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1.
Microb Ecol ; 85(2): 659-668, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35102425

ABSTRACT

Variation in microbial use of soil carbon compounds is a major driver of biogeochemical processes and microbial community composition. Available carbon substrates in soil include both low molecular weight-dissolved organic carbon (LMW-DOC) and volatile organic compounds (VOCs). To compare the effects of LMW-DOC and VOCs on soil chemistry and microbial communities under different moisture regimes, we performed a microcosm experiment with five levels of soil water content (ranging from 25 to 70% water-holding capacity) and five levels of carbon amendment: a no carbon control, two dissolved compounds (glucose and oxalate), and two volatile compounds (methanol and α-pinene). Microbial activity was measured throughout as soil respiration; at the end of the experiment, we measured extractable soil organic carbon and total extractable nitrogen and characterized prokaryotic communities using amplicon sequencing. All C amendments increased microbial activity, and all except oxalate decreased total extractable nitrogen. Likewise, individual phyla responded to specific C amendments-e.g., Proteobacteria increased under addition of glucose, and both VOCs. Further, we observed an interaction between moisture and C amendment, where both VOC treatments had higher microbial activity than LMW-DOC treatments and controls at low moisture. Across moisture and C treatments, we identified that Chloroflexi, Nitrospirae, Proteobacteria, and Verrucomicrobia were strong predictors of microbial activity, while Actinobacteria, Bacteroidetes, and Thaumarcheota strongly predicted soil extractable nitrogen. These results indicate that the type of labile C source available to soil prokaryotes can influence both microbial diversity and ecosystem function and that VOCs may drive microbial functions and composition under low moisture conditions.


Subject(s)
Microbiota , Soil , Soil/chemistry , Dissolved Organic Matter , Nitrogen/analysis , Carbon , Soil Microbiology , Bacteria , Proteobacteria , Water
2.
Ecology ; 102(12): e03553, 2021 12.
Article in English | MEDLINE | ID: mdl-34622940

ABSTRACT

Despite ever-increasing availability of detailed information about microbial community structure, relationships of microbial diversity with ecosystem functioning remain unclear. We investigated these relationships at the Coweeta Hydrologic Laboratory, where past forest disturbances (e.g., clear-cut) have altered both ecosystem processes (e.g., increased N export) and microbial communities (e.g., increased bacterial diversity). We sampled soils from disturbed and adjacent reference forests, characterized resident microbial communities, and measured several microbial C-cycle and N-cycle process rates. Microbial communities from historically disturbed soils exhibited altered ecosystem functioning, including generally higher rates of C- and N-cycle processes. Disturbed soil microbial communities also exhibited altered ecosystem multifunctionality, a composite variable consisting of all measured process rates as well as extracellular enzyme activities. Although we found few relationships between ecosystem functions and microbial alpha diversity, all functions were correlated with microbial community composition metrics, particularly r:K strategist ratios of bacterial phyla. Additionally, for both ecosystem multifunctionality and specific processes (i.e., C- and N-mineralization), microbial metrics significantly improved models seeking to explain variation in process rates. Our work sheds light on the links between microbial communities and ecosystem functioning and identifies specific microbial metrics important for modeling ecosystem responses to environmental change.


Subject(s)
Microbiota , Soil Microbiology , Forests , Nitrogen/analysis , Soil
3.
Environ Microbiol ; 23(11): 6405-6419, 2021 11.
Article in English | MEDLINE | ID: mdl-34347364

ABSTRACT

Despite the abundance of studies demonstrating the effects of drought on soil microbial communities, the role of land use legacies in mediating these drought effects is unclear. To assess historical land use influences on microbial drought responses, we conducted a drought-rewetting experiment in soils from two adjacent and currently forested watersheds with distinct land use histories: an undisturbed 'reference' site and a 'disturbed' site that was clear-cut and converted to agriculture ~60 years prior. We incubated intact soil cores at either constant moisture or under a drought-rewet treatment and characterized bacterial and fungal communities using amplicon sequencing throughout the experiment. Bacterial alpha diversity decreased following drought-rewetting while fungal diversity increased. Bacterial beta diversity also changed markedly following drought-rewetting, especially in historically disturbed soils, while fungal beta diversity exhibited little response. Additionally, bacterial beta diversity in disturbed soils recovered less from drought-rewetting compared with reference soils. Disturbed soil communities also exhibited notable reductions in nitrifying taxa, increases in putative r-selected bacteria, and reductions in network connectivity following drought-rewetting. Overall, our study reveals historical land use to be important in mediating responses of soil bacterial communities to drought, which will influence the ecosystem-scale trajectories of these environments under ongoing and future climate change.


