bluuebunny/crossref_metadata_2025 huggingface dataset:
An extensive (co-)expression analysis tool for the cytochrome P450 superfamily in Arabidopsis thaliana
Authors: Ehlting Jürgen , Sauveplane Vincent , Olry Alexandre , Ginglinger Jean-François , Provart Nicholas J , Werck-Reichhart Danièle
Published: April 2008

Background

Sequencing of the first plant genomes has revealed that cytochromes P450 have evolved to become the largest family of enzymes in secondary metabolism. The proportion of P450 enzymes with characterized biochemical function(s) is however very small. If P450 diversification mirrors evolution of chemical diversity, this points to an unexpectedly poor understanding of plant metabolism. We assumed that extensive analysis of gene expression might guide towards the function of P450 enzymes, and highlight overlooked aspects of plant metabolism.

Results

We have created a comprehensive database, 'CYPedia', describing P450 gene expression in four data sets: organs and tissues, stress response, hormone response, and mutants of Arabidopsis thaliana, based on public Affymetrix ATH1 microarray expression data. P450 expression was then combined with the expression of 4,130 re-annotated genes, predicted to act in plant metabolism, for co-expression analyses. Based on the annotation of co-expressed genes from diverse pathway annotation databases, co-expressed pathways were identified. Predictions were validated for most P450s with known functions. As examples, co-expression results for P450s related to plastidial functions/photosynthesis, and to phenylpropanoid, triterpenoid and jasmonate metabolism are highlighted here.

Conclusion

The large scale hypothesis generation tools presented here provide leads to new pathways, unexpected functions, and regulatory networks for many P450s in plant metabolism. These can now be exploited by the community to validate the proposed functions experimentally using reverse genetics, biochemistry, and metabolic profiling.
N-acetyltransferase 8, a positional candidate for blood pressure and renal regulation: resequencing, association and in silico study
Authors: Juhanson Peeter , Kepp Katrin , Org Elin , Veldre Gudrun , Kelgo Piret , Rosenberg Mai , Viigimaa Margus , Laan Maris
Published: April 2008

Background

Kidneys have an important function in blood pressure (BP) regulation and elevated BP may lead to kidney failure. Chr2p12-p13 region linked to BP traits in multiple studies harbours a potential candidate for BP and renal function, N-acetyltransferase 8 (NAT8) expressed in embryonic and adult kidney and associated with nephrotoxicity response.

Methods/Results

We report the first study exploring NAT8 as a potential candidate gene for blood pressure and kidney function. The resequencing (n = 42, random Estonian samples) identified 15 NAT8 polymorphisms, including 6 novel variants. The diversity of NAT8 5' upstream region (π/bp = 0.00320) exceeded up to 10 times the variation in the NAT8 genic region (π/bp = 0.00037) as well as the average variation (π/bp = 0.00040) for the promoters of 29 reference genes associated with hypertension. We suggest that a potential source for such high variation could be an active gene conversion process from NAT8B duplicate gene to NAT8. Similarly to NAT8, several reference genes with the most variable upstream regions have also duplicate copies. The NAT8 promoter SNPs were targeted with pilot quantitative association studies for blood pressure (n = 137, healthy unrelated individuals) and for the index of kidney function – estimated glomerular filtration rate (eGFR; n = 157 hypertensives with and without nephropathy). Minor alleles of these polymorphisms revealed a significant protective effect against elevated systolic BP as well as kidney failure in hypertension patients (p < 0.05; linear regression model, addictive effect).

Conclusion

The full resequencing and pilot association study of a novel positional candidate gene for blood pressure and renal function, human N-acetyltransferase 8, suggested a contribution of highly variable NAT8 promoter polymorphisms in determination of systolic blood pressure and eGFR. Based on in silico analysis, we raise the hypothesis that the alternative SNP alleles of the NAT8 upstream region may have differential effect on gene expression.
Clinical and prognostic analysis of hepatitis B virus infection in diffuse large B-cell lymphoma
Authors: Wang Feng , Xu Rui-hua , Luo Hui-yan , Zhang Dong-shen , Jiang Wen-qi , Huang Hui-qiang , Sun Xiao-fei , Xia Zhong-jun , Guan Zhong-zhen
Published: April 2008

Background

Hepatitis B virus (HBV) infection in diffuse large B-cell lymphoma (DLBCL) patients is a common complication in China. However, the clinical relevance of HBV infection with respect to DLBCL disease stages and patient survival remains unclear. The main objective of the current study was to analyze the clinical features and to evaluate the prognostic factors of HBV infection in DLBCL patients.

Methods

In this retrospective study, DLBCL patients were divided into two groups as HBsAg-positive (n = 81) and HBsAg-negative (n = 181) patients. The HBsAg-positive patients were further divided into two subgroups based on their hepatic function during chemotherapy. Various statistical analyses were used to determine the significance of the relevant clinical parameters.

Results

Compared with the HBsAg-negative group, the HBsAg-positive DLBCL group displayed a younger median onset age (46 year vs 51), more advanced stage at grade III/IV (58% vs 42%, p = 0.016), and more frequent hepatic dysfunction before (21% vs 5.5%, p < 0.001) and during (49.4% vs 16.6%, p < 0.001) chemotherapy. Female DLBCL patients exhibited a higher frequency of HBsAg positivity (p = 0.006). However, in both groups the median overall survival (OS) duration (55.8 vs 66.8 months) and response rates (91% vs 90.4%) were similar. In the HBsAg-positive DLBCL group, the poor prognostic factors were advanced stage (p < 0.001) and hepatic dysfunction during chemotherapy (p = 0.02). The OS of HBsAg-positive patients with hepatic dysfunction during chemotherapy was significantly shorter than those without liver dysfunction (p = 0.016), and the OS rates at 3 years were 48% and 72%, respectively. The use of rituximab did not increase the rates of liver dysfunction in HBsAg-positive DLBCL patients.

Conclusion

Compared with HBsAg-negative patients, the HBsAg-positive DLBCL patients had earlier onset and more advanced stage. The disease stage and hepatic dysfunction during chemotherapy and were two significant prognostic factors in the HBsAg-positive DLBCL patients. This study suggests that prophylactic treatment of HBV may be of great importance in the cases of HBsAg-positive patients.
Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1
Authors: Johnson Aimee M , O'Connell Mary J , Miyamoto Hiroshi , Huang Jiaoti , Yao Jorge L , Messing Edward M , Reeder Jay E
Published: April 2008

Background

Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC) in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive.

Methods

Flat panel detector-based cone beam computed tomography (FPDCT) was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT). Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1) protein expression.

Results

Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071) and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.). Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients.

Conclusion

FPDCT allows longitudinal monitoring of exophytic tumor growth in the UPII-SV40T model of BC that bypasses need for chemical carcinogens, which confound analysis of androgen effects. Androgens increase tumor cell growthin vitroandin vivoand decrease TSP1 expression, possibly explaining the therapeutic effect of castration. This effect may, in part, explain gender differences in BC incidence and implies anti-androgenic therapies may be effective in preventing and treating BC.
Clinical characterization and the mutation spectrum in Swedish adenomatous polyposis families
Authors: Kanter-Smoler Gunilla , Fritzell Kaisa , Rohlin Anna , Engwall Yvonne , Hallberg Birgitta , Bergman Annika , Meuller Johan , Grönberg Henrik , Karlsson Per , Björk Jan , Nordling Margareta
Published: April 2008

Background

The dominantly inherited condition familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. Finding the causative mutations has great implications for the families. Correlating the genotypes to the phenotypes could help to improve the diagnosis and follow-up of patients.

Methods

Mutation screening of APC and the clinical characterization of 96 unrelated FAP patients from the Swedish Polyposis Registry was performed. In addition to generally used mutation screening methods, analyses of splicing-affecting mutations and investigations of the presence of low-frequency mutation alleles, indicating mosaics, have been performed, as well as quantitative real-time polymerase chain reaction to detect lowered expression of APC.

Results

Sixty-one different APC mutations in 81 of the 96 families were identified and 27 of those are novel. We have previously shown that 6 of the 96 patients carried biallelic MUTYH mutations. The 9 mutation-negative cases all display an attenuated or atypical phenotype. Probands with a genotype (codon 1250–1464) predicting a severe phenotype had a median age at diagnosis of 21.8 (range, 11–49) years compared with 34.4 (range, 14–57) years among those with mutations outside this region (P < 0.017). Dense polyposis (> 1000) occurred in 75% of the probands with a severe phenotype compared with 30% in those with mutations outside this region. The morbidity in colorectal cancer among probands was 25% at a mean age of 37.5 years and 29% at a mean age of 46.6 years.

Conclusion

Using a variety of mutation-detection techniques, we have achieved a 100% detection frequency in classical FAP. Probands with APC mutations outside codon 1250–1464, although exhibiting a less-severe phenotype, are at high risk of having a colorectal cancer at diagnosis indicating that age at diagnosis is as important as the severity of the disease for colorectal cancer morbidity.
The Greig cephalopolysyndactyly syndrome
Authors: Biesecker Leslie G
Published: April 2008

The Greig cephalopolysyndactyly syndrome (GCPS) is a pleiotropic, multiple congenital anomaly syndrome. It is rare, but precise estimates of incidence are difficult to determine, as ascertainment is erratic (estimated range 1–9/1,000,000). The primary findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. The polydactyly is most commonly preaxial of the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. Other low frequency findings include central nervous system (CNS) anomalies, hernias, and cognitive impairment.

GCPS is caused by loss of function mutations in theGLI3transcription factor gene and is inherited in an autosomal dominant pattern. The disorder is allelic to the Pallister-Hall syndrome and one form of the acrocallosal syndrome.

Clinical diagnosis is challenging because the findings of GCPS are relatively non-specific, and no specific and sensitive clinical have been delineated. For this reason, we have proposed a combined clinical-molecular definition for the syndrome. Apresumptivediagnosis of GCPS can be made if the patient has the classic triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly. Patients with a phenotype consistent with GCPS (but which may not manifest all three attributes listed above) and aGLI3mutation may be diagnosed definitively with GCPS. In addition, persons with a GCPS-consistent phenotype who are related to a definitively diagnosed family member in a pattern consistent with autosomal dominant inheritance may be diagnosed definitively as well. Antenatal molecular diagnosis is technically straightforward to perform.

Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome.

Treatment of the disorder is symptomatic, with plastic or orthopedic surgery indicated for significant limb malformations.

The prognosis for typically affected patients is excellent. There may be a slight increase in the incidence of developmental delay or cognitive impairment. Patients with large deletions that includeGLI3may have a worse prognosis.

The Article is a work of the United States Government. Title 17 U.S.C 5 105 provides that copyright protection is not available for any work of the United States Government in the United States. The United States hereby grants to anyone a paid-up, nonexclusive, irrevocable worldwide license to reproduce, prepare derivative works, distribute copies to the public and perform publicly and display publicly the work, and also retains the nonexclusive right to do all of the above for or on behalf of the United States.
A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis
Authors: Smitten Allison L , Simon Teresa A , Hochberg Marc C , Suissa Samy
Published: April 2008

Introduction

The risk of malignancies in patients with rheumatoid arthritis (RA) has raised some concern, particularly with immunosuppressive approaches to disease management.

Methods

We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (lymphoma, lung, colorectal, and breast cancer) in patients with RA. A Medline search from 1990 to 2007 was conducted using specified search terms and predefined inclusion criteria for identification of relevant observational studies that provide estimates of relative risk of malignancy associated with RA. Study-specific estimates of the relative risk, as measured by standardized incidence ratios (SIRs) and estimated in comparison with the general population, were combined using a random effects model.

Results

A total of 21 publications were identified, of which 13 reported the SIR for overall malignancy, 14 for lymphoma, 10 for colorectal, 12 for lung, and 9 for breast cancer. Compared with the general population, the overall SIR estimates suggest that RA patients have approximately a two-fold increase in lymphoma risk (SIR 2.08, 95% confidence interval [CI] 1.80 to 2.39) and greater risk of Hodgkin than non-Hodgkin lymphoma. The risk of lung cancer was also increased with an SIR of 1.63 (95% CI 1.43 to 1.87). In contrast, a decrease in risk was observed for colorectal (SIR 0.77, 95% CI 0.65 to 0.90) and breast (SIR 0.84, 95% CI 0.79 to 0.90) cancer. The SIR for overall malignancy was 1.05 (95% CI 1.01 to 1.09).

Conclusion

Patients with RA appear to be at higher risk of lymphoma and lung cancer and potentially decreased risk for colorectal and breast cancer compared with the general population.
The influence of serum, glucose and oxygen on intervertebral disc cell growth in vitro: implications for degenerative disc disease
Authors: Johnson William EB , Stephan Simon , Roberts Sally
Published: April 2008

Introduction

The avascular nature of the human intervertebral disc (IVD) is thought to play a major role in disc pathophysiology by limiting nutrient supply to resident IVD cells. In the human IVD, the central IVD cells at maturity are normally chondrocytic in phenotype. However, abnormal cell phenotypes have been associated with degenerative disc diseases, including cell proliferation and cluster formation, cell death, stellate morphologies, and cell senescence. Therefore, we have examined the relative influence of possible blood-borne factors on the growth characteristics of IVD cells in vitro.

Methods

Bovine IVD cells were cultured either in monolayer to encourage cell proliferation or in alginate to induce chondrocytic differentiation. In both culture systems, cells were maintained with or without 20% serum, with or without 320 mg/dL glucose, and in atmospheric levels (~21%) of oxygen or 1% oxygen. Cell proliferation and viability, cell senescence, and collagen immunopositivity were assessed after 7 days. Statistical differences in these growth characteristics were tested using nonparametric analyses (n = 4 samples).

Results

In both culture systems, serum deprivation significantly inhibited IVD cell proliferation and increased cell positivity for senescence-associated beta-galactosidase (SA-β-gal), a marker of cell senescence. Conversely, IVD cells cultured in the presence of serum, but deprived of glucose, proliferated significantly more rapidly. In alginate cultures, this enhanced cell proliferation (through glucose deprivation) led to the formation of IVD cell clusters. Serum-deprived cells in monolayer, but not in alginate, adopted a stellate appearance. Oxygen deprivation alone had little effect on IVD cell proliferation or survival. Oxygen and glucose deprivation also had no significant effect on SA-β-gal positivity. IVD cell viability was markedly and significantly decreased in serum-deprived alginate cultures, but in all other conditions remained at or greater than approximately 95%. Glucose deprivation, but not serum or oxygen deprivation, inhibited synthesis of type I and type II collagen, both in monolayer and alginate cultures.

