bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment adherence of cancer patients to orally administered chemotherapy: Insights from a Greek study using a self-reported questionnaire
Authors: Saratsiotou Ioanna , Kordoni Maria , Bakogiannis Charalampos , Livadarou Eleftheria , Skarlos Dimosthenis , Kosmidis Paris A , Razis Evangelia
Published: August 2010

Purpose. The aim of this prospective observational study was to investigate the patterns of treatment adherence to orally administered chemotherapy of patients being treated for cancer.

Methods. Patients were asked to participate in the survey during their visits to the study centers’ pharmacists or doctors to obtain their oral medication from April 2008 until May 2009. The data were collected using a self-reported anonymous 7-page long questionnaire, which contained questions about their demographic profile, disease and treatment characteristics, and side-effects and adherence information, both intentional and nonintentional.

Results. 99 Patients completed the questionnaire. Missing values ranged from 1% to 8%. Unintended nonadherence to therapy was reported by 19 patients. The most important factor correlating with unintended nonadherence was the patient’s belief regarding treatment effectiveness since only 16.7% of the patients believing that their treatment is effective reported nonadherence as opposed to 62.5% for those that did not believe that treatment is effective ( p = 0.03). Intentional nonadherence was reported by 14 patients The most important factor correlating to intentional nonadherence was time since disease diagnosis, as nonadherence was reported by 33.3% of the patients having the disease less than 6 months, compared to 16.7% for those between 6 and 24 months and 8.3% for those between 2 and 5 years ( p = 0.01).

Conclusion. Greek patients seem to have similar nonadherence pattern as in other countries. Confidence in treatment efficacy appeared as a significant adherence determinant.
Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan
Authors: Yoshida Jin , Koda Shigeki , Nishida Shozo , Yoshida Toshiaki , Miyajima Keiko , Kumagai Shinji
Published: August 2010

Purpose. The aim of the present study was to evaluate the measurement of contamination by antineoplastic drugs for safer handling of such drugs by medical workers. We investigated the relationship between the contamination level of antineoplastic drugs and the conditions of their handling.

Methods. Air samples and wipe samples were collected from equipment in the preparation rooms of five hospitals (hospitals A—E). These samples were subjected to measurement of the amounts of cyclophosphamide (CPA), fluorouracil (5FU), gemcitabine (GEM), and platinum-containing drugs (Pt). Twenty-four-hour urine samples were collected from the pharmacists who handled or audited, the antineoplastic drugs were analyzed for CPA and Pt.

Results. Pt was detected from air samples inside BSC in hospital B. Antineoplastic drugs were detected from wipe samples of the BSC in hospitals A, B, D, and E and of other equipment in the preparation rooms in hospitals A, B, C, and D. Cyclophosphamide and 5FU were detected from wipe samples of the air-conditioner filter in hospital A, and CPA was detected from that in hospital D. Cyclophosphamide was detected from urine samples of workers in hospitals B, D, and E.

Conclusion. The contamination level of antineoplastic drugs was suggested to be related with the amount of drugs handled, cleaning methods of the equipment, and the skill level of the technique of maintaining negative pressure inside a vial. In order to reduce the contamination and exposure to antineoplastic drugs in the hospital work environment very close to zero, comprehensive safety precautions, including adequate mixing and cleaning methods was required in addition to BSC and closed system device.
Global Service Learning Project Influences Culturally Sensitive Care
Authors: Jones Ellen D. , Ivanov Luba L. , Wallace Debra , VonCannon Lois
Published: August 2010

Global service learning opportunities provided nursing students with the opportunity to experience a health care system that was unfamiliar to them and to interact with health care providers within that system. Service learning is a part of professional education that allows students to demonstrate their ability to apply and synthesize knowledge while it sharpens nursing students’ critical thinking skills. Faculty and students from a southeastern university combined a global health care experience with an integrated research—service learning project targeted at “needed services” in a rural Russian primary care clinic. The purpose of this global service learning project was to (a) offer nursing students a global health care learning experience and (b) examine the prevalence of components of the metabolic syndrome among the population of Kuzmolovsky, Russia, through screening activities. Students, with the help of a translator, conducted teaching sessions based on screening results. Programs were planned in advance and careful consideration was paid to treatment recommendations that would be readily available in Russia. Kuzmolovsky health care providers were so enthusiastic that faculty and students were requested to return. Students found that the global experience increased their self-confidence and that it offered insight into providing culturally sensitive care when working with populations from different cultures.
OASIS Update
Authors: Niewenhous Susan S.
Published: August 2010

