bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenetic relationship and virulence inference of Streptococcus Anginosus Group: curated annotation and whole-genome comparative analysis support distinct species designation
Authors: Olson Adam B , Kent Heather , Sibley Christopher D , Grinwis Margot E , Mabon Philip , Ouellette Claude , Tyson Shari , Graham Morag , Tyler Shaun D , Van Domselaar Gary , Surette Michael G , Corbett Cindi R
Published: December 2013

Background

The Streptococcus Anginosus Group (SAG) represents three closely related species of the viridans group streptococci recognized as commensal bacteria of the oral, gastrointestinal and urogenital tracts. The SAG also cause severe invasive infections, and are pathogens during cystic fibrosis (CF) pulmonary exacerbation. Little genomic information or description of virulence mechanisms is currently available for SAG. We conducted intra and inter species whole-genome comparative analyses with 59 publically availableStreptococcusgenomes and seven in-house closed high quality finished SAG genomes;S. constellatus(3),S. intermedius(2), andS. anginosus(2). For each SAG species, we sequenced at least one numerically dominant strain from CF airways recovered during acute exacerbation and an invasive, non-lung isolate. We also evaluated microevolution that occurred within two isolates that were cultured from one individual one year apart.

Results

The SAG genomes were most closely related toS. gordoniiandS. sanguinis, based on shared orthologs and harbor a similar number of proteins within each COG category as otherStreptococcusspecies. Numerous characterized streptococcus virulence factor homologs were identified within the SAG genomes including; adherence, invasion, spreading factors, LPxTG cell wall proteins, and two component histidine kinases known to be involved in virulence gene regulation. Mobile elements, primarily integrative conjugative elements and bacteriophage, account for greater than 10% of the SAG genomes.S. anginosuswas the most variable species sequenced in this study, yielding both the smallest and the largest SAG genomes containing multiple genomic rearrangements, insertions and deletions. In contrast, within theS. constellatusandS. intermediusspecies, there was extensive continuous synteny, with only slight differences in genome size between strains. WithinS. constellatuswe were able to determine important SNPs and changes in VNTR numbers that occurred over the course of one year.

Conclusions

The comparative genomic analysis of the SAG clarifies the phylogenetics of these bacteria and supports the distinct species classification. Numerous potential virulence determinants were identified and provide a foundation for further studies into SAG pathogenesis. Furthermore, the data may be used to enable the development of rapid diagnostic assays and therapeutics for these pathogens.
Assessment of hematopoietic failure due to Rpl11 deficiency in a zebrafish model of Diamond-Blackfan anemia by deep sequencing
Authors: Zhang Zhaojun , Jia Haibo , Zhang Qian , Wan Yang , Zhou Yang , Jia Qiong , Zhang Wanguang , Yuan Weiping , Cheng Tao , Zhu Xiaofan , Fang Xiangdong
Published: December 2013

Background

Diamond–Blackfan anemia is a rare congenital red blood cell dysplasia that develops soon after birth. RPL11 mutations account for approximately 4.8% of human DBA cases with defective hematopoietic phenotypes. However, the mechanisms by which RPL11 regulates hematopoiesis in DBA remain elusive. In this study, we analyzed the transcriptome using deep sequencing data from an Rpl11-deficient zebrafish model to identify Rpl11-mediated hematopoietic failure and investigate the underlying mechanisms.

Results

We characterized hematological defects in Rpl11-deficient zebrafish embryos by identifying affected hematological genes, hematopoiesis-associated pathways, and regulatory networks. We found that hemoglobin biosynthetic and hematological defects in Rpl11-deficient zebrafish were related to dysregulation of iron metabolism-related genes, including tfa, tfr1b, alas2 and slc25a37, which are involved in heme and hemoglobin biosynthesis. In addition, we found reduced expression of the hematopoietic stem cells (HSC) marker cmyb and HSC transcription factors tal1 and hoxb4a in Rpl11-deficient zebrafish embryos, indicating that the hematopoietic defects may be related to impaired HSC formation, differentiation, and proliferation. However, Rpl11 deficiency did not affect the development of other blood cell lineages such as granulocytes and myelocytes.

Conclusion

We identified hematopoietic failure of Rpl11-deficient zebrafish embryos using transcriptome deep sequencing and elucidated potential underlying mechanisms. The present analyses demonstrate that Rpl11-deficient zebrafish may serve as a model of DBA and may provide insights into the pathogenesis of mutant RPL11-mediated human DBA disease.
Epigenetic regulation of MDR1 gene through post-translational histone modifications in prostate cancer
Authors: Henrique Rui , Oliveira Ana Isabel , Costa Vera L , Baptista Tiago , Martins Ana Teresa , Morais António , Oliveira Jorge , Jerónimo Carmen
Published: December 2013

Background

Multidrug resistance 1 (MDR1) gene encodes for an ATP binding cassette transporter - P-glycoprotein (P-gp) - involved in chemoresistance to taxanes. MDR1 promoter methylation is frequent in prostate carcinoma (PCa), suggesting an epigenetic regulation but no functional correlation has been established. We aimed to elucidate the epigenetic mechanisms involved in MDR1 deregulation in PCa.

