bluuebunny/crossref_metadata_2025 huggingface dataset:
Uprooting and snapping of trees: structural determinants and ecological consequences
Authors: Putz Francis E. , Coley Phyllis D. , Lu Karen , Montalvo Arlee , Aiello Annette
Published: February 2008

The influence of mechanical and architectural properties of trees on growth rates, mortality rates, and relative probabilities of snapping and uprooting were examined on Barro Colorado Island, Republic of Panama. Of 310 fallen trees, 70% snapped, 25% uprooted, and 5% broke off at ground level. Stepwise discriminant analysis between snapped and uprooted trees indicated that of the variables measured, wood properties were the most important factors determining the type of death in trees. Uprooted trees tended to be larger, shorter for a given stem diameter, and to have denser, stiffer, and stronger wood than snapped trees. There were no significant differences between trees that snapped and trees that uprooted in the extent of buttress development or in the slope of the ground upon which they grew. Trees with low density wood grew faster in stem diameter than those with high density wood but also suffered higher mortality rates. After damage, many of the snapped trees sprouted; small trees sprouted more frequently than large trees. Sprouting is proposed as a means by which weak-wooded fast-growing trees partially compensate for being prone to snapping.
The mean diameter for stand density index
Authors: Zeide Boris
Published: February 2008

The average diameter used in power equations like Reineke's is neither the quadratic nor the arithmetic mean diameter. The diameter is a function of the equation's slope. As such it is a distinct stand variable which is not be to confused with other diameters.
Deterioration of severely defoliated balsam fir in relation to stand age, spacing, and foliar protection
Authors: Wall R. E.
Published: February 2008

Balsam fir (Abiesbalsamea (L.) Mill.) trees that had been heavily defoliated by the spruce budworm (Choristoneurafumiferana (Clem.) were felled and examined for decays and secondary insect activity during the declining phase of the budworm outbreak. Trees were sampled in (i) a 25- to 30-year-old stand that had been spaced a decade earlier to about 2.4 × 2.4 m and allowed to become defoliated, (ii) adjacent unspaced controls, (iii) a nearby mature (60- to 80-year-old) stand that had been defoliated, and (iv) and (v) spaced and unspaced plots that had been protected from defoliation by annual sprays of trichlorfon. Sampling was done annually over a 4-year period from preselected defoliated trees, and after the budworm population had collapsed from trees that had been intensively studied with respect to defoliation and mortality. Where defoliation was allowed to proceed unchecked (i) one-half of the spaced, (ii) one-third of the unspaced, and (iii) all of the mature trees died. The trees were attacked by wood wasps (Siricidae) and the sapwood-staining fungus, Amylostereumchailletii (Pers. ex Fr.) Boidin, followed by various stem-invading insects (Pissodesdubius Rand., Pityokteinessparsus Lee, Trypodendronlineatum (Oliv.), and Monochamusscutellatus Say) and by the sap-rot fungus Hirschioporusabietinus (Pers. ex Fr.) Donk. In surviving defoliated trees (i and ii) and in trees that had been protected by trichlorfon sprays (iv and v), numerous siricid injuries with associated pockets of stain caused by A. chailletii were found in the lower bole.
Evaluating oxidant injury to foliage of Pinusponderosa: a comparison of methods
Authors: Muir Patricia S. , Armentano Thomas V.
Published: February 2008

The importance of three sources of error in field assessments of oxidant injury to foliage of Pinusponderosa Dougl. ex Laws, was tested and included (i) differences in injury between upper and lower crowns; (ii) differences between observers; and (iii) differences among "hands-on," binocular, and spotting-scope scoring. Upper and lower crowns did not differ significantly in severity of chlorotic mottling or needle retention, but upper crowns had longer needles and more nonoxidant-induced foliar injury than lower crowns. Differences in injury scores between two experienced hands-on observers, both working on the same trees, were generally nonsignificant. Foliar injury scores observed with binoculars and spotting scopes ("remote methods") were not strongly correlated with hands-on assessments in upper crowns (most r2 ≤ 0.29). Remote methods generally underestimated population mean chlorotic mottling and needle retention in lower crowns. After correction for bias, remote methods generally met the criteria of accuracy and precision in assessing population mean needle retention but not the assessment of population mean chlorotic mottling in lower crowns. Coefficients of determination from regressions of remote on hands-on injury scores in lower crowns were usually modest (most r2 ≤ 0.62), suggesting that remote methods are generally inadequate for characterizing injury to individual trees.
The genetic structure and the conservation of the five natural populations of Pinusradiata
Authors: Moran G. F. , Bell J. C. , Eldridge K.G.
Published: February 2008

Pinusradiata is restricted to three mainland coastal populations in California and two island populations off Baja California, Mexico. In this study each population was divided into two geographic stands based on natural disjunctions within populations. In addition to the division mentioned above, each mainland population was also divided into a number of ecological stands based on ecological and environmental criteria. Genetic variation was measured by analysing 31 allozyme loci electrophoretically using germinated seed from 272 families across all stands and populations. Moderate levels of allozyme variation were found as shown by population averages for mean number of alleles per locus (1.79), percent polymorphic loci (46.4%, 0.99 criterion), and expected heterozygosity (0.098). In fact, the overall genetic diversity in P. radiata (HT = 0.117) is low compared with that of other conifers. In comparison with populations, the levels of allozyme variation in both ecological and geographic stands were slightly lower (means across ecological stands: A = 1.56, P = 39.3%, and He = 0.095). Of the total genetic diversity in P. radiata, 16.2% could be apportioned between populations, a high proportion for a conifer. In contrast, only 2.0 and 1.3% of the genetic diversity on average within mainland populations was between ecological and geographic stands, respectively. These results indicate a low level of genetic differentiation within populations, at least based on the ecological or geographic criteria used in this study. The implications and usefulness of these findings for the development of insitu conservation strategies are discussed.
Sawlog prices and quality differences in Canadian and United States Pacific coastal log markets
Authors: Constantino Luis F.
Published: February 2008

This paper introduces a methodology grounded on economic theory for comparing wood quality between regions. The methodology, which is based on index numbers, is applied to data on volumes and prices of sawlogs traded in the Canadian and United States Pacific Coastal Log Markets from 1957 through 1982. The quality of sawlogs traded was found to be higher on average in the United States than in Canada, but the U.S. advantage declined over time. The measure of wood quality is then used to adjust average log market prices for quality differences. Contrary to U.S. claims, the U.S. industry enjoyed a wood cost advantage during most of the sample period. The lower price of wood in Canada could be explained by its lower quality.
Leaf litter effect on plant species composition of deciduous forest treefall pits
Authors: Beatty Susan W. , Sholes Owen D. V.
Published: February 2008

In deciduous forests of central New York, treefall pits have rich soil, but low plant species richness. To test whether leaf litter limited species distributions, we removed litter in 10 randomly chosen pits in 1983 and compared them with controls over 3 years. Wire cages prevented litter accumulation in experimental plots. By year 1 (1984) litterless pits were significantly warmer and less moist than controls. From years 1 to 3 the average Coefficient of Community (CC) index between experimental mounds and pits increased 10-fold. No changes occurred in controls. Species composition of experimental pits became different from the controls. Species richness increased in litterless pits, with no change in other plots. Experimental and control mounds were similar in species composition all years, indicating no effect of the cage. Species responses to litter removal included: (i) enhanced germination, (ii) establishment, and (or) (iii) no change. All herbs showing increased germination or establishment were species previously restricted to mounds. The species that did not change were those already inhabiting pits. No species declined after litter removal. Litter removal in pits allowed several species to expand their distributions from mounds into litterless pits, without affecting existing pit species. The spatial heterogeneity accentuated by leaf litter accumulation does not facilitate coexistence of species in the forest community, but only limits species population sizes and spatial distributions.
Mortality of Scots pine following inoculation with the pinewood nematode, Bursaphelenchusxylophilus
Authors: Bedker Peter J. , Blanchette Robert A.
Published: February 2008

Thirteen-year-old Scots pine trees located in southeastern Iowa were inoculated with Bursaphelenchusxylophilus in the main bole of the tree or in the branches. Half of the trees were selected at random and destructively sampled 18 weeks after treatment. The remaining trees were harvested 50 weeks after treatment. Eighteen weeks after inoculation, 10 of the 20 branch-inoculated and 10 of the 20 stem-inoculated trees were dead or dying. Fifty weeks after inoculation, 6 of each of the remaining 10 branch- and stem-inoculated trees were dead or dying. In contrast, the control trees were symptomless at 18 and 50 weeks after treatment. An average of 224.7 nematodes/g were extracted from samples collected from inoculated branches. The numbers of nematodes and proportions of samples with nematodes declined from 18 to 50 weeks. In addition, B. xylophilus was recovered from stem samples collected from 15 of the 20 branch-inoculated trees. An average of 184.7 nematodes/g were recovered from samples collected at 1-m intervals from stem-inoculated trees. Significant differences (P < 0.01) in the distribution and numbers of nematodes in stem-inoculated trees were detected between trees with or without symptoms.
The use of electrical capacitance to determine growth and vigor of spruce and fir trees and stands in New Brunswick
Authors: MacDougall R. Glenn , MacLean David A. , Thompson Robert G.
Published: February 2008

A capacitance meter based on an integrating operational amplifier design was used to measure electrical capacitance of over 3400 trees in 90 spruce–fir stands in New Brunswick. Trends of capacitance were compared with trends of tree growth, tree characteristics, and defoliation by spruce budworm (Choristoneurafumiferana (Clem.)). Capacitance differed among tree species, with balsam fir (Abiesbalsamea (L.) Mill.) and white spruce (Piceaglauca (Moench) Voss) having generally higher values than red spruce (Picearubens Sarg.) and black spruce (Piceamariana (Mill.) B.S.P.). Capacitance also decreased with crown class and with increasing cumulative defoliation. Correlations between tree growth and capacitance ranged from about 0.6 to 0.7 for tree data, and 0.6 to 0.9 for stand data. Regressions between mean growth per stand and mean capacitance explained about 40 to 70% of the variability in growth. These results indicate that it is practical to use electrical capacitance measurements to assess tree growth and vigor.
Hybridization of a Rocky Mountain fir (Abiesconcolor) and a Mexican fir (Abiesreligiosa)
Authors: Clair J. B. St. , Critchfield W. B.
Published: February 2008