Home care agencies have passed the 6-month mark in working with the OASIS-C data set. As expected, daily usage has produced many questions regarding how to answer many of the items correctly. This article highlights a number of the questions received by the CMS concerning specific data items.
Is the Full-Range Model of Leadership Really a Full-Range Model of Effective Leader Behavior?
Authors: Michel John W. , Lyons Brian D. , Cho Jeewon
Published: August 2010

A field study was conducted to compare the three meta-categories assessed in the Managerial Practices Survey (MPS) with the “full-range” taxonomy assessed in the Multifactor Leadership Questionnaire (MLQ). Dyadic and group-level analyses found that subordinate job attitudes and boss-rated managerial effectiveness were predicted better by the MPS meta-categories than by the MLQ meta-categories. Results also suggested that at least one of the three meta-categories from the MPS was more important in predicting each effectiveness outcome than any of the meta-categories from the MLQ. Implications germane to leadership theory and research are further discussed.
A Novel Sternal Closure Technique With Implants Suitable for Complex Dehiscences
Authors: de Bucourt Maximilian , Swierzy Marc , Ismail Mahmoud , Gregor Jan , Webler Markus , Rückert Jens-Carsten
Published: August 2010

A novel sternum stabilization implant system is presented in a complex clinical case with previous pseudarthroses. The authors used the advanced closure system Sternal Talon of KLS Martin group and arranged 1 double and 2 single implants in an atypical fashion to fit the patient’s needs. One year later follow up has not revealed any recurrence of pain or pseudarthrotic signs such as crepitation.
Blackness as a barrier to citizenship and education: situating the example of Dilcia Yean and Violeta Bosico
Authors: Wigginton Sheridan
Published: August 2010

Pervasive anti-Haitian bias in the Dominican Republic has created a three-pronged barrier for the black population’s inclusion into the Dominican perception of national identity, citizenship and public education system. First, blacks born in the Dominican Republic are not typically considered to be truly Dominican. Rather, they are commonly thought to be Haitian. Second, this biased concept of Dominican identity and citizenship often makes it difficult for blacks to obtain a birth certificate needed to prove their status as Dominican citizens. Third, this undue burden of documentation results in restricted access to public schooling. Each of these issues is at play in the tangled international court battle of two black Dominican girls, Dilcia Yean and Violeta Bosico, who in 1998 sought to force the Dominican government to grant them birth certificates, and in turn, an education.
Educational relationships in out-of-school-time activities: are children in poverty missing out again?
Authors: Bullock Kate , Muschamp Yolande , Ridge Tess , Wikeley Felicity
Published: August 2010

Poverty may be the major obstacle to positive life chances in the UK. Ennals and Murphy (2005) suggest that escape from the poverty trap is more likely for those who remain in education after the age of 16. However, school life may bring problems for children from low income families, with learning assuming a lower priority than social acceptance (Ridge, 2005). This article argues that young people in poverty are also less likely to participate in other learning activities. The nature of learning in out-of-school-time settings is explored and the distinctive features of the educational relationships that underpin out-of-school-time learning are discussed. We conclude that children from disadvantaged backgrounds who have acquired an understanding of educational relationships are more likely to develop positive attitudes to learning. Strategies to redress the added disadvantage that non-participation in leisure activities creates for young people in low income families are suggested.
Quantification of the preexisting CD4 T-cell repertoire specific for human erythropoietin reveals its immunogenicity potential
Authors: Delluc Stéphanie , Ravot Gilles , Maillere Bernard
Published: August 2010

Antibody-mediated pure red cell aplasia is a rare but serious event resulting from the induction of neutralizing erythropoietin (Epo)–specific antibodies provoked by treatment with recombinant Epo. Because of the crucial role of CD4 T cells in humoral response, we have quantified the number of Epo-specific CD4 T cells in the blood of normal donors by in vitro stimulation. An important repertoire of preexisting Epo-specific T cells was observed in almost half of the donors, comparable with that of non–self-proteins. This observation suggests that, at the steady state, endogenous Epo weakly contributes to tolerance induction and may be ignored by the immune system. As a result, circulating Epo-specific CD4 T cells could be prone to be activated by altered batches of Epo, providing them with costimulatory signals. Our data also highlight the relevance of T-cell assays performed with normal donors to evaluate the potential immunogenicity of therapeutic proteins.
Detection of EBV genomes in plasmablasts/plasma cells and non-B cells in the blood of most patients with EBV lymphoproliferative disorders by using Immuno-FISH
Authors: Calattini Sara , Sereti Irini , Scheinberg Philip , Kimura Hiroshi , Childs Richard W. , Cohen Jeffrey I.
Published: August 2010

