bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic code translation displays a linear trade-off between efficiency and accuracy of tRNA selection
Authors: Johansson Magnus , Zhang Jingji , Ehrenberg Måns
Published: December 2011

Rapid and accurate translation of the genetic code into protein is fundamental to life. Yet due to lack of a suitable assay, little is known about the accuracy-determining parameters and their correlation with translational speed. Here, we develop such an assay, based on Mg
2+
concentration changes, to determine maximal accuracy limits for a complete set of single-mismatch codon–anticodon interactions. We found a simple, linear trade-off between efficiency of cognate codon reading and accuracy of tRNA selection. The maximal accuracy was highest for the second codon position and lowest for the third. The results rationalize the existence of proofreading in code reading and have implications for the understanding of tRNA modifications, as well as of translation error-modulating ribosomal mutations and antibiotics. Finally, the results bridge the gap between in vivo and in vitro translation and allow us to calibrate our test tube conditions to represent the environment inside the living cell.
A Hospital in Ilkhānid Iran: Toward a Socio-economic Reconstruction of the Rab‘-i Rashīdī
Authors: Khafipour Hani
Published: December 2011

In the first decade of the fourteenth century, Rashiīd al-Dīn Fazl Allāh penned a remarkable endowment deed in which he meticulously detailed his plans for the creation of a utopian community. He named it the Rab‘-i Rashīdī. In this document, he provides socio-economic data concerning the day-to-day operations of this settlement unparalleled in comparable texts. This article focuses on the hospital ward of the Rab‘-i Rashīdī, and provides a broader historical context for this medieval hospital and its personnel by examining the financial and monetary information in the endowment deed in order to piece together the inner workings of this community. In so doing, we are granted a rare opportunity to explore the daily lives of ordinary people whose endeavors, however significant, often went unnoticed.
Soviet Cultural Legacy in Tajikistan
Authors: Atai Farhad
Published: December 2011

This paper is a report on the Soviet cultural legacy in Tajikistan. It takes an in-depth look at the institutions that were created to manage artistic and cultural activities, budgeting, training and promotion under the Soviets. The paper suggests that, except for art and culture related to religion, other genres were enhanced, albeit with an emphasis on ideology. However, independence in 1992, along with the civil war that erupted immediately afterwards, had a devastating effect on art and culture in Tajikistan and on the lives of the artistic community. The paper is part of a comprehensive study of post-Soviet art and culture in Central Asia in the critical years immediately after the Soviet collapse. For this study, over one hundred interviews were conducted with officials, musicians, dancers, writers and singers, as well as visits to centers of art and culture in those republics.
Inferring convective responses to El Niño with atmospheric electricity
measurements at Shetland
Authors: Harrison R G , Joshi M , Pascoe K
Published: December 2011

Pacific ocean temperature anomalies associated with the El Niño–Southern Oscillation
(ENSO) modulate atmospheric convection and hence thunderstorm electrification. The
generated current flows globally via the atmospheric electric circuit, which can be
monitored anywhere on Earth. Atmospheric electricity measurements made at Shetland
(in Scotland) display a mean global circuit response to ENSO that is characterized by
strengthening during ‘El Niño’ conditions, and weakening during ‘La Niña’ conditions.
Examining the hourly varying response indicates that a potential gradient (PG)
increase around noon UT is likely to be associated with a change in atmospheric
convection and resultant lightning activity over equatorial Africa and Eastern Asia.
A secondary increase in PG just after midnight UT can be attributed to more shower
clouds in the central Pacific ocean during an ‘El Niño’.
Regulation of clathrin coat assembly by Eps15 homology domain–mediated interactions during endocytosis
Authors: Suzuki Ryohei , Toshima Junko Y. , Toshima Jiro
Published: December 2011

Clathrin-mediated endocytosis involves a coordinated series of molecular events regulated by interactions among a variety of proteins and lipids through specific domains. One such domain is the Eps15 homology (EH) domain, a highly conserved protein–protein interaction domain present in a number of proteins distributed from yeast to mammals. Several lines of evidence suggest that the yeast EH domain–containing proteins Pan1p, End3p, and Ede1p play important roles during endocytosis. Although genetic and cell-biological studies of these proteins suggested a role for the EH domains in clathrin-mediated endocytosis, it was unclear how they regulate clathrin coat assembly. To explore the role of the EH domain in yeast endocytosis, we mutated those of Pan1p, End3p, or Ede1p, respectively, and examined the effects of single, double, or triple mutation on clathrin coat assembly. We found that mutations of the EH domain caused a defect of cargo internalization and a delay of clathrin coat assembly but had no effect on assembly of the actin patch. We also demonstrated functional redundancy among the EH domains of Pan1p, End3p, and Ede1p for endocytosis. Of interest, the dynamics of several endocytic proteins were differentially affected by various EH domain mutations, suggesting functional diversity of each EH domain.
Neuronal dystonin isoform 2 is a mediator of endoplasmic reticulum structure and function
Authors: Ryan Scott D. , Ferrier Andrew , Sato Tadasu , O'Meara Ryan W. , De Repentigny Yves , Jiang Susan X. , Hou Sheng T. , Kothary Rashmi
Published: December 2011

