The nervous system might 'orthogonalize' to discriminate

It is still unclear how information is actually stored in biological neural networks. We propose here that information could be first orthogonalized and then stored. This could happen in a manner similar to how a set of vectors is transformed into a set of orthogonalized (i.e. mutually perpendicular) vectors. Orthogonalization may overcome the limits of conventional artificial networks, particularly the catastrophic interference caused by interference between stored inputs. The features needed to allow orthogonalization are common to biological networks, suggesting that it may be a common network mechanism. To illustrate this hypothesis, we characterize the underlying features that an archetypal biological network must have in order to perform orthogonalization, and point out that a number of actual networks show this archetypal network organization.     

Neural rate equations for bursting dynamics derived from conductance-based equations

A method of obtaining rate equations from conductance-based equations is developed and applied to fast-spiking and bursting neocortical neurons. It involves splitting systems of conductance-based equations into fast and slow subsystems, and averaging the effects of fast terms that drive the slowly varying quantities by showing that their average is closely proportional to the firing rate. The dependence of the firing rate on the injected current is then approximated in the analysis. The resulting behavior of the slow variables is then substituted back into the fast equations, with the further approximation of replacing the fast voltages in these terms by effective values. For bursting neurons the method yields two coupled limit-cycle oscillators: a self-exciting oscillator for the slow variables that commences limit-cycle oscillations at a critical current and modulates a fast spike-generating oscillator, thereby leading to slowly modulated bursts with a group of spikes in each burst. The dynamics of these coupled oscillators are then verified against those of the conductance-based equations. Finally, it is shown how to place the results in a form suitable for use in mean-field equations for neural population dynamics.     

Neural invasion in pancreatic cancer: a mutual tropism between neurons and cancer cells

Neural invasion by pancreatic cancer cells (PCC) worsens the prognosis and frequently limits curative resection. We established a novel in-vitro model in which T3M4-PCCs were co-cultured with either isolated myenteric plexus cells (MP) or dorsal root ganglia (DRG) of newborn rats within a three-dimensional extracellular matrix gel. The close vicinity of MP or DRG to T3M4-PCCs induced early morphologic changes on T3M4-PCCs at the migration front prior to the migration process with elongated and neurite-targeting PCCs, compared to round and non-grouping at the non-migrating front. T3M4-PCCs built cancer-cell clusters around the DRG or MP, a process which was accelerated by increasing number of T3M4-PCCs or neurons. These findings indicate that neuro-cancer interactions start prior to PCC migration and induce evident changes in cancer and nerve biology. These findings can be reproduced within the introduced 3D in-vitro migration assay which allows investigation in the early pathogenesis of neural PCC invasion.     

Aggression frequency and intensity, independent of testosterone levels, relate to neural activation within the dorsolateral subdivision of the ventromedial hypothalamus in the tree lizard Urosaurus ornatus

The mechanisms by which testosterone regulates aggression are unclear and may involve changes that alter the activity levels of one or more brain nuclei. We estimate neural activity by counting immunopositive cells against phosphorylated cyclic AMP response element binding protein (pCREB). We demonstrate increased pCREB immunoreactivity within the dorsolateral subdivision of the ventromedial hypothalamus (VMHdl) following an aggressive encounter in male tree lizards Urosaurus ornatus. This immunoreactivity is induced both by exposure to and performance of aggressive behaviors. This dual activation of the VMHdl suggests its possible role as an integration center for assessment and expression of aggressive behavior. Furthermore, pCREB induction was greater in encounters involving higher frequency and intensity of aggressive display, demonstrating a direct relationship between neural activation and behavior. The VMHdl is also rich in steroid receptors. In a second experiment involving hormone manipulations, testosterone treatment increased aggression levels, though it did not increase the number of pCREB positive cells within the VMHdl. This lack of an effect of testosterone on pCREB induction within the VMHdl may be due to induction arising from the behaviors of conspecifics (especially in low-testosterone, low-aggression individuals), variation in aggression mediated by other variables, or regulation of aggression by circuits outside of the VMHdl. Together, these findings support a notion of the VMHdl as a nucleus involved in integrating afferent and efferent information within the neural aggression-control circuit.     

Efficiency of neural networks for prediction of in vitro culture conditions and inoculum properties for optimum productivity

This study represents an ANN based computational scheming of physical, chemical and biological parameters at flask level for mass multiplication of plants through micropropagation using bioreactors of larger volumes. The optimal culture environment at small scale for Glycyrrhiza plant was predicted by using neural network approach in terms of pH and volume of growth medium per culture flask, incubation room temperature and month of inoculation along with inoculum properties in terms of inoculum size, fresh weight and number of explant per flask. This kind of study could be a model system in commercial propagation of various economically important plants in bioreactors using tissue culture technique. In present course of study the ANN was trained by implementing MATLAB neural network. A feed-forward back propagation type network was created for input vector (seven input elements), with single hidden layer (seven nodes) and one output unit in output layer. The ‘tansig’ and ‘purelin’ transfer functions were adapted for hidden and output layers respectively. The four training functions viz. traingda, trainrp, traincgf, traincgb were randomly selected to train four networks which further examined with available dataset. The efficiency of neural networks was concluded by the comparison of results obtained from this study with that of empirical data obtained from the detailed tissue culture experiments and designated as Target set (mean fresh weight biomass per culture flask after 40 days of in vitro culture duration). Efficiency of networks for better training initialization was judged on the basis of comparative analysis of ‘Mean Square Error at zero epoch’ for each network trained in which the least error at initial point was observed with trainrp followed by traincgb and traincgf. A comparative assessment between experimental target data range obtained from wet lab practice and all trained network output range for the efficiency of trained networks for least deviation from target range revealed the output range of network ‘trainrp’ was closest to the empirical target range while least comparison was worked out from network ‘traincgb’ which had output range more than the target decided and ultimately showed meaningless result.     

