bluuebunny/crossref_metadata_2025 huggingface dataset:
Policy strategies to address sustainability of Alaskan boreal forests in response to a directionally changing climate
Authors: Chapin F. Stuart , Lovecraft Amy L. , Zavaleta Erika S. , Nelson Joanna , Robards Martin D. , Kofinas Gary P. , Trainor Sarah F. , Peterson Garry D. , Huntington Henry P. , Naylor Rosamond L.
Published: September 2006

Human activities are altering many factors that determine the fundamental properties of ecological and social systems. Is sustainability a realistic goal in a world in which many key process controls are directionally changing? To address this issue, we integrate several disparate sources of theory to address sustainability in directionally changing social–ecological systems, apply this framework to climate-warming impacts in Interior Alaska, and describe a suite of policy strategies that emerge from these analyses. Climate warming in Interior Alaska has profoundly affected factors that influence landscape processes (climate regulation and disturbance spread) and natural hazards, but has only indirectly influenced ecosystem goods such as food, water, and wood that receive most management attention. Warming has reduced cultural services provided by ecosystems, leading to some of the few institutional responses that directly address the causes of climate warming, e.g., indigenous initiatives to the Arctic Council. Four broad policy strategies emerge: (i) enhancing human adaptability through learning and innovation in the context of changes occurring at multiple scales; (ii) increasing resilience by strengthening negative (stabilizing) feedbacks that buffer the system from change and increasing options for adaptation through biological, cultural, and economic diversity; (iii) reducing vulnerability by strengthening institutions that link the high-latitude impacts of climate warming to their low-latitude causes; and (iv) facilitating transformation to new, potentially more beneficial states by taking advantage of opportunities created by crisis. Each strategy provides societal benefits, and we suggest that all of them be pursued simultaneously.
Conditions for extreme sensitivity of protein diffusion in membranes to cell environments
Authors: Tserkovnyak Yaroslav , Nelson David R.
Published: September 2006

We study protein diffusion in multicomponent lipid membranes close to a rigid substrate separated by a layer of viscous fluid. The large-distance, long-time asymptotics for Brownian motion are calculated by using a nonlinear stochastic Navier–Stokes equation including the effect of friction with the substrate. The advective nonlinearity, neglected in previous treatments, gives only a small correction to the renormalized viscosity and diffusion coefficient at room temperature. We find, however, that in realistic multicomponent lipid mixtures, close to a critical point for phase separation, protein diffusion acquires a strong power-law dependence on temperature and the distance to the substrate
H,
making it much more sensitive to cell environment, unlike the logarithmic dependence on
H
and very small thermal correction away from the critical point.
Resisting (nuclear) power? Environmental regulation in South Africa
Authors: Death Carl
Published: October 2006

This article considers the resistance potential of Environmental Impact Assessments (EIAs) and their effects upon existing power relationships. It focuses upon the blocking of Eskom's proposed new test nuclear reactor by the environmental NGO Earthlife Africa, at Koeberg, South Africa, the site of Africa's only existing nuclear power plant. This was achieved through their engagement with, and contestation of, the South African EIA process. It occurred within a context of a globally uncertain future for the nuclear industry, and broader questions over the possible role of nuclear power in sustainable development. Whilst initially appearing as an example of environmental resistance against a big development project, by approaching the case through the lens of Michel Foucault's concept of governmentality the article suggests that Earthlife Africa's challenge reinforced existing power relationships and legitimised an essentially pro-development EIA process. This is particularly evident when considering the relationship between EIAs and established scientific authorities, and the problematic role of public participation. However, by regarding the EIA as an example of ‘bearing witness’ some sense of its resistance potential can be reclaimed. The article concludes by suggesting that a broader debate on nuclear power in South Africa is desirable, and that environmental NGOs should seriously consider the degree to which they accept and participate in the EIA process.
Ragged Red Fibers in Myotonic Dystrophy Type 2: Ragged Red Herring?
Authors: Walker Melanie , Born Donald E , Weiss Michael D
Published: September 2006

Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystem disorder with variable phenotypic expression, previously referred to as proximal myotonic myopathy. The genetic defect in DM2 is the result of a CCTG tetranucleotide repeat expansion on chromosome 3q in the gene for the transcriptional factor zinc finger protein 9. Though weakness is prominent, mitochondrial pathology has not been clearly associated with DM2. The authors present a patient with pathologic evidence for abundant ragged red fibers in a case of genetically proven DM2 and discuss the ramifications of such findings.
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) With Rapid Progression After Influenza Vaccination: A Report of Three Cases
Authors: Kelkar Praful
Published: September 2006

Influenza vaccination has been implicated to increase the risk of developing Gullain-Barre syndrome. Rarely vaccination is reported before relapse in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but there are no clearly documented reports of rapidly progressing CIDP with onset soon after influenza vaccination. The authors describe 3 patients who developed CIDP with rapid onset in close proximity to influenza vaccination followed by relapsing or chronic course.
Sporadic, Adult-Onset Nemaline Myopathy Presenting as Camptocormia (Bent-Spine Syndrome)
Authors: Gorson Kenneth C , Adelman Lester S , Pierson Christopher , Beggs Alan H
Published: September 2006