Dystonin/Bpag1 is a cytoskeletal linker protein whose loss of function in dystonia musculorum (dt) mice results in hereditary sensory neuropathy. Although loss of expression of neuronal dystonin isoforms (dystonin-a1/dystonin-a2) is sufficient to cause dt pathogenesis, the diverging function of each isoform and what pathological mechanisms are activated upon their loss remains unclear. Here we show that dt27mice manifest ultrastructural defects at the endoplasmic reticulum (ER) in sensory neurons corresponding to in vivo induction of ER stress proteins. ER stress subsequently leads to sensory neurodegeneration through induction of a proapoptotic caspase cascade. dt sensory neurons display neurodegenerative pathologies, including Ca2+dyshomeostasis, unfolded protein response (UPR) induction, caspase activation, and apoptosis. Isoform-specific loss-of-function analysis attributes these neurodegenerative pathologies to specific loss of dystonin-a2. Inhibition of either UPR or caspase signaling promotes the viability of cells deficient in dystonin. This study provides insight into the mechanism of dt neuropathology and proposes a role for dystonin-a2 as a mediator of normal ER structure and function.
Response: an empirical comparison of several recent epistatic interaction detection methods
Authors: Wang Yue , Liu Guimei , Feng Mengling , Wong Limsoon
Published: December 2011

Contact:  fayue1015@gmail.com
ESpritz: accurate and fast prediction of protein disorder
Authors: Walsh Ian , Martin Alberto J. M. , Di Domenico Tomàs , Tosatto Silvio C. E.
Published: December 2011

Motivation: Intrinsically disordered regions are key for the function of numerous proteins, and the scant available experimental annotations suggest the existence of different disorder flavors. While efficient predictions are required to annotate entire genomes, most existing methods require sequence profiles for disorder prediction, making them cumbersome for high-throughput applications.

Results: In this work, we present an ensemble of protein disorder predictors called ESpritz. These are based on bidirectional recursive neural networks and trained on three different flavors of disorder, including a novel NMR flexibility predictor. ESpritz can produce fast and accurate sequence-only predictions, annotating entire genomes in the order of hours on a single processor core. Alternatively, a slower but slightly more accurate ESpritz variant using sequence profiles can be used for applications requiring maximum performance. Two levels of prediction confidence allow either to maximize reasonable disorder detection or to limit expected false positives to 5%. ESpritz performs consistently well on the recent CASP9 data, reaching a Sw measure of 54.82 and area under the receiver operator curve of 0.856. The fast predictor is four orders of magnitude faster and remains better than most publicly available CASP9 methods, making it ideal for genomic scale predictions.

Conclusions: ESpritz predicts three flavors of disorder at two distinct false positive rates, either with a fast or slower and slightly more accurate approach. Given its state-of-the-art performance, it can be especially useful for high-throughput applications.

Availability: Both a web server for high-throughput analysis and a Linux executable version of ESpritz are available from: http://protein.bio.unipd.it/espritz/

Contact:  silvio.tosatto@unipd.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
Wnt Blockade With Dickkopf Reduces Intestinal Crypt Fission and Intestinal Growth in Infant Rats
Authors: Fauser Jane K. , Donato Rino P. , Woenig Joshua A. , Proctor Simon J. , Trotta Andrew P. , Grover Phulwinder K. , Howarth Gordon S. , Penttila Irmeli A. , Cummins Adrian G.
Published: December 2011

Objectives:

Intestinal crypt fission peaks during infancy. In human and experimental familial polyposis coli, increased crypt fission is due to activation of Wnt/β‐catenin signalling, but the molecular basis of crypt fission during intestinal growth has not been examined. The aim of this project was to investigate whether crypt fission and intestinal growth are affected by experimental blockade of the Wnt/β‐catenin signalling pathway.

Methods:

Hooded Wistar rats were given either the Wnt inhibitor, dickkopf (30 and 100 ng), daily or vehicle control intraperitoneally from days 11 to 15 and were killed at day 16. Intestinal morphometry was used to measure villous area, crypt area, percentage of crypt fission, and crypt mitotic count. Intestinal stem cells were assessed by expression of real time‐polymerase chain reaction for Lgr5 (a stem cell marker), and the number of β‐catenin–expressing crypts by immunostaining was determined after 100‐ng dickkopf treatment.

Results:

Dickkopf at 30 and 100 ng/day reduced villous area to 71% (P = 0.013) and 29% (P < 0.0001), crypt area to 42% (P = 0.0026) and 30% (P = 0.0067), and crypt fission to 51% (P = 0.006) and 29% (P < 0.0001), respectively, of control values. Mitotic count per crypt did not change. Lgr5 RNA expression and the number of β‐catenin–expressing crypts decreased in dickkopf‐treated animals.

