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This article uses the grey prediction theory to structure a new metaheuristic: grey prediction evolution algorithm based on the even grey model. The proposed algorithm considers the population series of evolutionary algorithms as a time series, and uses the even grey model as a reproduction operator to forecast the next population (without employing any mutation and crossover operators). It is theoretically proven that the reproduction operator based on the even grey model is adaptive. Additionally, the algorithmic search mechanism and its differences with other evolutionary algorithms are analyzed. The performance of the proposed algorithm is validated on CEC2005 benchmark functions and a test suite composed of six engineering constrained design problems. The comparison experiments show the effectiveness and superiority of the proposed algorithm. The proposed algorithm can be regarded as the first case of structuring metaheuristics by using the prediction theory. The novel algorithm is anticipated to influence two future works. The first is to propose more metaheuristics inspired by prediction theories (including some statistical algorithms). Another is that the theoretical results of these prediction systems can be used for this novel type of metaheuristics.

In this paper, a fiber-reinforced resin matrix composite missile wing with a wave-transparent function is studied, which has the function of wave-transparent and meets the requirements of the mechanical properties of the missile during flight, and the missile wing structure is made of aluminum alloy, carbon fiber composite material, and glass fiber composite material, and the weight reduction is about 30.3% compared with the overall aluminum alloy structure of the missile wing. In the design process, the finite element simulation method is used, the plastic deformation of aluminum alloy is fully considered, and the antenna is built into the airfoil of glass fiber composite material, which successfully realizes the wave-transparent function of the missile wing and provides a new design idea for the composite wing.

The System of General Assembly of Members of an academy or a society is the core of the academician system

“Carrying out scientific research” and “guiding, contacting and rewarding academic research” were the two major tasks undertaken by Academia Sinica. In the original system design, the second task was undertaken by the council.

After the establishment of the Second Council of Academia Sinica, the academician system began to be brewed and was formally put on the agenda at the Second Annual Meeting in March 1944.

After the council drew up The Regulations for the Election of Members of Academia Sinica in April 1947, they turned their focus to the election of the first batch of members of Academia Sinica.

Although the Chinese Academy of Sciences decided to establish an academician system within one to three years after the Academic Divisions and the membership system were set up, it failed to implement it. However, through supplementing more members of the Academic Divisions of the Chinese Academy of Sciences (CASAD) in 1957, the identity of those members began to change into CAS members. After this expansion, the CAS did not recruit any more members before the Cultural Revolution. Its Academic Divisions suffered ups and downs in the political movements and collapsed after the outbreak of the Cultural Revolution. When the Revolution was over and the National Science Congress and the Third Plenary Session of the 11th CPC Central Committee were held in 1978, China’s scientific cause started to embrace vigorous development. In 1979, the CAS resumed its activities among Academic Divisions. With the CAS co-opting more academic division members in 1980, it took a step further towards the academician system. This chapter studies the 1957 supplement of members of academic divisions and the 1980 co-optation of members of the academic divisions of Chinese Academy of Sciences, how the selection system was improved before and after the Cultural Revolution, and how membership came to include academic honors of academicians.

After a plan to establish the academician system ran aground in 1981, the call for the system did not disappear. The Chinese Academy of Sciences (CAS) finally established the membership system in 1994 by converting all academic division members into CAS Members, on the basis of the 1983 conversion of academic division members into the country’s highest academic honorary title in science and technology and the 1991 co-optation of its members.

The Chinese Academy of Sciences made legislative preparations for its academician system after it set up the academic divisions in 1955.

As early as the 17th century, the academician system was born in Europe as a product of the institutionalization of western modern scientific research. In 1666, the Academie des Sciences was established

According to The Regulations for the Election of Members of Academia Sinica, the official list of member candidates needed to be publicized for 4 months in order to listen to the criticisms from all sides. During the period of publicity, Bo Shang, Wang Hefu, Yuan Hanqing, Fu Ssu-Nien and others put forward sharp criticisms. The PCE attached great importance to the criticisms of all parties and made the authentic-named criticisms extremely confidential and submitted them to the council for discussion. The Fifth Annual Meeting of the council was held in March 1948, and the formal election of the first batch of members of Academia Sinica was conducted according to the scheduled procedures. In the formal election, some criticisms had an impact. After the election, although some scholars raised objections to individual candidates, on the whole, the member election was very successful. Almost all those elected were outstanding scholars in the academic circle, and their academic achievements represented the highest academic level in China at that time.

