Restoration of functional PAX6 in aniridia patient iPSC-derived ocular tissue models using repurposed nonsense suppression drugs

Congenital aniridia is a rare, pan-ocular disease causing severe sight loss, with only symptomatic intervention offered to patients. Approximately 40% of aniridia patients present with heterozygous nonsense variants in PAX6, resulting in haploinsufficiency. Translational readthrough inducing compounds (TRIDs) have the ability to weaken the recognition of in-frame premature stop codons (PTCs), permitting full-length protein to be translated. We have established induced pluripotent stem cell (iPSC)-derived 3D optic cups and 2D limbal epithelial stem cell (LESC) models from two aniridia patients with prevalent PAX6 nonsense mutations. Both in vitro models show reduced PAX6 protein levels, mimicking the disease. Repurposed TRIDs amlexanox and 2,6-diaminopurine (DAP), and positive control compounds ataluren and G418 were tested for their efficiency. Amlexanox was identified as the most promising TRID, increasing full-length PAX6 levels in both models, and rescuing the disease phenotype through normalization of VSX2 and cell proliferation in the optic cups and reduction of ABCG2 protein and SOX10 expression in LESC. This study highlights the significance of patient iPSC-derived cells as a new model system for aniridia and proposes amlexanox as a new putative treatment for nonsense-mediated aniridia

Avalia??o da qualidade de silagens de milho produzidas no distrito de Capoer?, Erechim/RS

Corn silage is one of the most important feed sources for ruminant production in the different regions of Brazil, including southern of Brazil, where they are mainly used in seasonal voids, moment of transition of forage availability, in the end of winter and summer seasons. The maize (Zea mays) became the main silage plant source, due it contains in this bromatological composition the most important requirements for its ensilage. The purpose of this study was to evaluate the bromatological quality of corn silages produced in the district of Capoer?, located at Erechim, state of Rio Grande do Sul, and was characterized as a case study, where the samples were collected in five different properties. After the samples were collected, the determinations of DM, MM, CP, EE, NDF and pH were carried out in Bromatology Laboratory at Federal University of Fronteira Sul (UFFS). In addition, thermographic reading of the silos was performed with a Thermographic Camera. The Dry Matter ranged from 38.81 to 31.74%. The CP content had high variability among the studied properties, being between 8.14 to 6.52%. It was concluded that, due to results of bromatological parameters, silages produced in the district of Capoer?, Erechim-RS, are in agreement with standards of good silage manufacturing.A silagem de milho ? uma das mais importantes fontes alimentares para a produ??o de ruminantes nas diversas regi?es do Brasil, incluindo o sul do Brasil, onde, s?o utilizadas, principalmente, nos chamados vazios estacionais, momento de transi??o da disponibilidade de forrageiras, no final das esta??es de inverno e de ver?o. O milho (Zea mays) se transformou no principal vegetal ensilado, devido ao mesmo conter em sua composi??o bromatol?gica os principais requisitos para a confec??o da mesma. O presente trabalho teve por objetivo avaliar a qualidade bromatol?gica das silagens de milho produzidas no distrito de Capoer?, localizado no munic?pio de Erechim, do estado do Rio Grande do Sul, caracterizando-se como um estudo de caso, onde as amostras foram coletadas em cinco diferentes propriedades da localidade. Ap?s a coleta das amostras, foram realizadas as determina??es de MS, MM, PB, EE, FD e pH, no laborat?rio de Bromatologia da Universidade Federal da Fronteira Sul (UFFS), al?m disso, foi realizado a leitura termogr?fica dos silos com uma c?mera termogr?fica. O teor de massa seca variou de 38,81 a 31,74%. O teor de PB teve alta variabilidade entre a propriedades estudadas, estando entre 8,14 a 6,52%. Concluiu-se que, em virtude dos resultados dos par?metros bromatol?gicos, as silagens produzidas no distrito de Capoer?, Erechim-RS, est?o de acordo com as boas normas de fabrica??o de silagens

Precision technologies to address dairy cattle welfare: focus on lameness, mastitis and body condition

Specific animal-based indicators that can be used to predict animal welfare have been the core of protocols for assessing the welfare of farm animals, such as those produced by the Welfare Quality project. At the same time, the contribution of technological tools for the accurate and realtime assessment of farm animal welfare is also evident. The solutions based on technological tools fit into the precision livestock farming (PLF) concept, which has improved productivity, economic sustainability, and animal welfare in dairy farms. PLF has been adopted recently; nevertheless, the need for technological support on farms is getting more and more attention and has translated into significant scientific contributions in various fields of the dairy industry, but with an emphasis on the health and welfare of the cows. This review aims to present the recent advances of PLF in dairy cow welfare, particularly in the assessment of lameness, mastitis, and body condition, which are among the most relevant animal-based indications for the welfare of cows. Finally, a discussion is presented on the possibility of integrating the information obtained by PLF into a welfare assessment framework.FE1B-06B2-126F | Jos? Pedro Pinto de Ara?joN/