Conclusions:

We conclude that intestinal crypt fission during infancy is mediated by Wnt signalling. It is possible that local treatment with Wnt agonists could be used to increase intestinal growth.
Phylogeographical footprint of colonial history in the global dispersal of human immunodeficiency virus type 2 group A
Authors: Faria Nuno R. , Hodges-Mameletzis Ioannis , Silva Joana C. , Rodés Berta , Erasmus Smit , Paolucci Stefania , Ruelle Jean , Pieniazek Danuta , Taveira Nuno , Treviño Ana , Gonçalves Maria F. , Jallow Sabelle , Xu Li , Camacho Ricardo J. , Soriano Vincent , Goubau Patrick , de Sousa João D. , Vandamme Anne-Mieke , Suchard Marc A. , Lemey Philippe
Published: December 2011

Human immunodeficiency virus type 2 (HIV-2) emerged in West Africa and has spread further to countries that share socio-historical ties with this region. However, viral origins and dispersal patterns at a global scale remain poorly understood. Here, we adopt a Bayesian phylogeographic approach to investigate the spatial dynamics of HIV-2 group A (HIV-2A) using a collection of 320 partial pol and 248 partial env sequences sampled throughout 19 countries worldwide. We extend phylogenetic diffusion models that simultaneously draw information from multiple loci to estimate location states throughout distinct phylogenies and explicitly attempt to incorporate human migratory fluxes. Our study highlights that Guinea-Bissau, together with Côte d’Ivoire and Senegal, have acted as the main viral sources in the early stages of the epidemic. We show that convenience sampling can obfuscate the estimation of the spatial root of HIV-2A. We explicitly attempt to circumvent this by incorporating rate priors that reflect the ratio of human flow from and to West Africa. We recover four main routes of HIV-2A dispersal that are laid out along colonial ties: Guinea-Bissau and Cape Verde to Portugal, Côte d’Ivoire and Senegal to France. Within Europe, we find strong support for epidemiological linkage from Portugal to Luxembourg and to the UK. We demonstrate that probabilistic models can uncover global patterns of HIV-2A dispersal providing sampling bias is taken into account and we provide a scenario for the international spread of this virus.
Behaviour of influenza A viruses differentially expressing segment 2 gene products in vitro and in vivo
Authors: Tauber Sandra , Ligertwood Yvonne , Quigg-Nicol Marlynne , Dutia Bernadette M. , Elliott Richard M.
Published: December 2011

The influenza A virus genome comprises eight segments of negative-sense RNA that encode up to 12 proteins. RNA segment 2 encodes three proteins, PB1, PB1-F2 and N40, that are translated from the same mRNA by ribosomal leaky scanning and reinitiation. PB1 is a subunit of the trimeric viral RNA polymerase. PB1-F2 has been reported to be a potential virulence factor, and has been shown to be involved in a number of activities including induction of apoptosis, regulation of virus replication and modulation of the immune response. No function has yet been ascribed to N40, which represents an N-terminally deleted form of PB1. Previous studies on PB1-F2 function mainly used viruses genetically engineered to prevent PB1-F2 expression by mutation of the PB1-F2 start codon. However, ablation of the start codon was shown to increase the expression level of the downstream protein N40. In the present study, we generated recombinant A/WSN/33 viruses carrying different combinations of PB1-F2- and N40-knockout mutations. Overexpression of N40 in a PB1-F2-deficient background had a detrimental effect on virus growth in vitro and in vivo. However, ablation of PB1-F2 or N40 expression individually was not disadvantageous for the virus. Primer-extension analyses revealed an increase in vRNA production by viruses that overexpressed N40. Our data suggest that the observed attenuation of mutant viruses in vitro and in vivo results from these changes in transcription and replication.
Coating Gold Particles with DNA (Biolistics)
Authors: Morgan Josh L. , Kerschensteiner Daniel
Published: December 2011

Imaging and reconstruction of developing neurons require cells that are labeled in a way that distinguishes them from their neighbors. This can be achieved with ballistic labeling, which refers to the delivery of a cell label by means of carrier particles (tungsten or gold) propelled from a pressurized gun. Ballistic delivery can reach many dispersed cells in one shot and can deploy a wide variety of cell markers to neurons in diverse preparations. The three most commonly used types of ballistic labels are carbocyanine dyes, dextran-conjugated fluorescent markers, and DNA plasmids. The primary advantage of ballistic labeling is that multiple dispersed cells can be labeled quickly in live or fixed tissue. This article describes a protocol for coating gold particles with plasmid DNA, which can be used to label developing ganglion cells in retinal flat mounts.
F-Actin Staining of Drosophila Testes
Authors: Bonaccorsi Silvia , Giansanti Maria G. , Cenci Giovanni , Gatti Maurizio
Published: December 2011

Preparations of Drosophila testes fixed with paraformaldehyde can be stained for F-actin according to the protocol described here. This staining procedure is particularly suitable for staining the male fusome and the cytokinetic contractile ring.
BAPTI and BAPTISM Birthdating of Neurons in Zebrafish
Authors: Pan Y. Albert , Caron Sophie J.C. , Schier Alexander F.
Published: December 2011

This protocol describes how the photoconvertible protein Kaede can be used to determine the birthdates of neurons in live zebrafish. The methods used are birthdating analysis by photoconverted fluorescent protein tracing in vivo (BAPTI) and BAPTI combined with subpopulation markers (BAPTISM). Because Kaede can be converted from green to red fluorescence at any developmental time point, it serves as a temporal landmark for cell birth. When it is used in combination with subpopulation markers, the eventual fate of a cell can be correlated with its birthdate. We describe how we used this method to study the development of trigeminal sensory neurons and discuss how the technique can be extended to the study of other organs.
High-Throughput Analysis of Mouse Embryos by Magnetic Resonance Imaging
Authors: Bamforth Simon D. , Schneider Jürgen E. , Bhattacharya Shoumo
Published: December 2011

