bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward understanding the variability in the language proficiencies of Arabic heritage speakers
Authors: Albirini Abdulkafi
Published: January 2013

Previous research on Arabic heritage speakers points to notable variability in the language proficiencies of Arabic heritage speakers, both as individuals and as groups (Albirini & Benmamoun, 2012; Albirini, Benmamoun, & Saadah, 2011). This study examines the language proficiencies of Egyptian and Palestinian heritage speakers, assesses the relationship between their L1 proficiency levels and other linguistic, socio-affective, socio-contextual, and demographic factors, and explores the relative significance of these factors in determining proficiency in heritage Arabic. A total of 20 Egyptian and 20 Palestinian heritage speakers completed an oral narrative that was used for assessing three dimensions of their language proficiencies, namely fluency, grammatical accuracy, and syntactic complexity. In addition, the participants filled in a 182-item questionnaire about the factors potentially influencing their heritage language skills, including language input, language use, language attitudes, ethnic identity, family role, community support, school, and demographics. The study also involved follow-up interviews with a sample of five Palestinian and five Egyptian participants.

The results showed that the Palestinian speakers outperformed their Egyptian counterparts in terms of language fluency, accuracy, complexity, and overall proficiency. Pearson and Spearman correlations indicated that language use, language input, family role, community support, and parents’ language correlate positively with language proficiency. Multiple regression analyses showed that language use (in terms of frequency, range, and contexts) is the only significant predictor of the variability in heritage language proficiency. Lastly, the interviews revealed that the Palestinian heritage speakers’ linguistic advantage over their Egyptian counterparts might be attributed to their commitment to Arabic as a main marker of their heritage and identity, the encouragement of their families to maintain their heritage language, and the wider social networks to which they had access. The implications of the study are discussed.
On the formability of hole-flanging by incremental sheet forming
Authors: Silva MB , Teixeira P , Reis A , Martins PAF
Published: January 2013

Hole-flanging by incremental sheet forming is developing as an innovative metal forming technology for flexible small batch-production of cylindrical or conical flanges in blanks with pre-cut holes. The process is seen as an alternative to hole-flanging by conventional press-working due to significant cost savings through the replacement of complex press-tools by simple dieless forming apparatuses and to widespread belief that the limiting forming ratio of hole-flanging by incremental sheet forming is always higher than that of hole-flanging by conventional press-working. This article focuses on the aforementioned assumption and investigates the influence of material failure by necking and fracture on the limiting forming ratio. The experimental work is performed in a CNC machining center and a hydraulic press equipped with apparatuses for multi-stage single point incremental forming and conventional press-tooling, and the strain loading paths resulting from each forming process are determined by circle grid analysis. Results in Aluminium AA1050-H111 and Titanium (grade 2) blanks demonstrate that contrary to what has often been said in the literature there are process operating conditions leading to higher limiting forming ratio of hole-flanging by conventional press-working than by incremental sheet forming due to closeness of the forming limit curve and fracture forming limit line in the principal strain space.
Brandscapes of control? Surveillance, marketing and the co-construction of subjectivity and space in neo-liberal capitalism
Authors: Wood David Murakami , Ball Kirstie
Published: January 2013

This article considers the emergence of the ‘brandscape’ as a new apparatus and a mode of order in neo-liberal capitalism. Simultaneously locating its emergence as a result of developments in marketing, urbanism, technology and surveillance, we discuss its characteristics, forms and potentialities. The brandscape is a marketing neologism that combines the concept of the ‘brand’ with ‘landscape’. Based on the notion of the brand, which seeks to give reassurance and familiarity to customers by semiotic visual codings of product ranges, brandscapes in consumer spaces have an inherent experiential quality and form the basis of the new affective economy. The brandscape recodes the consumer subject as a spatialised, desiring, networked body produced through a complex of marketing techniques designed to analyse buying behaviour, target consumers, and seduce them with strongly affective experiences. Working as immaterial labourers, through the constant provision of consumer data upon which the brandscape rests, consumers become exploited as well as exhilarated. Brandscapes also become securityscapes, as their boundaries and interiors are heavily policed to protect the dreams of safety and riskless living they proffer. However, as simulated consumer subjects are reinscribed onto the material, we note both the tendency to failure in the assumptions of the underpinning marketing processes and the competition to brandscapes from other visions of security and ubiquitous computing futures. But the problems of brandscapes provide the context for a move from biopolitical to neuropolitical control, as the brain, rather than affect, becomes the new site of contestation.
Exploring biological data: Mappings between ontology- and cluster-based representations
Authors: Jusufi Ilir , Kerren Andreas , Schreiber Falk
Published: January 2013

