bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of iron overload and dietary fat on indices of oxidative stress and hepatic fibrogenesis in rats
Authors: Brown Kyle E. , Dennery Phyllis A. , Ridnour Lisa A. , Fimmel Claus J. , Kladney Raleigh D. , Brunt Elizabeth M. , Spitz Douglas R.
Published: July 2003

Background/Aims: Oxidative stress is presumed to play an important role in hepatic fibrogenesis. Diets high in polyunsaturated fatty acids (PUFA) enhance fibrosis and have been associated with increased oxidative damage in some models of liver injury. The aim of this study was to determine the effects of dietary fat of varying PUFA content on iron‐induced oxidative stress and fibrosis.

Methods: Rats were given parenteral iron and diets supplemented with coconut oil, safflower oil or menhaden oil.

Results: Hepatic iron overload was associated with induction of heme oxygenase‐1, a sensitive indicator of oxidative stress, and with modest increases in hydroxyproline and procollagen I mRNA levels without histologically evident fibrosis, all of which were unaffected by dietary fat. In addition, iron loading was associated with increases in cysteine, γ‐glutamylcysteine and glutathione. Dietary fat brought about the expected alterations in peroxidizability, but did not alter indices of oxidative damage.

Conclusion: These data highlight the distinction between oxidative stress and oxidative damage and suggest that the former is not sufficient to elicit overt fibrosis. Furthermore, while hepatic iron overload leads to oxidative stress, there is an associated upregulation of antioxidant defenses involving thiol metabolism that may be a critical factor limiting the accumulation of oxidative damage.
Prolongation of QTc interval: relationship with etiology and severity of liver disease, mortality and liver transplantation
Authors: Bal Jasdeep Singh , Thuluvath Paul J
Published: July 2003

Background: A prolonged QTc interval has been reported in patients with liver disease. The objectives of our study were to determine whether a prolonged QTc interval was an independent predictor of mortality in patients with cirrhosis and to examine the effect of liver transplantation (LT) on QTc interval.

Patients and methods: We retrospectively studied two cohorts of patients – QTc interval was measured in 409 patients (pre‐transplant group), and in 162 patients (transplant group) before and 6 months after LT. QT interval (mean) corrected (QTc) for ventricular rate was read from a 12‐lead EKG. Patients with known cardiovascular disease or other risk factors that are known to cause a prolonged QTc interval were excluded.

Results: Pre‐transplant group. One hundred and sixty‐two patients (40%) had a prolonged QTc interval (>440 ms). By binary logistic regression, age (P=0.005), alcoholic cirrhosis (P=0.007) and Child–Pugh scores (P=0.007) were independent predictors of prolonged QTc interval. Sixty‐six patients died during a mean follow‐up of 8.9 years. Although the Kaplan–Meier survival curve showed a lower survival in patients with a prolonged QTc interval (P=0.03 by log rank test), when survival was adjusted for the Child–Pugh score by Cox regression survival analysis, there were no survival differences in patients with and without prolonged QTc interval. Cox regression analysis showed that the Child–Pugh score (hazard ratio 1.5, CI 1.3–1.6, s<0.001) was the only independent predictor of survival.

Transplant group. In this cohort, 91 patients (56%) had prolonged QTc (>440 ms) before LT. Mean QTc improved significantly after LT (429 ± 29 ms vs. 450 ± 39 ms P<0.002). Of the 91 patients with prolonged QTc, 50 (55%) normalized, three (3.3%) remained unchanged, 12 (13.3%) showed further prolongation, and 26 (28%) showed improvement but remained above normal limits. An additional nine patients who had normal QTc before LT developed prolonged QTc (>440 ms) after LT.

Conclusion: A prolonged QTc interval was common in patients with cirrhosis, but its presence had no independent effect on mortality. Prolonged QTc returns to normal values in about half of the patients after LT, suggesting that liver disease plays a role, but may not be the only factor in the pathogenesis of prolonged QTc.
No association between GSTP1 gene aberrant promoter methylation and prognosis in surgically resected hepatocellular carcinoma patients from the Basque Country (Northern Spain)
Authors: Anzola Monica , Cuevas Nerea , López‐Martínez Monica , Saiz Alberto , Burgos Juan José , Pancorbo Marian Martínez de
Published: July 2003

Aims: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, being linked etiologically to several factors. Glutathione‐S‐transferases (GSTs) are a family of enzymes that play an important role in detoxification. Hypermethylation of regulatory sequences at glutathione‐S‐transferase pi class gene (GSTP1) has been found in different human tumor types. In this study, we have studied the methylation status of the GSTP1 promoter region in patients from the Basque Country (Northern Spain) by methylation‐specific PCR (MSP).

Methods and results: GSTP1 aberrant promoter methylation was present in 24 of 117 (20.5%) tumor samples being associated with late stages of tumor progression. Patients with multiple HCCs showed different patterns of methylation, which could suggest a different clonal origin of multicentric HCC or different degrees of differentiation. No effect on disease‐free survival or overall survival was observed in patients with GSTP1 methylated who underwent curative resection.