Interspecific crosses of Abiesreligiosa (HBK.) Schlecht. & Cham, (oyamel) with Abiesconcolor (Gord. & Glend.) Lindl. ex Hildebr. var. concolor (white fir) and Abiesmagnifica A. Murr. (California red fir) were undertaken to explore the relationships between these species. The cross with A. magnifica produced no germinable seed, but many sound seeds were produced from the cross with A. concolor. These were sown in the nursery in 1968 and outplanted in 1970. In 1983, morphological characteristics of seven putative hybrids were compared with those of the A. concolor seed parent, herbarium specimens of A. religiosa, and published descriptions of both species. In addition, monoterpene composition of the putative hybrids was compared with that of the seed parent and two unrelated A. religiosa trees from the same provenance as the pollen parent. Results indicate that the putative hybrids are indeed hybrids between A. concolor and A. religiosa. This finding suggests that either taxonomic sections are not separated by reproductive barriers in Abies (as they are in Pinus) or that earlier classifications should be reconsidered.
Estimating fine-root production and turnover from biomass and decomposition data: a compartment-flow model
Authors: Santantonio D. , Grace J. C.
Published: February 2008

not available
Acupuncture and Immunomodulation
Authors: Cabioğlu Mehmet T. , Cetin B. Eren
Published: February 2008

Acupuncture is a well-known form of Asian medical treatment and it is used not only as an effective curative method but also to prevent illness and mai ntain health. It is used for the production of analgesic effect; stress related physical-mental disorders and homeostasis. Electroacupuncture (EA) stimulation, an application of electrical current on acupuncture needles, is one of the most popular types of this traditional therapy. In recent years, intensive studies have been carried out to explain the underlying mechanisms of the efficacy of acupuncture. An increase in the release of endogen opioid peptides is generally accepted to be a keystone pathway that affects the immune system after the acupuncture application. To understand the huge gap between specific skin point applications and immune responses, a vast number of accumulating data of experimental and clinical studies in the literature have been collected. This paper reviews the data to explain the updated mechanisms related to immune modulation via acupuncture therapy.
Du-zhong (Eucommia ulmoidesOliver) Leaf Extract Mediates Hypolipidemic Action in Hamsters Fed a High-Fat Diet
Authors: Choi Myung-Sook , Jung Un Ju , Kim Hye-Jin , Do Gyeong-Min , Jeon Seon-Min , Kim Myung-Joo , Lee Mi-Kyung
Published: February 2008

This study examined the effect of a Du-zhong (Eucommia ulmoides Oliver) leaf extract (0.175 g/100 g diet) that was supplemented with a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) on hyperlipidemic hamsters. Hamsters fed with Du-zhong leaf extract for 10 weeks showed a smaller size of epididymal adipocytes compared to the control group. The supplementation of the Du-zhong leaf extract significantly lowered the plasma levels of triglyceride, total cholesterol, LDL-cholesterol, non HDL-cholesterol, and free fatty acid, whereas it elevated the HDL-cholesterol/total cholesterol ratio and apolipoprotein A-I levels. The hepatic cholesterol concentration was lower in the Du-zhong group than in the control group. The plasma total cholesterol concentration was positively correlated with hepatic HMG- CoA reductase activity (r = 0.547, p < 0.05) and hepatic cholesterol concentration (r = 0.769, p < 0.001). The hepatic fatty acid synthase and HMG- CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters. Hepatic fatty acid synthase activity was positively correlated with plasma fatty acid concentration (r = 0.513, p < 0.05) that was lower in the Du-zhong group. These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.
The Antidepressant Effect ofGastrodia elataBl. on the Forced-Swimming Test in Rats
Authors: Chen Pei-Ju , Hsieh Ching-Liang , Su Kuan-Pin , Hou Yu-Chi , Chiang Hsiu-Mei , Lin I-Hsin , Sheen Lee-Yan
Published: February 2008

Depression is a common psychiatric disorder with a high morbidity and mortality rate. The pharmacotherapy used in clinic today is not suitable for all patients and causes certain side-effects. Thus, looking for alternative treatments with antidepressant effect and minimal side-effect is important. Gastrodia elata Bl. is a famous Chinese traditional medicine used for centuries. The aim of this study is to test the antidepressant effect of Gastrodia elata Bl. extract (GE) using forced-swimming test (FST). Sprague-Dawley rats were assigned to control, GE, and fluoxetine groups, treated with 10 ml/kg bw (body weight) water, 1 g/kg bw of GE, and 15 mg/kg bw of fluoxetine, respectively. Those samples were administered by gavage to rats 23.5, 4.5 and 1 hour prior to the test session of FST. After FST, the animals were sacrificed and their brains were collected for monoamines analysis. The results indicated that the duration of immobility was significantly decreased in GE group compared to the control (p < 0.05). The concentration of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and the ratio of 5-HIAA/5-HT in frontal cortex, amygdala, and hippocampus were not significantly different between GE and the control groups. However, administration of GE significantly increased the dopamine (DA) concentration (p < 0.05) and decreased the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) (p < 0.01) and DA turnover (p < 0.05) in striatum compared to the control. The results of this study show that Gastrodia elata Bl. extract modulates the turnover of DA in rats, and thus probably possesses antidepressant effect in rats.
Antioxidant and Hepatoprotective Activities of Cirsium setidens NAKAI against CCl4-Induced Liver Damage
Authors: Lee Sung Hyun , Heo Seong-Il , Li Lan , Lee Min Jie , Wang Myeong-Hyeon
Published: February 2008

