bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature, metabolic power and the evolution of endothermy
Authors: Clarke Andrew , Pörtner Hans‐Otto
Published: January 2010

Endothermy has evolved at least twice, in the precursors to modern mammals and birds. The most widely accepted explanation for the evolution of endothermy has been selection for enhanced aerobic capacity. We review this hypothesis in the light of advances in our understanding of ATP generation by mitochondria and muscle performance. Together with the development of isotope‐based techniques for the measurement of metabolic rate in free‐ranging vertebrates these have confirmed the importance of aerobic scope in the evolution of endothermy: absolute aerobic scope, ATP generation by mitochondria and muscle power output are all strongly temperature‐dependent, indicating that there would have been significant improvement in whole‐organism locomotor ability with a warmer body. New data on mitochondrial ATP generation and proton leak suggest that the thermal physiology of mitochondria may differ between organisms of contrasting ecology and thermal flexibility. Together with recent biophysical modelling, this strengthens the long‐held view that endothermy originated in smaller, active eurythermal ectotherms living in a cool but variable thermal environment. We propose that rather than being a secondary consequence of the evolution of an enhanced aerobic scope, a warmer body was the means by which that enhanced aerobic scope was achieved. This modified hypothesis requires that the rise in metabolic rate and the insulation necessary to retain metabolic heat arose early in the lineages leading to birds and mammals. Large dinosaurs were warm, but were not endotherms, and the metabolic status of pterosaurs remains unresolved.
Plant health and global change – some implications for landscape management
Authors: Pautasso Marco , Dehnen‐Schmutz Katharina , Holdenrieder Ottmar , Pietravalle Stéphane , Salama Nabeil , Jeger Mike J. , Lange Eckart , Hehl‐Lange Sigrid
Published: January 2010

Global change (climate change together with other worldwide anthropogenic processes such as increasing trade, air pollution and urbanization) will affect plant health at the genetic, individual, population and landscape level. Direct effects include ecosystem stress due to natural resources shortage or imbalance. Indirect effects include (i) an increased frequency of natural detrimental phenomena, (ii) an increased pressure due to already present pests and diseases, (iii) the introduction of new invasive species either as a result of an improved suitability of the climatic conditions or as a result of increased trade, and (iv) the human response to global change. In this review, we provide an overview of recent studies on terrestrial plant health in the presence of global change factors. We summarize the links between climate change and some key issues in plant health, including tree mortality, changes in wildfire regimes, biological invasions and the role of genetic diversity for ecosystem resilience. Prediction and management of global change effects are complicated by interactions between globalization, climate and invasive plants and/or pathogens. We summarize practical guidelines for landscape management and draw general conclusions from an expanding body of literature.
Temporal dysregulation of cortical gene expression in the isolation reared Wistar rat
Authors: Murphy Keith J. , Ter Horst Judith P. F. , Cassidy Andrew W. , DeSouza Ian E. J. , Morgunova Marina , Li Christine , Connole Laura M. , O’Sullivan Niamh C. , Loscher Jennifer S. , Brady Angela T. , Rombach Nanette , Connellan Joanna , McGettigan Paul A. , Scully Darren , Fedriani Rocio , Lukasz Bartlomiej , Moran Mary P. , McCabe Olive M. , Wantuch Caitlin M. , Hughes Zoe A. , Mulvany Sean K. , Higgins Desmond G. , Pangalos Menelas N. , Marquis Karen L. , O’Connor William T. , Ring Robert H. , Von Schack David , Regan Ciaran M.
Published: January 2010

J. Neurochem. (2010) 113, 601–614.

The critical sequence of molecular, neurotransmission and synaptic disruptions that underpin the emergence of psychiatric disorders like schizophrenia remain to be established with progress only likely using animal models that capture key features of such disorders. We have related the emergence of behavioural, neurochemical and synapse ultrastructure deficits to transcriptional dysregulation in the medial prefrontal cortex of Wistar rats reared in isolation. Isolation reared animals developed sensorimotor deficits at postnatal day 60 which persisted into adulthood. Analysis of gene expression prior to the emergence of the sensorimotor deficits revealed a significant disruption in transcriptional control, notably of immediate early and interferon‐associated genes. At postnatal day 60 many gene transcripts relating particularly to GABA transmission and synapse structure, for example Gabra4, Nsf, Syn2 and Dlgh1, transiently increased expression. A subsequent decrease in genes such as Gria2 and Dlgh2 at postnatal day 80 suggested deficits in glutamatergic transmission and synapse integrity, respectively. Microdialysis studies revealed decreased extracellular glutamate suggesting a state of hypofrontality while ultrastructural analysis showed total and perforated synapse complement in layer III to be significantly reduced in the prefrontal cortex of postnatal day 80 isolated animals. These studies provide a molecular framework to understand the developmental emergence of the structural and behavioural characteristics that may in part define psychiatric illness.
Angiotensin‐II type 1 receptor (AT1R) and alpha‐1D adrenoceptor form a heterodimer during pregnancy‐induced hypertension
Authors: Lourdes González‐Hernández M. de , Godínez‐Hernández D. , Bobadilla‐Lugo R. A. , López‐Sánchez P.
Published: January 2010

1 Pregnancy courses with low response to angiotensin II and adrenergic agonists. In preeclampsia, both effects are reverted. It is known that angiotensin II regulates adrenergic system. It is not known, however, the interaction between both systems receptors.

2 Our aim was to study if AT1R and α1D adrenoceptor heterodimerize in preeclampsia.

3 We used subrenal aorctic coarctation in pregnant rats. Aortic tissues were prepared for confocal imaging and coimmunoprecipitated for α1D and AT1receptors.