Ontologies and hierarchical clustering are both important tools in biology and medicine to study high-throughput data such as transcriptomics and metabolomics data. Enrichment of ontology terms in the data is used to identify statistically overrepresented ontology terms, giving insight into relevant biological processes or functional modules. Hierarchical clustering is a standard method to analyze and visualize data to find relatively homogeneous clusters of experimental data points. Both methods support the analysis of the same data set but are usually considered independently. However, often a combined view is desired: visualizing a large data set in the context of an ontology under consideration of a clustering of the data. This article proposes new visualization methods for this task. They allow for interactive selection and navigation to explore the data under consideration as well as visual analysis of mappings between ontology- and cluster-based space-filling representations. In this context, we discuss our approach together with specific properties of the biological input data and identify features that make our approach easily usable for domain experts.
Antiretroviral Therapy Adherence Support
Authors: Amico K. Rivet , Orrell Catherine
Published: January 2013

Dramatic increases in the evidence-base for intervention approaches to support antiretroviral therapy (ART) adherence have resulted in numerous reviews, syntheses, and guidelines/recommendations. This review characterizes the current state of the literature and identifies areas in need of additional targeted focus to better align research and practice. Leading recommendations for the process of intervention development (relevant to both rigorous research and real-world intervention planning) and strategies to consider in working with individuals, communities, and systems are provided. In order to move systematically toward the identification of what kinds of interventions work best for whom and when, attending to both intervention outcomes and “drivers” of observed effects or lack of effects in controlled research is critically important. Further, evidence emerging from practice should be aggressively added to research agendas to promote better synergies between the practice and research communities.
Lack of compliance of European Public Assessment Reports to guidelines for paediatric drug development before the introduction of paediatric investigation plans
Authors: Piana Chiara , Kliphuis Edward , Della Pasqua Oscar
Published: January 2013

Background

According to the International Conference on Harmonisation (ICH) and Food and Drug Administration (FDA) guidelines for paediatric clinical trials, bridging procedures can be used if disease progression, exposure–response relationships, and clinical endpoints are similar in adults and children. In these circumstances, confirmatory efficacy trials are not necessary; the evaluation of pharmacokinetics and safety ought to be sufficient for drug approval.

Purpose

The aim of this study was to assess whether the clinical trials and strategy for market approval authorisation (MAAs) in paediatric indications reflect the guidelines for bridging of adult data.

Methods

A total of 95 European Public Assessment Reports (EPARs) published between 1995 and 2007 were reviewed. From every report, data extraction was performed according to the phase of development, scope of analysis, number of dose levels, dosage form, and demographics of the subjects enrolled in the trial. Data analysis consisted of an initial grouping of the studies by the degree of compliance to bridging guidelines.

Results

Our analysis reveals that only 66% of the trials (n = 174) can be classified as needed, while 22% of the trials (n = 59) could have been designed and performed differently from the approved protocol (partially required). Moreover, 12% (n = 30) of the studies were deemed completely unnecessary.

Limitations

A potential limitation in our study was that the dates of start and completion of the clinical studies were not available. Therefore, some EPARs have been included that may reflect common practice in the period that precedes the introduction of the ICH E11 guidelines. Yet, this should not obscure the points identified with regard to the lack of compliance to guidelines before the introduction of the paediatric legislation and the requirements for a paediatric investigation plan.

Conclusions

Paediatric trials are desirable and necessary to address important unmet medical needs. However, the types of studies supporting regulatory approval do not always reflect the recommendations available in paediatric guidelines, which allow for extrapolation and bridging approaches. This situation may be explained by the lack of awareness about the prerequisites for the use of bridging concepts and of a clear process for evaluating different strategies in paediatric development.
National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial: Advancing the science of recruitment and breast cancer risk assessment in minority communities
Authors: McCaskill-Stevens Worta , Wilson John W , Cook Elise D , Edwards Cora L , Gibson Regina V , McElwain Diane L , Figueroa-Moseley Colmar D , Paskett Electra D , Roberson Noma L , Wickerham D Lawrence , Wolmark Norman
Published: January 2013

Background

One of the first chemoprevention trials conducted in the western hemisphere, the National Surgical Adjuvant Breast and Bowel Project’s (NSABP) Breast Cancer Prevention Trial (BCPT), demonstrated the need to evaluate all aspects of recruitment in real time and to implement strategies to enroll racial and ethnic minority women.

Purpose

The purpose of this report is to review various patient recruitment efforts the NSABP developed to enhance the participation of racial and ethnic minority women in the Study of Tamoxifen and Raloxifene (STAR) trial and to describe the role that the recruitment process played in the implementation and understanding of breast cancer risk assessment in minority communities.

Methods

The NSABP STAR trial was a randomized, double-blinded study comparing the use of tamoxifen 20 mg/day to raloxifene 60 mg/day, for a 5-year period, to reduce the risk of developing invasive breast cancer. Eligible postmenopausal women were required to have a 5-year predicted breast cancer risk of 1.66% based on the modified Gail Model. For the current report, eligibility and enrollment data were tabulated by race/ethnicity for women who submitted STAR risk assessment forms (RAFs).

