Expressed sequence tag analysis of Eimeria-stimulated intestinal intraepithelial lymphocytes in chickens

Intraepithelial lymphocytes (IELs) play a critical role in protective immune response to intestinal pathogens such as Eimeria, the etiologic agent of avian coccidiosis. A list of genes expressed by intestinal IELs of Eimeria-infected chickens was compiled using the expressed sequence tag (EST) strategy. The 14,409 ESTs consisted of 1851 clusters and 7595 singletons, which revealed 9446 unique genes in the data set. Comparison of the sequence data with chicken DNA sequences in GenBank identified 125 novel clones. This EST library will provide a valuable resource for profiling global gene expression in normal and pathogen-infected chickens and identifying additional unique immune-related genes.     

A small group of sulfated benzofurans induces steady-state submaximal inhibition of thrombin

Despite the development of promising direct oral anticoagulants, which are all orthosteric inhibitors, a sizable number of patients suffer from bleeding complications. We have hypothesized that allosterism based on the heparin-binding exosites presents a major opportunity to induce sub-maximal inhibition of coagulation proteases, thereby avoiding/reducing bleeding risk. We present the design of a group of sulfated benzofuran dimers that display heparin-binding site-dependent partial allosteric inhibition of thrombin against fibrinogen (ΔY?=?55–75%), the first time that a small molecule (MW??<?800) has been found to thwart macromolecular cleavage by a monomeric protease in a controlled manner. The work leads to the promising concept that it should be possible to develop allosteric inhibitors that reduce clotting, but do not completely eliminate it, thereby avoiding major bleeding complications that beset anticoagulants today.     

The association between cardiovascular disease gene mutations and recurrent pregnancy loss in the Lebanese population

Molecular Biology Reports - Recurrent pregnancy loss (RPL) is a problem affecting up to 5% of women of childbearing age due to many factors. Studies have shown that RPL and cardiovascular disease...     

Effect of mannose-binding lectin from peanut and pea on the stem borer Chilo partellus

A mannose-binding lectin found in vegetative tissues of peanut, Arachis hypogaea, was compared with mannose-binding lectin from pea, Pisum sativum, for toxic effects on larvae of the stem borer Chilo partellus (Swinhoe). After 10 days, the mortality of larvae fed on artificial diet containing 0.5% (m/m) peanut lectin was 46.2%. The mortality of larvae fed on 1.0% peanut lectin was similar (48.1%) but insects were significantly smaller than those of the 0.5% treatment. Larvae of both lectin treatments stopped feeding within three days. Larval size and mortality was not significantly reduced by 0.1% peanut lectin and 1% heat-treated lectin did not show toxic effects. The mannose-binding lectin from pea was not toxic to C. partellus at concentrations up to 1%. Peanut lectin bound to the apical membranes of columnar epithelial cells in the mid-gut of C. partellus. This suggests that peanut lectin has an antinutritive action and that it may protect vegetative tissues of peanut against insect pests.     

Role of sensory input from the lungs in control of muscle sympathetic nerve activity during and after apnea in humans.

We reasoned that, if the lung inflation reflex contributes importantly to apnea-induced sympathetic activation, such activation would be attenuated in bilateral lung transplant recipients (LTX). We measured muscle sympathetic nerve activity (MSNA; intraneural electrodes), heart rate, mean arterial pressure, tidal volume, end-tidal Pco(2), and arterial oxygen saturation in seven LTX and seven healthy control subjects (Con) before, during, and after 20-s end-expiratory breath holds. Our evidence for denervation in LTX was 1) greatly attenuated respiratory sinus arrhythmia and 2) absence of cough reflex below the level of the carina. During apnea, the temporal pattern and the peak increase in MSNA were virtually identical in LTX and Con (347 +/- 99 and 359 +/- 46% of baseline, respectively; P > 0.05). In contrast, the amount of MSNA present in the first 5 s after resumption of breathing was greater in LTX vs. Con (101 +/- 4 vs. 38 +/- 7% of baseline, respectively; P < 0.05). There were no between-group differences in apnea-induced hypoxemia or hypercapnia, hemodynamic, or ventilatory responses. Thus cessation of the rhythmic sympathoinhibitory feedback that normally accompanies eupneic breathing does not contribute importantly to sympathetic excitation during apnea. In contrast, vagal afferent input elicited by hyperventilation-induced lung stretch plays an important role in the profound, rapid sympathetic inhibition that occurs after resumption of breathing after apnea.     

