bluuebunny/crossref_metadata_2025 huggingface dataset:
AGORA: Assembly Guided by Optical Restriction Alignment
Authors: Lin Henry C , Goldstein Steve , Mendelowitz Lee , Zhou Shiguo , Wetzel Joshua , Schwartz David C , Pop Mihai
Published: August 2012

Background

Genome assembly is difficult due to repeated sequences within the genome, which create ambiguities and cause the final assembly to be broken up into many separate sequences (contigs). Long range linking information, such as mate-pairs or mapping data, is necessary to help assembly software resolve repeats, thereby leading to a more complete reconstruction of genomes. Prior work has used optical maps for validating assemblies and scaffolding contigs, after an initial assembly has been produced. However, optical maps have not previously been used within the genome assembly process. Here, we use optical map information within the popular de Bruijn graph assembly paradigm to eliminate paths in the de Bruijn graph which are not consistent with the optical map and help determine the correct reconstruction of the genome.

Results

We developed a new algorithm called AGORA: Assembly Guided by Optical Restriction Alignment. AGORA is the first algorithm to use optical map information directly within the de Bruijn graph framework to help produce an accurate assembly of a genome that is consistent with the optical map information provided. Our simulations on bacterial genomes show that AGORA is effective at producing assemblies closely matching the reference sequences.

Additionally, we show that noise in the optical map can have a strong impact on the final assembly quality for some complex genomes, and we also measure how various characteristics of the starting de Bruijn graph may impact the quality of the final assembly. Lastly, we show that a proper choice of restriction enzyme for the optical map may substantially improve the quality of the final assembly.

Conclusions

Our work shows that optical maps can be used effectively to assemble genomes within the de Bruijn graph assembly framework. Our experiments also provide insights into the characteristics of the mapping data that most affect the performance of our algorithm, indicating the potential benefit of more accurate optical mapping technologies, such as nano-coding.
MicroRNA-mRNA interactions in a murine model of hyperoxia-induced bronchopulmonary dysplasia
Authors: Dong Jie , Carey William A , Abel Stuart , Collura Christopher , Jiang Guoqian , Tomaszek Sandra , Sutor Shari , Roden Anja C , Asmann Yan W , Prakash Y S , Wigle Dennis A
Published: August 2012

Background

Bronchopulmonary dysplasia is a chronic lung disease of premature neonates characterized by arrested pulmonary alveolar development. There is increasing evidence that microRNAs (miRNAs) regulate translation of messenger RNAs (mRNAs) during lung organogenesis. The potential role of miRNAs in the pathogenesis of BPD is unclear.

Results

Following exposure of neonatal mice to 80% O2 or room air (RA) for either 14 or 29 days, lungs of hyperoxic mice displayed histological changes consistent with BPD. Comprehensive miRNA and mRNA profiling was performed using lung tissue from both O2 and RA treated mice, identifying a number of dynamically regulated miRNAs and associated mRNA target genes. Gene ontology enrichment and pathway analysis revealed that hyperoxia modulated genes involved in a variety of lung developmental processes, including cell cycle, cell adhesion, mobility and taxis, inflammation, and angiogenesis. MiR-29 was prominently increased in the lungs of hyperoxic mice, and several predicted mRNA targets of miR-29 were validated with real-time PCR, western blotting and immunohistochemistry. Direct miR-29 targets were further validated in vitro using bronchoalveolar stem cells.

Conclusion

In newborn mice, prolonged hyperoxia induces an arrest of alveolar development similar to that seen in human neonates with BPD. This abnormal lung development is accompanied by significant increases in the levels of multiple miRNAs and corresponding decreases in the levels of predicted mRNA targets, many of which have known or suspected roles in pathways altered in BPD. These data support the hypothesis that dynamic regulation of miRNAs plays a prominent role in the pathophysiology of BPD.
Translational regulation of Anopheles gambiae mRNAs in the midgut during Plasmodium falciparum infection
Authors: Mead Edward A , Li Meng , Tu Zhijian , Zhu Jinsong
Published: August 2012

Background

Malaria is caused by Plasmodium parasites, which are transmitted via the bites of infected Anopheline mosquitoes. Midgut invasion is a major bottleneck for Plasmodium development inside the mosquito vectors. Malaria parasites in the midgut are surrounded by a hostile environment rich in digestive enzymes, while a rapidly responding immune system recognizes Plasmodium ookinetes and recruits killing factors from the midgut and surrounding tissues, dramatically reducing the population of invading ookinetes before they can successfully traverse the midgut epithelium. Understanding molecular details of the parasite-vector interactions requires precise measurement of nascent protein synthesis in the mosquito during Plasmodium infection. Current expression profiling primarily monitors alterations in steady-state levels of mRNA, but does not address the equally critical issue of whether the proteins encoded by the mRNAs are actually synthesized.