Subject(s)
Microbiota , Soil , Droughts , Forests , Microbiota/genetics , Soil Microbiology
4.
ISME Commun ; 1(1): 48, 2021 Sep 10.
Article in English | MEDLINE | ID: mdl-37938278

ABSTRACT

Land use change has long-term effects on the structure of soil microbial communities, but the specific community assembly processes underlying these effects have not been identified. To investigate effects of historical land use on microbial community assembly, we sampled soils from several currently forested watersheds representing different historical land management regimes (e.g., undisturbed reference, logged, converted to agriculture). We characterized bacterial and fungal communities using amplicon sequencing and used a null model approach to quantify the relative importance of selection, dispersal, and drift processes on bacterial and fungal community assembly. We found that bacterial communities were structured by both selection and neutral (i.e., dispersal and drift) processes, while fungal communities were structured primarily by neutral processes. For both bacterial and fungal communities, selection was more important in historically disturbed soils compared with adjacent undisturbed sites, while dispersal processes were more important in undisturbed soils. Variation partitioning identified the drivers of selection to be changes in vegetation communities and soil properties (i.e., soil N availability) that occur following forest disturbance. Overall, this study casts new light on the effects of historical land use on soil microbial communities by identifying specific environmental factors that drive changes in community assembly.

5.
Front Microbiol ; 10: 2872, 2019.
Article in English | MEDLINE | ID: mdl-31921050

ABSTRACT

In Appalachian ecosystems, forest disturbance has long-term effects on microbially driven biogeochemical processes such as nitrogen (N) cycling. However, little is known regarding long-term responses of forest soil microbial communities to disturbance in the region. We used 16S and ITS sequencing to characterize soil bacterial (16S) and fungal (ITS) communities across forested watersheds with a range of past disturbance regimes and adjacent reference forests at the Coweeta Hydrologic Laboratory in the Appalachian mountains of North Carolina. Bacterial communities in previously disturbed forests exhibited consistent responses, including increased alpha diversity and increased abundance of copiotrophic (e.g., Proteobacteria) and N-cycling (e.g., Nitrospirae) bacterial phyla. Fungal community composition also showed disturbance effects, particularly in mycorrhizal taxa. However, disturbance did not affect fungal alpha diversity, and disturbance effects were not consistent at the fungal class level. Co-occurrence networks constructed for bacteria and fungi showed that disturbed communities were characterized by more connected and tightly clustered network topologies, indicating that disturbance alters not only community composition but also potential ecological interactions among taxa. Although bacteria and fungi displayed different long-term responses to forest disturbance, our results demonstrate clear responses of important bacterial and fungal functional groups (e.g., nitrifying bacteria and mycorrhizal fungi), and suggest that both microbial groups play key roles in the long-term alterations to biogeochemical processes observed following forest disturbance in the region.

6.
Ecology ; 99(2): 312-321, 2018 02.
Article in English | MEDLINE | ID: mdl-29315515

ABSTRACT

Long-term observations of ecological communities are necessary for generating and testing predictions of ecosystem responses to climate change. We investigated temporal trends and spatial patterns of soil fauna along similar environmental gradients in three sites of the McMurdo Dry Valleys, Antarctica, spanning two distinct climatic phases: a decadal cooling trend from the early 1990s through the austral summer of February 2001, followed by a shift to the current trend of warming summers and more frequent discrete warming events. After February 2001, we observed a decline in the dominant species (the nematode Scottnema lindsayae) and increased abundance and expanded distribution of less common taxa (rotifers, tardigrades, and other nematode species). Such diverging responses have resulted in slightly greater evenness and spatial homogeneity of taxa. However, total abundance of soil fauna appears to be declining, as positive trends of the less common species so far have not compensated for the declining numbers of the dominant species. Interannual variation in the proportion of juveniles in the dominant species was consistent across sites, whereas trends in abundance varied more. Structural equation modeling supports the hypothesis that the observed biological trends arose from dissimilar responses by dominant and less common species to pulses of water availability resulting from enhanced ice melt. No direct effects of mean summer temperature were found, but there is evidence of indirect effects via its weak but significant positive relationship with soil moisture. Our findings show that combining an understanding of species responses to environmental change with long-term observations in the field can provide a context for validating and refining predictions of ecological trends in the abundance and diversity of soil fauna.