Epstein-Barr virus (EBV) is present in B cells in the blood of healthy people; few studies have looked for EBV in other cell types in blood from patients with lymphoproliferative disorders. We use a new technique combining immunofluorescent cell-surface staining and fluorescent in situ hybridization to quantify both EBV copy number per cell and cell types in blood from patients with high EBV DNA loads. In addition to CD20+ B cells, EBV was present in plasmablast/plasma cells in the blood of 50% of patients, in monocytes or T cells in a small proportion of patients, and in “non-B, non-T, non-monocytes” in 69% of patients. The mean EBV copy number in B cells was significantly higher than in plasmablast/plasma cells. There was no correlation between EBV load and virus copy number per cell. Although we detected CD21, the EBV B-cell receptor, on EBV-infected B cells, we could not detect it on virus-infected T cells. These findings expand the range of cell types infected in the blood. Determining the number of EBV genomes per cell and the type of cells infected in patients with high EBV loads may provide additional prognostic information for the development of EBV lymphoproliferative diseases.
Highly-multiplexed SNP genotyping for genetic mapping and germplasm diversity studies in pea
Authors: Deulvot Chrystel , Charrel Hélène , Marty Amandine , Jacquin Françoise , Donnadieu Cécile , Lejeune-Hénaut Isabelle , Burstin Judith , Aubert Grégoire
Published: August 2010

Background

Single Nucleotide Polymorphisms (SNPs) can be used as genetic markers for applications such as genetic diversity studies or genetic mapping. New technologies now allow genotyping hundreds to thousands of SNPs in a single reaction.

In order to evaluate the potential of these technologies in pea, we selected a custom 384-SNP set using SNPs discovered in Pisum through the resequencing of gene fragments in different genotypes and by compiling genomic sequence data present in databases. We then designed an Illumina GoldenGate assay to genotype both a Pisum germplasm collection and a genetic mapping population with the SNP set.

Results

We obtained clear allelic data for more than 92% of the SNPs (356 out of 384). Interestingly, the technique was successful for all the genotypes present in the germplasm collection, including those from species or subspecies different from the P. sativum ssp sativum used to generate sequences. By genotyping the mapping population with the SNP set, we obtained a genetic map and map positions for 37 new gene markers.

Conclusion

Our results show that the Illumina GoldenGate assay can be used successfully for high-throughput SNP genotyping of diverse germplasm in pea. This genotyping approach will simplify genotyping procedures for association mapping or diversity studies purposes and open new perspectives in legume genomics.
Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion
Authors: de Backer Marijke WA , Brans Maike AD , Luijendijk Mieneke CM , Garner Keith M , van den Heuvel Dianne MA , Pasterkamp R Jeroen , Adan Roger AH
Published: August 2010

Background

Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.

Results

We fused the signal peptide from the Von Willebrand Factor (VWF) to a furin site followed by a processed form of the Agouti related protein (AgRP), AgRP83-132or α-melanocyte stimulating hormone.In vitro, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release.In vivoadministration of VWF-AgRP83-132, using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector.

Conclusions

This study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.
YAO is a nucleolar WD40-repeat protein critical for embryogenesis and gametogenesis in Arabidopsis
Authors: Li Hong-Ju , Liu Nai-You , Shi Dong-Qiao , Liu Jie , Yang Wei-Cai
Published: August 2010

Background

In flowering plants, gametogenesis generates multicellular male and female gametophytes. In the model system Arabidopsis, the male gametophyte or pollen grain contains two sperm cells and a vegetative cell. The female gametophyte or embryo sac contains seven cells, namely one egg, two synergids, one central cell and three antipodal cells. Double fertilization of the central cell and egg produces respectively a triploid endosperm and a diploid zygote that develops further into an embryo. The genetic control of the early embryo patterning, especially the initiation of the first zygotic division and the positioning of the cell plate, is largely unknown.

Results

Here we report the characterization of a mutation, yaozhe (yao), that causes zygote arrest and misplacement of cell plate of the zygote, leading to early embryo lethality. In addition, gametophyte development is partially impaired. A small portion of the mutant embryo sacs are arrested at four-nucleate stage with aberrant nuclear positioning. Furthermore, the competence of male gametophytes is also compromised. YAO encodes a nucleolar protein with seven WD-repeats. Its homologues in human and yeast have been shown to be components of the U3 snoRNP complex and function in 18S rRNA processing. YAO is expressed ubiquitously, with high level of expression in tissues under active cell divisions, including embryo sacs, pollen, embryos, endosperms and root tips.