On November 1, 1949, just one month after the founding of the People’s Republic of China, the Chinese Academy of Sciences was established. The institutes of Academia Sinica in Chinese mainland and the National Academy of Peiping had become an important foundation for the CAS to set up institutes.

Human hepatic C3A cells have been applied in bioartificial liver development, although these cells display low intrinsic cytochrome P450 3A4 (CYP3A4) enzyme activity. We aimed to enhance CYP3A4 enzyme activity of C3A cells utilizing CRISPR gene editing technology. We designed two CYP3A4 expression enhanced systems applying clustered regularly interspaced short palindromic repeats (CRISPR) gene technology: a CRISPR-on activation system including dCas9-VP64-GFP and two U6-sgRNA-mCherry elements, and a light-controlled CRISPR-on activation system combining our CRISPR-on activation system with an optical control system to facilitate regulation of CYP3A4 expression for various applications. Results of enzymatic activity assays displayed increased CYP3A4 activity in C3A cells expressing the CRISPR-on activation system compared with C3A cells. In addition, CYP3A4 activity increased in C3A cells expressing the light-controlled CRISPR-on activation system under blue light radiation compared with C3A cells. Notably, there was no statistical difference in the increase of CYP3A4 protein amounts induced by these two methods. After expansion in culture, C3A cells with the light-controlled CRISPR-on activation system exhibited no statistical difference in CYP3A4 mRNA levels between generations. Our findings provide a method to stably enhance functional gene expression in bioartificial liver cells with the potential for large-scale cell expansion.

CD133 is a pentaspan transmembrane protein that can serve as a biomarker for cancer stem cells, although its biochemical mechanism remains unclear. Here we report that CD133 expression enhances glioma cell tolerance of a nutrient-deprived microenvironment. Under starvation conditions, CD133-positive cells exhibited higher survival and decreased levels of apoptosis. These changes were dependent on activation of autophagy-associated gene signaling and were impaired by the autophagic inhibitor chloroquine. Furthermore, rapamycin up-regulated the level of autophagy and inversely reduced CD133 expression. Immunofluorescence confirmed that starvation promoted release of CD133 from the plasma membrane to the cytoplasm, with CD133 also partially co-localizing with LC3 upon starvation. Additionally, CD133 partially co-localized with Beclin1, Atg5, and lysosomes, indicating that CD133 directly participates in the autophagosome membrane fusion process and ultimately undergoes lysosomal degradation. Collectively, our results demonstrate that CD133 contributes to cell survival by regulating autophagy, and that targeting CD133-linked signaling and autophagy may be useful in improving anti-cancer treatments.

As a non-ligand-dependent activation protein, EGFRvIII is the most common mutant of EGFR, and its existence or especially its nuclear translocation in tumors can exacerbate the malignancy. Compared with the nuclear translocation of EGFR, which has been studied extensively, the specific mechanism by which EGFRvIII undergoes nuclear translocation has not yet been reported. Here, we found that EGFRvIII eventually reached the nucleus with the involvement of the Golgi and endoplasmic reticulum (ER) in glioma cells. In this process, syntaxin-6 was responsible for the identification and transport of EGFRvIII on Golgi. We also demonstrated that COPI mediated the reverse transport of EGFRvIII from the Golgi to ER, which process was also important for EGFRvIII's nuclear accumulation. EGFRvIII's nuclear translocation can significantly promote STAT3 phosphorylation and PKM2 nuclear localization. Finally, we showed that EGFRvIII's nuclear translocation obviously induced the growth of gliomas in an intracranial xenotransplantation experiment. These data suggested that searching methods that inhibit EGFRvIII entry into the nucleus will be effective glioma treatments.

