Corticotropin (ACTH) acts directly on amygdala neurons to down-regulate corticotropin-releasing hormone gene expression.

The hormone corticotropin (ACTH) is employed as therapy for diverse neurological disorders, but the mechanisms for its efficacy remain unknown. ACTH promotes the release of adrenal steroids (glucocorticoids), and most ACTH effects on the central nervous system (CNS) have been attributed to activation of glucocorticoid receptors. However, in several human disorders, ACTH has therapeutic actions that differ qualitatively or quantitatively from those of steroids. This study tested the hypothesis that ACTH directly influences limbic neurons via the recently characterized melanocortin receptors and focused on the effects of ACTH on the expression of corticotropin-releasing hormone (CRH), a neuropeptide involved in neuroimmune functions and in certain developmental seizures. The results demonstrated that ACTH potently reduced CRH expression in amygdala neurons. This down-regulation was not abolished by experimental elimination of steroids or by blocking their receptors and was reproduced by a centrally administered ACTH fragment that does not promote steroid release. Importantly, selective blocking of melanocortin receptors prevented ACTH-induced down-regulation of CRH expression. Taken together, these data indicate that ACTH activates central melanocortin receptors to modulate CRH gene expression in amygdala, supporting the notion that direct, steroid-independent actions of ACTH may account for some of its established clinical effects on the CNS

Comparison of coronal discoloration induced by White MTA and CEM Cement

Coronal discoloration of endodontically treated teeth is a challenge in clinical dentistry. This study aimed to compare coronal discoloration induced by White Mineral Trioxide Aggregate and Calcium-enriched mixture cement. Fifty single-rooted, unrestored premolar teeth extracted for orthodontic reasons were selected. After access cavity preparation, all the root canals were instrumented with MTWO rotary files up to #40.6%. The specimens were randomly assigned to two experimental groups, White Mineral Trioxide Aggregate and Calcium-enriched mixture cement groups (n = 20), and two control groups (n = 5). In the White Mineral Trioxide Aggregate and Calcium-enriched mixture cement groups, the material was condensed via the access cavity 3 mm below the cementoenamel junction to a thickness of 3 mm. Tooth color was assessed using computer analysis of digital images. Tooth color measurements were recorded at eight time intervals: before material placement (but after tooth preparation), at 24 h, 48 h, one week, two weeks, four weeks, eight weeks, and sixteen weeks after material placement. Data were analyzed using t-test, ANOVA, repeated measure ANOVA, and Tukey HSD tests. The significance level was set at 5% for all the tests. Cervical discoloration of teeth in both experimental groups significantly increased over time (p < 0.05). However, samples in the White Mineral Trioxide Aggregate group showed more discoloration in cervical regions than Calcium-enriched mixture cement specimens after two, four, eight, and sixteen weeks (p < 0.05). Applying both White Mineral Trioxide Aggregate and Calcium-enriched mixture cement induced coronal discoloration; however, White Mineral Trioxide Aggregate samples exhibited greater cervical discoloration than Calcium-enriched mixture cement specimens after two, four, eight, and sixteen weeks

Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability.

Febrile seizures are the most common type of developmental seizures, affecting up to 5% of children. Experimental complex febrile seizures involving the immature rat hippocampus led to a persistent lowering of seizure threshold despite an upregulation of inhibition. Here we provide a mechanistic resolution to this paradox by showing that, in the hippocampus of rats that had febrile seizures, the long-lasting enhancement of the widely expressed intrinsic membrane conductance Ih converts the potentiated synaptic inhibition to hyperexcitability in a frequency-dependent manner. The altered gain of this molecular inhibition-excitation converter reveals a new mechanism for controlling the balance of excitation-inhibition in the limbic system. In addition, here we show for the first time that h-channels are modified in a human neurological disease paradigm

Febrile seizures and mechanisms of epileptogenesis: insights from an animal model.

Temporal lobe epilepsy (TLE) is the most prevalent type of human epilepsy, yet the causes for its development, and the processes involved, are not known. Most individuals with TLE do not have a family history, suggesting that this limbic epilepsy is a consequence of acquired rather than genetic causes. Among suspected etiologies, febrile seizures have frequently been cited. This is due to the fact that retrospective analyses of adults with TLE have demonstrated a high prevalence (20-->60%) of a history of prolonged febrile seizures during early childhood, suggesting an etiological role for these seizures in the development of TLE. Specifically, neuronal damage induced by febrile seizures has been suggested as a mechanism for the development of mesial temporal sclerosis, the pathological hallmark of TLE. However, the statistical correlation between febrile seizures and TLE does not necessarily indicate a causal relationship. For example, preexisting (genetic or acquired) 'causes' that result independently in febrile seizures and in TLE would also result in tight statistical correlation. For obvious reasons, complex febrile seizures cannot be induced in the human, and studies of their mechanisms and of their consequences on brain molecules and circuits are severely limited. Therefore, an animal model was designed to study these seizures. The model reproduces the fundamental key elements of the human condition: the age specificity, the physiological temperatures seen in fevers of children, the length of the seizures and their lack of immediate morbidity. Neuroanatomical, molecular and functional methods have been used in this model to determine the consequences of prolonged febrile seizures on the survival and integrity of neurons, and on hyperexcitability in the hippocampal-limbic network. Experimental prolonged febrile seizures did not lead to death of any of the seizure-vulnerable populations in hippocampus, and the rate of neurogenesis was also unchanged. Neuronal function was altered sufficiently to promote synaptic reorganization of granule cells, and transient and long-term alterations in the expression of specific genes were observed. The contribution of these consequences of febrile seizures to the epileptogenic process is discussed

