The role of glutamate in the regulation of neurogenesis is well-established, but the role of vesicular glutamate transporters (VGLUTs) and excitatory amino acid transporters (EAATs) in controlling ...adult neurogenesis is unknown. Here we investigated the implication of VGLUTs in the differentiation of subventricular zone (SVZ)-derived neural precursor cells (NPCs). Our results show that NPCs express VGLUT1-3 and EAAT1-3 both at the mRNA and protein level. Their expression increases during differentiation closely associated with the expression of marker genes. In expression analyses we show that VGLUT1 and VGLUT2 are preferentially expressed by cultured SVZ-derived doublecortin+ neuroblasts, while VGLUT3 is found on GFAP+ glial cells. In cultured NPCs, inhibition of VGLUT by Evans Blue increased the mRNA level of neuronal markers doublecortin, B3T and MAP2, elevated the number of NPCs expressing doublecortin protein and promoted the number of cells with morphological appearance of branched neurons, suggesting that VGLUT function prevents neuronal differentiation of NPCs. This survival- and differentiation-promoting effect of Evans blue was corroborated by increased AKT phosphorylation and reduced MAPK phosphorylation. Thus, under physiological conditions, VGLUT1-3 inhibition, and thus decreased glutamate exocytosis, may promote neuronal differentiation of NPCs.
Studies about the set of positive equilibria (
E
+
) of kinetic systems have been focused on mass action, and not that much on power law kinetic (PLK) systems, even for PL-RDK systems (PLK systems ...where two reactions with identical reactant complexes have the same kinetic order vectors). For mass action, reactions with different reactants have different kinetic order rows. A PL-RDK system satisfying this property is called factor span surjective (PL-FSK). In this work, we show that a cycle terminal PL-FSK system with
E
+
≠
∅
and has independent linkage classes (ILC) is a poly-PLP system, i.e.,
E
+
is the disjoint union of log-parametrized sets. The key insight for the extension is that factor span surjectivity induces an isomorphic digraph structure on the kinetic complexes. The result also completes, for ILC networks, the structural analysis of the original complex balanced generalized mass action systems (GMAS) by Müller and Regensburger. We also identify a large set of PL-RDK systems where non-emptiness of
E
+
is a necessary and sufficient condition for non-emptiness of each set of positive equilibria for each linkage class. These results extend those of Boros on mass action systems with ILC. We conclude this paper with two applications of our results. Firstly, we consider absolute complex balancing (ACB), i.e., the property that each positive equilibrium is complex balanced, in poly-PLP systems. Finally, we use the new results to study absolute concentration robustness (ACR) in these systems. In particular, we obtain a species hyperplane containment criterion to determine ACR in the system species.
A decomposition of a chemical reaction network (CRN) is produced by partitioning its set of reactions. The partition induces networks, called subnetworks, that are "smaller" than the given CRN which, ...at this point, can be called parent network. A complex is called a common complex if it occurs in at least two subnetworks in a decomposition. A decomposition is said to be incidence independent if the image of the incidence map of the parent network is the direct sum of the images of the subnetworks' incidence maps. It has been recently discovered that the complex balanced equilibria of the parent network and its subnetworks are fundamentally connected in an incidence independent decomposition. In this paper, we utilized the set of common complexes and a developed criterion to investigate decomposition’s incidence independence properties. A framework was also developed to analyze decomposition classes with similar structure and incidence independence properties. We identified decomposition classes that can be characterized by their sets of common complexes and studied their incidence independence. Some of these decomposition classes occur in some biological and chemical models. Finally, a sufficient condition was obtained for the complex balancing of some power law kinetic (PLK) systems with incidence independent and complex balanced decompositions. This condition led to a generalization of the Deficiency Zero Theorem for some PLK systems.
