Identification of ortho-amino benzamides and nicotinamides as MCHr1 antagonists

Several potent and efficacious MCHr1 antagonists containing an ortho-amino benzamide or nicotinamide chemotype have been identified, exemplified by 28 and 50.     

年龄对健康人体感诱发电位高频振荡成份的影响

目的:观察健康人体感诱发电位高频振荡成份的特征.方法:分析年龄对健康人通过350 Hz～750Hz滤波提取的正中神经体感谤发电位高频振荡成份(HFOs)数量、时程、幅度的影响.结果:随年龄增大HFOs数量、时程呈增大趋势.结论:体感诱发电位高频振荡成份可以反映年龄特征.     

Cryopreservation of human teeth for future organization of a tooth bank--a preliminary study

This study was aimed at evaluating whether cryopreserved teeth can be used for future transplantation by examining the viability and differentiation capability of periodontal ligament (PDL) cells and measuring the hardness of dental hard tissue. Fifty-four teeth were divided into two groups, control and frozen teeth. A MTT assay and a TUNEL assay were performed for the examination of the viability and apoptotic death of PDL cells. Immunohistochemical staining for alkaline phosphatase was performed to observe whether the differentiation capability of PDL cells was maintained by the freezing and thawing procedure. Hardness was measured to detect whether dental hard tissue was affected by the freezing conditions. The MTT and TUNEL assays showed no significant difference in the viability of PDL cells between the two groups. The differentiation capability of PDL cells was maintained in frozen teeth as evidenced by alkaline phosphatase staining. The hardness of frozen teeth was not changed, but a longitudinal fracture was found in 25% of the frozen group. The viability and differentiation capability of PDL cells were maintained in a frozen environment; however, it is thought that a new cryopreservation method preventing fracture of dental hard tissue should be developed for clinical application.     

Trichomislin, a novel ribosome-inactivating protein, induces apoptosis that involves mitochondria and caspase-3

Trichomislin, a novel ribosome-inactivating protein, was cloned from the genome of Trichosanthes kirilowii Maxim. The gene was recombined to prokaryotic expression vector and the protein was purified by cation-exchange chromatography. The secondary structure of trichomislin was measured by circular-dichroism analysis and the ratios of alpha-helices and beta-sheets were calculated. Trichomislin could inhibit the synthesis of protein in rabbit reticulocyte lysate systems and its reaction mechanism was to inactivate ribosome as an rRNA N-glycosidase. Antitumor analyses indicated trichomislin induced the apoptosis and inhibited the growth of choriocarcinoma cells. Further investigation showed that trichomislin could bind to and enter choriocarcinoma cells, and then increase the caspase-3 activity in a time-dependent manner. At the same time, the concentration of cytochrome c in cytosol increased while that in mitochondria decreased. These results suggested that trichomislin induced apoptosis by releasing cytochrome c from mitochondria which then triggered the caspase family member activation.     

hNIS-IRES-eGFP dual reporter gene imaging

The human and rodent sodium iodide symporters (NIS) have recently been cloned and are being investigated as potential therapeutic and reporter genes. We have extended this effort by constructing an internal ribosomal entry site (IRES)-linked human NIS (hNIS)-enhanced green fluorescent protein (eGFP) hybrid reporter gene for both nuclear and optical imaging. A self-inactivating retroviral vector, termed pQCNIG, containing hNIS-IRES-eGFP dual reporter gene, driven by a constitutive CMV promoter, was constructed and used to generate RG2-pQCNIG cells and RG2-pQCNIG tumors. 131I-iodide and 99mTcO4-pertechnetate accumulation studies plus fluorescence microscopy and intensity assays were performed in vitro, and gamma camera imaging studies in RG2-pQCNIG and RG2 tumor-bearing athymic rats were performed. RG2-pQCNIG cells expressed high levels of hNIS protein and showed high intensity of eGFP fluorescence compared with RG2 wild-type cells. RG2-pQCNIG cells accumulated Na131I and 99mTcO4- to a 50:1 and a 170:1 tissue/medium ratio at 10 min, compared with 0.8:1.2 tissue/medium ratio in wild-type RG2 cells. A significant correlation between radiotracer accumulation and eGFP fluorescence intensity was demonstrated. RG2-pQCNIG and RG2 tumors were readily differentiated by in vivo gamma camera imaging; radiotracer uptake increased in RG2-pQCNIG but declined in RG2 tumors over the 50-min imaging period. Stomach and thyroid were the major organs of radionuclide accumulation. The IRES-linked hNIS-eGFP dual reporter gene is functional and stable in transduced RG2-pQCNIG cells. Optical and nuclear imaging of tumors produced from these cell lines provides the opportunity to monitor tumor growth and response to therapy. These studies indicate the potential for a wider application of hNIS reporter imaging and translation into patient studies using radioisotopes that are currently available for human use for both SPECT and PET imaging.     