4 We found that AT1R and α1D adrenoceptor heterodimerize in both, healthy and preeclamptic groups. In healthy pregnant rats, heterodimer is barely detected. In preeclamptic rats however, we found higher heterodimerization.

5 These results suggest that AT1R and α1D ‐adrenoceptor may form heterodimers, and may play a role in preeclampsia.
Old vs recent cross‐border cooperation: Portugal–Spain and Norway–Sweden
Authors: Medeiros Eduardo José Rocha
Published: January 2010

The two largest European Peninsulas (Iberian and Scandinavian) are both divided by a long and ancient frontier, which separates four old European nations: Portugal, Spain, Sweden and Norway. In the first case, the unusual stability of the border, which remains almost unchanged for more than 800 years, has contributed to strengthen a long ‘back‐to‐back’ existence, during most of this time. In the latter, however, successive changes in the border location, and historical alliances between the Nordic countries, created a more ‘face‐to‐face’ type of border and a more solid background for the cross‐border cooperation (CBC). Therefore, while the INTERREG‐A Community Initiative represented an important starting point for the CBC process in most parts of the Portuguese–Spanish border region (PSBR), it was just another important added value for the CBC in the Swedish–Norwegian border region (SNBR), since this process had already started in 1948, when Sweden, Norway, Iceland and Denmark established the joint Nordic Committee for Economic Cooperation, followed by the formation of the Nordic Council in 1951. With this in mind, this article analyses how such distinct CBC backgrounds contributed to the two different approaches and results obtained from the implementation of the INTERREG‐A in both studied border regions.
Evidence Complexity and Information Search in the Decision to Restate Prior‐Period Financial Statements
Authors: RICCHIUTE DAVID N.
Published: January 2010

Framed in the decision to restate financial statements, this study addresses whether behavior predicted by competing theories depends on the complexity of evidence. Two experiments observe the information‐search behavior of auditors responsible for investigating their firm's prior opinion. Experiment 1 shows that auditors confronted with few (many) summarized statements that replicate in form the materials used in prior research prefer to first search statements that are inconsistent (consistent) with the prior‐period accounting. This result generally corroborates research in accounting and confirms the predictions of information‐quantity theory in psychology. In contrast, experiment 1 also shows that, when materials mimic the detailed documents common in practice, the results are different: Auditors confronted either with few or with many detailed documents prefer to search inconsistent documents first. This result confirms the predictions of evidence‐complexity theory in psychology and shows that, compared to the materials on which prior research relies, detailed documents, such as memos, emails, letters, and analyses, drive information search toward inconsistent evidence. Experiment 2 probes further and finds that auditors evaluate documents bearing notes inscribed after the documents were prepared to be more inconsistent with the prior‐period accounting, and that the dispersion in search behavior may be reliably conditional on the presence of notes.
Novel ruthenium complexes as potential drugs for Chagas's disease: enzyme inhibition and in vitro/in vivo trypanocidal activity
Authors: Silva Jean Jerley Nogueira , Guedes Paulo Marcos Matta , Zottis Aderson , Balliano Tatiane Luciano , Nascimento Silva Francisco Ordelei , França Lopes Luiz Gonzaga , Ellena Javier , Oliva Glaucius , Andricopulo Adriano Defini , Franco Douglas Wagner , Silva João Santana
Published: January 2010

Background and purpose:  The discovery of the pharmacological functions of nitric oxide has led to the development of NO donor compounds as therapeutic agents. A new generation of ruthenium NO donors, cis‐[Ru(NO)(bpy)2L]Xn, has been developed, and our aim was to show that these complexes are able to lyse Trypanosoma cruzi in vitro and in vivo.

Experimental approach:  NO donors were incubated with T. cruzi and their anti‐T. cruzi activities evaluated as the percentage of lysed parasites compared to the negative control. In vivo, trypanocidal activity was evaluated by observing the levels of parasitaemia, survival rate and elimination of amastigotes in mouse myocardial tissue. The inhibition of GAPDH was monitored by the biochemical reduction of NAD+ to NADH.

Key results:  The NO donors cis‐[Ru(NO)(bpy)2L]Xn presented inhibitory effects on T. cruzi GAPDH (IC50 ranging from 89 to 153 µM). The crystal structure of the enzyme shows that the inhibitory mechanism is compatible with S‐nitrosylation of the active cysteine (cys166) site. Compounds cis‐[Ru(NO)(bpy)2imN](PF6)3 and cis‐[Ru(NO)(bpy)2SO3]PF6, at a dose of 385 nmol·kg−1, yielded survival rates of 80 and 60%, respectively, in infected mice, and eradicated any amastigotes from their myocardial tissue.

Conclusions and implications:  The ruthenium compounds exhibited potent in vitro and in vivo trypanocidal activities at doses up to 1000‐fold lower than the clinical dose for benznidazole. Furthermore, one mechanism of action of these compounds is via the S‐nitrosylation of Cys166 of T. cruzi GAPDH. Thus, these compounds show huge potential as candidates for the development of new drugs for the treatment of Chagas's disease.