Conclusions: We can conclude that GSTP1 promoter CpG island methylation appears to be a less common event during hepatocarcinogenesis in European populations than in Asian populations, being associated with late stages of tumor progression. These findings could also be useful to provide new therapeutic strategies through the use of demethylating agents.
High rate of long‐term virological response after a 1‐year course of interferon ± ribavirin in chronic hepatitis C relapsers. Results of a 191 patients randomized trial
Authors: Boucher Eveline J , Jacquelinet Sylvie , Canva Valérie , Turlin Bruno , Jacquelinet Christian , Colimon Ronald , Deugnier Yves , Guyader Dominique , Brissot Pierre
Published: July 2003

We investigated the long‐term efficacy of a 12‐month course of interferon (IFN)+ribavirin in chronic hepatitis C relapsers. We randomized 191 relapsers with a 2:1 ratio to receive 3 million units three times a week of interferon alpha (IFN α)‐2b+ribavirin (1–1.2 g/day) (group A=127 patients) or IFN α‐2b (group B=60 patients) of same dosage and duration for 1 year. General and hepatitis C data of group A and B patients were similar. The main goal of the study was to determine the rate of sustained virological response evaluated 1 year after treatment.

Results: Virological sustained response (SR) was 61% and 12% for groups A and B, respectively (P<0.001). A significant histological improvement was observed in both treatment groups. The Metavir activity score became significantly lower in the IFN+ribavirin group than in the IFN group (P<0/0001). The Metavir fibrosis scores remained unchanged. Also, at the end of the treatment, the virological response was 69% (88/127) for group A and 33% (20/60) for group B (P<0.001).

Conclusion: One‐year retreatment of relapsers with the combination of IFN+ribavirin led to 61% of virological SR and to a significant improvement of histological activity. Therefore, the therapeutic schedule presented here can be considered of particular interest for the retreatment of relapsers.
Fibrosis and glycogen stores depletion induced by prolonged biliary obstruction in the rat are ameliorated by metadoxine
Authors: Muriel Pablo , Deheza Rogelio
Published: July 2003

Background/Aims: To evaluate liver‐beneficial properties of metadoxine, not related with alcohol metabolism, bioactivation of external toxins or antioxidant mechanisms, the chronic bile duct ligation (BDL) model was used and results were compared with colchicine.

Methods: Seven groups (n=6) of male Wistar rats were used. Four groups were BDL and received metadoxine (60 mg/kg/12 h i.p.), colchicine (10 μg/rat/day/p.o.), both or vehicles; three groups were sham‐appropriate controls. Collagen content was determined by measuring hydroxyproline in liver samples; malondialdehyde (MDA) was used to estimate lipid peroxidation levels; glycogen was determined utilizing the anthrone reagent; gomory's trichromic stains of liver sections were performed.

Results: Collagen increased four‐fold by BDL, metadoxine, colchicine or both prevented fibrosis partially; MDA levels increased three‐fold by BDL and no treatment had any significant effect; glycogen was almost depleted in the cirrhotic group, metadoxine preserved glycogen; bilirubins, and alanine aminotransferase and γ‐glutamyltranspeptidase activities increased several‐fold in the BDL group, and both drugs prevented these effects partially. The histopathological analysis correlated with biochemical data.

Conclusions: Both compounds showed similar antifibrotic properties; metadoxine was more effective in preserving glycogen. Besides its antioxidant effects and its ability to induce alcohol metabolism, metadoxine possesses important antifibrotic and antinecrotic properties, and maintains energy stores efficiently.
Impact of high‐dose interferon induction and ribavirin therapy in patients with chronic hepatitis C relapsing after or not responding to interferon monotherapy
Authors: Steindl‐Munda Petra , Ferenci Peter , Brunner Harald , Nachbaur Karin , Datz Christian , Gschwantler Michael , Hofer Harald , Stauber Rudolf , Hackl Franz , Jessner Wolfgang , Rosenbeiger Martha , Gangl Alfred , Vogel Wolfgang ,   for the Austrian Hepatitis Study Group
Published: July 2003

Background/aims: Initial high‐dose interferon‐α induction therapy in combination with ribavirin improves sustained response rates in treatment‐naïve patients. This prospective, randomized, controlled study tested whether non‐responders or relapsers to interferon monotherapy also benefit from induction therapy.

Methods: Patients with chronic hepatitis C who had not responded to (n=75) or relapsed (n=80) after previous interferon therapy were randomized to receive three different interferon doses during the first 14 weeks of therapy (A: 10 MU IntronA®/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; B:5 MU/d for 14 weeks; C: 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. All patients received 1–1.2 g ribavirin/day throughout the whole study.

Results: The rates of viral clearance at any time on treatment were similar in all groups. Sustained response rates were also not different among the groups in interferon nonresponders (A 32%, B 29%, C 31%) and relapsers (A 64%, B 68%, C 71%), respectively, as well as in patients with different genotypes. As expected, sustained response rates were higher in patients with genotype non‐1 than in those with genotype 1.

Conclusion: High‐dose induction therapy does not improve the outcome of interferon/ribavirin therapy in interferon nonresponders or relapsers.
Glycine modulates cytokine secretion, inhibits hepatic damage and improves survival in a model of endotoxemia in mice
Authors: Bruck Rafael , Wardi Joram , Aeed Hussein , Avni Yona , Shirin Haim , Avinoach Ilana , Shahmurov Mark , Hershkoviz Rami
Published: July 2003

Background and aim: There is substantial experimental evidence that the amino acid glycine may have a role in protecting tissues against insults such as ischemia, hypoxia and reperfusion. Our aim was to investigate the ability of the amino acid glycine to prevent hepatic damage induced by injection of lipopolysaccharide and d‐galactosamine (d‐Gal), to modulate pro‐ and anti‐inflammatory cytokine levels, and to improve survival.