Results

A total of 184,460 RAFs were received, 145,550 (78.9%) from white women and 38,910 (21.1%) from minority women. Of the latter group, 21,444 (11.6%) were from African Americans/blacks, 7913 (4.5%) from Hispanics/Latinas, and 9553 (5.2%) from other racial or ethnic groups. The percentages of risk-eligible women among African Americans, Hispanics/Latinas, others, and whites were 14.2%, 23.3%, 13.7%, and 57.4%, respectively. Programs targeting minority enrollment submitted large numbers of RAFs, but the eligibility rates of the women referred from those groups tended to be lower than the rates among women referred outside of those programs. The average number of completed risk assessments increased among minority women over the course of the recruitment period compared to those from whites.

Limitations

We have not addressed all identified barriers to the recruitment of minorities in clinical research. Our risk assessments and recruitment results do not reflect the modified Gail Model for African Americans.

Conclusions

Recruitment strategies used in STAR for racial and ethnic minorities contributed to doubling the minority enrollment compared to that in the BCPT and increased the awareness of breast cancer risk assessment in minority communities. Incorporation of new information into models to improve the risk estimation of diverse populations should prove beneficial.
Parental perceptions of family adjustment in childhood developmental disabilities
Authors: Thompson Sandra , Hiebert-Murphy Diane , Trute Barry
Published: January 2013

Based on the adjustment phase of the double ABC-X model of family stress (McCubbin and Patterson, 1983) this study examined the impact of parenting stress, positive appraisal of the impact of child disability on the family, and parental self-esteem on parental perceptions of family adjustment in families of children with disabilities. For mothers, self-esteem and positive appraisal predicted maternal-perceived family adjustment and mediated the relationship between parenting stress and family adjustment. For fathers, while self-esteem and positive appraisal were not significant in directly predicting perceived family adjustment, self-esteem moderated the relationship between parenting stress and family adjustment. These results suggest that interventions that bolster self-esteem in parents may be useful in enhancing perceptions of family adjustment. Similarly, interventions that enhance mothers’ experiences of the positive aspects of parenting a child with disabilities hold potential to strengthen family adjustment.
A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models
Authors: Stennicke Henning R. , Kjalke Marianne , Karpf Ditte M. , Balling Kristoffer W. , Johansen Peter B. , Elm Torben , Øvlisen Kristine , Möller Flemming , Holmberg Heidi L. , Gudme Charlotte N. , Persson Egon , Hilden Ida , Pelzer Hermann , Rahbek-Nielsen Henrik , Jespersgaard Christina , Bogsnes Are , Pedersen Anette A. , Kristensen Anne K. , Peschke Bernd , Kappers Wendy , Rode Frederik , Thim Lars , Tranholm Mikael , Ezban Mirella , Olsen Eva H. N. , Bjørn Søren E.
Published: January 2013

Key Points

GlycoPEGylated FVIII (N8-GP) demonstrates the same efficacy and prolonged effect in animal models as native FVIII. Circulatory half-life of glycoPEGylated FVIII (N8-GP) is prolonged by approximately twofold in several species.
MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma
Authors: Horn Heike , Ziepert Marita , Becher Claudia , Barth Thomas F. E. , Bernd Heinz-Wolfram , Feller Alfred C. , Klapper Wolfram , Hummel Michael , Stein Harald , Hansmann Martin-Leo , Schmelter Christopher , Möller Peter , Cogliatti Sergio , Pfreundschuh Michael , Schmitz Norbert , Trümper Lorenz , Siebert Reiner , Loeffler Markus , Rosenwald Andreas , Ott German
Published: January 2013

Key Points

Outcome prediction in DLBCL. MYC status in concert with BCL2 and BCL6.
Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency
Authors: Drewniak Agata , Gazendam Roel P. , Tool Anton T. J. , van Houdt Michel , Jansen Machiel H. , van Hamme John L. , van Leeuwen Ester M. M. , Roos Dirk , Scalais Emmanuel , de Beaufort Carine , Janssen Hans , van den Berg Timo K. , Kuijpers Taco W.
Published: January 2013

Key Points

Human CARD9 deficiency is characterized by a selective neutrophil killing defect, resulting in invasive candidiasis.
Ikaros inhibits megakaryopoiesis through functional interaction with GATA-1 and NOTCH signaling
Authors: Malinge Sébastien , Thiollier Clarisse , Chlon Timothy M. , Doré Louis C. , Diebold Lauren , Bluteau Olivier , Mabialah Vinciane , Vainchenker William , Dessen Philippe , Winandy Susan , Mercher Thomas , Crispino John D.
Published: January 2013

Key Points

Ikaros inhibits megakaryocyte specification and terminal differentiation by suppressing key megakaryocyte genes. The GATA switch inhibits Ikaros expression during megakaryocyte development.
Mutations in the A3 domain of Von Willebrand factor inducing combined qualitative and quantitative defects in the protein
Authors: Legendre Paulette , Navarrete Ana-Maria , Rayes Julie , Casari Caterina , Boisseau Pierre , Ternisien Catherine , Caron Claudine , Fressinaud Edith , Goudemand Jenny , Veyradier Agnès , Denis Cécile V. , Lenting Peter J. , Christophe Olivier D.
Published: January 2013

