bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical and thermal properties of glass fiber-reinforced epoxy composite with matrix modification using liquid epoxidized natural rubber
Authors: Muhammad Yusri Helmi , Ahmad Sahrim
Published: March 2013

Glass fiber epoxy composites are widely used in industries. Liquid epoxidized natural rubber was added to epoxy as the matrix for a fiber-reinforced composite in order to improve its mechanical properties whilst E-glass fiber was used as the composite reinforcement. Flexural test, Izod impact test, tensile test, thermogravimetric analysis, and scanning electron microscopy were performed to investigate the effect of liquid epoxidized natural rubber addition and glass fiber loadings on the mechanical properties of the composite. It was observed that the flexural strength and flexural modulus of the samples increased with increasing glass fiber percentage with 9% as the maximum weight percentage recorded. The tensile strength and Young’s modulus increased with increasing glass fiber content until it reached the maximum value at 9 wt% of glass fiber. The same trend was observed with the impact value of the samples. All the tests were conducted for the composite with and without liquid epoxidized natural rubber addition. The presence of liquid epoxidized natural rubber improved the mechanical properties of the composites due to the plasticizing effect of the rubber particles in the matrix. Thermogravimetric analysis revealed the thermal stability of the composites whilst the scanning electron microscopy shows a heterogeneous dispersed phase of morphology. There was poor adhesion between the matrix polymer and glass fibers due to the use of untreated glass fibers.
A new three-dimensional braiding method for net shape fabrication of a complex perform with rounding chamfer
Authors: Geng Xiaojing , Liu Lifang , Yan Jianhua , Yu Jianyong
Published: March 2013

This paper presents a new three-dimensional method to braid a net-shape preform with rounding chamfer. This new method is mainly based on the 4-step method. It needs six steps to finish one cycle. For the traditional braiding method it needs eight steps to form a L- shape preform. Due to the different braiding processes referred above the yarn topology is different. After the preforms are impregnated with matrix, the interior unit cells between the two kinds of composite referred above are compared. The interior unit cell of the composite with rounding chamfer consists of four yarns while the other contains five yarns. The corner of the L-shape composite is cut to form the same dimensional rounding chamfer. The specimen of the two kinds of composites is tested. The flexural experiment shows that composite manufactured by the new method performs better due to the structural integrity.
Disposal of waste computer hard disk drive: data destruction and resources recycling
Authors: Yan Guoqing , Xue Mianqiang , Xu Zhenming
Published: March 2013

An increasing quantity of discarded computers is accompanied by a sharp increase in the number of hard disk drives to be eliminated. A waste hard disk drive is a special form of waste electrical and electronic equipment because it holds large amounts of information that is closely connected with its user. Therefore, the treatment of waste hard disk drives is an urgent issue in terms of data security, environmental protection and sustainable development. In the present study the degaussing method was adopted to destroy the residual data on the waste hard disk drives and the housing of the disks was used as an example to explore the coating removal process, which is the most important pretreatment for aluminium alloy recycling. The key operation points of the degaussing determined were: (1) keep the platter plate parallel with the magnetic field direction; and (2) the enlargement of magnetic field intensity B and action time t can lead to a significant upgrade in the degaussing effect. The coating removal experiment indicated that heating the waste hard disk drives housing at a temperature of 400 °C for 24 min was the optimum condition. A novel integrated technique for the treatment of waste hard disk drives is proposed herein. This technique offers the possibility of destroying residual data, recycling the recovered resources and disposing of the disks in an environmentally friendly manner.
Family Firms and Institutional Investors
Authors: Fernando Guy D. , Schneible Richard Arthur , Suh SangHyun
Published: March 2013

It is generally assumed that family firms emphasize socioemotional wealth, which exacerbates wealth expropriation from noncontrolling shareholders. We examine this issue in the context of nonfamily shareholders, specifically institutional investors, and find that institutional investors avoid investments in family firms. Furthermore, integrating institutional theory with a socioemotional wealth approach, we find that financial regulation can mitigate external investors’ concerns. These two results are important theoretically because they provide insight into the effect of agency problems specific to family firms and are important for management practice because they can provide guidance for family firms interested in new sources of capital.
National Styles of NGO Regulation
Authors: Bloodgood Elizabeth A. , Tremblay-Boire Joannie , Prakash Aseem
Published: March 2013

Why do Organisation for Economic Cooperation and Development (OECD) countries vary in their regulatory approach toward nongovernmental organizations (NGOs)? This article introduces an index to assess NGO regulation regarding barriers to entry, NGOs’ political capacity, and economic activity. Our cross-section analysis of 28 OECD countries offers preliminary evidence of systematic differences in NGO regulation between corporatist and pluralist systems. We suggest corporatist systems have more restrictive regulations because NGOs risk upsetting the political order and managed social consensus. In pluralist countries, NGOs face fewer restrictions because governments view them as substitutes for formal communication channels. We present two cases, Japan (corporatist) and the United States (pluralist), to illustrate this argument. In sum, macroinstitutional arrangements of political representation have a crucial bearing on national styles of NGO regulation. Future uses of this index include examining the effects of national context on international NGOs (INGOs), explaining variations in organizational structures and strategies among NGOs, and tracking variations in NGO–state relations over time.
Computed tomography carotid wall plaque characterization using a combination of discrete wavelet transform and texture features: A pilot study
Authors: Acharya UR , Sree S Vinitha , Mookiah MRK , Saba L , Gao H , Mallarini G , Suri J S
Published: March 2013

