bluuebunny/crossref_metadata_2025 huggingface dataset:
von Willebrand disease in women with menorrhagia: a systematic review
Authors: Shankar Meena , Lee Christine A. , Sabin Caroline A. , Economides Demetrios L. , Kadir Rezan A.
Published: December 2004

Objective  To determine the prevalence of von Willebrand disease in women presenting with menorrhagia.

Design  Systematic review of studies evaluating the prevalence of von Willebrand disease in women with menorrhagia.

Setting  Hospital outpatient clinics (mainly gynaecological) and population surveys.

Population  Women presenting with menorrhagia.

Methods  Relevant studies were extracted from MEDLINE search, bibliographies of identified articles and published proceedings of meetings and conferences.

Main outcome measures  Number of women with von Willebrand disease.

Results  Eleven studies were included, totalling 988 women with menorrhagia. One hundred and thirty‐one women were diagnosed to have von Willebrand disease with prevalences in individual studies ranging from 5% to 24%. The overall prevalence was 13% (95% CI 11–15.6%). The prevalence was higher in the European studies—18% (95% CI 15–23%) compared with that in North American studies—10% (95% CI 7.5–13%). This difference (P= 0.007) is likely to be the result of differences in the studies, which include method of recruitment of study population, method of assessing menstrual blood loss ethnic composition of study population, criteria for diagnosis and use of race‐ and ABO blood group‐specific values for von Willebrand factor.

Conclusions  The prevalence of von Willebrand disease is increased in women with menorrhagia and is the underlying cause in a small but significant group of women with menorrhagia across the world. Testing for this disorder should be considered when investigating women with menorrhagia, especially those of Caucasian origin, those with no obvious pelvic pathology or with additional bleeding symptoms.
Applying the Declining Population Paradigm: Diagnosing Causes of Poor Reproduction in the Marbled Murrelet
Authors: PEERY M. ZACHARIAH , BEISSINGER STEVEN R. , NEWMAN SCOTT H. , BURKETT ESTHER B. , WILLIAMS TONY D.
Published: December 2004

Abstract: We identified six approaches to diagnosing causes of population declines and illustrate the use of the most general one (“multiple competing hypotheses”) to determine which of three candidate limiting factors—food availability, nesting site availability, and nest predation—were responsible for the exceptionally poor reproduction of Marbled Murrelets ( Brachyramphus marmoratus) in central California. We predicted how six attributes of murrelet demography, behavior, and physiology should be affected by the candidate limiting factors and tested predictions with field data collected over 2 years. The average proportion of breeders, as estimated with radiotelemetry, was low (0.31) and varied significantly between years: 0.11 in 2000 and 0.50 in 2001. Murrelets spent significantly more time foraging in 2000 than in 2001, suggesting that low food availability limited breeding in 2000. In 2001, 50% of radio‐marked murrelets nested and 67% of females were in breeding condition, suggesting that enough nest sites existed for much of the population to breed. However, rates of nest failure and nest predation were high (0.84 and 0.67–0.81, respectively) and few young were produced, even when a relatively high proportion of murrelets bred. Thus, we suggest that reproduction of Marbled Murrelets in central California is limited by food availability in some years and by nest predation in others, but apparently is not limited by availability of nesting sites. The multiple‐competing‐hypotheses approach provides a rigorous framework for identifying causes of population declines because it integrates multiple types of data sets and can incorporate elements of other commonly used approaches.
Combining Strategies to Select Reserves in Fragmented Landscapes
Authors: ROTHLEY KRISTINA D. , BERGER CLAIRE N. , GONZALEZ CATHERINE , WEBSTER ELISABETH M. , RUBENSTEIN DANIEL I.
Published: December 2004

Abstract:  In the identification of reserve networks in fragmented landscapes with limited species‐specific data at hand, one approach is to use selection criteria, such as patch size, to rank the habitat patches' conservation value and evaluate reserve‐network alternatives. These criteria are assumed to be reasonable surrogates for the true network objectives. Caution is warranted, however, because the relationships between the selection criteria and the reserve‐network objectives may be inconsistent. Conflicts are also likely to arise because no single reserve network will be optimal with respect to multiple objectives (or selection criteria) simultaneously. Instead, reserve planners must compromise between conflicting demands. We field tested the relationships between a variety of selection criteria and the objectives of a reserve network for the sandplain natural communities on Martha's Vineyard Island, Massachusetts (U.S.A.). Selection criteria that correlated with the reserve‐network objectives were used in a multi‐objective integer program to identify the 10‐patch reserve networks that were optimal with each objective independently and those that offered optimal tradeoffs between the reserve‐network objectives. From these 10‐patch networks, one can select a final reserve network that provides the preferred compromise between the objectives.
Limited Utility of mtDNA Markers for Determining Connectivity among Breeding and Overwintering Locations in Three Neotropical Migrant Birds
Authors: LOVETTE IRBY J. , CLEGG SONYA M. , SMITH THOMAS B.
Published: December 2004