Results

MDR1 promoter methylation and P-gp expression were assessed in 121 PCa, 39 high-grade prostatic intraepithelial neoplasia (HGPIN), 28 benign prostatic hyperplasia (BPH) and 10 morphologically normal prostate tissue (NPT) samples, using quantitative methylation specific PCR and immunohistochemistry, respectively. PCa cell lines were exposed to a DNA methyltransferases inhibitor 5-aza-2′deoxycytidine (DAC) and histone deacetylases inhibitor trichostatin A (TSA). Methylation and histone posttranscriptional modifications status were characterized and correlated with mRNA and protein expression. MDR1 promoter methylation levels and frequency significantly increased from NPTs, to HGPIN and to PCa. Conversely, decreased or absent P-gp immunoexpression was observed in HGPIN and PCa, inversely correlating with methylation levels. Exposure to DAC alone did not alter significantly methylation levels, although increased expression was apparent. However, P-gp mRNA and protein re-expression were higher in cell lines exposed to TSA alone or combined with DAC. Accordingly, histone active marks H3Ac, H3K4me2, H3K4me3, H3K9Ac, and H4Ac were increased at the MDR1 promoter after exposure to TSA alone or combined with DAC.

Conclusion

Our data suggests that, in prostate carcinogenesis, MDR1 downregulation is mainly due to histone post-translational modifications. This occurs concomitantly with aberrant promoter methylation, substantiating the association with P-gp decreased expression.
Differential regulation of the rainbow trout (Oncorhynchus mykiss) MT-A gene by nuclear factor interleukin-6 and activator protein-1
Authors: Kling Peter , Modig Carina , Mujahed Huthayfa , Khalaf Hazem , von Hofsten Jonas , Olsson Per-Erik
Published: December 2013

Background

Previously we have identified a distal region of the rainbow trout (Oncorhynchus mykiss) metallothionein-A (rtMT-A) enhancer region, being essential for free radical activation of the rtMT-A gene. The distal promoter region included four activator protein 1 (AP1) cis-acting elements and a single nuclear factor interleukin-6 (NF-IL6) element. In the present study we used the rainbow trout hepatoma (RTH-149) cell line to further examine the involvement of NF-IL6 and AP1 in rtMT-A gene expression following exposure to oxidative stress and tumour promotion.

Results

Using enhancer deletion studies we observed strong paraquat (PQ)-induced rtMT-A activation via NF-IL6 while the AP1 cis-elements showed a weak but significant activation. In contrast to mammals the metal responsive elements were not activated by oxidative stress. Electrophoretic mobility shift assay (EMSA) mutation analysis revealed that the two most proximal AP1 elements, AP11,2, exhibited strong binding to the AP1 consensus sequence, while the more distal AP1 elements, AP13,4 were ineffective. Phorbol-12-myristate-13-acetate (PMA), a known tumor promoter, resulted in a robust induction of rtMT-A via the AP1 elements alone. To determine the conservation of regulatory functions we transfected human Hep G2 cells with the rtMT-A enhancer constructs and were able to demonstrate that the cis-elements were functionally conserved. The importance of NF-IL6 in regulation of teleost MT is supported by the conservation of these elements in MT genes from different teleosts. In addition, PMA and PQ injection of rainbow trout resulted in increased hepatic rtMT-A mRNA levels.

Conclusions

These studies suggest that AP1 primarily is involved in PMA regulation of the rtMT-A gene while NF-IL6 is involved in free radical regulation. Taken together this study demonstrates the functionality of the NF-IL6 and AP-1 elements and suggests an involvement of MT in protection during pathological processes such as inflammation and cancer.
The Caenorhabditis elegans interneuron ALA is (also) a high-threshold mechanosensor
Authors: Sanders Jarred , Nagy Stanislav , Fetterman Graham , Wright Charles , Treinin Millet , Biron David
Published: December 2013

Background

To survive dynamic environments, it is essential for all animals to appropriately modulate their behavior in response to various stimulus intensities. For instance, the nematode Caenorhabditis elegans suppresses the rate of egg-laying in response to intense mechanical stimuli, in a manner dependent on the mechanosensory neurons FLP and PVD. We have found that the unilaterally placed single interneuron ALA acted as a high-threshold mechanosensor, and that it was required for this protective behavioral response.

Results

ALA was required for the inhibition of egg-laying in response to a strong (picking-like) mechanical stimulus, characteristic of routine handling of the animals. Moreover, ALA did not respond physiologically to less intense touch stimuli, but exhibited distinct physiological responses to anterior and posterior picking-like touch, suggesting that it could distinguish between spatially separated stimuli. These responses required neither neurotransmitter nor neuropeptide release from potential upstream neurons. In contrast, the long, bilaterally symmetric processes of ALA itself were required for producing its physiological responses; when they were severed, responses to stimuli administered between the cut and the cell body were unaffected, while responses to stimuli administered posterior to the cut were abolished.

