bluuebunny/crossref_metadata_2025 huggingface dataset:
Antenatal catastrophic uterine rupture at 32 weeks of gestation after previous B‐Lynch suture
Authors: Pechtor K , Richards B , Paterson H
Published: April 2010

Please cite this paper as: Pechtor K, Richards B, Paterson H. Antenatal catastrophic uterine rupture at 32 weeks of gestation after previous B‐Lynch suture. BJOG 2010;117:889–891.
Dopamine D1 and D3 receptors are differentially involved in cue‐elicited cocaine seeking
Authors: Chen Liping , Xu Ming
Published: April 2010

J. Neurochem. (2010) 114, 530–541.

Environmental cues previously associated with reinforcing drugs can play a key role in relapse to drug seeking behaviors in humans. The mesocorticolimbic dopamine system plays a critical role in cocaine‐induced neurobiological changes. Dopamine D1 and D3 receptors modulate locomotor‐stimulant and positive reinforcing effects of cocaine, and cue‐induced reinstatement of cocaine‐seeking. Moreover, activation of the extracellular signal‐regulated kinase (ERK) induced by acute cocaine administration is regulated by both D1 and D3 receptors. How D1 and D3 receptors modulate the acquisition and extinction of cue‐elicited cocaine seeking behavior and associated changes in the MAPK signaling pathway in different brain regions, however, remains unclear. In the present study, we found that D1 receptor mutant mice failed to acquire conditioned place preference (CPP) while D3 receptor mutant mice show delayed CPP extinction compared with wild‐type mice. Moreover, ERK, but not the c‐jun N‐terminal kinase and p38, is activated in wild‐type and D3 receptor mutant mice but not in D1 receptor mutant mice following CPP acquisition. D3 receptor mutant mice also exhibit sustained ERK activation compared with wild‐type mice following extinction training. Our results suggest that D1 and D3 receptors differentially contribute to learned association between cues and the rewarding properties of cocaine by regulating, at least in part, ERK activation in specific areas of the brain.
Calcium‐permeable AMPA receptors are involved in the induction and expression of l‐DOPA‐induced dyskinesia in Parkinson’s disease
Authors: Kobylecki Christopher , Cenci M. Angela , Crossman Alan R. , Ravenscroft Paula
Published: April 2010

J. Neurochem.(2010)114, 409–511.

Overactivity of striatal α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) glutamate receptors is implicated in the pathophysiology ofl‐DOPA‐induced dyskinesia (LID) in Parkinson’s disease (PD). In this study, we evaluated the behavioural and molecular effects of acute and chronic blockade of Ca2+‐permeable AMPA receptors in animal models of PD and LID. The acute effects of the Ca2+‐permeable AMPA receptor antagonist 1‐trimethylammonio‐5‐(1‐adamantane‐methylammoniopentane) dibromide hydrobromide (IEM 1460) on abnormal involuntary movements (AIMs) in the 6‐hydroxydopamine (6‐OHDA)‐lesioned rat and LID in the MPTP‐lesioned non‐human primate were assessed. Subsequently, the effects of chronic treatment of 6‐OHDA‐lesioned rats with vehicle,l‐DOPA/benserazide (6/15 mg/kg, i.p.) + vehicle orl‐DOPA + IEM 1460 (3 mg/kg, i.p.) on behavioural and molecular correlates of priming for LID were evaluated. In the 6‐OHDA‐lesioned rat and MPTP‐lesioned non‐human primate, acute treatment with IEM 1460 (1–3 mg/kg) dose‐dependently reduced LID without adverse effects on motor performance. Chronic co‐treatment for 21 days with IEM 1460 reduced the induction of AIMs byl‐DOPA in the 6‐OHDA‐lesioned rat without affecting peak rotarod performance, and attenuated AIMs score by 75% followingl‐DOPA challenge (p < 0.05). Chronic IEM 1460 treatment reversedl‐DOPA‐induced up‐regulation of pre‐proenkephalin‐A, and normalised pre‐proenkephalin‐B mRNA expression in the lateral striatum, indicating an inhibition of both behavioural and molecular correlates of priming. These data suggest that Ca2+‐permeable AMPA receptors are critically involved in both the induction and subsequent expression of LID, and represent a potential target for anti‐dyskinetic therapies.
Early Onset Childhood Cicatricial Pemphigoid: A Case Report and Review of the Literature
Authors: Kharfi Monia , Khaled Aida , Anane Raja , Fazaa Becima , Kamoun Mohamed Ridha
Published: April 2010

Abstract:  Cicatricial pemphigoid is an extremely rare condition in children, since only 17 cases have been reported in the English literature, so far. We describe a new case in a 20‐month‐old boy, who is to our knowledge the youngest patient reported yet. The disorder had begun 10 months before he was referred to our department by mucosal crusted erosions of the oral and nasal cavities and conjunctivae. Cutaneous examination showed buccal erosions with limited mouth opening, entropion of the lower eyelids, trichiasis, cicatricial cornea, synechia of the nasal cavities and hypopigmented lesions of the abdomen. There were no anal or genital lesions. Cicatricial pemphigoid was confirmed by positive direct and indirect immunofluorescence on mucous biopsy. Systemic corticosteroids (2 mg/kg/day), maintained for 12 months, had led to complete healing of lesions. But due to cicatrization, synechia of the nasal cavities and corneal opacities, leading to a dramatic visual loss, have occurred. Dapsone 25 mg/day and topical ocular cyclosporine are now maintained to avoid relapse. Our review of the literature of all cases of CP showed that ocular and to a less degree, vulvar lesions are the most severe ones, due to the serious complications with scar formation.
The Effects of Regulated Premium Subsidies on Insurance Costs: An Empirical Analysis of Automobile Insurance
Authors: Weiss Mary A. , Tennyson Sharon , Regan Laureen
Published: April 2010

