bluuebunny/crossref_metadata_2025 huggingface dataset:
Composition and carbon dynamics of forests in northeastern North America in a future, warmer worldThis article is one of a selection of papers from NE Forests 2100: A Synthesis of Climate Change Impacts on Forests of the Northeastern US and Eastern Canada.
Authors: Mohan Jacqueline E. , Cox Roger M. , Iverson Louis R.
Published: February 2009

Increasing temperatures, precipitation extremes, and other anthropogenic influences (pollutant deposition, increasing carbon dioxide) will influence future forest composition and productivity in the northeastern United States and eastern Canada. This synthesis of empirical and modeling studies includes tree DNA evidence suggesting tree migrations since the last glaciation were much slower, at least under postglacial conditions, than is needed to keep up with current and future climate warming. Exceedances of US and Canadian ozone air quality standards are apparent and offset CO2-induced gains in biomass and predispose trees to other stresses. The deposition of nitrogen and sulfate in the northeastern United States changes forest nutrient availability and retention, reduces reproductive success and frost hardiness, causes physical damage to leaf surfaces, and alters performance of forest pests and diseases. These interacting stresses may increase future tree declines and ecosystem disturbances during transition to a warmer climate. Recent modeling work predicts warmer climates will increase suitable habitat (not necessarily actual distribution) for most tree species in the northeastern United States. Species whose habitat is declining in the northeastern United States currently occur in Canadian forests and may expand northward with warming. Paleoecological studies suggest local factors may interact with, even overwhelm, climatic effects, causing lags and thresholds leading to sudden large shifts in vegetation.
Temperature Treatment of Douglas-fir Seeds to Control the Seed Chalcid Megastigmusspermotrophus Wachtl
Authors: Ruth D. S. , Hedlin A. F.
Published: February 2009

Larvae of the chalcid Megastigmusspermotrophus in Douglas-fir seeds were killed when treated at 45 °C for 27 h (2-year-old seed) and for 33 h (1-year-old seed). Heat treatment of uninfested seed did not affect rate of germination of seedling growth.
A Sequential Extraction Procedure for Studying the Distribution of Organic Fractions in Forest Humus Layers
Authors: Lowe L. E.
Published: February 2009

A procedure is described for the separation of nine organic matter fractions from F and H horizons of forest floor materials formed under different vegetative cover. The extracts employed (and fractions obtained) were ethanol:benzene (A), dilute mineral acid (B), cold 0.1 N NaOH (H-1, F-1, F-2), and hot NaOH (H-2, F-3, F-4), with unextracted organic matter comprising the final fraction. Distribution between the fractions of carbon, and polysaccharides was investigated. Considerable variation was observed in the distribution of fractions among sites, and both between and within horizons. The significance of the fractions is discussed. It was concluded that the procedure was suitable for studying differences in distribution of organic fractions of forest floor materials, but required further modification for examination of the composition of fulvic fractions.
Evaluation of Fire-produced Seedbeds for Jack Pine Regeneration in Central Ontario
Authors: Chrosciewicz Z.
Published: February 2009

Burning and seeding were successfully used to regenerate jack pine after cutting in central Ontario. Two years after seeding, the depth of post-burn humus was measured under 2769 seedlings, of which 729 were dominant ones of known height. Generally, jack pine frequency distribution and heights of dominant jack pine were strongly affected by the depth of residual humus. The relationships were curvilinear and mostly inverse. They were subsequently used as guides in seedbed evaluation.
Annual Macroelement Transfer From PinusBanksiana Lamb. Forest to Soil
Authors: Foster Neil W.
Published: February 2009

The annual amounts of N, P, K, Ca, and Mg in litter-fall, throughfall, and stemflow were measured in a 30-year-old jack pine (Pinusbanksiana Lamb.) stand on a coarse glacial outwash soil in northern Ontario. Litter from ground vegetation and from the pine overstory was estimated. The nutrient content of precipitation was measured and the quantity of nutrients in leaf wash determined.Tree litter was the most important source of N, P, Ca, and Mg for the forest floor (51–69% of the total depending on the element), whereas throughfall supplied most K (54% of the total). Ground vegetation litter contributed significant amounts of nutrients (7–23% of the total depending on the element) but stemflow added little (1–8% of the total). Potassium in throughfall was derived mainly from leaf wash whereas N, P, Ca, and Mg in throughfall were derived primarily from precipitation entering the ecosystem. This jack pine forest floor received an annual total of 30 kg/ha of N, 22 kg/ha of Ca, 19 kg/ha of K, 3 kg/ha of Mg, and 2 kg/ha of P from the processes studied. Most of the nutrients in these totals were returning to the forest floor from the vegetation.
Etude d'un épandage aérien d'urée en forêt
Authors: Roberge M. R. , Gagnon J. D.
Published: February 2009

In September 1973, an aerial spraying of 336 kg/ha of urea was made over an area of 34 ha covered by firs 20–70 years old. Within the 35 permanent sample plots each comprising 0.04 ha and established at random on equidistant lines every 100 m, open cans had been placed one week before the spraying. They were taken 2 weeks after the end of the spraying and after checking that the urea intercepted by the trees had fallen. An average quantity of urea equivalent to 347 kg/ha was collected. Approximately 29% of the area received 336 ± 56 kg/ha of urea, 37% received less, and 34% received more. Five cylindrical cans having a diameter of 23 cm and a height of 24 cm in each of the 10 plots were sufficient to determine the exact rate of spraying, but at least 35 plots were necessary to know the distribution of urea in such an area. However, 10 cans were necessary to determine with sufficient accuracy the quantity of urea sprayed on each plot.
Structure and Edaphic Factors of an Alder Swamp in Northern Michigan
Authors: Parker George R. , Schneider G.
Published: February 2009