Conclusions

Phenotypic analysis indicated that YAO is required for the correct positioning of the first zygotic division plane and plays a critical role in gametogenesis in Arabidopsis. Since YAO is a nucleolar protein and its counterparts in yeast and human are components of the U3 snoRNP complex, we therefore postulate that YAO is most likely involved in rRNA processing in plants as well.
"Sleep disparity" in the population: poor sleep quality is strongly associated with poverty and ethnicity
Authors: Patel Nirav P , Grandner Michael A , Xie Dawei , Branas Charles C , Gooneratne Nalaka
Published: August 2010

Background

Little is known about the social determinants of sleep attainment. This study examines the relationship of race/ethnicity, socio-economic status (SES) and other factors upon sleep quality.

Methods

A cross-sectional survey of 9,714 randomly selected subjects was used to explore sleep quality obtained by self-report, in relation to socioeconomic factors including poverty, employment status, and education level. The primary outcome was poor sleep quality. Data were collected by the Philadelphia Health Management Corporation.

Results

Significant differences were observed in the outcome for race/ethnicity (African-American and Latino versus White: unadjusted OR = 1.59, 95% CI 1.24-2.05 and OR = 1.65, 95% CI 1.37-1.98, respectively) and income (below poverty threshold, unadjusted OR = 2.84, 95%CI 2.41-3.35). In multivariable modeling, health indicators significantly influenced sleep quality most prominently in poor individuals. After adjusting for socioeconomic factors (education, employment) and health indicators, the association of income and poor sleep quality diminished, but still persisted in poor Whites while it was no longer significant in poor African-Americans (adjusted OR = 1.95, 95% CI 1.47-2.58 versus OR = 1.16, 95% CI 0.87-1.54, respectively). Post-college education (adjusted OR = 0.47, 95% CI 0.31-0.71) protected against poor sleep.

Conclusions

A "sleep disparity" exists in the study population: poor sleep quality is strongly associated with poverty and race. Factors such as employment, education and health status, amongst others, significantly mediated this effect only in poor subjects, suggesting a differential vulnerability to these factors in poor relative to non-poor individuals in the context of sleep quality. Consideration of this could help optimize targeted interventions in certain groups and subsequently reduce the adverse societal effects of poor sleep.
Diet as prophylaxis and treatment for venous thromboembolism?
Authors: Cundiff David K , Agutter Paul S , Malone P Colm , Pezzullo John C
Published: August 2010

Background

Both prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored.

Methods and Findings

The literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment.

Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using anticoagulants as VTE prophylaxis. For both prophylaxis and treatment of VTE, we propose RCTs comparing standard anticoagulation with low VTE risk diets, and we discuss the statistical considerations for an example of such a trial.

Conclusions

Because of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials.
Simulation methods with extended stability for stiff biochemical Kinetics
Authors: Rué Pau , Villà-Freixa Jordi , Burrage Kevin
Published: August 2010

Background

With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows.

Results

In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK) τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes.

Conclusions

The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (bio)chemical systems.
Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type I interferons
Authors: Park Kiwon , Scott Alan L
Published: August 2010

TLR-mediated induction of cholesterol 25-hydoxylase transcription in dendritic cells and macrophages is dependent on IFN-α/IFN-β and signaling through INF-αR and STAT1.

The oxysterol-producing enzyme CH25H plays an important role in regulating lipid metabolism, gene expression, and immune activation. In vitro experiments using a panel of TLR agonists to activate BMDCs and macrophages demonstrated that Ch25h expression is induced rapidly, selectively, and robustly by the TLR ligands poly I:C and LPS. The mechanism of TLR3- and TLR4-induced transcription levels of Ch25h relies on the TRIF-mediated production of type I IFNs and requires signaling through the IFNαR and JAK/STAT1 pathway. Treatment of BMDCs and macrophages with IFN-α or IFN-β induces Ch25h in a STAT1-dependent manner. IFN-γ also up-regulated Ch25h expression by signaling through STAT1, suggesting that multiple pathways regulate the production of this enzyme. In addition, we demonstrated that regulation of Ch25h expression in vivo in lung-derived DCs and macrophages is dependent on signaling through the IFNαR and STAT1. The results suggest that the rapid induction of Ch25h and subsequent oxysterol synthesis may represent a component of the regulatory network that modulates the magnitude of innate immune reactions and possibly the nature and intensity of subsequent adaptive responses.
Disease-specific, neurosphere-derived cells as models for brain disorders
Authors: Matigian Nicholas , Abrahamsen Greger , Sutharsan Ratneswary , Cook Anthony L. , Vitale Alejandra M. , Nouwens Amanda , Bellette Bernadette , An Jiyuan , Anderson Matthew , Beckhouse Anthony G. , Bennebroek Maikel , Cecil Rowena , Chalk Alistair M. , Cochrane Julie , Fan Yongjun , Féron François , McCurdy Richard , McGrath John J. , Murrell Wayne , Perry Chris , Raju Jyothy , Ravishankar Sugandha , Silburn Peter A. , Sutherland Greg T. , Mahler Stephen , Mellick George D. , Wood Stephen A. , Sue Carolyn M. , Wells Christine A. , Mackay-Sim Alan
Published: August 2010

