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Frequency analysis is a fundamental function of the auditory system, and it is essential to study the auditory response properties using behavior-related sounds. Our previous study has shown that the inferior collicular (IC) neurons of CF-FM (constant frequency-frequency modulation) bats could be classified into single-on (SO) and double-on (DO) neurons under CF-FM stimulation. Here, we employed Pratt's roundleaf bats, Hipposideros pratti, to investigate the frequency selectivity of SO and DO neurons in response to CF and behavior-related CF-FM sounds using in vivo extracellular recordings. The results demonstrated that the bandwidths (BWs) of iso-frequency tuning curves had no significant differences between the SO and the DO neurons when stimulated by CF sounds. However, the SO neurons had significant narrower BWs than DO neurons when stimulated with CF-FM sounds. In vivo intracellular recordings showed that both SO and DO neurons had significantly shorter post-spike hyperpolarization latency and excitatory duration in response to CF-FM in comparison to CF stimuli, suggesting that the FM component had an inhibitory effect on the responses to the CF component. These results suggested that SO neurons had higher frequency selectivity than DO neurons under behavior-related CF-FM stimulation, making them suitable for detecting frequency changes during echolocation.

α-Ketoisocaproate (KIC) is used widely in the pharmaceutical and nutraceutical industries. In previous studies, we achieved a one-step biosynthesis of KIC from l-leucine, using an Escherichia coli whole-cell biocatalyst expressing an l-amino acid deaminase (l-AAD) from Proteus vulgaris. Herein, we report the fine-tuning of l-AAD gene expression in E. coli BL21 (DE3) at the transcriptional and translational levels to improve the KIC titer. By optimizing the plasmid origin with different copy numbers, modulating messenger RNA structure downstream of the initiation codon, and designing the sequences at the ribosome binding site, we increased biocatalyst activity to 31.77%, 24.89%, and 30.20%, respectively, above that achieved with BL21/pet28a-lad. The highest KIC titers reached 76.47 g·L-1, 80.29 g·L-1, and 81.41 g·L-1, respectively. Additionally, the integration of these three engineering strategies achieved an even higher KIC production of 86.55 g·L-1 and a higher l-leucine conversion rate of 94.25%. The enzyme-engineering strategies proposed herein may be generally applicable to the construction of other biocatalysts.

Phenylpyruvic acid (PPA) is widely used in the pharmaceutical, food, and chemical industries. Here, a two-step bioconversion process, involving growing and resting cells, was established to produce PPA from l-phenylalanine using the engineered Escherichia coli constructed previously. First, the biotransformation conditions for growing cells were optimized (l-phenylalanine concentration 20.0 g·L-1, temperature 35°C) and a two-stage temperature control strategy (keep 20°C for 12 h and increase the temperature to 35°C until the end of biotransformation) was performed. The biotransformation conditions for resting cells were then optimized in 3-L bioreactor and the optimized conditions were as follows: agitation speed 500 rpm, aeration rate 1.5 vvm, and l-phenylalanine concentration 30 g·L-1. The total maximal production (mass conversion rate) reached 29.8 ± 2.1 g·L-1 (99.3%) and 75.1 ± 2.5 g·L-1 (93.9%) in the flask and 3-L bioreactor, respectively. Finally, a kinetic model was established, and it was revealed that the substrate and product inhibition were the main limiting factors for resting cell biotransformation.

Influenza virus vaccine (IVV) is a promising research domain that is closely related to global health matters, which has been acknowledged not only by scientists and technology developers, but also by policy-makers. Meanwhile, patents encompass valuable technological information and reflect the latest technological inventions as well as the innovative capability of a nation. However, little research has examined this up-and-coming research field using patent bibliometric method. Thus, this paper (a) designs the technology classification system and search strategy for the identification of IVV; and (b) presents a longitudinal analysis of the global IVV development based on the European Patent Office (EPO) patents. Bibliometric analysis is used to rank countries, institutions, inventors and technology subfields contributing to IVV technical progress. The results show that the global trends of IVV are a multi-developing feature of variety but an uneven technical resource distribution. Although the synthetic peptide vaccine is a comparatively young field, it already demonstrates the powerful vitality and the enormous development space. With the worldwide competition increasing, all nations especially China should be looking to increase devotion, enhance capability and regard effectiveness of technological innovation.