Existing edaphic factors on two lowland study sites at Dunbar Forest have resulted in a rich and characteristic flora of about 100 species. Alnusrugosa (Du Roi) Spreng. dominates the better drained very fine sandy loam site. The poorly drained silty clay loam site is in a transitional stage of succession from alder to a mixed alder-ash (Fraxinusnigra Marsh) community.A drainage ditch constructed 6 years earlier across both sites has had little effect on water table fluctuation. However, of the two areas the poorly drained site was more influenced by the drainage. The ditch did not greatly change species composition, but resulted in a distribution shift among herbaceons species.
Distribution of Pine (Pinus spp.) in the South Nahanni and Flat Rivers Region, Northwest Territories
Authors: Scotter George W.
Published: February 2009

Specimens of jack pine (Pinusbanksiana Lamb.), Rocky Mountain lodgepole pine (Pinuscontorta spp. latifolia (Engelm.) Critchfield) and hybrids of those two species were collected in the South Nahanni and Flat Rivers region. Those collections extend the previously known range of pines within that region.
Microstrobili of Douglas-fir
Authors: Ho Rong H. , Owens John N.
Published: February 2009

In Douglas-fir (Pseudotsugamenziesii (Mirb.) Franco), microstrobilate size increases acropetally along the shoot. Microstrobili have an average of 64.5 microsporophylls and 27.3 bud scales. Microsporangia have an oblique-transverse dehiscence layer on the abaxial surface. There are 462 pollen grains per microsporangium and about 3 million pollen grains per gram.
Stomatal Characteristics of Pinusresinosa and Pinusstrobus in Relation to Transpiration and Antitranspirant Efficiency
Authors: Davies W. J. , Kozlowski T. T. , Lee K. J.
Published: February 2009

Transpiration rates were much higher in Pinusresinosa than P. strobus, reflecting greater stomatal size and frequency in the former. In both species silicone antitranspirant formed stomatal plugs and greatly reduced transpiration.
Respiration rate of cold-stored nursery stock
Authors: Driessche R. van den
Published: February 2009

Respiration rates of 3-year-old red pine (Pinusresinosa Ait.) and 3-year-old white spruce (Piceaglauca Moench. (Voss)) were measured in sealed containers at 4.5 °C. Increase in CO2 concentration was measured using an infrared gas analyser (IRGA). Respiration continued steadily, at 0.025–0.046 mg CO2 g−1 dry matter h−1 up to CO2 concentrations of 2%, which are similar to those encountered in storage bags. Respiration rate of white spruce tended to be higher than that of red pine at 4.5 °C, and measurements of dry matter loss over 49 and 107 days confirmed that both species decrease in dry weight by about 4% in 100 days of storage at this temperature.
Height growth and apical damage of white ash (Fraxinusamericana L.) from various latitudes outplanted in New Brunswick
Authors: Goldsmith F. B. , Boudreau P.
Published: February 2009

White ash (Fraxinusamericanus L.) collected from a total of 36 geographic areas (in New Brunswick, Ontario, Quebec, and 18 areas of the United States) were outplanted in New Brunswick. The seven hundred and eighty-three 3-year-old seedlings showed a height range from 76 to 25 cm; the height was correlated with latitude (positive) and persistence of the apical bud (negative). Material from more southerly states (Illinois, Tennessee, and Kentucky) survived but suffered the most heavy apical damage of all the material outplanted in New Brunswick. It is suggested that white ash from the northeast of the continent, especially that from New Brunswick, is more resistant to winter damage and local indigenous material is therefore recommended for planting. More southerly material showed purple discoloration of the foliage and crinkled leaf edges. There was little correlation between height of seedlings and elevation of the original populations.
Decay resistance owing to near-anaerobic conditions in black cottonwood wetwood
Authors: Kamp B. J. van der , Gokhale A. A. , Smith R. S.
Published: February 2009

Gases extracted from wetwood of unwounded black cottonwood (Populustrichocarpa Torrey and Gray) trunks near Vancouver, B.C., throughout 1974 contained less than 0.10% O2 for periods of 5 to 19 weeks during the summer, and an average of approximately 2.5% O2 in winter. CO2 ranged from an average of about 8.5% in summer to about 6% in winter. Decay tests using surface and completely sterilized cottonwood sapwood and wetwood blocks showed no significant weight loss (average 0.2%) after 10 weeks under near-anaerobic conditions (O2 at 0.08%), while parallel tests under aerobic conditions resulted in 42% average weight loss. Both test fungi (Polyporusdelectans Peck and Ganodermaapplanatum (Pers.) Pat.) survived 10 weeks under near-anaerobic conditions, but resumption of decay following this period was considerably delayed. It is suggested that in black cottonwood, wetwood is not necessarily a deleterious phenomenon but rather a condition that imparts considerable decay resistance to the inner wood of unwounded trees.
Soil nutrient levels and pH associated with Armillariellamellea on conifers in northern Idaho
Authors: Shields Jr. Walter J. , Hobbs Stephen D.
Published: February 2009