Subject(s)
Climate Change , Soil/chemistry , Animals , Antarctic Regions , Ecosystem , Soil Microbiology
7.
Environ Geochem Health ; 37(4): 675-87, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26173774

ABSTRACT

Whilst vehicular and industrial contributions to the airborne particulate budget are well explored, the input due to building demolition is relatively unknown. Air quality is of importance to human health, and it is well known that composition of airborne particles can have a significant influence on both chronic and acute health effects. Road dust (RD) was collected before and after the demolition of a large building to elucidate changes in elemental profile. Rainfall and PM10 mass concentration data aided interpretation of the elemental data. Quantification of Al, As, Ba, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Rh, S, Si, Sn, Ti, V and Zn was carried out. It was found that only Al, K, Mg, Si and S increased in concentration across all size fractions after the building demolition. Risk assessment was then carried out on elements with applicable reference dose values to assess the potential health risks due to the demolition. Significant risk to children was observed for chromium and aluminium exposure. PM10, monitored 40 metres from the demolition site, indicated no abnormal concentrations during the demolition; however, rainfall data were shown to affect the concentration of PM10. The elemental data observed in this study could possibly indicate the role of increased sulphur concentrations (in this case as a result of the demolition) on the buffer capacity of RD, hence leaching metals into rainwater.


Subject(s)
Construction Materials/analysis , Dust/analysis , Environmental Exposure/analysis , Environmental Pollutants/analysis , Metals/analysis , Particulate Matter/analysis , Child , Environmental Monitoring/methods , Environmental Pollutants/toxicity , Humans , Metals/toxicity , Particle Size , Rain , Risk Assessment , United Kingdom
8.
Br J Pharmacol ; 172(12): 2991-3002, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25651822

ABSTRACT

BACKGROUND AND PURPOSE: Store-operated calcium (SOC) channels are thought to play a critical role in immune responses, inflammatory diseases and chronic pain. The aim of this study was to explore the potential role and mechanisms of SOC channels in collagen-induced arthritis (CIA). EXPERIMENTAL APPROACH: The CIA mouse model was used to examine the effects of the SOC channel inhibitor YM-58483 on CIA and arthritic pain. Hargreaves' and von Frey hair tests were conducted to measure thermal and mechanical sensitivities of hind paws. elisa was performed to measure cytokine production, and haematoxylin and eosin staining was used to assess knee histological changes. Western blot analysis was performed to examine protein levels. KEY RESULTS: Pretreatment with 5 or 10 mg · kg(-1) of YM-58483 reduced the incidence of CIA, prevented the development of inflammation and pain hypersensitivity and other signs and features of arthritis disease. Similarly, treatment with YM-58483 after the onset of CIA: (i) reversed the clinical scores; (ii) reduced paw oedema; (iii) attenuated mechanical and thermal hypersensitivity; (iv) improved spontaneous motor activity; (v) decreased periphery production of IL-1ß, IL-6 and TNF-α; and (vi) reduced spinal activation of ERK and calmodulin-dependent PKII (CaMKIIα). CONCLUSIONS AND IMPLICATIONS: This study provides the first evidence that inhibition of SOC entry prevents and relieves rheumatoid arthritis (RA) and arthritic pain. These effects are probably mediated by a reduction in cytokine levels in the periphery and activation of ERK and CaMKIIα in the spinal cord. These results suggest that SOC channels are potential drug targets for the treatment of RA.


