Abstract:Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide the first line of host defence against microbial infection and tumors. NK cells are now considered to be an important part of the immune system by controlling microbial infections and tumor progression. Although they were discovered more than 40 years ago, NK cells have recently been attracting attention for their potential in immune-based therapies. Over the past few years many researchers have reported that NK cells as one of the main effector cells of the innate immune system, their activity and function are greatly influenced by the cell surface protein glycosylation modification and glycan-binding proteins (e.g. siglec, selectin and galectin) located on the surface of cells. For example, the immune evasion mechanisms from NK immunity using cell-surface glycans have been identified. The cancer cells use the certain types of cell-surface glycans to evade NK immunity, such as reducing NK activating receptor-mediated signaling, enhancing NK inhibitory receptor-mediated signaling, and modulating TRAIL-mediated killing. In addition, such siglec interacts with sialic acid-overexpressing cells to lead to inhibition of NK cells activation. Selectin combines with ligand to promote the immune function of NK cells. Galectin binds β-galactosides to mediate NK cells immune process. This review summarizes the recent progress of the certain types of glycans and glycan-binding proteins related to the immunological function of NK cells, and discusses the influence of abnormal glycan-binding proteins for the development of tumor, as well as their application prospect in immune-based therapies.

Abstract:Ubiquitin, a highly conserved 76-amino-acid polypeptide widely present in eukaryotic cells, is covalently attached to substrate proteins through the E1-E2-E3 cascade. Ubiquitination is involved in a myriad of cellular functions, including protein degradation, signal transduction, DNA damage and repair, transcription regulation, cell cycle progression, and tumorigenesis. In this review, we discuss the basic concept of protein ubiquitination, and focus on its roles in the initiation and progression of cancers, DNA damage response, and neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. These knowledge is staring to be exploited to develop both drugs and therapy strategies against these diseases.

Abstract:Individuals perform better when remembering and recognizing items that belong to themselves other than those belong to others, even if the ownership association between objects and subjects is only transient and imaginary. This is called the ownership effect in memory. This effect occurs also in young children and individuals with cognitive deficits. There is also cross-cultural difference in the appearance of this effect between individuals in Eastern and Western culture. Researchers have explored some internal mechanism of this effect, such as semantic organization, attention, self-choice and physical actions. At the time subjects watch items belong to themselves, there is an enhanced P300, which supplies an electrical proof that attention plays an important role in the ownership effect in memory. When subjects are to recognize items that are classified as their own in the prior ownership classification task, some brain regions in cortical midline structure, such as medial prefrontal cortex, cingulate cortex supramarginal gyri and parietal cortex, are activated. Future studies should consider the role of some other processing (such as reward learning) in this effect, and to explain this phenomenon from an evolutionary perspective by conducting studies with primates. Tapping the brain mechanism of individuals with cognitive impairment will be helpful to enrich studies in this field.

Abstract:Small molecules of free radicals play essential roles in maintaining normal physiological function in organisms. However, in a variety of pathological conditions, excessive accumulation of these substances might cause serious damage to tissues and organs due to their highly active, strong oxidization properties. For instance, reactive oxygen species (ROS) and reactive nitrogen species (RNS), two major small molecules active substances, are proved to participate in the pathogenesis of stroke. In particular, the role of reactive nitrogen in stroke onset is one of the hot spot in current stroke etiology study. In this publication, recent progress of the physical and pathological functions of RNS in stroke study are reviewed and prospected.

Abstract:Intermittent exotropia is a common pediatric ocular disease, which is also a hot research area in ophthalmology. In this study, we tested the tracking ability of children with intermittent exotropia using multiple object tracking (MOT) paradigm, and compared with amblyopic children and normal children. The experimental results showed that the tracking capacity of children whether with intermittent exotropia or amblyopia was significantly decreased as compared with normal children, and children with intermittent exotropia suffers the same degree of damage with children with amblyopia. It is the first report of the abnormal attentive ability of children with intermittent exotropia, which may be beneficial to future research of pathogenesis and early diagnosis of the disease.