The antioxidant activity and hepatoprotective potential of Cirsium setidens Nakai, a widely used medicinal plant, were investigated. The n-butanol (n-BuOH) fraction of leaves and roots of C. setidens had a higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than the other soluble fractions. The n- BuOH fraction of roots of C. setidens had a significant hepatoprotective activity at a dose of 500 mg/kg compared to that of a standard agent. The biochemical results were confirmed by histological observations indicating that C. setidens extract decreased ballooning degeneration in response to CCl4 treatment. The n-BuOH fraction reduced CCl4-induced liver injury in rats, and transcript levels of genes encoding antioxidant enzymes such as glutathione peroxidase 1 (GPO1), glutathione peroxidase 3 (GPO3) and superoxide dismutase (SOD1) were elevated in the livers of rats treated with this fraction (500 mg/kg). Based on these results, we suggest that the C. setidens extract has hepatoprotective effect related to its antioxidant activity.
Alleviating Effects of Active Fraction of Euonymus alatus Abundant in Flavonoids on Diabetic Mice
Authors: Fang Xian-Kang , Gao Yuan , Yang Hai-Yan , Lang Su-Mei , Wang Qiu-Juan , Yu Bo-Yang , Zhu Dan-Ni
Published: February 2008

Euonymus alatus (E. alatus) has been used as a folk medicine for diabetes in China for more than one thousand years. In order to identify major active components, effects of different fractions of E. alatus on the plasma glucose levels were investigated in normal mice and alloxan-induced diabetic mice. Our results show that ethyl acetate fraction (EtOAc Fr.) displayed significant effects on reducing plasma glucose. In oral glucose tolerance, EtOAc Fr. at 17.2 mg/kg could significantly decrease the blood glucose of both normal mice and diabetic mice. After 4 weeks administration of the EtOAc Fr, when compared with the diabetic control, there were significant difference in biochemical parameters, such as glycosylated serum protein, superoxide dismutase and malondial dehyde, triglyceride, and total cholesterol, between alloxan-induced diabetic mice and the control group. Additional histopathological studies of pancreatic islets also showed EtOAc Fr. has beneficial effects on diabetic mice. Chemical analysis with three-dimensional HPLC demonstrated that the major components from EtOAc Fr were flavonoids and phenolic acids, which had anti-oxidative effects on scavenging DPPH-radical in vitro. All these experimental results suggest that EtOAc Fr. is an active fraction of E. alatus and can prevent the progress of diabetes. The mechanism of E. alatus for glucose control may be by stimulating insulin release, improving glucose uptake and improving oxidative-stress.
The Extract ofHibiscus syriacusInducing Apoptosis by Activating p53 and AIF in Human Lung Cancer Cells
Authors: Cheng Yeung-Leung , Lee Shih-Chun , Harn Horng-Jyh , Huang Hsin-Chieh , Chang Wen-Liang
Published: February 2008

Natural products including plants, microorganisms and marine life provide rich resources for anticancer drug discovery. The root bark of Hibiscus syriacus has been used as an antipyretic, anthelmintic and antifungal agent in Asia. The antiproliferative effects of H. syriacus on human lung cancer cells were evaluated with bio-assays. The apoptotic activity was detected by Hoechst 33342 DNA staining and annexin V staining. The expression of caspases, p53, apoptosis induced factor (AIF), Bcl-2 and Bax were evaluated with Western blotting. The in vivo anticancer activity was evaluated using A549-xenograft model. The acetone extract of H. syriacus (HS-AE) exhibited a better cytotoxic effect on lung cancer cells than its methanol extract (HS-ME) or water extract (HS-WE). The IC50values of HS-AE on A549 (adenocarcinoma), H209 (squamous cell carcinoma) or H661 (large cell carcinoma) lung cancer cells ranged from 14 to 22 μg/ml after 48 hours of treatment. After 48 hours of exposure, HS-AE (15 μg/ml) induced A549 cell apoptosis to 48 ± 3.6% of the control. Using Western blotting, HS-AE appears to suppress the expression of p53 and AIF. The results of the in vivo study showed that HS-AE suppresses growth in A549 subcutaneous xenograft tumors. These results indicate that HS-AE exerts significant and dose-dependent antiproliferative effects on cancer cells in vitro and in vivo, which prompts us to further evaluate and elucidate the bioactive component(s) of H. syriacus.
Antiviral and Anti-proliferative Glycoproteins from the Rhizome ofSmilax glabraRoxb (Liliaceae)
Authors: Ooi Linda S. M. , Wong Elaine Y. L. , Chiu Lawrence C. M. , Sun Samuel S. M. , Ooi Vincent E. C.
Published: February 2008

