bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of vibration on pain during local anaesthesia injections
Authors: Nanitsos E , Vartuli R , Forte A , Dennison PJ , Peck CC
Published: May 2009

Background:  The “gate control” theory suggests pain can be reduced by simultaneous activation of nerve fibres that conduct non‐noxious stimuli. This study investigated the effects of vibration stimuli on pain experienced during local anaesthetic injections.

Methods:  In a preliminary study, subjects were asked to rate anticipated and actual pain from regional anaesthetic injections in the oral cavity. A second study compared, within subjects, pain from injections with and without a simultaneous vibration stimulus. Both infiltration and block anaesthetic injection techniques were assessed. In each subject, two similar injections were given and with one, a vibration stimulus was randomly allocated. Injection pain was assessed by visual analogue scale and McGill pain descriptors.

Results:  Both infiltration and block injections were painful (mean anticipated intensity: 31.25, actual: 17.82 mm on 100 mm scale). Pain intensity with and without vibration was 12.9 mm (range 0–67) and 22.2 mm (range 0–83) respectively (p = 0.00005, paired T‐test), and this effect was seen with both infiltration (p = 0.032) and block anaesthetic (p = 0.0001) injection subgroups. Furthermore, compared to no vibration‐stimulus injections, injections with vibration resulted in less pain descriptors chosen (p = 0.004), and the descriptors had a lower pain rating (p = 0.001).

Conclusions:  The results suggest that vibration can be used to decrease pain during dental local anaesthetic administration.
The effect of casein phosphopeptide‐amorphous calcium phosphate on erosive dentine wear
Authors: Ranjitkar S , Narayana T , Kaidonis JA , Hughes TE , Richards LC , Townsend GC
Published: May 2009

Background:  Erosive tooth wear is a growing concern in clinical dentistry. Our aims were to assess the effect of Tooth Mousse (TM) in managing erosive dentine wear in vitro.

Methods:  Opposing enamel and dentine specimens from 36 third molar teeth were worn under a load of 100 N for 75 000 cycles in electromechanical tooth wear machines. In experiment 1, TM was applied continuously at the wear interface and the mean dentine wear rate was compared with those of specimens subjected to continuous application of hydrochloric acid (HCl, pH 3.0) and deionized water (DW, pH 6.1) as lubricants. In experiment 2, specimens were subjected to TM application every 1600 cycles at both pH 3.0 and 6.1, and the mean dentine wear rates were compared with those of specimens worn with continuous application of HCl and DW lubricants.

Results:  Dentine wear was reduced significantly with continuous application of TM compared with HCl and DW lubricants. Specimens prepared with continuous TM application displayed smooth wear facets, whereas more pronounced microwear details were observed with HCl and DW lubricants.

Conclusions:  Both remineralization and lubrication seem to contribute to reduction in dentine wear associated with TM application, although lubrication appears to have a more pronounced effect.
Light activated disinfection: an alternative endodontic disinfection strategy
Authors: Lim Z , Cheng JL , Lim TW , Teo EG , Wong J , George S , Kishen A
Published: May 2009

Background:  An improved light activated disinfection technique utilizing a specific photosensitizer formulation, liquid optical‐conduit, oxygen‐carrier and light energy of appropriate wavelength has been introduced recently. This study tested the efficacy of this improved light activated disinfection on ex vivo biofilms of Enterococcus faecalis at two different stages of maturation.

Methods:  Eighty‐five tooth sections were prepared and endodontic biofilm of E. faecalis were grown within the root canal. In stage 1, conventional light activated disinfection (LAD), chemical disinfectant (sodium hypochlorite) and improved LAD were tested on four‐day‐old (immature) biofilms. In stage 2, conventional LAD, improved LAD and chemomechanical disinfection (alone and in combination with improved LAD) were tested on four‐week‐old (mature) biofilms.

Results:  Sodium hypochlorite and improved LAD showed the ability to significantly inactivate bacteria in four‐day‐old biofilms when compared to the control and LAD (p < 0.05). Inactivation of bacteria from deeper dentine was higher in improved LAD than sodium hypochlorite. In four‐week‐old biofilms, a combination of chemomechanical disinfection and improved LAD produced significant bacterial killing compared to either chemomechanical disinfection or improved LAD alone.

Conclusions:  This study highlighted the potential of improved LAD to kill bacteria within dentinal tubules. In combination with chemomechanical preparation, the improved LAD significantly inactivated four‐week‐old biofilm bacteria.
A retrospective analysis of 1000 consecutively placed implants in private practice
Authors: Nixon KC , Chen ST , Ivanovski S
Published: May 2009

Background:  There have been numerous reports evaluating clinical outcomes of implants placed in institutional settings, but there are few studies relating to implants placed in private practice. The aim of this retrospective study was to analyse the clinical outcomes of 1000 consecutively placed Straumann implants in private specialist periodontal practice.

Methods:  A hand‐search of patient records was undertaken to identify 1000 consecutively placed implants. Data extracted included patient demographics, details of implants placed, implant sites, timing of placement after extraction, hard and soft tissue augmentation procedures, loading protocols, type of prostheses and treatment outcomes (implant survival, implant success and complications).

Results:  The majority of implants (71.5 per cent) placed in patients aged 40 to 69, and the majority of patients (88.6 per cent) received 1 or 2 implants. During the period of the study, 9 implants were lost and 45 presented with complications requiring chairside intervention. A life table analysis showed 5 and 10‐year cumulative survival rates of 99.2 per cent and 98.4 per cent respectively, and 5 and 10‐year cumulative success rates of 93.1 per cent and 90.9 per cent respectively.

Conclusions:  With careful treatment planning and adherence to recommended surgical and prosthetic protocols, high implant survival and success rates can be achieved in a private practice setting.
Three‐year clinical evaluation of endodontically treated anterior teeth restored with a polyethylene fibre‐reinforced composite
Authors: Ayna B , Çelenk S , Atakul F , Uysal E
Published: May 2009

Background:  Polyethylene fibre‐reinforced composites (FRCs) have been under development for some time. However, there is a lack of data on the clinical performance of these restorations. The purpose of this descriptive study was to evaluate the clinical performance of endodontically treated anterior teeth restored using polyethylene FRCs.

Methods:  Eighty‐seven endodontically treated anterior teeth in 65 patients were restored with polyethylene FRCs. The restorations were placed by three operators. The patients were recalled for examinations every year for up to three years. The restorations were evaluated using modified Ryge and USPHS criteria.

Results:  A statistical analysis showed no significant difference in marginal irregularity, marginal discolouration, surface texture, wear/anatomic form, fracture and retention, radiographic appearance, or debonding between the baseline and three‐year results.

Conclusions:  Based on our three‐year examination results, polyethylene FRC restorations appear to be clinically successful.
An in vitro study of the antimicrobial activity of some endodontic medicaments and their bases using an agar well diffusion assay
Authors: Athanassiadis B , Abbott PV , George N , Walsh LJ
Published: May 2009

Background:  The aim of this study was to determine the in vitro antimicrobial activities of various endodontic medicaments and their bases against selected organisms using an agar diffusion assay.

Methods:  An agar well diffusion assay was used to test the antimicrobial action of some commonly used endodontic medicaments (Ledermix paste, Pulpdent paste, Ultracal paste, and a 50:50 mix of Ledermix and Pulpdent pastes) and their bases. Three bacterial species (E. faecalis, P. micros, P. intermedia) and one yeast (C. albicans) were selected. The diameters of growth inhibition zones and pH were assessed.

Results:  P. micros demonstrated the highest level of in vitro resistance. Pulpdent and Ultracal pastes had the highest pH (12.64 and 12.53, respectively). The addition of Pulpdent to Ledermix did not increase the zone sizes significantly.

Conclusions:  All the commercial products showed some in vitro antimicrobial activity. Ledermix paste and the 50:50 Ledermix/Pulpdent mixture being the most effective in this model. The known anti‐inflammatory/analgesic properties of Ledermix and the results from this agar model suggest that the 50:50 Ledermix/Pulpdent combination would be the preferred medicament for clinical use in symptomatic cases, even though the addition of calcium hydroxide to Ledermix did not appear to be synergistic in terms of enhancing the antimicrobial action.
Comparison of adult oral health in Australia, the USA, Germany and the UK
Authors: Crocombe LA , Mejia GC , Koster CR , Slade GD
Published: May 2009

Background:  Australian adults reportedly have poor oral health when compared to 28 other OECD countries. The Australian ranking was based on edentulism and caries experience data from selected age groups that apparently were collected in 1987–88. The objective of this study was to compare the oral health of Australian adults with that of three other western countries that have comprehensive oral health survey data.

Methods:  Published data were obtained from the NHANES 2003–2004, the Fourth German Oral Health Study 2005 and the UK Adult Dental Health Survey 1998. Data from the Australian NSAOH 2004–06 were analysed to generate comparable age‐specific estimates using nine dental clinical indicators, two measures of oral hygiene behaviour and two of dental attendance.

Results:  Australia had the best oral health based on two clinical indicators, was equal first on three indicators and ranked second in the remaining clinical indicators. Australia ranked first or second based on dental flossing, use of mouthwash and frequency of dental attendance.

Conclusions:  The oral health of the Australian adult population was among the best of the four nations studied.
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Authors: Vander Heiden Matthew G. , Cantley Lewis C. , Thompson Craig B.
Published: May 2009

Fuel Economy for Growing Cells

Sophisticated 21st-century analyses of the signaling pathways that control cell growth have led researchers back to the seminal work of Otto Warburg, who discovered in the 1920s that tumor cells generate their energy in an unusual way—by switching from mitochondrial respiration to glycolysis. The advantage conferred by this metabolic switch is puzzling because mitochondrial respiration is a more efficient way to produce ATP.

Vander Heiden
et al.

(p.
1029
) review arguments that rapidly growing cells have critical metabolic requirements that extend beyond ATP and that a better understanding of these requirements may shed new light on the “Warburg effect” and ultimately lead to new therapies for cancer.
ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation
Authors: Wellen Kathryn E. , Hatzivassiliou Georgia , Sachdeva Uma M. , Bui Thi V. , Cross Justin R. , Thompson Craig B.
Published: May 2009

Chromatin Modifier Modulates Gene Expression

Modification of chromatin structure is usually thought of as a global, relatively nonspecific way of modulating gene expression. However,

Wellen
et al.

(p.
1076
; see the Perspective by

Rathmell and Newgard

) demonstrate that such regulation helps link growth factor–stimulated increases in metabolism to appropriate changes in gene expression. Adenosine triphosphate (ATP)–citrate lyase (ACL), which converts citrate to acetyl–coenzyme A (CoA) in the mitochondria of mammalian cells during metabolism of glucose, was also found to be present in the nucleus, where it might regulate activity of histone acetyl transferases (HATs) by controlling the availability of acetyl-CoA. Indeed, depletion of ACL from cultured human colon carcinoma cells specifically decreased histone acetylation in the nucleus, but appeared not to affect the overall amount of acetylation of proteins in the cells. Loss of ACL in cultured mouse 3T3-L1 cells diminished the increase in histone acetylation normally associated with hormone-stimulated differentiation of these cells and inhibited the increase in expression of specific genes, such as that encoding the Glut4 glucose transporter. Thus, ACL may help cells link metabolic activity to changes in gene expression.
The Human K-Complex Represents an Isolated Cortical Down-State
Authors: Cash Sydney S. , Halgren Eric , Dehghani Nima , Rossetti Andrea O. , Thesen Thomas , Wang ChunMao , Devinsky Orrin , Kuzniecky Ruben , Doyle Werner , Madsen Joseph R. , Bromfield Edward , Erőss Loránd , Halász Péter , Karmos George , Csercsa Richárd , Wittner Lucia , Ulbert István
Published: May 2009

Down But Not Out

The K-complex, a defining characteristic of slow wave sleep, is the largest spontaneously occurring component of the healthy human electroencephalogram (EEG) but little is known about its physiological characteristics in the human cortex.

