A Ligand Peptide Motif Selected from a Cancer Patient Is a Receptor-Interacting Site within Human Interleukin-11

Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11Rα is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11Rα has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Electrochemical determination of antimalarial drug amodiaquine in maternal milk using a hemin-based electrode

Voltammetric analysis of amodiaquine using a hemin biosensor revealed a well-defined peak at 0.14 V (vs. Ag/AgCl), corresponding to the oxidation of amodiaquine at pH 7.0. The electrodic behavior indicated that the oxidation process was irreversible, and that it was controlled by diffusion. In addition to advantages such as high selectivity and sensitivity, the method developed could be used for the analysis of breast milk containing amodiaquine without any need for prior sample treatment, an important consideration in routine analysis laboratories. Measurements of the drug contained in breast milk were used to validate the technique. The detection limit for standard solutions was 3.30 mg L-1, and the quantification limit was 11.0 mg L-1. ©The Electrochemical Society

Impacto de biópsia pulmonar a céu aberto na insuficiência respiratória aguda refratária

OBJETIVO: Verificar o impacto dos resultados da biópsia pulmonar a céu aberto nas decisões que determinem mudanças nas estratégias de tratamento de pacientes críticos, com infiltrados pulmonares difusos e insuficiência respiratória aguda refratária, bem como na melhora de seu quadro clínico. MÉTODOS: Foram avaliados 12 pacientes com insuficiência respiratória aguda e sob ventilação mecânica, que foram submetidos à biópsia pulmonar a céu aberto (por toracotomia) após a ausência de resposta clínica ao tratamento padrão. RESULTADOS: A maior causa isolada de insuficiência respiratória aguda foi a infecção viral, identificada em 5 pacientes (40%). A avaliação pré-operatória da causa da insuficiência respiratória foi modificada em 11 pacientes (91,6%), e um diagnóstico específico foi feito em 100% dos casos. A taxa de mortalidade foi de 50%, a despeito das mudanças no regime terapêutico. Seis pacientes (50%) sobreviveram e obtiveram alta hospitalar. Todos os pacientes que obtiveram alta sobreviveram por pelo menos um ano após a biópsia pulmonar a céu aberto, totalizando uma taxa de sobrevida em um ano de 50% dentre os 12 pacientes estudados. Quanto aos pacientes que faleceram no hospital, o tempo de sobrevida após a biópsia pulmonar a céu aberto foi de 14 + 10,8 dias. CONCLUSÃO: Concluímos que a biópsia pulmonar a céu aberto é uma ferramenta útil no controle da insuficiência respiratória aguda quando não se observa melhora clínica após o tratamento padrão, já que pode resultar em um diagnóstico específico que requeira tratamento distinto, provavelmente diminuindo a taxa de mortalidade desses pacientes