Teaching bioreactors operation and scale-up of bioprocesses: Multidisciplinary training in a theoretical-practical course of one week

La biotecnología es un área emergente y prioritaria para países en vías de desarrollo. Los biorreactores son un equipo fundamental y se convierten en un elemento clave para el desarrollo e innovación en bioprocesos. El conocimiento de estos equipos es fundamental para lograr el crecimiento y desarrollo de microorganismos, células animales y vegetales, e inclusive la micropropagación de plantas. En una iniciativa conjunta por parte de los autores de este artículo y con el apoyo de las respectivas instituciones académicas, desde 2012 el Curso Internacional “Escalado de Bioprocesos y Entrenamiento en Operación de Biorreactores” se ha realizado por siete ocasiones. El objetivo del curso es ofrecer a la comunidad científica de Iberoamérica un entrenamiento Teórico - Práctico en bioprocesos. Producto de este curso, se ha capacitado a más de 1400 personas a través de conferencias y a 216 personas con las habilidades prácticas en el laboratorio. El curso ha permitido fomentar una red de contactos que operan en la consultoría y en la movilidad de personas. Además, uno de los productos destacados es la integración de un libro, que contribuye como una obra de consulta en el tema.Biotechnology is an emerging and priority area for developing countries. Bioreactors are essential equipment and a key element for development and innovation in bioprocesses. The knowledge of this equipment is essential to achieve the growth of microorganisms, animal and plant cells, and even the micropropagation of plants. In a joint initiative by the authors of this article, and with the support of the respective academic institutions, the International Course “Bioprocess Scaling and Training in Bioreactor Operation” has been held seven times since 2012. The objective of this course is to offer to the Latin American scientific community a theoretical and practical training in bioprocesses. As a result of this course, more than 1400 people have been trained through lectures and 216 people with practical skills in the laboratory. The course has promoted a network of contacts that operate in consulting and people mobility. In addition to the fact that one of the outstanding products is the integration of a book.Fil: Trujillo Roldán, Mauricio A.. Universidad Nacional Autónoma de México; MéxicoFil: Orozco Sánchez, Fernando. Universidad Nacional de Colombia. Sede Medellín; ColombiaFil: Valdez Cruz, Norma A.. Universidad Nacional Autónoma de México; MéxicoFil: Rodríguez Monroy, Mario. Instituto Politécnico Nacional. Centro de Desarrollo de Productos Bióticos; MéxicoFil: Busto, Víctor Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentin

Computational Design of Inhibitors Targeting the Catalytic β Subunit of Escherichia coli FOF1-ATP Synthase

With the uncontrolled growth of multidrug-resistant bacteria, there is an urgent need to search for new therapeutic targets, to develop drugs with novel modes of bactericidal action. FoF1-ATP synthase plays a crucial role in bacterial bioenergetic processes, and it has emerged as an attractive antimicrobial target, validated by the pharmaceutical approval of an inhibitor to treat multidrug-resistant tuberculosis. In this work, we aimed to design, through two types of in silico strategies, new allosteric inhibitors of the ATP synthase, by targeting the catalytic β subunit, a centerpiece in communication between rotor subunits and catalytic sites, to drive the rotary mechanism. As a model system, we used the F1 sector of Escherichia coli, a bacterium included in the priority list of multidrug-resistant pathogens. Drug-like molecules and an IF1-derived peptide, designed through molecular dynamics simulations and sequence mining approaches, respectively, exhibited in vitro micromolar inhibitor potency against F1. An analysis of bacterial and Mammalia sequences of the key structural helix-turn-turn motif of the C-terminal domain of the β subunit revealed highly and moderately conserved positions that could be exploited for the development of new species-specific allosteric inhibitors. To our knowledge, these inhibitors are the first binders computationally designed against the catalytic subunit of FOF1-ATP synthase. Keywords: FOF1-ATP synthase; allosteric inhibition; evolutionary and PPI algorithms; peptide design; structure-based drug design