Subject(s)
Anilides/pharmacology , Arthritis, Experimental/prevention & control , Arthritis, Rheumatoid/prevention & control , Calcium Channel Blockers/pharmacology , Thiadiazoles/pharmacology , Anilides/administration & dosage , Animals , Arthritis, Experimental/pathology , Arthritis, Rheumatoid/pathology , Calcium Channel Blockers/administration & dosage , Collagen/toxicity , Cytokines/metabolism , Dose-Response Relationship, Drug , Inflammation/pathology , Inflammation/prevention & control , Male , Mice , Mice, Inbred DBA , Pain/drug therapy , Pain/etiology , Thiadiazoles/administration & dosage
9.
Ecol Appl ; 23(3): 537-45, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23734484

ABSTRACT

In a 10-year study, we assessed the influence of five carbon (C) treatments on the labile C and nitrogen (N) pools of historically N-enriched plots on the Shortgrass Steppe Long Term Ecological Research site located in northeastern Colorado. For eight years, we applied sawdust, sugar, industrial lignin, sawdust + sugar, and lignin + sugar to plots that had received N and water additions in the early 1970s. Previous work showed that past water and N additions altered plant species composition and enhanced rates of nutrient cycling; these effects were still apparent 25 years later. We hypothesized that labile C amendments would stimulate microbial activity and suppress rates of N mineralization, whereas complex forms of carbon (sawdust and lignin) could enhance humification and lead to longer-term reductions in N availability. Results indicated that, of the five carbon treatments, sugar, sawdust, and sawdust + sugar suppressed N availability, with sawdust + sugar being the most effective treatment to reduce N availability. The year after treatments stopped, N availability remained less in the sawdust + sugar treatment plots than in the high-N control plots. Three years after treatments ended, reductions in N availability were smaller (40-60%). Our results suggest that highly labile forms of carbon generate strong short-term N sinks, but these effects dissipate within one year of application, and that more recalcitrant forms reduce N longer. Sawdust + sugar was the most effective treatment to decrease exotic species canopy cover and increase native species density over the long term. Labile carbon had neither short- nor long-term effects on exotic species. Even though the organic amendments did not contribute to recovery of the dominant native species Bouteloua gracilis, they were effective in increasing another native species, Carex eleocharis. These results indicate that organic amendments may be a useful tool for restoring some native species in the shortgrass steppe, though not all.


Subject(s)
Carbon/pharmacology , Ecosystem , Nitrogen/chemistry , Plants/drug effects , Colorado , Nitrogen/metabolism , Plants/classification , Species Specificity , Time Factors
10.
Biochem Biophys Res Commun ; 418(1): 17-21, 2012 Feb 03.
Article in English | MEDLINE | ID: mdl-22209844

ABSTRACT

The molecular signalling pathway of cell migration and whether it can occur independently of the release of intracellular calcium is still not completely understood. Therefore we investigated here the molecular mechanisms of CCL3 induced cell migration and the importance of intracellular calcium for chemotaxis in more detail. We show that CCL3 induced cell migration is dependent on activation of PLC. Several PKC inhibitors block the release of intracellular calcium independently of CCL3 activation and do not affect cell migration. This confirms that the release of intracellular calcium is not necessary for chemotaxis towards CCL3 and that PKC inhibitors should be used with caution in calcium release assays.


Subject(s)
Calcium Signaling , Calcium/metabolism , Cell Movement , Chemokine CCL3/physiology , Animals , CHO Cells , Chemokine CCL3/genetics , Chemokine CCL3/pharmacology , Chemotaxis/genetics , Chemotaxis/physiology , Cricetinae , Enzyme Activation , Estrenes/pharmacology , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/metabolism , Pyrrolidinones/pharmacology , Type C Phospholipases/metabolism
11.
Conserv Biol ; 22(6): 1544-51, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18759772

ABSTRACT

Antarctic ecosystems are often considered nearly pristine because levels of anthropogenic disturbance are extremely low there. Nevertheless, over recent decades there has been a rapid increase in the number of people, researchers and tourists, visiting Antarctica. We evaluated, over 10 years, the direct impact of foot traffic on the abundance of soil animals and soil properties in Taylor Valley within the McMurdo Dry Valleys region of Antarctica. We compared soils from minimally disturbed areas with soils from nearby paths that received intermediate and high levels of human foot traffic (i.e., up to approximately 80 passes per year). The nematodes Scottnema lindsayae and Eudorylaimus sp. were the most commonly found animal species, whereas rotifers and tardigrades were found only occasionally. On the highly trampled footpaths, abundance of S. lindsayae and Eudorylaimus sp. was up to 52 and 76% lower, respectively, than in untrampled areas. Moreover, reduction in S. lindsayae abundance was more pronounced after 10 years than 2 years and in the surface soil than in the deeper soil, presumably because of the longer period of disturbance and the greater level of physical disturbance experienced by the surface soil. The ratio of living to dead Eudorylaimus sp. also declined with increased trampling intensity, which is indicative of increased mortality or reduced fecundity. At one site there was evidence that high levels of trampling reduced soil CO(2) fluxes, which is related to total biological activity in the soil. Our results show that even low levels of human traffic can significantly affect soil biota in this ecosystem and may alter ecosystem processes, such as carbon cycling. Consequently, management and conservation plans for Antarctic soils should consider the high sensitivity of soil fauna to physical disturbance as human presence in this ecosystem increases.


