FTO (fat mass and obesity associated) was identified as an obesity-susceptibility gene by several independent large-scale genome association studies. A cluster of SNPs (single nucleotide polymorphism) located in the first intron of FTO was found to be significantly associated with obesity-related traits, such as body mass index, hip circumference, and body weight. FTO encodes a protein with a novel C-terminal α-helical domain and an N-terminal double-strand β-helix domain which is conserved in Fe(II) and 2-oxoglutarate-dependent oxygenase family. In vitro, FTO protein can demethylate single-stranded DNA or RNA with a preference for 3-methylthymine or 3-methyluracil. Its physiological substrates and function, however, remain to be defined. Here we report the generation and analysis of mice carrying a conditional deletion allele of Fto. Our results demonstrate that Fto plays an essential role in postnatal growth. The mice lacking Fto completely display immediate postnatal growth retardation with shorter body length, lower body weight, and lower bone mineral density than control mice, but their body compositions are relatively normal. Consistent with the growth retardation, the Fto mutant mice have reduced serum levels of IGF-1. Moreover, despite the ubiquitous expression of Fto, its specific deletion in the nervous system results in similar phenotypes as the whole body deletion, indicating that Fto functions in the central nerve system to regulate postnatal growth.

Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, and form chiasmata. The homologues connect via axial elements and numerous transverse filaments to form the synaptonemal complex. The synaptonemal complex is a critical component for chromosome pairing, segregation, and recombination. We previously identified a novel germ cell–specific HORMA domain encoding gene, Hormad1, a member of the synaptonemal complex and a mammalian counterpart to the yeast meiotic HORMA domain protein Hop1. Hormad1 is essential for mammalian gametogenesis as knockout male and female mice are infertile. Hormad1 deficient (Hormad1−/ −) testes exhibit meiotic arrest in the early pachytene stage, and synaptonemal complexes cannot be visualized by electron microscopy. Hormad1 deficiency does not affect localization of other synaptonemal complex proteins, SYCP2 and SYCP3, but disrupts homologous chromosome pairing. Double stranded break formation and early recombination events are disrupted in Hormad1−/ − testes and ovaries as shown by the drastic decrease in the γH2AX, DMC1, RAD51, and RPA foci. HORMAD1 co-localizes with γH2AX to the sex body during pachytene. BRCA1, ATR, and γH2AX co-localize to the sex body and participate in meiotic sex chromosome inactivation and transcriptional silencing. Hormad1 deficiency abolishes γH2AX, ATR, and BRCA1 localization to the sex chromosomes and causes transcriptional de-repression on the X chromosome. Unlike testes, Hormad1−/ − ovaries have seemingly normal ovarian folliculogenesis after puberty. However, embryos generated from Hormad1−/ − oocytes are hyper- and hypodiploid at the 2 cell and 8 cell stage, and they arrest at the blastocyst stage. HORMAD1 is therefore a critical component of the synaptonemal complex that affects synapsis, recombination, and meiotic sex chromosome inactivation and transcriptional silencing.

The anaphase promoting complex (APC) or cyclosome is a multi-subunit E3 ubiquitin ligase. Cdc20 [fizzy (fzy), or p55CDC] and Cdh1 [Hct1, srw1, or fizzy-related 1 (fzr1)] encode two adaptor proteins that bring substrates to APC. Both APC-Cdc20 and APC-Cdh1 are implicated in the control of mitosis through mediating ubiquitination of mitotic regulators such as cyclin B1 and securin. However, the importance of the function of Cdh1 in vivo and whether its function is redundant with that of Cdc20 are unclear. We report here the analysis of mice lacking Cdh1. We show that Cdh1 is essential for placenta development and its deficiency causes early lethality. Cdh1-deficient mouse embryonic fibroblasts entered replicative senescence prematurely due to stabilization of Ets2 and subsequent activation of p16Ink4a expression. These results uncovered an unexpected role of APC in maintaining replicative life span of murine embryonic fibroblasts. Further, Cdh1 heterozygous mice display defects in late-phase long-term potentiation (L-LTP) in the hippocampus and are deficient in contextual fear conditioning, suggesting a role of Cdh1 in learning and memory.

Programmable liposomes are designed to selectively produce various liposome-nanoparticle hybrids.