Abstract: For the past two decades, population declines in Neotropical migrant songbirds have been both a flagship conservation issue and the subject of intensive research initiatives. Nonetheless, the design of effective conservation measures for Neotropical migrants has been hindered by a lack of information on where and how migrant populations are regulated. This problem stems in large part from the difficulty of following individual long‐distance migrants throughout their annual cycles. As a result, there has been increasing interest in using genetic markers to determine patterns of connectivity between particular breeding populations and overwintering regions. In species with geographically structured genetic variation during the breeding season, genetic markers can be used to determine the origin of migrating and overwintering individuals. This information on demographic connectivity could be then used to infer the locations or seasons contributing to population trends of currently unknown origin. To date, genetic markers (primarily mitochondrial DNA) have been used to survey only a few species of migratory songbirds, with varying success. To provide examples of the geographic scale at which mtDNA markers are likely to prove most relevant to Neotropical migrant conservation, we surveyed breeding‐season variation in North American populations of three long‐distance migrant taxa: the Yellow‐breasted Chat (Icteria virens), Common Yellowthroat (Geothlypis trichas), and Nashville Warbler (Vermivora ruficapilla). We then used this information to screen individuals sampled at overwintering sites in Mexico and Central America. Genetic structure was only found at the broadest continent‐wide scale in all three species, which allowed us to assign overwintering individuals to eastern or western breeding lineages but did not allow us to assign overwintering individuals to breeding populations of origin on a finer scale suitable for assaying local demographic trends. Owing to mitochondrial homogeneity among widely separated breeding locations, mtDNA markers (especially when used alone) are unlikely to provide a panacea for the problem of interseasonal connectivity among migrant songbirds.
Forest Fragmentation Increases Nest Predation in the Eurasian Treecreeper
Authors: HUHTA ESA , AHO TEIJA , JÄNTTI ARI , SUORSA PETRI , KUITUNEN MARKKU , NIKULA ARI , HAKKARAINEN HARRI
Published: December 2004

Abstract:  We used long‐term breeding data to monitor the influences of fragmentation and habitat composition at different spatial scales on the reproductive success of Eurasian Treecreepers (Certhia familiaris) breeding in nest boxes. We collected data from the same forest patches (2.7–65.1 ha in size) during seven breeding seasons. Nest predation varied considerably over the years and was the primary cause of nesting failure (mean annual rate of 21.6 ± 12.8%). Nest predation explained most of the variation in fledgling production during the study period. Landscape‐level fragmentation (radius of 500 m from territory center) affected nest predation more than did fragmentation on the territory scale (radius of 200 m from territory center). In general, nest loss due to predation in fragmented landscapes (32.4%) was almost threefold that of less fragmented (12.0%) landscapes. Of the habitat variables, predation rate correlated positively with the density of edges between forest and open land and with the proportion of sapling stands on the spatial scale of 500 m around a nest. In the core area of a territory (radius of 30 m from territory center), a high density of trees increased the frequency of nest predation. Further, a high proportion of agricultural land close to a nest site increased nest losses of treecreepers, probably because of a high degree of mustelid predation. Our results showed that the spatial scale on which we examined nest predation is important and that even within moderately fragmented landscapes it is possible to detect fragmentation‐related nest predation.
Influence of Elevation, Land Use, and Landscape Context on Patterns of Alien Plant Invasions along Roadsides in Protected Areas of South‐Central Chile
Authors: PAUCHARD ANÍBAL , ALABACK PAUL B.
Published: December 2004

Abstract:  Alien plant species are a growing concern in protected areas, yet little information is available on the role of roads as corridors for alien species and the effects of elevation, land use, and landscape context in these invasions. These concerns are of particular interest in temperate zones of South America, where protected areas have high concentrations of endemic species. We studied roadside alien plant communities and forest‐road edges in Villarrica and Huerquehue national parks in the Andean portion of south‐central Chile. We sampled alien species and their abundance along 21 km of roads inside parks and 22 km outside parks, using 500‐m roadside transects. We also sampled plant species and recorded their abundance in 15 transects located perpendicular to forest‐road edges in four forest types. Of the 66 alien species encountered along roadsides, 61 were present outside parks and 39 inside parks. Elevation and alien species richness along roadsides were significantly and negatively correlated (R2=−0.56, p < 0.001). Elevation, land use, and their interaction explained 74% of the variation in alien species richness along roadsides (p < 0.001). Transects located in pasture or disturbed secondary forests had significantly more alien species. We found no significant edge effect on native and alien species richness in any forest type. Few alien species have percolated into forest interiors. Native and alien diversity in edge plots were not related. Almost half the alien species belonged to three families and 85% were native to Eurasia. Our results suggest that alien species are moving into parks along road corridors and that elevation and land use of the matrix influence these invasion processes. Our findings corroborate the importance of early detection and control of invasive species in protected areas and highlight the importance of considering surrounding matrix land use in developing conservation strategies for reserves.
Effect of Invasive Plant Species on Temperate Wetland Plant Diversity
Authors: HOULAHAN JEFF E. , FINDLAY C. SCOTT
Published: December 2004