Conclusion

C. elegans neurons are typically classified into three major groups: sensory neurons with specialized sensory dendrites, interneurons, and motoneurons with neuromuscular junctions. Our findings suggest that ALA can autonomously sense intense touch and is thus a dual-function neuron, i.e., an interneuron as well as a novel high-threshold mechanosensor.
The transtheoretical model (TTM) questionnaire for smoking cessation: psychometric properties of the Iranian version
Authors: Sarbandi Fatemeh , Niknami Shamsaddin , Hidarnia Alireza , Hajizadeh Ebrahim , Montazeri Ali
Published: December 2013

Background

The transtheoretical model (TTM) is a common framework for studies of smoking cessation. Using the TTM, several instruments were developed to measure to what extent interventions could make changes in people’s behavior. The current study aimed to test the validity and reliability of the Persian version of a TTM based questionnaire for smoking cessation in Iran.

Methods

This was a cross-sectional validation study among adult male smokers using the TTM Questionnaire. Backward-forward procedure was applied to translate the questionnaire from English into Persian (the Iranian language). The confirmatory factor analyses were performed to test validity. The internal consistency and stability of the questionnaire was examined using Cronbach’s alpha coefficient and Intraclass Correlation Coefficient (ICC).

Results

In all 150 male smokers were entered into the study. The mean age of participants was 36.51 ± 7.94 years. The results obtained from confirmatory factor analysis revealed that the data was fit to the model: the goodness of fit index (GFI) = 0.92; the comparative fit index (CFI) = 0.91; the root mean square error of approximation (RMSEA) = 0.065 (95% CI = 0.063-0.067), and the relative chi-square (x2/df) = 1.87, p < 0.001. The Cronbach’s alpha ranged from 0.60 to 0.84 indicating an acceptable result. Also Intraclass Correlation of Coefficient (ICC) ranged from 0.61 to 0.83 corresponding to a satisfactory finding.

Conclusion

The current study provided psychometric evidence for an appropriate, reliable, and valid tool to determine smoking behaviors among Iranian adult smokers. Indeed the findings from this study could be applied in designing smoking cessation interventions in Iran.
A cross-sectional pilot study of the Scottish early development instrument: a tool for addressing inequality
Authors: Woolfson Lisa Marks , Geddes Rosemary , McNicol Stephanie , Booth Josephine N , Frank John
Published: December 2013

Background

Early childhood is recognised as a key developmental phase with implications for social, academic, health and wellbeing outcomes in later childhood and indeed throughout the adult lifespan. Community level data on inequalities in early child development are therefore required to establish the impact of government early years’ policies and programmes on children’s strengths and vulnerabilities at local and national level. This would allow local leaders to target tailored interventions according to community needs to improve children’s readiness for the transition to school. The challenge is collecting valid data on sufficient samples of children entering school to derive robust inferences about each local birth cohort’s developmental status. This information needs to be presented in a way that allows community stakeholders to understand the results, expediting the improvement of preschool programming to improve future cohorts’ development in the early years. The aim of the study was to carry out a pilot to test the feasibility and ease of use in Scotland of the 104-item teacher-administered Early Development Instrument, an internationally validated measure of children’s global development at school entry developed in Canada.

Methods

Phase 1 was piloted in an education district with 14 Primary 1 teachers assessing a cohort of 154 children, following which the instrument was adapted for the Scottish context (Scottish Early Development Instrument: SEDI). Phase 2 was then carried out using the SEDI. Data were analysed from a larger sample of 1090 participants, comprising all Primary 1 children within this school district, evaluated by 68 teachers.

Results

The SEDI displayed adequate psychometric and discriminatory properties and is appropriate for use across Scotland without any further modifications. Children in the lowest socioeconomic status quintiles were 2–3 times more likely than children in the most affluent quintile to score low in at least one developmental domain. Even in the most affluent quintile though, 17% of children were ‘developmentally vulnerable’, suggesting that those in need cannot be identified by socioeconomic status alone.

Conclusions

The SEDI offers a feasible means of providing communities with a holistic overview of school readiness for targeting early years’ interventions.
Relations between the school physical environment and school social capital with student physical activity levels
Authors: Button Brenton , Trites Stephen , Janssen Ian
Published: December 2013

Background

The physical and social environments at schools are related to students’ moderate-to-vigorous physical activity (MVPA) levels. The purpose of this study was to explore the interactive effects of the school physical environment and school social capital on the MVPA of students while at school.

Methods

Data from 18,875 grade 6–10 students from 331 schools who participated in the 2009/10 Canadian Health Behaviour in School-Aged Children survey were analyzed using multi-level regression. Students answered questions on the amount of time they spend in MVPA at school and on their school’s social capital. Administrator reports were used to create a physical activity related physical environment score.

Results

The school physical environment score was positively associated with student MVPA at school (β = 0.040, p < .005). The association between the school social capital and MVPA was also positive (β = 0.074, p < .001). The difference in physical environments equated to about 20 minutes/week of MVPA for students attending schools with the lowest number of physical environment features and about 40 minutes/week for students attending schools with the lowest school social capital scores by comparison to students attending schools with the highest scores.

