Modeling fluctuations in default-mode brain network using a spiking neural network

Recently, numerous attempts have been made to understand the dynamic behavior of complex brain systems using neural network models. The fluctuations in blood-oxygen-level-dependent (BOLD) brain signals at less than 0.1 Hz have been observed by functional magnetic resonance imaging (fMRI) for subjects in a resting state. This phenomenon is referred to as a "default-mode brain network." In this study, we model the default-mode brain network by functionally connecting neural communities composed of spiking neurons in a complex network. Through computational simulations of the model, including transmission delays and complex connectivity, the network dynamics of the neural system and its behavior are discussed. The results show that the power spectrum of the modeled fluctuations in the neuron firing patterns is consistent with the default-mode brain network's BOLD signals when transmission delays, a characteristic property of the brain, have finite values in a given range.     

Anti-peptide antibody production elicited by in vitro immunization of human peripheral blood mononuclear cells

Human monoclonal antibodies have great potential for use in the treatment of various diseases. We have established an in vitro immunization protocol for inducing antigen-specific antibody production from human peripheral blood mononuclear cells (PBMCs). In the in vitro immunization protocol, PBMCs are pretreated with L-leucyl-L-leucine methyl ester (LLME) to remove suppressive cells, and are sensitized and cultured with a soluble antigen in the presence of IL-2, IL-4 and muramyl dipeptide for 8 d, and then an antigen-specific antibody is produced. In this study, we examined the novel possibility of an in vitro immunization protocol, specifically, whether LLME-treated PBMCs can be sensitized with a peptide antigen to produce an anti-peptide antibody. The results indicate that antigen-specific immune responses were elicited by a peptide antigen derived from rice allergen, a cholera toxin B subunit, and TNF-alpha as a sensitizing antigen in in vitro immunization. These results suggest that the in vitro immunization protocol is applicable in the generation of an anti-peptide antibody against various antigens, including food allergens, foreign antigens, and self-antigens.     

Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways

Background

Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The present study was carried out to investigate the anti-tumor properties of FE in human carcinoma cells and further examine the underlying mechanisms of its activities.

Methodology/Principal Finding

FE inhibits the growth of MCF-7, MDA-MB-231, HeLa, and HT1080 cells. FE-mediated apoptosis in MCF-7 cancer cells is accompanied by DNA fragmentation, nuclear condensation, and phosphatidylserine exposure. FE induces mitochondrial membrane permeabilization (MMP) through loss of mitochondrial membrane potential (ΔΨm) and regulation of the expression of Bcl-2 family members. Release of apoptosis-inducing factor (AIF) and cytochrome c precedes MMP. AIF release causes DNA fragmentation, the final stage of apoptosis, via a caspase-independent mitochondrial pathway. Additionally, FE was found to induce phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2, and apoptosis was found to be attenuated by inhibition of JNK. Furthermore, FE-mediated apoptosis was found to involve the generation of reactive oxygen species (ROS), which are responsible for the decrease of ΔΨm and phosphorylation of JNK, p38, and ERK1/2 kinases.

Conclusions/Significance

These data suggest that FE activates a caspase-independent apoptotic pathway in MCF-7 cancer cells through activation of ROS-mediated MAP kinases and regulation of the Bcl-2 family protein-mediated mitochondrial pathway. They also provide evidence that FE deserves further investigation as a natural anticancer and cancer preventive agent.     

Site-specific isotope labeling of long RNA for structural and mechanistic studies

A site-specific isotope labeling technique of long RNA molecules was established. This technique is comprised of two simple enzymatic reactions, namely a guanosine transfer reaction of group I self-splicing introns and a ligation with T4 DNA ligase. The trans-acting group I self-splicing intron with its external cofactor, 'isotopically labeled guanosine 5'-monophosphate' (5'-GMP), steadily gave a 5'-residue-labeled RNA fragment. This key reaction, in combination with a ligation of 5'-remainder non-labeled sequence, allowed us to prepare a site-specifically labeled RNA molecule in a high yield, and its production was confirmed with (15)N NMR spectroscopy. Such a site-specifically labeled RNA molecule can be used to detect a molecular interaction and to probe chemical features of catalytically/structurally important residues with NMR spectroscopy and possibly Raman spectroscopy and mass spectrometry.     

Synthesis of Isoprenyl Chalcone “Sophoradin”

Nicotine has been found an effective photosensitizer for DDT. At DDT: nicotine (1:5), DDT along with its formed degradation products DDD, DDE and DBP disappeared within 18 and 60 days under UV and sunlight respectively. Because of persistence, nicotine proved a superior photosensitizer to N,N′-diethylaniline. In DDT emulsifiable concentrates it led to high alkalinity but no DDT degradation up to 60 days at 20~25°C. 0.1 and 0.5% DDT emulsions from these formulations showed no adverse effect on Daucus carrota, Vicia faba, Brassica oleracea var. botrytis, and Dahlia sp., but showed mild to severe phytotoxicity against Pisum sativum and Cicer arietinum; caused by high concentration of nicotine. On Clerodendrum sp. in sunlight, these formulations showed over 20% faster DDT loss between 3~15 days of application. DDT-nicotine mixtures showed no synergism against Tribolium castaneum Herbst.     

Inhibition of osteoporosis due to restricted food intake by the fish oils DHA and EPA and perilla oil in the rat

Seven-week old female rats fed restricted foods including the fish oils Docosahesaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) and perilla oil with food intake decreased by 50%, had increases of fracture force and bone mineral density (BMD) and decreases in levels of Deoxypiridinoline (Dpd) and Calcium (Ca) in the urine, compared with those of rats with osteoporosis due to restricted soy bean oil food intake. Therefore, the fish oils DHA and EPA and perilla oil depressed excretion of urinary Ca and inhibited osteoporosis due to restricted food intake.