Abstract:  Invasive species are a major threat to global biodiversity and an important cause of biotic homogenization of ecosystems. Exotic plants have been identified as a particular concern because of the widely held belief that they competitively exclude native plant species. We examined the correlation between native and invasive species richness in 58 Ontario inland wetlands. The relationship between exotic and native species richness was positive even when we controlled for important covarying factors. In addition, we examined the relationship between the abundance of four native species ( Typha latifolia, T. angustifolia, Salix petiolaris, Nuphar variegatum) and four invasive species ( Lythrum salicaria, Hydrocharis morsus‐ranae, Phalaris arundinacea, Rhamnus frangula) that often dominate temperate wetlands and native and rare native species richness. Exotic species were no more likely to dominate a wetland than native species, and the proportion of dominant exotic species that had a significant negative effect on the native plant community was the same as the proportion of native species with a significant negative effect. We conclude that the key to conservation of inland wetland biodiversity is to discourage the spread of community dominants, regardless of geographical origin.
Usefulness of the Umbrella Species Concept as a Conservation Tool
Authors: ROBERGE JEAN‐MICHEL , ANGELSTAM PER
Published: December 2004

Abstract: In the face of limited funding, knowledge, and time for action, conservation efforts often rely on shortcuts for the maintenance of biodiversity. The umbrella species concept—proposed as a way to use species requirements as a basis for conservation planning—has recently received growing attention. We reviewed the literature to evaluate the concept's general usefulness. An umbrella species is defined as a species whose conservation is expected to confer protection to a large number of naturally co‐occurring species. This concept has been proposed as a tool for determining the minimum size for conservation areas, selecting sites to be included in reserve networks, and setting minimum standards for the composition, structure, and processes of ecosystems. Among the species suggested as potential umbrellas, most are large mammals and birds, but invertebrates are increasingly being considered. Eighteen research papers, most of which were based on hypothetical reserves or conservation networks, have provided evaluations of umbrella species schemes. These show that single‐species umbrellas cannot ensure the conservation of all co‐occurring species because some species are inevitably limited by ecological factors that are not relevant to the umbrella species. Moreover, they provide evidence that umbrella species from a given higher taxon may not necessarily confer protection to assemblages from other taxa. On the other hand, multi‐species strategies based on systematic selection procedures (e.g., the focal species approach) offer more compelling evidence of the usefulness of the concept. Evaluations of umbrella species schemes could be improved by including measures of population viability and data from many years, as well as by comparing the efficiency of the proposed scheme with alternative management strategies.
Wildfire Policy and Public Lands: Integrating Scientific Understanding with Social Concerns across Landscapes
Authors: DOMBECK MICHAEL P. , WILLIAMS JACK E. , WOOD CHRISTOPHER A.
Published: December 2004

Abstract: Efforts to suppress wildfires have become increasingly problematic in recent years as costs have risen, threats to firefighter safety have escalated, and detrimental impacts to ecosystems have multiplied. Wildfires that escape initial suppression often expand into large, high‐intensity summer blazes. Lost is the legacy of smaller fires that likely burned outside extreme weather and fuel conditions and resulted in less severe impacts. Despite the recognized need for modifications to existing policies and practices, resource agencies have been slow to respond. The spread of exotic species, climate change, and increasing human development in wildlands further complicates the issue. New policies are needed that integrate social and ecological needs across administrative boundaries and broad landscapes. These policies should promote a continuum of treatments with active management and reduction of fuel hazard in wildland‐urban interface zones and reintroduction of fire in wildlands. Management goals should focus on restoration of the long‐term ecological health of the land. Projects that reduce fuel loads but compromise the integrity of soil, water supplies, or watersheds will do more harm than good in the long run. Despite significant ecological concerns, learning to live with fire remains primarily a social issue that will require greater political leadership, agency innovation, public involvement, and community responsibility.
Patterns of Fire Severity and Forest Conditions in the Western Klamath Mountains, California
Authors: ODION DENNIS C. , FROST EVAN J. , STRITTHOLT JAMES R. , JIANG HONG , DELLASALA DOMINICK A. , MORITZ MAX A.
Published: December 2004

Abstract: The Klamath‐Siskiyou region of northwestern California and southwestern Oregon supports globally outstanding temperate biodiversity. Fire has been important in the evolutionary history that shaped this diversity, but recent human influences have altered the fire environment. We tested for modern human impacts on the fire regime by analyzing temporal patterns in fire extent and spatial patterns of fire severity in relation to vegetation structure, past fire occurrence, roads, and timber management in a 98,814‐ha area burned in 1987. Fire severity was mapped by the U.S. Department of Agriculture Forest Service as low, moderate, and high based on levels of canopy scorch and consumption. We found (1) a trend of increasing fire size in recent decades; (2) that overall fire‐severity proportions were 59% low, 29% moderate, and 12% high, which is comparable to both contemporary and historic fires in the region; (3) that multiaged, closed forests, the predominant vegetation, burned with much lower severity than did open forest and shrubby nonforest vegetation; (4) that considerably less high‐severity fire occurred where fire had previously be absent since 1920 in closed forests compared to where the forests had burned since 1920 (7% vs. 16%); (5) that nonforest vegetation burned with greater severity where there was a history of fire since 1920 and in roaded areas; and (6) that tree plantations experienced twice as much severe fire as multi‐aged forests. We concluded that fuel buildup in the absence of fire did not cause increased fire severity as hypothesized. Instead, fuel that is receptive to combustion may decrease in the long absence of fire in the closed forests of our study area, which will favor the fire regime that has maintained these forests. However, plantations are now found in one‐third of the roaded landscape. Together with warming climate, this may increase the size and severity of future fires, favoring further establishment of structurally and biologically simple plantations.
Integrating Landscape and Metapopulation Modeling Approaches: Viability of the Sharp‐Tailed Grouse in a Dynamic Landscape
Authors: AKÇAKAYA H. REŞIT , RADELOFF VOLKER C. , MLADENOFF DAVID J. , HE HONG S.
Published: December 2004