Eggshell damages lead to economic losses in the egg production industry and are a threat to human health. We examined 49-wk-old Rhode Island White hens (Gallus gallus) that laid eggs having shells with significantly different strengths and thicknesses. We used HiSeq 2000 (Illumina) sequencing to characterize the chicken transcriptome and whole genome to identify the key genes and genetic mutations associated with eggshell calcification. We identified a total of 14,234 genes expressed in the chicken uterus, representing 89% of all annotated chicken genes. A total of 889 differentially expressed genes were identified by comparing low eggshell strength (LES) and normal eggshell strength (NES) genomes. The DEGs are enriched in calcification-related processes, including calcium ion transport and calcium signaling pathways as revealed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Some important matrix proteins, such as OC-116, LTF and SPP1, were also expressed differentially between two groups. A total of 3,671,919 single-nucleotide polymorphisms (SNPs) and 508,035 Indels were detected in protein coding genes by whole-genome re-sequencing, including 1775 non-synonymous variations and 19 frame-shift Indels in DEGs. SNPs and Indels found in this study could be further investigated for eggshell traits. This is the first report to integrate the transcriptome and genome re-sequencing to target the genetic variations which decreased the eggshell qualities. These findings further advance our understanding of eggshell calcification in the chicken uterus.

Limited information is available regarding spatiotemporal variations of particles with median aerodynamic diameter < 2.5 μm (PM2.5) at high resolutions, and their relationships with meteorological factors in Beijing, China. This study aimed to detect spatiotemporal change patterns of PM2.5 from August 2013 to July 2014 in Beijing, and to assess the relationship between PM2.5 and meteorological factors.Daily and hourly PM2.5 data from the Beijing Environmental Protection Bureau (BJEPB) were analyzed separately. Ordinary kriging (OK) interpolation, time-series graphs, Spearman correlation coefficient and coefficient of divergence (COD) were used to describe the spatiotemporal variations of PM2.5. The Kruskal-Wallis H test, Bonferroni correction, and Mann-Whitney U test were used to assess differences in PM2.5 levels associated with spatial and temporal factors including season, region, daytime and day of week. Relationships between daily PM2.5 and meteorological variables were analyzed using the generalized additive mixed model (GAMM).Annual mean and median of PM2.5 concentrations were 88.07 μg/m3 and 71.00 μg/m3, respectively, from August 2013 to July 2014. PM2.5 concentration was significantly higher in winter (P < 0.0083) and in the southern part of the city (P < 0.0167). Day to day variation of PM2.5 showed a long-term trend of fluctuations, with 2-6 peaks each month. PM2.5 concentration was significantly higher in the night than day (P < 0.0167). Meteorological factors were associated with daily PM2.5 concentration using the GAMM model (R2 = 0.59, AIC = 7373.84).PM2.5 pollution in Beijing shows strong spatiotemporal variations. Meteorological factors influence the PM2.5 concentration with certain patterns. Generally, prior day wind speed, sunlight hours and precipitation are negatively correlated with PM2.5, whereas relative humidity and air pressure three days earlier are positively correlated with PM2.5.

Decidualization is a crucial process for successful embryo implantation and pregnancy in humans. Defects in decidualization during early pregnancy are associated with several pregnancy complications, such as pre-eclampsia, intrauterine growth restriction and recurrent pregnancy loss. However, the mechanism underlying decidualization remains poorly understood. In the present study, we performed a systematic analysis of decidualization-related genes using text mining. We identified 286 genes for humans and 287 genes for mice respectively, with an overlap of 111 genes shared by both species. Through enrichment test, we demonstrated that although divergence was observed, the majority of enriched gene ontology terms and pathways were shared by both species, suggesting that functional categories were more conserved than individual genes. We further constructed a decidualization-related protein-protein interaction network consisted of 344 nodes connected via 1,541 edges. We prioritized genes in this network and identified 12 genes that may be key regulators of decidualization. These findings would provide some clues for further research on the mechanism underlying decidualization.

