bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivoresponse to electrochemically aligned collagen bioscaffolds
Authors: Kishore Vipuil , Uquillas Jorge Alfredo , Dubikovsky Alexandra , Alshehabat Musa A. , Snyder Paul W. , Breur Gert J. , Akkus Ozan
Published: December 2011

Collagen‐based biomaterials are a viable option for tendon reconstruction and repair. However, the weak mechanical strength of collagen constructs is a major limitation. We have previously reported a novel methodology to form highly oriented electrochemically aligned collagen (ELAC) threads with mechanical properties converging on those of the natural tendon. In this study, we assessed thein vivoresponse of rabbit patellar tendon (PT) to braided ELAC bioscaffolds. Rabbit PTs were incised longitudinally and the ELAC bioscaffold was inlaid in one limb along the length of the tendon. The contralateral limb served as the sham‐operated control. Rabbits were euthanized at 4 or 8 months postoperatively. High‐resolution radiographs revealed the absence of ectopic bone formation around the bioscaffolds. Four months post‐implantation, the histological sections showed that the ELAC bioscaffold underwent limited degradation and was associated with a low‐grade granulomatous inflammation. Additionally, quantitative histology revealed that the cross‐sectional areas of PTs with the ELAC bioscaffold were 29% larger compared with the controls. Furthermore, ELAC‐treated PTs were significantly stiffer compared with the controls. The volume fraction of the tendon fascicle increased in the ELAC‐treated PT compared with the controls. By 8 months, the ELAC bioscaffold was mostly absorbed and the enlargement in the area of tendons with implants subsided along with the resolution of the granulomatous inflammation. We conclude that ELAC is biocompatible and biodegradable and has the potential to be used as a biomaterial for tendon tissue engineering applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 400–408, 2012.
Chemical composition, antioxidant and antimicrobial properties of Rapa Catozza Napoletana (Brassica rapa L. var. rapa DC.) seed meal, a promising protein source of Campania region (southern Italy) horticultural germplasm
Authors: Carlo Tenore Gian , Troisi Jacopo , Di Fiore Raffaele , Basile Adriana , Novellino Ettore
Published: December 2011

BACKGROUND: The present study is the first effort in a comprehensive evaluation of the nutritive and biological properties of the meal from Rapa Catozza Napoletana (RCN) (Brassica rapa L. var. rapa) cultivar seeds as a new and alternative source of proteins.

RESULTS: RCN seed meal revealed a good protein content (382.0 g kg−1) compared with conventional Brassica defatted meals. Total glucosinolates (6.0 g kg−1) were comparable to or even lower than those reported for other yellow‐ and brown‐seeded cultivars. Low levels of both sinapine and phytic acid (10.0 and 10.0 g kg−1 respectively) suggest a minor influence of these compounds on meal mineral availability. The meal revealed quite a high polyphenolic content (13.0 g kg−1) composed of flavonol and hydroxycinnamic derivatives. With regard to meal biological properties, a higher radical‐scavenging potential than reducing capacity and a broad antimicrobial spectrum, mainly against food‐borne pathogens, were detected.

CONCLUSION: RCN seed meal could be highly regarded as a component of human nutrition and animal feed for its good protein content, desirable amino acid profile and low antinutrient concentration. Results for the sample indicated appreciable antiradical activity and good properties for meal stability. Copyright © 2011 Society of Chemical Industry
Tiliroside, a glycosidic flavonoid, inhibits carbohydrate digestion and glucose absorption in the gastrointestinal tract
Authors: Goto Tsuyoshi , Horita Mayuka , Nagai Hiroyuki , Nagatomo Akifumi , Nishida Norihisa , Matsuura Youichi , Nagaoka Satoshi
Published: December 2011

Scope Recent studies have reported that tiliroside, a glycosidic flavonoid, possesses anti‐diabetic activities. In the present study, we investigated the effects of tiliroside on carbohydrate digestion and absorption in the gastrointestinal tract.

Methods and results This study showed that tiliroside inhibits pancreatic α‐amylase (IC50 = 0.28 mM) in vitro. Tiliroside was found as a noncompetitive inhibitor of α‐amylase with Ki values of 84.2 μM. In male ICR mice, the increase in postprandial plasma glucose levels was significantly suppressed in the tiliroside‐administered group. Tiliroside treatment also suppressed hyperinsulinemia after starch administration. Tiliroside administration inhibited the increase of plasma glucose levels in an oral glucose tolerance test, but not in an intraperitoneal glucose tolerance test. In human intestinal Caco‐2 cells, the addition of tiliroside caused a significant dose‐dependent inhibition of glucose uptake. The inhibitory effects of both sodium‐dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) inhibitors (phlorizin and phloretin, respectively) on glucose uptake were significantly inhibited in the presence of tiliroside, suggesting that tiliroside inhibited glucose uptake mediated by both SGLT1 and GLUT2.