A stepwise discriminant function analysis, based on soil chemical properties at the growing site, was used to differentiate conifers with root decay caused by Armillariellamellea (Vahl. ex Fr.) Karst. from conifers without A. mellea decay. Discriminant functions developed for Douglas-fir (Pseudotsugamenziesii (Mirb.) Franco) and grand fir (Abiesgrandis (Doug.) Lindl.) were significant. Low soil nitrogen and pH were associated with decayed Douglas-fir; low soil calcium and phosphorus and high soil potassium were associated with decayed grand fir.
Comparison of indicator variables for estimating growth reduction associated with Phellinusweirii root rot in Douglas-fir plantations
Authors: Bloomberg W. J. , Wallis G. W.
Published: February 2009

Total height, annual height increment, annual diameter at breast height (dbh) increment, ratio of total height to dbh, and ratio of annual height increment to annual dbh increment were assessed as indicator variables for estimating growth reduction associated with Phellinusweirii root rot of Douglas-fir (Pseudotsugamenziesii). Generally, height variables were more sensitive indicators than dbh. Total height by 2-cm-dbh classes, ratio of total height to dbh, and ratio of annual height increment to annual dbh increment were more sensitive and less variable than the other indicators. Ratio of total height to dbh was a more consistent and sensitive indicator of growth reduction than all other variables. Application of this ratio in estimating height growth reduction in three plantations indicated reductions in infected trees of 1 to 8 m over periods of 2 to 24 years, averaging 0.9 to 1.7% annually.
Stem form response to repeated pruning of young black walnut trees
Authors: Funk David T.
Published: February 2009

Five-year-old walnut trees were pruned for 3 consecutive years to remove branches from 0, 20, 40, 60, or 80% of the total length of the main stem. Increasing the amount of branch removal caused greater height growth, more cylindrical stems, and more stem sprouts, with the most pronounced response to the 60 and 80% pruning treatments. The response may be related to the relatively slow growth of the trees, wide spacing in the plantation, and early initiation and annual repetition of the pruning treatments.
Sprouting ability of advance growth in undisturbed hardwood stands
Authors: Powell Douglas S. , Tryon E. H.
Published: February 2009

We studied eight species of hardwoods to evaluate their ability to produce seedling sprouts (trees with stems that sprouted from a stump less than 2 in. (5 cm) in diameter at ground level) in the advance growth of undisturbed, mature stands on high-quality upland sites in West Virginia. The most reliable criterion used to measure this ability was the percentage of seedling sprouts, which indicated relatively good ability for white oak and black cherry; intermediate ability for dogwood, hickory, and white ash; and relatively poor ability for red maple, northern red oak, and sugar maple. Since the two oaks were at opposite ends of the spectrum, the results suggest that factors other than the ability to produce seedling sprouts may explain the growth of virtually pure oak stands on high-quality sites.
Radiocarbon dates on peat and tree remains from James Bay area, subarctic Quebec
Authors: Dionne Jean-Claude
Published: February 2009

14C dates on peat and tree remains from the southern part of James Bay Lowlands, subarctic Quebec, indicate that forests and peatland conditions began at least 1000 years after the deglaciation of the area. Inception of forest and organic deposition in bogs varies within the main geological events of the late-glacial and postglacial times in the area: the drainage of glacial Lake Ojibway, the Tyrrell Sea transgression, and the emergence. The oldest age recorded for the beginning of peat deposition is 6890 ± 120 years before present (BP) at an elevation of 240 m and the youngest age is 3830 ± 120 years BP at an elevation of 60 m. A delay ranging from 400 to 900 years between forest occupation and the establishment of bog conditions is recorded.
Decomposition and nutrient release in Douglas-fir needle litter in relation to stand development
Authors: Edmonds Robert L.
Published: February 2009

Decomposition rates and changes in the nutrient content of needle litter were examined in an age sequence of Douglas-fir (Pseudotsugamenziesii (Mirb.) Franco) stands in western Washington. The stands at the initiation of the study were 11, 24, 44, 75, and 97 years old. Nylon litter bags (1 mm mesh) containing needles from the 44-year-old stand were placed in the stands in February 1975. Bags were collected after 3, 6, 12, and 24 months, weighed, and analyzed for N, P, K, Ca, Mg, Mn, and lignin. Decomposition constants (k values) were determined. After 2 years, maximum decomposition rate occurred in the 24-year-old stand, where temperature and moisture conditions were most favorable. Low litter moisture tended to inhibit decomposition in summer. Values of k determined from 1-year weight loss data and percent needle lignin after 2 years were significantly different between stands. Values of k determined from weight loss were greater than those determined from litter fall weight: forest floor weight ratios. Loss of elements from litter bags after 2 years was in the following sequence in all stands, N < Mn < Ca < Mg < P < K. Annual stand net productivity was strongly correlated to N + K loss from litter bags (r = 0.96).
Role of oxidative stress in ischemia–reperfusion-induced alterations in myofibrillar ATPase activities and gene expression in the heartThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).
Authors: Maddika Srilekha , Elimban Vijayan , Chapman Donald , Dhalla Naranjan S.
Published: February 2009