Abstract

State regulation of rates is sometimes used as a means to make automobile insurance more affordable to consumers by restricting insurer profits and pricing practices. Incentive distortions arising from this type of rate regulation might lead to higher accident rates and higher insurance loss costs. Annual state‐level panel data for the time period 1980–1998 are used to investigate these effects, using empirical methods that recognize the endogenous determination of states’ regulatory choices. Results suggest that rate regulation that systematically suppresses (some or all) drivers’ insurance premiums is associated with significantly higher average loss costs and higher insurance claim frequency.
A Re‐Evaluation of Story Grammars*
Authors: Frisch Alan M. , Perlis Donald
Published: April 2010

Black and Wilensky (1979) have made serious methodological errors in analyzing story grammars, and in the process they have committed additional errors in applying formal language theory. Our arguments involve clarifying certain aspects of knowledge representation crucial to a proper treatment of story understanding.

Particular criticisms focus on the following shortcomings of their presentation: 1) an erroneous statement from formal language theory, 2) misapplication of formal language theory to story grammars, 3) unsubstantiated and doubtful analogies with English grammar, 4) various non sequiturs concerning the generation of non‐stories, 5) a false claim based on the artificial distinction between syntax and semantics, and 6) misinterpretation of the role of story grammars in story understanding.

We conclude by suggesting appropriate criteria for the evaluation of story grammars.
Concentrations of Opiates and Psychotropic Agents in Polydrug Overdoses: A Surprising Correlation Between Morphine and Antidepressants
Authors: Minett William J. , Moore Tara L. , Juhascik Matthew P. , Nields Henry M. , Hull Mindy J.
Published: April 2010

Abstract: The relationship between postmortem concentrations of morphine and co‐detected psychoactive drugs in fatal overdoses is examined. Morphine and other drugs were detected in 161 medicolegal autopsy cases. Subsets of these morphine‐positive cases based on drug class were established, including opioids, antidepressants, ethanol, benzodiazepines, and “other.” Each subset was split into high or low concentration groups based on median drug concentrations. Morphine concentrations of the [high] and [low] groups were compared, with no significant difference in morphine concentration identified in the opioid, ethanol, or benzodiazepine subsets. The “other” drug class was too heterogeneous for statistical assessment. Morphine concentrations did show a significant direct relationship (p = 0.01) with antidepressants, namely increased concentrations of antidepressant drugs are associated with an increased concentration of morphine. This trend probably remains even after excluding cocaine‐positive cases. The unsuspected finding that postmortem concentrations of antidepressants positively correlate with morphine levels may be important in the treatment of depression in drug addicts.
Mechanism of Death in Hanging: A Historical Review of the Evolution of Pathophysiological Hypotheses
Authors: Clément Renaud , Redpath Margaret , Sauvageau Anny
Published: April 2010

Abstract:  In cases of hanging, the exact mechanism leading to death has yet to be elucidated. Most of our contemporary knowledge is still based on writings from the end of the 19th and the beginning of the 20th century. This article reviews the historic experiments that shaped our current theories. Medico‐legal textbooks written in English and French from 1870 to 1930 were reviewed. Various animals, such as rabbits, mice, and dogs, have been used to develop animal models of hanging. Limited human studies on cadavers and judicial hangings have provided some additional insight into the pathophysiology of death by hanging. The main pathophysiological theories described were respiratory asphyxia, interruption to cerebral blood flow because of occlusion of vessels in the neck, and cardiac inhibition secondary to nerve stimulation. The relative contributions of each of these theories to death in cases of hanging is still debated today.
Ricochet of a Bullet in the Spinal Canal: A Case Report and Review of the Literature on Bullet Migration
Authors: Farrugia Audrey , Raul Jean‐sébastien , Géraut Annie , Ludes Bertrand
Published: April 2010

Abstract:  Ricochet of a bullet in the spinal canal is well known by neurosurgeons but relatively not a common event in usual medico‐legal autopsy practice. This article presents a homicide case of a penetrating gunshot injury of the lumbar spine through the T12‐L1 intervertebral foramen with active movement of the projectile within the spinal canal to the L5‐S1 level. This case illustrates a bullet intradural and intramedullary active movement because of a ricochet of the body of T12 with active redirection of the path. In the current literature, different types of migration in caudal or cranial direction, intradural, or intramedullary are reported. If spontaneous migration of T10 to S1 seems to be more frequent, some authors reported a C1 to S2 migration. Such migration could be asymptomatic or induce neurological impairment. The medico‐legal consequences of these migrations within the spinal canal are described.
Predictive value of clinical and radiological findings in inflicted traumatic brain injury
Authors: Ilves Pilvi , Lintrop Mare , Talvik Inga , Sisko Annika , Talvik Tiina
Published: April 2010

Aims:  The aim of this study is to evaluate the value of early radiological investigations in predicting the long‐term neurodevelopmental outcome of infants with inflicted traumatic brain injury (ITBI).

Methods:  Clinical and radiological investigations of 24 infants with ITBI were performed during the acute phase of injury (1–3 days), and during the early (4 days up to 3 months) and late (>9 months) postinjury phases. The clinical outcome in survivors (n = 22) was based on the Rankin Disability Scale and the Glasgow Outcome Score.

