Costimulatory Effect of Fas in Mouse T Lymphocytes

To induce proper immune responses, T lymphocytes require two types of stimuli, antigen-specific and costimulatory signals. Among costimulatory molecules, CD28-engagement promotes the survival and proliferation of both naive and memory T cells. In addition, it is now believed that Fas may play a role in T cell activation in the human system. It is, however, controversial whether Fas can act as a costimulatory signal in the murine system. Thus, we investigated fundamental differences in the capacity to induce proliferation of T cells between Fas and CD28 in mice. Fas-mediated T cell proliferation was observed only with a full mitogenic dose of anti-CD3 antibodies, whereas CD28 engagement was able to enhance T cell proliferation in the presence of a suboptimal level of anti-CD3 antibody. Furthermore, Fas-engaged T cells showed faster response in the upregulation of CD25 and CD69 expression than CD28-engaged ones. Here, we report that Fas might play a role in mature T cell activation in the mouse system through a different mechanism from that in CD28 costimulation.     

Layered structure of UASB granules gives microbial populations resistance to toxic chemicals

To investigate the effect of granular structure on resistance to toxic chemicals in UASB (Upflow Anaerobic Sludge Blanket) reactors, normal and broken granules were examined for their ability to degrade acetate with and without the addition of toluene or trichloroethylene as a toxic chemical. Without a toxic chemical, both normal and broken granules degraded the acetate at the same volumetric degradation rate (3.21 mM h–1). However, when 500 l l–1 of toluene or trichloroethylene was added, the acetate-degradation rate of the broken granules was about a third of the rate with normal granules. Therefore, the layered structure of the UASB granules seems to give microbial populations the ability to resist toxic chemicals.     

Association of Erythropoietin-Stimulating Agent Responsiveness with Mortality in Hemodialysis and Peritoneal Dialysis Patients

Erythropoiesis-stimulating agent (ESA) responsiveness has been reported to be associated with increased mortality in hemodialysis (HD) patients. ESA requirement to obtain the same hemoglobin (Hb) level is different between HD and peritoneal dialysis (PD) patients. In this study, we investigated the impact of ESA responsiveness on mortality between both HD and PD patients. Prevalent HD and PD patients were selected from the Clinical Research Center registry for end-stage renal disease, a prospective cohort study in Korea. ESA responsiveness was estimated using an erythropoietin resistant index (ERI) (U/kg/week/g/dL). Patients were divided into three groups by tertiles of ERI. ESA responsiveness was also assessed based on a combination of ESA dosage and hemoglobin (Hb) levels. The primary outcome was all-cause mortality. A total of 1,594 HD and 876 PD patients were included. The median ESA dose and ERI were lower in PD patients compared with HD patients (ESA dose: 4000 U/week vs 6000 U/week, respectively. P<0.001, ERI: 7.0 vs 10.4 U/kg/week/g/dl, respectively. P<0.001). The median follow-up period was 40 months. In HD patients, the highest ERI tertile was significantly associated with higher risk for all-cause mortality (HR 1.96, 95% CI, 1.07 to 3.59, P = 0.029). HD patients with high-dose ESA and low Hb levels (ESA hypo-responsiveness) had a significantly higher risk of all-cause mortality (HR 2.24, 95% CI, 1.16 to 4.31, P = 0.016). In PD patients, there was no significant difference in all-cause mortality among the ERI groups (P = 0.247, log-rank test). ESA hypo-responsiveness was not associated with all-cause mortality (HR = 1.75, 95% CI, 0.58 to 5.28, P = 0.319). Our data showed that ESA hypo-responsiveness was associated with an increased risk of all-cause mortality in HD patients. However, in PD patients, ESA hypo-responsiveness was not related to all-cause mortality. These finding suggest the different prognostic value of ESA responsiveness between HD and PD patients.     