CD44 is a widely known cancer stem cells marker in various cancers and validated to function in tumor growth, survival and tumor metastasis. In this study, we first established C3A-derived liver cancer stem cells by OSKM method [OCT4, SOX2, KLF4, and c-MYC], termed C3A-induced cancer stem cells (C3A-iCSCs) which acquired self-renewal and stemness abilities. Then we found CD44 was positive in C3A-iCSCs and mainly located in cell nuclear. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) results showed nuclear CD44 combined promoter regions of c-MYC and SOX2. These results suggested that CD44 participated in C3A-iCSCs transcriptional regulation. To explore CD44 overall influence in liver cancer stem cells, CD44 was knocked out in C3A-iCSCs using CRISPR/Cas9 technology. Our results showed a dramatic increase in the expression of stem cell markers OCT4, SOX2 and NANOG in CD44- C3A-iCSCs compared with that in CD44+ C3A-iCSCs. Tumor derived from CD44- C3A-iCSCs also displayed well-differentiated tumor cells compared to CD44+ C3A-iCSCs, which suggested CD44- C3A-iCSCs derived tumor cells exhibited lower malignant degree. Our data indicated nuclear CD44 in liver cancer stem cells is responsible for the poorly differentiated highly malignant tumor cells by maintenance of low stemness state.

The morbidity problem of the GM(1,1) power model in parameter identification is discussed by using multiple and rotation transformation of vectors. Firstly we consider the morbidity problem of the special matrix and prove that the condition number of the coefficient matrix is determined by the ratio of lengths and the included angle of the column vector, which could be adjusted by multiple and rotation transformation to turn the matrix to a well-conditioned one. Then partition the corresponding matrix of the GM(1,1) power model in accordance with the column vector and regulate the matrix to a well-conditioned one by multiple and rotation transformation of vectors, which completely solve the instability problem of the GM(1,1) power model. Numerical results show that vector transformation is a new method in studying the stability problem of the GM(1,1) power model.

Then the relative error uniform upper bounds between the GM(1,1,W) model and GM(1,1,C) model were deduced.The quantitative relation between the relative error uniform upper bound and the developing coefficient was obtained.The result provides a criterion for whether the connotation model can be substituted reasonably by the whitenization model. The solution of a whitenization GM(1,1) model, called GM(1,1,W), instead of a connotation GM(1,1) model (GM(1,1,C)) is usually used to forecast the trend of a grey system. This paper discusses the relative error between the solutions of these two models. First, the relative error upper bounds are derived when the developing coefficient a is located in two applicable ranges, (-2,0 and 0,2). Treating the relative error upper bound as a function of a and the observation time k, its properties are researched to obtain the upper bound of this relative error upper bound function, which can be called the relative error uniform upper bound. The relation between this uniform upper bound and the data sequence length n is ultimately demonstrated. The research indicates that the relative error between the solutions of GM(1,1,W) and GM(1,1,C) is less than 3.31% when the developing coefficient a is within the range -1/(n+1), 2/(n+2) (n?4), and hence GM(1,1,C) can be replaced appropriately with GM(1,1,W). However, the relative error between the solutions of these two models may exceed 19.97% when the developing coefficient a is out of the range -1/(n+1), 2/(n+2), and in this case, GM(1,1,C) cannot be replaced fittingly with GM(1,1,W). Therefore, this work provides a criterion for whether the connotation model can be substituted reasonably by the whitenization model.

The multiscale carbon nanotube-hybridized carbon fiber was prepared by a newly developed aerosol-assisted chemical vapour deposition. Scanning electron microscopy and transmission electron microscope were carried out to characterize this multiscale material. Compared with the original carbon fibers, the fabrication of this hybrid fiber resulted in an almost threefold increase of BET surface area to reach 2.22 m 2 /g. Meanwhile, there was a slight degradation of fiber tensile strength within 10%, while the fiber modulus was not significantly affected. The interfacial shearing strength of a carbon fiber-reinforced polymer composite with carbon nanotube-hybridized carbon fiber and an epoxy matrix was determined from the single fiber pull-out tests of microdroplet composite. Due to an efficient increase of load transfer at the fiber/matrix interfaces, the interracial shear strength of composite reinforced by carbon nanotube-hybridized carbon fiber is almost 94% higher than that of one reinforced by the original carbon fiber. Based on the fractured morphologies of the composites, the interfacial reinforcing mechanisms were discussed through proposing different types of carbon nanotube fracture modes along with fiber pulling out from epoxy composites.

The purpose of this article is to find a way to prepare multiscale material, namely, carbon nanotube-hybridized carbon fiber (CNT/CF) with a low degradation of mechanical properties. Using a facile aerosol-assisted chemical vapor deposition method, a novel route was described to fabricate CNT/CF. The essential of this technique was in situ formation of catalyst (Fe) nanoparticles via pyrolysis of ferrocene–acetone aerosol right before CNTs growth. Through optimizing aerosol supply and process parameters, a uniform coverage of CNTs was successfully grafted onto the carbon fiber surface to obtain a multiscale (hierarchical) structure. The strong anchorage between the as-synthesized CNTs and carbon fiber substrate was confirmed by ultrasonic bath treatment. Compared with the as-received carbon fibers, single fiber tensile testing results demonstrated that the tensile strengths of CNT-hybridized carbon fiber slightly degraded within 10% at all the correspondingly given gauge lengths.

