Neuronal HMGB1 in nucleus accumbens regulates cocaine reward memory.

Cocaine is a common abused drug that can induce abnormal synaptic and immune responses in the central nervous system (CNS). High mobility group box 1 (HMGB1) is one kind of inflammatory molecules that is expressed both on neurons and immune cells. Previous studies of HMGB1 in the CNS have largely focused on immune function, and the role of HMGB1 in neurons and cocaine addiction remains unknown. Here, we show that cocaine exposure induced the translocation and release of HMGB1 in the nucleus accumbens (NAc) neurons. Gain and loss of HMGB1 in the NAc bidirectionally regulate cocaine-induced conditioned place preference. From the nucleus to the cytosol, HMGB1 binds to glutamate receptor subunits (GluA2/GluN2B) on the membrane, which regulates cocaine-induced synaptic adaptation and the formation of cocaine-related memory. These data unveil the role of HMGB1 in neurons and provide the evidence for the HMGB1 involvement in drug addiction.

Periodic and Spatial Spreading of Alkanes and Alcanivorax Bacteria in Deep Waters of the Mariana Trench.

In subduction zones, serpentinization and biological processes may release alkanes to the deep waters, which would probably result in the rapid spread of Alcanivorax However, the timing and area of the alkane distribution and associated enrichment of alkane-degrading microbes in the dark world of the deep ocean have not been explored. In this study, we report the richness (up to 17.8%) of alkane-degrading bacteria, represented by Alcanivorax jadensis, in deep water samples obtained at 3,000 to 6,000 m in the Mariana Trench in two cruises. The relative abundance of A. jadensis correlated with copy numbers of functional almA and alkB genes, which are involved in alkane degradation. In these water samples, we detected a high flux of alkanes, which probably resulted in the prevalence of A. jadensis in the deep waters. Contigs of A. jadensis were binned from the metagenomes for examination of alkane degradation pathways and deep sea-specific pathways, which revealed a lack of nitrate and nitrite dissimilatory reduction in our A. jadensis strains. Comparing the results for the two cruises conducted close to each other, we suggest periodic release of alkanes that may spread widely but periodically in the trench. Distribution of alkane-degrading bacteria in the world's oceans suggests the periodic and remarkable contributions of Alcanivorax to the deep sea organic carbon and nitrogen sources.IMPORTANCE In the oligotrophic environment of the Mariana Trench, alkanes as carbohydrates are important for the ecosystem, but their spatial and periodic spreading in deep waters has never been reported. Alkane-degrading bacteria such as Alcanivorax spp. are biological signals of the alkane distribution. In the present study, Alcanivorax was abundant in some waters, at depths of up to 6,000 m, in the Mariana Trench. Genomic, transcriptomic, and chemical analyses provide evidence for the presence and activities of Alcanivorax jadensis in deep sea zones. The periodic spreading of alkanes, probably from the subductive plates, might have fundamentally modified the local microbial communities, as well as perhaps the deep sea microenvironment.

The Enigmatic Genome of an Obligate Ancient Spiroplasma Symbiont in a Hadal Holothurian.

Protective symbiosis has been reported in many organisms, but the molecular mechanisms of the mutualistic interactions between the symbionts and their hosts are unclear. Here, we sequenced the 424-kbp genome of "Candidatus Spiroplasma holothuricola," which dominated the hindgut microbiome of a sea cucumber, a major scavenger captured in the Mariana Trench (6,140 m depth). Phylogenetic relationships indicated that the dominant bacterium in the hindgut was derived from a basal group of Spiroplasma species. In this organism, the genes responsible for the biosynthesis of amino acids, glycolysis, and sugar transporters were lost, strongly suggesting endosymbiosis. The highly decayed genome consists of two chromosomes and harbors genes coding for proteolysis, microbial toxin, restriction-methylation systems, and clustered regularly interspaced short palindromic repeats (CRISPRs), composed of three cas genes and 76 CRISPR spacers. The holothurian host is probably protected against invading viruses from sediments by the CRISPRs/Cas and restriction systems of the endosymbiotic spiroplasma. The protective endosymbiosis indicates the important ecological role of the ancient Spiroplasma symbiont in the maintenance of hadal ecosystems.IMPORTANCE Sea cucumbers are major inhabitants in hadal trenches. They collect microbes in surface sediment and remain tolerant against potential pathogenic bacteria and viruses. This study presents the genome of endosymbiotic spiroplasmas in the gut of a sea cucumber captured in the Mariana Trench. The extreme reduction of the genome and loss of essential metabolic pathways strongly support its endosymbiotic lifestyle. Moreover, a considerable part of the genome was occupied by a CRISPR/Cas system to provide immunity against viruses and antimicrobial toxin-encoding genes for the degradation of microbes. This novel species of Spiroplasma is probably an important protective symbiont for the sea cucumbers in the hadal zone.