Conclusions

The findings suggest that school social capital may be a more important factor in increasing students MVPA than the school physical environment. The results of this study may help inform interventions aimed at increasing student physical activity levels.
Profiles of cytokines secreted by isolated human endometrial cells under the influence of chorionic gonadotropin during the window of embryo implantation
Authors: Srivastava Akhilesh , Sengupta Jayasree , Kriplani Alka , Roy Kallol K , Ghosh Debabrata
Published: December 2013

Background

Several studies have indicated that human pre-implantation embryo-derived chorionic gonadotropin (hCG) may influence the implantation process by its action on human endometrial epithelial and stromal cells. Despite reports indicating that hCG acts on these cells to affect the production of several cytokines and growth factors (e.g., MIF, IGF-I, VEGF, LIF, IL-11, GMCSF, CXL10 and FGF2), our understanding of the integral influence of hCG on paracrine interactions between endometrial stromal and epithelial cells during implantation is very limited.

Methods

In the present study, we examined the profile of 48 cytokines in the conditioned media of primary cell cultures of human implantation stage endometrium. Endometrial epithelial cells (group 1; n = 20), stromal cells (group 2; n = 20), and epithelial plus stromal cells (group 3; n = 20) obtained from mid-secretory stage endometrial samples (n = 60) were grown on collagen and exposed to different doses (0, 1, 10 and 100 IU/ml) of rhCG for 24 h in vitro. Immunochemical and qRT-PCR methods were used to determine cytokine profiles. Enrichment and process networks analyses were implemented using a list of cytokines showing differential secretion in response to hCG.

Results

Under basal conditions, endometrial epithelial and stromal cells exhibited cell type-specific profiles of secreted cytokines. Administration of hCG (100 IU) resulted in significantly (P < 0.05) different cytokine secretion profiles indicative of macropinocytic transport (HGF, MCSF) in epithelial cells, signal transduction (CCL4, FGF2, IL-1b, IL-6, IL-17, VEGF) in stromal cells, and epithelial-mesenchymal transition (FGF2, HGF, IL-1b, TNF) in mixed cells. Overall, the administration of hCG affected cytokines involved in the immune response, chemotaxis, inflammatory changes, proliferation, cell adhesion and apoptosis.

Conclusions

CG can influence the function of the endometrium during blastocyst implantation via its differential action on endometrial epithelial and stromal cells. CG may also affect complex paracrine processes in the different endometrial cell types.
Self-compliance-improved resistive switching using Ir/TaO
x
/W cross-point memory
Authors: Prakash Amit , Jana Debanjan , Samanta Subhranu , Maikap Siddheswar
Published: December 2013

Resistive switching properties of a self-compliance resistive random access memory device in cross-point architecture with a simple stack structure of Ir/TaO
x
/W have been investigated. A transmission electron microscope and atomic force microscope were used to observe the film properties and morphology of the stack. The device has shown excellent switching cycle uniformity with a small operation of ±2.5 V and a resistance ratio of >100. The device requires neither any frorming-process nor current compliance limit for repeatable operation in contrast to conventional resistive random access memory devices. The effect of bottom electrode morphology and surface roughness is also studied. The improvement is due to the enhanced electric field at the nanotips in the bottom electrode and the defective TaO
x
switching layer which enable controlled filament formation/rupture. The device area dependence of the low resistance state indicates multifilament formation. The device has shown a robust alternating current endurance of >105 cycles and a data retention of >104 s.
Differential inhibition of LINE1 and LINE2 retrotransposition by vertebrate AID/APOBEC proteins
Authors: Lindič Nataša , Budič Maruška , Petan Toni , Knisbacher Binyamin A , Levanon Erez Y , Lovšin Nika
Published: December 2013

Background

The role of AID/APOBEC proteins in the mammalian immune response against retroviruses and retrotransposons is well established. G to A hypermutations, the hallmark of their cytidine deaminase activity, are present in several mammalian retrotransposons. However, the role of AID/APOBEC proteins in non-mammalian retroelement restriction is not completely understood.

Results

Here we provide the first evidence of anti-retroelement activity of a reptilian APOBEC protein. The green anole lizard A1 protein displayed potent DNA mutator activity and inhibited ex vivo retrotransposition of LINE1 and LINE2 ORF1 protein encoding elements, displaying a mechanism of action similar to that of the human A1 protein. In contrast, the human A3 proteins did not require ORF1 protein to inhibit LINE retrotransposition, suggesting a differential mechanism of anti-LINE action of A1 proteins, which emerged in amniotes, and A3 proteins, exclusive to placental mammals. In accordance, genomic analyses demonstrate differential G to A DNA editing of LINE retrotransposons in the lizard genome, which is also the first evidence for G to A DNA editing in non-mammalian genomes.

Conclusion

Our data suggest that vertebrate APOBEC proteins differentially inhibit the retrotransposition of LINE elements and that the anti-retroelement activity of APOBEC proteins predates mammals.
Phenotypic variability and identification of novel YARS2 mutations in YARS2 mitochondrial myopathy, lactic acidosis and sideroblastic anaemia
Authors: Riley Lisa G , Menezes Minal J , Rudinger-Thirion Joëlle , Duff Rachael , de Lonlay Pascale , Rotig Agnes , Tchan Michel C , Davis Mark , Cooper Sandra T , Christodoulou John
Published: December 2013

Background

Mutations in the mitochondrial tyrosyl-tRNA synthetase (YARS2) gene have previously been identified as a cause of the tissue specific mitochondrial respiratory chain (RC) disorder, Myopathy, Lactic Acidosis, Sideroblastic Anaemia (MLASA). In this study, a cohort of patients with a mitochondrial RC disorder for who anaemia was a feature, were screened for mutations in YARS2.

