Effects of tumor necrosis factor antagonist treatment on hepatitis C-related immunological abnormalities

BACKGROUND: Chronic hepatitis C infection is frequently associated with a mixed cryoglobulinaemia and circulating auto-antibodies, especially anti-smooth muscle cells (SMA) and anti-liver/kidney/microsome type 1 (LKM-1) anti-tissue antibodies. Treatments with TNF antagonists favour the emergence of auto-antibodies, and particularly anti-dsDNA antibodies. OBJECTIVE: To determine the impact of TNF antagonists on hepatitis C-related immune abnormalities. METHODS: We prospectively monitored for 14 weeks, six patients with actively replicating chronic hepatitis C, initiating an anti-TNF treatment for an associated rheumatoid arthritis. RESULTS: Anti-nuclear and anti-dsDNA antibodies were induced in two and three patients, respectively. Treatment had no impact on the production of antibodies against extractable nuclear antigens, and it did not induce anti-tissues antibodies in any patient. Cryoglobulinaemia appeared in 2/6 patients, and it persisted in 2 others. No patient developed any news signs of autoimmunity. HCV viraemia remained unchanged. CONCLUSIONS: Induction of auto-antibodies by TNF antagonist treatments does not involve anti-tissues antibodies, even in patients with actively replicating chronic hepatitis C prone to produce anti-SMA and anti-LKM-1 antibodies. In contrast, TNF antagonists may favour emergence of cryoglobulinaemia in such patients.     

Eight-carbon volatiles in mushrooms and fungi: properties, analysis, and biosynthesis

Eight-carbon volatiles are ubiquitous among fungi and characteristic of the fungal aroma. They are the product of the oxidation and cleavage of the fatty acid linoleic acid and are classified as oxylipins, molecules taking part in a wide range of biological processes. Their involvement in the fungal aroma, interactions with pests and pathogens, and reproductive events are reviewed here, as well as the enzymic systems involved in their biosynthesis.     

Anabolic signaling and protein synthesis in human skeletal muscle after dynamic shortening or lengthening exercise

We hypothesized a differential activation of the anabolic signaling proteins protein kinase B (PKB) and p70 S6 kinase (p70(S6K)) and subsequent differential stimulation of human muscle protein synthesis (MPS) after dynamic shortening or lengthening exercise. Eight healthy men [25 +/- 5 yr, BMI 26 +/- 3 kg/m(-2) (means +/- SD)] were studied before and after 12 min of repeated stepping up to knee height, and down again, while carrying 25% of their body weight, i.e., shortening exercise with the "up" leg and lengthening exercise with contralateral "down" leg. Quadriceps biopsies were taken before and 3, 6, and 24 h after exercise. After exercise, over 2 h before the biopsies, the subjects ingested 500 ml of water containing 45 g of essential amino acids and 135 g of sucrose. Rates of muscle protein synthesis were determined via incorporation over time of [1-(13)C]leucine (相似文献   

Comprehensive expression profiling of the pectin methylesterase gene family during silique development in Arabidopsis thaliana

Pectin methylesterases (PME, EC. 3.1.1.11) are enzymes that demethylesterify plant cell wall pectins in muro. In Arabidopsis thaliana, putative PME proteins are thought to be encoded by a 66-member gene family. This study used real-time RT-PCR to gain an overview of the expression of the entire family at eight silique developmental stages, in flower buds and in vegetative tissue in the Arabidopsis. Only 15% of the PMEs were not expressed at any of the developmental stages studied. Among expressed PMEs, expression data could be clustered into five distinct groups: 19 PMEs highly or uniquely expressed in floral buds, 4 PMEs uniquely expressed at mid-silique developmental stages, 16 PMEs highly or uniquely expressed in silique at late developmental stages, 16 PMEs mostly ubiquitously expressed, and 1 PME with a specific expression pattern, i.e. not expressed during early silique development. Comparison of expression and phylogenetic profiles showed that, within phylogenetic group 2, all but one PME belong to the floral bud expression group. Similar results were shown for a subset of one of the phylogenetic group, which differed from others by containing most of the PMEs that do not possess any PRO part next to their catalytic part. Expression data were confirmed by two promoter:GUS transgenic plant analysis revealing a PME expressed in pollen and one in young seeds. Our results highlight the high diversity of PME expression profiles. They are discussed with regard to the role of PMEs in fruit development and cell growth.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Responses of sawgrass and spikerush to variation in hydrologic drivers and salinity in Southern Everglades marshes

Aboveground net primary production (ANPP) by the dominant macrophyte and plant community composition are related to the changing hydrologic environment and to salinity in the southern Everglades, FL, USA. We present a new non-destructive ANPP technique that is applicable to any continuously growing herbaceous system. Data from 16 sites, collected from 1998 to 2004, were used to investigate how hydrology and salinity controlled sawgrass (Cladium jamaicense Crantz.) ANPP. Sawgrass live biomass showed little seasonal variation and annual means ranged from 89 to 639 gdw m⁻². Mortality rates were 20–35% of live biomass per 2 month sampling interval, for biomass turnover rates of 1.3–2.5 per year. Production by C. jamaicense was manifest primarily as biomass turnover, not as biomass accumulation. Rates typically ranged from 300 to 750 gdw m⁻² year⁻¹, but exceeded 1000 gdw m⁻² year⁻¹ at one site and were as high as 750 gdw m⁻² year⁻¹ at estuarine ecotone sites. Production was negatively related to mean annual water depth, hydroperiod, and to a variable combining the two (depth-days). As water depths and hydroperiods increased in our southern Everglades study area, sawgrass ANPP declined. Because a primary restoration goal is to increase water depths and hydroperiods for some regions of the Everglades, we investigated how the plant community responded to this decline in sawgrass ANPP. Spikerush (Eleocharis sp.) was the next most prominent component of this community at our sites, and 39% of the variability in sawgrass ANPP was explained by a negative relationship with mean annual water depth, hydroperiod, and Eleocharis sp. density the following year. Sawgrass ANPP at estuarine ecotone sites responded negatively to salinity, and rates of production were slow to recover after high salinity years. Our results suggest that ecologists, managers, and the public should not necessarily interpret a decline in sawgrass that may result from hydrologic restoration as a negative phenomenon.     

