The effects of wildfire severity and pyrodiversity on bat occupancy and diversity in fire-suppressed forests.

Wildfire is an important ecological process that influences species' occurrence and biodiversity generally. Its effect on bats is understudied, creating challenges for habitat management and species conservation as threats to the taxa worsen globally and within fire-prone ecosystems. We conducted acoustic surveys of wildfire areas during 2014-2017 in conifer forests of California's Sierra Nevada Mountains. We tested effects of burn severity and its variation, or pyrodiversity, on occupancy and diversity for the 17-species bat community while accounting for imperfect detection. Occupancy rates increased with severity for at least 6 species and with pyrodiversity for at least 3. Two other species responded negatively to pyrodiversity. Individual species models predicted maximum occupancy rates across burn severity levels but only one species occurred most often in undisturbed areas. Species richness increased from approximately 8 species in unburned forests to 11 in pyrodiverse areas with moderate- to high-severity. Greater accessibility of foraging habitats, as well as increased habitat heterogeneity may explain positive responses to wildfire. Many bat species appear well adapted to wildfire, while a century of fire suppression and forest densification likely reduced habitat quality for the community generally. Relative to other taxa, bats may be somewhat resilient to increases in fire severity and size; trends which are expected to continue with accelerating climate change.

Cross talk of pp125(FAK) and pp59(Lyn) non-receptor tyrosine kinases to insulin-mimetic signaling in adipocytes.

Signaling molecules downstream from the insulin receptor, such as the insulin receptor substrate protein 1 (IRS-1), are also activated by other receptor tyrosine kinases. Here we demonstrate that the non-receptor tyrosine kinases, focal adhesion kinase pp125(FAK) and Src-class kinase pp59(Lyn), after insulin-independent activation by phosphoinositolglycans (PIG), can cross talk to metabolic insulin signaling in rat and 3T3-L1 adipocytes. Introduction by electroporation of neutralizing antibodies against pp59(Lyn) and pp125(FAK) into isolated rat adipocytes blocked IRS-1 tyrosine phosphorylation in response to PIG but not insulin. Introduction of peptides encompassing either the major autophosphorylation site of pp125(FAK), tyrosine 397, or its regulatory loop with the twin tyrosines 576 and 577 inhibited PIG-induced IRS-1 tyrosine phosphorylation and glucose transport. PIG-induced pp59(Lyn) kinase activation and pp125(FAK) tyrosine phosphorylation were impaired by the former and latter peptide, respectively. Up-regulation of pp125(FAK) by integrin clustering diminished PIG-induced IRS-1 tyrosine phosphorylation and glucose transport in nonadherent but not adherent adipocytes. In conclusion, PIG induced IRS-1 tyrosine phosphorylation by causing (integrin antagonized) recruitment of IRS-1 and pp59(Lyn) to the common signaling platform molecule pp125(FAK), where cross talk of PIG-like structures and extracellular matrix proteins to metabolic insulin signaling may converge, possibly for the integration of the demands of glucose metabolism and cell architecture.

Redistribution of glycolipid raft domain components induces insulin-mimetic signaling in rat adipocytes.

Caveolae and caveolin-containing detergent-insoluble glycolipid-enriched rafts (DIG) have been implicated to function as plasma membrane microcompartments or domains for the preassembly of signaling complexes, keeping them in the basal inactive state. So far, only limited in vivo evidence is available for the regulation of the interaction between caveolae-DIG and signaling components in response to extracellular stimuli. Here, we demonstrate that in isolated rat adipocytes, synthetic intracellular caveolin binding domain (CBD) peptide derived from caveolin-associated pp59(Lyn) (10 to 100 microM) or exogenous phosphoinositolglycan derived from glycosyl-phosphatidylinositol (GPI) membrane protein anchor (PIG; 1 to 10 microM) triggers the concentration-dependent release of caveolar components and the GPI-anchored protein Gce1, as well as the nonreceptor tyrosine kinases pp59(Lyn) and pp125(Fak), from interaction with caveolin (up to 45 to 85%). This dissociation, which parallels redistribution of the components from DIG to non-DIG areas of the adipocyte plasma membrane (up to 30 to 75%), is accompanied by tyrosine phosphorylation and activation of pp59(Lyn) and pp125(Fak) (up to 8- and 11-fold) but not of the insulin receptor. This correlates well to increased tyrosine phosphorylation of caveolin and the insulin receptor substrate protein 1 (up to 6- and 15-fold), as well as elevated phosphatidylinositol-3' kinase activity and glucose transport (to up to 7- and 13-fold). Insulin-mimetic signaling by both CBD peptide and PIG as well as redistribution induced by CBD peptide, but not by PIG, was blocked by synthetic intracellular caveolin scaffolding domain (CSD) peptide. These data suggest that in adipocytes a subset of signaling components is concentrated at caveolae-DIG via the interaction between their CBD and the CSD of caveolin. These inhibitory interactions are relieved by PIG. Thus, caveolae-DIG may operate as signalosomes for insulin-independent positive cross talk to metabolic insulin signaling downstream of the insulin receptor based on redistribution and accompanying activation of nonreceptor tyrosine kinases.

