BackgroundThe prognostic role of perineural invasion in gastric cancer is controversial. Here, we present a systemic review and meta-analysis of the association between perineural invasion and survival in resectable gastric cancer patients.MethodsA comprehensive literature search for relevant reports published up to April 2013 was performed using PubMed, Embase, Web of Science and Wanfang Data. Studies that investigated the role of perineural invasion with a sample size greater than 100 were included and analyzed.ResultsA total of 30,590 gastric cancer patients who had undergone curative gastrectomy from twenty-four studies were included. The median rate of perineural invasion positive was 40.9% (6.8%–75.6%). Fourteen studies investigated overall survival unadjusted for other variables in 23,233 gastric cancer patients. The relative hazard estimates ranged from 0.568–7.901 with a combined random effects estimate of 2.261 (95% CI = 1.841–2.777, P = 0.000). The effect of perineural invasion on overall survival adjusted for other prognostic factors was reported in 17 studies incorporating 8,551 cases. The hazard estimates ranged from 0.420–8.110 with a pooled random effects estimates of 1.484 (95% CI = 1.237–1.781, P = 0.000). There was heterogeneity between the studies (Q = 49.22, I-squared = 67.5%, P = 0.000). Disease-free survival was investigated adjusted in four studies incorporating 9,083 cases and the pooled fixed hazard ratio estimate was 1.371(95% CI = 1.230–1.527, P = 0.000).ConclusionPerineural invasion is an independent prognostic factor affecting overall survival and disease-free survival of gastric cancer patients who had undergone the curative resection. This effect is independent of lymph node status, tumor size and the depth of invasion as well as a range of other biological variables on multivariate analysis. Large prospective studies are now needed to establish perineural invasion as an independent prognostic marker for gastric cancer.

BackgroundSomaclonal variation generally occurs in plants regenerated from tissue culture. However, fundamental issues regarding molecular characteristics, mutation rates and mutation spectra of plant somatic variation as well as their phenotypic relevance have been addressed only recently. Moreover, these studies have reported highly discrepant results in different plant species and even in the same plant genotype.Methodology/principal findingsWe investigated heritable genomic variation induced by tissue culture in rice by whole genome re-sequencing of an extensively selfed somaclonal line (TC-reg-2008) and its wild type (WT) donor (cv. Hitomebore). We computed the overall mutation rate, single nucleotide polymorphisms (SNPs), small scale insertions/deletions (Indels) and mobilization of transposable elements (TEs). We assessed chromosomal distribution of the various types of genomic variations, tested correlations between SNPs and Indels, and examined concomitancy between TE activity and its cytosine methylation states. We also performed gene ontology (GO) analysis of genes containing nonsynonymous mutations and large-effect mutations, and assayed effects of the genomic variations on phenotypes under both normal growing condition and several abiotic stresses. We found that heritable somaclonal genomic variation occurred extensively in rice. The genomic variations distributed non-randomly across each of the 12 rice chromosomes, and affected a large number of functional genes. The phenotypic penetrance of the genomic variations was condition-dependent.Conclusions/significanceTissue culture is a potent means to generate heritable genetic variations in rice, which bear distinct difference at least in space (chromosomal distribution) from those occurred under natural settings. Our findings have provided new information regarding the mutation rate and spectrum as well as chromosomal distribution pattern of somaclonal variation in rice. Our data also suggest that rice possesses a strong capacity to canalize genetic variations under normal growing conditions to maintain phenotypic robustness, which however can be released by certain abiotic stresses to generate variable phenotypes.

Fatty liver disease is regularly observed in cultured large yellow croaker, and the disease leads to lower growth rates and reduced harvest yields. The goal of this study was to achieve a more detailed understanding of the physiological and molecular changes in response to high‐fat diet‐induced fatty liver in large yellow croaker. Large yellow croaker fed a high‐fat diet (HFD) for 9 weeks developed hepatic steatosis characterized by histological observation and significantly increased plasma triglyceride levels and serum alanine aminotransferase (ALT) activities. However, no significant differences in serum total protein, glucose, cholesterol, non‐esterified free fatty acids (NEFA), aspartate aminotransferase, high‐density lipoprotein and low‐density lipoprotein were observed between the normal diet and the high‐fat diet (HFD) group. The fatty acid composition of tissue lipids was not affected significantly by dietary lipid levels. Gene expression analysis demonstrated that the HFD decreased fatty acid synthase expression and increased PPARγ expression, but had no effect on lipoprotein lipase and PPARα expression. These results suggest that the HFD‐induced physiological changes and fatty liver may be due to the alteration of related gene expression. As such, further investigations of the metabolic pathways and differentially expressed genes are of particular significance in the mechanistic study and understanding of HFD‐induced fatty liver disease.

Plants utilize a two-tiered immune system consisting of pattern recognition receptor (PRR)-triggered immunity (PTI) and effector-triggered immunity (ETI) to defend themselves against pathogenic microbes. The receptor protein kinase BAK1 plays a central role in multiple PTI signaling pathways in Arabidopsis. However, double mutants made by BAK1 and its closest paralog BKK1 exhibit autoimmune phenotypes, including cell death resembling a typical nucleotide-binding leucine-rich repeat protein (NLR)-mediated ETI response. The molecular mechanisms of the cell death caused by the depletion of BAK1 and BKK1 are poorly understood. Here, we show that the cell-death phenotype of bak1 bkk1 is suppressed when a group of NLRs, ADR1s, are mutated, indicating the cell-death of bak1 bkk1 is the consequence of NLR activation. Furthermore, introduction of a Pseudomonas syringae effector HopB1, which proteolytically cleaves activated BAK1 and its paralogs via either gene transformation or bacterium-delivery, results in a cell-death phenotype in an ADR1s-dependent manner. Our study thus pinpoints that BAK1 and its paralogs are likely guarded by NLRs.

SUMMARYBRI1-ASSOCIATED KINASE 1 (BAK1) was initially identified as a co-receptor of the brassinosteroid (BR) receptor BRI1. Genetic analyses also revealed that BAK1 and its closest homolog BAK1-LIKE 1 (BKK1) regulate a BR-independent cell-death control pathway. The double null mutant bak1 bkk1 displays a salicylic acid-and light-dependent cell-death phenotype even without pathogen invasion. Molecular mechanisms of the spontaneous cell death mediated by BAK1 and BKK1 remain unknown. Here we report our identification of a suppressor of bak1 bkk1 (sbb1-1). Genetic analyses indicated that cell-death symptoms in a weak double mutant, bak1-3 bkk1-1, were completely suppressed by the loss-of-function mutation in SBB1, which encodes a nucleoporin (NUP) 85-like protein. Genetic analyses also demonstrated that individually knocking out three other nucleoporin genes from the SBB1-located sub-complex was also able to rescue the celldeath phenotype of bak1-3 bkk1-1. In addition, a DEAD-box RNA helicase, DRH1, was identified in the same protein complex as SBB1 via a proteomic approach. The drh1 mutation also rescues the cell-death symptoms of bak1-3 bkk1-1. Further analyses indicated that export of poly(A) + RNA was greatly blocked in the nup and drh1 mutants, resulting in accumulation of significant levels of mRNAs in the nuclei. Over-expression of a bacterial NahG gene to inactivate salicylic acid also rescues the cell-death phenotype of bak1-3 bkk1-1. Mutants suppressing cell-death symptoms always showed greatly reduced salicylic acid contents. These results suggest that nucleocytoplasmic trafficking, especially of molecules directly or indirectly involved in endogenous salicylic acid accumulation, is critical in BAK1-and BKK1-mediated cell-death control.