bluuebunny/crossref_metadata_2025 huggingface dataset:
Appearing Socially Competent: The Effects of a Friend's Presence on the Socially Anxious
Authors: Pontari Beth A.
Published: February 2009

As hypothesized, while introducing themselves to another person via video, participants high in social anxiety appeared more socially competent with a friend present than when alone. We also examined three potential explanations for this effect and found that while sharing information about themselves on video, most participants high in social anxiety were verbally prompted by their friends. Furthermore, on an open ended question, participants high in social anxiety expressed less negative self-focused thoughts with a friend present than when alone, but friends' presence did not affect their self-reports of anxiety. As predicted, the presence of friends had no effect on social performance or anxiety for participants low in social anxiety. Although more research is needed to ascertain how being with a friend versus alone results in better social performance for people high in social anxiety, friends' support may be part of a repertoire of “safe” social interaction strategies.
The Effect of Red on Avoidance Behavior in Achievement Contexts
Authors: Elliot Andrew J. , Maier Markus A. , Binser Martin J. , Friedman Ron , Pekrun Reinhard
Published: February 2009

This research tests whether the perception of red in an achievement context evokes avoidance behavior without conscious awareness and also examines the context specificity of the hypothesized red effect. In Experiment 1, participants were briefly shown red or green on the cover of an analogies test that they would ostensibly take (an achievement context) or rate on likability of (a nonachievement context) in an adjacent lab. Those shown red, relative to those shown green, knocked fewer times on the door of the adjacent lab in the achievement context; no red—green difference in knocking was observed in the nonachievement context. In Experiment 2, participants were briefly shown red, green, or gray on the cover of an IQ test that they would ostensibly take. Those shown red moved their body away from the test cover to a greater degree than did those shown green or gray. This research contributes to incipient work on color psychology and to the more established literature on the automatic link between evaluation and behavior.
Representations of the stem-cell cloning fraud: from scientific breakthrough to managing the stake and interest of science
Authors: Augoustinos Martha , Russin Amelia , LeCouteur Amanda
Published: February 2009

The meteoric rise of Professor Wu Sook Hwang who had claimed to have successfully cloned embryonic stem cells in two landmark papers published in Science (2004, 2005) came to an abrupt end when it was discovered that the findings reported in both papers had been deliberately fabricated. Given the heightened expectations associated with therapeutic-cloning advances and their potential for alleviating a range of illnesses, this recent case of scientific fraud generated considerable controversy and public interest across the world. This paper examines a sample of texts taken predominantly from the British newsprint media that reported on both the so-called scientific “breakthrough” (as it was initially reported) and the subsequent fraud. Using Gilbert and Mulkay’s analysis of scientists’ discourse as a theoretical framework, our analysis focuses on how competing repertoires of science were mobilized by the media and the scientific community to account for the fraud. Specifically, we demonstrate how the empiricist repertoire of science was repeatedly mobilized in the initial reporting of the stem-cell “breakthrough” which functioned to warrant the scientific veracity and promissory potential of the findings. In contrast, when this so-called “breakthrough” was discovered to be fraudulent, a contingent repertoire was invoked to construct Hwang as a “bad apple,” who was unrepresentative of the scientific community in general. We also detail the use of a Truth-Will-Out rhetorical device which in a similar way functioned to warrant the practice of embryonic stem-cell research specifically and the institution of science, more generally.
Public feeling for science: The Hwang affair and Hwang supporters
Authors: Kim Jongyoung
Published: February 2009

This ethnography investigates how the Hwang affair occurred, how Dr. Woo Suk Hwang attracted supporters, and how groups supporting Hwang evolved. Instead of interpreting Hwang supporters as abnormal people with psychological problems, this study situates them in concrete, messy, and ambiguous contexts in which they struggle to understand the Hwang affair. Distrustful of scientific authorities and official institutions, they have linked Korean nationalism with the hopes and dreams of stem cell research, created conspiracy theories to explain Hwang’s fall, and criticized Korean elites. In particular, this paper emphasizes how Hwang supporters are motivated by admiration of a Korean scientist with humble beginnings (Dr. Hwang), the hope of curing disease through stem cell research, and the desire to build an advanced nation through science. In describing this process, I pay attention to how public feeling for science is produced and how it has evolved in the interactions among government, media, and the Hwang supporters’ organizations. In addition, I argue that institutional incompetence deepens public distrust and as a result fuels the formation and activities of Hwang supporters.
Public engagement in research funding: a study of public capabilities and engagement methodology
Authors: Rowe Gene , Rawsthorne Dee , Scarpello Tracey , Dainty Jack R.
Published: February 2009

One trend in public engagement concerns involving the public in research priority setting. In this study members of the public were asked to select which of four potential projects (about food-related topics, presented by scientists) ought to be funded. The aim of the study was twofold: to trial and evaluate a method of engaging with the public about science, and to study the factors used by the public in making funding allocation decisions. Results suggest that, while participants enjoyed the process and appeared to learn from it, they were not particularly “representative”—a common problem with engagement approaches of this type. Results also suggest that participants’ funding decisions were largely based on factors such as “benefit to society” and “personal relevance,” though aspects such as the “likeability” and “trustworthiness” of the speaker may have played a role. Implications for involving the public in funding policy decisions are discussed.
Public bioethics and public engagement: the politics of “proper talk”
Authors: Moore Alfred
Published: February 2009

