Mixtures of <i><i>g</i></i>-Priors in Generalized Linear Models

<p>Mixtures of Zellner’s <i>g</i>-priors have been studied extensively in linear models and have been shown to have numerous desirable properties for Bayesian variable selection and model averaging. Several extensions of <i>g</i>-priors to generalized linear models (GLMs) have been proposed in the literature; however, the choice of prior distribution of <i>g</i> and resulting properties for inference have received considerably less attention. In this article, we unify mixtures of <i>g</i>-priors in GLMs by assigning the truncated Compound Confluent Hypergeometric (tCCH) distribution to 1/(1 + <i>g</i>), which encompasses as special cases several mixtures of <i>g</i>-priors in the literature, such as the hyper-<i>g</i>, Beta-prime, truncated Gamma, incomplete inverse-Gamma, benchmark, robust, hyper-<i>g</i>/<i>n</i>, and intrinsic priors. Through an integrated Laplace approximation, the posterior distribution of 1/(1 + <i>g</i>) is in turn a tCCH distribution, and approximate marginal likelihoods are thus available analytically, leading to “Compound Hypergeometric Information Criteria” for model selection. We discuss the local geometric properties of the <i>g</i>-prior in GLMs and show how the desiderata for model selection proposed by Bayarri et al., such as asymptotic model selection consistency, intrinsic consistency, and measurement invariance may be used to justify the prior and specific choices of the hyper parameters. We illustrate inference using these priors and contrast them to other approaches via simulation and real data examples. The methodology is implemented in the R package BAS and freely available on CRAN. Supplementary materials for this article are available online.</p

Expression analysis of three SERK-like genes in barley under abiotic and biotic stresses

<p>Somatic embryogenesis receptor-like kinases (SERKs), a subfamily of receptor-like kinases, showed important roles in plant response to abiotic and biotic stresses in addition to embryogenesis and organogenesis in numerous plant species. In the present study, three orthologs of <i>SERK</i> genes (<i>HvSERK1/2/3</i>) were isolated from barley, and their expression patterns during <i>in vitro</i> culture of microspores as well as their responses to different stresses including salinity and powdery mildew were characterized. Sequence analysis suggested that three <i>HvSERK</i> genes were highly conserved in the grass family. Subcellular localization showed the HvSERK1 protein located on the plasma membrane. The <i>HvSERK1</i> transcript was up-regulated during the microspore culture period, suggesting its roles in microspore embryogenesis. <i>HvSERK1</i> and <i>HvSERK3</i> showed the highest expression level in the leaves; however no difference was detected for <i>HvSERK2</i> expression in different plants’ tissues. Under salt stress, all three <i>HvSERK</i> genes were quickly induced in microspore-derived embryogenic calli, whereas only <i>HvSERK1</i> was up-regulated in the roots of barley seedlings. Moreover, only <i>HvSERK2</i> was induced in the barley leaves upon powdery mildew inoculation. These results suggest that barley <i>SERK</i> genes may participate in barley microspores’ development and plant response toward salt and fungal stress, and the function of them has some evolutionary changes.</p

c-Met Targeting Enhances the Effect of Irradiation and Chemical Agents against Malignant Colon Cells Harboring a <i>KRAS</i> Mutation

<div><p>Although EGFR-targeted therapy has been beneficial to colorectal cancer patients, several studies have showed this clinical benefit was restricted to patients with wild-type <i>KRAS</i> exon 2 colorectal cancer. Therefore, it is crucial to explore efficient treatment strategies in patients with <i>KRAS</i> mutations. c-Met is an emerging target for the development of therapeutics against colorectal cancer. In this study, we first used the SW620 cell line, which has an activating <i>KRAS</i> mutation, to generate a stable cell line with conditional regulation of c-Met, which is an essential gene for growth and an oncogene. Using this approach, we evaluated the benefits of combined c-Met-targeted therapy with irradiation or chemical agents. In this cell line, we observed that the proliferation and migration of SW620 cells were reduced by the induction of c-Met shRNA. Furthermore, c-Met knockdown enhanced the anti-proliferative effects of 5-FU and Taxol but not cisplatin, irinotecan or sorafenib. These enhancements were also observed in another colon cancer cells line HCT-116, which also has a <i>KRAS</i> mutation. The response of SW620 cells to irradiation was also enhanced by c-Met knockdown. This method and obtained data might have important implications for exploring the combinatory effects of targeted therapies with conventional medications. Moreover, the data suggested that the combination of c-Met-targeted therapy with chemotherapy or irradiation might be an effective strategy against colorectal cancer harboring a <i>KRAS</i> mutation.</p></div

The effects of c-Met conditional knockdown on cell proliferation and migration.

