bluuebunny/crossref_metadata_2025 huggingface dataset:
Geological conservation in the nineteenth and early twentieth centuries
Authors: Thomas Barry A. , Warren Lynda M.
Published: June 2008

Before the middle of the twentieth century there were very few geological reserves in Britain and there was no government legislation to protect them. In other countries and especially in the USA, there were many more such sites protected by a number of legislative processes. In nineteenth century Britain most of the land was owned by comparatively few wealthy people and common land was being steadily reduced through increasing numbers of Enclosure Acts. This meant that there were very few opportunities for conservation action especially as there was no legal basis for doing so other than through land ownership. In the USA the situation was completely different. The westward expansion was in full swing resulting in an increasing amount of federal land holdings owned by Congress. This, together with a desire of the federal government to save special sites for future generations, resulted in the extensive National Parks created by statute and the cultural and national monuments protected by the 1906 Preservation of American Antiquities Act. It took another forty years for Britain to have similar legislation.
Geodiversity: the origin and evolution of a paradigm
Authors: Gray Murray
Published: June 2008

‘Geodiversity’ can be defined as the range of geological, geomorphological and soil features. Although the word itself was first used only in the early 1990s, the principles behind its application to nature conservation have a longer history. For example, the search for representative sites has been a guiding principle for conservation site selection in the UK since the Second World War, and can also be detected as the basis for new site selection criteria in the USA, Ireland and many other countries. It is also starting to be used as a means of analysing the existing World Heritage Sites list and may become one factor in assessing new site applications. The word was first widely adopted in Tasmania and has a status equal to biodiversity within the Australian Natural Heritage Charter. Despite some opposition, the term is increasingly being used around the world, but has been adopted most enthusiastically in the UK, where many Geodiversity Audits, Local Geodiversity Action Plans and Company Geodiversity Action Plans have been published or are planned. A national Geodiversity Action Plan will be published in 2008. The term has also been adopted in national planning guidance in the UK and, as a result, is finding its way into regional and local planning policies. The paper concludes with some speculations about its future use in geoconservation.
The role of the British Geological Survey in the history of geoconservation
Authors: McMillan Andrew A.
Published: June 2008

Over its 172 year history, the British Geological Survey (formerly the Geological Survey of Great Britain) has, through underpinning core activities, its archive and databases and its experienced field staff, provided the geological basis for geoconservation. Evolving activities of the Survey from primary survey and collecting to revision mapping to 3D/4D-modelling reflect changing national needs. In turn, BGS has developed its capability to provide new geological interpretations and a range of publications raising the profile of Earth sciences, both for professionals and for the popular market. Today, BGS's input through networks to geodiversity projects and to newly designated regions such as Geoparks marks a major transition towards a proactive geoconservation agenda in the twenty-first century.
The history of geoconservation in England: legislative and policy milestones
Authors: Prosser Colin D.
Published: June 2008

England, and the UK more widely, have robust and mature statutory and voluntary frameworks for delivering geoconservation. Critical to achieving this advanced position was the inclusion of geoconservation within the first nature conservation legislation enacted in Britain in 1949. The development of this legislation benefited greatly from the wisdom of a number of committees set up to inform government thinking. Many of these committees were advised by the scientific community, including geologists and geomorphologists. The work and influence of these committees in establishing geoconservation as part of statutory nature conservation is explored, and the main statutory and policy milestones which have guided and shaped geoconservation in England since 1949 are described. The rise of the voluntary geoconservation movement in the late 1980s is also explored.
Molecular Mechanisms of Presynaptic Differentiation
Authors: Jin Yishi , Garner Craig C.
Published: June 2008

Information processing in the nervous system relies on properly localized and organized synaptic structures at the correct locations. The formation of synapses is a long and intricate process involving multiple interrelated steps. Decades of research have identified a large number of molecular components of the presynaptic compartment. In addition to neurotransmitter-containing synaptic vesicles, presynaptic terminals are defined by cytoskeletal and membrane specializations that allow highly regulated exo- and endocytosis of synaptic vesicles and that maintain precise registration with postsynaptic targets. Functional studies at multiple levels have revealed complex interactions between the transport of vesicular intermediates, the presynaptic cytoskeleton, growth cone navigation, and synaptic targets. With the advent of finer anatomical, physiological, and molecular tools, great insights have been gained toward the mechanistic dissection of functionally redundant processes controlling the specificity and dynamics of synapses. This review highlights the recent findings pertaining to the cellular and molecular regulation of presynaptic differentiation.
Effect of electrical stimulation of the LES on LES pressure in a canine model
Authors: Sanmiguel Claudia P. , Hagiike Masanobu , Mintchev Martin P. , Cruz Ryan Dela , Phillips Edward H. , Cunneen Scott A. , Conklin Jeffrey L. , Soffer Edy E.
Published: June 2008