Several studies have developed dynamical models to understand the underlying mechanisms of insulin signaling, a signaling cascade that leads to the translocation of glucose, the human body’s main ...source of energy. Fortunately, reaction network analysis allows us to extract properties of dynamical systems without depending on their model parameter values. This study focuses on the comparison of insulin signaling in healthy state (INSMS or INSulin Metabolic Signaling) and in type 2 diabetes (INRES or INsulin RESistance) using reaction network analysis. The analysis uses network decomposition to identify the different subsystems involved in insulin signaling (e.g., insulin receptor binding and recycling, GLUT4 translocation, and ERK signaling pathway, among others). Furthermore, results show that INSMS and INRES are similar with respect to some network, structo-kinetic, and kinetic properties. Their differences, however, provide insights into what happens when insulin resistance occurs. First, the variation in the number of species involved in INSMS and INRES suggests that when irregularities occur in the insulin signaling pathway, other complexes (and, hence, other processes) get involved, characterizing insulin resistance. Second, the loss of concordance exhibited by INRES suggests less restrictive interplay between the species involved in insulin signaling, leading to unusual activities in the signaling cascade. Lastly, GLUT4 losing its absolute concentration robustness in INRES may signify that the transporter has lost its reliability in shuttling glucose to the cell, inhibiting efficient cellular energy production. This study also suggests possible applications of the equilibria parametrization and network decomposition, resulting from the analysis, to potentially establish absolute concentration robustness in a species.
•Reaction network analysis is applied to gain insights on insulin signaling pathway.•Decomposition theory can be used to identify functional modules of insulin signaling.•Discordance in insulin-resistant suggests less restrictive interplay between species.•GLUT4 loses its robustness property (ACR) in insulin-resistant cells.
This work introduces a novel approach to study properties of positive equilibria of a chemical reaction network
N
endowed with Hill-type kinetics
K
, called a Hill-type kinetic (HTK) system
N
,
K
, ...including their multiplicity and concentration robustness in a species. We associate a unique poly-PL kinetic (PYK) system
N
,
K
PY
to the given HTK system, where PYK is a positive linear combination of PL functions. The associated system has the key property that its equilibria sets coincide with those of the Hill-type system. This allows us to identify two novel subsets of the (HTKs), called PL-equilibrated and PL-complex balanced kinetics, to which recent results on absolute concentration robustness (ACR) of species and complex balancing at positive equilibria of PL kinetic systems can be applied. Our main results also include the Shinar–Feinberg ACR Theorem for PL-equilibrated HT-RDK systems (i.e., subset of complex factorizable HTK systems), which establishes a foundation for the analysis of ACR in HTK systems, and the extension of the results of Müller and Regensburger on generalized mass action systems to PL-complex balanced HT-RDK systems. In addition, we derive the theory of balanced concentration robustness in an analogous manner to ACR for PL-equilibrated systems. Finally, we provide further extensions of our results to a more general class of kinetics, which include quotients of poly-PL functions.
This paper studies chemical kinetic systems which decompose into weakly reversible complex factorizable (CF) systems. Among power law kinetic systems, CF systems (denoted as PL-RDK systems) are those ...where branching reactions of a reactant complex have identical rows in the kinetic order matrix. Mass action and generalized mass action systems (GMAS) are well-known examples. Schmitz’s global carbon cycle model is a previously studied non-complex factorizable (NF) power law system (denoted as PL-NDK). We derive novel conditions for the existence of weakly reversible CF-decompositions and present an algorithm for verifying these conditions. We discuss methods for identifying independent decompositions, i.e., those where the stoichiometric subspaces of the subnetworks form a direct sum, as such decompositions relate positive equilibria sets of the subnetworks to that of the whole network. We then use the results to determine the positive equilibria sets of PL-NDK systems which admit an independent weakly reversible decomposition into PL-RDK systems of PLP type, i.e., the positive equilibria are log-parametrized, which is a broad generalization of a Deficiency Zero Theorem of Fortun et al. (MATCH Commun. Math. Comput. Chem. 81:621–638, 2019).