In 30% of stroke victims, the cause of stroke has been found to be the stenosis caused by plaques in the carotid artery. Early detection of plaque and subsequent classification of the same into symptomatic and asymptomatic can help the clinicians to choose only those patients who are at a higher risk of stroke for risky surgeries and stenosis treatments. Therefore, in this work, we have proposed a non-invasive computer-aided diagnostic technique to classify the detected plaque into the two classes. Computed tomography (CT) images of the carotid artery images were used to extract Local Binary Pattern (LBP) features and wavelet energy features. Significant features were then used to train and test several supervised learning algorithm based classifiers. The Support Vector Machine (SVM) classifier with various kernel configurations was evaluated using LBP and wavelet features. The SVM classifier presented the highest accuracy of 88%, sensitivity of 90.2%, and specificity of 86.5% for radial basis function (RBF) kernel function. The CT images of the carotid artery provide unique 3D images of the artery and plaque that could be used for calculating percentage of stenosis. Our proposed technique enables automatic classification of plaque into asymptomatic and symptomatic with high accuracy, and hence, it can be used for deciding the course of treatment. We have also proposed a single-valued integrated index ( Atheromatic Index) using the significant features which can provide a more objective and faster prediction of the class.
Tidal energy resource characterization: methodology and field study in Admiralty Inlet, Puget Sound, WA (USA)
Authors: Polagye B , Thomson J
Published: March 2013

Tidal energy resource characteristics are presented from a multi-year field study in northern Admiralty Inlet, Puget Sound, WA (USA). Measurements were conducted as part of a broader effort to characterize the physical and biological environment at this location ahead of a proposed tidal energy project. The resource is conceptually partitioned into deterministic, meteorological, and turbulent components. Metrics with implications for device performance are used to describe spatial variations in the tidal resource. The performance differences between passive and fixed yaw turbines are evaluated at these locations. Results show operationally significant variations in the tidal resource over length scales less than 100 m, likely driven by large eddies shed from a nearby headland. Finite-record length observations of tidal currents are shown to be acceptable for estimating device performance, but unsuitable for direct investigation of design loads.
The Time Has Come for Embracing Interdisciplinary Perspectives
Authors: Salas Eduardo
Published: March 2013

This article outlines a few reflections on the need to embrace, support, and apply interdisciplinary perspectives in the study of team dynamics.
Paradoxical Role of 3-Methyladenine in Pyocyanin-Induced Toxicity in 1321N1 Astrocytoma and SH-SY5Y Neuroblastoma Cells
Authors: McFarland Amelia J. , Grant Gary D. , Perkins Anthony V. , Flegg Cameron , Davey Andrew K. , Allsopp Tristan J. , Renshaw Gillian , Kavanagh Justin , McDermott Catherine M. , Anoopkumar-Dukie Shailendra
Published: March 2013

The role of autophagy in pyocyanin (PCN)-induced toxicity in the central nervous system (CNS) remains unclear, with only evidence from our group identifying it as a mechanism underlying toxicity in 1321N1 astrocytoma cells. Therefore, the aim of this study was to further examine the role of autophagy in PCN-induced toxicity in the CNS. To achieve this, we exposed 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells to PCN (0-100 μmol/L) and tested the contribution of autophagy by measuring the impact of the autophagy inhibitor 3-methyladenine (3-MA) using a series of biochemical and molecular markers. Pretreatment of 1321N1 astrocytoma cells with 3-MA (5 mmol/L) decreased the PCN-induced acidic vesicular organelle and autophagosome formation as measured using acridine orange and green fluorescent protein-LC3 -LC3 fluorescence, respectively. Furthermore, 3-MA (5 mmol/L) significantly protected 1321N1 astrocytoma cells against PCN-induced toxicity. In contrast pretreatment with 3-MA (5 mmol/L) increased PCN-induced toxicity in SH-SY5Y neuroblastoma cells. Given the influence of autophagy in inflammatory responses, we investigated whether the observed effects in this study involved inflammatory mediators. The PCN (100 μmol/L) significantly increased the production of interleukin-8 (IL-8), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) in both cell lines. Consistent with its paradoxical role in modulating PCN-induced toxicity, 3-MA (5 mmol/L) significantly reduced the PCN-induced production of IL-8, PGE2, and LTB4 in 1321N1 astrocytoma cells but augmented their production in SH-SY5Y neuroblastoma cells. In conclusion, we show here for the first time the paradoxical role of autophagy in mediating PCN-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells and provide novel evidence that these actions may be mediated by effects on IL-8, PGE2, and LTB4 production.
Selective Halo Effects Arising From Improving the Interpersonal Skills of Frontline Employees
Authors: Dagger Tracey S. , Danaher Peter J. , Sweeney Jillian C. , McColl-Kennedy Janet R.
Published: March 2013