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson’s disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson’s disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery.
Strategies of actin reorganisation in plant cells
Authors: Smertenko Andrei P. , Deeks Michael J. , Hussey Patrick J.
Published: August 2010

Spatial-temporal flexibility of the actin filament network (F-actin) is essential for all basic cellular functions and is governed by a stochastic dynamic model. In this model, actin filaments that randomly polymerise from a pool of free actin are bundled with other filaments and severed by ADF/cofilin. The fate of the severed fragments is not known. It has been proposed that the fragments are disassembled and the monomeric actin recycled for the polymerisation of new filaments. Here, we have generated tobacco cell lines and Arabidopsis plants expressing the actin marker Lifeact to address the mechanisms of F-actin reorganisation in vivo. We found that F-actin is more dynamic in isotropically expanding cells and that the density of the network changes with a periodicity of 70 seconds. The depolymerisation rate, but not the polymerisation rate, of F-actin increases when microtubules are destabilised. New filaments can be assembled from shorter free cytoplasmic fragments, from the products of F-actin severing and by polymerisation from the ends of extant filaments. Thus, remodelling of F-actin might not require bulk depolymerisation of the entire network, but could occur via severing and end-joining of existing polymers.
Assembly of fibrillin microfibrils governs extracellular deposition of latent TGFβ
Authors: Massam-Wu Teresa , Chiu Maybo , Choudhury Rawshan , Chaudhry Shazia S. , Baldwin Andrew K. , McGovern Amanda , Baldock Clair , Shuttleworth C. Adrian , Kielty Cay M.
Published: August 2010

Control of the bioavailability of the growth factor TGFβ is essential for tissue formation and homeostasis, yet precisely how latent TGFβ is incorporated into the extracellular matrix is unknown. Here, we show that deposition of a large latent TGFβ complex (LLC), which contains latent TGFβ-binding protein 1 (LTBP-1), is directly dependent on the pericellular assembly of fibrillin microfibrils, which interact with fibronectin during higher-order fibrillogenesis. LTBP-1 formed pericellular arrays that colocalized with microfibrils, whereas fibrillin knockdown inhibited fibrillar LTBP-1 and/or LLC deposition. Blocking α5β1 integrin or supplementing cultures with heparin, which both inhibited microfibril assembly, disrupted LTBP-1 deposition and enhanced Smad2 phosphorylation. Full-length LTBP-1 bound only weakly to N-terminal pro-fibrillin-1, but this association was strongly enhanced by heparin. The microfibril-associated glycoprotein MAGP-1 (MFAP-2) inhibited LTBP-1 binding to fibrillin-1 and stimulated Smad2 phosphorylation. By contrast, fibulin-4, which interacted strongly with full-length LTBP-1, did not induce Smad2 phosphorylation. Thus, LTBP-1 and/or LLC deposition is dependent on pericellular microfibril assembly and is governed by complex interactions between LTBP-1, heparan sulfate, fibrillin-1 and microfibril-associated molecules. In this way, microfibrils control TGFβ bioavailability.
Nucleotides that are essential but not conserved; a sufficient L-tryptophan site in RNA
Authors: Majerfeld Irene , Chocholousova Jana , Malaiya Vikas , Widmann Jeremy , McDonald Daniel , Reeder Jens , Iyer Matthew , Illangasekare Mali , Yarus Michael , Knight Rob
Published: August 2010

Conservation is often used to define essential sequences within RNA sites. However, conservation finds only invariant sequence elements that are necessary for function, rather than finding a set of sequence elements sufficient for function. Biochemical studies in several systems—including the hammerhead ribozyme and the purine riboswitch—find additional elements, such as loop–loop interactions, required for function yet not phylogenetically conserved. Here we define a critical test of sufficiency: We embed a minimal, apparently sufficient motif for binding the amino acid tryptophan in a random-sequence background and ask whether we obtain functional molecules. After a negative result, we use a combination of three-dimensional structural modeling, selection, designed mutations, high-throughput sequencing, and bioinformatics to explore functional insufficiency. This reveals an essential unpaired G in a diverse structural context, varied sequence, and flexible distance from the invariant internal loop binding site identified previously. Addition of the new element yields a sufficient binding site by the insertion criterion, binding tryptophan in 22 out of 23 tries. Random insertion testing for site sufficiency seems likely to be broadly revealing.
Missense suppressor mutations in 16S rRNA reveal the importance of helices h8 and h14 in aminoacyl-tRNA selection
Authors: McClory Sean P. , Leisring Joshua M. , Qin Daoming , Fredrick Kurt
Published: August 2010

