bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnic Differences in Positive Alcohol Expectancies During Childhood: The Pittsburgh Girls Study
Authors: Chung Tammy , Hipwell Alison , Loeber Rolf , White Helene Raskin , Stouthamer‐Loeber Magda
Published: April 2008

Background:  Positive expectancies about alcohol’s effects are more likely to be endorsed with increasing age through adolescence, and the strength of positive alcohol expectancies in children appears to differ by ethnicity. Little is known about the extent to which differences in a measure’s psychometric properties as a function of development and ethnicity may account for changes that are observed over time and ethnic differences. This study used measurement invariance methods to examine ethnic differences in the development of alcohol expectancies, and examined risk factors associated with girls’ positive expectancies.

Methods:  African‐American (56%) and Caucasian (44%) girls (n = 570) in the age 7 cohort of the Pittsburgh Girls Study, and the girl’s primary caretaker, were followed annually for 4 years (ages 7–10). Girls reported on alcohol expectancies at each wave, and physical aggression at Year 1. In Year 1, caretakers reported on neighborhood drug use, their own substance‐related problems, and depression in the girl. Structural equation modeling was used to examine measurement invariance of positive alcohol expectancies, and to test associations of risk factors to initial level and change in expectancies.

Results:  Five of 8 positive alcohol expectancy items showed measurement equivalence for African‐American and Caucasian girls in cross‐sectional, but not longitudinal, analyses. Measurement equivalence over ages 7–10 was demonstrated for Caucasian girls, and over ages 7–8 and 9–10 (i.e., a two‐part model) for African‐American girls. Risk factor analyses indicated that, for Caucasian girls, greater physical aggression was associated with higher initial positive expectancies.

Conclusions:  Some developmental change and ethnic differences in the performance of positive expectancy items were identified, highlighting the utility of measurement invariance methods. Risk factor analyses suggest the potential benefit of targeted alcohol prevention interventions for certain girls.
Ethanol and Pain Sensitivity: Effects in Healthy Subjects Using an Acute Pain Paradigm
Authors: Perrino Albert C. , Ralevski Elizabeth , Acampora Gregory , Edgecombe Javon , Limoncelli Diana , Petrakis Ismene L.
Published: April 2008

Background:  The primary objective of this study was to determine whether healthy subjects without a history of heavy alcohol use or a family history of alcoholism exhibit a concentration‐dependent analgesic effect of ethanol. In a preliminary fashion, we also compared this sample to a group of subjects with a strong positive family history for alcoholism (FHP) to test the secondary hypothesis that FHP individuals will be more sensitive to the analgesic effects of alcohol compared to healthy subjects who are negative for a family history of alcoholism (FHN).

Methods:  Forty‐one healthy FHN subjects and 19 FHP subjects participated. Test days included an ethanol high concentration (breathalyzer = 0.100 g/dl), ethanol low concentration (breathalyzer = 0.040 g/dl) or placebo. The infusion of ethanol was via computerized pump to achieve a steady‐state (“clamp”) ethanol concentration. Noxious electrical stimulation and pain assessments were performed prior to start of placebo/ethanol infusion and at the 60‐min infusion mark. The applied current was progressively increased until the pain was reported as 5 or higher on an 11‐point Verbal Numeric Scale (VNS). Outcome variables included measures of pain threshold and tolerance and Visual Analog Scales of mood states.

Results:  Among FHN subjects there was a significant ethanol concentration effect on pain tolerance (F = 3.0, p = 0.05). The average change in pain stimuli required to reach a VNS of 5 or greater were (−2.4, −1.0, and 2.2 mAmps respectively) for high concentration, low concentration, and placebo. There were no ethanol concentration related differences in pain threshold. The analgesic effect of ethanol was not correlated with changes in mood states, suggesting an independent analgesic effect of the drug. A comparison of FHP to FHN subjects produced no differences on pain responses.

Conclusion:  The findings support the hypothesis that in healthy subjects intravenous ethanol administration has a concentration effect on pain tolerance but not on pain threshold. Additional studies are planned to further elucidate the mechanisms of ethanol’s analgesic effects.
The Association Between Alcohol Consumption and Biomarkers of Alcohol Exposure With Total Serum Immunoglobulin E Levels
Authors: Friedrich Nele , Husemoen Lise Lotte N. , Petersmann Astrid , Nauck Matthias , Völzke Henry , Linneberg Allan
Published: April 2008

Background: A number of studies have shown that self‐reported alcohol intake is positively associated with total serum immunoglobin E (IgE) levels. The purpose of the present study was to investigate the association of self‐reported alcohol consumption and different biomarkers of alcohol exposure to total serum IgE levels in a general adult population.

Methods: A total of 3,443 subjects aged 20 to 79 years from the population‐based cross‐sectional Study of Health in Pomerania (SHIP) were included in the analyses. Information on alcohol consumption and serum carbohydrate‐deficient transferrin (CDT), gamma‐glutamyl transferase (GGT), aspartate‐amino transferase (ASAT), andalanine‐amino transferase (ALAT) levels were measured. Multivariable linear regression models were performed separately in atopic and nonatopic subjects.