Biomedical literature is an essential source of biomedical evidence. To translate the evidence for biomedicine study, researchers often need to carefully read multiple articles about specific biomedical issues. These articles thus need to be highly related to each other. They should share similar core contents, including research goals, methods, and findings. However, given an article r, it is challenging for search engines to retrieve highly related articles for r. In this paper, we present a technique PBC (Passage-based Bibliographic Coupling) that estimates inter-article similarity by seamlessly integrating bibliographic coupling with the information collected from context passages around important out-link citations (references) in each article. Empirical evaluation shows that PBC can significantly improve the retrieval of those articles that biomedical experts believe to be highly related to specific articles about gene-disease associations. PBC can thus be used to improve search engines in retrieving the highly related articles for any given article r, even when r is cited by very few (or even no) articles. The contribution is essential for those researchers and text mining systems that aim at cross-validating the evidence about specific gene-disease associations.

AIM:The aim of this study was to systemically evaluate the therapeutic efficacy of cytokine-induced killer (CIK) cells for the treatment of non-small cell lung cancer. MATERIALS AND METHODS:A computerized search of randomized controlled trials for CIK cell-based therapy was performed. The overall survival, clinical response rate, immunological assessment and side effects were evaluated. RESULTS:Overall, 17 randomized controlled trials of non-small cell lung cancer (NSCLC) with a total of 1172 patients were included in the present analysis. Our study showed that the CIK cell therapy significantly improved the objective response rate and overall survival compared to the non-CIK cell-treated group. After CIK combined therapy, we observed substantially increased percentages of CD3+, CD4+, CD4+CD8+, CD3+CD56+ and NK cells, whereas significant decreases were noted in the percentage of CD8+ and regulatory T cell (Treg) subgroups. A significant increase in Ag-NORs was observed in the CIK-treated patient group (p = 0.00001), whereas carcinoembryonic antigen (CEA) was more likely to be reduced to a normal level after CIK treatment (p = 0.0008). Of the possible major side effects, only the incidence of fever in the CIK group was significantly higher compared to the group that received chemotherapy alone. CONCLUSION:The CIK cell combined therapy demonstrated significant superiority in the overall survival, clinical response rate, and T lymphocytes responses and did not present any evidence of major adverse events in patients with NSCLC.

Efficiently obtaining full-length cDNA for a target gene is the key step for functional studies and probing genetic variations. However, almost all sequenced domestic animal genomes are not 'finished'. Many functionally important genes are located in these gapped regions. It can be difficult to obtain full-length cDNA for which only partial amino acid/EST sequences exist. In this study we report a general pipeline to obtain full-length cDNA, and illustrate this approach for one important gene (Ovocleidin-17, OC-17) that is associated with chicken eggshell biomineralization. Chicken OC-17 is one of the best candidates to control and regulate the deposition of calcium carbonate in the calcified eggshell layer. OC-17 protein has been purified, sequenced, and has had its three-dimensional structure solved. However, researchers still cannot conduct OC-17 mRNA related studies because the mRNA sequence is unknown and the gene is absent from the current chicken genome. We used RNA-Seq to obtain the entire transcriptome of the adult hen uterus, and then conducted de novo transcriptome assembling with bioinformatics analysis to obtain candidate OC-17 transcripts. Based on this sequence, we used RACE and PCR cloning methods to successfully obtain the full-length OC-17 cDNA. Temporal and spatial OC-17 mRNA expression analyses were also performed to demonstrate that OC-17 is predominantly expressed in the adult hen uterus during the laying cycle and barely at immature developmental stages. Differential uterine expression of OC-17 was observed in hens laying eggs with weak versus strong eggshell, confirming its important role in the regulation of eggshell mineralization and providing a new tool for genetic selection for eggshell quality parameters. This study is the first one to report the full-length OC-17 cDNA sequence, and builds a foundation for OC-17 mRNA related studies. We provide a general method for biologists experiencing difficulty in obtaining candidate gene full-length cDNA sequences.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer mortality worldwide. The development and progression of HCC is a complicated process, involving the deregulation of multiple genes that are essential to cell biological processes. Recently, microRNAs (miRNAs) have been suggested to be closely associated with tumorigenesis. Our study showed that miR-184 is upregulated in HCC cell lines and tissues. Overexpression of miR-184 in HCC cells increased cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-184 reduced cell proliferation, tumorigenicity, and cell cycle progression. Additionally, we identified SOX7 as a direct target of miR-184. Ectopic expression of miR-184 led to downregulation of the SOX7 protein, resulting in upregulation of c-Myc, Cyclin D1, and phosphorylation of Rb. Our findings suggested that miR-184 represents a potential onco-miR and plays an important role in HCC progression by suppressing SOX7 expression.

