bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental hyperbilirubinemia and CNS toxicity in mice humanized with theUDP glucuronosyltransferase 1(UGT1) locus
Authors: Fujiwara Ryoichi , Nguyen Nghia , Chen Shujuan , Tukey Robert H.
Published: March 2010

High levels of unconjugated bilirubin (UCB) in newborn children is associated with a reduction in hepatic UDP glucuronosyltransferase (UGT) 1A1 activity that can lead to CNS toxicity, brain damage, and even death. Little is known regarding those events that lead to UCB accumulation in brain tissue, and therefore, we sought to duplicate this condition in mice. The humanUGT1locus, encoding all 9-UGT1Agenes includingUGT1A1, was expressed inUgt1−/−mice. Because the most common clinical condition associated with jaundice in adults is Gilbert’s syndrome, which is characterized by an allelic polymorphism in theUGT1A1promoter, hyperbilirubinemia was monitored in humanizedUGT1mice that expressed either the Gilbert’sUGT1A1*28allele [Tg(UGT1A1*28)Ugt1−/−mice] or the normalUGT1A1*1allele [Tg(UGT1A1*1)Ugt1−/−mice]. AdultTg(UGT1A1*28)Ugt1−/−mice expressed elevated levels of total bilirubin (TB) compared withTg(UGT1A1*1)Ugt1−/−mice, confirming that the promoter polymorphism associated with theUGT1A1*28allele contributes to hyperbilirubinemia in mice. However, TB accumulated to near toxic levels during neonatal development, a finding that is independent of the Gilbert’sUGT1A1*28promoter polymorphism. Whereas serum TB levels eventually returned to adult levels, TB clearance in neonatal mice was not associated with hepatic UGT1A1 expression. In ∼10% of the humanizedUGT1mice, peak TB levels culminated in seizures followed by death. UCB deposition in brain tissue and the ensuing seizures were associated with developmental milestones and can be prevented by enhancing regulation of theUGT1A1gene in neonatal mice.
Drosophila
Parkin requires PINK1 for mitochondrial translocation and ubiquitinates Mitofusin
Authors: Ziviani Elena , Tao Ran N. , Whitworth Alexander J.
Published: March 2010

Loss of the E3 ubiquitin ligase Parkin causes early onset Parkinson's disease, a neurodegenerative disorder of unknown etiology. Parkin has been linked to multiple cellular processes including protein degradation, mitochondrial homeostasis, and autophagy; however, its precise role in pathogenesis is unclear. Recent evidence suggests that Parkin is recruited to damaged mitochondria, possibly affecting mitochondrial fission and/or fusion, to mediate their autophagic turnover. The precise mechanism of recruitment and the ubiquitination target are unclear. Here we show in
Drosophila
cells that PINK1 is required to recruit Parkin to dysfunctional mitochondria and promote their degradation. Furthermore, PINK1 and Parkin mediate the ubiquitination of the profusion factor Mfn on the outer surface of mitochondria. Loss of
Drosophila PINK1
or
parkin
causes an increase in Mfn abundance in vivo and concomitant elongation of mitochondria. These findings provide a molecular mechanism by which the PINK1/Parkin pathway affects mitochondrial fission/fusion as suggested by previous genetic interaction studies. We hypothesize that Mfn ubiquitination may provide a mechanism by which terminally damaged mitochondria are labeled and sequestered for degradation by autophagy.
4.0-Å resolution cryo-EM structure of the mammalian chaperonin TRiC/CCT reveals its unique subunit arrangement
Authors: Cong Yao , Baker Matthew L. , Jakana Joanita , Woolford David , Miller Erik J. , Reissmann Stefanie , Kumar Ramya N. , Redding-Johanson Alyssa M. , Batth Tanveer S. , Mukhopadhyay Aindrila , Ludtke Steven J. , Frydman Judith , Chiu Wah
Published: March 2010

The essential double-ring eukaryotic chaperonin TRiC/CCT (TCP1-ring complex or chaperonin containing TCP1) assists the folding of ∼5–10% of the cellular proteome. Many TRiC substrates cannot be folded by other chaperonins from prokaryotes or archaea. These unique folding properties are likely linked to TRiC’s unique heterooligomeric subunit organization, whereby each ring consists of eight different paralogous subunits in an arrangement that remains uncertain. Using single particle cryo-EM without imposing symmetry, we determined the mammalian TRiC structure at 4.7-Å resolution. This revealed the existence of a 2-fold axis between its two rings resulting in two homotypic subunit interactions across the rings. A subsequent 2-fold symmetrized map yielded a 4.0-Å resolution structure that evinces the densities of a large fraction of side chains, loops, and insertions. These features permitted unambiguous identification of all eight individual subunits, despite their sequence similarity. Independent biochemical near-neighbor analysis supports our cryo-EM derived TRiC subunit arrangement. We obtained a Cα backbone model for each subunit from an initial homology model refined against the cryo-EM density. A subsequently optimized atomic model for a subunit showed ∼95% of the main chain dihedral angles in the allowable regions of the Ramachandran plot. The determination of the TRiC subunit arrangement opens the way to understand its unique function and mechanism. In particular, an unevenly distributed positively charged wall lining the closed folding chamber of TRiC differs strikingly from that of prokaryotic and archaeal chaperonins. These interior surface chemical properties likely play an important role in TRiC’s cellular substrate specificity.
A zinc-binding site by negative selection induces metallodrug susceptibility in an essential chaperonin
Authors: Cun Shujian , Sun Hongzhe
Published: March 2010