Impairment of spatial learning by estradiol treatment in female mice is attenuated by estradiol exposure during development

High doses of estradiol (E(2)) can impair spatial learning in the Morris water maze, in ovariectomized mice, but the same dose has no effect on adult castrated males. Here, we test the hypothesis that this sex difference is caused by neonatal actions of E(2). In Experiment 1, C57BL/6J pups were given daily estradiol benzoate (EB) or oil injections from the day of birth until postnatal Day 3. Adults were gonadectomized and received EB (s.c.) or oil 28 h before the first day of training, and 4 h before each of four daily training sessions on the Morris water maze. Females given oil as neonates, and EB prior to training displayed the poorest performance. Females that received EB as neonates and EB prior to training were insensitive to the deleterious effects of adult EB and performed better than males given the same hormone treatments. We conducted a second experiment using aromatase enzyme knockout (ArKO) mice. Adult male and female ArKO and wild-type (WT) littermates were gonadectomized and received either injections of oil or EB prior to and during water maze training (as described above). Hormone treatment failed to affect performance, yet, female but not male ArKO mice showed impaired learning compared to WT littermates. Thus, exposure to estradiol during neonatal development can counteract the deleterious effects of EB on adult spatial learning.     

NAD(P)H:quinone oxidoreductase 1 activity reduces hypertrophy in 3T3-L1 adipocytes

The nuclear factor E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway responds to oxidative stress via control of several antioxidant defense gene expressions. Recent efforts demonstrate that Nrf2 modulates development of adiposity and adipogenesis. One of the major Nrf2-regulated proteins, NAD(P)H:quinone oxidoreductase 1 (NQO1), is implicated in the development of adipose tissue and obesity. However, little is known about in situ disposition of Nrf2, Keap1, and NQO1 during adipogenesis in isolated adipocytes. Based on literature data, we hypothesized that adipocyte differentiation would increase expression of the Nrf2/Keap1 pathway and NQO1. Using murine 3T3-L1 preadipocytes, we mapped an increase in NQO1 protein at limited clonal expansion and postmitotic growth arrest (Days 1-3) stages and a decrease in terminally differentiated (Day 8) adipocytes that lasted for several days afterward. Conversely, NQO1, Nrf2, and Keap1 mRNA expressions were all increased in differentiated adipocytes (Days 11-14), indicating a discrepancy between steady-state mRNA levels and resulting protein. Treatment of differentiated 3T3-L1 adipocytes with glycogen synthase kinase-3β (GSK-3β) inhibitor, LiCl, led to 1.9-fold increase in NQO1 protein. Sulforaphane enhanced NQO1 protein (10.5-fold) and blunted triglyceride and FABP4 accumulation. The decrement in triglyceride content was partially reversed when NQO1 activity was pharmacologically inhibited. These data demonstrate a biphasic response of Nrf2 and NQO1 during adipocyte differentiation that is regulated by Keap1- and GSK-3β-dependent mechanisms, and that hypertrophy is negatively regulated by NQO1 activity.     

A supramolecular assembly formed by influenza A virus genomic RNA segments

The influenza A virus genome consists of eight viral RNAs (vRNAs) that form viral ribonucleoproteins (vRNPs). Even though evidence supporting segment-specific packaging of vRNAs is accumulating, the mechanism ensuring selective packaging of one copy of each vRNA into the viral particles remains largely unknown. We used electron tomography to show that the eight vRNPs emerge from a common 'transition zone' located underneath the matrix layer at the budding tip of the virions, where they appear to be interconnected and often form a star-like structure. This zone appears as a platform in 3D surface rendering and is thick enough to contain all known packaging signals. In vitro, all vRNA segments are involved in a single network of intermolecular interactions. The regions involved in the strongest interactions were identified and correspond to known packaging signals. A limited set of nucleotides in the 5' region of vRNA 7 was shown to interact with vRNA 6 and to be crucial for packaging of the former vRNA. Collectively, our findings support a model in which the eight genomic RNA segments are selected and packaged as an organized supramolecular complex held together by direct base pairing of the packaging signals.     

Highly sensitive quenched fluorescent substrate of Legionella major secretory protein (msp) based on its structural analysis

Legionella pneumophila has been shown to secrete a protease termed major secretory protein (Msp). This protease belongs to the M4 family of metalloproteases and shares 62.9% sequence similarity with pseudolysin (EC 3.4.24.26). With the aim of developing a specific enzymatic assay for the detection and quantification of Msp, the Fluofast substrate library was screened using both enzymes in parallel. Moreover, based on the crystal structure of pseudolysin, a model of the Msp structure was built. Screening of the peptide library identified a lead substrate specifically cleaved by Msp that was subsequently optimized by rational design. The proposed model for Msp is consistent with the enzymatic characteristics of the studied peptide substrates and provides new structural information useful for the characterization of the protease. This study leads to the identification of the first selective and high affinity substrate for Msp that is able to detect picomolar concentrations of the purified enzyme. The identified substrate could be useful for the development of a novel method for the rapid detection of Legionella.