Key Points

VWF A3 domain mutations inducing defective collagen binding and impaired protein production.
Platelet activation and inhibition in polycythemia vera and essential thrombocythemia
Authors: Patrono Carlo , Rocca Bianca , De Stefano Valerio
Published: January 2013

Persistently enhanced platelet activation has been characterized in polycythemia vera (PV) and essential thrombocythemia (ET) and shown to contribute to a higher risk of both arterial and venous thrombotic complications. The incidence of major bleeding complications is also somewhat higher in PV and ET than in the general population. Although its efficacy and safety was assessed in just 1 relatively small trial in PV, low-dose aspirin is currently recommended in practically all PV and ET patients. Although for most patients with a thrombosis history the benefit/risk profile of antiplatelet therapy is likely to be favorable, in those with no such history this balance will depend critically on the level of thrombotic and hemorrhagic risks of the individual patient. Recent evidence for a chemopreventive effect of low-dose aspirin may tilt the balance of benefits and harm in favor of using aspirin more broadly, but the potential for additional benefits needs regulatory scrutiny and novel treatment guidelines. A clear pharmacodynamic rationale and analytical tools are available for a personalized approach to antiplatelet therapy in ET, and an improved regimen of low-dose aspirin therapy should be tested in a properly sized randomized trial.
Non-parsimonious evolution of hagfish Dlx genes
Authors: Fujimoto Satoko , Oisi Yasuhiro , Kuraku Shigehiro , Ota Kinya G , Kuratani Shigeru
Published: January 2013

Background

The number of members of theDlxgene family increased during the two rounds of whole-genome duplication that occurred in the common ancestor of the vertebrates. Because theDlxgenes are involved in the development of the cranial skeleton, brain, and sensory organs, their expression patterns have been analysed in various organisms in the context of evolutionary developmental biology. SixDlxgenes have been isolated in the lampreys, a group of living jawless vertebrates (cyclostomes), and their expression patterns analysed. However, little is known about theDlxgenes in the hagfish, the other cyclostome group, mainly because the embryological analysis of this animal is difficult.

Results

To identify the hagfishDlxgenes and describe their expression patterns, we cloned the cDNA from embryos of the Japanese inshore hagfishEptatretus burgeri. Our results show that the hagfish has at least sixDlxgenes and one pseudogene. In a phylogenetic analysis, the hagfishDlxgenes and those of the lampreys tended to be excluded from the clade of the gnathostomeDlxgenes. In several cases, the lampreyDlxgenes clustered with the clade consisting of two hagfish genes, suggesting that independent gene duplications have occurred in the hagfish lineage. Analysis of the expression of these genes showed distinctive overlapping expression patterns in the cranial mesenchymal cells and the inner ear.

Conclusions

Independent duplication, pseudogenization, and loss of theDlxgenes probably occurred in the hagfish lineage after its split from the other vertebrate lineages. This pattern is reminiscent of the non-parsimonious evolution of its morphological traits, including its inner ear and vertebrae, which indicate that this group is an early-branching lineage that diverged before those characters evolved.
Late HIV diagnosis is a major risk factor for intensive care unit admission in HIV-positive patients: a single centre observational cohort study
Authors: Shrosbree Julia , Campbell Lucy J , Ibrahim Fowzia , Hopkins Phillip , Vizcaychipi Marcela , Strachan Stephanie , Post Frank A
Published: January 2013

Background

HIV positive patients are at risk of infectious and non-infectious complications that may necessitate intensive care unit (ICU) admission. While the characteristics of patients requiring ICU admission have been described previously, these studies did not include information on the denominator population from which these cases arose.

Methods

We conducted an observational cohort study of ICU admissions among 2751 HIV positive patients attending King’s College Hospital, South London, UK. Poisson regression models were used to identify factors associated with ICU admission.

Results

The overall incidence rate of ICU admission was 1.0 [95% CI 0.8, 1.2] per 100 person-years of follow up, and particularly high early (during the first 3 months) following HIV diagnosis (12.4 [8.7, 17.3] per 100 person-years compared to 0.37 [0.27, 0.50] per 100 person-years thereafter; incidence rate ratio 33.5 [23.4, 48.1], p < 0.001). In time-updated analyses, AIDS and current CD4 cell counts of less than 200 cells/mm3 were associated with an increased incidence of ICU admission while receipt of combination antiretroviral therapy (cART) was associated with a reduced incidence of ICU admission. Late HIV diagnosis (initial CD4 cell count <350 or AIDS within 3 months of HIV diagnosis) applied to 81% of patients who were first diagnosed HIV positive during the study period and who required ICU admission. Late HIV diagnosis was significantly associated with ICU admission in the first 3 months following HIV diagnosis (adjusted incidence rate ratio 8.72, 95% CI 2.76, 27.5).

