Differential effect of lithium on the circadian oscillator in young and old hamsters

Lithium is one of the most commonly used drugs in the prophylaxis and treatment of bipolar disorder. It is also known to lengthen circadian period in several organisms. Previously, we reported that there was the association between lengthening circadian period by lithium and GSK-3 protein and its enzyme activity in the mouse suprachiasmatic nucleus (SCN). In this study, we show that lithium affects the circadian oscillator in young and old hamster SCN, in an age-dependent manner. We found that basal levels of phosphorylated GSK-3 (pGSK-3) protein expression in old hamsters are much lower than that in young hamsters. Furthermore, in the old hamsters, lithium did not affect the period of the locomotor activity rhythm or pGSK-3 expression, while changing period and pGSK-3 in the younger animals. These results indicate that the content of pGSK-3 in the SCN has an important role in age-dependent effects of lithium on the circadian oscillator.     

High production of (2s,3s)-3-hydroxy-2-methylbutanoate by immobilized plant cells of Marchantia polymorpha

Cultured plant cells of Marchantia polymorpha were examined for their ability to reduce beta-keto ester, 2-methyl-3-oxobutanoate. The cells reduced ethyl 2-methyl-3-oxobutanoate to predominantly yield the anti-product, ethyl (2S,3S)-3-hydroxy-2-methylbutanoate, with 92% diastereomeric excess and over 99% enantiomeric excess. The use of immobilized cells of M. polymorpha in calcium alginate gel improved the diastereomeric excess of the product (97% de). In addition, the large-scale reduction of 75 g of ethyl 2-methyl-3-oxobutanoate with immobilized M. polymorpha gave the product with 97% de and >99% ee in 92% yield.     

Suppression of the bacterial antigen-specific T cell response and the dendritic cell migration to the lymph nodes by osteopontin

Osteopontin (OPN) has been reported to enhance the interferon (IFN)-gamma-producing Th1-type T cell response through the induction of interleukin (IL)-12 and the suppression of IL-10. We therefore investigated whether OPN could enhance Th1 induction by vaccination against bacterial antigen in vivo. Unexpectedly, the co-inoculation of OPN suppressed the induction of IFN-gamma-producing CD4(+) T cells and T cell proliferative response after the subcutaneous heat-killed Listeria monocytogenes(HKLM) immunization. These results suggest that OPN down-regulates T cell priming. Since dendritic cells (DC) play a pivotal role in T cell priming, we next analyzed the effects of OPN on DC. The addition of OPN into the culture of either bone marrow-derived immature DC or an immature DC line JAWSII showed no effects on the expression of MHC class II, CD80, and CD86 molecules before and after HKLM stimulation. Consistently, in vitro OPN-treated DC showed a normal antigen-presenting function to an established Listeria-specific Th1-type T cells. However, when the DC were transferred into the footpad with HKLM and OPN, the migration of the transferred DC into the regional LN was suppressed in comparison to the DC transferred with HKLM alone. Furthermore, the addition of OPN into the culture of the DC line and HKLM severely suppressed the HKLM-induced expression of CCR7 chemokine receptor which is an important factor in the migration of DC into LN. All the results suggest the existence of an OPN-mediated negative feedback mechanism in the T cell immune response through the regulation of DC migration.     

Identification of active sequences in human laminin α5 G domain

Human laminin‐511 (α5β1γ1) and its truncated protein, laminin‐511 E8 fragment, bind to integrin α6β1 and have been widely used for embryonic stem cell and induced pluripotent stem cell culture under feeder‐free conditions. In this study, we focused on human laminin α5 chain G domain, which is thought to be critical for the biological functions of laminin‐511, and screened its biologically active sequences using a synthetic peptide library. We synthesized 115 peptides (hA5G1‐hA5G115) covering the entire laminin α5 chain G domain and evaluated cell attachment activity using both the peptide‐coated plate and peptide‐chitosan matrix (peptide‐ChtM) assays. Seventeen peptides demonstrated cell attachment activity in the assays. Both hA5G18 and hA5G26‐coated plates and hA5G74‐ChtMs promoted integrin β1‐mediated cell attachment. These findings are useful for the study of molecular mechanisms of laminin‐511, and the active peptides have a potential for use as a molecular probe for cell adhesion receptors.     

Virucidal Effect of Cold Atmospheric Gaseous Plasma on Feline Calicivirus,a Surrogate for Human Norovirus

Minimal food-processing methods are not effective against foodborne viruses, such as human norovirus (NV). It is important, therefore, to explore novel nonthermal technologies for decontamination of foods eaten fresh, minimally processed and ready-to-eat foods, and food contact surfaces. We studied the in vitro virucidal activity of cold atmospheric gaseous plasma (CGP) against feline calicivirus (FCV), a surrogate of NV. Factors affecting the virucidal activity of CGP (a so-called radio frequency atmospheric pressure plasma jet) were the plasma generation power, the exposure time and distance, the plasma feed gas mixture, and the virus suspension medium. Exposure to 2.5-W argon (Ar) plasma caused a 5.55 log₁₀ unit reduction in the FCV titer within 120 s. The reduction in the virus titer increased with increasing exposure time and decreasing exposure distance. Of the four plasma gas mixtures studied (Ar, Ar plus 1% O₂, Ar plus 1% dry air, and Ar plus 0.27% water), Ar plus 1% O₂ plasma treatment had the highest virucidal effect: more than 6.0 log₁₀ units of the virus after 15 s of exposure. The lowest virus reduction was observed with Ar plus 0.27% water plasma treatment (5 log₁₀ unit reduction after 120 s). The highest reduction in titer was observed when the virus was suspended in distilled water. Changes in temperature and pH and formation of H₂O₂ were not responsible for the virucidal effect of plasma. The oxidation of viral capsid proteins by plasma-produced reactive oxygen and nitrogen species in the solution was thought to be responsible for the virucidal effect. In conclusion, CGP exhibits virucidal activity in vitro and has the potential to combat viral contamination in foods and on food preparation surfaces.     