α-Keto-γ-methylthiobutyric acid (KMTB), a keto derivative of l-methionine, has great potential for use as an alternative to l-methionine in the poultry industry and as an anti-cancer drug. This study developed an environment friendly process for KMTB production from l-methionine by an Escherichia coli whole-cell biocatalyst expressing an engineered l-amino acid deaminase (l-AAD) from Proteus vulgaris. We first overexpressed the P. vulgaris l-AAD in E. coli BL21 (DE3) and further optimized the whole-cell transformation process. The maximal molar conversion ratio of l-methionine to KMTB was 71.2% (mol/mol) under the optimal conditions (70 g/L l-methionine, 20 g/L whole-cell biocatalyst, 5 mM CaCl2, 40°C, 50 mM Tris-HCl [pH 8.0]). Then, error-prone polymerase chain reaction was used to construct P. vulgaris l-AAD mutant libraries. Among approximately 104 mutants, two mutants bearing lysine 104 to arginine and alanine 337 to serine substitutions showed 82.2% and 80.8% molar conversion ratios, respectively. Furthermore, the combination of these mutations enhanced the catalytic activity and molar conversion ratio by 1.3-fold and up to 91.4% with a KMTB concentration of 63.6 g/L. Finally, the effect of immobilization on whole-cell transformation was examined, and the immobilized whole-cell biocatalyst with Ca2+ alginate increased reusability by 41.3% compared to that of free cell production. Compared with the traditional multi-step chemical synthesis, our one-step biocatalytic production of KMTB has an advantage in terms of environmental pollution and thus has great potential for industrial KMTB production.

BACKGROUND:The effectiveness of immunotherapy for high-grade glioma (HGG) patients remains controversial. To evaluate the therapeutic efficacy of dendritic cells (DCs) alone in the treatment of HGG, we performed a systematic review and meta-analysis in terms of patient survival with relevant published clinical studies. MATERIALS AND METHODS:A total of 409 patients, including historical cohorts, nonrandomized and randomized controls with HGG, were selected for the meta-analysis. RESULTS:The treatment of HGG with DCs was associated with a significantly improved one-year survival (OS) (p0.05), whereas CD56+ lymphocyte subset were significantly increased after DC treatment (p = 0.0001). Furthermore, the levels of IFN-γ in the peripheral blood of HGG patients, which reflect the immune function of the patients, were significantly increased after DC immunotherapy (p

BACKGROUND: Increasing evidence indicated plasma D-dimer could be regarded as a marker in cancers, however, its role in gastric cancer is still largely unknown. METHODS: Plasma D-dimer levels were measured by enzyme linked fluorescent immunoassays and evaluated by receiver operating characteristic (ROC) curves for peritoneal dissemination in gastric cancer and healthy subjects. The overall survival (OS) characteristics were determined using Kaplan-Meier and Cox regression analyses. RESULTS: The average of the plasma D-dimer levels for gastric cancer patients was significantly higher than the healthy subjects. A Spearman correlation analysis showed that plasma D-dimer levels correlated with the depth of invasion, lymph node metastasis, peritoneal dissemination, distant metastasis, tumor size and TNM stage. The mean plasma D-dimer level was 2.20 ± 1.51 µg/mL in peritoneal dissemination patients and 1.01 ± 0.79 µg/mL in non-peritoneal dissemination patients (P

An immune imbalance in the cytokine profile exerts a profound influence on the progression of hepatitis B virus (HBV) infections and hepatocellular carcinoma (HCC). The present study evaluated the immune status of T helper (Th) 17 and Th1 cells in patients with HBV-related and non-HBV-related HCC.We randomly enrolled 150 patients with HCC. Blood samples and tissue samples were obtained. The distributions and phenotypic features of Th17 and Th1 cells were determined by flow cytometry and/or immunohistochemistry.Compared to corresponding non-tumor regions, the levels of Th17 and Th1 cells were significantly increased in tumors of patients with HCC (P