Results: In nonatopic subjects positive associations between self‐reported alcohol consumption as well as all considered biomarkers of alcohol exposure and total serum IgE levels were found. Further the results also suggested positive associations between alcohol consumption as well as alcohol biomarkers and total serum IgE level in atopic subjects, even though not all tests for linear trend reached statistical significance.

Conclusions: In conclusion, biomarkers of alcohol exposure were positively associated with total serum IgE levels supporting that the positive association between self‐reported alcohol intake and IgE levels observed in previous studies is real and not due to misclassification of alcohol intake or confounding by other factors that may be linked to both alcohol intake and total serum IgE levels.
Immunological Detection of in Vitro Formed Phosphatidylethanol—An Alcohol Biomarker—With Monoclonal Antibodies
Authors: Nissinen Antti E. , Mäkelä Sanna M. , Vuoristo Jussi T. , Liisanantti Marja K. , Hannuksela Minna L. , Hörkkö Sohvi , Savolainen Markku J.
Published: April 2008

Background:  Phosphatidylethanol (PEth) is a promising new marker for detecting long‐term alcohol abuse with excellent sensitivity and specificity. Current methods are based on the high performance liquid chromatography–mass spectrometric method and therefore require high levels of expertise and expensive instrumentation. This study was designed to generate PEth‐specific monoclonal antibodies for PEth immunoassay development.

Methods:  C57/BL6 mice were immunized with PEth in 3 different carriers, mouse serum albumin, mouse high‐density lipoproteins, and human low‐density lipoprotein (LDL). Mouse splenocytes were fused with a mouse myeloma cell line using the hybridoma technique. Mouse IgM‐producing cell lines were selected by limiting dilutions. Binding characteristics of the anti‐PEth antibodies were studied using luminometric immunoassays and sequence analysis of the variable region mRNA sequences of the antibodies. Produced antibodies were purified by chromatographic methods. PEth was detected with these antibodies in fluorescence immunoassay and flow cytometric analysis.

Results:  We generated monoclonal cell lines (2B1 and 2E9) that produce IgM antibodies binding specifically to PEth but not to structurally or chemically similar phospholipids, such as phosphatidylcholine, phosphatidic acid, and cardiolipin. We show here that these anti‐PEth antibodies can be used to detect PEth in a fluorescent PEth assay and FACS analysis of human red blood cell samples spiked with PEth.

Conclusions:  The present study shows that PEth‐specific monoclonal antibodies can be generated using traditional hybridoma technique. Immunogenicity of PEth was enhanced using human LDL as an immunization carrier. The generated monoclonal anti‐PEth antibodies, 2B1 and 2E9 bind to PEth in fluid phase and in biological membranes.
The Relative Contribution of Genes and Environment to Alcohol Use in Early Adolescents: Are Similar Factors Related to Initiation of Alcohol Use and Frequency of Drinking?
Authors: Poelen Evelien A. P. , Derks Eske M. , Engels Rutger C. M. E. , Van Leeuwe Jan F. J. , Scholte Ron H. J. , Willemsen Gonneke , Boomsma Dorret I.
Published: April 2008

Background:  The present study assessed the relative contribution of genes and environment to individual differences in initiation of alcohol use and frequency of drinking among early adolescents and examined the extent to which the same genetic and environmental factors influence both individual differences in initiation of alcohol use and frequency of drinking.

Methods:  Questionnaire data collected by the Netherlands Twin Register were available for 694 twin pairs aged of 12 to 15 years. Bivariate genetic model fitting analyses were conducted in mx. We modeled the variance of initiation of alcohol use and frequency of drinking as a function of three influences: genetic effects, common environmental effects, and unique environmental effects. Analyses were performed conditional on sex.

Results:  Findings indicated that genetic factors were most important for variation in early initiation of alcohol use (83% explained variance in males and 70% in females). There was a small contribution of common environment (2% in males, 19% in females). In contrast, common environmental factors explained most of the variation in frequency of drinking (82% in males and females). In males the association between initiation and frequency was explained by common environmental factors influencing both phenotypes. In females, there was a large contribution of common environmental factors that influenced frequency of drinking only. There was no evidence that different genetic or common environmental factors operated in males and females.

Conclusion:  Different factors were involved in individual differences in early initiation of alcohol use and frequency of drinking once adolescents have started to use alcohol.
Enhanced Ethanol Inhibition of RecombinantN‐methyl‐D‐aspartate Receptors by Magnesium: Role of NR3A Subunits
Authors: Jin Chun , Thetford Smothers C. , Woodward John J.
Published: April 2008

Background: The effects of ethanol on brain function are thought to be partly because of altered activity of ion channels that regulate synaptic activity. Results from previous studies from this lab and others have shown that ethanol inhibits the function of theN‐methyl‐d‐aspartate (NMDA) receptors, a calcium‐permeable ion channel activated by the neurotransmitter glutamate. Factors that influence the acute sensitivity of NMDA receptors to ethanol may be critical in determining how neurons and neuronal networks respond to the presence of ethanol. In this study, we have examined the effect of physiologically relevant concentrations of magnesium on the ethanol sensitivity of recombinant NMDA receptors and how ethanol inhibition under these conditions is influenced by the NR3A subunit.