Life cycle assessment of lithium-ion batteries and vanadium redox flow batteries-based renewable energy storage systems

Renewable energy has become an important alternative to fossil energy, as it is associated with lower greenhouse gas emissions. However, the intermittent characteristic of renewables urges for energy storage systems, which play an important role in matching the supply and demand of renewable-based electricity. The life cycle of these storage systems results in environmental burdens, which are investigated in this study, focusing on lithium-ion and vanadium flow batteries for renewable energy (solar and wind) storage for grid applications. The impacts are assessed through a life cycle assessment covering the batteries supply phase, their use and end-of-life, with experimental data from test set-ups. The battery composition is investigated in detail as a factor for the final impacts, by comparing two types of cathodes for the lithium-ion battery and the use of recycled electrolyte for the vanadium flow battery. Results indicate that the vanadium-based storage system results in overall lower impacts when manufactured with 100% fresh raw materials, but the impacts are significantly lowered if 50% recycled electrolyte is used, with up to 45.2% lower acidification and 11.1% lower global warming potential. The new lithium-ion battery cathode chemistry results in overall higher impacts, with 41.7% more particulate matter and 52.2% more acidification

Influence of cations Ca2+, Mg2+ and Zn2+ on the flotation and surface charge of smithsonite and dolomite with sodium oleate and sodium silicate.

using sodium oleate and sodium silicate. Microflotation test results demonstrated recoveries of 95% and 5% for smithsonite and dolomite, respectively, from 2.5 ? 10?5 M sodium oleate and 50 mg/L sodium silicate at pH 9.5. The smithsonite was depressed by the cations Ca2+ and Mg2+ and, the dolomite was depressed by Zn2+ cations, which was probably caused by the reaction of these cations with the oleate anions in the solution, decreasing the concentration of collector available for adsorption onto the minerals. The powerful depression of smithsonite caused by Ca2+ cations compared with that caused by Mg2+ cations can be considered to have occurred because of the higher concentration of Ca2+ in the solution. From the zeta potential measurements at pH 9.5, we concluded that the predominant species of oleate and of sodium silicate were adsorbed onto both minerals, and the silicate species prevented the adsorption of oleate anions onto dolomite. The decrease in the negative zeta potential of both minerals after cation conditioning can be related to the electrostatic attraction between the cations and the negative sites on their surfaces. The negative zeta potential of smithsonite increased at a concentration of 1 ? 10?6MCa2+ and Mg2+,whereas the potential decreases at a concentration of 1 ? 10?3 M, which can be related to a lower concentration of oleate anions being available for adsorption

Code2know ? um prot?tipo de sistema de ensino de programa??o baseado em juiz online

O presente trabalho prop?e o desenvolvimento de prot?tipo de um sistema baseado em juiz online com foco no ensino de programa??o. Com o objetivo de aperfei?oar os aspectos desses sistemas, como usabilidade, escalabilidade e um feedback claro aos alunos. O trabalho busca preencher lacunas existentes nos sistemas atuais, que muitas vezes s?o h?bridos entre competi??o e ensino. O sistema proposto visa melhorar o ambiente de aprendizado, permitindo que os alunos resolvam exerc?cios com casos de teste p?blicos e recebam o feedback personalizado de acordo com a exce??o obtida no processo de submiss?o. Como resultado foi obtido uma prova de conceito do sistema, com as funcionalidades b?sicas para ser implantado em sala de aula

Engineered Saccharomyces cerevisiae for lignocellulosic valorization: a review and perspectives on bioethanol production

The biorefinery concept, consisting in using renewable biomass with economical and energy goals, appeared in response to the ongoing exhaustion of fossil reserves. Bioethanol is the most prominent biofuel and has been considered one of the top chemicals to be obtained from biomass. Saccharomyces cerevisiae, the preferred microorganism for ethanol production, has been the target of extensive genetic modifications to improve the production of this alcohol from renewable biomasses. Additionally, S. cerevisiae strains from harsh industrial environments have been exploited due to their robust traits and improved fermentative capacity. Nevertheless, there is still not an optimized strain capable of turning second generation bioprocesses economically viable. Considering this, and aiming to facilitate and guide the future development of effective S. cerevisiae strains, this work reviews genetic engineering strategies envisioning improvements in 2nd generation bioethanol production, with special focus in process-related traits, xylose consumption, and consolidated bioprocessing. Altogether, the genetic toolbox described proves S. cerevisiae to be a key microorganism for the establishment of a bioeconomy, not only for the production of lignocellulosic bioethanol, but also having potential as a cell factory platform for overall valorization of renewable biomasses.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020, the PhD grants [SFRH/BD/ 130739/2017 to CEC; SFRH/BD/146367/2019 to POS; SFRH/ BD/132717/2017 to SLB], the MIT-Portugal Program [PhD Grant PD/BD/128247/2016 to JTC], BioTecNorte operation [NORTE-01-0145-FEDER-000004] and Biomass and Bioenergy Research Infrastructure (BBRI)- LISBOA-01-0145-FEDER- 022059] funded by the European Regional Development Fund (ERDF) under the scope of Norte2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Prognostic value of disability on mortality: 15-year follow-up of the Bambuí Cohort Study of Aging

