Using Model Proteins to Study Tyrosine Oxidation-Reduction: Reversible Voltammograms, Long-Lived Radicals and Detailed Design of the Radical Site

Amino acid radicals have been found as key components in a number of biological redox processes. In specific, redox−active tyrosine residues play an essential role in DNA biosynthesis and photosynthesis, among other processes. The thermodynamic and kinetic properties of one−electron redox reactions involving tyrosine have long been obscured by the highly unstable nature of the products of tyrosine oxidation. Remarkable control of these species is achieved within natural proteins. Proteins must, therefore, provide interactions to the amino acid cofactor to generate, control and direct the redox chemistry within the protein milieu. Electrochemical characterization of redox−active tyrosine residues inside natural radical proteins is highly challenging due to potential oxidation of other cofactors and residues. Numerous small−molecule models have been generated in which factors that affect tyrosine/phenol redox chemistry have been elucidated, such as hydrogen−bonding. Although these models have contributed to our knowledge about these systems, these lack the protein environment that certainly renders a stabilizing environment for these species. We have developed a de novo−designed model protein family in which to study these reactions. The family of α3X proteins consists of a well−structured, pH−stable, three−helix bundle with a single redox−active residue within the core of the protein. Construction and characterization of tyrosine−containing (α 3Y, α 3Y−K29H, and α 3Y−K36H) and tyrosine−analogue−containing (2MP− α 3C, 3MP− α 3C, and 4MP− α 3C) proteins are described in this dissertation work. Electrochemical characterization of α 3Y and 2MP− α 3C by Square Wave Voltammetry has allowed us to obtain fully reversible voltammograms and formal reduction potentials for the long−lived neutral radicals formed within these proteins. In the case of α 3Y, we have also found that the protein scaffold is intimately involved in the electron transfer process. We have also achieved the introduction of a tyrosine−histidine interacting pair in two α 3Y variants. This interacting complex is of great interest and will provide insights into how interaction with these basic residues might impact tyrosine redox chemistry within a protein scaffold. In addition, the solution NMR structure of 4MP− α 3C is reported and compared to the previously determined 2MP− α 3C structure. Key structural features are described that are likely to have a major impact on the protein redox properties

Concepciones de los profesores : perspectivas para su estudio en contextos culturales diversos

Esta comunicación realiza una revisión, de diversos trabajos sobre concepciones de los profesores, para determinar tendencias que permitan abordar investigaciones sobre sus concepciones acerca del fenómeno de la diversidad cultural y sus implicaciones en la enseñanza. Se pudo establecer que en las tres perspectivas identificadas, las concepciones del conocimiento científico, profesional y escolar aportan referenciales valiosos. Este es el caso de posiciones que involucran en sus estudios y análisis aspectos históricos, sociales y políticos de actividad científica y docente. También cuentan las historias de vida, origen étnico de los participantes, como los aspectos situacionales que están involucradas en el desarrollo de la clase

IMMUNEPOTENT CRP enhances cyclophosphamide-induced cytotoxicity through a caspase independent but ROS dependent mechanism in triple negative-breast cancer cells

Background: Breast cancer (BC) is one of the leading causes of cancer death worldwide. Cyclophosphamide (CYP) remains a mainstay in cancer therapy mainly in the triple negative breast cancer subtype (TNBC) in spite of harmful adverse effects and cell death-resistances. To face this, combination of chemotherapies and immunotherapies has been proposed. IMMUNEPOTENT CRP (ICRP) is an immunotherapy that has cytotoxic effects in several cancer cells without affecting peripheral blood mononuclear cells (PBMC) and CD3+ cells, beside improving clinical parameters of chemotherapy-treated patients. The aim of this study was to evaluate the mechanism of cytotoxicity induced by ICRP in combination with CYP (ICRP+CYP) in TNBC cells and their effect in healthy cells. Methods: For this purpose, human and murine breast adenocarcinoma, MDA-MB-231 and 4T1 cells, beside PBMC were treated for 24 hours with ICRP, CYP or ICRP+CYP in different combination ratios for the assessment of cell death. Flow cytometry was used to determine biochemical characteristics of cell death. Results: ANN/PI assays showed that ICRP+CYP induce cell cycle arrest in TNBC cells and potentiated cell death characterized by loss of mitochondrial membrane potential, reactive oxygen species (ROS) production and caspases activation. In addition, ICRP+CYP-cell death is ROS-dependent and caspases-independent in MDA-MB-231 and 4T1 cells. On the other hand, ICRP did not affect CYP-cytotoxicity in PBMC. Conclusions: For all the above, we can propose that the combination of ICRP with CYP is an effective combination therapy, promoting their use even in tumoral cells with defects on proteins implicated in the apoptotic pathway