The molecular basis of the induced-fit mechanism that determines the fidelity of protein synthesis remains unclear. Here, we isolated mutations in 16S rRNA that increase the rate of miscoding and stop codon read-through. Many of the mutations clustered along interfaces between the 30S shoulder domain and other parts of the ribosome, strongly implicating shoulder movement in the induced-fit mechanism of decoding. The largest subset of mutations mapped to helices h8 and h14. These helices interact with each other and with the 50S subunit to form bridge B8. Previous cryo-EM studies revealed a contact between h14 and the switch 1 motif of EF-Tu, raising the possibility that h14 plays a direct role in GTPase activation. To investigate this possibility, we constructed both deletions and insertions in h14. While ribosomes harboring a 2-base-pair (bp) insertion in h14 were completely inactive in vivo, those containing a 2-bp deletion retained activity but were error prone. In vitro, the truncation of h14 accelerated GTP hydrolysis for EF-Tu bearing near-cognate aminoacyl-tRNA, an effect that can largely account for the observed miscoding in vivo. These data show that h14 does not help activate EF-Tu but instead negatively controls GTP hydrolysis by the factor. We propose that bridge B8 normally acts to counter inward rotation of the shoulder domain; hence, mutations in h8 and h14 that compromise this bridge decrease the stringency of aminoacyl-tRNA selection.
Academic self‐handicapping: Relationships with learning specific and general self‐perceptions and academic performance over time
Authors: Gadbois Shannon A. , Sturgeon Ryan D.
Published: August 2010

Background. Academic self‐handicapping (ASH) tendencies, strategies students employ that increase their chances of failure on assessments while protecting self‐esteem, are correlated with classroom goal structures and to learners' general self‐perceptions and learning strategies. In particular, greater ASH is related to poorer academic performance but has yet to be examined with respect to learners' performance across a series of tests.

Aims. This research was designed to examine the relationship between students' ASH tendencies and their self‐concept clarity, learning strategies, and performance on a series of tests in a university course.

Sample. A total of 209 (153 female; 56 male) Canadian university psychology students participated in this study.

Methods. Participants' ASH tendencies, self‐concept clarity, approaches to learning, and self‐regulatory learning strategies were assessed along with expected grades and hours of study in the course from which they were recruited. Finally, students' grades were obtained for the three tests for the course from which they were recruited.

Results. Students reporting greater self‐handicapping tendencies reported lower self‐concept clarity, lower academic self‐efficacy, greater test anxiety, more superficial learning strategies, and scored lower on all tests in the course. The relationships of ASH scores and learner variables with performance varied across the three performance indices. In particular, ASH scores were more strongly related to second and third tests, and prior performances were accounted for. ASH scores accounted for a relatively small but significant proportion of variance for all three tests.

Conclusions. These results showed that ASH is a unique contributing factor in student performance outcomes, and may be particularly important after students complete the initial assessment in a course.
Sample size planning with the cost constraint for testing superiority and equivalence of two independent groups
Authors: Guo Jiin‐Huarng , Chen Hubert J. , Luh Wei‐Ming
Published: August 2010

The allocation of sufficient participants into different experimental groups for various research purposes under given constraints is an important practical problem faced by researchers. We address the problem of sample size determination between two independent groups for unequal and/or unknown variances when both the power and the differential cost are taken into consideration. We apply the well‐known Welch approximate test to derive various sample size allocation ratios by minimizing the total cost or, equivalently, maximizing the statistical power. Two types of hypotheses including superiority/non‐inferiority and equivalence of two means are each considered in the process of sample size planning. A simulation study is carried out and the proposed method is validated in terms of Type I error rate and statistical power. As a result, the simulation study reveals that the proposed sample size formulas are very satisfactory under various variances and sample size allocation ratios. Finally, a flowchart, tables, and figures of several sample size allocations are presented for practical reference.
Social dimensions of judgments of integrity in public figures
Authors: Sparks Paul , Farsides Tom
Published: August 2010

The notion of ‘integrity’ remains relatively unexplored in the social psychological literature, despite it being central to some important theoretical perspectives (notably, self‐affirmation theory). It is an eminently positive – and well‐used – epithet in descriptions of public figures. The two studies reported here addressed laypeople's conceptions of integrity. The findings indicate that in relation to eight public figures, the best general predictor of judgments of integrity was perceptions of ‘sincerity’ (characterized by attributes such as genuine and honest). For three of the public figures strongly linked to civil rights issues, judgments of integrity were also predicted by perceptions of ‘standing for something’. The findings suggest that the social character of integrity merits further psychological research attention.
A feasibility study of mindfulness‐based cognitive therapy for individuals with borderline personality disorder
Authors: Sachse Sandy , Keville Saskia , Feigenbaum Janet
Published: August 2010

