate, ethanolamine, diethanolamine and triethanolamine was tested under repeated use conditions covering the requested uses. After the second and third contacts, perchlorate was detected at ca. 0.3 μg/kg food. Ethanolamine, diethanolamine and triethanolamine were not detected in any of the three contacts at an estimated limit of detection of 0.03 mg/kg food. The available in vitro studies on the substance confirmed the lack of concern for genotoxicity, as anticipated by the dissociation of the substance into authorised non-genotoxic substances. Therefore, the CEP Panel concluded that the substance is not of safety concern for the consumer if used, under the condition requested by the applicant, as an additive at up to 0.15% w/w in rigid PVC for repeated use bottles intended for contact with water. Additionally, the migration of triethanolamine and perchlorate should not exceed the specific migration limits (SMLs) of 50 μg/kg food and 2 μg/kg food, respectively, set in the Regulation (EU) 10/2011. This evaluation also covers acidic foods such as fruit juices that can reasonably be foreseen to be in contact., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Some anaerobic bacteria use biotin-dependent Na + -translocating decarboxylases (Bdc) of β-keto acids or their thioester analogs as key enzymes in their energy metabolism. Glutaconyl-CoA decarboxylase (Gcd), a member of this protein family, drives the endergonic translocation of Na + across the membrane with the exergonic decarboxylation of glutaconyl-CoA (Δ G 0 ' ≈-30 kJ/mol) to crotonyl-CoA. Here, we report on the molecular characterization of Gcd from Clostridium symbiosum based on native PAGE, size exclusion chromatography (SEC) and laser-induced liquid bead ion desorption mass spectrometry (LILBID-MS). The obtained molecular mass of ca. 400 kDa fits to the DNA sequence-derived mass of 379 kDa with a subunit composition of 4 GcdA (65 kDa), 2 GcdB (35 kDa), GcdC1 (15 kDa), GcdC2 (14 kDa), and 2 GcdD (10 kDa). Low-resolution structural information was achieved from preliminary electron microscopic (EM) measurements, which resulted in a 3D reconstruction model based on negative-stained particles. The Gcd structure is built up of a membrane-spanning base primarily composed of the GcdB dimer and a solvent-exposed head with the GcdA tetramer as major component. Both globular parts are bridged by a linker presumably built up of segments of GcdC1, GcdC2 and the 2 GcdDs. The structure of the highly mobile Gcd complex represents a template for the global architecture of the Bdc family., (Copyright © 2020 Vitt, Prinz, Hellwig, Morgner, Ermler and Buckel.)

Quinone methide precursors 2 and 3 were protected with a photoreactive 2-nitrobenzyl group and conjugated to peptide nucleic acids (PNA) using a Huisgen click reaction. After brief irradiation at 365 nm, cross-linking with complementary RNA strands started and was analyzed with an ALFexpress sequencer. When this method was used, the gel temperature had a major influence on apparent rates. Quinone methides are known to form transient as well as stable bonds with nucleotides. Although both were detected at 25 °C, analysis at 57 °C only recorded the stable types of cross-links, suggesting much slower alkylation kinetics. Linker 11 allowed us to attach quinone methides to internal positions of the PNA/RNA duplex and to capture a model of miR-20a with good efficiency.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of N,N-bis(2-hydroxyethyl)stearylamine partially esterified with saturated C16/C18 fatty acids (SABOFOG F1), FCM No 1081, which is intended to be used as an antistatic and anti-fog agent in all types of polymers at up to 2% w/w. It was requested for use in contact with dry food, acidic foods and alcoholic beverages (represented by simulants E, B and C, respectively) with storage up to 6 months at ambient temperature. The migration data provided did not enable the assessment of the safety of applications intended for contact with foods represented by simulants B and C. In the migrate into simulant E, the non-esterified N,N-bis(2-hydroxyethyl)stearylamine was the main constituent. Its mono- and di-esters migrated to a lower extent. According to the data provided, the Panel concluded that the substance does not raise concern for genotoxicity and accumulation in humans. Based on the results of 28-day oral toxicity study with SABOFOG F1 and on the 90-day oral toxicity study with the read-across substance bis(2-hydroxyethyl)oleylamine, the Panel considered the current SML(T) of 1.2 mg/kg food provided a margin sufficiently large to accommodate the uncertainties related to the read-across approach. Overall, the CEP Panel concluded that N,N-bis(2-hydroxyethyl)stearylamine, of which at least ■■■■■ is partially or fully esterified with saturated C16/C18 fatty acids is not of safety concern for the consumer when used at up to 2% (w/w) in all polymers intended for contact with foods represented by simulant E for up to 6 months at room temperature. Additionally, the migration of the sum of N,N-bis(2-hydroxyethyl)stearylamine and its mono- and di-ester, calculated as N,N-bis(2-hydroxyethyl)stearylamine, should not exceed 1.2 mg/kg, i.e. the SML(T) for FCM substances 19 and 20, in which also the migration of the mono- and di-ester of N,N-bis(2-hydroxyethyl)stearylamine should be included., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) was asked by the European Commission to review whether the authorisation of 'wood flour and fibres, untreated' (FCM No 96) is still in accordance with Regulation (EC) No 1935/2004. The additive was included in the list of additives for use in plastic food contact materials (FCM) based on the assumption of its inertness. No toxicological evaluation underlying the inclusion of this entry in the positive list is available. In a literature search, general information on the chemical composition of wood was retrieved showing that wood may contain toxic components and contaminants. The information on migration of substances from wood was found to be limited to its use in the production of wine. Data on migration of substances resulting from the use of wood (flour, fibres) as plastic additive were not available. The Panel therefore concluded that there is insufficient information to support that the current authorisation of 'wood flour and fibres, untreated' (FCM No 96) is still in accordance with Regulation (EC) No 1935/2004. As a second step, as requested by the mandate, the Panel set out criteria for future evaluations of wood and similar materials from plant origin as additives for plastic for food contact applications. The Panel noted that due to the chemical differences in composition of plant materials, the safety of migrants from these materials must be evaluated on a case-by-case basis, considering beyond species also origin, processing, treatment for compatibilisation with the host polymer and assessment of the low molecular weight constituents migrating into food. Migration of substances resulting from using wood or other plant materials should be tested comparatively in samples made with and without the additive. Toxicological data should cover the substances detected in this analysis., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

