Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage

The activity of fumagillin, a mycotoxin produced by Aspergillus fumigatus, has not been studied in depth. In this study, we used a commercial fumagillin on cultures of two cell types (A549 pneumocytes and RAW 264.7 macrophages). This toxin joins its target, MetAP2 protein, inside cells and, as a result, significantly reduces the electron chain activity, the migration, and the proliferation ability on the A549 cells, or affects the viability and proliferation ability of the RAW 264.7 macrophages. However, the toxin stimulates the germination and double branch hypha production of fungal cultures, pointing out an intrinsic resistant mechanism to fumagillin of fungal strains. In this study, we also used a fumagillin non-producer A. fumigatus strain (∆fmaA) as well as its complemented strain (∆fmaA::fmaA) and we tested the fumagillin secretion of the fungal strains using an Ultra High-Performance Liquid Chromatography (UHPLC) method. Furthermore, fumagillin seems to protect the fungus against phagocytosis in vitro, and during in vivo studies using infection of immunosuppressed mice, a lower fungal burden in the lungs of mice infected with the ∆fmaA mutant was demonstrated.This research was funded by the Basque Government: grant number IT1362-19. X.G. and S.C.-S. received a Ph.D. fellowship from the Basque Government; and U.P.-C. from the University of the Basque Country

Safety of 27 flavouring compounds providing a milky-vanilla flavour and belonging to different chemical groups for use as feed additives in all animal species (FEFANA asbl)

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of 27 compounds to provide a milky-vanilla flavour belonging to different chemical groups, when used as sensory additives in feed for all animal species. Fifteen of the 27 compounds were tested in tolerance studies in chickens for fattening, piglets and cattle for fattening. No adverse effects were observed in the tolerance studies at 10-fold the intended level. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the 15 tested compounds were safe for these species at the proposed use level and conclusions were extrapolated to all animal species. For the remaining 12 compounds, read-across from structurally similar compounds tested in tolerance trials and belonging to the same chemical group was applied. The FEEDAP Panel concluded that these 12 compounds were safe for all animal species at the proposed use level. No safety concern would arise for the consumer from the use of the 27 compounds up to the highest levels considered safe for target animals. No new data were submitted on the safety for the user that would allow the FEEDAP Panel to change its previous conclusion for 5-methylhept-2-en-4-one [07.139], 5-methylfurfural [13.001] and 4-phenylbut-3-en-2-one [07.024]. The concentrations considered safe for the target species are unlikely to have detrimental effects on the environment for all the compounds

Assessment of the application for renewal of the authorisation of Amaferm® (fermentation product of Aspergillus oryzae NRRL 458) as a feed additive for dairy cows

AMAFERM® is a fermentation product produced by Aspergillus oryzae NRRL 458, containing alpha-amylase and cellulase enzyme activities, authorised for use as a feed additive for cows. This scientific opinion concerns the renewal of the authorisation of this additive for its use in dairy cows. In its former opinion, the EFSA Panel on Additives and Product or Substances used in Animal Feed (FEEDAP), based on the data and knowledge available at that time, concluded that the additive is safe for cows, for the consumers and the environment. In that assessment, the Panel also concluded that the additive is non-irritant or a dermal sensitiser but should be considered a potential respiratory sensitiser. The applicant provided new information regarding the characterisation of the additive in terms of enzyme activities as well as information concerning the production strain. Regarding the enzyme activities in the fermentation product, weaknesses and limitations in the methods of analysis were noted. The information regarding the production strain did not permit to confirm its taxonomic classification, moreover uncertainty remains regarding the presence of viable cells/spores in the final product. Therefore, the FEEDAP Panel could not confirm the previously drawn conclusions regarding the safety of the production strain and consequently could not confirm the safety for the target species and consumers. There was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation

Safety and efficacy of muramidase from Trichoderma reesei DSM 32338 as a feed additive for turkeys for fattening, turkeys reared for breeding, chickens reared for breeding and other poultry species reared for breeding

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of muramidase produced by Trichoderma reesei DSM 32338. The additive is considered safe for turkeys for fattening, turkeys reared for breeding, chickens reared for laying/breeding and other poultry species reared for breeding up to the maximum recommended dose of 45,000 LSU(F)/kg feed. The additive is considered safe for the consumer and the environment. No conclusions can be reached on the potential of the additive for skin/eye irritancy and skin sensitisation. The additive should be considered a potential respiratory sensitiser. The additive has the potential to be efficacious as a zootechnical additive in turkeys for fattening, turkeys reared for breeding, chickens reared for laying/breeding and other poultry species reared for breeding when added to feed at 25,000 LSU(F)/kg feed

Safety of l-threonine produced by fermentation with Escherichia coli CGMCC 11473 as a feed additive for all animal species

The l-threonine under assessment is produced by fermentation with a genetically modified strain of Escherichia coli and it is intended to be used as a nutritional additive for all animal species. In 2017 the Panel on Additives and products or Substances used in Animal Feed (FEEDAP) of EFSA issued an opinion on the safety and efficacy of the product. In that assessment, the Panel could not conclude on the safety of the additive for the target species, consumers and the environment due to the lack of data regarding the characterisation of the production strain and the resulting product. The applicant provided additional data on the identity of the production strain, the genetic modification, the susceptibility to antibiotics and the absence of cells and recombinant DNA of the production strain in the final product. The recipient strain is safe and the genetic modification does not raise concerns. Moreover, viable cells or DNA of the production strain were not detected in the final product. With this new information the FEEDAP Panel concluded that l-threonine produced by E. coli CGMCC 11473 is safe for the all animal species, the consumers and the environment. The FEEDAP Panel could not conclude on the potential of the additive to be irritant to skin and eyes or on the skin sensitisation potential. It was concluded that there is a risk of exposure to endotoxins by inhalation for persons handling the additive

