PhospholipaseA2: a key regulator of inflammatory signalling and a connector to fibrosis development in atherosclerosis

Atherosclerosis is a progressive inflammatory disease that takes place in the intima of the arterial wall. It is characterized by activation of endothelial cells, proliferation of smooth muscle cells and macrophages, accumulation of lipoproteins, deposition of extracellular matrix components and enhanced lipolytic enzyme activity. Phospholipase A(2) (PLA(2)) has been postulated to play an important role in the inflammatory process of atherosclerosis, but its molecular mechanism is uncertain. The secretory PLA(2) is expressed at increased levels in an atherosclerotic plaque and may hydrolyze low-density lipoproteins (LDL). This action promotes the production of pro-inflammatory lipids such as lysophospholipids, unsaturated fatty acids and eicosanoids. The current review highlights recent findings on how LDL-derived lipid mediators, generated by sPLA_2 modification of LDL, regulate pro-inflammatory activation and intracellular signaling in macrophages. Moreover, the review discusses how PLA_2 enzymes regulate signalling that promotes collagen accumulation and fibrotic plaque development. PLA_2 could therefore function as a connector between inflammation and fibrosis, the latter being an endpoint of chronic inflammation.     

The effects of chronic immune stimulation on muscle growth in rainbow trout

Successful production of aquaculture species depends on efficient growth with low susceptibility to disease. Therefore, selection programs have focused on rapid growth combined with disease resistance. However, chronic immune stimulation diminishes muscle growth (a syndrome referred to as cachexia), and decreases growth efficiency in production animals, including rainbow trout. In mammals, recent results show that increased levels of pro-inflammatory cytokines, such as those seen during an immune assault, specifically target myosin and MyoD and inhibit muscle growth. This suggests that increased disease resistance in fish, a desired trait for production, may actually decrease the growth of muscle, the main aquacultural commodity. To test this possibility, a rainbow trout model of cachexia was developed and characterized. A six-week study was conducted in which rainbow trout were chronically immune stimulated by repeated injections of LPS. Growth indices were monitored, and whole body and muscle proximate analyses, real-time PCR, and Western blotting were conducted to examine the resulting cachectic phenotype. Muscle ratio was decreased in fish chronically immunostimulated, however expression levels of MyoD2 and myosin were not decreased compared to fish that were not immunostimulated, indicating that while muscle accretion was altered, the mechanism by which it occurred was somewhat different than that characterized in mammals. Microarray analysis was used to compare gene expression in fish that had been chronically immunostimulated versus those that had not to identify possible alternative mechanisms of cachexia in fish.     

Allelic and phenotypic spectrum of plasma triglycerides

The genetic underpinnings of both normal and pathological variation in plasma triglyceride (TG) concentration are relatively well understood compared to many other complex metabolic traits. For instance, genome-wide association studies (GWAS) have revealed 32 common variants that are associated with plasma TG concentrations in healthy epidemiologic populations. Furthermore, GWAS in clinically ascertained hypertriglyceridemia (HTG) patients have shown that almost all of the same TG-raising alleles from epidemiologic samples are also associated with HTG disease status, and that greater accumulation of these alleles reflects the severity of the HTG phenotype. Finally, comprehensive resequencing studies show a burden of rare variants in some of these same genes - namely in LPL, GCKR, APOB and APOA5 - in HTG patients compared to normolipidemic controls. A more complete understanding of the genes and genetic variants associated with plasma TG concentration will enrich our understanding of the molecular pathways that modulate plasma TG metabolism, which may translate into clinical benefit. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.     

The chromodomain-containing NH<Subscript>2</Subscript>-terminus of Chromator interacts with histone H1 and is required for correct targeting to chromatin

The chromodomain protein, Chromator, can be divided into two main domains, a NH₂-terminal domain (NTD) containing the chromodomain (ChD) and a COOH-terminal domain (CTD) containing a nuclear localization signal. During interphase Chromator is localized to chromosomes; however, during cell division Chromator redistributes to form a macro molecular spindle matrix complex together with other nuclear proteins that contribute to microtubule spindle dynamics and proper chromosome segregation during mitosis. It has previously been demonstrated that the CTD is sufficient for targeting Chromator to the spindle matrix. In this study, we show that the NTD domain of Chromator is required for proper localization to chromatin during interphase and that chromosome morphology defects observed in Chromator hypomorphic mutant backgrounds can be largely rescued by expression of this domain. Furthermore, we show that the ChD domain can interact with histone H1 and that this interaction is necessary for correct chromatin targeting. Nonetheless, that localization to chromatin still occurs in the absence of the ChD indicates that Chromator possesses a second mechanism for chromatin association and we provide evidence that this association is mediated by other sequences residing in the NTD. Taken together these findings suggest that Chromator's chromatin functions are largely governed by the NH₂-terminal domain whereas functions related to mitosis are mediated mainly by COOH-terminal sequences.     