Acid-sensing ion channels promote the inflammation and migration of cultured rat microglia.

Microglia, the major immune cells in central nervous system, act as the surveillance and scavenger of immune defense and inflammatory response. Previous studies suggest that there might be close relationship between acid-sensing ion channels (ASICs) and inflammation, however, the exact role of ASICs in microglia during inflammation remains elusive. In the present study, we identified the existence of ASICs in the primary cultured rat microglia and explored their functions. By using reverse transcriptase polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), western blotting, and immunofluorescence experiments, we demonstrated that ASIC1, ASIC2a, and ASIC3 were existed in cultured and in situ rat microglia. After lipopolysaccharide (LPS) stimulation, the expressions of microglial ASIC1 and ASIC2a were upregulated. Meanwhile, ASIC-like currents and acid-induced elevation of intracellular calcium were increased, which could be inhibited by the nonspecific ASICs antagonist amiloride and specific homomeric ASIC1a blocker PcTx1. In addition, both inhibitors reduced the expression of inflammatory cytokines, including inducible nitric oxide synthase and cyclooxygenase 2 stimulated by LPS. Furthermore, we also observed significant increase in the expression of ASIC1 and ASIC2a in scrape-stimulated microglial migration. Amiloride and PcTx1 prevented the migration by inhibiting ERK phosphorylation. Taken together, these results suggest that ASICs participate in neuroinflammatory response, which will provide a novel therapeutic strategy for controlling the inflammation-relevant neuronal diseases.

The Use of Protein-Protein Interactions for the Analysis of the Associations between PM2.5 and Some Diseases.

Nowadays, pollution levels are rapidly increasing all over the world. One of the most important pollutants is PM2.5. It is known that the pollution environment may cause several problems, such as greenhouse effect and acid rain. Among them, the most important problem is that pollutants can induce a number of serious diseases. Some studies have reported that PM2.5 is an important etiologic factor for lung cancer. In this study, we extensively investigate the associations between PM2.5 and 22 disease classes recommended by Goh et al., such as respiratory diseases, cardiovascular diseases, and gastrointestinal diseases. The protein-protein interactions were used to measure the linkage between disease genes and genes that have been reported to be modulated by PM2.5. The results suggest that some diseases, such as diseases related to ear, nose, and throat and gastrointestinal, nutritional, renal, and cardiovascular diseases, are influenced by PM2.5 and some evidences were provided to confirm our results. For example, a total of 18 genes related to cardiovascular diseases are identified to be closely related to PM2.5, and cardiovascular disease relevant gene DSP is significantly related to PM2.5 gene JUP.

Classifying ten types of major cancers based on reverse phase protein array profiles.

Gathering vast data sets of cancer genomes requires more efficient and autonomous procedures to classify cancer types and to discover a few essential genes to distinguish different cancers. Because protein expression is more stable than gene expression, we chose reverse phase protein array (RPPA) data, a powerful and robust antibody-based high-throughput approach for targeted proteomics, to perform our research. In this study, we proposed a computational framework to classify the patient samples into ten major cancer types based on the RPPA data using the SMO (Sequential minimal optimization) method. A careful feature selection procedure was employed to select 23 important proteins from the total of 187 proteins by mRMR (minimum Redundancy Maximum Relevance Feature Selection) and IFS (Incremental Feature Selection) on the training set. By using the 23 proteins, we successfully classified the ten cancer types with an MCC (Matthews Correlation Coefficient) of 0.904 on the training set, evaluated by 10-fold cross-validation, and an MCC of 0.936 on an independent test set. Further analysis of these 23 proteins was performed. Most of these proteins can present the hallmarks of cancer; Chk2, for example, plays an important role in the proliferation of cancer cells. Our analysis of these 23 proteins lends credence to the importance of these genes as indicators of cancer classification. We also believe our methods and findings may shed light on the discoveries of specific biomarkers of different types of cancers.