Methods: Mice were challenged with an intraperitoneal injection of d‐Gal (16 mg/mouse) and lipopolysaccharide (LPS, 1 μg/mouse). The intervention group also received an intraperitoneal injection of glycine (150 mg/kg) in two doses: 24 h before and just after LPS challenge. Serum cytokine levels were measured 2 h after challenge, and liver enzymes and histology were determined 16 h after LPS. Separate groups of mice received the same treatment and the survival rate was determined 24 h and ten days after endotoxin administration. In in vitro experiments, cultured mononuclear cells were stimulated by LPS, and TNF‐α and IL‐10 secretion were measured, in the presence or absence of glycine.

Results: In the glycine‐treated mice, the serum levels of liver enzymes and TNF‐α, the histologic necroinflammation score and the mortality rate were significantly reduced compared to control mice (P<0.001). Serum IL‐10 levels in the glycine‐treated mice were increased (P<0.01). In vitro studies in cultured lymphocytes isolated from either normal or glycine pretreated mice, demonstrated a significant and dose‐dependent inhibition of LPS‐induced TNF‐α secretion and increase in IL‐10 response after treatment with glycine (P<0.01). In conclusion, glycine reduces hepatic damage and improves survival rate in this mouse model of endotoxemia. The protective effect of glycine is associated with modulation of TNF‐α and IL‐10 secretion.
CC531s colon carcinoma cells induce apoptosis in rat hepatic endothelial cells by the Fas/FasL‐mediated pathway
Authors: Vekemans Katrien , Timmers Maarten , Vermijlen David , De Zanger Ronald , Wisse Eddie , Braet Filip
Published: July 2003

The mechanisms involved in colorectal carcinoma with liver metastasis are not well known. Metastasizing colon carcinoma cells express more FasL than primary colon carcinoma cells and cancer cells induce apoptosis in hepatocytes by the Fas/FasL pathway. Therefore, this study focused on Fas/FasL expression and functionality in rat liver sinusoidal endothelial cells (LSECs) and CC531s colon carcinoma cellsin vitroandin vivo. RT‐PCR and immunochemistry revealed Fas and FasL in LSECs and CC531s, respectively. Functionality of Fas was assessedin vitroby incubation with human recombinant FasL (1–100 ng/ml) with or without enhancer. At concentrations of 10 and 100 ng/ml with enhancer, respectively 21% and 44% of endothelial cells showed signs of apoptosis using Hoechst 33342/propidium iodide staining and electron microscopy. In co‐cultures, apoptosis could be detected in endothelial cells neighboring the CC531s and could be inhibited by an antagonistic FasL antibody. Moreover, 18 h after mesenteric injection of CC531s, the sinusoidal endothelium revealed disruption. In conclusion, (i) CC531s cells induce apoptosis in LSECsin vitroby using Fas/FasL; (ii) CC531s cells damage the sinusoidal endothelial liningin vivo; and (iii) this might provide FasL‐positive tumor cells a gateway towards the hepatocytes.
Insulin resistance/β‐cell function and serum ferritin level in non‐diabetic patients with hepatitis C virus infection
Authors: Furutani Masanori , Nakashima Toshiaki , Sumida Yoshio , Hirohama Akihisa , Yoh Takaharu , Kakisaka Yuko , Mitsuyoshi Hironori , Senmaru Hiroshi , Okanoue Takeshi
Published: July 2003

Background/Aims: Since impaired glucose tolerance and iron overload are frequently demonstrated in hepatitis C virus (HCV)‐related liver diseases, in this study we investigated insulin resistance, pancreatic β‐cell function, i.e., insulin secretion, and serum ferritin levels in patients with HCV infection, especially non‐diabetic patients.

Methods: Homeostasis model assessments for insulin resistance (HOMA‐IR) and β‐cell function (HOMA‐β) were performed in 92 HCV‐infected patients.

Results: The levels of plasma immunoreactive insulin (IRI), HOMA‐IR, and HOMA‐β were significantly correlated with fasting plasma glucose (FPG) levels. Among the 86 non‐diabetics (with an FPG of <126 mg/dl), IRI, HOMA‐IR, and HOMA‐β were significantly higher in patients with liver cirrhosis than in patients with persistently normal alanine aminotransferase levels. The IRI and HOMA‐IR values, but not the HOMA‐β values, were correlated with both serum transaminase and ferritin levels in the 65 non‐diabetic chronic hepatitis patients.

Conclusion: Insulin resistance was connected with impaired glucose tolerance and the severity of liver diseases in non‐diabetic patients with HCV infection. Iron overload may be responsible for insulin resistance, or vice versa. Pancreatic β‐cell function was unrelated to the patients' serum ferritin levels.
Antiapoptotic and protective effects of roscovitine on ischemia–reperfusion injury of the rat liver
Authors: Topaloglu Serdar , Abbasoglu Osman , Ayhan Ayse , Sokmensuer Cenk , Kılınc Kamer
Published: July 2003

Objective: This study was designed to investigate the role of apoptosis on liver IR injury and to determine the effects of roscovitine on this process.