Cash
et al.

(p.
1084
) investigated the intracortical origin of K-complexes in humans undergoing surgery for epileptic seizures. In simultaneous subdural EEG and intracortical multisite microelectrode recordings, K complexes represented cortical downstates reflecting a decrease in neural firing. These down-states are a fundamental mode of cortical operation that have been well studied in animals and may contribute to sleep preservation and memory consolidation.
Comment on “Functional Traits and Niche-Based Tree Community Assembly in an Amazonian Forest”
Authors: Lake Jeffrey K. , Ostling Annette
Published: May 2009

Kraft
et al
. (Reports, 24 October 2008, p. 580) used a variety of metrics describing the distribution of functional traits within a tropical forest community to demonstrate simultaneous environmental filtering and niche differentiation. We discuss how these results could have arisen from sampling design and statistical assumptions, suggesting alternative approaches that could better resolve these questions.
Exploration of Victoria Crater by the Mars Rover Opportunity
Authors: Squyres S. W. , Knoll A. H. , Arvidson R. E. , Ashley J. W. , Bell J. F. , Calvin W. M. , Christensen P. R. , Clark B. C. , Cohen B. A. , de Souza P. A. , Edgar L. , Farrand W. H. , Fleischer I. , Gellert R. , Golombek M. P. , Grant J. , Grotzinger J. , Hayes A. , Herkenhoff K. E. , Johnson J. R. , Jolliff B. , Klingelhöfer G. , Knudson A. , Li R. , McCoy T. J. , McLennan S. M. , Ming D. W. , Mittlefehldt D. W. , Morris R. V. , Rice J. W. , Schröder C. , Sullivan R. J. , Yen A. , Yingst R. A.
Published: May 2009

“Lake” Victoria?

After having explored the Eagle and Endurance craters, which are separated by only 800 meters, the Mars Exploration Rover Opportunity spent 2 years at Victoria, a much larger impact crater located 6 kilometers south across Meridiani Planum. Sedimentary rocks previously analyzed at Eagle and Endurance point to local environmental conditions that included abundant liquid water in the ancient past. Now, an analysis of rocks in the walls of Victoria by

Squyres
et al.

(p.
1058
) reveals that the aqueous alteration processes that operated at Eagle and Endurance also acted at Victoria. In addition, sedimentary layering in the crater walls preserves evidence of ancient windblown dunes.
Bone Assemblages Track Animal Community Structure over 40 Years in an African Savanna Ecosystem
Authors: Western David , Behrensmeyer Anna K.
Published: May 2009

Death Mirrors Life

The accuracy with which fossil assemblages represent the actual composition of ancient ecological communities is very often uncertain. One way to assess the degree of fidelity between living and dead assemblages is to patiently compare modern living communities and the records they leave behind them in real time.
Western and Behrensmeyer
(p.
1061
) recorded the composition of vertebrate herbivore communities in the Amboseli reserve in Kenya over four decades and compared this to the assemblages of bones left behind as the animals died. The results suggest a high level of fidelity of life-to-death assemblages, both in the composition and the relative abundance of species. Thus, older fossil assemblages might indeed give a reliable picture of past and extinct communities.
Driving on Biomass
Authors: Ohlrogge John , Allen Doug , Berguson Bill , DellaPenna Dean , Shachar-Hill Yair , Stymne Sten
Published: May 2009

Burning biomass to produce electricity for battery-driven vehicles can power more travel and displace more petroleum than converting it to ethanol or other fermentation products.
Reflections from the Silver Screen

Bioethics at the Movies
Sandra Shapshay, Ed.

Johns Hopkins University Press, Baltimore, MD, 2009. 400 pp. $55. ISBN 9780801890772. Paper, $25. ISBN 9780801890789.
Authors: Sugarman Jeremy
Published: May 2009

The contributors explore how popular films have dealt with basic bioethical concerns such as birth, abortion, genetic selection, personhood, quality of life, aging, and death.
Plagiarism Sleuths
Authors: Couzin-Frankel Jennifer , Grom Jackie
Published: May 2009

A Texas group is trolling through publications worldwide hunting for signs of duplicated material. The thousands of articles they've flagged online raise questions about standards in publishing—and about the group's own tactics.
An Unprecedented Dilemma: One University, Two Political Systems
Authors: Stone Richard
Published: May 2009

The University of Macau's plans for a new campus in mainland China pose a challenge to preserving academic freedom in the former colony.
Past Pandemics Provide Mixed Clues to H1N1's Next Moves
Authors: Cohen Jon
Published: May 2009

Influenza researchers trying to predict where the swine flu outbreak is headed are looking to the past for clues about the seasonality and geography of pandemic flu, the relationship between the new virus and existing ones, and the behavior of this new H1N1's parent viruses in swine.
Appearances Can Deceive, Even With Standard Reagents
Authors: Xin Hao
Published: May 2009