Conclusion These findings indicate that the anti‐diabetic effects of tiliroside are at least partially mediated through inhibitory effects on carbohydrate digestion and glucose uptake in the gastrointestinal tract.
Reproducibility and repeatability of quantitative sodium magnetic resonance imaging in vivo in articular cartilage at 3 T and 7 T
Authors: Madelin Guillaume , Babb James S. , Xia Ding , Chang Gregory , Jerschow Alexej , Regatte Ravinder R.
Published: December 2011

Osteoarthritis is a degenerative disease of articular cartilage that may be associated with a loss of glycosaminoglycans. Quantitative sodium magnetic resonance imaging is highly specific to glycosaminoglycan content and could be used to assess the biochemical degradation of cartilage in early osteoarthritis. However, the reproducibility and repeatability of this technique are not well documented. The aim of this study is to test the reproducibility and repeatability of sodium quantification in cartilage in vivo using intraday and interday acquisitions at 3 T and 7 T, with a radial 3D sequence, with and without fluid suppression. Fluid suppression was obtained by adiabatic inversion recovery (IR WURST) and is expected to improve the sensitivity of the method to glycosaminoglycan content. The root mean square of coefficients of variation are all in the range of 7.5–13.6%. No significant intermagnet, intersequence, intraday, and interday differences in the coefficients of variation were observed. Sodium quantification using IR WURST gave values closer to those reported in the literature for healthy cartilage (220–310 mM) than radial 3D. In conclusion, IR WURST was more accurate in context of sodium measurement, with a reproducibility and repeatability comparable to other compositional magnetic resonance imaging techniques of cartilage. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Obesity and metabolic syndrome in adolescent survivors of standard risk childhood acute lymphoblastic leukemia in Saudi Arabia
Authors: Aldhafiri Fahad , Al‐Nasser Abdullah , Al‐Sugair Abdulaziz , Al‐Mutairi Hanan , Young David , Reilly John J
Published: December 2011

Background

This study estimated prevalence of unhealthy weight status and metabolic syndrome (MS) amongst Saudi survivors of standard risk ALL.

Procedure

We recruited 56 survivors, mean age 13.4 years (SD 4.1), a mean of 9.1 years (SD 4.1) post‐diagnosis. The BMI for age was used to define weight status relative to national (Saudi) and international (Cole et al., Cole‐IOTF, WHO, and CDC) reference data. We measured body composition by dual‐energy X‐ray absorptiometry (DXA), waist circumference, blood pressure, lipid profile (HDL‐C, Triglycerides), fasting glucose and insulin.

Results

According to international definitions based on BMI for age, around half of the sample had unhealthy weight status. All of the approaches based on BMI for age underestimated overfatness, present in 27/51 (53%) of the sample according to DXA. Prevalence of MS was 7.1% (3/42 of those over 9‐years old) and 5.4% (3/56) by applying the International Diabetes Federation (IDF) definition and National Cholesterol Education Program Third Adult Treatment panel Guidelines (NCEP III), respectively. However, MS by the NCEP III definition was present in 19% of the overweight and obese survivors and 7.1% of the sample had at least two of the components of MS.

Conclusion

Unhealthy body weight and overfatness may be common amongst adolescent Saudi survivors of standard risk ALL, though overweight and obesity may be no more common than in the general Saudi adolescent population. Defining weight status using BMI underestimates overfatness. Ideally, body composition and cardiometabolic risk factors should be monitored at late effects clinics. Pediatr Blood Cancer 2012; 59: 133–137. © 2011 Wiley Periodicals, Inc.
Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma
Authors: de Oliveira Reis Adriana Helena , de Carvalho Ivna Néria Silva Ribamar , de Sousa Damasceno Paula Batista , Ferman Sima Esther , Lucena Evandro , Lopez‐Camelo Jorge Santiago , Seuánez Héctor N. , Vargas Fernando Regla
Published: December 2011

Background

Retinoblastoma (RB) accounts for 3% of all childhood malignancies, with different incidences around the world. This malignancy results from loss‐of‐function of both RB1 alleles although other genes, like MDM2 and MDM4, have been proposed to be involved in tumor development.

Procedure

We genotyped rs2279744T>G and rs937283A>G in MDM2, and rs4252668T>C and rs116197192G>A in MDM4, in 104 unrelated RB patients and 104 controls. Sixty‐month survival Kaplan–Meier curves and χ2‐tests were performed for estimating the putative effect of MDM2 and MDM4 alleles on disease progression and survival of RB patients.

Results

MDM2 rs2279744G was significantly more frequent in controls, indicating an apparently protective effect on RB development. However, survival of patients who carried a constitutional RB1 mutation was significantly lower with rs2279744TG or GG than with rs2279744TT. Presence of rs2279744G and a constitutional RB1 mutation was sixfold more frequent in the 0–12 month age group than other age groups at onset of symptoms (P = 0.0401). MDM4 rs4252668C was present at a significantly higher frequency in controls while the frequency of MDM4 rs116197192G was significantly higher in RB patients, suggesting that this allele might increase the risk of developing RB.

Conclusion

Our results indicate that MDM2 and MDM4 polymorphisms may influence development and/or survival in RB. Pediatr Blood Cancer 2012; 59: 39–43. © 2011 Wiley Periodicals, Inc.
SIX1 protein expression selectively identifies blastemal elements in Wilms tumor
Authors: Sehic Daniel , Karlsson Jenny , Sandstedt Bengt , Gisselsson David
Published: December 2011

Background

Wilms tumor (WT) is the most common renal neoplasm in children. Histologically, most WTs consist of three tissue elements: blastema, epithelium, and stroma. Some cases also show diffuse or focal anaplastic features. Previous studies have shown that a predominance of blastemal cells in post‐chemotherapy WT specimens is associated with a poor clinical course. However, there is currently no molecular marker for blastemal cells, and risk stratification for post‐nephrectomy treatment is therefore often based on clinico‐histological parameters alone.

