Abstract:The tumor suppressor TP53 gene, which encodes p53 protein, is a hotspot of all time in molecular oncology. p53 suppresses tumor initiation and progression through its regulation of many downstream genes. Recent studies have revealed that microRNAs (miRNAs) interact with the p53 pathway and form a complex regulatory network. On one hand, p53 promotes cell cycle arrest and induces cell apoptosis and senescence to suppress tumorigenesis by regulating the transcription and post-transcriptional maturation of multiple miRNAs. On the other hand, many miRNAs fine-tune the p53 pathway through regulation of TP53 and its upstream regulators or downstream effectors. The miR-34s family, directly transactivated by p53 represents a large number of p53-regulated miRNAs. They exert their tumor suppressing function via targeted inhibition of multiple key molecules in the p53 pathway. Furthermore, miR-34s enhance p53 activity through a feedback loop by inhibiting silent information regulator 1(SIRT 1). Investigation on the interaction between miRNAs and p53 is essential to fully understand the underline mechanisms of p53 tumor suppressing action.

Abstract:Since the inverse relationship between plasma high-density lipoprotein cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD) have been well-established, it has always been a hot spot on how to regulate HDL-C levels for the treatment of CAD-related disease. High and low HDL levels are closely related to its own production and metabolism, which are primarily determined by corresponding regulatory genes. It has been suggested that plasma HDL-C levels have a strong inherited basis with heritability estimates of 40%～60%, showing the great significance in discussing variants causes associated with HDL-C levels. Candidate gene, genome-wide linkage, and most recently genome-wide association (GWA) studies have identified several genetic variations for plasma HDL-C levels. However, the functional role of some variants remains unknown, and they do not always have relation to the risk of CAD. This review will be summarized on the structure of HDL, its metabolism and production, as well as the genetic causes of high and low HDL-C. Notably, recent genetic findings from candidate gene and the GWA studies will be the focus of this text aiming at elucidating the important genetic factors affecting HDL-C concentrations. Comprehensive study on genetics conferring to high and low HDL-C levels using integrative approaches is essential to reveal their relationships with CAD and explore novel pathways on the treatment of CAD.

Abstract:With the development of the new generation of biotechnology and bioinformatics, studies on the transcriptome of eukaryotes have detected a number of long non-coding RNAs (lncRNAs) and the lncRNAs may play key functional roles in gene expression and regulation. Currently, high-throughput RNA-Seq has become the main technique for lncRNA study and several bioinformatic methods have been used to process and analyze the sequencing data for exploring lncRNAs' information including sequence, structure, expression, function and so on. This paper represents a pipeline for the lncRNA prediction based on RNA-Seq, and the relevant bioinformatic methods are reviewed comprehensively. We also discussed several challenges and future works related to the lncRNA study.

Abstract:In this review, we mainly discuss the origin and the development of statistical learning research, as well as constraints and brain neural bases of statistical learning. Researches of statistical learning originated from the studies on speech segmentation in human infants since 1990's. From then on, lots of studies have explored statistical learning on both non-linguistic continuous sound streams and visual shape sequences. Evidence from these researches suggest that statistical learning is involved in discovering and extracting regularities, and it is domain-general. However, statistical learning in different domains is constrained by domain-related factors. For example, statistical learning in language(s) is constrained by language-specific factors; while non-linguistic statistical learning is constrained by stimulus characteristics and presentation modality. In recent years, several studies have examined the temporal course of statistical learning by employing event-related potentials (ERPs) technique and investigated its neural substrates by using functional magnetic resonance imaging (fMRI) technique. ERPs studies consistently found that a negative ERP component at around 400 ms was related with the extraction of regularities, and findings of fMRI studies suggested that statistical learning mainly involved left superior temporal gyrus, right striatum and right medial temporal memory system.

Abstract:It has been widely assumed that, in vivo, all the initiation of RNA transcription occurs using NTPs only, but it was observed recently that one kind of smalls RNA, nanoRNAs, could also serve as primers for transcription initiation. Perhaps a balance exists between nanoRNA-initiated transcription and NTP-initiated transcription, and altering this balance could significantly impact the global gene expression. The phenomenon of nanoRNAs initiation transcription challenged a few of traditional understandings in molecular biology, such as transcriptional initiation，the functional mechanisms of small RNAs and coupling relations between RNA decay and RNA transcription, thips henomenon also provided a new opportunity of deepening the research in molecular biology.

