Fibroblast phenotypes in different lung diseases

BACKGROUND: The “seed and soil” hypothesis emphasizes the importance of interactions between tumor cells and their microenvironment. CAFs (Cancer associated fibroblasts) are important components of the tumor microenvironment. They were widely involved in cancer cells growth and metastasis. Fibroblasts may also play a role in inflammatory disease. The phenotype conversion of fibroblasts in lung diseases has not been investigated previously. We hypothesized that fibroblasts phenotypes may vary among different types of lung disease. METHODS: The study included six types of lung tissues, ranging from normal lung to lung adenocarcinoma with lymphatic metastasis. Para-carcinoma tissues which were 2-cm-away from the tumor focus were also included in the analysis. The expression of target proteins including alpha-SMA (smooth muscle actin), FAP (fibroblast activation protein), vimentin, E-cadherin, and CK-19 (cytokeratin-19) were examined by immunohistochemistry. TGF-beta(transforming growth factor) and Twist were detected simultaneously in all samples. RESULTS: A progressive increase in the levels of alpha-SMA, vimentin and CK-19 was observed in correlation to the degree of malignancy from normal lung tissue to lung adenocarcinoma with lymphatic metastasis, whereas E-cadherin expression showed the opposite trend. TGF-beta and Twist were detected in cancer tissues and inflammatory pseudotumors. None of the proteins were detected in para-carcinoma tissues. CONCLUSIONS: Fibroblast phenotypes varied according to the type and degree of lung malignancy and fibroblasts phenotypic conversion occurs as a gradual process with specific spatiotemporal characteristics. Similar fibroblast phenotypes in inflammatory diseases and cancer tissues suggested a correlation between inflammation and cancer and implied a common mechanism underlying the formation of fibroblasts in inflammatory diseases and lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13019-014-0147-z) contains supplementary material, which is available to authorized users

Rain-induced changes in soil CO2 flux and microbial community composition in a tropical forest of China

Rain-induced soil CO2 pulse, a rapid excitation in soil CO2 flux after rain, is ubiquitously observed in terrestrial ecosystems, yet the underlying mechanisms in tropical forests are still not clear. We conducted a rain simulation experiment to quantify rain-induced changes in soil CO2 flux and microbial community composition in a tropical forest. Soil CO2 flux rapidly increased by ~83% after rains, accompanied by increases in both bacterial (~51%) and fungal (~58%) Phospholipid Fatty Acids (PLFA) biomass. However, soil CO2 flux and microbial community in the plots without litters showed limited response to rains. Direct releases of CO2 from litter layer only accounted for ~19% increases in soil CO2 flux, suggesting that the leaching of dissolved organic carbon (DOC) from litter layer to the topsoil is the major cause of rain-induced soil CO2 pulse. In addition, rain-induced changes in soil CO2 flux and microbial PLFA biomass decreased with increasing rain sizes, but they were positively correlated with litter-leached DOC concentration rather than total DOC flux. Our findings reveal an important role of litter-leached DOC input in regulating rain-induced soil CO2 pulses and microbial community composition, and may have significant implications for CO2 losses from tropical forest soils under future rainfall changes

Global Bifurcation in 2

We consider the systems of (-1)mu(2m)=λu+λv+uf(t,u,v),  t∈(0,1),  u(2i)(0)=u(2i)(1)=0, and 0≤i≤m-1,  (-1)mv(2m)=μu+μv+vg(t, u,v),  t∈(0,1),  v(2i)(0)=v(2i)(1)=0,  0≤i≤m-1, where λ,μ∈R are real parameters. f,g:[0,1]×R2→R are Ck,k≥3 functions and f(t,0,0)=g(t,0,0)=0,t∈[0,1]. It will be shown that if the functions, f and g are “generic” then the solution set of the systems consists of a countable collection of 2-dimensional, Ck manifolds

Bryophyte diversity is related to vascular plant diversity and microhabitat under disturbance in karst caves

