Phosphodiesterase activity in neutrophils from horses with chronic obstructive pulmonary disease

Neutrophils are recruited to the lungs of horses with chronic obstructive pulmonary disease (COPD) and exhibit increased activity after antigen challenge. Phosphodiesterase type4 (PDE4) inhibitors have been shown to attenuate human neutrophil activation. The aim of this study was to establish the PDE isoenzyme profile of equine neutrophils using isoenzyme selective inhibitors to determine if these compounds should be evaluated in horses with COPD. Total cAMP and cGMP dependent PDE activity was no different in neutrophils from normal (156.2+/-7.1 and 6.8+/-0.6 pmol/min/mg for cAMP and cGMP, respectively) and COPD susceptible horses (146.0+/-10.2 and 5.5+/-0.6 pmol/min/mg for cAMP and cGMP, respectively). The PDE4 inhibitors, CDP840 and rolipram, caused significant, concentration related and almost complete inhibition of PDE activity (IC(50) values=8.8+/-0.1 x 10(-9) and 7.3+/-0.2 x 10(-9)M for CDP840; 1.2+/-0.1 x 10(-6) and 1.1+/-0.1 x 10(-6)M for rolipram in normal and COPD susceptible horses, respectively). The inhibitory effects of the mixed PDE3/ PDE4 inhibitor, zardaverine were of similar magnitude and potency to rolipram. However, the limited inhibitory effects of the PDE3 inhibitor, siguazodan, suggest that zardaverine is acting primarily via PDE4 inhibition. These results indicate that PDE4 is the predominant isoenzyme present in the equine neutrophil and inhibition of PDE activity using selective PDE4 inhibitors may, therefore, modulate equine neutrophil activation in horses with COPD.     

The effectiveness of a single dose of doramectin pour-on in the control of gastrointestinal nematodes in yearling stocker cattle

Three field studies were conducted to determine the efficacy of a single dose of doramectin pour-on in the control of gastrointestinal nematode infections in yearling stocker calves on pasture. These 140-day studies were carried out between October 1995 and March 1996 in Tennessee (TN), between January and June 1997 in Louisiana (LA), and between May and September 1997 in Wisconsin (WI). Calves with patent nematode infections were equally allocated to treatments (doramectin pour-on, at 500 microg/kg body weight or untreated control) and pastures as randomized complete-block designs (LA and TN studies) or completely at random (WI study). There were six pasture replicates per treatment at each site, with each pasture replicate accommodating six calves at the TN site (36 calves per treatment), five calves at the LA site (30 calves per treatment), and seven calves at the WI site (42 calves per treatment). Fecal samples for nematode egg counts were collected on Day 0, and at 28-day intervals thereafter. Body weights were recorded on Day 0 and at 28-day intervals until study termination. Nematode egg output of the doramectin-treated groups was reduced over the entire grazing period compared to those in the untreated control groups, resulting in average daily weight-gain advantages of 0.055 kg (p < or = 0.05) for the TN study, 0.208 kg (p < or = 0.05) for the LA study, and 0.116 kg (p < or = 0.05) for the WI study.     

Endotoxin and dietary amines may increase plasma 5-hydroxytryptamine in the horse

Uptake of 5-hydroxytryptamine (5-HT) into platelets is an important mechanism by which low plasma concentrations are maintained, and platelet activation may therefore result in significant release of this vasoconstrictor. The present study examined the kinetics of active uptake of radiolabelled [3H]5-HT by washed equine platelets in vitro, and investigated the effects on this process of 4 other naturally occurring monoamines which may be released from the caecum in conditions of carbohydrate overload. The release of [3H]5-HT by platelets was also studied, since platelet accumulation and activation has been associated with acute laminitis. Release of [3H]5-HT was measured in response to platelet activating factor (PAF), unlabelled 5-HT and the indirect activation of platelets by endotoxin in the presence of blood leucocytes. Km value for the uptake of 5-HT by equine platelets was 2.4 +/- 0.6 micromol/l and the Vmax was 8.3 +/- 0.6 pmol [3H]5-HT/10(7) platelets/min. The rate of uptake of 5 micromol/l [3H]5-HT was significantly decreased by the uptake inhibitors fluvoxamine and clomipramine. The 4 other monoamines examined all inhibited the uptake of [3H]5-HT in a noncompetitive manner, decreasing Vmax by between 17 and 82%. Incubation of platelets with LPS (0.1 mg/ml) in the absence of leucocytes did not result in significant release of [3H]5-HT; however, in the presence of leucocytes 3.8 +/- 1.7 pmol [3H]5-HT/10(7) platelets (mean +/- s.e.) were released. This release was significantly inhibited by parthenolide and WEB2086, but not by aspirin. This suggests that PAF from activated leucocytes was responsible for the 5-HT release. These data show that 5-HT uptake by equine platelets is a saturable process operating most efficiently at substrate concentrations in the low micromolar range. The noncompetitive inhibition of 5-HT uptake by other naturally occurring monoamines may result in increased plasma concentrations of 5-HT, as would its release by endotoxin. Such a rise in plasma 5-HT concentrations may contribute to selective vasoconstriction in the equine digital circulation.     