Gastric electrical stimulation modulates lower esophageal sphincter pressure (LESP). High-frequency neural stimulation (NES) can induce gut smooth muscle contractions. To determine whether lower esophageal sphincter (LES) electrical stimulation (ES) can affect LESP, bipolar electrodes were implanted in the LES of four dogs. Esophageal manometry during sham or ES was performed randomly on separate days. Four stimuli were used: 1) low-frequency: 350-ms pulses at 6 cycles/min; 2) high-frequency-1: 1-ms pulses at 50 Hz; 3) high-frequency-2: 1-ms pulses at 20 Hz; and 4) NES: 20-ms bipolar pulses at 50 Hz. Recordings were obtained postprandially. Tests consisted of three 20-min periods: baseline, stimulation/sham, and poststimulation. The effect of NES was tested under anesthesia and following IV administration of l-NAME and atropine. Area under the curve (AUC) and LESP were compared among the three periods, by ANOVA and t-test, P < 0.05. Data are shown as means ± SD. We found that low-frequency stimulation caused a sustained increase in LESP: 32.1 ± 12.9 (prestimulation) vs. 43.2 ± 18.0 (stimulation) vs. 50.1 ± 23.8 (poststimulation), P < 0.05. AUC significantly increased during and after stimulation. There were no significant changes with other types of ES. With NES, LESP initially rose and then decreased below baseline (LES relaxation). During NES, NG-nitro-l-arginine methyl ester increased both resting LESP and the initial rise in LESP and markedly diminished the relaxation. Atropine lowered resting LESP and abolished the initial rise in LESP. In conclusion, low frequency ES of the LES increases LESP in conscious dogs. NES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.
Regulatory mechanism governing the diurnal rhythm of intestinal H+/peptide cotransporter 1 (PEPT1)
Authors: Saito Hirofumi , Terada Tomohiro , Shimakura Jin , Katsura Toshiya , Inui Ken-ichi
Published: June 2008

The intestinal H+/peptide cotransporter 1 (PEPT1) plays important roles as a nutrient and drug transporter. Previously, we reported that rat intestinal PEPT1 showed a diurnal rhythm and that this rhythm is closely related to the feeding schedule. Furthermore, we also demonstrated that transcription factors, Sp1, Cdx2, and peroxisome proliferator-activated receptor-α (PPAR-α) contribute to the basal, intestine-specific, and fasting-induced expression of PEPT1, respectively. In this study, to clarify the molecular mechanism governing the diurnal rhythm of PEPT1 expression, we compared expression profiles of these transcription factors under two kinds of feeding schedules. The intestinal Sp1 and Cdx2 did not show a circadian accumulation of mRNA or response to the daytime feeding regimen. Plasma free fatty acids, endogenous PPAR-α ligands, exhibited a robust circadian fluctuation in phase with that of PEPT1. However, subsequent experiments using PPAR-α-null mice revealed the absence of any association between the circadian rhythm of PEPT1 and PPAR-α. We then focused on the clock genes (Clock, Bmal1, Per1–2, and Cry1) and clock-controlled gene, albumin D site-binding protein (DBP). A robust and coordinated circadian expression of the clock genes was observed, and daytime feeding entirely inverted the phase except for Clock. The expression of DBP was in phase with that of PEPT1 in both groups. Electrophoretic mobility shift assays and reporter assays revealed that DBP has the ability to bind the DBP binding site located in the distal promoter region of the rat PEPT1 gene and induce the transcriptional activity. These findings indicate that DBP plays pivotal roles in the circadian oscillation of PEPT1.
A vascular endothelial growth factor mimetic accelerates gastric ulcer healing in an iNOS-dependent manner
Authors: Dudar Genevieve K. , D'Andrea Luca D. , Di Stasi Rossella , Pedone Carlo , Wallace John L.
Published: June 2008

Angiogenesis is crucial to all types of wound healing, including gastric ulcer healing. The most potent promoter of angiogenesis is vascular endothelial growth factor (VEGF). We hypothesized that a 15-amino acid peptide designed to mimic the angiogenic action of VEGF would accelerate gastric ulcer healing. Gastric ulcers were induced in mice by serosal application of acetic acid. Treatment with the VEGF mimetic accelerated gastric ulcer healing when administered orally or intraperitoneally, at a dose of 50 ng/kg or greater. Such healing was not observed when the reverse sequence pentadecapeptide or the full-length VEGF protein was administered. Contrary to our hypothesis, the VEGF mimetic did not significantly increase angiogenesis in the ulcerated stomach. The enhancement of ulcer healing by the VEGF mimetic occurred independently of cyclooxygenase-2 (COX-2) activity but was blocked by inhibitors of inducible nitric oxide synthase (iNOS). These results demonstrate that a VEGF mimetic is a potent stimulus for gastric ulcer healing, even when given orally. The effects of the mimetic were independent of stimulatory effects on angiogenesis and COX-2 activity but were dependent on iNOS-derived NO production.
Muscle mechanoreflex augments arterial baroreflex-mediated dynamic sympathetic response to carotid sinus pressure
Authors: Yamamoto Kenta , Kawada Toru , Kamiya Atsunori , Takaki Hiroshi , Shishido Toshiaki , Sunagawa Kenji , Sugimachi Masaru
Published: June 2008

Although the muscle mechanoreflex is one of the pressor reflexes during exercise, its interaction with dynamic characteristics of the arterial baroreflex remains to be quantitatively analyzed. In anesthetized, vagotomized, and aortic-denervated rabbits ( n = 7), we randomly perturbed isolated carotid sinus pressure (CSP) using binary white noise while recording renal sympathetic nerve activity (SNA) and arterial pressure (AP). We estimated the transfer functions of the baroreflex neural arc (CSP to SNA) and peripheral arc (SNA to AP) under conditions of control and muscle stretch of the hindlimb (5 kg of tension). The muscle stretch increased the dynamic gain of the neural arc while maintaining the derivative characteristics [gain at 0.01 Hz: 1.0 ± 0.2 vs. 1.4 ± 0.6 arbitrary units (au)/mmHg, gain at 1 Hz: 1.7 ± 0.6 vs. 2.7 ± 1.4 au/mmHg; P < 0.05, control vs. stretch]. In contrast, muscle stretch did not affect the peripheral arc. In the time domain, muscle stretch augmented the steady-state response at 50 s (−1.1 ± 0.3 vs. −1.7 ± 0.7 au; P < 0.05, control vs. stretch) and negative peak response (−2.1 ± 0.5 vs. −3.1 ± 1.5 au; P < 0.05, control vs. stretch) in the SNA step response. A simulation experiment using the results indicated that the muscle mechanoreflex would accelerate the closed-loop AP regulation via the arterial baroreflex.
EGF mediates calcium-activated chloride channel activation in the human bronchial epithelial cell line 16HBE14o−: involvement of tyrosine kinase p60c-src
Authors: Jeulin Claudette , Seltzer Virginie , Bailbé Danielle , Andreau Karine , Marano Francelyne
Published: June 2008