Results

In this study, we used sucrose density gradient centrifugation to isolate actively translating Anopheles gambiae mRNAs based upon their association with polyribosomes (polysomes). The proportion of individual gene transcripts associated with polysomes, which is determined by RNA deep sequencing, reflects mRNA translational status. This approach led to identification of 1017 mosquito transcripts that were primarily regulated at the translational level after ingestion of Plasmodium falciparum-infected blood. Caspar, a negative regulator of the NF-kappaB transcription factor Rel2, appears to be substantially activated at the translational levels during Plasmodium infection. In addition, transcripts of Dcr1, Dcr2 and Drosha, which are involved in small RNA biosynthesis, exhibited enhanced associations with polysomes after P. falciparum challenge. This observation suggests that mosquito microRNAs may play an important role in reactions against Plasmodium invasion.

Conclusions

We analyzed both total cellular mRNAs and mRNAs that are associated with polysomes to simultaneously monitor transcriptomes and nascent protein synthesis in the mosquito. This approach provides more accurate information regarding the rate of protein synthesis, and identifies some mosquito factors that might have gone unrecognized because expression of these proteins is regulated mainly at the translational level rather than at the transcriptional level after mosquitoes ingest a Plasmodium-infected blood meal.
Jasmonate and ethylene dependent defence gene expression and suppression of fungal virulence factors: two essential mechanisms of Fusarium head blight resistance in wheat?
Authors: Gottwald Sven , Samans Birgit , Lück Stefanie , Friedt Wolfgang
Published: August 2012

Background

Fusarium head blight (FHB) caused by Fusarium species like F. graminearum is a devastating disease of wheat (Triticum aestivum) worldwide. Mycotoxins such as deoxynivalenol produced by the fungus affect plant and animal health, and cause significant reductions of grain yield and quality. Resistant varieties are the only effective way to control this disease, but the molecular events leading to FHB resistance are still poorly understood. Transcriptional profiling was conducted for the winter wheat cultivars Dream (moderately resistant) and Lynx (susceptible). The gene expressions at 32 and 72 h after inoculation with Fusarium were used to trace possible defence mechanisms and associated genes. A comparative qPCR was carried out for selected genes to analyse the respective expression patterns in the resistant cultivars Dream and Sumai 3 (Chinese spring wheat).

Results

Among 2,169 differentially expressed genes, two putative main defence mechanisms were found in the FHB-resistant Dream cultivar. Both are defined base on their specific mode of resistance. A non-specific mechanism was based on several defence genes probably induced by jasmonate and ethylene signalling, including lipid-transfer protein, thionin, defensin and GDSL-like lipase genes. Additionally, defence-related genes encoding jasmonate-regulated proteins were up-regulated in response to FHB. Another mechanism based on the targeted suppression of essential Fusarium virulence factors comprising proteases and mycotoxins was found to be an essential, induced defence of general relevance in wheat. Moreover, similar inductions upon fungal infection were frequently observed among FHB-responsive genes of both mechanisms in the cultivars Dream and Sumai 3.

Conclusions

Especially ABC transporter, UDP-glucosyltransferase, protease and protease inhibitor genes associated with the defence mechanism against fungal virulence factors are apparently active in different resistant genetic backgrounds, according to reports on other wheat cultivars and barley. This was further supported in our qPCR experiments on seven genes originating from this mechanism which revealed similar activities in the resistant cultivars Dream and Sumai 3. Finally, the combination of early-stage and steady-state induction was associated with resistance, while transcript induction generally occurred later and temporarily in the susceptible cultivars. The respective mechanisms are attractive for advanced studies aiming at new resistance and toxin management strategies.
Production of fungal and bacterial growth modulating secondary metabolites is widespread among mycorrhiza-associated streptomycetes
Authors: Schrey Silvia D , Erkenbrack Eric , Früh Elisabeth , Fengler Svenja , Hommel Kerstin , Horlacher Nadine , Schulz Dirk , Ecke Margret , Kulik Andreas , Fiedler Hans-Peter , Hampp Rüdiger , Tarkka Mika T
Published: August 2012

Background

Studies on mycorrhiza associated bacteria suggest that bacterial-fungal interactions play important roles during mycorrhiza formation and affect plant health. We surveyed Streptomyces Actinobacteria, known as antibiotic producers and antagonists of fungi, from Norway spruce mycorrhizas with predominantly Piloderma species as the fungal partner.

Results

Fifteen Streptomyces isolates exhibited substantial variation in inhibition of tested mycorrhizal and plant pathogenic fungi (Amanita muscaria, Fusarium oxysporum, Hebeloma cylindrosporum, Heterobasidion abietinum, Heterobasidion annosum, Laccaria bicolor, Piloderma croceum). The growth of the mycorrhiza-forming fungus Laccaria bicolor was stimulated by some of the streptomycetes, and Piloderma croceum was only moderately affected. Bacteria responded to the streptomycetes differently than the fungi. For instance the strain Streptomyces sp. AcM11, which inhibited most tested fungi, was less inhibitory to bacteria than other tested streptomycetes. The determined patterns of Streptomyces-microbe interactions were associated with distinct patterns of secondary metabolite production. Notably, potentially novel metabolites were produced by strains that were less antagonistic to fungi. Most of the identified metabolites were antibiotics (e.g. cycloheximide, actiphenol) and siderophores (e.g. ferulic acid, desferroxiamines). Plant disease resistance was activated by a single streptomycete strain only.