The glycoproteins possessing antiviral and anti-proliferative activities were isolated from the Chinese medicinal herb Smilax glabra (known as tufuling), by extraction with 0.2 M NaCl , ammonium sulfate precipitation, fetuin-agarose affinity chromatography and gel filtration. The molecular mass of the fetuin-binding glycoprotein (designated SGPF2) was estimated to be about 58 kDa, with a major protein subunit of 26 kDa. The non-fetuin binding glycoproteins (in the unadsorbed fraction) were further separated into 5 different subfractions (SGPF1a–SGPF1e) with anion-exchange chromatography, all of which also contained the major band at 26 kDa. All the isolated proteins of 26 kDa had similar N-terminal amino acid sequences, implying that they were probably the isoforms originated putatively from a multigene family with different binding affinity and ionic strength. The glycoprotein SGPF2 exhibited antiviral activity against respiratory syncytial virus (RSV) with a median inhibitory concentration (IC50) of 62.5 μg/ml and Herpes simplex virus type 1 (HSV-1) had an IC50of 31.3 μg/ml. The glycoprotein potencies for antiviral activity appeared to depend on the molecules' binding affinity for fetuin, that is, the fetuin-binding protein was more potent than the non-fetuin binding proteins. Further examination revealed that these glycoproteins also had the ability to suppress the proliferation of MCF-7 cells. The possible mechanism of anti-proliferative action as analyzed by DNA flow cytometry indicated that they could induce apoptosis mediated via sub-G1phase of the MCF-7 cell cycle. For example, there was an increase by 75.8% of the control level of apoptosis after incubation with SGPF1a.
SUPERSYMMETRIC KUPER CAMASSA–HOLM EQUATION AND GEODESIC FLOW: A NOVEL APPROACH
Authors: GUHA PARTHA
Published: February 2008

We use the logarithmic 2-cocycle and the action of V ect (S1) on the space of pseudodifferential symbols to derive one particular type of supersymmetric KdV equation, known as Kuper-KdV equation. This equation was formulated by Kupershmidt and it is different from the Manin–Radul–Mathieu type equation. The two Super KdV equations behave differently under a supersymmetric transformation and Kupershmidt version does not preserve SUSY transformation. In this paper we study the second type of supersymmetric generalization of the Camassa–Holm equation correspoding to Kuper-KdV equation via standard embedding of super vector fields into the Lie algebra of graded pseudodifferential symbols. The natural lift of the action of superconformal group SDiff yields SDiff module. This method is particularly useful to construct Moyal quantized systems.
COMPACTNESS OF D-ISOSPECTRAL METRICS
Authors: KANG HYUNSUK
Published: February 2008

We generalise the compactness of isospectral metrics in the C∞-topology modulo gauge equivalence in dimension three to the case for Schrödinger operators with bounded potentials, as well as the finiteness of diffeomorphism types of isospectral manifolds.
A cystine-cysteine shuttle mediated by xCT facilitates cellular responses to S-nitrosoalbumin
Authors: Zhu Jun , Li Sheng , Marshall Zermeena M. , Whorton A. R.
Published: February 2008

We have shown previously that extracellular cysteine is necessary for cellular responses to S-nitrosoalbumin. In this study we have investigated mechanisms involved in accumulation of extracellular cysteine outside vascular smooth muscle cells and characterized the role of cystine-cysteine release in transfer of nitric oxide (NO)-bioactivity. Incubation of cells with cystine led to cystine uptake, reduction, and cysteine release. The process was inhibitable by extracellular glutamate, suggesting a role for system xc− amino acid transporters. Smooth muscle cells express this transporter constitutively and induction of the light chain component (xCT) by either diethyl maleate or 3-morpholino-sydnonimine (SIN-1) led to glutamate-inhibitable cystine uptake and an increased rate of cysteine release from cells. Likewise, overexpression of xCT in smooth muscle cells or endothelial cells led to glutamate-inhibitable cysteine release. The resulting extracellular cysteine was found to be required for transfer of NO from extracellular S-nitrosothiols into cells via system L transporters leading to formation of cellular S-nitrosothiols. Cysteine release coupled to cystine uptake was also found to be required for cellular responses to S-nitrosoalbumin and facilitated S-nitrosoalbumin-mediated inhibition of epidermal growth factor signaling. These data show that xCT expression can constitute a cystine-cysteine shuttle whereby cystine uptake drives cysteine release. Furthermore, we show that extracellular cysteine provided by this shuttle mechanism is necessary for transfer of NO equivalents and cellular responses to S-nitrosoablumin.
Role of extracellular superoxide in neutrophil activation: interactions between xanthine oxidase and TLR4 induce proinflammatory cytokine production
Authors: Lorne Emmanuel , Zmijewski Jaroslaw W. , Zhao Xia , Liu Gang , Tsuruta Yuko , Park Young-Jun , Dupont Hervé , Abraham Edward
Published: February 2008

Reactive oxygen species (ROS) contribute to neutrophil activation and the development of acute inflammatory processes in which neutrophils play a central role. However, there is only limited information concerning the mechanisms through which extracellular ROS, and particularly cell membrane-impermeable species, such as superoxide, enhance the proinflammatory properties of neutrophils. To address this issue, neutrophils were exposed to superoxide generating combinations of xanthine oxidase and hypoxanthine or lumazine. Extracellular superoxide generation induced nuclear translocation of nuclear factor-κB (NF-κB) and increased neutrophil production of the NF-κB-dependent cytokines tumor necrosis factor-α (TNF-α) and macrophage inhibitory protein-2 (MIP-2). In contrast, there were no changes in TNF-α or MIP-2 expression when neutrophils lacking Toll-like receptor-4 (TLR4) were exposed to extracellular superoxide. Immunoprecipitation, confocal microscopy, and fluorescence resonance energy transfer (FRET) studies demonstrated association between TLR4 and xanthine oxidase. Exposure of neutrophils to heparin attenuated binding of xanthine oxidase to the cell surface as well as interactions with TLR4. Heparin also decreased xanthine oxidase-induced nuclear translocation of NF-κB as well as production of proinflammatory cytokines. These results demonstrate that extracellular superoxide has proinflammatory effects on neutrophils, predominantly acting through an TLR4-dependent mechanism that enhances nuclear translocation of NF-κB and increases expression of NF-κB-dependent cytokines.
Selective binding of RGMc/hemojuvelin, a key protein in systemic iron metabolism, to BMP-2 and neogenin
Authors: Kuns-Hashimoto Robin , Kuninger David , Nili Mahta , Rotwein Peter
Published: February 2008