This scientific opinion of the EFSA Panel on Food Contact Materials, Enzymes and Processing aids (CEP Panel) is on the safety assessment of trimellitic acid, tris(2-ethylhexyl) ester, intended to be used as a plasticiser in the manufacture of soft poly(vinyl chloride) (PVC) materials and articles, such as wrap films (single uses) and tubing (repeated uses) at up to approximately 10% and 40%, respectively. Under the tested conditions, the substance migrated up to 165 μg/kg food from wrap films and was not detected in food simulant in contact with tubing. Based on the three reported in vitro genotoxicity studies, the Panel concluded that the substance does not raise concern for genotoxicity. The lowest no observed adverse effect level (NOAEL), derived from a 90-day oral toxicity study, was 225 mg/kg body weight (bw) per day. Based on data on toxicokinetic and metabolism, the substance does not give rise to concern for accumulation in humans. The substance does not cause developmental effects as induced by phthalic acid, bis(2-ethylhexyl) ester (DEHP). Assuming that impurities migrate pro-rata to a migration of the substance up to 5 mg/kg food, their estimated migration does not raise a safety concern. The Panel concluded that the substance does not raise safety concern for the consumer when used in the manufacture of soft PVC under the conditions requested by the applicant for (i) single use wrap films in contact with food for which simulants A, B and D1 are assigned, as well as (ii) tubing for repeated contacts with food for which simulants A and B are assigned. Overall, the use of the substance does not raise a safety concern if its migration does not exceed 5 mg/kg food. Due to the additional contribution from other sources of exposures, the application of an allocation factor should be considered., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

For a few years, mineral oils and their potential adverse health effects have been a constant issue of concern in many regulatory areas such as food, cosmetics, other consumer products, and industrial chemicals. Analytically, two fractions can be distinguished: mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH). This paper aims at assessing the bioaccumulative potential and associated histopathological effects of MOSH as well as the carcinogenic potential of MOAH for consumer-relevant mineral oils. It also covers the absorption, distribution, metabolism, and excretion of MOSH and MOAH upon oral and dermal exposures. The use and occurrence of consumer-relevant, highly refined mineral oils in food, cosmetics and medicinal products are summarized, and estimates for the exposure of consumers are provided. Also addressed are the challenges in characterizing the substance identity of mineral oil products under REACH. Evidence from more recent autopsy and biopsy studies, along with information on decreasing food contamination levels, indicates a low risk for adverse hepatic lesions that may arise from the retention of MOSH in the liver. With respect to MOAH, at present there is no indication of any carcinogenic effects in animals dermally or orally exposed to highly refined mineral oils and waxes. Such products are used not only in cosmetics but also in medicinal products and as additives in food contact materials. The safety of these mineral oil-containing products is thus indirectly documented by their prevalent and long-term use, with a simultaneous lack of clinical and epidemiological evidence for adverse health effects.