This article is commented on by Machado et al., pp. 258–259 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00662.x and to view a related paper in this issue by Guedes et al. visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00576.x
A cannabinoid receptor, sensitive to O‐1918, is involved in the delayed hypotension induced by anandamide in anaesthetized rats
Authors: Zakrzeska Agnieszka , Schlicker Eberhard , Baranowska Marta , Kozłowska Hanna , Kwolek Grzegorz , Malinowska Barbara
Published: January 2010

Background and purpose: Intravenous injection of the endocannabinoid anandamide induces complex cardiovascular changes via cannabinoid CB1, CB2and vanilloid TRPV1 receptors. Recently, evidence has been accumulating thatin vitro, but notin vivo, anandamide relaxes blood vessels, via an as yet unidentified, non‐CB1vascular cannabinoid receptor, sensitive to O‐1918 (1,3‐dimethoxy‐5‐2‐[(1R,6R)‐3‐methyl‐6‐(1‐methylethenyl)‐2‐cyclohexen‐1‐yl]‐benzene). We here examined whether the anandamide‐induced hypotension in urethane‐anaesthetized rats was also mediated via a non‐CB1vascular cannabinoid receptor.

Experimental approach: Effects of two antagonists (O‐1918 and cannabidiol) of the non‐CB1vascular cannabinoid receptor on anandamide‐induced changes in mean, systolic and diastolic blood pressure (MBP, SBP, DBP), mesenteric (MBF) and renal (RBF) blood flow and heart rate (HR) in urethane‐anaesthetized rats was examined.

Key results: In anaesthetized rats, anandamide (1.5–3 µmol·kg−1) and its stable analogue methanandamide (0.5 µmol·kg−1) caused a delayed and prolonged decrease in MBP, SBP, DBP, MBF and RBF by about 10–30% of the respective basal values without changing HR. In pithed rats, anandamide (3 µmol·kg−1) decreased blood pressure by about 15–20% of the basal value without affecting HR, MBF and RBF. All vascular changes were reduced by about 30–70% by cannabidiol and O‐1918 (3 µmol·kg−1, each).

Conclusions and implications: Non‐CB1cannabinoid vascular receptors, sensitive to O‐1918, contribute to the hypotensive effect of anandamide in anaesthetized rats. Activation of these receptors may be therapeutically important as the endocannabinoid system could be activated as a compensatory mechanism in various forms of hypertension.
TheGinkgo bilobaextract EGb 761®and its main constituent flavonoids and ginkgolides increase extracellular dopamine levels in the rat prefrontal cortex
Authors: Yoshitake T , Yoshitake S , Kehr J
Published: January 2010

Background and purpose: Experimental and clinical data suggest that extracts ofGinkgo bilobaimprove cognitive function. However, the neurochemical correlates of these effects are not yet fully clarified. The purpose of this study was to examine the effects of acute and repeated oral administration of the standardized extract EGb 761®on extracellular levels of dopamine, noradrenaline and serotonin (5‐HT), and the dopamine metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the prefrontal cortex (PFC) and striatum of conscious rats.

Experimental approach: Monoamines and their metabolites were monitored by the use of microdialysis sampling and HPLC with electrochemical or fluorescence detection.

Key results: A single oral dose of EGb 761 (100 mg·kg−1) had no effect on monoamine levels. However, following chronic (100 mg·kg−1/14 days/once daily) treatment, the same dose significantly increased extracellular dopamine and noradrenaline levels, while 5‐HT levels were unaffected. Chronic treatment with EGb 761 showed dose‐dependent increases in frontocortical dopamine levels and, to a lesser extent, in the striatum. The extracellular levels of HVA and DOPAC were not affected by either acute or repeated doses. Treatment with the main constituents of EGb 761 revealed that the increase in dopamine levels was mostly caused by the flavonol glycosides and ginkgolide fractions, whereas bilobalide treatment was without effect.

Conclusions and implications: The present results demonstrate that chronic but not acute treatment with EGb 761 increased dopaminergic transmission in the PFC. This finding may be one of the mechanisms underlying the reported effects ofG. bilobain improving cognitive function.
Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice
Authors: Huang Chi‐Chang , Lo Chiu‐Ping , Chiu Chih‐Yang , Shyur Lie‐Fen
Published: January 2010

Background and purpose:  Elephantopus scaber L. (Asteraceae) is a traditional herbal medicine with anti‐cancer effects. We evaluated the in vitro and in vivo efficacy of a major sesquiterpene lactone constituent of E. scaber, deoxyelephantopin (DET), against mammary adenocarcinoma and the underlying molecular mechanism.

Experimental approach:  A variety of cellular assays, immunoblotting and immunohistochemistry, as well as both orthotopic and metastatic TS/A tumour models in BALB/c mice, were used. Test mice were pretreated and post‐treated with DET or paclitaxel and mammary tumour growth evaluated.

Key results:  DET (≤2 µg·mL−1) significantly inhibited colony formation, cell proliferation, migration and invasion of TS/A cells and induced G2/M arrest and apoptosis in TS/A cells. c‐Jun N‐terminal kinase‐mediated p21Waf1/Cip1 expression and caspase activation cascades were up‐regulated by DET, effects suppressed by N‐acetyl‐L‐cysteine. Moreover, tumour necrosis factor α‐induced matrix metalloproteinase‐9 enzyme activity and expression and nuclear factor‐kappa B activation were abolished by DET. Pretreatment with DET was more effective than paclitaxel, for profound suppression of orthotopic tumour growth (99% vs. 68% reduction in tumour size) and lung metastasis of TS/A cells (82% vs. 63% reduction in metastatic pulmonary foci) and prolonged median survival time (56 vs. 37 days, P < 0.01) in mice. The levels of cyclooxygenase‐2 and vascular endothelial growth factor in metastatic lung tissues of TS/A‐bearing mice were attenuated by DET.