Subject(s)
Conservation of Natural Resources/methods , Ecosystem , Human Activities , Invertebrates/physiology , Soil/analysis , Soil/parasitology , Animals , Antarctic Regions , Carbon Dioxide/analysis , Conservation of Natural Resources/statistics & numerical data , Humans , Population Density , Walking
12.
J Pharmacol Exp Ther ; 314(3): 1274-89, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15951399

ABSTRACT

Recent data has suggested that the 5-hydroxytryptamine (5-HT)(1A) receptor is involved in cognitive processing. A novel 5-HT(1A) receptor antagonist, 4-cyano-N-{2R-[4-(2,3-dihydrobenzo[1,4]-dioxin-5-yl)-piperazin-1-yl]-propyl}-N-pyridin-2-yl-benzamide HCl (lecozotan), which has been characterized in multiple in vitro and in vivo pharmacological assays as a drug to treat cognitive dysfunction, is reported. In vitro binding and intrinsic activity determinations demonstrated that lecozotan is a potent and selective 5-HT(1A) receptor antagonist. Using in vivo microdialysis, lecozotan (0.3 mg/kg s.c.) antagonized the decrease in hippocampal extracellular 5-HT induced by a challenge dose (0.3 mg/kg s.c.) of 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT) and had no effects alone at doses 10-fold higher. Lecozotan significantly potentiated the potassium chloride-stimulated release of glutamate and acetylcholine in the dentate gyrus of the hippocampus. Chronic administration of lecozotan did not induce 5-HT(1A) receptor tolerance or desensitization in a behavioral model indicative of 5-HT(1A) receptor function. In drug discrimination studies, lecozotan (0.01-1 mg/kg i.m.) did not substitute for 8-OH-DPAT and produced a dose-related blockade of the 5-HT(1A) agonist discriminative stimulus cue. In aged rhesus monkeys, lecozotan produced a significant improvement in task performance efficiency at an optimal dose (1 mg/kg p.o.). Learning deficits induced by the glutamatergic antagonist MK-801 [(-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] (assessed by perceptually complex and visual spatial discrimination) and by specific cholinergic lesions of the hippocampus (assessed by visual spatial discrimination) were reversed by lecozotan (2 mg/kg i.m.) in marmosets. The heterosynaptic nature of the effects of lecozotan imbues this compound with a novel mechanism of action directed at the biochemical pathologies underlying cognitive loss in Alzheimer's disease.


Subject(s)
Acetylcholine/metabolism , Cognition/drug effects , Dioxanes/pharmacology , Glutamic Acid/metabolism , Hippocampus/drug effects , Piperazines/pharmacology , Serotonin 5-HT1 Receptor Antagonists , Serotonin Antagonists/pharmacology , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Alzheimer Disease/drug therapy , Animals , Callithrix , Columbidae , Discrimination Learning/drug effects , Female , Ganglia, Spinal/drug effects , Hippocampus/metabolism , Macaca mulatta , Male , Methoxydimethyltryptamines/antagonists & inhibitors , Microdialysis , Rats , Rats, Sprague-Dawley , Saimiri
13.
Gen Hosp Psychiatry ; 23(6): 301-10, 2001.
Article in English | MEDLINE | ID: mdl-11738460

