Structural implications of the DFD-in domain in computer-aided molecular design of MAP kinase interacting kinase 2 inhibitors.

Protein translation is a key process on cell development and proliferation that is often deregulated in cancer. MAP kinase interacting kinases 1 and 2(Mnk1/2) play a pivotal role in regulating the capdependent translation through phosphorylation ofeIF4E transcription factor. Thus, Mnk1/2 targeting have been proposed as a novel therapeutic strategy that would minimize side-effects in contrast to other therapies. For this reason, there is a growing interestin designing in silico new Mnk1/2 inhibitors which demands from reliable structural models. Interestingly,the catalytic domain of Mnk proteins are characterized by a DFD motif instead of the characteristicDFG motif of other kinases. However, Mnk2 structural models described in literature are DFG mutated and do not contain the activation loop. Molecular design techniques have been applied to obtain a structural model of the full wild type Mnk2 protein including the activation loop. The effect of the loop on the interaction mechanism of well-known ligands has been evaluated. Obtained results suggest that the presence of the activation loop is determinant for the correct prediction of the active site and it is essential for the design of new inhibitors

Lipoma of the Uterine Corpus: Exceptional Eventuality Combined with an Ovarian Thecoma

Uterine lipomas are very uncommon with symptoms that are similar to leiomyomas. Their diagnosis is always histological although some radiological methods may suggest their existence prior to surgery. They are sometimes associated with endometrial pathology, but there are no previous reported cases related to ovarian thecoma. Their prognosis is excellent. Clinical, radiological, morphologic, and immunohistochemical findings are shown which correspond to uterine lipoma associated with endometrial polyps and ovarian thecoma

Role of transport performance on neuron cell morphology

The compartmental model is a basic tool for studying signal propagation in neurons, and, if the model parameters are adequately defined, it can also be of help in the study of electrical or fluid transport. Here we show that the input resistance, in different networks which simulate the passive properties of neurons, is the result of an interplay between the relevant conductances, morphology and size. These results suggest that neurons must grow in such a way that facilitates the current flow. We propose that power consumption is an important factor by which neurons attain their final morphological appearance.Comment: 9 pages with 3 figures, submitted to Neuroscience Letter

Die Struktur der Synapsen im Nucleus dentatus des Menschen

The knowledge of the morphology of the synapse in the dentate nucleus is limited to the work of Cajal , who described the afferent fibers but not their end-formations. A. Jakob also described the afferent fibers in man with the Golgi method but was no more successful than Cajal . In this contribution the nature of the synapse was investigated with the unreduced variant of the silver carbonate technique of del Rio Hortega . The afferent fibers from the amiculum surround the neurons and their processes with a complicated network of fibers which contains numerous endbulbs and rings and form small plexus. There are three types of end-formations: a) those with an accentuation of the afferent fibers around the proximal segments of the dendrites; b) those with approximately even distribution of the afferent fibers around the pericaryon and the dendrites; c) those with numerous baskets which surround the processes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47692/1/441_2004_Article_BF00345077.pd

Update of the recommendations for the determination of biomarkers in colorectal carcinoma: National Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology

In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplifcation of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly diferentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide, which, like the previous one, will remain open to any necessary revision in the future

Neuroglia at the crossroads of homoeostasis, metabolism and signalling: evolution of the concept

Ever since Rudolf Virchow in 1858 publicly announced his apprehension of neuroglia being a true connective substance, this concept has been evolving to encompass a heterogeneous population of cells with various forms and functions. We briefly compare the 19th–20th century perspectives on neuroglia with the up-to-date view of these cells as an integral, and possibly integrating, component of brain metabolism and signalling in heath and disease. We conclude that the unifying property of otherwise diverse functions of various neuroglial cell sub-types is to maintain brain homoeostasis at different levels, from whole organ to molecular

Beyond Hebb: Exclusive-OR and Biological Learning

A learning algorithm for multilayer neural networks based on biologically plausible mechanisms is studied. Motivated by findings in experimental neurobiology, we consider synaptic averaging in the induction of plasticity changes, which happen on a slower time scale than firing dynamics. This mechanism is shown to enable learning of the exclusive-OR (XOR) problem without the aid of error back-propagation, as well as to increase robustness of learning in the presence of noise.Comment: 4 pages RevTeX, 2 figures PostScript, revised versio

Enhancing neural-network performance via assortativity

The performance of attractor neural networks has been shown to depend crucially on the heterogeneity of the underlying topology. We take this analysis a step further by examining the effect of degree-degree correlations -- or assortativity -- on neural-network behavior. We make use of a method recently put forward for studying correlated networks and dynamics thereon, both analytically and computationally, which is independent of how the topology may have evolved. We show how the robustness to noise is greatly enhanced in assortative (positively correlated) neural networks, especially if it is the hub neurons that store the information.Comment: 9 pages, 7 figure

PROXIMO-DISTAL INCREASE OF ENZYMIC ACTIVITY IN THE DORSAL SPINAL TRACTS *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65919/1/j.1471-4159.1964.tb06151.x.pd