GroES is an indispensable chaperonin virtually found throughout all life forms. Consequently, mutations of this protein must be critically scrutinized by natural selection. Nevertheless, the homolog from a potentially virulent gastric pathogen,
Helicobacter pylori
, strikingly features a histidine/cysteine-rich C terminus that shares no significant homology with other family members. Additionally, three more (H45, C51, and C53) are uniquely present in its apical domain. The statistical analyses show that these residues may have originated from negative selection, presumably driven by either dependent or independent amino acid mutations. In the absence of the C-terminal metal-binding domain, the mutant protein still exhibits a substantial capacity for zinc binding in vivo. The biochemical properties of site-directed mutants indicate that H45, C51, and C53 make up an oxidation-sensitive zinc-binding site that may donate the bound metal to a zinc acceptor. Of interest, bismuth antiulcer drugs strongly bind at this site (
K
d
of approximately 7 × 10
-26
 M), replacing the bound zinc and consequently inducing the disruption of the quaternary structure. Because biological features by negative selection are usually inert to change during evolution, this study sheds light on a promising field whereby medicines can be designed or improved to specifically target the residues that uniquely evolved in pathogenic proteins so as to retard the emergence of drug resistance.
Large-scale conformational sampling of proteins using temperature-accelerated molecular dynamics
Authors: Abrams Cameron F. , Vanden-Eijnden Eric
Published: March 2010

We show how to apply the method of temperature-accelerated molecular dynamics (TAMD) in collective variables [Maragliano L, Vanden-Eijnden E (2006)
Chem Phys Lett
426:168–175] to sample the conformational space of multidomain proteins in all-atom, explicitly solvated molecular dynamics simulations. The method allows the system to hyperthermally explore the free-energy surface in a set of collective variables computed at the physical temperature. As collective variables, we pick Cartesian coordinates of centers of contiguous subdomains. The method is applied to the GroEL subunit, a 55-kDa, three-domain protein, and HIV-1 gp120. For GroEL, the method induces in about 40 ns conformational changes that recapitulate the
t
 → 
r
′′
transition and are not observed in unaccelerated molecular dynamics: The apical domain is displaced by 30 Å, with a twist of 90° relative to the equatorial domain, and the root-mean-squared deviation relative to the
r
′′
conformer is reduced from 13 to 5 Å, representing fairly high predictive capability. For gp120, the method predicts both counterrotation of inner and outer domains and disruption of the so-called bridging sheet. In particular, TAMD on gp120 initially in the CD4-bound conformation visits conformations that deviate by 3.6 Å from the gp120 conformer in complex with antibody F105, again reflecting good predictive capability. TAMD generates plausible all-atom models of the so-far structurally uncharacterized unliganded conformation of HIV-1 gp120, which may prove useful in the development of inhibitors and immunogens. The fictitious temperature employed also gives a rough estimate of 10 kcal/mol for the free-energy barrier between conformers in both cases.
Analytic index for a family of Dirac–Ramond operators
Authors: Alvarez Orlando , Windey Paul
Published: March 2010

We derive a cohomological formula for the analytic index of a family of Dirac–Ramond operators and exhibit its modular properties.
Reduced voltage sensitivity in a K
+
-channel voltage sensor by electric field remodeling
Authors: González-Pérez Vivian , Stack Katherine , Boric Katica , Naranjo David
Published: March 2010

Propagation of the nerve impulse relies on the extreme voltage sensitivity of Na
+
and K
+
channels. The transmembrane movement of four arginine residues, located at the fourth transmembrane segment (S4), in each of their four voltage-sensing domains is mostly responsible for the translocation of 12 to 13 e
o
across the transmembrane electric field. Inserting additional positively charged residues between the voltage-sensing arginines in S4 would, in principle, increase voltage sensitivity. Here we show that either positively or negatively charged residues added between the two most external sensing arginines of S4 decreased voltage sensitivity of a Shaker voltage-gated K
+
-channel by up to ≈50%. The replacement of Val363 with a charged residue displaced inwardly the external boundaries of the electric field by at least 6 Å, leaving the most external arginine of S4 constitutively exposed to the extracellular space and permanently excluded from the electric field. Both the physical trajectory of S4 and its electromechanical coupling to open the pore gate seemed unchanged. We propose that the separation between the first two sensing charges at resting is comparable to the thickness of the low dielectric transmembrane barrier they must cross. Thus, at most a single sensing arginine side chain could be found within the field. The conserved hydrophobic nature of the residues located between the voltage-sensing arginines in S4 may shape the electric field geometry for optimal voltage sensitivity in voltage-gated ion channels.
Mitotic chromosomes are constrained by topoisomerase II–sensitive DNA entanglements
Authors: Kawamura Ryo , Pope Lisa H. , Christensen Morten O. , Sun Mingxuan , Terekhova Ksenia , Boege Fritz , Mielke Christian , Andersen Anni H. , Marko John F.
Published: March 2010

