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More than 300 missense mutations in PSEN1 gene have been correlated to the early-onset Alzheimer's disease (EOAD), but given the high diversity of PS1 (the PSEN1 gene product) substrates and the involvement of PS1 in multiple biological functions, different mutants may represent different EOAD etiologies, and how each mutant contributes to the EOAD remains to be further investigated. Here we report the identification of a novel PSEN1 p.Tyr159Ser in a family with multiple EOAD cases. The mutant PS1 protein (PS1

Bone marrow stromal cell antigen 2 (BST-2), also known as CD317 or tetherin, has been identified as a host restriction factor that suppresses the release of enveloped viruses from host cells by physically tethering viral particles to the cell surface, however, this host defense can be subverted by multiple viruses. For example, human immunodeficiency virus (HIV)-1 encodes a specific accessory protein, viral protein U (Vpu), to counteract BST-2 by binding to it and directing its lysosomal degradation. Thus, blocking the interaction between Vpu and BST-2 will provide a promising strategy for anti-HIV therapy. Here, we report a NanoLuc Binary Technology (NanoBiT)-based high-throughput screening assay to detect inhibitors that disrupt the Vpu-BST-2 interaction. Out of more than 1000 compounds screened, four inhibitors were identified with strong activity at nontoxic concentrations. In subsequent cell-based BST-2 degradation assays, inhibitor Y-39983 HCl restored the cell-surface and total cellular level of BST-2 in the presence of Vpu. Furthermore, the Vpu-mediated enhancement of pesudotyped viral particle production was inhibited by Y-39983 HCl. Our findings indicate that our newly developed assay can be used for the discovery of potential antiviral molecules with novel mechanisms of action.

With the advantages of long-distance contactless identification and data storage capacity, the use of radio frequency identification (RFID) technology in the fields of manufacturing, transportation and logistics has been widely reported. Fatigue of workers plays a critical role in impacting the manufacturing efficiency because it reduces productivity and increases accident rates. Therefore, the workers’ fatigue must be well examined and addressed. This paper thus proposes an analytic approach to use RFID captured production data and builds an effective method for mining the structural insight to predict the fatigue trajectory in workplace from a huge number of RFID data which may be full of inaccurate, incomplete and missing records. In this research, realistic processing time is used to measure the workers’ fatigue. Based on a general framework for the fatigue examination, the proposed approach is able to estimate the employees’ fatigue trajectory within designated period of time using RFID-enabled production data. Different genders and shifts are considered to find the key impact factors on fatigue.

The melanoma antigen gene family A (MAGEA) family of proteins comprises of cancer-testis antigens that are highly expressed in a number of tumours but are minimally expressed in normal cells. Due to its expression characteristics, this protein family has become a popular target for anti-cancer drugs and immunotherapy research over recent years. Although, elevated expression levels of MAGEA6 has been found in different types of tumours, there remains to be insufficient information on the function of MAGEA6 and its associated gene regulation pathways. The present study used Transwell, Cell Counting Kit-8 and wound healing assays to analyse the effects of MAGEA6 on Eca109 cell invasion, migration and proliferation. The main functions and pathways involved in MAGEA6 were predicted by Illumina Hiseq screening for mutually regulated genes and core genes. Eca109 cell line with a high expression of MAGEA6 was a stable cell line obtained by transfection in the early stage, and this cell line was used in subsequent experiments. Transcriptome sequencing was performed on this cell line and the Eca109 cell line that normally expressed MAGEA6. It was revealed that a high expression of MAGEA6 conferred a significant stimulating effect on cell proliferation whilst also significantly increasing cell invasion and migration. Transcriptomic analysis identified 14 differentially expressed genes and 13 core regulatory genes closely associated with MAGEA6 expression regulation, such as methylsterol monooxygenase 1 (MSMO1). The present study suggest that MAGEA6 positively regulated MSMO1 expression, which may serve an oncogenic role in cells through this regulatory effect. Overall, this provided a novel route of investigation for an in-depth study of the regulatory function of MAGEA6.