Many scientists are discovering to their dismay that a cottage industry of faux biochemical reagents has sprung up to take advantage of China's hefty increases in R&D funding.
Kinetics and Longevity of Antibody Response to Influenza A H5N1 Virus Infection in Humans
Authors: Kitphati Rungrueng , Pooruk Phisanu , Lerdsamran Hatairat , Poosuwan Siriwan , Louisirirotchanakul Suda , Auewarakul Prasert , Chokphaibulkit Kulkanya , Noisumdaeng Pirom , Sawanpanyalert Pathom , Puthavathana Pilaipan
Published: May 2009

Anti-H5N1 antibody was determined by microneutralization, hemagglutination inhibition, and Western blotting assays in serial blood samples collected from eight Thai patients, including four fatal cases and four survivors. The antibody was detected as early as 5 days and, typically, with an increase in titer in paired blood at about 15 days after disease onset. The anti-H5 antibody response was long-lasting, for almost 5 years in cases which can be followed that far. In addition, cross-neutralizing activity to related clade 1 viruses was observed.
Evaluation of Chimeric Japanese Encephalitis and Dengue Viruses for Use in Diagnostic Plaque Reduction Neutralization Tests
Authors: Johnson Barbara W. , Kosoy Olga , Hunsperger Elizabeth , Beltran Manuela , Delorey Mark , Guirakhoo Farshad , Monath Thomas
Published: May 2009

The plaque reduction neutralization test (PRNT) is a specific serological test used to identify and confirm arbovirus infection in diagnostic laboratories and monitor immunological protection in vaccine recipients. Wild-type (wt) viruses used in the PRNT may be difficult to grow and plaque titrate, such as the dengue viruses (DENV), and/or may require biosafety level 3 (BSL3) containment, such as West Nile virus (WNV), St. Louis encephalitis virus (SLEV), and Japanese encephalitis virus (JEV). These requirements preclude their use in diagnostic laboratories with only BSL2 capacity. In addition, wt JEV falls under the jurisdiction of the select-agent program and can be used only in approved laboratories. The chimeric vaccine viruses ChimeriVax-WNV and -SLEV have previously been shown to elicit antibody reactivity comparable to that of parental wt WNV and SLEV. ChimeriVax viruses provide advantages for PRNT, as follows: they grow more rapidly than most wt flaviviruses, produce large plaques, require BSL2 conditions, and are not under select-agent restrictions. We evaluated the ChimeriVax-DENV serotype 1 (DENV1), -DENV2, -DENV3, -DENV4, and -JEV for use in PRNT on sera from DENV- and JEV-infected patients and from JEV vaccine recipients. Serostatus agreement was 100% between the ChimeriVax-DENV serotypes and wt prototype DENV and 97% overall with ChimeriVax-JEV compared to prototype Nakayama JEV, 92% in a subgroup of JEV vaccine recipients, and 100% in serum from encephalitis patients naturally infected with JEV. ChimeriVax-DENV and -JEV plaque phenotype and BSL2 requirements, combined with sensitive and specific reactivity, make them good substitutes for wt DENV and JEV in PRNT in public health diagnostic laboratories.
Development of a Disk Diffusion Method for Testing
Moraxella catarrhalis
Susceptibility Using Clinical and Laboratory Standards Institute Methods: a SENTRY Antimicrobial Surveillance Program Report
Authors: Bell Jan M. , Turnidge John D. , Jones Ronald N.
Published: May 2009

Currently, there is no Clinical and Laboratory Standards Institute (CLSI) disk diffusion method for testing
Moraxella catarrhalis
susceptibility. We examined 318 clinical strains of
M. catarrhalis
obtained as part of the SENTRY (Asia-Pacific) Antimicrobial Surveillance Program, plus two ATCC strains. MICs were determined by the CLSI standard broth microdilution method, and zone diameters were determined on Mueller-Hinton agar incubated in 5% CO
2
. All strains were examined for the presence of BRO-1 and BRO-2 β-lactamases by using molecular techniques. Tentative zone diameter interpretive criteria were successfully developed for 19 antimicrobial agents, including nine β-lactams, using current MIC interpretive criteria where available or wild-type cutoff values where no prior criteria were available. The proposed interpretive criteria were highly accurate, with ≤0.7% very major (falsely susceptible) and ≤1.0% major (falsely resistant) errors, respectively.
Clonal Complexes and Diversity of Exotoxin Gene Profiles in Methicillin-Resistant and Methicillin-Susceptible
Staphylococcus aureus
Isolates from Patients in a Spanish Hospital
Authors: Argudín M. A. , Mendoza M. C. , Méndez F. J. , Martín M. C. , Guerra B. , Rodicio M. R.
Published: May 2009

Molecular epidemiology studies have allowed the identification of the methicillin (meticillin)-resistant (MRSA) and methicillin-susceptible (MSSA) clonal complexes (CCs) and clones of
Staphylococcus aureus
circulating in a Spanish hospital recently. Of 81 isolates tested, 32.1% were MRSA. Most of them carried staphylococcal cassette chromosome
mec
(SCC
mec
) IVc (88.5%) and belonged to CC5 (88.5%; multilocus sequence typing types ST125 [mainly associated with
spa
type t067], ST5, and ST228). A higher diversity was found among MSSA isolates (67.9%). Eighty percent shared the genetic background of major MRSA lineages (CC5 [38.2%; ST125 and ST5], CC30 [25.5%; ST30], CC45 [14.5%; ST45 and ST47], and CC8 [1.8%; ST8]), but CC12, CC15, CC51, and CC59 were also detected. Many exotoxin genes were present in each of the 81 isolates, independent of whether they were involved in sepsis (11 to 22) or other types of infections (13 to 21), and they appeared in 73 combinations. The relevant data are that (i) all isolates were positive for hemolysin and leukotoxin genes (98.8% for
lukED
and 25.9% for
lukPV
); (ii) all contained an enterotoxin gene cluster (
egc
with or without
seu
), frequently with one or more genes encoding classical enterotoxins; (iii) about half were positive for
tst
and 95% were positive for exfoliatin-encoding genes (
eta
,
etb
, and/or
etd
); and (iv) the four
agr
groups were detected, with
agrII
(55.6%) and
agrIII
(23.5%) being the most frequent. Taken together, results of the present study suggest a frequent acquisition and/or loss of exotoxin genes, which may be mediated by efficient intralineage transfer of mobile genetic elements and exotoxin genes therein and by eventual breakage of interlineage barriers.
Partial
atlE
Sequencing of
Staphylococcus epidermidis
Strains from Prosthetic Joint Infections
Authors: Sivadon V. , Rottman M. , Quincampoix J.-C. , Prunier E. , Le Moal M. , de Mazancourt P. , Hoffmeyer P. , Lortat-Jacob A. , Piriou P. , Judet T. , Bernard L. , Gaillard J.-L.
Published: May 2009