农业科研事业单位人才结构浅析——以湖南省棉花科学研究所为例

分析了湖南省棉花科学研究所2008年与2013年人才状况,对目前人才队伍建设中存在的主要问题以及可能发展的趋势进行了研究,在此基础上提出了一些对策。     

Zinc mediation of the binding of human growth hormone to the human prolactin receptor

Human growth hormone (hGH) elicits a diverse set of biological activities including lactation that derives from binding to the prolactin (PRL) receptor. The binding affinity of hGH for the extracellular binding domain of the hPRL receptor (hPRLbp) was increased about 8000-fold by addition of 50 micromolar ZnCl2. Zinc was not required for binding of hGH to the hGH binding protein (hGHbp) or for binding of hPRL to the hPRLbp. Other divalent metal ions (Ca2+, Mg2+, Cu2+, Mn2+, and Co2+) at physiological concentrations did not support such strong binding. Scatchard analysis indicated a stoichiometry of one Zn2+ per hGH.hPRLbp complex. Mutational analysis showed that a cluster of three residues (His18, His21, and Glu174) in hGH and His188 from the hPRLbp (conserved in all PRL receptors but not GH receptors) are probable Zn2+ ligands. This polypeptide hormone.receptor "zinc sandwich" provides a molecular mechanism to explain why nonprimate GHs are not lactogenic and offers a molecular link between zinc deficiency and its association with altered functions of hGH.     

Paleontology and Chronology of Two Evolutionary Transitions by Hybridization in the Bahamian Land Snail Cerion

The late Quaternary fossil record of the Bahamian land snail Cerion on Great Inagua documents two transitions apparently resulting from hybridization. In the first, a localized modern population represents the hybrid descendants of a 13,000-year-old fossil form from the same area, introgressed with the modern form now characteristic of the adjacent regions. In the second case, a chronocline spanning 15,000 to 20,000 years and expressing the transition of an extinct fossil form to the modern form found on the south coast was documented by morphometry of fossils dated by amino acid racemization and radiocarbon. Hybrid intermediates persisted for many thousands of years.     

Coiled-coil irregularities and instabilities in group A Streptococcus M1 are required for virulence

Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the approximately 3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.     

Enhanced motility in NIH 3T3 fibroblasts that overexpress gelsolin.

Increasing the content of the actin-binding protein gelsolin in cultured mouse fibroblasts by up to 125 percent by gene transfection proportionally enhanced the rate at which the cells migrated through porous filters toward a gradient of serum and closed a wound made on a confluent monolayer of cells in a tissue culture dish. These results provide direct evidence that gelsolin, which promotes both actin assembly and disassembly in vitro, is an important element in fibroblast locomotion and demonstrate that the manipulation of intracellular machinery can increase cell motility.     

Biological feedbacks in global desertification

Studies of ecosystem processes on the Jornada Experimental Range in southern New Mexico suggest that longterm grazing of semiarid grasslands leads to an increase in the spatial and temporal heterogeneity of water, nitrogen, and other soil resources. Heterogeneity of soil resources promotes invasion by desert shrubs, which leads to a further localization of soil resources under shrub canopies. In the barren area between shrubs, soil fertility is lost by erosion and gaseous emissions. This positive feedback leads to the desertification of formerly productive land in southern New Mexico and in other regions, such as the Sahel. Future desertification is likely to be exacerbated by global climate warming and to cause significant changes in global biogeochemical cycles.