Genetic studies in the mouse are crucial for uncovering new genes and signaling pathways associated with development. The identification of murine models with developmental malformations in high-throughput mutagenesis screens is made difficult because, after mid-embryogenesis, the embryo is opaque. Traditional phenotyping methods such as histological sectioning are labor intensive and destructive. We have developed and optimized a novel method for high-throughput multiembryo magnetic resonance imaging (MRI). Here we present our method for processing 32 mouse embryos for analysis by MRI. We describe the MR system, imaging software, and the reconstruction of two-dimensional (2D) and three-dimensional (3D) images. We also discuss the applications of this technique, highlight its advantages, and point out some disadvantages. Using this approach, we can identify developmental malformations in mutant embryos at high spatial resolution (voxel size 25.4 × 25.4 × 24.4 µm). This technique can be easily used for mouse mutagenesis screens and thus provides an important tool for identifying new mouse models for human diseases.
Experimental Strategies for the Identification of DNA-Binding Proteins
Authors: Carey Michael F. , Peterson Craig L. , Smale Stephen T.
Published: December 2011

This article describes approaches for identifying proteins that bind conserved or functional DNA motifs. It discusses the use of consensus sequence databases to identify candidate proteins capable of binding a DNA motif of interest and then explains the potential uses of sophisticated mass spectrometry technology. DNA-binding proteins are most commonly identified by electrophoretic mobility-shift assay (EMSA) or DNase I footprinting. Each of these methods is described, and their advantages and limitations are outlined. It is important to stress that each of the strategies discussed in this article may identify one or more proteins that bind a DNA element of interest. However, none of the strategies will necessarily lead to the protein that is the functionally relevant regulator of the control element in the context of the endogenous locus. Regardless of how a DNA-binding protein is isolated and identified, it merely becomes a candidate regulator of the gene of interest.
Software Tools, Data Structures, and Interfaces for Microscope Imaging
Authors: Stuurman Nico , Swedlow Jason R.
Published: December 2011

The arrival of electronic photodetectors in biological microscopy has led to a revolution in the application of imaging in cell and developmental biology. The extreme photosensitivity of electronic photodetectors has enabled the routine use of multidimensional data acquisition spanning space and time and spectral range in live cell and tissue imaging. These techniques have provided key insights into the molecular and structural dynamics of living biology. However, digital photodetectors offer another advantage—they provide a linear mapping between the photon flux coming from the sample and the electronic sample they produce. Thus, an image presented as a visual representation of the sample is also a quantitative measurement of photon flux. These quantitative measurements are the basis of subsequent processing and analysis to improve signal contrast, to compare changes in the concentration of signal, and to reveal changes in cell structure and dynamics. For this reason, many laboratories and companies have committed their resources to software development, resulting in the availability of a large number of image-processing and analysis packages. In this article, we review the software tools for image data analysis that are now available and give some examples of their use in imaging experiments to reveal new insights into biological mechanisms. In our final section, we highlight some of the new directions for image analysis that are significant unmet challenges and present our own ideas for future directions.
Children and Families’ Involvement in Social Work Decision Making
Authors: Gallagher Michael , Smith Mark , Hardy Mark , Wilkinson Heather
Published: December 2011

This review summarises the research literature on children’s and parents’ involvement in social work decision making, which is regarded, in policy terms, as increasingly important. In practice, however, it tends to be messy, difficult and compromised. Different individuals or groups may have different understandings of participation and related concepts, while differences of age and disability also mediate effective user engagement. The literature highlights common themes in effective participatory practice with both children and their parents. Central to this are the establishment of relationships of trust and respect, clear communication and information and appropriate support to participate.
Overexpression of T‐LAK cell‐originated protein kinase predicts poor prognosis in patients with stage I lung adenocarcinoma
Authors: Wei Di‐Cing , Yeh Yi‐Chen , Hung Jung‐Jyh , Chou Teh‐Ying , Wu Yu‐Chung , Lu Pei‐Jung , Cheng Hui‐Chuan , Hsu Yu‐Lin , Kuo Yu‐Lun , Chen Kuan‐Yu , Lai Jin‐Mei
Published: December 2011

Tumor recurrence is the most common cause of disease failure after surgical resection in early‐stage lung adenocarcinoma. Identification of clinically relevant prognostic markers could help to predict patients with high risk of disease recurrence. A meta‐analysis of available lung adenocarcinoma microarray datasets revealed that T‐LAK cell‐originated protein kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have shown that TOPK can promote cell migration, invasion, and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis of 203 patients diagnosed with pathological stage I lung adenocarcinoma was carried out to examine the expression of TOPK by immunohistochemistry (IHC). The prognostic significance of TOPK overexpression was examined. Overexpression of TOPK (IHC score >3) was detected in 67.0% of patients, and these patients were more frequently characterized with disease recurrence and angiolymphatic invasion. Using multivariate analysis, patient age (>65 years old; P = 0.002) and TOPK overexpression (IHC score >3; P < 0.001) significantly predicted a shortened overall survival. Moreover, TOPK overexpression (IHC score >3; P = 0.005) also significantly predicted a reduced time to recurrence in the patients. Our results indicate that overexpression of TOPK could predetermine the metastatic capability of tumors and could serve as a significant prognostic predictor of shortened overall survival and time to recurrence. (Cancer Sci 2012; 103: 731–738)
Rapid genetic diversification within dog breeds as evidenced by a case study on Schnauzers
Authors: Streitberger K. , Schweizer M. , Kropatsch R. , Dekomien G. , Distl O. , Fischer M. S. , Epplen J. T. , Hertwig S. T.
Published: December 2011