BACKGROUND: Disability is a concern in the context of population ageing. The extent of an individual’s disability is a major determinant of whether or not they require long-term care or survival time. We investigated the effect of three disability domains as predictors of all-cause mortality over 15-year follow-up in a Brazilian socioeconomically disadvantaged and multiracial older adult population. METHODS: We estimated Cox proportional hazards models using data from 1333 community-dwelling individuals aged 60 and older from the Bambuí Cohort Study of Ageing. Disability was defined as a great difficulty or not being able to perform one and two or more activities in each domain: mobility, instrumental activities of daily living (IADL) and basic activities of daily living (BADL). RESULTS: The overall mortality rate was 46.1 per 1000 person-years at risk (pyrs) and it was higher in men. Among men, the fully adjusted Hazard Ratios (HRs) were 1.92 (95%CI: 1.43-2.58), 2.07 (95%CI: 1.53-2.79) and 1.65 (95%CI: 1.11-2.45), and among women 1.75 (95%CI: 1.38-2.21), 1.43 (95%CI: 1.11-1.84) and 1.43 (95%CI: 1.05-1.95), for two or more disability in mobility tasks, IADLs and BADLs, respectively, compared to those with no difficulty or some difficulty to perform all the tasks. CONCLUSION: A similar risk of death for mobility, IADL and BADL in both genders was found, suggesting that any of these domains can be used to identify risk of all-cause mortality among older adults. The number of activities with limitations in each domain was an important factor

A fractional dispersion model for overland solute transport

An edited version of this paper was published by AGU. Copyright 2006 American Geophysical Union.Using the kinematic-wave overland flow equation and a fractional dispersion-advection equation, a process-oriented, physically-based model is developed for overland solute transport. Two scenarios, one consisting of downslope and the other of upslope rainstorm movements, are considered for numerical computations. Under these conditions, the hydrograph displays a long-tailed distribution due to the variation in flow velocity in both time and distance. The solute transport exhibits a complex behavior. Pollutographs are characterized by a steep rising limb, with a peak, and a long, stretched receding limb; whereas the solute concentration distributions feature a rapid receding limb followed by a long stretched rising limb. Downslope moving storms cause much higher peak in both hydrographs and pollutographs than do upslope moving storms. Both hydrographs and the pollutographs predicted by the fractional dispersion model are in good agreement with the data measured experimentally using a soil flume and a moving rainfall simulator

MYCOBIOTA ASSOCIATED WITH Eucalyptus grandis HILL EX MAIDEN LUMBER DURING AIR DRYING

O objetivo principal deste trabalho foi o de acompanhar a secagem ao ar livre da madeira serrada de Eucalyptus grandis conduzida na regi\ue3o de Lavras, MG e identificar a micobiota associada \ue0 madeira em diversas fases da secagem. As t\ue1buas foram cortadas de oito toras de 3,0 m de comprimento, oriundas de tr\ueas \ue1rvores, com 27 anos de idade, plantadas em \ue1rea experimental da UFLA. Dos resultados, p\uf4de-se concluir que a secagem da madeira de Eucalyptus grandis ao ar livre, iniciada em janeiro, consumiu 158 dias at\ue9 atingir umidade pr\uf3xima a 12,5%. A curva de secagem foi representada por uma equa\ue7\ue3o logar\uedtmica com coeficiente de determina\ue7\ue3o (R2) igual a 98,3%. Os fungos causadores de bolores superficiais e de manchas tiveram maior ocorr\ueancia no in\uedcio da secagem. As mais altas freq\ufc\ueancias de fungos, verificadas no in\uedcio da secagem, foram observadas para Penicillium spp. e Pestalotiopsis sp. O fungo Lentinus lepideus ocorreu com maior freq\ufc\ueancia no final da secagem.This work\u2019s main objective was to follow the air-drying of Eucalyptus grandis lumber, carried out in Lavras, MG, and to identify the mycobiota associated with the lumber at various phases of drying. The lumbers were obtained from eight 3.0 meter long logs from 27 year-old trees, planted in an experimental area of UFLA. Results showed that the air-drying of Eucalyptus grandis, started in January, demanded 158 days to achieve moisture content around 12.5 %. The moisture content-time curve was represented by a logarithmic equation with coefficient of determination equal to 98.3 %. The highest occurrence of fungi that cause surface mold and stain was observed at the beginning of the drying. The highest frequencies of fungi were verified at the beginning of the drying for Penicillium spp and Pestalotiopsis sp. The fungus Lentinus lepideus occurred with higher frequency at the end of the drying