<p>(A) Effect of c-Met knockdown on cell proliferation. SW620, SW620-Scr and SW620-shRNA cells were treated with or without DOX (400 nM) for 72 h. The cells were then seeded in 96-well plates and cultivated for 1–5 days. Cell proliferation was determined using an Alamar Blue assay. The values are expressed as the mean ± SD. (B) and (C) Effect of c-Met knockdown on cell migration. SW620, SW620-Scr and SW620-shRNA cells were treated with DOX (400 nM) for 72 h. Cell migration was then determined using a transwell migration assay. (B) Representative results of the migration assay. (C) The number of migrating cells was expressed as a percentage of SW620 cells without DOX treatment. The data are shown as the mean ± SD. **P<0.01.</p

Relative expression levels of <i>Ta-SGT1</i> in spikes of scab-resistant wheat variety Wangshuibai (WSB) and its susceptible mutant NAUH117 at different times after inoculation with <i>Fg</i>.

<p>(A) <i>Ta-SGT1</i> was constitutively expressed in both WSB and NAUH117, and no obvious change was detected after inoculation with <i>Fg</i>. Nonetheless, an approximately 6-fold lower expression level of <i>Ta-SGT1</i> transcript was detected in the susceptible mutant NAUH117 than that in resistant WSB. (B) The FHB symptom of spikes of Yangmai158 and transgenic plants at 21 days after <i>Fusarium</i> inoculation, scale bar represents 1cm.</p

Hydrogen peroxide accumulation in leaves of <i>Hv-SGT1</i> over-expressing plants and the WT Yangmai 158.

<p>Hydrogen peroxide accumulated in Yangmai 158 (A), and <i>Hv-SGT1</i> over-expressing lines OX-323 (B) and OX-330 (C). (D) Whole-cell ROI accumulation. (E) Oxidative burst at the <i>Bgt</i> interaction site. (F) Comparison of the percentage of cells with H₂O₂ accumulation throughout the entire cell or only around the infection sites in wild-type Yangmai 158 and the transgenic plants (* means p < 0.05).</p

Characterization of the transgenic wheat of <i>Hv-SGT1</i>.

<p>(A) PCR and PCR-Southern blot of four transgenic lines that over-expressing <i>Hv-SGT1</i> (OX), and the non-transformed control Yangmai 158. The plasmid <i>pBI220.6-Hv-SGT1</i> and Yangmai 158 were used as the positive and negative controls, respectively. (B) qRT-PCR of the expression of <i>Hv-SGT1</i> in the four transgenic lines and Yangmai 158. ** p < 0.01 compared with the control. (C) Reduced disease symptoms in transgenic plants. Seedling resistance of transgenic line or wild-type plants was assessed following <i>in vitro</i> infection with the native pathogen population (Sumai 3). (D) Microscopic observation of <i>Bgt</i> hyphae spreading after DioC6 staining of the transgenic plants and Yangmai 158. (E) Quantitative comparisons of the percentage of infection sites with secondary hyphae (SH), the average number of hyphal branches and average hyphal length emerging on the leaves of infection sites. Means (± SE) were calculated using the measurements from five seedlings, and at least 30 infection sites for each seedling. Significance was determined according to paired sample <i>t</i>-test method (b indicates <i>P</i> < 0.05).</p

Subcellular localization of Hv-SGT1-GFP fusion protein by transient expression via biolistic bombardment.

<p>(A–B) Detected GFP under blue emitting light (nucleus stainning with DAPI) and visible light (merged), and green emitting light of the onion epidermis cell and (E) in the merged figure of the <i>H</i><i>. villosa</i> epidermis cell, indicating that GFP was sub-celluarly located to the whole cell. (C–D) Detected Hv-SGT1-GFP under blue emitting light (nucleus stainning with DAPI) and visible light (merged), and green emitting light of the onion epidermis cell and (F) in the merged figure of the <i>H</i><i>. villosa</i> epidermis cell, indicating that the Hv-SGT1 was subcelluarly located to the nuclei and cytoplasm.</p

Effects of c-Met knockdown on the antitumor activity of 5-FU chemotherapy in nude mice bearing human colon cancer SW620 xenografts.

<p>(A) and (B) Antitumor efficacy in the SW620 model with 5-FU, PHA-665752 (PHA), or 5-FU plus PHA-665752 (5-FU + PHA) treatments. (A) Representative image of the SW620 model. (B) Tumor weight changes in the SW620 model. The data are shown as the mean ± SD (n = 8). (C) and (D) Ki67-positive staining and statistics for cells per field of view from paraffin-embedded sections of SW620 tumors treated with 5-FU, PHA or 5-FU plus PHA. Scale bar  = 20 µm. (E) and (F) TUNEL-positive staining and statistics for cells per field of view from paraffin-embedded sections of SW620 tumors treated with 5-FU, PHA or 5-FU plus PHA. Scale bar  = 20 µm. *P<0.05 and **P<0.01.</p

NADPH-_OX activities in transgenic and WT plants.

<p>Each point represents the mean of three replicates. Bars indicate ±SE, Mean values followed by different letters are significantly different from each other (b* indicates P < 0.01 and b indicates P < 0.05).</p