Lipids,lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

Lipids are essential for mammalian cells to maintain many physiological functions. Emerging evidence has shown that cancer cells can develop specific alterations in lipid biosynthesis and metabolism to facilitate their survival and various malignant behaviors. To date, the precise role of cellular lipids and lipid metabolism in viral oncogenesis is still largely unclear with only a handful of literature covering this topic to implicate lipid metabolism in oncogenic virus associated pathogenesis. In this review, we focus on the role of lipid biosynthesis and metabolism in the pathogenesis of the Kaposi’s sarcoma-associated herpesvirus, a common causative factor for cancers arising in the immunocompromised settings.

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Comparative transcriptional profiling and evolutionary analysis of the GRAM domain family in eukaryotes

The GRAM domain was found in glucosyltransferases, myotubularins and other membrane-associated proteins. So far, functions for majority of these proteins are yet to be uncovered. In order to address the evolutionary and functional significance of this family members, we have performed a comprehensive investigation on their genome-wide identification, phylogenetic relationship and expression divergence in five different organisms representing monocot/dicot plants, vertebrate/invertebrate animals and yeast, namely, Oryza sativa, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster and Saccharomyces cerevisiae, respectively. We have identified 65 members of GRAM domain family from these organisms. Our data revealed that this family was an ancient group and various organisms had evolved into different family sizes. Large-scale genome duplication and divergence in both expression patterns and functions were significantly contributed to the expansion and retention of this family. Mouse and Drosophila members showed higher divergences in their proteins as indicated by higher Ka/Ks ratios and possessed multiple domains in various combinations. However, in plants, their protein functions were possibly retained with a relatively low divergence as signified by lower Ka/Ks ratios and only one additional domain was combined during evolution. On the other hand, this family in all five organisms exhibited high divergence in their expression patterns both at tissue level and under various biotic and abiotic stresses. These highly divergent expression patterns unraveled the complexity of functions of GRAM domain family. Each member may play specialized roles in a specific tissue or stress condition and may function as regulators of environmental and hormonal signaling.     

Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China

Background

Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define the true frequency of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF in Chinese stroke patients, and to elucidate predictors of newly detected AF.

Methods

Patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled in a prospective, multicenter cohort study of 6-day Holter monitoring within 7 days after stroke onset at 20 sites in China between 2013 and 2015. Independent predictors of newly-detected AF were determined by multivariate analysis.

Results

Among 1511 patients with ischemic stroke and TIA (mean age 63 years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring (56/1262, 4.4%). A history of heart failure (OR?=?4.70, 95%CI, 1.64–13.5), advanced age (OR?=?1.06, 95%CI, 1.04–1.09), NIHSS at admission (OR?=?1.06, 95%CI, 1.02–1.10), blood high density lipoprotein (HDL) (OR?=?1.52, 95%CI, 1.09–2.13), together with blood triglycerides (OR?=?0.64, 95%CI, 0.45–0.91) were independently associated with newly-detected AF.

Conclusions

Contrary to previous reports, AF-associated stroke is frequent (20%) in China if systemically sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF detection in patients with recent ischemic stroke and TIA in China. Advanced age, history of heart failure, and higher admission NIHSS and higher level of HDL were independent indicators of newly-detected AF.

Trial registration

NCT02156765 (June 5, 2014).

     

Deep sequencing reveals clonal evolution patterns and mutation events associated with relapse in B-cell lymphomas

Background

Molecular mechanisms associated with frequent relapse of diffuse large B-cell lymphoma (DLBCL) are poorly defined. It is especially unclear how primary tumor clonal heterogeneity contributes to relapse. Here, we explore unique features of B-cell lymphomas - VDJ recombination and somatic hypermutation - to address this question.