Procedure

In the present study, three public gene expression microarray datasets, including 82 WTs and 8 normal fetal kidneys, were used to establish a consensus gene expression profile of WT. By bioinformatic analyses, 17 genes overexpressed in WT compared to fetal kidney were then selected for evaluation of their protein expression in WT cell lines and in the different histological components in paraffin‐embedded WT tissue sections by immunofluorescence.

Results

Most of the evaluated proteins were expressed in all three common histological components. A prominent exception was SIX1, being expressed predominantly in blastemal elements in 24/25 pediatric cases containing blastema. Anaplastic elements exhibited highly variable SIX1‐positivity. The SIX2 protein, known to be co‐expressed with SIX1 during nephrogenesis, only exhibited blastemal‐predominant expression in half of the SIX2 evaluated cases.

Conclusions

Genes highly expressed in WT compared to fetal kidney are generally overexpressed in all of the three common WT tissue elements. An exception is the predominant expression of SIX1 in blastemal cells, hereby identifying this protein as a candidate marker for blastema. Pediatr Blood Cancer 2012; 59: 62–68. © 2011 Wiley Periodicals, Inc.
Poverty and unemployment: A cultural approach
Authors: Grosso Jean‐Luc , Smith Teresa L.
Published: December 2011

For years, policymakers, business leaders, human resources professionals, and economists have attempted to explain the existence of unemployment. Unemployment inhibits the economic growth of a nation and contributes to the problem of ongoing poverty, which cannot be lessened without that growth. Understanding the causes of unemployment and developing policies and programs to decrease it are vitally important for nations around the world, but one key variable in the study of unemployment has been overlooked. That variable is culture. This article will show that culture can significantly explain cross‐national differences in unemployment rates and offers a link to understanding the global problem of poverty that plagues nations today. © 2012 Wiley Periodicals, Inc.
The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase
Authors: Zheng Xuehua , Zhang Liping , Zhai Jing , Chen Yunyun , Luo Haibin , Hu Xiaopeng
Published: December 2011

Sulindac (SLD) exhibits both the highest inhibitory activity towards human aldose reductase (AR) among popular non‐steroidal anti‐inflammatory drugs and clear beneficial clinical effects on Type 2 diabetes. However, the molecular basis for these properties is unclear. Here, we report that SLD and its pharmacologically active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective as un‐competitive inhibitors of AR in vitro. Crystallographic analysis reveals that π–π stacking favored by the distinct scaffold of SLDs is pivotal to their high AR inhibitory activities. These results also suggest that SLD sulfone could be a potent lead compound for AR inhibition in vivo.
Biosynthesis of the pyoverdine siderophore of Pseudomonas aeruginosa involves precursors with a myristic or a myristoleic acid chain
Authors: Hannauer Mélissa , Schäfer Mathias , Hoegy Françoise , Gizzi Patrick , Wehrung Patrick , Mislin Gaëtan L.A. , Budzikiewicz Herbert , Schalk Isabelle J.
Published: December 2011

Pyoverdine I (PVDI) is the major siderophore produced by Pseudomonas aeruginosa to import iron. Biosynthesis of this chelator involves non‐ribosomal peptide synthetases and other enzymes. PvdQ is a periplasmic enzyme from the NTN hydrolase family and is involved in the final steps of PVDI biosynthesis. A pvdQ mutant produces two non‐fluorescent PVDI precursors with a higher molecular mass than PVDI. In the present study, we describe the use of mass spectrometry to determine the structure of these PVDI precursors and show that they both contain a unformed chromophore like ferribactin, and either a myristic or myristoleic chain that must be removed before PVDI is secreted into the extracellular medium.
Mediated power and outsourcing relationships
Authors: Handley Sean M. , Benton W.C.
Published: December 2011

Mediated power is often used by firms to control the behaviors or influence the decisions of other members of the value chain. Interestingly, significant contributions in the academic literature offer consistent evidence that the use of mediated power has a negative impact on the quality of inter‐organizational relationships. Yet, there is a dearth of empirical research investigating the conditions under which the use of mediated power is more or less prevalent. Utilizing dyadic data collected on 102 outsourcing relationships, this study evaluates how the buying firm's dependence on the service provider, asserted importance of the outsourced activity, and difficulties with other inter‐organizational control mechanisms are related to their reliance on mediated power. Results from our hierarchical regression analysis support the hypotheses that the use of mediated power is diminished when the buyer is currently more dependent on the service provider due to switching difficulties and the buyer has a higher expectation of future supply market consolidation. Similar hypotheses regarding the effect of the strategic importance of the outsourced activity and entry barriers to the service provider's market were not supported. The results also support the hypothesis that the use of mediated power is more pronounced when the buyer experiences contract management difficulties, but the same is not true when the buyer has difficulty in monitoring the provider. To our knowledge, these findings represent the first empirical explanation of conditions which either attenuate or exacerbate the use of mediated power by outsourcing organizations.
Effects of flow volume and grain size on mobility of dry granular flows of angular rock fragments: A functional relationship of scaling parameters
Authors: Cagnoli B. , Romano G. P.
Published: December 2011

