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The parA and parB genes of Pseudomonas aeruginosa are located approximately 8 kb anticlockwise from oriC. ParA is a cytosolic protein present at a level of around 600 molecules per cell in exponential phase, but the level drops about fivefold in stationary phase. Overproduction of full-length ParA or the N-terminal 85 amino acids severely inhibits growth of P. aeruginosa and P. putida. Both inactivation of parA and overexpression of parA in trans in P. aeruginosa also lead to accumulation of anucleate cells and changes in motility. Inactivation of parA also increases the turnover rate (degradation) of ParB. This may provide a mechanism for controlling the level of ParB in response to the growth rate and expression of the parAB operon.The ubiquitous superfamily of Walker-type ATPases is involved in many bacterial processes (7,34,45). One subfamily of these proteins, the ParA proteins, normally functions with a second protein, ParB, and in plasmid systems the combination of ParA and ParB has been associated with better-than-random segregation of low-copy-number plasmids (6,19,23). Although the plasmid partitioning systems fall into two groups on the basis of the ATPase type of component A (type I with Walker-type ATPase and type II with actin-like ATPase), the two groups seem to be unified in the general mechanism of plasmid pairing and directional separation of plasmid molecules prior to cell division. The ParB-like protein binds a centromere-like sequence and is proposed to form pairs of the plasmid molecules (12,17,30,54). The separation of replicons and their transfer towards opposite poles of the dividing cell correlate with the ability of the ParA-like protein to form a dynamic scaffold in the cells (1,3,11,41), its ATPase activity, and its ability to interact with the ParB-parS complex.Duplication of bacterial chromosomes is part of the cell cycle events leading to cell division. Data gathered during the last decade have revealed the role of many different proteins involved in replication and segregation, as well as the spatial and temporal sequence of these processes (4, 14). However, there are still many questions concerning the directional separation of chromosomes to the progeny cells and the regulation of this process. The discovery of highly conserved homologues of ParA (Walker-type ATPase) and ParB encoded by bacterial chromosomes in close vicinity to oriC (5, 18, 36, 44, 47) suggested a role for these proteins in chromosome segregation. To date, the potential roles of both the ParA and ParB proteins in cell biology have been related to regulatory cell cycle check points (8,16,37,44,48,49), positioning of oriC domains (38, 50), separation of replicated origins (37), and the translocation of the proteins to fixed cell locations (55, 61). Studies on chromosomal ParA and ParB also revealed a lack of uniformity in their action in different organisms despite the high degree of conservation at the levels of sequence and genetic organization (5,20,21,26,32,40,44,55,56,60).The aim of the work described in th...

Deletions leading to complete or partial removal of ParB were introduced into the Pseudomonas aeruginosa chromosome. Fluorescence microscopy of fixed cells showed that ParB mutants lacking the C-terminal domain or HTH motif formed multiple, less intense foci scattered irregularly, in contrast to the one to four ParB foci per cell symmetrically distributed in wild-type P. aeruginosa. All parB mutations affected both bacterial growth and swarming and swimming motilities, and increased the production of anucleate cells. Similar effects were observed after inactivation of parA of P. aeruginosa. As complete loss of ParA destabilized its partner ParB it was unclear deficiency of which protein is responsible for the mutant phenotypes. Analysis of four parB mutants showed that complete loss of ParB destabilized ParA whereas three mutants that retained the N-terminal 90 aa of ParB did not. As all four parB mutants demonstrate the same defects it can be concluded that either ParB, or ParA and ParB in combination, plays an important role in nucleoid distribution, growth and motility in P. aeruginosa.

While the essential role of episomal par loci in plasmid DNA partitioning has long been appreciated, the function of chromosomally encoded par loci is less clear. The chromosomal parA-parB genes are conserved throughout the bacterial kingdom and encode proteins homologous to those of the plasmidic Type I active partitioning systems. The third conserved element, the centromere-like sequence called parS, occurs in several copies in the chromosome. Recent studies show that the ParAParB-parS system is a key player of a mitosis-like apparatus ensuring proper intracellular localization of certain chromosomal regions such as oriC domain and their active and directed segregation. Moreover, the chromosomal par systems link chromosome segregation with initiation of DNA replication and the cell cycle. Suggested Reviewers:Opposed Reviewers:Dear Prof. Chattoraj, Please find enclosed the revised version of the review on ParABS chromosomal systems. The manuscript has been modified according to your suggestions. I removed the controversial "mitotic-like" term from the title and replaced it in the text by mitosis-like. I am hoping you will find this version f the review acceptable for publication. Yours sincerely. Grazyna Jagura-Burdzy Cover LetterThe manuscript has been already modified according to reviewers' suggestions in its previous revised version with the exception of "the mitotic-like" term (see below). The controversial "mitotic-like" term has been removed from the title and replaced it in the text by mitosis-like (when appropriate). Additional subtle changes have been introduced according to Editor-in-Chief suggestions. *Response to ReviewsThe review presents up-to-date evidence on the role chromosomally encoded ParAParB-parS systems play in the chromosome segregation in different bacterial species highlighting their function in linking chromosome segregation with initiation of DNA replication and the cell cycle.

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Motor unit (MU) potentials were recorded from brachial biceps of healthy subjects aged 5.5-79 years. The subjects were subdivided into young (5.5-19 year) and adult (37.5-79 year) groups, between which single MU discharge characteristics were compared. Firing rates were in the ranges of 8.3-21.7 s −1 (mean 12.87 s −1 ) and 5.9-18.7 s −1 (mean 11.08 s −1 ) for young and adult groups, respectively. Standard deviations (S.D.) of interspike intervals (ISIs) were in the range 4.84-11.57 ms (mean 8.39 ms) for the young group and 4.26-12.23 ms (mean 7.76 ms) for the adult group. Both differences were statistically significant (P < 0.001). Special attention was paid to the previously developed method of ISI variability analysis, which enabled the comparison of MUs with respect to afterhyperpolarization (AHP) duration of their motoneurones (MNs). The results show that AHP duration increases gradually with increasing age, which is in line with the transformation of muscle properties towards a slower phenotype. This transformation seems to be a continuous process, covering the entire lifespan of a human being, from childhood to senescence. The results presented here are significant for their insight into the ageing process of the neuromuscular system. The age-related change in AHP duration has not been investigated previously in human studies and has been met with ambiguous results in animal studies.

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