Conclusions

Late HIV diagnosis was a major risk factor for early ICU admission in our cohort. Earlier HIV diagnosis allowing cART initiation at CD4 cell counts of 350 cells/mm3 is likely to have a significant impact on the need for ICU care.
Early application of pulsed electromagnetic field in the treatment of postoperative delayed union of long-bone fractures: a prospective randomized controlled study
Authors: Shi Hong-fei , Xiong Jin , Chen Yi-xin , Wang Jun-fei , Qiu Xu-sheng , Wang Yin-he , Qiu Yong
Published: January 2013

Background

Pulsed electromagnetic field (PEMF) is reported to be an effective adjunct for the management of nonunion long-bone fractures. Most studies implement PEMF treatment after 6 months or longer of delayed union or nonunion following fracture treatment. Despite these variations in treatment, the early application of PEMF following a diagnosis of a postoperative delayed union has not been specifically analyzed. In this study, the outcomes of postoperative delayed union of long-bone fractures treated with an early application of PEMF were evaluated as compared with a sham-treated control group.

Methods

In this prospective, randomized controlled study, a total of 58 long-bone fracture patients, who presented with delayed union of between 16 weeks and 6 months, were randomly split into two groups and subjected to an early application of PEMF or sham treatment. Clinical and radiological assessments were performed to evaluate the healing status. Treatment efficacy was assessed at three month intervals.

Results

Patients in the PEMF group showed a higher rate of union than those in the control group after the first three months of treatment, but this difference failed to achieve statistical significance. At the end of the study, PEMF treatment conducted for an average of 4.8 months led to a success rate of 77.4%. This was significantly higher than the control, which had an average duration of 4.4 months and a success rate of 48.1%. The total time from operation to the end of the study was a mean of 9.6 months for patients in the PEMF group.

Conclusions

Fracture patients treated with an early application of PEMF achieved a significantly increased rate of union and an overall reduced suffering time compared with patients that receive PEMF after the 6 months or more of delayed union, as described by others.
Effects of microcurrent stimulation on Hyaline cartilage repair in immature male rats (Rattus norvegicus)
Authors: de Campos Ciccone Carla , Zuzzi Denise Cristina , Neves Lia Mara Grosso , Mendonça Josué Sampaio , Joazeiro Paulo Pinto , Esquisatto Marcelo Augusto Marretto
Published: January 2013

Background

In this study, we investigate the effects of microcurrent stimulation on the repair process of xiphoid cartilage in 45-days-old rats.

Methods

Twenty male rats were divided into a control group and a treated group. A 3-mm defect was then created with a punch in anesthetized animals. In the treated group, animals were submitted to daily applications of a biphasic square pulse microgalvanic continuous electrical current during 5 min. In each application, it was used a frequency of 0.3 Hz and intensity of 20 μA. The animals were sacrificed at 7, 21 and 35 days after injury for structural analysis.

Results

Basophilia increased gradually in control animals during the experimental period. In treated animals, newly formed cartilage was observed on days 21 and 35. No statistically significant differences in birefringent collagen fibers were seen between groups at any of the time points. Treated animals presented a statistically larger number of chondroblasts. Calcification points were observed in treated animals on day 35. Ultrastructural analysis revealed differences in cell and matrix characteristics between the two groups. Chondrocyte-like cells were seen in control animals only after 35 days, whereas they were present in treated animals as early as by day 21. The number of cuprolinic blue-stained proteoglycans was statistically higher in treated animals on days 21 and 35.

Conclusion

We conclude that microcurrent stimulation accelerates the cartilage repair in non-articular site from prepuberal animals.
Predictive factors affecting cecal intubation failure in colonoscopy trainees
Authors: Park Hong-Jun , Hong Jin-Heon , Kim Hyun-Soo , Kim Bo-Ra , Park So-Yeon , Jo Ki-Won , Kim Jae-Woo
Published: January 2013

Background

Successful cecal intubation (SCI) is not only a quality indicator but also an important marker in a colonoscopy trainee’s progress. We conducted this study to determine factors predicting SCI in colonoscopy trainees, and to compare these factors before and after trainees achieve technical competence.

Methods

Design of this study was a cross-sectional studies of two time series design for one year at a single center. From March 2011 to February 2012, a total 2,050 subjects who underwent colonoscopy by four first-year gastrointestinal fellows were enrolled at Christian hospital, Wonju, Republic of Korea. Four gastrointestinal fellows have filled out the colonoscopic documentation. Main outcome measurement was predictive factors affecting cecal intubation failure and learning curves.

Results

Colonoscopy was successfully completed to the cecum in 1,720 patients (83.9%). Success rates gradually increased as trainees performed more colonoscopies: the rate of SCI was 62% in the first 50 cases, and grew to 93% by the 250th case. Logistic regression analysis of factors affecting cecal intubation failure showed that female gender, low BMI (BMI < 18.5 kg/m2), poor bowel preparation, and past history of stomach surgery were more often associated with cecal intubation failure, particularly before the trainees achieved technical competence.