The interface between reinforcing fiber and matrix is a crucial element in composite performance. Homogeneous and interconnected carbon nanotubes (CNTs) were deposited onto the surface of carbon fibers to produce multiscale reinforcement by electrophoretic deposition (EPD). Single fiber tensile tests showed that the tensile strength and Weibull modulus of the resulting multiscale materials were increased by 16 and 41%, respectively. Compared with as-received carbon fibers, CNTs-deposited carbon fibers provided the decreased surface energy by 20% and the increased adhesion work by 22% using modified Wilhelmy method. Results from single fiber pull-out testing showed that a significant improvement (up to 68.8%) of interfacial shear strength was obtained for the composites containing by CNTs/Carbon fiber multiscale reinforcement. All results strongly suggest that EPD process can provide a feasible platform for improving interface properties of advanced composites.

Vertically aligned carbon nanotube (CNT) arrays have been grown onto the carbon fiber fabric using a catalytic chemical vapor deposition (CCVD) method. The as-synthesized CNT arrays are about 20 μm in height, and the nanotube has a mean inner and outer diameter of 2.6 nm, 5.5 nm, respectively. The CNT-grafted carbon fabric shows a hydrophobic property with a contact angle over 145°, and the single CNT-grafted carbon fiber shows a sharp increase of dynamic contact angle in de-ionized water from original 71.70° to about 103°, but a little increase does in diiodomethane or E-51 epoxy resin. However, the total surface energy of carbon nanotube-grafted carbon fiber is almost as same as that of as-received carbon fiber. After CNTs growth, single fiber tensile tests indicated a slight tensile strength degradation within 10% for all different lengths of fibers, while the fiber modulus has not been significantly damaged. Compared with the as-received carbon fibers, a nearly 110% increase of interfacial shear strength (IFSS) from 65 to 135 MPa has been identified by single fiber pull-out tests for the micro-droplet composite, which is reinforced by as-received carbon fiber or CNT-grafted carbon fiber.

An anti-oxidative polyimide nano-coating on carbon fibers was obtained by electrophoretic deposition of polyamic acid nano-emulsion. The polyamic acid nano-emulsion was synthesized using pyromellitic dianhydride and 4,4-oxydianiline in N,N-dimethylacetamide solution. The polyamic acid nano-emulsion with an average particle size of 320 nm was electrophoretic deposition on carbon fibers and transferred into polyimide after imidization at 280 °C. The properties of polyimide-coated carbon fibers were characterized using field-emission scanning electron microscope, X-ray photoelectron spectroscopy, Fourier transforms infrared spectroscopy and thermogravimetric analysis. The results showed that a continuous and uniform polyimide nano-coating of 80–100 nm was formed on carbon fibers. The polyimide-coated carbon fibers displayed an excellent thermal stability up to 500 °C in air.

The development of functional profiling technologies provides opportunity for high-throughput functional genomics studies. We describe a cell-based screening system to identify novel human genes associated with cell proliferation. The method integrates luciferase reporter gene activity, fluorescence stain, automated microscopy and cellular phenotype assays. We successfully used the system to screen 409 novel human genes cloned by our lab and found that 27 genes significantly up-regulated promoter-Renilla luciferase reporter plasmid (pRL) activity. Among them, five genes, TRAF3IP3, ZNF306, ZNF250, SGOL1, and ZNF434, were determined through morphological observation, calcein AM fluorescence stain, MTT assay and cell cycle analysis to be associated with cell proliferation. Furthermore, we showed that the gene TRAF3IP3, which initially was identified to specifically interact with TRAF3, stimulated cell growth by modulating the c-Jun N-terminal kinase (JNK) pathway, and RNAi of TRAF3IP3 confirmed that the effect was physiological and necessary. In summary, we integrated a rapid and efficient system for screening novel growth regulatory genes. Using the new screening system we identified five genes associated with cell proliferation for the first time.

