Epitope-imprinted polymers: design principles of synthetic binding partners for natural biomacromolecules

Molecular imprinting (MI) has been explored as an increasingly viable tool for molecular recognition in various fields. However, imprinting of biologically relevant molecules like proteins is severely hampered by several problems. Inspired by natural antibodies, the use of epitopes as imprinting templates has been explored to circumvent those limitations, offering lower costs and greater versatility. Here, we review the latest innovations in this technology, as well as different applications where MI polymers (MIPs) have been used to target biomolecules of interest. We discuss the several steps in MI, from the choice of epitope and functional monomers to the different production methods and possible applications. We also critically explore how MIP performance can be assessed by various parameters. Last, we present perspectives on future breakthroughs and advances, offering insights into how MI techniques can be expanded to new fields such as tissue engineering.This work was supported by Project NORTE-01-0145-FEDER-000021 supported by the Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); by the European Union Framework Program for Research and Innovation HORIZON 2020, under the Twinning grant agreement no. 810850–Achilles, European Research Council grant agreement no. 772817; and by FCT/MCTES (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia, e Ensino Superior) through PhD grant PD/BD/143039/2018 for S.P.B.T., financed through the Doctoral Program in Advanced Therapies for Health (PATH) (FSE/POCH/ PD/169/2013), project PTDC/NAN-MAT/30595/2017, and individual contract 2020.03410. CEECIND for R.M.A.D. N.A.P. acknowledges support from the Cockrell Family Chair Foundation; the Institute for Biomaterials, Drug Delivery, and Regenerative Medicine; and the UT-Portugal Collaborative Research Program

Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs

Tendon injuries and tendinopathies are increasingly prevalent health problems currently lacking effective treatments. Tissue engineering offers promising strategies to boost the low innate regenerative ability of tendons. Within this context, the simultaneous leveraging of both physical and biochemical cues by engineered scaffolding systems can be explored to promote a stronger tenogenic response from stem cells. Here, molecularly imprinted polymeric nanoparticles (MINPs) against transforming growth factor (TGF)-β3 are combined with bioinspired anisotropic hydrogels to produce tenogenesis-inductive constructs. MINPs are first solid phase-imprinted against a TGF-β3 epitope, achieving an affinity comparable to monoclonal antibodies. MINPs and magnetically-responsive microfibers are then encapsulated together with adipose-derived stem cells within gelatin-based hydrogels, applying a magnetostatic field during gelation to align the microfibers. The created anisotropic microstructure guides cell growth and elongation unidirectionally, while MINPs act as artificial receptors for TGF-β3, potentiating its paracrine action in the cellular microenvironment. The combination of both stimuli proves effective at increasing TGF-β signaling, which promotes the expression of tendon-associated genes and corresponding protein synthesis, suggesting that microstructural cues and biomolecule sequestration act in tandem to direct cell fate commitment. Overall, this system recapitulates several elements of tendon development, constituting a promising strategy for the regeneration of this tissue

Prenatal diagnosis of mosaic ring chromosome 16 - a rare event with uncertain prognosis

Ring chromosomes are rare cytogenetic findings (prenatal frequency ~ 0.0075%) often associated with an abnormal phenotype, depending of the chromosomal origin, genetic content and the presence of a mosaic. Supernumerary ring chromosome 16 [r(16)] is rarely observed and mosaicism makes the genotype/phenotype correlation difficult. We report a de novo mosaic r(16) detected after prenatal diagnosis in a woman referred for advanced maternal age. Multiplex ligation-dependent probe amplification (MLPA) for aneuploidy testing of chromosomes 13, 18, 21 and X was normal. Karyotype was 47,XX,+r[10]/46,XX[15]. Chromosomal microarray analysis (CMA) on DNA obtained from long-term cultured amniocytes did not detect any alterations. MLPA with a pericentromeric probe kit on an uncultured sample showed a chromosome 16 gain, encompassing 16p11.2 and 16q11.2 regions, including TGFB1I1, AHSP, VPS35 and ORC6 genes, leading to partial characterization of the r(16). Although no phenotype has been correlated with overexpression of these genes, the 16p11.2 region is associated with neurodevelopmental disorders. Nevertheless individuals with microduplication of 16p11.2 and normal development have been described. The lack of a precise definition of genetic content of the r(16) and its mosaic form leads to uncertain prognosis of clinical outcome.N/

Bologna process, higher education and a few considerations about the New University