ABSTRACT

This report describes the rates of recovery and remission from minor depression or dysthymia in primary care patients three months after completing a randomized controlled treatment trial. The subjects were primary care patients who received > or =4 treatment sessions with Problem-Solving Treatment, paroxetine, or placebo and who completed an independent assessment 3 months after the study (201 with minor depression, 229 with dysthymia). The 17-item Hamilton Rating Scale for Depression (HAMD), semistructured questions about postintervention depression treatments, and baseline medical comorbidity, neuroticism, and social function were the primary measures. For minor depression 76% and for dysthymia 68% of subjects who were in remission at the end of the 11-week treatment trial were recovered (HAMD < or =6) three months after the treatment trial. Of patients who were not in remission at 11 weeks, for minor depression 37% and for dysthymia 31% went on to achieve remission at 25 weeks. The majority of patients chose not to use antidepressants or psychotherapy after the trial. Patients with minor depression that had greater baseline social function and lower neuroticism scores were more likely to be recovered. For patients with minor depression, these findings suggest a need for some matching of continuation and maintenance treatment to patient characteristics rather than uniform, automatic treatment recommendations. Because of the chronic, relapsing nature of dysthymia, practical improvements in encouraging effective continuation and maintenance phases of treatment are indicated.


Subject(s)
Depressive Disorder/therapy , Dysthymic Disorder/therapy , Primary Health Care , Adolescent , Adult , Attitude to Health , Depressive Disorder/diagnosis , Depressive Disorder/drug therapy , Dysthymic Disorder/diagnosis , Dysthymic Disorder/drug therapy , Female , Humans , Male , Middle Aged , Paroxetine/therapeutic use , Problem Solving , Psychiatric Status Rating Scales , Selective Serotonin Reuptake Inhibitors/therapeutic use , Severity of Illness Index , Surveys and Questionnaires
15.
J Fam Pract ; 50(5): 405-12, 2001 May.
Article in English | MEDLINE | ID: mdl-11350703

ABSTRACT

OBJECTIVE: The researchers evaluated the effectiveness of paroxetine and Problem-Solving Treatment for Primary Care (PST-PC) for patients with minor depression or dysthymia. STUDY DESIGN: This was an 11-week randomized placebo-controlled trial conducted in primary care practices in 2 communities (Lebanon, NH, and Seattle, Wash). Paroxetine (n=80) or placebo (n=81) therapy was started at 10 mg per day and increased to a maximum 40 mg per day, or PST-PC was provided (n=80). There were 6 scheduled visits for all treatment conditions. POPULATION: A total of 241 primary care patients with minor depression (n=114) or dysthymia (n=127) were included. Of these, 191 patients (79.3%) completed all treatment visits. OUTCOMES: Depressive symptoms were measured using the 20-item Hopkins Depression Scale (HSCL-D-20). Remission was scored on the Hamilton Depression Rating Scale (HDRS) as less than or equal to 6 at 11 weeks. Functional status was measured with the physical health component (PHC) and mental health component (MHC) of the 36-item Medical Outcomes Study Short Form. RESULTS: All treatment conditions showed a significant decline in depressive symptoms over the 11-week period. There were no significant differences between the interventions or by diagnosis. For dysthymia the remission rate for paroxetine (80%) and PST-PC (57%) was significantly higher than for placebo (44%, P=.008). The remission rate was high for minor depression (64%) and similar for each treatment group. For the MHC there were significant outcome differences related to baseline level for paroxetine compared with placebo. For the PHC there were no significant differences between the treatment groups. CONCLUSIONS: For dysthymia, paroxetine and PST-PC improved remission compared with placebo plus nonspecific clinical management. Results varied for the other outcomes measured. For minor depression, the 3 interventions were equally effective; general clinical management (watchful waiting) is an appropriate treatment option.


Subject(s)
Antidepressive Agents/therapeutic use , Depression/therapy , Dysthymic Disorder/therapy , Paroxetine/therapeutic use , Primary Health Care , Psychotherapy/methods , Adolescent , Adult , Antidepressive Agents/administration & dosage , Depression/diagnosis , Depression/drug therapy , Double-Blind Method , Dysthymic Disorder/diagnosis , Dysthymic Disorder/drug therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Paroxetine/administration & dosage , Problem Solving , Psychiatric Status Rating Scales , Remission Induction , Severity of Illness Index , Treatment Outcome
16.
Am J Geriatr Psychiatry ; 8(4): 318-26, 2000.
Article in English | MEDLINE | ID: mdl-11069272

ABSTRACT

The authors compared symptomatic and functional characteristics between older (age > or =60; n=91) and younger (age 18-59; n=125) primary care patients with dysthymia. Three of six significantly different depression symptoms were of moderate-to-large effect size, with the older group having a lower proportion reporting the symptom. The older group had a worse physical health function score but a better mental health function score. There appears to be a core of symptoms and functional impairment that generalizes across the age span. There are also significant age differences. Growing older appears to have an impact on the nature of what it means to have dysthymia.


