Blocking TREM-1 signaling prolongs survival of mice with Pseudomonas aeruginosa induced sepsis

TREM-1 is a recently discovered receptor expressed on neutrophils and macrophages. Blocking of TREM-1 signaling improves the survival of mice with bacterial sepsis. However, the precise mechanism by which TREM-1 modulates the inflammatory responses is poorly defined. In this study, we investigated the role of TREM-1 in Pseudomonas aeruginosa-induced peritonitis. Our results showed that TREM-1 was not expressed on lymphocytes but emerged on the cell surface of neutrophils and peritoneal macrophages. Blockade of TREM-1 signaling significantly prolonged survival of mice with P. aeruginosa-induced peritonitis. However, blocking TREM-1 signaling had no effect on macrophage phagocytosis in vitro. Interestingly, the expression of the costimulatory molecules CD40 and CD86 on macrophages was significantly decreased after blocking TREM-1 signaling. Furthermore, interfering with TREM-1 engagement led to significant reduction of pro-inflammatory mediators such as IL-1, TNF-α, MCP-1 and IFN-γ. Therefore, our results showed that TREM-1 could be a potential therapeutic target for bacterial sepsis.     

Systemic administration of anti-NGF increases A-type potassium currents and decreases pancreatic nociceptor excitability in a rat model of chronic pancreatitis

We have previously shown that pancreatic sensory neurons in rats with chronic pancreatitis (CP) display increased excitability associated with a decrease in transient inactivating potassium currents (I(A)), thus accounting in part for the hyperalgesia associated with this condition. Because of its well known role in somatic hyperalgesia, we hypothesized a role for the nerve growth factor (NGF) in driving these changes. CP was induced by intraductal injection of trinitrobenzene sulfonic acid (TNBS) in rats. After 3 wk, anti-NGF antibody or control serum was injected intra-peritoneally daily for 1 wk. This protocol was repeated in another set of experiments in control rats (receiving intraductal PBS instead of TNBS). Pancreatic nociceptors labeled with the dye Dil were identified, and patch-clamp recordings were made from acutely dissociated DRG neurons. Sensory neurons from anti-NGF-treated rats displayed a lower resting membrane potential, increased rheobase, decreased burst discharges in response to stimulatory current, and decreased input resistance compared with those treated with control serum. Under voltage-clamp condition, neuronal I(A) density was increased in anti-NGF-treated rats compared with rats treated with control serum. However, anti-NGF treatment had no effect on electrophysiological parameters in neurons from control rats. The expression of Kv-associated channel or ancillary genes Kv1.4, 4.1, 4.2, 4.3, and DPP6, DPP10, and KCHIPs 1-4 in pancreas-specific nociceptors was examined by laser-capture microdissection and real-time PCR quantification of mRNA levels. No significant differences were seen among those. These findings emphasize a key role for NGF in maintaining neuronal excitability in CP specifically via downregulation of I(A) by as yet unknown mechanisms.     

Novel loci for field resistance to black-streaked dwarf and stripe viruses identified in a set of reciprocal introgression lines of rice (Oryza sativa L.)

Rice black-streaked dwarf virus (RBSDV) and stripe virus (RSV) are the two chronic viral diseases causing great damage to rice (Oryza sativa L.) production in China, and both are transmitted by the small brown planthopper (SBPH, Laodelphax striatellus Fallén). Quantitative trait loci (QTL) affecting field resistance to these two viral diseases were identified using QTL mapping software in a set of reciprocal introgression lines derived from the cross between Lemont and Teqing. A panel of 119 landraces was used for marker confirmation and allele mining. A total of 17 quantitative resistance loci (QRL) for the infection incidences of RBSDV and RSV were discovered and belong to 16 regions on all chromosomes except chromosome 12. Among them, 12 QRL were confirmed by association mapping, and many novel alleles at these loci were mined from the set of landraces. Only one region was found to be responsible for the genetic overlap between the field resistance against RBSDV and RSV, which was reported to be associated with SBPH resistance. The favorable alleles at the above novel and/or overlapping loci should be effective for marker-assisted selection breeding for resistance against the two diseases and the insect. Different strategies of varietal development and effective deployment against the two viral diseases are also discussed.     

Systemic understanding of Lactococcus lactis response to acid stress using transcriptomics approaches

Journal of Industrial Microbiology & Biotechnology - During fermentation, acid stress caused by the accumulation of acidic metabolites seriously affects the metabolic activity and production...     

Identification of a GntR family regulator BusRTha and its regulatory mechanism in the glycine betaine ABC transport system of Tetragenococcus halophilus

Extremophiles - Glycine betaine is one of the most effective compatible solutes of the halophilic lactic acid bacterium Tetragenococcus halophilus, the transportation of which is essential for its...     