We have analyzed the topological organization of chromatin inside mitotic chromosomes. We show that mitotic chromatin is heavily self-entangled through experiments in which topoisomerase (topo) II is observed to reduce mitotic chromosome elastic stiffness. Single chromosomes were relaxed by 35% by exogenously added topo II in a manner that depends on hydrolysable adenosine triphosphate (ATP), whereas an inactive topo II cleavage mutant did not change chromosome stiffness. Moreover, experiments using type I topos produced much smaller relaxation effects than topo II, indicating that chromosome relaxation by topo II is caused by decatenation and/or unknotting of double-stranded DNA. In further experiments in which chromosomes are first exposed to protease to partially release protein constraints on chromatin, ATP alone relaxes mitotic chromosomes. The topo II–specific inhibitor ICRF-187 blocks this effect, indicating that it is caused by endogenous topo II bound to the chromosome. Our experiments show that DNA entanglements act in concert with protein-mediated compaction to fold chromatin into mitotic chromosomes.
ScripTree: scripting phylogenetic graphics
Authors: Chevenet François , Croce Olivier , Hebrard Maxime , Christen Richard , Berry Vincent
Published: March 2010

Summary: There is a large amount of tools for interactive display of phylogenetic trees. However, there is a shortage of tools for the automation of tree rendering. Scripting phylogenetic graphics would enable the saving of graphical analyses involving numerous and complex tree handling operations and would allow the automation of repetitive tasks. ScripTree is a tool intended to fill this gap. It is an interpreter to be used in batch mode. Phylogenetic graphics instructions, related to tree rendering as well as tree annotation, are stored in a text file and processed in a sequential way.

Availability: ScripTree can be used online or downloaded at www.scriptree.org, under the GPL license.

Implementation: ScripTree, written in Tcl/Tk, is a cross-platform application available for Windows and Unix-like systems including OS X. It can be used either as a stand-alone package or included in a bioinformatic pipeline and linked to a HTTP server.

Contact:  chevenet@ird.fr
SDOP-DB: a comparative standardized-protocol database for mouse phenotypic analyses
Authors: Tanaka Nobuhiko , Waki Kazunori , Kaneda Hideki , Suzuki Tomohiro , Yamada Ikuko , Furuse Tamio , Kobayashi Kimio , Motegi Hiromi , Toki Hideaki , Inoue Maki , Minowa Osamu , Noda Tetsuo , Takao Keizo , Miyakawa Tsuyoshi , Takahashi Aki , Koide Tsuyoshi , Wakana Shigeharu , Masuya Hiroshi
Published: March 2010

Summary: This article reports the development of SDOP-DB, which can provide definite, detailed and easy comparison of experimental protocols used in mouse phenotypic analyses among institutes or laboratories. Because SDOP-DB is fully compliant with international standards, it can act as a practical foundation for international sharing and integration of mouse phenotypic information.

Availability: SDOP-DB (http://www.brc.riken.jp/lab/bpmp/SDOP/)

Contact:  hmasuya@brc.riken.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
An effective model for natural selection in promoters
Authors: Hoffman Michael M. , Birney Ewan
Published: March 2010

We have produced an evolutionary model for promoters, analogous to the commonly used synonymous/nonsynonymous mutation models for protein-coding sequences. Although our model, called Sunflower, relies on some simple assumptions, it captures enough of the biology of transcription factor action to show clear correlation with other biological features. Sunflower predicts a binding profile of transcription factors to DNA sequences, in which different factors compete for the same potential binding sites. The parametrized model simultaneously estimates a continuous measurement of binding occupancy across the genomic sequence for each factor. We can then introduce a localized mutation, rerun the binding model, and record the difference in binding profiles. A single mutation can alter interactions both upstream and downstream of its position due to potential overlapping binding sites, and our statistic captures this domino effect. Over evolutionary time, we observe a clear excess of low-scoring mutations fixed in promoters, consistent with most changes being neutral. However, this is not consistent across all promoters, and some promoters show more rapid divergence. This divergence often occurs in the presence of relatively constant protein-coding divergence. Interestingly, different classes of promoters show different sensitivity to mutations, with phosphorylation-related genes having promoters inherently more sensitive to mutations than immune genes. Although there have previously been a number of models attempting to handle transcription factor binding, Sunflower provides a richer biological model, incorporating weak binding sites and the possibility of competition. The results show the first clear correlations between such a model and evolutionary processes.
Effects of a community intervention to reduce the serving of alcohol to intoxicated patrons
Authors: Warpenius Katariina , Holmila Marja , Mustonen Heli
Published: March 2010

AimsTo assess the effects of an alcohol prevention programme to reduce the serving of alcoholic beverages to intoxicated clients on licensed premises.

Research designA controlled pre‐ (2004) and post‐intervention study (2006) design.

InterventionA community‐based programme combining law enforcement, responsible beverage service training, information campaigns and policy initiatives in one Finnish town (Jyväskylä).

Participants and measurementsA male actor pretended to be clearly under the influence of alcohol and tried to buy a pint of beer at licensed premises. For the baseline measurement, every bar and nightclub was visited in the intervention and the control areas (94 licensed premises in total). Post‐intervention data were gathered with the same principles (100 licensed premises in total). A researcher observed every visit and documented the results.

ResultsIn the post‐intervention study there was a statistically significant increase in refusals to serve denials alcohol to the actor in the intervention area (from 23% to 42% of the licensed premises) compared to refusals in the control area (from 36% to 27% of the licensed premises).