Although frontline customer service employees play a vital role in many firms, their part in service delivery is often underappreciated. The interaction between frontline employees and customers creates an impression of what is to come in the service experience. A key question is whether this interaction spills over to other unrelated aspects of the business. We conduct a quasi-experiment across two medical clinics, one of which had its frontline employees trained to improve their interpersonal skills. We find that not only does the training create positive perceptions of the service provided by frontline employees, but also increases perceptions of service quality attributes not related to these employees. That is, customer perceptions of the interpersonal skills of frontline employees “spillover” to other service quality attributes. However, this spillover effect does not impact all service attributes uniformly; rather, it is restricted to only credence attributes which customers find difficult to evaluate. We term this a selective halo effect. This finding demonstrates that customer perceptions of the interpersonal skills of frontline employees extend well beyond the range in which they perform their expected duties. Our article builds on attribute evaluability theory and information economic theory by demonstrating the existence of a selective halo effect. Further, we develop a classification system that managers can use to predict which attributes are most likely to be influenced by a selective halo effect. We encourage managers to think of frontline employees as “barometers of the business,” and to invest in continued training for these key personnel.
The impact of dramatic events on public debate concerning accommodation of Islam in Europe
Authors: Vanparys Nathalie , Jacobs Dirk , Torrekens Corinne
Published: March 2013

Using the data of the EURISLAM project, this article investigates the impact of dramatic events on the public debate with regard to Islam in Belgium, the Netherlands, France, Germany, Switzerland and the UK. It assesses the extent to which dramatic events such as 9/11, the bombings in Madrid and London and the murder of Theo Van Gogh in Amsterdam impacted on the debate on multiculturalism, notably the accommodation of Western-European institutions to Islam. In this contribution, we analyse the overall evolution of public debate in the written press on Muslims, and more particularly Muslim rights, for the period 1999–2009. Our aim is to empirically analyse the transitions that the public debate on Islam in Europe has undergone in the wake of the most dramatic terrorist acts perpetrated by Muslim extremists during the last decade. We hypothesize that dramatic violent events involving Muslim extremists had an impact on the number of claims about Muslims and Islam in general, but not on the debate about religious rights for Muslims in Europe. Descriptive analysis and time series plus intervention analysis were undertaken to test these hypotheses.1
Detection and minimally invasive treatment of early squamous lung cancer
Authors: Daniels Johannes M.A. , Sutedja Thomas G.
Published: March 2013

Non-small cell lung cancer (NSCLC) is the most common cause of cancer deaths worldwide. The majority of patents presenting with NSCLC have advanced disease, which precludes curative treatment. Early detection and treatment might result in the identification of more patients with early central lung cancer and improve survival. In addition, the study of early lung cancer improves understanding of lung carcinogenesis and might also reveal new treatment targets for advanced lung cancer. Bronchoscopic investigation of the central airways can reveal both early central lung cancer in situ (stage 0) and other preinvasive lesions such as dysplasia. In the current review we discuss the detection of early squamous lung cancer, the natural history of preinvasive lesions and whether biomarkers can be used to predict progression to cancer. Finally we will review the staging and management of preinvasive lung cancer lesions and the different therapeutic modalities that are available.
Absence of long-range diffusion of OmpA in E. coliis not caused by its peptidoglycan binding domain
Authors: Verhoeven Gertjan S , Dogterom Marileen , den Blaauwen Tanneke
Published: March 2013

Background

It is widely believed that integral outer membrane (OM) proteins in bacteria are able to diffuse laterally in the OM. However, stable, immobile proteins have been identified in the OM of Escherichia coli. In explaining the observations, a hypothesized interaction of the immobilized OM proteins with the underlying peptidoglycan (PG) cell wall played a prominent role.

Results

OmpA is an abundant outer membrane protein in E. coli containing a PG-binding domain. We use FRAP to investigate whether OmpA is able to diffuse laterally over long-range (> ~100 nm) distances in the OM. First, we show that OmpA, containing a PG binding domain, does not exhibit long-range lateral diffusion in the OM. Then, to test whether PG interaction was required for this immobilization, we genetically removed the PG binding domain and repeated the FRAP experiment. To our surprise, this did not increase the mobility of the protein in the OM.

Conclusions

OmpA exhibits an absence of long-range (> ~100 nm) diffusion in the OM that is not caused by its PG binding domain. Therefore, other mechanisms are needed to explain this observation, such as the presence of physical barriers in the OM, or strong interactions with other elements in the cell envelope.
A 1,681-locus consensus genetic map of cultivated cucumber including 67 NB-LRR resistance gene homolog and ten gene loci
Authors: Yang Luming , Li Dawei , Li Yuhong , Gu Xingfang , Huang Sanwen , Garcia-Mas Jordi , Weng Yiqun
Published: March 2013

Background

Cucumber is an important vegetable crop that is susceptible to many pathogens, but no disease resistance (R) genes have been cloned. The availability of whole genome sequences provides an excellent opportunity for systematic identification and characterization of the nucleotide binding and leucine-rich repeat (NB-LRR) type R gene homolog (RGH) sequences in the genome. Cucumber has a very narrow genetic base making it difficult to construct high-density genetic maps. Development of a consensus map by synthesizing information from multiple segregating populations is a method of choice to increase marker density. As such, the objectives of the present study were to identify and characterize NB-LRR type RGHs, and to develop a high-density, integrated cucumber genetic-physical map anchored with RGH loci.