The authors report a case of sporadic, late-onset nemaline myopathy presenting with camptocormia (bent-spine syndrome). The patient had slowly progressive, painless weakness of the thoracic and lumbar paraspinal muscles developing over 5 years, sparing limb muscles. Creatine kinase was normal, and electrodiagnostic studies showed fibrillation potentials and myopathic motor units restricted to the paraspinal musculature. Magnetic resonance imaging demonstrated muscle atrophy and T2 hyperintensity of the paraspinal muscles. Biopsy of a thoracic paraspinal muscle demonstrated numerous nemaline rods on the modified Gomori trichrome stain, confirmed by electron microscopy and immunofluorescence. The patient was of Ashkenazi-Jewish descent, but no other family members were affected, and DNA analysis excluded deletion of the nebulin gene. Although isolated head-drop has been reported as a rare presenting feature of nemaline myopathy, isolated bent-spine syndrome has not been described. The absence of the nebulin gene deletion suggests that other mutations may be linked to nemaline myopathy in Ashkenazi patients.
Long-term maternal effect on offspring immune response in song sparrowsMelospiza melodia
Authors: Reid Jane M , Arcese Peter , Keller Lukas F , Hasselquist Dennis
Published: September 2006

Knowledge of the causes of variation in host immunity to parasitic infection and the time-scales over which variation persists, is integral to predicting the evolutionary and epidemiological consequences of host–parasite interactions. It is clear that offspring immunity can be influenced by parental immune experience, for example, reflecting transfer of antibodies from mothers to young offspring. However, it is less clear whether such parental effects persist or have functional consequences over longer time-scales, linking a parent's previous immune experience to future immune responsiveness in fully grown offspring. We used free-living song sparrows (Melospiza melodia) to quantify long-term effects of parental immune experience on offspring immune response. We experimentally vaccinated parents with a novel antigen and tested whether parental vaccination influenced the humoral antibody response mounted by fully grown offspring hatched the following year. Parental vaccination did not influence offspring baseline antibody titres. However, offspring of vaccinated mothers mounted substantially stronger antibody responses than offspring of unvaccinated mothers. Antibody responses did not differ between offspring of vaccinated and unvaccinated fathers. These data demonstrate substantial long-term effects of maternal immune experience on the humoral immune response of fully grown offspring in free-living birds.
Anti-parasite treatment removes negative effects of environmental pollutants on reproduction in an Arctic seabird
Authors: Bustnes Jan O , Erikstad Kjell E , Hanssen Sveinn A , Tveraa Torkild , Folstad Ivar , Skaare Janncehe U
Published: September 2006

Recent studies have shown that the detrimental effects of anthropogenic pollutants may be worse if organisms are exposed to natural stress. In this study, we examined whether negative effects of organochlorines (OCs) could be influenced by parasites. In two breeding seasons, we administered an anti-helminthic drug to groups of breeding glaucous gulls (Larus hyperboreus), whereas control groups were placebo treated. In all birds, blood residues of the most important OCs in the study population (hexachlorobenzene, oxychlordane,p,p′-dichlorodiphenyldichloroethylene and polychlorinated biphenyl), were measured. The relationships between OCs and fitness components (i.e. nesting success and return rate between breeding seasons) were then compared between the birds receiving anti-parasite treatment and the controls. Among untreated males, higher blood residues of OCs were associated with lowered nesting success, while in males receiving anti-parasite treatment, there was no detrimental effect of OCs on fitness. Return rate was not affected by treatment or OCs. Our findings suggest that parasites may be an important factor in triggering reproductive effects of such pollutants, and that relatively low levels of OCs may have serious reproductive consequences in natural populations when stress from other sources is high.
Negotiation of mutualism: rhizobia and legumes
Authors: Akçay Erol , Roughgarden Joan
Published: September 2006

The evolution and persistence of biological cooperation have been an important puzzle in evolutionary theory. Here, we suggest a new approach based on bargaining theory to tackle the question. We present a mechanistic model for negotiation of benefits between a nitrogen-fixing nodule and a legume plant. To that end, we first derive growth rates for the nodule and plant from metabolic models of each as a function of material fluxes between them. We use these growth rates as pay-off functions in the negotiation process, which is analogous to collective bargaining between a firm and a workers' union. Our model predicts that negotiations lead to the Nash bargaining solution, maximizing the product of players' pay-offs. This work introduces elements of cooperative game theory into the field of mutualistic interactions. In the discussion of the paper, we argue for the benefits of such an approach in studying the question of biological cooperation.
Explicitly correlated potential energy surface of , including relativistic and adiabatic corrections
Authors: Kutzelnigg Werner , Jaquet Ralph
Published: September 2006

After a short historical account of the theory of the

ion, two
ab initio
methods are reviewed that allow the computation of the ground-state potential energy surface (PES) of

in the Born–Oppenheimer (BO) approximation, with microhartree or even sub-microhartree accuracy, namely the R12 method and the method of explicitly correlated Gaussians. The BO-PES is improved by the inclusion of relativistic effects and adiabatic corrections. It is discussed how non-adiabatic effects on rotation and vibration can be simulated by corrections to the moving nuclear masses. The importance of the appropriate analytic fit to the computed points of the PES for the subsequent computation of the rovibronic spectrum is addressed. Some recent extensions of the computed PES in the energy region above the barrier to linearity are reviewed. This involves a large set of input geometries and the correct treatment of the dissociation asymptotics, including the coupling with the first excited singlet state. Some comments on this state as well as on the lowest triplet state of

are made. The paper ends with a few remarks on the ion

.
Phycicoccus jejuensis gen. nov., sp. nov., an actinomycete isolated from seaweed
Authors: Lee Soon Dong
Published: September 2006