Plant diversity, habitat properties, and their relationships in karst caves remain poorly understood. We surveyed vascular plant and bryophyte diversities and measured the habitat characteristics in six karst caves in south China with different disturbance histories (one had been disturbed by poultry feeding, three had been disturbed by tourism, and two were undisturbed). The plant diversity differences among the six caves were analyzed using cluster analysis, and the relationships of plant diversity and microhabitat were assessed using canonical correspondence analysis. We found a total of 43 angiosperm species from 27 families, 20 lycophyte and fern species from 9 families, and 20 species of bryophytes from 13 families in the six caves. Habitat characteristics including light intensity, air relative humidity, air temperature, and soil properties varied among the caves. The plant diversity in karst caves was not rich, but the species composition was unique. The caves with high disturbance had the lowest species richness, numbers of individuals, and Shannon-Wiener diversity indices but the highest Simpson’s dominance indices. The caves with less disturbance had the highest numbers of species, numbers of individuals, and Shannon-Wiener diversity indices but the lowest Simpson’s dominance indices. The disturbed caves were often dominated by drought-tolerant, tenacious mosses (bryophytes), while the relatively undisturbed caves contained abundant liverworts (bryophytes), which were better adapted to humid environments. Plant diversity in karst caves was closely related to habitat heterogeneity, light and water status, and nutrient availability. Tourism and poultry farming were associated with the degradation of vegetation in some karst caves. Protecting and restoring bryophytes might facilitate the settlement, growth, and succession of vascular plants in karst caves. Bryophytes can be used as indicators of overall plant diversity and restoration status in karst caves

Causal effects of specific gut microbiota on bone mineral density: a two-sample Mendelian randomization study

BackgroundRecent studies have reported that the gut microbiota is essential for preventing and delaying the progression of osteoporosis. Nonetheless, the causal relationship between the gut microbiota and the risk of osteoporosis has not been fully revealed.MethodsA two-sample Mendelian randomization (MR) analysis based on a large-scale genome-wide association study (GWAS) was conducted to investigate the causal relationship between the gut microbiota and bone mineral density (BMD). Instrumental variables for 211 gut microbiota taxa were obtained from the available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. The summary-level data for BMD were from the Genetic Factors for Osteoporosis (GEFOS) Consortium, which involved a total of 32,735 individuals of European ancestry. The inverse variance-weighted (IVW) method was performed as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses by using multiple methods. Finally, a reverse MR analysis was applied to evaluate reverse causality.ResultsAccording to the IVW method, we found that nine, six, and eight genetically predicted gut microbiota were associated with lumbar spine (LS) BMD, forearm (FA) BMD, and femoral neck (FN) BMD, respectively. Among them, the higher genetically predicted Genus Prevotella9 level was correlated with increased LS-BMD [β = 0.125, 95% confidence interval (CI): 0.050–0.200, P = 0.001] and FA-BMD (β = 0.129, 95% CI: 0.007–0.251, P = 0.039). The higher level of genetically predicted Family Prevotellaceae was associated with increased FA-BMD (β = 0.154, 95% CI: 0.020–0.288, P = 0.025) and FN-BMD (β = 0.080, 95% CI: 0.015–0.145, P = 0.016). Consistent directional effects for all analyses were observed in both the MR-Egger and weighted median methods. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on BMD (P > 0.05). In reverse MR analysis, there was no evidence of reverse causality between LS-BMD, FA-BMD, and FN-BMD and gut microbiota (P > 0.05).ConclusionGenetic evidence suggested a causal relationship between the gut microbiota and BMD and identified specific bacterial taxa that regulate bone mass variation. Further exploration of the potential microbiota-related mechanisms of bone metabolism might provide new approaches for the prevention and treatment of osteoporosis

Causal effects of specific gut microbiota on musculoskeletal diseases: a bidirectional two-sample Mendelian randomization study