High oxidative stability and catalytic efficiency are required for the alkaline α-amylases to keep the enzymatic performance under the harsh conditions in detergent industries. In this work, we attempted to significantly improve both the oxidative stability and catalytic efficiency of an alkaline α-amylase from Alkalimonas amylolytica by engineering the five oxidation-prone methionine residues around the catalytic domain via a systematic approach. Specifically, based on the tertiary structure analysis, five methionines (Met 145, Met 214, Met 229, Met 247 and Met 317) were individually substituted with oxidation-resistant threonine, isoleucine and alaline, respectively. Among the created 15 mutants, 7 mutants M145A, M145I, M214A, M229A, M229T, M247T and M317I showed significantly enhanced oxidative stability or catalytic efficiency. In previous work, we found that the replacement of M247 with leucine could significantly improve the oxidative stability. Thus, these 8 positive mutants (M145A, M145I, M214A, M229A, M229T, M247T, M247L and M317I) were used to conduct the second round of combinational mutations. Among the constructed 85 mutants (25 two-point mutants, 36 three-point mutants, 16 four-point mutants and 8 five-point mutants), the mutant M145I-214A-229T-247T-317I showed a 5.4-fold increase in oxidative stability and a 3.0-fold increase in catalytic efficiency. Interestingly, the specific activity, alkaline stability and thermal stability of this mutant were also increased. The increase of salt bridge and hydrogen bonds around the catalytic domain contributed to the significantly improved catalytic efficiency and stability, as revealed by the three-dimensional structure model of wild-type alkaline α-amylase and its mutant M145I-214A-229T-247T-317I. With the significantly improved oxidative stability and catalytic efficiency, the mutant M145I-214A-229T-247T-317I has a great potential as a detergent additive, and this structure-guided systems engineering strategy may be useful for the protein engineering of the other microbial enzymes to fulfill industrial requirements.

BACKGROUND: The expression of survivin is a promising prognostic indicator for some carcinomas. However, evidence for the prognostic value of survivin with respect to survival in hepatocellular carcinoma remains controversial. AIM: To conduct a systematic review of studies evaluating survivin expression in hepatocellular carcinoma as a prognostic indicator. METHODS: The relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases, and two meta-analyses were performed. One studied the association between survivin expression and the overall survival of patients with hepatocellular carcinoma, whereas the other studied the association between survivin expression and disease-free survival. Studies were pooled, and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted. RESULTS: Fourteen eligible studies with a total of 890 patients were included in this study. Two meta-analyses were performed according to the different outcomes by which prognosis was valued. The combined HR of the overall survival studies was 2.33 (95% CI: 1.65-3.31). The combined HR of disease-free survival studies was 2.13 (95% CI: 1.65-2.75). These data appeared to be significant when stratified by detection method, the language of publication, and HR estimate. The heterogeneities were highly significant (I(2)>50%) when subgroup analyses of overall survival rate were conducted, whereas little heterogeneity was found when subgroup analyses of disease-free survival rate were carried out. The positive expression of survivin in the cytoplasm was significantly correlated with poor prognosis in HCC (HR>1). CONCLUSIONS: This study showed that survivin expression was correlated with poor prognosis in patients with hepatocellular carcinoma, regardless whether they were assessed by overall survival or disease-free survival.