Conclusions

Mycorrhiza associated streptomycetes appear to have an important role in inhibiting the growth of fungi and bacteria. Additionally, our study indicates that the Streptomyces strains, which are not general antagonists of fungi, may produce still un-described metabolites.
Quantitative evaluation of an automatic segmentation method for 3D reconstruction of intervertebral scoliotic disks from MR images
Authors: Claudia Chevrefils , Farida Cheriet , Guy Grimard , Marie-Claude Miron , Carl-Eric Aubin
Published: August 2012

Background

For some scoliotic patients the spinal instrumentation is inevitable. Among these patients, those with stiff curvature will need thoracoscopic disk resection. The removal of the intervertebral disk with only thoracoscopic images is a tedious and challenging task for the surgeon. With computer aided surgery and 3D visualisation of the interverterbral disk during surgery, surgeons will have access to additional information such as the remaining disk tissue or the distance of surgical tools from critical anatomical structures like the aorta or spinal canal. We hypothesized that automatically extracting 3D information of the intervertebral disk from MR images would aid the surgeons to evaluate the remaining disk and would add a security factor to the patient during thoracoscopic disk resection.

Methods

This paper presents a quantitative evaluation of an automatic segmentation method for 3D reconstruction of intervertebral scoliotic disks from MR images. The automatic segmentation method is based on the watershed technique and morphological operators. The 3D Dice Similarity Coefficient (DSC) is the main statistical metric used to validate the automatically detected preoperative disk volumes. The automatic detections of intervertebral disks of real clinical MR images are compared to manual segmentation done by clinicians.

Results

Results show that depending on the type of MR acquisition sequence, the 3D DSC can be as high as 0.79 (±0.04). These 3D results are also supported by a 2D quantitative evaluation as well as by robustness and variability evaluations. The mean discrepancy (in 2D) between the manual and automatic segmentations for regions around the spinal canal is of 1.8 (±0.8) mm. The robustness study shows that among the five factors evaluated, only the type of MRI acquisition sequence can affect the segmentation results. Finally, the variability of the automatic segmentation method is lower than the variability associated with manual segmentation performed by different physicians.

Conclusions

This comprehensive evaluation of the automatic segmentation and 3D reconstruction of intervertebral disks shows that the proposed technique used with specific MRI acquisition protocol can detect intervertebral disk of scoliotic patient. The newly developed technique is promising for clinical context and can eventually help surgeons during thoracoscopic intervertebral disk resection.
Conspicuity of breast lesions at different b values on diffusion-weighted imaging
Authors: Chen Xin , He Xi-Jing , Jin Rui , Guo You-Min , Zhao Xian , Kang Hua-Feng , Mo Li-Ping , Wu Qian
Published: August 2012

Background

Diffusion-weighted (DW) imaging has shown potential to differentiate between malignant and benign breast lesions. However, different b values have been used with varied sensitivity and specificity. This study aims to prospectively evaluate the influence of b value on the detection and assessment of breast lesions.

Methods

Institutional review board approval and informed patient consent were obtained. Between February 2010 and September 2010, sixty women suspected of having breast cancer by clinical examination and mammography underwent bilateral breast MRI and DW imaging (with maximum b values of 600, 800, and 1000 s/mm2). Conspicuity grades of lesions at different b values on DW images were performed. Signal intensity and apparent diffusion coefficient (ADC) values were recorded and compared among different b values by the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and receiver operating characteristic (ROC) curve.

Results

Fifty-seven lesions from 52 recruited patients including 39/57 (68%) malignant and 18/57 (32%) benign were confirmed with pathology. DCE MRI accurately detected 53 lesions with the sensitivity of 93.0% and specificity of 66.7%, and DW imaging accurately detected 51 lesions with the sensitivity of 89.5% and specificity of 100%. There were no significant differences in conspicuity grades compared among the three b values (P = 0.072), although the SNR and CNR of breast lesions decreased significantly with higher b values. Mean ADCs of malignant lesions (b = 600 s/mm2, 1.07 ± 0.26 × 10-3 mm2/s; b = 800 s/mm2, 0.96 ± 0.22 × 10-3 mm2/s; b = 1000 s/mm2, 0.92 ± 0.26 × 10-3 mm2/s) were significantly lower than those of benign lesions (b = 600 s/mm2, 1.55 ± 0.40 × 10-3 mm2/s; b = 800 s/mm2, 1.43 ± 0.38 × 10-3 mm2/s; b = 1000 s/mm2, 1.49 ± 0.38 × 10-3 mm2/s) with all P values <0.001, but there were no significant differences among the three b values (P = 0.303 and 0.840 for malignant and benign lesions, respectively). According to the area under the ROC curves, which were derived from ADC and differentiate malignant from benign lesions, no significant differences were found among the three b values (P = 0.743).

Conclusions

DW imaging is a potential adjunct to conventional MRI in the differentiation between malignant and benign breast lesions. Varying the maximum b value from 600 to 1000 s/mm2 does not influence the conspicuity of breast lesions on DW imaging at 1.5 T.
Cell culture model predicts human disease: Altered expression of junction proteins and matrix metalloproteinases in cervical dysplasia
Authors: Kivi Niina , Rönty Mikko , Tarkkanen Jussi , Auvinen Petri , Auvinen Eeva
Published: August 2012

Background

Cervical cancer is necessarily caused by human papillomaviruses, which encode three oncogenes manifesting their functions by interfering with a number of cellular proteins and pathways: the E5, E6, and E7 proteins. We have earlier found in our microarray studies that the E5 oncogene crucially affects the expression of cellular genes involved in adhesion and motility of epithelial cells.