Results:  Five out of 24 infants (21%) had a poor neurodevelopmental outcome (death and severe disability), 17 infants (71%) had different developmental problems and 2 infants were normal at the mean age of 62 (54–70) (95% CI) months. A low initial Glasgow Coma Scale score of 8 or below [p < 0.05, OR 13.0 (1.3–133.3)], the development of brain oedema [p < 0.005, OR 13.0 (1.6–773)], focal changes in the basal ganglia during the acute phase [p < 0.01, OR 45 (2.1–937.3)], the development of new intracerebral focal changes early postinjury [p < 0.05, OR 24.1(1.0–559.1)], a decrease in white matter [p < 0.01, OR 33 (1.37–793.4)] and the development of severe atrophy before 3 months postinjury [p < 0.05, OR 24 (11.0–559.1)] were significantly correlated with a poor neurodevelopmental outcome.

Conclusions:  Early clinical and radiological findings in ITBI are of prognostic value for neurodevelopmental outcome.
Impact of Fiber Volume Fraction and Resin Viscosity With Die-Detached Tapered Chamber in Resin Injection Pultrusion
Authors: Jeswani A. L. , Roux J. A.
Published: April 2010

Complete wetout of the dry fiber reinforcement by the liquid resin depends strongly on the fiber volume fraction and the resin viscosity of the part being manufactured by rein injection pultrusion. High fiber volume fractions and high resin viscosity values yield high pressures in the tapered resin injection chamber; this work investigates the use of a an injection chamber detached from the pultrusion die in order to lower the resin pressures inside the injection chamber caused by the injection chamber tapering. A 3D finite volume technique was developed to simulate the flow of resin through the glass rovings for a variety of resin viscosities and fiber volume fractions. The results illustrate the impact of the tapering of the injection chamber walls on the minimum injection pressure necessary to achieve complete fiber matrix wetout and the resin pressure induced inside the tapered injection chamber. The results provide important injection chamber design information.
Bent belt-beam gauge: Extending low-pressure measurement limits in a hot-cathode ionization vacuum gauge by combining multiple methods
Authors: Watanabe Fumio
Published: April 2010

A commercially viable, extremely high vacuum hot-cathode ionization gauge that can measure pressures as low as 5.4×10−12 Pa, by reducing the limits imposed by soft x rays, electron-stimulated desorption (ESD), and outgassing, is reported. The gauge construction includes a cylindrical grid, which is closed at both ends; ions are drawn from the grid through a long, axial slit made in the cylindrical surface. Thus, the ion beam that emerges forms a “belt.” This beltlike ion beam is guided on a curved path by a cylindrical sector deflector and terminates on a plate collector arranged after a beam trajectory rotation of 230°. These elements are embedded in a solid cylinder of 0.2% BeCu alloy, which has a low emissivity (radiation factor) and high thermal conductivity. As a result, the effects of heat radiation and outgassing (caused by the hot-cathode filament) and soft x-ray photoemission (the grid is the soft x-ray source) are reduced in the deflector/collector region. This electrode arrangement can also greatly decrease the flux of soft x rays and ESD in the direction of the belt ion beam because it sets to 90° the angle between the extracted gas-phase ion beam and the maximum flux of soft x rays and ESD. In addition, it achieves an extremely low-pressure measurement limit by minimizing loss in the ion transport, and because the collector is well hidden, being located after the large deflection of the ion beam.
Coordinated Punishment of Defectors Sustains Cooperation and Can Proliferate When Rare
Authors: Boyd Robert , Gintis Herbert , Bowles Samuel
Published: April 2010

Learning to Work Together

In group endeavors, there is often a tension between working for the greater good of the group as a whole versus working for one's own benefit. Sometimes these paths coincide and sometimes they do not; furthermore, the choices made by other group members can influence the calculation of which path to take. A pair of studies now approaches this challenge from experimental and theoretical points of view. In a forest or fishery, harvesting of wood or food needs to take into account the renewable character of the resource, as well as spatial heterogeneity.

Janssen
et al.

(p.
613
; see the Perspective by

Putterman

) show that communication among the group members is key, both to establishing a maintainable rate of harvesting, as well as enforcement via punishment of noncompliers.

Boyd
et al.

(p.
617
; see the Perspective by

Putterman

) develop a model showing that punishment, which is a costly activity, is most effectively levied when implemented with the approval of group members; that is, coordinated punishment works to the benefit of the whole, whereas individual actions do not.
Maternal Control of Haplodiploid Sex Determination in the Wasp
Nasonia
Authors: Verhulst Eveline C. , Beukeboom Leo W. , van de Zande Louis
Published: April 2010

The Wasps and the Bees

Sex development in bees and wasps depends on whether or not they develop from a haploid unfertilized egg (resulting in males) or diploid fertilized egg (resulting in females). Although these ploidy-level developmental processes are conserved among bees and wasps, the mechanisms that direct development down a male or female pathway differ significantly. By examining the sex-determining genes in the parasitoid wasp
Nasonia
,

Verhulst
et al.

(p.
620
) have shown that a maternal messenger RNA (mRNA) is necessary to initiate the female pathway. The mRNA operates in combination with conserved maternal and paternal genes to produce females, which explains why females are diploids. In unfertilized eggs, maternal provisioning of the gene transcript is too low to initiate the female pathway.
Matters of Scale
Authors: McGill Brian J.
Published: April 2010

Recognition of the scale dependence of ecological processes helps explain the distribution and abundance of organisms.
d
-Amino Acids Trigger Biofilm Disassembly
Authors: Kolodkin-Gal Ilana , Romero Diego , Cao Shugeng , Clardy Jon , Kolter Roberto , Losick Richard
Published: April 2010

Biofilm Today, Gone Tomorrow

Most bacteria can form complex, matrix-containing multicellular communities known as biofilms, which protect residents from environmental stresses such as antibiotic exposure. However, as biofilms age, nutrients become limiting and waste products accumulate, and biofim disassembly is triggered. Now

Kolodkin-Gal
et al.

