bluuebunny/crossref_metadata_2025 huggingface dataset:
Citigroup and Judicial Immunity in ERISA: An Emerging Trend?
Authors: Rifkin Mark C. , Guiney Matthew M.
Published: May 2010

On August 31, 2009, Judge Stein of the Southern District of New York granted defendant Citigroup’s motion to dismiss a complaint for breach of fiduciary duty filed by participants in Citigroup’s 401(k) plans. The action sought to recover plan losses suffered as a result of Citigroup stock’s staggering losses. Judge Stein dismissed the action after concluding that the plans’ trustees were “immune from judicial inquiry” in connection with the plans’ investments in Citigroup stock. Judge Stein’s decision conferring judicial immunity on plan fiduciaries appears contrary to ERISA, departs from relevant precedent and curtails rigorous protections afforded to retirement savings. If upheld, this rule will effectively bar most actions against fiduciaries concerning plan investments in company stock.
OT for IT: Which Information Technology Employees Are Entitled to Overtime Pay?
Authors: Bannon Patrick J.
Published: May 2010

The widespread practice of treating most information technology employees as exempt from overtime pay rests on a shaky legal foundation. In recent years, plaintiffs’ lawyers have forced major employers to pay millions of dollars to various categories of IT employees who claimed that they were legally entitled to overtime pay. Determining which IT employees are truly exempt from the requirement of overtime pay can be challenging, but a careful analysis of the law allows some tentative conclusions to be drawn. Employers of IT employees would be well advised to assess their overtime exposure and consider options for reducing it.
Unemployment Insurance in the 21st Century
Authors: Kilgour John G.
Published: May 2010

The federal—state employer-funded unemployment insurance system of the United States is about 75 years old. It worked fairly well in the 20th century, with occasional help from Washington during spells of high unemployment. The current recession that began in 2008 is testing the system severely. From an employment perspective, it is the worse economic contraction since the Great Depression of the 1930s. In addition to the permanent Extended Benefit program enacted in 1970, which may be triggered on a state-by-state basis, there have been several other extensions of fully federally funded benefits. The Emergency Unemployment Compensation program of 2008 now contains four tiers and has been extended several times. It is possible that some unemployment compensation recipients may now be entitled to 99 weeks of benefits, all but the first 26 paid for by the federal general fund. This article examines the various elements of unemployment insurance with particular attention to the benefit extensions and related matters associated with the current recession. It then analyses the longer run implications of this development.
Moving Criminal Justice Organizations Toward Adoption of Evidence-Based Practice via Advanced Workshop Training in Motivational Interviewing: A Research Note
Authors: Hartzler Bryan , Espinosa Erin M.
Published: May 2010

The National Institute of Corrections urges use of motivational interviewing (MI) techniques by its workforce, and it is incumbent on criminal justice organizations to find effective methods of personnel training in this evidence-based practice. The current study evaluates impact of a 2-day, advanced MI workshop on personnel skills. Utilizing a validated skill instrument, four cohorts of juvenile justice personnel (aggregate N = 87) completed skill assessments at the outset and conclusion of an advanced MI workshop. Results indicated robust and reliable skill improvements across cohorts and skill domains, with nearly 80% of trainees attaining a proficiency criterion upon leaving the workshop. Furthermore, individual personnel with lesser reported education evidenced both lesser preworkshop skill and greater skill improvement such that postworkshop skills approximated more educated peers. Study findings reinforced the value of the professional training workshop as a practical and effective means of preparing personnel for monitored implementation of MI.
Role of midkine in cadmium-induced liver, heart and kidney damage
Authors: Yazihan Nuray , Mehtap Kacar Kocak  , Akcil Ethem , Erdem Onur , Sayal Ahmet
Published: May 2010