Conclusions and implications:  Our data provide evidence for the suppression of mammary adenocarcinoma by DET with several mechanisms and suggest that DET has potential as a chemopreventive agent for breast cancer.
Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in rats
Authors: Zhang Y , Guzinski M , Eger II EI , Laster MJ , Sharma M , Harris RA , Hemmings Jr HC
Published: January 2010

Background and purpose:  Results from several studies point to voltage‐gated Na+ channels as potential mediators of the immobility produced by inhaled anaesthetics. We hypothesized that the intrathecal administration of tetrodotoxin, a drug that blocks Na+ channels, should enhance anaesthetic potency, and that concurrent administration of veratridine, a drug that augments Na+ channel opening, should reverse the increase in potency.

Experimental approach:  We measured the change in isoflurane potency for reducing movement in response to a painful stimulus as defined by MAC (minimum alveolar concentration of anaesthetic required to abolish movement in 50% of subjects) caused by intrathecal infusion of various concentrations of tetrodotoxin into the lumbothoracic subarachnoid space of rats, and the change in MAC caused by the administration of a fixed dose of tetrodotoxin plus various doses of intrathecal veratridine.

Key results:  Intrathecal infusion of tetrodotoxin (0.078–0.63 µM) produced a reversible dose‐related decrease in MAC, of more than 50% at the highest concentration. Intrathecal co‐administration of veratridine (1.6–6.4 µM) reversed this decrease in a dose‐related manner, with nearly complete reversal at the highest veratridine dose tested.

Conclusions and implications:  Intrathecal administration of tetrodotoxin increases isoflurane potency (decreases isoflurane MAC), and intrathecal administration of veratridine counteracts this effect in vivo. These findings are consistent with a role for voltage‐gated Na+ channel blockade in the immobility produced by inhaled anaesthetics.
Origin of stratified basal ice in outlet glaciers of Vatnajökull and Öræfajökull, Iceland
Authors: LARSON GRAHAME J. , LAWSON DANIEL E. , EVENSON EDWARD B. , KNUDSEN ÓSKAR , ALLEY RICHARD B. , PHANIKUMAR MANTHA S.
Published: January 2010

Larson, G.J., Lawson, D.E., Evenson, E.B., Knudsen, Ó., Alley, R.B. & Phanikumar, M.S. 2010: Origin of stratified basal ice in outlet glaciers of Vatnajökull and Öræfajökull, Iceland. Boreas, Vol. 39, pp. 457–470. 10.1111/j.1502‐3885.2009.00134.x. ISSN 0300‐9483.

During the period 2000–2005, we collected samples of englacial ice, vent water, frazil/anchor ice and stratified basal ice from warm‐based outlet glaciers of Vatnajökull and Öræfajökull, Iceland, and analysed them for 3H, 18O and D. Results of 3H analyses show that the stratified basal ice contains 3H from atmospheric thermonuclear testing and is younger than the englacial ice. Results of the 18O and D analyses show that frazil/anchor and stratified basal ice are both enriched by an average of 2.4‰ in 18O and 11‰ in D relative to vent water. These values are consistent with fractionation during partial freezing of supercooled subglacial water in an open system, one in which the remaining water is continuously removed and replenished by water of similar composition. The isotopic data and field observations do not support either a regelation or a thermal ad‐freeze‐on origin for the stratified basal ice.
Team Formation and Self‐serving Biases
Authors: Corgnet Brice
Published: January 2010

There is extensive evidence which indicates that people learn positively about themselves. We build on this finding to develop a model of team formation. We show that under complete information learning positively about oneself prevents efficient team formation. Agents becoming overconfident tend to ask for an excessive share of the group outcome. Positive learning generates divergence in workers' beliefs and hampers efficient team formation. Interestingly, in a context of incomplete information regarding the partner's ability, extensive learning biases may reduce the divergence in agents' beliefs and facilitate efficient team formation as a result. We apply our model to coauthorship and organizational issues.
Trip Chaining: Who Wins Who Loses?
Authors: De Palma Andre , Dunkerley Fay , Proost Stef
Published: January 2010

This paper studies how trip chaining (combining commuting and shopping or commuting and child care) affects market competition: in particular, pricing and the equilibrium number of firms as well as welfare. We use a monopolistic competition framework, where firms sell differentiated products as well as offering differentiated jobs to households, who are all located at some distance from the firms. The symmetric equilibriums with and without the option of trip chaining are compared. We show analytically that introducing the trip chaining option reduces the profit margin of the firms in the short run, but increases welfare. The welfare gains are, however, smaller than the transport cost savings. In the free‐entry long‐run equilibrium, the number of firms decreases but welfare is higher. A numerical illustration gives orders of magnitude of the different effects.
How Levels of Interactivity in Tutorials Affect Students’ Learning of Modeling Transportation Problems in a Spreadsheet
Authors: Seal Kala Chand , Przasnyski Zbigniew H. , Leon Linda A.
Published: January 2010

Do students learn to model OR/MS problems better by using computer‐based interactive tutorials and, if so, does increased interactivity in the tutorials lead to better learning? In order to determine the effect of different levels of interactivity on student learning, we used screen capture technology to design interactive support materials for modeling and solving the transportation problem in a spreadsheet. A controlled experiment was carried out and the results indicate a general support for the effectiveness of interactive tutorials in enhancing students’ learning of modeling concepts. However, the study also found that excessive interactivity increased the cognitive load for the students and hindered their learning by making it difficult for them to consolidate concepts, integrate previous knowledge, and create meaningful mental models of the process.
Absenteeism in Undergraduate Business Education: A Proposed Model and Exploratory Investigation*
Authors: Burke Lisa A.
Published: January 2010

One issue in undergraduate business education remaining underexamined is student absenteeism. In this article, the literature on undergraduate absenteeism is reviewed culminating in a proposed conceptual framework to guide future research, and an exploratory investigation of management students’ attitudes about absenteeism is conducted. Implications for research practice are discussed.
Obama in Asia: West Looks East After the “End of History”
Authors: MAHBUBANI KISHORE
Published: January 2010

Twenty years after the fall of the Berlin Wall and the triumphant celebrations of the West, a new chapter of history has opened featuring the rising powers of Asia, led by China. Though embracing free markets, China has looked to its Confucian traditions instead of liberal democracy as the best route to good governance.