As a result of strong artificial selection, the domesticated dog has arguably become one of the most morphologically diverse vertebrate species, which is mirrored in the classification of around 400 different breeds. To test the influence of breeding history on the genetic structure and variability of today's dog breeds, we investigated 12 dog breeds using a set of 19 microsatellite markers from a total of 597 individuals with about 50 individuals analysed per breed. High genetic diversity was noted over all breeds, with the ancient Asian breeds (Akita, Chow Chow, Shar Pei) exhibiting the highest variability, as was indicated chiefly by an extraordinarily high number of rare and private alleles. Using a Bayesian clustering method, we detected significant genetic stratification within the closely related Schnauzer breeds. The individuals of these three recently differentiated breeds (Miniature, Standard and Giant Schnauzer) could not be assigned to a single cluster each. This hidden genetic structure was probably caused by assortative mating owing to breeders’ preferences regarding coat colour types and the underlying practice of breeding in separate lineages. Such processes of strong artificial disruptive selection for different morphological traits in isolated and relatively small lineages can result in the rapid creation of new dog types and potentially new breeds and represent a unique opportunity to study the evolution of genetic and morphological differences in recently diverged populations.
Airway inflammation evaluated in a human nasal lipopolysaccharide challenge model by investigating the effect of a CXCR2 inhibitor
Authors: Virtala R. , Ekman A.‐K. , Jansson L. , Westin U. , Cardell L. O.
Published: December 2011

Background

The existence of a link between inflammation in upper and lower airways is well established. It may therefore be assumed that the nose could be used to study inflammatory events in the lower airways.

Objective

This study aimed to evaluate a lipopolysaccharide (LPS) nasal challenge model by investigating the effect of the CXCR2 inhibitor AZD8309 on neutrophilic inflammation.

Methods

A total of 18 healthy volunteers were randomized in a placebo‐controlled, double‐blind, cross‐over study. AZD8309 or placebo was dosed for 3 days. Subjects were challenged nasally with LPS (50 μg/nostril), and nasal lavage was performed 6 and 24 h later. Leucocytes, neutrophils and inflammatory mediators were assessed in the lavage fluid. The outcome was compared with data from analogous experiments performed in a model of inhaled LPS followed by induced sputum. This trial was registered in the Current Controlled Trials register (ISRCTN trial number: ISRCTN46666382).

Results

The leucocytes in nasal lavage consisted to 99% of neutrophils on average. Treatment with AZD8309 reduced the leucocyte count to 48% of placebo 6 h after the LPS challenge. There was also a reduction in LTB4 levels to 45% of placebo after 6 h and in the neutrophil elastase activity after 24 h. No major adverse events were seen with either AZD8309 or placebo. The nasal LPS model induced only minimal local irritation and no signs of systemic inflammation.

Conclusions and Clinical Relevance

LPS‐induced neutrophil recruitment was reduced by inhibition of CXCR2. This outcome mimicked the response previously seen in a lower airway LPS model. Hence, the nasal model offers a convenient and well‐tolerated alternative for pharmacological evaluation of anti‐inflammatory drugs affecting neutrophilic migration and activity.
Attenuating crosstalk noise with simultaneous source full waveform inversion★
Authors: Guitton Antoine , Díaz Esteban
Published: December 2011

For some acquisition geometries, the cost of Full Waveform Inversion (FWI) can be considerably reduced by inverting simultaneously encoded shots. Encoded‐shot strategies have the undesirable effect of leaving crosstalk noise in the final result. For FWI, changing the coding sequence periodically mitigates this effect. Another alternative is to use preconditioning, whereby the gradient is smoothed at every iteration along predefined directions. Preconditioning steers the solution towards accurate models while attenuating crosstalk artefacts. It also increases convergence speed and robustness to noise present in the data.
Evaluation of cleaning capacity and instrumentation time of manual, hybrid and rotary instrumentation techniques in primary molars
Authors: Pinheiro S. L. , Araujo G. , Bincelli I. , Cunha R. , Bueno C.
Published: December 2011

Pinheiro SL, Araujo G, Bincelli I, Cunha R, Bueno C. Evaluation of cleaning capacity and instrumentation time of manual, hybrid and rotary instrumentation techniques in primary molars. International Endodontic Journal, 45, 379–385, 2012.

Aim  To compare the cleaning effectiveness of manual, hybrid and rotary instrumentation techniques in primary molar teeth.

Methodology  Fifteen primary molars were selected. After endodontic access, the teeth were immersed in a medium containing Enterococcus faecalis and divided into three groups, according to the root canal instrumentation technique: group 1 – manual, group 2 – hybrid and group 3 – nickel–titanium (NiTi) rotary files. For microbiological evaluation, comparisons before and after instrumentation were performed using the paired Student’s t‐test. One‐way anova complemented with the Student’s t‐test was used to compare the percentage of microbial reduction. Instrumentation time was evaluated by Kruskal–Wallis and Student–Newman–Keuls tests. Images obtained under scanning electron microscopy were analysed by three blinded examiners, and kappa statistics was used to evaluate calibration among examiners. The most frequent results among examiners were analysed using Kruskal–Wallis and Student–Newman–Keuls tests.

Results  The hybrid technique required a significantly longer instrumentation time than the manual and rotary techniques (P < 0.05). All techniques tested were able to significantly reduce the number of E. faecalis (P < 0.05). The hybrid technique was associated with the highest intracanal bacterial reduction, with a statistically significant difference compared with manual instrumentation (P = 0.01). Manual instrumentation resulted in the lowest amount of debris and the highest amount of smear layer when compared with the rotary and hybrid techniques (P < 0.05). There was no difference between rotary and hybrid instrumentation in the removal of debris and smear layer.

Conclusion  The use of NiTi rotary files is an option for root canal instrumentation in primary teeth.
Comparison of the force required to fracture roots vertically after ultrasonic and Masserann removal of broken instruments
Authors: Gerek M. , Başer E. D. , Kayahan M. B. , Sunay H. , Kaptan R. F. , Bayırlı G.
Published: December 2011

Gerek M, Başer ED, Kayahan MB, Sunay H, Kaptan RF, Bayırlı G. Comparison of the force required to fracture roots vertically after ultrasonic and Masserann removal of broken instruments. International Endodontic Journal, 45, 429–434, 2012.

Aim  To evaluate the force required to fracture roots vertically after the removal of broken instruments using ultrasonic tips and a Masserann kit.

Methodology  Thirty‐nine extracted human anterior teeth with single and straight roots were used. The crown of each tooth was removed until the full length of the tooth was 13 mm. All canals were instrumented with the step‐back technique to a size 25 K‐file. The teeth were randomly divided into three groups: two experimental groups and a control group. The size 30 K‐files used for the test were notched to a depth of half of the instrument with a No. 2 round bur at a point 3 mm from the tip to facilitate breakage of the file at this point. The fractured instruments were removed from the canals using ultrasonic tips or a Masserann kit. The samples were subjected to a continual vertical loading, using a universal testing machine. For each root, the force at the time of fracture was recorded in Newtons. The results were analysed statistically using one‐way anova and Tukey HSD test.

Results  The force required to fracture the roots vertically was significantly higher in the control group than the experimental groups (P < 0.01). The roots from which the broken instruments had been removed using ultrasonic tips required more force to fracture than roots in the Masserann group; however, the difference was not statistically significant.

Conclusion  Removal of a fractured instrument from the middle third of the root decreased the force required to fracture the root vertically, regardless of the technique used for instrument removal. There was not difference between the ultrasonic technique and the Masserann technique.
Physical and mechanical properties of a thermomechanically treated NiTi wire used in the manufacture of rotary endodontic instruments
Authors: Pereira E. S. J. , Peixoto I. F. C. , Viana A. C. D. , Oliveira I. I. , Gonzalez B. M. , Buono V. T. L. , Bahia M. G. A.
Published: December 2011

Pereira ESJ, Peixoto IFC, Viana ACD, Oliveira II, Gonzalez BM, Buono VTL, Bahia MGA. Physical and mechanical properties of a thermomechanically treated NiTi wire used in the manufacture of rotary endodontic instruments. International Endodontic Journal, 45, 469–474, 2012.

Aim  To compare physical and mechanical properties of one conventional and one thermomechanically treated nickel–titanium (NiTi) wire used to manufacture rotary endodontic instruments.

Methodology  Two NiTi wires 1.0 mm in diameter were characterized; one of them, C‐wire (CW), was processed in the conventional manner, and the other, termed M‐Wire (MW), received an additional heat treatment according to the manufacturer. Chemical composition was determined by energy‐dispersive X‐ray spectroscopy, phase constitution by XRD and the transformation temperatures by DSC. Tensile loading/unloading tests and Vickers microhardness measurements were performed to assess the mechanical behaviour. Data were analysed using analysis of variance (α = 0.05).

Results  The two wires showed approximately the same chemical composition, close to the 1 : 1 atomic ratio, and the β‐phase was the predominant phase present. B19′ martensite and the R‐phase were found in MW, in agreement with the higher transformation temperatures found in this wire compared with CW, whose transformation temperatures were below room temperature. Average Vickers microhardness values were similar for MW and CW (P = 0.91). The stress at the transformation plateau in the tensile load–unload curves was lower and more uniform in the M‐Wire, which also showed the smallest stress hysteresis and apparent elastic modulus.

Conclusions  The M‐Wire had physical and mechanical properties that can render endodontic instruments more flexible and fatigue resistant than those made with conventionally processed NiTi wires.
Life in varying environments: experimental evidence for delayed effects of juvenile environment on adult life history
Authors: Helle Heikki , Koskela Esa , Mappes Tapio
Published: December 2011

1. The effects of environment experienced during early development on phenotype as an adult has started to gain vast amounts of interest in various taxa. Some evidence on long‐term effects of juvenile environment is available, but replicated experimental studies in wild animals are still lacking.

2. Here we report the first replicated experiment in wild mammals which examines the long‐term effects of juvenile and adult environments on individual fitness (reproduction, survival and health). The early development of bank vole (Myodes glareolus) individuals took place in either food‐supplemented or un‐supplemented outdoor enclosures. After the summer, adult individuals were reciprocally changed to either a similar or opposite resource environment to overwinter.

3. Adult environment had an overriding effect on reproductive success of females so that females overwintering in food‐supplemented enclosures had a higher probability of breeding and advanced the initiation of breeding. However, the characteristics of their litters were determined by juvenile environment: females initially grown in food‐supplemented conditions subsequently produced larger litters with bigger pups and a male‐biased sex ratio.

4. In males, individuals growing in un‐supplemented conditions had the highest survival irrespective of adult environment during winter, whereas in females, neither the juvenile nor adult environments affected their survival significantly. The physiological condition of voles in spring, as determined by haematological parameters, was also differentially affected by juvenile (plasma proteins and male testosterone) and adult (haematocrit) environments.

5. Our results suggest that (i) life‐history trajectories of voles are not strictly specialized to a certain environment and (ii) the plastic life‐history responses to present conditions can actually be caused by delayed effects of the juvenile environment. More generally, the results are important for understanding the mechanisms of delayed life‐history effects as well as recognizing their population dynamic consequences.
Dark pixel intensity determination and its applications in normalizing different exposure time and autofluorescence removal
Authors: PANG Z. , LAPLANTE N.E. , FILKINS R. J.
Published: December 2011

The purpose of this study is to investigate how to scale pixel intensity acquired from one exposure time to another. This is required when comparing grayscale images acquired at different exposure times and other image processing such as autofluorescence removal. Pixel intensity is linear to exposure time as long as images are acquired at the linear range of a camera, but importantly there exists an intercept, which is set by the camera. We termed this intercept as dark pixel intensity, as it is the pixel intensity under conditions of no light and zero exposure time. Dark pixel intensity is determined by camera's readout noise (electron/pixel), gain, and DC offset. Knowing dark pixel intensity, image acquired from one exposure time can be linearly scaled to an image at a different exposure time. Dark pixel intensity can be directly measured by obtaining an image at no light and zero (or minimum) exposure time. It can be also indirectly calculated by capturing images at a series of exposure times. Finally, the prestained and poststained images were acquired at their optimal exposures and autofluorescence was completely removed by normalizing images with the exposure time ratio and dark pixel intensity followed by subtraction.
The impact of fibrosis and steatosis on early viral kinetics in HCV genotype 1–infected patients treated with Peg‐IFN‐alfa‐2a and ribavirin
Authors: Guedj H. , Guedj J. , Negro F. , Lagging M. , Westin J. , Bochud P.‐Y. , Bibert S. , Neumann A. U. ,   for the DITTO‐HCV study group
Published: December 2011

Summary.  Hepatitis C viral (HCV) kinetics after initiation of interferon‐based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1–infected patients treated with pegylated interferon alfa‐2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of ≥2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second‐phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second‐phase slope, that is, ≥0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first‐phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings.
A novel regulatory role of the Rnf complex of Azoarcus sp. strain BH72
Authors: Sarkar Abhijit , Köhler Jörg , Hurek Thomas , Reinhold‐Hurek Barbara
Published: December 2011

The superfamily of PII proteins contains the most widely distributed signalling proteins in nature. Remarkable is the variety of targets whose activity is affected by protein–protein interactions. Here we identified as novel partner for interaction with GlnK an Rnf complex, known to couple the energy of ion transport to reduce ferredoxins. The endophytic diazotrophic betaproteobacterium Azoarcus sp. strain BH72 harbours two rnf‐like clusters in the genome, of which only the rnf1 cluster was induced under conditions of N2 fixation under control of the transcriptional activator NifA. Rapid inactivation (‘DraT‐independent switch off’) of nitrogenase activity upon ammonium upshift was dependent on the Rnf1 complex. Membrane sequestration of GlnK in steady‐state N‐surplus conditions occurred in its unmodified form, signalling N‐surplus, and was dependent on presence of the Rnf1 complex, suggesting physical interaction. In vitro binding studies by Far‐Western analysis indicated interactions of RnfC1 with specifically GlnK but not with GlnB. As ammonium upshift led to decreased activity of the Rnf1 complex in membranes, it might be inactivated by GlnK binding, leading to an interruption of electron flow to nitrogenase and thus a rapid, DraT‐independent nitrogenase switch off. Our data imply a hitherto unknown interaction partner for a PII‐like protein and an additional process under its control.
Gastrointestinal extracellular electrical recordings: fact or artifact?
Authors: O’Grady G.
Published: December 2011

Extracellular electrical recordings underpin an important literature of basic and clinical motility science. In the November 2011 edition of Neurogastroenterology and Motility, Sanders and colleagues reported that contraction artifacts could be recorded from in vitro murine gastric tissues using extracellular electrodes, and that true extracellular bioelectrical activity could not be detected when the contractions were suppressed. The authors interpret their findings to mean that previous extracellular studies have generally assayed contraction artifacts, rather than bioelectrical activity, and suggest that movement suppression is an obligatory control for extracellular experiments. If their interpretation is correct, these claims would be significant, requiring a reinterpretation of many studies, and posing major challenges for future in vivo and especially clinical work. However, a demonstration that motion artifacts can be recorded from murine in vitro tissue does not necessarily mean that other extracellular studies also represented artifacts. This viewpoint evaluates a recently published by Sanders and colleagues in light of the competing literature, and finds a considerable volume of evidence to support the veracity of GI extracellular electrical recordings. It is reasoned from biophysical principles, technical considerations, and experimental studies that motion artifacts cannot explain GI extracellular electrical recordings in general, and that bioelectrical fact and artifact can be readily and reliably distinguished in most contexts. Calls for obligatory motion suppression for extracellular studies are therefore not supported. However, the artifacts recorded by Sanders and colleagues nevertheless serve as a reminder that educated caution is needed when recording, filtering and interpreting extracellular data.
Accommodation of the abdomen to its content: integrated abdomino‐thoracic response
Authors: Burri E. , Cisternas D. , Villoria A. , Accarino A. , Soldevilla A. , Malagelada J.‐R. , Azpiroz F.
Published: December 2011

Background  We previously showed that changes in intra‐abdominal content induce a volume‐dependent muscular response of the anterior abdominal wall and the diaphragm. We aimed to determine the contribution of the thorax to abdominal accommodation and the influence of the intra‐abdominal expansion rate.

Methods  Gas (1440 mL total load) was infused into the colon of nine healthy subjects, while abdomino‐thoracic perimeters (by tape measure), electromyography (EMG) activity of the diaphragm (via six ring electrodes over an esophageal tube in the hiatus), intercostals and anterior abdominal wall (via five pairs of surface electrodes) and the position of the diaphragm by ultrasonography were measured. Infusion rates of 24, 48, and 96 mL min−1 were tested on separate days.

Key Results  Gas infusion induced anterior abdominal wall contraction (18 ± 1% EMG increment; P < 0.001) with relatively modest girth increment (4.9 ± 0.9 mm; P = 0.001), diaphragmatic relaxation (by 15 ± 1%; P < 0.001) with cephalad displacement (by 23 ± 6 mm; P = 0.005), and intercostal contraction (by 19 ± 2%; P < 0.001) with increased thoracic perimeter (by 2.0 ± 0.5 mm; P = 0.009). Responses were similar with the three infusion rates.

Conclusions & Inferences  Accommodation of intra‐abdominal loads involves a volume‐related integrated abdomino‐thoracic response regardless of the expansion rate.
Oxidative stress induces unfolding protein response and inflammation in nasal polyposis
Authors: Jeanson L. , Kelly M. , Coste A. , Guerrera I. C. , Fritsch J. , Nguyen‐Khoa T. , Baudouin‐Legros M. , Papon J.‐F. , Zadigue P. , Prulière‐Escabasse V. , Amselem S. , Escudier E. , Edelman A.
Published: December 2011

Background:

Nasal polyposis, a chronic inflammatory disease affecting the upper airways, is a valuable and accessible model to investigate the mechanisms underlying chronic inflammation. The main objective of this study was to investigate a potential involvement of the unfolded protein response (UPR) in the context of oxidative stress and inflammation in nasal epithelial cells from nasal polyps (NP).

Methods:

Epithelial cells from NP (n = 20) and normal mucosa (Controls, n = 15) in primary culture were analyzed by global proteomic approach and cell biology techniques for the glucose‐regulated protein 78 (GRP78), the spliced X‐box‐binding protein 1 (sXBP‐1), the glucose‐regulated protein 94 (GRP94), and the calreticulin (immunoblot, mass spectrometry, immunocytochemistry).

Results:

Proteomics analysis of human nasal epithelial cells in culture revealed the activation of the unfolded protein response in NP. Systematic cell biology and biochemical analysis of two markers (GRP78, sXBP‐1) in the presence and absence of oxidative stress in NP showed a susceptibility of the unfolded protein response to oxidative stress compared to controls at least partially linked to an abnormal redox state of the protein disulfide‐isomerase 4. This unfolded protein response was correlated with mitochondrial depolarization and secretion of interleukin 8 (IL‐8) and leukotriene B4 (LTB4) and was prevented by mitochondrial antioxidant.

Conclusions:

We show the existence of UPR in nasal epithelial cells that is linked to oxidative stress leading to IL‐8 and LTB4 secretions. These mechanisms may participate in chronic inflammation in nasal polyposis.
A novel allele, HLA‐A*66:14, identified in a Brazilian volunteer bone marrow donor
Authors: Wowk P. F. , Mattar S. B. , Rodrigues F. , da Graça Bicalho M.
Published: December 2011

The new allele might have arisen from HLA‐A*66:01 through a point mutation at codon 182.1 (ACG→GCG) resulting in a non‐conservative change from threonine to alanine.