It has been postulated that a cognitive approach may lend itself well to the study of transferred epithets, as this traditional rhetoric device possesses all the essences of metaphor from the perspective of Cognitive Linguistics. Transferred epithet metaphors are gradually cognitively cultivated upon human beings’ repetitive and recursive experiences of the real world and it has been well established that they cannot be separated from culture’s limitations or reformulation. The coupling between experientialism and culture in transferred epithet metaphors necessitates the establishment of a double paradigm to comprehensively and profoundly delve into the twofold restraints.

To investigate the effect of 1800 MHz electromagnetic radiation (EMR) on apoptosis, we exposed NIH/3T3 cells at 1800 MHz with a specific absorption rate (SAR) of 2 W/kg intermittently for 12, 24, 36, and 48 h. After exposure, Cell Counting Kit-8 (CCK-8) and flow cytometry were used to detect cell viability and apoptosis, the expression of p53, a molecule with the key role in apoptosis, was measured by real-time qPCR, western blot, and immunofluorescence, and images of the structure of the mitochondria, directly reflecting apoptosis, were captured by electron microscopy. The results showed that the viability of cells in the 12, 36, and 48 h exposure groups significantly decreased compared with the sham groups, after 48 h of exposure, the percentage of late apoptotic cells in the exposure group was significantly higher. Real-time qPCR results showed that p53 mRNA in the 48 h exposure group was 1.4-fold of that in the sham group, significant differences of p53 protein fluorescence expression were observed between the exposure groups and the sham groups after 24 h and 48 h. The mitochondrial swelling and vesicular morphology were found in the electron microscopy images after 48 h exposure. These findings demonstrated 1800 MHz, SAR 2 W/kg EMR for 48 h may cause apoptosis in NIH/3T3 cells and that this apoptosis might be attributed to mitochondrial damage and upregulation of p53 expression.

Background Acute cerebral infarction with adenomyosis in a young woman has been rarely reported. Case presentation We describe a 34-year-old young woman who presented headache and fever (38°C) for 4 days and left limb weakness for 1 day during her menstrual phase. Laboratory test data showed: Hemoglobin (HGB) (112g/L, normal: 120-150 g/L), Carcinoembryonic antigen 125 (CA125) (937.70U/ml, normal: 0-35 U/ml), D-Dimer (27.4mg/L, normal: 0-1.5mg/L). Magnetic resonance imaging (MRI) indicated acute cerebral infarction in right basal ganglia and subcortical region of right frontotemporal lobe. Further, brain computed tomography angiography (CTA) showed that the M1 segment of right middle cerebral artery was strictured and the distal branches of right middle cerebral artery were significantly less than those on the opposite side. No obvious abnormality was found in cranial magnetic resonance venogram (MRV). She had a 5-year history of adenomyosis. No tumors were found by whole body positron emission tomography-computed tomography (PET-CT). We treated this patient by using anti-infective therapy for 1 week and using anticoagulant therapy with low molecular weight heparin for 2 weeks. Subsequently, the anticoagulant therapy was discontinued and replaced by antiplatelet therapy with poliovir. We followed up this patient for 4 months, and no recurrence of cerebral infarction was found. Conclusions Acute cerebral infarction with adenomyosis may be related to elevated D-Dimer, elevated CA125, anemia, menstruation and fever. Our report suggests that acute cerebral infarction with adenomyosis can occur not only in middle-aged women but also in young women, and fever during menstrual phase in a woman with adenomyosis may be a factor leading to acute cerebral infarction.

