Abstract:The endogenous electric fields at the wound site had been found since 18th century, while its biological significance in wound healing, organ regeneration and development was unveiled until recent year. Here we summarized the mechanisms of the generation of endogenous electric fields and its significance in different biological events. Moreover, the ion flux behind the endogenous electric fields was introduced as well.

Abstract:Previous studies generally focused on the cell colony and the obtained information was commonly the average of many cell individuals. However, each cell has a different behavior, which is known as cell heterogeneity. Single cell analysis can accurately obtain valuable information of each cell in the microenvironment and thus there is an urgent need for single cell analysis. Many methods have been successfully employed to single cell analysis, such as flow cytometry, fluorescence microscopy, capillary electrophoresis and microfluidic chips. In these methods, single cells are usually stained by a fluorescent label (e.g. fluorescein, quantum dots, green fluorescent protein, etc.) and then detected via the fluorescent signal. However, simultaneous analysis of multiple parameters in a single cell is always challenging because of the overlap in fluorescent spectrum. In addition, the linear range of the fluorescence method is relatively narrow, making difficulty for accurate quantification, especially when comparing signals with considerable difference. To meet these challenges, a new method based on inductively coupled plasma mass spectrometry (ICP-MS) has emerged for single cell analysis. Intracellular elements can be determined directly by ICP-MS at a single cell level. In combination with labeling techniques(e.g. element labeling of an antibody), biomolecules in single cells can also be determined via elements analysis by ICP-MS. This paper summaries both the ICP-MS-based methodology and selected applications in immunoassay, disease detection, drug screen, and nanoanalysis at a single cell level. A prospective of this method and its applications is also discussed.

Abstract:Crystal cellulose that biosynthesized by the cellulose synthetase (CesA), is the structural framework and the most important components of the cell wall of higher plants. During the process of biological evolution, CesA aggregates on the plasma membrane and forms super-molecular terminal complexes (TCs) which have the two types of arrangement: TCs and rosettes TCs, synthesizing Ⅰα and Ⅰβ crystal cellulose, respectively. Due to the unbranched structure, the adjacent cellulose chains can quickly stack side by side to form microfibre under the hydrogen bonds and Van der Waals' force (VDW). As a result, tightly crystal super-molecular structure of microfibre work as a natural barrier and makes it become an obstacle to the degradation which is known as biomass recalcitrance. However, concentrated acids and ionic liquids can diffuse among the microfibre efficiently and break β-1, 4-glucosidic bonds and hydrogen bonds, and eventually destroy the crystal structure of cellulose. Crystal cellulose can also be degraded by biological enzymes, which is quite different from chemical treatments which both require extremely acting conditions. Cellulases can hydrolysis crystal cellulose at room temperature, but only the certain surface of microfibre can be interacted with celluases, so the accessibility of cellulose surface further reduce the efficiency of hydrolysis. Therefore, the combination of physical and chemical pretreatments can break the biomass recalcitrance and then cellulases can spread into microfibre which resulting in the specific binding rates of enzyme-substrate increased. Finally, it can realize the degradation and conversion of natural crystal cellulose with low-cost and green high-efficiency.

Abstract:The role of emotional information and internal motivation in older adults’ decision-making process was explored in this review. The role was embodied in the following four aspects: self-related of tasks influence the invest of cognitive resources; older adults pay more attention to emotional information related to decisions, give preference to positive information and are sensitive to the way of decision-making tasks described. Future research should consider more direct ERPs evidence. For example, use ERPs technique to monitor older adults’ decision-making in order to discriminate the information types that older adults used and their emotional and motivational responses. This method could contribute to precisely discern the effect of emotional information and internal motivation on information search. Furthermore, future research should also study the neutral mechanism of older adults’ decision-making process from the perspective of neurobiology.

Abstract:Next generation sequencing (NGS) technologies boosted genomic and medical research, particularly for identification of disease-causing variants. Although most types of genetic variants could be identified through NGS data analysis, there are still some limitations, such as length variations of short tandem repeats (STRs). Many genetic diseases are known to be caused by expansions of STRs, especially neurological disorders, such as Huntington disease. However, almost none of existing tools could detect STRs expanded longer than sequencing read length based on NGS. To break through the limitation, we developed a novel method for detecting length variations of STRs and estimating the length of expansions based on paired-end NGS. We applied our method in a clinical study of motor neuron disease using whole-exome sequencing and successfully identified a disease-causing expansion of STR. Our method firstly used special features of depth of read coverage at STRs to address the variant calling problem. It has widely application value in human genetic disease research and inspirational value in developing new NGS data processing tools.

Abstract:Combinatorial analyses including enzymatic analysis and atomic force microscopy (AFM) were used to gain more insights into structure of the alkali-denatured plasmid pBR322 DNA (DNA Ⅳ). Among the restriction enzymes tested, PstⅠ was able to cleave the pBR322 DNA Ⅳ molecules, indicative of the existence of an intact restriction site in the denatured DNA. AFM images revealed that PstⅠ-treated DNA Ⅳ molecules contained an individual node. The contour length of the condensed molecules was decreased by about 11% compared to DNA Ⅳ. Intriguingly, the Escherichia coli topoisomerase Ⅳ, a type Ⅱ topoisomerase, also introduced nodes into DNA Ⅳ while keeping the molecules in a closed form. The two types of DNA were similar to each other in terms of the contour length and the size of the node based on the AFM analysis. These findings suggest that specific base-paired regions exist in DNA Ⅳ, and that cleavages at these regions may lead to DNA node.

