Effects of MTNR1B variants on fasting glucose levels in a Korean population

Fasting glucose level is the most basic and widely used indicator of diabetes. Several genome wide association studies have reported that the gene encoding melatonin receptor 1B (MTNR1B) exerts a major effect on serum fasting glucose levels. We tested for the association between single nucleotide polymorphisms (SNPs) in the MTNR1B gene and fasting glucose levels in a Korean population consisting of 8,229 subjects taken from two community-based cohorts. The mean age of the subjects in the study population was 51.9 years. For this study, we selected 363 SNPs located in the MTNR1B gene, which is located on chromosome 11. Multivariate linear regression models were used to test for genotypic effects on fasting glucose levels while adjusting for age and sex under an additive model. The MTNR1B SNP most highly associated with fasting glucose levels was rs10830962 (p=1.95×10^?5), followed by rs3847554 (p=3.16×10^?4). Replication of these initial findings is important to better understand the correlation between MTNR1B variations and their effects, especially in Asian populations.     

Biochemical analysis of a Chinese cabbage phytocystatin-1

The phytocystatins are inhibitors of papain-like cysteine proteinases that are implicated in defense mechanisms and the regulation of protein turnover. BCPI-1, a Brassica rapa (Chinese cabbage) phytocystatin isolated from flower buds, contains an extended C-terminal region that contains a single Cys residue at position 102. In an effort to investigate the role of the C-terminus and this Cys residue in BCPI-1 activity, purified recombinant proteins of BCPI-1, including wild-type BCPI-1 (wtBCPI-1), N-terminus BCPI-1 (BCPI-1??C), C-terminus BCPI-1 (BCPI-1??N), and BCPI-1 with a single Cys residue exchange to Ser (BCPI-1C102S), were generated and their inhibitory activities against papain were investigated. Kinetic analysis revealed that the monomeric forms of wtBCPI-1 (K _i = 6.84 ± 0.3 × 10^?8 M) inhibited papain more efficiently than the dimeric forms of wtBCPI-1 (K _i = 1.01 ± 0.5 × 10^?7 M). Experiments with recombinant BCPI-1C102S demonstrated that the dimerization of wtBCPI-1 caused by the formation of an intermolecular disulfide bond at the cysteine residue. The inhibitory activity of the recombinant proteins, except BCPI-1??N, was reduced in the pH range of 7.0?C11.5 and was highly stable over a wide range of temperatures. Thus, dimerization mediated by the cysteine residue in the extended C-terminal region and alkaline conditions reduced the inhibitory activity of BCPI-1.     

Gliosis in the Mice Hippocampus Without Neuronal Death After Systemic Administration of High Dosage of Tetanus Toxin

Tetanus toxin (TeT), an exotoxin, has been studied to cause tetanus in mammalian brains, and it can block the release of some neurotransmitters and affect seizure propagation. In the present study, we investigated neuronal damage/death and glial changes in the mouse hippocampus after systemic administration (intraperitoneal injection) of TeT 10 and 100 ng/kg. In both the 10 and 100 ng/kg TeT-treated groups, no neuronal death occurred in any subregions of the mouse hippocampus until 24 h post-treatment; however, there were changes in glia in the hippocampus depending on time course and dosage. The morphology of GFAP-immunoreactive astrocytes and Iba-1-immunoreactive microglia was apparently changed in the 100 ng/kg TeT treated-group compared to the 10 ng/kg TeT treated-group. In the 100 ng/kg TeT treated-group, they were increased in size and their immunoreactivity was distinctively increased from 12 h post-treatment. We also found that their protein levels were increased in the hippocampus at 12 h post-treatment of 100 ng/kg TeT. In conclusion, these results indicate that the systemic administration of 100 ng/kg TeT induced a distinctive microglia changes in the mouse hippocampus without any neuronal death/damage.     