Flows of angular rock fragments are released down a concave upward chute in the laboratory to study their mobility. This mobility is measured as the reciprocal of the apparent coefficient of friction that is equal to the vertical drop of the center of mass of the granular material divided by its horizontal distance of travel. Our experiments show that the finer the grain size (with all the other features the same), the larger the mobility of the center of mass. We believe this to be due to the fact that in finer grain size flows there are less agitated particles per unit of flow mass, so that these flows dissipate less energy per unit of travel distance. Our experiments show also that the larger the volume (with all the other features the same), the larger the apparent coefficient of friction. We believe this to be so because the frontal portion of a flow reaches the less steep part of a curved slope and stops before the rear portion, preventing the rear portion and the center of mass from traveling farther downhill. This phenomenon (which is more prominent in larger‐volume flows, whose rear and frontal ends are more distant) counteracts the decrease of energy dissipation per unit of flow mass because of the decrease of particle agitation per unit of flow mass that is expected when the volume of a flow increases (with all the other features the same). Our analysis generates a functional relationship between the dimensionless apparent coefficient of friction and a scaling parameter whose numerator is equal to the mean grain size multiplied by the cube root of the deposit volume and whose denominator is the square of the channel width. The purpose of our experiments is to understand the dynamics of rock avalanches and dense pyroclastic flows.
On the Use of the Distortion-Sensitivity Approach in Examining the Role of Linguistic Abilities in Speech Understanding in Noise
Authors: Goverts S. Theo , Huysmans Elke , Kramer Sophia E. , de Groot Annette M. B. , Houtgast Tammo
Published: December 2011

Purpose

Researchers have used the distortion-sensitivity approach in the psychoacoustical domain to investigate the role of auditory processing abilities in speech perception in noise (van Schijndel, Houtgast, & Festen, 2001; Goverts & Houtgast, 2010). In this study, the authors examined the potential applicability of the distortion-sensitivity approach for investigating the role of linguistic abilities in speech understanding in noise.

Method

The authors applied the distortion-sensitivity approach by measuring the processing of visually presented masked text in a condition with manipulated syntactic, lexical, and semantic cues and while using the Text Reception Threshold (George et al., 2007; Kramer, Zekveld, & Houtgast, 2009; Zekveld, George, Kramer, Goverts, & Houtgast, 2007) method. Two groups that differed in linguistic abilities were studied: 13 native and 10 non-native speakers of Dutch, all typically hearing university students.

Results

As expected, the non-native subjects showed substantially reduced performance. The results of the distortion-sensitivity approach yielded differentiated results on the use of specific linguistic cues in the 2 groups.

Conclusion

The results show the potential value of the distortion-sensitivity approach in studying the role of linguistic abilities in speech understanding in noise of individuals with hearing impairment.
Fluorescent protein barrel fluctuations and oxygen diffusion pathways in mCherry
Authors: Chapagain Prem P. , Regmi Chola K. , Castillo William
Published: December 2011

Fluorescent proteins (FPs) are valuable tools as biochemical markers for studying cellular processes. Red fluorescent proteins (RFPs) are highly desirable for in vivo applications because they absorb and emit light in the red region of the spectrum where cellular autofluorescence is low. The naturally occurring fluorescent proteins with emission peaks in this region of the spectrum occur in dimeric or tetrameric forms. The development of mutant monomeric variants of RFPs has resulted in several novel FPs known as mFruits. Though oxygen is required for maturation of the chromophore, it is known that photobleaching of FPs is oxygen sensitive, and oxygen-free conditions result in improved photostabilities. Therefore, understanding oxygen diffusion pathways in FPs is important for both photostabilites and maturation of the chromophores. In this paper, we use molecular dynamics calculations to investigate the protein barrel fluctuations in mCherry, which is one of the most useful monomeric mFruit variant. We employ implicit ligand sampling to determine oxygen pathways from the bulk solvent into the mCherry chromophore in the interior of the protein. We also show that these pathways can be blocked or altered and barrel fluctuations can be reduced by strategic amino acid substitutions.
Experimental measurements within a phase change metallurgical reactor
Authors: Bertrand C. , Désilets M. , Soucy G.
Published: December 2011

The measurement of solidification front evolution is essential for the optimization and control of many important metallurgical processes. However, this measurement is tedious, imprecise, and time consuming. More generally, industry needs reliable instruments for the thermal characterization of phase change reactors. This paper enables researchers with means and instruments to study the thermal behavior of processes involving the transformation of phase change materials up to 1000 °C. In this work, an original experimental setup is described to analyze the behavior of two high temperature phase change materials: zinc and molten salts. In particular, it is possible to evaluate the 2D solid solidification front evolution with time. The measurements done with zinc show the presence of two thermal regimes. A solidification rate of 20 mm h−1 is measured with two different approaches: thermocouples and a mechanical probe. Finally, an infrared camera is also used to make the link between the external thermal behavior and the solidification front evolution inside the reactor. When implemented within an inverse numerical method, the use of this instrument as a new external sensor looks promising.
Synthesis, Functionalization and Reductive Degradation of Multibrominated Disulfide-containing Hyperbranched Polymers
Authors: Popescu Delia-Laura , Tsarevsky Nicolay V.
Published: December 2011