Objectives. Mindfulness‐based cognitive therapy (MBCT) was originally developed to prevent relapse in recurrent depression. More recently it has been applied to individuals at high risk of suicide or currently suffering with anxiety and depression. The aim of this study was to consider the feasibility of MBCT for individuals with a diagnosis of borderline personality disorder (BPD).

Design. The design of the study was a repeated measures, quasi‐experimental design employing within‐subject and between‐subject comparisons of a sample of participants with BPD. Based on previous studies and theoretical models of the effect of mindfulness and of cognitive therapy, pre‐ and post‐group measures of mindfulness, depression, anxiety, dissociation, impulsivity, experiential avoidance, and attention were obtained.

Method. Participants attended an 8‐week adapted MBCT (MBCT‐a) group intervention. A total of 22 participants were assessed pre‐ and post‐intervention and were subsequently divided for analysis into two groups: treatment completers (N= 16) and non‐completers (number of sessions attended < 4; N= 6).

Results. The study found that MBCT‐a is acceptable to individuals with BPD. Using intention to treat analyses, only attentional control improved. However, post hoc analyses of treatment improvers (N= 9) identified changes in mindfulness and somatoform dissociation. A dose‐effect analysis suggested a weak improvement in mindfulness, experiential avoidance, state anxiety, and somatoform dissociation.

Conclusions. This study suggests that further exploration of MBCT for use with individuals with BPD is merited. The study lends tentative support for attentional and avoidance models of the effects of mindfulness.
In search of a framework for the treatment of alexithymia
Authors: Vanheule Stijn , Verhaeghe Paul , Desmet Mattias
Published: August 2010

Purpose. Clinical observations and controlled studies indicate that the treatment of alexithymic patients is most difficult. Moreover, stronger degrees of alexithymia predict worse therapy outcome. We argue that in order to make therapy for alexithymia‐related disorders fruitful, a conceptualization of alexithymia in terms of interpersonally imbedded affect regulation is needed.

Methods and results. Based on a re‐interpretation of Freud's actual neurosis via Lacan's theory and contemporary attachment theory, we present a theoretical framework that incorporates these points. This framework helps us to explain why classic psychotherapeutic approaches fail, and to formulate principles for an alternative psychoanalytic therapeutic approach that addresses the theoretically discerned difficulties. A clinical vignette is used to examine how these principles can be implemented in clinical practice.

Conclusion. Therapy with actual‐neurotic alexithymic patients should focus on distressing situations, starting from which a three‐step logic can be deployed. During therapy, mental representations on difficult situations in patients' lives need to be constructed by (1) putting into words the chain of events that makes up the distressing situation; (2) making the patient's appraisal of the difficult situation explicit; and (3) addressing affective responses and discussing the patient's way of dealing with the difficult situation.
Pulsed electrodeposition and unique properties of one-dimensional Bi-based nanostructures in porous alumina membranes
Authors: Li Liang , Dou Xincun , Wang Hongqiang , Li Guanghai , Zhang Lide
Published: August 2010

One-dimensional (1D) Bi-based nanostructures are promising thermoelectric materials and, furthermore, are very interesting systems for studying physical and chemical properties in the nanoscale, owing to their anisotropic character. The main challenges in this area are to control the diameter, orientation, and alloy composition with precision, and thereby to gain ready access to junction and superlattice structures. Here, we review our recent contributions toward advances in pulsed electrodeposition-based routes to fabricate Bi-based nanostructures. As a main theme, porous anodic alumina membranes (AAMs) have been employed as effective templates to fabricate Bi elementary, alloy, junction, and superlattice structures, and unique properties are demonstrated.
CRMP5 Interacts with Tubulin to Inhibit Neurite Outgrowth, Thereby Modulating the Function of CRMP2
Authors: Brot Sébastien , Rogemond Véronique , Perrot Valérie , Chounlamountri Naura , Auger Carole , Honnorat Jérôme , Moradi-Améli Mahnaz
Published: August 2010