MicroRNA-34a (miR-34a) modulation therapy has shown great promise to treat hepatocellular carcinoma (HCC). 2'-Hydroxy-2,4,4',5,6'-pentamethoxychalcone, termed Rubone, has been shown to specifically upregulate miR-34a expression in HCC cells and considered as novel anticancer agent. However, the extremely low aqueous solubility of Rubone hampers its use in cancer treatment. In the present study, surface-stabilized nanoparticles-based delivery strategy was engaged to overcome this impediment. In our preparation, Rubone was encapsulated in the micelles composed of polyethylenimine-poly(epsilon-caprolactone) (PEI-PCL) through hydrophobic interactions, which were subsequently stabilized with anionic carboxymethyl dextran CMD via electronic interaction. We found that Rubone-encapsulating nanoparticles are dispersed well in aqueous solution. The results further demonstrated that Rubone could be efficiently delivered in HCC cells by nanoparticles and upregulate miR-34a expression, which in turn led to inhibition of proliferation, migration, and increased apoptosis of HCC cells. In vivo experiments showed that Rubone can be preferentially delivered into tumor tissues by CMD-stabilized PEI-PCL nanoparticles after intravenous administration and significantly inhibited tumor growth. Furthermore, low cytotoxicity of the nanoparticles was observed in vitro and in vivo analyses, indicating a good compatibility of generated nanoparticles. The obtained results suggest that CMD-stabilized PEI-PCL nanoparticles may serve as a novel approach for small-molecule-modulator-mediated miR-34a restoration for HCC therapy.

Inactivated vaccines are widely used for prevention of viral disease. Both humoral and cellular immune responses have been shown to play important roles in the control and clearance of virus infections. CpG motif containing oligodeoxynucleotides (ODN) have recently gained considerable interest and been used as vaccine adjuvant due to their potent abilities to modulate host immune response. In this study, CpG-ODN adjuvant and inactivated viral particles of enterovirus 71 (EV71) were co-encapsulated into nanoparticles (NP) generated by using protamine sulfate (PS) and carboxymethyl β-glucan (CMG) through a self-assembly approach. The administration of EV71 nanovaccine elicited not only specific anti-EV71 neutralizing antibody response, but also cellular immune response characterized by strong productions of IFN-α and IFN-γ. The results suggest that CMG/PS-based nanovehicles hold a great potential to be a novel platform for nanovaccine development against viral disease.

The aim of this study was to detect the presence and mutation of human papillomavirus 18 E5 gene in esophageal carcinoma tissue specimens from Tangshan region, a high-incidence area of China. 94 esophageal carcinoma tissue specimens with diagnosis of HPV18 positive were obtained by a pathology department in Tangshan, from 2011 to 2013. DNA of all 94 samples was extracted, and the quality of the DNA extraction was tested by a β-globin PCR. Type-specific PCR was performed to detect the presence of HPV18 E5 gene in extracted DNA of tissue specimens. The PCR products of E5 gene were sequenced and the mutation sites were analyzed. Our results showed that the quality of DNA extraction in these tissue samples were 100% qualified. 34/94(36%) of specimens could detect the presence of HPV18 E5 DNA sequences, and 4/34(12%) of samples occurred sequence mutation. 3/4(75%) of the mutations happened in the initiation codon sites. This study revealed that HPV18 E5 may play an important role in progression of esophageal carcinoma.

Turn-taking is a common scene in our daily life, however, the neural mechanism behind it is not fully understood yet. Researchers have proposed several theories to explain this phenomenon, and one of these theories is the oscillator model. In this model, the brains of the speaker and the listener are described as two "oscillators" and become mutually entrained during turn-taking. EEG hyperscanning is a method for studying two or more individuals simultaneously with the objective of elucidating how co-variations in their neural activity are influenced by their behavioral and social interactions. Turn-taking, as a frequent social interaction, could be investigated with EEG hyperscanning technique. In this paper, we designed an experiment allowing us to simultaneously record the EEG signals of the subjects during turn-taking in conversations, and depicted the method to measure the "hyperconnectivity" (functional connectivity between the two brains) by means of Partial Directed Coherence. Our study showed that: (1) there are significant hyperconnectivity links between the speaker and the listener; (2) The hyperconnectivity links mostly direct from the speaker to the listener; (3) Hyperconnectivity links in Beta band are much denser than those in Alpha band; (4) The T8 electrode plays a key role in the hyperconnectivity network.