Conclusion

Several patient characteristics were identified that may predict difficulty of cecal intubation in colonoscopy trainees. Particularly, low BMI, inadequate bowel cleansing, and previous stomach operation were predictors of cecal intubation failure before the trainees have reached technical competency. The results could be informative so that trainees enhance the success rate regarding better colonoscopy training programs.
Cryo-electron tomography reveals four-membrane architecture of the Plasmodium apicoplast
Authors: Lemgruber Leandro , Kudryashev Mikhail , Dekiwadia Chaitali , Riglar David T , Baum Jake , Stahlberg Henning , Ralph Stuart A , Frischknecht Friedrich
Published: January 2013

Background

The apicoplast is a plastid organelle derived from a secondary endosymbiosis, containing biosynthetic pathways essential for the survival of apicomplexan parasites. TheToxoplasmaapicoplast clearly possesses four membranes but in relatedPlasmodiumspp. the apicoplast has variably been reported to have either three or four membranes.

Methods

Cryo-electron tomography was employed to image merozoites ofPlasmodium falciparumandPlasmodium bergheifrozen in their near-native state. Three-dimensional reconstructions revealed the number of apicoplast membranes and the association of the apicoplast with other organelles. Routine transmission electron microscopy of parasites preserved by high-pressure freezing followed by freeze substitution techniques was also used to analyse apicoplast morphology.

Results

Cryo-preserved parasites showed clearly four membranes surrounding the apicoplast. A wider gap between the second and third apicoplast membranes was frequently observed. The apicoplast was found in close proximity to the nucleus and to the rhoptries. The apicoplast matrix showed ribosome-sized particles and membranous whorls.

Conclusions

ThePlasmodiumapicoplast possesses four membranes, as do the apicoplasts of other apicomplexan parasites. This is consistent with a four-membraned secondary endosymbiotic plastid ancestor.
ARTD10 substrate identification on protein microarrays: regulation of GSK3β by mono-ADP-ribosylation
Authors: Feijs Karla LH , Kleine Henning , Braczynski Anne , Forst Alexandra H , Herzog Nicolas , Verheugd Patricia , Linzen Ulrike , Kremmer Elisabeth , Lüscher Bernhard
Published: January 2013

Background

Although ADP-ribosylation has been described five decades ago, only recently a distinction has been made between eukaryotic intracellular poly- and mono-ADP-ribosylating enzymes. Poly-ADP-ribosylation by ARTD1 (formerly PARP1) is best known for its role in DNA damage repair. Other polymer forming enzymes are ARTD2 (formerly PARP2), ARTD3 (formerly PARP3) and ARTD5/6 (formerly Tankyrase 1/2), the latter being involved in Wnt signaling and regulation of 3BP2. Thus several different functions of poly-ADP-ribosylation have been well described whereas intracellular mono-ADP-ribosylation is currently largely undefined. It is for example not known which proteins function as substrate for the different mono-ARTDs. This is partially due to lack of suitable reagents to study mono-ADP-ribosylation, which limits the current understanding of this post-translational modification.

Results

We have optimized a novel screening method employing protein microarrays, ProtoArrays®, applied here for the identification of substrates of ARTD10 (formerly PARP10) and ARTD8 (formerly PARP14). The results of this substrate screen were validated using in vitro ADP-ribosylation assays with recombinant proteins. Further analysis of the novel ARTD10 substrate GSK3β revealed mono-ADP-ribosylation as a regulatory mechanism of kinase activity by non-competitive inhibition in vitro. Additionally, manipulation of the ARTD10 levels in cells accordingly influenced GSK3β activity. Together these data provide the first evidence for a role of endogenous mono-ADP-ribosylation in intracellular signaling.

Conclusions

Our findings indicate that substrates of ADP-ribosyltransferases can be identified using protein microarrays. The discovered substrates of ARTD10 and ARTD8 provide the first sets of proteins that are modified by mono-ADP-ribosyltransferases in vitro. By studying one of the ARTD10 substrates more closely, the kinase GSK3β, we identified mono-ADP-ribosylation as a negative regulator of kinase activity.
Relationship between parent and child pedometer-determined physical activity: a sub-study of the CANPLAY surveillance study
Authors: Craig Cora L , Cameron Christine , Tudor-Locke Catrine
Published: January 2013

Background

Understanding parental influences on their children’s physical activity (PA) provides insight into developing effective family-based interventions. This study examines whether children’s objectively monitored PA is associated with that of their parents.

Methods

Participants (children and parents) were recruited to a sub-study of the Canadian Fitness and Lifestyle Research Institute’s annual Canadian Physical Activity Levels among Youth (CANPLAY) surveillance study. In total, 539 of 1,187 eligible children (age range 5–19 years) and at least one of their parents participated. Participants logged pedometer steps for 7 days. Descriptive statistics were used to examine parental mean daily steps by their children’s age, sex and steps/day. Associations between steps/day for parents and children (controlling for their age and sex) were estimated using general linear and logistic regression.