Juvenile hemochromatosis is a severe and rapidly progressing hereditary disorder of iron overload, and it is caused primarily by defects in the gene encoding repulsive guidance molecule c/hemojuvelin (RGMc/HJV), a recently identified protein that undergoes a complicated biosynthetic pathway in muscle and liver, leading to cell membrane-linked single-chain and heterodimeric species, and two secreted single-chain isoforms. RGMc modulates expression of the hepatic iron regulatory factor, hepcidin, potentially through effects on signaling by the bone morphogenetic protein (BMP) family of soluble growth factors. To date, little is known about specific pathogenic defects in disease-causing RGMc/HJV proteins. Here we identify functional abnormalities in three juvenile hemochromatosis-linked mutants. Using a combination of approaches, we first show that BMP-2 could interact in biochemical assays with single-chain RGMc species, and also could bind to cell-associated RGMc. Two mouse RGMc amino acid substitution mutants, D165E and G313V (corresponding to human D172E and G320V), also could bind BMP-2, but less effectively than wild-type RGMc, while G92V (human G99V) could not. In contrast, the membrane-spanning protein, neogenin, a receptor for the related molecule, RGMa, preferentially bound membrane-associated heterodimeric RGMc and was able to interact on cells only with wild-type RGMc and G92V. Our results show that different isoforms of RGMc/HJV may play unique physiological roles through defined interactions with distinct signaling proteins and demonstrate that, in some disease-linked RGMc mutants, these interactions are defective.
VE-cadherin and β-catenin binding dynamics during histamine-induced endothelial hyperpermeability
Authors: Guo Mingzhang , Breslin Jerome W. , Wu Mack H. , Gottardi Cara J. , Yuan Sarah Y.
Published: February 2008

β-Catenin plays an important role in the regulation of vascular endothelial cell-cell adhesions and barrier function by linking the VE-cadherin junction complex to the cytoskeleton. The purpose of this study was to evaluate the effect of β-catenin and VE-cadherin interactions on endothelial permeability during inflammatory stimulation by histamine. We first assessed the ability of a β-catenin binding polypeptide known as inhibitor of β-catenin and T cell factor (ICAT) to compete β-catenin binding to VE-cadherin in vitro. We then overexpressed recombinant FLAG-ICAT in human umbilical vein endothelial cells (HUVECs) to study its impact on endothelial barrier function controlled by cell-cell adhesions. The binding of β-catenin to VE-cadherin was quantified before and after stimulation with histamine along with measurements of transendothelial electrical resistance (TER) and apparent permeability to albumin ( Pa) under the same conditions. The results showed that ICAT bound to β-catenin and competitively inhibited binding of the VE-cadherin cytoplasmic domain to β-catenin in a concentration-dependent manner. Overexpression of FLAG-ICAT in endothelial cell monolayers did not affect their basal permeability properties, as indicated by unaltered TER and Pa; however, the magnitude and duration of histamine-induced decreases in TER were significantly augmented. Likewise, the increase in Pa in the presence of histamine was exacerbated. Overexpression of FLAG-ICAT also significantly decreased the level of β-catenin-associated VE-cadherin following histamine stimulation. Taken together, these data suggest that inflammatory agents like histamine cause a transient and reversible disruption of binding between β-catenin and VE-cadherin, during which endothelial permeability is elevated.
Simultaneous pulmonary trunk and pulmonary arterial wave intensity analysis in fetal lambs: evidence for cyclical, midsystolic pulmonary vasoconstriction
Authors: Smolich Joseph J. , Mynard Jonathan P. , Penny Daniel J.
Published: February 2008

The physiological basis of a characteristically low blood flow to the fetal lungs is incompletely understood. To determine the potential role of pulmonary vascular interaction in this phenomenon, simultaneous wave intensity analysis (WIA) was performed in the pulmonary trunk (PT) and left pulmonary artery (LPA) of 10 anesthetized late-gestation fetal sheep instrumented with PT and LPA micromanometer catheters to measure pressure (P) and transit-time flow probes to obtain blood velocity ( U). Studies were performed at rest and during brief complete occlusion of the ductus arteriosus to augment pulmonary vasoconstriction ( n = 4) or main pulmonary artery to abolish wave transmission from the lungs ( n = 3). Wave intensity (d IW) was calculated as the product of the P and U rates of change. Forward and backward components of d IW were determined after calculation of wave speed. PT and LPA WIA displayed an early systolic forward compression wave (FCWis) increasing P and U, and a late systolic forward expansion wave decreasing P and U. However, a marked midsystolic fall in LPA U to near-zero was related to an extremely prominent midsystolic backward compression wave (BCWms) that arose ∼5 cm distal to the LPA, was threefold larger than the PT BCWms ( P < 0.001), of similar size to FCWis at rest ( P > 0.6), larger than FCWis following ductal occlusion ( P < 0.05) and abolished after main pulmonary artery occlusion. These findings suggest that the absence of pulmonary arterial midsystolic forward flow which accompanies a low fetal lung blood flow is due to a BCWms generated in part by cyclical vasoconstriction within the pulmonary microcirculation.
Experimental autoimmune prostatitis induces chronic pelvic pain
Authors: Rudick Charles N. , Schaeffer Anthony J. , Thumbikat Praveen
Published: February 2008

