Description: Background: Staphylococcus aureus is the major cause of hospital-acquired and community-acquired pneumonia. Host defense to S.aureus infection is largely mediated by the innate immune system. gammadelta T cells play an important role in innate immunity to many infectious diseases. However, less is known about the role of these cells during S.aureus-induced pneumonia. In this study, we examined the response and the role of gammadelta T cells to pulmonary S.aureusinfection. Results: Mice infected with S. aureus intranasally showed rapid gammadelta T cells accumulation in the lung. Deficiency of gammadelta T cells led to attenuated bacterial clearance and less tissue damage in lung compared with WT mice. Moreover, TCR-delta/mice exhibited impaired neutrophilrecruitment and reduced cytokine production at the site of infection. The gammadelta T cells in response to pulmonary S. aureus infection mainly secreted IL-17 and gammadelta T cells deficiency reduced IL-17 production, which might regulate the production of neutrophil-inducingcytokine/chemokine in the S. aureus-infected lungs Conclusions: Accumulation of gammadelta T cells in the lungs to S. aureus infection is beneficial for bacteria clearance and also contributes to the tissue damage. These cells were the primary source of IL-17, which might influence the recruitment of neutrophils at the early stage of infection.

Description: Background: The mechanisms that underlie autophagy in cerebral ischemia remain poorly defined. Myeloid cell leukemia-1 (Mcl1), an anti-apoptotic member of the Bcl-2 family of proteins, regulates the balance between autophagy and apoptosis. However, little is known regarding its expression profile and contribution to cell fate in the brain following ischemic stroke. Results: In this study, we investigated the expression profile and cellular distribution of Mcl1 in brains from transient middle cerebral artery occlusion (MCAO) model rats. Brain slices from sham-operated control rats showed minimal immunoreactivity for Mcl1. Mcl1 was mainly produced in neurons. Immunoreactivity for Mcl1 increased as early as 4 hours after MCAO, peaked at 24 hours, and then declined, but still remained high, at 72 hours. Mcl1 positive cells never colocalized with either cleaved caspase-3 or terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells. Both microtubule-associated protein 1 light chain 3 (LC3) and beclin-1 were evident in ischemic brain between 4 and 72 hours after MCAO. Most cells with strong LC3 staining were also labeled with beclin-1. Beclin-1 did colocalize with caspase-3 or Mcl1. Beclin-1/caspase-3 positive cells displayed the characteristic features of apoptosis including cell shrinkage and pyknotic nuclei, whereas beclin-1/Mcl1 positive cells had normal morphology. Pretreatment with 3-methyladenine attenuated autophagy without affecting the level of Mcl1 protein. Conclusions: These findings demonstrate that the expression of Mcl1 is involved in the survival of neuronal cells. In addition, the coexpression of Mcl1 with beclin-1 may attenuate beclin-1-dependent autophagy during ischemic stroke in rats.

Description: Microtubules (Mts), which consist of α/β-tubulin heterodimers, are involved in cancer development and metastasis. Tubulin cofactor A (TBCA) plays crucial roles in modulating tubulin folding and α/β-tubulin heterodimer polymerization. Here, we identified the aberrant expression of TBCA in clear cell renal cell carcinoma (ccRCC) specimens as well as cell lines, and revealed the function of TBCA as a novel positive regulator in ccRCC progression, invasion, and metastasis. qRT-PCR, Western blot, and immunohistochemistry assays confirmed TBCA was significantly highly expressed in ccRCC specimens and cell lines compared to their corresponding normal kidney tissues and HKC. Accordingly, the influence of TBCA on cell proliferation, apoptosis, and invasion/migration was detected through overexpression and knockdown of endogenous TBCA protein level in ccRCC cells via plasmids. Silencing of TBCA expression inhibited the proliferation of 786-O cells and Caki-1 cells and promoted the apoptosis of 786-O cells. Down-regulation of TBCA expression also reduced the invasion and migration ability of 786-O cells. Interestingly, overexpression of TBCA did not induce bio-characteristics that directly contrasted to those of TBCA knockdown. Importantly, exploration of the mechanism showed that TBCA could function via modulating cytoskeleton integration and influencing cell cycle progress. Furthermore, down-regulation of TBCA expression in 786-O and Caki-1 cells affected cytoskeleton integration and cell size, induced S/G2 cell cycle arrest, and led to cyclineA/E and CDK2 aberrant expression. By investigating novel roles of TBCA in regulation of ccRCC cell progression, invasion, and metastasis, our study identified that TBCA may be a potential molecular target for ccRCC therapy. © 2013 Wiley Periodicals, Inc.

