Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis

Activation of the hepatocyte growth factor (HGF) receptor c-met results in the regulation of cell-matrix interactions, including the MAPK-dependent stimulation of epithelial cell morphogenesis. In the present study we demonstrate that HGF stimulates the localization of ERK to sites of cell-matrix interactions and that this is mediated by the tyrosine phosphorylation-dependent association of inactive ERK and the focal adhesion complex protein paxillin. In addition, paxillin was found to associate with the upstream MAP kinases Raf and MEK, resulting in a complex that can mediate localized ERK activation. Mutation of the ERK binding site in paxillin prevented HGF-stimulated ERK-paxillin association and eliminated HGF-induced cell spreading and branching process formation. These experiments reveal that paxillin-dependent ERK activation at sites of cell-matrix interaction is critical for HGF-stimulated epithelial morphogenesis.     

On some features of historical morphogenesis

The results of the analysis of the diversity dynamics and phylogenetic schemes of various taxa (from species up to classes) show that taxa of different ranks evolved as separate integral natural systems. The main trends in the diversity dynamics of classes and orders are quite different from those of genera and families. The diversity dynamics of genera and families reflect the adaptive essence of these taxonomic categories in the evolution. About five short episodes of mass appearances of genera and families took place in the Phanerozoic. The taxonomic categories of classes and orders are characterized by the archetypes of these groups, and their diversity decreased in the evolution. The appearance of these taxa is not connected with the mass extinctions and changes in the abiotic environment.     

Human memory: Novelty, association and the brain

The hippocampus has been clearly implicated in memory, but its precise role is unclear. Recent imaging studies suggest that the hippocampus is particularly concerned with the detection of novelty, as opposed to the prefrontal cortex, which seems more concerned with encoding associations.     

On optimal hierarchy of load-bearing biological materials

Load-bearing biological materials such as shell, mineralized tendon and bone exhibit two to seven levels of structural hierarchy based on constituent materials (biominerals and proteins) of relatively poor mechanical properties. A key question that remains unanswered is what determines the number of hierarchical levels in these materials. Here we develop a quasi-self-similar hierarchical model to show that, depending on the mineral content, there exists an optimal level of structural hierarchy for maximal toughness of biocomposites. The predicted optimal levels of hierarchy and cooperative deformation across multiple structural levels are in excellent agreement with experimental observations.     

The association between razor clam consumption and memory in the CoASTAL cohort

This study represents a preliminary effort to examine the potential impacts of chronic, low level domoic acid (DA) exposure on memory in the CoASTAL cohort over the first four years of data collection (Wave 1). Five hundred and thirteen adult men and women representing three Native American Tribes were studied annually with standard measures of cognition and razor clam consumption (a known vector of DA exposure) over a four-year period. In addition, a pilot metric of DA concentration exposure was used which took into consideration average DA concentration levels in source beaches, as well as the amount consumed. Based upon generalized estimating equations (GEE) analysis, controlling for age, sex, race, year, education level, tribe, and employment status, findings indicated that high razor clam consumers (15 or more per month) had isolated decrements on some measures of memory (p = 0.02–0.03), with other cognitive functions unaffected. The relatively lower memory scores were still within normal limits, and were thus not clinically significant. The pilot DA exposure metric had no association with any other aspect of cognition or behavior. There is a possible association between long-term, low-level exposure to DA through heavy razor clam consumption and memory functioning.     

On associative memory

The information storing capacity of certain associative and auto-associative memories is calculated. For example, in a 100×100 matrix of 1 bit storage elements more than 6,500 bits can be stored associatively, and more than 688,000 bits in a 1,000×1,000 matrix. Asymptotically, the storage capacity of an associative memory increases proportionally to the number of storage elements. The usefulness of associative memories, as opposed to conventional listing memories, is discussed — especially in connection with brain modelling.     

On immunological memory

Immunological memory may not represent a special characteristic of lymphocytes but simply reflect low-level responses driven by antigen that is re-encountered or persists within the host. T-cell memory is important to control persistent infections within the individual host and cannot be transmitted to offspring because of MHC polymorphism and MHC-restricted T-cell recognition. In contrast, antibody memory is transmissible from mother to offspring and may function essentially to protect offspring during the phase of physiological immuno-incompetence before, at and shortly after birth. This physiological immuno-incompetence is a result of MHC polymorphism and the dangers of the graft-versus-host and host-versus-graft reaction between mother and embryo, which necessitate immunosuppression of the mother and immuno-incompetence of the offspring. One may argue therefore that immunological memory of transmissible immunological experience is the basis on which MHC-restricted T-cell recognition could develop or coevolve.     