A marine actinomycete strain, designated KSW2-15T, was isolated from a dried seaweed sample collected from a sandy beach on the coast of Jeju in the Republic of Korea. The organism produced non-motile, non-endospore-forming, Gram-positive, coccoid cells. The colonies were circular, translucent and yellow in colour with entire margins.meso-Diaminopimelic acid was present as the diamino acid of the peptidoglycan. The acyl type of the muramic acid was acetyl. Mycolic acids were not present. The predominant menaquinone was MK-8(H4). The polar lipids were phosphatidylethanolamine, phosphatidylinositol and diphosphatidylglycerol. The major cellular fatty acids were of the saturated, unsaturated and iso-branched methyl types. The DNA G+C content was 74 mol%. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain KSW2-15Tformed a loose association with ‘CandidatusNostocoida limicola’, within the radiation of the familyIntrasporangiaceaeof the suborderMicrococcineae. The organism showed the highest levels of sequence similarity with ‘CandidatusNostocoida limicola’ (96.1 %),Terrabacter tumescens(96.1 %) andTerrabacter terrae(96.0 %). The levels of 16S rRNA gene sequence similarity between the isolate and members of other genera of the familyIntrasporangiaceaewere in the range 92.1–95.5 %. On the basis of the polyphasic evidence, the isolate should be classified within a novel genus and species, for which the namePhycicoccus jejuensisgen. nov., sp. nov. is proposed. The type strain ofPhycicoccus jejuensisis strain KSW2-15T(=KCCM 42315T=NRRL B-24460T).
Microcella alkaliphila sp. nov., a novel member of the family Microbacteriaceae isolated from a non-saline alkaline groundwater, and emended description of the genus Microcella
Authors: Tiago Igor , Morais Paula V. , da Costa Milton S. , Veríssimo António
Published: September 2006

A high-G+C-content Gram-positive bacterium, designated as strain AC4rT, was isolated from a highly alkaline, non-saline groundwater environment (pH 11.4). This organism formed small rod-shaped cells, was aerobic, heterotrophic, catalase-positive and oxidase-negative and had an optimum growth temperature of 35 °C and an optimum pH of 9.5. The strain possessed a B2β-type cell-wall peptidoglycan, with d-Orn as the diagnostic diamino acid. The major respiratory quinones were unsaturated menaquinones with 13 and 14 isoprene units. The predominant fatty acids were anteiso-15 : 0, iso-16 : 0, iso-14 : 0 and iso-15 : 0. The G+C content of the DNA was 67.1 mol%. In a 16S rRNA gene sequence analysis, strain AC4rT showed the highest level of similarity (99.2 %) to the type strain of Microcella putealis; however, the DNA–DNA reassociation value between these two organisms was low (38.3 %). On the basis of phylogenetic analysis, the DNA–DNA reassociation value and distinct phenotypic characteristics, strain AC4rT represents a novel species within the genus Microcella, for which the name Microcella alkaliphila sp. nov. is proposed. The type strain is AC4rT (=LMG 22690T=CIP 108473T).
Mesonia mobilis sp. nov., isolated from seawater, and emended description of the genus Mesonia
Authors: Nedashkovskaya Olga I. , Kim Seung Bum , Zhukova Natalia V. , Kwak Jangryul , Mikhailov Valery V. , Bae Kyung Sook
Published: September 2006

The taxonomic position of a novel marine, heterotrophic, strictly aerobic, gliding and yellow-pigmented bacterium, designated strain KMM 6059T, was determined. 16S rRNA gene sequence analysis revealed that this strain represents a member of the genus Mesonia. Phenotypic and chemotaxonomic data showed that the isolate represents a novel species of the genus Mesonia, for which the name Mesonia mobilis sp. nov. is proposed. The type strain is KMM 6059T (=KCTC 12708T=LMG 23670T). An emended description of the genus Mesonia based on the new data is also given.
Syntrophomonas cellicola sp. nov., a spore-forming syntrophic bacterium isolated from a distilled-spirit-fermenting cellar, and assignment of Syntrophospora bryantii to Syntrophomonas bryantii comb. nov.
Authors: Wu Chenggang , Liu Xiaoli , Dong Xiuzhu
Published: September 2006

A spore-forming, anaerobic, syntrophic fatty-acid-oxidizing bacterium, strain 19J-3T, was isolated from a distilled-spirit-fermenting cellar in Hebei Province, China. The cells were slightly curved rods with a spore at the end of the cell. The optimal temperature for growth was around 37 °C and growth occurred in the range 25–45 °C. The pH range for growth was 6.5–8.5 and the optimum pH was 7.0–7.5. Crotonate was the only substrate that allowed the strain to grow in pure culture. However, the strain could oxidize saturated fatty acids with four to nine carbon atoms syntrophically in co-culture with Methanobacterium formicicum DSM 1535T. The strain was not able to utilize sulfate, sulfite, thiosulfate, DMSO, nitrate, fumarate or Fe(III) as electron acceptor. The DNA base composition was 48.8 mol% G+C. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain 19J-3T was related to members of the family Syntrophomonadaceae and most closely to Syntrophospora bryantii DSM 3014T (94.3 % similarity) and Syntrophomonas wolfei subsp. wolfei DSM 2245T (93.6 % similarity). Considering the phylogenetic relationship and phenotypic features, strain 19J-3T (=CGMCC 1.5041T=JCM 13582T) is designated as the type strain of a novel species of the genus Syntrophomonas, Syntrophomonas cellicola sp. nov. Based on the close phylogenetic relationship between the genera Syntrophospora and Syntrophomonas, the presence of sporulation-specific genes in the genome of Syntrophomonas wolfei subsp. wolfei DSM 2245T and the description of a spore-forming member of Syntrophomonas, ‘Syntrophomonas erecta subsp. sporosyntropha’, we propose the assignment of Syntrophospora bryantii to the genus Syntrophomonas as Syntrophomonas bryantii comb. nov.
Marinomonas ostreistagni sp. nov., isolated from a pearl-oyster culture pond in Sanya, Hainan Province, China
Authors: Lau Ken W. K. , Ren Jianping , Wai Natalie L. M. , Lau Simon C. L. , Qian Pei-Yuan , Wong Po-Keung , Wu Madeline
Published: September 2006