(p.
627
) have found that
d
-amino acids found in conditioned medium from mature biofilms of
Bacillus subtilis
prevent biofilm formation and trigger existing biofilm disassembly.
Fifty Years of U.S. Embargo: Cuba's Health Outcomes and Lessons
Authors: Drain Paul K. , Barry Michele
Published: April 2010

Despite sanctions' impacts on medicine and medical supplies, Cuban health outcomes are comparable to those of developed countries.
DNA Returned to Tribe, Raising Questions About Consent
Authors: Couzin-Frankel Jennifer
Published: April 2010

After a 6-year legal battle, Arizona State University has now agreed to return more than 100 DNA samples to the Havasupai, a tiny tribe of Native Americans who charged that their DNA had been collected by university researchers without proper consent, and pay $700,000, among other concessions.
Beyond Clotting: The Powers of Platelets
Authors: Leslie Mitch
Published: April 2010

Platelets are known for thwarting blood loss, but new research shows these simplified cells defend against microbes and perform other duties—and they're also drug targets in sepsis and other conditions.
Safety and Immunogenicity of a 13-Valent Pneumococcal Conjugate Vaccine Compared to Those of a 7-Valent Pneumococcal Conjugate Vaccine Given as a Three-Dose Series with Routine Vaccines in Healthy Infants and Toddlers
Authors: Esposito Susanna , Tansey Susan , Thompson Allison , Razmpour Ahmad , Liang John , Jones Thomas R. , Ferrera Giuseppe , Maida Alessandro , Bona Gianni , Sabatini Caterina , Pugni Lorenza , Emini Emilio A. , Gruber William C. , Scott Daniel A. , Principi Nicola
Published: April 2010

A 13-valent pneumococcal conjugate vaccine (PCV13) has been developed to improve protection against pneumococcal disease beyond that possible with the licensed 7-valent vaccine (PCV7). This study compared the safety and immunogenicity of PCV13 with those of PCV7 when given as part of the pediatric vaccination schedule recommended in Italy. A total of 606 subjects were randomly assigned to receive either PCV13 or PCV7 at 3, 5, and 11 months of age; all subjects concomitantly received diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzaetype B (DTaP-HBV-IPV/Hib) vaccine. Vaccine reactions were monitored. Antibody responses to DTaP-HBV-IPV/Hib antigens, serotype-specific anticapsular polysaccharide IgG responses, and antipneumococcal opsonophagocytic assay (OPA) activity were measured 1 month after the two-dose primary series and 1 month after the toddler dose. Overall, the safety profile of PCV13 was similar to that of PCV7. The response to DTaP-HBV-IPV/Hib antigens was substantially the same with both PCV13 and PCV7. PCV13 elicited antipneumococcal capsular IgG antibodies to all 13 vaccine serotypes, with notable increases in concentrations seen after the toddler dose. Despite a lower immunogenicity for serotypes 6B and 23F after the primary series of PCV13, responses to the seven common serotypes were comparable between the PCV13 and PCV7 groups when measured after the toddler dose. PCV13 also elicited substantial levels of OPA activity against all 13 serotypes following both the infant series and the toddler dose. In conclusion, PCV13 appeared comparable to PCV7 in safety profile and immunogenicity for common serotypes, demonstrated functional OPA responses for all 13 serotypes, and did not interfere with immune responses to concomitantly administered DTaP-HBV-IPV/Hib vaccine.
Cytomegalovirus Infection- and Age-Dependent Changes in Human CD8
+
T-Cell Cytokine Expression Patterns
Authors: Faist Benjamin , Fleischer Bernhard , Jacobsen Marc
Published: April 2010

T cells are strongly affected by immune aging, a phenomenon that leads to increased susceptibility to infections and decreased vaccination efficacy in elderly individuals. Cytomegalovirus (CMV) infection induces vigorous T-cell immune responses in humans and is thought to be a driving force of immune aging. In the present study we analyzed CMV-induced quantitative and qualitative differences in the cytokine-expressing T-cell repertoire from individuals of different age groups after
in vitro
stimulation. The CMV pp65 peptide pool and the superantigen
Staphylococcus
enterotoxin B (SEB) induced higher proportions of CD8
+
effector T cells expressing gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor in the oldest study group, while only SEB induced increased responses in the middle-aged study group. Notably, CMV-specific multiple cytokine expression patterns revealed higher proportions of IFN-γ- and TNF-α-coexpressing CD8
+
T cells exclusively in the oldest study group. These qualitative differences were absent in SEB-induced CD8
+
effector T cells, although quantitative differences were detected. We report age-dependent qualitative changes in CMV-specific CD8
+
T-cell cytokine patterns which are biocandidate markers of immune exhaustion in elderly individuals.
Core Antigen Expression Is Associated with Hepatic Necroinflammation in e Antigen-Negative Chronic Hepatitis B Patients with Low DNA Loads
Authors: Huang Yi-Hsiang , Hung Hung-Hsu , Chan Che-Chang , Lai Chiung-Ru , Chu Chi-Jen , Huo Teh-Ia , Lee Pui-Ching , Su Chien-Wei , Lan Keng-Hsin , Huang Hui-Chun , Lee I-Cheng , Lin Han-Chieh , Lee Shou-Dong
Published: April 2010