Results

From the Gy14 draft genome, 70 NB-containing RGHs were identified and characterized. Most RGHs were in clusters with uneven distribution across seven chromosomes. In silico analysis indicated that all 70 RGHs had EST support for gene expression. Phylogenetic analysis classified 58 RGHs into two clades: CNL and TNL. Comparative analysis revealed high-degree sequence homology and synteny in chromosomal locations of these RGH members between the cucumber and melon genomes.

Fifty-four molecular markers were developed to delimit 67 of the 70 RGHs, which were integrated into a genetic map through linkage analysis. A 1,681-locus cucumber consensus map including 10 gene loci and spanning 730.0 cM in seven linkage groups was developed by integrating three component maps with a bin-mapping strategy. Physically, 308 scaffolds with 193.2 Mbp total DNA sequences were anchored onto this consensus map that covered 52.6% of the 367 Mbp cucumber genome.

Conclusions

Cucumber contains relatively few NB-LRR RGHs that are clustered and unevenly distributed in the genome. All RGHs seem to be transcribed and shared significant sequence homology and synteny with the melon genome suggesting conservation of these RGHs in the Cucumis lineage. The 1,681-locus consensus genetic-physical map developed and the RGHs identified and characterized herein are valuable genomics resources that may have many applications such as quantitative trait loci identification, map-based gene cloning, association mapping, marker-assisted selection, as well as assembly of a more complete cucumber genome.
Targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR): protocol for a randomised controlled trial
Authors: O’Brien Claire , Bray Emma P , Bryan Stirling , Greenfield Sheila M , Haque M Sayeed , Hobbs FD Richard , Jones Miren I , Jowett Sue , Kaambwa Billingsley , Little Paul , Mant Jonathan , Penaloza Cristina , Schwartz Claire , Shackleford Helen , Varghese Jinu , Williams Bryan , McManus Richard J
Published: March 2013

Background

Self-monitoring of hypertension with self-titration of antihypertensives (self-management) results in lower systolic blood pressure for at least one year. However, few people in high risk groups have been evaluated to date and previous work suggests a smaller effect size in these groups. This trial therefore aims to assess the added value of self-management in high risk groups over and above usual care.

Methods/Design

The targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR) trial will be a pragmatic primary care based, unblinded, randomised controlled trial of self-management of blood pressure (BP) compared to usual care. Eligible patients will have a history of stroke, coronary heart disease, diabetes or chronic kidney disease and will be recruited from primary care. Participants will be individually randomised to either usual care or self-management. The primary outcome of the trial will be difference in office SBP between intervention and control groups at 12 months adjusted for baseline SBP and covariates. 540 patients will be sufficient to detect a difference in SBP between self-management and usual care of 5 mmHg with 90% power. Secondary outcomes will include self-efficacy, lifestyle behaviours, health-related quality of life and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative analysis will gain insights into patients’ views, experiences and decision making processes.

Discussion

The results of the trial will be directly applicable to primary care in the UK. If successful, self-management of blood pressure in people with stroke and other high risk conditions would be applicable to many hundreds of thousands of individuals in the UK and beyond.

Trial Registration

ISRCTN87171227
Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation
Authors: Toricelli Mariana , Melo Fabiana HM , Peres Giovani B , Silva Débora CP , Jasiulionis Miriam G
Published: March 2013

Background

Anoikisresistance is one of the abilities acquired along tumor progression. This characteristic is associated with metastasis development, since tumorigenic cells must survive independently of cell-matrix interactions in this process. In our laboratory, it was developed a murine melanocyte malignant transformation model associated with a sustained stressful condition. After subjecting melan-a melanocytes to 1, 2, 3 and 4 cycles of anchorage impediment,anoikisresistant cells were established and named 1C, 2C, 3C and 4C, respectively. These cells showed altered morphology and PMA independent cell growth, but were not tumorigenic, corresponding to pre-malignant cells. After limiting dilution of 4C pre-malignant cells, melanoma cell lines with different characteristics were obtained. Previous data from our group showed that increased Timp1 expression correlated withanoikis-resistant phenotype. Timp1 was shown to confer anchorage-independent growth capability to melan-a melanocytes and render melanoma cells more aggressive when injected into mice. However, the mechanisms involved inanoikisregulation by Timp1 in tumorigenic cells are not clear yet.

Methods

The β1-integrin and Timp1 expression were evaluated by Western blotting and CD63 protein expression by flow cytometry using specific antibodies. To analyze the interaction among Timp1, CD63 and β1-integrin, immunoprecipitation assays were performed,anoikisresistance capability was evaluated in the presence or not of the PI3-K inhibitors, Wortmannin and LY294002. Relative expression ofTIMP1andCD63in human metastatic melanoma cells was analyzed by real time PCR.

Results

Differential association among Timp1, CD63 and β1-integrins was observed in melan-a melanocytes, 4C pre-malignant melanocytes and 4C11- and 4C11+ melanoma cells. Timp1 present in conditioned medium of melanoma cells rendered melan-a melanocytesanoikis-resistant through PI3-K signaling pathway independently of Akt activation. In human melanoma cell lines, in which TIMP1 and beta-1 integrin were also found to be interacting,TIMP1andCD63levels together was shown to correlate significantly with colony formation capacity.