Abstract: The lack of management experience at the landscape scale and the limited feasibility of experiments at this scale have increased the use of scenario modeling to analyze the effects of different management actions on focal species. However, current modeling approaches are poorly suited for the analysis of viability in dynamic landscapes. Demographic (e.g., metapopulation) models of species living in these landscapes do not incorporate the variability in spatial patterns of early successional habitats, and landscape models have not been linked to population viability models. We link a landscape model to a metapopulation model and demonstrate the use of this model by analyzing the effect of forest management options on the viability of the Sharp‐tailed Grouse ( Tympanuchus phasianellus) in the Pine Barrens region of northwestern Wisconsin (U.S.A.). This approach allows viability analysis based on landscape dynamics brought about by processes such as succession, disturbances, and silviculture. The landscape component of the model (LANDIS) predicts forest landscape dynamics in the form of a time series of raster maps. We combined these maps into a time series of patch structures, which formed the dynamic spatial structure of the metapopulation component (RAMAS). Our results showed that the viability of Sharp‐tailed Grouse was sensitive to landscape dynamics and demographic variables such as fecundity and mortality. Ignoring the landscape dynamics gave overly optimistic results, and results based only on landscape dynamics (ignoring demography) lead to a different ranking of the management options than the ranking based on the more realistic model incorporating both landscape and demographic dynamics. Thus, models of species in dynamic landscapes must consider habitat and population dynamics simultaneously.
Forest Structure and Fire Susceptibility in Volcanic Landscapes of the Eastern High Cascades, Oregon
Authors: PERRY DAVID A. , JING HUANG , YOUNGBLOOD ANDREW , OETTER DOUG R.
Published: December 2004

Abstract: Multidimensional forest health initiatives—those designed to restore and protect forest integrity in the large sense—require, among other things, a better understanding of the relationship between the structure of forests and (1) their susceptibility to wildfires outside the range of natural variability and (2) the level of treatment (if any) required to lower susceptibility into an acceptable range. Within the ponderosa pine zone (Pinus ponderosa Dougl. ex Laws.) on the eastern slopes of Oregon's Cascade Range, an average of 86% of trees >5 cm in diameter at breast height (dbh) were less than 101 years old, the density of young trees correlating negatively with the density of old trees (>150 yrs). Species composition differed significantly between age classes: 72% of trees older than 150 years were ponderosa pine, whereas 83% of trees younger than 101 years were either grand fir (Abies grandis[Dougl.] Lindl.) or lodgepole pine (Pinus contortaDougl. ex). Loud Crown bulk density calculated to reflect the multiple canopy layer structure of these stands (CBDm) averaged 0.049 kg/m3, compared to 0.093 kg/m3using the standard approach ( p < 0.001), indicating that the latter significantly overestimates risk of active crown fire in stands with complex canopy structure. Nevertheless, modeling with CBDm predicts that under severe but plausible weather conditions (late summer fuel moisture and 48‐kph winds) crown kill would exceed 70% on 5 of 14 plots and 50% on an additional 5 plots. Models also predict that thinning trees of <20 cm dbh, coupled with controlled burning to reduce logging slash, would prevent torching (fire moving from the ground into crowns) on all plots, even under extreme fire conditions (low fuel moisture and 80‐kph winds). The amount of thinning required to prevent spread from crown to crown (active crown fire) varied widely among plots and depended on the degree of risk deemed acceptable. The relationship between stand basal area and the critical wind speed required to maintain active crown fire followed a negative power law (r2= 0.92), implying that over certain ranges small changes in basal area result in relatively large changes in susceptibility (assuming that changes in basal area are due to addition or removal of smaller trees). Landsat thematic mapper correlates reasonably well with CBDm ( r2= 0.80) and may provide a tool for rapid risk assessment.
Selection of Priority Areas for Fish Conservation in Guadiana River Basin, Iberian Peninsula
Authors: FILIPE A. F. , MARQUES T. A. , S. SEABRA  , TIAGO P. , RIBEIRO F. , DA COSTA L. MOREIRA , COWX I. G. , COLLARES‐PEREIRA M. J.
Published: December 2004