Methods: Recombinant cDNAs encoding NMDA receptor subunits were expressed in human embryonic kidney 293 cells. Whole‐cell patch‐clamp electrophysiology was used to measure currents induced by rapid application of glutamate in the absence and presence of ethanol.

Results: In magnesium‐free recording solution, ethanol inhibited glutamate‐mediated currents in cells transfected with NMDA receptor subunits. The magnitude of ethanol inhibition was significantly enhanced when recordings were carried out in media containing 1 mM magnesium. This effect was reversible and required magnesium‐sensitive receptors. Magnesium did not enhance ethanol inhibition of glycine‐activated NR1/NR3A/NR3B receptors. However, NR3A co‐expression prevented the enhancement of ethanol’s inhibitory effect on receptors composed of NR2A but not NR2B subunits.

Conclusions: These results suggest that under physiological conditions, NR3A may be an important regulator of the acute ethanol sensitivity of brain NMDA receptors.
Upregulation of β‐Catenin Levels in Superior Frontal Cortex of Chronic Alcoholics
Authors: Al‐Housseini Ali M. , Sivanandam Thamil Mani , Bradbury Edward L. , Tannenberg Rudi K. , Dodd Peter R. , Gu Qiang
Published: April 2008

Background:  Chronic and excessive alcohol misuse results in neuroadaptive changes in the brain. The complex nature of behavioral, psychological, emotional, and neuropathological characteristics associated with alcoholism is likely a reflection of the network of proteins that are affected by alcohol‐induced gene expression patterns in specific brain regions. At the molecular level, however, knowledge remains limited regarding alterations in protein expression levels affected by chronic alcohol abuse. Thus, novel techniques that allow a comprehensive assessment of this complexity will enable the simultaneous assessment of changes across a group of proteins in the relevant neural circuitry.

Methods:  A proteomics analysis was performed using antibody microarrays to determine differential protein levels in superior frontal cortices between chronic alcoholics and age‐ and gender‐matched control subjects. Seventeen proteins related to the catenin signaling pathway were analyzed, including α‐, β‐, and δ‐catenins, their upstream activators cadherin‐3 (type I cadherin) and cadherin‐5 (type II cadherin), and 5 cytoplasmic regulators c‐Src, CK1ε, GSK‐3β, PP2A‐Cα, and APC, as well as the nuclear complex partner of β‐catenin CBP and 2 downstream genes Myc and cyclin D1. ILK, Gα1, Gβ1, and Gβ2, which are activity regulators of GSK‐3β, were also analyzed.

Results:  Both α‐ and β‐catenin showed significantly increased levels, while δ‐catenin did not change significantly, in chronic alcoholics. In addition, the level of the β‐catenin downstream gene product Myc was significantly increased. Average levels of the catenin regulators c‐Src, CK1ε, and APC were also increased in chronic alcoholics, but the changes were not statistically significant.

Conclusion:  Chronic and excessive alcohol consumption leads to an upregulation of α‐ and β‐catenin levels, which in turn increase downstream gene expressions such as Myc that is controlled by β‐catenin signaling. This study showed that the β‐catenin signal transduction pathway was upregulated by chronic alcohol abuse, and prompts further investigation of mechanisms underlying the upregulation of α‐ and β‐catenins in alcoholism, which may have considerable pathogenic and therapeutic relevance.
The Sankey Diagram in Energy and Material Flow Management
Authors: Schmidt Mario
Published: April 2008

The Sankey diagram is an important aid in pointing up inefficiencies and potential for savings in connection with resource use. This article, the second of a pair, examines the use of Sankey diagrams in operational material flow management. The previous article described the development of the diagram and its use in the past.

Simple Sankey diagrams follow the requirement of conservation of energy or mass and allow a physical view of production systems. Advanced diagrams integrate stocks of materials beside the flows or show the different (ecological) quality of the materials. For the purpose of management, however, a further step is necessary: to illustrate the economic value of the energy and material flows and to use information from cost accounting. The use of flow charts showing added value or the costs of energy and material flows is particularly important for production systems. This article describes examples of each of these uses as well as assumptions that must be taken into account for Sankey diagrams to be used as an effective aid for decision‐making in business and public policy.
Tissue Doppler Derived Isovolumic Acceleration in Patients after Atrial Repair for Dextrotransposition of the Great Arteries
Authors: Arnold Raoul , Gorenflo Matthias , Böttler Petra , Eichhorn Joachim , Jung Christian , Goebel Björn
Published: April 2008