O presente artigo analisa o que se convencionou chamar de Processo de Bolonha, isto é, a produção de uma “política pública de um meta-Estado para um meta-campo universitário”, constituindo-se em uma política educacional supranacional, comum aos estados-membros da União Européia, com vista à construção de um “espaço europeu de educação superior”. O processo político e de reformas institucionais, realizado por cada governo nacional, conduzirá ao estabelecimento efetivo do novo sistema europeu de educação superior até 2010, incluindo atualmente 45 países – todos os da UE e outros 18 países europeus não pertencentes a ela. Nesse sentido, por se tratar de um vastíssimo número de “subsistemas nacionais” e de instituições educativas, atribui-se um grande protagonismo às questões relativas à “garantia de qualidade”. Analisam-se, igualmente, as recentes transformações na educação superior no Brasil, em que o projeto da chamada “Universidade Nova” e o Programa de Apoio a Planos de Reestruturação e Expansão das Universidades Federais (REUNI) constituem-se nas manifestações mais claras do reordenamento desse nível de ensino (seguindo os parâmetros de Bolonha), que já experimentara grandes transformações nos governos de Fernando Henrique Cardoso (1995-2002) e teve prosseguimento nos governos de Luiz Inácio Lula da Silva (2003-2006; 2007), embora com distintos matizes.This article analyzes what is conventionally known as the Bologna Process, or the making of a “public policy of a meta-State for a University meta-field” that corresponds to a supranational educational policy for all the European Union membership States, with the goal of building a “European higher education space.” The political process and the institutional reforms of each national government intends to establish the new European higher education system until 2010, with 45 countries – the number reflects current developments, including the EU membership States and 18 non-EU countries. Given the high quantity and the myriads of “national subsystems” and educational institutions involved, “quality assurance” becomes a major task in this process. We analyze, in the same way, the recent higher education changes in Brazil, where the so-called “New University” project and the Program of Support for the Restructuring and Expansion of Brazilian Federal Universities (REUNI, in Portuguese) are the clearest expressions of the reshaping of the higher education system (in accordance with the Bologna standards) after the dramatic changes made by Fernando Henrique Cardoso´s government (1995-2002) and continued by Luiz Inácio Lula da Silva´s government (2003-2006; 2007), despite some differences between both administrations

Práticas de cultivo para a cultura do abacaxi no Estado do Tocantins.

Com esta publicação, a Secretaria da Agricultura, da Pecuária e do Desenvolvimento Agrário do Tocantins e a Embrapa Mandioca e Fruticultura, com o apoio do Ministério da Agricultura Pecuária e Abastecimento, disponibilizam para o público interessado em geral, mais especificamente para os produtores de abacaxi do Estado do Tocantins, um importante conjunto de informações referentes à exploração racional dessa cultura. Esta publicação é o resultado do trabalho e da competência da equipe multidisciplinar e multi-institucional da produção integrada de abacaxi do Tocantins, composta por profissionais com alto grau de experiência e qualificação acadêmica, que dedicou, e continua dedicando, esforços e talento para desenvolver e adaptar tecnologias sustentáveis para a produção de frutos de qualidade e de acordo com os padrões atuais de exigência do mercado consumidor. O conteúdo deste trabalho é fundamentado em dez anos de atividades de pesquisa, ensino e transferência de tecnologias no agronegócio do abacaxi tocantinense, e tem como objetivo orientar as diversas classes de abacaxicultores do Estado. Os temas são apresentados de forma clara e objetiva e, por envolver todos os aspectos da cadeia produtiva da cultura, o 'Sistema de produção integrada para a cultura do abacaxi no estado do Tocantins' constitui material de consulta de elevada qualidade técnica e de grande valor informativo. Por fim, é importante destacar o papel das instituições parceiras a seguir relacionadas que, numa atuação integrada e articulada contribuíram significativamente para a o desenvolvimento de todas as tecnologias aqui apresentadas altamente importantes para as diversas regiões produtora de abacaxi do Estado Tocantins: Embrapa Mandioca e Fruticultura; Superintendência Federal de Agricultura, Pecuária e Abastecimento no Estado do Tocantins; Instituto de Desenvolvimento Rural do Estado do Tocantins (RURALTINS); Agência de Defesa Agropecuária do Tocantins (ADAPEC); Cooperativa Agroindustrial do Tocantins (COAPA);. Serviço Nacional de Aprendizagem do Cooperativismo no Estado do Tocantins (SESCOOP/TO); Serviço Brasileiro de Apoio às Micro e Pequenas Empresas (SEBRAE); Universidade Federal do Tocantins, Campus Universitário de Gurupi; Produtores rurais (abacaxicultores) do Tocantins.bitstream/item/117894/1/Doc-211.pd

Biomaterials for sequestration of growth factors and modulation of cell behavior

Growth factors (GFs) are proteins secreted by cells that regulate a variety of biological processes. Although they have long been proposed as potent therapeutic agents, their administration in a soluble form has proven costly and ineffective due to their short halfâ lives in biological environments. Biomaterialâ based approaches are increasingly sought as alternatives to improve the efficacy or, ideally, replace the need for exogenous administration of GFs in regenerative medicine strategies. The means by which these systems evolve from biomaterials for conventional controlled release of GFs to the recent extracellular matrix (ECM)â inspired approaches for sequestering these labile molecules and regulating their spatiotemporal activity and presentation are reviewed. Focus is placed on biomaterials functionalized either with ECM components, which show promiscuous GF binding, or with targeted GF ligands (antibodies, aptamers, or peptides). The potential of synthetic platforms with abiotic affinity as costâ effective alternatives to the current biological ligands is also discussed. Overall, the various GF sequestering systems developed so far have remarkably improved the activity of GFs at reduced doses and, in some cases, completely avoided the need for their exogenous administration to guide cell fates. These bioinspired concepts thus enable the rational exploration of the full therapeutic potential of GFs in regenerative medicine.The authors acknowledge the financial support from project NORTE-01- 0145-FEDER-000021 supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant Agreement No 739572— The Discoveries CTR EU, Twinning Grant agreement No 810850— Achilles, European Research Council Grant Agreement No 772817; FCT/MCTES (Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia, e Ensino Superior), and the Fundo Social Europeu através do Programa Operacional do Capital Humano (FSE/POCH) in the framework of Ph.D. Grant PD/169/2013–PD/BD/143039/2018 for S.P.B.T., and project Grant PTDC/NAN-MAT/30595/2017