Abstract:Translational medicine is a new concept in the field of international medicine.It is people-oriented research based on clinical practice, putting forward scientific questions, carrying out in-depth research, and finally translating basic research into clinical practice. It causes great concerns in basic medicine, clinical medicine, preventive medicine as well as biological pharmaceutical industry and other areas since the concept has been raised. This review introduces the concept and development of translational medicine as well as the recent achievements in the study of translational medicine in China.

Abstract:Science China Life Sciences in 2011: a Retrospect

Abstract:Neurons in primary visual cortex (V1) have periodical responses to smoothly drifting gratings, but only have transient responses to the static stimuli that evoke drastic responses at the initial tens of milliseconds. This hints that the information of stimuli could be processed primarily in this initial period. Study on neuronal responses during this period is critical for understanding the characters of neuronal responses to the static stimuli. We investigated the temporal response time courses of V1 neurons to six stimulus durations (5, 10, 20, 30, 40, and 　50 ms) of static gratings. Responses to the static stimuli were denoted by the time course curves which were the contours of the Peri-Stimulus Time Histograms (PSTHs) with a resolution of 1 ms bin. Along with the prolongation of the stimulus duration, PSTH curves to different stimulus durations reflected the evolution of responses to the static stimuli. All the data were collected from the anesthetized cat V1 with extracellular unit recording. V1 neurons showed wave-like response curves that grew up after a short latency to the stimulus onset and then dropped off gradually due to the stimulus offset. When stimulus duration prolonged, the time and width of the main peak (the first peak, the largest one, of PSTH response curve) increased and saturated at 30 ms stimulus duration that we tested. Magnitudes of most main peaks were almost equal except that the response peak to the 5 ms stimulus duration was significantly lower than those to the others. There were also offset response peaks which were evoked by the stimulus offset, but were smaller than the main peaks and contained less information about visual stimuli. The magnitude of the offset responses increased with the stimulus duration, so it could be regarded as the aftereffects of the stimulus offset. Statistically, the response durations (represented by 2 ? half peak width) of V1 neurons to different stimulus durations were not shorter than 39 ms (even the stimulus duration was as short as 5 or 10 ms), which might be the physiological basis of the visual persistence (the duration of perception for a visual stimulus is longer than the physical presentation) at the primary visual cortex level. On the other hand, the time differences of the main and offset peaks were longer than the corresponding stimulus durations, suggesting that the offset responses were delayed by the onset responses. This may be a kind of mechanism to ensure that the information processed by V1 neurons is not disrupted by the offset responses or the onset responses of another stimulus. Furthermore, the similarity of the minimal response duration (39 ms) and the minimal time peak (36 ms) between the main peak and offset peak suggest that the minimal time (response duration) necessary for V1 neurons to process information is at least about 35～40 ms even for the stimuli presented for a time shorter than 30 ms. These results illustrate that with this very short period of time V1 neurons can code the main characters of visual stimuli and transmit the enough information about the stimuli to the high visual cortex. The 35～40 ms may be the essential time for V1 neurons to process visual information.

Abstract:In our previous reports, BMP9 has shown potent function to induce osteogenic differentiation of mesenchymal stem cells, however, the underlying molecular mechanism of BMP9-induced osteogenesis is needed to be deep explored. In this study, BMP9 was introduced into mesenchymal stem cells by recombinant adenoviruses protocol, then, in vitro and in vivo assays were conducted to evidence whether BMP9 can regulate osteogenic differentiation of mesenchymal stem cells through ERK1/2 kinase pathway. The results showed that BMP9 can activate ERK1/2 kinase through increase the phosphorylated form of ERK1/2 kinase. ERK1/2 kinase inhibitor PD98059 can increase the ALP activity, OPN expression and calcium deposition of C3H10T1/2 cells induced by BMP9. Furthermore, PD98059 also led to enhancement of Runx2 activity and activation of canonical Smad pathway stimulated by BMP9. When ERK1/2 kinase was silenced by RNA interference, BMP9-activated Smad pathway was further enhanced. Moreover, ALP activity, calcium deposition and in invo ectopic bone formation were accordingly increased along with knockdown of ERK1/2 kinase. Taken together, those results intensively suggested that BMP9 can activate ERK1/2 kinase, and inhibition of ERK1/2 kinase can enhance BMP9-induced osteogenic differentiation of mesenchymal stem cells. ERK1/2 are highly capable of negatively regulate BMP9-induced osteoblastic differentiation of mesenchymal stem cells.