Abstract:Mycobacterium tuberculosis is a successful pathogen of human being that causes about millions people death annually. M. tuberculosis posses an unique cellular envelop which can protect itself from the attack of immune system and harsh environment. The mycobacterial cell wall consists of inner membrane, peptidoglycan/arabinogalactan layers, a mycolic acid-containing layer, and the outer capsular layer. ESX secretion system is involved in transporting substrates through cellular envelop to extracellular environment. ESX secretion system has five pathways: ESX1-5. ESX-1 pathway contributes most in pathogenicity of M. tuberculosis and became a continuing concern on interaction between M. tuberculosis and host. EspB shares a co-dependent secretion way with ESAT-6, a key virulence of ESX-1which is responsible for the escape of M. tuberculosis from host cell to cytoplasm. We solved the crystal structure of EspB from M. tuberculosis. EspB posses conserved WxG domain and YxxxD domain, and so does other substrates of ESX-1 pathway. Research on EspB shows that it can interact with a component of secretion apparatus-EccC. We suppose that WxG domain and YxxxD domain may function together as a signal peptide for the recognition of secretion apparatus during the secretion of EspB. In addition, EspB heptamer has a relative rigid structure and a large enough inner-diameter for the transport of ESAT-6/CFP-10 dimer, which makes it possible to function as a channel for ESAT-6/CFP-10.

Abstract:Hepatocellular carcinoma (HCC) has an extremely poor prognosis which is caused mainly by high frequency of metastatic recurrence. We previously reported that high interleukin (IL)-2 levels in peritumoral tissue were closely associated with a decreased incidence of intrahepatic tumor recurrence in patients with hepatitis B virus (HBV)-associated HCC, and the immune staining of IL-2 primarily was found in tumor-surrounding hepatocytes. However, whether hepatocytes can express IL-2 in vitro and underlying mechanism remain to be investigated. Here, we compared IL-2 expression levels in peritumoral tissue from HCC patients between HBV-positive group and HBV-negative group. We then overexpressed HBV x protein (HBx) in immortalized human liver cell line THLE-2, and mimic microenvironmental oxidative stress with hydrogen peroxide (H₂O₂) treatment in vitro. We demonstrated that hepatocytes can express IL-2 in vitro through MAP3K7/NF-κB pathway in the presence of both HBx stimulation and mild oxidative stress. Targeting microenvironmental oxidative stress offers a promise for prevention and therapy of HBV-associated HCC metastatic recurrence.

Abstract:This paper proposed the “self-checking” algorithm to improve the detection accuracy of multiple moving targets in time-series fluorescence images, such as vesicles. The main idea of this algorithm is to construct a multi-kernel function superposition model and use the model to fit the data at the indistinguishable moment; the number of vesicles and the central positions of vesicles are determined from the set based on χ²-statistics of the residuals in least-square fits of the models to the image data. By comparing the detection accuracy with or without the “self-checking” algorithm in simulated images, we found that the detection accuracy with the “self-checking” algorithm was improved significantly. Meanwhile, we proposed an optimized flow chart of vesicle tracking which was applied to analyze the vesicles in mice β cells. We found that the number of vesicle traces will increase and the average docking time of vesicles will decrease after glucose stimulation based on our tracking analysis. This is because β cells will release insulin to regulate glucose balance with the help of vesicle translocation and secretion after glucose stimulation. In a word, we quantified the vesicles activity in mice β cell by tracking analysis on subcellular level.

Abstract:Inferring the gene regulatory networks (GRNs) structure is the research basis of functional genomics. GRNs can help to understand the regulatory mechanism among genes, exploring the essence of complex life system. Traditional Bayesian network methods cannot handle large-scale networks due to their high computational complexity, while information theory-based methods cannot identify the directions of regulatory interactions and also suffer from false positive/negative problems. By using the ordered conditional mutual information (CMI) and limited parent node genes, in this work, we present a novel algorithm (namely OCMIPN) to fast infer GRNs from gene expression data. OCMIPN first uses ordered conditional mutual information to construct an initial GRN relation network. Then, according to the priori knowledge of gene regulatory network topology structure, BN method is employed to generate final GRNs by limiting the number of parent nodes for each gene, which significantly reduces the computational complexity. Tested on the synthetic networks as well as real biological molecular networks with different sizes and topologies, the results show that OCMIPN can infer RGNs with higher accuracy and low computational times. The OCMIPN’s performance outperforms other state-of-the-art methods, such as LASSO, ARACNE, ScanBMA and LBN.