Surface Vulnerability of Cerebral Cortex to Major Depressive Disorder

Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process.     

Serum- and Glucocorticoid-Inducible Kinase-1 (SGK-1) Plays a Role in Membrane Trafficking in Caenorhabditis elegans

The mammalian serum- and glucocorticoid-inducible kinase SGK1 regulates the endocytosis of ion channels. Here we report that in C. elegans sgk-1 null mutants, GFP-tagged MIG-14/Wntless, the sorting receptor of Wnt, failed to localize to the basolateral membrane of intestinal cells; instead, it was mis-sorted to lysosomes. This effect can be explained in part by altered sphingolipid levels, because reducing glucosylceramide biosynthesis restored the localization of MIG-14::GFP. Membrane traffic was not perturbed in general, as no obvious morphological defects were detected for early endosomes, the Golgi apparatus, and the endoplasmic reticulum (ER) in sgk-1 null animals. The recycling of MIG-14/Wntless through the Golgi might be partially responsible for the observed phenotype because the subcellular distribution of two plasma membrane cargoes that do not recycle through the trans-Golgi network (TGN) was affected to a lesser degree. Consistently, knockdown of the ArfGEF gbf-1 altered the distribution of SGK-1 at the basolateral membrane of intestinal cells. In addition, we found that sgk-1(RNAi) induced unfolded protein response in the ER, suggesting at least an indirect role of SGK-1 early in the secretory pathway. We propose that SGK-1 function is required for lipid homeostasis and that it acts at different intracellular trafficking steps.     

The Expression Level and Prognostic Value of Y-Box Binding Protein-1 in Rectal Cancer

The aims of this study were to simultaneously evaluate the expression of Y-box binding protein-1 (YB-1) in non-neoplastic rectal tissue and rectal cancer tissue, and to collect clinical follow-up data for individual patients. Additionally, we aimed to investigate the developmental functions and prognostic value of YB-1 in rectal cancer. We performed immunohistochemical studies to examine YB-1 expression in tissue samples from 80 patients with rectal cancer, 30 patients with rectal tubular adenoma, and 30 patients with rectitis. The mean YB-1 histological scores for rectal cancer, rectal tubular adenoma, and rectitis tissue specimens were 205.5, 164.3, and 137.7, respectively. Shorter disease-free and overall survival times were found in patients with rectal cancer who had higher YB-1 expression than in those with lower expression (38.2 months vs. 52.4 months, P = 0.013; and 44.4 months vs. 57.3 months, P = 0.008, respectively). Our results indicate that YB-1 expression is higher in rectal cancer tissue than in rectal tubular adenoma and rectitis tissue and that it may be an independent prognostic factor for rectal cancer.     

Altered Localization of p120 Catenin in the Cytoplasm Rather than the Membrane Correlates with Poor Prognosis in Esophageal Squamous Cell Carcinoma

Background

P120 catenin (p120ctn), a regulator of cell adhesion, has previously been found in many malignancies, and suggested a role in invasion, metastasis and survival. The aim of this study was to investigate correlations between altered localization of p120ctn and clinical-pathological characteristics in esophageal squamous cell carcinoma (ESCC).

Methods

Immunohistochemical staining for p120^ctn was performed on tissue samples from 118 patients with ESCC. The expression of p120^ctn was scored for intensity and cellular localization by Image-pro Plus 6.0. Correlations between immunohistochemical staining of p120^ctn and pathological characteristics and clinical prognosis were determined using SPSS 18.0 software.

Results

Membrane expression of p120^ctn in ESCCs was lower than that in adjacentnormal esophageal epithelial tissues (P = 0.041), while overall cellular expression of p120^ctn was not different between the two tissue types (P = 0.787). Furthermore, neither overall cellular expression nor localized membrane expression was associated with histological and clinical variables. The high ratio of membrane expression to overall cellular expression (M/C) of p120^ctn was inversely associated with lymph node invasion (P = 0.001), tumor differentiation (P = 0.012) and advanced tumor stage (P = 0.005); however, it was poorly associated with T stage (P = 0.274). The high M/C ratio of p120^ctn was inversely correlated with poor survival; the 5-year OS (overall survival) and the 5-year DFS (disease free survival) for the high M/C ratio group were significantly higher than those of the low M/C ratio group (41.0% vs. 6.7%, P = 0.000; 44.1% vs. 24.9%, P = 0.007). Both the M/C ratio of p120^ctn and N status were independent variables for the prediction of overall survival (P = 0.007 and P = 0.027). The M/C of p120^ctn predicted a 0.49-fold risk of ESCC death (p = 0.007, 95% CI 0.29–0.83).