Particulate atmospheric pollutants interact with the human airway epithelium, which releases cytokines, chemokines, and EGF receptor (EGFR) ligands leading to proinflammatory responses. There is little information concerning the short-term effects of EGFR activation by extracellular ligands on ionic regulation of airway surface lining fluids. We identified in the membrane of human epithelial bronchial cells (16HBE14o− line) an endogenous calcium- and voltage-dependent, outwardly rectifying small-conductance chloride channel (CACC), and we examined the effects of EGF on CACC activity. Ion channel currents were recorded with the patch-clamp technique. In cell-attached membrane patches, CACC were activated by exposure of the external surface of the cells to physiological concentrations of EGF without any change in cytosolic Ca2+ concentration ([Ca2+]i) and inhibited by tyrphostin AG-1478 (an inhibitor of EGFR that also blocks EGF-dependent Src family kinase activation). EGF activation of c-Src protein in 16HBE14o− cells was observed, and the signaling pathway elicited by EGFR was blocked by tyrphostin AG-1478. In excised inside-out membrane patches CACC were activated by exposure of the cytoplasmic face of the channels to the human recombinant Src(p60c-src) kinase with endogenous or exogenous ATP and inhibited by λ-protein phosphatase. Secretion of EGFR ligands by epithelial airway cells exposed to pollutants would then elicit a rapid and direct ionic response of CACC mediated by EGFR activation via a Src kinase family-dependent signaling pathway.
Increased central facilitation of antagonist reciprocal inhibition at the onset of dorsiflexion following explosive strength training
Authors: Geertsen Svend S. , Lundbye-Jensen Jesper , Nielsen Jens B.
Published: June 2008

At the onset of dorsiflexion disynaptic reciprocal inhibition (DRI) of soleus motoneurons is increased to prevent activation of the antagonistic plantar flexors. This is caused by descending facilitation of transmission in the DRI pathway. Because the risk of eliciting stretch reflexes in the ankle plantar flexors at the onset of dorsiflexion is larger the quicker the movement, it was hypothesized that DRI may be increased when subjects are trained to perform dorsiflexion movements as quickly as possible For this purpose, 14 healthy human subjects participated in explosive strength training of the ankle dorsiflexor muscles 3 times a week for 4 wk. Test sessions were conducted before, shortly after, and 2 wk after the training period. The rate of torque development measured at 30, 50, 100, and 200 ms after onset of voluntary explosive isometric dorsiflexion increased by 24–33% ( P < 0.05). DRI was measured as the depression of the soleus H reflex following conditioning stimulation of the peroneal nerve (1.1 × motor threshold) at an interval of 2–3 ms. At the onset of dorsiflexion the amount of DRI measured relative to DRI at rest increased significantly from 6% before the training to 22% after the training ( P < 0.05). We speculate that DRI at the onset of movement may be increased in healthy subjects following explosive strength training to ensure efficient suppression of the antagonist muscles as the dorsiflexion movement becomes faster.
Seven days of oral taurine supplementation does not increase muscle taurine content or alter substrate metabolism during prolonged exercise in humans
Authors: Galloway Stuart D. R. , Talanian Jason L. , Shoveller Anna K. , Heigenhauser George J. F. , Spriet Lawrence L.
Published: June 2008

This study examined 1) the plasma taurine response to acute oral taurine supplementation (T), and 2) the effects of 7 days of T on muscle amino acid content and substrate metabolism during 2 h of cycling at ∼60% peak oxygen consumption (V̇o2peak). In the first part of the study, after an overnight fast, 7 volunteers (28 ± 3 yr, 184 ± 2 cm, 88.0 ± 6.6 kg) ingested 1.66 g oral taurine doses with breakfast (8 AM) and lunch (12 noon), and blood samples were taken throughout the day. In the second part of the study, eight men (22 ± 1 yr, 181 ± 1 cm, 80.9 ± 3.8 kg, 4.21 ± 0.16 l/min V̇o2peak) cycled for 2 h after 7 days of placebo (P) ingestion (6 g glucose/day) and again following 7 days of T (5 g/day). In the first part of the study, plasma taurine was 64 ± 4 μM before T and rose rapidly to 778 ± 139 μM by 10 AM and remained elevated at noon (359 ± 56 μM). Plasma taurine reached 973 ± 181 μM at 1 PM and was 161 ± 31 μM at 4 PM. In the second part of the study, seven days of T had no effect on muscle taurine content (mmol/kg dry muscle) at rest (P, 44 ± 15 vs. T, 42 ± 15) or after exercise (P, 43 ± 12 vs. T, 43 ± 11). There was no difference in muscle glycogen or other muscle metabolites between conditions, but there were notable interaction effects for muscle valine, isoleucine, leucine, cystine, glutamate, alanine, and arginine amino acid content following exercise after T. These data indicate that 1) acute T produces a 13-fold increase in plasma taurine concentration; 2) despite the ability to significantly elevate plasma taurine for extended periods throughout the day, 7 days of T does not alter skeletal muscle taurine content or carbohydrate and fat oxidation during exercise; and 3) T appears to have some impact on muscle amino acid response to exercise.
Habitual exercise and arterial aging
Authors: Seals Douglas R. , DeSouza Christopher A. , Donato Anthony J. , Tanaka Hirofumi
Published: June 2008

Aging affects the function and structure of arteries and increases the risk of cardiovascular diseases (CVD). In healthy sedentary adults, aging is associated with increased stiffness (reduced compliance) of large elastic arteries; impaired vascular endothelial function, including reductions in endothelium-dependent dilation (EDD), release of tissue-type plasminogen activator (fibrinolytic capacity) and endothelial progenitor cell number and function; increased intima-media wall thickness (IMT); and peripheral vasoconstriction (decreased basal leg blood flow). Habitual physical activity/increased aerobic exercise capacity is associated with reduced risk of CVD. Compared with their sedentary peers, adults who regularly perform aerobic exercise demonstrate smaller or no age-associated increases in large elastic artery stiffness, reductions in vascular endothelial function, and increases in femoral artery IMT. A short-term, moderate-intensity aerobic exercise intervention (brisk daily walking for 12 wk) improves carotid artery compliance and can restore vascular endothelial function in previously sedentary middle-aged and older adults. Reduced oxidative stress may be an important mechanism contributing to these effects. Habitual resistance exercise increases (high-intensity) or does not affect (moderate-intensity) large elastic artery stiffness, and prevents/restores the age-associated reduction in basal leg blood flow independent of changes in leg fat-free mass. Habitual exercise favorably modulates several expressions of arterial aging, thus preserving vascular function and possibly reducing the risk of CVD.
Tumor Suppression by p53 in the Absence of Atm
Authors: Bailey S. Lawrence , Gurley Kay E. , Hoon-Kim Kyung , Kelly-Spratt Karen S. , Kemp Christopher J.
Published: June 2008

Oncogenes can induce p53 through a signaling pathway involving p19/Arf. It was recently proposed that oncogenes can also induce DNA damage, and this can induce p53 through the Atm DNA damage pathway. To assess the relative roles of Atm, Arf, and p53 in the suppression of Ras-driven tumors, we examined susceptibility to skin carcinogenesis in 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate (TPA)–treated Atm- and p53-deficient mice and compared these results to previous studies on Arf-deficient mice. Mice with epidermal-specific deletion of p53 showed increased papilloma number and progression to malignant invasive carcinomas compared with wild-type littermates. In contrast, Atm-deficient mice showed no increase in papilloma number, growth, or malignant progression. γ-H2AX and p53 levels were increased in both Atm+/+ and Atm−/− papillomas, whereas Arf−/− papillomas showed much lower p53 expression. Thus, although there is evidence of DNA damage, signaling through Arf seems to regulate p53 in these Ras-driven tumors. In spontaneous and radiation-induced lymphoma models, tumor latency was accelerated in Atm−/−p53−/− compound mutant mice compared with the single mutant Atm−/− or p53−/− mice, indicating cooperation between loss of Atm and loss of p53. Although p53-mediated apoptosis was impaired in irradiated Atm−/− lymphocytes, p53 loss was still selected for during lymphomagenesis in Atm−/− mice. In conclusion, in these models of oncogene- or DNA damage–induced tumors, p53 retains tumor suppressor activity in the absence of Atm. (Mol Cancer Res 2008;6(7):1185–92)
The Nuclear Factor-κB and p53 Pathways Function Independently in Primary Cells and Transformed Fibroblasts Responding to Genotoxic Damage
Authors: Nesic Dobrila , Grumont Raelene , Gerondakis Steve
Published: June 2008

With nuclear factor-κB (NF-κB) and p53 functions generally having disparate outcomes for cell survival and cell division, understanding how these pathways are coordinated following a common activation signal such as DNA damage has important implications for cancer therapy. Conflicting reports concerning NF-κB and p53 interplay in different cell line models prompted a reexamination of this issue using mouse primary thymocytes and embryonic fibroblasts, plus fibroblasts transformed by E1A12S. Here, we report that following the treatment of these cells with a range of stress stimuli, p53 and NF-κB were found to regulate cell cycling and survival independently. (Mol Cancer Res 2008;6(7):1193–203)
Vascular Endothelial Growth Factor Receptor-1 Regulates Postnatal Angiogenesis Through Inhibition of the Excessive Activation of Akt
Authors: Nishi Jun-ichiro , Minamino Tohru , Miyauchi Hideyuki , Nojima Aika , Tateno Kaoru , Okada Sho , Orimo Masayuki , Moriya Junji , Fong Guo-Hua , Sunagawa Kenji , Shibuya Masabumi , Komuro Issei
Published: June 2008

Vascular endothelial growth factor (VEGF) binds both VEGF receptor-1 (VEGFR-1) and VEGF receptor-2 (VEGFR-2). Activation of VEGFR-2 is thought to play a major role in the regulation of endothelial function by VEGF. Recently, specific ligands for VEGFR-1 have been reported to have beneficial effects when used to treat ischemic diseases. However, the role of VEGFR-1 in angiogenesis is not fully understood. In this study, we showed that VEGFR-1 performs “fine tuning” of VEGF signaling to induce neovascularization. We examined the effects of retroviral vectors expressing a small interference RNA that targeted either the VEGFR-1 gene or the VEGFR-2 gene. Deletion of either VEGFR-1 or VEGFR-2 reduced the ability of endothelial cells to form capillaries. Deletion of VEGFR-1 markedly reduced endothelial cell proliferation and induced premature senescence of endothelial cells. In contrast, deletion of VEGFR-2 significantly impaired endothelial cell survival. When VEGFR-1 expression was blocked, VEGF constitutively activated Akt signals and thus induced endothelial cell senescence via a p53-dependent pathway. VEGFR-1
+/−
mice exhibited an increase of endothelial Akt activity and showed an impaired neovascularization in response to ischemia, and this impairment was ameliorated in VEGFR-1
+/−
Akt1
+/−
mice. These results suggest that VEGFR-1 plays a critical role in the maintenance of endothelial integrity by modulating the VEGF/Akt signaling pathway.
Role of Nox2-Based NADPH Oxidase in Bone Marrow and Progenitor Cell Function Involved in Neovascularization Induced by Hindlimb Ischemia
Authors: Urao Norifumi , Inomata Hyoe , Razvi Masooma , Kim Ha Won , Wary Kishore , McKinney Ronald , Fukai Tohru , Ushio-Fukai Masuko
Published: June 2008