Abstract:  We developed a species‐by‐species approach for selecting protected areas for conservation of native freshwater fishes in semiarid regions, with catchment as the fundamental landscape unit for conservation efforts. Input data were composed of occurrences of freshwater fishes and landscape variables, and general quantification of occurrence, abundance, and endemicity of each fish species, to derive an index of conservation value for each species. Probability of occurrence of each species was performed with logistic‐regression analysis based on the landscape variables and extrapolated to the entire study area with a geographic information system. We estimated the conservation value of a stream reach by summing the predicted probability of occurrence of each species multiplied by its corresponding conservation value. To define and select reserves, we used a threshold that maximizes conservation value of the stream reaches but identifies the minimum number of reaches for protection. The approach was applied to native freshwater fishes in the Guadiana River basin (southern Iberian Peninsula), which are threatened by the construction of two major dams. We used the data from 1 sampling year (1999) to produce the models, which were validated based on data collected in 2000 and 2001. We used variables of climate (3), geomorphology (4), hydrology (7), and human influence (6) to build the predictive models, which revealed that native species occur over a wide range of riverine habitats, with stream order and location in the basin the most frequently selected variables. The conservation value of species varied considerably, with Anaecypris hispanica the highest‐ranked species. The catchments selected for reserves were the mainstream of the Guadiana River (upstream and downstream of the Alqueva and Pedrogão reservoirs) and the Degebe, Ardila, and Enxoé catchments. Our approach is a pragmatic way to address the urgent need to protect Guadiana native fish species in light of the ongoing anthropogenic degradation of aquatic environments.
Death Rides the Forest: Perceptions of Fire, Land Use, and Ecological Restoration of Western Forests
Authors: KAUFFMAN J. BOONE
Published: December 2004

Abstract: Large wild fires occurring in forests, grasslands, and chaparral in the last few years have aroused much public concern. Many have described these events as “catastrophes” that must be prevented through aggressive increases in forest thinning. Yet the real catastrophes are not the fires themselves but those land uses, in concert with fire‐suppression policies that have resulted in dramatic alterations to ecosystem structure and composition. The first step in the restoration of biological diversity (forest health) of western landscapes must be to implement changes in those factors that have caused degradation or are preventing recovery. This includes changes in policies and practices that have resulted in the current state of wildland ecosystems. Restoration entails much more than simple structural modifications achieved though mechanical means. Restoration should be undertaken at landscape scales and must allow for the occurrence of dominant ecosystem processes, such as the natural fire regimes achieved through natural and/or prescribed fires at appropriate temporal and spatial scales.
Characterization and functional role of voltage gated cation conductances in the glucagon‐like peptide‐1 secreting GLUTag cell line
Authors: Reimann F. , Maziarz M. , Flock G. , Habib A. M. , Drucker D. J. , Gribble F. M.
Published: December 2004

Glucagon‐like peptide‐1 (GLP‐1) is released from intestinal L‐cells in response to nutrient ingestion. It is currently under therapeutic evaluation because it enhances insulin secretion in type 2 diabetes. Previous studies using the GLP‐1 secreting cell line GLUTag have shown that the cells are electrically active, and that the action potential frequency is regulated by nutrients. In this study we characterize voltage gated currents underlying this electrical activity and correlate the electrophysiological findings with gene expression determined by microarrays. Whole cell voltage clamp experiments designed to separate different ionic components revealed rapidly inactivating sodium currents sensitive to tetrodotoxin, calcium currents sensitive to nifedipine and ω‐conotoxin GVIA, and sustained as well as rapidly inactivating potassium currents, which were sensitive to TEA and 4‐AP, respectively. In perforated patch experiments we also observed hyperpolarization‐activated currents which were inhibited by ZD7288. The amplitude of the sodium current was ∼10 times that of the other depolarizing currents and tetrodotoxin abolished action potential firing. In secretion experiments, however, nifedipine, but not tetrodotoxin, ω‐conotoxin GVIA or ZD7288, inhibited glucose‐induced GLP‐1 release. Consistent with this finding, the intracellular Ca2+ response to glucose was impaired by nifedipine but not by tetrodotoxin. Thus, in GLUTag cells, GLP‐1 release is not dependent on the firing of Na+‐carrying action potentials but requires membrane depolarization and Ca2+ entry through L‐type Ca2+ channels. Understanding the characteristics of the currents and the molecular identification of the underlying channels in GLP‐1 secreting cells might facilitate the development of agents to enhance GLP‐1 secretion in vivo.
Hypothalamic paraventricular nucleus differentially supports lumbar and renal sympathetic outflow in water‐deprived rats
Authors: Stocker Sean D. , Hunwick Kimberly J. , Toney Glenn M.
Published: December 2004

The present study sought to determine whether the hypothalamic paraventricular nucleus (PVN) contributes in a time‐dependent manner to the differential patterning of lumbar and renal sympathetic nerve activity (SNA) in water‐deprived rats. Mean arterial blood pressure (MAP) and both lumbar SNA (LSNA) and renal SNA (RSNA) were recorded simultaneously in control, 24 and 48 h water‐deprived rats, and the PVN was inhibited bilaterally with microinjection of the GABAA agonist muscimol (100 pmol in 100 nl per side). Inhibition of the PVN significantly decreased RSNA in 48 h water‐deprived rats but not in 24 h water‐deprived or control rats (48 h, −17 ± 4%; 24 h, −2 ± 5%; control, 4 ± 6%; P < 0.05). In addition, injection of muscimol significantly decreased LSNA in 48 and 24 h water‐deprived rats but not in control rats (48 h, −41 ± 4%; 24 h, −14 ± 6%; control, −3 ± 2%; P < 0.05). Interestingly, the decrease in LSNA was significantly greater than the decrease in RSNA of 24 and 48 h water‐deprived rats (P < 0.05). Inhibition of the PVN also significantly decreased MAP to a greater extent in 48 and 24 h water‐deprived rats compared to control rats (48 h, −34 ± 5 mmHg; 24 h, −26 ± 4 mmHg; control, −15 ± 3 mmHg; P < 0.05). When 48 h water‐deprived rats were acutely rehydrated by giving access to tap water 2 h before experiments, inhibition of the PVN with muscimol did not alter LSNA (−12 ± 8%) or RSNA (7 ± 4%) but did produce a small decrease in MAP (−15 ± 4 mmHg) that was not different from control rats. In a parallel set of experiments, acute rehydration of 48 h water‐deprived rats significantly attenuated the increased Fos immunoreactivity in PVN neurones that project to the spinal cord or rostral ventrolateral medulla. Collectively, the present findings suggest that PVN autonomic neurones are synaptically influenced during water deprivation, and that these neurones differentially contribute to LSNA and RSNA in water‐deprived rats.
Protein synthesis rates in human muscles: neither anatomical location nor fibre‐type composition are major determinants
Authors: Mittendorfer B. , Andersen J. L. , Plomgaard P. , Saltin B. , Babraj J. A. , Smith K. , Rennie M. J.
Published: December 2004