Intrahepatic hepatitis B virus (HBV) core antigen (HBcAg) is a hallmark of viral replication in hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B (CHB). The aim of this study was to evaluate the role of HBcAg in HBeAg-negative CHB. One hundred six HBeAg-negative CHB patients who underwent ultrasonographically guided liver biopsy were reviewed for their HBV DNA load and clinical and histological data. Factors associated with the expression of intrahepatic HBcAg were analyzed. Among the patients, 35 (33%) were positive for HBcAg by immunohistostaining. In patients whose HBV DNA loads were higher than 107copies (cp)/ml, nearly one-half (52%) had detectable HBcAg. Compared with HBcAg-negative patients, HBcAg-positive patients had higher serum alanine transaminase (ALT) and HBV DNA levels and more-severe hepatic necroinflammation. High serum ALT level (>160 U/liter) and HBV viral load were the determinants of HBcAg expression in multivariate analysis. Large amounts of HBcAg expression were frequently detected in patients with high DNA loads, and the patterns of HBcAg distribution were not related to histological activity or HBV DNA levels. In patients with lower HBV DNA loads, the expression of HBcAg was the key factor associated with active hepatic necroinflammation (hazard ratio = 11.25; 95% confidence interval [CI], 1.42 to 89.26;P= 0.022). In conclusion, the expression of HBcAg is not frequent in HBeAg-negative CHB. The expression of intrahepatic HBcAg indicates active hepatic necroinflammation, even in patients with low HBV DNA load. Both HBV viral load and HBcAg expression have implications in the pathogenesis of HBeAg-negative CHB.
Multicenter Collaborative Study for Standardization ofCandida albicansGenotyping Using a Polymorphic Microsatellite Marker
Authors: Garcia-Hermoso Dea , MacCallum Donna M. , Lott Timothy J. , Sampaio Paula , Serna Maria-José Buitrago , Grenouillet Fréderic , Klaassen Corné H. W. , Bretagne Stéphane
Published: April 2010

Microsatellite-based genotyping forCandida albicanscan give discrepant results between laboratories when expressed in fragment sizes, because their determination depends on electrophoretic conditions. The interlaboratory reproducibility was assessed in six laboratories provided with an allelic ladder. Despite variations in size determinations, alleles were correctly assigned, making data transportable between laboratories.
Evolution of Endogenous Sequences of
Banana Streak Virus
: What Can We Learn from Banana (
Musa
sp.) Evolution?
Authors: Gayral Philippe , Blondin Laurence , Guidolin Olivier , Carreel Françoise , Hippolyte Isabelle , Perrier Xavier , Iskra-Caruana Marie-Line
Published: April 2010

Endogenous plant pararetroviruses (EPRVs) are viral sequences of the family
Caulimoviridae
integrated into the nuclear genome of numerous plant species. The ability of some endogenous sequences of
Banana streak viruses
(eBSVs) in the genome of banana (
Musa
sp.) to induce infections just like the virus itself was recently demonstrated (P. Gayral et al., J. Virol. 83:6697-6710, 2008). Although eBSVs probably arose from accidental events, infectious eBSVs constitute an extreme case of parasitism, as well as a newly described strategy for vertical virus transmission in plants. We investigated the early evolutionary stages of infectious eBSV for two distinct BSV species—GF (BSGFV) and Imové (BSImV)—through the study of their distribution, insertion polymorphism, and structure evolution among selected banana genotypes representative of the diversity of 60 wild
Musa
species and genotypes. To do so, the historical frame of host evolution was analyzed by inferring banana phylogeny from two chloroplast regions—
matK
and
trnL-trnF
—as well as from the nuclear genome, using 19 microsatellite loci. We demonstrated that both BSV species integrated recently in banana evolution, circa 640,000 years ago. The two infectious eBSVs were subjected to different selective pressures and showed distinct levels of rearrangement within their final structure. In addition, the molecular phylogenies of integrated and nonintegrated BSVs enabled us to establish the phylogenetic origins of eBSGFV and eBSImV.
Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway
Authors: Winter Jeremiah N. , Fox Todd E. , Kester Mark , Jefferson Leonard S. , Kimball Scot R.
Published: April 2010

The mammalian target of rapamycin (mTOR) assembles into two distinct multiprotein complexes known as mTORC1 and mTORC2. Of the two complexes, mTORC1 acts to integrate a variety of positive and negative signals to downstream targets that regulate cell growth. The lipid second messenger, phosphatidic acid (PA), represents one positive input to mTORC1, and it is thought to act by binding directly to mTOR, thereby enhancing the protein kinase activity of mTORC1. Support for this model includes findings that PA binds directly to mTOR and addition of PA to the medium of cells in culture results in activation of mTORC1. In contrast, the results of the present study do not support a model in which PA activates mTORC1 through direct interaction with the protein kinase but, instead, show that the lipid promotes mTORC1 signaling through activation of the ERK pathway. Moreover, rather than acting directly on mTORC1, the results suggest that exogenous PA must be metabolized to lysophosphatidic acid (LPA), which subsequently activates the LPA receptor endothelial differentiation gene (EDG-2). Finally, in contrast to previous studies, the results of the present study demonstrate that leucine does not act through phospholipase D and PA to activate mTORC1 and, instead, show that the two mediators act through parallel upstream signaling pathways to activate mTORC1. Overall, the results demonstrate that leucine and PA signal through parallel pathways to activate mTORC1 and that PA mediates its effect through the ERK pathway, rather than through direct binding to mTOR.
Regulation of vimentin intermediate filaments in endothelial cells by hypoxia
Authors: Liu Tiegang , Guevara Oscar E. , Warburton Rod R. , Hill Nicholas S. , Gaestel Matthias , Kayyali Usamah S.
Published: April 2010