Methods

In order to biologically validate our previous experimental findings we performed immunohistochemical staining of a representative set of tissue samples from different grades of high-risk human papillomavirus associated cervical disease as well as normal squamous and columnar cervical epithelium. Three-dimensional collagen raft cultures established from E5-expressing and control epithelial cells were also examined. The expression of p16, matrix metalloproteinase (MMP) -7, MMP-16, cytokeratin (CK) 8/18, laminin, E-cadherin and beta-catenin was studied.

Results

In agreement with our previous microarray studies, we found intense staining for E-cadherin and beta-catenin in adherens junctions even in high-grade cervical lesions. Staining for MMP-16 was increased in severe disease as well. No significant change in staining for MMP-7 and cytokeratin 8/18 along with the grade of cervical squamous epithelial disease was observed.

Conclusions

Here we have confirmed, using tissue material from human papillomavirus associated lesions, some of the cellular gene expression modifications that we earlier reported in an experimental system studying specifically the E5 oncogene of papillomaviruses. These findings were partially surprising in the context of cervical carcinogenesis and emphasize that the complexity of carcinogenesis is not yet fully understood. Microarray approaches provide a wide overwiev of gene expression in experimental settings, which may yield biologically valid biomarkers for disease diagnostics, prognosis, and follow-up.
Targeting filamin A reduces K-RAS–induced lung adenocarcinomas and endothelial response to tumor growth in mice
Authors: Nallapalli Rajesh K , Ibrahim Mohamed X , Zhou Alex X , Bandaru Sashidar , Sunkara Sai Naresh , Redfors Björn , Pazooki David , Zhang Yin , Borén Jan , Cao Yihai , Bergo Martin O , Akyürek Levent M
Published: August 2012

Background

Many human cancer cells express filamin A (FLNA), an actin-binding structural protein that interacts with a diverse set of cell signaling proteins, but little is known about the biological importance of FLNA in tumor development. FLNA is also expressed in endothelial cells, which may be important for tumor angiogenesis. In this study, we defined the impact of targeting Flna in cancer and endothelial cells on the development of tumors in vivo and on the proliferation of fibroblasts in vitro.

Methods

First, we used a Cre-adenovirus to simultaneously activate the expression of oncogenic K-RAS and inactivate the expression of Flna in the lung and in fibroblasts. Second, we subcutaneously injected mouse fibrosarcoma cells into mice lacking Flna in endothelial cells.

Results

Knockout of Flna significantly reduced K-RAS–induced lung tumor formation and the proliferation of oncogenic K-RAS–expressing fibroblasts, and attenuated the activation of the downstream signaling molecules ERK and AKT. Genetic deletion of endothelial FLNA in mice did not impact cardiovascular development; however, knockout of Flna in endothelial cells reduced subcutaneous fibrosarcoma growth and vascularity within tumors.

Conclusions

We conclude that FLNA is important for lung tumor growth and that endothelial Flna impacts local tumor growth. The data shed new light on the biological importance of FLNA and suggest that targeting this protein might be useful in cancer therapeutics.
Proteomic analysis of plasma membranes isolated from undifferentiated and differentiated HepaRG cells
Authors: Sokolowska Izabela , Dorobantu Cristina , Woods Alisa G , Macovei Alina , Branza-Nichita Norica , Darie Costel C
Published: August 2012

Liver infection with hepatitis B virus (HBV), a DNA virus of the Hepadnaviridae family, leads to severe disease, such as fibrosis, cirrhosis and hepatocellular carcinoma. The early steps of the viral life cycle are largely obscure and the host cell plasma membrane receptors are not known. HepaRG is the only proliferating cell line supporting HBV infection in vitro, following specific differentiation, allowing for investigation of new host host-cell factors involved in viral entry, within a more robust and reproducible environment. Viral infection generally begins with receptor recognition at the host cell surface, following highly specific cell-virus interactions. Most of these interactions are expected to take place at the plasma membrane of the HepaRG cells. In the present study, we used this cell line to explore changes between the plasma membrane of undifferentiated (−) and differentiated (+) cells and to identify differentially-regulated proteins or signaling networks that might potentially be involved in HBV entry. Our initial study identified a series of proteins that are differentially expressed in the plasma membrane of (−) and (+) cells and are good candidates for potential cell-virus interactions. To our knowledge, this is the first study using functional proteomics to study plasma membrane proteins from HepaRG cells, providing a platform for future experiments that will allow us to understand the cell-virus interaction and mechanism of HBV viral infection.
The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ
Authors: Hashioka Sadayuki , Klegeris Andis , McGeer Patrick L
Published: August 2012

Backgrounds

Increasing evidence shows that the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) possesses potent anti-inflammatory and immunomodulatory properties. It is tempting to evaluate the potential of SAHA as a therapeutic agent in various neuroinflammatory and neurodegenerative disorders.