Methods

Twelve patients were screened for YARS2 mutations by Sanger sequencing. Clinical data were compared. Functional assays were performed to confirm the pathogenicity of the novel mutations and to investigate tissue specific effects.

Results

PathogenicYARS2 mutations were identified in three of twelve patients screened. Two patients were found to be homozygous for the previously reported p.Phe52Leu mutation, one severely and one mildly affected. These patients had different mtDNA haplogroups which may contribute to the observed phenotypic variability. A mildly affected patient was a compound heterozygote for two novel YARS2 mutations, p.Gly191Asp and p.Arg360X. The p.Gly191Asp mutation resulted in a 38-fold loss in YARS2 catalytic efficiency and the p.Arg360X mutation did not produce a stable protein. The p.Phe52Leu and p.Gly191Asp/p.Arg360X mutations resulted in more severe RC deficiency of complexes I, III and IV in muscle cells compared to fibroblasts, but had relatively normal YARS2 protein levels. The muscle-specific RC deficiency can be related to the increased requirement for RC complexes in muscle. There was also a failure of mtDNA proliferation upon myogenesis in patient cells which may compound the RC defect. Patient muscle had increased levels of PGC1-α and TFAM suggesting mitochondrial biogenesis was activated as a potential compensatory mechanism.

Conclusion

In this study we have identified novel YARS2 mutations and noted marked phenotypic variability among YARS2 MLASA patients, with phenotypes ranging from mild to lethal, and we suggest that the background mtDNA haplotype may be contributing to the phenotypic variability. These findings have implications for diagnosis and prognostication of the MLASA and related phenotypes.
RETRACTED ARTICLE: Genomic amplification and high expression of EGFR are key targetable oncogenic events in malignant peripheral nerve sheath tumor
Authors: Du Xiaoling , Yang Jilong , Ylipää Antti , Zhu Ze
Published: December 2013

Background

The dismal outcome of malignant peripheral nerve sheath tumor (MPNST) highlights the necessity of finding new therapeutic methods to benefit patients with this aggressive sarcoma. Our purpose was to investigate epidermal growth factor receptor (EGFR) as a potential therapeutic target in MPNSTs.

Patients and methods

We performed a microarray based-comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center (MD Anderson) and 26 patients from Tianjin Medical University Cancer Institute & Hospital (TMUCIH). Fluorescence in situ hybridization (FISH) method was used to validate the gene amplification detected by aCGH analysis. Another independent cohort of 56 formalin fixed paraffin embedded (FFPE) MPNST samples was obtained to explore EGFR protein expression by immunohistochemical analysis. Cell biology detection and validation were performed on human MPNST cell lines ST88-14 and STS26T.

Results

aCGH and pathway analysis of the 51 MPNSTs identified significant gene amplification events in EGFR pathway, including frequent amplifications of EGFR gene itself, which was subsequently validated by FISH assay. High expression of EGFR protein was associated with poor disease-free and overall survival of human MPNST patients. In human MPNST cell lines ST88-14 and STS26T, inhibition of EGFR by siRNA or Gefitinib led to decreased cell proliferation, migration, and invasion accompanied by attenuation of PI3K/AKT and MAPK pathways.

Conclusion

These results suggest that EGFR is a potential therapeutic target for MPNST.
High throughput screening of CO2-tolerating microalgae using GasPak bags
Authors: Liu Zheng , Zhang Fan , Chen Feng
Published: December 2013

Background

Microalgae are diverse in terms of their speciation and function. More than 35,000 algal strains have been described, and thousands of algal cultures are maintained in different culture collection centers. The ability of CO2 uptake by microalgae varies dramatically among algal species. It becomes challenging to select suitable algal candidates that can proliferate under high CO2 concentration from a large collection of algal cultures.

Results

Here, we described a high throughput screening method to rapidly identify high CO2 affinity microalgae. The system integrates a CO2 mixer, GasPak bags and microplates. Microalgae on the microplates will be cultivated in GasPak bags charged with different CO2 concentrations. Using this method, we identified 17 algal strains whose growth rates were not influenced when the concentration of CO2 was increased from 2 to 20% (v/v). Most CO2 tolerant strains identified in this study were closely related to the species Scenedesmus and Chlorococcum. One of Scenedesmus strains (E7A) has been successfully tested in in the scale up photo bioreactors (500 L) bubbled with flue gas which contains 10-12% CO2.

Conclusion

Our high throughput CO2 testing system provides a rapid and reliable way for identifying microalgal candidate strains that can grow under high CO2 condition from a large pool of culture collection species. This high throughput system can also be modified for selecting algal strains that can tolerate other gases, such as NOx, SOx, or flue gas.
Psychosocial outcomes of a non-dieting based positive body image community program for overweight adults: a pilot study
Authors: Bloom Lisa , Shelton Beth , Bengough Melissa , Brennan Leah
Published: December 2013

Background

The limited success of traditional diet focused obesity interventions has led to the development of alternative non-dieting approaches. The current study evaluated the impact of a community based non-dieting positive body image program for overweight/obese people on a range of psychosocial outcomes. The characteristics of this real-world sample presenting for a non-dieting weight management intervention are also described.