This article uses notions of “public talk” and “regulation as facilitation” to develop an account of public bioethics in the UK as a form of scientific governance, drawing on document analysis and expert interviews. First, this article will show the “ethical” problematization of scientific governance in the UK through the emergence of the Human Genetics Commission (HGC), Nuffield Council on Bioethics (NCB), and Human Fertilisation and Embryology Authority (HFEA). Second, it will argue that an “ethical” model has emerged alongside and partially displaced a “technical” model of expertise in scientific governance. The article will introduce the notion of “proper talk,” a set of techniques for facilitating ethical debate, characterized by the active elicitation of public engagement and the inclusion of emotions and subjectivity. The article then questions whether the authority to categorize publics and identify “proper” ethical positions reintroduces problems of expertise in a new form.
The Effects of Grain-boundary Orientations on Failure Behavior in F.C.C. Polycrystalline Systems
Authors: Jawad F.F. , Zikry M.A.
Published: February 2009

A multiple-slip rate-dependent crystalline constitutive formulation that is coupled to the evolutionary equations of mobile and immobile dislocation densities is used with specialized finite-element methodologies to obtain a detailed microstructural prediction of the inelastic deformation and interrelated physical mechanisms that affect different failure modes in f.c.c. crystalline materials. The effects of grain and grain-boundary (GB) orientations, grain shape and size, GB strength, and mechanical properties on the inelastic finite deformation and failure mode mechanisms in polycrystalline aggregates with Σ3 and Σ17b GBs have been investigated. Results from this study are consistent with experimental observations that microstructures with desired material properties, such as resistivity to crack nucleation, can be potentially achieved by the control of grain aggregate size and CSL GB orientations. Furthermore, it is also shown that transgranular failure modes can occur in aggregates with a high frequency of Σ3 GBs, whereas intergranular fracture modes can occur with a high frequency of Σ17b GBs.
Characters of Fatigue Damage of Smooth-surface Samples by the Effective Short Fatigue Crack Criterion
Authors: Bing Yang  , Ming Fei Feng  , Zhong Yan Zhai
Published: February 2009

Characters of fatigue damage of smooth-surface samples are experimentally drawn through investigation on evolutionary crack sizes, density values, and growth rates of 1Cr18Ni9Ti welded metal. Previous effective short fatigue crack (ESFC) criterion, which consists of three interrelated concepts, i.e., ESFCs, dominant ESFC (DESFC), and density of ESFCs, is employed with a viewpoint of damage localization. Results reveal that the damage is subject to microstructural short crack (MSC), physical short crack (PSC), and long crack (LC) stages. ESFCs and DESFC contribute to fatigue damage directly. The ESFCs sizes increase randomly and competitively, and exhibit a sudden increase when the ESFCs coalesce with each other to form the DESFC. But the DESFC size always increases stably. With the DESFC size increasing and the crack tips transferring, the non-ESFCs, in the form of the density of ESFCs, contribute to fatigue damage indirectly at the initial district of DESFC and then the crack tip districts. The density always increases in MSC stage. After reaching the maximum value at the transition point between MSC and PSC stages, it decreases rapidly in PSC stage, and then, tends to a saturation value in LC stage. The growth rates of ESFCs decrease randomly in MSC stage and then wave around the dominant growth rate in PSC stage. While the growth rate of DESFC shows a stable decrease in MSC stage and a constant increase in PSC stage. The behavior of DESFC is the result of the interactive and evolutionary collective action of short cracks, and therefore it is a reasonable description and quantification for the fatigue damage of smooth-surface samples.
Numerical Prediction of Ductile Failure Onset under Tensile and Compressive Stress States
Authors: Vaz M. , De Santi N. , De Souza Neto E.A.
Published: February 2009

Prediction of ductile failure onset in fracture-free materials has instigated several research works in the last few years. The literature shows basically two general approaches: (i) post-processed fracture indicators and (ii) damage-based material modeling. The former has shown successful to predict failure initiation in specific forming operations, whereas the latter has proved greater potential in assessing failure processes under general stress—strain paths. This work extends an existing isotropic damage model to account for separately tensile and compressive stress effects. Material modeling is based on finite strain elastoplasticity fully coupled to the damage evolution law. An assessment of some post-processed failure indicators is also presented. The damage model and fracture criteria are verified against tensile tests of notched specimens (tensile-dominant stress states) and the upsetting test of cylindrical billets (compressive-dominant stress states).
Degradation Experiments and Analysis of Corrosion Damage
Authors: Pidaparti Ramana M. , Koombua Kittisak , Abdelsayed Ihab , Sharma Himanshu
Published: February 2009

