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Neste artigo, que é originalmente um discurso de posse no Instituto Otto Suhr na Universidade Livre de Berlin, Axel Honneth esboça o programa de uma teoria intersubjetiva do reconhecimento, utilizando esta última categoria como o núcleo conceitual de uma Teoria Crítica da sociedade na qual a experiência pré-cientifica de desrespeito às expectativas sociais se conecta à formação de demandas emancipatórias.
Polo-like kinase 1 (PLK1) is a crucial regulator of cell cycle progression. It is established that the activation of PLK1 depends on the coordinated action of Aurora-A and Bora. Nevertheless, very little is known about the spatiotemporal regulation of PLK1 during G2, specifically, the mechanisms that keep cytoplasmic PLK1 inactive until shortly before mitosis onset. Here, we describe PLK1 dimerization as a new mechanism that controls PLK1 activation. During the early G2 phase, Bora supports transient PLK1 dimerization, thus fine-tuning the timely regulated activation of PLK1 and modulating its nuclear entry. At late G2, the phosphorylation of T210 by Aurora-A triggers dimer dissociation and generates active PLK1 monomers that support entry into mitosis. Interfering with this critical PLK1 dimer/monomer switch prevents the association of PLK1 with importins, limiting its nuclear shuttling, and causes nuclear PLK1 mislocalization during the G2-M transition. Our results suggest a novel conformational space for the design of a new generation of PLK1 inhibitors.
O presente estudo tem como objetivo investigar a ideia de reconhecimento jurídico na teoria de Axel Honneth, o que se dará mediante análise da obra Luta por Reconhecimento. Honneth, ancorado nas teorias de Hegel e Mead, estabelece o papel do direito como esfera de reconhecimento individual e seu potencial de asseguramento do autorrespeito. Empreende-se uma reconstrução da teoria honnethiana no atinente aos papéis desempenhados pelo direito na teoria da Luta por Reconhecimento de Axel Honneth, para em seguida, a partir da leitura que o autor desenvolve da teoria de Thomas Marshall, analisar o papel desempenhado pelos direitos subjetivos fundamentais como medium de sedimentação e ampliação de novas formas de reconhecimento e cidadania.
The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS) and of adenosine triphosphate (ATP). We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to explain the underlying mechanisms controlling complex biological processes like aging and development.
Stationarity of the constituents of the body and of its functionalities is a basic requirement for life, being equivalent to survival in first place. Assuming that the resting state activity of the brain serves essential functionalities, stationarity entails that the dynamics of the brain needs to be regulated on a time-averaged basis. The combination of recurrent and driving external inputs must therefore lead to a non-trivial stationary neural activity, a condition which is fulfiled for afferent signals of varying strengths only close to criticality. In this view, the benefits of working in the vicinity of a second-order phase transition, such as signal enhancements, are not the underlying evolutionary drivers, but side effects of the requirement to keep the brain functional in first place. It is hence more appropriate to use the term 'self-regulated' in this context, instead of 'self-organized'.
We present a deterministic workflow for genotyping single and double transgenic individuals directly upon nascence that prevents overproduction and reduces wasted animals by two-thirds. In our vector concepts, transgenes are accompanied by two of four clearly distinguishable transformation markers that are embedded in interweaved, but incompatible Lox site pairs. Following Cre-mediated recombination, the genotypes of single and double transgenic individuals were successfully identified by specific marker combinations in 461 scorings.
Here we present a formal description of Biremis panamae Barka, Witkowski et Weisenborn sp. nov., which was isolated from the marine littoral environment of the Pacific Ocean coast of Panama. The description is based on morphology (light and electron microscopy) and the rbcL, psbC and SSU sequences of one clone of this species. The new species is included in Biremis due to its morphological features; i.e. two marginal rows of foramina, chambered striae, and girdle composed of numerous punctate copulae. The new species also possesses a striated valve face which is not seen in most known representatives of marine littoral Biremis species. In this study we also present the relationship of Biremis to other taxa using morphology, DNA sequence data and observations of auxosporulation. Our results based on these three sources point to an evolutionary relationship between Biremis, Neidium and Scoliopleura. The unusual silicified incunabular caps present in them are known otherwise only in Muelleria, which is probably related to the Neidiaceae and Scoliotropidaceae. We also discuss the relationship between Biremis and the recently described Labellicula and Olifantiella.
Organ-on-a-chip technology has the potential to accelerate pharmaceutical drug development, improve the clinical translation of basic research, and provide personalized intervention strategies. In the last decade, big pharma has engaged in many academic research cooperations to develop organ-on-a-chip systems for future drug discoveries. Although most organ-on-a-chip systems present proof-of-concept studies, miniaturized organ systems still need to demonstrate translational relevance and predictive power in clinical and pharmaceutical settings. This review explores whether microfluidic technology succeeded in paving the way for developing physiologically relevant human in vitro models for pharmacology and toxicology in biomedical research within the last decade. Individual organ-on-a-chip systems are discussed, focusing on relevant applications and highlighting their ability to tackle current challenges in pharmacological research.
Knowledge of consumers' willingness to pay (WTP) is a prerequisite to profitable price-setting. To gauge consumers' WTP, practitioners often rely on a direct single question approach in which consumers are asked to explicitly state their WTP for a product. Despite its popularity among practitioners, this approach has been found to suffer from hypothetical bias. In this paper, we propose a rigorous method that improves the accuracy of the direct single question approach. Specifically, we systematically assess the hypothetical biases associated with the direct single question approach and explore ways to de-bias it. Our results show that by using the de-biasing procedures we propose, we can generate a de-biased direct single question approach that is accurate enough to be useful for managerial decision-making. We validate this approach with two studies in this paper.
Background: Modulation of cortical excitability by transcranial magnetic stimulation (TMS) is used for investigating human brain functions. A common observation is the high variability of long-term depression (LTD)-like changes in human (motor) cortex excitability. This study aimed at analyzing the response subgroup distribution after paired continuous theta burst stimulation (cTBS) as a basis for subject selection.
Methods: The effects of paired cTBS using 80% active motor threshold (AMT) in 31 healthy volunteers were assessed at the primary motor cortex (M1) corresponding to the representation of the first dorsal interosseous (FDI) muscle of the left hand, before and up to 50 min after plasticity induction. The changes in motor evoked potentials (MEPs) were analyzed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM) and computed ABC analysis.
Results: The probability density distribution of the MEP changes from baseline was tri-modal, showing a clear separation at 80.9%. Subjects displaying at least this degree of LTD-like changes were n = 6 responders. By contrast, n = 7 subjects displayed a paradox response with increase in MEP. Reassessment using ABC analysis as alternative approach led to the same n = 6 subjects as a distinct category.
Conclusion: Depressive effects of paired cTBS using 80% AMT endure at least 50 min, however, only in a small subgroup of healthy subjects. Hence, plasticity induction by paired cTBS might not reflect a general mechanism in human motor cortex excitability. A mathematically supported criterion is proposed to select responders for enrolment in assessments of human brain functional networks using virtual brain lesions.