Hypoxia triggers responses in endothelial cells that play roles in many conditions including high-altitude pulmonary edema and tumor angiogenesis. Signaling pathways activated by hypoxia modify cytoskeletal and contractile proteins and alter the biomechanical properties of endothelial cells. Intermediate filaments are major components of the cytoskeleton whose contribution to endothelial physiology is not well understood. We have previously shown that hypoxia-activated signaling in endothelial cells alters their contractility and adhesiveness. We have also linked p38-MAP kinase signaling pathway leading to HSP27 phosphorylation and increased actin stress fiber formation to endothelial barrier augmentation. We now show that vimentin, a major intermediate filament protein in endothelial cells, is regulated by hypoxia. Our results indicate that exposure of endothelial cells to hypoxia causes vimentin filament networks to initially redistribute perinuclearly. However, by 1 hour hypoxia these networks reform and appear more continuous across cells than under normoxia. Hypoxia also causes transient changes in vimentin phosphorylation, and activation of PAK1, a kinase that regulates vimentin filament assembly. In addition, exposure to 1 hour hypoxia increases the ratio of insoluble/soluble vimentin. Overexpression of phosphomimicking mutant HSP27 (pmHSP27) causes changes in vimentin distribution that are similar to those observed in hypoxic cells. Knocking-down HSP27 destroys the vimentin filamentous network, and disrupting vimentin filaments with acrylamide increases endothelial permeability. Both hypoxia- and pmHSP27 overexpression-induced changes are reversed by inhibition of phosphatase activity. In conclusion hypoxia causes redistribution of vimentin to a more insoluble and extensive filamentous network that could play a role in endothelial barrier stabilization. Vimentin redistribution appears to be mediated through altering the phosphorylation of the protein and its interaction with HSP27.
The P2Y2receptor mediates the epithelial injury response and cell migration
Authors: Boucher Ilene , Rich Celeste , Lee Albert , Marcincin Meredith , Trinkaus-Randall Vickery
Published: April 2010

Injury to epithelial cells results in the release of ATP and stimulation of purinergic receptors and is thought to alter cell migration and wound repair. Medium from the injured cells triggers Ca2+mobilization and phosphorylation of ERK, both of which are inhibited if the medium is pretreated with apyrase. To understand the wound repair mechanism that occurs with injury, our goal was to determine which purinergic receptor(s) was the critical player in the wound response. We hypothesize that the P2Y2receptor is the key player in the response of corneal epithelial cells to cell damage and subsequent repair events. Cells transfected with short interfering RNA to either P2Y2or P2Y4were stimulated either by injury or addition of UTP and imaged using fluo 3-AM to monitor changes in fluorescence. When cells with downregulated P2Y2receptors were injured or stimulated with UTP, the intensity of the Ca2+release was reduced significantly. However, when cells with downregulated P2Y4receptors were stimulated, only the UTP-induced Ca2+response was reduced significantly. In addition, downregulation of the P2Y2receptor inhibited wound closure compared with unstimulated cells or cells transfected with nontargeting sequence. This downregulation resulted also in an attenuation in phosphorylation of Src and ERK. Together, these data indicate that the P2Y2receptor plays a major biological role in the corneal injury response and repair mechanisms.
Ca2+ release from the sarcoplasmic reticulum is required for sustained TRPM4 activity in cerebral artery smooth muscle cells
Authors: Gonzales Albert L. , Amberg Gregory C. , Earley Scott
Published: April 2010

The melastatin transient receptor potential (TRP) channel TRPM4 is a critical regulator of vascular smooth muscle cell membrane potential and contractility. Activation of the channel is Ca2+-dependent, but prolonged exposure to high (>1 μM) levels of intracellular Ca2+ causes rapid (within ∼2 min) desensitization of TRPM4 currents under conventional whole cell and inside-out patch-clamp conditions. The goal of the present study was to establish a novel method to record sustained TRPM4 currents in smooth muscle cells under near-physiological conditions. Using the amphotericin B-perforated patch-clamp technique, we recorded and characterized sustained (up to 30 min) transient inward cation currents (TICCs) in freshly isolated cerebral artery myocytes. In symmetrical cation solutions, TICCs reversed at 0 mV and had an apparent unitary conductance of 25 pS. Replacement of extracellular Na+ with the nonpermeable cation N-methyl-d-glucamine abolished the current. TICC activity was attenuated by the TRPM4 blockers fluflenamic acid and 9-phenanthrol. Selective silencing of TRPM4 expression using small interfering RNA diminished TICC activity, suggesting that the molecular identity of the responsible ion channel is TRPM4. We used the perforated patch-clamp method to test the hypothesis that TRPM4 is activated by intracellular Ca2+ signaling events. We found that TICC activity is independent of Ca2+ influx and ryanodine receptor activity but is attenuated by sarco(endo)plasmic reticulum Ca2+-ATPase inhibition and blockade of inositol 1,4,5-trisphosphate receptor-mediated Ca2+ release from the sarcoplasmic reticulum. Our findings suggest that TRPM4 channels in cerebral artery myocytes are regulated by Ca2+ release from inositol 1,4,5-trisphosphate receptor on the sarcoplasmic reticulum.
Fetal growth restriction alters transcription factor binding and epigenetic mechanisms of renal 11β-hydroxysteroid dehydrogenase type 2 in a sex-specific manner
Authors: Baserga Mariana , Kaur Rajwinderjit , Hale Merica A. , Bares Allyson , Yu Xing , Callaway Christopher W. , McKnight Robert A. , Lane Robert H.
Published: April 2010