Objective. The purpose of this study was to assess the efficacy and safety of Taeeumjowi-tang (TJ001) as well as to estimate obesity-related factors. Methods. This was a 12-week trial with 5 visits. A total of 102 participants of both genders were randomized to either TJ001 (n = 57) group or the placebo group (n = 55). Subjects were administered 7 g of either TJ001 or placebo 3 times a day. The primary outcome was a rate of subjects who lost 5% or more of initial weight. Secondary outcomes included anthropometric parameters, lipid profiles, and body fat composition. Results. The subject response rate of ≥5% weight loss compared to baseline was similar in both groups, and no statistically significant difference was observed (P = 0.87). Changes in anthropometric parameters were greater during the first 4 weeks in the treatment group (P < 0.0001). There were no significant changes in both within groups and between groups for lipid profile and body fat composition. No adverse event was reported in either group. Conclusion. Although the difference between the groups regarding a rate of subjects who lost 5% or more of initial weight did not show statistical significance, TJ001 appears to be beneficial in safely controlling weight.

BackgroundSilibinin is the major active molecule of silymarin, the mixture of flavonolignans extracted from Cirsium japonicum. It has been used for the treatment of hepatitis and inflammation-related diseases. In the present study, the effects of silibinin on allergic inflammation and its signaling were investigated in the induced human mast cells.MethodsCell growth inhibition induced by silibinin was measured by MTS assay. Histamine release was measured by enzyme immunoassay. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) secreted protein levels and mRNA levels were measured by the ELISA assay and RT-PCR, respectively. The NF-κB promoter activity was examined by a luciferase assay.ResultsSilibinin suppressed the growth of HMC-1 cells and also reduced the production and mRNA expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8. Moreover, silibinin inhibited the nuclear translocation of nuclear factor (NF)-κB through inhibition of the phosphorylation of IκBα and suppressed NF-κB transcriptional activity in stimulated HMC-1 cells.ConclusionsTaken together, these results indicate that silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells, suggesting that silibinin could be used for the treatment of mast cell-derived allergic inflammatory diseases.

Aging is a progressive process related to the accumulation of oxidative damage and neuroinflammation. We tried to find the anti-amnesic effect of the Scutellaria baicalens Georgia (SBG) ethanol extract and its major ingredients. The antioxidative effect of SBG on the mice model with memory impairment induced by chronic injection of D-galactose and sodium nitrate was studied. The Y-maze test was used to evaluate the learning and memory function of mice. The activities of superoxide dismutase, catalase and the content of malondialdehyde in brain tissue were used for the antioxidation activities. Neuropathological alteration and expression of bcl-2 protein were investigated in the hippocampus by immunohistochemical staining. ROS, neuroinflammation and apoptosis related molecules expression such as Cox-2, iNOS, procaspase-3, cleaved caspase-3, 8 and 9, bcl-2 and bax protein and the products of iNOS and Cox-2, NO, PGE2, were studied using LPS-activated Raw 264.7 cells and microglia BV2 cells. The cognition of mice was significantly improved by the treatment of baicalein and 50 and 100 mg/kg of SBG in Y-maze test. Both SBG groups showed strong antioxidation, antiinflammation effects with significantly decreased iNOS and Cox-2 expression, NO and PGE2 production, increased bcl-2 and decreased bax and cleaved caspase-3 protein expression in LPS induced Raw 264.7 and BV2 cells. We also found that apoptotic pathway was caused by the intrinsic mitochondrial pathway with the decreased cleaved caspase-9 and unchanged cleaved caspase-8 expression. These findings suggest that SBG, especially high dose, 100 mg/kg, improved the memory impairments significantly and showed antioxidation, antiinflammation and intrinsic caspase-mediated apoptosis effects.

Self-formation of colloidal oil droplets in water or water droplets in oil not only has been regarded as fascinating fundamental science but also has been utilized in an enormous number of applications in everyday life. However, the creation of three-dimensional (3D) architectures by a liquid droplet and an immiscible liquid interface has been less investigated than other applications. Here, we report interfacial energy-driven spontaneous self-formation of a 3D plasmonic optical structure at room temperature without an external force. Based on the densities and interfacial energies of two liquids, we simulated the spontaneous formation of a plasmonic optical structure when a water droplet containing metal ions meets an immiscible liquid polydimethylsiloxane (PDMS) interface. At the interface, the metal ions in the droplet are automatically reduced to form an interfacial plasmonic layer as the liquid PDMS cures. The self-formation of both an optical cavity and integrated plasmonic nanostructure significantly enhances the fluorescence by a magnitude of 1000. Our findings will have a huge impact on the development of various photonic and plasmonic materials as well as metamaterials and devices.