Ischemia–reperfusion (IR) in the heart has been shown to produce myofibrillar remodeling and depress Ca2+ sensitivity of myofilaments; however, the mechanisms for these alterations are not clearly understood. In view of the role of oxidative stress in cardiac dysfunction due to IR, isolated rat hearts were subjected to global ischemia for 30 min followed by a 30-minute period of reperfusion. IR was found to induce cardiac dysfunction, as reflected by depressed LVDP, +dP/dt, and –dP/dt, and elevated LVEDP, and to reduce myofibrillar Ca2+-stimulated ATPase activity. These changes were simulated by perfusing the hearts with a mixture of xanthine plus xanthine oxidase, which is known to generate oxyradicals. The alterations in cardiac function and myofibrillar Ca2+-stimulated ATPase in IR hearts were attenuated by pretreatment with antioxidants (superoxide dismutase plus catalase, and N-acetylcysteine) and leupeptin, an inhibitor of Ca2+-dependent protease. The levels of mRNA for myosin heavy chain isoforms (α-MHC and β-MHC) and myosin light chain (MLC1) were depressed in IR hearts. These changes in gene expression due to IR were prevented upon perfusing the hearts with superoxide plus catalase, with N-acetylcysteine, or with leupeptin. The results suggest that oxidative stress due to IR injury and associated proteolysis play an important role in inducing changes in myofibrillar Ca2+-stimulated ATPase activity and gene expression in the heart.
Transient outward potassium channel regulation in healthy and diabetic heartsThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).
Authors: Gallego Mónica , Alday Aintzane , Urrutia Janire , Casis Oscar
Published: February 2009

Diabetic patients have a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death, and show important alterations in the electrocardiogram, most of these related to the repolarization. In myocytes isolated from diabetic hearts, the transient outward K+current (Ito) is the repolarizing current that is mainly affected. Type 1 diabetes alters Itoat 3 levels: the recovery of inactivation, the responsiveness to physiologic regulators, and the functional expression of the channel. Diabetes slows down Itorecovery of inactivation because it triggers the switching from fast-recovering Kv4.x channels to the slow-recovering Kv1.4. Diabetic animals also have decreased responsiveness of Itotowards the sympathetic nervous system; thus, the diabetic heart develops a resistance to its physiologic regulator. Finally, diabetes impairs support of various trophic factors required for the functional expression of the channel and reduces Itoamplitude by decreasing the amount of Kv4.2 and Kv4.3 proteins.
Role of antioxidant activity of taurine in diabetesThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).
Authors: Schaffer Stephen W. , Azuma Junichi , Mozaffari Mahmood
Published: February 2009

The unifying hypothesis of diabetes maintains that reactive oxygen species (ROS) generated in the mitochondria of glucose-treated cells promote reactions leading to the development of diabetic complications. Although the unifying hypothesis attributes the generation of oxidants solely to impaired glucose and fatty acid metabolism, diabetes is also associated with a decline in the levels of the endogenous antioxidant taurine in a number of tissues, raising the possibility that changes in taurine status might also contribute to the severity of oxidant-mediated damage. There is overwhelming evidence that taurine blocks toxicity caused by oxidative stress, but the mechanism underlying the antioxidant activity remains unclear. One established antioxidant action of taurine is the detoxification of hypochlorous acid. However, not all of the antioxidant actions of taurine are related to hypochlorous acid because they are detected in isolated cell systems lacking neutrophils. There are a few studies showing that taurine either modulates the antioxidant defenses or blocks the actions of the oxidants, but other studies oppose this interpretation. Although taurine is incapable of directly scavenging the classic ROS, such as superoxide anion, hydroxyl radical, and hydrogen peroxide, there are numerous studies suggesting that it is an effective inhibitor of ROS generation. The present review introduces a novel antioxidant hypothesis, which takes into consideration the presence of taurine-conjugated tRNAs in the mitochondria. Because tRNA conjugation is required for normal translation of mitochondrial-encoded proteins, taurine deficiency reduces the expression of these respiratory chain components. As a result, flux through the electron transport chain decreases. The dysfunctional respiratory chain accumulates electron donors, which divert electrons from the respiratory chain to oxygen, forming superoxide anion in the process. Restoration of taurine levels increases the levels of conjugated tRNA, restores respiratory chain activity, and increases the synthesis of ATP at the expense of superoxide anion production. The importance of this and other actions of taurine in diabetes is discussed.
Timing of induction of cardiomyocyte differentiation for in vitro cultured mesenchymal stem cells: a perspective for emergenciesThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).
Authors: Tokcaer-Keskin Zeynep , Akar A. Ruchan , Ayaloglu-Butun Fatma , Terzioglu-Kara Ece , Durdu Serkan , Ozyurda Umit , Ugur Mehmet , Akcali Kamil C.
Published: February 2009

Mesenchymal stem cells (MSCs) have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, and cardiomyocytes. Several established methods are presently available for in vitro isolation of MSCs from bone marrow. However, the duration necessary to culture them can be a major handicap to cell-based therapies needed for such urgent cardiovascular conditions as acute myocardial infarction and acute hindlimb ischemia. The best timing of cardiomyocyte differentiation induction after MCS isolation and expansion is still an unresolved issue. Our goal was to investigate the possibility of obtaining functional cardiomyocytes from rat MSC within a shorter time period. We examined MSCs’ colony-forming capacity, CD90 and CD34 immunoreactivity during the 14 days of culturing. Cardiomyocyte differentiation was induced by 5-azacytidine. Immunohistochemic staining, together with intracellular Ca2+ measurement experiments, revealed that MSCs do not differentiate into any specific cell lineage but show the characteristics of MSCs on both the 9th and 14th days of the culture. To check the potential for differentiation into cardiomyocytes, experiments with caffeine application and depolarization with KCl were performed. The cells possessed some of the specific biochemical features of contracting cells, with slightly higher capacities on the 14th day. Cells from 9th and 14th days of the culture that were treated with 5-azacytidine had a higher expression of cardiac-specific markers such as troponin I, α-sarcomeric actin, and MEF2D compared with the control groups. This study illustrates that it is possible to get functional cardiomyocytes from in vitro MSC culture in a shorter time period than previously achieved. This reduction in time may provide emergency cases with access to cell-based therapies that may have previously been unavailable.
SEARCHES FOR THE STANDARD MODEL HIGGS BOSON AT THE CDF EXPERIMENT
Authors: WANG SONG-MING
Published: February 2009