Background: Ventricular dysfunction represents one of the major problems in the long‐term follow‐up of patients after atrial repair for dextrotransposition of the great arteries. We aimed to study the role of tissue Doppler derived isovolumic acceleration (IVA) to detect early myocardial dysfunction in these patients. Methods: Twenty‐four patients with dextrotransposition of the great arteries (D‐TGA) that underwent atrial repair (Senning procedure: n = 12; Mustard procedure: n = 12) in infancy were examined at the age of 21 [12–33] years (median [range]) using tissue Doppler analysis of IVA and peak systolic myocardial velocity at rest and during exercise. 12 age‐matched healthy subjects served as controls. Results: At rest, IVA and peak systolic myocardial velocity were reduced in the systemic ventricle (SV) of patients. IVA correlated with peak systolic myocardial velocity (r = 0.76, P < 0.001). During exercise, IVA, but not peak systolic myocardial velocity, increased significantly in the SV of patients (rest: 1.03 ± 0.44 cm/sec2; 1 W/kg: 1.80 ± 1.22 cm/sec2; 2 W/kg: 2.85 ± 1.26 cm/sec2). In the subpulmonary ventricle, IVA was significantly lower in patients compared to the controls (patients: 1.45 ± 0.49 cm/sec2 vs. controls: 2.31 ± 0.43 cm/sec2, P < 0.05). IVA but not peak systolic myocardial velocity was able to discriminate between patients and healthy subjects. Conclusions: IVA is superior to peak systolic myocardial velocity to assess a reduction in functional reserve of both ventricles in patients after atrial repair for D‐TGA.
Side Effects of High‐Dose Dobutamine Are Not Prevented by Normal Saline Infusion in Dobutamine Stress Echocardiography
Authors: Hecker Tracy , De Pasquale Carmine G. , Perry Rebecca , Brown Lynn , Koutsounis Hari , Joseph Majo X.
Published: April 2008

High‐dose dobutamine used in dobutamine stress echocardiography (DSE) has hemodynamically based side effects due to a variable combination of β1 (inotropic) and β2 (vasodilator) effects. Of concern is the development of an “empty ventricle syndrome” associated with intracavitary or outflow tract obstruction and resultant symptomatic hypotension. This study was undertaken to determine whether the concurrent administration of normal saline (N/S) would decrease symptoms, limit the development of left ventricular outflow tract (LVOT) obstruction and hypotension by maintaining left ventricular volume. One hundred patients, mean age 66 years ± 12, presenting for a DSE were randomized into two groups. One group (n = 50) received N/S at a rate of 800 ml/hour during the test, the second group received dobutamine alone. Patients were instructed to report and quantify symptoms on a scale of 1 to 10. Echocardiographic measurements of end systolic volume (ESV) and LVOT gradients were taken prior to dobutamine and at peak dose. There was no difference in symptom scores (3.5 ± 5.1(N/S) vs. 3.0 ± 4.7, P = 0.6), change in systolic blood pressure (BP) (−0.74 mmHg ± 33 (N/S) vs. −0.89 ± 35, P = 0.9) maximum LVOT gradient at peak (16.4 mmHg ± 16.1 (N/S) vs. 13.9 mmHg ± 9, P = 0.4), or ESV at peak (17.9 mL ± 13.4 (N/S) vs. 15.5 ml ± 10.6, P = 0.37). Furthermore, there was no difference in the number of patients (10/50 (20%) in both groups) who developed a significant LVOT gradient, defined as greater than 20 mmHg at peak dose. Despite the sound theoretical basis of N/S infusion to protect against “empty ventricle syndrome” during DSE this randomized trial does not demonstrate any symptomatic or hemodynamic benefit.
Utility of Right Ventricular Tissue Doppler Imaging: Correlation with Right Heart Catheterization
Authors: Rajagopalan Navin , Simon Marc A. , Shah Hemal , Mathier Michael A. , López‐Candales Angel
Published: April 2008

Objectives: The objective of this study was to correlate tissue Doppler imaging of the right ventricle (RV) with pulmonary hemodynamics in patients referred for right heart catheterization. Methods: Seventy subjects (mean age 54 ± 13; 35 males) prospectively underwent tissue Doppler imaging of the RV and right heart catheterization within 1 day of each other. Peak systolic velocity and strain were measured at the RV free wall and correlated with pulmonary hemodynamics. Results: RV myocardial velocity demonstrated no correlation with any hemodynamic variable. While RV strain demonstrated significant correlation with cardiac index (r =−0.61; P < 0.001), correlations with transpulmonary gradient (r = 0.26; P < 0.05) and pulmonary vascular resistance (r = 0.30; P < 0.05) were weaker. Subgroup analysis revealed that in patients with left ventricular systolic dysfunction (n = 31), RV strain showed no correlation with any hemodynamic variable. In patients with normal left ventricular systolic function (n = 39), correlations were significant between RV strain and mean pulmonary artery pressure (r = 0.59; P < 0.001), pulmonary vascular resistance (r = 0.60; P < 0.001), and cardiac index (r =−0.67; P < 0.001). Conclusions: RV myocardial strain correlates significantly with pulmonary hemodynamics in patients with pulmonary hypertension and normal left ventricular function. However, there is no correlation with RV performance in patients with left ventricular dysfunction.
Can the Emergency Department Algorithm Detect Changes in Access to Care?
Authors: Lowe Robert A. , Fu Rongwei
Published: April 2008

Objectives:  The “emergency department algorithm” (EDA) uses emergency department (ED) diagnoses to assign probabilities that a visit falls into each of four categories: nonemergency, primary care–treatable emergency, preventable emergency needing ED care, and nonpreventable emergency. The EDA’s developers report that it can evaluate the medical safety net because patients with worse access to care will use EDs for less urgent conditions. After the Oregon Health Plan (OHP, Oregon’s expanded Medicaid program) underwent cutbacks affecting access to care in 2003, the authors tested the ability of the EDA to detect changes in ED use.