Collapsin response mediator proteins (CRMPs) are involved in signaling of axon guidance and neurite outgrowth during neural development and regeneration. Among these, CRMP2 has been identified as an important actor in neuronal polarity and axon outgrowth, these activities being correlated with the reorganization of cytoskeletal proteins. In contrast, the function of CRMP5, expressed during brain development, remains obscure. Here, we find that, in contrast to CRMP2, CRMP5 inhibits tubulin polymerization and neurite outgrowth. Knockdown of CRMP5 expression by small interfering RNA confirms its inhibitory functions. CRMP5 forms a ternary complex with MAP2 and tubulin, the latter involving residues 475-522 of CRMP5, exposed at the molecule surface. Using different truncated CRMP5 constructs, we demonstrate that inhibition of neurite outgrowth by CRMP5 is mediated by tubulin binding. When both CRMP5 and CRMP2 are overexpressed, the inhibitory effect of CRMP5 abrogates neurite outgrowth promotion induced by CRMP2, suggesting that CRMP5 acts as a dominant signal. In cultured hippocampal neurons, CRMP5 shows no effect on axon growth, whereas it inhibits dendrite outgrowth and formation, at an early developmental stage, correlated with its strong expression in neurites. At later stages, when dendrites begin to extend, CRMP5 expression is absent. However, CRMP2 is constantly expressed. Overexpression of CRMP5 with CRMP2 inhibits CRMP2-induced outgrowth both on the axonal and dendritic levels. Deficiency of CRMP5 expression enhanced the CRMP2 effect. This antagonizing effect of CRMP5 is exerted through a tubulin-based mechanism. Thus, the CRMP5 binding to tubulin modulates CRMP2 regulation of neurite outgrowth and neuronal polarity during brain development.
The Gata3 Transcription Factor Is Required for the Survival of Embryonic and Adult Sympathetic Neurons
Authors: Tsarovina Konstantina , Reiff Tobias , Stubbusch Jutta , Kurek Dorota , Grosveld Frank G. , Parlato Rosanna , Schütz Günther , Rohrer Hermann
Published: August 2010

The transcription factor Gata3 is essential for the development of sympathetic neurons and adrenal chromaffin cells. As Gata3 expression is maintained up to the adult stage, we addressed its function in differentiated sympathoadrenal cells at embryonic and adult stages by conditional Gata3 elimination. Inactivation of Gata3 in embryonicDBH-expressing neurons elicits a strong reduction in neuron numbers due to apoptotic cell death and reduced proliferation. No selective effect on noradrenergic gene expression (THandDBH) was observed. Interestingly, Gata3 elimination inDBH-expressing neurons of adult animals also results in a virtually complete loss of sympathetic neurons. In the Gata3-deficient population, the expression of anti-apoptotic genes (Bcl-2,Bcl-xL, andNFκB) is diminished, whereas the expression of pro-apoptotic genes (Bik,Bok, andBmf) was increased. The expression of noradrenergic genes (THandDBH) is not affected. These results demonstrate that Gata3 is continuously required for maintaining survival but not differentiation in the sympathetic neuron lineage up to mature neurons of adult animals.
NCAM-Induced Neurite Outgrowth Depends on Binding of Calmodulin to NCAM and on Nuclear Import of NCAM and fak Fragments
Authors: Kleene Ralf , Mzoughi Mounir , Joshi Gunjan , Kalus Ina , Bormann Ulrich , Schulze Christian , Xiao Mei-Fang , Dityatev Alexander , Schachner Melitta
Published: August 2010

The neural cell adhesion molecule NCAM plays important functional roles not only during nervous system development, but also in the adult after injury and in synaptic plasticity. Homophilic binding of NCAM triggers intracellular signaling events resulting in cellular responses such as neurite outgrowth that require NCAM palmitoylation-dependent raft localization and activation of the nonreceptor tyrosine kinases fyn and fak. In this study, we show that stimulation of NCAM by a function-triggering NCAM antibody results in proteolytic processing of NCAM and fak. The C-terminal fragment of NCAM, consisting of the intracellular domain, the transmembrane domain, and a stub of the extracellular domain, and the N-terminal fragment of fak are imported into the nucleus. NCAM-stimulated fak activation, generation, and nuclear import of NCAM and fak fragments as well as neurite outgrowth are abolished by mutation of the calmodulin binding motif in the intracellular domain of NCAM that is responsible for the calcium-dependent binding of calmodulin to NCAM. This mutation interferes neither with NCAM cell surface expression, palmitoylation, and raft localization nor with fyn activation. The way by which the transmembrane NCAM fragment reaches the nucleus in a calmodulin- and calcium-dependent manner is by endocytotic transport via the endoplasmic reticulum and the cytoplasm. The generation and nuclear import of NCAM and phosphorylated fak fragments resulting from NCAM stimulation may represent a signal pathway activating cellular responses in parallel or in association with classical kinase- and phosphorylation-dependent signaling cascades.