Quantitative John–Nirenberg inequalities at different scales

Given a family Z = { · Z Q } of norms or quasi-norms with uniformly bounded triangle inequality constants, where each Q is a cube in Rn, we provide an abstract estimate of the form f − fQ,μZ Q ≤ c(μ)ψ(Z) f BMO(dμ) for every function f ∈ BMO(dμ), where μ is a doubling measure in Rn and c(μ) and ψ(Z) are positive constants depending on μ and Z, respectively. That abstract scheme allows us to recover the sharp estimate f − fQ,μL p Q, dμ(x) μ(Q) ≤ c(μ)p f BMO(dμ), p ≥ 1 for every cube Q and every f ∈ BMO(dμ), which is known to be equivalent to the John–Nirenberg inequality, and also enables us to obtain quantitative counterparts when L p is replaced by suitable strong and weak Orlicz spaces and L p(·) spaces. Besides the aforementioned results we also generalize [(Ombrosi in Isr J Math 238:571-591, 2020), Theorem 1.2] to the setting of doubling measures and obtain a new characterization of Muckenhoupt’s A∞ weightsJ. C. M.-P. is supported by the Basque Government through the BERC 2018-2021 program and by Spanish Ministry of Science, Innovation and Universities through BCAM Severo Ochoa accreditation SEV-2017-0718. He is also supported by MINECO through the MTM2017-82160-C2-1-P project funded by (AEI/FEDER, UE), acronym “HAQMEC”, through ”la Caixa” Grant, and through the MATHROCKS project, funded by European Commission with Grant Agreement Number 777778 (H2020- MSCA-RISE-2017). He is also grateful to the people of the Universidad de Buenos Aires and the Universidad Nacional del Sur for their hospitality during his visit to Argentina in 2019. E.R. is partially supported by Grants UBACyT 20020170200057BA and PIP (CONICET) 11220110101018. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant agreement No 777822. I.P.R.-R. is partially supported by Grants PICT 2018-02501 and PICT 2019-00018 (Agencia I+D+i) and by Grant UMA18-FEDERJA-002 (FEDER). Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Funding for open access charge: Universidad de Málaga / CBU

Concepciones de los profesores : perspectivas para su estudio en contextos culturales diversos

Esta comunicación realiza una revisión, de diversos trabajos sobre concepciones de los profesores, para determinar tendencias que permitan abordar investigaciones sobre sus concepciones acerca del fenómeno de la diversidad cultural y sus implicaciones en la enseñanza. Se pudo establecer que en las tres perspectivas identificadas, las concepciones del conocimiento científico, profesional y escolar aportan referenciales valiosos. Este es el caso de posiciones que involucran en sus estudios y análisis aspectos históricos, sociales y políticos de actividad científica y docente. También cuentan las historias de vida, origen étnico de los participantes, como los aspectos situacionales que están involucradas en el desarrollo de la clase

Las propuestas de conocimiento escolar : entre el conocimiento científico y el escolar

Se presentan algunos resultados de tres estudios de caso en los que se analizan consideraciones sobre el conocimiento científico como referente en la elaboración y desarrollo de las propuestas de conocimiento escolar en las clases de ciencias, así como la relación con otros posibles referentes. El análisis de las entrevistas realizadas a profesores de ciencias, de la unidad didáctica por ellos diseñada y la grabación audiovisual del desarrollo de las clases, permiten establecer posibles relaciones entre las declaraciones de los profesores sobre el conocimiento científico y las propuestas de conocimiento escolar. Los resultados permiten señalar la necesidad de analizar las particularidades epistemológicas sobre el conocimiento escolar, se plantean tres niveles diferentes en la constitución del conocimiento escolar

Incidence of complications in breast reconstruction with autologous tissue in a third level hospital

Background: The objective of this study is to analyze the incidence of complications after breast reconstruction with pedicled or free flaps at the hospital general de Mexico "Dr. Eduardo Liceaga”. Methods: A retrospective, single-center study, including 44 female patients, who underwent immediate or delayed breast reconstruction after breast cancer, between 2019 and 2020, and had at least a 2-year follow up, evaluating the association between patient risk factors (age, history of radiotherapy, presence of overweight or obesity and immediate or delayed reconstruction) with the presence of complications such as seroma, hematoma, wound infection or wound dehiscence. We analyzed data with SPSS software, v23.0. Results: There was no statistically significant difference for the presence of complications associated with risk factors studied. Conclusions: We need more prospective, multicenter studies, including larger sample and strict follow up of patients