TRPML2 is the least structurally characterized mammalian transient receptor potential mucolipin ion channel. The TRPML family hallmark is a large extracytosolic/lumenal domain (ELD) between transmembrane helices S1 and S2. We present crystal structures of the tetrameric human TRPML2 ELD at pH 6.5 (2.0 Å) and 4.5 (2.95 Å), corresponding to the pH values in recycling endosomes and lysosomes. Isothermal titration calorimetry shows Ca 2+ binding to the highly acidic central pre-pore loop which is abrogated at low pH, in line with a pH-dependent channel regulation model. Small angle X-ray scattering confirms the ELD dimensions in solution. Changes in pH or Ca 2+ concentration do not affect the protein's secondary structure, but can influence ELD oligomer integrity according to native mass spectrometry. Our data thus complete the set of high-resolution views of human TRPML channel ELDs and reveal some structural responses to the conditions the TRPML2 ELD encounters as the channel traffics through the endolysosomal system., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Land cover change is a dynamic phenomenon driven by synergetic biophysical and socioeconomic effects. It involves massive transitions from natural to less natural habitats and thereby threatens ecosystems and the services they provide. To retain intact ecosystems and reduce land cover change to a minimum of natural transition processes, a dense network of protected areas has been established across Europe. However, even protected areas and in particular the zones around protected areas have been shown to undergo land cover changes. The aim of our study was to compare land cover changes in protected areas, non-protected areas, and 1 km buffer zones around protected areas and analyse their relationship to climatic and socioeconomic factors across Europe between 2000 and 2012 based on earth observation data. We investigated land cover flows describing major change processes: urbanisation, afforestation, deforestation, intensification of agriculture, extensification of agriculture, and formation of water bodies. Based on boosted regression trees, we modelled correlations between land cover flows and climatic and socioeconomic factors. The results show that land cover changes were most frequent in 1 km buffer zones around protected areas (3.0% of all buffer areas affected). Overall, land cover changes within protected areas were less frequent than outside, although they still amounted to 18,800 km2 (1.5% of all protected areas) from 2000 to 2012. In some parts of Europe, urbanisation and intensification of agriculture still accounted for up to 25% of land cover changes within protected areas. Modelling revealed meaningful relationships between land cover changes and a combination of influencing factors. Demographic factors (accessibility to cities and population density) were most important for coarse-scale patterns of land cover changes, whereas fine-scale patterns were most related to longitude (representing the general east/west economic gradient) and latitude (representing the north/south climatic gradient)., Competing Interests: The authors have declared that no competing interests exist.

Native mass spectrometry is applied for the investigation of proteins and protein complexes worldwide. The challenge in native mass spectrometry is maintaining the features of the proteins of interest, such as oligomeric state, bound ligands, or the conformation of the protein complex, during transfer from solution to gas phase. This is an essential prerequisite to allow conclusions about the solution state protein complex, based on the gas phase measurements. Therefore, soft ionization techniques are required. Widely used for the analysis of protein complexes are nanoelectro spray ionization (nESI) mass spectrometers. A newer ionization method is laser induced liquid bead ion desorption (LILBID), which is based on the release of protein complexes from solution phase via infrared (IR) laser desorption. We use both methods in our lab, depending on the requirements of the biological system we are interested in. Here we benchmark the performance of our LILBID mass spectrometer in comparison to a nESI instrument, regarding sample conditions, buffer and additive tolerances, dissociation mechanism and applicability towards soluble and membrane protein complexes. Graphical Abstract ᅟ.

Other than more widely used methods, the use of styrene maleic acid allows the direct extraction of membrane proteins from the lipid bilayer into SMALPs keeping it in its native lipid surrounding. Here we present the combined use of SMALPs and LILBID-MS, allowing determination of oligomeric states of membrane proteins of different functionality directly from the native nanodiscs.

Background: Chronic non-communicable diseases entail high impact on health systems in Brazil and worldwide. Among the most frequent are the musculoskeletal conditions which comprise a group of diseases that influence individuals' physical status, quality of life and functional capacity. Epidemiological studies investigating the scale of such conditions in the adult population are scarce in Brazil. This study estimates the prevalence of chronic musculoskeletal conditions and their association with demographic, socioeconomic, behavioural and clinical factors., Methods: Cross-sectional study with data from Brazil's 2013 National Health Survey (Pesquisa Nacional de Saúde), a nationwide household survey of 60,202 adults. Musculoskeletal conditions were specified by self-reported medical diagnosis of arthritis or rheumatism and self-reported spinal disorders. The variables were examined using a hierarchical model of determination. Prevalences of musculoskeletal conditions were calculated with their respective 95% confidence intervals for Brazil and its five regions. Prevalence ratios (PRs) were obtained by Poisson regression with robust variance., Results: Of the 60,202 individuals evaluated, 21.6% presented musculoskeletal conditions, with higher prevalences for females, older adults, indigenous, those living with a partner, low education, no occupational activity, those living in the South Region of Brazil, in rural areas, daily smokers, sedentary, obese, those who did not drink alcohol, with depressive symptoms or suffering from three or more chronic diseases. Multivariate analysis identified strong associations with advanced age (PR = 3.61; 95% CI 3.27-3.98), depressive symptoms (PR = 1.69; 95% CI 1.57-1.81) and multimorbidity (PR = 1.94; 95% CI 1.77-2.12)., Conclusions: The results show high prevalence of musculoskeletal conditions in Brazil's adult population. Considering the process of aging and steady growth in chronic diseases, this study underlines the need for health policies directed to prevention, treatment and rehabilitation for people affected by chronic musculoskeletal conditions.