Results

We performed high-throughput sequencing of rearranged VDJ junctions in 14 pairs of matched diagnosis-relapse tumors, among which 7 pairs were further characterized by exome sequencing. We identify two distinctive modes of clonal evolution of DLBCL relapse: an early-divergent mode in which clonally related diagnosis and relapse tumors diverged early and developed in parallel; and a late-divergent mode in which relapse tumors developed directly from diagnosis tumors with minor divergence. By examining mutation patterns in the context of phylogenetic information provided by VDJ junctions, we identified mutations in epigenetic modifiers such as KMT2D as potential early driving events in lymphomagenesis and immune escape alterations as relapse-associated events.

Conclusions

Altogether, our study for the first time provides important evidence that DLBCL relapse may result from multiple, distinct tumor evolutionary mechanisms, providing rationale for therapies for each mechanism. Moreover, this study highlights the urgent need to understand the driving roles of epigenetic modifier mutations in lymphomagenesis, and immune surveillance factor genetic lesions in relapse.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0432-0) contains supplementary material, which is available to authorized users.     

Ultrasonic Elastography Research Based on a Multicenter Study: Adding Strain Ratio after 5-Point Scoring Evaluation or Not

Background

This study aimed to confirm whether strain ratio should be added after evaluation of lesions with 5-point elasticity scoring for differentiating benign and malignant breast lesions on ultrasonographic elastography(UE).

Materials and Methods

From June 2010 to March 2012, 1080 consecutive female patients with breast lesions were recruited into a multicenter retrospective study, which involved 8 centers across China. Each institutional ethic review board approved the study, and all the patients gave written informed consent. All the patients underwent the UE procedure and the strain ratios were calculated and the final diagnosis was made by histological findings. The sensitivity, specificity, accuracy, PPV and NPV were calculated for each of the two evaluation systems and the areas under the ROC curve were compared.

Results

The strain ratios of benign lesions (mean, 2.6±2.0) and malignant lesions (mean,7.9±5.8) were significantly different (p <0.01). When the cutoff point was 3.01, strain ratio method had 79.8% sensitivity, 82.8% specificity, and 81.3% accuracy, while the 5-point scoring method had 93.1% sensitivity, 73.0% specificity, and 76.8% accuracy. The areas under the ROC curve with the strain ratio method and 5-point scoring method were 0.863 and 0.865, respectively(p>0.05). The strain ratio method shows better a diagnosis performance of the lesions with elasticity score 3 and 4.

Conclusions

Although the two UE methods have similar diagnostic performance, separate calculation of the strain ratios seems compulsory, especially for the large solid breast lesions and the lesions with elasticity score 3 and 4.     

Rice blast resistance gene Pikahei-1(t), a member of a resistance gene cluster on chromosome 4, encodes a nucleotide-binding site and leucine-rich repeat protein

Pikahei-1(t) is the strongest quantitative trait locus (QTL) for blast resistance in upland rice cv. Kahei, which has strong field resistance to the rice blast disease. A high-quality bacterial artificial chromosome library was used to fine-map Pikahei-1(t) within ~300 kb on the 31-Mb region on rice chromosome 4. Of the 42 predicted open reading frames, seven resistance gene analogs (RGAs) with the nucleotide-binding site and leucine-rich repeat (NBS-LRR) domain were identified. Among these, RGA1, 2, 3, 5, and 7, but not RGA4 and 6, were found to be expressed in Kahei and monogenic lines containing Pikahei-1(t). Blast inoculation of transgenic rice lines carrying the genomic fragment of each RGA revealed that only RGA3 was associated with blast resistance. On the basis of these results, we concluded that RGA3 is the Pikahei-1(t) and named it Pi63. Pi63 encoded a typical coiled-coil-NBS-LRR protein and showed isolate-specificity. These results suggest that Pi63 behaves like a typical Resistance (R) gene, and the strong and broad-spectrum resistance of Kahei is dependent on natural pyramiding of multiple QTLs. The blast resistance levels of Pi63 were closely correlated with its gene expression levels, indicating a dose-dependent response of Pi63 function in rice resistance. Pi63 is the first cloned R gene in the R gene cluster on rice chromosome 4, and its cloning might facilitate genomic dissection of this cluster region.