Aggregatibacter actinomycetemcomitans induces detachment and death of human gingival epithelial cells and fibroblasts via elastase release following leukotoxin‐dependent neutrophil lysis

Aggregatibacter actinomycetemcomitans is considered to be associated with periodontitis. Leukotoxin (LtxA), which destroys leukocytes in humans, is one of this bacterium's major virulence factors. Amounts of neutrophil elastase (NE), which is normally localized in the cytoplasm of neutrophils, are reportedly increased in the saliva of patients with periodontitis. However, the mechanism by which NE is released from human neutrophils and the role of NE in periodontitis is unclear. In the present study, it was hypothesized that LtxA induces NE release from human neutrophils, which subsequently causes the breakdown of periodontal tissues. LtxA‐treatment did not induce significant cytotoxicity against human gingival epithelial cells (HGECs) or human gingival fibroblasts (HGFs). However, it did induce significant cytotoxicity against human neutrophils, leading to NE release. Furthermore, NE and the supernatant from LtxA‐treated human neutrophils induced detachment and death of HGECs and HGFs, these effects being inhibited by administration of an NE inhibitor, sivelestat. The present results suggest that LtxA mediates human neutrophil lysis and induces the subsequent release of NE, which eventually results in detachment and death of HGECs and HGFs. Thus, LtxA‐induced release of NE could cause breakdown of periodontal tissue and thereby exacerbate periodontitis.     

Skill-Specific Changes in Somatosensory Nogo Potentials in Baseball Players

Athletic training is known to induce neuroplastic alterations in specific somatosensory circuits, which are reflected by changes in somatosensory evoked potentials and event-related potentials. The aim of this study was to clarify whether specific athletic training also affects somatosensory Nogo potentials related to the inhibition of movements. The Nogo potentials were recorded at nine cortical electrode positions (Fz, Cz, Pz, F3, F4, C3, C4, P3 and P4) in 12 baseball players (baseball group) and in 12 athletes in sports, such as track and field events and swimming, that do not require response inhibition, such as batting for training or performance (sports group). The Nogo potentials and Go/Nogo reaction times (Go/Nogo RTs) were measured under a somatosensory Go/Nogo paradigm in which subjects were instructed to rapidly push a button in response to stimulus presentation. The Nogo potentials were obtained by subtracting the Go trial from the Nogo trial. The peak Nogo-N2 was significantly shorter in the baseball group than that in the sports group. In addition, the amplitude of Nogo-N2 in the frontal area was significantly larger in the baseball group than that in the sports group. There was a significant positive correlation between the latency of Nogo-N2 and Go/Nogo RT. Moreover, there were significant correlations between the Go/Nogo RT and both the amplitude of Nogo-N2 and Nogo-P3 (i.e., amplitude of the Nogo-potentials increases with shorter RT). Specific athletic training regimens may induce neuroplastic alterations in sensorimotor inhibitory processes.     

SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration

After significant injury, the liver must maintain homeostasis during the regenerative process. We hypothesized the existence of mechanisms to limit hepatocyte proliferation after injury to maintain metabolic and synthetic function. A screen for candidates revealed suppressor of cytokine signaling 2 (SOCS2), an inhibitor of growth hormone (GH) signaling, was strongly induced after partial hepatectomy. Using genetic deletion and administration of various factors we investigated the role of SOCS2 during liver regeneration. SOCS2 preserves liver function by restraining the first round of hepatocyte proliferation after partial hepatectomy by preventing increases in growth hormone receptor (GHR) via ubiquitination, suppressing GH pathway activity. At later times, SOCS2 enhances hepatocyte proliferation by modulating a decrease in serum insulin-like growth factor 1 (IGF-1) that allows GH release from the pituitary. SOCS2, therefore, plays a dual role in modulating the rate of hepatocyte proliferation. In particular, this is the first demonstration of an endogenous mechanism to limit hepatocyte proliferation after injury.     

The bacterial cell division protein FtsZ forms rings in swarmer cells of Proteus mirabilis

Bacterial FtsZ assembles and constricts after chromosomal segregation in the course of cell division. Here we examined the localization of FtsZ in multinucleated swarmer cells of Proteus mirabilis by immunostaining. FtsZ was found to localize to the point of karyomitosis in swarmer cells of P. mirabilis, which is equivalent to filamentous mutants of Escherichia coli defective in the ftsI or ftsQ genes that are involved in later steps of cell division. Thus our findings suggest that the appearance of swarmer cells results from cellular functions immediately after FtsZ assembly.     

Identification of Mutations Involved in the Requirement of Potassium for Growth of Typical Melissococcus plutonius Strains

Melissococcus plutonius is a fastidious honeybee pathogen, and the addition of KH₂PO₄ to culture medium is required for its growth. Using genome sequences and a newly developed vector, we showed that mutations in genes encoding Na⁺/H⁺ antiporter and cation-transporting ATPase are involved in the potassium requirement for growth.     

ATM regulates Cdt1 stability during the unperturbed S phase to prevent re-replication

Ataxia-telangiectasia mutated (ATM) plays crucial roles in DNA damage responses, especially with regard to DNA double-strand breaks (DSBs). However, it appears that ATM can be activated not only by DSB, but also by some changes in chromatin architecture, suggesting potential ATM function in cell cycle control. Here, we found that ATM is involved in timely degradation of Cdt1, a critical replication licensing factor, during the unperturbed S phase. At least in certain cell types, degradation of p27^Kip1 was also impaired by ATM inhibition. The novel ATM function for Cdt1 regulation was dependent on its kinase activity and NBS1. Indeed, we found that ATM is moderately phosphorylated at Ser1981 during the S phase. ATM silencing induced partial reduction in levels of Skp2, a component of SCF^Skp2 ubiquitin ligase that controls Cdt1 degradation. Furthermore, Skp2 silencing resulted in Cdt1 stabilization like ATM inhibition. In addition, as reported previously, ATM silencing partially prevented Akt phosphorylation at Ser473, indicative of its activation, and Akt inhibition led to modest stabilization of Cdt1. Therefore, the ATM-Akt-SCF^Skp2 pathway may partly contribute to the novel ATM function. Finally, ATM inhibition rendered cells hypersensitive to induction of re-replication, indicating importance for maintenance of genome stability.