Structure-activity relationships of dopaminergic 5-hydroxy-2-aminotetralin derivatives with functionalized N-alkyl substituents.

5-Hydroxy-2-aminotetralin derivatives in which one N-alkyl substituent carries a functional group have been prepared and their dopaminergic activities compared with those of 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) and known ergolines. Several members of the series demonstrated high affinities in dopamine (DA) receptor binding and DA agonist properties in the rotational behavior model in the range of known potent ergolines. The results suggest that the accessory binding site for the larger N-alkyl substituent of the 5-hydroxy-2-aminotetralins can accommodate various neutral and bulky functionalities and is probably identical with the site(s) to which the 8-substituents of the ergolines bind.

Interaction of ergot alkaloids and their combination (co-dergocrine) with alpha-adrenoceptors in the CNS.

Co-dergocrine (Hydergine), composed of four dihydrogenated peptide ergot alkaloids (dihydroergocornine, dihydroergocristine, dihydro-alpha-ergokryptine and dihydro-beta-ergokryptine), has been reported to interact with alpha-adrenoceptors. The effect of the combination and its individual components on alpha-adrenoceptors subtypes in the rat brain was investigated in the present study. All five ergot drugs displaced [3H]rauwolscine, [3H]clonidine and [3H]WB 4101 from specific binding sites in membrane preparations from rat and bovine brain at nanomolar concentrations. In rat cerebral occipital cortex slices, the ergot drugs inhibited 1-noradrenaline-stimulated cyclic AMP formation (alpha 1-adrenoceptor test) and facilitated electrically evoked noradrenaline release (alpha 2-adrenoceptor test) at nanomolar concentrations. The results from the functional tests suggest that the ergot drugs have a slightly higher affinity to alpha 2-adrenoceptors which are antagonised in a competitive manner. The alpha 1-adrenoceptors are antagonised by the ergot drugs in a non-competitive manner. The relative order of potency at both receptor types was similar in that dihydroergocornine, dihydro-alpha-ergokryptine and dihydro-beta-ergokryptine were equipotent, whereas dihydroergocristine was less potent. The effect of the combination of the ergot alkaloids at both alpha-adrenoceptors appears to reflect the summation of the contributions of its components. The differences seen in the functional tests were less pronounced in the binding tests.

Acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reduces dopamine and serotonin but accelerates norepinephrine metabolism in the rat brain. Effect of chronic pretreatment with MPTP.

Acute administration of MPTP (a synthetic heroin substitute) at 10-30 mg/kg (s.c.) produced 'Straub tail' phenomena, piloerection and reduced pelvis elevation in rats. The same dose decreased the concentrations of dopamine metabolites and reduced the rate of dopamine synthesis in the striatum. MPTP also reduced the metabolism of serotonin but accelerated that of norepinephrine in their corresponding terminal areas. The effects on central monoamines probably were not due to an agonistic action of MPTP on dopaminergic and serotonergic receptors, since MPTP only exhibited micromolar affinity to the corresponding binding sites. Furthermore, MPTP failed to induce rotational behavior in animals with unilateral nigrostriatal lesions. Chronic treatment of rats with MPTP (10 mg/kg s.c., daily for 3 weeks) did not result in massive degenerative changes in the nigrostriatal system. Histochemical analysis showed intact dopaminergic neurons. Striatal dopamine levels only were reduced by 10%. Dopaminergic neurons in rats chronically treated with MPTP responded normally to a pharmacological stimulus increasing their transmitter synthesis. Chronic treatment did not affect their response to an acute injection of MPTP.

Muscarinic receptors on intact, cultured neurons. Characterization by [3H]quinuclidinylbenzilate binding.