Description: Background: High-resolution cytogenetic map can provide not only important biological information on genome organization but also solid foundation for genetic and genomic research. The progress in the molecular and cytogenetic studies has created the basis for developing the cytogenetic map in cucumber (Cucumis sativus L.). Results: Here, the cytogenetic maps of four cucumber chromosomes (chromosomes 1, 3--5) were constructed by fluorescence in situ hybridization (FISH) analysis on cucumber pachytene chromosomes. Together with our previously constructed cytogenetic maps of three cucumber chromosomes (chromosomes 2, 6--7), cucumber has a complete cytogenetic map with 76 anchoring points between the genetic, the cytogenetic and the draft genome assembly maps. To compare our pachytene FISH map directly to the genetic linkage and draft genome assembly maps, we used a standardized map unit---relative map position (RMP) to produce the comparative map alignments. The alignments allowed a global view of the relationship of genetic and physical distances along each cucumber chromosome, and accuracy and coverage of the draft genome assembly map. Conclusions: We demonstrated a good correlation between positions of the markers in the linkage and physical maps, and essentially complete coverage of chromosome arms by the draft genome assembly. Our study not only provides essential information for the improvement of sequence assembly but also offers molecular tools for cucumber genomics research, comparative genomics and evolutionary study.

Description: Background: Excessive circular fatty acid, particlarly saturated fatty acid, can result in insulin resistance in skeletal muscle, but other adverse effects of fatty acid accumulation in myocytes remain unclear. Methods: Differentiated C2C12 myotubes were used. The effects of palmitate on cell viability, glucose uptake, gene expression and myotube loss were evaluated by MTT assay, 2NBDG uptake, qRT-PCR, Western Blot and crystal staining-based myotube counting, respectively. In some expreiments, oleate was administrated, or the inhibitors of signaling pathways were applied. Results: Palmitate-induced cellular insulin resistance was clarified by the reduced Akt phosphorylation, glucose uptake and Glut4 expression. Palmitate-caused myotube loss was clearly observed under microscope and proved by myotube counting and expression analysis of myotube marker genes. Moreover, palmitate-induced transcriptional suppression of three health benefit myokine genes (FNDC5, CTRP15 and FGF21) was found, and the different involvement of p38 and PI3K in the transcription of these genes was noticed. Conclusions: Palmitate-induced insulin resistance accompanys myotube loss and the impaired expression of FNDC5, CTRP15 and FGF21genes in C2C12 myotubes. These results provide novel evidence indicating the negative role of high concentration of palmitate in myotubes.

Description: We previously found that miR-26a could suppress tumor growth and metastasis of hepatocellular carcinoma (HCC). Since angiogenesis is important for tumor growth and metastasis, in this study, we further investigated the possible roles of miR-26a in tumor angiogenesis. Down-regulation of miR-26a was found to correlate with an increased angiogenic potential of HCC. Through gain- and loss-of-function studies, miR-26a was demonstrated to significantly inhibit vascular endothelial growth factor A (VEGFA) expression in HCC cells and then suppress the promoting effects of HCC cells on in vitro proliferation, migration and capillary tube formation of endothelial cells, as well as in vivo tumor angiogenesis of HCC. Hepatocyte growth factor (HGF) was identified as a target of miR-26a. HGF simulation antagonized the effects induced by miR-26a up-regulation. In contrast, silencing HGF induced the similar effects to miR-26a. We further disclosed that miR-26a exerted its antiangiogenesis function, at least in part, by inhibiting HGF- hepatocyte growth factor receptor (cMet) and its downstream signaling pathway, in turn, suppressing VEGFA production in HCC cells and impairing VEGFR2-signaling in endothelial cells. HCC patients who had high miR-26a, low HGF, low VEGFA or low microvessel density (MVD) in tumor tissues had a better prognosis with longer overall survival (OS) and time to recurrence (TTR). In multivariate analysis, miR-26a, or in combination with HGF, was demonstrated to be an independent prognostic indicator for OS and TTR of HCC patients. Conclusion : miR-26a could suppress tumor angiogenesis of HCC through HGF-cMet signaling, and it is a new hopeful therapeutic target and prognostic marker for HCC. (H epatology 2013;)

Description: In this paper, using the data of sunsynchronous satellite DEMETER, we investigated the storm-time variations of ELF/VLF waves during the intense CME-driven storms from 2005 to 2009. The results show that there is a good correlation between the enhancement of ELF/VLF waves and the CME events. Immidately following the enhanced wave activity driven by CMEs during the initial phase, the wave intensity decreases temporarily at the beginning of storm main phase. The strongest waves predominantly occur from the late main phase to early recovery phase. The ELF waves below 3 kHz are significantly intensified during the whole storm time, while the high-frequency waves above 3 kHz seem strengthened only during the late main and early recovery phase. The ELF waves below 3 kHz can exist in a wide L-shell range, with the intensity peaking at L ~ 3-4. High-frequency waves at f  〉 9 kHz exist mostly outside the plasmapause. The stronger ELF/VLF waves on the dayside can last longer time than those on the nightside.