Increased CD11b+ Gr‐1+ cell population in the placenta after infection with Toxoplasma gondii

Toxoplasma gondii is an obligate intracellular protozoan pathogen that can cross the placenta, resulting in congenital toxoplasmosis with severe fetal brain abnormalities. The molecular mechanisms of immune responses against T. gondii infection in the placenta have largely remained unclear. An analytical method for characterizing phenotypes of immune cells in the placenta by flow cytometry was established and it was found that numbers of CD11b⁺ Gr‐1⁺ cells in the placenta increased significantly after T. gondii infection. These results suggest that innate immune responses play an important role in immunity against T. gondii infection via the feto‐maternal interface.     

Satellite remote sensing data can be used to model marine microbial metabolite turnover

Sampling ecosystems, even at a local scale, at the temporal and spatial resolution necessary to capture natural variability in microbial communities are prohibitively expensive. We extrapolated marine surface microbial community structure and metabolic potential from 72 16S rRNA amplicon and 8 metagenomic observations using remotely sensed environmental parameters to create a system-scale model of marine microbial metabolism for 5904 grid cells (49 km²) in the Western English Chanel, across 3 years of weekly averages. Thirteen environmental variables predicted the relative abundance of 24 bacterial Orders and 1715 unique enzyme-encoding genes that encode turnover of 2893 metabolites. The genes'' predicted relative abundance was highly correlated (Pearson Correlation 0.72, P-value <10⁻⁶) with their observed relative abundance in sequenced metagenomes. Predictions of the relative turnover (synthesis or consumption) of CO₂ were significantly correlated with observed surface CO₂ fugacity. The spatial and temporal variation in the predicted relative abundances of genes coding for cyanase, carbon monoxide and malate dehydrogenase were investigated along with the predicted inter-annual variation in relative consumption or production of ∼3000 metabolites forming six significant temporal clusters. These spatiotemporal distributions could possibly be explained by the co-occurrence of anaerobic and aerobic metabolisms associated with localized plankton blooms or sediment resuspension, which facilitate the presence of anaerobic micro-niches. This predictive model provides a general framework for focusing future sampling and experimental design to relate biogeochemical turnover to microbial ecology.     

Impact of Obstructive Sleep Apnea on Liver Fat Accumulation According to Sex and Visceral Obesity

Rationale

Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention.

Objectives

To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences.

Methods

Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography.

Results

Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ≥25 kg/m² or visceral fat area ≥100 cm²), in only males without visceral obesity, percent sleep time with oxygen saturation <90%, in addition to BMI, insulin resistance, and serum triglyceride values, was independently correlated with liver fat accumulation (R² = 15.1%, P<0.001). In males, percent sleep time of oxygen saturation <90% was also a determining factor for alanine aminotransferase values regardless of visceral fat area. In contrast, OSA was not associated with liver fat accumulation or alanine aminotransferase values in females whether or not visceral obesity was absent.

Conclusions

Sex differences in the visceral fat-dependent impact of OSA on liver fat accumulation existed. Although the mechanisms are not known and ethnic differences may exist in addition to the specific criteria of visceral obesity in Japan, the treatment of male patients with OSA might be favorable from the viewpoint of preventing liver fat accumulation and liver dysfunction even in patients without obvious visceral fat accumulation.     

Negative Impact of Skeletal Muscle Loss after Systemic Chemotherapy in Patients with Unresectable Colorectal Cancer

Background

Skeletal muscle depletion (sarcopenia) is closely associated with limited physical ability and high mortality. This study evaluated the prognostic significance of skeletal muscle status before and after chemotherapy in patients with unresectable colorectal cancer (CRC).

Methods

We conducted a retrospective analysis of 215 consecutive patients with unresectable CRC who underwent systemic chemotherapy. Skeletal muscle cross-sectional area was measured by computed tomography. We evaluated the prognostic value of skeletal muscle mass before chemotherapy and the rate of skeletal muscle change in cross-sectional area after chemotherapy.

Results

One-hundred-eighty-two patients met our inclusion criteria. There were no significant differences in progression-free survival (PFS) or overall survival (OS) associated with skeletal muscle mass before chemotherapy. However, 22 patients with skeletal muscle loss (>5%) after chemotherapy showed significantly shorter PFS and OS compared with those without skeletal muscle loss (PFS, log-rank p = 0.029; OS, log-rank p = 0.009). Multivariate Cox regression analysis revealed that skeletal muscle loss after chemotherapy (hazard ratio, 2.079; 95% confidence interval, 1.194–3.619; p = 0.010) was independently associated with OS.

Conclusions

Skeletal muscle loss after chemotherapy was an independent, negative prognostic factor in unresectable CRC.