A Gram-negative, aerobic, halophilic, neutrophilic, rod-shaped, non-pigmented, polar-flagellated bacterium, UST010306-043T, was isolated from a pearl-oyster culture pond in Sanya, Hainan Province, China in January 2001. This marine bacterium had an optimum temperature for growth of between 33 and 37 °C. On the basis of 16S rRNA gene sequence analysis, the strain was closely related to Marinomonas aquimarina and Marinomonas communis, with 97.5–97.7 and 97.1 % sequence similarity, respectively. Levels of DNA–DNA relatedness to the type strains of these species were well below 70 %. Analyses of phylogenetic, phenotypic and chemotaxomonic characteristics showed that strain UST010306-043T was distinct from currently established Marinomonas species. A novel species with the name Marinomonas ostreistagni sp. nov. is proposed to accommodate this bacterium, with strain UST010306-043T (=JCM 13672T=NRRL B-41433T) as the type strain.
Kribbia dieselivorans gen. nov., sp. nov., a novel member of the family Intrasporangiaceae
Authors: Jung Seo-Youn , Kim Hee-Sik , Song Jae Jun , Lee Seung-Goo , Oh Tae-Kwang , Yoon Jung-Hoon
Published: September 2006

Two Gram-positive, catalase-positive, irregular short rod- or coccoid-shaped bacterial strains, N113Tand R33, were isolated from an enrichment culture with diesel oil-degradation activity and their taxonomic positions were investigated using a polyphasic approach. Phenotypic, phylogenetic and genetic similarities indicated that strains N113Tand R33 were representatives of the same species. Phylogenetic analysis based on 16S rRNA gene sequences showed that strains N113Tand R33 form a lineage independent from those of members of the familyIntrasporangiaceae. The novel isolates had cell-wall peptidoglycan based onmeso-diaminopimelic acid, MK-8(H4) as the predominant menaquinone and 10-methyl-C18 : 0, iso-C16 : 0, C18 : 1ω9c, C16 : 0and C18 : 0as the major cellular fatty acids. The DNA G+C contents were 69.6–69.9 mol%. These chemotaxonomic properties, together with phylogenetic distinctiveness, distinguish the two novel strains from recognized members of the familyIntrasporangiaceae. On the basis of phenotypic, phylogenetic and genetic data, strains N113T(=KCTC 19143T=JCM 13585T) and R33 are classified as representatives of a novel genus and species,Kribbia dieselivoransgen. nov., sp. nov., within the familyIntrasporangiaceae.
The L-Type voltage-gated calcium channel Cav1.3 mediates consolidation, but not extinction, of contextually conditioned fear in mice
Authors: McKinney Brandon C. , Murphy Geoffrey G.
Published: October 2006

Using pharmacological techniques, it has been demonstrated that both consolidation and extinction of Pavlovian fear conditioning are dependent to some extent upon L-type voltage-gated calcium channels (LVGCCs). Although these studies have successfully implicated LVGCCs in Pavlovian fear conditioning, they do not provide information about the specific LVGCC isoform involved. Both of the major LVGCC subtypes found in the brain (Cav1.2 and Cav1.3) are targets of the pharmacological manipulations used in earlier work. In this study, we used mice in which the gene for the pore-forming subunit (α1D) Cav1.3 was deleted (Cav1.3 knockout mice) to elucidate its contribution to consolidation and extinction of conditioned fear. We find that Cav1.3 knockout mice exhibit significant impairments in consolidation of contextual fear conditioning. However, once sufficiently overtrained, the Cav1.3 knockout mice exhibit rates of extinction that are identical to that observed in wild-type mice. We also find that Cav1.3 knockout mice perform as well as wild-type mice on the hidden platform version of the Morris water maze, suggesting that the consolidation deficit in conditioned fear observed in the Cav1.3 knockout mice is not likely the result of an inability to encode the context, but may reflect an inability to make the association between the context and the unconditioned stimulus.
Staining Membrane-Bound Proteins with Ponceau S
Authors: Stochaj Wayne R. , Berkelman Tom , Laird Nancy
Published: October 2006

INTRODUCTION

Because Ponceau S is relatively insensitive (~1 μg of protein), only the most abundant proteins will be visible. However, it is a reversible stain that can be removed completely with H2O prior to processing the blots. After staining, a soft lead pencil can be used to record the presence of visible proteins and molecular-weight markers, which will help when aligning the proteins detected on the membrane by western analysis with those in a total protein-stained gel or membrane. Ponceau S is compatible with both nitrocellulose and PVDF membranes.
Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects
Authors: Aruna D. , Naidu M. U. R.
Published: September 2006

Aims

Ginkgo biloba is available as an over‐the‐counter drug and reported to cause haemorrhage when coadministered with other antiplatelet agents. We set out to study the interactions of G. biloba with cilostazol and clopidogrel.