Will China manage to achieve high growth and a harmonious society through a strong state and long‐range planning that puts messy Western democracy and its short‐term mindset to shame? Or, in the end, will the weak rule of law and absence of political accountability in a one‐party state undermine its promise?

Francis Fukuyama and Kishore Mahbubani, the Singaporean thinker who has become the apostle of non‐Western modernity, debate these issues.

In this section we also republish a collective memoir by George H.W. Bush, Mikhail Gorbachev, Margaret Thatcher and François Mitterrand, recalling their fears and hopes two decades ago as they brought the Cold War to an end.
Iran at the Crossroads
Authors: BANI‐SADR ABOLHASSAN
Published: January 2010

As the confrontation between the West and Iran over uranium enrichment comes to a head, the internal confrontation in Iran between the partisans of divine sovereignty, allied with the Revolutionary Guard, and popular sovereignty continues to simmer.

In this section, the first president of the Islamic Republic, a leading cleric of the opposition, the Iranian human rights activist and Nobel Laureate Shirin Ebadi and a former British intelligence agent ponder what lies ahead.
Growth of Arterioles in Chronically Stimulated Adult Rat Skeletal Muscle
Authors: HANSEN‐SMITH FAY , EGGINTON S. , HUDLICKA O.
Published: January 2010

Objective: The purpose of this study was to test the hypothesis that capillary growth induced by chronic electrical stimulation of skeletal muscle is accompanied by the growth of small arterioles.

Methods: Lower limb flexor muscles of Sprague‐Dawley rats were stimulated by electrodes implanted in the vicinity of the peroneal nerve at 10 Hz for 8 h/d for 2 and 7 days. Cryostat sections from the proximal, middle, and distal regions of the extensor digitorum longus muscle (EDL) were fluorescently immunolabeled with α‐smooth muscle actin (αSMA) and myosin heavy chain (MHC) to identify mature (αSMA and MHC‐positive) and immature (αSMA‐positive, MHC‐negative) arterioles. The fluorescent derivative of the lectin Griffonia simplicifolia I (GSI) was used to identify all microvessels, including arterioles, capillaries, and venules.

Results: The number of vessels positive for GSI or αSMA surrounding muscle fibers was similar in all three muscle regions (proximal, middle, distal). The mean values ±SEM for GSI‐positive vessels from all regions were similar in control (4.3 ± 0.07) and 2‐day stimulated (4.7 ± 0.08) but higher in 7‐day stimulated muscles (6.7 ± 0.1, p < 0.05), thus confirming the previous findings on capillary growth. A similar increase was found in the number of αSMA‐positive vessels ≤10 µm outer diameter (1.3 ± 0.09 versus 0.4 ± 0.03 around muscle fibers in controls). The density of terminal arterioles (≤10 µm) was slightly but not significantly higher after 2 days of stimulation (19.5 ± 4 versus 15.6 ± 2 profiles/mm2 in control muscles) and significantly higher after 7 days (33 ± 7). While a similar increase was observed in the density of preterminal arterioles >10 µm (17 ± 3 control, 22 ± 3 at 2 days and 40 ± 5 at 7 days), the density of MHC‐positive vessels muscles stimulated for 7 days was unchanged. Seven‐day stimulated muscle also had a fivefold higher density of microvessel profiles <10 µm that were only partially surrounded by αSMA. This considerably exceeds the relative increase in the number of capillaries and thus supports the concept of arteriolar growth by transformation from capillaries.

Conclusions: Chronic electrical stimulation results in an early increase in the number of immature (MHC‐negative), but not mature (MHC‐positive) arterioles, a process that accompanies the increase in capillarization. The great increase in the number of microvessels only partially covered by αSMA suggests arteriolization of capillaries as a contributing mechanism in this growth.
Angiogenesis in P‐ and E‐Selectin‐Deficient Mice
Authors: HARTWELL D.W. , BUTTERFIELD C.E. , FRENETTE P.S. , KENYON B.M. , HYNES R.O. , FOLKMAN J. , WAGNER DENISA D.
Published: January 2010

Objectives: Several observations reported earlier indicated that the selectins, in particular E‐selectin, might be involved in angiogenesis; however, mice deficient in the endothelial selectins develop normally. To clarify the role of endothelial selectins in angiogenesis, we have studied experimentally induced angiogenesis in selectin‐deficient mice.

Methods: Hydron pellets containing either basic fibroblast growth factor or the inflammatory cytokine tumor necrosis factor α were implanted into the corneas of wild‐type and P‐ and/or E‐selectin‐deficient mice.

Results: The lengths and circumferential range of the newly formed blood vessels in the corneas of the endothelial selectin‐deficient mice were similar to those of wild‐type mice.

Conclusion: The endothelial selectins are not essential in experimentally induced angiogenesis in vivo.
Heel‐Skin Microvascular Blood Perfusion Responses to Sustained Pressure Loading and Unloading
Authors: MAYROVITZ HARVEY N. , SMITH JOSHUA
Published: January 2010

Objective: Sustained heel pressure during surgery and during acute and longterm care residence can cause heel blood flow deprivation sufficient to cause pressure ulcers. Because little is known about the amount and distribution of heel blood perfusion changes under these conditions, the aim of this study was to characterize the main features of these changes.