An HIV-1 cell-cell fusion system was developed to screen HIV-1 entry inhibitors that block cell-cell fusion. In this system, the pEGFP-Tat plasmid was constructed and cotransfected into effector cells (HEK-293T) with HIV-1 envelope plasmid. TZM-bl cell, a genetically engineered cell line that expresses CD4, CXCR4, CCR5 as well as Tat-inducible β-galactosidase and luciferase reporter gene, was used as target cell. Thus, the co-culture of target cells and effector cells allows the cell fusion via Env and the activity of the fusion inhibitor can be quantified by measuring the reporter protein expression. The experimental parameters were optimized and 11 anti-HIV-1 agents including CCR5 antagonist maraviroc, reverse transcription inhibitor zidovudine (AZT) and integrase inhibitor raltegravir were tested. The result showed that the system exhibited high specificity and sensitivity. Two of eight tested anti-HIV-1 agents were found to block the cell-cell fusion. The system is suitable for efficient screening of HIV-1 cell-cell fusion inhibitors.旨在建立一个细胞-细胞融合系统，高效筛选对HIV-1 病毒细胞-细胞间传播有抑制作用的药物。构建了pEGFP-Tat 质粒，将pEGFP-Tat 质粒和HIV-1 包膜质粒共转染HEK-293T 细胞，成为表达Tat 蛋白和包膜蛋白的效应细胞，然后与表达CD4 及辅助受体和β-半乳糖苷酶、荧光素酶双报告基因的靶细胞TZM-bl 融合，建立了细胞-细胞融合系统，并进行条件优化，确定了最佳的融合体系。用阳性融合抑制剂maraviroc 以及没有融合抑制作用的AZT 和raltegravir 作用于该体系，证明该系统可以特异性有效筛选具有细胞融合抑制作用的药物。用该系统测试了8 个样本，发现两种样品对融合有一定的抑制作用。该方法背景值低，特异性强，可用来高效筛选具有切断HIV-1 病毒细胞-细胞间传播作用的抗病毒药物。.

Fifteen new DOPA-derived pyrrole alkaloids, named baculiferins A-O (2-16), were isolated from the Chinese marine sponge Iotrochota baculifera, together with the known alkaloids purpurone (1) and ningalin A (17). Most of the new compounds contain one to three O-sulfate units. Their structures were determined by extensive spectroscopic analysis including (1)H and (13)C NMR (COSY, HMQC, HMBC) and ESIMS data. A possible pathway for the biosynthetic origin of the isolated alkaloids is proposed, in which DOPA is assumed to be a joint biogenetic precursor. Baculiferins C, E-H, and K-N (4, 6-9, 12-15) were found to be potent inhibitors against the HIV-1 IIIB virus in both, MT4 and MAGI cells. Additional bioassay revealed that baculiferins could dramatically bind to the HIV-1 target proteins Vif, APOBEC3G, and gp41, for which structure-activity relationships are discussed.

Here, we report the anti-human immunodeficiency virus (HIV) potency and underlying mechanisms of a Keggin polyoxometalate (PT-1, K6HPTi2W10O40). Our findings showed that PT-1 exhibited highly potent effects against a diverse group of HIV type 1 (HIV-1) strains and displayed low cytotoxicity and genotoxicity. The time-addition assay revealed that PT-1 acted at an early stage of infection, and these findings were supported by the observation that PT-1 had more potency against Env-pseudotyped virus than vesicular stomatitis virus glycoprotein (VSVG) pseudotyped virus. Surface plasmon resonance binding assays and flow cytometry analysis showed that PT-1 blocked the gp120 binding site in the CD4 receptor. Moreover, PT-1 bound directly to gp41 NHR (N36 peptide), thereby interrupting the core bundle formation of gp41. In conclusion, our data suggested that PT-1 may be developed as a new anti-HIV-1 agent through its effects on entry inhibition.