Corrosion is one of the most damaging mechanisms in many engineering structures. To better understand how corrosion growth process takes place in AA 2024-T3 materials, research is being conducted to capture and systematically characterize the corrosion process, and develop simulation models. The objective of this study is to systematically investigate the degradation of major chemical elements (Al and Cu) in AA 2024-T3 as a function of the exposure time and electrochemical parameters during the corrosion process through experiments and develop an artificial neural network (ANN) model for the analysis and prediction. Experiments were conducted on AA 2024-T3 specimens under controlled electrochemical conditions. The chemical element map was developed through energy dispersive spectrometry technique for evaluation purposes. Based on the experimental data, an ANN model is developed for the analysis and prediction of degradation of major chemical elements at various exposure time and electrochemical parameters during the corrosion process. A very good performance of the neural network is achieved after training and validation with the experimental data. The degradation of the major chemical elements and material loss at various electrochemical parameters as a function of time was studied through ANN analysis.
A Comparison of Demand-Side Water Management Strategies Using Disaggregate Data
Authors: Coleman Eric A.
Published: February 2009

Using data from Salt Lake City, Utah, for the years 1999-2002, a water demand model was developed, and the effects of price and nonprice public policies estimated. The demand for water is found to be price inelastic except in summer months. The effects of a public information campaign to reduce water use were also estimated and found to be moderately effective. The household level panel data used in this study give more accurate estimates of these elasticities than found in previous research.
A Comparative Review of Thermography as a Breast Cancer Screening Technique
Authors: Kennedy Deborah A. , Lee Tanya , Seely Dugald
Published: February 2009

Breast cancer is the most frequently diagnosed cancer of women in North America. Despite advances in treatment that have reduced mortality, breast cancer remains the second leading cause of cancer induced death. Several well established tools are used to screen for breast cancer including clinical breast exams, mammograms, and ultrasound. Thermography was first introduced as a screening tool in 1956 and was initially well accepted. However, after a 1977 study found thermography to lag behind other screening tools, the medical community lost interest in this diagnostic approach. This review discusses each screening tool with a focus brought to thermography. No single tool provides excellent predictability; however, a combination that incorporates thermography may boost both sensitivity and specificity. In light of technological advances and maturation of the thermographic industry, additional research is required to confirm the potential of this technology to provide an effective non-invasive, low risk adjunctive tool for the early detection of breast cancer.
Antiangiogenic and Proapoptotic Activities of Allyl Isothiocyanate Inhibit Ascites Tumor Growth in Vivo
Authors: Kumar Akhilesh , D'Souza Saritha S. , Tickoo Sanjay , Salimath Bharathi P. , Singh H.B.
Published: February 2009

The authors investigate the antiangiogenic and proapoptotic effects of mustard essential oil containing allyl isothiocyanate (AITC) and explore its mechanism of action on Ehrlich ascites tumor (EAT) cells. Swiss albino mice transplanted with EAT cells were used to study the effect of AITC. AITC was effective at a concentration of 10 μm as demonstrated by the inhibition of proliferation of EAT cells when compared with the normal HEK293 cells. It significantly reduced ascites secretion and tumor cell proliferation by about 80% and inhibited vascular endothelial growth factor expression in tumor-bearing mice in vivo. It also reduced vessel sprouting and exhibited potent antiangiogenic activity in the chorioallantoic membrane and cornea of the rat. AITC arrested the growth of EAT cells by inducing apoptosis and effectively arrested cell cycle progression at the G1 phase. The results clearly suggest that AITC inhibits tumor growth by both antiangiogenic and proapoptotic mechanisms.
Reaction sintering and joining nickel aluminide to AISI 316 stainless steel by self-propagating high temperature synthesis
Authors: Qin L. , Hu J. , Cui C. , Wang H. , Guo Z.
Published: February 2009

Self-propagating high temperature synthesis (SHS) is a process whereby reactants are ignited to spontaneously transform to products in an exothermic reaction. The aim of this study is to propose a method to join nickel aluminide with AISI 316 stainless steel by SHS and to study the combustion synthesis of nickel aluminide. From the heat of combustion synthesis junctions were formed between annular AISI 316 stainless steel and a powder metallurgy compact of Ni and Al blends. The Al mole ratio for testing the joining grade in the initial powder mixture varied from 25 at.-% to 40 at.-%. In order to check the sufficiency of the SHS reaction, the test temperature was compared with the thermodynamic calculation values. The metallographic analysis indicated that NiAl and Ni3Al were formed in the joint layer.
Ultrasonic brazing of aluminium matrix composites assisted by operation of melting and squeezing
Authors: Zhao W. W. , Yan J. C. , Fu Q. J.
Published: February 2009

Particle-reinforced aluminium metal matrix composites were ultrasonically brazed. In situ compositing technology of a particle-reinforced bond is described in this article. The joints with lower strength showed a structure of composite material/bond metal/composite material after ultrasonic brazing. The double liquid–solid zones in the base material close to the bond were fabricated by means of melting the base materials at a relatively higher temperature. Then pressure was applied to the samples, the double liquid–solid zones and the bond were mixed with each other and a particle-reinforced bond formed. The microstructure of the particle-reinforced bond is very similar to that of the base composite materials. The shear strength of the bonds was improved dramatically.
Effect of boron on removal of iron from aluminium melts
Authors: Gao J. W. , Shu D. , Wang J. , Sun B. D.
Published: February 2009