Description: p73, a structural and functional homolog of p53, plays an important role in tumor carcinogenesis. Previous studies have suggested that the association between the p73 G4C14-to-A4T14 polymorphism and the risk of lung cancer, but the results have not been entirely consistent. We examined whether the p73 G4C14-to-A4T14 polymorphism was related to the risk of developing lung cancer in a Chinese population. The p73 G4C14-to-A4T14 polymorphism was genotyped in 293 lung cancer patients and 380 cancer-free controls of Han nationality in North China using PCR-RFLP. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). We observed that compared with the GC/GC genotype, the genotypes containing AT allele (GC/AT + AT/AT genotypes) were associated with significantly increased susceptibility to lung cancer (OR, 1.48; 95% CI, 1.08–2.02; P  = 0.014). In addition, compared with the GC/GC genotype, the GC/AT genotype was also significantly associated with increased susceptibility to lung cancer (OR, 1.46; 95% CI, 1.06–2.02; P  = 0.046). Our findings suggest that the p73 G4C14-to-A4T14 polymorphism contributes to the risk of developing lung cancer in Chinese population. © 2012 Wiley Periodicals, Inc.

Description: Immunoparalysis is an important pathological mechanism in sepsis. However, an effective small molecule therapy is lacking. Here, we show that ouabain, a Na + ,K + -ATPase ligand, can reverse immunoparalysis in vitro , in vivo , and in clinical samples. Notably, the effect of ouabain was critically dependent on TNF-α expression. However, ouabain had opposing effects on the stability of TNF-α mRNA: Ouabain triggered miR-181 transcription, which promoted TNF-α mRNA degradation and induced immunoparalysis, and ouabain triggered the nuclear export of human antigen R (HuR), which stabilized TNF-α mRNA and suppressed immuno-paralysis. Interestingly, because the miR-181 binding site is located within the HuR binding site in the 3′-untranslated region of TNF-α, in ouabain-treated cells, HuR competed with miR-181 for binding to TNF-α mRNA and recruited TNF-α mRNA to stress granules, thereby stabilizing TNF-α mRNA and reversing immunoparalysis. Ouabain also induced GM-CSF and interferon-γ expression in a HuR-dependent manner. Hence, the fine-tuning of TNF-α mRNA stability by HuR and miR181 plays a crucial role in immunoparalysis, and Na + ,K + -ATPase ligands are promising agents for immunoparalysis therapy. Ouabain, a Na + ,K + -ATPase ligand, is shown as the first small molecule able to reverse sepsis-induced immunoparalysis in rodents and in clinical samples through a novel mechanism resulting in TH1 cytokines post-transcriptional reprogramming in monocytes.

Description: Background: CO and FT orthologs, belonging to the BBX and PEBP family, respectively, have important and conserved roles in the photoperiod regulation of flowering time in plants. Soybean genome experienced at least three rounds of whole genome duplications (WGDs), which resulted in multiple copies of about 75% of genes. Subsequent subfunctionalization is the main fate for paralogous gene pairs during the evolutionary process. Results: The phylogenic relationships revealed that CO orthologs were widespread in the plant kingdom while FT orthologs were present only in angiosperms. Twenty-eight CO homologous genes and twenty-four FT homologous genes were gained in the soybean genome. Based on the collinear relationship, the soybean ancestral CO ortholog experienced three WGD events, but only two paralogous gene pairs (GmCOL1/2 and GmCOL5/13) survived in the modern soybean. The paralogous gene pairs, GmCOL1/2 or GmCOL5/13, showed similar expression patterns in pair but different between pairs, indicating that they functionally diverged. GmFTL1 to 7 were derived from the same ancestor prior to the whole genome triplication (WGT) event, and after the Legume WGD event the ancestor diverged into two branches, GmFTL3/5/7 and GmFTL1/2/4/6. GmFTL7 were truncated in the N-terminus compared to other FT-lineage genes, but ubiquitously expressed. Expressions of GmFTL1 to 6 were higher in leaves at the flowering stage than that at the seedling stage. GmFTL3 was expressed at the highest level in all tissues except roots at the seedling stage, and its circadian pattern was different from the other five ones. The transcript of GmFTL6 was highly accumulated in seedling roots. The circadian rhythms of GmCOL5/13 and GmFT1/2/4/5/6 were synchronized in a day, demonstrating the complicate relationship of CO-FT regulons in soybean leaves. Over-expression of GmCOL2 did not rescue the flowering phenotype of the Arabidopsis co mutant. However, ectopic expression of GmCOL5 did rescue the co mutant phenotype. All GmFTL1 to 6 showed flower-promoting activities in Arabidopsis. Conclusions: After three recent rounds of whole genome duplications in the soybean, the paralogous genes of CO-FT regulons showed subfunctionalization through expression divergence. Then, only GmCOL5/13 kept flowering-promoting activities, while GmFTL1 to 6 contributed to flowering control. Additionally, GmCOL5/13 and GmFT1/2/3/4/5/6 showed similar circadian expression profiles. Therefore, our results suggested that GmCOL5/13 and GmFT1/2/3/4/5/6 formed the complicate CO-FT regulons in the photoperiod regulation of flowering time in soybean.