The understanding of the dynamics behind the breaking of the electroweak symmetry is one of the most important goals in the field of high energy physics. In the Standard Model (SM) Higgs mechanism plays a key role in the symmetry breaking, one manifestation of which is spin-0 Higgs boson. Thus the search for the Higgs boson is one of the flag-ship analyses at the Tevatron. Over the past few years the CDF experiment has made significant improvements in its sensitivity on the search for the SM Higgs boson. In this paper we summarize CDF's most recent results on the searches for the SM Higgs boson production at the Tevatron using data samples of integrated luminosities up to 3 fb-1. We also present the Tevatron's latest combined results on the SM Higgs boson search, and discuss the possibility that it could be found at the Tevatron in the near future.
Multidrug Resistance in Bacteria
Authors: Nikaido Hiroshi
Published: February 2009

Large amounts of antibiotics used for human therapy, as well as for farm animals and even for fish in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. Multidrug resistance in bacteria may be generated by one of two mechanisms. First, these bacteria may accumulate multiple genes, each coding for resistance to a single drug, within a single cell. This accumulation occurs typically on resistance (R) plasmids. Second, multidrug resistance may also occur by the increased expression of genes that code for multidrug efflux pumps, extruding a wide range of drugs. This review discusses our current knowledge on the molecular mechanisms involved in both types of resistance.
Knockdown of ATP8B1 expression leads to specific downregulation of the bile acid sensor FXR in HepG2 cells: effect of the FXR agonist GW4064
Authors: Martínez-Fernández Pilar , Hierro Loreto , Jara Paloma , Alvarez Luis
Published: February 2009

Farnesoid X receptor (FXR) is a bile acid-sensing nuclear receptor that controls bile acid homeostasis. It has been suggested that downregulation of FXR contributes to the pathogenesis of an inherited disorder of bile secretion caused by mutations in ATP8B1. We have investigated the relationship between ATP8B1 knockdown and FXR downregulation in the human hepatoblastoma cell line HepG2. Transfection of HepG2 cells with ATP8B1 small interfering RNA (siRNA) duplexes led to a 60% reduction in the endogenous levels of ATP8B1 mRNA and protein and a concomitant decrease in FXR mRNA and protein content, as well as in FXR phosphorylation. This decrease was accompanied by a marked reduction in mRNA levels of a subset of FXR targets, such as bile salt export pump ( ABCB11), small heterodimer partner, and uridine 5′-diphosphate-glucuronosyltransferase. ATP8B1 inhibition specifically targeted FXR since mRNA expression of other prominent nuclear receptors, such as pregnane X receptor and constitutive androstane receptor, or liver-enriched transcription factors, such as hepatocyte nuclear factor 1α ( HNF-1α) and HNF-4α, was not altered. The expression of other key genes involved in bile acid synthesis, detoxification, and transport also remained unchanged upon ATP8B1 knockdown. Supporting the specificity of the effect, siRNA-mediated silencing of ABCB11, whose defect is associated with another inherited disorder of bile secretion, did not affect FXR expression. Treatment with the synthetic FXR agonist GW4064 was able to partially neutralize ATP8B1 siRNA-mediated FXR downregulation and fully counteract inhibition of FXR target genes. Collectively these findings indicate that ATP8B1 knockdown specifically downregulates FXR, and this action can be circumvented by treatment with FXR agonists.
Activation of caspase-3 may not contribute to postresuscitation myocardial dysfunction
Authors: Radhakrishnan Jeejabai , Ayoub Iyad M. , Gazmuri Raúl J.
Published: February 2009

We have previously reported that postresuscitation myocardial dysfunction is accompanied by the release of cytochrome c and caspase-3 activation. We now investigated the role of caspase-3 activation by examining whether such process prompts apoptotic DNA fragmentation, whether caspase-3 inhibition attenuates myocardial dysfunction, and whether myocardial protective effects of sodium-hydrogen exchanger isoform-1 (NHE-1) inhibition involve caspase-3 inhibition using a rat model of ventricular fibrillation (VF) of closed-chest resuscitation. Resuscitation after 4 or 8 min of untreated VF caused significant reductions in left ventricular stroke work index averaging 23% of sham control rats at 4 h postresuscitation. Left ventricular dysfunction was accompanied by increases in cytosolic cytochrome c, decreases in pro- and cleaved caspase-9 fragments, increases in 17-kDa caspase-3 fragments, and increases in caspase-3 activity indicating the activation of the mitochondrial apoptotic pathway but without evidence of apoptotic DNA fragmentation. In addition, levels of heat shock protein 70 were increased and levels of X-linked inhibitor of apoptosis protein and αβ-crystallin were preserved, all of which can exert antiapoptotic effects. In a separate series, the caspase-3 inhibitor z-Asp-Glu-Val-Asp chloromethyl ketone given before the induction of VF failed to prevent postresuscitation myocardial dysfunction despite reductions in caspase-3 activity (2.3 ± 0.5 vs. 1.3 ± 0.5 pmol fluorophore AFC released·mg protein−1·min−1; P < 0.03). Treatment with the NHE-1 inhibitor cariporide had no effect on caspase-3 activity. Accordingly, in this rat model of VF and severe postresuscitation myocardial dysfunction, activation of caspase-3 did not lead to DNA fragmentation or contribute to myocardial dysfunction. Concomitant activation of intrinsic antiapoptotic mechanisms could play a protective role downstream to caspase-3 activation.
Ischemic preconditioning affects hexokinase activity and HKII in different subcellular compartments throughout cardiac ischemia-reperfusion
Authors: Gürel Ebru , Smeele Kirsten M. , Eerbeek Otto , Koeman Anneke , Demirci Cihan , Hollmann Markus W. , Zuurbier Coert J.
Published: February 2009

