Probabilistic model-based functional parcellation reveals a robust, fine-grained subdivision of the striatum.

The striatum is involved in many different aspects of behaviour, reflected by the variety of cortical areas that provide input to this structure. This input is topographically organized and is likely to result in functionally specific signals. Such specificity can be examined using functional clustering approaches. Here, we propose a Bayesian model-based functional clustering approach applied solely to resting state striatal functional MRI timecourses to identify intrinsic striatal functional modules. Data from two sets of ten participants were used to obtain parcellations and examine their robustness. This stable clustering was used to initialize a more constrained model in order to obtain individualized parcellations in 57 additional participants. Resulting cluster time courses were used to examine functional connectivity between clusters and related to the rest of the brain in a GLM analysis. We find six distinct clusters in each hemisphere, with clear inter-hemispheric correspondence and functional relevance. These clusters exhibit functional connectivity profiles that further underscore their homologous nature and are consistent with existing notions on segregation and integration in parallel cortico-basal ganglia loops. Our findings suggest that multiple territories within both the affective and motor regions can be distinguished solely using resting state functional MRI from these regions.

Basic domains target protein subunits of the RNase MRP complex to the nucleolus independently of complex association.

The RNase MRP and RNase P ribonucleoprotein particles both function as endoribonucleases, have a similar RNA component, and share several protein subunits. RNase MRP has been implicated in pre-rRNA processing and mitochondrial DNA replication, whereas RNase P functions in pre-tRNA processing. Both RNase MRP and RNase P accumulate in the nucleolus of eukaryotic cells. In this report we show that for three protein subunits of the RNase MRP complex (hPop1, hPop4, and Rpp38) basic domains are responsible for their nucleolar accumulation and that they are able to accumulate in the nucleolus independently of their association with the RNase MRP and RNase P complexes. We also show that certain mutants of hPop4 accumulate in the Cajal bodies, suggesting that hPop4 traverses through these bodies to the nucleolus. Furthermore, we characterized a deletion mutant of Rpp38 that preferentially associates with the RNase MRP complex, giving a first clue about the difference in protein composition of the human RNase MRP and RNase P complexes. On the basis of all available data on nucleolar localization sequences, we hypothesize that nucleolar accumulation of proteins containing basic domains proceeds by diffusion and retention rather than by an active transport process. The existence of nucleolar localization sequences is discussed.

A branch site mutation leading to aberrant splicing of the human tyrosine hydroxylase gene in a child with a severe extrapyramidal movement disorder.

We report a branch site mutation in the gene of the enzyme tyrosine hydroxylase (TH): a -24t > a substitution two bases upstream of the adenosine in the branchpoint sequence (BPS) of intron 11. As normal lariat formation is therefore prevented, alternative splicing takes place; use of the BPS of intron 12 results in skipping of exon 12, whereas the use of a cryptic branch site in intron 11 leads to partial retention of this intron in the mRNA. This leads in both cases to an aberrant protein product. In the one case, skipping of exon 12 results in the absence of 32 amino acids. In the other, retention of 36 nucleotides of intron 11 in the mRNA results in the incorporation of twelve additional amino acids. The functional consequences of this mutation for the patient, who is also heterozygous for another previously identified mutation, become apparent in a severe clinical phenotype.

A common point mutation in the tyrosine hydroxylase gene in autosomal recessive L-DOPA-responsive dystonia in the Dutch population.

This report concerns one new mutation in the tyrosine hydroxylase (TH) gene in three patients originating from three unrelated Dutch families with autosomal recessive L-DOPA-responsive dystonia (DRD). In this study, all exons of the TH gene were amplified by the polymerase chain reaction and subjected to analyses by single-strand conformation polymorphism. An aberrant migration pattern was observed for exon 6 of the TH gene in all patients. Direct sequencing of the coding region of exon 6 revealed the presence of one novel missense mutation. An a698g transition resulted in the substitution of the evolutionary conserved arginine 233 by a histidine (R233H). All patients were homozygous for the mutation. This new mutation in the TH gene was confirmed by restriction enzyme analysis with the restriction enzyme HhaI. Thus, a high proportion of defective TH alleles may be R233H in The Netherlands.

Stability of St. Louis encephalitis virus in the airborne state.

The aerosol stability of St. Louis encephalitis (SLE) virus was studied over a 6-hr period at a temperature of 21 C and relative humidity values of 23, 46, 60, and 80%. Aerosols were generated from and collected in 0.75% bovine albumin-buffered saline, and spores of Bacillus subtilis var. niger were used as the tracer to determine the physical decay of the aerosols. Aerosol samples were titrated in BHK-21 cell monolayers for surviving SLE virus. The results of this study indicated that, under the test conditions employed, relative humidity had no influence on the stability of SLE virus in the airborne state.