In many animals the rate of protein synthesis is higher in slow‐twitch, oxidative than fast‐twitch, glycolytic muscles. To discover if muscles in the human body also show such differences, we measured [13C]leucine incorporation into proteins of anatomically distinct muscles of markedly different fibre‐type composition (vastus lateralis, triceps, soleus) after an overnight fast and during infusion of a mixed amino acid solution (75 mg amino acids kg−1 h−1) in nine healthy, young men. Type‐1 fibres contributed 83 ± 4% (mean ±s.e.m.) of total fibres in soleus, 59 ± 3% in vastus lateralis and 22 ± 2% in triceps. The basal myofibrillar and sarcoplasmic protein fractional synthetic rates (FSR, % h−1) were 0.034 ± 0.001 and 0.064 ± 0.001 (soleus), 0.031 ± 0.001 and 0.060 ± 0.001 (vastus), and 0.027 ± 0.001 and 0.055 ± 0.001 (triceps). During amino acid infusion, myofibrillar protein FSR increased to 3‐fold, and sarcoplasmic to 2‐fold basal values (P < 0.001). The differences between muscles, although significant statistically (triceps versus soleus and vastus lateralis, P < 0.05), were within ∼15%, biologically probably insignificant. The rates of collagen synthesis were not affected by amino acid infusion and varied by < 5% between muscles and experimental conditions.
Cyclic AMP‐dependent Cl− secretion induced by thromboxane A2 in isolated human colon
Authors: Horikawa Naoki , Suzuki Tomoyuki , Uchiumi Takaoki , Minamimura Tetsuji , Tsukada Kazuhiro , Takeguchi Noriaki , Sakai Hideki
Published: December 2004

Increased release of thromboxane A2 (TXA2) has been shown to be involved in inflammatory bowel diseases. In the present study, we have investigated the effect of a stable TXA2 analogue (STA2) on the electrical parameters in isolated human colonic mucosa. In the human mucosa set between Ussing chambers, STA2 stimulated Cl− secretion in a concentration‐dependent manner with an EC50 of 0.06 μm. The STA2‐induced Cl− secretion was significantly inhibited by ONO‐3708 (10 μm), a specific TXA2 receptor antagonist. The effect of STA2 (0.3 μm) was independent of the colonic segment from which the tissue was obtained, from caecum to rectum. Chromanol 293B, an inhibitor of the cAMP‐dependent KvLQT1 channel, attenuated the STA2‐induced Cl− secretion in the human colonic mucosa (IC50 value 1.18 μm). We found that KvLQT1 mRNA and protein were expressed in all the tested segments of the human colon. The STA2‐induced Cl− secretion was significantly inhibited by 8‐bromo‐2′‐monobutyryladenosine‐3′,5′‐cyclic monophosphorothioate (50 μm), a membrane‐permeant cAMP antagonist. STA2 (0.3 μm) significantly increased the intracellular cAMP levels and the short‐circuit current via TXA2 receptor in a human colonic cell line. These results suggest that the TXA2‐induced Cl− secretion in the colon is mediated via the cAMP pathway in addition to the Ca2+–calmodulin pathway which was previously reported.
Cardiac troponin C (TnC) and a site I skeletal TnC mutant alter Ca2+versus crossbridge contribution to force in rabbit skeletal fibres
Authors: Moreno‐Gonzalez Alicia , Fredlund Jennifer , Regnier Michael
Published: December 2004