Pregnancy Loss Following Coxsackievirus B3 Infection in Mice during Early Gestation Due toHigh Expression of Coxsackievirus-Adenovirus Receptor (CAR) in Uterus and Embryo

Coxsackieviruses are important pathogens in children and the outcomes of neonatal infection can be serious or fatal. However, the outcomes of coxsackievirus infection during early gestation are not well defined. In this study, we examined the possibility of vertical transmission of coxsackievirus B3 (CVB3) and the effects of CVB3 infection on early pregnancy of ICR mice. We found that the coxsackievirus and adenovirus receptor (CAR) was highly expressed not only in embryos but also in the uterus of ICR mice. CVB3 replicated in the uterus 1 to 7 days post-infection (dpi), with the highest titer at 3 dpi. The pregnancy loss rate in mice infected with CVB3 during early gestation was 38.3%, compared to 4.7% and 2.7% in mock-infected and UV-inactivated-CVB3 infected pregnant mice, respectively. These data suggest that the uterus and embryo, which express abundant CAR, are important targets of CVB3 and that the vertical transmission of CVB3 during early gestation induces pregnancy loss.     

Immunosensor for detection of Legionella pneumophila using surface plasmon resonance

Immunosensor using surface plasmon resonance (SPR) onto self-assembled protein G layer was developed for the detection of Legionella pneumophila. A self-assembled protein G layer on gold (Au) surface was fabricated by adsorbing a mixture of 11-mercaptoundecanoic acid (MUA) and hexanethiol (molar ratio of 1:2) and the activation process for chemical binding between free amine (-NH(2)) of protein G and 11-(MUA) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDAC) in series. The formation of self-assembled protein G layer on Au substrate and the binding of antibody and antigen in series were confirmed by SPR spectroscopy. The surface morphology analyses of self-assembled protein G layer on Au substrate and monoclonal antibody against L. pneumophila immobilized on protein G were performed by atomic force microscope (AFM). The immunosensor for detection of L. pneumophila using SPR was developed and its detection limit could find up to 10(5) cells/ml.     

The role of FGF signaling in guiding coordinate movement of cell groups: Guidance cue and cell adhesion regulator?

Cell migration influences cell-cell interactions to drive cell differentiation and organogenesis. To support proper development, cell migration must be regulated both temporally and spatially. Mesoderm cell migration in the Drosophila embryo serves as an excellent model system to study how cell migration is controlled and influences organogenesis. First, mesoderm spreading transforms the embryo into a multilayered form during gastrulation and, subsequently, cells originating from the caudal visceral mesoderm (CVM) migrate along the entire length of the gut. Here we review our studies, which have focused on the role of fibroblast growth factor (FGF) signaling, and compare and contrast these two different cell migration processes: mesoderm spreading and CVM migration. In both cases, FGF acts as a chemoattractant to guide cells’ directional movement but is likely not the only signal that serves this role. Furthermore, FGF likely modulates cell adhesion properties since FGF mutant phenotypes share similarities with those of cell adhesion molecules. Our working hypothesis is that levels of FGF signaling differentially influence cells’ response to result in either directional movement or changes in adhesive properties.     

Neuroprotection by NGF and BDNF Against Neurotoxin-Exerted Apoptotic Death in Neural Stem Cells Are Mediated Through Trk Receptors,Activating PI3-Kinase and MAPK Pathways

Neural stem cells (NSC) undergo apoptotic cell death during development of nervous system and in adult. However, little is known about the biochemical regulation of neuroprotection by neurotrophin in these cells. In this report, we demonstrate that Staurosporine (STS) and Etoposide (ETS) induced apoptotic cell death of NSC by a mechanism requiring Caspase 3 activation, poly (ADP-ribose) polymerase and Lamin A/C cleavage. Although C17.2 cells revealed higher mRNA level of p75 neurotrophin receptor (p75^NTR) compared with TrkA or TrkB receptor, neuroprotective effect of both nerve growth factor (NGF) and brain-derived growth factor (BDNF) mediated through the activation of tropomyosin receptor kinase (Trk) receptors. Moreover, both NGF and BDNF induced the activation of the phosphatidylinositide 3 kinase (PI3K)/Akt and the mitogen-activated protein kinase (MAPK) pathway. Inhibition of Trk receptor by K252a reduced PARP cleavage as well as cell viability, whereas inhibition of p75^NTR did not affect the effect of neurotrophin on neurotoxic insults. Thus our studies indicate that the protective effect of NGF and BDNF in NSC against apoptotic stimuli is mediated by the PI3K/Akt and MAPK signaling pathway via Trk receptors. An erratum to this article can be found at