Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures.

The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures.

Molecular codes in biological and chemical reaction networks.

Shannon's theory of communication has been very successfully applied for the analysis of biological information. However, the theory neglects semantic and pragmatic aspects and thus cannot directly be applied to distinguish between (bio-) chemical systems able to process "meaningful" information from those that do not. Here, we present a formal method to assess a system's semantic capacity by analyzing a reaction network's capability to implement molecular codes.

Spatial rule-based modeling: a method and its application to the human mitotic kinetochore.

A common problem in the analysis of biological systems is the combinatorial explosion that emerges from the complexity of multi-protein assemblies. Conventional formalisms, like differential equations, Boolean networks and Bayesian networks, are unsuitable for dealing with the combinatorial explosion, because they are designed for a restricted state space with fixed dimensionality. To overcome this problem, the rule-based modeling language, BioNetGen, and the spatial extension, SRSim, have been developed.

Spinal interleukin-6 is an amplifier of arthritic pain in the rat.

Objective: Significant joint pain is usually widespread beyond the affected joint, which results from the sensitization of nociceptive neurons in the central nervous system (central sensitization). This study was undertaken to explore whether the proinflammatory cytokine interleukin-6 (IL-6) in the joint induces central sensitization, whether joint inflammation causes the release of IL-6 from the spinal cord, and whether spinal IL-6 contributes to central sensitization.

Methods: In anesthetized rats, electrophysiologic recordings of spinal cord neurons with sensory input from the knee joint were made.

Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune-mediated arthritis.

Objective: Clinical and preclinical evidence suggests that somatostatin exhibits potent antiinflammatory and antinociceptive properties. However, it is not known which of the 5 somatostatin receptor subtypes (SSTRs 1-5) is involved in these actions. The purpose of this study was to assess the effects of the stable somatostatin analogs octreotide and pasireotide (SOM230) in a mouse model of antigen-induced arthritis (AIA).

Production of pyomelanin, a second type of melanin, via the tyrosine degradation pathway in Aspergillus fumigatus.

Aspergillus fumigatus is the most important airborne fungal pathogen of immunosuppressed humans. A. fumigatus is able to produce dihydroxynaphthalene melanin, which is predominantly present in the conidia.

Apoptosis inhibition of alveolar macrophages upon interaction with conidia of Aspergillus fumigatus.

The opportunistic human pathogenic fungus Aspergillus fumigatus (Af) causes the majority of cases of invasive aspergillosis. Because Af enters the human body through inhalation of airborne conidia, the interaction of conidia with the innate immune system (alveolar macrophages) plays a key role in the etiology of aspergillosis. Therefore, it is of central interest to investigate response mechanisms of alveolar macrophages upon interaction with Af.