RESEARCH OF GENETIC POLYMORPHISM OF 5-HTT IN CHILDHOOD AUTISM

Objective To reveal the relationship between the 5-HTTLPR and the Chinese Han nationality children with CA, compared the distribution of the 5-HTTLPR between the Han Chinese children with CA and healthy Han Chinese children ,and analyzed the association between the 5-HTTLPR and clinical symptoms of the Han Chinese children with CA. Methods Genomic DNAs of fifty subjects including 25 autistic children and 25 controls were extracted from blood samples. PCR amplification using Oligonucleotide primers flanking 5-HTTLPR was performed. Results ① Three kinds of alleles including the S (short) allele, the L (long) allele and the VL allele were found , and the 5-HTTLPR genotypes shown were S/S, L/L, S/L and L/VL. ② Allele frequencies did not differ significantly in patient groups in comparison with the control sample. No significant difference was identified between the observed 5-HTTLPR genotype distribution of the patient groups and control group. ③ The distribution of homozygous and heterozygous subjects between the two groups differed significantly. ④ The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor. ⑤ The allele frequency of healthy Han Chinese population and that of healthy Japanese population were similar. The frequency of S allele in not only autistic subjects but also healthy children in this study was considerably more than that in Caucasians and the frequency of L allele in our subjects decreased correspondingly. Conclusion ① A significant difference in the allele frequency between the Han Chinese and Caucasian populations was found. ② The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor of the patients. ③ The homozygote and the L allele were positively relevant to CA and they might be the risk factors of CA. The heterozygote and the S allele were negatively relevant to CA and they might be the protective factors of CA.

Cellular mechanism of cardiac alternans： an unresolved chicken or egg problem

T-wave alternans, a specific form of cardiac alternans, has been associated with the increased suscep- tibility to cardiac arrhythmias and sudden cardiac death （SCD）. Plenty of evidence has related cardiac alternans at the tissue level to the instability of voltage kinetics or Ca^2＋ handling dynamics at the cellular level. However, to date, none of the existing experiments could identify the exact cellular mechanism of cardiac alternans due to the bi-directional coupling between voltage kinetics and Ca^2＋ handling dynamics. Either of these systems could be the origin of alternans and the other follows as a secondary change, therefore making the cellular mechanism of alternans a difficult chicken or egg problem. In this context, theoretical analysis combined with experimental techniques provides a possibility to explore this problem. In this review, we will summarize the experimental and theoretical advances in understanding the cellular mechanism of alternans. We focus on the roles of action potential duration （APD） restitution and Ca^2＋ handling dynamics in the genesis of alternans and show how the theoretical analysis combined with experimental techniques has provided us a new insight into the cellular mechanism of alternans. We also discuss the possible reasons of increased propensity for alternans in heart failure （HF） and the new possible therapeutic targets. Finally, according to the level of electrophysiological recording techniques and theoretical strategies, we list some critical experimental or theoretical challenges which may help to determine the origin of alternans and to find more effective therapeutic tar- gets in the future.

Changes of paired-pulse evoked responses during the development of epileptic activity in the hippocampus

Dysfunction of inhibitory synaptic transmission can destroy the balance between excitatory and inhibitory synaptic inputs in neurons,thereby inducing epileptic activity.The aim of the paper is to investigate the effects of successive excitatory inputs on the epileptic activity induced in the absence of inhibitions.Paired-pulse orthodromic and antidromic stimulations were used to test the changes in the evoked responses in the hippocampus.Picrotoxin(PTX),γ-aminobutyric acid(GABA) type A(GABA A) receptor antagonist,was added to block the inhibitory synaptic transmission and to establish the epileptic model.Extracellular evoked population spike(PS) was recorded in the CA1 region of the hippocampus.The results showed that the application of PTX induced a biphasic change in the paired-pulse ratio of PS amplitude.A short latency increase of the second PS(PS2) was later followed by a reappearance of PS2 depression.This type of depression was observed in both orthodromic and antidromic paired-pulse responses,whereas the GABAergic PS2 depression [called paired-pulse depression(PPD)] during baseline recordings only appeared in orthodromic-evoked responses.In addition,the depression duration at approximately 100 ms was consistent with a relative silent period observed within spontaneous burst discharges induced by prolonged application of PTX.In conclusion,the neurons may ignore the excitatory inputs and intrinsically generate bursts during epileptic activity.The depolarization block could be the mechanisms underlying the PPD in the absence of GABA A inhibitions.The distinct neuronal responses to stimulations during different epileptic stages may implicate the different antiepileptic effects of electrical stimulation.

Effects of carnosine on the evoked potentials in hippocampal CA1 region

Objective： To directly examine the effects ofcarnosine on neuronal excitation and inhibition in rat hippocampus in vivo. Methods： Artificial cerebrospinal fluid with carnosine was directly administrated over the exposed rat hippocampus. The changes of neuron activity in the CA1 region of hippocampus were evaluated by orthodromically- and antidromically-evoked potentials, as well as paired-pulse stimulation paradigm. Results： In both orthodromic and antidromic response potentials, carnosine transformed population spikes （PSs） with single spike into epileptiform multiple spikes. In addition, similar to the effect of 7-aminobutyric acidA （GABAA） antagonist picrotoxin, camosine decreased paired-pulse stimulating depression significantly. However, no significant change was observed in the spontaneous field potentials during the application of carnosine. Conclusion： The results indicate a disinhibition-induced excitation effect of carnosine on the CA1 pyramidal neurons. It provides important information against the application of carnosine as a potential anticonvulsant in clinical treatment.

Sielectric Properties of Terahertz Windows Materials for Bio-sample Measurement

We presented the dielectric properties of three m aterials for bio-sample measurem entusing TH z transmission spectroscopy. The m aterials , PE, COC and PV D F, have sufficient transmittance. The results demonstrate that PVDF membranes are suitablemedia for TH z transmission spectrum above 0.3 TH 7. However, it is not property m easure the solution sam pie because of the water existed afar active processng by ethanol. In this paper, the refractive hdex, the absorption coefficient, and the corn plex dieieccric functions in the THz region are compared for each material. From the measured dielectric properties, the loss m ethanism of TH z tadiation for each material is also discussed.

Aggregation-induced emission （ALE） dye loaded polymer nanoparticles for gene silencing in pancreatic cancer and their in vitro and in vivo biocompatibility evaluation

We have developed aggregation-induced emission （AIE） dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration （FDA） approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction （PCR） indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.

A Highly Sensitive In-Situ Turbidity Sensor With Low Power Consumption

A highly sensitive in-situ turbidity sensor with the low power consumption was proposed and evaluated in this study. To meet the practical requirements of the in-situ detection, we have designed the light scattering path, watertight mechanical structure, and ultra-weak scattering light detecting method. Experiments showed that the sensor had a sensitivity of 0.0076 FTU with the concentration range of 0 - 25 FTU and the R-square of 0.9999. The sensor could withstand the water pressure in depth of 1000m and had the low power consumption in the active mode 10.4mA, sleep mode 65 pA with a supply voltage of 8.4V. Southern China Sea buoy experiments indicated that the sensor could work well in the actual in-situ environment. In comparison with sensors of other companies, our sensor had relatively more comprehensive performance.