The glycolytic enzyme hexokinase (HK) is suggested to play a role in ischemic preconditioning (IPC). In the present study we determined how ischemic preconditioning affects HK activity and HKI and HKII protein content at five different time points and three different subcellular fractions throughout cardiac ischemia-reperfusion. Isolated Langendorff-perfused rat hearts (10 groups of 7 hearts each) were subjected to 35 min ischemia and 30 min reperfusion (control groups); the IPC groups were pretreated with 3 times 5-min ischemia. IPC was without effect on microsomal HK activity, and only decreased cytosolic HK activity at 35 min ischemia, which was mimicked by decreased cytosolic HKII, but not HKI, protein content. In contrast, mitochondrial HK activity at baseline and during reperfusion was elevated by IPC, without changes during ischemia. No effect of IPC on mitochondrial HK I protein content was observed. However, mitochondrial HK II protein content during reperfusion was augmented by IPC, albeit not following the IPC stimulus. It is concluded that IPC results in decreased cytosolic HK activity during ischemia that could be explained by decreased HKII protein content. IPC increased mitochondrial HK activity before ischemia and during reperfusion that was only mimicked by increased HK II protein content during reperfusion. IPC was without effect on the phosphorylation status of HK before ischemia. We conclude that IPC is associated with 1) a biphasic response of increased mitochondrial HK activity before and after ischemia, 2) decreased cytosolic HK activity during ischemia, and 3) cellular redistribution of HKII but not HKI.
Clinical Potential of Nicorandil to Inhibit Major Cardiac Events in Hemodialysis Patients with Suspected Myocardial Ischemia
Authors: Nishimura Masato , Tokoro Toshiko , Nishida Masaya , Hashimoto Tetsuya , Kobayashi Hiroyuki , Yamazaki Satoru , Imai Ryo , Okino Koji , Iwamoto Noriyuki , Takahashi Hakuo , Ono Toshihiko
Published: February 2009

Background/Aims: We examined whether nicorandil, which is a hybrid of an adenosine triphosphate-sensitive potassium channel opener and a nitrate, could inhibit major adverse cardiac events (MACE) in maintenance hemodialysis patients with suspected myocardial ischemia. Methods: We enrolled 148 asymptomatic patients on maintenance hemodialysis, who had exhibited potential myocardial ischemia as assessed by myocardial fatty acid imaging. The end-point was MACE including cardiac death and non-fatal acute myocardial infarction. A propensity-matched analysis was performed. Results: Over a mean duration of follow-up of 2.8 ± 1.6 years in the 82 propensity-matched patients (41 in the nicorandil group and 41 in the non-nicorandil group), we observed 17 cardiac deaths and 12 cases of nonfatal myocardial infarction. The incidence of MACE was lower (p = 0.0365) in the nicorandil group (10/41, 24.4%) than in the non-nicorandil group (19/41, 46.3%). On stepwise Cox hazard analysis, MACE was significantly inhibited by administration of nicorandil (hazard risk, 0.387; 95% CI 0.178–0.842; p = 0.0168). Kaplan-Meier survival estimates revealed that MACE-free survival rates at 3 years were 80.5 and 58.5% in patients with and without nicorandil, respectively. Conclusions: Oral administration of nicorandil may offer new potential for the inhibition of MACE in hemodialysis patients.
Virological Response and Hepatocarcinogenesis in Lamivudine-Resistant Hepatitis B Virus Genotype C Patients Treated with Lamivudine plus Adefovir Dipivoxil
Authors: Akuta Norio , Suzuki Fumitaka , Kawamura Yusuke , Yatsuji Hiromi , Sezaki Hitomi , Suzuki Yoshiyuki , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Arase Yasuji , Ikeda Kenji , Kumada Hiromitsu
Published: February 2009

Aims: The long-term efficacy of adefovir dipivoxil in combination with lamivudine to chronic hepatitis B virus (HBV) infection is still unclear. Methods: Virological response and hepatocarcinogenesis during lamivudine + adefovir were investigated in 183 lamivudine-resistant Japanese patients with chronic genotype C-dominant HBV infection. As the predictors of virological response, an assessment of clinical parameters and a nucleotide (nt) sequence analysis of the negative regulatory element to core gene (nt 1611–2450) were performed at the start of adefovir. Results: The cumulative HBV-DNA non-detectable and ALT normalization rates were 93.6 and 97.6% at the end of 3 years, respectively. Multivariate analysis identified total bilirubin, AST, and nt substitutions (nt 1762, 1768, 1846, 1896, 2134, 2288, 2441) as determinants of early non-detectable HBV-DNA. The yearly incidence of hepatocellular carcinoma (HCC) during the first 3 years was 2.7%. At the diagnosis of HCC, ALT normalization, HBV-DNA non-detectable, and HBeAg-seronegative conversion rates were 75.0, 83.3, and 57.1%, respectively. Furthermore, the cumulative HBV-DNA non-detectable and ALT normalization rates were not significantly different according to the development of HCC or not. Conclusions: Lamivudine-resistant patients treated with lamivudine + adefovir could achieve the excellent virological response and biochemical response, but the low hepatitis activity was not enough to suppress hepatocarcinogenesis.
Delayed Neonatal Closure of the Ductus Arteriosus Following Early in utero Exposure to Indomethacin in the Rat
Authors: Momma Kazuo , Toyoshima Katsuaki , Ito Kiyomi , Sugiyama Kiyoshi , Imamura Shinichiro , Sun Fang , Nakanishi Toshio
Published: February 2009