Abstract:In order to detect and investigate neuronal firing activity during high-frequency stimulation (HFS), thereby to reveal the mechanisms of deep brain stimulation (DBS) in the treatment of neurological diseases, this project studied the changes of spike waveforms during HFS. Orthodromic-HFS (O-HFS) trains with a duration of 1～2 min and a frequency of 100 or 200 Hz were applied to the afferent fibers (i.e., the Schaffer collaterals) of the hippocampal CA1 region of anesthetized rats. Multi-channel spike signals were recorded in the downstream area of HFS by a microelectrode array. The features of the spike waveforms, such as amplitude and half-height width, were extracted from the sorted unit spikes of interneurons activated by HFS through single synaptic transmissions. The results show that the spike amplitudes decreased and the half-height widths increased significantly during HFS. The percent ratios of the waveform features, compared to their baseline values, show that the amplitude of falling-phase and the amplitude of rising-phase decreased by ～20% and ～40%, respectively, while the half-height widths increased by more than 10%. In addition, the decrease of amplitudes (up to 50%) and the increase of half-height widths (up to 20%) were enhanced during synchronized firings of a large population of neurons or during the O-HFS trains of 100 Hz, a stimulation frequency causing greater excitation to neurons than 200 Hz. Presumably, the excitation of O-HFS could elevate the membrane potentials of downstream neurons and change the kinetics of the ionic channels of the membrane, thereby result in the waveform changes of action potentials. The results support the hypothesis that DBS has excitatory modulation effect on neurons. The study provides guidance for accurately analyzing neuronal unit spike activity during high-frequency stimulation and also provides important clues for revealing the mechanisms underlying the treatment of brain diseases by DBS.

Abstract:The influenza A virus M2 proton channel, is the target of anti-flu medications, amantadine and rimantadine. The functions of M2 is closely related to its conformation changes. While extensive progresses have been made regarding the structure-function relationship for the transmembrane helix, there have been much fewer studies for the other membrane associated segment, the C-terminal amphiphilic helix. We carried out FRET experiments by introducing into the amphiphilic helix an unnatural amino acid, PheCN, as the donor for the W residue located in the transmembrane helix. This allowed us to study the global conformation change of these membrane associated structures under channel activation or drug inhibition. The distance between amphipathic helix and transmembrane helix increased upon channel activation in the acidic environment. The degree of this distance increase was not affected by drug inhibition. Therefore we speculate that the conformation change of amphipathic helix is not related to the proton channel activity, but is more likely associated with the protein’s role in virus budding.

Abstract:Glutathione S-transferase Alpha1 and Alpha 4 (GSTA1 and GSTA4) are crucial for detoxifying a variety of endogenous and exogenous toxic compounds. However, GSTA1/4 expression is reduced in cholestatic patients. The molecular mechanism of GSTA1/4 down-regulation remains elusive. Here, we treated human hepatoma HepG2 cells with tumor necrosis factor alpha (TNFα) and measured the expression of GSTA1/4, nuclear factor kappa B (NF-κB) and NF-E2 related factor 2 (Nrf2) by quantitative real-time quantitative polymerase chain reaction (qPCR) and Western blotting. We found that expression of GSTA1/4 was repressed by TNFα at both the mRNA and the protein level in a dose- and time-dependent manner. Furthermore, inhibiting the NF-κB signaling pathway could attenuate the TNFα induced reduction in GSTA1/4 expression in the HepG2 cells. Our findings indicate that down-regulation of GSTA1/4 expression in HepG2 cells is likely triggered by TNFα and mediated by activation of the NF-κB signaling pathway.

Abstract:Substitutions of residues introduced by gene mutations can impact protein structures and often alternate protein properties. Identifying substitution-related structural changes is crucial for understanding their effects in biological functions. With the explosive numbers of experimentally determined protein structures, more and more wild-type-mutant structures have been used in comparable studies of structural biology. In this work, we constructed a structure-pair database, named DRSP, which collected non-redundant pairs of proteins with single residue substitutions in the entire Protein Data Bank. DRSP demonstrates abundant information for mutant-structure prediction and protein design. More importantly, DRSP presents the superimposed pairs of wild-type-mutant structures for backbone-perturbation studies, which are very important for the highly accurate structure modeling. DRSP is available at http:// www.labshare.cn/drsp/index.php.

Abstract:Particle filter (PF) algorithm has been applied in neural decoding, but rarely in movement trajectory reconstruction of hippocampal place cells. According to the response characteristics of place cells, the state space population encoding model of movement trajectory was established with quadratic exponential Poisson’s equation in this paper, the performance of the PF algorithm was investigated with respective simulated data and real data in movement trajectory reconstruction. And the results were then compared with extended Kalman filter (EKF) and unscented Kalman filter (UKF) algorithms. For the simulated data, the number of place cells needed by the PF is less than that of the others, under the same reconstruction precision. For the real data, correlation coefficient and root mean square error between true trajectories and reconstructed trajectories by the PF are superior to that of by the EKF algorithm and by the UKF algorithm. These results demonstrate that not only does the PF algorithm efficiently utilize encoding information of place cells population, but also has an outstanding movement trajectory reconstruction performance. It would provide powerful technique support for further research in spatial cognitive mechanism.