Methods

A randomized, open‐label, crossover study of 10 healthy male volunteers. The dosage schedules were 120 mg G. biloba, 240 mg G. biloba, 100 mg cilostazol, 200 mg cilostazol, 75 mg clopidogrel, 150 mg clopidogrel, 120 mg G. biloba+ 100 mg cilostazol and 120 mg G. biloba+ 75 mg clopidogrel. Platelet aggregation, platelet count, bleeding time and clotting time were measured 0 and 6 h after drug administration. Platelet aggregation was performed using a dual channel aggregometer, by the turbimetric technique using adenosine diphosphate 5 µmol and 10 µmol, and collagen 1 µg ml−1.

Results

Platelet inhibition with the combination of G. biloba and clopidogrel or cilostazol was not statistically significant compared with individual doses of drugs, with all the three aggregants. There was significant (P < 0.05) potentiation of prolongation of bleeding time with the combination of cilostazol and G. biloba compared with individual doses of both the drugs. There was no significant change in clotting time and platelet count.

Conclusions

Coadministration of G. biloba either with cilostazol or clopidogrel did not enhance antiplatelet activity compared with individual agents. Ginkgo biloba potentiated the bleeding time prolongation effect of cilostazol. There was no significant correlation between prolongation of bleeding time and inhibition of platelet aggregation.
Lack of a pharmacokinetic interaction between steady‐state roflumilast and single‐dose midazolam in healthy subjects
Authors: Nassr Nassr , Lahu Gezim , Von Richter Oliver , Reutter Felix , Knoerzer Dietrich , Zech Karl , Erb Katharina A. , Schug Barbara , Blume Henning , Hermann Robert
Published: September 2006

What is already known about this subject

• Cytochrome P450 (CYP) 3A4 plays a prominent role in the metabolism of many drugs, which in turn implies, that changes in the activity of this enzyme caused by, for example, co‐administered drugs, might result in clinically significant drug interactions.

• Roflumilast, a targeted PDE4 inhibitor in clinical development for the treatment of COPD and asthma, is partly metabolized by CYP3A4, and thus may have the potential to inhibit its activity.

What this study adds

• The results of this study show that therapeutic steady‐state concentrations of roflumilast and its active metabolite roflumilast N‐oxide do not alter the disposition of the CYP3A substrate midazolam.

• Therefore, roflumilast treatment has a low susceptibility to alter the clearance of drugs metabolized by CYP3A4.

Aims

The aim of this study was to investigate the effects of roflumilast, an investigational PDE4 inhibitor for the treatment of COPD and asthma, on the pharmacokinetics of the CYP3A probe drug midazolam and its major metabolites.

Methods

In an open, randomized (for midazolam treatment sequence) study, 18 healthy male subjects received single doses of midazolam (2 mg oral and 1 mg i.v., 1 day apart) alone, repeated doses of roflumilast (500 µg once daily for 14 days) alone, and repeated doses of roflumilast together with single doses of midazolam (2 mg oral and 1 mg i.v., 1 day apart).

Results

A comparison of clearance and peak and systemic exposure to midazolam following administration of roflumilast indicated no effect of roflumilast dosed to steady state on the pharmacokinetics of midazolam. Point estimates (90% CI) were 0.97 (0.84, 1.13) for the AUC of i.v. midazolam and 0.98 (0.82, 1.17) for that of oral midazolam with and without roflumilast.

Conclusions

Therapeutic steady state concentrations of roflumilast and its N‐oxide do not alter the disposition of the CYP3A substrate midazolam in healthy subjects. This finding suggests that roflumilast is unlikely to alter the clearance of drugs that are metabolized by CYP3A4.
cDNA cloning and substrate specificity of equine tryptase, a possible mediator in equine heaves
Authors: Dacre K. J. , McAleese S. M. , Knight P. , McGorum B. C. , Pemberton A.D.
Published: October 2006

Background
Mast cell mediators are believed to play a central role in inflammatory lung disorders such as human allergic and occupational asthma. Equine heaves is characterized by reversible neutrophilic airway inflammation and airway obstruction, primarily due to bronchospasm and mucus hypersecretion, following exposure of susceptible horses to organic stable dusts. As such, heaves shares many similarities with human occupational dust‐induced asthma and therefore it is proposed that mast cells may also be implicated in the pathogenesis of heaves. Tryptase, a mast cell‐specific proteinase, can be used as an indicator of biological mast cell activity.

Objective
The aim of this study was to determine the cDNA sequence of equine tryptase and to investigate its substrate specificity in order to rationalize its enzymatic activity.

Methods
RT‐PCR cloning was used to sequence equine tryptase. Substrate specificity of equine tryptase was investigated using arginine and lysine containing substrates.

Results
The cDNA and deduced amino acid (Aa) sequences for equine tryptase shared strong identity with other tryptases. Unusually for a trypsin‐like proteinase however, equine tryptase has alanine at residue 216, rather than glycine, which confers increased arginine substrate specificity in vitro and may restrict fibrinogenolysis in vivo.