Background: Indomethacin is used to close the patent ductus arteriosus in premature infants and for tocolysis of preterm labor. Clinically and experimentally, early in utero exposure to indomethacin induces the paradoxical delay of postnatal closure of the ductus arteriosus. Objectives: To clarify the pharmacological nature of the delay of closure of the ductus arteriosus in the rat. Methods: We studied early in utero exposure to indomethacin (dose and timing) in addition to other drugs, inducing a delay in postnatal ductal closure. Pregnant rats at near term were studied by cesarean section on gestational day 21 (D21), incubated in room air at 33°C, followed by rapid whole-body freezing. Results: The delay in closure of the ductus arteriosus was dose dependent. A large dose of indomethacin (10 mg/kg) 1 or 2 days before birth induced a delay of 3–4 times. A timing study revealed maximum delay with administration of indomethacin 2 days before birth and minimum delay with administration 5 days before. Aspirin, ibuprofen, the selective COX1 inhibitor SC 560, the selective COX2 inhibitor rofecoxib and a prostaglandin EP4 receptor blocker, ONO-208, all delayed neonatal ductal closure following maternal administration on D19 and D20. Conclusions: The delay by indomethacin was dose dependent. The maximum delay was induced by 2 doses of 10 mg/kg indomethacin on D19 and D20. The delay was induced by a decreased stimulus to the prostaglandin EP4 receptor system in the last 2 days in utero. The delay was temporary with recovery 3 days or more after exposure.
Hypoglycemia Rates in the First Days of Life among Term Infants Born to Diabetic Mothers
Authors: Maayan-Metzger Ayala , Lubin Daniel , Kuint Jacob
Published: February 2009

Objectives: To discover the risk factors for developing hypoglycemia in newborns born to diabetic mothers and to characterize the rates of glucose concentrations in the first two days of life. Methods: Retrospective recordings of medical charts of 576 healthy term infants of diabetic mothers during an 18-month period. We determined the following pre-feeding glucose concentrations: ‘normoglycemia’ (≥47 mg/dl = 2.6 mmol/l), ‘mild hypoglycemia’ (40–46 mg/dl = 2.2– 2.5 mmol/l), ‘moderate hypoglycemia’ (30–39 mg/dl = 1.7–2.1 mmol/l) and ‘severe hypoglycemia’ (<30 mg/dl = 1.7 mmol/l). Results: Glucose concentrations below ‘normoglycemia’ and ‘severe hypoglycemia’ were observed in 280 (48.6%) and 23 (4%) of the infants, respectively. The main risk factors for developing glucose concentrations below ‘normoglycemia’ in the first day of life were large size for gestational age and maternal insulin-dependent diabetes mellitus. ‘Severe hypoglycemia’ was more common among infants born to mothers who needed insulin (either type A2 or insulin-dependent diabetes mellitus). Infants born to mothers with insulin-dependent diabetes mellitus were less mature, heavier, large for their gestational age and exhibited more ‘severe and moderate hypoglycemia’ in the first day of life as compared to infants born to diabetes type A1 and A2 mothers. In addition, infants who were large for gestational age tended to have more ‘moderate hypoglycemia’ when born to diabetes type A1 mothers compared to small and appropriate-for-gestational-age infants. Thirty infants (5%) still had hypoglycemia on the second day of life. This subgroup of infants did not differ with regard to maternal-type diabetes. Conclusions: Infants born to diabetic mothers tend to have a high rate of hypoglycemia on the first day of life when a relatively high cut-off point (≥47 mg/dl = 2.6 mmol/l) is used. Infants born large for gestational age as well as those born to mothers with juvenile diabetes mellitus are at higher risk and should be closely monitored.
Thyroid Hormone Level Positively Regulates NOS and cGMP in the Developing Rat Cerebellum
Authors: Serfőző Zoltán , de Vente Jan , Elekes Károly
Published: February 2009