Methods

We examined the effects of SAHA on interferon (IFN)-γ-induced neurotoxicity of human astrocytes and on IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT) 3 in human astrocytes. We also studied the effects of SAHA on the astrocytic production of two representative IFN-γ-inducible inflammatory molecules, namely IFN-γ-inducible T cell α chemoattractant (I-TAC) and intercellular adhesion molecule-1 (ICAM-1).

Results

SAHA significantly attenuated the toxicity of astrocytes activated by IFN-γ towards SH-SY5Y human neuronal cells. In the IFN-γ-activated astrocytes, SAHA reduced the STAT3 phosphorylation. SAHA also inhibited the IFN-γ-induced astrocytic production of I-TAC, but not ICAM-1. These results indicate that SAHA suppresses IFN-γ-induced neurotoxicity of human astrocytes through inhibition of the STAT3 signaling pathway.

Conclusion

Due to its anti-neurotoxic and anti-inflammatory properties, SAHA appears to have the therapeutic or preventive potential for a wide range of neuroinflammatory disorders associated with activated astrocytes.
Identification of nonessential regions of the nsp2 protein of an attenuated vaccine strain (HuN4-F112) of highly pathogenic porcine reproductive and respiratory syndrome virus for replication in marc-145 cell
Authors: Xu Yan-Zhao , Zhou Yan-Jun , Zhang Shan-Rui , Tong Wu , Li Ling , Jiang Yi-Feng , Tong Guang-Zhi
Published: August 2012

Background

The regions in the middle of nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) have been shown to be nonessential for PRRSV replication, and these nonessential regions are different in various viral strains.

Finding

In this study, the nonessential regions of the nsp2 of an attenuated vaccine strain (HuN4-F112) of highly pathogenic porcine reproductive and respiratory syndrome virus were identified based on an infectious cDNA clone of HuN4-F112. The results demonstrated that the segments of nsp2 [amino acids (aa) 480 to 667] tolerated deletions. Characterization of the mutants demonstrated that those with small deletions did not affect the viral growth on Marc-145 cells, but deletion of these regions led to earlier PRRSV replication increased (before 36 h after infectious in vitro).

Conclusion

The functional roles of nsp2 variable middle region for PRRSV HuN4-F112 replication have been identified. Our results also suggested that none-essential region might be an ideal insertion region to express foreign gene in PRRSV genome.
Intensity modulated radiotherapy in early stage Hodgkin lymphoma patients: Is it better than three dimensional conformal radiotherapy?
Authors: De Sanctis Vitaliana , Bolzan Chiara , D’Arienzo Marco , Bracci Stefano , Fanelli Alessandro , Cox Maria Christina , Valeriani Maurizio , Osti Mattia F , Minniti Giuseppe , Chiacchiararelli Laura , Enrici Riccardo Maurizi
Published: August 2012

Background

Cure rate of early Hodgkin Lymphoma are high and avoidance of late toxicities is of paramount importance. This comparative study aims to assess the normal tissue sparing capability of intensity-modulated radiation therapy (IMRT) versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of dose-volume parameters and normal tissue complication probability (NTCP) for different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients.

Methods

Ten HL patients were actually treated with 3D-CRT and all treatments were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus, heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose-volume histograms generated by TPS were analyzed to predict the NTCP for the considered organs at risk, according to different endpoints.

Results

Regarding dose-volume parameters no statistically significant differences were recorded for heart and origin of coronary arteries. We recorded statistically significant lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1 p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to the spinal cord was lower with IMRT (30.2 vs 19.9, p <0.001). Higher V10 with IMRT for thyroid (64.8 vs 95, p = 0.0019) and V5 for lungs (30.3 vs 44.8, p = 0.03, for right lung and 28.9 vs 48.1, p = 0.001 for left lung) were found, respectively. Higher V5 and V10 for breasts were found with IMRT (V5: 4.14 vs 20.6, p = 0.018 for left breast and 3.3 vs 17, p = 0.059 for right breast; V10: 2.5 vs 13.6 p = 0.035 for left breast and 1.7 vs 11, p = 0.07 for the right breast.) As for the NTCP, our data point out that IMRT is not always likely to significantly increase the NTCP to OARs.

Conclusions

In HL male patients IMRT seems feasible and accurate while for women HL patients IMRT should be used with caution.
The incidence of venous thromboembolism in cervical cancer: a nationwide population-based study
Authors: Tsai Shiang-Jiun , Ruan Ying-Xu , Lee Ching-Chih , Lee Moon-Sing , Chiou Wen-Yen , Lin Hon-Yi , Hsu Feng-Chun , Su Yu-Chieh , Hung Shih-Kai
Published: August 2012

Background

Venous thromboembolism (VTE) is a life-threatening condition that occurs as a complication of cervical cancer. The aim of this study was to evaluate the incidence of VTE in cervical cancer patients during a 5-year follow-up.

Methods

The study analyzed data deposited between 2003 and 2008 in the National Health Insurance Research Database (NHIRD), provided by the National Health Research Institutes in Taiwan. Totally, 1013 cervical cancer patients after treatment and 2026 appendectomy patients were eligible. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the VTE risk.