Conclusion
Cloning and sequencing of the mast cell proteinase equine tryptase will allow molecular probing of its expression in the lung of control and heaves‐affected horses. Further work is warranted to determine the biological relevance of the unique alanine 216 substitution in the molecular sequence of the equine tryptase substrate‐binding pocket.
Temporal and spatial variability in growth and condition of dab (Limanda limanda) and sprat (Sprattus sprattus) larvae in the Irish Sea
Authors: LEE ORLA , DANILOWICZ BRET S. , DICKEY‐COLLAS MARK
Published: September 2006

Variability in the high mortality rate during early life stages is considered to be one of the principal determinants of year‐class variability in fish stocks. The influence of water column stability on the spatial distribution of fish larvae and their prey is widely acknowledged. Water column stability may also impact growth through the early life history of fishes, and consequently alter the probability of survival to maturity by limiting susceptibility to predation and starvation. As a test of this concept, the variability in condition and growth of dab (Limanda limanda) and sprat (Sprattus sprattus) larvae was investigated in relation to seasonal stratification of the water column in the north‐western Irish Sea. RNA/DNA ratios and otolith microincrement analysis were used to estimate nutritional status and recent growth rates of larvae captured on four cruises in May and June of 1998 and 1999. Dab and sprat larvae were less abundant in 1999 and were in poorer condition with lower growth rates than in 1998. Dab larvae of <13 mm also exhibited spatial variability with higher RNA/DNA ratios at the seasonal tidal‐mixing front compared with stratified and mixed water masses. However, the growth and nutritional status of sprat larvae was uncorrelated to water column stability, meaning the more favourable feeding conditions generally associated with the stratified pool and tidal‐mixing front in the Irish Sea were not reflected in the growth and condition of these larvae. This suggests that the link between stability, production and larval growth is more complicated than inferred by some previous studies. The existence of spatio‐temporal heterogeneity in the growth and condition of these larvae has implications for larval survival and the recruitment success of these species in the Irish Sea.
Effects of floods on fish assemblages in an intermittent prairie stream
Authors: FRANSSEN NATHAN R. , GIDO KEITH B. , GUY CHRISTOPHER S. , TRIPE JEFF A. , SHRANK SALLY J. , STRAKOSH TIMOTHY R. , BERTRAND KATIE N. , FRANSSEN COURTNEY M. , PITTS KRISTEN L. , PAUKERT CRAIG P.
Published: October 2006

1. Floods are major disturbances to stream ecosystems that can kill or displace organisms and modify habitats. Many studies have reported changes in fish assemblages after a single flood, but few studies have evaluated the importance of timing and intensity of floods on long‐term fish assemblage dynamics.

2. We used a 10‐year dataset to evaluate the effects of floods on fishes in Kings Creek, an intermittent prairie stream in north‐eastern, Kansas, U.S.A. Samples were collected seasonally at two perennial headwater sites (1995–2005) and one perennial downstream flowing site (1997–2005) allowing us to evaluate the effects of floods at different locations within a watershed. In addition, four surveys during 2003 and 2004 sampled 3–5 km of stream between the long‐term study sites to evaluate the use of intermittent reaches of this stream.

3. Because of higher discharge and bed scouring at the downstream site, we predicted that the fish assemblage would have lowered species richness and abundance following floods. In contrast, we expected increased species richness and abundance at headwater sites because floods increase stream connectivity and create the potential for colonisation from downstream reaches.

4. Akaike Information Criteria (AIC) was used to select among candidate regression models that predicted species richness and abundance based on Julian date, time since floods, season and physical habitat at each site. At the downstream site, AIC weightings suggested Julian date was the best predictor of fish assemblage structure, but no model explained >16% of the variation in species richness or community structure. Variation explained by Julian date was primarily attributed to a long‐term pattern of declining abundance of common species. At the headwater sites, there was not a single candidate model selected to predict total species abundance and assemblage structure. AIC weightings suggested variation in assemblage structure was associated with either Julian date or local habitat characteristics.

5. Fishes rapidly colonised isolated or dry habitats following floods. This was evidenced by the occurrence of fishes in intermittent reaches and the positive association between maximum daily discharge and colonisation events at both headwater sites.

6. Our study suggests floods allow dispersal into intermittent habitats with little or no downstream displacement of fishes. Movement of fishes among habitats during flooding highlights the importance of maintaining connectivity of stream networks of low to medium order prairie streams.
Optimising enzymatic maceration in pretreatment of carrot juice concentrate by response surface methodology
Authors: Sun Ying , Wang Zhengfu , Wu Jihong , Chen Fang , Liao Xiaojun , Hu Xiaosong
Published: September 2006

In this paper, enzyme preparation for carrot pulp maceration was screened out and enzymatic maceration processing condition of the carrot pulp was optimised by response surface methodology for carrot juice concentrate. Pectinex Smash XXL was the best commercial enzyme preparation than Pectinex Ultra SP‐L, Pectinase FNP‐1 and cellulose FNC‐1 employed in the carrot juice processing in the study. The effect of enzyme concentration and incubation time and their complex interaction on juice β‐carotene content, juice yield and viscosity in the maceration process was studied by using experiments of central composite rotatable design. The results indicated that under the optimal conditions that the enzyme concentration was 100 mL t−1 and incubation time was 80 min, the juice β‐carotene content was ≥54.2 mg kg−1, the juice yield ≥63.5% and the juice viscosity ≤2.1 mPa S.
Sensitive and Specific Radioreceptor Assay for Calcitonin Gene‐Related Peptide
Authors: Wimalawansa Sunil J.
Published: September 2006

