The identification of Smad proteins as molecular components of the transforming growth factor-β (TGF-β) signaling cascade has enhanced our understanding of how ligand-mediated activation of TGF-β receptors leads to modulation of target gene transcription. Recent studies have identified a distinct, structurally related class of Smads which inhibits, rather than transduces, TGF-β family signals. The molecular mechanism of action and the exact signaling pathways that are targeted by antagonistic Smads are not completely understood. These proteins appear to participate in autoregulatory negative (...) feedback loops in which signaling initiated by specific TGF-β family ligands induces the expression of an inhibitory Smad that then functions to modulate the amplitude or duration of signaling. Negative feedback circuits such as these play important roles in fine-tuning the activity of multifunctional signaling molecules during embryonic patterning and in response to pathologic stimuli in adults. BioEssays 21:382–390, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

This study is aimed to address the problems associated with questionnaire-based research. Twelve hypothetical cases are presented and checked for ethical validity. The problems are categorized under seven headings: Whether the participation of the subject is truly voluntary; whether consent to participate in the study has been obtained or proxy consent is required; whether consent to participate has been obtained from "authentic" participants and their privacy is protected; whether participants are fully informed before they consent to participate; whether the validity (...) of questionnaire-based research has been determined in terms of its possible harm; how the roles of the research ethics committee are defined; and what content should be presented in reports and articles. It is important that the ethics of questionnaire-based research should be reviewed with consideration to maintaining a balance between the protection of a subject's human rights and the promotion of research for the improvement of medical science and health care. (shrink)

Specificities of enzymes involved in plant specialized metabolism, including flavonoid biosynthesis, are generally promiscuous. This enzyme promiscuity has served as an evolutionary basis for new enzyme functions and metabolic pathways in land plants adapting to environmental challenges. This phenomenon may lead, however, to inefficiency in specialized metabolism and adversely affect metabolite‐mediated plant survival. How plants manage enzyme promiscuity for efficient specialized metabolism is, thus, an open question. Recent studies of flavonoid biosynthesis addressing this issue have revealed a conserved strategy, namely, (...) a homolog of chalcone isomerase with no catalytic activity binds to chalcone synthase, a key flavonoid pathway enzyme, to narrow (or rectify) the enzyme's highly promiscuous product specificity. Reducing promiscuity via specific protein–protein interactions among metabolic enzymes and proteins may be a solution adopted by land plants to achieve efficient operation of specialized metabolism, while the intrinsic promiscuity of enzymes has likely been retained incidentally. (shrink)

In 1981, the Atlantic Council's Energy Policy Committee, in collaboration with the Japanese Committee for Energy Policy Promotion and the Japanese Institute of Energy Economics, published a joint policy paper entitled 'U.S.-Japan Energy Relationships in the 1980s.'.

Trata-se de uma resenha da tradução de Celi Hirata das Questões sobre a Liberdade, a Necessidade e o Acaso de Thomas Hobbes.

Carbon and nitrogen are essential elements for life. Glucose as a carbon source and glutamine as a nitrogen source are important nutrients for cell proliferation. About 100 years ago, it was discovered that cancer cells that have acquired unlimited proliferative capacity and undergone malignant evolution in their host manifest a cancer‐specific remodeling of glucose metabolism (the Warburg effect). Only recently, however, was it shown that the metabolism of glutamine‐derived nitrogen is substantially shifted from glutaminolysis to nucleotide biosynthesis during malignant progression (...) of cancer—which might be referred to as a “second” Warburg effect. In this review, address the mechanism and relevance of this metabolic shift of glutamine‐derived nitrogen in human cancer. We also examine the clinical potential of anticancer therapies that modulate the metabolic pathways of glutamine‐derived nitrogen. This shift may be as important as the shift in carbon metabolism, which has long been known as the Warburg effect. (shrink)

O presente estudo argumenta que, para Hobbes, a retórica constituiu-se como um importante aparato linguístico e conceitual disponível em seu tempo, sobretudo para a descrição dos fenômenos físicos na ciência experimental nascente no contexto do século XVII inglês. Considerando que os parâmetros epistêmicos na descrição desta ciência estavam por se desenvolver, Hobbes buscou soluções nas doutrinas das artes do bem falar, a começar em sua antropologia. A noção de conato em Hobbes indica o peso da tradição retórica clássica em sua (...) filosofia, com destaque para Aristóteles, os estoicos e Quintiliano. Veremos como a retórica, articulada à física e à ética, constituiu um relevante paradigma de expressão e de investigação de Thomas Hobbes sobre o conato e vai além do ornamento do texto em seu estudo sobre os corpos. (shrink)

Many studies have reported neural correlates of visual awareness across several brain regions, including the sensory, parietal, and frontal areas. In most of these studies, participants were instructed to explicitly report their perceptual experience through a button press or verbal report. It is conceivable, however, that explicit reporting itself may trigger specific neural responses that can confound the direct examination of the neural correlates of visual awareness. This suggests the need to assess visual awareness without explicit reporting. One way to (...) achieve this is to develop a technique to predict the visual awareness of participants based on their peripheral responses. Here, we used eye movements and pupil sizes to decode trial-by-trial changes in the awareness of a stimulus whose visibility was deteriorated due to adaptation-induced blindness. In the experiment, participants judged whether they perceived a target stimulus and rated the confidence they had in their perceptual judgment, while their eye movements and pupil sizes were recorded. We found that not only perceptual decision but also perceptual confidence can be separately decoded from the eye movement and pupil size. We discuss the potential of this technique with regard to assessing visual awareness in future neuroimaging experiments. (shrink)