Results

The 5-year cumulative risk for VTE was significantly higher in the cervical cancer group than in the control group (3.3% vs 0.3%, p < 0.001). The hazard ratio for VTE was 10.14 times higher in the cervical cancer group than in the controls. The combined presence of more comorbidities was associated with a higher risk for VTE. Furthermore, cervical cancer patients without VTE had a significantly higher survival (75.3% vs 30.3%, p < 0.001).

Conclusions

The cumulative risk of VTE was significantly higher in cervical cancer patients, and these patients also had lower survival rates. Strategies to reduce these risks need to be examined.
Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes
Authors: Almansa Raquel , Socias Lorenzo , Sanchez-Garcia Monica , Martín-Loeches Ignacio , del Olmo Milagros , Andaluz-Ojeda David , Bobillo Felipe , Rico Lucia , Herrero Agueda , Roig Vicente , San-Jose C Alicia , Rosich Sara , Barbado Julia , Disdier Carlos , de Lejarazu Raúl Ortiz , Gallegos Maria C , Fernandez Victoria , Bermejo-Martin Jesus F
Published: August 2012

Background

Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment.

Findings

By using Agilent microarray chips,we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection.

Conclusion

Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.
Pathway control in the self-construction of complex precipitation forms in a Cu(II)-oxalate system
Authors: Toth Agota , Horvath Dezso , Kukovecz Akos , Maselko Maciej , Baker Anne , Ali Shareen , Maselko Jerzy
Published: August 2012

Text Abstract

Background

Many biological systems contain complex precipitation patterns. These structures are considered to be the result of finely tuned and genetically encoded developmental pathways. The amount of encoded information needed to generate and manipulate these structures is poorly understood. Investigating the dynamics of spontaneous pattern formation in non-biological systems provides insights to the physio-chemical phenomena that biological systems must have harnessed for living systems and that modern scientists need to understand for complex nano-technological applications.

Results

Here we show that highly complex, precipitation patterns similar to those found in biological systems can be formed in simple Cu(II)-oxalate systems. In these Cu(II)-oxalate systems, structures are constructed by a hierarchy of multiple processes that are precisely self-organized in space and time to form interconnected causal networks that generate complex and diverse structures dependent on construction trajectories that can be controlled by minor variations of initial conditions.

Conclusions

Highly complex precipitation patterns similar to those found in biological systems can be generated without a correspondingly complex set of instructions. Our result has implications for understanding early biotic systems that existed prior to the evolution of sophisticated genetic machinery. From an applications perspective, processes and structures that occur spontaneously are the building blocks for novel system chemistry based technologies where products are self-constructed. We also provide a simple model of chemical system that generates biomimetic structures for the study of fundamental processes involved in chemical self-construction.
Degradation of biodegradable plastic mulch films in soil environment by phylloplane fungi isolated from gramineous plants
Authors: Koitabashi Motoo , Noguchi Masako T , Sameshima-Yamashita Yuka , Hiradate Syuntaro , Suzuki Ken , Yoshida Shigenobu , Watanabe Takashi , Shinozaki Yukiko , Tsushima Seiya , Kitamoto Hiroko K
Published: August 2012

To improve the biodegradation of biodegradable plastic (BP) mulch films, 1227 fungal strains were isolated from plant surface (phylloplane) and evaluated for BP-degrading ability. Among them, B47-9 a strain isolated from the leaf surface of barley showed the strongest ability to degrade poly-(butylene succinate-co-butylene adipate) (PBSA) and poly-(butylene succinate) (PBS) films. The strain grew on the surface of soil-mounted BP films, produced breaks along the direction of hyphal growth indicated that it secreted a BP-degrading enzyme, and has directly contributing to accelerating the degradation of film. Treatment with the culture filtrate decomposed 91.2 wt%, 23.7 wt%, and 14.6 wt% of PBSA, PBS, and commercially available BP polymer blended mulch film, respectively, on unsterlized soil within 6 days. The PCR-DGGE analysis of the transition of soil microbial community during film degradation revealed that the process was accompanied with drastic changes in the population of soil fungi and Acantamoeba spp., as well as the growth of inoculated strain B47-9. It has a potential for application in the development of an effective method for accelerating degradation of used plastics under actual field conditions.
Psychometric properties of the Iranian version of Diabetes Empowerment Scale (IR-DES-28)
Authors: Mahjouri Mohammad Yoosef , Arzaghi Seyed Masoud , Heshmat Ramin , Khashayar Patricia , Esfahani Ensieh Nasli , Larijani Bagher
Published: August 2012

Background

This study was designed to determine the primary psychometric properties of the Iranian version of the Diabetes Empowerment Scale (IR-DES-28).

Methods

After translating the questionnaire into Persian, re-translating it into English and obtaining the confirmation of the diabetes specialists regarding the accuracy of the translated questionnaire, 100 patients with type 2 diabetes selected using a systematic random sampling method completed the Iranian-DES-28. The validity of IR-DES-28 was evaluated by construct, concurrent and criterion validity, whereas its reliability was assessed by test re-test, internal consistency and splitting method.