The Role of Physical Activity in Harm Reduction among Betel Quid Chewers from a Prospective Cohort of 419,378 Individuals

ObjectiveTo assess the benefits of regular exercise in reducing harms associated with betel quid (BQ) chewing.MethodsThe study cohort, 419,378 individuals, participated in a medical screening program between 1994 and 2008, with 38,324 male and 1,495 female chewers, who consumed 5–15 quids of BQ a day. Physical activity of each individual, based on “MET-hour/week”, was classified as “inactive” or “active”, where activity started from a daily 15 minutes/day or more of brisk walking (≥3.75 MET-hour/week). Hazard ratios for mortality and remaining years in life expectancy were calculated.ResultsNearly one fifth (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold increase in oral cancer risk; and a 2-3-fold increase in mortality from lung, esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling of all-cause mortality. More than half of chewers were physically inactive (59%). Physical activity was beneficial for chewers, with a reduction of all-cause mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years, compared to non-chewers, but being active, chewers improved their health by gaining 2.5 years. The improvement, however, fell short of offsetting the harms from chewing.ConclusionsChewers had serious health consequences, but being physically active, chewers could mitigate some of these adverse effects, and extend life expectancy by 2.5 years and reduce mortality by one fifth. Encouraging exercise, in addition to quitting chewing, remains the best advice for 1.5 million chewers in Taiwan.     

Microbulbifer hainanensis sp. nov., a moderately halopilic bacterium isolated from mangrove sediment

Antonie van Leeuwenhoek - A new bacterium was successfully isolated from a mangrove sediment sample in Haikou City, Hainan Province, China. The organism is a Gram-negative, rod-shaped, non-motile...     

Dynamic Alterations to α-Actinin Accompanying Sarcomere Disassembly and Reassembly during Cardiomyocyte Mitosis

Although mammals are thought to lose their capacity to regenerate heart muscle shortly after birth, embryonic and neonatal cardiomyocytes in mammals are hyperplastic. During proliferation these cells need to selectively disassemble their myofibrils for successful cytokinesis. The mechanism of sarcomere disassembly is, however, not understood. To study this, we performed a series of immunofluorescence studies of multiple sarcomeric proteins in proliferating neonatal rat ventricular myocytes and correlated these observations with biochemical changes at different cell cycle stages. During myocyte mitosis, α-actinin and titin were disassembled as early as prometaphase. α-actinin (representing the sarcomeric Z-disk) disassembly precedes that of titin (M-line), suggesting that titin disassembly occurs secondary to the collapse of the Z-disk. Sarcomere disassembly was concurrent with the dissolution of the nuclear envelope. Inhibitors of several intracellular proteases could not block the disassembly of α-actinin or titin. There was a dramatic increase in both cytosolic (soluble) and sarcomeric α-actinin during mitosis, and cytosolic α-actinin exhibited decreased phosphorylation compared to sarcomeric α-actinin. Inhibition of cyclin-dependent kinase 1 (CDK1) induced the quick reassembly of the sarcomere. Sarcomere dis- and re-assembly in cardiomyocyte mitosis is CDK1-dependent and features dynamic differential post-translational modifications of sarcomeric and cytosolic α-actinin.     

Additive Effect between IL-13 Polymorphism and Cesarean Section Delivery/Prenatal Antibiotics Use on Atopic Dermatitis: A Birth Cohort Study (COCOA)

Background

Although cesarean delivery and prenatal exposure to antibiotics are likely to affect the gut microbiome in infancy, their effect on the development of atopic dermatitis (AD) in infancy is unclear. The influence of individual genotypes on these relationships is also unclear. To evaluate with a prospective birth cohort study whether cesarean section, prenatal exposure to antibiotics, and susceptible genotypes act additively to promote the development of AD in infancy.

Methods

The Cohort for Childhood of Asthma and Allergic Diseases (COCOA) was selected from the general Korean population. A pediatric allergist assessed 412 infants for the presence of AD at 1 year of age. Their cord blood DNA was subjected to interleukin (IL)-13 (rs20541) and cluster-of-differentiation (CD)14 (rs2569190) genotype analysis.

Results

The combination of cesarean delivery and prenatal exposure to antibiotics associated significantly and positively with AD (adjusted odds ratio, 5.70; 95% CI, 1.19–27.3). The association between cesarean delivery and AD was significantly modified by parental history of allergic diseases or risk-associated IL-13 (rs20541) and CD14 (rs2569190) genotypes. There was a trend of interaction between IL-13 (rs20541) and delivery mode with respect to the subsequent risk of AD. (P for interaction = 0.039) Infants who were exposed prenatally to antibiotics and were born by cesarean delivery had a lower total microbiota diversity in stool samples at 6 months of age than the control group. As the number of these risk factors increased, the AD risk rose (trend p<0.05).

Conclusion

Cesarean delivery and prenatal antibiotic exposure may affect the gut microbiota, which may in turn influence the risk of AD in infants. These relationships may be shaped by the genetic predisposition.