Phosphorylation of cysteine string protein on Serine 10 triggers 14-3-3 protein binding

Cysteine string protein (CSP) is a neuronal chaperone that maintains normal neurotransmitter exocytosis and is essential for preventing presynaptic neurodegeneration. CSP is phosphorylated in vivo on a single residue, Ser10, and this phosphorylation regulates its cellular functions, although the molecular mechanisms involved are unclear. To identify novel phosphorylation-specific binding partners for CSP, we used a pull-down approach using synthetic peptides and recombinant proteins. A single protein band was observed to bind specifically to a Ser10-phosphorylated CSP peptide (residues 4-14) compared to a non-phosphorylated peptide. This band was identified as 14-3-3 protein of various isoforms using mass spectrometry and Western blotting. PKA phosphorylation of full-length CSP protein stimulated 14-3-3 binding, and this was abolished in a Ser10-Ala mutant CSP, confirming the binding site as phospho-Ser10. As both CSP and 14-3-3 proteins are implicated in neurotransmitter exocytosis and neurodegeneration, this novel phosphorylation-dependent interaction may help maintain the functional integrity of the synapse.     

Molecular Analysis of the β-Globin Gene Cluster in the Niokholo Mandenka Population Reveals a Recent Origin of the βS Senegal Mutation

A large and ethnically well-defined Mandenka sample from eastern Senegal was analyzed for the polymorphism of the beta-globin gene cluster on chromosome 11. Five RFLP sites of the 5' region were investigated in 193 individuals revealing the presence of 10 different haplotypes. The frequency of the sickle-cell anemia causing mutation (beta(S)) in the Mandenka estimated from this sample is 11.7%. This mutation was found strictly associated with the single Senegal haplotype. Approximately 600 bp of the upstream region of the beta-globin gene were sequenced for a subset of 94 chromosomes, showing the presence of four transversions, five transitions, and a composite microsatellite polymorphism. The sequence of 22 beta(S) chromosomes was also identical to the previously defined Senegal haplotype, suggesting that this mutation is very recent. Monte Carlo simulations (allowing for a specific balancing selection model, a logistic growth of the population, and variable initial frequencies of the Senegal haplotype) were used to estimate the age of the beta(S) mutation. Resulting maximum-likelihood estimates are 45-70 generations (1,350-2,100 years) for very different demographic scenarios. Smallest confidence intervals (25-690 generations) are obtained under the hypothesis that the Mandenka population is large (N(e) >5,000) and stationary or that it has undergone a rapid demographic expansion to a current size of >5,000 reproducing individuals, which is quite likely in view of the great diversity found on beta(A) chromosomes.     

Informative and misinformative interactions in a school of fish

Quantifying distributed information processing is crucial to understanding collective motion in animal groups. Recent studies have begun to apply rigorous methods based on information theory to quantify such distributed computation. Following this perspective, we use transfer entropy to quantify dynamic information flows locally in space and time across a school of fish during directional changes around a circular tank, i.e., U-turns. This analysis reveals peaks in information flows during collective U-turns and identifies two different flows: an informative flow (positive transfer entropy) from fish that have already turned to fish that are turning, and a misinformative flow (negative transfer entropy) from fish that have not turned yet to fish that are turning. We also reveal that the information flows are related to relative position and alignment between fish and identify spatial patterns of information and misinformation cascades. This study offers several methodological contributions and we expect further application of these methodologies to reveal intricacies of self-organisation in other animal groups and active matter in general.     

An outbreak of adenovirus type 7 infection in children in Montreal

Thirteen infants and children with adenovirus type 7 infection proved by virus isolation are described. High fever, cough and dyspnea were the most frequent findings; in infants under 1 year of age wheezing was common. Four patients required artificial ventilation. Lobar collapse, consolidation and hyperinflation were frequent radiologic findings. None of the symptoms responded to antibiotic therapy or bronchodilator drugs. Three patients died (mortality rate of 23%). Pathologic findings were compatible with adenovirus type 7 pneumonia, and were characterized by a necrotizing bronchitis and bronchiolitis, patchy alveolar fibrinopurulent exudate and hyaline membrane formation. Some intra-alveolar epithelial cells showed strikingly abnormal nuclei and rare typical halo-outlined intranuclear inclusions were seen. Only one of eight survivors had evidence of significant chronic chest disease.     

Proliferative capacity and DNA content of aging human diploid cells in culture: A cytophotometric and autoradiographic analysis

Using a combination of DNA-cytophotometry and tritiated thymidine-autoradiography, we have shown that the majority of nondividing cells in serially propagated human diploid cell populations have the 2C DNA content consistent with their being arrested in the G₁ phase of the diploid cell cycle. Unlabeled 4C cells appear increasingly with time in culture. These may be arrested G₂ diploids or they may be G₁ tetraploids, since there is an associated increase in polyploidy in older cultures as evidenced by the appearance of labeled 8C cells.