Results

Psychometric analysis confirmed the reliability and validity of the IR-DES-28 in three subscales: Self-awareness and managing psychological aspects of diabetes (α=0.80), goal achievement ability (α=0.50), the ability of setting goals (α=0.79). Test-retest reliability, evaluated through Pearson coefficient correlation, was equal to 0.74 (P <0.01). The total score of IR-DES-28 and that of the extracted subscales were correlated with HbA1c levels (metabolic control) (P <0.01). The findings also supported the concurrent validity of the questionnaire.

Conclusion

The validity and reliability of the Iranian-DES scale is acceptable. Thus, the scale could be an appropriate instrument in evaluating the empowerment-based education programs.
Improved neurologically intact survival with the use of an automated, load-distributing band chest compression device for cardiac arrest presenting to the emergency department
Authors: Hock Ong Marcus Eng , Fook-Chong Stephanie , Annathurai Annitha , Ang Shiang Hu , Tiah Ling , Yong Kok Leong , Koh Zhi Xiong , Yap Susan , Sultana Papia
Published: August 2012

Introduction

It has been unclear if mechanical cardiopulmonary resuscitation (CPR) is a viable alternative to manual CPR. We aimed to compare resuscitation outcomes before and after switching from manual CPR to load-distributing band (LDB) CPR in a multi-center emergency department (ED) trial.

Methods

We conducted a phased, prospective cohort evaluation with intention-to-treat analysis of adults with non-traumatic cardiac arrest. At these two urban EDs, systems were changed from manual CPR to LDB-CPR. Primary outcome was survival to hospital discharge, with secondary outcome measures of return of spontaneous circulation, survival to hospital admission and neurological outcome at discharge.

Results

A total of 1,011 patients were included in the study, with 459 in the manual CPR phase (January 01, 2004, to August 24, 2007) and 552 patients in the LDB-CPR phase (August 16, 2007, to December 31, 2009). In the LDB phase, the LDB device was applied in 454 patients (82.3%). Patients in the manual CPR and LDB-CPR phases were comparable for mean age, gender and ethnicity. The mean duration from collapse to arrival at ED (min) for manual CPR and LDB-CPR phases was 34:03 (SD16:59) and 33:18 (SD14:57) respectively. The rate of survival to hospital discharge tended to be higher in the LDB-CPR phase (LDB 3.3% vs Manual 1.3%; adjusted OR, 1.42; 95% CI, 0.47, 4.29). There were more survivors in LDB group with cerebral performance category 1 (good) (Manual 1 vs LDB 12, P = 0.01). Overall performance category 1 (good) was Manual 1 vs LDB 10, P = 0.06.

Conclusions

A resuscitation strategy using LDB-CPR in an ED environment was associated with improved neurologically intact survival on discharge in adults with prolonged, non-traumatic cardiac arrest.
Optineurin mediates negative regulation of Rab8 function by TBC1D17, a GTPase activating protein
Authors: Vaibhava Vipul , Nagabhushana Ananthamurthy , Chalasani Madhavi Latha Somaraju , Sudhakar Cherukuri , Kumari Asha , Swarup Ghanshyam
Published: August 2012

Rab GTPases regulate various membrane trafficking pathways but the mechanisms by which GTPase activating proteins recognize specific Rabs are not clear. Rab8 is involved in controlling several functions including the trafficking of transferrin receptor from early endosome to recycling endosome. Here we provide evidence to show that TBC1D17, a Rab GTPase activating protein, through its catalytic activity, regulates Rab8-mediated endocytic trafficking of transferrin receptor. Optineurin, a Rab8-binding effector protein, mediates interaction and colocalisation of TBC1D17 with Rab8. A non-catalytic region of TBC1D17 is required for direct interaction with optineurin. Co-expression of Rab8, but not other Rabs tested, rescues the inhibition of transferrin receptor trafficking by TBC1D17. Activated GTP-bound form of Rab8 is localized to the tubules emanating from the endocytic recycling compartment. Through its catalytic activity, TBC1D17 inhibits recruitment of Rab8 to the tubules and reduces colocalisation between transferrin receptor and Rab8. Knockdown of optineurin or TBC1D17 resulted in enhanced recruitment of Rab8 to the tubules. A glaucoma-associated mutant of optineurin, E50K causes enhanced inhibition of Rab8 by TBC1D17 resulting in defective endocytic recycling of transferrin receptor. Our results show that TBC1D17, through its interaction with optineurin, regulates Rab8-mediated endocytic recycling of transferrin receptor and recruitment of Rab8 to the tubules. We describe a mechanism of regulating a Rab GTPase by an effector protein (optineurin) that acts as an adaptor to bring together a Rab (Rab8) and its GTPase activating protein (TBC1D17).
Functional involvement of Rab1A in microtubule-dependent anterograde melanosome transport in melanocytes
Authors: Ishida Morié , Ohbayashi Norihiko , Maruta Yuto , Ebata Yuka , Fukuda Mitsunori
Published: August 2012