Partial
atlE
sequencing (
atlE
nucleotides 2782 to 3114 [
atlE
2782-3114
]) was performed in 41
Staphylococcus epidermidis
isolates from prosthetic joint infections (PJIs) and 44 isolates from skin as controls. The
atlE
2782-3114
allele 1 (type strain sequence) was significantly more frequent in PJI strains (38/41 versus 29/44 in controls;
P
= 0.0023). Most PJI strains were positive for
mecA
,
icaA
/
icaD
, and IS
256
, and most belonged to the sequence type 27 subgroup, suggesting the involvement of few related clones.
Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases
Authors: Zielonka Jörg , Bravo Ignacio G. , Marino Daniela , Conrad Elea , Perković Mario , Battenberg Marion , Cichutek Klaus , Münk Carsten
Published: May 2009

The mammalian APOBEC3 (A3) proteins comprise a multigene family of cytidine deaminases that act as potent inhibitors of retroviruses and retrotransposons. The A3 locus on the chromosome 28 of the horse genome contains multiple A3 genes: two copies of A3Z1, five copies of A3Z2, and a single copy of A3Z3, indicating a complex evolution of multiple gene duplications. We have cloned and analyzed for expression the different equine A3 genes and examined as well the subcellular distribution of the corresponding proteins. Additionally, we have tested the functional antiretroviral activity of the equine and of several of the human and nonprimate A3 proteins against the
Equine infectious anemia virus
(EIAV), the
Simian immunodeficiency virus
(SIV), and the
Adeno-associated virus type 2
(AAV-2). Hematopoietic cells of horses express at least five different A3s: A3Z1b, A3Z2a-Z2b, A3Z2c-Z2d, A3Z2e, and A3Z3, whereas circulating macrophages, the natural target of EIAV, express only part of the A3 repertoire. The five A3Z2 tandem copies arose after three consecutive, recent duplication events in the horse lineage, after the split between Equidae and Carnivora. The duplicated genes show different antiviral activities against different viruses: equine A3Z3 and A3Z2c-Z2d are potent inhibitors of EIAV while equine A3Z1b, A3Z2a-Z2b, A3Z2e showed only weak anti-EIAV activity. Equine A3Z1b and A3Z3 restricted AAV and all equine A3s, except A3Z1b, inhibited SIV. We hypothesize that the horse A3 genes are undergoing a process of subfunctionalization in their respective viral specificities, which might provide the evolutionary advantage for keeping five copies of the original gene.
Formation of Syncytia Is Repressed by Tetraspanins in Human Immunodeficiency Virus Type 1-Producing Cells
Authors: Weng Jia , Krementsov Dimitry N. , Khurana Sandhya , Roy Nathan H. , Thali Markus
Published: May 2009

In vitro propagation studies have established that human immunodeficiency virus type 1 (HIV-1) is most efficiently transmitted at the virological synapse that forms between producer and target cells. Despite the presence of the viral envelope glycoprotein (Env) and CD4 and chemokine receptors at the respective surfaces, producer and target cells usually do not fuse with each other but disengage after the viral particles have been delivered, consistent with the idea that syncytia, at least in vitro, are not required for HIV-1 spread. Here, we tested whether tetraspanins, which are well known regulators of cellular membrane fusion processes that are enriched at HIV-1 exit sites, regulate syncytium formation. We found that overexpression of tetraspanins in producer cells leads to reduced syncytium formation, while downregulation has the opposite effect. Further, we document that repression of Env-induced cell-cell fusion by tetraspanins depends on the presence of viral Gag, and we demonstrate that fusion repression requires the recruitment of Env by Gag to tetraspanin-enriched microdomains (TEMs). However, sensitivity to fusion repression by tetraspanins varied for different viral strains, despite comparable recruitment of their Envs to TEMs. Overall, these data establish tetraspanins as negative regulators of HIV-1-induced cell-cell fusion, and they start delineating the requirements for this regulation.
Impaired Quality of the Hepatitis B Virus (HBV)-Specific T-Cell Response in Human Immunodeficiency Virus Type 1-HBV Coinfection
Authors: Chang J. Judy , Sirivichayakul Sunee , Avihingsanon Anchalee , Thompson Alex J. V. , Revill Peter , Iser David , Slavin John , Buranapraditkun Supranee , Marks Pip , Matthews Gail , Cooper David A. , Kent Stephen J. , Cameron Paul U. , Sasadeusz Joe , Desmond Paul , Locarnini Stephen , Dore Gregory J. , Ruxrungtham Kiat , Lewin Sharon R.
Published: May 2009