Subject(s)
Aging/psychology , Dysthymic Disorder/psychology , Health Status , Mental Health , Adult , Age Factors , Aged , Confounding Factors, Epidemiologic , Depression/etiology , Female , Humans , Male , Middle Aged , Primary Health Care , Psychiatric Status Rating Scales , Randomized Controlled Trials as Topic , Severity of Illness Index
17.
J Pharmacol Exp Ther ; 295(1): 337-45, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10991999

ABSTRACT

The purpose of this study was to evaluate the effects of a novel neuroactive steroid, Co 2-6749 (GMA-839; WAY-141839; 3alpha, 21-dihydroxy-3beta-trifluoromethyl-19-nor-5beta-pregnan-20-one), on gamma-aminobutyric acid(A) receptors in vitro and to define its anxiolytic-like effects and side effect profile in vivo. Co 2-6749 fully inhibited [(35)S]t-butylbicyclophosphorothionate binding in rat brain cortical membranes with an IC(50) value of 230 nM and in human gamma-aminobutyric acid(A) receptor subunit combinations of alpha1beta2gamma2L, alpha2beta2gamma2L, alpha3beta2gamma2L, alpha4beta3gamma2L, alpha5beta2gamma2L, and alpha6beta3gamma2L receptors (IC(50) values of 200, 200, 96, 2300, 210, and 2000 nM). Rats were trained in a Geller-Seifter operant conflict paradigm. Co 2-6749 caused a dose-related increase in punished responding with a minimum effective dose of 1.6 mg/kg, p.o., a wide therapeutic index relative to a decrease in unpunished responding and relative to ataxia, and no tolerance. Additionally, ethanol caused less than a 2-fold shift to the left in the dose-response function of Co 2-6749 in the rotorod procedure in rats. In a pigeon conflict paradigm, punished responding was maximally increased to 784% of vehicle control by 30 mg/kg, p.o., with a 2-h duration and no effect on unpunished responding at this dose. Similarly, punished responding in squirrel monkeys was maximally increased to 1774% of control by 10 mg/kg, p.o., with no effect on unpunished responding at this dose. With robust anxiolytic-like activity across species, a large separation between anxiolytic-like effects and sedation/ataxia, a minimal interaction with ethanol, a lack of tolerance, and apparent oral bioavailability, Co 2-6749 makes an ideal candidate for development as a novel anxiolytic drug.


Subject(s)
Anti-Anxiety Agents/pharmacology , GABA Modulators/pharmacology , Pregnanolone/analogs & derivatives , Receptors, GABA-A/drug effects , Alprazolam/pharmacology , Animals , Bridged Bicyclo Compounds, Heterocyclic/metabolism , Cell Line , Columbidae , Conflict, Psychological , Humans , Male , Motor Activity/drug effects , Pregnanolone/pharmacology , Rats , Rats, Sprague-Dawley , Saimiri
18.
J Pharmacol Exp Ther ; 295(1): 382-91, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10992005

ABSTRACT

The discriminative stimulus (DS) effects of 4-aminopyridine (4-AP) were evaluated in 36 male Sprague-Dawley rats that were trained to discriminate 4-AP from saline in a standard two-lever food reinforced drug discrimination procedure. 4-AP along with its structural analogs 3-aminopyridine (3-AP), 2-aminopyridine (2-AP), and 2,3-diaminopyridine (2,3-DIAP) produced dose-dependent increases in the percentage of responses on the 4-AP-associated lever with full substitution at one or more doses. 2,6-Diaminopyridine (2, 6-DIAP) and 3,4-diaminopyridine (3,4-DIAP) produced dose-dependent increases in the percentage of responses on the 4-AP-associated lever but only partially substituted for 4-AP. Neither 4-dimethylaminopyridine (4-DMAP) nor pyridine substituted for 4-AP. Substitution studies were also conducted with indirect dopamine, norepinephrine, serotonin, and acetylcholine agonists, and gamma-aminobutyric acid A (GABA(A)) agonists and antagonists. The norepinephrine reuptake inhibitor tomoxetine, but not nisoxetine or imipramine, produced dose-dependent increases in the percentage of responses on the 4-AP-associated lever and partially substituted for 4-AP. In addition, antagonism studies were conducted using indirect dopamine, norepinephrine, serotonin, acetylcholine antagonists, and GABA(A) agonists as pretreatments to the training dose of 4-AP. The benzodiazepine agonists chlordiazepoxide and diazepam dose dependently attenuated the DS effects of 4-AP. The present results demonstrate that the K-channel blocker 4-AP can be trained as a DS in rats and the DS effects of 4-AP are likely mediated through blockade of voltage-dependent K-channels. The results also demonstrate a novel interaction between benzodiazepines and K-channels.