To prepare HIV-1 Vif and hAPOBEC3G and to produce their antibodies, the full length gene fragment of HIV-1 vif was amplified by PCR from a plasmid of HIV-1 NL4.3 cDNA, and the APOBEC3G gene was obtained by RT-PCR from the total RNA of H9 cells. The resulting DNA construct was cloned into a prokaryotic expression vector (pET-32a). Recombinant pET-vif and pET-APOBEC3G were expressed respectively in Eserichia coli BL21 (DE3) as an insoluble protein. The vector also contained a six-histidine tag at the C-terminus for convenient purification and detection. To express and purify the HIV-1 Vif and hAPOBEC3G in E.coli cells, the accuracy of inserted gene and specificity of proteins were detected by the two enzyme digestion method, SDS-PAGE, and Western blotting. Rabbits were then immunized by Vif or APOBEC3G protein and serum samples were tested by indirect ELISA to determine the level of antibodies. Immunoenzyme and immunofluorescence assays were performed to identify the specificity of polyclonal antibodies. The titer of the anti-Vif antibodies was 1:204800, and that of the anti-APOBEC3G antibodies was 1:102400. Thus the antibodies could detect the antigen expression in the cells, demonstrating that fusion proteins with high purity and their corresponding polyclonal antibodies with high titer and specificity were achieved.

Replacement of downregulated tumor‐suppressive microRNA (Ts‐miRNA) is recognized as an alternative approach for tumor gene therapy. However, in situ monitoring of miRNA replacement efficacy in a real‐time manner via noninvasive imaging is continually challenging. Here, glutathione (GSH)‐activated light‐up peptide‐polysaccharide‐inter‐polyelectrolyte nanocomplexes are established through self‐assembly of carboxymethyl dextran with disulfide‐bridged (“S—S”) oligoarginine peptide (S‐Arg4), in which microRNA‐34a (miR‐34a) and indocyanine green (ICG) are simultaneously embedded and the nanocomplexes are subsequently stabilized by intermolecular cross‐linking. Upon confinement within the robust nanocomplexes, the near‐infrared fluorescence (NIRF) of ICG is considerably quenched (“off”) due to the aggregation‐caused quenching effect. However, after intracellular delivery, the disulfide bond in S‐Arg4 can be cleaved by intracellular GSH, which leads to the dissociation of nanocomplexes and triggers the simultaneous release of miR‐34a and ICG. The NIRF of ICG is concomitantly activated through dequenching of the aggregated ICG. Very interestingly, a good correlation between time‐dependent increase in NIRF intensity and miR‐34a replacement efficacy is found in nanocomplexes‐treated tumor cells and tumor tissues through either intratumoral or intravenous injections. Systemic nanocomplexes‐mediated miR‐34a replacement significantly suppresses the growth of HepG‐2‐ and MDA‐MB‐231‐derived tumor xenografts, and provides a pronounced survival benefit in these animal models.

Quantitative real-time PCR of the EGFP mRNA for 5-AZA-CdR treated Hep G2 cell lines. (PDF 114Â kb)

Aquatic sampling sites around the Haihe river estuary of Bohai Sea. All five sites are 15 km from the coastal line and 20 km apart. (PDF 755Â kb)

The optimal check time for TDQ test with repetitive tests of 5-AZA-CdR treatment. (PDF 11Â kb)

Metastatic relapse, development of drug resistance in cancer cells and adverse side effects of chemotherapeutic agents are the major obstacles for effective chemotherapy against triple-negative breast cancer. To address these problems, miR-34a, a potent endogenous tumor suppressive molecule in breast cancer, was co-encapsulated with doxorubicin (DOX) into hyaluronic acid (HA)-chitosan (CS) nanoparticles (NPs) and simultaneously delivered into breast cancer cells for improved therapeutic effects of drug. DOX-miR-34a co-loaded HA-CS NPs were successfully prepared through ionotropic gelation method in water. In vitro and in vivo experiments showed that miR-34a and DOX can be efficiently encapsulated into HA-CS NPs and delivered into tumor cells or tumor tissues and enhance anti-tumor effects of DOX by suppressing the expression of non-pump resistance and anti-apoptosis proto-oncogene Bcl-2. In addition, intracellular restoration of miR-34a inhibited breast cancer cell migration via targeting Notch-1 signaling. The obtained data suggest that co-delivery of DOX and miR-34a could achieve synergistic effects on tumor suppression and nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy.