Hepatits B virus (HBV)-specific T cells play a key role both in the control of HBV replication and in the pathogenesis of liver disease. Human immunodeficiency virus type 1 (HIV-1) coinfection and the presence or absence of HBV e (precore) antigen (HBeAg) significantly alter the natural history of chronic HBV infection. We examined the HBV-specific T-cell responses in treatment-naïve HBeAg-positive and HBeAg-negative HIV-1-HBV-coinfected (n= 24) and HBV-monoinfected (n= 39) Asian patients. Peripheral blood was stimulated with an overlapping peptide library for the whole HBV genome, and tumor necrosis factor alpha and gamma interferon cytokine expression in CD8+T cells was measured by intracellular cytokine staining and flow cytometry. There was no difference in the overall magnitude of the HBV-specific T-cell responses, but the quality of the response was significantly impaired in HIV-1-HBV-coinfected patients compared with monoinfected patients. In coinfected patients, HBV-specific T cells rarely produced more than one cytokine and responded to fewer HBV proteins than in monoinfected patients. Overall, the frequency and quality of the HBV-specific T-cell responses increased with a higher CD4+T-cell count (P= 0.018 and 0.032, respectively). There was no relationship between circulating HBV-specific T cells and liver damage as measured by activity and fibrosis scores, and the HBV-specific T-cell responses were not significantly different in patients with either HBeAg-positive or HBeAg-negative disease. The quality of the HBV-specific T-cell response is impaired in the setting of HIV-1-HBV coinfection and is related to the CD4+T-cell count.
Functional Analysis of Glycoprotein L (gL) from Rhesus Lymphocryptovirus in Epstein-Barr Virus-Mediated Cell Fusion Indicates a Direct Role of gL in gB-Induced Membrane Fusion
Authors: Plate Aileen E. , Smajlović Jasmina , Jardetzky Theodore S. , Longnecker Richard
Published: May 2009

Glycoprotein L (gL), which complexes with gH, is a conserved herpesvirus protein that is essential for Epstein-Barr virus (EBV) entry into host cells. The gH/gL complex has a conserved role in entry among herpesviruses, yet the mechanism is not clear. To gain a better understanding of the role of gL in EBV-mediated fusion, chimeric proteins were made using rhesus lymphocryptovirus (Rh-LCV) gL (Rh gL), which shares a high sequence homology with EBV gL but does not complement EBV gL in mediating fusion with B cells. A reduction in fusion activity was observed with chimeric gL proteins that contained the amino terminus of Rh gL, although they retained their ability to process and transport gH/gL to the cell surface. Amino acids not conserved within this region in EBV gL when compared to Rh gL were further analyzed, with the results mapping residues 54 and 94 as being functionally important for EBV-mediated fusion. All chimeras and mutants displayed levels of cell surface expression similar to that of wild-type gL and interacted with gH and gp42. Our data also suggest that the role of gL involves the activation or recruitment of gB with the gH/gL complex, as we found that reduced fusion of Rh gL, EBV/Rh-LCV chimeras, and gL point mutants could be restored by replacing EBV gB with Rh gB. These observations demonstrate a distinction between the role of gL in the processing and trafficking of gH to the cell surface and a posttrafficking role in cell-cell fusion.
Effect of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Polymorphism Leu-214 on Replication Capacity and Drug Susceptibility
Authors: Puertas Maria Carmen , Buzón Maria Jose , Artese Anna , Alcaro Stefano , Menendez-Arias Luis , Perno Carlo Federico , Clotet Bonaventura , Ceccherini-Silberstein Francesca , Martinez-Picado Javier
Published: May 2009

A negative association between polymorphism Leu-214 and type-1 thymidine analogue mutations (TAM1) and a positive association with a clinically favorable virological response to thymidine analogue-based combination antiretroviral therapy have been described. In this study, the impact of Leu-214 on replication capacity and resistance to zidovudine (ZDV) of viruses containing TAM1 or TAM2 was determined. Leu-214 decreased the growth rate of viruses bearing Tyr-215, as well as their resistance to ZDV. This observation was confirmed by structural and molecular modeling data, suggesting a regulatory role for Leu-214 in the emergence and phenotypic resistance of TAM1.
Pharmacovirological Impact of an Integrase Inhibitor on Human Immunodeficiency Virus Type 1 cDNA Species In Vivo
Authors: Goffinet Christine , Allespach Ina , Oberbremer Lena , Golden Pamela L. , Foster Scott A. , Johns Brian A. , Weatherhead Jason G. , Novick Steven J. , Chiswell Karen E. , Garvey Edward P. , Keppler Oliver T.
Published: May 2009

Clinical trials of the first approved integrase inhibitor (INI), raltegravir, have demonstrated a drop in the human immunodeficiency virus type 1 (HIV-1) RNA loads of infected patients that was unexpectedly more rapid than that with a potent reverse transcriptase inhibitor, and apparently dose independent. These clinical outcomes are not understood. In tissue culture, although their inhibition of integration is well documented, the effects of INIs on levels of unintegrated HIV-1 cDNAs have been variable. Furthermore, there has been no report to date on an INI's effect on these episomal species in vivo. Here, we show that prophylactic treatment of transgenic rats with the strand transfer INI GSK501015 reduced levels of viral integrants in the spleen by up to 99.7%. Episomal two-long-terminal-repeat (LTR) circles accumulated up to sevenfold in this secondary lymphoid organ, and this inversely correlated with the impact on the proviral burden. Contrasting raltegravir's dose-ranging study with HIV patients, titration of GSK501015 in HIV-infected animals demonstrated dependence of the INI's antiviral effect on its serum concentration. Furthermore, the in vivo 50% effective concentration calculated from these data best matched GSK501015's in vitro potency when serum protein binding was accounted for. Collectively, this study demonstrates a titratable, antipodal impact of an INI on integrated and episomal HIV-1 cDNAs in vivo. Based on these findings and known biological characteristics of viral episomes, we discuss how integrase inhibition may result in additional indirect antiviral effects that contribute to more rapid HIV-1 decay in HIV/AIDS patients.
EFFECTIVE DYNAMICS FOR SOLITONS IN THE NONLINEAR KLEIN–GORDON–MAXWELL SYSTEM AND THE LORENTZ FORCE LAW
Authors: LONG EAMONN , STUART DAVID
Published: May 2009