Bone marrow (BM) is the major reservoir for endothelial progenitor cells (EPCs). Postnatal neovascularization depends on not only angiogenesis but also vasculogenesis, which is mediated through mobilization of EPCs from BM and their recruitment to the ischemic sites. Reactive oxygen species (ROS) derived from Nox2-based NADPH oxidase play an important role in postnatal neovascularization; however, their role in BM and EPC function is unknown. Here we show that hindlimb ischemia of mice significantly increases Nox2 expression and ROS production in BM-mononuclear cells (BMCs), which is associated with an increase in circulating EPC-like cells. Mice lacking Nox2 show reduction of ischemia-induced flow recovery, ROS levels in BMCs, as well as EPC mobilization from BM. Transplantation of wild-type (WT)-BM into Nox2-deficient mice rescues the defective neovascularization, whereas WT mice transplanted with Nox2-deficient BM show reduced flow recovery and capillary density compared to WT-BM transplanted control. Intravenous infusion of WT- and Nox2-deficient BMCs into WT mice reveals that neovascularization and homing capacity are impaired in Nox2-deficient BMCs in vivo. In vitro, Nox2-deficient c-kit
+
Lin
−
BM stem/progenitor cells show impaired chemotaxis and invasion as well as polarization of actins in response to stromal derived factor (SDF), which is associated with blunted SDF-1–mediated phosphorylation of Akt. In conclusion, Nox2-derived ROS in BM play a critical role in mobilization, homing, and angiogenic capacity of EPCs and BM stem/progenitor cells, thereby promoting revascularization of ischemic tissue. Thus, NADPH oxidase in BM and EPCs is potential therapeutic targets for promoting neovascularization in ischemic cardiovascular diseases.
Protein Kinase D Is a Key Regulator of Cardiomyocyte Lipoprotein Lipase Secretion After Diabetes
Authors: Kim Min Suk , Wang Fang , Puthanveetil Prasanth , Kewalramani Girish , Hosseini-Beheshti Elham , Ng Natalie , Wang Yanni , Kumar Ujendra , Innis Sheila , Proud Christopher G. , Abrahani Ashraf , Rodrigues Brian
Published: June 2008

The diabetic heart switches to exclusively using fatty acid (FA) for energy supply and does so by multiple mechanisms including hydrolysis of lipoproteins by lipoprotein lipase (LPL) positioned at the vascular lumen. We determined the mechanism that leads to an increase in LPL after diabetes. Diazoxide (DZ), an agent that decreases insulin secretion and causes hyperglycemia, induced a substantial increase in LPL activity at the vascular lumen. This increase in LPL paralleled a robust phosphorylation of Hsp25, decreasing its association with PKCδ, allowing this protein kinase to phosphorylate and activate protein kinase D (PKD), an important kinase that regulates fission of vesicles from the golgi membrane. Rottlerin, a PKCδ inhibitor, prevented PKD phosphorylation and the subsequent increase in LPL. Incubating control myocytes with high glucose and palmitic acid (Glu+PA) also increased the phosphorylation of Hsp25, PKCδ, and PKD in a pattern similar to that seen with diabetes, in addition to augmenting LPL activity. In myocytes in which PKD was silenced or a mutant form of PKCδ was expressed, high Glu+PA were incapable of increasing LPL. Moreover, silencing of cardiomyocyte Hsp25 allowed phorbol 12-myristate 13-acetate to elicit a significant phosphorylation of PKCδ, an appreciable association between PKCδ and PKD, and a vigorous activation of PKD. As these cells also demonstrated an additional increase in LPL, our data imply that after diabetes, PKD control of LPL requires dissociation of Hsp25 from PKCδ, association between PKCδ and PKD, and vesicle fission. Results from this study could help in restricting cardiac LPL translocation, leading to strategies that overcome contractile dysfunction after diabetes.
Endothelial Cells Provide Feedback Control for Vascular Remodeling Through a Mechanosensitive Autocrine TGF-β Signaling Pathway
Authors: Baker Aaron B. , Ettenson David S. , Jonas Michael , Nugent Matthew A. , Iozzo Renato V. , Edelman Elazer R.
Published: June 2008