Calcitonin gene‐related peptide is a 37‐amino‐acid neuropeptide which has a direct action on the heart and is an extremely potent vasodilator. Immunoreactive calcitonin gene‐related peptide is present in plasma, cerebrospinal fluid and in other tissues. We have previously established the specific binding characteristics of this neuropeptide to the cerebellar membranes. This paper describes a sensitive, rapid and specific radioreceptor assay for the measurement of receptor‐active calcitonin gene‐related peptide in tissues and in plasma extracts using cerebellar membrane preparations as the binding agent. This assay should prove a valuable tool in studies of the physiology of this vasoactive neuropeptide and of its involvement in disease.
Role of Anterior Peri‐Third Ventricular Structures in the Regulation of Supraoptic Neuronal Activity and Neurohypophysical Hormone Secretion in the Rat
Authors: Leng G. , Blackburn R. E. , Dyball R. E. J. , Russell J. A.
Published: September 2006

Neurohypophysical hormone release, and the electrical activity of single neurons of the supraoptic nucleus, were monitored in urethane‐anaesthetized rats. Immediately after electrolytic lesions of the region anterior and ventral to the third ventricle (AV3V region), supraoptic neurons showed little spontaneous activity and their responses to ip injection of hypertonic saline were severely impaired; corresponding deficits were found in the secretion of both oxytocin and vasopressin. Similar deficits in oxytocin secretion were also found in rats following electrolytic lesions which destroyed all or part of the subfornical organ; however the effects of the lesions were not additive: rats with lesions of both the AV3V region and the subfornical organ region showed a similar degree of impairment of osmotically stimulated oxytocin secretion to rats with lesions of either site alone. Such deficits might occur either as a result of destruction of osmoresponsive projections to the magnocellular nuclei, or as a result of destruction of an afferent input which is essential for the full expression of the innate osmosensitivity of supraoptic neurons. To test the latter possibility, supraoptic neurons in AV3V‐lesioned rats were activated by continuous application of glutamate, and then tested with ip injection of hypertonic saline. Five of seven cells tested responded significantly to the hyperosmotic stimulus, though the responses were significantly weaker than observed in sham‐lesioned rats. We suggest that the innate osmosensitivity of supraoptic neurons does contribute to their responses to systemic osmotic stimulation, but that expression of this innate osmosensitivity requires inputs from the AV3V region and/or the subfornical organ, some of which may also be osmoresponsive. Electrical stimulus pulses applied to the AV3V region influenced the electrical activity of most supraoptic neurons strongly: the predominant response was a short‐latency, short‐duration inhibition followed by long‐latency, long‐duration excitation. Whereas intracerebroventricular administration of the angiotensin II antagonist saralasin reduced spontaneous or osmotically induced activity of supraoptic neurons, the neuronal responses to AV3V stimulation were impaired only with relatively high doses of saralasin. We conclude that angiotensin ll‐sensitive neurons are an important component of the afferent pathways that sustain the excitability of supraoptic neurons, but that angiotensin is probably not the major transmitter of the projection from the AV3V region to the supraoptic nucleus.
Nα‐Acetyl‐Vasopressin‐ and Nα‐Acetyl‐Oxytocin‐Like Substances: Isolation and Characterization in the Rat Neurointermediate Pituitary and Presence in the Brain
Authors: Liu Bin , Burbach J. Peter H.
Published: September 2006

Post‐translational modifications of vasopressin and oxytocin in pituitary and brain were investigated in view of recent evidence that oxytocin is partly Nα‐acetyfated in the bovine pineal gland. Two peptides were isolated from the neurointermediate lobe of the rat pituitary gland and characterized as Nα‐acetyl‐vasopressin and Nα‐acetyl‐oxytocin, based on chromatographic and immunological properties as well as the blocked N‐terminus. In the neurointermediate pituitary the acetylated forms represented approximately 1% of the vasopressin and oxytocin contents. These two peptides were also detected in some, but not all, investigated brain areas. The highest degree of acetylation was found in the pineal gland. In all regions acetylation of oxytocin was more abundant than that of vasopressin. The data indicate that acetylation of vasopressin and oxytocin generally occurs as a post‐translational modification. They support the concept that acetylation may represent a mechanism aimed to control bioactivity of the neurohypophyseal hormones.
The Carboxy‐Terminal Glycopeptide of the Vasopressin Precursor in the Guinea‐Pig: Release Studies Using a Specific and Sensitive Homologous Radioimmunoassay
Authors: Fairhall K. M. , Robinson I. C. A. F.
Published: September 2006

The glycopeptide corresponding to the C‐terminal portion of the vasopressin precursor (CPP)has been isolated from guinea‐pig posterior pituitary glands and used to generate a specific and sensitive radioimmunoassay. The antiserum is directed to the peptide rather than sugar moieties, and detects two components in pituitary extracts: CPP itself, and a biosynthetic intermediate (NP‐CPP) containing both neurophysin and CPP sequences. Release of CPP from neurointermediate lobes incubated in vitro was stimulated five‐fold by high K+ in a Ca2+ dependent manner: in vivo studies suggest that CPP is released under conditions stimulating vasopressin release. Chronic dehydration depleted neural lobe stores of CPP in parallel with other vasopressin‐related components, and plasma levels of CPP were raised from 68±18 to 320 + 89 fmol/ml (SEM, n = 6). In anaesthetized guinea‐pigs, intraperitoneal injections of increasingamounts of hypertonic saline increased plasma levels of CPP in a graded manner compared with isotonic saline injections. Acute haemorrhage also stimulated CPP release into plasma, and the half‐time of clearance of CPP after infusion to steady state levels in guinea‐pig plasma was 24 min. Cerebrospinal fluid withdrawn from the cisterna magna also contained detectable amounts of CPP (390 + 25 fmol/ml) suggesting that CPP is released from both hypophysical and extra‐hypophysical projections. This assay may now be used to study the biosynthesis, processing and release of endogenous CPP under different physiological conditions.
Ultradian Rhythm of Growth Hormone Secretion in Unrestrained, Conscious Male Rabbits: Role of Endogenous Somatostatint†
Authors: Minamitani Naoto , Chihara Kazuo , Kaji Hidesuke , Kodama Hitoshi , Kita Tetsuya , Fujita Takuo
Published: September 2006