Methods: Heel blood perfusion by laser Doppler imaging (LDI, 40 × 40 mm scans) was measured in 11 vascularly normal persons before (10 minutes), during heel loading (40 minutes) and after off‐loading (20 minutes). Loading was done with subjects supine and one heel on a transparent plate through which LDI data were obtained during loading. Analysis were on progressively increasing areas around the central compression site using 10 × 10, 20 × 20 × 20, 30 × 30, and 40 × 40 mm assay areas at each of multiple time points during the 70‐minute test.

Results: (1) Heel perfusion is rapidly and significantly reduced on loading (P < 0.01) with the greatest reduction within the central heel area; (2) perfusion remains uniformly depressed throughout the loading interval; (3) off‐loading is associated with a rapid onset, specially heterogeneous hyperemia which exceeds baseling (P < 0.01) for 10 minutes.

Conclusions: The present seminal findings may serve as a guide to develop sorely needed microvascular tests to help classify heel breakdown risk on a patient‐by‐patient basis.
A New In Vivo Microvascular Preparation of the Hamster Ovary
Authors: SWEENEY TERRENCE E. , BONADIO JASON A. , FREIMAN MICHAEL A. , GETTS ROGER T. , LLOYD BENJAMIN T. , MCKEOWN KYLE , PLATT MICHAEL P. , WON JULIE H.
Published: January 2010

Ovarian function in the cycling female is intimately related to and dependent upon significant microvascular regulation and restructuring. To enable investigation of the microvascular determinants of ovarian function, we present an in vivo preparation of the golden hamster ovary. The preparation does not compromise the ovarian vascular supply. The viability and responsiveness of the preparation were confirmed by quantifying arteriolar responses to vasoactive agents in 17 hamsters. Small surface arterioles (mean diameter 15–16 µm) responded with statistically significant changes in diameter to adenosine and oxygen and showed significant, dose‐dependent constriction in response to norepinephrine and the NO synthase inhibitor l‐NAME. Other key findings included extremely high microvascular permeability that varied with the day of the estrous cycle and functionally significant architectural features of the utero‐ovarian vascular network. Potential applications of the preparation include elucidation of the role of the microvasculature in follicular development and luteal regression, investigation of utero‐ovarian crossregulation, and development of a model for the study of ovarian angiogenesis and vascular regression.
α4β1‐Integrin Activation Is Necessary for High‐Efficiency T‐Cell Subset Interactions with VCAM‐1 under Flow
Authors: LIM YAW‐CHYN , WAKELIN MATTHEW W. , HENAULT LORI , GOETZ DOUGLAS J. , YEDNOCK TED , CABAÑAS CARLOS , SANCHEZ‐MADRID FRANCISCO , LICHTMAN ANDREW H. , LUSCINSKAS FRANCIS W.
Published: January 2010

Objective: The purpose of this study was to examine the relationship between α4β1‐integrin state of activation on CD4+ T‐cell subsets and their adhesive interaction to VCAM‐1 under flow.

Methods: Human CD4+ memory and naive T‐cells were freshly isolated and effector‐helper T‐cell subsets, Th1 and Th2 cells, were differentiated in vitro from CD4+ naive T‐cells. The expression of activation/ligand induced epitopes on β1‐integrins of each T‐cell subset was assessed using mAb HUTS21 and mAb 15/7. T‐cell subsets attachment and rolling on VCAM‐1 was determined under defined flow conditions and the rates of attachment (ka), accumulation, and instantaneous rolling velocities were correlated to their β1‐integrin activation epitope expression.

Results: A subset of memory T‐cells constitutively express activation/ligand induced epitopes on β1‐integrins recognized by mAb HUTS21 and 15/7, whereas expression levels on naive T‐cells is low or not detectable. Consistent with an activated phenotype, memory T‐cells exhibit significantly higher rates of attachment and accumulation on VCAM‐1 under flow as compared to naive T‐cells. Interestingly, the expression of activation/ligand induced epitopes on β1‐integrins on Th2 cells and the ability of these cells to interact with VCAM‐1 are comparable to memory T‐cells. In contrast, Th1 cells did not interact as efficiently with VCAM‐1, which correlated with lower expression of activation/ligand induced epitopes on these cells. VCAM‐1 interactions are inhibited completely by pretreatment of the T‐cells with blocking mAb to α4‐integrins or β1‐integrins, indicating that α4β1 is the predominant T‐cell integrin involved.

Conclusions: Memory T‐cells express constitutively active α4β1‐integrins, as compared to naive T‐cells, which mediate high rates of initial attachment and sustained high‐affinity adhesive interactions with VCAM‐1 under flow conditions in vitro. Similarly, in vitro differentiated Th2 cells but not Th1 cells, which also express elevated levels of activated α4β1‐integrins, are capable of sustaining high‐affinity adhesive interactions with VCAM‐1. The differences observed in β1‐integrin activation on T‐cell subsets may underlie selective recruitment patterns of T‐cell subsets in vivo. Microcirculation (2000) 7, 201–214.
Effects of Myocardial Edema on the Development of Myocardial Interstitial Fibrosis
Authors: DAVIS K.L. , LAINE G.A. , GEISSLER H.J. , MEHLHORN U. , BRENNAN M. , ALLEN S.J.
Published: January 2010

Objective: The mechanism by which chronic myocardial edema causes cardiac dysfunction is poorly understood. We hypothesized that myocardial edema triggers cardiac fibrosis development resulting in cardiac dysfunction. Since collagen is the most abundant constituent of the interstitial matrix, we examined the effects of edema development on cardiac collagen metabolism.

Methods: We utilized a chronic pulmonary artery banded rat model that produces right ventricular hypertrophy with myocardial edema and left ventricular edema without hypertrophy or hyperplasia. Wet to dry ratios (index of edema), collagen type I and III concentrations, prolyl 4‐hydroxylase (P4‐H) and collagen type I and III mRNA levels, collagenase activity and transforming growth factor‐β were measured in both ventricles.

Results: Right and left ventricular wet to dry ratios were significantly elevated from 1 to 28 days after pulmonary artery banding compared to sham rats. Right and left ventricular collagen types I and III and P4‐H mRNA levels increased significantly at 3 days followed by significant increases in right and left ventricular collagen concentration 7 days after pulmonary artery banding. Right ventricular collagenase activity increased at 3 days while left ventricular collagenase activity decreased 7 days after PA banding.

Conclusions: We conclude that myocardial edema preceded the observed increase in collagen deposition and that edema may have triggered increased collagen synthesis by fibroblasts, leading to fibrosis development.
Localized Adenovirus‐Mediated Gene Transfer Into Vascular Smooth Muscle in the Hamster Cheek Pouch
Authors: FRAME MARY D. , MIANO JOSEPH M. , YANG JAY , RIVERS RICHARD J.
Published: January 2010

Objective: Our purpose was to develop a method for adenovirus delivery to the hamster cheek pouch to experimentally target gene transfer in tissue used for microvascular studies.

Methods: Separate constructs were tested with transgenes for lacZ or green fluorescent protein (GFP) driven by three promoters: RSV, CMV, and SM22. With university approval, adenovirus was delivered in anesthetized (pentobarbital, 70 mg/kg) hamsters (n = 28) by using either a vascular systemic injection or tissue infiltration (interstitial space behind the pouch). During 3 days, animals receiving infiltration gained the expected weight, whereas those receiving vascular injection lost weight; no other behavior changes were noted.

Results: On day 3 postadenoviral delivery (infiltration), expression of lacZ (histology, β‐galactosidase) or GFP (fluorescence microscopy) was confirmed across the tissue (CMV and RSV promoters) and exclusively in vascular smooth muscle cells (specific SM22 promoter), without evidence of tissue inflammation. In vitro microvascular experiments verified normal responses in the cheek pouch of day 3 postadenoviral delivery animals. We tested local dilation to methacholine, adenosine, remote dilation to methacholine, adenosine, nitroprusside, and LM609 (αvβ3 integrin agonist), flow‐dependent dilation, and flow recruitment.

Conclusions: Thus, this method enables targeted, cell‐specific gene transfer to one tissue important for microvascular studies, without significant systemic exposure and without adverse inflammation.
Validation of Walkway Tribometers: Establishing a Reference Standard*
Authors: Powers Christopher M. , Blanchette Mark G. , Brault John R. , Flynn Jim , Siegmund Gunter P.
Published: January 2010

Abstract: Tribometers are mechanical devices used to measure walkway coefficient of friction (COF) for the purpose of assessing slip risk. The purpose of this study was to define a tribometer reference standard and use it to assess the performance of various tribometers. Eighty subjects were randomly assigned to walk across one of four wet walkway surfaces (polished black granite, porcelain, vinyl composition tile, and ceramic tile) to establish the relative slipperiness of each surface. Eleven tribometers were subsequently used to measure and rank the COF of all four surfaces. Our results revealed that only four of the 11 tribometers (Wessex pendulum, Sigler pendulum, Mark II, and Mark III) met our compliance criteria by both correctly ranking all four surfaces and differentiating between surfaces of varying degrees of slipperiness. Our protocol demonstrates that human gait‐based measures of slipperiness can be used to create reference standards against which tribometer measurements can be validated.
Comparative Analysis of the Effects of Heat on the PCR‐Amplification of Various Sized DNA Fragments Extracted from Sus Scrofa Molars*
Authors: Rees Kelly A. , Cox Margaret J.
Published: January 2010

Abstract:  This study examined the effects of heat on the amplification of DNA from the dental pulp of Sus scrofa molars and investigated the protection afforded to the pulp tissue by the dental enamel, alveolar process, and soft tissue of the head. Segments of defleshed maxilla and mandible encasing the first molar (n = 60) were subject to a range of temperatures for 15 min. Dental pulps were retrieved. Amplifications using three‐primer and four‐primer multiplexes showed no degradation of the largest fragment following exposure to 450°C. Amplifications in the three‐primer multiplex (283 bp) were successful following exposure to 525°C in maxillary samples only. This study revealed the enamel density of maxillary molars to be greater than mandibular molars in Sus scrofa. Following incineration of intact heads for 15 min (n = 10) and 1 h (n = 4) at an average temperature of 625°C, amplifications of the largest fragment (450 bp) were successful from both maxillary and mandibular teeth.
The Utility of the Samworth and Gowland Age‐at‐Death “Look‐up” Tables in Forensic Anthropology*
Authors: Passalacqua Nicholas V.
Published: January 2010