BackgroundRecent observational studies and clinical trials demonstrated an association between gut microbiota and musculoskeletal (MSK) diseases. Nonetheless, whether the gut microbiota composition has a causal effect on the risk of MSK diseases remains unclear.MethodsBased on large-scale genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between gut microbiota and six MSK diseases, namely osteoporosis (OP), fracture, sarcopenia, low back pain (LBP), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Instrumental variables for 211 gut microbiota taxa were obtained from the largest available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. And the summary-level data for six MSK diseases were derived from published GWAS. The inverse-variance weighted (IVW) method was conducted as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses using multiple methods. The Bonferroni-corrected test was used to determine the strength of the causal relationship between gut microbiota and various MSK diseases. Finally, a reverse MR analysis was applied to evaluate reverse causality.ResultsAccording to the IVW method, we found 57 suggestive causal relationships and 3 significant causal relationships between gut microbiota and MSK diseases. Among them, Genus Bifidobacterium (β: 0.035, 95% CI: 0.013–0.058, p = 0.0002) was associated with increased left handgrip strength, Genus Oxalobacter (OR: 1.151, 95% CI: 1.065–1.245, p = 0.0003) was correlated with an increased risk of LBP, and Family Oxalobacteraceae (OR: 0.792, 95% CI: 0.698–0.899, p = 0.0003) was linked with a decreased risk of RA. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on MSK diseases (p > 0.05). Reverse MR analysis showed fracture may result in a higher abundance of Family Bacteroidales (p = 0.030) and sarcopenia may lead to a higher abundance of Genus Sellimonas (p = 0.032).ConclusionGenetic evidence suggested a causal relationship between specific bacteria taxa and six MSK diseases, which highlights the association of the “gut-bone/muscle” axis. Further exploration of the potential microbiota-related mechanisms of bone and muscle metabolism might provide novel insights into the prevention and treatment of MSK diseases

TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein

Background The tripartite motif (TRIM) family of proteins plays a key role in the developmental growth and therapeutic resistance of many tumors. However, the regulatory mechanisms and biological functions of TRIM proteins in human glioblastoma (GBM) are not yet fully understood. In this study, we focused on TRIM56, which emerged as the most differentially expressed TRIM family member with increased expression in GBM. Methods Western blot, real-time quantitative PCR (qRT-PCR), immunofluorescence (IF) and immunohistochemistry (IHC) were used to study the expression levels of TRIM56 and cIAP1 in GBM cell lines. Co-immunoprecipitation (co-IP) was used to explore the specific binding between target proteins and TRIM56. A xenograft animal model was used to verify the tumor promoting effect of TRIM56 on glioma in vivo. Results We observed elevated expression of TRIM56 in malignant gliomas and revealed that TRIM56 promoted glioma progression in vitro and in a GBM xenograft model in nude mice. Analysis of the Human Ubiquitin Array and co-IPs showed that cIAP1 is a protein downstream of TRIM56. TRIM56 deubiquitinated cIAP1, mainly through the zinc finger domain (amino acids 21–205) of TRIM56, thereby reducing the degradation of cIAP1 and thus increasing its expression. TRIM56 also showed prognostic significance in overall survival of glioma patients. Conclusions TRIM56-regulated post-translational modifications may contribute to glioma development through stabilization of cIAP1. Furthermore, TRIM56 may serve as a novel prognostic indicator and therapeutic molecular target for GBM.publishedVersio

Water sorptivity of unsaturated fractured sandstone: fractal modeling and neutron radiography experiment

The spontaneous imbibition of water into the matrix and gas-filled fractures of unsaturated porous media is an important phenomenon in many geotechnical applications. Previous studies have focused on the imbibition behavior of water in the matrix, but few works have considered spontaneous imbibition along fractures. In this work, a new fractal model, considering the water losses from the fracture to the matrix, was established to predict the sorptivity of rough-walled fracture. A fractal model, considering the fractal dimension of tortuosity, was modified to estimate the sorptivity of the matrix. Both of the models have a time exponent α and can be simplified to the classical Lucas–Washburn (L–W) equation with α = 0.50. To verify the proposed models, quantitative data on the imbibition of water in both the matrix and the fracture of unsaturated sandstone were acquired by neutron radiography. The results show that the motion of the wetting front in both the matrix and the fracture does not obey the L–W equation. Both theory and experimental observations indicate that fracture can significantly increase spontaneous imbibition in unsaturated sandstone by capillary action. Compared with the classical L–W equation, the models proposed in this study offers a better description of the dynamic imbibition behaviour of water in unsaturated fractured sandstone and, thus, more reliable predictions of the sorptivity of the matrix and the fracture. Moreover, a new method to estimate the time exponent of rough-walled fracture in sandstone was also provided