Intrauterine growth restriction (IUGR) increases the risk of serious adult morbidities such as hypertension. In an IUGR rat model of hypertension, we reported a persistent decrease in kidney 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) mRNA and protein levels from birth through postnatal (P) day 21. This enzyme deficiency can lead to hypertension by limiting renal glucocorticoid deactivation. In the present study, we hypothesized that IUGR affects renal 11β-HSD2 epigenetic determinants of chromatin structure and alters key transcription factor binding to the 11β-HSD2 promoter in association with persistent downregulation of its mRNA expression. To test this hypothesis, we performed bilateral uterine artery ligation on embryonic day 19.5 pregnant rats and harvested kidneys at day 0 (P0) and P21. Key transcription factors that can affect 11β-HSD2 expression include transcriptional enhancers specificity protein 1 (SP1) and NF-κB p65 and transcriptional repressors early growth response factor (Egr-1) and NF-κB p50. Our most important findings were as follows: 1) IUGR significantly decreased SP1 and NF-κB (p65) binding to the 11β-HSD2 promoter in males, while it increased Egr-1 binding in females and NF-κB (p50) binding in males; 2) IUGR increased CpG methylation status, as well as modified the pattern of methylation in several CpG sites of 11β-HSD2 promoter at P0 also in a sex-specific manner; and 3) IUGR decreased trimethylation of H3K36 in exon 5 of 11β-HSD2 at P0 and P21 in both genders. We conclude that IUGR is associated with altered transcriptional repressor/activator binding in connection with increased methylation in the 11β-HSD2 promoter region in a sex-specific manner, possibly leading to decreased transcriptional activity. Furthermore, IUGR decreased trimethylation of H3K36 of the 11β-HSD2 gene in both genders, which is associated with decreased transcriptional elongation. We speculate that alterations in transcription factor binding and chromatin structure play a role in in utero reprogramming.
Stress activation of IL-6 neurons in the hypothalamus
Authors: Jankord Ryan , Zhang Rong , Flak Jonathan N. , Solomon Matia B. , Albertz Jennifer , Herman James P.
Published: April 2010

An emerging literature attests to the ability of psychological stress to alter the inflammatory cytokine environment of the body. While the ability of stress to cause cytokine release is well established, the neural pathways involved in this control have yet to be identified. This study tests the hypothesis that IL-6 neurons of the hypothalamo-neurohypophyseal system (HNS), a neural pathway proposed to secrete IL-6 into the circulation, are activated in response to psychological stress. Colocalization studies confirm robust expression of IL-6 in cell bodies and fibers of vasopressin (but not oxytocin) neurons of the paraventricular (PVN) and supraoptic nucleus (SON) of the rat hypothalamus. In response to restraint, there was a greater increase in c-Fos expression in SON IL-6-positive (IL-6+) neurons. In addition, both psychogenic (restraint) or systemic stress (hypoxia) lead to phosphorylated ERK induction only in IL-6+ magnocellular neurons, indicating selective activation of the MAPK signaling pathway in the IL-6 subset of magnocellular neurons. Finally, restraint upregulated IL-6 mRNA expression in both the PVN and SON, which was accompanied by a four-fold increase in circulating IL-6. The data indicate that noninflammatory stressors selectively activate IL-6 magnocellular neurons, upregulate IL-6 gene expression in the PVN and SON, and increase plasma IL-6. In summary, results show that IL-6 neurons of the HNS are a recruited component of the response to psychological stress.
Mechanisms of burn-induced impairment in gastric slow waves and emptying in rats
Authors: Sallam Hanaa S. , Oliveira Hermes M. , Liu Suhuan , Chen Jiande D. Z.
Published: April 2010

Delayed gastric emptying is common following severe large cutaneous burns; however, the mechanisms of burn-induced delayed gastric emptying remain unknown. The aim of this study was to explore the possible involvement of hyperglycemia and cyclooxygenase-2 receptors in the burn-induced gastric dysrhythmias. Gastric slow waves and gastric emptying were assessed in rats 6 h following sham or burn injury. Animals were randomized to one sham-burn and seven burn groups: untreated; two groups of saline treated (control); insulin treated (5 IU/kg); cyclooxygenase-2 inhibitor treated (10 mg/kg); ghrelin treated (2 nmol/rat); and gastric electrical stimulation treated. It was found that 1) severe burn injury impaired gastric slow waves postprandially and delayed gastric emptying; 2) the impairment in gastric slow waves included a decrease in the slow-wave frequency and in the percentage of normal slow waves, and an increase in the percentage of bradygastria ( P = 0.001, 0.01, and 0.01, respectively vs. preburn values). None of the gastric slow-wave parameters was significantly correlated with gastric emptying; 3) cyclooxygenase-2 inhibitor normalized burn-induced delayed gastric emptying ( P = 0.3 vs. sham-burn), but not gastric dysrhythmias ( P < 0.002 vs. sham), whereas insulin normalized both gastric emptying ( P = 0.4 vs. sham-burn) and gastric dysrhythmias ( P = 0.3 vs. sham-burn); 4) both gastric electrical stimulation and ghrelin accelerated burn-induced delayed gastric emptying ( P = 0.002 and 0.04, respectively, vs. untreated burn). In conclusion, hyperglycemia alters gastric slow-wave activity and delayed gastric emptying, while cyclooxygenase-2 inhibition delays gastric emptying without altering gastric slow-wave activity.
Modulation by salt intake of the vascular response mediated through adenosine A2Areceptor: role of CYP epoxygenase and soluble epoxide hydrolase
Authors: Nayeem Mohammed A. , Zeldin Darryl C. , Boegehold Matthew A. , Morisseau Christophe , Marowsky Anne , Ponnoth Dovenia S. , Roush Kevin P. , Falck John R.
Published: April 2010