Method

Overweight and obese participants enrolled in the eight week ‘No More Diets’ (NMD) group program completed self-report questionnaires assessing disordered eating thoughts and behaviours, body image, motivation for exercise and psychopathology pre- and post-treatment.

Results

Participants (n = 17; 16 female) were aged between 19 and 78 years, with a BMI ranging from 25.2 kg/m2(Overweight) to 55.9 kg/m2(Severely Obese). They reported elevated levels of eating disorder pathology, body shape preoccupation, depression, anxiety and stress compared to community norms (p < .05). Following treatment there were significant improvements in reported body shape preoccupation, shape concern and eating attitudes (p < .05), and clinically significant changes (small to medium effect sizes; 0.3-0.35) for improvements in reported weight concern, eating competence, stress and health evaluation. There were no changes in reported dietary restraint, emotional eating and uncontrolled eating, or eating concern (p > .05).

Conclusion

Individuals presenting for the NMD program demonstrated increased eating disorder pathology and more generalised psychopathology compared to community norms. The NMD program was particularly beneficial for body image and shape concern. Addressing these body image factors may help to address some of the perpetuating factors of obesity and disordered eating, which are often not addressed in the traditional diet-based weight loss interventions.
Direct production of organic acids from starch by cell surface-engineered Corynebacterium glutamicum in anaerobic conditions
Authors: Tsuge Yota , Tateno Toshihiro , Sasaki Kengo , Hasunuma Tomohisa , Tanaka Tsutomu , Kondo Akihiko
Published: December 2013

We produced organic acids, including lactate and succinate, directly from soluble starch under anaerobic conditions using high cell-density cultures of Corynebacterium glutamicum displaying α-amylase (AmyA) from Streptococcus bovis 148 on the cell surface. Notably, reactions performed under anaerobic conditions at 35 and 40°C, which are higher than the optimal growth temperature of 30°C, showed 32% and 19%, respectively, higher productivity of the organic acids lactate, succinate, and acetate compared to that at 30°C. However, α-amylase was not stably anchored and released into the medium from the cell surface during reactions at these higher temperatures, as demonstrated by the 61% and 85% decreases in activity, respectively, from baseline, compared to the only 8% decrease at 30°C. The AmyA-displaying C. glutamicum cells retained their starch-degrading capacity during five 10 h reaction cycles at 30°C, producing 107.8 g/l of total organic acids, including 88.9 g/l lactate and 14.0 g/l succinate. The applicability of cell surface-engineering technology for the production of organic acids from biomass by high cell-density cultures of C. glutamicum under anaerobic conditions was demonstrated.
Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas
Authors: Renner Marcus , Wolf Thomas , Meyer Hannah , Hartmann Wolfgang , Penzel Roland , Ulrich Alexis , Lehner Burkhard , Hovestadt Volker , Czwan Esteban , Egerer Gerlinde , Schmitt Thomas , Alldinger Ingo , Renker Eva Kristin , Ehemann Volker , Eils Roland , Wardelmann Eva , Büttner Reinhard , Lichter Peter , Brors Benedikt , Schirmacher Peter , Mechtersheimer Gunhild
Published: December 2013

Background

High-grade soft tissue sarcomas are a heterogeneous, complex group of aggressive malignant tumors showing mesenchymal differentiation. Recently, soft tissue sarcomas have increasingly been classified on the basis of underlying genetic alterations; however, the role of aberrant DNA methylation in these tumors is not well understood and, consequently, the usefulness of methylation-based classification is unclear.

Results

We used the Infinium HumanMethylation27 platform to profile DNA methylation in 80 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 14 representative sarcoma cell lines. The primary samples were partitioned into seven stable clusters. A classification algorithm identified 216 CpG sites, mapping to 246 genes, showing different degrees of DNA methylation between these seven groups. The differences between the clusters were best represented by a set of eight CpG sites located in the genes SPEG, NNAT, FBLN2, PYROXD2, ZNF217, COL14A1, DMRT2 and CDKN2A. By integrating DNA methylation and mRNA expression data, we identified 27 genes showing negative and three genes showing positive correlation. Compared with non-neoplastic fat, NNAT showed DNA hypomethylation and inverse gene expression in myxoid liposarcomas, and DNA hypermethylation and inverse gene expression in dedifferentiated and pleomorphic liposarcomas. Recovery of NNAT in a hypermethylated myxoid liposarcoma cell line decreased cell migration and viability.