In this study, cell microarray technology is used to identify novel human genes associated with CRE pathway activation. By reverse transfection, expression plasmids containing full-length cDNAs were cotransfected with the reporter plasmid pCRE-d2EGFP to monitor the activation of the CRE pathway via enhanced green fluorescence protein (EGFP) expression. Of the 575 predominantly novel genes screened, 22 exhibited relatively higher EGFP fluorescence compared with a negative control. After a functional validation with a dual luciferase reporter system that included both cis- and trans-luciferase assays, 4 of the 22 genes (RNF41, C8orf32, C6orf208, and MEIS3P1) were confirmed as CRE-pathway activators. Western blot analysis revealed that RNF41 can promote CREB phosphorylation. These results demonstrate the successful combination of cell microarray technology with this reporting system and the potential of this tool to characterize functions of novel genes in a highly parallel format.

To review the research progress of the biomechanics of proximal row carpal instability (IPRC).The related literature concerning IPRC was extensively reviewed. The biomechanical mechanism of the surrounding soft tissue in maintaining the stability of the proximal row carpal (PRC) was analyzed, and the methods to repair or reconstruct the stability and function of the PRC were summarized from two aspects including basic biomechanics and clinical biomechanics.The muscles and ligaments of the PRC are critical to its stability. Most scholars have reached a consensus about biomechanical mechanism of the PRC, but there are still controversial conclusions on the biomechanics mechanism of the surrounding soft tissue to stability of distal radioulnar joint when the triangular fibrocartilage complex are damaged and the biomechanics mechanism of the scapholunate ligament. At present, there is no unified standard about the methods to repair or reconstruct the stability and function of the PRC. So, it is difficult for clinical practice.Some strides have been made in the basic biomechanical study on muscle and ligament and clinical biomechanical study on the methods to repair or reconstruct the stability and function of PRC, but it will be needed to further study the morphology of carpal articular surface and the adjacent articular surface, the pressure of distal carpals to proximal carpal and so on.

In the present study, a cell-based high-throughput assay is established to identify novel human genes associated with cell viability. The assay relies on the down-regulation of Renilla luciferase (pRL) activity in a 96-well format. In addition, 2-color fluorescence probes were used to distinguish living and dead cells. As the positive control, the authors used the expression vectors encoding Bax, TNFRSF1A, and TAJ, which were widely known to effectively induce programmed cell death. They screened 409 novel genes (including alternative mRNA splicing forms) cloned in their laboratory and found that 39 genes could significantly down-regulate pRL activity. A subsequent fluorescence-based assay revealed that 4 of the 39 genes (PIP5KL1, OLFM1, RNF122, FAM26B) were associated with cell viability. Further function assays validated that the 4 genes were able to induce both necrosis and apoptosis. These results therefore indicate that a rapid and effective screening system has been developed, which should shed light on some functions of novel genes.

The simple and continuous deposition of carbon nanotubes onto the surface of carbon fiber tows, using ethanol as a dispersive medium, was achieved by the electrophoretic process. The resulting materials showed a uniform distribution of carbon nanotubes on the fiber surface. Such a continuous process provides industrial potential for preparing a multiscale carbon nanotube-carbon fiber reinforcement.

Carbon nanotubes/carbon fiber hybrid material was prepared by ultrasonically assisted electrophoretic deposition. X-ray photoelectron spectroscopy (XPS) indicated that oxygen containing functional groups of the carbon nanotubes were obviously increased after acid treatment. Scanning electron microscopy (SEM) results showed that ultrasonically assisted EPD increased the amount and uniformity of carbon nanotubes whereas only sparse deposition formed without ultrasonic. Deposition sites increased by introduction of ultrasonic in the EPD process have been suggested as a possible mechanism. Results of the mechanical property tests showed that single fiber tensile strength, Weibull modulus and the interfacial shear strength (IFSS) were significantly improved by 16.0%, 40.7% and 68.8%, respectively.