Reductively degradable hyperbranched polymethacrylates with multiple peripheral alkyl bromide groups were synthesized by the azobis(2-isobutyronitrile)-initiated copolymerization of diethylene glycol methyl ether methacrylate or oligo(ethylene oxide) methyl ether methacrylate with the disulfide-containing crosslinker bis(2-methacryloyloxyethyl)disulfide (2.5–10.0 mol-% relative to the monomer) in the presence of carbon tetrabromide (10–40-fold excess relative to the radical initiator) as efficient chain transfer agent. The alkyl bromide groups initiated the atom-transfer radical polymerization of methyl methacrylate, and star copolymers with hyperbranched disulfide-containing cores were formed. Both the macroinitiators and the star copolymers derived from them were degraded in reducing environment.
Metabolite profiling of wheat flag leaf and grains during grain filling phase as affected by sulfur fertilisation
Authors: Zörb Christian , Steinfurth Dorothee , Gödde Victoria , Niehaus Karsten , Mühling Karl H.
Published: December 2011

Increasing prices for wheat products and fertilisers call for an adjusted agricultural management to maintain yield and to improve product quality. With the increased use of sulfur-free fertilisers in modern cropping systems and the decrease of atmospheric sulfur emissions by industry, sulfur has become a major limiting factor for crop production. The presented data showed that by using GC-MS it was possible to quantitatively detect a set of 72 different metabolites including amino acids, organic acids, sugars, sugar phosphates, and sugar alcohols, phenolic compounds and nucleotides from wheat grains and flag leaves of a pot experiment. A principal component analysis (PCA) revealed a clear separation of flag leaves and grains and a clear separation of non-fertilised and fertilised flag leaves. It could further be shown by PCA, that the low level sulfur fertilisation is also separated from the higher fertilised grains. A considerable influence of the sulfur fertilisation not only on sulfur rich amino acids but also on the sugar metabolism was detected. With increasing sulfur fertilisation six sugars and sugar derivates in the grain such as glucose-6P, galactose, trehalose, cellobiose, melibiose, fumarate, glycerate and the nucleotide uracil were enhanced. Therefore, it was concluded that photosynthesis was limited in developing plants suffering from sulfur deficiency. Late sulfur fertilisation is a procedure that can help to prevent sulfur deficiency. A latent sulfur deficiency at ear emergence can be compensated by late sulfur fertilisation, as wheat plants can replenish sulfate deficits within a short time.
Modelling and validation of dielectric properties of human skin in the MHz region focusing on skin layer morphology and material composition
Authors: Huclova Sonja , Erni Daniel , Fröhlich Jürg
Published: December 2011

Human skin consists of several layers with distinct dielectric properties. Physiological processes leading to changes in dielectric properties of the specific layers can potentially be non-invasively monitored employing dielectric spectroscopy. So far no comprehensive skin and underlying tissue model is available for this purpose in the frequency range between 1 and 100 MHz. Focusing on this dispersion-dominated frequency region, different multilayer skin models are investigated. First, with sublayers obtained from two-phase mixtures, second, three-phase mixtures of shelled cell-like ellipsoids and finally, multiphase mixtures obtained from numerical models of single cells generated using a flexible surface parametrization method. All models are numerically evaluated using the finite-element method and a fringing field sensor on the top of the multilayer system serving as a probe. Furthermore, measurements with the sensor probing skin in vivo were performed. The validity of the models was tested by removing the uppermost skin layer, the stratum corneum (SC). It was found that only a three-phase mixture (extracellular medium, cell membrane and cytoplasm) at least can qualitatively reproduce the measured dispersion still occurring without the SC if the model is set up without a priori knowledge of the dispersive behaviour as e.g. a Cole–Cole fit to measured data. Consequently, microstructural features of tissue have to be part of any accurate skin model in the MHz region.
Identifying small interfering RNA loci from high-throughput sequencing data
Authors: Hardcastle Thomas J. , Kelly Krystyna A. , Baulcombe David C.
Published: December 2011

Motivation: Small interfering RNAs (siRNAs) are produced from much longer sequences of double-stranded RNA precursors through cleavage by Dicer or a Dicer-like protein. These small RNAs play a key role in genetic and epigenetic regulation; however, a full understanding of the mechanisms by which they operate depends on the characterization of the precursors from which they are derived.

Results: High-throughput sequencing of small RNA populations allows the locations of the double-stranded RNA precursors to be inferred. We have developed methods to analyse small RNA sequencing data from multiple biological sources, taking into account replicate information, to identify robust sets of siRNA precursors. Our methods show good performance on both a set of small RNA sequencing data in Arabidopsis thaliana and simulated datasets.

Availability: Our methods are available as the Bioconductor (www.bioconductor.org) package segmentSeq (version 1.5.6 and above).

Contact:  tjh48@cam.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Linear lupus panniculitis of the scalp presenting as alopecia along Blaschko’s lines: A distinct variant of lupus panniculitis in East Asians?
Authors: CHEN Yi‐An , HSU Chao‐Kai , LEE Julia Yu‐Yun , YANG Chao‐Chun
Published: December 2011