Accumulation of the widespread environmental toxin cadmium (Cd) in tissues results in toxicity. Cd, which can induce a broad spectrum of biological effects, is a toxic substance and is associated with inflammation and apoptosis. Midkine (MK) has fibrinolytic, antiapoptotic, transforming, angiogenetic and chemotactic activities. After Cd toxicity, we found increased MK expression in liver cells in an in vitro cell culture model. The aim of this study was to determine the possibility of relationship between tissue MK expression levels, tumor necrosis factor α(TNF-α) levels and apoptosis in a chronic Cd toxicity model in rats. Male Wistar rats were exposed to Cd at the dose of 15 parts per million (ppm) for 8 weeks. MK levels were measured in kidney, heart and liver tissue by enzyme-linked-immunosorbent assay (ELISA). MK messenger RNA (mRNA) expression was evaluated by RT-PCR. Tissue apoptosis level was evaluated with tissue caspase-3 activity levels. Accumulation of Cd in liver is higher than the kidney and heart. Cd-treated rats had significantly higher tissue TNF-α and caspase-3 levels when compared with the control rats (p < 0.001). MK mRNA and protein levels were also significantly upregulated in the Cd-treated group (p < 0.05, p < 0.001, respectively). When compared with apoptosis in tissues, it was more prominent in the liver than kidney and heart. MK level is found increased 3, 1.7 and 1.3× folds in liver, kidney and heart, respectively. Our results showed that chronic Cd administration induces inflammation and apoptosis in rat liver, kidney and heart. MK involved in damage mechanisms of Cd-induced tissues. Further studies will show the underlying mechanism of increased MK expression in Cd toxicity.
Brevetoxin 2 alters expression of apoptotic, DNA damage, and cytokine genes in Jurkat cells
Authors: Murrell Rachel N , Gibson James E
Published: May 2010

Brevetoxins are potent neurotoxins that exert their toxicity through activation of voltage-gated sodium channels. Exposure to brevetoxins cause severe respiratory inflammation in marine mammals and humans. Brevetoxin activation of voltage-gated sodium channels on immune cells can lead to several biological responses including cell proliferation, gene transcription, cytokine production and even apoptosis. Jurkat E6-1 T cells were treated with brevetoxin 2 for 4 hours at a dose previously shown to induce apoptosis and DNA damage. Changes in gene expression were then assessed via PCR arrays. Gene expression analysis revealed significant change in expression of 17 genes related to apoptosis, 21 genes related to DNA damage signaling, and 19 genes encoding common cytokines. The gene expression data supports the idea that brevetoxins trigger complex reactions involving both inflammation and cell death.
Broken by Design
Authors: Sovacool Benjamin K.
Published: May 2010

This article argues that the corporation is a type of technology, and that as a technology it is failing society. The article begins by exploring the history of the corporation and posits that it is a social technology that is distinct in its function (creating profit for shareholders and generating wealth), process (growth and expansion), structure (adherence to a pyramidal arrangement of managers) and personhood (a permanent legal identity conferred by the law). The article then explores how corporations consolidate wealth and perpetuate inequality, socialise many of their risks to the public sector, commodify human beings and the natural environment, and bestow massive external costs to society at large. Since many of these aspects of corporate activity are invisible, recognising them may offer an important first step towards their reform.
Colonialism and the Development of Electricity
Authors: Rao Srinivasa , Lourdusamy John
Published: May 2010

Drawing from the social constructivist approach to the study of science, technology and society, this article tries to examine the role of legal, economic, political and environmental factors in determining the course of the development of electricity in the Madras Presidency under British colonial rule. Apart from these factors, the impact of historical events such as the two World Wars on the trajectories of electrification is also analysed. The combination of circumstances that influenced the development of electricity in a colonised territory was quite peculiar in many ways and significantly shaped its ultimate character.
Measuring Research and Development in Developing Countries
Authors: Gaillard Jacques
Published: May 2010

This article seeks to present the main characteristics of Research and Development (R&D) in developing countries using mainly available R&D statistics and to draw some implications for the Frascati Manual methodologies and its application. The main characteristics presented include trends and concentrations, relative share of Highly Qualified Skills (HQS) abroad, R&D expenditures, impact factor and the relative importance of international collaboration. R&D statistics in developing countries are still scarce, particularly in Africa. Furthermore, they may not fully explain the characteristics of R&D in developing countries, for example, the dynamics of R&D systems, R&D practices, informal behaviours and contributions, just to mention a few. It is, therefore, argued that beyond indicators, there is a need for complementary surveys to derive, inter alia, descriptors and narratives. In the concluding part, the particular characteristics of R&D in developing countries and the resulting consequences for R&D measurement are discussed, focusing on implications and recommendations, in view of a possible addition and/or future revision of the Frascati Manual.
Piezoaeroelastic Modeling and Analysis of a Generator Wing with Continuous and Segmented Electrodes
Authors: De Marqui Carlos , Erturk Alper , Inman Daniel J.
Published: May 2010

