Characterization of fibroblast growth factor 1 binding heparan sulfate domain.

Fibroblast growth factors FGF-1 and FGF-2 mediate their biological effects via heparan sulfate-dependent interactions with cell surface FGF receptors. While the specific heparan sulfate domain binding to FGF-2 has been elucidated in some detail, limited information has been available concerning heparan sulfate structures involved in the recognition of FGF-1. In the current study we present evidence that the minimal FGF-1 binding heparan sulfate sequence comprises 5-7 monosaccharide units and contains a critical trisulfated IdoA(2-OSO3)-GlcNSO3(6-OSO3) disaccharide unit. N-Sulfated heparan sulfate decasaccharides depleted of FGF-1 binding domains showed dose-dependent and saturable binding to FGF-2. These data indicate that the FGF-1 binding domain is distinct from the minimal FGF-2 binding site, previously shown to contain an IdoA(2-OSO3) residue but no 6-O-sulfate groups. We further show that the FGF-1 binding heparan sulfate domain is expressed in human aorta heparan sulfate in an age-related manner in contrast to the constitutively expressed FGF-2 binding domain. Reduction of heparan sulfate O-sulfation by chlorate treatment of cells selectively impedes binding to FGF-1. The present data implicate the 6-O-sulfation of IdoA(2-OSO3)-GlcNSO3 units in cellular heparan sulfate in the control of the biological activity of FGF-1.     

The relationship between postpartum vaginal discharge symptoms and progesterone profile characteristics in lactating dairy cows in Denmark

In this paper, the effect of clinical symptoms of uterine inflammation on progesterone profile characteristics was quantified in dairy cows. A continuous scale based on visual observation of vaginal discharge (the previously developed D-index) was used to describe the clinical symptoms. Progesterone profiles in milk were used to describe the ovarian cycles, and to determine the distinguishing features of these profiles, a multivariate statistical procedure (principal component analysis) was performed.Significant negative effects of the D-index were seen during the first and second postpartum ovarian cycles. The D-index had a significant effect on the shape of progesterone profiles and the length of the ovarian cycles but it only accounted for a small proportion of the variation in these ovarian cycle features. The D-index was not a significant risk factor for the length of postpartum anovulatory period in the present study.     

Gastroprotective,cytoprotective and antioxidant effects of Oleum cinnamomi on ethanol induced damage

Peptic ulcer disease is a gastrointestinal disorder defined by mucosal damage and free oxygen radicals associated with peptic ulcer and gastritis. Cinnamon is a traditional herb used for many diseases and it has also effects as an antioxidant, anti-inflammatory, antispasmodic and anti-ulcerative. Our research is based on oxidative stress and effects of Oleum cinnamomi on stomach, liver and kidney disorders induced by ethanol. In our experiment, 2–3 month old male Sprague–Dawley rats were used. One hour before the mucosal damage induced by 70 % ethanol, O. cinnamomi (2.5 ml/kg) was added into the groups. Gastric pH, analysis of gastric mucus and ulcer index were calculated from samples obtained from the stomach. Superoxide dismutase (SOD), malondialdehyde and catalase (CAT) levels were determined in stomach, liver and kidney homogenates and erythrocyte hemolysate. Histopathological examination of stomach, liver and kidney were determined with H&E staining. The non-treated ulcerative group showed higher scores than the control group which was treated with O. cinnamomi, when ulcer scores, gastric mucus and pH level of stomach are compared. Increased lipid peroxidation levels were observed in the liver, kidney and erythrocyte hemolysate. SOD activity was decreased in liver whereas increased in stomach of ethanol treated ulcerative groups. CAT levels were increased in stomach and liver of ethanol treated rats. Histopathological findings showed that ethanol treatment cause multiply organ damage such as stomach, liver and kidney injury. O. cinnamomi treatment protected these tissues from ethanol-induced damage. Consequently, the current investigation shows that O. cinnamomi has protective effects on ethanol-induced oxidative and mucosal damage.     