On recency and echoic memory

In short-term memory, the tendency for the last few (recency) items from a verbal sequence to be increasingly well recalled is more pronounced if the items are spoken rather than written. This auditory recency advantage has been quite generally attributed to echoic memory, on the grounds that in the auditory, but not the visual, mode, sensory memory persists just long enough to supplement recall of the most recent items. This view no longer seems tenable. There are now several studies showing that an auditory recency advantage occurs not only in long-term memory, but under conditions in which it cannot possibly be attributed to echoic memory. Also, similar recency phenomena have been discovered in short-term memory when the items are lip-read, or presented in sign-language, rather than heard. This article provides a partial review of these studies, taking a broad theoretical position from which these particular recency phenomena are approached as possible exceptions, to a general theory according to which recency is due to temporal distinctiveness. Much of the fresh evidence reviewed is of a somewhat preliminary nature and it is as yet unexplained by any theory of memory. The need for additional, converging experimental tests is obvious; so too is the need for further theoretical development. Several alternative theoretical resolutions are mentioned, including the possibility that enhanced recency may reflect movement, from sequentially occurring stimulus features, and the suggestion that it may be associated with the primary linguistic mode of the individuals concerned. But special weight is attached to the conjecture that all these recency phenomena might be accounted for in terms of distinctiveness or discriminability. On this view, the enhanced recency effects observed with certain modes, including the auditory mode, are attributed to items possessing greater temporal discriminability in those modes.     

Signaling in morphogenesis: transport cues in morphogenesis

Extracellular transport processes play critical roles in morphogenesis. While diffusive transport effects on morphogenesis are well illustrated in examples like blood capillary architecture and in cell morphogenetic responses to the local extracellular protein environment, the effects of fluid convection, although important in many developing and regenerating tissues, are not well understood. Convective forces are present whenever a hydrated tissue undergoes dynamic mechanical strain, and so convection could not only dominate the transport of large molecules like proteins, but might also serve as a mechanism for mechanosensing. The complex interdependence of mechanical forces, protein transport and extracellular morphogen gradients needs to be elucidated in a comprehensive way in order for the importance of transport on morphogenesis to be fully appreciated.     

On growth and form: control of cell morphogenesis in fission yeast

In the past year, we have gained considerable insight into the process of cell morphogenesis and the establishment of positional information in fission yeast. The highlights include a better understanding of the role of the microtubule cytoskeleton in the control of cell shape, as well as the identification of novel genes essential for the establishment of cell polarity and for the positioning of the site of cell division.     

Cognitive association formation in human memory revealed by spatiotemporal brain imaging

Cognitive theory posits association by juxtaposition or by fusion. We employed the measurement of event-related brain potentials (ERPs) to a concept fusion task in order to explore memory encoding of these two types of associations between word pairs, followed by a memory test for original pair order. Encoding processes were isolated by subtracting fusion task ERPs corresponding to pairs later retrieved quickly from ERPs corresponding to pairs later retrieved slowly, separately for pairs fused successfully and unsuccessfully (i.e., juxtaposed). Analyses revealed that the encoding of these two types of associations yields different ERP voltage polarities, scalp topographies, and brain sources extending over the entire time course of processing.     

ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory

The Abl-interactor (Abi) family of adaptor proteins has been linked to signaling pathways involving the Abl tyrosine kinases and the Rac GTPase. Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. Here we demonstrate that Abi2 modulates cell morphogenesis and migration in vivo. Homozygous deletion of murine abi2 produced abnormal phenotypes in the eye and brain, the tissues with the highest Abi2 expression. In the absence of Abi2, secondary lens fiber orientation and migration were defective in the eye, without detectable defects in proliferation, differentiation, or apoptosis. These phenotypes were consistent with the localization of Abi2 at adherens junctions in the developing lens and at nascent epithelial cell adherens junctions in vitro. Downregulation of Abi expression by RNA interference impaired adherens junction formation and correlated with downregulation of the Wave actin-nucleation promoting factor. Loss of Abi2 also resulted in cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. These findings support a role for Abi2 in the regulation of cytoskeletal dynamics at adherens junctions and dendritic spines, which is critical for intercellular connectivity, cell morphogenesis, and cognitive functions.     

Growth and morphogenesis in Streptomyces

In this report we propose a model of apical growth for streptomycetes. The apical tip is considered as a multilayered wall that expands by an inside-to-outside mechanism of growth. It is also assumed that each layer is made up of peptidoglycan blocks, each of them being the result of the biosynthetic activity of a wall-synthesizing unit or membrane-associated growth zone. According to our model, apical growth occurs as follows: as a consequence of the hydrostatic pressure and the cleavage of some bonds, the layers are pushed and forced to slide (one with respect to the other), migrating from the center of the tip (at the inside of the wall) towards a peripheral location (at the outside of the wall). The model also incorporates a mechanism by which apical growth can be regulated and coordinated with the replication of the chromosome.     

Bioelectromagnetics in morphogenesis

Understanding the factors that allow biological systems to reliably self-assemble consistent, highly complex, four dimensional patterns on many scales is crucial for the biomedicine of cancer, regeneration, and birth defects. The role of chemical signaling factors in controlling embryonic morphogenesis has been a central focus in modern developmental biology. While the role of tensile forces is also beginning to be appreciated, another major aspect of physics remains largely neglected by molecular embryology: electromagnetic fields and radiations. The continued progress of molecular approaches to understanding biological form and function in the post genome era now requires the merging of genetics with functional understanding of biophysics and physiology in vivo. The literature contains much data hinting at an important role for bioelectromagnetic phenomena as a mediator of morphogenetic information in many contexts relevant to embryonic development. This review attempts to highlight briefly some of the most promising (and often underappreciated) findings that are of high relevance for understanding the biophysical factors mediating morphogenetic signals in biological systems. These data originate from contexts including embryonic development, neoplasm, and regeneration.