How floral displays affect geitonogamy in an upward foraging bumblebee‐pollinated protandrous plant

Reducing geitonogamy (pollen transfer among flowers within the same plant) has been suggested as a major selective force for plants with multiple flowers. The occurrence of geitonogamy is generally different among flowers within inflorescences; however, no researchers have examined whether plants enlarge their display size without increasing the possibility of geitonogamy by presenting more flowers at positions where they are less likely to be geitonogamously pollinated. We observed that bumblebee pollinators foraged upward within the tower‐shaped inflorescences of protandrous Megacodon stylophorus (C. B. Clarke) Harry Sm. Because M. stylophorus did not strictly bloom bottom‐up, there were substantial frequencies of geitonogamous pollination resulting from upward and horizontal pollen transfer. Although there was a strong correlation between total numbers of flowers plants produced and numbers of flowers presented on single days, proportions of flowers possibly geitonogamously pollinated were weakly correlated with total numbers of flowers. This might have been because plants with more resources enlarged their display size by producing more flowers on lower floors where flowers had a low probability of being geitonogamously pollinated. This study shows that the tower‐shaped inflorescences of M. stylophorus enlarge their size without more cost of geitonogamous mating, suggesting that geitonogamy acts as an important selective agent in the evolution of inflorescence architectures.     

LINC01342 promotes the progression of ovarian cancer by absorbing microRNA-30c-2-3p to upregulate HIF3A

Ovarian cancer (OC) is a highly prevalent gynecologic malignancy and its mortality is extremely high. Therefore, the development of novel therapeutic approaches for OC is of great significance. In this study, LINC01342 was upregulated in OC tissue in the GSE38666 microarray and in tumor tissue samples collected in our center. The silencing of LINC01342 suppressed the proliferative and metastatic capacities of A2780 and HO8910 cells. Subcellular distribution assays showed that LINC01342 was mainly enriched in the cytoplasm. Subsequently, the downregulation of microRNA-30c-2-3p was proven to be the target of LINC01342. The silencing of microRNA-30c-2-3p enhanced the clonality and migratory capacity of OC cells. Moreover, the silencing of microRNA-30c-2-3p could reverse the inhibited migration and clonality in OC cells caused by LINC01342 knockdown. In addition, hypoxia-inducible factor 3 subunit α (HIF3A) was proven to be the target gene of microRNA-30c-2-3p, which was upregulated. HIF3A was negatively regulated by microRNA-30c-2-3p but positively regulated by LINC01342 in OC cells. An RNA binding protein immunoprecipitation assay showed that microRNA-30c-2-3p, LINC01342, and HIF3A could bind to argonaute RISC catalytic component 2. The overexpression of HIF3A reversed the inhibited migration and clonality in OC cells with LINC01342 knockdown. By analyzing the follow-up data from the enrolled OC patients, the LINC01342 and HIF3A levels were negatively correlated with prognosis, while the microRNA-30c-2-3p level was positively correlated with the same. In short, the upregulated LINC01342 in OC absorbs microRNA-30c-2-3p to release HIF3A. Thus, upregulated HIF3A expression accelerates the progression of OC.     

Dual role of SnoN in mammalian tumorigenesis

SnoN is an important negative regulator of transforming growth factor beta signaling through its ability to interact with and repress the activity of Smad proteins. It was originally identified as an oncoprotein based on its ability to induce anchorage-independent growth in chicken embryo fibroblasts. However, the roles of SnoN in mammalian epithelial carcinogenesis have not been well defined. Here we show for the first time that SnoN plays an important but complex role in human cancer. SnoN expression is highly elevated in many human cancer cell lines, and this high level of SnoN promotes mitogenic transformation of breast and lung cancer cell lines in vitro and tumor growth in vivo, consistent with its proposed pro-oncogenic role. However, this high level of SnoN expression also inhibits epithelial-to-mesenchymal transdifferentiation. Breast and lung cancer cells expressing the shRNA for SnoN exhibited an increase in cell motility, actin stress fiber formation, metalloprotease activity, and extracellular matrix production as well as a reduction in adherens junction proteins. Supporting this observation, in an in vivo breast cancer metastasis model, reducing SnoN expression was found to moderately enhance metastasis of human breast cancer cells to bone and lung. Thus, SnoN plays both pro-tumorigenic and antitumorigenic roles at different stages of mammalian malignant progression. The growth-promoting activity of SnoN appears to require its ability to bind to and repress the Smad proteins, while the antitumorigenic activity can be mediated by both Smad-dependent and Smad-independent pathways and requires the activity of small GTPase RhoA. Our study has established the importance of SnoN in mammalian epithelial carcinogenesis and revealed a novel aspect of SnoN function in malignant progression.