Micro and macro-habitat associations in saproxylic beetles: implications for biodiversity management

Restoration of habitats is critically important in preventing full realization of the extinction debt owed as a result of anthropogenic habitat destruction. Although much emphasis has been placed on macrohabitats, suitable microhabitats are also vital for the survival of most species. The aim of this large-scale field experiment was to evaluate the relative importance of manipulated microhabitats, i.e., dead wood substrates of spruce (snags, and logs that were burned, inoculated with wood fungi or shaded) and macrohabitats, i.e., stand types (clear-cuts, mature managed forests, and forest reserves) for species richness, abundance and assemblage composition of all saproxylic and red-listed saproxylic beetles. Beetles were collected in emergence traps in 30 forest stands in 2001, 2003, 2004 and 2006. More individuals emerged from snags and untreated logs than from burned and shaded logs, but species richness did not differ among substrates. Assemblage composition differed among substrates for both all saproxylics and red-listed saproxylic species, mainly attributed to different assemblage composition on snags. This suggests that the practise of leaving snags for conservation purposes should be complemented with log supplementation. Clear-cuts supported fewer species and different assemblages from mature managed forests and reserves. Neither abundance, nor species richness or assemblage composition differed between reserves and mature managed forests. This suggests that managed stands subjected to selective cutting, not clear-felling, maintain sufficient old growth characteristics and continuity to maintain more or less intact assemblages of saproxylic beetles. Thus, alternative management methods, e.g., continuity forestry should be considered for some of these stands to maintain continuity and conservation values. Furthermore, the significantly higher estimated abundance per ha of red-listed beetles in reserves underlines the importance of reserves for maintaining viable populations of rare red-listed species and as source areas for saproxylic species in boreal forest landscapes.     

Transformation of Trichothecenes in Ileal Digesta and Faeces from Pigs

The capacity of pig gastrointestinal microflora to metabolise the trichothecenes 3-acetyl-deoxynivalenol (3-acDON) and nivalenol (NIV) was investigated. 3-acDON was deacetylated to DON in anaerobic incubations with pig faeces collected at different pig farms. Furthermore, both 3-acDON and NIV were metabolised to the corresponding de-epoxy metabolite in these incubates. Five pigs, in which the gastrointestinal microflora lacked the ability to transform 3-acDON and NIV to their corresponding de-epoxidated metabolites, were given low levels of DON in the feed for seven weeks. The gastrointestinal micro-organisms did not acquire the de-epoxidation ability during the seven week long exposure period. At the end of the exposure period, faeces from pigs with a known de-epoxidation ability was spread out in the pens and left for 24 hours. One week after the faeces had been spread out in the pens, the de-epoxidation ability was found in faecal incubations from four out of five experimental pigs. This change in metabolic ability of the intestinal de-epoxidation ability was not accompanied by any detectable changes in the DNA-profiles of the bacterial community composition. The results show that the intestinal de-epoxidation ability is common at pig farms in the Uppsala area, and that the ability may be transferred between pigs in a stock.     

NMR assignment of a KlbA intein precursor from Methanococcus jannaschii

The backbone and side chain resonance assignments of a precursor of the KlbA intein from Methanococcus jannaschii have been determined, based on triple-resonance experiments with the uniformly [¹³C,¹⁵N]-labeled protein.     

HIV-1 coinfection and morphine coexposure severely dysregulate hepatitis C virus-induced hepatic proinflammatory cytokine release and free radical production: increased pathogenesis coincides with uncoordinated host defenses

Coinfection with human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV) is a global problem that is more prevalent in injection drug users because they have a higher risk for acquiring both viruses. The roles of inflammatory cytokines and oxidative stress were examined in HIV-1- and HCV-coinfected human hepatic cells. Morphine (the bioactive product of heroin), HIV-1 Tat and the MN strain gp120 (gp120(MN)) proteins, and X4 HIV-1(LAI/IIIB) and R5 HIV-1(SF162) isolates were used to study the mechanisms of disease progression in HCV (JFH1)-infected Huh7.5.1 cell populations. HCV increased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release and augmented production of reactive oxygen species (ROS), nitric oxide (NO), and 3-nitrotyrosine (3-NT) in Huh7.5.1 cells. Morphine preferentially affected R5-tropic, but not X4-tropic, HIV-1 interactions with Huh7.5.1 cells. HIV-1 proteins or isolates increased cytokine release in HCV-infected cells, while adding morphine to coinfected cells caused complex imbalances, significantly disrupting cytokine secretion depending on the cytokine, morphine concentration, exposure duration, and particular pathogen involved. Production of ROS, NO, and 3-NT increased significantly in HCV- and HIV-1-coexposed cells while exposure to morphine further increased ROS. The proteasome inhibitor MG132 significantly decreased oxyradicals, cytokine levels, and HCV protein levels. Our findings indicate that hepatic inflammation is increased by combined exposure to HCV and HIV-1, that the ubiquitin-proteasome system and NF-κB contribute to key aspects of the response, and that morphine further exacerbates the disruption of host defenses. The results suggest that opioid abuse and HIV-1 coinfection each further accelerate HCV-mediated liver disease by dysregulating immune defenses.