Subject(s)
4-Aminopyridine/pharmacology , Discrimination Learning/drug effects , Potassium Channel Blockers , Animals , Cholinergic Agents/pharmacology , Dopamine Agents/pharmacology , Dose-Response Relationship, Drug , Excitatory Amino Acid Antagonists/pharmacology , Male , Pinacidil/pharmacology , Prazosin/pharmacology , Rats , Rats, Sprague-Dawley , Serotonin Agents/pharmacology
19.
Plant Mol Biol ; 42(6): 847-56, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10890532

ABSTRACT

We have isolated two cDNAs from geranium, PhETR1 and PhETR2. The deduced amino acid sequences of PhETR1 anti PhETR2 share 78% and 79% identity with ETR1 from Arabidopsis thaliana respectively. These genes are members of a multigene family and are expressed at moderate levels in leaves, pedicels, sepals, pistils and petals, and at very low levels in roots. PhETR1 and PhETR2 mRNAs are expressed in geranium florets long before they are receptive to pollination and transcript levels remain constant throughout floral development. Message levels of PhETR1 and PhETR2 in pistils and receptacles are unaffected by self-pollination or treatment with 1 micro/l ethylene that induces petal abscission. Our results indicate that the amount of PhETR1 and PHETR2 mRNA is not indicative of the level of sensitivity of geranium florets to ethylene.


Subject(s)
Ethylenes/pharmacology , Magnoliopsida/drug effects , Plant Proteins/genetics , Pollen/physiology , RNA, Messenger/drug effects , Receptors, Cell Surface/genetics , Amino Acid Sequence , Blotting, Southern , Cloning, Molecular , DNA, Complementary/chemistry , DNA, Complementary/genetics , DNA, Plant/genetics , Gene Expression Regulation, Developmental/drug effects , Gene Expression Regulation, Plant/drug effects , Magnoliopsida/genetics , Magnoliopsida/physiology , Molecular Sequence Data , Protein Isoforms/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Transcription, Genetic/drug effects
20.
J Appl Physiol (1985) ; 88(5): 1614-22, 2000 May.
Article in English | MEDLINE | ID: mdl-10797121

ABSTRACT

The US-Russian joint quail embryo project was designed to study the effects of microgravity on development of Japanese quail embryos incubated aboard Mir. For this part of the project, eyes from embryonic days 14 and 16 (E14 and E16) flight embryos were compared with eyes from several groups of ground-based control embryos. Measurements were recorded for eye weights; eye, corneal, and scleral ring diameters; and numbers of bones in scleral ossicle rings. Transparency of E16 corneas was documented, and immunohistochemical staining was performed to observe corneal innervation. In addition, corneal ultrastructure was observed at the electron microscopic level. Except for corneal diameter of E16 flight embryos, compared with that of one of the sets of controls, results reported here indicate that eye development occurred normally in microgravity. Fixation by cracking the shell and placing the egg in paraformaldehyde solution did not adequately preserve corneal nerves or cellular ultrastructure.


Subject(s)
Coturnix/embryology , Eye/embryology , Weightlessness , Animals , Cornea/embryology , Cornea/innervation , Embryo, Nonmammalian/anatomy & histology , Embryo, Nonmammalian/innervation , Embryo, Nonmammalian/physiology , Embryo, Nonmammalian/ultrastructure , Immunohistochemistry , Microscopy, Electron , Nervous System/metabolism , Russia , Sclera/embryology , Space Flight , United States
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