18 Morphology, 16s rRNA gene sequences, and internally transcribed (ITS) regions: towards a meaningful systematic framework for the cyanobacteria

The establishment and growth of Nereocystis luetkeana communities are limited by many environmental and biotic factors. Temperature, light quantity and quality, turbidity, salinity, wave motion, and competition for space and light all determine where populations of this annual kelp will establish and persist from season to season. Like much of the nearshore marine vegetation in Puget Sound and the San Juan Archipelago, Nereocystis is negatively impacted by anthropogenic disturbances, such as shoreline development and sediment loading from terrestrial erosion. These events can alter or eliminate optimal habitat and conditions that support adult populations, as well as interfere with the development of the microscopic life stages. Various techniques to establish a Nereocystis bed in the northern waters of Washington, USA are examined and will serve as a model for future restoration efforts. Techniques being investigated are as follows: 1) out-planting Nereocystis during different seasons; 2) out-planting at different stages of maturity, i.e., zoospore and microscopic sporophyte (0.5–1.0 mm blade length) from cultures; 3) out-planting directly on natural substratum versus at elevated positions; 4) transplanting juveniles (10 cm stipe length); and, 5) seeding natural substratum with out-planted sori (sporophylls), bypassing the lab culturing phase. Results of this study will help define the optimal restoration procedure, including environmental parameters, for Nereocystis in order to aid coastal managers in the implementation of nearshore restoration projects. Preliminary results will be presented.     

Flavivirus isolations from mosquitoes collected from Saibai Island in the Torres Strait, Australia, during an incursion of Japanese encephalitis virus

Adult mosquitoes (Diptera: Culicidae) were collected in January and February 2000 from Saibai Island in the Torres Strait of northern Australia, and processed for arbovirus isolation during a period of Japanese encephalitis (JE) virus activity on nearby Badu Island. A total of 84 210 mosquitoes were processed for virus isolation, yielding six flavivirus isolates. Viruses obtained were single isolates of JE and Kokobera (KOK) and four of Kunjin (KUN). All virus isolates were from members of the Culex sitiens Weidemann subgroup, which comprised 53.1% of mosquitoes processed. Nucleotide sequencing and phylogenetic analysis of the pre-membrane region of the genome of JE isolate TS5313 indicated that it was closely related to other isolates from a sentinel pig and a pool of Cx. gelidus Theobald from Badu Island during the same period. Also molecular analyses of part of the envelope gene of KUN virus isolates showed that they were closely related to other KUN virus strains from Cape York Peninsula. The results indicate that flaviviruses are dynamic in the area, and suggest patterns of movement south from New Guinea and north from the Australian mainland.     

Arbovirus surveillance using FTATM cards in modified CO2‐baited encephalitis virus surveillance traps in the Northern Territory,Australia

In 2016, modified CO₂‐baited encephalitis virus surveillance (EVS) traps were evaluated for flavivirus surveillance in the Northern Territory, Australia. The traps were fitted with honey‐soaked nucleic acid preservation cards (FTA^TM) for mosquitoes to expectorate virus while feeding on the cards. Cards were tested for the presence of selected arboviruses, with two cards testing positive for Kunjin virus and Alfuy, while sentinel chickens tested in parallel also showed Kunjin virus activity at the same time. The results from the cards and vector mosquito feeding rates indicate that CO₂‐baited EVS traps coupled with honey‐baited FTA^TM cards are an effective tool for broad‐scale arbovirus surveillance.     

Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis--one species on the basis of genetic evidence

Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are members of the Bacillus cereus group of bacteria, demonstrating widely different phenotypes and pathological effects. B. anthracis causes the acute fatal disease anthrax and is a potential biological weapon due to its high toxicity. B. thuringiensis produces intracellular protein crystals toxic to a wide number of insect larvae and is the most commonly used biological pesticide worldwide. B. cereus is a probably ubiquitous soil bacterium and an opportunistic pathogen that is a common cause of food poisoning. In contrast to the differences in phenotypes, we show by multilocus enzyme electrophoresis and by sequence analysis of nine chromosomal genes that B. anthracis should be considered a lineage of B. cereus. This determination is not only a formal matter of taxonomy but may also have consequences with respect to virulence and the potential of horizontal gene transfer within the B. cereus group.