Melanosomes are transported to the cell periphery of melanocytes by coordination between bidirectional microtubule-dependent movements and unidirectional actin-dependent movement. Although both the mechanism of the actin-dependent melanosome transport and the mechanism of the microtubule-dependent retrograde melanosome transport in mammalian skin melanocytes have already been determined, almost nothing is known about the mechanism of the microtubule-dependent anterograde melanosome transport. Small GTPase Rab proteins are common regulators of membrane traffic in all eukaryotes, and in this study we performed genome-wide screening for Rab proteins that are involved in anterograde melanosome transport by expressing 60 different constitutive active (and negative) mutants and succeeded in identifying Rab1A, originally described as a Golgi-resident Rab, as a prime candidate. Endogenous Rab1A protein was found to be localized on mature melanosomes in melanocytes, and its functional ablation either by siRNA-mediated knockdown or by overexpression of a cytosolic form of Rab1A-GTPase-activating protein/TBC1D20 induced perinuclear melanosome aggregation. The results of time-lapse imaging further revealed that long-range anterograde melanosome movements were specifically suppressed in Rab1A-deficient melanocytes, whereas retrograde melanosome transport occurred normally. Taken together, these findings indicate that Rab1A is the first crucial component of the anterograde melanosome transport machinery to be identified in mammalian skin melanocytes.
Cofactor-dependent maturation of mammalian sulfite oxidase links two mitochondrial import pathways
Authors: Klein Julian M. , Schwarz Guenter
Published: August 2012

Sulfite oxidase (SO) catalyzes the metabolic detoxification of sulfite to sulfate within the intermembrane space of mitochondria. The enzyme follows a complex maturation pathway, including mitochondrial transport and processing, integration of two prosthetic groups, the molybdenum-cofactor (Moco) and heme, as well as homodimerization. Here, we have identified the sequential and cofactor-dependent maturation steps of SO. The N-terminal bipartite targeting signal of SO was required but not sufficient for mitochondrial localization. In absence of Moco, most of SO, although processed by the inner membrane peptidase of mitochondria, was found in the cytosol. Moco binding was required to induce mitochondrial trapping and retention, thus ensuring unidirectional translocation of SO. In absence of the N-terminal targeting sequence, SO assembled in the cytosol, suggesting an important function for the leader sequence in preventing premature cofactor binding. In vivo, heme binding and dimerization were prohibited in absence of Moco and only occurred after Moco integration. In conclusion, the identified molecular hierarchy of SO maturation represents a novel link between the canonical presequence pathway and folding-trap mechanisms of mitochondrial import.
Sarcophytonins F and G, New Dihydrofuranocembranoids from a Dongsha Atoll Soft Coral Sarcophyton sp.
Authors: Chen Shin-Pin , Chen Bo-Wei , Dai Chang-Feng , Sung Ping-Jyun , Wu Yang-Chang , Sheu Jyh-Horng
Published: August 2012

Two new dihydrofuranocembranoids 1 and 2 with three known sarcophytonin A (3), sarcophytonin C (4), and sarcophytoxide (5) have been isolated from a Dongsha Atoll soft coral Sarcophyton sp. The structures of metabolites were elucidated on the basis of extensive spectroscopic analysis and cytotoxic activity of 1–5 against the proliferation of a limited panel of cancer cell lines was measured.
Bile aspiration and hydrodissection to prevent complications in hepatic RFA close to the gallbladder
Authors: Levit Elena , Bruners Philipp , Günther Rolf W , Mahnken Andreas H
Published: August 2012

Background

Radiofrequency ablation (RFA) of liver tumors is a mainstay of interventional oncology. Its application, however, is limited by tumor size and location with lesions located within 1 cm to the gallbladder being at increased risk for complications.

Purpose

To evaluate the safety of hepatic RFA after bile aspiration with or without additional hydrodissection for lesions adjacent to the gallbladder.

Material and Methods

Six patients undergoing RFA of tumors with a distance of less than 1 cm to the gallbladder were retrospectively identified from a computer database. All patients underwent RFA combined with percutaneous bile aspiration from the gallbladder. In four patients additional hydrodissection was performed. Technical success and post-interventional complications were assessed by reviewing images and patient charts.

Results

Ablations were successfully completed in 5/6 patients. In one patient with incomplete ablation re-ablation was performed 2 months after the initial procedure. Minor complications occurred in three patients, including right-sided pleural effusion, hematoma in the gallbladder fossa, and intralesional hemorrhage in one patient each. There were no cases with cholecystitis or damage to the gallbladder during follow-up.

Conclusion

Bile aspiration with or without additional hydrodissection permits safe RFA of tumors located close to the gallbladder.
Views of general practitioners in Grampian about undergraduate psychiatric teaching
Authors: Wilson S , Eagles J M , Mckenzie H
Published: August 2012

This paper reports the free-text responses of general practitioners (GPs) in the Grampian area to a questionnaire about their experiences of undergraduate psychiatry teaching. Most respondents were senior GPs whose undergraduate training had taken place a number of years ago. Respondents varied in their perceptions of the quality of their psychiatric teaching. However, they reported common themes such as the bias of undergraduate teaching towards disorders which are less relevant to their practice, and the benefits of postgraduate training in psychiatry. We suggest that medical schools need to bear the needs of the non-psychiatrist in mind when developing curricula in psychiatry.