BACKGROUND AND AIMS:To identify and validate N-glycan biomarkers in gastric cancer (GC) and to elucidate their underlying molecular mechanism of action. METHODS:In total, 347 individuals, including patients with GC (gastric cancer) or atrophic gastritis and healthy controls, were randomly divided into a training group (n=287) and a retrospective validation group (n=60). Serum N-glycan profiling was achieved with DNA sequencer-assisted/fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Two diagnostic models were constructed based on the N-glycan profiles using logistic stepwise regression. The diagnostic performance of each model was assessed in retrospective, prospective (n=60), and follow-up (n=40) cohorts. Lectin blotting was performed to determine total core-fucosylation, and the expression of genes involved in core-fucosylation in GC was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS:We identified at least 9 N-glycan structures (peaks) and the levels of core fucose residues and fucosyltransferase were significantly decreased in GC. Two diagnostic models, designated GCglycoA and GCglycoB, were constructed to differentiate GC from control and atrophic gastritis. The areas under the receiver operating characteristic (ROC) curves (AUC) for both GCglycoA and GCglycoB were higher than those for CEA, CA19-9, CA125 and CA72-4. Compared with CEA, CA19-9, CA125 and CA72-4, the sensitivity of GCglycoA increased 29.66%, 37.28%, 56.78% and 61.86%, respectively, and the accuracy increased 10.62%, 16.82%, 25.67% and 28.76%, respectively. For GCglycoB, the sensitivity increased 27.97%, 35.59%, 55.09% and 60.17% and the accuracy increased 21.26%, 24.64%, 31.40% and 34.30% compared with CEA, CA19-9, CA125 and CA72-4, respectively. After curative surgery, the core fucosylated peak (peak 3) and the total core fucosylated N-glycans (sumfuc) were reversed. CONCLUSIONS:The results indicated that the diagnostic models based on N-glycan markers are valuable and noninvasive alternatives for identifying GC. We concluded that decreased core-fucosylation in both tissue and serum from GC patients may result from the decreased expression of fucosyltransferase.

The homing of mesenchymal stem cells to injured tissue, which is important for the correction of conditions such as ischemia-reperfusion injury (IRI) and immunolesions, has been performed previously, but with poor efficiency. Substantial improvements in engraftment are required to derive clinical benefits from MSC transplantation. Chemokines are the most important factors that control cellular migration. Stromal derived factor-1 (SDF-1) is up-regulated during tissue/organ ischemia damage, and its cognate receptor, chemokine receptor 4 (CXCR4), is involved in stem cell migration. The aim of our study was to investigate CXCR4 expression in MSCs and to validate both its role in mediating migration to transplanted kidneys and its immunoregulatory effects in renal protection. Specifically, the present study was designed to investigate the short-term tissue homing of MSCs carrying genetically modified CXCR4 in a rat renal transplantation model. We tested the hypothesis that MSCs with CXCR4 over-expression can more efficiently regulate immunological reactions. Lentiviral vectors were used to over-express CXCR4 or to introduce a short hairpin ribonucleic acid (shRNA) construct targeting endogenous CXCR4 in rat MSCs. MSCs were labeled with enhanced green fluorescent protein (eGFP). After cell sorting, recipient kidneys were regionally perfused; recipient animals were injected with transduced MSCs, native MSCs, or PBS via tail vein following renal transplantation; and the effects of MSC injection were observed.

OBJECTIVE: The prognostic significance of survivin for the survival of patients with gastric cancer remains controversial. Thus, the objective of this study was to conduct a systematic review of the literature evaluating survivin expression in gastric cancer as a prognostic indicator. METHODS: Relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases. A meta-analysis of the association between survivin expression and overall survival in patients with gastric cancer was performed. Studies were pooled and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted. RESULTS: Final analysis of 1365 patients from 16 eligible studies was performed. Combined HR suggested that survivin expression had an unfavorable impact on survival of gastric cancer patients (HR=1.39, 95% CI: 1.16-1.68). The unfavorable impact also appeared significant when stratified according to the studies categorized by patients' ethnicity, detection methods, type of sample, and HR estimate. The combined HR in the English literature showed an inverse effect on survival (HR=1.40, 95% CI: 1.13-1.75), while HR in the non-English literature did not (HR=1.38, 95% CI: 0.93-2.05). When stratified according to the location of survivin expression, combined HR showed that expression in cytoplasm was significantly associated with poor prognosis of gastric cancer patients (HR=1.46, 95% CI: 1.12-1.90). While expression in nucleus was not significantly associated with poor prognosis (HR=1.29, 95% CI: 0.72-2.31), the heterogeneity was highly significant (chi-squared=11.5, I(2)=74%, p=0.009). CONCLUSIONS: This study showed that survivin expression was associated with a poor prognosis in patients with gastric cancer. Cytoplasmic expression of survivin may be regarded as a prognostic factor for gastric cancer patients. In contrast, survivin expression in nucleus did not have a significant impact on patients' overall survival.