Methods:  All visits to 22 Oregon EDs during 2002 were compared with visits during 2004. For each payer category, mean probabilities that ED visits fell into each of the four categories were compared before versus after the OHP cutbacks.

Results:  The largest change in mean probabilities after the cutbacks was 2%. Attempts to enhance the sensitivity of the EDA through other analytic strategies were unsuccessful. By contrast, ED visits by the uninsured increased from 6,682/month in 2002 to 9,058/month in 2004, and the proportion of uninsured visits leading to hospital admission increased by 51%.

Conclusions:  The EDA was less useful in demonstrating changes in access to care than were other, simpler measures. Methodologic concerns with the EDA that may account for this limitation are discussed. Given the widespread adoption of the EDA among health policy researchers, the authors conclude that further refinement of the methodology is needed.
Productivity and Career Paths of Previous Recipients of Society for Academic Emergency Medicine Research Grant Awards
Authors: Young Kelly D. ,   on behalf of the 2005–2006 and 2006–2007 Society for Academic Emergency Medicine Grants Committees
Published: April 2008

Objectives:  The objective was to assess productivity of previous recipients of Society for Academic Emergency Medicine (SAEM) grant awards.

Methods:  All previous recipients of SAEM Research Training Grants, Neuroscience Research Awards, Scholarly Sabbatical Awards, and Emergency Medical Services (EMS) Research Fellowship awards funded through 2004 were identified through SAEM’s records and surveyed. Award categories assessed were those still offered by SAEM at the time of the survey and therefore excluded the Geriatric Research Award. The 2005–2006 SAEM Grants Committee developed a survey using previous publications assessing productivity of training grants and fellowship awards and refined it through consensus review and limited pilot testing. We assessed measures of academic productivity (numbers of publications and additional grants awarded), commitment to an academic career, satisfaction with the SAEM award, and basic demographic information.

Results:  Overall response rate was 70%; usable data were returned by all seven Research Training Grant awardees, both Neuroscience awardees, four of five Scholarly Sabbatical awardees, and six of 14 EMS Research Fellowship awardees. Of those who gave demographic information, 78% (14/18) were male and 94% (16/17) were non‐Hispanic white. All the respondents remained in academics, and 14 of 19 felt that they will definitely be in academics 5 years from the time of the survey. They have a median of 1.8 original research publications per year since the end of their grant period, and 74% (14/19) have received subsequent federal funding. All found the SAEM award to be helpful or very helpful to their careers.

Conclusions:  Previous recipients of the SAEM grant awards show evidence of academic productivity in the form of subsequent grant funding and research publications, and the majority remain committed to and satisfied with their academic research careers.
Factors influencing recruitment patterns of Golden Perch (Macquaria ambigua oriens) within a hydrologically variable and regulated Australian tropical river system
Authors: Roberts D. T. , Duivenvoorden L. J. , Stuart I. G.
Published: April 2008

Abstract –  The links between river flows, water temperature, river regulation and recruitment variability of Golden Perch, Macquaria ambigua oriens, were investigated from the Fitzroy Basin, Queensland. The dominant age classes determined by interpreting growth marks observed in otoliths were variable among rivers. Positive correlations between the age frequency and monthly river flow volumes were greatest in summer (December–March) conversely, autumn, winter and spring river flows correlated poorly for most rivers. Water temperature exhibits strong seasonality across the basin with mean monthly temperatures >23 °C generally occurring between October and April. These data indicate the combination of water temperature and increased river flows are important factors for recruitment. The degree of river regulation is also suspected of contributing to increased variability in dominant age classes within rivers. This assessment highlights the importance of timing of river flows in mitigating the negative effects of river regulation on golden perch populations.
Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts
Authors: Cury P. R. , Canavez F. , De Araújo V. C. , Furuse C. , De Araújo N. S.
Published: April 2008

Background and Objective:  Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human gingival fibroblasts.

Material and Methods:  Fibroblasts were stimulated for 48 h with 10−4 or 10−9 m Substance P; untreated fibroblasts served as controls. The expression of MMP‐1, ‐2, ‐3, ‐7 and ‐11 and of TIMP‐1 and ‐2 was evaluated using real‐time polymerase chain reaction and western blotting.

Results:  There was a significant, concentration‐dependent stimulatory effect of Substance P on MMP‐1, ‐2, ‐3 and ‐7 and TIMP‐2 gene expression (p < 0.05), and a probable effect on MMP‐11 (p = 0.06). At the higher concentration (10−4 m Substance P), MMP‐1, ‐2, ‐3, ‐7 and ‐11 and TIMP‐2 showed the greatest up‐regulation; at the lower concentration (10−9 m Substance P), MMP‐1, ‐3 and ‐7 and TIMP‐2 exhibited diminished up‐regulation, with MMP‐2 and ‐11 showing down‐regulation (p < 0.05). Expression of TIMP‐1 was not affected by Substance P (p > 0.05). Western blotting confirmed that Substance P up‐regulated MMP‐1, ‐2, ‐3 and ‐11 and TIMP‐2. MMP‐1, ‐3 and ‐11 and TIMP‐2 showed greater up‐regulation at the higher Substance P concentration and diminished up‐regulation at the lower concentration. MMP‐2 was up‐regulated to a similar degree at both Substance P concentrations.