Bacterial inclusion bodies are industrially exploitable amyloids

Altres ajuts: CERCA Programme/Generalitat de CatalunyaUnderstanding the structure, functionalities and biology of functional amyloids is an issue of emerging interest. Inclusion bodies, namely protein clusters formed in recombinant bacteria during protein production processes, have emerged as unanticipated, highly tunable models for the scrutiny of the physiology and architecture of functional amyloids. Based on an amyloidal skeleton combined with varying amounts of native or native-like protein forms, bacterial inclusion bodies exhibit an unusual arrangement that confers mechanical stability, biological activity and conditional protein release, being thus exploitable as versatile biomaterials. The applicability of inclusion bodies in biotechnology as enriched sources of protein and reusable catalysts, and in biomedicine as biocompatible topographies, nanopills or mimetics of endocrine secretory granules has been largely validated. Beyond these uses, the dissection of how recombinant bacteria manage the aggregation of functional protein species into structures of highly variable complexity offers insights about unsuspected connections between protein quality (conformational status compatible with functionality) and cell physiology

Laccases: structure, function, and potential application in water bioremediation

The global rise in urbanization and industrial activity has led to the production and incorporation of foreign con‑ taminant molecules into ecosystems, distorting them and impacting human and animal health. Physical, chemical, and biological strategies have been adopted to eliminate these contaminants from water bodies under anthropo‑ genic stress. Biotechnological processes involving microorganisms and enzymes have been used for this purpose; specifcally, laccases, which are broad spectrum biocatalysts, have been used to degrade several compounds, such as those that can be found in the efuents from industries and hospitals. Laccases have shown high potential in the biotransformation of diverse pollutants using crude enzyme extracts or free enzymes. However, their application in bioremediation and water treatment at a large scale is limited by the complex composition and high salt concentra‑ tion and pH values of contaminated media that afect protein stability, recovery and recycling. These issues are also associated with operational problems and the necessity of large-scale production of laccase. Hence, more knowledge on the molecular characteristics of water bodies is required to identify and develop new laccases that can be used under complex conditions and to develop novel strategies and processes to achieve their efcient application in treating contaminated water. Recently, stability, efciency, separation and reuse issues have been overcome by the immobilization of enzymes and development of novel biocatalytic materials. This review provides recent information on laccases from diferent sources, their structures and biochemical properties, mechanisms of action, and applica‑ tion in the bioremediation and biotransformation of contaminant molecules in water. Moreover, we discuss a series of improvements that have been attempted for better organic solvent tolerance, thermo-tolerance, and operational stability of laccases, as per process requirements.Instituto de Fisiología Vegeta

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Conservation of the mycelia of the medicinal mushroom Humphreya coffeata (Berk.) Stey. in sterile distilled water

Currently, there is a growing interest in obtaining and studying the biologically active compounds from higher basidiomycetes, such as Ganoderma lucidum, Lentinus edodes and Inonotus obliquus [1], but the techniques for safe long-term storage are time-consuming, susceptible to contamination, and do not prevent genetic and physiological changes during long-term maintenance [2]. A recent strategy for obtaining biologically active compounds is using mycelia submerged cultures of these mushrooms, cultured under controlled laboratory conditions [1]. However, obtaining spores of these fungi under these conditions is difficult, and in most cases the way to obtain the spores is unknown [1]. Therefore, the strategy for mycelium storage seems to be more appropriated and simple.• A modification of Castellani's method [3–7] is proposed for higher basidiomycetes, by using the mycelium of Humphreya coffeata (Berk.) Stey., whose culture filtrates demonstrated bioactivity against lymphoma cells [8]. • H. coffeata (Berk.) Stey. was grown on malt extract agar with filter paper disks that were removed after 4 days, placed in tubes with sterile distilled water, and stored at 4 °C. • Filter paper disks with H. coffeata (Berk.) Stey. stored at 4 °C were confirmed to be viable for up to 18 months, with no visible morphological alterations