Conclusions

Our results show that Timp1 is assembled in a supramolecular complex containing CD63 and β1-integrins along melanoma genesis and confersanoikisresistance by activating PI3-K signaling pathway, independently of Akt phosphorylation. In addition, our data pointTIMP1, mainly together withCD63, as a potential biomarker of melanoma.
Direct measurement of the spin gaps in a gated GaAs two-dimensional electron gas
Authors: Huang Tsai-Yu , Liang Chi-Te , Chen Yang Fang , Simmons Michelle Y , Kim Gil-Ho , Ritchie David A
Published: March 2013

We have performed magnetotransport measurements on gated GaAs two-dimensional electron gases in which electrons are confined in a layer of the nanoscale. From the slopes of a pair of spin-split Landau levels (LLs) in the energy-magnetic field plane, we can perform direct measurements of the spin gap for different LLs. The measured g-factor g is greatly enhanced over its bulk value in GaAs (0.44) due to electron–electron (e-e) interactions. Our results suggest that both the spin gap and g determined from conventional activation energy studies can be very different from those obtained by direct measurements.
Transcriptional analysis of the innate immune response of ducks to different species-of-origin low pathogenic H7 avian influenza viruses
Authors: Maughan Michele N , Dougherty Lorna S , Preskenis Lauren A , Ladman Brian S , Gelb Jack , Spackman Erica V , Keeler Calvin L
Published: March 2013

Background

Wild waterfowl, including ducks, represent the classic reservoir for low pathogenicity avian influenza (LPAI) viruses and play a major role in the worldwide dissemination of AIV. AIVs belonging to the hemagglutinin (H) 7 subtype are of epidemiological and economic importance due to their potential to mutate into a highly pathogenic form of the virus. Thus far, however, relatively little work has been conducted on elucidating the host-pathogen interactions of ducks and H7 LPAIVs. In the current study, three H7 LPAIVs isolated from either chicken, duck, or turkey avian species were evaluated for their comparative effect on the transcriptional innate immune response of ducks.

Results

Three H7 LPAIV isolates, chicken-origin (A/chicken/Maryland/MinhMa/2004), duck-origin (A/pintail/Minnesota/423/1999), and turkey-origin (A/turkey/Virginia/SEP-67/2002) were used to infect Pekin ducks. At 3 days post-infection, RNA from spleen tissue was used for transcriptional analysis using the Avian Innate Immune Microarray (AIIM) and quantitative real-time RT-PCR (qRT-PCR). Microarray analysis revealed that a core set of 61 genes was differentially regulated in response to all three LPAIVs. Furthermore, we observed 101, 135, and 628 differentially expressed genes unique to infection with the chicken-, duck-, or turkey-origin LPAIV isolates, respectively. qRT-PCR results revealed significant (p<0.05) induction of IL-1β, IL-2, and IFNγ transcription, with the greatest induction observed upon infection with the chicken-origin isolate. Several key innate immune pathways were activated in response to LPAIV infection including the toll-like receptor and RIG-I-like receptor pathways.

Conclusions

Pekin ducks elicit a unique innate immune response to different species-of-origin H7 LPAIV isolates. However, twelve identifiable genes and their associated cell signaling pathways (RIG-I, NOD, TLR) are differentially expressed regardless of isolate origin. This core set of genes are critical to the duck immune response to AI. These data provide insight into the potential mechanisms employed by ducks to tolerate AI viral infection.
Thyroid heterogeneity, as indicated by the CV of ultrasonographic intensities, correlates with anti-thyroid peroxidase antibodies in euthyroid Hashimoto’s thyroiditis
Authors: Wakita Yosuke , Nagasaki Toshiki , Nagata Yuki , Imanishi Yasuo , Yamada Shinsuke , Yoda Koichiro , Emoto Masanori , Ishimura Eiji , Inaba Masaaki
Published: March 2013

Objective

To prospectively evaluate the heterogeneous appearance of the thyroid gland, reflecting inflammation and destruction in euthyroid Hashimoto’s thyroiditis (HT), we investigated the clinical utilities of the heterogeneity index (HI) [the coefficient of variance (CV) of the ultrasonographic (US) intensities], focusing on anti-thyroid peroxidase antibodies (TPO-Ab), which represent not only disease activity but also subsequent thyroid destruction of HT.

Methods

Forty-four consecutive patients with euthyroid HT [60.5 ± 2.7 years old (mean ± SE)] and 30 age-matched normal controls were studied. HI was calculated as the CV (SD/mean) of US intensities of either four points per lobe of the thyroid gland along a horizontal line at the depth of the right common carotid artery. Evaluation included serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), anti-thyroid peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (Tg-Ab), thyroglobulin and thyroid volume.

Results

While no differences were observed for TSH, FT4 and FT3, thyroglobulin and thyroid volume between the two groups, HI exhibited a tendency towards a significant difference (3.59 ± 0.20% in HT patients vs 3.23 ± 0.19% in normal group, p = 0.089). In HT patients, there was a significant and positive correlation of HI with TPO-Ab (r = 0.396, p = 0.034), whereas such a correlation was absent in normal controls. In both groups, there were no significant correlations of HI with Tg-Ab, FT3, FT4 or TSH.