Drosophila Lin-7 is a component of the Crumbs complex in epithelia and photoreceptor cells and prevents light-induced retinal degeneration

The Drosophila Crumbs protein complex is required to maintain epithelial cell polarity in the embryo, to ensure proper morphogenesis of photoreceptor cells and to prevent light-dependent retinal degeneration. In Drosophila, the core components of the complex are the transmembrane protein Crumbs, the membrane-associated guanylate kinase (MAGUK) Stardust and the scaffolding protein DPATJ. The composition of the complex and some of its functions are conserved in mammalian epithelial and photoreceptor cells. Here, we report that Drosophila Lin-7, a scaffolding protein with one Lin-2/Lin-7 (L27) domain and one PSD-95/Dlg/ZO-1 (PDZ) domain, is associated with the Crumbs complex in the subapical region of embryonic and follicle epithelia and at the stalk membrane of adult photoreceptor cells. DLin-7 loss-of-function mutants are viable and fertile. While DLin-7 localization depends on Crumbs, neither Crumbs, Stardust nor DPATJ require DLin-7 for proper accumulation in the subapical region. Unlike other components of the Crumbs complex, DLin-7 is also enriched in the first optic ganglion, the lamina, where it co-localizes with Discs large, another member of the MAGUK family. In contrast to crumbs mutant photoreceptor cells, those mutant for DLin-7 do not display any morphogenetic abnormalities. Similar to crumbs mutant eyes, however, DLin-7 mutant photoreceptors undergo progressive, light-dependent degeneration. These results support the previous conclusions that the function of the Crumbs complex in cell survival is independent from its function in photoreceptor morphogenesis.     

A synthetic peptide corresponding to residues 301-320 of human Wnt-1 promotes PC12 cell adhesion and hippocampal neural stem cell differentiation

Wnt signaling cascades play a crucial role in the maintenance of stem cell niches in many tissues as well as in embryonic patterning and cell-fate determination. Wnt signaling pathways have been well studied; however, the precise binding mechanism of Wnt protein to its receptor has not yet been clarified. Here we show the design and synthesis of seven novel peptide candidates for a receptor-binding site of human Wnt-1 based on its hydrophilicity and beta-turn profiles. Among these Wnt-derived peptides, only WP7, which corresponds to residues 301-320 of human Wnt-1, bound to the soluble receptor for Wnt-1, mouse Frizzled-1/Fc chimera, promoted PC12 cell adherence, increased level of cytosolic beta-catenin in PC12 cells, and induced adhesion and neuronal differentiation of hippocampal neural precursor cells. These results suggest that residues 301-320 of human Wnt-1 is one of the receptor-binding sites and that WP7 may activate the canonical Wnt pathway. When combined with an appropriate matrix, the action of this Wnt-derived peptide, WP7, can be limited to within a location, and therefore could be useful in the regeneration of many tissues, without fear of tumor generation.     

Kallikrein-kinin in stem cell therapy

The tissue kallikrein-kinin system exerts a wide spectrum of biological activities in the cardiovascular, renal and central nervous systems. Tissue kallikrein-kinin modulates the proliferation, viability, mobility and functional activity of certain stem cell populations, namely mesenchymal stem cells(MSCs), endothelial progenitor cells(EPCs), mononuclear cell subsets and neural stem cells. Stimulation of these stem cells by tissue kallikrein-kinin may lead to protection against renal, cardiovascular and neural damage by inhibiting apoptosis, inflammation, fibrosis and oxidative stress and promoting neovascularization. Moreover, MSCs and EPCs genetically modified with tissue kallikrein are resistant to hypoxia- and oxidative stress-induced apoptosis, and offer enhanced protective actions in animal models of heart and kidney injury and hindlimb ischemia. In addition, activation of the plasma kallikrein-kinin system promotes EPC recruitment to the inflamed synovium of arthritic rats. Conversely, cleaved high molecular weight kininogen, a product of plasma kallikrein, reduces the viability and vasculogenic activity of EPCs. Therefore, kallikrein-kinin provides a new approach in enhancing the efficacy of stem cell therapy for human diseases.     

The aberrant spermatogenesis of the Haplothrips simplex (Buffa) (Thysanoptera): ultrastructural study

The aberrant spermatogenesis of the haploid insect Haplothrips simplex (Thysanoptera) is described. The process, which occurs in the pupal instars, is characterized by two mitotic divisions, the second of which gives rise to two different-sized spermatids: the larger spermatids have a nucleus with diffuse chromatin and proceed into spermiogenesis, while the small spermatids have pycnotic nuclei and degenerate. Both types of spermatids contain two centrioles parallely rather than orthogonally oriented. The occurrence of two centrioles supports a close relationship between Thysanoptera and Phthyraptera. Before the beginning of spermiogenesis, however, the functional spermatids show the unusual presence of a third parallel centriole which is formed by the duplication of one of the two pre-existing centrioles.