We studied the relative contributions of Ca2+ binding to troponin C (TnC) and myosin binding to actin in activating thin filaments of rabbit psoas fibres. The ability of Ca2+ to activate thin filaments was reduced by replacing native TnC with cardiac TnC (cTnC) or a site I‐inactive skeletal TnC mutant (xsTnC). Acto‐myosin (crossbridge) interaction was either inhibited using N‐benzyl‐p‐toluene sulphonamide (BTS) or enhanced by lowering [ATP] from 5.0 to 0.5 mm. Reconstitution with cTnC reduced maximal force (Fmax) by ∼1/3 and the Ca2+ sensitivity of force (pCa50) by 0.17 unit (P < 0.001), while reconstitution with xsTnC reduced Fmax by ∼2/3 and pCa50 by 0.19 unit (P < 0.001). In both cases the apparent cooperativity of activation (nH) was greatly decreased. In control fibres 3 μm BTS inhibited force to 57% of Fmax while in fibres reconstituted with cTnC or xsTnC, reconstituted maximal force (rFmax) was inhibited to 8.8% and 14.3%, respectively. Under control conditions 3 μm BTS significantly decreased the pCa50, but this effect was considerably reduced in cTnC reconstituted fibres, and eliminated in xsTnC reconstituted fibres. In contrast, when crossbridge cycle kinetics were slowed by lowering [ATP] from 5 to 0.5 mm in xsTnC reconstituted fibres, pCa50 and nH were increased towards control values. Combined, our results demonstrate that when the ability of Ca2+ binding to activate thin filaments is compromised, the relative contribution of strong crossbridges to maintain thin filament activation is increased. Furthermore, the data suggest that at low levels of Ca2+, the level of thin filament activation is determined primarily by the direct effects of Ca2+ on tropomyosin mobility, while at higher levels of Ca2+ the final level of thin filament activation is primarily determined by strong cycling crossbridges.
Postnatal masculinization alters the HPA axis phenotype in the adult female rat
Authors: Seale J. V. , Wood S. A. , Atkinson H. C. , Harbuz M. S. , Lightman S. L.
Published: December 2004

The ability of postnatal testosterone propionate (TP) to masculinize both behaviour and gonadal cyclicity in the female rat is well documented. We have investigated whether postnatal androgen also has an organizational effect on another sexually dimorphic neuroendocrine system – the hypothalamo‐pituitary‐adrenal (HPA) axis. Female rats were exposed to a single injection of testosterone propionate (TP) or oil within 24 h of birth. As adults, rats were either ovariectomized and given 17β‐oestradiol replacement (OVXE2) or sham ovariectomized with cholesterol implants (SHOVX). An automated sampling system collected blood from unanaesthetized adult female rats every 10 min over a 24‐h period, during a mild psychological stress (noise) and following an immunological lipopolysaccharide stress (LPS). Neonatal TP‐treated SHOVX rats had a significant reduction in the number, height, frequency and amplitude of corticosterone pulses over the basal 24‐h period, compared to both the neonatal oil‐treated and TP‐treated OVXE2 animals. The corticosterone response to both noise and LPS was also significantly decreased for the TP‐treated SHOVX females. Three hours post‐LPS administration, TP females had significantly lower values of paraventricular nucleus (PVN) corticotrophin releasing hormone (CRH), arginine vasopressin (AVP) and anterior pituitary proopiomelanocortin (POMC) mRNAs and greater PVN glucocorticoid receptor (GR) mRNA expression compared to the oil‐treated controls. E2 replacement in adult TP rats normalized all the mRNA levels, except for PVN GR mRNA which did fall towards the levels of the oil‐control animals. A single injection of TP within 24 h of birth disrupts the development of the characteristic female pattern of corticosterone secretion and the normal female HPA response to stress, resulting in a pattern similar to that seen in males. These effects can be reversed by E2 treatment in the adult TP female rat.
A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development
Authors: Zambrano E. , Rodríguez‐González G. L. , Guzmán C. , García‐Becerra R. , Boeck L. , Díaz L. , Menjivar M. , Larrea F. , Nathanielsz P. W.
Published: December 2004

Nutrient restriction during pregnancy and lactation impairs growth and development. Recent studies demonstrate long‐term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. We determined effects of maternal protein restriction (50% control protein intake) during fetal development and/or lactation in rats on the reproductive system of male progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups: CC, RR, CR and RC. We report findings in male offspring only. Maternal protein restriction increased maternal serum corticosterone, oestradiol and testosterone (T) concentrations at 19 days gestation. Pup birth weight was unchanged but ano‐genital distance was increased by maternal protein restriction (P < 0.05). Testicular descent was delayed 4.4 days in RR, 2.1 days in CR and 2.2 days in RC and was not related to body weight. Body weight and testis weight were reduced in RR and CR groups at all ages with the exception of CR testis weight at 270 days postnatal age (PN). At 70 days PN luteinizing hormone and T concentrations were reduced in RR, CR and RC. mRNA for P450 side chain cleavage (P450scc) was reduced in RR and CR at 21 days PN but was unchanged at 70 days PN. Fertility rate was reduced at 270 days PN in RC and sperm count in RR and RC. We conclude that maternal protein delays sexual maturation in male rats and that some effects only emerge in later life.
The ATP hydrolysis and phosphate release steps control the time course of force development in rabbit skeletal muscle
Authors: Sleep John , Irving Malcolm , Burton Kevin
Published: December 2004

