Initial Condition Estimation in Flux Tube Simulations using Machine Learning

Space weather has become an essential field of study as solar flares, coronal mass ejections, and other phenomena can severely impact Earth's life as we know it. The solar wind is threaded by magnetic flux tubes that extend from the solar atmosphere to distances beyond the solar system boundary. As those flux tubes cross the Earth's orbit, it is essential to understand and predict solar phenomena' effects at 1 AU, but the physical parameters linked to the solar wind formation and acceleration processes are not directly observable. Some existing models, such as MULTI-VP, try to fill this gap by predicting the background solar wind's dynamical and thermal properties from chosen magnetograms and using a coronal field reconstruction method. However, these models take a long time, and their performance increases with good initial guesses regarding the simulation's initial conditions. To address this problem, we propose using varied machine learning techniques to obtain good initial guesses that can accelerate MULTI-VP's computational time

Colistin heteroresistance in Klebsiella pneumonia and its association with slow-growing subpopulations within biofilms

The emergence of multidrug-resistant strains of Klebsiella pneumoniae is a growing clinical concern that is leading to the re-introduction of the old and toxic colistin as a salvage therapy. However, several cases of heteroresistance to this antimicrobial have been recently reported in planktonic studies. Therefore, the understanding of the conditions that trigger heteroresistance is attracting considerable research interest. In this scope, this work aimed to more comprehensively study the response of K. pneumoniae biofilms to colistin and to inspect the occurrence of heteroresistance in biofilm-cells.K. pneumoniae presented susceptibility to colistin in its planktonic form, though biofilms presented an enhanced resistance. The population analysis profiles pointed out the existence of a slow-growing sub-population resistant to colistin within a K. pneumoniae strain that seemed to be exclusively associated with biofilms. This resistant sub-population is characterized by a small colony morphology (diameter around 5 mm), which remains unchangeable, and a completely different response to colistin compared to the observed in the wild-type morphotype. Colistin was ineffective in this small colony variant since it was never achieved any reduction in biofilm-cells viability. These findings suggest that heteroresistance is linked to biofilm formation and to a morphological distinct sub-population. Moreover, this is the first evidence that biofilm formation can trigger the emergence of heteroresistance from an apparently susceptible strain

Fostering innovation in the treatment of chronic polymicrobial cystic fibrosis-associated infections exploring aspartic acid and succinic acid as ciprofloxacin adjuvants

Cystic fibrosis (CF) disease provokes the accumulation of thick and viscous sputum in the lungs, favoring the development of chronic and polymicrobial infections. Pseudomonas aeruginosa is the main bacterium responsible for these chronic infections, and much of the difficulty involved in eradicating it is due to biofilm formation. However, this could be mitigated using adjuvant compounds that help or potentiate the antibiotic action. Therefore, the main goal of this study was to search for substances that function as adjuvants and also as biofilm-controlling compounds, preventing or dismantling P. aeruginosa biofilms formed in an in vitro CF airway environment. Dual combinations of compounds with subinhibitory (1 and 2 mg/L) and inhibitory concentrations (4 mg/L) of ciprofloxacin were tested to inhibit the bacterial growth and biofilm formation (prophylactic approach) and to eradicate 24-h-old P. aeruginosa populations, including planktonic cells and biofilms (treatment approach). Our results revealed that aspartic acid (Asp) and succinic acid (Suc) restored ciprofloxacin action against P. aeruginosa. Suc combined with 2 mg/L of ciprofloxacin (Suc-Cip) was able to eradicate bacteria, and Asp combined with 4 mg/L of ciprofloxacin (AspCip) seemed to eradicate the whole 24-h-old populations, including planktonic cells and biofilms. Based on biomass depletion data, we noted that Asp induced cell death and Suc seemed somehow to block or reduce the expression of ciprofloxacin resistance. As far as we know, this kind of action had not been reported up till now. The presence of Staphylococcus aureus and Burkholderia cenocepacia did not affect the efficacy of the AspCip and SucCip therapies against P. aeruginosa and, also important, P. aeruginosa depletion from polymicrobial communities did not create a window of opportunity for these species to thrive. Rather the contrary, Asp and Suc also improved ciprofloxacin action against B. cenocepacia. Further studies on the cytotoxicity using lung epithelial cells indicated toxicity of SucCip caused by the Suc. In conclusion, we provided evidences that Asp and Suc could be potential ciprofloxacin adjuvants to eradicate P. aeruginosa living within polymicrobial communities. AspCip and SucCip could be promising therapeutic options to cope with CF treatment failures.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020— Programa Operacional Regional do Norte. The authors acknowledge COMPETE2020 and FCT for the project POCI-01-0145-FEDER-029841 and for Scientific Employment Stimulus 2017 (CEECIND/01507/2017) provided to ASinfo:eu-repo/semantics/publishedVersio

Impact of postharvest preservation methods on nutritional value and bioactive properties of mushrooms