Effect of boron on iron removal and the feasibility of formation of iron borides in Al melt were studied. The iron composition was not reduced by the addition of boron. Analysis using SEM/EDX and XRD indicated the formation of titanium and vanadium borides in the melt and no iron borides were detected. Thermodynamic calculations proved that iron cannot react with the added boron in the melt to form iron borides under the experimental conditions, and the lowest Fe concentration that can be purified by boron addition is ∼11·7 wt-%.
Evolution of solidification microstructure of centrifugal cast Ti–6Al–4V alloy
Authors: Sui Y. W. , Li B. S. , Liu A. H. , Guo J. J. , Fu H. Z.
Published: February 2009

Ti–6Al–4V alloy castings were obtained with different centrifugal holding time in induction skull melting. The effects of centrifugal radius, riser and centrifugal holding time on the solidification microstructure of centrifugal cast Ti–6Al–4V alloy were investigated in detail. Results show that, under a certain centrifugal holding time, the average grain size of Ti–6Al–4V alloy castings decreases with the increasing in centrifugal radius. The microstructure of the Ti–6–Al–4V alloy casting with riser is finer. Meanwhile, the grain size increases greatly as the centrifugal holding time decreasing from 15 to 1·5 min.
‘Spalling’ of SAC Pb free solders when used with nickel substrates
Authors: Snugovsky L. , Snugovsky P. , Perovic D. D. , Rutter J. W.
Published: February 2009

The term “spalling” refers to the formation in a solder joint of a second layer of intermetallic compound, in addition to and separate from the usual single layer that normally forms on the substrate. It has been observed in Pb-free solders of the SAC type when used in conjunction with a nickel finish. Explanations offered to account for this phenomenon have been based on thermodynamic phase equilibria observed in isothermal sections of the Sn corner of the Cu–Ni–Sn system at temperatures 20°C or more above the solidification temperature of the solder, and without regard to reactions that occur at low temperatures, during freezing. Recent measurement of the liquidus projection of the Sn corner of the Cu–Ni–Sn system as shown the occurrence of a ternary quasiperitectic reaction in the composition range in which “spalling” is observed. Evaluation of the effect of this quasiperitectic reaction shows that its operation during freezing of the solder can account for the “spalling” phenomenon.
The time course of the transcriptomic response of Sinorhizobium meliloti1021 following a shift to acidic pH
Authors: Hellweg Christoph , Pühler Alfred , Weidner Stefan
Published: February 2009

Background

The symbiotic soil bacterium Sinorhizobium meliloti often has to face low pH in its natural habitats. To identify genes responding to pH stress a global transcriptional analysis of S. meliloti strain 1021 following a pH shift from pH 7.0 to pH 5.75 was carried out. In detail, oligo-based whole genome microarrays were used in a time course experiment. The monitoring period covered a time span of about one hour after the pH shift. The obtained microarray data was filtered and grouped by K-means clustering in order to obtain groups of genes behaving similarly concerning their expression levels throughout the time course.

Results

The results display a versatile response of S. meliloti 1021 represented by distinct expression profiles of subsets of genes with functional relation. The eight generated clusters could be subdivided into a group of four clusters containing genes that were up-regulated and another group of four clusters containing genes that were down-regulated in response to the acidic pH shift. The respective mean expression progression of the four up-regulated clusters could be described as (i) permanently and strong, (ii) permanently and intermediate, (iii) permanently and progressive, and (iv) transiently up-regulated. The expression profile of the four down-regulated clusters could be characterized as (i) permanently, (ii) permanently and progressive, (iii) transiently, and (iv) ultra short down-regulated. Genes coding for proteins with functional relation were mostly cumulated in the same cluster, pointing to a characteristic expression profile for distinct cellular functions. Among the strongest up-regulated genes lpiA, degP1, cah, exoV and exoH were found. The most striking functional groups responding to the shift to acidic pH were genes of the exopolysaccharide I biosynthesis as well as flagellar and chemotaxis genes. While the genes of the exopolysaccharide I biosynthesis (exoY, exoQ, exoW, exoV, exoT, exoH, exoK exoL, exoO, exoN, exoP) were up-regulated, the expression level of the flagellar and chemotaxis genes (visR, motA, flgF, flgB, flgC, fliE, flgG, flgE, flgL, flbT, mcpU) simultaneously decreased in response to acidic pH. Other responding functional groups of genes mainly belonged to nitrogen uptake and metabolism (amtB, nrtB, nirB, nirD), methionine metabolism (metA, metF, metH, metK, bmt and ahcY) as well as ion transport systems (sitABCD, phoCD). It is noteworthy, that several genes coding for hypothetical proteins of unknown function could be identified as up-regulated in response to the pH shift.

Conclusion

It was shown that the short term response to acidic pH stress does not result in a simple induction or repression of genes, but in a sequence of responses varying in their intensity over time. Obviously, the response to acidic pH is not based on a few specific genes, but involves whole sets of genes associated with various cellular functions.
Optimal use of tandem biotin and V5 tags in ChIP assays
Authors: Kolodziej Katarzyna E , Pourfarzad Farzin , de Boer Ernie , Krpic Sanja , Grosveld Frank , Strouboulis John
Published: February 2009

Background

Chromatin immunoprecipitation (ChIP) assays coupled to genome arrays (Chip-on-chip) or massive parallel sequencing (ChIP-seq) lead to the genome wide identification of binding sites of chromatin associated proteins. However, the highly variable quality of antibodies and the availability of epitopes in crosslinked chromatin can compromise genomic ChIP outcomes. Epitope tags have often been used as more reliable alternatives. In addition, we have employed protein in vivo biotinylation tagging as a very high affinity alternative to antibodies. In this paper we describe the optimization of biotinylation tagging for ChIP and its coupling to a known epitope tag in providing a reliable and efficient alternative to antibodies.

Results

Using the biotin tagged erythroid transcription factor GATA-1 as example, we describe several optimization steps for the application of the high affinity biotin streptavidin system in ChIP. We find that the omission of SDS during sonication, the use of fish skin gelatin as blocking agent and choice of streptavidin beads can lead to significantly improved ChIP enrichments and lower background compared to antibodies. We also show that the V5 epitope tag performs equally well under the conditions worked out for streptavidin ChIP and that it may suffer less from the effects of formaldehyde crosslinking.

Conclusion

The combined use of the very high affinity biotin tag with the less sensitive to crosslinking V5 tag provides for a flexible ChIP platform with potential implications in ChIP sequencing outcomes.
A-002 (Varespladib), a phospholipase A2inhibitor, reduces atherosclerosis in guinea pigs
Authors: Leite Jose O , Vaishnav Ushma , Puglisi Michael , Fraser Heather , Trias Joaquim , Fernandez Maria Luz
Published: February 2009

Background

The association of elevated serum levels of secretory phospholipase A2(sPLA2) in patients with cardiovascular disease and their presence in atherosclerotic lesions suggest the participation of sPLA2enzymes in this disease. The presence of more advanced atherosclerotic lesions in mice that overexpress sPLA2enzymes suggest their involvement in the atherosclerotic process. Therefore, the sPLA2family of enzymes could provide reasonable targets for the prevention and treatment of atherosclerosis. Thus, A-002 (varespladib), an inhibitor of sPLA2enzymes, is proposed to modulate the development of atherosclerosis.

Methods

Twenty-four guinea pigs were fed a high saturated fat, high cholesterol diet (0.25%) for twelve weeks. Animals were treated daily with A-002 (n = 12) or vehicle (10% aqueous acacia; n = 12) by oral gavage. After twelve weeks, animals were sacrificed and plasma, heart and aorta were collected. Plasma lipids were measured by enzymatic methods, lipoprotein particles size by nuclear magnetic resonance, aortic cytokines by a colorimetric method, and aortic sinus by histological analyses.

Results

Plasma total cholesterol, HDL cholesterol and triglycerides were not different among groups. However, the levels of inflammatory cytokines interleukin (IL)-10, IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly reduced in the treatment group. This group also had a significant 27% reduction in cholesterol accumulation in aorta compared with placebo group. Morphological analysis of aortic sinus revealed that the group treated with A-002 reduced atherosclerotic lesions by 24%.

Conclusion

The use of A-002 may have a beneficial effect in preventing diet-induced atherosclerosis in guinea pigs.
Isolation of osteogenic progenitors from human amniotic fluid using a single step culture protocol
Authors: Antonucci Ivana , Iezzi Irene , Morizio Elisena , Mastrangelo Filiberto , Pantalone Andrea , Mattioli-Belmonte Monica , Gigante Antonio , Salini Vincenzo , Calabrese Giuseppe , Tetè Stefano , Palka Giandomenico , Stuppia Liborio
Published: February 2009

Background

Stem cells isolated from amniotic fluid are known to be able to differentiate into different cells types, being thus considered as a potential tool for cellular therapy of different human diseases. In the present study, we report a novel single step protocol for the osteoblastic differentiation of human amniotic fluid cells.

Results

The described protocol is able to provide osteoblastic cells producing nodules of calcium mineralization within 18 days from withdrawal of amniotic fluid samples. These cells display a complete expression of osteogenic markers (COL1, ONC, OPN, OCN, OPG, BSP, Runx2) within 30 days from withdrawal. In order to test the ability of these cells to proliferate on surfaces commonly used in oral osteointegrated implantology, we carried out cultures onto different test disks, namely smooth copper, machined titanium and Sandblasted and Acid Etching titanium (SLA titanium). Electron microscopy analysis evidenced the best cell growth on this latter surface.

Conclusion

The described protocol provides an efficient and time-saving tool for the production of osteogenic cells from amniotic fluid that in the future could be used in oral osteointegrated implantology.
Comparison of molecular dynamics and superfamily spaces of protein domain deformation
Authors: Velázquez-Muriel Javier A , Rueda Manuel , Cuesta Isabel , Pascual-Montano Alberto , Orozco Modesto , Carazo José-María
Published: February 2009

Background

It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space).

Results

Our analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary. The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily. Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases.

Conclusion

Theoretically, we obtained two conclusions. First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability. Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability. Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity. We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or ab initio protein folding.
BioSunMS: a plug-in-based software for the management of patients information and the analysis of peptide profiles from mass spectrometry
Authors: Cao Yuan , Wang Na , Ying Xiaomin , Li Ailing , Wang Hengsha , Zhang Xuemin , Li Wuju
Published: February 2009

Background

With wide applications of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), statistical comparison of serum peptide profiles and management of patients information play an important role in clinical studies, such as early diagnosis, personalized medicine and biomarker discovery. However, current available software tools mainly focused on data analysis rather than providing a flexible platform for both the management of patients information and mass spectrometry (MS) data analysis.

Results

Here we presented a plug-in-based software, BioSunMS, for both the management of patients information and serum peptide profiles-based statistical analysis. By integrating all functions into a user-friendly desktop application, BioSunMS provided a comprehensive solution for clinical researchers without any knowledge in programming, as well as a plug-in architecture platform with the possibility for developers to add or modify functions without need to recompile the entire application.

Conclusion

BioSunMS provides a plug-in-based solution for managing, analyzing, and sharing high volumes of MALDI-TOF or SELDI-TOF MS data. The software is freely distributed under GNU General Public License (GPL) and can be downloaded from http://sourceforge.net/projects/biosunms/.
Switching from premixed insulin to glargine-based insulin regimen improves glycaemic control in patients with type 1 or type 2 diabetes: a retrospective primary care-based analysis
Authors: Sharplin Peter , Gordon Jason , Peters John R , Tetlow Anthony P , Longman Andrea J , McEwan Philip
Published: February 2009

Background

Insulin glargine (glargine) and premixed insulins (premix) are alternative insulin treatments. This analysis evaluated glycaemic control in 528 patients with type 1 (n = 183) or type 2 (n = 345) diabetes, after switching from premix to a glargine-based regimen, using unselected general practice (GP) data.

Methods

Data for this retrospective observational analysis were extracted from a UK GP database (The Health Improvement Network). Patients were required to have at least 12 months of available data, before and after, switching from premix to a glargine-based regimen. The principal analysis was the change in HbA1c after 12 months of treatment with glargine; secondary analyses included change in weight, bolus usage and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable assessment of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables.

Results

Both cohorts showed significant reduction in mean HbA1c 12 months after the switch: by -0.67% (p < 0.001) in the type 1 cohort and by -0.53% (p < 0.001) in the type 2 cohort (adjusted data). The size of HbA1c improvement was positively correlated with baseline HbA1c; patients with a baseline HbA1c ≥ 10% had the greatest mean reduction in HbA1c, by -1.7% (p < 0.001) and -1.2% (p < 0.001), respectively. The proportion of patients receiving co-bolus prescriptions increased in the type 1 (mean 24.6% to 95.1%, p < 0.001) and type 2 (mean 16.2% to 73.9%, p < 0.001) cohorts. There was no significant change in weight in either cohort. Total mean insulin use increased in type 2 diabetes patients (from 0.67 ± 1.35 U/Kg to 0.88 ± 1.33 U/Kg, p < 0.001) with a slight decrease in type 1 diabetes patients (from 1.04 ± 2.51 U/Kg to 0.98 ± 2.58 U/Kg, p < 0.001).

Conclusion

In everyday practice, patients with type 1 or type 2 diabetes inadequately controlled by premix insulins experienced significant improvement in glycaemic control over 12 months after switching to a glargine-based insulin regimen. These findings support the use of a basal-bolus glargine-based regimen in patients poorly controlled on premix.
Surface displaced alfa-enolase of Lactobacillus plantarum is a fibronectin binding protein
Authors: Castaldo Cristiana , Vastano Valeria , Siciliano Rosa Anna , Candela Marco , Vici Manuela , Muscariello Lidia , Marasco Rosangela , Sacco Margherita
Published: February 2009

Background

Lactic acid bacteria of the genus Lactobacillus and Bifidobacterium are one of the most important health promoting groups of the human intestinal microbiota. Their protective role within the gut consists in out competing invading pathogens for ecological niches and metabolic substrates. Among the features necessary to provide health benefits, commensal microorganisms must have the ability to adhere to human intestinal cells and consequently to colonize the gut. Studies on mechanisms mediating adhesion of lactobacilli to human intestinal cells showed that factors involved in the interaction vary mostly among different species and strains, mainly regarding interaction between bacterial adhesins and extracellular matrix or mucus proteins. We have investigated the adhesive properties of Lactobacillus plantarum, a member of the human microbiota of healthy individuals.

Results

We show the identification of a Lactobacillus plantarum LM3 cell surface protein (48 kDa), which specifically binds to human fibronectin (Fn), an extracellular matrix protein. By means of mass spectrometric analysis this protein was identified as the product of the L. plantarum enoA1 gene, coding the EnoA1 alfa-enolase. Surface localization of EnoA1 was proved by immune electron microscopy. In the mutant strain LM3-CC1, carrying the enoA1 null mutation, the 48 kDa adhesin was not anymore detectable neither by anti-enolase Western blot nor by Fn-overlay immunoblotting assay. Moreover, by an adhesion assay we show that LM3-CC1 cells bind to fibronectin-coated surfaces less efficiently than wild type cells, thus demonstrating the significance of the surface displaced EnoA1 protein for the L. plantarum LM3 adhesion to fibronectin.

Conclusion

Adhesion to host tissues represents a crucial early step in the colonization process of either pathogens or commensal bacteria. We demonstrated the involvement of the L. plantarum Eno A1 alfa-enolase in Fn-binding, by studying LM3 and LM3-CC1 surface proteins. Isolation of LM3-CC1 strain was possible for the presence of expressed enoA2 gene in the L. plantarum genome, giving the possibility, for the first time to our knowledge, to quantitatively compare adhesion of wild type and mutant strain, and to assess doubtless the role of L. plantarum Eno A1 as a fibronectin binding protein.
Brachytherapy versus radical hysterectomy after external beam chemoradiation: a non-randomized matched comparison in IB2-IIB cervical cancer patients
Authors: Cetina Lucely , Garcia-Arias Alicia , Candelaria Myrna , Cantú David , Rivera Lesbia , Coronel Jaime , Bazan-Perkins Blanca , Flores Vladimir , Gonzalez Aaron , Dueñas-González Alfonso
Published: February 2009

Background

A current paradigm in the treatment of cervical cancer with radiation therapy is that intracavitary brachytherapy is an essential component of radical treatment. This is a matched retrospective comparison of the results of treatment in patients treated with external beam chemoradiation (EBRT-CT) and radical hysterectomy versus those treated with identical chemoradiation followed by brachytherapy.

Methods

In this non-randomized comparison EBRT-CT protocol was the same in both groups of 40 patients. In the standard treated patients, EBRT-CT was followed by one or two intracavitary Cesium (low-dose rate) applications within 2 weeks of finishing external radiation to reach a point A dose of at least 85 Gy. In the surgically treated patients, radical hysterectomy with bilateral pelvic lymph node dissection and para-aortic lymph node sampling were performed within 7 weeks after EBRT-CT. Response, toxicity and survival were evaluated.

Results

A total of 80 patients were analyzed. The patients receiving EBRT-CT and surgery were matched with the standard treated cases. There were no differences in the clinicopathological characteristics between groups or in the delivery of EBRT-CT. The pattern of acute and late toxicity differed. Standard treated patients had more chronic proctitis while the surgically treated had acute complications of surgery and hydronephrosis. At a maximum follow-up of 60 months, median follow-up 26 (2–31) and 22 (3–27) months for the surgery and standard therapy respectively, eight patients per group have recurred and died. The progression free and overall survival are the same in both groups.

Conclusion

The results of this study suggest that radical hysterectomy can be used after EBRT-CT without compromising survival in FIGO stage IB2-IIB cervical cancer patients in settings were brachytherapy is not available. A randomized study is needed to uncover the value of surgery after EBRT-CT.
Indexing TNF-αgene expression using a gene-targeted reporter cell line
Authors: Yan Ziying , Lei-Butters Diana , Engelhardt John F , Leno Gregory H
Published: February 2009

Background

Current cell-based drug screening technologies utilize randomly integrated reporter genes to index transcriptional activity of an endogenous gene of interest. In this context, reporter expression is controlled by known genetic elements that may only partially capture gene regulation and by unknown features of chromatin specific to the integration site. As an alternative technology, we applied highly efficient gene-targeting with recombinant adeno-associated virus to precisely integrate a luciferase reporter gene into exon 1 of the HeLa cell tumor necrosis factor-alpha (TNF-α) gene. Drugs known to induceTNF-αexpression were then used to compare the authenticity of gene-targeted and randomly integrated transcriptional reporters.

Results

TNF-α-targeted reporter activity reflected endogenousTNF-αmRNA expression, whereas randomly integratedTNF-αreporter lines gave variable expression in response to transcriptional and epigenetic regulators. 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), currently used in cancer clinical trials to induceTNF-αgene transcription, was only effective at inducing reporter expression fromTNF-αgene-targeted cells.

Conclusion

We conclude that gene-targeted reporter cell lines provide predictive indexing of gene transcription for drug discovery.
A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land
Authors: Emiliani Giovanni , Fondi Marco , Fani Renato , Gribaldo Simonetta
Published: February 2009

Background

The pioneering ancestor of land plants that conquered terrestrial habitats around 500 million years ago had to face dramatic stresses including UV radiation, desiccation, and microbial attack. This drove a number of adaptations, among which the emergence of the phenylpropanoid pathway was crucial, leading to essential compounds such as flavonoids and lignin. However, the origin of this specific land plant secondary metabolism has not been clarified.

Results

We have performed an extensive analysis of the taxonomic distribution and phylogeny of Phenylalanine Ammonia Lyase (PAL), which catalyses the first and essential step of the general phenylpropanoid pathway, leading from phenylalanine to p-Coumaric acid and p-Coumaroyl-CoA, the entry points of the flavonoids and lignin routes. We obtained robust evidence that the ancestor of land plants acquired a PALviahorizontal gene transfer (HGT) during symbioses with soil bacteria and fungi that are known to have established very early during the first steps of land colonization. This horizontally acquired PAL represented then the basis for further development of the phenylpropanoid pathway and plant radiation on terrestrial environments.

Conclusion

Our results highlight a possible crucial role of HGT from soil bacteria in the path leading to land colonization by plants and their subsequent evolution. The few functional characterizations of sediment/soil bacterial PAL (production of secondary metabolites with powerful antimicrobial activity or production of pigments) suggest that the initial advantage of this horizontally acquired PAL in the ancestor of land plants might have been either defense against an already developed microbial community and/or protection against UV.

Reviewers

This article was reviewed by Purificación López-García, Janet Siefert, and Eugene Koonin.
A comparative genomics study of genetic products potentially encoding ladderane lipid biosynthesis
Authors: Rattray Jayne E , Strous Marc , Op den Camp Huub JM , Schouten Stefan , Jetten Mike SM , Damsté Jaap S Sinninghe
Published: February 2009

Background

The fatty acids of anaerobic ammonium oxidizing (anammox) bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway.

Results

Gene clusters encoding enzymes of fatty acid biosynthesis in the anammox bacterium Kuenenia stuttgartiensis and 137 other organisms were analysed and compared in silico to gain further insight into the pathway of (ladderane) fatty acid biosynthesis. In K. stuttgartiensis four large gene clusters encode fatty acid biosynthesis. Next to the regular enzyme complex needed for fatty acid biosynthesis (FASII), the presence of four putative S-adenosyl-methionine (SAM) radical enzymes, two enzymes similar to phytoene desaturases and many divergent paralogues of β-ketoacyl-ACP synthase (fabF) were unusual. Surprisingly, extensive synteny was observed with FASII gene clusters in the deltaproteobacterium Desulfotalea psychrophila. No ladderane lipids were detected in lipid extracts of this organism but we did find unusual polyunsaturated hydrocarbons (PUHC), not detected in K. stuttgartiensis.

Conclusion

We suggest that the unusual gene clusters of K. stuttgartiensis and D. psychrophila encode a novel pathway for anaerobic PUFA biosynthesis and that K. stuttgartiensis further processes PUFA into ladderane lipids, in similar fashion to the previously proposed route of ladderane lipid biosynthesis. However, the presence of divergent paralogues of fabF with radically different active site topologies may suggest an alternative pathway where ladderane moieties are synthesised externally and are recruited into the pathway of fatty acid biosynthesis.

Reviewers

This article was reviewed by Dr Michael Galperin (nominated by Prof E. Koonin), Dr Andrei Osterman and Dr Jeremy Selengut.
Knockdown of astrocyte elevated gene-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells
Authors: Liu Haiyan , Song Xianrang , Liu Chunxi , Xie Li , Wei Ling , Sun Ruopeng
Published: February 2009

Background

Astrocyte elevated gene-1 (AEG-1) was originally characterized as a HIV-1-inducible gene in primary human fetal astrocyte. Recent studies highlight a potential role of AEG-1 in promoting tumor progression and metastasis. The aim of this study was to investigate if AEG-1 serves as a potential therapeutic target of human neuroblastoma.

Methods

We employed RNA interference to reduce AEG-1 expression in human neuroblastoma cell lines and analyzed their phenotypic changes.

Results

We found that the knockdown of AEG-1 expression in human neuroblastoma cells significantly inhibited cell proliferation and apoptosis. The specific downregulation induced cell arrest in the G0/G1 phase of cell cycle. In the present study, we also observed a significant enhancement of chemo-sensitivity to cisplatin and doxorubicin by knockdown of AEG-1.

Conclusion

Our study suggests that overexpressed AEG-1 enhance the tumorogenic properties of neuroblastoma cells. The inhibition of AEG-1 expression could be a new adjuvant therapy for neuroblastoma.
The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype
Authors: Ruijs Marielle WG , Broeks Annegien , Menko Fred H , Ausems Margreet GEM , Wagner Anja , Oldenburg Rogier , Meijers-Heijboer Hanne , van't Veer Laura J , Verhoef Senno
Published: February 2009

Background

CHEK2has previously been excluded as a major cause of Li-Fraumeni syndrome (LFS). One particularCHEK2germline mutation, c.1100delC, has been shown to be associated with elevated breast cancer risk. The prevalence ofCHEK2*1100delC differs between populations and has been found to be relatively high in the Netherlands. The question remains nevertheless whetherCHEK2germline mutations contribute to the Li-Fraumeni phenotype.

Methods

We have screened 65 DutchTP53-negative LFS/LFL candidate patients forCHEK2germline mutations to determine their contribution to the LFS/LFL phenotype.

Results

We identified six index patients with aCHEK2sequence variant, four with the c.1100delC variant and two sequence variants of unknown significance, p.Phe328Ser and c.1096-?_1629+?del.

Conclusion

Our data show thatCHEK2is not a major LFS susceptibility gene in the Dutch population. However,CHEK2might be a factor contributing to individual tumour development inTP53-negative cancer-prone families.