Materials and methods: Rat livers pretreated with roscovitine received 60 min right lobe ischemia followed by 4 h (n=8) and 24 h (n=8) reperfusion. Tissue injury was evaluated by serum alanine aminotransferase, aspartate aminotransferase, tissue malondialdehyde, myeloperoxidase measurements and histological examination. Dead (apoptotic and necrotic) hepatocytes were determined by trypan blue dye and apoptosis was evaluated with M30 monoclonal antibody.

Results: Administration of roscovitine significantly decreased both apoptotic and dead hepatocyte counts compared to controls (P<0.01). Liver transaminase levels were decreased significantly in the roscovitine‐pretreated groups (P<0.05). In the groups evaluated 24 h after reperfusion, MPO levels (P<0.02) and leukocyte infiltration on histologic sections were decreased significantly in the roscovitine‐administered group compared to its control.

Conclusions: This study indicates that hepatocyte apoptosis may play a role in the development of IR injury of the liver. Administration of roscovitine may be beneficial in preventing this injury.
Alternative medicines and the liver
Authors: Fogden Edward , Neuberger James
Published: July 2003

Complementary and Alternative Medicine (CAM) is a heterogeneous group of theories and practices that are becoming increasingly popular in the West – between 20% and 65% of patients use CAM on a regular basis. In the UK, CAM is provided by over a third of general practitioners as well as by hospitals. The subject of much debate in both the lay and medical press, CAM is subject to increasing scrutiny from clinical research. In this review, we discuss the available evidence for herbal medicines, including that for silymarin, glycyrrhizin, Chinese herbal medicines and other herbal mixtures. We also review evidence regarding the safety of herbal medicines, both in terms of hepatotoxicity and drug interactions. We conclude that although CAM may be of benefit in the treatment of liver disease, the available evidence is insufficient to recommend any of the available therapies. CAM has not yet been well studied in liver disease and rigorous evaluation with well‐designed double‐blind randomised controlled trails is required. Doctors need to be aware of the widespread use of CAM, ask their patients specifically regarding their use of CAM and be aware of the potential for hepatotoxicity and interactions.
Simian AIDS: an historical perspective
Authors: Gardner M.B.
Published: August 2003

Abstract: The author has had the unique opportunity to participate, over the last 35 years, in the retrovirus research field that proceeded and followed the discovery of human, simian and feline AIDS. The onset of human AIDS was certainly unanticipated, but in retrospect, the warning signs had been present for at least a decade in captive macaques. I will briefly summarize the key scientific knowledge and ‘mindset’ leading up to these events and will outline the major contributions and unanswered questions arising from the simian model of AIDS.
Dynamics of Simian immunodeficiency virus‐specific cytotoxic T‐cell responses in tissues
Authors: Veazey Ronald S. , Lifson Jeffrey D. , Schmitz Jörn E. , Kuroda Marcelo J. , Piatak Michael , Pandrea Ivona , Purcell Jeannette , Bohm Rudolf , Blanchard James , Williams Kenneth C. , Lackner Andrew A.
Published: August 2003

Abstract:  Although the dynamics of human immunodeficiency virus and Simian immunodeficiency virus (SIV)‐specific cytotoxic T cells (CTLs) have been well documented in the blood, little is known regarding CTL development in other tissues. In this study, seven Mamu‐A*01+ macaques were inoculated with SIVmac. Two macaques were killed at 21 days of infection, and SIV gag p11C tetramer responses were measured in the blood, axillary and mesenteric lymph nodes, spleen, bone marrow, and thymus. Three with clinical signs of disease were killed and similarly examined. Four macaques were followed throughout disease progression, and intestinal biopsies and blood were examined at regular time points after inoculation. In animals followed prospectively, peak early tetramer responses were detected in the blood (3.9–19% of CD3+ CD8+ T cells) between day 14–21 post‐inoculation (p.i.). After day 49, tetramer responses in the blood diminished and remained relatively stable through day 200, ranging from 0.7–6.5% of CD3+ CD8+ T cells. In contrast, tetramer‐positive T cells increased in the intestine in later stages of infection (100–200 days p.i.) in all four infected animals (peak values from 5.3 to 28.8%). Percentages of tetramer‐positive cells were consistently higher in the intestine than in the blood in all four animals after day 100. In animals with acquired immunodeficiency syndrome, percentages of CTL in tissues were variable, but were consistently higher in the intestine and spleen compared with blood. These data suggest that while high CTL responses develop at a similar rate, and magnitude in both peripheral and mucosal lymphoid tissues in primary SIV infection, mucosal CTL responses may predominate later in the course of the disease.
Antigenic variations in the CD4 induced sites of the CCR5‐tropic, pathogenic SHIVsf162p3 gp120 variants
Authors: Hsu M. , Buckner C. , Harouse J. , Gettie A. , Blanchard J. , Robinson J.E. , Cheng‐Mayer C.
Published: August 2003