BACKGROUND: Junctional adhesion molecule 2 (Jam2) is a member of the JAM superfamily. JAMs are localized at intercellular contacts and participated in the assembly and maintenance of junctions, and control of cell permeability. Because Jam2 is highly expressed in the luminal epithelium on day 4 of pregnancy, this study was to determine whether Jam2 plays a role in uterine receptivity and blastocyst attachment in mouse uterus. METHODOLOGY/PRINCIPAL FINDINGS: Jam2 is highly expressed in the uterine luminal epithelium on days 3 and 4 of pregnancy. Progesterone induces Jam2 expression in ovariectomized mice, which is blocked by progesterone antagonist RU486. Jam2 expression on day 4 of pregnancy is also inhibited by RU486 treatment. Leukemia inhibitory factor (LIF) up-regulates Jam2 protein in isolated luminal epithelium from day 4 uterus, which is blocked by S3I-201, a cell-permeable inhibitor for Stat3 phosphorylation. Under adhesion assay, recombinant Jam2 protein increases the rate of blastocyst adhesion. Both soluble recombinant Jam2 and Jam3 can reverse this process. CONCLUSION: Jam2 is highly expressed in the luminal epithelium of receptive uterus and up-regulated by progesterone and LIF via tyrosine phosphorylation of Stat3. Jam2 may play a role in the interaction between hatched blastocyst and receptive uterus.

BACKGROUND: Delayed implantation is a developmental arrest at the blastocyst stage and a good model for embryo implantation. MicroRNAs (miRNAs) have been shown to be involved in mouse embryo implantation through regulating uterine gene expression. This study was to have an integrative analysis on global miRNA and mRNA expression in mouse uterus under delayed implantation and activation through Illumina sequencing. METHODOLOGY/PRINCIPAL FINDINGS: By deep sequencing and analysis, we found that there are 20 miRNAs up-regulated and 42 miRNAs down-regulated at least 1.2 folds, and 268 genes up-regulated and 295 genes down-regulated at least 2 folds under activation compared to delayed implantation, respectively. Many different forms of editing in mature miRNAs are detected. The percentage of editing at positions 4 and 5 of mature miRNAs is significantly higher under delayed implantation than under activation. Although the number of miR-21 reference sequence under activation is slightly lower than that under delayed implantation, the total level of miR-21 under activation is higher than that under delayed implantation. Six novel miRNAs are predicted and confirmed. The target genes of significantly up-regulated miRNAs under activation are significantly enriched. CONCLUSIONS: miRNA and mRNA expression patterns are closely related. The target genes of up-regulated miRNAs are significantly enriched. A high level of editing at positions 4 and 5 of mature miRNAs is detected under delayed implantation than under activation. Our data should be valuable for future study on delayed implantation.

Knowledge of protein domains that function as the biological effectors for diverse post-translational modifications of histones is critical for understanding how nuclear and epigenetic programs are established. Indeed, mutations of chromatin effector domains found within several proteins are associated with multiple human pathologies, including cancer and immunodeficiency syndromes. To date, relatively few effector domains have been identified in comparison to the number of modifications present on histone and non-histone proteins. Here we describe the generation and application of human modified peptide microarrays as a platform for high-throughput discovery of chromatin effectors and for epitope-specificity analysis of antibodies commonly utilized in chromatin research. Screening with a library containing a majority of the Royal Family domains present in the human proteome led to the discovery of TDRD7, JMJ2C, and MPP8 as three new modified histone-binding proteins. Thus, we propose that peptide microarray methodologies are a powerful new tool for elucidating molecular interactions at chromatin.

Knowledge of protein domains that function as the biological effectors for diverse post-translational modifications of histones is critical for understanding how nuclear and epigenetic programs are established. Indeed, mutations of chromatin effector domains found within several proteins are associated with multiple human pathologies, including cancer and immunodeficiency syndromes. To date, relatively few effector domains have been identified in comparison to the number of modifications present on histone and non-histone proteins. Here we describe the generation and application of human modified peptide microarrays as a platform for high-throughput discovery of chromatin effectors and for epitope-specificity analysis of antibodies commonly utilized in chromatin research. Screening with a library containing a majority of the Royal Family domains present in the human proteome led to the discovery of TDRD7, JMJ2C, and MPP8 as three new modified histone-binding proteins. Thus, we propose that peptide microarray methodologies are a powerful new tool for elucidating molecular interactions at chromatin. [ABSTRACT FROM AUTHOR]