Conclusions

This is the first report of the close relation between heterogeneity of US of the thyroid gland and TPO-Ab in euthyroid HT patients before the heterogeneity becomes distinguishable from normal thyroid glands. Furthermore, at this stage, subsequent thyroid destruction in HT might be already be predicted through the heterogeniety of the thyroid tissue.
Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium
Authors: Wang Yiying , Wang Yue , Li Jie , Cragun Janiel , Hatch Kenneth , Chambers Setsuko K , Zheng Wenxin
Published: March 2013

Lynch syndrome (LS), an autosomal dominant inherited cancer susceptibility syndrome, also known as hereditary non-polyposis colon cancer (HNPCC), is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. LS is the most common presentation of hereditary colorectal cancer (CRC), accounting for about 2–5% of all CRC cases. More recently, it is found that a similar number of endometrial cancers is also due to one of the MMR gene mutations. There has been significant progress in LS-related CRC in terms of molecular pathogenesis, risks, genetic basis, and cancer prevention. In contrast, the advance about LS-related endometrial cancer (EC) is very much limited. In this commentary, we summarize the main clinicopathologic features of LS-related EC and propose universal screening for LS in individuals with endometrial cancer.
RNA sequencing reveals sexually dimorphic gene expression before gonadal differentiation in chicken and allows comprehensive annotation of the W-chromosome
Authors: Ayers Katie L , Davidson Nadia M , Demiyah Diana , Roeszler Kelly N , Grützner Frank , Sinclair Andrew H , Oshlack Alicia , Smith Craig A
Published: March 2013

Background

Birds have a ZZ male: ZW female sex chromosome system and while the Z-linked DMRT1 gene is necessary for testis development, the exact mechanism of sex determination in birds remains unsolved. This is partly due to the poor annotation of the W chromosome, which is speculated to carry a female determinant. Few genes have been mapped to the W and little is known of their expression.

Results

We used RNA-seq to produce a comprehensive profile of gene expression in chicken blastoderms and embryonic gonads prior to sexual differentiation. We found robust sexually dimorphic gene expression in both tissues pre-dating gonadogenesis, including sex-linked and autosomal genes. This supports the hypothesis that sexual differentiation at the molecular level is at least partly cell autonomous in birds. Different sets of genes were sexually dimorphic in the two tissues, indicating that molecular sexual differentiation is tissue specific. Further analyses allowed the assembly of full-length transcripts for 26 W chromosome genes, providing a view of the W transcriptome in embryonic tissues. This is the first extensive analysis of W-linked genes and their expression profiles in early avian embryos.

Conclusion

Sexual differentiation at the molecular level is established in chicken early in embryogenesis, before gonadal sex differentiation. We find that the W chromosome is more transcriptionally active than previously thought, expand the number of known genes to 26 and present complete coding sequences for these W genes. This includes two novel W-linked sequences and three small RNAs reassigned to the W from the Un_Random chromosome.
Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration
Authors: Song Minjung , Lavasani Mitra , Thompson Seth D , Lu Aiping , Ahani Bahar , Huard Johnny
Published: March 2013

Introduction

Loss of adult stem cell function during aging contributes to impaired tissue regeneration. Here, we tested the aging-related decline in regeneration potential of adult stem cells residing in the skeletal muscle.

Methods

We isolated muscle-derived stem/progenitor cells (MDSPCs) from progeroid Zmpste24-deficient mice (Zmpste24-/-) with accelerated aging phenotypes to investigate whether mutation in lamin A has an adverse effect on muscle stem/progenitor cell function.

Results

Our results indicate that MDSPCs isolated from Zmpste24-/- mice show reduced proliferation and myogenic differentiation. In addition, Zmpste24-/- MDSPCs showed impaired muscle regeneration, with a limited engraftment potential when transplanted into dystrophic muscle, compared with wild-type (WT) MDSPCs. Exposure of progeroid Zmpste24-/- MDSPCs to WT MDSPCs rescued the myogenic differentiation defect in vitro.

Conclusions

These results demonstrate that adult stem/progenitor cell dysfunction contributes to impairment of tissue regeneration and suggest that factors secreted by functional cells are indeed important for the therapeutic effect of adult stem cells.
Two Populations of Glucocorticoid Receptor-Binding Sites in the Male Rat Hippocampal Genome
Authors: Polman J. Annelies E. , de Kloet E. Ronald , Datson Nicole A.
Published: March 2013

In the present study, genomic binding sites of glucocorticoid receptors (GR) were identified in vivo in the rat hippocampus applying chromatin immunoprecipitation followed by next-generation sequencing. We identified 2470 significant GR-binding sites (GBS) and were able to confirm GR binding to a random selection of these GBS covering a wide range of P values. Analysis of the genomic distribution of the significant GBS revealed a high prevalence of intragenic GBS. Gene ontology clusters involved in neuronal plasticity and other essential neuronal processes were overrepresented among the genes harboring a GBS or located in the vicinity of a GBS. Male adrenalectomized rats were challenged with increasing doses of the GR agonist corticosterone (CORT) ranging from 3 to 3000 μg/kg, resulting in clear differences in the GR-binding profile to individual GBS. Two groups of GBS could be distinguished: a low-CORT group that displayed GR binding across the full range of CORT concentrations, and a second high-CORT group that displayed significant GR binding only after administering the highest concentration of CORT. All validated GBS, in both the low-CORT and high-CORT groups, displayed mineralocorticoid receptor binding, which remained relatively constant from 30 μg/kg CORT upward. Motif analysis revealed that almost all GBS contained a glucocorticoid response element resembling the consensus motif in literature. In addition, motifs corresponding with new potential GR-interacting proteins were identified, such as zinc finger and BTB domain containing 3 (Zbtb3) and CUP (CG11181 gene product from transcript CG11181-RB), which may be involved in GR-dependent transactivation and transrepression, respectively. In conclusion, our results highlight the existence of 2 populations of GBS in the rat hippocampal genome.
Phosphorylation of Chs2p regulates interaction with COPII
Authors: Jakobsen Mia Kyed , Cheng Zhiliang , Lam Sheung Kwan , Roth-Johnson Elizabeth , Barfield Robyn M. , Schekman Randy
Published: March 2013