Abstract: In vivo passage of non‐pathogenic, CCR5‐tropic simian/human immunodeficiency virus (SHIV) – SHIVsf162 resulted in a pathogenic isolate, SHIVsf162p3. In an attempt to characterize envelope (Env)‐mediated properties that may contribute to its pathogenicity, major (P3 major) and minor (P3 minor) Env gp120 variants were cloned from the plasma of a SHIVsf162p3‐infected animal, and expressed in the context of luciferase reporter viruses. Entry mediated by these envelopes and susceptibility to neutralization by CD4 induced‐site (CD4i) antibodies (MAbs) was analyzed in comparison to parental SF162. Sequence analysis revealed that the P3 major and minor variant Envs contained 14 and 17 amino acid changes, respectively, compared with SF162. The rank order of entry mediated by the three envelopes was P3 major > SF162 > P3 minor, whereas the reverse order was observed for susceptibility to neutralization by CD4i MAbs. Since CD4i epitopes overlap the coreceptor (CoR) binding site, these findings suggest that the amino acid changes accumulated upon in vivo passage of SHIVsf162 result in Env gp120 structural rearrangements that modulate the exposure and/or conformation of the CoR binding site. This, in turn, led to increased entry and infectivity of the P3 major variant and may be responsible, in part, for the enhanced pathogenicity of SHIVsf162p3.
Microarray analysis of cytokine and chemokine genes in the brains of macaques with SHIV‐encephalitis
Authors: Sui Yongjun , Potula Raghava , Pinson David , Adany Istvan , Li Zhuang , Day Jason , Buch Eisha , Segebrecht Jane , Villinger Francois , Liu Zhenqian , Huang Mingzhao , Narayan Opendra , Buch Shilpa
Published: August 2003

Abstract:  Human immunodeficiency virus (HIV)‐encephalitis results from a cascade of viral–host interactions that lead to cytokine and chemokine imbalance, which then leads to neuropathologic manifestations of the disease. These include macrophage/microglia activation, astrocytosis and neuronal dysfunction or death. As the molecular mechanisms of this process are poorly understood, we used Atlas human cytokine or cytokine receptor microarray analysis to highlight gene expression profiles that accompanied encephalitis in Simian human immunodeficiency virus (SHIV) 89.6P‐infected macaques. Of the 277 genes screened, marked upregulation of monocyte chemoattractant protein‐1, interferon‐inducible peptide IP‐10 and interleukin‐4 were observed specifically in the encephalitic brains. These genes are collectively known to promote macrophage infiltration and activation and virus replication. In contrast, genes regulating neurotrophic functions, such as brain‐derived neurotrophic factor were downregulated. We also found that some of the apoptosis genes were up‐ or down‐regulated. These data provide a comprehensive spectrum of gene expression that underscores the two major clinical manifestations of this unique syndrome: enhanced virus replication in brain macrophages and dystrophic changes in neurons.
Theory of plant defensive level: example of process and pitfalls in development of ecological theory
Authors: Stamp N.
Published: August 2003

Several hypotheses appear regularly in the literature as explanations for the level of plant defense, i.e. why some plants are so well defended and others are not. These hypotheses include optimal defense, carbon: nutrient balance, growth rate and growth‐differentiation balance. However, there is considerable dissatisfaction with the progress with the plant defense hypotheses. At least part of the dissatisfaction with the hypotheses and research framed by them arises from the nature of the development of theory. Progress toward a mature stage requires attention to how theory develops (e.g. clearly distinguishing between the theoretical domain and the subset that can be tested, establishing criteria of robustness, properly accounting for discrepancies). In addition, part of the dissatisfaction with the development of the theory stems from inadequate approaches, such as failure to identify and test assumptions in experimental designs, confusing the hypotheses and their predictions, choosing a subsystem (e.g. plant age or part) that may be inappropriate for the test, and defaulting to a less precise hypothesis for explanation of the results.
Topological properties of food webs: from real data to community assembly models
Authors: Montoya Jose M. , Solé Ricard V.
Published: August 2003

We explore patterns of trophic connections between species in the largest and highest‐quality empirical food webs to date, introducing a new topological property called the link distribution frequency (i.e. degree distribution), defined as the frequency of species SL with L links. Non‐trivial differences are shown in link distribution frequencies between species‐rich and species‐poor communities, which might have important consequences for the responses of ecosystems to disturbances. Coarse‐grained topological properties observed, as species richness‐connectance and number of links‐species richness relationships, provide no support for the theory of links‐species scaling law or constant connectance across empirical food webs investigated. We further explore these observations by means of simulated food webs resulting from multitrophic assembly models using different functional responses between species. Species richness‐connectance and links‐species richness relationships of empirical food webs are reproduced by our models, but degree distributions are not properly predicted, suggesting the need of new theoretical approximations to food web assembly. The best agreement between empirical and simulated webs occurs for low values of interaction strength between species, corroborating previous empirical and theoretical findings where weak interactions govern food web dynamics.
An experimental analysis of self‐thinning in juvenile steelhead trout
Authors: Keeley Ernest R.
Published: August 2003

Mobile animal populations have been proposed to decline in density according to a slope based on the allometry of metabolic requirements or space requirements. In salmonid fishes, metabolic rate and food consumption scale to body mass by the exponent 0.87 and 0.73, respectively; whereas the territory size of steelhead trout scales to body mass by the exponent 0.86. Experimental cohorts of juvenile steelhead trout (Oncorhynchus mykiss) were used to test the hypothesis that mobile animal populations composed of individuals with indeterminate growth decline in density as a result of self‐thinning. After controlling for experimentally manipulated levels of food abundance and stocking density, cohorts of steelhead trout declined in density with increasing body size according to a slope closest to the allometry of food consumption. Densities of steelhead trout were inversely related to average mass by the exponent −0.74. Despite the similarity to the food consumption slope, a relatively wide confidence interval also precluded distinguishing the slope either the metabolic rate or territory size slopes. Data from the literature were also examined to determine if there was general support for the idea of self‐thinning in natural populations of stream‐dwelling salmonid fish. Although not all data suggest that populations of salmonids in streams decline as a result of density‐dependent intraspecific competition, at least some appear to fit the idea of self‐thinning; especially when density is above a minimum level of habitat saturation.
Ecological dynamics of extinct species in empty habitat networks. 1. The role of habitat pattern and quantity, stochasticity and dispersal
Authors: León‐Cortés Jorge L. , Lennon Jack J. , Thomas Chris D.
Published: August 2003

We examined a remnant host plant (Primula veris L.) habitat network that was last inhabited by the rare butterfly Hamearis lucina L. in north Wales in 1943, to assess the relative contribution of several spatial parameters to its regional extinction. We first examined relationships between P. veris characteristics and H. lucina eggs in surviving H. lucina populations, and used these to predict the suitability and potential carrying capacity of the habitat network in north Wales. This resulted in an estimate of roughly 4500 eggs (ca 227 adults). We developed a discrete space, discrete time metapopulation model to evaluate the relative contribution of dispersal distance, habitat and environmental stochasticity as possible causes of extinction. We simulated the potential persistence of the butterfly in the current network as well as in three artificial (historical and present) habitat networks that differed in the quantity (current and X3) and fragmentation of the habitat (current and aggregated). We identified that reduced habitat quantity and increased isolation would have increased the probability of regional extinction, in conjunction with environmental stochasticity and H. lucina's dispersal distance. This general trend did not change in a qualitative manner when we modified the ability of dispersing females to stay in, and find suitable habitats (by changing the size of the grid cells used in the model). Contrary to most metapopulation model predictions, system persistence declined with increasing migration rate, suggesting that the mortality of migrating individuals in fragmented landscapes may pose significant risks to system‐wide persistence. Based on model predictions for the present landscape we argue that a major programme of habitat restoration would be required for a re‐established metapopulation to persist for >100 years.
Dissecting components of population‐level variation in seed production and the evolution of masting behavior
Authors: Koenig Walter D. , Kelly Dave , Sork Victoria L. , Duncan Richard P. , Elkinton Joseph S. , Peltonen Mikko S. , Westfall Robert D.
Published: August 2003

Mast‐fruiting or masting behavior is the cumulative result of the reproductive patterns of individuals within a population and thus involves components of individual variability, between‐individual synchrony, and endogenous cycles of temporal autocorrelation. Extending prior work by Herrera, we explore the interrelationships of these components using data on individual seed production in 59 populations of plants from 24 species spanning a large range of annual variability, from species exhibiting strong masting to others with little annual variability in seed production. Estimates of population and individual variability were not biased by sample size or average overall seed production when based on untransformed seed production values, but these values declined as log‐transformed seed production increased. Population variability was more strongly correlated with individual variability (r=0.86) than individual synchrony (r=0.73). These latter two components were also significantly correlated (r=0.45), but randomizations confirm that they need not covary closely. Thus, selection can act separately on inter‐annual variability and between‐individual synchrony. We illustrate the potential for such fine‐tuned selection on seed production patterns by discussing several examples and by demonstrating significant differences in components of population‐level variation in seed production among species related to their life‐history.
Environmental noise and population dynamics of the ciliated protozoa Tetrahymena thermophila in aquatic microcosms
Authors: Laakso Jouni , Löytynoja Katja , Kaitala Veijo
Published: August 2003

Population theory predicts that the reddened environmental noise, especially in combination with high population growth rate, reddens population dynamics, increases population variability and strengthens environment–population correlation. We tested these predictions with axenic populations of ciliated protozoa Tetrahymena thermophila. Populations with low and high growth rate were cultured in a stable environment, and in environments with sublethal temperature fluctuations that had blue, white and red spectra (i.e. negatively autocorrelated, uncorrelated, or positively autocorrelated, respectively). Population size and biomass of individuals were determined at 3‐h intervals for 18 days.

Dynamics of all populations were reddened, suggesting that internal mechanisms can redden the population spectra. However, population dynamics were reddest, variability highest, and environment–population correlation strongest in the red environment as predicted. Contrary to theoretical predictions and previous empirical findings, population growth rate (rmax being equal to 0.05 and 0.3 h−1) had no effect on population dynamics.

Mean cell size and variability of cell size were affected by the presence and type of environmental noise suggesting that the physiological consequences of variability depend on colour. Environmental variability decreased mean population size and biomass and the decrease was strongest in rapidly fluctuating blue and white environments. The latter finding implies that rapid fluctuations are physiologically stressful, an effect that is not accounted for in the basic population models.
Biotic and abiotic factors affecting ectomycorrhizal diversity in boreal mixed‐woods
Authors: Kernaghan G. , Widden P. , Bergeron Y. , Légaré S. , Paré D.
Published: August 2003

Ectomycorrhizal (ECM) diversity was measured in 12 mixed‐wood stands in the Abitibi region of north‐western Québec. Stands were of similar age and were situated on similar mineral soil deposits, but supported varying proportions of ECM host trees. Host roots were sampled in a manner that enabled their separation into species on the basis of wood anatomy. Shannon diversity indices for the ECM colonizing each host species were determined on the basis of ECM anatomy. The diversity of overstory trees, understory plants and host roots, as well as overstory tree composition, root density and pertinent abiotic factors were measured and used as independent variables in multiple regressions against ECM diversity. We found a positive relationship between overstory tree diversity and ECM diversity, which appears related to fungal host specificity. Although no direct relationship was seen between ECM diversity and soil factors, levels of exchangeable base cations were related to ECM fungal species composition which correlated with ECM diversity at the scale sampled.
Scale‐dependent indirect interactions between two prey species through a shared predator
Authors: Östman Örjan , Ives Anthony R.
Published: August 2003

We investigated the potential for indirect interactions between two prey species, pea aphids (Acyrthosiphon pisum) and potato leafhoppers (Empoasca fabae), through a shared predator (Nabis spp.), and how these interactions may change across three spatial scales. In greenhouse experiments using small clusters of plants containing pea aphids and/or potato leafhoppers, the predation rates on both pea aphids and potato leafhoppers were independent of the presence of the other species, indicating no indirect interactions. In greenhouse experiments using cages containing 48 plants, when aphids and leafhoppers were confined to separate plants among which nabids could move, pea aphids had a positive effect on the survival of potato leafhoppers from predation. The positive effect of aphids on leafhoppers occurred because nabids spent more time on plants harboring aphids, thereby drawing nabids away from plants containing leafhoppers. Finally, we measured the abundance of nabids in a large‐scale experiment designed to manipulate the abundances of pea aphids and potato leafhoppers in alfalfa fields. Fields with high aphid density contained more nabids, thereby suggesting that pea aphids will have a negative indirect effect on potato leafhoppers by increasing the density of nabids within fields. Potato leafhoppers had no indirect effects on pea aphids at any scale. This study shows that indirect interactions between prey species may depend upon spatial scale, because the factors affecting a predator's diet choice on a small scale may differ from those factors affecting a predator's distribution at larger scales.
The significance of predation in nest site selection of turtles: an experimental consideration of macro‐ and microhabitat preferences
Authors: Spencer Ricky‐John , Thompson Michael B.
Published: August 2003

Nest selection has important consequences for fitness in freshwater turtles, as nest predation is extremely high in most populations. However, nest predation has rarely been considered a major factor affecting nest site selection. Thermal qualities of a nest are often suggested as a factor influencing maternal choice of nest site because incubation temperature affects offspring performance and growth, as well as the sex ratio of the clutch in species with temperature dependent sex determination (TSD). Yet experimental manipulations of the nesting environment (habitat and threat) to test factors influencing maternal nest site selection in turtles are uncommon. In this paper, we show that nest site selection in an Australian turtle (Emydura macquarii) with genetically determined sex determination (GSD) exists at two spatial scales, with predation as the major factor affecting the location of a nest. Females prefer to nest in areas where nest predation is minimal but when the risk of direct predation is increased, they trade‐off minimising nest predation with survival by locating their nests closer to shore. However, experimentally reducing cover demonstrated that females prefer to nest in open areas, which are more common closer to shore. Hence females are forgoing preferred microhabitat to locate their nests away from shore to minimise nest predation. Despite a preference for open nesting areas, females exhibit similar repeatability of microenvironment selection to a North American species with TSD. Repeatability of nesting overstory vegetation in the North American turtle, Chrysemys picta, suggests that females may exert some control over the thermal qualities of the nests; a key assumption in theoretical models of the microevolution and adaptive significance of TSD in reptiles. Incubation temperature is one factor that may affect microhabitat preferences in both turtles but other factors (e.g. predation and soil moisture) affected by microhabitat may be critical in the evolution of repeatability of overstory cover.
Preference and performance of a gall‐inducing sawfly: plant vigor, sex, gall traits and phenology
Authors: Fritz Robert S. , Crabb Beau A. , Hochwender Cris G.
Published: August 2003

We performed an experiment on preference and performance of the leaf galling sawfly, Phyllocolpa leavitti (Hymenoptera: Tenthredinidae), to test predictions of the plant vigor hypothesis, the sex‐biased herbivory hypothesis, and the enemy‐free space hypothesis. We cut ramets on 8 male and 6 female genets of Salix discolor to induce large, vigorous shoots. Shoots on an undamaged ramet of the same genet served as a control. We measured shoot length, length of galled and ungalled leaves, gaps along the margin of the leaf fold, and node position of each leaf fold. We collected and determined the survival and stage of mortality of each leaf fold on 50 treatment and 100 control shoots per ramet. Cutting ramets induced longer shoots and leaves on treatment compared to control ramets. The density of P. leavitti was significantly greater on the treatment ramets, supporting the preference prediction of the plant vigor hypothesis. Density of P. leavitti did not differ between the sexes, which failed to support one prediction of sex‐biased herbivory. Survival of P. leavitti did not differ between the treatments, contrary to the performance prediction of the plant vigor hypothesis. There was, however, a large effect of plant sex on sawfly survival – the probability of survival was more than twice as great on female plants than on male plants. This supports the prediction of sex‐biased herbivory hypothesis that herbivore fitness should vary between plant sexes, but is opposite to the expected direction of higher survival on male plants. Gaps that form along the margin of the leaf fold explained a significant amount of variation in survival. An increase in gap number by 1 decreased sawfly survival by 50%. Since gap number is positively related to leaf length, this implies selection to oviposit on shorter leaves, which is also contrary to the performance prediction of the plant vigor hypothesis. Finally, leaf folds formed later in the oviposition period had a higher probability of survival, suggesting selection favoring later phenology of the sawfly. This study refuted the performance prediction of the plant vigor hypothesis, but it provided insights into the traits that should be under natural selection to provide enemy‐free space in this insect‐plant interaction.
A long‐term study of non‐native‐heartworm transmission among coyotes in a Mediterranean ecosystem
Authors: Sacks Benjamin N. , Woodward David L. , Colwell Arthur E.
Published: August 2003