Mechanical forces are potent modulators of the growth and hypertrophy of vascular cells. We examined the molecular mechanisms through which mechanical force and hypertension modulate endothelial cell regulation of vascular homeostasis. Exposure to mechanical strain increased the paracrine inhibition of vascular smooth muscle cells (VSMCs) by endothelial cells. Mechanical strain stimulated the production of perlecan and heparan sulfate glycosaminoglycans by endothelial cells. By inhibiting the expression of perlecan with an antisense vector we demonstrated that perlecan was essential to the strain-mediated effects on endothelial cell growth control. Mechanical regulation of perlecan expression in endothelial cells was governed by a mechanotransduction pathway requiring autocrine transforming growth factor β (TGF-β) signaling and intracellular signaling through the ERK pathway. Immunohistochemical staining of the aortae of spontaneously hypertensive rats demonstrated strong correlations between endothelial TGF-β, phosphorylated signaling intermediates, and arterial thickening. Further, studies on ex vivo arteries exposed to varying levels of pressure demonstrated that ERK and TGF-β signaling were required for pressure-induced upregulation of endothelial HSPG. Our findings suggest a novel feedback control mechanism in which net arterial remodeling to hemodynamic forces is controlled by a dynamic interplay between growth stimulatory signals from VSMCs and growth inhibitory signals from endothelial cells.
Ischemic Postconditioning Inhibits Apoptosis After Focal Cerebral Ischemia/Reperfusion Injury in the Rat
Authors: Xing Bianzhi , Chen Hui , Zhang Min , Zhao Dongming , Jiang Rui , Liu Xiuheng , Zhang Suming
Published: June 2008

Background and Purpose—

Ischemic postconditioning (Postcond) is defined as a series of intermittent interruptions of blood flow in the early phase of reperfusion that mechanically alters the hydrodynamics of reperfusion. A recent study showed that Postcond reduced infarct size in cerebral ischemia/reperfusion (I/R) injury. However, little is known about the mechanisms of Postcond in cerebral I/R injury. In the present study, we investigated the effects of Postcond in focal cerebral I/R injury in the rat middle cerebral artery occlusion model.

Methods—

Adult male Sprague-Dawley rats were treated with Postcond after 60 minutes of occlusion (beginning of reperfusion). Neurologic scores and infarct volumes were assessed at 24 and 72 hours. Oxidative stress was evaluated by malondialdehyde assay, and apoptosis-related molecules were studied by Western blotting.

Results—

Postcond treatment upregulated Bcl-2 and heat-shock protein 70 expression and downregulated cytochrome
c
release to the cytosol, Bax translocation to the mitochondria, and caspase-3 activity. Postcond treatment also reduced infarct volumes and oxidative stress levels and improved neurologic scores compared with the I/R-only group.

Conclusions—

These findings indicate that Postcond inhibits focal cerebral I/R injury. This neuroprotective effect is likely achieved by antiapoptotic mechanisms.
Transient Global Amnesia
Authors: Enzinger Christian , Thimary Felix , Kapeller Peter , Ropele Stefan , Schmidt Reinhold , Ebner Franz , Fazekas Franz
Published: June 2008

Background and Purpose—

A hypoxic-ischemic origin of transient global amnesia (TGA) has been suggested on the basis of the observation of infarctlike diffusion-weighted imaging (DWI) abnormalities in some affected individuals. We tested this hypothesis by comparing vascular risk factors, magnetic resonance imaging (MRI) markers of cerebral small-vessel disease, and other evidence of a cerebrovascular disorder between TGA patients with (DWI+) and without (DWI−) DWI lesions and normal community-based controls.

Methods—

We retrospectively identified 86 patients hospitalized for TGA (mean±SD age, 65.9±10.9 years; 62% female). Brain MRI at 1.5 T was assessed for DWI lesions exhibiting restricted diffusion (ie, DWI+), white-matter hyperintensities, lacunes, and chronic infarcts (median time lag to clinical onset, 66.6±54.6 hours). Vascular risk factors and findings from duplex sonography, ECG, and echocardiography were recorded. A 1:2 age- and sex-matched sample of 172 elderly subjects (mean±SD age, 65.6±9.3 years; 62% female) free of neuropsychiatric disease served for comparison.

Results—

DWI lesions were observed in 10 patients with TGA (11.5%; mean±SD age, 68.3±5.4 years; 8 women). They were all small and located in the mesiotemporal region (9 left hemisphere, 5 right hemisphere). The vascular risk profile of TGA patients and concomitant changes on brain MRI were comparable with those of healthy controls and did not show significant differences between DWI+ and DWI− subjects. A comprehensive diagnostic workup also provided no evidence for a higher rate of cerebrovascular disorder-related abnormalities in either the total group of TGA patients or TGA DWI+ patients.

Conclusions—

These findings do not support a cerebrovascular etiology of TGA, even in those individuals showing acute DWI lesions. Other pathophysiologic mechanisms need to be explored.
Serum Calcium as Prognosticator in Ischemic Stroke
Authors: Ovbiagele Bruce , Starkman Sidney , Teal Philip , Lyden Patrick , Kaste Markku , Davis Stephen M. , Hacke Werner , Fierus Monika , Saver Jeffrey L.
Published: June 2008

Background and Purpose—

Calcium (Ca
2+
) plays a role in the cellular and molecular pathways of ischemic neuronal death. We evaluated the impact of both early and delayed Ca
2+
levels on clinical outcomes from acute ischemic stroke.

Methods—

The relations between blood calcium level obtained early (<4.5 hours), and delayed (72 to 96 hours) after ischemic stroke onset versus clinical outcomes were analyzed in 826 subjects enrolled in an international trial in the Virtual International Stroke Trials Archive. Subjects were categorized into Ca
2+
quartiles. Outcome measures analyzed included baseline and 72- to 96-hour stroke severity, as well as 3-month functional and global disability scales. The independent effect of calcium on outcome was evaluated by median and logistic regression analysis.

Results—

Six hundred and fifty-nine (80%) of the trial subjects had complete baseline data including Ca
2+
levels. Bivariately, the highest delayed Ca
2+
quartile (versus lowest) was associated with lesser stroke severity and better 3-month functional and independence scale outcomes (all
P
<0.001), but no significant outcome differences were noted among early Ca
2+
levels. In multivariable analysis, delayed Ca
2+
in the highest quartile (versus lowest quartile) was associated with greater 3-month independence score on the Barthel Index scale (76.9 versus 55.4,
P
=0.006). No other significant outcome differences were noted between highest and lowest quartiles for both early and delayed Ca
2+
quartiles.