We consider the nonlinear Klein–Gordon–Maxwell system derived from the Lagrangian [Formula: see text] on four-dimensional Minkowski space-time, where ϕ is a complex scalar field and Fμν = ∂μ𝔸ν - ∂ν𝔸μ is the electromagnetic field. For appropriate nonlinear potentials [Formula: see text], the system admits soliton solutions which are gauge invariant generalizations of the non-topological solitons introduced and studied by Lee and collaborators for pure complex scalar fields. In this article, we develop a rigorous dynamical perturbation theory for these solitons in the small e limit, where e is the electromagnetic coupling constant. The main theorems assert the long time stability of the solitons with respect to perturbation by an external electromagnetic field produced by the background current 𝕁B, and compute their effective dynamics to O(e). The effective dynamical equation is the equation of motion for a relativistic particle acted on by the Lorentz force law familiar from classical electrodynamics. The theorems are valid in a scaling regime in which the external electromagnetic fields are O(1), but vary slowly over space-time scales of [Formula: see text], and δ = e1 - k for [Formula: see text] as e → 0. We work entirely in the energy norm, and the approximation is controlled in this norm for times of [Formula: see text].
ON SPECTRAL RENORMALIZATION GROUP
Authors: FRÖHLICH JÜRG , GRIESEMER MARCEL , SIGAL ISRAEL MICHAEL
Published: May 2009

The operator-theoretic renormalization group (RG) methods are powerful analytic tools to explore spectral properties of field-theoretical models such as quantum electrodynamics (QED) with non-relativistic matter. In this paper, these methods are extended and simplified. In a companion paper, our variant of operator-theoretic RG methods is applied to establishing the limiting absorption principle in non-relativistic QED near the ground state energy.
Irreversibility in Economics
Authors: Perrings Charles , Brock William
Published: May 2009

Three independent literatures have contributed to the understanding of irreversibility in economics. The first focuses on the future opportunities forgone by investments with irreversible consequences. The second considers irreversibility (and hysteresis) in the context of the dynamics of systems characterized by multiple equilibria. The third, with roots in complex systems theory, focuses on entrainment—a phenomenon recognized in economics as lock-in or lock-out. This paper disentangles the different strands in the economic analysis of irreversibility in order to identify the core ideas involved and to connect them to arguments in the parallel literatures on sustainability and uncertainty.
Zip3 (Slc39a3) functions in zinc reuptake from the alveolar lumen in lactating mammary gland
Authors: Kelleher Shannon L. , Lopez Veronica , Lönnerdal Bo , Dufner-Beattie Jodi , Andrews Glen K.
Published: May 2009

The lactating mammary gland is composed of multiple cell types that tightly coordinate the accumulation, production, and secretion of milk components, including essential metals such as zinc (Zn). Our previous studies in animal and cell models implicated the Zn transporter Zip3 (Slc39a3) in mammary gland Zn acquisition. Herein, we investigated this hypothesis directly by utilizing Zip3-null mice. Our data verify that Zip3 is expressed in secretory mammary cells; however, Zip3 does not play a major role in Zn import from the maternal circulation. Importantly, the primary localization of Zip3 was associated with the luminal membrane of the secretory mammary cells. Consistent with this localization, Zn transfer studies using 65Zn revealed that Zn retention in the secreted milk pool and milk Zn concentration was higher in Zip3-null compared with wild-type mice. Although total mammary gland Zn concentration was not altered, Zip3-null mice also had altered mammary tissue architecture, increased number of apoptotic cells, and reduced mammary gland weight implicating subtle changes in Zip3-mediated intracellular Zn pools in apoptosis regulation. Taken together, our data indicate that Zip3 does not participate in the acquisition of Zn from maternal circulation for secretion into milk but, in contrast, primarily plays a role in the reuptake and cellular retention of Zn in the mammary gland from the previously secreted milk pool, thus regulating cellular function.
Chronic prenatal hypoxia sensitizes β-adrenoceptors in the embryonic heart but causes postnatal desensitization
Authors: Lindgren Isa , Altimiras Jordi
Published: May 2009

Prenatal hypoxia in mammals causes fetal growth restriction and catecholaminergic overstimulation that, in turn, alter signaling pathways associated with adrenergic receptors. β-Adrenoceptors (β-ARs) are essential for fetal cardiac development and regulation of cardiac contractility. We studied the effects of chronic prenatal hypoxia on cardiac β-AR signaling and the incidence of alterations in the juvenile β-AR system due to the embryonic treatment. We measured functional β-AR density (Bmax) through binding with [3H]CGP-12177 and the effect of agonists on β-AR-dependent contractility (pEC50) through concentration-response curves to epinephrine. Eggs from broiler chickens were incubated in normoxia (N, 21% O2) or chronic hypoxia (H, 14% O2). Cardiac tissue from embryos and juveniles was used (15 and 19 day of embryonic development and 14 and 35 days posthatching, E19, E15, P14, and P35, respectively). Relative cardiac enlargement was found in the hypoxic groups at E15, E19, and P14, but not P35. Bmax significantly decreased in E19H. Bmax more than doubled posthatching but decreased from P14 to P35. The sensitivity to epinephrine was lower in E19N compared with E15N, but hypoxia increased the sensitivity to agonist in both E15H and E19H. Despite maintained receptor density, the P35H juvenile displayed a decreased sensitivity to β-AR agonist, something that was not seen in P14H. The postnatal decrease in β-AR sensitivity as an effect of chronic prenatal hypoxia, without a concomitant change in β-AR density, leads us to conclude that the embryonic hypoxic challenge alters the future progression of β-AR signaling and may have important implications for cardiovascular function in the adult.
Specific expression and regulation of glucose transporters in zebrafish ionocytes
Authors: Tseng Yung-Che , Chen Ruo-Dong , Lee Jay-Ron , Liu Sian-Tai , Lee Shyh-Jye , Hwang Pung-Pung
Published: May 2009