Trafficking of the chitin synthase Chs2p from the endoplasmic reticulum (ER) to the bud-neck in late mitosis is tightly regulated by the cell cycle via phosphorylation of serine residues in the N-terminus of the protein. Here, we describe the effects of Chs2p phosphorylation on interaction with coat protein complex II (COPII). Identification of a cdc5ts mutant, which fails to transport Chs2p-3xGFP to the bud-neck and instead accumulates the protein in intracellular punctae, led us to discover that Chs2p-3xGFP accumulates at ER exit sites in metaphase arrested wild-type cells. Using an in vitro ER vesicle formation assay we show that phosphorylation of Chs2p by the cyclin dependent kinase CDK1 prevents packaging into COPII vesicles, while dephosphorylation of Chs2p by the phosphatase Cdc14p stimulates selection into the vesicles. We find that the cytoplasmic N-terminal domain of Chs2p, which contains the CDK1 phosphorylation sites, interacts with the COPII component Sec24p in a yeast two-hybrid assay and that phosphomimetic substitutions of serines at the CDK1 consensus sites reduces the interaction. Our data suggest that dephosphorylation functions as a molecular switch for regulated ER exit of Chs2p.
Brain and Muscle Arnt-like 1 is a Key Regulator of Myogenesis
Authors: Chatterjee Somik , Nam Deokhwa , Guo Bingyan , Kim Ji M. , Winnier Glen E. , Lee Jeongkyung , Berdeaux Rebecca , Yechoor Vijay K. , Ma Ke
Published: March 2013

The circadian clock network is an evolutionarily conserved mechanism that imparts temporal regulation to diverse biological processes. Brain and muscle Arnt-like 1 (Bmal1), an essential transcriptional activator of the clock, is highly expressed in skeletal muscle. However, whether this key clock component impacts myogenesis, a temporally regulated event that requires the sequential activation of myogenic regulatory factors, is not known. Here we report a novel function of Bmal1 in controlling myogenic differentiation through direct transcriptional activation of components of the canonical Wnt signaling cascade, a major inductive signal for embryonic and postnatal muscle growth. Genetic loss of Bmal1 in mice leads to reduced total muscle mass and Bmal1-deficient primary myoblasts exhibit significantly impaired myogenic differentiation accompanied by markedly blunted expression of key myogenic regulatory factors. Conversely, forced expression of Bmal1 enhances differentiation of C2C12 myoblasts. This cell-autonomous effect of Bmal1 is mediated by Wnt signaling as both expression and activity of Wnt components are markedly attenuated by inhibition of Bmal1, and activation of the Wnt pathway partially rescues the myogenic defect in Bmal1-deficient myoblasts. We further reveal direct association of Bmal1 with promoters of canonical Wnt pathway genes, and as a result of this transcriptional regulation, Wnt signaling components exhibit intrinsic circadian oscillation. Collectively, our study demonstrates that the core clock gene, Bmal1, is a positive regulator of myogenesis, which may represent a temporal regulatory mechanism to fine-tune myocyte differentiation.
Crystal clear insights into how the dynein motor moves
Authors: Carter Andrew P.
Published: March 2013

Dyneins are motor proteins that move along microtubules. They have many roles in the cell. They drive the beating of cilia and flagella, move cargos in the cytoplasm and function in the mitotic spindle. Dyneins are large and complex protein machines. Until recently, the way they move was poorly understood. In 2012, two high-resolution crystal structures of the >2500-amino-acid dynein motor domain were published. This Commentary will compare these structures and integrate the findings with other recent studies in order to suggest how dynein works. The dynein motor produces movement in a manner that is distinct from myosin and kinesin, the other cytoskeletal motors. Its powerstroke is produced by ATP-induced remodelling of a protein domain known as the linker. It binds to microtubules through a small domain at the tip of a long stalk. Dynein communicates with the microtubule-binding domain by an unconventional sliding movement of the helices in the stalk coiled-coil. Even the way the two motor domains in a dynein dimer walk processively along the microtubule is unusual.
Epigenetic modulation of the miR-200 family is associated with transition to a breast cancer stem cell-like state
Authors: Lim YatYuen , Wright Josephine A. , Attema Joanne L. , Gregory Philip A. , Bert Andrew G. , Smith Eric , Thomas Daniel , Drew Paul A. , Khew-Goodall Yeesim , Goodall Gregory J.
Published: March 2013