Conclusions—

Elevated 72- to 96-hour serum Ca
2+
levels independently predict greater independence 3 months after ischemic stroke, but very early serum Ca
2+
appear not to have any prognostic significance.
Prevalence and Correlates of Silent Cerebral Infarcts in the Framingham Offspring Study
Authors: Das Rohit R. , Seshadri Sudha , Beiser Alexa S. , Kelly-Hayes Margaret , Au Rhoda , Himali Jayandra J. , Kase Carlos S. , Benjamin Emelia J. , Polak Joseph F. , O'Donnell Christopher J. , Yoshita Mitsuhiro , D'Agostino Ralph B. , DeCarli Charles , Wolf Philip A.
Published: June 2008

Background and Purpose—

Previous estimates of the prevalence of silent cerebral infarction (SCI) on MRI in community-based samples have varied between 5.8% and 17.7% depending on age, ethnicity, presence of comorbidities, and imaging techniques. We document the prevalence and risk factors associated with SCI at midlife in the community-based Framingham sample.

Methods—

Our study sample comprised 2040 Framingham Offspring (53% female; mean age, 62±9 years) who attended the sixth examination (1996–1998), underwent volumetric brain MRI (1999–2005,) and were free of clinical stroke at MRI. We examined the age- and sex-specific prevalences and the clinical correlates of SCI using multivariable logistic regression models.

Results—

At least 1 SCI was present in 10.7% of participants; 84% had a single lesion. SCI was largely located in the basal ganglia (52%), other subcortical (35%) areas, and cortical areas (11%). Prevalent SCI was associated with the Framingham Stroke Risk Profile score (OR, 1.27; 95% CI, 1.10–1.46); stage I hypertension was determined by JNC-7 criteria (OR,1.56; CI,1.15–2.11), an elevated plasma homocysteine in the highest quartile (OR, 2.23; CI, 1.42–3.51), atrial fibrillation (OR, 2.16; CI, 1.07–4.40), carotid stenosis >25% (OR, 1.62; 1.13–2.34), and increased carotid intimal-medial thickness above the lowest quintile (OR, 1.65; CI, 1.22–2.24).

Conclusion—

The prevalence and distribution of SCI in the Framingham Offspring are comparable to previous estimates. Risk factors previously associated with clinical stroke were also found to be associated with midlife SCI. Our results support current guidelines emphasizing early detection and treatment of stroke risk factors.
Les Villes De Juda Au Temps D'Ozias
Authors: Feuillet R.
Published: June 2008

Dans cette étude nous nous proposons, à la lumière des compte-rendus plus récents, d'établir le bilan des fouilles dans les villes de Juda, pour le milieu du 8e siècle c'est-à-dire le règne d'Ozias. Certes, en Archéologie, il est difficile de fixer des dates rigoureuses et nous ne pouvons isoler, dans les niveaux du Fer II, ce qui concerne la période autour de 750; un tel découpage risquerait d'être fort arbitraire. Mais, pour chaque ville, il est possible de grouper les éléments qui permettront une vue d'ensemble sur son activité, ses richesses, son développement pour le temps que nous étudions. Une telle enquête nous invitera à comparer et à faire le point, à donner quelques conclusions générales. • Il est évident que, pour la clarté de cette étude, il nous faudra rappeler brièvement l'histoire antérieure de chaque site, tant sur le plan biblique que sur le plan archéologique.
The Song of Songs
Authors: Segal M.H.
Published: June 2008

The theme of this fascinating monument of ancient Hebrew poetry is the celebration of the love between a damsel and her swain. It is undoubtedly a lawful love to be sanctioned by marriage. The damsel speaks of their bed and their home (i 16-17), and of the mandrakes which married women used to help them in getting children (vii 14; cf. Gen. xxx 14-15), but the consummation of their love is still in the future (vii 13). The damsel is still in the home of her mother (iii 4, viii 2). They are indeed already in a somewhat intimate personal relationship, as is apparent from their detailed description of the beauty of each other's body (iv 1-5, vii 2-6, v 10-16), but the damsel is still in her virginity, "a garden inclosed, a fountain sealed" as described by the swain (iv 12). The damsel repeatedly warns against stirring up the love to too high a degree (ii 7, iii 5, viii 4). They are evidently a betrothed couple very near their marriage. But in one poem, not at the end of the Song, there is a description of the consummation of their love under the figure of a garden with its delicious fruits and a reference to the banquetting of the marriage feast. It is in that poem alone that the swain calls the damsel 'bride', 'my sister the bride' (iv 8-v 1).
Nagid-Shepherd
Authors: Glück J.J.
Published: June 2008

(a) ngd and nqd originated from one common root which meant shepherding.
Despoiling the Egyptians
Authors: Coats George W.
Published: June 2008

Georg FOHRER and Martin NOTH label the motif describing spoil taken from the Egyptians a subsidiary theme in the Exodus traditions 1). In the following paper we propose 1) to challenge their relegation of the motif to a subordinate position, and 2) to offer a definition of the motif's function in Israel's memory of the Exodus event.
Peshitta Institute Communications Viii
Authors: Running Leona G.
Published: June 2008