The time course of isometric force development following photolytic release of ATP in the presence of Ca2+ was characterized in single skinned fibres from rabbit psoas muscle. Pre‐photolysis force was minimized using apyrase to remove contaminating ATP and ADP. After the initial force rise induced by ATP release, a rapid shortening ramp terminated by a step stretch to the original length was imposed, and the time course of the subsequent force redevelopment was again characterized. Force development after ATP release was accurately described by a lag phase followed by one or two exponential components. At 20°C, the lag was 5.6 ± 0.4 ms (s.e.m., n= 11), and the force rise was well fitted by a single exponential with rate constant 71 ± 4 s−1. Force redevelopment after shortening–restretch began from about half the plateau force level, and its single‐exponential rate constant was 68 ± 3 s−1, very similar to that following ATP release. When fibres were activated by the addition of Ca2+ in ATP‐containing solution, force developed more slowly, and the rate constant for force redevelopment following shortening–restretch reached a maximum value of 38 ± 4 s−1 (n= 6) after about 6 s of activation. This lower value may be associated with progressive sarcomere disorder at elevated temperature. Force development following ATP release was much slower at 5°C than at 20°C. The rate constant of a single‐exponential fit to the force rise was 4.3 ± 0.4 s−1 (n= 22), and this was again similar to that after shortening–restretch in the same activation at this temperature, 3.8 ± 0.2 s−1. We conclude that force development after ATP release and shortening–restretch are controlled by the same steps in the actin–myosin ATPase cycle. The present results and much previous work on mechanical–chemical coupling in muscle can be explained by a kinetic scheme in which force is generated by a rapid conformational change bracketed by two biochemical steps with similar rate constants – ATP hydrolysis and the release of inorganic phosphate – both of which combine to control the rate of force development.
Kinetics of muscle contraction and actomyosin NTP hydrolysis from rabbit using a series of metal–nucleotide substrates
Authors: Burton Kevin , White Howard , Sleep John
Published: December 2004

Mechanical properties of skinned single fibres from rabbit psoas muscle have been correlated with biochemical steps in the cross‐bridge cycle using a series of metal–nucleotide (Me·NTP) substrates (Mn2+ or Ni2+ substituted for Mg2+; CTP or ITP for ATP) and inorganic phosphate. Measurements were made of the rate of force redevelopment following (1) slack tests in which force recovery followed a period of unloaded shortening, or (2) ramp shortening at low load terminated by a rapid restretch. The form and rate of force recovery were described as the sum of two exponential functions. Actomyosin‐Subfragment 1 (acto‐S1) Me·NTPase activity and Me·NDP release were monitored under the same conditions as the fibre experiments. Mn·ATP and Mg·CTP both supported contraction well and maintained good striation order. Relative to Mg·ATP, they increased the rates and Me·NTPase activity of cross‐linked acto‐S1 and the fast component of a double‐exponential fit to force recovery by ∼50% and 10–35%, respectively, while shortening velocity was moderately reduced (by 20–30%). Phosphate also increased the rate of the fast component of force recovery. In contrast to Mn2+ and CTP, Ni·ATP and Mg·ITP did not support contraction well and caused striations to become disordered. The rates of force recovery and Me·NTPase activity were less than for Mg·ATP (by 40–80% and 50–85%, respectively), while shortening velocity was greatly reduced (by ∼80%). Dissociation of ADP from acto‐S1 was little affected by Ni2+, suggesting that Ni·ADP dissociation does not account for the large reduction in shortening velocity. The different effects of Ni2+ and Mn2+ were also observed during brief activations elicited by photolytic release of ATP. These results confirm that at least one rate‐limiting step is shared by acto‐S1 ATPase activity and force development. Our results are consistent with a dual rate‐limitation model in which the rate of force recovery is limited by both NTP cleavage and phosphate release, with their relative contributions and apparent rate constants influenced by an intervening rapid force‐generating transition.
Ionic conductances in sustentacular cells of the mouse olfactory epithelium
Authors: Vogalis Fivos , Hegg Colleen C. , Lucero Mary T.
Published: December 2004

The electrical properties of sustentacular cells (SCs) in the olfactory epithelium (OE) were investigated in tissue slices taken from neonatal mice (P0–P4). Conventional whole‐cell recordings were obtained from SCs and also from olfactory receptor neurones (ORNs) insitu. SCs had a larger apparent cell capacitance (Ccell) (18.6 ± 0.5 pF) than ORNs (4.4 ± 0.4 pF) and a lower apparent membrane resistance (Rm) (160 ± 11 MΩversus 664 ± 195 MΩ, respectively). When corrected for a seal resistance of 1 GΩ, these mean Rm values were increased to 190 MΩ and 2 GΩ in SCs and ORNs, respectively. SCs generated a TTX (1 μm)‐resistant voltage‐activated Na+ current (INa) that had a peak density at −38 mV of −44 pA pF−1 and supported action potential firing. Peak current density of INa in neurones was 510 ± 96 pA pF−1. The outward K+ current in SCs was composed (> 70%) of a TEA (2 mm)‐sensitive component that was mediated by the opening of large‐conductance (237 ± 10 pS; BK) channels. The resting leak conductance (gL) of SCs was permeable to monovalent cations and anions and was largely inhibited by substitution of external Na+ with NMDG and by internal F− with gluconate. gL deactivated up to 50% at potentials negative of −70 mV and was inhibited by 18β‐glycyrrhetinic acid (20 μm). SCs were identified using fluorescent dyes (Lucifer Yellow and Alexa Fluor 488) in the whole‐cell patch pipette‐filling solution. Our findings indicate that SCs in the OE of neonates are electrically excitable and are distinguishable from neurones by a having a resting gL.