Summary
Clonostachys rosea is a promising saprophytic filamentous fungus that belongs to phylum Ascomycota. Clonostachys rosea is widespread around the world and exists in many kinds of habitats, ...with the highest frequency in soil. As an excellent mycoparasite, C. rosea exhibits strong biological control ability against numerous fungal plant pathogens, nematodes and insects. These behaviours are based on the activation of multiple mechanisms such as secreted cell‐wall‐degrading enzymes, production of antifungal secondary metabolites and induction of plant defence systems. Besides having significant biocontrol activity, C. rosea also functions in the biodegradation of plastic waste, biotransformation of bioactive compounds, as a bioenergy sources and in fermentation. This mini review summarizes information about the biology and various applications of C. rosea and expands on its possible uses.
Airway epithelial cells are the first cells to be challenged upon contact with the conidia of
Aspergillus
. In response, they express pattern-recognition receptors that play fundamental roles as ...sentinels and mediators of pulmonary innate immunity. The C-type lectin Dectin-1 is expressed predominantly on the surface of myeloid lineage cells. We examined the induction, regulation, and functions of Dectin-1 in pulmonary epithelial cells by challenging human bronchial epithelial (HBE) cells with
A. fumigatus
. Inflammatory, antimicrobial peptide genes and reactive oxygen species (ROS) were quantified, with and without knockdown of Dectin-1. We found that
A. fumigatus
induced the expression of Dectin-1 mRNA and protein in HBE cells in a toll-like receptor (TLR) 2-dependent manner. In addition,
A. fumigatus
-mediated generation of ROS was dependent on the upregulation of Dectin-1. Moreover,
A. fumigatus
actively induced the expression of TNFα, GM-CSF, IL8, HBD2, and HBD9. Knockdown of Dectin-1 inhibited TNFα, IL8, HBD2, and HBD9 expression. Hence, Dectin-1 was required for the upregulation of pro-inflammatory cytokines and antimicrobial peptides. Finally, knockdown of TLR2 significantly inhibited Dectin-1 upregulation. Our results demonstrate the novel induction of Dectin-1 in human bronchial epithelial cells and its critical role in the innate immune response against
A. fumigatus
in non-phagocytic cells.
Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an ...antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib-treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line 786-O was chronically treated with sunitinib and assayed for AXL, MET, epithelial-mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by short hairpin RNA or inhibition by cabozantinib, the multi-tyrosine kinases inhibitor that targets vascular endothelial growth factor receptor, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT-associated gene expression changes, including upregulation of Snail and β-catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/human umbilical vein endothelial cell co-culture models. The suppression of AXL or MET expression and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment-induced prometastatic behavior in cell culture and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and promotes prometastatic behavior and angiogenesis. The inhibition of AXL and MET activity may overcome resistance induced by prolonged sunitinib therapy in metastatic RCC.
The impact of central Asian aridification on the low latitude North Pacific Ocean since the late Miocene remains unclear. To address this question, we systematically studied an abyssal manganese ...nodule from the northwestern Pacific Ocean, which is expected to be sensitive to eolian dust sourced from central Asia. Geochemical variations and the fossilized remains of magnetotactic bacteria within the studied nodule manifest two prominent Asian aridification events at ∼8–7 Ma and 3.6–0 Ma. These results suggest that central Asian aridification impacted both primary productivity and abyssal microbial activity in the NW Pacific Ocean via eolian dust inputs. In contrast to the Pliocene aridification event, the late Miocene event was associated with a primary productivity bloom that is not evident in coeval global primary productivity records, which indicates that the ∼8–7 Asian aridification event was likely due to NE Tibetan Plateau uplift rather than to global cooling.
Plain Language Summary
Central Asian aridification since the late Miocene has had a significant influence on climate, temperature, and North Pacific Ocean productivity through eolian dust inputs transported by westerlies. However, it is unclear whether the low latitude of NW Pacific Ocean responded to this aridification. We systematically analyzed the geochemistry and magnetism of a NW Pacific manganese nodule, and find that Asian aridification since, the late Miocene impacted biogeochemical cycling and abyssal microbial activity in the NW Pacific Ocean via eolian dust input. Our results imply that these two prominent Asian aridification events at around 8–7 Ma and ca. 3.6 Ma can be attributed to the NE Tibetan Plateau uplift and global cooling, respectively.
Key Points
A manganese nodule from the NW Pacific carries a paleoclimatic record of Asian aridification since the Late Miocene
Asian aridification impacted biogeochemical cycling and abyssal microbial activity in the NW Pacific Ocean
Major Asian aridification events at ∼8–7 Ma and ∼3.6–0 Ma may be attributed to NE Tibetan Plateau uplift and global cooling, respectively
Abyssal manganese nodules have been explored widely for their economic potential and paleoenvironmental significance. Debate about whether biogenic or physical‐chemical processes are responsible for ...their formation remains because of difficulties in quantifying ancient microbiological contributions. To address this question, we investigated microbial fossils in manganese nodules from the western Pacific Ocean by integrating scanning electron microscope, transmission electron microscope, and synchrotron transmission X‐ray microscope observations. Our results suggest that the nodules host abundant fossil biogenic magnetite and manganese‐oxidizing bacteria. These organisms engage in redox reactions or live in environments with redox gradients. By combining magnetic properties and observations of fossil biogenic magnetite morphology, we estimate magnetofossil abundances and further assess fossil biogenic manganese oxide in nodules. Our results imply that manganese nodule formation appears to be dominated by biomineralization with an additional terrestrial contribution. Extensive biomineralization in ultralow‐productivity oceanic environments suggests that manganese nodule formation is an important aspect of biogeochemical cycling in abyssal seafloor environments.