Results

Children’s mean steps/day did not differ by parents’ age or sex, nor by whether one or both parents participated in the study. There were quantifiable relationships between parents’ and children’s steps/day. For every 1,000 step increase in a father’s steps/day, his son’s increased by 329–407 steps/day and his daughter’s increased by 273 steps/day (adjusted model only). Every 1,000 step increase in a mother’s steps/day was associated with 263–439 extra steps/day for her son’s steps/day and 195–219 steps/day for her daughter. A 3,000 step increment in a father’s or mother’s steps/day was associated with 1.9-2.5 fold increase in the odds that their child’s activity level would be in the upper two tertiles of steps/day.

Conclusions

These cross-sectional data indicate that children’s PA is related to that of their parents in distinct and quantifiable ways. Interventions are warranted to evaluate the direction of this relationship, confirm the magnitude of influence, and illuminate mediating and moderating mechanisms by which both parents may have influence over their own children’s PA.
Bipolar resistive switching in p-type Co3O4 nanosheets prepared by electrochemical deposition
Authors: Younis Adnan , Chu Dewei , Lin Xi , Lee Jiunn , Li Sean
Published: January 2013

Metal oxide nanosheets have potential applications in novel nanoelectronics as nanocrystal building blocks. In this work, the devices with a structure of Au/p-type Co3O4 nanosheets/indium tin oxide/glass having bipolar resistive switching characteristics were successfully fabricated. The experimental results demonstrate that the device have stable high/low resistance ratio that is greater than 25, endurance performance more than 200 cycles, and data retention more than 10,000 s. Such a superior performance of the as-fabricated device could be explained by the bulk film and Co3O4/indium tin oxide glass substrate interface effect.
Effect of TiO2 rutile nanorods on the photoelectrodes of dye-sensitized solar cells
Authors: Jung Young Hee , Park Kyung-Hee , Oh Jeong Seok , Kim Do-Heyoung , Hong Chang Kook
Published: January 2013

In order to enhance the electron transport on the photoelectrodes of dye-sensitized solar cells, one-dimensional rutile nanorods were prepared using electrospun TiO2 nanofibers. The grain size of the nanorods increased with increasing temperature. Electrochemical impedance spectroscopy measurements revealed reduced interface resistance of the cells with the one-dimensional rutile nanorods due to the improved electron transport and the enhanced electrolyte penetration. Intensity-modulated photocurrent/photovoltage spectroscopy showed that the one-dimensional rutile nanorods provided the electrons with a moving pathway and suppressed the recombination of photogenerated electrons. However, an excessive quantity of rutile nanorods created an obstacle to the electrons moving in the TiO2 thin film. The photoelectrode with 7 wt.% rutile nanorods optimized the performance of the dye-sensitized solar cells.
Porcine epidemic diarrhea virus E protein causes endoplasmic reticulum stress and up-regulates interleukin-8 expression
Authors: Xu Xingang , Zhang Honglei , Zhang Qi , Dong Jie , Liang Yabing , Huang Yong , Liu Hung-Jen , Tong Dewen
Published: January 2013

Background

Porcine epidemic diarrhea virus (PEDV) is an important pathogen in swine and is responsible for substantial economic losses. Previous studies suggest that the PEDV E protein plays an important role in the viral assembly process. However, the subcellular localization and other functions of PEDV E protein still require more research.

Methods

The subcellular localization and function of PEDV E protein were investigated by examining its effects on cell growth, cell cycle progression, interleukin-8 (IL-8) expression and cell survival.

Results

The results show that plenty of PEDV E protein is localized in the ER, with small quantities localized in the nucleus. The PEDV E protein has no effect on the intestinal epithelial cells (IEC) growth, cell cycle and cyclin A expression. The cells expressing PEDV E protein express higher levels of IL-8 than control cells. Further studies show that PEDV E protein induced endoplasmic reticulum (ER) stress and activated NF-κB which is responsible for the up-regulation of IL-8 and Bcl-2 expression.

Conclusions

This study shows that the PEDV E protein is localized in the ER and the nucleus and it can cause ER stress. The PEDV E protein had no effect on the IEC growth and cell cycle. In addition, the PEDV E protein is able to up-regulate IL-8 and Bcl-2 expression.
Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics
Authors: Fujioka Shinsuke , Sundal Christina , Wszolek Zbigniew K
Published: January 2013

Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments.
Analysis of prevalence of PTSD and its influencing factors among college students after the Wenchuan earthquake
Authors: Fu Yan , Chen Yongshun , Wang Jin , Tang Xiaohui , He Jieyun , Jiao Miaorui , Yu Chunhua , You Guiying , Li Junying
Published: January 2013

Background

This study explored the prevalence and severity of post-traumatic stress disorder (PTSD) in college students who lived in earthquake center one year after the Wenchuan earthquake on May 12, 2008, the factors affecting the prevalence of PTSD was also investigated.