ConclusionPrevious research has documented that multi‐component community‐based interventions can have a significant impact on over‐serving of alcohol when training and house policies are combined with effective law enforcement. The present findings also demonstrate that comprehensive Responsible Beverage Service (RBS) interventions applied at a local community level can be effective in decreasing service to intoxicated clients in a Nordic context.
ADH1B*2 allele is protective against alcoholism but not chronic liver disease in the Hungarian population
Authors: Toth Reka , Pocsai Zsuzsa , Fiatal Szilvia , Szeles Gyorgy , Kardos Laszlo , Petrovski Beata , McKee Martin , Adany Roza
Published: March 2010

Background  Standardized death rates from chronic liver diseases (CLDs) in Hungary are much higher than the European Union average. Carrying the alcohol dehydrogenase 1B 48His allele (rs1229984 or ADH1B*2) could decrease the risk of alcoholism, but with persistent drinking may confer a greater risk of CLDs. The aim of this study was to assess the prevalence of this polymorphism in the Hungarian population and its association with alcohol consumption and with CLDs.

Methods and results  A total of 278 cases with diagnosed CLDs and 752 controls without any alterations in liver function, all males aged 45–64, were screened for ADH1B Arg48His polymorphism. ADH1B*2 allele frequencies in controls and cases were 8.31% and 4.50%, respectively (χ2 = 9.2; P = 0.01). Carrying the ADH1B*2 allele was associated with significantly lower odds ratio (OR) for drinking frequency (OR = 0.63; P = 0.003), the number of positive answers on CAGE (Cut‐down, Annoyed, Guilt, Eye‐opener) assessment (OR = 0.58; P = 0.005) and a positive CAGE status (OR = 0.55; P = 0.007). There was a significant association between ADH1B*2 and CLDs (OR = 0.50; P = 0.003), but it disappeared after adjusting for CAGE status and scores (OR = 0.67 P = 0.134; OR = 0.67 P = 0.148, respectively) and weakened after adjusting for drinking frequency (OR = 0.61; P = 0.045). Among heavy drinkers the presence of ADH1B*2 did not increase the risk of cirrhosis but there was a significant interaction between genotype and CAGE status (P = 0.003, P = 0.042), with ADH1B*2 conferring reduced risk of CLDs in CAGE negatives.

Conclusion  In Hungarians, the ADH1B 48His allele reduces the risk of alcoholism, but not the risk of chronic liver disease among heavy drinkers.
Ambient temperature and risk of death from accidental drug overdose in New York City, 1990–2006
Authors: Bohnert Amy S. B. , Prescott Marta R. , Vlahov David , Tardiff Kenneth J. , Galea Sandro
Published: March 2010

Background Mortality increases as ambient temperature increases. Because cocaine affects core body temperature, ambient temperature may play a role in cocaine‐related mortality in particular. The present study examined the association between ambient temperature and fatal overdoses over time in New York City.

Methods Mortality data were obtained from the Office of the Chief Medical Examiner for 1990 to 2006, and temperature data from the National Oceanic and Atmospheric Association. We used generalized additive models to test the relationship between weekly average temperatures and counts of accidental overdose deaths in New York City, controlling for year and average length of daylight hours.

Results We found a significant relation between ambient temperature and accidental overdose fatality for all models where the overdoses were due in whole or in part to cocaine (all P < 0.05), but not for non‐cocaine overdoses. Risk of accidental overdose deaths increased for weeks when the average temperature was above 24°Celsius.

Conclusions These results suggest a strong relation between temperature and accidental overdose mortality that is driven by cocaine‐related overdoses rising at temperatures above 24°Celsius; this is a substantially lower temperature than prior estimates. To put this into perspective, approximately 7 weeks a year between 1990 and 2006 had an average weekly temperature of 24 or above in New York City. Heat‐related mortality presents a considerable public health concern, and cocaine users constitute a high‐risk group.
Time‐trends in gastroprotection with nonsteroidal anti‐inflammatory drugs (NSAIDs)
Authors: VALKHOFF V. E. , VAN SOEST E. M. , STURKENBOOM M. C. J. M. , KUIPERS E. J.
Published: March 2010

Aliment Pharmacol Ther 31, 1218–1228

Background  Preventive strategies are advocated in patients at risk of upper‐gastrointestinal complications associated with nonsteroidal anti‐inflammatory drugs (NSAIDs).

Aim  To examine time‐trends in preventive strategies.

Methods  In a study population comprising 50 126 NSAID users ≥50 years from the Integrated Primary Care Information database, we considered two preventive strategies: co‐prescription of gastroprotective agents and prescription of a cyclooxygenase‐2‐selective inhibitor. In patients with ≥1 risk factor (history of upper‐gastrointestinal bleeding/ulceration, age >65 years, use of anticoagulants, aspirin, or corticosteroids), correct prescription was defined as the presence of a preventive strategy and under‐prescription as the absence of one. In patients with no risk factors, correct prescription was defined as the lack of a preventive strategy, and over‐prescription as the presence of one.

Results  Correct prescription rose from 6.9% in 1996 to 39.4% in 2006 (P < 0.01) in high‐risk NSAID users. Under‐prescription fell from 93.1% to 59.9% (P < 0.01). In the complete cohort, over‐prescription rose from 2.9% to 12.3% (P < 0.01).

Conclusions  Under‐prescription of preventive strategies has steadily decreased between 1996 and 2006; however, 60% of NSAID users at increased risk of NSAID complications still do not receive adequate protection.
‘His mam, my dad, my girlfriend, loads of people used to bring him up’: the value of social support for (ex) offender fathers
Authors: Walker Liz
Published: March 2010

This research analyses key findings from qualitative research conducted with (ex) offender fathers and their probation officers. This paper focuses on the critical role of family and social support for (ex) offender fathers who seek to build and maintain relationships with their children. The research reported in this paper shows that the men receive social support, both formal and informal from a wide ranging and complex network of family, friends and practitioners, which facilitates and enables their commitment to fathering. Drawing on social support theory, I argue that identification of support networks recognizes the productive possibilities of vulnerable families which constitute a source of strength and connection to be nurtured in contexts of adversity. This strengths‐based paradigm advocates the need to identify and facilitate family, friendship and professional networks in the context of social work with offenders and their families.
Research Review: Economic evidence for interventions in children's social care: revisiting the What Works for Children project
Authors: Stevens Madeleine , Roberts Helen , Shiell Alan
Published: March 2010

Evidence about the cost‐effectiveness of interventions in children's services can help decision‐makers make more efficient use of scarce resources. We returned to six somewhat disparate interventions on which we had collated research evidence identified by service planners and practitioners as relevant to the well‐being of children in the course of the Economic and Social Research Council‐funded What Works for Children project. These are home visiting, parenting, cognitive–bahavioural therapy, mentoring, traffic calming and breakfast club interventions. We aimed to explore the nature and extent of evidence on cost‐benefit and cost effectiveness for these measures. We conducted searches for studies that looked at the costs as well as the effectiveness of the six interventions and found 24 studies matching our inclusion criteria. The studies were diverse in terms of study design and economic methods (including economic modelling and willingness to pay). Studies relating to parenting programmes and traffic calming gave the most positive indication that the interventions may be cost‐effective for the outcomes in question. The remainder of the studies did not give a clear picture, in large part because of a lack of demonstration that the intervention was effective.
Rapid and unexpected effects of piscivore introduction on trophic position and diet of perch (Perca flavescens) in lakes recovering from acidification and metal contamination
Authors: LUEK ANDREAS , MORGAN GEORGE E. , WISSEL BJÖRN , GUNN JOHN M. , RAMCHARAN CHARLES W.
Published: March 2010

1. Yellow perch (Perca flavescens) are often the only surviving fish species in acidified lakes. We studied four lakes along a gradient of recovery from acidification and that had different food web complexities. All had abundant yellow perch, two had low piscivore abundance, one had a well‐established piscivore population and one was manipulated by introducing piscivorous smallmouth bass (Micropterus dolomieu). We hypothesised that there would be strong effects on perch abundance, behaviour and diet induced by the presence of piscivores.

2. In the manipulated lake, the bass reduced yellow perch abundance by 75% over a 2‐year period. Concomitantly, perch use of the pelagic habitat fell from 48 to 40%.

3. In contrast to findings from less disturbed systems, yellow perch in the littoral zone of the manipulated lake did not strongly shift from zooplankton to benthic food sources after the arrival of piscivores. Diet analysis using stable carbon isotopes revealed a strong continued reliance on zooplankton in all lakes, independent of the degree of piscivory. The failure to switch to benthos in the refuge area of the littoral zone is most likely related to the depauperate benthos communities in these formerly acidified lakes.

4. Yellow perch in lakes recovering from acidification face a considerable ecological challenge as the necessary switch to benthic diet is hindered by a low abundance of benthos. The arrival of piscivores in these recovering lakes imposes further restrictions on perch access to food items. We infer that future recovery of perch populations (and higher trophic levels) will have to be preceded by the re‐establishment of diverse benthic macroinvertebrate communities in these lakes.
An antibody profile of systemic lupus erythematosus detected by antigen microarray
Authors: Fattal Ittai , Shental Noam , Mevorach Dror , Anaya Juan‐Manuel , Livneh Avi , Langevitz Pnina , Zandman‐Goddard Gisele , Pauzner Rachel , Lerner Miriam , Blank Miri , Hincapie Maria‐Eugenia , Gafter Uzi , Naparstek Yaakov , Shoenfeld Yehuda , Domany Eytan , Cohen Irun R.
Published: February 2010

Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self‐antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self‐antigens. The aim was to detect sets of antibody reactivities characteristic of SLE patients in each of various clinical states – SLE patients with acute lupus nephritis, SLE patients in renal remission, and SLE patients who had never had renal involvement. The analysis produced two novel findings: (i) an SLE antibody profile persists independently of disease activity and despite long‐term clinical remission, and (ii) this SLE antibody profile includes increases in four specific immunoglobulin G (IgG) reactivities to double‐stranded DNA (dsDNA), single‐stranded DNA (ssDNA), Epstein–Barr virus (EBV) and hyaluronic acid; the profile also includes decreases in specific IgM reactivities to myeloperoxidase (MPO), CD99, collagen III, insulin‐like growth factor binding protein 1 (IGFBP1) and cardiolipin. The reactivities together showed high sensitivity (> 93%) and high specificity for SLE (> 88%). A healthy control subject who had the SLE antibody profile was later found to develop clinical SLE. The present study did not detect antibody reactivities that differentiated among the various subgroups of SLE subjects with statistical significance. Thus, SLE is characterized by an enduring antibody profile irrespective of clinical state. The association of SLE with decreased IgM natural autoantibodies suggests that these autoantibodies might enhance resistance to SLE.
Laboratory evaluation of the physicochemical properties of a new root canal sealer based on Copaifera multijuga oil‐resin
Authors: Garrido A. D. B. , Lia R. C. C. , França S. C. , Da Silva J. F. , Astolfi‐Filho S. , Sousa‐Neto M. D.
Published: March 2010

Garrido ADB, Lia RCC, França SC, da Silva JF, Astolfi‐Filho S, Sousa‐Neto MD. Laboratory evaluation of the physicochemical properties of a new root canal sealer based on Copaifera multijuga oil‐resin. International Endodontic Journal, 43, 283–291, 2010.

Aim  To compare a new root canal sealer based on Copaifera multijuga oil‐resin (Biosealer) using three other established sealers (Sealer 26®, Endofill® and AH plus®) in terms of their physicochemical properties.

Methodology  The study was carried out according to the requirements of Specification Number 57 of the American Dental Association (ADA) and consisted of the following tests: setting time, flow, film thickness, dimensional stability, radiopacity and solubility/disintegration. Data were analysed statistically using anova and Tukey’s test for multiple comparisons. The significance level was set at 5% for all analyses.

Results  Sealer 26® and AH Plus® had the longest setting time (P < 0.05). All materials presented flow in with the ADA’s guidelines. Regarding film thickness, Sealer 26® did not have a satisfactory performance, as it had a higher mean value than the maximum allowed by the ADA (0.05 mm), being significantly different from the other materials (P < 0.05), which had mean values for film thickness in accordance with the ADA’s recommendations. Regarding the solubility and disintegration, only Endofill® did not meet the ADA’s specifications and presented the worst results of all materials (P < 0.05). Sealer 26® presented the greatest dimensional changes and differed significantly from all other sealers (P < 0.05). Biosealer had the lowest radiopacity values and was significantly different from the other sealers (P < 0.05).

Conclusion  The experimental sealer based on Copaifera multijuga oil‐resin presented satisfactory results in the physicochemical tests required by the ADA.
An audit of intra‐oral digital radiographs for endodontics
Authors: Austin R. , Dunne S. , Robinson B.
Published: March 2010

Aim  The aim of this study was to improve the quality of digital radiographs taken during endodontic treatment at King's College Hospital Dental Institute, UK. There were three phases. The first phase compared the Schick CDR system with Digora Optime. The second and third phases involved ways of improving the quality of the digital radiographs produced by the Schick CDR system.

Methodology  The Faculty of General Dental Practitioners Royal College of Surgeons of England (FGDP) guidelines on Selection Criteria for Dental Radiography and Guidance Notes for Dental Practitioners on the Safe Use of X‐Ray Equipment‐National Radiological Protection Board enabled the use of a three point quality scale (one excellent, two diagnostically acceptable, three unacceptable), which took into consideration sensor angulation, positioning, contrast and focusing. The recommended FGDP guidelines are not less than 70% images scoring excellent. For the first phase 50 exposures recorded with the Schick CDR system were compared with 50 recorded using Digora Optime. For the second and third phases 50 radiographs for each phase were evaluated with images generated by the Schick system with training provided between the phases.

Results  Images produced by the Schick system showed an inferior quality compared with the images generated by the Digora method. Both systems failed to reach the desired quality FGDP standard of 70% excellent (Schick 55% Digora 69%). Comparison of the results in the second and third phases showed that training the operator improved the quality but recommended the purchase of a size 1 or 0 Schick sensors to improve positioning errors.

Conclusions  This study was carried out in order to minimise the ionising radiation dose to patients and to maximise the clinical and administrative benefits of using a digital system. It demonstrated an improvement in the quality of radiographs across all criteria measured up to and beyond the desired standard, from 55% of radiographs scoring excellent in the first phase to 80% in the third phase. As a result of the study it was decided to install the Schick CDR system because of the speed it produced images even though the first phase of this study demonstrated inferior image quality. The audit had clear, measurable standards with explicit targets. The audits have been through the entire audit cycle, data collection, change and a further data collection to provide evidence of the benefit of the change. A third data collection, demonstrated an ongoing commitment to quality.
An audit of the technical quality of orthograde endodontic treatment performed by undergraduate dental students on an endodontic clinic
Authors: Adams N.S. , Tanday A.K. , Darby K.A. , Lumley P.J.
Published: March 2010

Aim  The aim of this study was to investigate the technical quality of orthograde endodontic treatment performed by undergraduate dental students on an endodontic special study module.

Methodology  A retrospective radiographic analysis of the technical standard of endodontic treatment performed by undergraduate final year students undertaking an endodontic study module between 2001 and 2007 was undertaken. The module was staffed by specialist endodontists or specialist registrars with an interest in endodontics. All students completed a voluntary one term special study module for 12–14 sessions. Teeth were treated using stainless steel or Nickel Titanium instruments. Prior to using rotary Nickel Titanium instruments on patients, students were required to satisfactorily complete 10 root canals in extracted teeth using rotary Nickel Titanium instruments. All radiographs of completed endodontic treatment were assessed as to the technical quality of the root filling. Two calibrated observers assessed the radiographs under standard conditions using a lightbox and SDI radiograph viewer. The root fillings in each canal were assessed by length, satisfactory being within 0–2 mm of the radiographic apex, quality of obturation (absence of voids) classified as satisfactory, and taper, with the radiographic appearance of a uniform taper classed as satisfactory.

Results  A total of 506 root canals were evaluated in 218 teeth. The final radiograph was unsuitable in two teeth. The remaining sample size was 504 canals in 216 teeth (51 anterior, 29 premolar, 136 molar). Overall 394 individual root canals (78.1%) and 155 teeth (72.4%) were classed as satisfactory. For anterior teeth 45/51 (88.2%) canals and teeth were satisfactory, for premolars 32/38 canals (82.4%) and 22/29 teeth (75.8%) and molars 317/415 (76.6%) canals and 88/136 teeth (64.7%). No instruments were fractured during the study.

Conclusions  Overall 78.1% of canals and 72.4% of teeth met the criteria of root filling within 2 mm of the radiographic apex, no voids and uniform taper. There was a bias to treating molar teeth, which constituted 63% of the sample. This study shows that a high degree of compliance is achieved on a dedicated endodontic clinic. Furthermore, rotary nickel titanium instruments can be safely used by undergraduate students with appropriate supervision
Effect of transport and storage conditions on recovery of root canal isolates
Authors: Alsunaien T. , Pratten J. , Ng Y.‐L. , Gulabivala K. , Ready D.
Published: March 2010

Aim  To evaluate the effect of transport media and storage temperatures on the survival of two root canal isolates, Prevotella oralis and Fusobacterium nucleatum over time.

Methodology  A standardised inoculum of each bacterium was prepared and transferred via sterile paper points into triplicate 1 mL volumes of transport media (Phosphate buffer saline[PBS]; Viability medium Göteberg [VMG III]; Reduced transport fluid [RTF]; RTF plus 20% glycerol; Commercial Dental Transport Medium [DTM] and Skimmed milk plus 20% glycerol) The samples were placed at room temperature (22 °C), 4 °C and ‐20 °C and the number of colony forming units (cfu) determined at 0 (base line), 1, 4 and 24 h after inoculation. The percentage of cells surviving in each storage medium at each time period was calculated using the number of viable cfu at 0 h as the baseline.

Results  All the tested media were capable of maintaining bacterial viability for up to 1 h regardless of the temperature. Storage at 4 °C in RTF after 4 h gave the best bacterial survival rate among the transport media used. Median percentage survival rates were 82% for P. oralis to 92% for F. nucleatum. In order to store samples for longer than 4 h before microbiological processing then storage at ‐20 °C, in skimmed milk medium was the most effective medium in assisting bacterial recovery with 75% and 82% survival for F. nucleatum and P. oralis, respectively while PBS was the least effective (0–3% survival).

Conclusion  Due to the loss of bacterial viability during sample storage and transport, samples should ideally be processed within the first hour after collection. However, if this is not possible, the results from this study suggest samples should either be: (i) placed in RTF and stored at 4 °C for no more than 4 h; or (ii) for overnight storage, samples should be placed in skimmed milk medium plus 20% glycerol at ‐20 °C.
The effect of various mixing techniques on the surface microhardness of mineral trioxide aggregate
Authors: Nekoofar M. H. , Aseeley Z. , Dummer P. M. H.
Published: March 2010

Nekoofar MH, Aseeley Z, Dummer PMH. The effect of various mixing techniques on the surface microhardness of mineral trioxide aggregate. International Endodontic Journal, 43, 312–320, 2010.

Aim  To evaluate the influence of various mixing procedures including ultrasonic vibration, trituration of customized encapsulated mineral trioxide aggregate (MTA) and condensation on the Vickers surface microhardness of MTA.

Methodology  ProRoot® MTA Original, ProRoot® MTA (white), MTA‐Angelus® (grey) and MTA White Angelus® (white) were prepared using several mixing techniques including ultrasonic vibration, trituration of customized encapsulated MTA and conventional condensation. Twelve experimental groups (four materials: three techniques) were evaluated, each with 35 samples. All samples were incubated after preparation and subjected to Vickers surface microhardness testing after 4 and 28 days. Data was were subjected to a two‐way anova.

Result  At 28 days, the surface microhardness value was significantly greater for all experimental groups compared to 4 days after mixing (P < 0.00001). The application of ultrasonic energy to MTA produced significantly higher surface microhardness values compared to the other mixing techniques at both 4 and 28 days (P < 0.0001). However, no significant difference existed between condensation and trituration techniques at both time intervals. Regardless of the mixing technique employed, a significant difference (P < 0.0001) was observed in surface microhardness value between all types of MTA apart from between Angelus grey and ProRoot white at both 4 and 28 days, both of which produced the highest values.

Conclusion  Compared to trituration and condensation techniques, the application of ultrasonic energy to MTA produced a significantly higher surface microhardness value at both 4 and 28 days. Irrespective of mixing technique, ProRoot white and Angelus grey had the highest surface microhardness values. Trituration of encapsulated, premeasured MTA and water provides a standardiszed method of mixing that produces MTA slurries with more controllable handling characteristics.
Evaluation of biological debris on endodontic instruments after cleaning and sterilization procedures
Authors: Popovic J. , Gasic J. , Zivkovic S. , Petrovic A. , Radicevic G.
Published: March 2010

Popovic J, Gasic J, Zivkovic S, Petrovic A, Radicevic G. Evaluation of biological debris on endodontic instruments after cleaning and sterilization procedures. International Endodontic Journal, 43, 336–341, 2010.

Aim  To examine the presence of biological debris and the level of contamination on reusable endodontic instruments those were subjected to different cleaning methods prior to sterilization.

Methodology  One hundred and eighty endodontic instruments from eighteen dental practices were analysed. These practices used different decontamination protocols for reusable instruments. The presence of organic debris was detected by the use of Van Gieson’s stain. Forty‐eight new stainless steel hand instruments were used as controls. The samples were examined by light microscopy.

Results  Residual biological debris was observed in 96% of the samples. The mean value of maximum biological contamination was 34% in the group in which the instruments were brushed manually and immersed in alcohol, 25% in the group in which commercially available disinfectants were used and 5% in the group in which the instruments were cleaned ultrasonically. There was a statistically significant difference in the mean values with respect to the cleaning protocol applied (P < 0.001).

Conclusions  The methods used to clean endodontic instruments appear to be generally ineffective for the removal of biological debris. The best method was the one that included mechanical, chemical and ultrasonic cleaning of instruments.
Contrasting patterns of nuclear microsatellite genetic structure of Fraxinus mandshurica var. japonica between northern and southern populations in Japan
Authors: Hu Li‐Jiang , Uchiyama Kentaro , Saito Yoko , Ide Yuji
Published: March 2010

Aim  The aim of this study is to detect extant patterns of population genetic structure of Fraxinus mandshurica var. japonica in Japan, and to provide insights into the post‐glacial history of this species during the Holocene.

Location  Hokkaido and Honshu islands, Japan (including the Oshima and Shimokita peninsulas).

Methods  We examined nine polymorphic nuclear microsatellite loci to assess genetic variation within and among 15 populations across almost the entire range of the species in Japan. Extant patterns of geographical structure were analysed using Bayesian clustering, Monmonier’s algorithm, analysis of molecular variance, Mantel tests and principal coordinates analysis. Recent bottlenecks within populations and regional genetic variation were also assessed.

Results  Northern populations (Hokkaido Island and the Shimokita Peninsula) formed a single homogeneous deme, maintaining the highest level of allelic diversity on the Oshima Peninsula. By contrast, southern populations (Honshu Island) demonstrated strong substructure on both coasts. Specifically, populations on the Pacific side of Honshu exhibited significant bottlenecks and erosion of allelic diversity but preserved distinct subclusters diverging from widespread subclusters on the Japan Sea side of this island.

Main conclusions  Genetic evidence and life history traits suggest that F. mandshurica occupied cryptic northern refugia on the Oshima Peninsula during the Last Glacial Maximum, which is reflected in the species’ extant northern distribution. Strong geographical structure in southern populations, in agreement with fossil pollen records, suggests geographical isolation by mountain ranges running north–south along Honshu. Given that this tree species is cold‐adapted and found in riparian habitats, populations on the Pacific side of Honshu probably contracted into higher‐elevation swamps during warm post‐glacial periods, leading to a reduction of effective population sizes and rare allelic richness.
Ecological biogeography of Malagasy non‐volant mammals: community structure is correlated with habitat
Authors: Muldoon Kathleen M. , Goodman Steven M.
Published: March 2010

Aim  To examine the relationship between ecoregions, as a proxy for regional climate and habitat type, and mammalian community structure, defined by species composition and richness (e.g. taxonomic structure) and ecological diversity (e.g. ecological structure) of non‐volant species.

Location  Madagascar.

Methods  Faunal lists of non‐volant mammal species occurring in 35 communities from five World Wildlife Fund ecoregions were collected from published and unpublished sources. Species were assigned to ecological groups defined by trophic status, locomotor habits, activity cycle and body mass. We used Mantel tests, cluster analysis and principal coordinates analysis to evaluate geographic patterning in taxonomic composition and species richness. We used stepwise multiple discriminant analysis to characterize patterns in the ecological diversity of the mammalian communities from each ecoregion. Communities from transitional habitats (e.g. representing more than one ecoregion) were used to test the predictive power of the analyses.

Results  Non‐volant mammal communities divided into clusters that correspond to ecoregions. There was a strong distance effect in the taxonomic structure of communities across the island and within both humid and dry forest communities, but this effect was weak within humid forest communities. Mammalian species richness was significantly lower in dry forest than in humid forest communities. The ecological structure of communities was also correlated with ecoregions. Changes in the relative percentages of omnivory, arboreal quadrupedalism, terrestrial/arboreal quadrupedalism and two body mass classes accounted for 98.1% of the variation in ecological structure. Transitional communities were projected in intermediate positions by the discriminant model.

Main conclusions  Our analysis demonstrates that the broad‐scale habitat and climate variables captured by the ecoregion model have shaped the assembly of non‐volant mammal communities in Madagascar over evolutionary time. The spatial pattern is consistent with ecological sorting of species ranges along environmental gradients. Historical processes, such as recent extinction and migration, may have also affected the structure of mammal communities, although these factors have played a secondary role.