The profiles of growth hormone (GH) secretion were examined by obtaining serial blood samples every 15 min for a 5 to 24 h observation period from freely‐moving, conscious male rabbits chronically implanted with a right atrial cannula. The effects of restraint or surgical stress on GH secretion were also investigated in these animals. Four days after cannulation of the right atrium, plasma GH levels remained low without oscillation, during a 5 h observation period (1100 to 1600 h) with the mean (± SEM) value of 1.6±0.2 ng/ml. Individual rabbits exhibited a spontaneous, pulsatile GH secretion 7 days after the surgery. Mean 6 h GH levels were 5.6 ± 0.8 ng/ml at 7 days after the surgery, 6.3 ± 0.6 ng/ml at 14 days and 7.0 ± 1.2 ng/ml at 28 days. Therefore, the animals, 7 to 14 days after cannulation, were used to analyse the pulsatile pattern of GH secretion throughout 6 to 24 h. Two episodes of 45 min immobilization stress, separated by 75 min, caused a complete suppression of the spontaneous GH secretion (mean 6 h GH levels, 2.2 ± 0.1 ng/ml vs control, 5.0 ± 0.5 ng/ml, P<0.01). No surges appeared after the first restraint stress. In 14 non‐treated rabbits, plasma GH levels fluctuated in an episodic manner throughout the study with the peaks of 14.2 + 0.7 ng/ml, the nadirs of 2.6 ± 0.2 ng/ml and the peak to peak intervals of 2.20 ± 0.17 h. The iv administration of normal goat λ‐globulin (NGG) affected neither GH secretory patterns nor baseline levels of plasma GH. In contrast, the iv administration of anti‐sornatostatin goat λ‐globulin (ASG) caused a significant increase in the amplitude of plasma GH peaks (38.8±1.9 vs NGG‐treated, 13.7 ± 0.8 ng/ml, P<0.001) as well as the trough level (13.5 ± 0.6 vs NGG, 2.9 ± 0.1 ng/ml, P<0.001) during a 24 h observation period. Also, ASG treatment increased numbers of plasma GH peaks per day (18.8±2.7 vs NGG, 12.2 ± 0.8, P < 0.05) with concomitant shortening of the peak to peak interval (1.25 ± 0.10 vs NGG, 2.03±0.12h, P<0.01).

These findings suggest: 1) that GH is episodically secreted throughout the day in conscious male rabbits, 2) that surgical and restraint stresses suppress the spontaneous GH secretion, and 3) that endogenous somatostatin might rather play a tonic inhibitory role in GH release in conscious male rabbits, since ASG treatment resulted in sustained marked increases of plasma GH levels irrespective of the stage in GH pulsatile rhythm.
Adrenergic and Noradrenergic Regulation of Pulsatile Luteinizing Hormone Release*
Authors: Gallo Robert V. , Bona‐Gallo Antonella , O'Sullivan David
Published: September 2006

The object of this study was to further define the roles of both norepinephrine (NE) and epinephrine (EPIN) in regulating pulsatile luteinizing hormone (LH) release in 4‐day ovariectomized rats, in particular to examine the effect of decreasing NE synthesis on pulsatile LH secretion in animals with already greatly depleted levels of brain EPIN. Rats were injected ip with vehicle or drug at ‐27, ‐20, ‐5 and ‐ 3 h relative to the onset of a 3‐h blood sampling period. Hypothalamic‐preoptic area (HPOA) levels of NE and EPIN were determined by high‐performance liquid chromatography. Compared to controls, FLA‐63 (25 mg/kg, a dopamine‐ß‐ hydroxylase inhibitor), given at ‐ 3 h, produced 50% and 22% declines in HPOA‐NE and EPIN, respectively, and reductions in pulse amplitude and frequency. LY134046 (50 mg/kg, a phenylethanolamine N‐methyltransferase inhibitor), given at ‐ 27, ‐ 20 and ‐ 5 h, or ‐27, ‐20, ‐5 and ‐3 h, produced no change in NE, 88% and 86% declines in EPIN, respectively, and reductions in pulse frequency only. Each LY134046 treatment protocol produced the same decline in EPIN and pulse frequency. Thus, EPIN levels were maximally decreased by three LY134046 injections. When rats were given LY134046 at ‐27, ‐20 and ‐5 h, and FLA‐63 at ‐3 h, compared to rats treated with LY134046 alone, there was no further decrease in HPOA‐EPIN (82% decline), a 46% decline in NE, a further reduction in pulse frequency and a reduction in pulse amplitude. This further suppression of LH release must be due to a reduction in HPOA‐NE levels since no further decrease in EPIN levels occurred. These data demonstrate within the same animal that NE and EPIN are both stimulatory to pulsatile LH release. NE stimulates the amplitude and frequency, and EPIN stimulates the frequency of pulsatile LH secretion.