Key Points
Abyssal ferromanganese nodules host abundant fossil biogenic magnetite and manganese oxide produced in environments with redox gradients
Redox reactions fueled abyssal microbial activity and contributed to biomass production in microecosystems within nodules
Manganese nodule formation appears to be dominated by biomineralization
Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. ...Here we report that taurine-upregulated gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC) tissues. In a cohort of 192 NSCLC patients, the lower expression of TUG1 was associated with a higher TNM stage and tumor size, as well as poorer overall survival (P<0.001). Univariate and multivariate analyses revealed that TUG1 expression serves as an independent predictor for overall survival (P<0.001). Further experiments revealed that TUG1 expression was induced by p53, and luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1 was a direct transcriptional target of p53. TUG1 knockdown significantly promoted the proliferation in vitro and in vivo. Moreover, the lncRNA-mediated regulation of the expression of HOX genes in tumorigenesis and development has been recently receiving increased attention. Interestingly, inhibition of TUG1 could upregulate homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of PRC2, and was H3K27 trimethylated. This TUG1-mediated growth regulation is in part due to specific modulation of HOXB7, thus participating in AKT and MAPK pathways. Together, these results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7. The p53/TUG1/PRC2/HOXB7 interaction might serve as targets for NSCLC diagnosis and therapy.
We investigate the dependence of black hole accretion rate (BHAR) on host-galaxy star formation rate (SFR) and stellar mass (M*) in the CANDELS/GOODS-South field in the redshift range of . Our sample ...consists of galaxies, allowing us to probe galaxies with and/or . We use sample-mean BHAR to approximate long-term average BHAR. Our sample-mean BHARs are derived from the Chandra Deep Field-South 7 Ms observations, while the SFRs and M* have been estimated by the CANDELS team through spectral energy distribution fitting. The average BHAR is correlated positively with both SFR and M*, and the BHAR-SFR and BHAR-M* relations can both be described acceptably by linear models with a slope of unity. However, BHAR appears to be correlated more strongly with M* than SFR. This result indicates that M* is the primary host-galaxy property related to supermassive black hole (SMBH) growth, and the apparent BHAR-SFR relation is largely a secondary effect due to the star-forming main sequence. Among our sources, massive galaxies ( ) have significantly higher BHAR/SFR ratios than less massive galaxies, indicating that the former have higher SMBH fueling efficiency and/or higher SMBH occupation fraction than the latter. Our results can naturally explain the observed proportionality between and M* for local giant ellipticals and suggest that their is higher than that of local star-forming galaxies. Among local star-forming galaxies, massive systems might have higher compared to dwarfs.
The objective of this study is to analyse the factors affecting late toxicity for nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT).
Seven hundred and ...eighty-nine consecutive NPC patients treated with IMRT at our centre from January 2003 to February 2008 were retrospectively analysed. Radiotherapy-related complications were categorised using the RTOG Late Radiation Morbidity Scoring Criteria and the Common Terminology Criteria for Adverse Events (Version 3.0). Two hundred and thirty-three patients were treated with IMRT alone (group 1) and 556 patients underwent cisplatin-based chemotherapy (group 2).
Median follow-up was 65 months (range, 4-106 months). The 5-year major late toxicity rate was significantly greater in group 2 than group 1 (63.2% vs 42.0%, P<0.001). Multivariate analyses showed that N category, T category and chemotherapy were significant factors. The maximal dose (Dmax) to the temporal lobe was a significant factor affecting temporal lobe injury (TLI), with a hazard ratio of 1.26 (95% confidence interval (CI), 1.18-1.35; P<0.001) per 1-Gy increase. The 5-year TLI rate increased from 0.8% for 284 lobes with Dmax <65.77 Gy to 27.1% for 176 lobes with greater doses (P<0.001). Logistic regression showed that the hazard ratio attributed to the parotid gland mean dose was 1.36 (95% CI, 1.21-1.53; P<0.001) per 1-Gy increase. Chemotherapy was not a significant factor (P=0.211).
With the application of IMRT, the incidence of radiation-related complications has been reduced except for TLI. The significant factors affecting the risk of TLI included T category, chemotherapy and Dmax.
Intestinal IgA, which is regulated by gut microbiota, has a crucial role in maintenance of intestinal homeostasis and in protecting the intestines from inflammation. However, the means by which ...microbiota promotes intestinal IgA responses remain unclear. Emerging evidence suggests that the host can sense gut bacterial metabolites in addition to pathogen-associated molecular patterns and that recognition of these small molecules influences host immune response in the intestines and beyond. We reported here that microbiota metabolite short-chain fatty acid acetate promoted intestinal IgA responses, which was mediated by "metabolite-sensing" GPR43. GPR43
mice demonstrated lower levels of intestinal IgA and IgA
gut bacteria compared with those in wild type (WT) mice. Feeding WT but not GPR43
mice acetate but not butyrate promoted intestinal IgA response independent of T cells. Acetate promoted B-cell IgA class switching and IgA production in vitro in the presence of WT but not GPR43
dendritic cells (DCs). Mechanistically, acetate-induced DC expression of Aldh1a2, which converts Vitamin A into its metabolite retinoic acid (RA). Moreover, blockade of RA signaling inhibited the acetate induction of B-cell IgA production. Our studies thus identified a new pathway by which microbiota promotes intestinal IgA response through its metabolites.
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