Background: Despite depression being one of the most prevalent mental disorders in the world, access to treatment is still insufficient, especially in low- and middle-income countries. The aim of this study is to investigate differences in access to treatment for depression according to socio-demographic characteristics, geographical area and multi-morbidity in a nationally representative sample of individuals with depression., Methods: This study analyses data from the National Health Survey (Pesquisa Nacional de Saúde - PNS), a Brazilian household-based nationwide survey, which comprises 60,202 adults (aged 18 years or older). Depression was evaluated through the Patient Health Questionnaire-9 (PHQ-9). Prevalence Ratios and corresponding 95 % confidence intervals (95%CI) were calculated using Poisson regression., Results: The general prevalence of depression was 7.9 % (95 % CI 7.5 to 8.3). Among those with depression, 78.8 % did not receive any treatment, and 14.1 % received only pharmacotherapy. Multivariable analyses showed that being female, white, aged between 30 and 69 years, living in regions other than the North, having higher education and having multi-morbidities were independently associated with higher likelihood of access to any treatment., Conclusions: Most Brazilians with clinically relevant depressive symptoms are not receiving any treatment. Access to care is unequal, with the poor and those living in low resource areas having higher difficulties to access mental health care. Understanding these disparities is important for the provision of effective interventions aimed at reducing the prevalence of depression and inequities in access to mental health care.

A cross-sectional population-based study was conducted in Pelotas, Rio Grande do Sul, in 2014 with the aim of measuring the prevalence and factors associated with depressive symptoms among the elderly. Sampling was carried out by clusters in two stages. All the elderly people (≥ 60 years) living in the selected households were invited to participate. The occurrence of depressive symptoms was measured using GDS-10 (Geriatric Depression Scale) with ≥ 5cut-off. Information for 1,451 elderly people was obtained. The prevalence of depressive symptoms was 15.2% (95% CI 13.2 to 17.2). After multivariate analysis, the occurrence of depressive symptoms was higher among women, the elderly in economically straitened circumstances, those who were out of work, the physically inactive, those with worse self-reported health and those with functional disability. Greater attention should be given to the identification of depressive symptoms among the elderly and associated factors to inform policy and planning interventions for treatment and management of this ailment at the collective level.

Organisms developed different photoreceptors to be able to adapt to changing environmental light conditions. Phytochromes are red/far-red (r/fr) photochromic photoreceptors that belong to the classical photoreceptors along with cryptochromes and phototropins. They convert absorbed light into a biological signal by switching between two states in a light-dependent manner therefore enabling the light control downstream signalling. Their P fr conformation is the biological active form in plants, but until now only a structure of the ground state (P r ) was solved. Here, the authors provide information about structural changes occurring during photoconversion within phytochrome B and identify possible interaction sites for its N-terminal extension (NTE) utilising hydrogen/deuterium exchange rate analyses of its amide backbone. Especially, the newly identified light-dependency of two regions in the NTE are of particular interest for understanding the involvement of the phytochrome's NTE in the regulation of its downstream signalling.

Protein kinase C iota is required for various cell biological processes including epithelial tissue polarity and organ morphogenesis. To gain mechanistic insight into different roles of this kinase, it is essential to identify specific substrate proteins in their cellular context. The analog-sensitive kinase method provides a powerful tool for the identification of kinase substrates under in vivo conditions. However, it has remained a major challenge to establish screens based on this method in multicellular model organisms. Here, we report the methodology for in vivo conditions using the analog-sensitive kinase method in a genetically-tractable vertebrate model organism, the zebrafish. With this approach, kinase substrates can uniquely be labeled in the developing zebrafish embryo using bulky ATPγS analogs which results in the thiophosphorylation of substrates. The labeling of kinase substrates with a thiophosphoester epitope differs from phosphoesters that are generated by all other kinases and allows for an enrichment of thiophosphopeptides by immunoaffinity purification. This study provides the foundation for using the analog-sensitive kinase method in the context of complex vertebrate development, physiology, or disease.