A 32‐year‐old Taiwanese man presented to our clinic with a 6‐month history of linear hair loss in a wavy and curved pattern across the parietal and occipital scalp, resembling the distribution of Blaschko’s lines. Physical examination showed interfollicular erythema and follicular plugging without skin atrophy or sclerotic change. Histopathology revealed a lymphoplasmacytic infiltrate in the perifollicular dermis and subcutis with abundant mucin deposition, consistent with the diagnosis of lupus panniculitis. Treatment with hydroxychloroquine and local steroid injection resulted in complete hair regrowth but recurrence was noted. Linear lupus panniculitis of the scalp presenting as alopecia along Blaschko’s lines had so far been reported exclusively in five East Asians. Apart from classical lupus panniculitis, it had distinct clinical and histopathological features such as younger age of onset, male predominance, reversible clinical course without scarring, fewer associations with systemic lupus erythematosus, exclusive involvement of scalp, sparse inflammatory infiltration, abundant mucin deposition, higher degree of hyaline fat degeneration and negative results of immunofluorescent studies. Therefore, we propose linear lupus panniculitis of the scalp to be a distinct variant of lupus panniculitis and should be included in the differential diagnosis for focal or linear alopecia, especially in East Asians.
eNOS [Glu298Asp] polymorphism, erectile function and ocular pressure in type 2 diabetes
Authors: Hermans Michel P. , Ahn Sylvie A. , Rousseau Michel F.
Published: December 2011

Eur J Clin Invest 2012; 42 (7): 729–737

Background  Imbalance in nitric oxide (NO), an atheroprotective vasodilator, is associated with endothelial dysfunction, cardiovascular diseases (CVD) and diabetic complications. Various endothelial NO synthase (eNOS) polymorphisms may affect NO bioavailability, thereby promoting adverse cardiovascular milieu.

Materials and methods  To analyze glucose homeostasis, cardiometabolic phenotype, and micro‐ and macroangiopathies associated with eNOS G894T gene polymorphism in type 2 diabetes (T2DM). 210 T2DM outpatients (mean age (1SD) 70 (12); diabetes duration 19 (9) years; males:females 64:36%; metabolic syndrome 87%) had insulin sensitivity and b‐cell function modelled with HOMA, alongside routine laboratory and endothelin measurements.

Results  GG, GT and TT genotypes represented 48% (n = 100), 39% (n = 83) and 13% (n = 27). Overall microangiopathy (retinopathy, neuropathy and/or nephropathy) was present in 74%, and overall macroangiopathy (CAD, PAD and/or TIA/stroke) in 45%. The TT genotype did not translate into a more severe vascular phenotype, as TT patients carrying the proposed risk genotype did not suffer a higher rate of micro‐ and macrovascular complications. On the other hand, erectile dysfunction, present in 60% of males (n = 135), was much more prevalent in TT males: 57% [GG & GT] vs. 93% in TT (p 0.0088). Ocular hypertension/glaucoma frequency (18% of the whole group) was also markedly different, albeit in opposing directions, between eNOS G894T gene polymorphism subgroups: 21% [GG & GT] vs. 0% prevalence (TT; p 0.0057).

Conclusions  eNOS G894T gene polymorphism in homozygous TT carriers translates into opposing effects on erectile function (detrimental) and ocular hypertension/glaucoma (protective) in T2DM, without affecting glucose homeostasis determinants or the presence of micro‐ and macrovascular complications.
Patient/Caregiver‐reported recombinant factor VIIa (rFVIIa) dosing: home treatment of acute bleeds in the Dosing Observational Study in Hemophilia (DOSE)
Authors: YOUNG G. , SHAPIRO A. D. , WALSH C. E. , GRUPPO R. A. , GUT R. Z. , COOPER D. L.
Published: December 2011

Summary.  Patients with congenital haemophilia with inhibitors experience acute bleeds managed with bypassing agents, such as recombinant FVIIa (rFVIIa). Home‐based treatment and dosing patterns in the US remain poorly described. This study aimed to assess the prescribed and actual rFVIIa dosing in frequently bleeding inhibitor patients (≥4 bleeds in 3 months) prescribed first‐line therapy with rFVIIa. Patients or caregivers recorded daily diaries, including the details of all bypassing agent infusions for 3–6 months. Median (range) initial rFVIIa dose prescribed for joint, muscle and other bleeds was 167.5 (61.0–289.0) mcg kg−1. Additional rFVIIa doses prescribed were 90 (61–270) mcg kg−1 at an interval of 2.5–3 (1–24) h. The actual initial rFVIIa dose reported by patients/caregivers for 158 bleeds was 212 (59–400) mcg kg−1, with total dose per episode of 695 (74–21257) mcg kg−1. Patient/caregiver‐reported average dose per bleed was 146 (40–400) mcg kg−1 across 5 (1–106) infusions. The initial rFVIIa dose was higher for haemarthrosis (223 [59–400] mcg kg−1) than muscle bleeds (148 [74–300] mcg kg−1; P = 0.07). Initial and mean dose per day changed as treatment progressed. The DOSE study indicates that frequently bleeding inhibitor patients are prescribed and use higher rFVIIa dosing for all bleed types than recommended in the package insert (90 mcg kg−1). The rFVIIa dosing was highly variable within and across bleed types, with higher initial doses used for joint bleeds than muscle and other bleed types, particularly in the first days of treatment. This suggests that patients/caregivers have adopted home treatment strategies based on physician discretion and individual responses and experience.
The effects of exposure to particulate matter and neighbourhood deprivation on gestational hypertension
Authors: Vinikoor‐Imler Lisa C. , Gray Simone C. , Edwards Sharon E. , Miranda Marie Lynn
Published: December 2011

Vinikoor‐Imler LC, Gray SC, Edwards SE, Miranda ML. The effects of exposure to particulate matter and neighbourhood deprivation on gestational hypertension. Paediatric and Perinatal Epidemiology 2012; 26: 91–100.