Conclusions

Our analysis represents the first comprehensive integration of DNA methylation and transcriptional data in primary high-grade soft tissue sarcomas. We propose novel biomarkers and genes relevant for pathogenesis, including NNAT as a potential tumor suppressor in myxoid liposarcomas.
Intensive Chemotherapy for Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Intercontinental Trial ALL IC-BFM 2002
Authors: Stary Jan , Zimmermann Martin , Campbell Myriam , Castillo Luis , Dibar Eduardo , Donska Svetlana , Gonzalez Alejandro , Izraeli Shai , Janic Dragana , Jazbec Janez , Konja Josip , Kaiserova Emilia , Kowalczyk Jerzy , Kovacs Gabor , Li Chi-Kong , Magyarosy Edina , Popa Alexander , Stark Batia , Jabali Yahia , Trka Jan , Hrusak Ondrej , Riehm Hansjörg , Masera Giuseppe , Schrappe Martin
Published: December 2013

Purpose

From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups.

Patients and Methods

For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP] option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster [BFM] option).

Results

At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI.

Conclusion

The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.
Effects of Exercise on Treatment-Related Adverse Effects for Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Systematic Review
Authors: Gardner Jason R. , Livingston Patricia M. , Fraser Steve F.
Published: December 2013

Purpose

Androgen-deprivation therapy is a commonly used treatment for men with prostate cancer; however, the adverse effects can be detrimental to patient health and quality of life. Exercise has been proposed as a strategy for ameliorating a range of these treatment-related adverse effects. We conducted a systematic review of the literature regarding the effects of exercise on treatment-related adverse effects in men receiving androgen-deprivation therapy for prostate cancer.

Methods

An online electronic search of the Cochrane Library, EMBASE, MEDLINE, CINAHL, SPORTDiscus, and Health Source databases was performed to identify relevant peer-reviewed articles published between January 1980 and June 2013. Eligible study designs included randomized controlled trials as well as uncontrolled trials with pre- and postintervention data. Information was extracted regarding participant and exercise intervention characteristics as well as the effects of exercise on bone health, body composition, physical performance, cardiometabolic risk, fatigue, and quality of life.

Results

Ten studies were included, with exercise interventions involving aerobic and/or resistance training. Exercise training demonstrated benefits in muscular strength, cardiorespiratory fitness, functional task performance, lean body mass, and fatigue, with inconsistent effects observed for adiposity. The impact of exercise on bone health, cardiometabolic risk markers, and quality of life are currently unclear.

Conclusion

Among patients with prostate cancer treated with androgen-deprivation therapy, appropriately prescribed exercise is safe and may ameliorate a range of treatment-induced adverse effects. Ongoing research of high methodologic quality is required to consolidate and expand on current knowledge and to allow the development of specific evidence-based exercise prescription recommendations.
Novel cardiovascular gene functions revealed via systematic phenotype prediction in zebrafish
Authors: Musso Gabriel , Tasan Murat , Mosimann Christian , Beaver John E. , Plovie Eva , Carr Logan A. , Chua Hon Nian , Dunham Julie , Zuberi Khalid , Rodriguez Harold , Morris Quaid , Zon Leonard , Roth Frederick P. , MacRae Calum A.
Published: December 2013

Comprehensive functional annotation of vertebrate genomes is fundamental to biological discovery. Reverse genetic screening has been highly useful for determination of gene function, but is untenable as a systematic approach in vertebrate model organisms given the number of surveyable genes and observable phenotypes. Unbiased prediction of gene-phenotype relationships offers a strategy to direct finite experimental resources towards likely phenotypes, thus maximizing de novo discovery of gene functions. Here we prioritized genes for phenotypic assay in zebrafish through machine learning, predicting the effect of loss of function of each of 15,106 zebrafish genes on 338 distinct embryonic anatomical processes. Focusing on cardiovascular phenotypes, the learning procedure predicted known knockdown and mutant phenotypes with high precision. In proof-of-concept studies we validated 16 high-confidence cardiac predictions using targeted morpholino knockdown and initial blinded phenotyping in embryonic zebrafish, confirming a significant enrichment for cardiac phenotypes as compared with morpholino controls. Subsequent detailed analyses of cardiac function confirmed these results, identifying novel physiological defects for 11 tested genes. Among these we identified tmem88a, a recently described attenuator of Wnt signaling, as a discrete regulator of the patterning of intercellular coupling in the zebrafish cardiac epithelium. Thus, we show that systematic prioritization in zebrafish can accelerate the pace of developmental gene function discovery.
p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells
Authors: Mardaryev Andrei N. , Gdula Michal R. , Yarker Joanne L. , Emelianov Vladimir N. , Poterlowicz Krzysztof , Sharov Andrey A. , Sharova Tatyana Y. , Scarpa Julie A. , Chambon Pierre , Botchkarev Vladimir A. , Fessing Michael Y.
Published: December 2013