Genotoxicity of drinking water from three Korean cities

Organic content of drinking tap water from Seoul, Taejon, and Suwon was extracted with an XAD-2 resin column and organic solvents. Four doses of the extract equivalent to 4, 2, 1, and 0.5 l water were tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100 in the presence and absence of S9 mix. The organic extracts of the water from all three cities were mutagenic in TA 98 without S9 mix and in TA 100 with and without S9 mix. The highest number of revertants per plate was found in the absence of S9 mix. Three doses of the extract (equivalent to 22, 11, and 3.7 l water) were also tested in the bone marrow micronucleus test using BDF1 mice. At the highest dose, a significant increase of the micronucleus frequency was observed. The time required to be on the effect, however, varied with the source of the water. Our results indicate that the drinking tap waters from the three cities were genotoxic clearly in the bacterial test and also in the in vivo assay with mice. As we found no genotoxicity of the source water as seen in a previous study, it is likely that the chlorination process leads to the genotoxicity of the tap water.     

Differential activation of individual subunits in heteromeric kainate receptors

Neuronal kainate receptors are assembled from subunits with dissimilar specificities for agonists and antagonists. The composite biophysical behavior of heteromeric kainate receptors is determined by intersubunit interactions whose nature is unclear. Here we use dysiherbaine, a selective kainate receptor agonist, to show that GluR5 subunits assembled in heteromeric GluR5/KA-2 kainate receptor complexes can gate current without concomitant activation of their partner KA-2 subunits. A long-lasting interaction between dysiherbaine and GluR5 subunits elicits a tonic current from GluR5/KA-2 receptors; subsequent cooperative gating of KA-2 subunits can be elicited by both agonists, such as glutamate, and some classically defined antagonists, such as CNQX. This study demonstrates that each type of subunit within a heteromeric kainate receptor contributes a distinct conductance upon activation by agonist binding, and therefore provides insight into the biophysical function of ionotropic glutamate receptors.     

Putative resistance genes of cereals: structure and expected function

Sequences of two recently cloned genes playing a role in resistance against wheat pathogens (receptor-like kinase Lrk10 and Cre3 genes) were used to search for similarity of cereal clones included in the NCBI database. We found 23 clones with similarity to the Cre3 gene with predicted NBS and LRR domains, and 50 clones with serine/threonine kinase function and similarity to the new receptor-like kinase gene Lrk10 from wheat. In those two groups of clones some conservative nucleotide sequences were identified. Two sequences are identical between the majority of resistance gene candidate clones with a high similarity to Lrk10, and two sequences are identical between the majority of resistance gene candidate clones with similarity to the Cre3 gene.     

Vibrational resonance in a randomly connected neural network

A randomly connected network is constructed with similar characteristics (e.g., the ratio of excitatory and inhibitory neurons, the connection probability between neurons, and the axonal conduction delays) as that in the mammalian neocortex and the effects of high-frequency electrical field on the response of the network to a subthreshold low-frequency electrical field are studied in detail. It is found that both the amplitude and frequency of the high-frequency electrical field can modulate the response of the network to the low-frequency electric field. Moreover, vibrational resonance (VR) phenomenon induced by the two types of electrical fields can also be influenced by the network parameters, such as the neuron population, the connection probability between neurons and the synaptic strength. It is interesting that VR is found to be related with the ratio of excitatory neurons that are under high-frequency electrical stimuli. In summary, it is suggested that the interaction of excitatory and inhibitory currents is also an important factor that can influence the performance of VR in neural networks.