There is a group of seventeenth-century Syriac mss of Susanna that presents a complex picture of mixture and confusion. 1) In collating the Susanna mss. I did not happen to meet first the source of the confusion; hence in the ms. of this group which I first met, 17a10, it seemed that the scribe had been interrupted as he reached the end of the second question-and-answer set, and when he returned to his copying he somehow got hold of a different Vorlage and continued from the end of v. 54 instead of the end of v. 58, thus repeating the second set and making three sets of Daniel's question and an elder's reply, instead of the two sets actually involved in the story.
Élie a L'Horeb
Authors: Carlson R.A.
Published: June 2008

La tradition concernant le prophète Élie de Tisbé est un des sommets littéraires de l'oeuvre deutéronomiste 1). Nous voudrions dans cet article souligner certains aspects caractéristiques de la composition et du style de la tradition intégrale dans la forme qu'elle revêt actuellement. Si ces points étaient passés sous silence on serait amené à porter un jugement inexact sur le contenu et l'intention de la transmission de cette tradition depuis son origine jusqu'à la rédaction finale. Ce risque est particulièrement sensible quand on analyse l'histoire d'Élie à l'Horeb en 1 Reg. xix. La partie centrale de ce récit qui rapporte une théophanie est presque toujours mal interprétée parce qu'on néglige l'importance du jeu subtile qu'y entretient la structure littéraire avec le propos idéologique. Le but de cet article est par conséquent de faire à nouveau l'analyse de 1 Reg. xix en partant du caractère de la légende d'Élie en général. Il est donc opportun de partir des idées de WELLHAUSEN sur ce chapitre et de développer également les vues plus récentes à ce sujet.
Carrie Judd Montgomery: Pioneering Contributor to Three Religious Movements
Authors: Albrecht Daniel E.
Published: June 2008

When on February 26, 1879 a young woman was miraculously raised from her deathbed at the prophetic word of an obscure healer some three hundred miles away, 1 it was heralded as one of the most amazing miracles of modern times.2 Little did Carrie Faith Judd know, that as she took her first steps in more than two years, she would soon be propelled into a life of ministry that would destine her to become "one of the best known women in America. "3 No one could have predicted that a frail, sickly, timid teenager, who so narrowly escaped death, would become known around the world for her innovative leadership within three Evangelical movements. In the "Age of Enterprise," Carrie Judd Montgomery (1858-1946) symbolized the American religious leader as an entrepreneur. Her innovative ministries were born out of a deep love for God that expressed itself by seeking out and serving human need in a variety of creative forms. Montgomery was a unique mixture of gentle refinement and trailblazing pragmatism, quiet dignity and efficient promotion, tender compassion and tough-minded executive abilities. Historical amnesia, has frequently cloaked the contributions of women to the thought and life of religious movements. Regardless of that fact, Montgomery was, in her time, one of the most celebrated proponents of the divine healing message. As a gifted writer, public speaker, and religious entrepreneur, she led the way for numerous other evangelical ministries. This creative Episcopalian woman exercised a profound influence within three evangelical movements: the faith healing movement, the Christian and Missionary Alliance (C&MA), and the fledgling Pentecostal movement. Although little is remembered or known about Montgomery in religious circles today, as an evangelical pacesetter and a Pentecostal forerunner, her life and work deserve renewed reflection and serious study.
The Proceedings of the Leaders' Meetings (1908-1911) and of the International Pentecostal Council (1912-1914)1
Authors: van der Laan Cornelis
Published: June 2008

In 1912 some prominent leaders of the Pentecostal movement in Europe decided to form an International Consultative Council that would meet once or twice a year. At least four such meetings were held before the First World War prematurely ended the venture. In this article the cause, proceedings and significance of the council will be considered. Extensive attention is given to the preceding Leaders' Meetings that were held during the international conferences as from 1908 and eventually would lead to the formation of the Consultative Council.
Cecil H. Polhill-Pentecostal Layman
Authors: Hocken Peter
Published: June 2008

Old Etonian missionary on the borders of Tibet and an English country squire at noisy multi-racial meetings in the back streets of Los Angeles: such contrasts suggest an interesting life, the life of Cecil Henry Polhill. However, this study is undertaken not for curiosity's sake, but because Polhill was a significant figure in the origins of the Pentecostal movement. Like his friend, the Revd. Alexander Boddy, vicar of All Saints, Monkwearmouth, Sunderland in north-east England, Cecil Polhill was a Pentecostal pioneer who remained until his death a faithful member of the established Church of England. Unlike Boddy, Polhill has not until now attracted any researcher. 1
Links and Parallels between Black and White Charismatic Churches in South Africa and the States: Potential for Cultural Transformation
Authors: Poewe Karla
Published: June 2008

In the study of early and late twentieth century South African independent churches, a rigid differentiation is usually made between African and European charismatic movements and independent churches. This paper rejects such a simplistic view and argues, instead, that there are important historical links between recent White and older Black charismatic movements and independent churches. More importantly, the parallels between them have to do with processes of formation which are based on the use of common core symbols of transition from the Old Testament and on similar spiritual experiences which are seen to confirm Biblical texts and to be confirmed by them. Charismatic movements have arisen among Blacks and Whites, rich and poor and have tended to achieve personal and group transformations through prophecy, vision, music, and worship.
Diversity: Religions and the Study of Religion
Authors: Van Den Heever Gerhard
Published: June 2008

In this essay an overview of the theoretical issues pertaining to the collection of essays assembled is given. Addressing the issue of dizversity in religions and in the study of religion the argument is made that religions as lived phenomena constitute discursive formations in which diversity as a problem is an index of encounter. However it is especially the way this strategy of reducing the many to the one in the history of theorising religion that comes in view. In this context, the political nature of religion as discourse and the discourse of the study of religion is discussed with particular reference to the history of Christianisation of South Africa, religion in education, and the history of theorising religion.