A hot-pressing aided exothermic synthesis (HPES) technique was developed to fabricate NiAl matrix composites reinforced with TiB2 and TiC particles which were in situ reaction synthesized from elemental powders. These particles were uniformly dispersed in the matrix. The resulting products were hot isostatically pressed to nearly complete densification. It was found that the tensile yield strengths of the composites at 900 degrees C were about two times stronger than that of unreinforced NiAl and were approximately three times stronger at 980 degrees C. The interfaces between NiAl and TiC or TiB2 were atomically flat, sharp and free from any interfacial phases in most cases, however, a thin interfacial amorphous layer or overlapped interfacial layer was observed at the interfaces in some cases. This type of interfacial structure may be beneficial to the strength of the composites. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

Ternary Ni-Al-Fe alloys with different Fe additions have been synthesized by mechanical alloying of elemental powder mixtures. The effects of Fe-substitution for Al in an equi-atomic NiAl alloy on the mechanical alloying process and on the final Ni-Al-Fe alloys were investigated experimentally. Lower Fe additions have been found to prolong the milling time prior to explosive formation of the NiAl(Fe) compound, while ≥ 15 at % Fe addition has been found not only to eliminate the explosive reaction during milling but also to produce a Ni-based supersaturated solid solution (the 15 at % Fe addition results in the formation of an amorphous-like phase). The addition of Fe improves the plastic deformation ability of the alloys and hinders the tendency of fracture during milling, resulting in the formation of larger alloy particles. Upon heating, the as-milled samples with lower Fe addition remain as NiAl(Fe) compound, whereas the Ni-based supersaturated solid solutions decompose into a mixture of compounds of β-(Ni, Fe) (Al, Fe) + γ′-(Ni, Fe)3Al. It is suggested that the ternary addition into the binary intermetallic compound might be a possible route to improve ductility by forming the dual phase of β + γ′.

In 1953, due to needs of self-development and national construction, in view of experiences of Soviet Academy of Sciences, the Party Leadership Group of Chinese Academy of Sciences decided to take the cultivation of scientific cadres as one of the central tasks and the cultivation of postgraduates as one of the focal points, following which the formulation of Interim Regulations on Postgraduate Cultivation by Chinese Academy of Sciences (hereinafter referred to as Regulations) was carried out. The Regulations was formulated in 1955 and issued in August, 1955. Its contents were obviously edified by the Soviet policies and systems for cultivating scientific cadres; however, to formulate regulations on postgraduate cultivation applicable for China’s actual conditions, Chinese Academy of Sciences didn’t indiscriminately imitate them, but made discreet screening and modification, with the absorption of many comments and suggestions from inside and outside of the Academy. The formulation of the Regulations laid momentous systematic foundation for Chinese Academy of Sciences to rapidly play an important role in China’s postgraduate education in the next ten years since then. The Regulations also provided reference basis for China’s institutions of higher learning to accumulate experiences on postgraduate education, and thus facilitated the development of postgraduate education towards the normalized direction.

TMEM166 is a novel programmed cell death-related molecule. In this report, we constructed a recombinant adenovirus 5-TMEM166 vector (Ad5-TMEM166) and evaluated its expression and anti-tumor activities in vitro and in vivo. Cell viability analysis revealed that the adenovirus-mediated increase of TMEM166 inhibited tumor cell growth in a dose- and time-dependent manner. This inhibitory effect was mediated by both autophagy (via inhibition of mTOR and activation of p70S6K) and apoptosis (via caspase-3 activation), both of which contributed to cell death and suppression of tumorigenicity. Our data indicated that Ad5-TMEM166 may be a novel gene therapy candidate for cancer.

In the present study, we characterized the function of HS1-binding protein 3 (HS1BP3), which is mutated in essential tremor and may be involved in lymphocyte activation. We found that HS1BP3 localized to the mitochondria and endoplasmic reticulum partially. Overexpression of HS1BP3 induced apoptosis in HEK293T and HeLa cell lines. When these cell lines were transfected with HS1BP3, they exhibited nuclear DNA condensation, externalization of phosphatidylserine (PS), and cleavage of poly ADP ribose polymerase (PARP). Furthermore, suppression of HS1BP3 or HS1 expression attenuates HS1BP3 induced apoptosis. In addition, HS1BP3 enhanced activator protein 1 (AP-1)-mediated transcription in a dose-dependent manner. Therefore, we conclude that HS1BP3 regulates apoptosis via HS1 and stimulates AP-1-mediated transcription.