Pain is the hallmark of patients with chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS). Despite numerous hypotheses, the etiology and pathogenesis remain unknown. To better understand CP/CPPS, we used a murine experimental autoimmune prostatitis model to examine the development, localization, and modulation of pelvic pain. Pelvic pain was detected 5 days after antigen instillation and was sustained beyond 30 days, indicating the development of chronic pain. The pain was attenuated by lidocaine treatment into the prostate, but not into the bladder or the colon, suggesting that pain originated from the prostate. Experimental autoimmune prostatitis histopathology was confined to the prostate with focal periglandular inflammatory infiltrates in the ventral, dorsolateral, and anterior lobes of the mouse prostate. Inflammation and pelvic pain were positively correlated and increased with time. Morphologically, the dorsolateral prostate alone showed significantly increased neuronal fiber distribution, as evidenced by increased protein gene product 9.5 expression. Pelvic pain was attenuated by treatment with the neuromodulator gabapentin, suggesting spinal and/or supraspinal contribution to chronic pain. These results provide the basis for identifying mechanisms that regulate pelvic pain and the testing of therapeutic agents that block pain development in CP/CPPS.
Sex and the renin-angiotensin system: inequality between the sexes in response to RAS stimulation and inhibition
Authors: Sullivan Jennifer C.
Published: February 2008

The purpose of this review is to examine sex differences in response to stimulation and inhibition of the renin-angiotensin system (RAS). The RAS plays a prominent role in the development of chronic renal disease, and there are known sex differences not only in the expression level of components of the RAS but also in how males and females respond to perturbations of the RAS. In men, renal injury increases in parallel with increased activation of the RAS, while in women, increases in ANG II do not necessarily translate into increases in renal injury. Moreover, both epidemiological and experimental studies have noted sex differences in the therapeutic benefits following angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment. Despite these differences, RAS inhibitors are the most commonly prescribed drugs for the treatment of chronic renal disease, irrespective of sex. This review will examine how males and females respond to stimulation and inhibition of the RAS, with a focus on renal disease.
Effect of chronic endothelin receptor antagonism on cerebrovascular function in type 2 diabetes
Authors: Harris Alex K. , Elgebaly Mostafa M. , Li Weiguo , Sachidanandam Kamakshi , Ergul Adviye
Published: February 2008

Diabetes increases the risk of stroke and contributes to poor clinical outcomes in this patient population. Myogenic tone of the cerebral vasculature, including basilar arteries, plays a key role in controlling cerebral blood flow. Increased myogenic tone is ameliorated with ET receptor antagonism in Type 1 diabetes. However, the role of endothelin-1 (ET-1) and its receptors in cerebrovascular dysfunction in Type 2 diabetes, a common comorbidity in stroke patients, remains poorly elucidated. Therefore, we hypothesized that 1) cerebrovascular dysfunction occurs in the Goto-Kakizaki (GK) model of Type 2 diabetes, and 2) pharmacological antagonism of ETAreceptors ameliorates, while ETBreceptor blockade augments vascular dysfunction. GK or control rats were treated with antagonists to either ETA(atrasentan, 5 mg·kg−1·day−1) or ETB(A-192621, 15 or 30 mg·kg−1·day−1) receptors for 4 wk and vascular function of basilar arteries was assessed using a wire myograph. GK rats exhibited increased sensitivity to ET-1. ETAreceptor antagonism caused a rightward shift, indicating decreased sensitivity in diabetes, while it increased sensitivity to ET-1 in control rats. Endothelium-dependent relaxation was impaired in diabetes. ETAreceptor blockade restored relaxation to control values in the GK animals with no significant effect in Wistar rats and ETBblockade with 30 mg·kg−1·day−1A-192621 caused paradoxical constriction in diabetes. These studies demonstrate that cerebrovascular dysfunction occurs and may contribute to altered regulation of myogenic tone and cerebral blood flow in diabetes. While ETAreceptors mediate vascular dysfunction, ETBreceptors display differential effects. These results underscore the importance of ETA/ETBreceptor balance and interactions in cerebrovascular dysfunction in diabetes.
Role of angiotensin II in the enhancement of ammonia production and secretion by the proximal tubule in metabolic acidosis
Authors: Nagami Glenn T.
Published: February 2008