Chromatin structural states and their remodelling, including higher-order chromatin folding and three-dimensional (3D) genome organisation, play an important role in the control of gene expression. The role of 3D genome organisation in the control and execution of lineage-specific transcription programmes during the development and differentiation of multipotent stem cells into specialised cell types remains poorly understood. Here, we show that substantial remodelling of the higher-order chromatin structure of the epidermal differentiation complex (EDC), a keratinocyte lineage-specific gene locus on mouse chromosome 3, occurs during epidermal morphogenesis. During epidermal development, the locus relocates away from the nuclear periphery towards the nuclear interior into a compartment enriched in SC35-positive nuclear speckles. Relocation of the EDC locus occurs prior to the full activation of EDC genes involved in controlling terminal keratinocyte differentiation and is a lineage-specific, developmentally regulated event controlled by transcription factor p63, a master regulator of epidermal development. We also show that, in epidermal progenitor cells, p63 directly regulates the expression of the ATP-dependent chromatin remodeller Brg1, which binds to distinct domains within the EDC and is required for relocation of the EDC towards the nuclear interior. Furthermore, Brg1 also regulates gene expression within the EDC locus during epidermal morphogenesis. Thus, p63 and its direct target Brg1 play an essential role in remodelling the higher-order chromatin structure of the EDC and in the specific positioning of this locus within the landscape of the 3D nuclear space, as required for the efficient expression of EDC genes in epidermal progenitor cells during skin development.
Cas9 effector-mediated regulation of transcription and differentiation in human pluripotent stem cells
Authors: Kearns Nicola A. , Genga Ryan M. J. , Enuameh Metewo S. , Garber Manuel , Wolfe Scot A. , Maehr René
Published: December 2013

The identification of the trans-acting factors and cis-regulatory modules that are involved in human pluripotent stem cell (hPSC) maintenance and differentiation is necessary to dissect the operating regulatory networks in these processes and thereby identify nodes where signal input will direct desired cell fate decisions in vitro or in vivo. To deconvolute these networks, we established a method to influence the differentiation state of hPSCs with a CRISPR-associated catalytically inactive dCas9 fused to an effector domain. In human embryonic stem cells, we find that the dCas9 effectors can exert positive or negative regulation on the expression of developmentally relevant genes, which can influence cell differentiation status when impinging on a key node in the regulatory network that governs the cell state. This system provides a platform for the interrogation of the underlying regulators governing specific differentiation decisions, which can then be employed to direct cellular differentiation down desired pathways.
Trans-splicing with the group I intron ribozyme from Azoarcus
Authors: Dolan Gregory F. , Müller Ulrich F.
Published: December 2013

Group I introns are ribozymes (catalytic RNAs) that excise themselves from RNA primary transcripts by catalyzing two successive transesterification reactions. These cis-splicing ribozymes can be converted into trans-splicing ribozymes, which can modify the sequence of a separate substrate RNA, both in vitro and in vivo. Previous work on trans-splicing ribozymes has mostly focused on the 16S rRNA group I intron ribozyme from Tetrahymena thermophila. Here, we test the trans-splicing potential of the tRNAIle group I intron ribozyme from the bacterium Azoarcus. This ribozyme is only half the size of the Tetrahymena ribozyme and folds faster into its active conformation in vitro. Our results showed that in vitro, the Azoarcus and Tetrahymena ribozymes favored the same set of splice sites on a substrate RNA. Both ribozymes showed the same trans-splicing efficiency when containing their individually optimized 5′ terminus. In contrast to the previously optimized 5′-terminal design of the Tetrahymena ribozyme, the Azoarcus ribozyme was most efficient with a trans-splicing design that resembled the secondary structure context of the natural cis-splicing Azoarcus ribozyme, which includes base-pairing between the substrate 5′ portion and the ribozyme 3′ exon. These results suggested preferred trans-splicing interactions for the Azoarcus ribozyme under near-physiological in vitro conditions. Despite the high activity in vitro, however, the splicing efficiency of the Azoarcus ribozyme in Escherichia coli cells was significantly below that of the Tetrahymena ribozyme.
Endovascular treatment of chronic mesenteric ischemia in an adolescent male: case report
Authors: Al-Hammash Sadiq Muhammed , Al-Ethawi Abd El-Salam Dawood , Ismail Kasim Abbas
Published: December 2013

Chronic mesenteric ischemia (CMI) is a condition characterized by inadequate blood flow to the bowel resulting from stenosis of one or more of the three mesenteric arteries. Fibromuscular dysplasia is the most common cause in children and young adults; whereas atherosclerosis is the most common cause in the elderly. Treatment is mandatory in symptomatic patients, because it may lead to malnutrition, bowel infarction or even death.Herein, we present the case of a 14-year old male, diagnosed with CMI who underwent percutaneous balloon angioplasty (PTA) followed by stent placement with immediate positive results.
Features of finishing of furniture fronts of MDF
Authors: Новоселова  , Novoselova Irina
Published: December 2013

In article questions of determining optimal process parameters of the operation composi-tion of Krakolet IF490 / 74 special effects, Italian company "Serlak", used in the production of hiding coatings on MDF. For this purpose a series of experiments was made of multifactorial planning in processing the results of which mathematical model was obtained allowing you accurately determine the progress of the process flow of decoration, depending on the technological properties of Krakolet, changing in the process of preparing its working composition.
Summary assessment of properties of refinishing coating
Authors: Новоселова  , Novoselova Irina , Патютько  , Patyutko A.
Published: December 2013

In the article the results of a question of preservation of protective and decorative properties of nitrocellulose lacquer coating applied to a substrate of synthetic veneer. The author´s task was to determine the quality of the coatings, which were kept in storage conditions, and operated in a residential area within the warranty period of service of furniture products. The quality of coatings decreases with time due to changes in color, dirt collection, light changes, local swelling (decorative features change), crac-king, delamination, fracture.