Conclusion

This study demonstrates that factors present in serum interact with other nutrients, notably glucose, to play a major role in regulating the behaviour of IVD cells. These findings suggest that IVD cell phenotypes seen in degenerative disc disease may arise through the cells' response to altered vascularisation and nutrient supply.
Progressive myopathy and defects in the maintenance of myotendinous junctions in mice that lack talin 1 in skeletal muscle
Authors: Conti Francesco J. , Felder Amanda , Monkley Sue , Schwander Martin , Wood Malcolm R. , Lieber Richard , Critchley David , Müller Ulrich
Published: April 2008

The development and function of skeletal muscle depend on molecules that connect the muscle fiber cytoskeleton to the extracellular matrix (ECM).β1 integrins are ECM receptors in skeletal muscle, and mutations that affect the α7β1 integrin cause myopathy in humans. In mice, β1 integrins control myoblast fusion, the assembly of the muscle fiber cytoskeleton, and the maintenance of myotendinous junctions (MTJs). The effector molecules that mediate β1 integrin functions in muscle are not known. Previous studies have shown that talin 1 controls the force-dependent assembly of integrin adhesion complexes and regulates the affinity of integrins for ligands. Here we show that talin 1 is essential in skeletal muscle for the maintenance of integrin attachment sites at MTJs. Mice with a skeletal muscle-specific ablation of the talin 1 gene suffer from a progressive myopathy. Surprisingly, myoblast fusion and the assembly of integrin-containing adhesion complexes at costameres and MTJs advance normally in the mutants. However, with progressive ageing, the muscle fiber cytoskeleton detaches from MTJs. Mechanical measurements on isolated muscles show defects in the ability of talin 1-deficient muscle to generate force. Collectively, our findings show that talin 1 is essential for providing mechanical stability to integrin-dependent adhesion complexes at MTJs, which is crucial for optimal force generation by skeletal muscle.
The TTG1-bHLH-MYB complex controls trichome cell fate and patterning through direct targeting of regulatory loci
Authors: Zhao Mingzhe , Morohashi Kengo , Hatlestad Greg , Grotewold Erich , Lloyd Alan
Published: April 2008

A network of three classes of proteins consisting of bHLH and MYB transcription factors, and a WD40 repeat protein, TRANSPARENT TESTA GLABRA1(TTG1), act in concert to activate trichome initiation and patterning. Using YFP-TTG1 translational fusions, we show that TTG1 is expressed ubiquitously in Arabidopsis leaves and is preferentially localized in the nuclei of trichomes at all developmental stages. Using a conditional transgenic allele,we demonstrate that TTG1 directly targets the same genes as the bHLH protein GLABRA3 (GL3). In vivo binding of the R2R3-MYB protein GLABRA1 (GL1) to the promoters of GLABRA2 (GL2), TRANSPARENT TESTA GLABRA2 (TTG2), CAPRICE (CPC) and ENHANCER OF TRIPTYCHON AND CAPRICE1 (ETC1) establishes that these genes are major transcriptional targets for the TTG1-bHLH-MYB regulatory complex. By co-precipitation, we confirm that TTG1 associates with GL3 and GL1 in vivo,forming a complex. The loss of TTG1 and GL1 through mutation, affects the subcellular distribution of GL3. Using particle bombardment, we show that TTG1, GL3, GL1 and the homeodomain protein GL2 do not move between adjacent epidermal cells, while the R3-MYB, CPC, does move to neighboring cells. These data support a model for the TTG1 complex directly regulating activators and repressors and the movement of repressors to affect trichome patterning on the Arabidopsis leaf.
TheArabidopsisCOP9 signalosome is essential for G2 phase progression and genomic stability
Authors: Dohmann Esther M. N. , Levesque Mitchell P. , De Veylder Lieven , Reichardt Ilka , Jürgens Gerd , Schmid Markus , Schwechheimer Claus
Published: April 2008

The COP9 signalosome (CSN) is required for the full activity of cullin-RING E3 ubiquitin ligases (CRLs) in eukaryotes. CSN exerts its function on CRLs by removing the ubiquitin-related NEDD8 conjugate from the cullin subunit of CRLs. CSN seems, thereby, to control CRL disassembly or CRL subunit stability. In Arabidopsis thaliana, loss of CSN function leads to constitutive photomorphogenic (cop) seedling development and a post-germination growth arrest. The underlying molecular cause of this growth arrest is currently unknown. Here, we show that Arabidopsis csn mutants are delayed in G2 phase progression. This cell cycle arrest correlates with the induction of the DNA damage response pathway and is suggestive of the activation of a DNA damage checkpoint. In support of this hypothesis, we detected gene conversion events in csn mutants that are indicative of DNA double-strand breaks. DNA damage is also apparent in mutants of the NEDD8 conjugation pathway and in mutants of the E3 ligase subunits CULLIN4, COP1 and DET1, which share phenotypes with csn mutants. In summary, our data suggest that Arabidopsis csn mutants undergo DNA damage, which might be the cause of the delay in G2 cell cycle progression.
Post-meiotic transcription inDrosophilatestes
Authors: Barreau Carine , Benson Elizabeth , Gudmannsdottir Elin , Newton Fay , White-Cooper Helen
Published: April 2008

Post-meiotic transcription was accepted to be essentially absent from Drosophila spermatogenesis. We identify 24 Drosophila genes whose mRNAs are most abundant in elongating spermatids. By single-cyst quantitative RT-PCR, we demonstrate post-meiotic transcription of these genes. We conclude that transcription stops in Drosophila late primary spermatocytes, then is reactivated by two pathways for a few loci just before histone-to-transition protein-to-protamine chromatin remodelling in spermiogenesis. These mRNAs localise to a small region at the distal elongating end of the spermatid bundles, thus they represent a new class of sub-cellularly localised mRNAs. Mutants for a post-meiotically transcribed gene (scotti), are male sterile, and show spermatid individualisation defects, indicating a function in late spermiogenesis.
Study of the improved algorithm for correlation integral method and its application to surge precursor identification
Authors: Sun T , Xu G H , Zhang C M
Published: April 2008