Conclusions

The reduced M/C ratio of p120^ctn acted as an independent prognostic factor for ESCC patient survival and for the migration and invasive behavior of the disease.     

Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits

Background

Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer’s disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent.

Results

Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignficant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples.

Conclusions

These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD.

     

DomeTree: a canonical toolkit for mitochondrial DNA analyses in domesticated animals

Mitochondrial DNA (mtDNA) is widely used in various genetic studies of domesticated animals. Many applications require comprehensive knowledge about the phylogeny of mtDNA variants. Herein, we provide the most up‐to‐date mtDNA phylogeny (i.e. haplogroup tree or matrilineal genealogy) and a standardized hierarchical haplogroup nomenclature system for domesticated cattle, dogs, goats, horses, pigs, sheep, yaks and chickens. These high‐resolution mtDNA haplogroup trees based on 1240 complete or near‐complete mtDNA genome sequences are available in open resource DomeTree ( http://www.dometree.org ). In addition, we offer the software MitoToolPy ( http://www.mitotool.org/mp.html ) to facilitate the mtDNA data analyses. We will continuously and regularly update DomeTree and MitoToolPy.     

Sustainable limits to crop residue harvest for bioenergy: maintaining soil carbon in Australia's agricultural lands

The use of crop residues for bioenergy production needs to be carefully assessed because of the potential negative impact on the level of soil organic carbon (SOC) stocks. The impact varies with environmental conditions and crop management practices and needs to be considered when harvesting the residue for bioenergy productions. Here, we defined the sustainable harvest limits as the maximum rates that do not diminish SOC and quantified sustainable harvest limits for wheat residue across Australia's agricultural lands. We divided the study area into 9432 climate‐soil (CS) units and simulated the dynamics of SOC in a continuous wheat cropping system over 122 years (1889 – 2010) using the Agricultural Production Systems sIMulator (APSIM). We simulated management practices including six fertilization rates (0, 25, 50, 75, 100, and 200 kg N ha^?1) and five residue harvest rates (0, 25, 50, 75, and 100%). We mapped the sustainable limits for each fertilization rate and assessed the effects of fertilization and three key environmental variables – initial SOC, temperature, and precipitation – on sustainable residue harvest rates. We found that, with up to 75 kg N ha^?1 fertilization, up to 75% and 50% of crop residue could be sustainably harvested in south‐western and south‐eastern Australia, respectively. Higher fertilization rates achieved little further increase in sustainable residue harvest rates. Sustainable residue harvest rates were principally determined by climate and soil conditions, especially the initial SOC content and temperature. We conclude that environmental conditions and management practices should be considered to guide the harvest of crop residue for bioenergy production and thereby reduce greenhouse gas emissions during the life cycle of bioenergy production.     

miRTex: A Text Mining System for miRNA-Gene Relation Extraction

MicroRNAs (miRNAs) regulate a wide range of cellular and developmental processes through gene expression suppression or mRNA degradation. Experimentally validated miRNA gene targets are often reported in the literature. In this paper, we describe miRTex, a text mining system that extracts miRNA-target relations, as well as miRNA-gene and gene-miRNA regulation relations. The system achieves good precision and recall when evaluated on a literature corpus of 150 abstracts with F-scores close to 0.90 on the three different types of relations. We conducted full-scale text mining using miRTex to process all the Medline abstracts and all the full-length articles in the PubMed Central Open Access Subset. The results for all the Medline abstracts are stored in a database for interactive query and file download via the website at http://proteininformationresource.org/mirtex. Using miRTex, we identified genes potentially regulated by miRNAs in Triple Negative Breast Cancer, as well as miRNA-gene relations that, in conjunction with kinase-substrate relations, regulate the response to abiotic stress in Arabidopsis thaliana. These two use cases demonstrate the usefulness of miRTex text mining in the analysis of miRNA-regulated biological processes.