Conclusion:  In gingival fibroblast cells, Substance P at the higher concentration (10−4 m) induced greater up‐regulation of MMP‐1, ‐3 and ‐11 and TIMP‐2 expression, but at the lower concentration (10−9 m) induced diminished up‐regulation, which may represent a mechanism for modulating periodontal breakdown.
Cellular responses of rat periodontal ligament cells under hypoxia and re‐oxygenation conditions in vitro
Authors: Amemiya H. , Matsuzaka K. , Kokubu E. , Ohta S. , Inoue T.
Published: April 2008

Background and Objective:  The aim of this study was to investigate the responses of periodontal ligament cells under hypoxia and re‐oxygenation conditions in vitro.

Material and Methods:  Periodontal ligament fibroblasts were isolated from rat incisors. In the hypoxia group, cells were incubated in 2% O2 for 1–3 d. In the re‐oxygenation group, cells were first incubated under the same conditions as the hypoxia group for 24 h and then were returned to normoxic conditions and cultured for 1–2 additional days.

Results:  Proliferation ratios increased in all groups in a time‐dependent manner. Proliferation ratios in both the hypoxia and re‐oxygenation groups were significantly higher than in the control group on days 2 and 3. Alkaline phosphatase activity was significantly higher in the hypoxia group than in the control and the re‐oxygenation groups. The expression of bone sialoprotein mRNA was significantly higher in the hypoxia group than in the control group on days 1 and 2. The expression of vascular endothelial growth factor mRNA was significantly higher in the hypoxia group than in the control group on days 1 and 2. In the re‐oxygenation group, the level of expression of bone sialoprotein mRNA and vascular endothelial growth factor mRNA were similar to those of the control group. The expression of heat shock protein 70 mRNA in the hypoxia group was similar to that in the control group, whereas in the re‐oxygenation group it was statistically higher than in the other groups.

Conclusion:  These results suggest that periodontal ligament cells maintain their osteogenic ability in hypoxia and re‐oxygenation conditions in vitro.
Vesicle Docking in Regulated Exocytosis
Authors: Verhage Matthijs , Sørensen Jakob B.
Published: April 2008

In electron micrographs, many secretory and synaptic vesicles are found ‘docked’ at the target membrane, but it is unclear why and how. It is generally assumed that docking is a necessary first step in the secretory pathway before vesicles can acquire fusion competence (through ‘priming’), but recent studies challenge this. New biophysical methods have become available to detect how vesicles are tethered at the target membrane, and genetic manipulations have implicated many genes in tethering, docking and priming. However, these studies have not yet led to consistent working models for these steps. In this study, we review recent attempts to characterize these early steps and the cellular factors to orchestrate them. We discuss whether assays for docking, tethering and priming report on the same phenomena and whether all vesicles necessarily follow the same linear docking–priming–fusion pathway. We conclude that most evidence to date is consistent with such a linear pathway assuming several refinements that imply that some vesicles can be nonfunctionally docked (‘dead‐end’ docking) or, conversely, that the linear pathway can be greatly accelerated (crash fusion).
Rab5 Activation by Toll‐Like Receptor 2 is Required for Trypanosoma cruzi Internalization and Replication in Macrophages
Authors: Maganto‐Garcia Elena , Punzon Carmen , Terhorst Cox , Fresno Manuel
Published: April 2008

Trypanosoma cruzi can infect and replicate in macrophages. During invasion, T. cruzi interacts with different macrophage receptors to induce its own phagocytosis. However, the nature of those receptors and the molecular mechanisms involved are poorly understood. In this study, we demonstrate that T. cruzi metacyclic trypomastigotes but not epimastigotes were able to induce Rab5 activation and binding to the early endosomes in peritoneal macrophages. In this process, active Rab5 colocalized with parasites in the phagosome and with the Rab5A effector molecule early endosomal antigen 1. Phagosome formation and T. cruzi internalization were inhibited in Raw 264.7 macrophages expressing a dominant‐negative form of Rab5 [(S34N)Rab5]. Using T. cruzi membrane extracts, we verified that the Rab5 activation depends on the interaction between parasite surface molecules and macrophages surface molecule. In addition, during infection of macrophages, phosphatidylinositol 3‐kinase (PI3K) pathway was activated. Assays carried out using a selective PI3K inhibitor (LY294002) showed that the PI3K activation is essential for Rab5 activation by T. cruzi infection and for the entrance and intracellular replication of T. cruzi in macrophages. Moreover, using macrophages from knockout mice, we found that activation of Rab5, fusion of early endosomes and phagocytosis induced by T. cruzi infection involved Toll‐like receptor (TLR)2 but were independent of TLR4 receptors.
Laser Surface Processing of B4C–TiB2 Eutectic
Authors: Polotai Anton V. , Foreman John F. , Dickey Elizabeth C. , Meinert Kenneth
Published: April 2008