The expression of miR-203 has been reported to be significantly down-regulated in esophageal cancer. We showed here that overexpression of miR-203 in esophageal cancer cells dramatically increased cell apoptosis and inhibited cell proliferation, migration and invasion as well as tumor growth and down-regulated miR-21 expression. We subsequently identified that small GTPase Ran was a target gene of miR-203. Furthermore, Ran restoration partially counteracted the tumor suppressive effects of miR-203 and increased miR-21 expression. Taken together, our findings suggest that miR-203 may act as novel tumor suppressor in esophageal cancer through down-regulating the expression of Ran and miR-21.

Cell morphology is the research foundation in many applications related to the estimation of cell status, drug response, and toxicity screening. In biomedical field, the quantitative phase detection is an inevitable trend for living cells. In this paper, the morphological change of HeLa cells treated with methanol of different concentrations is detected using digital holographic microscopy. The compact image-plane digital holographic system is designed based on fiber elements. The quantitative phase image of living cells is obtained in combination with numerical analysis. The statistical analysis shows that the area and average optical thickness of HeLa cells treated with 12.5% or 25% methanol reduce significantly, which indicates that the methanol with lower concentration could cause cellular shrinkage. The area of HeLa cells treated with 50% methanol is similar to that of normal cells(P>0.05), which reveals the fixative effect of methanol with higher concentration. The maximum optical thickness of the cells treated with 12.5%, 25%, and 50% methanol is greater than that of untreated cells, which implies the pyknosis of HeLa cells under the effect of methanol. All of the results demonstrate that digital holographic microscopy has supplied a noninvasive imaging alternative to measure the morphological change of label-free living cells.

Introduction A potent mesenchymal stem cell (MSC) population was recently isolated from the Wharton's jelly of human umbilical cord (UC). The aim of the current experiments was to determine the potential of human UC-derived MSC (UC-MSC) in cartilage healing. Materials and methods Chondrogenic differentiation of collagen hydrogel-embedded cells was induced in standard chondrocyte conditioning medium and further detected by real-time PCR, histochemistry and immunohistochemistry analyses. Cell viability and apoptosis of the MSCs in the collagen I hydrogels were monitored using apoptosis detection kit. Results Cells isolated from UC were positive for MSC biomarkers and negative for haematopoietic lineage and endothelial biomarkers and possess the capacity to differentiate along osteogenic lineage. UC-MSCs embedded in collagen hydrogel can undergo chondrogenesis characterised by significantly increased expressions of collagen II, aggrecan, COMP (cartilage oligomeric matrix protein) and sox9 after exposed cells-embedded hydrogels to chondrogenic factors. The most of cells remained viable throughout the hydrogels after 3 weeks of cultivation in chondrogenic differentiation medium. Conclusions Collagen hydrogel can provide an appropriate 3-D environment for the chondrogenesis of UC-MSCs. UC-MSCs embedded in biocompatible scaffold may have great potential for cartilage engineering.