Background: Mushrooms are a good source of protein, dietary fibre, vitamins, minerals and phenolic compounds. However, mushrooms are a very perishable food and the implementation of preservation methods is essential to extend their shelf-life. The preservation methods for mushrooms can be classified into three categories: thermal (drying/freezing), chemical (edible coatings, films and washing solutions) and physical (packing, irradiation, pulsed electric field and ultrasound) processes. These processes can change the nutritional value and bioactive properties of this commodity. Scope and approach: The goal of this review is to critically update and discuss the existing information about the effect of postharvest preservation methods on the nutritional value and bioactive properties of edible mushrooms. Key findings and conclusions: Drying, especially when high temperatures are applied, can cause the degradation of polysaccharides, proteins and flavour compounds. Freezing is one of the best methods to extend mushrooms’ shelf life but cause the loss of vitamins. Edible coatings and films improve the total sugar, ascorbic acid and bioactive compounds preservation during the storage period. Washing solutions decrease amino acids content. Gamma and electron-beam irradiation decrease the unsaturated fatty acid content, whereas UV-B irradiation significantly increases the vitamin D content. However, there is still limited information about the impact of chemical processes, packaging, pulsed electric field and ultrasound on the nutritional composition and bioactive properties of mushrooms, opening research opportunities for future. This review presents technological and economic alternatives that may support the mushroom processing industries to obtain value-added edible mushrooms and related products.The authors are grateful to the European Agricultural Fund for Rural Development (EAFRD), through the Rural Development Program (PDR2020), within the scope of Project MicoCoating [PDR2020-101- 031472] and European Regional Development Fund (ERDF) through the Competitiveness and Internationalization Operational Program (POCI), within the scope of project MicoBioExtract [POCI-01-0247-FEDER- 033939]. We would also like to thank the National Funds from FCT - Fundação para a Ciência e a Tecnologia through project UID/Multi/50016/2019, FCT/MEC (PIDDAC) - IF/00588/2015 and FCT individual PhD grant number SFRH/BD/145301/2019. The authors are also grateful to FCT, Portugal for financial support through national funds FCT/MCTES to CIMO [UIDB/00690/2020] and national funding by FCT, P.I., through the institutional scientific employment programcontract for L. Barros.info:eu-repo/semantics/publishedVersio

Antimicrobial resistance three ways: healthcare crisis, major concepts, and the relevance of biofilms

Worldwide, infections are resuming their role as highly effective killing diseases, as current treatments are failing to respond to the growing problem that is antimicrobial resistance (AMR). The social and economical burden of AMR seems ever rising, with health- and research-related organizations rushing to collaborate on a worldwide scale to find effective solutions. Resistant bacteria are spreading even in first-world nations, being found not only in healthcare-related settings, but also in food and in the environment. In this mini-review, the impact of AMR in healthcare systems and the major bacteria behind it are highlighted. Ecological aspects of AMR evolution and the complexity of its molecular mechanisms are explained. Major concepts, such as intrinsic, acquired, and adaptive resistance, as well as tolerance and heteroresistance, are also clarified. More importantly, the problematic of biofilms and their role in AMR, namely its main resistance and tolerance mechanisms, is elucidated. Finally, some of the most promising anti-biofilm strategies being investigated are reviewed. Much is still to be done regarding the study of AMR and the discovery of new anti-biofilm strategies. Gladly, considerable research on this topic is generated every day and increasingly concerted actions are being engaged globally to try and tackle this problem.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge COMPETE2020 and FCT for the project POCI-01-0145-FEDER-029841, and FCT for the PhD Grants of Andreia Magalhães [grant number SFRH/BD/132165/2017] and Tânia Grainha [grant number SFRH/BD/136544/2018].info:eu-repo/semantics/publishedVersio

Relatório de Primavera 2022

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Validation of Rare Structural Variants in Portuguese Azoospermic Patients

Azoospermia affects approximately 15% of infertile males. Despite considerable research efforts in the last decades, in the majority of cases the cause remains unidentified. Chromosomal abnormalities and Yq microdeletions have been thoroughly studied, yet only account for 17% of azoospermic men. In fact, little is known about the contribution of the hemizygous X-linked and autosomal genes to male infertility. This study focuses on the validation of rare deletions encompassing candidate genes on the X chromosome and on the autosomes, previously identified by Affymetrix 6.0 SNP Array, in a cohort of 166 Portuguese individuals with severe spermatogenic impairment (non-obstructive azoospermia and severe oligozoospermia). As expected, the protein-coding genes CXORF48, and MAGEA8, as well as a miRNA (hsa-mir-4330) could not be amplified by PCR from the single X chromosome of the patients suspected of carrying deletions. These rearrangements will be further validated by aCGH (array Comparative Genomic Hybridization). Additionally, by MLPA analysis on 11p13 we confirmed a large deletion (~1Mb) spanning the WT1 gene - a conserved transcription factor known to play a crucial role in gonadal differentiation. A retrospective clinical evaluation of this patient revealed partial gonadal dysgenesis, consistent with a causal role for the newly discovered deletion. These results reveal new candidate genes for a role in spermatogenic pathways and suggest that haploinsufficiency of proteins important for the development of the male reproductive system can lead to spermatogenic dysfunction

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DR beta 1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition. A GWAS in a large case-control cohort of European ancestry identifies two genomic regions, the MHC class II gene HLA-DRB1 and an upstream locus of VRK1, that are associated with the most severe phenotype of spermatogenic failure

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Mammals in Portugal: a data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications