bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of NF‐κB activation with designed ankyrin‐repeat proteins targeting the ubiquitin‐binding/oligomerization domain of NEMO
Authors: Wyler Emanuel , Kaminska Monika , Coïc Yves‐Marie , Baleux Françoise , Véron Michel , Agou Fabrice 
Published: August 2007

AbstractThe link between the NF‐κB signal transduction pathway and cancer is now well established. Inhibiting this pathway is therefore a promising approach in the treatment of certain cancers through a pro‐apoptotic effect in malignant cells. Owing to its central role in the pathway, the IκB kinase (IKK) complex is a privileged target for designing inhibitors. Previously, we showed that oligomerization of NEMO is necessary for IKK activation and defined a minimal oligomerization domain (CC2‐LZ) for NEMO, and we developed NEMO peptides inhibiting NF‐κB activation at the level of the IKK complex. To improve the low‐affinity inhibitors, we used ribosome display to select small and stable proteins with high affinity against the individual CC2‐LZ because the entire NEMO protein is poorly soluble. Several binders with affinities in the low nanomolar range were obtained. When expressed in human cells, some of the selected molecules, despite their partial degradation, inhibited TNF‐α‐mediated NF‐κB activation while having no effect on the basal activity. Controls with a naive library member or null plasmid had no effect. Furthermore, we could show that this NF‐κB inhibition occurs through a specific interaction between the binders and the endogenous NEMO, resulting in decreased IKK activation. These results indicate that in vitro selections with the NEMO subdomain alone as a target may be sufficient to lead to interesting compounds that are able to inhibit NF‐κB activation.
Patterns of protein–protein interactions in salt solutions and implications for protein crystallization
Authors: Dumetz André C. , Snellinger‐O'Brien Ann M. , Kaler Eric W. , Lenhoff Abraham M. 
Published: August 2007

AbstractThe second osmotic virial coefficients of seven proteins—ovalbumin, ribonuclease A, bovine serum albumin, α‐lactalbumin, myoglobin, cytochrome c, and catalase—were measured in salt solutions. Comparison of the interaction trends in terms of the dimensionless second virial coefficient b2 shows that, at low salt concentrations, protein–protein interactions can be either attractive or repulsive, possibly due to the anisotropy of the protein charge distribution. At high salt concentrations, the behavior depends on the salt: In sodium chloride, protein interactions generally show little salt dependence up to very high salt concentrations, whereas in ammonium sulfate, proteins show a sharp drop in b2 with increasing salt concentration beyond a particular threshold. The experimental phase behavior of the proteins corroborates these observations in that precipitation always follows the drop in b2. When the proteins crystallize, they do so at slightly lower salt concentrations than seen for precipitation. The b2 measurements were extended to other salts for ovalbumin and catalase. The trends follow the Hofmeister series, and the effect of the salt can be interpreted as a water‐mediated effect between the protein and salt molecules. The b2 trends quantify protein–protein interactions and provide some understanding of the corresponding phase behavior. The results explain both why ammonium sulfate is among the best crystallization agents, as well as some of the difficulties that can be encountered in protein crystallization.
The solution structure of the ZnF UBP domain of USP33/VDU1
Authors: Allen Mark D. , Bycroft Mark 
Published: August 2007

AbstractUSP33/VDU1 is a deubiquitinating enzyme that binds to the von Hippel–Lindau tumor suppressor protein. It also regulates thyroid hormone activation by deubiquitinating type 2 iodothyronine deiodinase. USP33/VDU1 contains a ZF UBP domain, a protein module found in many proteins in the ubiquitin–proteasome system. Several ZF UBP domains have been shown to bind ubiquitin, and a structure of a complex of the ZF UBP domain of isoT/USP5 and ubiquitin is available. In the present work, the solution structure of the ZF UBP domain of USP33/VDU1 has been determined by NMR spectroscopy. The structure differs from that of the USP5 domain, which contains only one of the three Zn ions present in the USP33/VDU1 structure. The USP33/VDU1 ZnF UBP domain does not bind to ubiquitin.
Impaired expression of indoleamine 2, 3‐dioxygenase in monocyte‐derived dendritic cells in response to Toll‐like receptor‐7/8 ligands
Authors: Furset Gro , Fløisand Yngvar , Sioud Mouldy 
Published: August 2007

SummaryThe effects of immunostimulatory RNAs (isRNAs) on the expression of immuno‐suppressive factors are largely unknown. Indoleamine 2,3‐dioxygenase (IDO) is a key negative regulator of immune responses and it has been implicated in hampering immunity against tumours. Here we show that the activation of Toll‐like receptors (TLR)‐7/8 with isRNAs or R848, a specific ligand for TLR7/8, can induce IDO expression in human monocytes, but not in monocyte‐derived dendritic cells (moDC). In contrast to TLR7/8 agnosists, treatment of the same moDC with interferon‐γ‐induced IDO expression. Treatment of monocytes with 2′‐O‐methyl uridine‐modified isRNAs alone does not induce IDO, but totally abrogated the effects of unmodified isRNAs. Like isRNAs, synthetic viral RNAs and cytomegalovirus (CMV) induced IDO in monocytes, whereas TLR2 ligand lipopeptide Pam3Cys exhibited no effect. Furthermore, IDO positive monocytes suppressed autologous T‐cell activation. Collectively, these data indicate for first time that the potency of TLR7/8 signalling pathways to induce IDO expression in monocytes is silenced when the cells are programmed to differentiate into dendritic cells. The immunosuppressive properties of IDO might confer an advantage to CMV‐infected monocytes to escape T‐cell responses. The findings that 2′‐O‐methyl modified RNAs can block isRNA‐induced IDO expression would facilitate the design of new TLR inhibitors.
Determination of pattern centre in EBSD using the moving‐screen technique
Authors: CARPENTER D. A. , PUGH J. L. , RICHARDSON G. D. , MOONEY L. R. 
Published: August 2007

SummaryThe ‘moving‐screen’ or ‘pattern magnification’ method of calibration for electron backscatter diffraction (EBSD) was reformulated to develop a high‐precision technique requiring no crystallographic knowledge of the specimen and no initial estimates of the calibration parameters. The technique depends upon the accurate displacement of the screen and camera assembly. Corresponding points are selected, interactively, from EBSD patterns. It is suggested that, as an alternative, the selection of points from the Hough transform could lead to a completely automated routine.
Quantification of the 3D microstructure of SC surfaces
Authors: CHINGA GARY , JOHNSEN PER OLAV , DOUGHERTY ROBERT , BERLI ELISABETH LUNDEN , WALTER JOACHIM 
Published: August 2007

SummaryThis study presents the development of an ImageJ plugin for surface characterization. Based on gradient analysis, parameters, such as the gradient magnitude, orientation, mean resultant vector and surface area are derived. A comparative study of supercalendered (SC) papers was performed to verify the surface representations yielded by a laser profilometer. The surface representations of samples covered with carbon and gold were compared to untreated samples. The results confirm the suitability of gold coating for reducing the artefacts encountered on laser profilometry surface representations of paper. In addition, a complete scanning electron microscopy analysis is performed on the assessed samples to quantify the surface fraction covered by mineral fillers and to reveal the true 3D microstructure of SC surfaces. The influence of filler coverage and filler type on the gloss level of commercial SC papers is evaluated. The relationship between the surface topography, gloss and PPS roughness for a series of commercial SC papers is established.
Grain size measurement by EBSD in complex hot deformed metal alloy microstructures
Authors: MINGARD K.P. , ROEBUCK B. , BENNETT E.G. , THOMAS M. , WYNNE B.P. , PALMIERE E.J. 
Published: August 2007

SummaryThe measurement of grain size by EBSD has been studied to enable representative quantification of the microstructure of hot deformed metal alloys with a wide grain size distributions. Variation in measured grain size as a function of EBSD step size and noise reduction techniques has been assessed. Increasing the EBSD step size from 5% to 20% of the approximate mean grain size results in a change in calculated arithmetic mean grain size of approximately 15% and standard noise reduction techniques can produce a further change in reported size of up to 20%. The distribution of measured grain size is found not to be log‐normal, with a long tail of very small sizes in agreement with a computer simulation of linear intercept and areal grain size measurements through randomly oriented grains. Comparison of EBSD with optical measurements of grain size on the same samples shows that, because of the ability of EBSD to distinguish twins and resolve much smaller grains a difference of up to 50% in measured grain size results.
Integrative use of spatial, genetic, and demographic analyses for investigating genetic connectivity between migratory, montane, and sedentary caribou herds
Authors: BOULET MARYLÈNE , COUTURIER SERGE , CÔTÉ STEEVE D. , OTTO ROBERT D. , BERNATCHEZ LOUIS 
Published: September 2007

AbstractGenetic differentiation is generally assumed to be low in highly mobile species, but this simplistic view may obscure the complex conditions and mechanisms allowing genetic exchanges between specific populations. Here, we combined data from satellite‐tracked migratory caribou (Rangifer tarandus), microsatellite markers, and demographic simulations to investigate gene flow mechanisms between seven caribou herds of eastern Canada. Our study included one montane, two migratory, and four sedentary herds. Satellite‐tracking data indicated possibilities of high gene flow between migratory herds: overlap of their rutting ranges averaged 10% across years and 9.4% of females switched calving sites at least once in their lifetime. Some migratory individuals moved into the range of the sedentary herds, suggesting possibilities of gene flow between these herds. Genetic differentiation between herds was weak but significant (FST = 0.015): migratory and montane herds were not significantly distinct (FSTall ≤ 0.005), whereas sedentary herds were more differentiated (FST = 0.018–0.048). Geographical distances among sedentary herds limited gene flow. Historical estimates of gene flow were higher from migratory herds into sedentary herds (4Nmall > 9) than vice‐versa (4Nmall < 5), which suggests migratory herds had a demographic impact on sedentary herds. Demographic simulations showed that an effective immigration rate of 0.0005 was sufficient to obtain the empiricalFSTof 0.015, while a null immigration rate increased the simulatedFSTto > 0.6. In conclusion, the weak genetic differentiation between herds cannot be obtained without some genetic exchanges among herds, as demonstrated by genetic and spatial data.
Genetic differentiation across a latitudinal gradient in two co‐occurring butterfly species: revealing population differences in a context of climate change
Authors: ZAKHAROV EVGUENI V. , HELLMANN JESSICA J. 
Published: September 2007

AbstractGenetic differentiation within a species’ range is determined by natural selection, genetic drift, and gene flow. Selection and drift enhance genetic differences if populations are sufficiently isolated, while gene flow precludes differentiation and local adaptation. Over large geographical areas, these processes can create a variety of scenarios, ranging from admixture to a high degree of population differentiation. Genetic differences among populations may signal functional differences within a species’ range, potentially leading to population or ecotype‐specific responses to global change. We investigated differentiation within the geographical range of two butterfly species along a broad latitudinal gradient. This gradient is the primary axis of climatic variation, and many ecologists expect populations at the poleward edge of this gradient to expand under climate change. Our study species inhabit a shared ecosystem and differ in body size and resource specialization; both also find their poleward range limit on an island. We find evidence for divergence of peripheral populations from the core in both taxa, suggesting the potential for genetic distinctiveness at the leading edge of climate change. We also find differences between the species in the extent of peripheral differentiation with the smaller and more specialized species showing greater population divergence (microsatellites and mtDNA) and reduced gene flow (mtDNA). Finally, gene flow estimates in both species differed strongly between two marker types. These findings suggest caution in assuming that populations are invariant across latitude and thus will respond as a single ecotype to climatic change.
Molecular evolution of the Li/li chemical defence polymorphism in white clover (Trifolium repens L.)
Authors: OLSEN K. M. , SUTHERLAND B. L. , SMALL L. L. 
Published: September 2007

AbstractWhite clover (Trifolium repens) is naturally polymorphic for cyanogenesis (hydrogen cyanide release following tissue damage). The ecological factors favouring cyanogenic and acyanogenic plants have been examined in numerous studies over the last half century, making this one of the best‐documented examples of an adaptive polymorphism in plants. White clover cyanogenesis is controlled by two, independently segregating Mendelian genes: Ac/ac controls the presence/absence of cyanogenic glucosides; and Li/li controls the presence/absence of their hydrolysing enzyme, linamarase. In this study, we examine the molecular evolution and population genetics of Li as it relates to the cyanogenesis polymorphism. We report here that Li exists as a single‐copy gene in plants possessing linamarase activity, and that the absence of enzyme activity in li/li plants is correlated with the absence of much or all of the gene from the white clover genome. Consistent with this finding, we confirm by reverse transcription–polymerase chain reaction that Li gene expression is absent in plants lacking enzyme activity. In a molecular population genetic analysis of Li and three unlinked genes using a worldwide sample of clover plants, we find an absence of nucleotide variation and statistically significant deviations from neutrality at Li; these findings are consistent with recent positive directional selection at this cyanogenesis locus.
Birthweight distributions by gestational age: comparison of LMP‐based and ultrasound‐based estimates of gestational age using data from the Swedish Birth Registry
Authors: Haglund Bengt 
Published: September 2007

SummaryStudies based on data from the US have reported that the birthweight distribution at gestational age 28–31 weeks is bimodal with a second peak occurring at approximately 3300 g, suggesting that there is misclassification of term infants. In these studies, gestational ages were estimated from the date of the last menstrual period (LMP), and it has been suggested that ultrasound‐based estimates of gestational age would eliminate the problem with bimodal birthweight distributions. Swedish data include both measures, thus offering an opportunity for comparison. All singleton births in Sweden from 1993 to 2002 with information on birthweight were included in the study (n = 917 901). Both LMP‐ and ultrasound‐based estimates of gestational age were available for 75.1% of the births. Two possible sources of misclassification were considered: measurement error, assuming that ultrasound‐based estimates are better, and data entry errors. An algorithm for assessment of data entry errors was developed; 67.4% of the births were left for the analyses of data ‘cleaned’ from data entry errors.Based on the entire study population, the LMP‐based birthweight curves for lower‐gestational‐age preterm births were bimodal, with a second peak around 3500 g. The bimodal distribution was greatly attenuated when using ultrasound‐based gestational age categories, but did not disappear. After cleaning the data, the LMP‐based birthweight distributions for infants at gestational ages <32 weeks were no longer bimodal, and were very similar to the ultrasound‐based curves. In conclusion, data entry errors are more likely to cause the bimodality in the birthweight distribution among preterm infants than measurement errors in the LMP‐based gestational age estimate.
Postoperative intra‐abdominal adhesions: a personal view
Authors: Ellis H. 
Published: September 2007

AbstractThis paper reviews a near half century of interest and personal involvement in the topic of intra‐abdominal adhesions. During this time, much has been learned about the aetiology of this condition, which results from the presence of ischaemic or foreign material in the peritoneal cavity. This knowledge, in turn, has led to modifications in our operative practices. While for many years a rather neglected subject, recent studies have stressed the complications that may result from adhesions, in particular small bowel obstruction, and have documented the clinical burden of adhesions on the health services. For over a century, surgeons have investigated means of preventing or at least modifying the formation of adhesions. At first, these were carried out in a quite arbitrary manner, but in more recent times, there has been a more rational approach, based on our clearer knowledge of their aetiology.
Biology of the peritoneum in normal homeostasis and after surgical trauma
Authors: Van Der Wal J. B. C. , Jeekel J. 
Published: September 2007