[3H]Quinuclidinylbenzilate (QNB) was used to identify muscarinic cholinergic receptors on intact, cultured neurons from fetal rat brains. Scatchard analysis revealed a single binding site with a dissociation constant Kd = approximately or equal to 170 pM. The rank order of potency of cholinergic drugs to displace [3H]QNB from intact neurons was similar to that observed using isolated membranes of brain homogenates. No difference in the rank order was observed with cultures of neurons from different brain regions which vary in their neuronal composition.

Classification of drugs according to receptor binding profiles.

The affinity for eight different neurotransmitter receptors of about forty drugs, used for the treatment of various central nervous system disorders, was determined following in vitro receptor binding assays. Our findings indicate that, in spite of widely varying chemical structures and often poorly understood mechanisms of action, the similarities in the "affinity profiles" permit a clinically meaningful classification of these drugs. Such an approach would thus be useful in the assessment of newly synthesized compounds at an early stage of drug development.

Respiratory infections: their role in airway responsiveness and pathogenesis of asthma.

A clear relationship between viral upper respiratory infections and exacerbations of asthma has been established in numerous clinical studies. However, a unifying concept to explain how respiratory viruses bring about these changes has not been established unless it is the ability of viral illnesses to promote the inflammatory process. These changes in inflammation potentially encompass several organ systems: airway epithelium, the autonomic nervous system, and immediate hypersensitivity reactions. Thus, enhanced airway reactivity in viral respiratory infections represents a complex orchestration of many factors and functions to create the end result of bronchial hyperresponsiveness. Insight into precisely how the respiratory virus initiates these changes should provide valuable and new information into the pathogenesis of asthma. Therefore, not only is virus-induced asthma an important clinical problem, but it may also serve as a window to mechanisms of airway hyperreactivity and asthma.

Pharmacological profile of the abeorphine 201-678, a potent orally active and long lasting dopamine agonist.

The central dopaminergic effects of an abeorphine derivative 201-678 were compared to those of apomorphine and bromocriptine in different model systems. After oral administration, this compound induced contralateral turning in rats with 6-hydroxydopamine induced nigral lesions and exhibited strong anti-akinetic properties in rats with 6-hydroxydopamine induced hypothalamic lesions. It decreased dopamine metabolism in striatum and cortex, but did not modify noradrenaline and serotonin metabolism in the rat brain. 201-678 counteracted the in vivo increase of tyrosine hydroxylase activity induced by gamma-butyrolactone. In vitro it stimulated DA-sensitive adenylate cyclase and inhibited acetylcholine release from rat striatal slices. This compound had high affinity for 3H-dopamine and 3H-clonidine binding sites. These results indicate that 201-678 is a potent, orally active dopamine agonist with a long duration of action. Furthermore it appears more selective than other dopaminergic drugs.

The structure of bergenin.

X-ray analysis of the 3,4,8,10,11-penta-acetate (3) of bergenin has confirmed the earlier structural assignments.

Reconstructive preprosthetic surgery.

The overall health of an edentulous patient may be significantly affected when added to the multiple medical and psychiatric problems common to the elderly. A patient who has a significant oral prosthetic problem may be helped with current reconstructive preprosthetic surgical techniques.

Proliferation of myocytes on different ECM-components of animal/human origin in vitro.

For the purpose of tissue regeneration gels of reconstituted basement membrane have been suggested as a vehicle to transfer autologous cells. Results do look promising, but it should be considered that extracellular matrix (ECM) gel (Matrigel) is a soluble extract of Engelbreth-Holm-Swarm (EHS) mouse tumor. Therefore objections arising concerning possible risks complicate clinical use in human subjects. Aim of this study was to determine whether ECM-components of human origin can be used as substitutes for tissue engineering tasks as proposed previously. Proliferation capability and viability of primary rat myocytes and rat myocyte cell lines were determined on days 1, 2, 4 and 8 after inocculation of the cells. Pooled data suggest that an appropriate combination of human ECM and human Collagen Type IV may represent an approach with good prospects.

Smoking and wound healing: a review.

It is now generally accepted that smoking impairs wound healing. This article briefly reviews wound healing and a number of local and systemic responses to smoking which may have deleterious effects on wound healing. It is important that dentists fully understand the deleterious effects of smoking on wound healing and that they fully explain to their patients who smoke the compromised tissue response and surgical results that can be anticipated.

Transfer of the glycosylphosphatidylinositol-anchored 5'-nucleotidase CD73 from adiposomes into rat adipocytes stimulates lipid synthesis.