Correlation integral method (CIM) is a perfect method for the detection of stall and surge. However, CIM is very time-consuming due to its computational complexity. This paper aims to resolve the disadvantage. First, the segmented computation of correlation integral (CI) is deduced; second, the mapping criterion is given; finally the improved correlation integral method (ICIM) is proposed. The criterion can search the repeated subset of points and pair of subsets efficiently, which aids the ICIM in eliminating all redundancy caused by the overlapping of consecutive time windows. By applying ICIM to the detection of surge precursor in centrifugal compressors, it is illustrated that CI has a sharp decline more than 1.5 s prior to the fully developed surge. Also the processing time of ICIM is much shorter than that of CIM. The explicit detection of surge precursor, its rapid recognition, and the resulting longer time available for the feedback preventing the surge are the principal advantages of this approach. These studies are significant for CIM and will boost its application in numerous fields, especially in the detection of stall and surge.
An analytical model to study the radial stiffness and spoke load distribution in a modern racing bicycle wheel
Authors: Mínguez J M , Vogwell J
Published: April 2008

A theoretical study has been carried out to analyse the behaviour of the structural components used with a modern spoked bicycle wheel when loaded at the hub axle and supported at the rim. The work has involved developing some general equations for calculating the contributions which the axially loaded spokes and the bending flexure of the rim make to hub displacement and hence hub-to-rim wheel stiffness. The work considers the effect which the spoke tightening preload has on the distribution of load throughout the wheel and also the influence it has on wheel stiffness. The developed theory has been applied to some modern racing cycle wheels which have just a few spokes and use a relatively rigid, part tubular cross-section rim. Such designs are evaluated, using actual mechanical properties, and their behaviour is discussed against more traditional multi-spoke wheel designs which have relatively much more flexible rims. The theory has been compared with the results obtained from experimentally load testing a bicycle wheel using 12 and 18 spoke variants.
New electro-vibroimpact system
Authors: Nguyen V D , Woo K C
Published: April 2008

In this paper, a new vibro-impact mechanism based on a solenoid-actuated vibrator and its optimization are presented. The vibratory unit deploying electro-mechanical interactions of a conductor with oscillating magnetic field has been realized. The combination of resonance in an RLC circuit and a solenoid is found to create an oscillatory motion to the metal bar within the solenoid. This results in impacts of the metal bar on an obstacle block. Unanimously, the electromagnetic force generated within the solenoid acts as a non-linear electromagnetic spring. Hence, a vibro-impact mechanism gets created. This system is improved by adding a solid-state relay in series to the RLC circuit, which switches the power supply on and off periodically in accordance to a train of square waves produced by a function generator. This new control over the supplied harmonic voltage allows a small scale in the geometry of the vibratory unit but significantly increases the magnitude of impact forces and the progression rates obtained. This implies a very promising deployment of the mechanism in actual soil conditions.
Delivering phonological and phonics training within whole‐class teaching
Authors: Shapiro Laura R. , Solity Jonathan
Published: April 2008

Background Early, intensive phonological awareness and phonics training is widely held to be beneficial for children with poor phonological awareness. However, most studies have delivered this training separately from children's normal whole‐class reading lessons.

Aims We examined whether integrating this training into whole class, mixed‐ability reading lessons could impact on children with poor phonological awareness, whilst also benefiting normally developing readers.

Sample Teachers delivered the training within a broad reading programme to whole classes of children from Reception to the end of Year 1 (N = 251). A comparison group of children received standard teaching methods (N = 213).

Method Children's literacy was assessed at the beginning of Reception, and then at the end of each year until 1 year post‐intervention.

Results The strategy significantly impacted on reading performance for normally developing readers and those with poor phonological awareness, vastly reducing the incidence of reading difficulties from 20% in comparison schools to 5% in intervention schools.

Conclusions Phonological and phonics training is highly effective for children with poor phonological awareness, even when incorporated into whole‐class teaching.
Humour mediates the facilitative effect of bizarreness in delayed recall
Authors: Worthen James B. , Deschamps Joseph D.
Published: April 2008

The first empirical study focused exclusively on the influence of bizarre elaboration on memory (Delin, 1968) indicated a significant relationship between bizarreness and recall after a 15‐week delay. However, that study was strongly criticized on methodological grounds. The present study offers a conceptual replication of Delin's historically significant study which sought to verify his influential, yet criticized, results and to test the possibility that a humour response mediates the relationship between bizarre elaboration and recall using multiple regression procedures. In keeping with Delin's findings, the results of the present study suggest that bizarre elaboration facilitates both free and cued recall after a substantial delay. The results also suggest that the facilitative effects of bizarreness are mediated by humour. The findings are discussed in the context of a comprehensive theory of bizarreness effects.
The case for polygraph testing of sex offenders
Authors: Grubin Don
Published: April 2008

Purpose. To describe the issues associated with the post‐conviction testing of sex offenders (CST).

