Mathematical Modeling of the Neuronal Processes in Sugar Addiction

It has already been demonstrated that the body responds to enhanced intake of sugar and is conducive to a natural form of addiction. There are substantial neurochemical changes in the brain (especially dopamine and acetylcholine systems) similar to other addictive drugs. A mathematical model comprised by a system of delayed leaky integrate-and-re equations is established to simulate the effects of sugar on a reward-circuitry. Simulations with Neuron suggest agreement with the neurobiological hypotheses of hyperactivity of neural systems due to binge sugar intake

Dioecious Silene latifolia plants show sexual dimorphism in the vegetative stage

<p>Abstract</p> <p>Background</p> <p>Prior to this study, no differences in gene expression between male and female dioecious plants in the vegetative state had been detected. Among dioecious plants displaying sexual dimorphism, <it>Silene latifolia </it>is one of the most studied species. Although many sexually dimorphic traits have been described in <it>S. latifolia</it>, all of them are quantitative, and they usually become apparent only after the initiation of flowering.</p> <p>Results</p> <p>We present RT-PCR-based evidence that in <it>S. latifolia</it>, sexual dimorphism in gene expression is present long before the initiation of flowering. We describe three ESTs that show sex-specific (two male specific and one female specific) transcription at the rosette stage before the first flowering season.</p> <p>Conclusions</p> <p>To our knowledge, this study provides the first molecular evidence of early pre-flowering sexual dimorphism in angiosperms.</p

Quantifying gene network connectivity in silico: Scalability and accuracy of a modular approach

Large, complex data sets that are generated from microarray experiments, create a need for systematic analysis techniques to unravel the underlying connectivity of gene regulatory networks. A modular approach, previously proposed by Kholodenko and co-workers, helps to scale down the network complexity into more computationally manageable entities called modules. A functional module includes a gene\u27s mRNA, promoter and resulting products, thus encompassing a large set of interacting states. The essential elements of this approach are described in detail for a three-gene model network and later extended to a ten-gene model network, demonstrating scalability. The network architecture is identified by analysing in silico steady-state changes in the activities of only the module outputs, communicating intermediates, that result from specific perturbations applied to the network modules one at a time. These steady-state changes form the system response matrix, which is used to compute the network connectivity or network interaction map. By employing a known biochemical network, the accuracy of the modular approach and its sensitivity to key assumptions are evaluated

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities