Georeferenced responses distinguishing between residential and absentee owners.

<p>Georeferenced responses distinguishing between residential and absentee owners.</p

Results of Standard and Bayesian spatial autoregressive probit models.

<p>Results of Standard and Bayesian spatial autoregressive probit models.</p

Variable descriptions and associated descriptive statistics for samples of overall, residential, and absentee-only family forest owners.

<p>Variable descriptions and associated descriptive statistics for samples of overall, residential, and absentee-only family forest owners.</p

Marginal effects on willingness-to-harvest probability from Standard and Bayesian spatial autoregressive probit models*.

<p>Marginal effects on willingness-to-harvest probability from Standard and Bayesian spatial autoregressive probit models*.</p

Supplementary document for Multiscale imaging of corneal endothelium damage and Rho-kinase inhibitor application in mouse models of acute ocular hypertension - 6824181.pdf

Supplemental Informatio

Supplementary document for Multiscale imaging of corneal endothelium damage and Rho-kinase inhibitor application in mouse models of acute ocular hypertension - 6831136.pdf

Supplemental Inf

Image_1_High serum IL-17A is associated with bone destruction in newly diagnosed multiple myeloma patients.jpeg

BackgroundMultiple myeloma (MM) is a malignant proliferative disease of the blood system, characterized by the abnormal growth of clonal plasma cells in the bone marrow. The bone marrow microenvironment (BMM) is highly critical in the pathological process of MM. Many studies have shown that serum interleukin-17A (IL-17A) plays a key role in various infectious diseases, autoimmune diseases, and cancers. However, more clinical studies need to be performed to further prove the influence of serum IL-17A levels on multiple myeloma patients.MethodsAmong a total of 357 participants in our institution’s MM cohort, 175 were eligible for the retrospective study. Multivariate regression models adjusted by potential confounding factors, the violin plots, the generalized additive model and smooth curve fittings, receiver operating characteristic (ROC) curve, and Kaplan–Meier (K-M) curve analysis were applied to the research.ResultsA total of 175 patients with newly diagnosed MM were enrolled in this study. The multivariate linear regression analysis showed that serum IL-17A level in MM patients correlated with the degree of bone lesions and fracture incidence (fully adjusted model, pbone lesion fracture ConclusionThis retrospective study found that higher levels of serum IL-17A were independently correlated with higher severity of bone disease and fracture incidence in newly diagnosed MM patients. High serum IL-17A level was related to poor best overall efficacy in the light chain type. High serum IL-17A was also associated with poor PFS and OS in the light chain type and OS in the IgA type subgroup.</p

Table_1_High serum IL-17A is associated with bone destruction in newly diagnosed multiple myeloma patients.xlsx

BackgroundMultiple myeloma (MM) is a malignant proliferative disease of the blood system, characterized by the abnormal growth of clonal plasma cells in the bone marrow. The bone marrow microenvironment (BMM) is highly critical in the pathological process of MM. Many studies have shown that serum interleukin-17A (IL-17A) plays a key role in various infectious diseases, autoimmune diseases, and cancers. However, more clinical studies need to be performed to further prove the influence of serum IL-17A levels on multiple myeloma patients.MethodsAmong a total of 357 participants in our institution’s MM cohort, 175 were eligible for the retrospective study. Multivariate regression models adjusted by potential confounding factors, the violin plots, the generalized additive model and smooth curve fittings, receiver operating characteristic (ROC) curve, and Kaplan–Meier (K-M) curve analysis were applied to the research.ResultsA total of 175 patients with newly diagnosed MM were enrolled in this study. The multivariate linear regression analysis showed that serum IL-17A level in MM patients correlated with the degree of bone lesions and fracture incidence (fully adjusted model, pbone lesion fracture ConclusionThis retrospective study found that higher levels of serum IL-17A were independently correlated with higher severity of bone disease and fracture incidence in newly diagnosed MM patients. High serum IL-17A level was related to poor best overall efficacy in the light chain type. High serum IL-17A was also associated with poor PFS and OS in the light chain type and OS in the IgA type subgroup.</p

Additional file 1: Figure S1. of mTOR inhibition improves the immunomodulatory properties of human bone marrow mesenchymal stem cells by inducing COX-2 and PGE2

mTOR inhibition has no effect on induction regulatory T cells of MSCs. MSCs were pretreated with or without rapamycin for 4 h and cocultured with human CD4 T cells for 5 days; the proportion of CD4+CD25hiCD127– cells was analyzed by flow cytometry (A, representative data; B, pooled data). Data represent mean ± SD of four independent experiments. **p < 0.01. N.S. not significant. Figure S2. Knockdown of TSC1 has no effect on immunomodulatory functions of MSCs. (A) MSCs were infected with lentivirus carrying scrambled shRNA (shNC) or TSC1-specific shRNAs (shTSC1_1, shTSC1_2); TSC1 knockdown efficiency was assessed by quantitative RT-PCR. (B) MSCs with or without TSC1 knockdown were cocultured with PBMCs at the indicated ratio; flow cytometry showed the PBMC proliferation after 5 days. Data represent mean ± SD of three independent experiments. **p < 0.01. N.S. not significant. Figure S3. mTOR inhibition in MSCs does not influence the expression of inflammatory cytokine receptors. MSCs were pretreated with 10 nM or 100 nM rapamycin for 4 h; IFN-γ and TNF-α receptor IFNGR1, IFNGR2, TNFR1, TNFR2 mRNA expression was measured by quantitative RT-PCR at the indicated time. Cells without pretreatment with rapamycin were indicated as control. Data represent mean ± SD of three independent experiments. Figure S4. Knockdown of TSC2 does not show an obvious difference in expression of COX-2. (A) MSCs with or without TSC2 knockdown were treated with 10 ng/ml TNF-α plus 20 ng/ml IFN-γ for 24 h. COX-2 mRNA expression was measured by quantitative RT-PCR. (B) MSCs with or without TSC2 knockdown were treated with 10 ng/ml TNF-α plus 20 ng/ml IFN-γ for 8 h. The protein level of COX-2 was measured by Western blot. Data represent mean ± SD of three independent experiments. N.S. not significant. Table S1. Primer sequences used for real-time PCR. (ZIP 13342 kb

Fatty acid DSF binds and allosterically activates histidine kinase RpfC of phytopathogenic bacterium <i>Xanthomonas campestris</i> pv. <i>campestris</i> to regulate quorum-sensing and virulence

<div><p>As well as their importance to nutrition, fatty acids (FA) represent a unique group of quorum sensing chemicals that modulate the behavior of bacterial population in virulence. However, the way in which full-length, membrane-bound receptors biochemically detect FA remains unclear. Here, we provide genetic, enzymological and biophysical evidences to demonstrate that in the phytopathogenic bacterium <i>Xanthomonas campestris</i> pv. <i>campestris</i>, a medium-chain FA diffusible signal factor (DSF) binds directly to the N-terminal, 22 amino acid-length sensor region of a receptor histidine kinase (HK), RpfC. The binding event remarkably activates RpfC autokinase activity by causing an allosteric change associated with the dimerization and histidine phosphotransfer (DHp) and catalytic ATP-binding (CA) domains. Six residues were found essential for sensing DSF, especially those located in the region adjoining to the inner membrane of cells. Disrupting direct DSF-RpfC interaction caused deficiency in bacterial virulence and biofilm development. In addition, two amino acids within the juxtamembrane domain of RpfC, Leu¹⁷² and Ala¹⁷⁸, are involved in the autoinhibition of the RpfC kinase activity. Replacements of them caused constitutive activation of RpfC-mediated signaling regardless of DSF stimulation. Therefore, our results revealed a biochemical mechanism whereby FA activates bacterial HK in an allosteric manner, which will assist in future studies on the specificity of FA-HK recognition during bacterial virulence regulation and cell-cell communication.</p></div