Arguments. Post‐conviction sex offender testing (PCSOT) is used widely in sex offender treatment and supervision programmes, but it is not without controversy. Much of the criticism of PCSOT, however, arises because of confusion between it and other applications of polygraphy. It is argued that the evidence for accuracy and utility, although not definitive, is sufficient to justify the use of PCSOT. Ethical issues are also addressed.

Conclusion. Whatever the pros and cons of polygraph use in other settings, PCSOT can make a valuable contribution to sex offender treatment and management.
Of Spies, a Ship and a Videotape—Stop, Pause, Play, Rewind, Play: Inspection and Use of the Videotape of the Rainbow Warrior Court Proceedings
Authors: Tobin Rosemary
Published: April 2008

In New Zealand access to court files in criminal proceedings is at the discretion of a judge or registrar. This article traces the way the rationale for the discretion changed over the last 20 years as the two French agents involved in the Rainbow Warrior bombing sought to prevent access to the court file containing the videotape showing their guilty pleas to a charge of manslaughter. Open justice and freedom of expression do not directly govern the exercise of the discretion but they are an essential part of the balancing process now undertaken by the courts when requests are made to access court files.
Plasma PCSK9 Concentrations Correlate with LDL and Total Cholesterol in Diabetic Patients and Are Decreased by Fenofibrate Treatment
Authors: Lambert Gilles , Ancellin Nicolas , Charlton Francesca , Comas Daniel , Pilot Julia , Keech Anthony , Patel Sanjay , Sullivan David R , Cohn Jeffrey S , Rye Kerry-Anne , Barter Philip J
Published: April 2008

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment.

Methods: We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9. We measured circulating PCSK9 concentrations in 115 diabetic patients from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study before and after fenofibrate treatment.

Results: We found that plasma PCSK9 concentrations correlate with total (r = 0.45, P = 0.006) and LDL (r = 0.54, P = 0.001) cholesterol but not with triglycerides or HDL cholesterol concentrations in that cohort. After 6 weeks of treatment with comicronized fenofibrate (200 mg/day), plasma PCSK9 concentrations decreased by 8.5% (P = 0.041 vs pretreatment). This decrease correlated with the efficacy of fenofibrate, as judged by a parallel reduction in plasma triglycerides (r = 0.31, P = 0.015) and LDL cholesterol concentrations (r = 0.27, P = 0.048).

Conclusions: We conclude that this decrease in PCSK9 explains at least in part the LDL cholesterol–lowering effects of fenofibrate. Fenofibrate might be of interest to further reduce cardiovascular risk in patients already treated with a statin.
Expanding Assay Dynamics: A Combined Competitive and Direct Assay System for the Quantification of Proteins in Multiplexed Immunoassays
Authors: Hartmann Michael , Schrenk Monika , Döttinger Anette , Nagel Sarah , Roeraade Johan , Joos Thomas O , Templin Markus F
Published: April 2008

Background: The concurrent detection and quantification of analytes that vary widely in concentration present a principal problem in multiplexed assay systems. Combining competitive and sandwich immunoassays permits coverage of a wide concentration range, and both highly abundant molecules and analytes present in low concentration can be quantified within the same assay.

Methods: The use of different fluorescence readout channels allows the parallel use of a competitive system and a sandwich configuration. The 2 generated assay signals are combined and used to calculate the amount of analyte. The measurement range can be adjusted by varying the competitor concentration, and an extension of the assay system’s dynamic range is possible.

Results: We implemented the method in a planar protein microarray–based autoimmune assay to detect autoantibodies against 13 autoantigens and to measure the concentration of a highly abundant protein, total human IgG, in one assay. Our results for autoantibody detection and IgG quantification agreed with results obtained with commercially available assays. The use of 2 readout channels in the protein microarray–based system reduced spot-to-spot variation and intraassay variation.

Conclusions: By combining a direct immunoassay with a competitive system, analytes present in widely varying concentrations can be quantified within a single multiplex assay. Introducing a second readout channel for analyte quantification is an effective tool for spot-to-spot normalization and helps to lower intraassay variation.
The Perfect Storm: Obesity, Adipocyte Dysfunction, and Metabolic Consequences
Authors: de Ferranti Sarah , Mozaffarian Dariush
Published: April 2008

Background: As the prevalence of adiposity soars in both developed and developing nations, appreciation of the close links between obesity and disease increases. The strong relationships between excess adipose tissue and poor health outcomes, including cardiovascular disease, diabetes, and cancer, mandate elucidation of the complex cellular, hormonal, and molecular pathophysiology whereby adiposity initiates and maintains adverse health effects.