Insecticides with novel modes of action: Mechanism, selectivity and cross-resistance

Efforts have been made during the past two decades to develop insecticides with selective properties that act specifically on biochemical sites present in particular insect groups, but whose properties differ from other insecticides. This approach has led to the discovery of compounds that affect the hormonal regulation of molting and developmental processes in insects; for example, ecdysone agonists, juvenile hormone mimics and chitin synthesis inhibitors. In addition, compounds that selectively interact with the insect nicotinic acetylcholine receptor, such as imidacloprid, acetamiprid and thiamethoxam, have been introduced for the control of aphids, whiteflies and other insect species. Natural products acting selectively on insect pests, such as avermectins, spinosad and azadirachtin, have been introduced for controlling selected groups of insect pests. Compounds acting on the nervous site that controls the sucking pump of aphids and whiteflies, such as pymetrozine, or respiration, such as diafenthiuron, have been introduced for controlling sucking pests. All the above compounds are important components in pest and resistance management programs.     

Angiotensin II stimulates the production of NO and peroxynitrite in endothelial cells

Angiotensin II(ANG II) produces vasoconstriction by a direct action on smooth musclecells via AT₁ receptors. Thesereceptors are also present in the endothelium, but their function ispoorly understood. This study was therefore undertaken to determinewhether ANG II elicits the release of nitric oxide (NO) from cultured rat aortic endothelial cells. NO production, measured by theaccumulation of nitrite and nitrate, was enhanced by10⁷ M ANG II. Thebiological activity of the NO released by ANG II action was evaluatedby measuring its guanylate cyclase-stimulating activity in smoothmuscle cells. The guanosine 3',5'-cyclic monophosphate (cGMP) content of smooth muscle cells was significantly increased byexposure of supernatant from ANG II-stimulated endothelial cells. Theseeffects resulted from the activation of NO synthase, as they wereinhibited by the L-arginineanalogs. These ANG II actions were mediated by theAT₁ receptor, as shown by theirinhibition by the AT₁ antagonistlosartan. The cGMP production by reporter cells was inhibited by thecalmodulin antagonist W-7, suggesting that ANG II activates endothelialcalmodulin-dependent NO synthase. This hypothesis is also supported bythe increase of intracellular free calcium induced by ANG II inendothelial cells. ANG II also stimulated luminol-enhancedchemiluminescence in endothelial cells. This effect was inhibited byN-monomethyl-L-arginine andsuperoxide dismutase, suggesting that this luminol-enhancedchemiluminescence reflected an increase in peroxynitrite production.Thus ANG II stimulates NO release from macrovascular endothelium, whichmay modulate the direct vasoconstrictor effect of ANG II on smoothmuscle cells. However, this beneficial effect may be counteracted bythe simultaneous production of peroxynitrite, which could contribute toseveral pathological processes in the vascular wall.

     

A study of extracellular matrix-cell adhesion peptidic epitopes related to human serum amyloid A (SAA)

Summary Serum amyloid A (SAA), an acute-phase protein, exists normally in the serum while complexed with high-density lipoprotein 3 (SAA-HDL₃). Its levels increase markedly during inflammatory diseases. The pentapeptide Tyr-Ile-Gly-Ser-Asp (YIGSR-like) and the tripeptide Arg-Gly-Asn (RGD-like), related to the cell adhesion domains of laminin and fibronectin, respectively, exist in SAA within close proximity (YIGSDKYFHARGNY; amino acid residues 29–42). A structure-function study of linear and head-to-tail cyclic peptides, related to the amino acid residues 29–42) and 70–76 (GRGAEDS) of human SAA, was performed in order to evaluate their ability to inhibit adhesion of human T-lymphocytes to surfaces coated with extracellular matrix purified from bovine corneal cells.