High-salt intake can change the effect of adenosine on arterial tone in mice. The aim of this study was to clarify the mechanism by which this occurs. Using aortas from mice fed a 4% NaCl (HS) or 0.45% NaCl (NS) diet for 4–5 wks, concentration-response curves for ACh, 5′- N-ethylcarboxamidoadenosine (NECA; adenosine analog) and 2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxamidoadenosine hydrochloride hydrate [CGS-21680; A2Aadenosine receptor (A2AAR) agonist] were obtained with Nω-nitro-l-arginine methyl ester (l-NAME; nitric oxide inhibitor, 10−4M), methylsulfonyl-propargyloxyphenylhexanamide [MS-PPOH; a CYP (cytochrome P-450) epoxygenase blocker, 10−5M including CYP2J2], 12-(3-adamantan-1-yl-ureido)dodecanoic acid [AUDA; soluble epoxide hydrolase (sEH) blocker, 10−5M], dibromo-dodecenyl-methylsulfimide [DDMS; CYP ω-hydroxylase (CYP4A blocker), 10−5M], glibenclamide (KATPchannel blocker; 10−5M) and 5-hydroxydecanoate (5-HD; mitochondrial-KATPchannel blocker, 10−4M). HS dose response to ACh (10−7− 10−5M) was not different from NS ( P > 0.05). Relaxation to 10−6M NECA was greater in the HS group (28.4 ± 3.9%) than in the NS group (4.1 ± 2.3%). Relaxation to 10−6M CGS-21680 was also greater in HS (27.9 ± 4.5%) than in NS (4.9 ± 2.2%). l-NAME was able to block the dose response of ACh (10−7− 10−5M) equally in both HS and NS ( P > 0.05), whereas l-NAME did not block CGS-21680-induced response in HS. In HS the CGS-21680 response was greatly reduced by MS-PPOH (to 4.7 ± 2.0%) and 5-HD (to 8.9 ± 2.2%), and also abolished by glibenclamide (−1.0 ± 5.9%). In NS, the CGS-21680 response was increased by AUDA (to 26.3 ± 3.4%) and DDMS (to 27.2 ± 3.0%). Compared with NS, HS vessels showed increased CYP2J2 and A2AAR expression (46 and 74% higher, respectively) but decreased sEH, CYP4A, and A1AR expression (75, 30, and 55% lower, respectively). These data suggest that in mice fed NS-containing diet, upregulation of arterial A1receptor causes vasoconstriction via increased sEH and CYP4A proteins. However, in mice fed HS-containing diet, upregulation of A2Areceptor protein triggers vascular relaxation through ATP-sensitive (K+) channels via upregulation of CYP2J2 enzyme.
Calcium Balance and Mechanotransduction in Rat Cochlear Hair Cells
Authors: Beurg Maryline , Nam Jong-Hoon , Chen Qingguo , Fettiplace Robert
Published: April 2010

Auditory transduction occurs by opening of Ca2+-permeable mechanotransducer (MT) channels in hair cell stereociliary bundles. Ca2+clearance from bundles was followed in rat outer hair cells (OHCs) using fast imaging of fluorescent indicators. Bundle deflection caused a rapid rise in Ca2+that decayed after the stimulus, with a time constant of about 50 ms. The time constant was increased by blocking Ca2+uptake into the subcuticular plate mitochondria or by inhibiting the hair bundle plasma membrane Ca2+ATPase (PMCA) pump. Such manipulations raised intracellular Ca2+and desensitized the MT channels. Measurement of the electrogenic PMCA pump current, which saturated at 18 pA with increasing Ca2+loads, indicated a maximum Ca2+extrusion rate of 3.7 fmol·s−1. The amplitude of the Ca2+transient decreased in proportion to the Ca2+concentration bathing the bundle and in artificial endolymph (160 mM K+, 20 μM Ca2+), Ca2+carried 0.2% of the MT current. Nevertheless, MT currents in endolymph displayed fast adaptation with a submillisecond time constant. In endolymph, roughly 40% of the MT current was activated at rest when using 1 mM intracellular BAPTA compared with 12% with 1 mM EGTA, which enabled estimation of the in vivo Ca2+load as 3 pA at rest. The results were reproduced by a model of hair bundle Ca2+diffusion, showing that the measured PMCA pump density could handle Ca2+loads incurred from resting and maximal MT currents in endolymph. The model also indicated the endogenous mobile buffer was equivalent to 1 mM BAPTA.
Magnetoencephalography Demonstrates Multiple Asynchronous Generators During Human Sleep Spindles
Authors: Dehghani Nima , Cash Sydney S. , Rossetti Andrea O. , Chen Chih Chuan , Halgren Eric
Published: April 2010

Sleep spindles are ∼1 s bursts of 10–16 Hz activity that occur during stage 2 sleep. Spindles are highly synchronous across the cortex and thalamus in animals, and across the scalp in humans, implying correspondingly widespread and synchronized cortical generators. However, prior studies have noted occasional dissociations of the magnetoencephalogram (MEG) from the EEG during spindles, although detailed studies of this phenomenon have been lacking. We systematically compared high-density MEG and EEG recordings during naturally occurring spindles in healthy humans. As expected, EEG was highly coherent across the scalp, with consistent topography across spindles. In contrast, the simultaneously recorded MEG was not synchronous, but varied strongly in amplitude and phase across locations and spindles. Overall, average coherence between pairs of EEG sensors was ∼0.7, whereas MEG coherence was ∼0.3 during spindles. Whereas 2 principle components explained ∼50% of EEG spindle variance, >15 were required for MEG. Each PCA component for MEG typically involved several widely distributed locations, which were relatively coherent with each other. These results show that, in contrast to current models based on animal experiments, multiple asynchronous neural generators are active during normal human sleep spindles and are visible to MEG. It is possible that these multiple sources may overlap sufficiently in different EEG sensors to appear synchronous. Alternatively, EEG recordings may reflect diffusely distributed synchronous generators that are less visible to MEG. An intriguing possibility is that MEG preferentially records from the focal core thalamocortical system during spindles, and EEG from the distributed matrix system.