Cyanamide mode of action during inhibition of onion (Allium cepa L.) root growth involves disturbances in cell division and cytoskeleton formation

Cyanamide is an allelochemical produced by hairy vetch (Vicia villosa Roth.). Its phyotoxic effect on plant growth was examined on roots of onion (Allium cepa L.) bulbs. Water solution of cyanamide (2–10 mM) restricted growth of onion roots in a dose-dependent manner. Treatment of onion roots with cyanamide resulted in a decrease in root growth rate accompanied by a decrease in accumulation of fresh and dry weight. The inhibitory effect of cyanamide was reversed by its removal from the environment, but full recovery was observed only for tissue treated with this chemical at low concentration (2–6 mM). Cytological observations of root tip cells suggest that disturbances in cell division may explain the strong cyanamide allelopathic activity. Moreover, in cyanamide-treated onion the following changes were detected: reduction of mitotic cells, inhibition of proliferation of meristematic cells and cell cycle, and modifications of cytoskeleton arrangement

P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions

Conservation of Forest Birds: Evidence of a Shifting Baseline in Community Structure

Quantifying changes in forest bird diversity is an essential task for developing effective conservation actions. When subtle changes in diversity accumulate over time, annual comparisons may offer an incomplete perspective of changes in diversity. In this case, progressive change, the comparison of changes in diversity from a baseline condition, may offer greater insight because changes in diversity are assessed over longer periods of times. Our objectives were to determine how forest bird diversity has changed over time and whether those changes were associated with forest disturbance.We used North American Breeding Bird Survey data, a time series of Landsat images classified with respect to land cover change, and mixed-effects models to associate changes in forest bird community structure with forest disturbance, latitude, and longitude in the conterminous United States for the years 1985 to 2006. We document a significant divergence from the baseline structure for all birds of similar migratory habit and nest location, and all forest birds as a group from 1985 to 2006. Unexpectedly, decreases in progressive similarity resulted from small changes in richness (<1 species per route for the 22-year study period) and modest losses in abundance (-28.7 - -10.2 individuals per route) that varied by migratory habit and nest location. Forest disturbance increased progressive similarity for Neotropical migrants, permanent residents, ground nesting, and cavity nesting species. We also documented highest progressive similarity in the eastern United States.Contemporary forest bird community structure is changing rapidly over a relatively short period of time (e.g., approximately 22 years). Forest disturbance and forest regeneration are primary factors associated with contemporary forest bird community structure, longitude and latitude are secondary factors, and forest loss is a tertiary factor. Importantly, these findings suggest some regions of the United States may already fall below the habitat amount threshold where fragmentation effects become important predictors of forest bird community structure

P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice

Background: Neuronal accumulation of misfolded microtubule-associated protein tau is a hallmark of neuropathology in Alzheimer’s disease, frontotemporal dementia, and other tauopathies, and has been a therapeutic target. Microglia can spread tau pathology by secreting tau-containing exosomes, although the specific molecular target is yet to be identified for the therapeutic intervention. P2X purinoceptor 7 (P2RX7) is an ATP-gated cation channel, enriched in microglia and triggers exosome secretion. The purpose of the study is to examine the therapeutic effect of an orally applicable, CNS-penetrant P2RX7 specific inhibitor on the early disease stage of a tauopathy mouse model. Methods: Three-months-old P301S tau mice were treated with P2RX7-specific inhibitor GSK1482160 or vehicle for 30 days, followed by behavioral, biochemical and immunohistochemical assessment. GSK1482160 was also tested for exosome secretion from primary cultured murine astrocytes, neurons and microglia in vitro. Results: Oral administration of GSK1482160 significantly reduced accumulation of MC1+ and Alz50+ misfolded tau in hippocampal regions, which was accompanied with reduced accumulation of Tsg101, an exosome marker, in hippocampal neurons. Proximity ligation assay demonstrated complex formation of Alz50+ tau and Tsg101 in hippocampal neurons, which was reduced by GSK1482160. On the other hand, GSK1482160 had no effect on microglial ramification or CD68 expression, which was significantly enhanced in P301S mice, or pro/anti-inflammatory cytokine gene expression. Strikingly, GSK1482160-treated P301S mice show significantly improved working and contextual memory as determined by Y-maze and fear conditioning tests. GSK1482160 also significantly increased accumulation of Tsg101 and CD81 in microglia in vivo, suggesting its suppression of P2RX7-induced exosome secretion from microglia. This effect was confirmed in vitro, as ATP-induced secretion of tau-containing exosome was significantly suppressed by GSK1482160 treatment from primary murine microglia, but not from neurons or astrocytes. Discussion: The oral administration of P2RX7 inhibition mitigates disease phenotypes in P301S mice, likely by suppressing release of microglial exosomes. P2RX7 could be a novel therapeutic target for the early stage tauopathy development

Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters

Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P &lt; 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P &gt; 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P &lt; 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P &gt; 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P &gt; 0.05 for all). Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.Originally included in thesis in manuscript form.</p