The miR-200 family is a key regulator of EMT, however its role in controlling the transition between cancer stem cell-like and non-stem cell-like phenotypes is not well understood. We utilized immortalized human mammary epithelial cells (HMLE) to investigate the regulation of the miR-200 family during their conversion to a stem-like phenotype. HMLE cells were found to be capable of spontaneous conversion from a non-stem to a stem-like phenotype and this conversion was accompanied by the loss of miR-200 expression. Stem-like cell fractions isolated from metastatic breast cancers also displayed loss of miR-200 indicating similar molecular changes may occur during breast cancer progression. The phenotypic change observed in HMLE cells was directly controlled by miR-200 as restoration of its expression decreased stem-like properties while promoting a transition to an epithelial phenotype. Investigation of the mechanisms controlling miR-200 expression revealed both DNA methylation and histone modifications were significantly altered in the stem-like and non-stem phenotypes. In particular, in the stem-like phenotype, the miR-200b-200a-429 cluster was silenced primarily through polycomb group-mediated histone modifications whereas the miR-200c-141 cluster was repressed by DNA methylation. These results indicate that the miR-200 family plays a critical role in the transition between stem-like and non-stem phenotypes and that distinct epigenetic-based mechanisms regulate each miR-200 gene in this process. Therapy targeted against miR-200 family members and epigenetic modifications may therefore be applicable to breast cancer.
RNF168 forms a functional complex with RAD6 during the DNA damage response
Authors: Liu Chao , Wang Degui , Wu Jiaxue , Keller Jennifer , Ma Teng , Yu Xiaochun
Published: March 2013

Protein ubiquitination plays an important role in initiating the DNA damage response. Following DNA damage, E2 ubiquitin conjugating enzymes are crucial for catalyzing substrate ubiquitination that recruits downstream DNA repair factors to DNA lesions. To identify novel E2 conjugating enzymes important for initiating the DNA-damage-induced ubiquitination cascade, we screened most of the known E2 enzymes and found that RAD6A and RAD6B function together with RNF168 in the ionizing radiation (IR)-induced DNA damage response. Similarly to RNF168-deficient cells, RAD6A- or RAD6B-deficient cells exhibit a reduction in DNA-damage-induced protein ubiquitination. Correspondingly, DNA-damage-induced foci formation of DNA damage repair proteins, such as BRCA1 and 53BP1, is impaired in the absence of RAD6A or RAD6B. Moreover, the RNF168–RAD6 complex targeted histone H1.2 for ubiquitination in vitro and regulated DNA-damage-induced histone H1.2 ubiquitination in vivo. Collectively, these data demonstrate that RNF168, in complex with RAD6A or RAD6B, is activated in the DNA-damage-induced protein ubiquitination cascade.
Quaking and PTB control overlapping splicing regulatory networks during muscle cell differentiation
Authors: Hall Megan P. , Nagel Roland J. , Fagg W. Samuel , Shiue Lily , Cline Melissa S. , Perriman Rhonda J. , Donohue John Paul , Ares Manuel
Published: March 2013

Alternative splicing contributes to muscle development, but a complete set of muscle-splicing factors and their combinatorial interactions are unknown. Previous work identified ACUAA (“STAR” motif) as an enriched intron sequence near muscle-specific alternative exons such as Capzb exon 9. Mass spectrometry of myoblast proteins selected by the Capzb exon 9 intron via RNA affinity chromatography identifies Quaking (QK), a protein known to regulate mRNA function through ACUAA motifs in 3′ UTRs. We find that QK promotes inclusion of Capzb exon 9 in opposition to repression by polypyrimidine tract-binding protein (PTB). QK depletion alters inclusion of 406 cassette exons whose adjacent intron sequences are also enriched in ACUAA motifs. During differentiation of myoblasts to myotubes, QK levels increase two- to threefold, suggesting a mechanism for QK-responsive exon regulation. Combined analysis of the PTB- and QK-splicing regulatory networks during myogenesis suggests that 39% of regulated exons are under the control of one or both of these splicing factors. This work provides the first evidence that QK is a global regulator of splicing during muscle development in vertebrates and shows how overlapping splicing regulatory networks contribute to gene expression programs during differentiation.
Electrochemical reduction of U(VI) in H2SO4at gold nanoporous film electrode
Authors: Sharma Manoj K. , Aggarwal Suresh K.
Published: March 2013

Gold nanoporous film (AuNPF) was grown on gold substrate by electrochemical oxidation of the gold electrode at 5 V for 180 s in phosphate buffer (pH 7.4) followed by reduction of the oxidized gold with ascorbic acid solution. Atomic force microscopy (AFM) showed the porous nature of the prepared film. In cyclic voltammetric (CV) studies, anodic shift of 141 mV in the cathodic peak potential for the reduction of UO22+in 0.5 M H2SO4was observed at the AuNPF electrode, showing evidence of its enhanced electrochemical activity as compared to that of the bare Au electrode. The charge transfer studies done using electrochemical impedance spectroscopy indicated similar rates of the heterogeneous electron-transfer kinetics at the bare Au and the AuNPF electrodes. The Cottrell plots obtained from the chronoamperometric experiments showed the Cottrell linearity at the bare Au electrode. In contrast, the Cottrell plot of the AuNPF electrode showed deviation from the linearity at longer times and this is characteristic of the thin-layer diffusion coupled with the electron transfer. Therefore, the observed anodic shift at the AuNPF electrode for the reduction of UO22+was attributed to the contribution from thin-layer diffusion within the gold nanoporous film.