Occludin phosphorylation: identification of an occludin kinase in brain and cell extracts as CK2.

In epithelial and endothelial cells, tight junctions limit paracellular flux of ions, proteins and other macromolecules. However, mechanisms regulating tight junction function are not clear. Occludin, a tight junction protein, undergoes phosphorylation changes in several situations but little is known about occludin kinases. A recombinant C-terminal fragment of occludin is a substrate for a kinase in crude extracts of brain. This activity was purified about 10000-fold and identified as CK2 (casein kinase 2) by peptide mass fingerprinting, immunoblotting and mutation of CK2 sites within the occludin sequence. CK2 is therefore a candidate kinase for regulation of occludin phosphorylation in vivo.

A computer-based auditory sequential pattern test for school-aged children.

OBJECTIVE: One type of test commonly used to assess auditory processing disorders (APD) is the Frequency Pattern Test, in which triads of pure tones of two different frequencies are presented, and participants are required to accurately report the sequence of tones, typically using a verbal response. The test is widely used clinically, but in its current format, is an under-exploited means of addressing some candidate processes, such as temporal ordering and frequency discrimination, which might be affected in APD. Here we describe a computer-based version of an auditory pattern perception test, the BirdSong Game, which was designed to be an engaging research tool for use with school-aged children. METHODS: In this study, 128 children aged 6-10 with normal peripheral hearing were tested. The BirdSong Game application was used to administer auditory sequential pattern tests, via a touch-screen presentation and response interface. A conditioning step was included prior to testing, in order to ensure that participants were able to adequately discriminate between the test tones, and reliably describe the difference using their own vocabulary. Responses were collected either verbally or manually, by having participants press cartoon images on the touch-screen in the appropriate sequence. The data was examined for age, gender and response mode differences. RESULTS: Findings on the auditory tests indicated a significant maturational effect across the age range studied, with no difference between response modes or gender. CONCLUSIONS: The BirdSong Game is sensitive to maturational changes in auditory sequencing ability, and the computer-based design of the test has several advantages which make it a potentially useful clinical and research tool.

The neuroprotective action of JNK3 inhibitors based on the 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold.

Imidazole-based structures of p38 inhibitors served as a starting point for the design of JNK3 inhibitors. Construction of a 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold led to the synthesis of the (S)-enantiomers, which exhibited p38/JNK3 IC50 ratio of up to 10 and were up to 20 times more potent inhibitors of JNK3 than the relevant (R)-enantiomers. The JNK3 inhibitory potency correlated well with inhibition of c-Jun phosphorylation and neuroprotective properties of the compounds in low K+-induced cell death of rat cerebellar granule neurones.