In Mediterranean ecosystems, abiotic factors are known to affect vertebrate population dynamics, but little is known about how these factors affect population dynamics of parasites. We conducted a 9‐year investigation of the roles of temperature, precipitation, and vector abundance as determinants of transmission of the non‐native canine heartworm (Dirofilaria immitis), a dangerous parasite of pets, among coyotes (Canis latrans), an important reservoir, in north‐coastal California. Dates of heartworm transmission and total annual transmission were determined, respectively, from lengths and numbers of heartworms found in known‐age coyotes. Vector host‐seeking activity was assessed through weekly mosquito trapping. Within years, heartworm transmission occurred only when cumulative temperatures were sufficient to allow larval heartworms to develop to the infective stage (as predicted by an existing degree‐day model), and when suitable vectors were available. Most (95%) heartworms infected their hosts between 1 July and 14 September. The onset of transmission periods always occurred after the peak in vector host‐seeking activity and varied annually. Transmission periods ended before temperatures became limiting due to absence of vectors. The timing of host‐seeking activity of the primary vector species,Ochlerotatus sierrensis, also was correlated with the onset of warming temperatures such that parasite and vector phenology were synchronized. For this reason (partly), the variation in timing of seasonal warming had no detectable effect on total annual transmission. Abundance of host‐seekingOc. sierrensiswas positively correlated with annual precipitation, and annual heartworm transmission was positively correlated with abundance of host‐seekingOc. sierrensis. Annual transmission also was positively correlated with abundance of a less numerous vector species,Anopheles punctipennis, and was directly correlated with precipitation. This study demonstrates that multiannual variability in temperature, which affects seasonality of transmission, has little effect on annual transmission, but that precipitation is a driving force determining annual transmission. These findings imply that in California, and possibly other Mediterranean climate zones, it is especially important to preventively treat pets in summers following high‐rainfall winters.
The long‐term relationship between plant diversity and total plant biomass depends on the mechanism maintaining diversity
Authors: Fox Jeremy W.
Published: August 2003

The relationship between plant diversity and total plant biomass is of great current interest in ecology. Niche differences among plants are widely thought to promote both plant coexistence, and higher biomass in more diverse polycultures. Using simple mechanistic models, I demonstrate that not all niche differences among plants are equally likely to promote high total biomass in polyculture. In particular, transgressive overyielding (when a polyculture of plants outperforms any monoculture) occurs for a wide range of parameter values when plants coexist in polyculture due to differences in resource use. Transgressive overyielding occurs only for a limited set of parameter values when specialist herbivores mediate plant coexistence, and is impossible when generalist herbivores mediate coexistence. Niche differences among plants promote high biomass in polyculture only when plants coexist in polyculture at the expense of other trophic levels – that is, by converting into biomass resources that would otherwise be bound in herbivores, or exist in a free state. A major challenge for future work will be to identify the joint consequences of different coexistence mechanisms for plant diversity and ecosystem performance.
Flibanserin, a potential antidepressant drug, lowers 5‐HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5‐HT1A receptors
Authors: Invernizzi Roberto William , Sacchetti Giuseppina , Parini Stefania , Acconcia Sabrina , Samanin Rosario
Published: July 2003

Using in vivo intracerebral microdialysis in conscious, freely moving rats, we examined the effect of flibanserin, a potential antidepressant drug with high affinity for human 5‐HT1A receptors and four–50‐fold lower affinity for 5‐HT2A and D4 receptors, on basal extracellular concentrations of serotonin (5‐hydroxytryptamine, 5‐HT), dopamine (DA) and noradrenaline (NA) in selected regions of the rat brain.

Flibanserin at 3 and 10 mg kg−1 significantly reduced extracellular 5‐HT in the prefrontal cortex (by 30 and 45%) and dorsal raphe (35 and 44%), but had no effect on extracellular 5‐HT in the ventral hippocampus. The 3 and 10 mg kg−1 doses raised extracellular NA to a similar extent in the prefrontal cortex (47 and 50%). In all, 10 mg kg−1 raised extracellular DA in the prefrontal cortex (63%) whereas 3 mg kg−1 had no significant effect.

Pretreatment with the selective 5‐HT1A receptor antagonist WAY100,635 (0.3 mg kg−1) 30 min before 10 mg kg−1 flibanserin completely antagonized the latter's effects on extracellular 5‐HT, DA and NA in the prefrontal cortex. WAY100,635 by itself had no effect on cortical extracellular monoamines.

The results show that the stimulation of 5‐HT1A receptors plays a major role in the effect of flibanserin on brain extracellular 5‐HT, DA and NA.

British Journal of Pharmacology (2003) 139, 1281–1288. doi:10.1038/sj.bjp.0705341