Content: In this report we review adipocyte metabolism and function in the context of energy imbalance and postprandial nutrient excess, including adipocyte hypertrophy and hyperplasia, adipocyte dysfunction, and other systemic consequences. We also discuss implications for laboratory evaluation and clinical care, including the role of lifestyle modifications. Chronic energy imbalance produces adipocyte hypertrophy and hyperplasia, endoplasmic reticulum stress, and mitochondrial dysfunction. These processes lead to increased intracellular and systemic release of adipokines, free fatty acids, and inflammatory mediators that cause adipocyte dysfunction and induce adverse effects in the liver, pancreatic β-cells, and skeletal muscle as well as the heart and vascular beds. Several specialized laboratory tests can quantify these processes and predict clinical risk, but translation to the clinical setting is premature. Current and future pharmacologic interventions may target these pathways; modest changes in diet, physical activity, weight, and smoking are likely to have the greatest impact.

Summary: Adipocyte endoplasmic reticulum and mitochondrial stress, and associated changes in circulating adipokines, free fatty acids, and inflammatory mediators, are central to adverse health effects of adiposity. Future investigation should focus on these pathways and on reversing the adverse lifestyle behaviors that are the fundamental causes of adiposity.
Legitimate Collaboration: The Administration of Santo Tomás Internment Camp and Its Histories, 1942–2003
Authors: Ward James Mace
Published: April 2008

During World War II the Japanese Imperial Army concentrated several thousand Allied civilians at the Santo Tomás Internment Camp in Manila, the Philippines. Internee and Japanese administrators subsequently collaborated extensively to run the camp. Since its liberation in 1945, however, the camp's English-language historians have tended to tell the camp experience as a resistance story. This article explores both the history of the camp and its historiography through archival and published sources. It argues that the tendency to recast collaboration into resistance stems from an understanding of collaboration as inherently illegitimate. By conceiving of collaboration as a behavioral category within which lies a spectrum of moral and political legitimacy, the historian can work against this inclination to misunderstand the past.
Making Wilderness Work: Frank Church and the American Wilderness Movement
Authors: Dant Sara
Published: April 2008

Idaho Senator Frank Church (served 1957–1981) is one of the most important and underappreciated participants in the politics of the American wilderness movement. Church neither originated the wilderness idea nor crafted the language of the original Wilderness Act, but he made wilderness work. Although his legislative compromises and pragmatic politics sometimes infuriated wilderness purists, they were essential to the passage of all three wilderness bills: the Wilderness Act of 1964, the Eastern Wilderness Areas Act of 1974, and the Endangered American Wilderness Act of 1978. As his legislative record demonstrates, Church was not only at the vanguard of the evolving definition of wilderness in America but also established a viable process for designating wilderness areas. Church's coalition-building vision of wilderness as a communally defined natural space, not necessarily “untrammeled by man,” became the standard for wilderness designation, and his enduring legacy is a model of citizen cooperation.
Comparison of Diploid and Triploid Largemouth Bass Growth and Maturation through Age 1 in Puerto Rico
Authors: Neal J. Wesley , Noble Richard L.
Published: April 2008

Triploid largemouth bass Micropterus salmoides could be valuable both in sport fish management and in food fish production. This study compared the growth and reproductive development of diploid and triploid largemouth bass through age 1 in Lucchetti Reservoir, Puerto Rico. We produced and stocked 487 diploids and 477 triploids tagged with binary coded wire tags and recaptured these fish over 2 years. Growth rates, condition (relative weight (Wr)), and reproductive investment (gonadosomatic index (GSI)) were compared for diploid and triploid fish. Rates of mean daily growth did not differ between diploids (0.81 mm/d; SE = 0.07) and triploids (0.91 mm/d; SE = 0.09) as juveniles or overall through age 1. Diploid largemouth bass exhibited advanced reproductive development during age 1, while triploids did not. Mean GSI was higher for diploid females (mean = 1.98; SE = 0.81) than for triploid females (mean = 0.29; SE = 0.05), but male mean GSI did not significantly differ between the two groups. No difference in Wr was observed. Experimental fish in this study reached maturity in the middle of the spawning season at age 1 and therefore may not have reproduced. Additional research on triploid largemouth bass beyond age 1 is necessary to determine whether sterile triploids have growth advantages over reproductive adult diploids.
Marcadores genéticos e auto-imunes do diabetes melito tipo 1: da teoria para a prática
Authors: Silva Maria Elizabeth Rossi da , Mory Denise , Davini Elaine
Published: April 2008

O diabetes melito tipo 1 auto-imune (DM1A) resulta da destruição auto-imune seletiva das células-beta pancreáticas produtoras de insulina. O principal determinante genético de suscetibilidade para o DM1A está em genes do complexo principal de histocompatibilidade, no cromossomo 6p211.3 (locus IDDM1), responsável por 40% ou mais da agregação familiar dessa doença. O maior risco é conferido pelo genótipo do antígeno leucocitário humano HLA-DR3-DQA1* 0501-DQB1*0201/DR4-DQA1*0301-QB1*0302, e o haplótipo HLA-DR15-DQA1* 0102-DQB1*0602 é associado à proteção. Três outros loci relacionados à predisposição a DM1A são o número variável de freqüências repetidas (VNTR) do gene da insulina (IDDM2), que confere 10% da suscetibilidade genética, o antígeno-4 associado ao linfócito T citotóxico (CTLA-4) e o protein tyrosine phosphatasis nonreceptor-type 22 (PTPN22). Muitos outros genes suspeitos de predispor à auto-imunidade estão sendo investigados. O DM1A é freqüentemente associado com doença auto-imune tiroidiana, doença celíaca, doença de Addison e várias outras doenças auto-imunes, caracterizadas por auto-anticorpos órgãos-específicos, relacionados aos mesmos determinantes genéticos. Esses anticorpos são úteis na detecção de auto-imunidade órgão-específica antes do aparecimento da doença clínica, prevenindo comorbidades.
Organização de um serviço de assistência ao paciente com diabetes melito tipo 1
Authors: Tschiedel Balduino , Cé Gislaine Vissoky , Geremia César , Mondadori Paula , Speggiorin Silvana , Puñales Marcia K. C.
Published: April 2008

Neste artigo são apresentadas as bases para a organização de um serviço especializado em diabetes na infância e na adolescência. É mostrado o modo como foi implementado o Instituto da Criança com Diabetes do Rio Grande do Sul (ICD) e a esquematização de seu trabalho. Seus objetivos são: diminuir hospitalizações por situações agudas, diminuir a freqüência de complicações crônicas e capacitar recursos humanos. São atendidos, em regime ambulatorial e de hospital-dia, 1.315 pacientes, majoritariamente diabetes melito tipo 1, de maneira gratuita, pelo Sistema Único de Saúde (SUS), por meio de convênio com o Grupo Hospitalar Conceição, Ministério da Saúde. Um programa educativo diário é realizado, com aulas de 45 minutos de duração, que fazem parte da atenção ao paciente e à sua família. Mostra-se uma diminuição das internações hospitalares, de 2004 a 2007, de 7,5% para 2,7%. Também são apresentados os diversos esquemas terapêuticos seguidos pela equipe interdisciplinar do instituto no atendimento às diferentes faixas etárias.
Adjuvantes no tratamento da hiperglicemia do diabetes melito tipo 1
Authors: Gabbay Mônica de A. Lima
Published: April 2008

Desde o Diabetes Control and Complications Trial (DCCT), a terapia insulínica intensiva tem sido direcionada para alcançar valores de glicemia e hemoglobina glicada (HbA1c) tão próximos do normal quanto a segurança permita. Entretanto, a hiperglicemia (especialmente a hiperglicemia pós-prandial) e a hipoglicemia continuam a ser um problema no manejo do diabetes tipo 1. O objetivo de associar outras drogas à terapia insulínica é diminuir a glicemia pós-prandial. A terapia adjunta pode ser dividida em três grupos, conforme seu mecanismo de ação: 1. Aumento da ação da insulina (metformina e tiazolidinedionas); 2. Alteração da liberação de nutrientes no trato gastrintestinal (acarbose e amilina); 3. Outros modos de ação [pirenzepina, fator de crescimento insulina-símile (IGF-1) e peptídeo semelhante ao glucagon 1 (GLP-1). Muitos desses agentes mostraram, em estudos de curto prazo, diminuição de 0,5% a 1% na HbA1c, diminuir a hiperglicemia pós-prandial e as doses diárias de insulina.
Diabetes auto-imune latente do adulto ou diabetes melito tipo 2 magro?
Authors: Calsolari Maria Regina , Rosário Pedro W. Souza do , Reis Janice Sepúlveda , Silva Saulo Cavalcanti da , Purisch Saulo
Published: April 2008

A prevalência do diabetes auto-imune latente do adulto (LADA) varia em virtude da população estudada, dos critérios usados e dos anticorpos avaliados. Em 256 pacientes com menos de 25 anos, encontramos 26 (10,2%) com anticorpos anti-GAD (GADA) positivos, dos quais 16 (6,3%) evoluíram sem necessidade de insulina inicialmente. Embora exista controvérsias, sugere-se como critérios diagnósticos de LADA: idade entre 25 e 65 anos; ausência de cetoacidose ou hiperglicemia sintomática no diagnóstico ou imediatamente após, sem necessidade de insulina por 6 a 12 meses; e presença de auto-anticorpos (especialmente GADA). A auto-imunidade e a resistência insulínica coexistem no LADA, e a contribuição desses fatores parece estar refletida nos títulos de GADA. Um subgrupo similar aos diabéticos tipo 2, fenotipicamente e na progressão para necessidade de insulina, parece ser melhor identificado pela presença de baixos títulos de GADA, sobretudo isolados. Por outro lado, indivíduos com altos títulos de GADA e múltiplos anticorpos apresentam fenótipo mais próximo do diabetes melito do tipo 1 (DM1) clássico e são de maior risco para falência prematura das células-beta. Comparados aos diabéticos GADA-negativos, pacientes com LADA apresentam maior prevalência de outros auto-anticorpos (anti-TPO, anti-21-hidroxilase e associados à doença celíaca) e maior freqüência de genótipos e haplótipos de risco para DM1. Pacientes com altos títulos de GADA podem ser beneficiados, retardando a falência das células-beta, com a insulinização precoce e evitando-se o uso de sulfoniluréias. Em oposição, pacientes com baixos títulos de GADA aparentemente não teriam prejuízos em serem conduzidos da mesma forma que pacientes portadores de diabetes melito tipo 2 (DM2) (GADA-negativos).