Background Mucosa-associated lymphoid tissue (MALT) lymphoma comprises approximately 8% of all non-Hodgkin lymphomas and is the most common lymphoma in the gastro-intestinal tract. It is caused by genetic abnormalities or bacterial infections/chronic inflammation. B-cell lymphoma/leukemia 10 (BCL10) overexpression and nuclear expression have been associated with high-grade MALT lymphomas with genetic abnormalities that are unresponsive to Helicobacter pylori eradication treatment. To explore the molecular mechanism of BCL10 overexpression on the pathogenesis and malignant phenotype of MALT lymphoma, we generated EµSR-BCL10 transgenic mice. Procedure By generation of heterozygous and homozygous EuSR-BCL10 mice and showing BCL10 expression levels in these mice, we quantitatively examined relation of MZ B cell expansion and inhibition of caspase-8 activity with BCL10 protein level. We also investigated API2 and caspase-8 expression by Western blot and their interaction with BCL10 by co-immunoprecipitation. Results MZ B-cell expansion is directly related to BCL10 protein level in a dose-dependent manner. The activity of caspases-8 and -3, but not caspase-9, was inhibited with increasing of BCL10 protein level. Expanded MZ B cells showed selective survival under stimulation of anti-immunoglobulin M, but not dexamethasone, γ-irradiation, or anti-CD95, implying that overexpressed BCL10 exerts anti-apoptotic effects through B-cell antigen receptor (BCR) pathway. Overexpressed BCL10 protein co-immunoprecipitated with caspase-8 and API2 protein, suggesting an in vivo interaction of them. Conclusion Our data demonstrate a novel effect of overexpressed BCL10 in the pathogenesis of high-grade MALT lymphoma by increasing expression of API2 and it then forming a protein complex with BCL10/caspase-8 leading to caspase-8 activity suppression. Pediatr Blood Cancer 2012; 58: 865–871. © 2011 Wiley Periodicals, Inc.

tetherin cDNA was amplified from total RNA prepared from HeLa cells by RT-PCR, then cloned into the eukaryotic expression vector pEGFP-C3. The generated pEGFP-Tetherin construct was transfected into COS-1 to determine the expression and the subcellular localization of GFP-Tetherin fusion protein. Under CLSM the localization of GFP-Tetherin fusion protein distributed outside the nucleus and co-localized with TGN in COS-1 cells.

Abstract 3694 Mucosa-associated lymphoid tissue (MALT) lymphoma comprises approximately 8% of all non-Hodgkin lymphomas and is the most common lymphoma in the gastrointestinal tract. B-cell lymphoma/leukemia 10 (BCL10) overexpression and nuclear expression has been associated with high-grade MALT lymphomas unresponsive to H. pylori eradication treatment. To explore the molecular mechanism of BCL10 overexpression on the pathogenesis and malignant phenotype of MALT lymphoma, we generated EμSR-BCL10 transgenic mice. Results in our previous report showed that predisposition to marginal zone B-cell lymphoma (MZL) development was enhanced in these transgenic mice. MALT lymphoma precursor cells - marginal zone (MZ) B cells - are expanded in BCL10 transgenic mice. Constitutive activation of both canonical and noncanonical NF-κB pathways was identified in these MZ B cells. Elevated expression of BAFF, a NF-κB downstream gene, may be in part responsible for increased tumor cell survival in MALT lymphomas. In this continuing study, quantitative analysis of BCL10 protein levels and the extent of MZ B cell expansion in heterozygous (Tg/+) and homozygous (Tg/Tg) EμSR-BCL10 transgenic mice demonstrated a direct pathogenic effect of BCL10 protein on MALT lymphomagenesis. The activities of caspase-8 and caspase-3, but not caspase-9, were inhibited with increasing BCL10 protein levels in a dose-dependent manner. Apoptosis induced by anti-IgM was selectively inhibited in MZ B cells from transgenic mice, but no differences were observed following treatment with dexamethasone, γ-irradiation or anti-CD95, implying that overexpressed BCL10 exerts anti-apoptotic effects through the B-cell antigen receptor pathway. Expression of API2, another NF-κB downstream gene, was also elevated in a dose-dependent manner with BCL10 protein level in the MZ B cells. Overexpressed BCL10 protein co-immunoprecipitated with caspase-8 and API2, suggesting an in vivo interaction leading to inhibition of caspase-8 activity. Our current data suggests a novel effect of overexpressed BCL10 in the pathogenesis of high-grade MALT lymphoma by increasing expression of API2 and recruitment of API2 and caspase-8 to form a protein complex leading to the suppression of caspase-8 activity in MZ B cells. Disclosures: No relevant conflicts of interest to declare.