Impaired Autophagy and Exosomes Release by Long-Term mTOR Pathway Activation Promotes Hepatocellular Carcinoma Occurrence and Invasion

Mammalian target of rapamycin (mTOR) is highly expressed in various types of hepatocellular carcinoma (HCC). Clinically, HCC cases without inflammation and cirrhosis are also increasingly common, especially in patients with nonalcoholic fatty liver disease, more and more patients develop HCC, which is only characterized by hepatic steatosis. However, the molecular mechanisms underlying the development of non-inflammatory HCC remain unclearly. Our previous study demonstrated that overactivation of mTOR pathway in the liver promotes de novo lipid synthesis and eventually spontaneous formation of non-inflammatory HCC. The continuous activation of mTOR pathway, on the one hand, promotes the de novo synthesis of lipids, resulting in the production of a large amount of lipid in the liver; on the other hand, it inhibits autophagy, resulting in the inability of lipid to be removed in time and accumulate in the liver. Accumulated lipid peroxidation eventually develops into HCC. In addition, the continuously activated mTOR pathway inhibited the release of exosomes by reducing the expression of Rab27A, and in vitro experiments confirmed that hepatoma cells after Rab27A knockout were more prone to invasion and metastasis. The reduced release of exosomes may impair intercellular communication, especially with immune cells, thereby making HCC more prone to invasion and metastasis with less inflammation

Bacterial endosymbiont Cardinium cSfur genome sequence provides insights for understanding the symbiotic relationship in Sogatella furcifera host

Background: Sogatella furcifera is a migratory pest that damages rice plants and causes severe economic losses. Due to its ability to annually migrate long distances, S.furcifera has emerged as a major pest of rice in several Asian countries. Symbiotic relationships of inherited bacteria with terrestrial arthropods have significant implications. The genus Cardinium is present in many types of arthropods, where it influences some host characteristics. We present a report of a newly # identified strain of the bacterial endosymbiont Cardinium cSfur in S. furcifera. Result: From the whole genome of S. furcifera previously sequenced by our laboratory, we assembled the whole genome sequence of Cardinium cSfur. The sequence comprised 1,103,593 bp with a GC content of 39.2%. The phylogenetic tree of the Bacteroides phylum to which Cardinium cSfur belongs suggests that Cardinium cSfur is closely related to the other strains (Cardinium cBtQ1 and cEper1) that are members of the Amoebophilaceae family. Genome comparison between the host-dependent endosymbiont including Cardinium cSfur and freeliving bacteria revealed that the endosymbiont has a smaller genome size and lower GC content, and has lost some genes related to metabolism because of its special environment, which is similar to the genome pattern observed in other insect symbionts. Cardinium cSfur has limited metabolic capability, which makes it less contributive to metabolic and biosynthetic processes in its host. From our findings, we inferred that, to compensate for its limited metabolic capability, Cardinium cSfur harbors a relatively high proportion of transport proteins, which might act as the hub between it and its host. With its acquisition of the whole operon related to biotin synthesis and glycolysis related genes through HGT event, Cardinium cSfur seems to be undergoing changes while establishing a symbiotic relationship with its host. Conclusion: A novel bacterial endosymbiont strain (Cardinium cSfur) has been discovered. A genomic analysis of the endosymbiont in S. furcifera suggests that its genome has undergone certain changes to facilitate its settlement in the host. The envisaged potential reproduction manipulative ability of the new endosymbiont strain in its S. furcifera host has vital implications in designing eco-friendly approaches to combat the insect pest

The Genomes of Oryza sativa: A History of Duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

VOT and VFT-Based hybrid digital hysteresis control for UPS inverter

When the digital hysteresis current control (DHCC) strategy is applied to control the uninterruptible power supply (UPS) inverter, here are some issues such as large hysteresis tracking error caused by sampling interval and severe switching frequency swing caused by rapid change rate of inductor current. To address these issues, this paper presents a digital control strategy based on the hybrid digital hysteresis current control (HDHCC) of variable opening time (VOT) and variable falling time (VFT) for UPS inverter. Firstly, the HDHCC structure is established and the working principle of the inverter system is described in detail. Then, the tracking error and switching frequency error of the DHCC are derived. Based on the performance requirement of quasi-constant frequency control of UPS inverter, VOT and VFT control criteria without the dependency of circuit parameters are given. The experimental results demonstrate that the hybrid digital hysteresis control strategy based on VOT and VFT has the advantages of high current tracking accuracy, accurate switching frequency control, small output voltage waveform distortion, and simple implementation

Decoupled Unipolar Hysteresis Current Control for Single-Phase Grid-Tied Inverter Without Current Zero-Crossing Distortion

A digital controlled unipolar hysteresis current control strategy applied to the single-phase grid-connected inverter is studied in the paper. In view of the problem of current zero-crossing distortion in the traditional unipolar hysteresis current control based on finite state machines (FSM), a new unipolar hysteresis current control strategy based on current decoupling is proposed. By introducing a virtual zero-sequence current, the single-phase full-bridge inverter is decoupled into two independent half-bridge inverter units, which are controlled by two bipolar hysteresis current control loops under the constraints of a finite state machine. Therefore, the operation rules of the FSM ensure the frequency doubling output of the unipolar modulation, and the virtual two-phase decoupled current eliminates the zero-crossing distortion problem of inverter output current. Finally, the effectiveness and feasibility of the proposed method were verified by building a 1kW single-phase full-bridge grid-connected inverter in the laboratory

Distribution of Substitutions per Silent Site (Ks) for Homolog Pairs in Segmental, Tandem, and Background Duplications

<p>In (A), contributions from the recent segmental duplication on Chromosomes 11 and 12 are colored in red. The tandem duplication data are shown on two different scales, one to emphasize the magnitude of the zero peak (B) and another to highlight the exponential decay (C). Background duplications are shown in (D).</p

Functional Classifications from GO, Focused on Plant-Specific Categories Outlined by Gramene

<p>(A) compares predicted genes from <i>Arabidopsis</i> and Beijing <i>indica</i>. (B) compares predicted genes from Beijing <i>indica</i> with nr-KOME cDNAs. We ignore categories with less than 0.1% of the genes.</p

Graphical View of All Duplicated Segments

<p>The 12 chromosomes are depicted along the perimeter of a circle, not in order but slightly rearranged so as to untangle the connections between segments. Overall, we cover 65.7% of the genome.</p