La economía mexicana se ha caracterizado por un crecimiento reducido acompañado de una elevada desigualdad del ingreso y pobreza. Con el objetivo de estimar la relación y la causalidad de la ...desigualdad y la pobreza en el crecimiento económico, se estableció un modelo de datos de panel a escala estatal, con el fin de relacionar el coeficiente de Gini y el índice de pobreza con la tasa de crecimiento del producto interno bruto (PIB). El coeficiente de la variable de la educación media superior resultó positivo, lo que sugiere que la formación educativa es relevante para promover el crecimiento. Los resultados muestran que el coeficiente de Gini y la proporción de la pobreza sobre el total de la población tienen una correlación inversa con el crecimiento económico. La prueba de Granger indica un efecto de causalidad de la desigualdad y la pobreza en el crecimiento
The NMDA antagonist memantine preferentially inhibits extrasynaptic NMDA receptors, which are overactivated upon stroke and thought to disturb neuroplasticity. We hypothesized that memantine enhances ...post-ischemic neurological recovery, brain remodeling, and plasticity. C57BL6/j mice were exposed to intraluminal middle cerebral artery occlusion. Starting 72 hours post-stroke, vehicle or memantine (4 or 20 mg/kg/day) were subcutaneously delivered over 28 days. Neurological recovery, perilesional tissue remodeling and contralesional pyramidal tract plasticity were evaluated over 49 days. Memantine, delivered at 20 but not 4 mg/kg/day, persistently improved motor-coordination and spatial memory. Secondary striatal atrophy was reduced by memantine. This delayed neuroprotection was associated with reduced astrogliosis and increased capillary formation around the infarct rim. Concentrations of BDNF, GDNF, and VEGF were bilaterally elevated by memantine in striatum and cortex. Anterograde tract tracing studies revealed that memantine increased contralesional corticorubral sprouting across the midline in direction to the ipsilesional red nucleus. In the contralesional motor cortex, the NMDA receptor subunit GluN2B, which is predominantly expressed in extrasynaptic NMDA receptors, was transiently reduced by memantine after 14 days, whereas GluN2A and PSD-95, which preferentially co-localize with synaptic NMDA receptors, were increased after 28 days. Our data suggest the utility of memantine for enhancing post-acute stroke recovery.
Absolute concentration robustness (ACR) and concordance are novel concepts in the theory of robustness and stability within Chemical Reaction Network Theory. In this paper, we have extended Shinar ...and Feinberg’s reaction network analysis approach to the insulin signaling system based on recent advances in decomposing reaction networks. We have shown that the network with 20 species, 35 complexes, and 35 reactions is concordant, implying at most one positive equilibrium in each of its stoichiometric compatibility class. We have obtained the system’s finest independent decomposition consisting of 10 subnetworks, a coarsening of which reveals three subnetworks which are not only functionally but also structurally important. Utilizing the network’s deficiency-oriented coarsening, we have developed a method to determine positive equilibria for the entire network. Our analysis has also shown that the system has ACR in 8 species all coming from a deficiency zero subnetwork. Interestingly, we have shown that, for a set of rate constants, the insulin-regulated glucose transporter GLUT4 (important in glucose energy metabolism), has stable ACR.
Linear conjugacy of chemical kinetic systems Nazareno, Allen L; Eclarin, Raymond Paul L; Mendoza, Eduardo R ...
Mathematical biosciences and engineering : MBE,
01/2019, Letnik:
16, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Two networks are said to be linearly conjugate if the solution of their dynamic equations can be transformed into each other by a positive linear transformation. The study on dynamical equivalence in ...chemical kinetic systems was initiated by Craciun and Pantea in 2008 and eventually led to the Johnston-Siegel Criterion for linear conjugacy (JSC). Several studies have applied Mixed Integer Linear Programming (MILP) approach to generate linear conjugates of MAK (mass action kinetic) systems, Bio-CRNs (which is a subset of Hill-type kinetic systems when the network is restricted to digraphs), and PL-RDK (complex factorizable power law kinetic) systems. In this study, we present a general computational solution to construct linear conjugates of any "rate constant-interaction function decomposable" (RID) chemical kinetic systems, wherein each of its rate function is the product of a rate constant and an interaction function. We generate an extension of the JSC to the complex factorizable (CF) subset of RID kinetic systems and show that any non-complex factorizable (NF) RID kinetic system can be dynamically equivalent to a CF system via transformation. We show that linear conjugacy can be generated for any RID kinetic systems by applying the JSC to any NF kinetic system that are transformed to CF kinetic system.
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