The formation of a directionally solidified non‐oxide eutectic surface layer based on the 75 mol% B4C and 25 mol% TiB2 eutectic composition has been developed using a continuous‐wave, high‐power, CO2 laser. To prevent the oxidation of nonoxide compounds and to reduce thermal stress formation, an atmospherically controlled furnace capable of back‐heating samples up to 1100°C during the laser processing has been employed. The effect of the laser scan rate on the eutectic microstructure formation is investigated. It is found that at relatively slow laser scan rates, ∼2–4 mm/s, the formation of a colony‐type eutectic microstructure with submicrometer scale features is observed. At higher heating rates up to 42 mm/s, disordered eutectic grains with nanometer‐scale TiB2 lamellae form. The dependence of the TiB2 interlamellar spacing on the crystallization rate in the laser solidified B4C–TiB2 eutectic has the same general trend as in the eutectic produced by a floating zone method. However, this method allows the production of much smaller microstructural length scales, on the order of 100 nm, as a consequence of the high crystallization velocity.
China's Economy in 2007/2008: Coping with Problems of Runaway Growth
Authors: Wong John
Published: April 2008

Fuelled by high domestic investment and rapid export expansion, China's economy grew by 11.4 percent in 2007, the highest increase since 1994 and the fifth consecutive year of double‐digit growth. Such spectacular growth performance is unprecedented in the world s economic history. However, the Chinese Government is again worried about a possible “hard landing” for the economy, as no economy can sustain very strong growth for extremely long period without overheating. Cracks in China s economy are indeed emerging. The consumer price index shot up to 6.9 percent in November 2007, the highest level in a decade, with the annual inflation for 2007 rising to 4.8 percent, well above the governments “comfort level” of 3 percent. This prompted China s top leadership to declare that reducing economic overheating and curbing inflation would be the top policy priorities for 2008. To contain such cost‐push inflation, the government has to tackle its root causes, such as excessive liquidity, which is caused by the undervaluation of the renminbi, which in turn is attributable to China s chronic external and internal macroeconomic imbalances. High growth is likely to continue in 2008, at around 10 percent, with inflation of 5–6 percent expected, despite the anticipated tighter macroeconomic control measures and the more troubled external economic environment (e.g. the expected US economic slowdown). Regardless, China s fundamental problems associated with runaway growth will largely remain. In addition, if the US economy slips into a serious recession, the Chinese economy will not be able to decouple from it and escape unscathed.
Local “Land Finance” in China's Urban Expansion: Challenges and Solutions
Authors: Cao Guangzhong , Feng Changchun , Tao Ran
Published: April 2008

This paper considers the issue of local “land finance” in the context of China's fast urban expansion. In an analysis of China s land requisition and public leasing system we argue that low‐cost land acquisition is the fundamental cause of land‐related distortions that have occurred during China s urbanization. Granting farmers the power to negotiate directly with land users during urban expansion, combined with coordinated land tax reforms to consolidate local tax bases is the key to China achieving both equity and land use efficiency in urban expansion.
Payment for Environmental Services: The Sloping Land Conversion Program in Ningxia Autonomous Region of China
Authors: Zhang Lei , Tu Qin , Mol Arthur P. J.
Published: April 2008

China's Sloping Land Conversion Program has been implemented since 2002. It aims to achieve goals of ecological recovery and poverty alleviation, by retiring steeply sloping land from crop production and freeing surplus agricultural labor for off‐farm activities. Given the huge investment that has been poured into it, and its ecological and social impacts, this government‐initiated program has attracted significant academic attention and triggered a flood of debate. Since 2004, the debate has concentrated on the sustainability of the program. Although targets have been overachieved in some provinces, concern has still emerged regarding the livelihood of farmers after subsidies stop. The present paper analyzes the implementation of the Sloping Land Conversion Program in Ningxia Autonomous Region, with a focus on the required social capital for sustained participation of farmers and the development of off‐farm economic activities.
The impact of fishing‐induced mortality on the evolution of alternative life‐history tactics in brook charr
Authors: Thériault Véronique , Dunlop Erin S. , Dieckmann Ulf , Bernatchez Louis , Dodson Julian J.
Published: April 2008

Although contemporary trends indicative of evolutionary change have been detected in the life‐history traits of exploited populations, it is not known to what extent fishing influences the evolution of alternative life‐history tactics in migratory species such as salmonids. Here, we build a model to predict the evolution of anadromy and residency in an exploited population of brook charr, Salvelinus fontinalis. Our model allows for both phenotypic plasticity and genetic change in the age and size at migration by including migration reaction norms. Using this model, we predict that fishing of anadromous individuals over the course of 100 years causes evolution in the migration reaction norm, resulting in a decrease in average probabilities of migration with increasing harvest rate. Moreover, we show that differences in natural mortalities in freshwater greatly influence the magnitude and rate of evolutionary change. The fishing‐induced changes in migration predicted by our model alter population abundances and reproductive output and should be accounted for in the sustainable management of salmonids.
A review of quantitative genetic components of fitness in salmonids: implications for adaptation to future change
Authors: Carlson Stephanie M. , Seamons Todd R.
Published: April 2008