Gestational hypertension, pre‐eclampsia and eclampsia are conditions that affect the health of both mothers and infants during and after pregnancy. Recent research indicates the importance of considering environmental, social and individual contributors to poor pregnancy outcomes. Our research examined particulate matter (PM) concentrations as one measure of environmental exposure and neighbourhood quality as one measure of the social environment. We used these measures, as well as maternal characteristics, to predict the risk of gestational hypertension (including pre‐eclampsia and eclampsia). North Carolina Detailed Birth Record data for 2000–2003 were obtained and geocoded for all singleton births. Levels of PM10 and PM2.5 were determined using air quality data from the US Environmental Protection Agency. Information on a woman's residential neighbourhood was determined from 2000 Census data. Modified Poisson regression models clustered by tract were used to examine the associations between PM levels, neighbourhood deprivation and maternal characteristics with gestational hypertension. Analysis was restricted to women residing within 20 km of a PM monitor. Both PM10 and PM2.5 were associated with gestational hypertension; the risk ratios for an interquartile range (IQR) increase in exposure were 1.07 [95% confidence interval (CI) 1.04, 1.11] for PM10 (IQR: 3.92 µg/m3) and 1.11 [95% CI 1.08, 1.15] for PM2.5 (IQR: 2.24 µg/m3). Living in a neighbourhood with increased levels of deprivation was also associated with gestational hypertension. Any smoking during pregnancy, younger age and higher level of education were inversely associated with risk of gestational hypertension. Compared with non‐Hispanic White women, non‐Hispanic Black women were at higher risk of gestational hypertension, whereas Hispanic women were at lower risk. Increased levels of PM and neighbourhood deprivation, as well as certain individual characteristics, were associated with higher risk of gestational hypertension.
Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity
Authors: Knop F. K. , Aaboe K. , Vilsbøll T. , Vølund A. , Holst J. J. , Krarup T. , Madsbad S.
Published: December 2011

Aims: People with type 2 diabetes mellitus (T2DM) are characterized by reduced incretin effect and inappropriate glucagon levels. We evaluated α and β‐cell responses to oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI) in lean and obese persons with T2DM or normal glucose tolerance (NGT) to elucidate the impact of obesity on the incretin effect and incretin hormone and glucagon responses.

Methods: Four hour 50‐g OGTT and IIGI were performed in (i) Eight obese patients with T2DM [mean body mass index (BMI): 37 (range: 35–41) kg/m2]; (ii) Eight obese subjects with NGT [BMI: 33 (35–38) kg/m2]; (iii) Eight lean patients with T2DM [BMI: 24 (22–25) kg/m2]; and (iv) Eight lean healthy subjects [BMI: 23 (20–25) kg/m2].

Results: The incretin effect was significantly (p < 0.05) reduced in patients with T2DM {obese: 7 ± 7% [mean ± standard error of the mean (SEM)]; lean: 29 ± 8%; p = 0.06)} and was lower in obese subjects (41 ± 4%) than in lean subjects with NGT (53 ± 4%; p < 0.05). Obese subjects with NGT were also characterized by elevated fasting plasma glucagon levels, but the inappropriate glucagon responses to OGTT found in the T2DM patients were not evident in these subjects.

Conclusions: Our findings suggest that reduced incretin effect and fasting hyperglucagonaemia constitute very early steps in the pathophysiology of T2DM detectable even in obese people who despite their insulin‐resistant state have NGT.
The increased dipeptidyl peptidase‐4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin‐treated patients
Authors: Fadini G. P. , Albiero M. , Menegazzo L. , de Kreutzenberg S. V. , Avogaro A.
Published: December 2011

Aim: Dipeptidyl peptidase (DPP)‐4 in responsible for incretin degradation and some observations suggest that DPP‐4 activity is increased in type 2 diabetes (T2D). We aimed to assess the effect of T2D and glucose control on DPP‐4 activity.

Methods: In the first set (SET1) of patients, we compared plasma DPP‐4 activity between 30 T2D and 20 age‐ and sex‐matched non‐diabetic subjects. In the second set (SET2), we measured serum DPP‐4 activity in 42 T2D patients before and after a trial of glucose control achieved by add‐on basal insulin therapy (NCT00699686). Serum/plasma DPP‐4 activity was determined using chromogenic and fluorigenic substrates, as well as several positive and negative controls.

Results: In SET1, plasma DPP‐4 activity was significantly higher in T2D vs. controls (32.2 ± 1.2 U/l vs. 21.2 ± 1.1 U/l, p < 10−6). From a meta‐analysis of the literature, we found that T2D is associated with a 33% increase in DPP‐4 activity compared to controls. In SET2, serum DPP‐4 activity was not lowered by intensified glucose control, despite an average haemoglobin A1c (HbA1c) reduction of 1.5%. In both sets of diabetic patients, the use of metformin was associated with a significantly lower DPP‐4 activity, independently of age, sex, body mass index and HbA1c.