Safety and efficacy of the additive consisting of muramidase produced by Trichoderma reesei DSM 32338 (Balancius™) for use in weaned piglets (DSM Nutritional products Ltd)

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of muramidase produced by Trichoderma reesei DSM 32338 (Balancius™) as a feed additive for weaned piglets. The additive has been previously assessed by the FEEDAP Panel in the context of other applications, and in the current assessment the applicant requests for an extension of use. Based on the data available in a sub-chronic oral toxicity study, the Panel concluded that the additive is safe for weaned piglets at the maximum recommended level of 65,000 LSU(F)/kg feed. The additive is safe for the consumers and the environment but should be considered a potential respiratory sensitiser. The Panel could not conclude on the potential of the additive for skin/eye irritancy and skin sensitisation. The additive has the potential to be efficacious as a zootechnical additive for weaned piglets at the dose of 50,000 LSU(F)/kg feed

Assessment of the application for renewal of authorisation of PHYZYME® XP 5000 G/L (6-phytase) for chickens for fattening, laying hens, turkeys for fattening, ducks for fattening, weaned piglets, pigs for fattening and sows for reproduction

PHYZYME\uae XP 5000 G/L is a feed additive that contains 6-phytase produced by a genetically modified strain of Schizosaccharomyces pombe. The applicant requested for the renewal of the authorisation for PHYZYME\uae XP 5000 G and L to be used as a feed additive in chickens for fattening, laying hens, turkeys for fattening, ducks for fattening, piglets (weaned), pigs for fattening and sows. This scientific opinion concerns the renewal of the authorisation of the additive for those species. To support the request, the applicant provided evidence that the additive in the market complies with the conditions of the authorisation. According to the information provided by the applicant, no new evidence has been identified that would make the FEEDAP Panel reconsider the previous conclusions regarding the safety for the target species, consumer, user and environment. The application for renewal of the authorisation did not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive. Therefore, there was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation

Assessment of the application for renewal of authorisation of Bactocell® (Pediococcus acidilactici CNCM I-4622) as a feed additive for weaned piglets, pigs for fattening, minor porcine species (weaned and for fattening), chickens for fattening, laying hens and minor avian species for fattening and for laying and its extension of use to all growing pigs and all avian species

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on Bactocell\uae (Pediococcus acidilactici CNCM I-4622) in the context of the renewal of the authorisation for weaned piglets, pigs for fattening, minor porcine species (weaned and for fattening), chickens for fattening, laying hens and minor avian species for fattening and for laying when used as a zootechnical feed additive (gut flora stabiliser) in feed or in water for drinking. In addition, the applicant requested the extension of use for suckling piglets, minor pig species (growing/for fattening), chickens reared for laying, chickens reared for breeding purposes, chickens for breeding purposes, turkeys and minor avian species (including non-food producing/ornamental birds) reared for laying/breeding purposes and for breeding purposes when used as in feed or in water for drinking. The applicant has provided evidence that the additive currently on the market complies with the conditions of authorisation. The additive is safe for the target species, consumers and the environment as well. The additive is non-irritant to skin and eyes and is not a dermal sensitiser but should be considered a respiratory sensitiser. Considering the high dusting potential of the formulations, exposure of users by inhalation is very likely. The additive, at the level of 1  7 109 CFU/kg feed (5  7 108 when delivered in water), has the potential to be efficacious in the new species proposed: chickens reared for laying, chickens reared for breeding purposes, chickens for breeding purposes, turkeys and minor avian species reared for laying/breeding purposes and for breeding purposes (including non-food producing/ornamental birds) and in suckling piglets and minor porcine species (growing/for fattening)

Efficacy of a feed additive consisting of Bacillus subtilis FERM BP‐07462, Enterococcus lactis FERM BP‐10867 and Clostridium butyricum FERM BP‐10866 (BIO‐THREE®) for chickens for fattening and reared for laying, turkeys for fattening and reared for breeding, and all avian species for rearing/fattening or reared for laying/breeding (TOA BIOPHARMA Co., Ltd.)

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the efficacy of Bacillus subtilis FERM BP-07462, Enterococcus lactis FERM BP-10867 and Clostridium butyricum FERM BP-10866 (BIO-THREE (R)) as a zootechnical feed additive to be used as a gut flora stabiliser for chickens for fattening and reared for laying, turkeys for fattening and reared for breeding, and all avian species for rearing/fattening or reared for laying/breeding. In a previous opinion, the FEEDAP Panel could not conclude on the efficacy of BIO-THREE (R) for the target species at the proposed conditions of use. The applicant has provided a new study in chickens for fattening as supplementary information to support the efficacy of BIO-THREE (R) for the target species. Considering the previously submitted studies and the new submitted trial, the Panel concluded that the additive is efficacious for chickens for fattening and reared for laying, turkeys for fattening and reared for breeding, and all avian species for rearing/fattening or reared for laying/breeding under the proposed conditions of use