Salmonine fishes are commonly subjected to strong, novel selective pressures due to anthropogenic activities and global climate change, often resulting in population extinction. Consequently, there is considerable interest in predicting the long‐term evolutionary trajectories of extant populations. Knowledge of the genetic architecture of fitness traits is integral to making these predictions. We reviewed the published, peer‐reviewed literature for estimates of heritability and genetic correlation for fitness traits in salmonine fishes with two broad goals in mind: summarization of published data and testing for differences among categorical variables (e.g., species, life history type, experimental conditions). Balanced coverage of variables was lacking and estimates for wild populations and behavioral traits were nearly absent. Distributions of heritability estimates were skewed toward low values and distributions of genetic correlations toward large, positive values, suggesting that significant potential for evolution of traits exists. Furthermore, experimental conditions had a direct effect on h2 estimates, and other variables had more complex effects on h2 and rG estimates, suggesting that available estimates may be insufficient for use in models to predict evolutionary change in wild populations. Given this and other inherent complicating factors, making accurate predictions of the evolutionary trajectories of salmonine fishes will be a difficult task.
Potential for anthropogenic disturbances to influence evolutionary change in the life history of a threatened salmonid
Authors: Williams John G. , Zabel Richard W. , Waples Robin S. , Hutchings Jeffrey A. , Connor William P.
Published: April 2008

Although evolutionary change within most species is thought to occur slowly, recent studies have identified cases where evolutionary change has apparently occurred over a few generations. Anthropogenically altered environments appear particularly open to rapid evolutionary change over comparatively short time scales. Here, we consider a Pacific salmon population that may have experienced life‐history evolution, in response to habitat alteration, within a few generations. Historically, juvenile fall Chinook salmon (Oncorhynchus tshawytscha) from the Snake River migrated as subyearlings to the ocean. With changed riverine conditions that resulted from hydropower dam construction, some juveniles now migrate as yearlings, but more interestingly, the yearling migration tactic has made a large contribution to adult returns over the last decade. Optimal life‐history models suggest that yearling juvenile migrants currently have a higher fitness than subyearling migrants. Although phenotypic plasticity likely accounts for some of the change in migration tactics, we suggest that evolution also plays a significant role. Evolutionary change prompted by anthropogenic alterations to the environment has general implications for the recovery of endangered species. The case study we present herein illustrates the importance of integrating evolutionary considerations into conservation planning for species at risk.
Evolutionary consequences of habitat loss for Pacific anadromous salmonids
Authors: McClure Michelle M. , Carlson Stephanie M. , Beechie Timothy J. , Pess George R. , Jorgensen Jeffrey C. , Sogard Susan M. , Sultan Sonia E. , Holzer Damon M. , Travis Joseph , Sanderson Beth L. , Power Mary E. , Carmichael Richard W.
Published: April 2008

Large portions of anadromous salmonid habitat in the western United States has been lost because of dams and other blockages. This loss has the potential to affect salmonid evolution through natural selection if the loss is biased, affecting certain types of habitat differentially, and if phenotypic traits correlated with those habitat types are heritable. Habitat loss can also affect salmonid evolution indirectly, by reducing genetic variation and changing its distribution within and among populations. In this paper, we compare the characteristics of lost habitats with currently accessible habitats and review the heritability of traits which show correlations with habitat/environmental gradients. We find that although there is some regional variation, inaccessible habitats tend to be higher in elevation, wetter and both warmer in the summer and colder in the winter than habitats currently available to anadromous salmonids. We present several case studies that demonstrate either a change in phenotypic or life history expression or an apparent reduction in genetic variation associated with habitat blockages. These results suggest that loss of habitat will alter evolutionary trajectories in salmonid populations and Evolutionarily Significant Units. Changes in both selective regime and standing genetic diversity might affect the ability of these taxa to respond to subsequent environmental perturbations. Both natural and anthropogenic and should be considered seriously in developing management and conservation strategies.
Big dams and salmon evolution: changes in thermal regimes and their potential evolutionary consequences
Authors: Angilletta Michael J. , Ashley Steel E. , Bartz Krista K. , Kingsolver Joel G. , Scheuerell Mark D. , Beckman Brian R. , Crozier Lisa G.
Published: April 2008

Dams designed for hydropower and other purposes alter the environments of many economically important fishes, including Chinook salmon (Oncorhynchus tshawytscha). We estimated that dams on the Rogue River, the Willamette River, the Cowlitz River, and Fall Creek decreased water temperatures during summer and increased water temperatures during fall and winter. These thermal changes undoubtedly impact the behavior, physiology, and life histories of Chinook salmon. For example, relatively high temperatures during the fall and winter should speed growth and development, leading to early emergence of fry. Evolutionary theory provides tools to predict selective pressures and genetic responses caused by this environmental warming. Here, we illustrate this point by conducting a sensitivity analysis of the fitness consequences of thermal changes caused by dams, mediated by the thermal sensitivity of embryonic development. Based on our model, we predict Chinook salmon likely suffered a decrease in mean fitness after the construction of a dam in the Rogue River. Nevertheless, these demographic impacts might have resulted in strong selection for compensatory strategies, such as delayed spawning by adults or slowed development by embryos. Because the thermal effects of dams vary throughout the year, we predict dams impacted late spawners more than early spawners. Similar analyses could shed light on the evolutionary consequences of other environmental perturbations and their interactions.