Acidosis and angiotensin II stimulate ammonia production and transport by the proximal tubule. We examined the modulatory effect of the type 1 angiotensin II receptor blocker losartan on the ability of metabolic acidosis to stimulate ammonia production and secretion by mouse S2 proximal tubule segments. Mice given NH4Cl for 7 days developed metabolic acidosis (low serum bicarbonate concentration) and increased urinary excretion of ammonia. S2 tubule segments from acidotic mice displayed higher rates of ammonia production and secretion compared with those from control mice. However, when losartan was coadministered in vivo with NH4Cl, both the acidosis-induced increase in urinary ammonia excretion and the adaptive increase in ammonia production and secretion of microperfused S2 segments were largely blocked. In renal cortical tissue, losartan blocked the acid-induced increase in brush-border membrane NHE3 expression but had no effect on the acid-induced upregulation of phosphate-dependent glutaminase or phosphoenolpyruvate carboxykinase 1 in cortical homogenates. Addition of angiotensin II to the microperfusion solution enhanced ammonia secretion and production rates in tubules from NH4Cl-treated and control mice in a losartan-inhibitable manner. These results demonstrate that a 7-day acid challenge induces an adaptive increase in ammonia production and secretion by the proximal tubule and suggest that during metabolic acidosis, angiotensin II signaling is necessary for adaptive enhancements of ammonia excretion by the kidney and ammonia production and secretion by S2 proximal tubule segments, as mediated, in part, by angiotensin receptor-dependent enhancement of NHE3 expression.
Nicotine-activated descending facilitation on spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats
Authors: Pan Shwu-Fen , Peng Hsien-Yu , Chen Chi-Chung , Chen Mei-Jung , Lee Shin-Da , Cheng Chen-Li , Shyu Jyh-Cherng , Liao Jiuan-Miaw , Chen Gin-Den , Lin Tzer-Bin
Published: February 2008

This study was conducted to investigate the possible neurotransmitter that activates the descending pathways coming from the dorsolateral pontine tegmentum (DPT) to modulate spinal pelvic-urethra reflex potentiation. External urethra sphincter electromyogram (EUSE) activity in response to test stimulation (TS, 1/30 Hz) and repetitive stimulation (RS, 1 Hz) on the pelvic afferent nerve of 63 anesthetized rats were recorded with or without microinjection of nicotinic cholinergic receptor (nAChR) agonists, ACh and nicotine, to the DPT. TS evoked a baseline reflex activity with a single action potential (1.00 ± 0.00 spikes/stimulation, n = 40), whereas RS produced a long-lasting reflex potentiation (16.14 ± 0.96 spikes/stimulation, n = 40) that was abolished by d-2-amino-5-phosphonovaleric acid (1.60 ± 0.89 spikes/stimulation, n = 40) and was attenuated by 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (7.10 ± 0.84 spikes/stimulation, n = 40). ACh and nicotine microinjections to DPT both produced facilitation on the RS-induced reflex potentiation (23.57 ± 2.23 and 28.29 ± 2.36 spikes/stimulation, P < 0.01, n = 10 and 20, respectively). Pretreatment of selective nicotinic receptor antagonist, chlorisondamine, reversed the facilitation on RS-induced reflex potentiation caused by nicotine (19.41 ± 1.21 spikes/stimulation, P < 0.01, n = 10) Intrathecal WAY-100635 and spinal transection at the T1level both abolished the facilitation on reflex potentiation resulting from the DPT nicotine injection (12.86 ± 3.13 and 15.57 ± 1.72 spikes/stimulation, P < 0.01, n = 10 each). Our findings suggest that activation of nAChR at DPT may modulate N-methyl-d-aspartic acid-dependent reflex potentiation via descending serotonergic neurotransmission. This descending modulation may have physiological/pathological relevance in the neural controls of urethral closure.
The impact of aging on kidney repair
Authors: Schmitt Roland , Cantley Lloyd G.
Published: February 2008

The process of normal aging affects organ homeostasis as well as responses to acute and chronic injury. In view of the rapid growth in the elderly population, it is increasingly important for us to develop a mechanistic understanding of how these age-dependent changes can impact the susceptibility and response of the kidney to injurious stimuli. In this overview, we focus on the current understanding of those mechanisms by reviewing how cellular changes in the aging kidney might lead to a diminished proliferative reserve, an increased tendency for apoptosis, alterations in growth factor profiles, and changes in potential progenitor and immune cell functions. A better understanding of these processes may help us to define new targets for studying kidney repair and could ultimately lead to new therapeutic strategies that are specifically tailored for treatment of the elderly population.
Modeling GABA Alterations in Schizophrenia: A Link Between Impaired Inhibition and Altered Gamma and Beta Range Auditory Entrainment
Authors: Vierling-Claassen Dorea , Siekmeier Peter , Stufflebeam Steven , Kopell Nancy
Published: February 2008

The disorganized symptoms of schizophrenia, including severely disordered thought patterns, may be indicative of a problem with the construction and maintenance of cell assemblies during sensory processing and attention. The gamma and beta frequency bands (15–70 Hz) are believed relevant to such processing. This paper addresses the results of an experimental examination of the cortical response of 12 schizophrenia patients and 12 control subjects when presented with auditory click-train stimuli in the gamma/beta frequency band during measurement using magnetoencephalography (MEG), as well as earlier work by Kwon et al. These data indicate that control subjects show an increased 40-Hz response to both 20- and 40-Hz stimulation as compared with patients, whereas schizophrenic subjects show a preference for 20-Hz response to the same driving frequencies. In this work, two computational models of the auditory cortex are constructed based on postmortem studies that indicate cortical interneurons in schizophrenic subjects have decreased GAT-1 (a GABA transporter) and GAD67(1 of 2 enzymes responsible for GABA synthesis). The models transition from control to schizophrenic frequency response when an extended inhibitory decay time is introduced; this change captures a possible effect of these GABA alterations. Modeling gamma/beta range auditory entrainment in schizophrenia provides insight into how biophysical mechanisms can impact cognitive function. In addition, the study of dynamics that underlie auditory entrainment in schizophrenia may contribute to the understanding of how gamma and beta rhythms impact cognition in general.