Conclusion: DPP‐4 activity is increased in T2D, but is not lowered by glucose control, suggesting that hyperglycaemia is not a direct determinant of DPP‐4 activity. However, metformin may indirectly reduce DPP‐4 activity.
Value Differentiation in Adolescence: The Role of Age and Cultural Complexity
Authors: Daniel Ella , Schiefer David , Möllering Anna , Benish‐Weisman Maya , Boehnke Klaus , Knafo Ariel
Published: December 2011

Living in complex social worlds, individuals encounter discordant values across life contexts, potentially resulting in different importance of values across contexts. Value differentiation is defined here as the degree to which values receive different importance depending on the context in which they are considered. Early and mid‐adolescents (N = 3,497; M = 11.45 years, SD = 0.87 and M = 16.10 years, SD = 0.84, respectively) from 4 cultural groups (majority and former Soviet Union immigrants in Israel and Germany) rated their values in 3 contexts (family, school, and country). Value differentiation varied across individuals. Early adolescents showed lower value differentiation than mid‐adolescents. Immigrant (especially first generation) adolescents, showed higher value differentiation than majority adolescents, reflecting the complex social reality they face while negotiating cultures.
Children’s Developing Commitments to Joint Goals
Authors: Hamann Katharina , Warneken Felix , Tomasello Michael
Published: December 2011

This study investigated young children’s commitment to a joint goal by assessing whether peers in collaborative activities continue to collaborate until all received their rewards. Forty‐eight 2.5‐ and 3.5‐year‐old children worked on an apparatus dyadically. One child got access to her reward early. For the partner to benefit as well, this child had to continue to collaborate even though there was no further reward available to her. The study found that 3.5‐year‐olds, but not 2.5‐year‐olds, eagerly assisted their unlucky partner. They did this less readily in a noncollaborative control condition. A second study confirmed that 2.5‐year‐old children understood the task structure. These results suggest that children begin to appreciate the normative dimensions of collaborative activities during the 3rd year of life.
Are Political Connections a Blessing or a Curse? Evidence from CEO Turnover in China
Authors: You Jiaxing , Du Guqian
Published: December 2011

Manuscript Type: Empirical

Research Question/Issue: This paper investigates the issue of forced CEO turnover in China and summarizes the economic consequences of political connections within the framework of corporate governance.

Research Findings/Insights: Using a large sample of listed firms in China from 2005 to 2008, we find that politically connected CEOs are less likely to be fired and that the sensitivity of forced turnover to firm performance is weaker for connected CEOs than for their non‐connected peers. This suggests that CEOs in a transition economy tend to use their political resources for their own good. We also find a significantly positive relationship between the political connections of retained CEOs and future firm performance only when firm profitability is below the industry median. These findings suggest that the value of political connections is contingent on a firm's operating performance, and that the benefits of political connections may outweigh their costs when firms do not meet their profitability targets.

Theoretical/Academic Implications: This study is the first to examine how the political ties of CEOs relate to their forced turnover. It integrates agency theory with resource dependence theory and contributes to the ongoing debate on the role of political connections in emerging markets. It also takes a step toward reconciling the mixed evidence for the effects of political connections on firm performance by demonstrating a sharp difference between firms under different operating statuses.

Practitioner/Policy Implications: This study offers insights to policy makers who are interested in improving corporate governance in transitional economies such as China, where CEOs have close connections with the government. It also provides a deep perspective for the boards in politically connected firms, allowing them to deal with the relationship between top management and the government in a healthy way.
Semantic priming increases left hemisphere theta power and intertrial phase synchrony
Authors: Salisbury Dean F. , Taylor Grantley
Published: December 2011

Information is stored in distributed cortical networks, but it is unclear how distributed stores are synthesized into a unified percept. Activation of local circuits in the gamma range (30 < < 80 Hz), and distributed stores in the low theta range (3–5 Hz) may underlie perceptual binding. Words have a crucial role in semantic memory. Within memory, the activation of distributed semantic stores is facilitated by conceptually related previous items, termed semantic priming. We sought to detect event‐related brain oscillations (EROs) sensitive to semantic activation and priming. Here, we show that low theta evoked power and intertrial phase locking (4–5 Hz) from 250–350 msec over left hemisphere language areas was greater to related than to unrelated words. Theta band event‐related oscillations over left hemisphere language areas may provide a brain signature for semantic activation across distributed stores being facilitated by semantic priming.
β‐Site APP‐cleaving enzyme 1 trafficking and Alzheimer’s disease pathogenesis
Authors: Tan Jiangli , Evin Geneviève
Published: December 2011

J. Neurochem. (2012) 120, 869–880.

β‐Site APP‐cleaving enzyme (BACE1) cleaves the amyloid precursor protein (APP) at the β‐secretase site to initiate the production of Aβ peptides. These accumulate to form toxic oligomers and the amyloid plaques associated with Alzheimer’s disease (AD). An increase of BACE1 levels in the brain of AD patients has been mostly attributed to alterations of its intracellular trafficking. Golgi‐associated adaptor proteins, GGA sort BACE1 for export to the endosomal compartment, which is the major cellular site of BACE1 activity. BACE1 undergoes recycling between endosome, trans‐Golgi network (TGN), and the plasma membrane, from where it is endocytosed and either further recycled or retrieved to the endosome. Phosphorylation of Ser498 facilitates BACE1 recognition by GGA1 for retrieval to the endosome. Ubiquitination of BACE1 C‐terminal Lys501 signals GGA3 for exporting BACE1 to the lysosome for degradation. In addition, the retromer mediates the retrograde transport of BACE1 from endosome to TGN. Decreased levels of GGA proteins and increased levels of retromer‐associated sortilin have been associated with AD. Both would promote the co‐localization of BACE1 and the amyloid precursor protein in the TGN and endosomes. Decreased levels of GGA3 also impair BACE1 degradation. Further understanding of BACE1 trafficking and its regulation may offer new therapeutic approaches for the treatment of Alzheimer’s disease.