Abstract:To explore the expression of GB1 in mouse uterus from day 1 to day 8 of pregnancy (D1～D8) and the role in placenta establishment, semi-quantitative reverse transcription polymerase chain reaction (semi-qRT-PCR), immunohistochemistry and Western blotting were applied to detect the expression levels of GB1 mRNA and protein respectively from D1 to D8. Besides, EPCs and decidual cell were dissected out from D8.5 uterus and then added different concentrations of GABA, GABA B receptor agonists baclofen and antagonists 2-hydroxysaclofen. In vitro attachment and outgrowth assays were performed in EPCs, and transwell chambeer was performed in decidual cells. In vivo, mouse from D8 to D13 were treated by intraperitoneal injection of different concentrations of GABA . On D14, the placenta structure was examined with the histological method. The results suggested that GB1 mRNA and protein dynamic expressed from D1 to D8 uterus. 100 μmol/L GABA and 5 μmol/L baclofen promoted EPCs outgrowth and surppressed decidual cells invasion. At the same time, 20 μmol/L 2-hydroxysaclofen could reversed both of the functions of GABA on EPCs and decidual cells. The histological structures of placentas changed appearantly on D14. In the layer of labrinthine, the cells arranged crowdly and maternal blood and fetal rat vascular decreased number or dysplasia. In spongiotrophoblast, cytotrophoblast cells becomed smaller and glycogen cells decreased or disappeared. The combined results indicated during the early-middle mouse placenta establishment GABA signal was in favour of trophoblasts invasion but played converse role in decidual cells and damaged placenta structure.

Abstract:Tipα (TNF-α-inducing protein) from Helicobacter pylori is identified as a new carcinogenic factor. Tipα induces high expression of TNF-α through NF-κB activation, thus promoting host inflammation and tumor progression. The homodimer of Tipα as its active form for functional performances is cross-linked by a pair of inter-molecular disulfide bridges (Cys25-Cys25 and Cys27 and Cys27). Tipα (25～192) was cloned into pET22b and expressed as soluble protein in E. coli strain BL21 (DE3). Recombinant active Tipα was first purified through Ni²⁺-chelating chromatography, and then further purified by cation-exchange chromatography and size-exclusion chromatography to get the pure homodimer protein. Native Tipα and SeMet Tipα were crystallized and optimized using hanging drop and microbatch methods, with diffraction to 2.2? and 2.6?, respectively. These crystals belonged to C2 space group with similar unit-cell parameters. The native protein crystal had unit-cell parameters a=127.01?, b=47.57?, c=96.5?, α=γ=90°, β=127.5°. An attempt to solve the three-dimensional structure of this protein by MAD method is under way.

Abstract:We previously demonstrated that leucine zippers fused to intein could increase secretion of spliced B-domain-deleted coagulation factor Ⅷ (BDD-FⅧ) protein and activity by dual-vector based BDD-FⅧ gene transfected cell in vitro through improving protein trans-splicing. In this study, a pair of plasmid vectors expressing human BDD-FⅧ heavy and light chain fused with lucine zipper and split Ssp DnaB intein was co-injected into C57BL/6 mice via the portal vein. Fourty-eight hours post-injection, the level of heavy chain and FⅧ coagulation activity in collected plasma were determined and shown as (298±67) μg/L and (1.15±0.29) U/ml respectively, greater than that of control mice injected with both vectors without leucine zippers ((179±59) μg/L and (0.58±0.19) U/ml). It demonstrated that leucine zippers fused intein could increase FⅧ coagulation activity in plasma of mice with intein-based dual-vector BDD-FⅧ gene delivery through improved protein trans-splicing. It provided evidence for ongoing hemophilia A gene therapy using dual-AAV vecors.