Programmed cell death can be divided into apoptosis and autophagic cell death. We describe the biological activities of TMEM166 (transmembrane protein 166, also known as FLJ13391), which is a novel lysosome and endoplasmic reticulum-associated membrane protein containing a putative TM domain. Overexpression of TMEM166 markedly inhibited colony formation in HeLa cells. Simultaneously, typical morphological characteristics consistent with autophagy were observed by transmission electron microscopy, including extensive autophagic vacuolization and enclosure of cell organelles by double-membrane structures. Further experiments confirmed that the overexpression of TMEM166 increased the punctate distribution of MDC staining and GFP-LC3 in HeLa cells, as well as the LC3-II/LC3-I proportion. On the other hand, TMEM166-transfected HeLa and 293T cells succumbed to cell death with hallmarks of apoptosis including phosphatidylserine externalization, loss of mitochondrial transmembrane potential, caspase activation and chromatin condensation. Kinetic analysis revealed that the appearance of autophagy-related biochemical parameters preceded the nuclear changes typical of apoptosis in TMEM166-transfected HeLa cells. Suppression of TMEM166 expression by small interference RNA inhibited starvation-induced autophagy in HeLa cells. These findings show for the first time that TMEM166 is a novel regulator involved in both autophagy and apoptosis.

Apoptosis is a genetically determined cell suicide program. Mitochondria play a central role in this process and various molecules have been shown to regulate apoptosis in this organelle. In the present study, we firstly identified that protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondrial protein, which may induce apoptosis in HEK293T and HeLa cell lines. PTPIP51 transfection resulted in the externalization of phosphatidylserine (PS), activation of caspase-3, cleavage of PARP, and condensation of nuclear DNA. Further investigation revealed that PTPIP51 over-expression caused a decrease in mitochondrial membrane potential and release of cytochrome c, suggesting that it may be involved in a mitochondria/cytochrome c mediated apoptosis pathway. We also found that a putative TM domain near the N terminus of PTPIP51 is required for its targeting to mitochondria, as evidenced by the finding that deletion of the PTPIP51 TM domain prevented the protein's mitochondiral localization. Furthermore, this deletion significantly influenced the ability of PTPIP51 to induce apoptosis. Taken together, the results of the present study suggest that PTPIP51 is a mitochondrial protein with apoptosis-inducing function and that the N-terminal TM domain is required for both the correct targeting of the protein to mitochondria and its apoptotic functions.

Protein kinases are involved in comprehensive cellular processes and also implicated in many human diseases. SH3-binding domain kinase 1 (SBK1) was first cloned and characterized in rat and the human cDNA was cloned in our lab in 2006, but the expression and function of endogenous protein have not been well studied in human. In this follow up study, we screened a panel of cell lines and tissues, as well as a tumor tissue array for SBK1 expression at both RNA and protein levels. To detect the protein, we generated the first rabbit polyclonal antibody against human SBK1. We show that the SBK1 is expressed in most of the cells and tissues examined, and the protein is highly up-regulated in ovarian serous adenocarcinoma while down-regulated in esophagus squamous cell carcinoma and stomach adenocarcinoma. When over-expressed in an ovarian cancer cells SK-OV-3 by adenovirus infection, SBK1 protected the cells from apoptosis induced by the viral infection, therefore promoting cancer cell survival. Given that a missense mutation K92E in human SBK1 was identified recently from ovarian mucinous carcinoma, together, these results suggest that the wide-spread expression pattern of human SBK1 may predict a broad cellular function, and its dysregulated in certain cancers suggests an involvement of the protein in the pathogenesis of human cancers.

Background Estrogen receptor α (ERα) is a transcription factor whose activity is affected by multiple regulatory cofactors. In an effort to identify the human genes involved in the regulation of ERα, we constructed a high-throughput, cell-based, functional screening platform by linking a response element (ERE) with a reporter gene. This allowed the cellular activity of ERα, in cells cotransfected with the candidate gene, to be quantified in the presence or absence of its cognate ligand E2. Results From a library of 570 human cDNA clones, we identified zinc finger protein 131 (ZNF131) as a repressor of ERα mediated transactivation. ZNF131 is a typical member of the BTB/POZ family of transcription factors, and shows both ubiquitous expression and a high degree of sequence conservation. The luciferase reporter gene assay revealed that ZNF131 inhibits ligand-dependent transactivation by ERα in a dose-dependent manner. Electrophoretic mobility shift assay clearly demonstrated that the interaction between ZNF131 and ERα interrupts or prevents ERα binding to the estrogen response element (ERE). In addition, ZNF131 was able to suppress the expression of pS2, an ERα target gene. Conclusion We suggest that the functional screening platform we constructed can be applied for high-throughput genomic screening candidate ERα-related genes. This in turn may provide new insights into the underlying molecular mechanisms of ERα regulation in mammalian cells.