Thyroid hormones and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling play a significant role in the structural development of the cerebellum, respectively. In the present study, the possible contribution of neuronal NO synthase (NOS) and cGMP in the thyroid hormone-induced structural changes was investigated in the cerebella of postnatal rats at different hormone levels. Animals were treated from postnatal day 4 until days 7, 14, and 21, by i.p. injection of 1 μg thyroxine (T4)/10 g body weight/4 days, or p.o. with 100 μg 6-n-propyl-2-thyouracil (PTU)/10 g body weight/day. Control groups consisted of i.p. and p.o. vehicle controls and PTU/T4-treated animals. Measurement of serum fT4, TSH as well as total T3 and T4 concentration of the cerebellar tissue indicated the changed thyroid status. nNOS extensively expressed in growing parallel fibers revealed by quantitative Western blot and layer analysis of immunohistochemically labeled coronal sections. Simultaneously, the cGMP concentration increased and the distribution of cGMP-immunoreactive (cGMP-IR) material in Purkinje cell perikarya and in the molecular layer expanded during cerebellar development. T4 increased nNOS and cGMP level, and accelerated the development of nNOS-IR parallel fibers and cGMP-IR molecular layer. In contrast, PTU retarded the development by decreasing nNOS and cGMP concentration and slowing down layer formation. A single dose of T4 could rescue the PTU-induced changes. Results suggest that the contribution of nNOS- NO/cGMP signaling in thyroid hormone regulated structural maturation of the cerebellum. The possible involvement of neurotrophins, calcium, and apoptotic events in this process was discussed.
Isolation, Culture and Characterization of Cardiac Progenitor Cells Derived from Human Embryonic Heart Tubes
Authors: Zhang Xi , Zhang Chuan-Sen , Liu Yan-Chun , Yang Xiang-Qun , Xiong Shao-Hu , Wen Yu , Jiang Er-Peng , Li Rui , Zhang Zhi-Ying , Liu Fang , Ye Yong
Published: February 2009

A variety of studies have reported on the isolation and expansion of cardiac stem cells from adult hearts. However, there is little information concerning cardiac stem/progenitor cells derived from embryonic hearts/heart tubes. To provide more evidence for embryonic heart-derived stem/progenitor cells, Nkx2.5+ human cardiac progenitorcells (hCPCs) were isolated and cloned from human heart tubes. The cells stained positive for Nkx2.5 and Oct-4, and negative for α-smooth muscle actin (α-SMA), cytokeratin, factor-VIII, α-sarcomeric actin and c-Kit. GATA-4 expression of Nkx2.5+ hCPCs was higher than that of embryonic limb bud mesenchymal cells of the control group (p < 0.05). These cells were passaged continuously for >3 months (23 passages) and proliferated actively in vitro. After being treated with 5-azacytidine, Nkx2.5+ hCPCs underwent cardiomyogenic differentiation. Ultrastructural observation confirmed that the longitudinal section of these cardiomyogenic differentiation cells clearly revealed typical sarcomeres and intercalated discs. α-MHC, α-sarcomeric actin and GATA-4 levels were increased in Nkx2.5+ hCPCs treated with 5-azacytidine compared to untreated cells. Nkx2.5+ hCPCs exhibited positive staining and had a higher expression for α-SMA when cocultured with canine vascular endothelial cells. After Nkx2.5+ hCPCs were treated with endothelin-1, all cells displayed spontaneous electrical activity and spontaneous beating. Connexin-40 and -45 were stained positive in the treated cells. In conclusion, Nkx2.5+ hCPCs derived from heart tubes have been isolated and cloned in vitro. These cells are capable of long-term self-renewal and possess a potential to differentiate into cardiac muscle-like cells, cardiac pacemaking cells and smooth muscle-like cells. They could have a significant impact on cardiac regeneration medicine and developmental biology.
A Randomized Controlled Trial of Angiography Versus Intravascular Ultrasound-Directed Bare-Metal Coronary Stent Placement (The AVID Trial)
Authors: Russo Robert J. , Silva Patricia D. , Teirstein Paul S. , Attubato Michael J. , Davidson Charles J. , DeFranco Anthony C. , Fitzgerald Peter J. , Goldberg Steven L. , Hermiller James B. , Leon Martin B. , Ling Frederick S. , Lucisano Jennifer E. , Schatz Richard A. , Wong S. Chiu , Weissman Neil J. , Zientek David M.
Published: February 2009

Background—

AVID (Angiography Versus Intravascular ultrasound-Directed stent placement) is a multicenter, randomized controlled trial designed to assess the effect of intravascular ultrasound (IVUS)-directed stent placement on the 12-month rate of target lesion revascularization (TLR).

Methods and Results—

After elective coronary stent placement and an optimal angiographic result (<10% stenosis), 800 patients were randomized to Angiography- or IVUS-directed therapy. Blinded IVUS was performed in the Angiography group without further therapy. In the IVUS group, IVUS criteria for optimal stent placement (<10% area stenosis, apposition, and absence of dissection) were applied. Final minimum stent area was 6.90�2.43 mm
2
in the Angiography group and 7.55�2.82 mm
2
in the IVUS group (
P
=0.001). In the IVUS group, only 37% with inadequate expansion (<90%) received further therapy. The 12-month TLR rate was 12.0% in the Angiography group and 8.1% in the IVUS group (
P
=0.08, 95% confidence level [CI], [−8.3% to 0.5%]). When vessels with a distal reference diameter <2.5 mm by core laboratory angiography measurement were excluded from analysis, the 12-month TLR rate was 10.1% in the Angiography group and 4.3% in the IVUS group (
P
=0.01, 95% CI, [−10.6% to −1.2%]). With a prestent angiographic stenosis of ≥70%, the TLR rate was lower in the IVUS group compared with the Angiography group (3.1% versus 14.2%;
P
=0.002; 95% CI, [−18.4% to −4.2%]).

Conclusions—

IVUS-directed bare-metal stent placement results in larger acute stent dimensions without an increase in complications and a significantly lower 12-month TLR rate for vessels ≥2.5 mm by angiography and for vessels with high-grade prestent stenosis. However, for the entire sample analyzed on an intention-to-treat basis, IVUS-directed bare-metal stent placement does not significantly reduce the 12-month TLR rate when compared with stent placement guided by angiography alone. In addition, IVUS evaluation of adequate stent expansion is underutilized by experienced operators.