BACKGROUND AND PURPOSE: In addition to predominant localization at detergent-insoluble, glycolipid-enriched plasma membrane microdomains (DIGs), glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-proteins) have been found associated with lipid droplets (LDs) and adiposomes. Adiposomes are vesicles that are released from adipocytes in response to anti-lipolytic and lipogenic signals, such as H(2)O(2), palmitate and the antidiabetic sulfonylurea drug, glimepiride, and harbour (c)AMP-degrading GPI-proteins, among them the 5-nucleotidase CD73. Here the role of adiposomes in GPI-protein-mediated information transfer was studied. EXPERIMENTAL APPROACH: Adiposomes were incubated with isolated rat adipocytes under various conditions. Trafficking of CD73 and lipid synthesis were analysed. KEY RESULTS: Upon blockade of GPI-protein trafficking, CD73 specifically associated with DIGs of small, and to a lower degree, large, adipocytes. On reversal of the blockade, CD73 appeared at cytosolic LD in time- adiposome concentration- and signal (H(2)O(2) > glimepiride > palmitate)-dependent fashion. The salt- and carbonate-resistant association of CD73 with structurally intact DIGs and LD was dependent on its intact GPI anchor. Upon incubation with small and to a lower degree, large adipocytes, adiposomes increased lipid synthesis in the absence or presence of H(2)O(2), glimepiride and palmitate and improved the sensitivity toward these signals. Upregulation of lipid synthesis by adiposomes was dependent on the translocation of CD73 with intact GPI anchors from DIGs to LD. CONCLUSIONS: The signal-induced transfer of GPI-anchored CD73 from adiposomes via DIGs to LD of adipocytes mediates paracrine upregulation of lipid synthesis within the adipose tissue.

Determination of cholecystokinin tetrapeptide and cholecystokinin octapeptide sulfate in different rat brain regions by high-pressure liquid chromatography with electrochemical detection.

A method for the determination of cholecystokinins in biological material, based on high-pressure liquid chromatography with direct electrochemical detection (HPLC-EC), is described. Using this method, the levels of cholecystokinin tetrapeptide and octapeptide sulfate in rat brain cortex, hippocampus, striatum, and brain stem were measured and found to be comparable to those reported using radioimmunoassay methods. We show that HPLC-EC is sensitive enough to accurately determine neuropeptides in brain tissue without prior derivatization and is therefore, due to its simplicity, an attractive alternative to existing methods.

Signalling via caveolin: involvement in the cross-talk between phosphoinositolglycans and insulin.

In recent years, a number of cross-talk systems have been identified which feed into the insulin signalling cascade at the level of insulin receptor substrate (IRS) tyrosine phosphorylation, e.g., receptor and non-receptor tyrosine kinases and G-protein-coupled receptors. At the molecular level, a number of negative modulator and feedback systems somehow interacting with the beta-subunit (catecholamine-, phorbolester-, or tumor necrosis factor-alpha-induced serine/threonine phosphorylation, carboxy-terminal trimming by a thiol-dependent protease, association of inhibitory/regulatory proteins such as RAD, PC1, PED, alpha2-HS-glycoprotein) have been identified as candidate mechanisms for the impairment of insulin receptor function by elevations in the activity and/or amount of the corresponding modification enzymes/inhibitors. Both decreased responsiveness and sensitivity of the insulin receptor beta-subunit for insulin-induced tyrosine autophosphorylation have been demonstrated in several cellular and animal models of metabolic insulin resistance as well as in the adipose tissue and skeletal muscle of diabetic patients and obese Pima Indians compared to non-obese subjects. Therefore, induction of the insulin signalling cascade by bypassing the defective insulin receptor kinase may be useful for the therapy of non-insulin dependent diabetes mellitus. During the past two decades, phosphoinositolglycans (PIGs) of various origin have been demonstrated to exert potent insulin-mimetic metabolic effects upon incubation with cultured or isolated muscle and adipose cells. However, it remained to be elucidated whether these compounds actually manage to trigger insulin signalling and if so at which level of hierarchy within the signalling cascade the site of interference is located. Recent studies using isolated rat adipocytes and chemically synthesized PIG compounds point to IRS1/3 tyrosine phosphorylation by p59Lyn kinase as the site of cross-talk, the negative regulation of which by interaction with caveolin is apparently abrogated by PIG. This putative mechanism is thus compatible with the recently formulated caveolin signalling hypothesis, the supporting data for which are reviewed here. Though we have not obtained experimental evidence for the involvement of PIG in physiological insulin action, the potential cross-talk between insulin and PIG signalling, including the caveolae/detergent-insoluble glycolipid-enriched rafts as the compartments where the corresponding signalling components are concentrated, thus represent novel targets for signal transduction therapy.