AbstractThe peritoneum is a serous membrane, which has a protective function for the contents of the abdominal cavity. It maintains homeostasis by allowing exchange of molecules and production of peritoneal fluid, thus providing an environment in which intra‐abdominal organs can function properly. When traumatized, whether by surgery or due to inflammatory processes, a series of responses come into action to regenerate the injured part of the peritoneum. The inflammatory reaction causes influx of inflammatory cells but also activates resident mesothelial cells, ultimately leading to a fibrinous exudate. Depending on the severity of the trauma this exudate is transient due to fibrinolysis, or becomes more dense as a result of fibroblasts persisting, leading to fibrinous adhesions. A pivotal role is taken by the enzyme plasmin and its promotors and inhibitors; it is mainly the tissue‐type plasminogen activator/plasminogen activator inhibitor ratio which determines the rate of fibrinolysis and therefore the rate of adhesion formation. The rate of injury determines the rate and extent of the inflammatory response to that injury; in its turn the inflammatory reaction determines the extent of adhesion formation. One should realize this when performing intra‐abdominal surgery, which is in fact operating inside the peritoneal organ.
BAYESIAN BETA REGRESSION: APPLICATIONS TO HOUSEHOLD EXPENDITURE DATA AND GENETIC DISTANCE BETWEEN FOOT‐AND‐MOUTH DISEASE VIRUSES
Authors: Branscum Adam J. , Johnson Wesley O. , Thurmond Mark C. 
Published: August 2007

SummaryThere is considerable interest in understanding how factors such as time and geographic distance between isolates might influence the evolutionary direction of foot‐and‐mouth disease. Genetic differences between viruses can be measured as the proportion of nucleotides that differ for a given sequence or gene. We present a Bayesian hierarchical regression model for the statistical analysis of continuous data with sample space restricted to the interval (0, 1). The data are modelled using beta distributions with means that depend on covariates through a link function. We discuss methodology for: (i) the incorporation of informative prior information into an analysis; (ii) fitting the model using Markov chain Monte Carlo sampling; (iii) model selection using Bayes factors; and (iv) semiparametric beta regression using penalized splines. The model was applied to two different datasets.
The prevalence of intellectual disability in a major UK prison
Authors: Hayes Susan , Shackell Phil , Mottram Pat , Lancaster Rachel 
Published: September 2007

Accessible summary

This research aimed to find out how many people in a big English prison had a learning disability.
One‐tenth of the people in the prison were chosen to take part. There were 140 prisoners involved in the study.
The prisoners were asked questions about their lives and took tests to see if they had a learning disability.
The researchers found there were more people with learning disabilities in prison than people had thought before.
People in prison who have a learning disability need extra help.
People who have a learning disability also need special help when they leave prison and go back to live in the community.

SummaryOver‐representation of people with learning disability in prisons has been demonstrated in many Western jurisdictions. This was the first comprehensive research in a UK prison. The research used a random 10% sample of a prison population (n = 140). A semi‐structured interview, the Wechsler Adult Intelligence Scale – III (UK version) and the Vineland Adaptive Behavior Scales (VABS) Interview Edition were administered. On the Wechsler Adult Intelligence Scale – III, UK version (WAIS‐III (UK)), 7.1% of participants achieved standard scores below 70 and a further 23.6% were in the 70–79 (borderline) range. The VABS results indicated that 10.1% had standard scores below 70 and a further 33.3% were in the borderline range. The results indicate that the prevalence of intellectual (or learning) disability as measured on either or both of the WAIS‐III (UK) or the Vineland Adaptive Behavior Scales is higher than previous research in the UK has indicated. The results have implications for provision of services in prison and post‐release.
ULTRAPLANKTON BIOMASS, PRODUCTIVITY AND EFFICIENCY IN LAC MATAMEC, A PRECAMBRIAN SHIELD LAKE1,2
Authors: Ross P. E. , Duthie H. C. 
Published: August 2007

ABSTRACTIn extremely oligotrophic Lac Matamec (Quebec, Canada) the ultraplankton (<15 μm) represented 47% of total phytoplankton biomass but accounted for 71% of the primary production and was 2.5 times more photosynthetically efficient than larger phytoplankton. Cell surface area was a good predictor of efficiency, while cell numbers and bio‐mass were not. High surface:volume ratios may explain the high efficiency of the ultraplankton.