Methods

2987 students studying at the senior normal school in Tibetan autonomous region which was one of the most devastated regions were selected for this study. The PTSD Checklist-Civilian Version (PCL-C) was used as a screening instrument.

Results

A total of 420 cases (14.1%) were diagnosed with PTSD, among which mild, moderate, severe and extreme symptoms were reported in 122, 185, 106 and 7 cases, respectively. The PTSD prevalence in college students lived in the severely affected area was significantly higher than that in the less severe area (P < 0.001). According to the multivariate logistic regression analysis, the students who were injured in the earthquake, those lost their first degree relative, and those confronted with dead bodies were more likely to express PTSD. Male students were more prone than female students to develop PTSD. However, the students who received psychological tutorship were less prone to express PTSD.

Conclusions

At one year after the earthquake, the PTSD rate in college students in the severely affected area was high. The social support, psychological help and rehabilitation project should be strengthened to improve their ability to cope with the trauma.
A comparative study on the antioxidant activity of methanolic extracts from different parts of Morus alba L. (Moraceae)
Authors: Khan Muhammad Ali , Rahman Aziz Abdur , Islam Shafiqul , Khandokhar Proma , Parvin Shahnaj , Islam Md Badrul , Hossain Mosharrof , Rashid Mamunur , Sadik Golam , Nasrin Shamima , Mollah M Nurul Haque , Alam AHM Khurshid
Published: January 2013

Background

Antioxidants play an important role to protect damage caused by oxidative stress (OS). Plants having phenolic contents are reported to possess antioxidant properties. The present study was designed to investigate the antioxidant properties and phenolic contents (total phenols, flavonoids, flavonols and proanthrocyanidins) of methanolic extracts from Morus alba (locally named as Tut and commonly known as white mulberry) stem barks (TSB), root bark (TRB), leaves (TL) and fruits (TF) to make a statistical correlation between phenolic contents and antioxidant potential.

Methods

The antioxidant activities and phenolic contents of methanolic extractives were evaluated by in vitro standard method using spectrophotometer. The antioxidant activities were determined by total antioxidant capacity, DPPH (1,1-diphenyl-2-picrylhydrazine) radical scavenging assay, hydroxyl radical scavenging assay, ferrous reducing antioxidant capacity and lipid peroxidation inhibition assay methods.

Results

Among the extracts, TSB showed the highest antioxidant activity followed by TRB, TF and TL. Based on DPPH and hydroxyl radical scavenging activity, the TSB extract was the most effective one with IC50 37.75 and 58.90 μg/mL, followed by TRB, TF and TL with IC50 40.20 and 102.03; 175.01 and 114.63 and 220.23 and 234.63 μg/mL, respectively. The TSB extract had the most potent inhibitory activity against lipid peroxidation with IC50 145.31 μg/mL. In addition, the reducing capacity on ferrous ion was in the following order: TSB > TRB > TL > TF. The content of phenolics, flavonoids, flavonols and proanthocyanidins of TSB was found to be higher than other extractives.

Conclusion

The results indicate high correlation and regression (p-value <0 .001) between phenolic contents and antioxidant potentials of the extracts, hence the Tut plant could serve as effective free radical inhibitor or scavenger which may be a good candidate for pharmaceutical plant-based products. However, further exploration is necessary for effective use in both modern and traditional system of medicines.
Non-autoimmune subclinical hypothyroidism due to a mutation in TSH receptor: report on two brothers
Authors: Cerbone Manuela , Agretti Patrizia , De Marco Giuseppina , Improda Nicola , Pignata Claudio , Santamaria Francesca , Tonacchera Massimo , Salerno Mariacarolina
Published: January 2013

Subclinical hypothyroidism (SH) is a condition characterized by a mild persistent thyroid failure. The main cause is represented by autoimmune thyroiditis, but mutations in genes encoding proteins involved in TSH pathway are thought to be responsible for SH, particularly in cases arising in familial settings. Patients with the syndrome of TSH unresponsiveness may have compensated or overt hypothyroidism with a wide spectrum of clinical and morphological alterations depending on the degree of impairment of TSH-receptor (TSH-R) function. We describe the case of two brothers with non autoimmune SH carrying the same heterozygous mutation in the extracellular domain of TSH-R and presenting with different clinical, biochemical and morphological features. The first one had only a slight persistent elevation of TSH, a normal thyroid ultrasound and did never require l- thyroxine (L-T4) replacement treatment. The second one had a neonatal persistent moderate TSH levels increase associated with a thyroid gland hypoplasia and was treated with L-T4 since the first months of life.

These two cases support the recent association of TSH-R mutations inheritance as an autosomal dominant pattern with variable expressivity and suggest that the decision to start replacement therapy in patients with persistent SH due to TSH resistance should be individualized.