Abstract:  Accurate age‐at‐death estimates are crucial to forensic anthropologists when onstructing biological profiles aimed at narrowing a missing‐persons list and to allow for timely and efficient identification of an unknown victim. The present contribution evaluates the utility of three new age‐at‐death estimation techniques recently proposed by Samworth and Gowland (2007). Results indicate that, in the samples under study, the Samworth and Gowland estimates from the pubic symphysis and auricular surface perform similar to alternate phase methods. The combined method does not appear to further enhance either the precision or the accuracy of the single pubic symphysis age‐at‐death estimate. In conclusion, these new methods seem to be more robust to distribution deviations than originally proposed by Samworth and Gowland (2007). They are therefore suitable for immediate and reliable forensic usage in the United States and worthy of further research for their use in North American forensic contexts.
Denatured Ricin Can Be Detected as Native Ricin by Immunological Methods, but Nontoxic In Vivo
Authors: Kumar Om , Pradhan Santwana , Sehgal Payal , Singh Yamini , Vijayaraghavan Rajagopalan
Published: January 2010

Abstract:  Ricin is a glycoprotein from Ricinus communis seeds. It is known to have diverse toxic effects on cells of different visceral organs. In the present study, we purified and denatured ricin in a boiling water bath for different time intervals. We further made an attempt to identify native and denatured ricin by immunobased detection systems. All the antigen/antibody‐based assays identified native and denatured ricin. On SDS–PAGE, only native ricin was observed. In western blotting, ricin boiled for 3.75 min gave a strong band on X‐ray film. On native polyacryl amide gel electrophoresis, native and denatured ricin gave ricin band in 60‐kDa region. The denatured ricin did cause mortality up to 25 mg/kg, while 5 and 10 μg/kg of native ricin caused 50% and 100% mortality, respectively. Detection of native and denatured ricin is very difficult, and the investigating agencies, forensic scientists, and analysts should be very careful while interpreting the results.
The role of intracellular symbiotic bacteria in the amino acid nutrition of embryos from the black bean aphid, Aphis fabae
Authors: Bermingham J. , Wilkinson T. L.
Published: January 2010

Aphids are well‐known for their symbiotic relationship with intracellular bacteria of the genus Buchnera (γ‐Proteobacteria). The symbiosis has a nutritional basis in that the bacteria supplement the aphid diet of phloem sap through the provision of essential amino acids. To date, few studies have considered the spatial complexity of the association, particularly the delineation of the symbiosis into embryo and maternal compartments. Here, we generate aposymbiotic (bacteria‐free) embryos of the black bean aphid, Aphis fabae (Scopoli) (Hemiptera: Aphididae), as our experimental model and demonstrate that embryos reared in culture media require an external supply of essential amino acids. Analysis of individual amino acid deletions from the culture medium indicate that the key individual amino acids for embryo growth are phenylalanine and valine derived from the maternal tissues, and tryptophan derived from Buchnera. These results are discussed in relation to our current limited understanding of nutrient supply to aphid embryos.
Host plant species affects the quality of the generalist Trichoplusia ni as a host for the polyembryonic parasitoid Copidosoma floridanum
Authors: Lampert Evan C. , Bowers M. Deane
Published: January 2010

Diet of herbivorous insects can influence both the herbivores and their natural enemies. We examined the direct and indirect effects of diet on the interactions between the polyphagous herbivore Trichoplusia ni Hübner (Lepidoptera: Noctuidae) and its polyembryonic parasitoid Copidosoma floridanum Ashmead (Hymenoptera: Encyrtidae). To determine how host plant species and host plant iridoid glycoside content affect host caterpillars and their parasitoids, parasitized and unparasitized T. ni were given leaves of either Plantago lanceolata L., which contains the iridoid glycosides aucubin and catalpol, Plantago major L. (Plantaginaceae), which contains only aucubin, or Taraxacum officinale F.H. Wigg (Asteraceae), which contains neither. Survival of unparasitized T. ni was much lower when fed P. major compared with the other two host plants, whereas pupae were smallest when fed T. officinale and developed most slowly when fed P. lanceolata as larvae. Neither aucubin nor catalpol were detected in intact Plantago‐fed T. ni larvae or their hemolymph, and only trace amounts of aucubin were detected in frass, suggesting that these compounds are mostly metabolized in the midgut and are not encountered by the parasitoid. Copidosoma floridanum clutch size was almost doubled when reared from P. lanceolata‐fed T. ni compared with T. officinale‐fed larvae and tripled compared with P. major‐fed larvae, although the percent of parasitoids surviving to adulthood was uniformly high regardless of host diet. The observed variation in C. floridanum fitness among host diets is likely mediated by the effect of the diets on host quality, which in turn may be influenced more by other factors in the host plants than their iridoid glycoside profiles. Interactions between plant metabolites, generalist herbivores like T. ni, and their parasitoids may be predominantly indirect.
Tritrophic effects of organic and conventional fertilisers on a cereal‐aphid‐parasitoid system
Authors: Garratt Michael P. D. , Leather Simon R. , Wright Denis J.
Published: January 2010

The impact of parasitoids on pests varies between conventional and low‐intensity agricultural systems. Although the impacts on parasitoid natural enemies of many practices within these agricultural systems are well understood, the role of fertilisers has been less well studied. The effects of organic‐based and conventional fertilisers on Hordeum vulgare L. (Poaceae), the aphid Metopolophium dirhodum Walker (Hemiptera: Aphididae), and its parasitoid Aphidius ervi Haliday (Hymenoptera: Braconidae) was investigated using cage release experiments and measures of aphid and parasitoid fitness were taken. Barley tiller number and aphid weight were increased by fertilisers, particularly under conventional treatments. Adult parasitoid size correlated positively with that of the host, M. dirhodum, whereas percentage parasitism was not affected by fertiliser treatment or host size. The results suggest that the increased parasitoid impact observed in some low‐intensity or organic systems is not a direct result of fertiliser treatment. Our results indicate that fertiliser treatments that improve cereal‐aphid fitness will improve parasitoid fitness as measured by parasitoid size but may not influence percentage parasitism.