Glucose, a carbohydrate metabolite, plays a major role in the energy supply for fish iono- and osmoregulation, and the way that glucose is transported in ionocytes is a critical process related to the functional operations of ionocytes. Eighteen members of glucose transporters (GLUTs, SLC2A) were cloned and identified from zebrafish. Previously, Na+,K+-ATPase-rich (NaR), Na+-Cl−cotransporter-expressing (NCC), H+-ATPase-rich (HR), and glycogen-rich (GR) cells have been identified to be responsible for Ca2+uptake, Cl−uptake, Na+uptake, and the energy deposition, respectively, in zebrafish skin/gills. The purpose of the present study was to test the hypothesis of whether GLUT isoforms are specifically expressed and function in ionocytes to supply energy for ion regulatory mechanisms. On the basis of translational knockdown of foxi3a/ 3b (2 transcriptional factors related to the ionocytes' differentiation) and triple in situ hybridization/immunocytochemistry, 3 GLUT isoforms, zglut1a, - 6, and - 13.1, were specifically localized in NaR/NCC cells, GR cells, and HR cells, respectively. mRNA expression of zglut1a in embryos and adult gills were stimulated by the low Ca2+or low Cl−freshwater, which has been previously reported to upregulate the functions (monitored by epithelial Ca2+channel, NCC mRNA) of NaR/NCC cells, respectively while that of zglut13.1 was stimulated only by low Na+, a situation to upregulate the function (monitored by carbonic anhydrase 15a mRNA) of HR cells. On the other hand, ambient ion compositions did not affect the zglut6 mRNA expression. Taken together, zGLUT1a, -6, and 13.1, the specific transporters in NaR/NCC cells, GR cells, and HR cells, may absorb glucose into the respective cells to fulfill different physiological demands.
Physiological consequences of gill remodeling in goldfish (Carassius auratus) during exposure to long-term hypoxia
Authors: Mitrovic Dejana , Dymowska Agnieszka , Nilsson Goran E. , Perry Steve F.
Published: May 2009

Goldfish ( Carassius auratus) acclimated to 7°C and exposed to hypoxia (∼10 mmHg) for 7 days exhibited a pronounced remodeling of the gill consisting of the removal of an interlamellar cell mass (ILCM). Subsequent experiments were designed to assess the impact of gill remodeling and the associated increase in functional lamellar surface area on the distribution of branchial ionocytes and Cl−flux across the gill. Despite the increased functional lamellar surface area during hypoxia, there was no corresponding increase in Cl−loss or efflux of the extracellular marker polyethylene glycol (PEG 4000). However, when hypoxic fish were returned to normoxic water for 12 h, rates of Cl−and PEG efflux were markedly stimulated in keeping with an increased surface area for solute movement. Similarly, the rate of branchial Cl−uptake was reduced (105 ± 22 vs. 45 ± 8 μmol·kg−1·h−1) in normoxic and hypoxic fish, respectively, but then stimulated (345 μmol·kg−1·h−1) upon reestablishment of normoxic conditions. Hypoxia (7 days) was accompanied by a significant decrease in the total cross-sectional area of branchial ionocytes owing to a decrease in their numbers and individual sizes. Thus, despite experiencing an increase in functional lamellar surface area, hypoxic goldfish limit branchial Cl−loss likely by a hypoxia-mediated decrease in paracellular permeability. In normoxic fish, the ionocytes were largely confined to the outer edges of the ILCM. During hypoxia, preexisting ionocytes migrated with the shrinking ILCM, while a smaller proportion of newly differentiated cells appeared below the surface of the ILCM. The capacity to maintain a population of ionocytes in contact with the water is an appropriate strategy to retain ionoregulatory capabilities regardless of whether the lamellae are uncovered or covered.
Forced catch-up growth after fetal protein restriction alters the adipose tissue gene expression program leading to obesity in adult mice
Authors: Bol V. V. , Delattre A-I. , Reusens B. , Raes M. , Remacle C.
Published: May 2009

A mismatch between fetal and postnatal environment can permanently alter the body structure and physiology and therefore contribute later to obesity and related disorders, as revealed by epidemiological studies. Early programming of adipose tissue might be central in this observation. Moreover, adipose tissue secretes adipokines that provide a molecular link between obesity and its related disorders. Therefore, our aim was to investigate whether a protein restriction during fetal life, followed by catch-up growth could lead to obesity in 9-mo-old male mice and could alter the adipose tissue gene expression profile. Dams were fed a low-protein (LP) or an isocaloric control (C) diet during gestation. Postnatal catch-up growth was induced in LP offspring by feeding dams with control diet and by culling LP litters to four pups instead of eight in the C group. At weaning, male mice were fed by lab chow alone (C) or supplemented with a hypercaloric diet (HC), to induce obesity (C-C, C-HC, LP-C, and LP-HC groups). At 9 mo, LP offspring featured increased relative fat mass, hyperglycemia, hypercholesterolemia, and hyperleptinemia. Using a microarray designed to study the expression of 89 genes involved in adipose tissue differentiation/function, we demonstrated that the expression profile of several genes were dependent upon the maternal diet. Among the diverse genes showing altered expression, we could identify genes encoding several enzymes involved in lipid metabolism. These results indicated that offspring submitted to early mismatched nutrition exhibited alterations in adipose tissue gene expression that probably increases their susceptibility to overweight when challenged after weaning with a HC diet.