Review on computational methods for Lyapunov functions

Lyapunov functions are an essential tool in the stability analysis of dynamical systems, both in theory and applications. They provide sufficient conditions for the stability of equilibria or more general invariant sets, as well as for their basin of attraction. The necessity, i.e. the existence of Lyapunov functions, has been studied in converse theorems, however, they do not provide a general method to compute them. Because of their importance in stability analysis, numerous computational construction methods have been developed within the Engineering, Informatics, and Mathematics community. They cover different types of systems such as ordinary differential equations, switched systems, non-smooth systems, discrete-time systems etc., and employ di_erent methods such as series expansion, linear programming, linear matrix inequalities, collocation methods, algebraic methods, set-theoretic methods, and many others. This review brings these different methods together. First, the different types of systems, where Lyapunov functions are used, are briefly discussed. In the main part, the computational methods are presented, ordered by the type of method used to construct a Lyapunov function

Top soil salinity prediction in South-Western part of Urmia Lake with ground water data

Drying of Urmia Lake in the north-west of Iran threatens all the agricultural lands around the Lake. Therefore, soil salinity appears to be the major threat to the agricultural lands in the area. The aim of the present study was to investigate the spatial variation of top soil salinity by taking into account of underground water quality data as secondary information. The research was performed on a grid of 500 m in an area of 5000 ha. Soil samples were gathered during the autumn of 2009 and were repeated in the spring of 2010. Electrical conductivity of soil samples was measured in a 1:2.5 soil to water suspension. Then covariance functions were build for each data set and soil salinity prediction were done on a grid of 100 m using kriging estimator with taking into account the mean variation. Afterwards sodium activity ratio derived from underground water quality database was used as covariate to develop cross-semivarograms in prediction of top soil salinity using cokriging method. Results demonstrated that soil salinity varied from values lower than 0.5 to more than 35 dSm-1 as a function of distance to the Lake. Cross-validating the results from salinity predictions using only kriging estimator to that of cokriging with sodium activity ratio data revealed that kriging offered better estimations with ME of 0.04 for autumn 2009 and -0.12 for spring 2010. Cokriging estimator had more smoother and diffused boundaries than that of kriging and resulted in more bias estimations (ME= -0.11 and -0.21 for first and second data sets). Although kriging method had better performance in top soil salinity prediction, but cokring method resulted in smoother boundaries and reduced the negative effects of mean variation in the area

TOP SOIL SALINITY PREDICTION IN SOUTH-WESTERN PART OF URMIA LAKE WITH GROUND WATER DATA

Drying of Urmia Lake in the north-west of Iran threatens all the agricultural lands around the Lake. Therefore, soil salinity appears to be the major threat to the agricultural lands in the area. The aim of the present study was to investigate the spatial variation of top soil salinity by taking into account of underground water quality data as secondary information. The research was performed on a grid of 500 m in an area of 5000 ha. Soil samples were gathered during the autumn of 2009 and were repeated in the spring of 2010. Electrical conductivity of soil samples was measured in a 1:2.5 soil to water suspension. Then covariance functions were build for each data set and soil salinity prediction were done on a grid of 100 m using kriging estimator with taking into account the mean variation. Afterwards sodium activity ratio derived from underground water quality database was used as covariate to develop cross-semivarograms in prediction of top soil salinity using cokriging method. Results demonstrated that soil salinity varied from values lower than 0.5 to more than 35 dSm-1 as a function of distance to the Lake. Cross-validating the results from salinity predictions using only kriging estimator to that of cokriging with sodium activity ratio data revealed that kriging offered better estimations with ME of 0.04 for autumn 2009 and -0.12 for spring 2010. Cokriging estimator had more smoother and diffused boundaries than that of kriging and resulted in more bias estimations (ME= -0.11 and -0.21 for first and second data sets). Although kriging method had better performance in top soil salinity prediction, but cokring method resulted in smoother boundaries and reduced the negative effects of mean variation in the area