Tyr-MIF-1 and hemorphin can act as opiate agonists as well as antagonists in the guinea pig ileum.

The brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) was tested for its effects on electrically stimulated contractions in the guinea pig ileum assay. Tyr-MIF-1 acted as an opiate agonist in reducing these contractions. Its IC50 was about 9 microM, and its effects were reversed by naloxone and CTOP. The ability of Tyr-MIF-1 also to antagonize the inhibitory effects of opiates on electrically stimulated contractions was more evident in the ileum removed from a guinea pig tolerant to morphine or after partial inactivation of opiate receptors with beta-CNA. Similar results were observed with hemorphin. The endogenous peptide Tyr-MIF-1 and the blood-derived peptide hemorphin, therefore, can act as agonists as well as antagonists in the guinea pig ileum. The effects as antagonists are best observed in preparations of ileum with reduced receptor reserve (tolerant or beta-CNA treated) and are consistent with the idea that properties of endogenous peptides as opiate antagonists are enhanced in the tolerant state.     

Macrophages as APC and the dendritic cell myth

Dendritic cells have been considered an immune cell type that is specialized for the presentation of Ag to naive T cells. Considerable effort has been applied to separate their lineage, pathways of differentiation, and effectiveness in Ag presentation from those of macrophages. This review summarizes evidence that dendritic cells are a part of the mononuclear phagocyte system and are derived from a common precursor, responsive to the same growth factors (including CSF-1), express the same surface markers (including CD11c), and have no unique adaptation for Ag presentation that is not shared by other macrophages.     

Cognitive individualism and the child as scientist program

In this paper, I examine the charge that Gopnik and Meltzoff’s ‘Child as Scientist’ program, outlined and defended in their 1997 book Words, Thoughts and Theories is vitiated by a form of ‘cognitive individualism’ about science. Although this charge has often been leveled at Gopnik and Meltzoff’s work, it has rarely been developed in any detail.I suggest that we should distinguish between two forms of cognitive individualism which I refer to as ‘ontic’ and ‘epistemic’ cognitive individualism (OCI and ECI respectively). I then argue - contra Ronald Giere – that Gopnik and Meltzoff’s commitment to OCI is relatively unproblematic, since it is an easily detachable part of their view. By contrast, and despite their explicit discussion of the issue, their commitment to ECI is much more problematic.     

Ecosystems and the Biosphere as Complex Adaptive Systems

Ecosystems are prototypical examples of complex adaptive systems, in which patterns at higher levels emerge from localized interactions and selection processes acting at lower levels. An essential aspect of such systems is nonlinearity, leading to historical dependency and multiple possible outcomes of dynamics. Given this, it is essential to determine the degree to which system features are determined by environmental conditions, and the degree to which they are the result of self-organization. Furthermore, given the multiple levels at which dynamics become apparent and at which selection can act, central issues relate to how evolution shapes ecosystems properties, and whether ecosystems become buffered to changes (more resilient) over their ecological and evolutionary development or proceed to critical states and the edge of chaos. Received 14 April 1998; accepted 26 May 1998.     

Mitotic kinases as drivers of the epithelial-to-mesenchymal transition and as therapeutic targets against breast cancers

Biological therapies against breast cancer patients with tumors positive for the estrogen and progesterone hormone receptors and Her2 amplification have greatly improved their survival. However, to date, there are no effective biological therapies against breast cancers that lack these three receptors or triple-negative breast cancers (TNBC). TNBC correlates with poor survival, in part because they relapse following chemo- and radio-therapies. TNBC is intrinsically aggressive since they have high mitotic indexes and tend to metastasize to the central nervous system. TNBCs are more likely to display centrosome amplification, an abnormal phenotype that results in defective mitotic spindles and abnormal cytokinesis, which culminate in aneuploidy and chromosome instability (known causes of tumor initiation and chemo-resistance). Besides their known role in cell cycle control, mitotic kinases have been also studied in different types of cancer including breast, especially in the context of epithelial-to-mesenchymal transition (EMT). EMT is a cellular process characterized by the loss of cell polarity, reorganization of the cytoskeleton, and signaling reprogramming (upregulation of mesenchymal genes and downregulation of epithelial genes). Previously, we and others have shown the effects of mitotic kinases like Nek2 and Mps1 (TTK) on EMT. In this review, we focus on Aurora A, Aurora B, Bub1, and highly expressed in cancer (Hec1) as novel targets for therapeutic interventions in breast cancer and their effects on EMT. We highlight the established relationships and interactions of these and other mitotic kinases, clinical trial studies involving mitotic kinases, and the importance that represents to develop drugs against these proteins as potential targets in the primary care therapy for TNBC.     

蝗灾同水旱灾害一样凶猛

小小的蝗虫怎么会成了灾?还被称为“天灾”,与水、旱并称三大自然灾害,因何而起,如何能治?