Unmanned air vehicles (UAVs) and micro air vehicles (MAVs) constitute unique application platforms for vibration-based energy harvesting. Generating usable electrical energy during their mission has the important practical value of providing an additional energy source to run small electronic components. Electrical energy can be harvested from aeroelastic vibrations of lifting surfaces of UAVs and MAVs as they tend to have relatively flexible wings compared to their larger counterparts. In this work, an electromechanically coupled finite element model is combined with an unsteady aerodynamic model to develop a piezoaeroelastic model for airflow excitation of cantilevered plates representing wing-like structures. The electrical power output and the displacement of the wing tip are investigated for several airflow speeds and two different electrode configurations (continuous and segmented). Cancelation of electrical output occurs for typical coupled bending-torsion aeroelastic modes of a cantilevered generator wing when continuous electrodes are used. Torsional motions of the coupled modes become relatively significant when segmented electrodes are used, improving the broadband performance and altering the flutter speed. Although the focus is placed on the electrical power that can be harvested for a given airflow speed, shunt damping effect of piezoelectric power generation is also investigated for both electrode configurations.
Beyond Evidence-Based Practice: Nine Ideal Features of a Mental Health Intervention
Authors: Bond Gary R. , Drake Robert E. , Becker Deborah R.
Published: May 2010

Objectives: Recognizing the limitations of conventional frameworks for identifying evidence-based interventions, we sought to develop a comprehensive set of criteria that would have practical and policy relevance. Methods: We identify nine ideal attributes of a mental health practice (well defined, reflecting client goals, consistent with societal goals, effective, minimum side effects, positive long-term outcomes, reasonable costs, easy to implement, and adaptable to diverse communities and client subgroups). Using a case study approach, we applied these criteria to the Individual Placement and Support (IPS) model of supported employment. Findings: IPS generally satisfies all nine criteria, though the evidence is more limited in some areas. Conclusions: This framework provides a template that could be used to evaluate other social work interventions.
Renata Adler Memorial Research Center for Child Welfare and Protection, Tel-Aviv University
Authors: Ronen Tammie
Published: May 2010

The Renata Adler Memorial Research Center for Child Welfare and Protection operates within the Bob Shapell School of Social Work at Tel-Aviv University in Israel. The main aims of this research center are to facilitate study and knowledge about the welfare of children experiencing abuse or neglect or children at risk and to link such knowledge to possible trainings and applications. In conjunction with its development of new innovative studies, the center is meeting the urgent social and educational challenges of the new millennium by opening a new graduate program to train social workers in conducting direct, evidence-based interventions with children. This article describes the aims, functions, activities, and future plans of the center against the backdrop of Israeli children’s social welfare needs, the social work profession, and empirical, clinical, and practice trends.
Ethnic/Racial Differences in the Prevalence of Injurious Spanking and Other Child Physical Abuse in a National Survey of Adolescents
Authors: Oscea Hawkins Alesia , Kmett Danielson Carla , de Arellano Michael A. , Hanson Rochelle F. , Ruggiero Kenneth J. , Smith Daniel W. , Saunders Benjamin E. , Kilpatrick Dean G.
Published: May 2010

Limited research has examined whether similar patterns in injurious spanking and other forms of child physical abuse (CPA) exist across specific ethnic/racial groups. The authors examined and compared differences in the lifetime prevalence of injurious spanking and CPA in two national samples of adolescents across ethnic/racial groups and over time. Participants were 4,023 youth (12—17 years) and 3,614 youth (12—17 years) who participated in the 1995 National Survey of Adolescents (NSA) and 2005 National Survey of Adolescents—Replication (NSA-R), respectively. Adolescents, who were identified through random digit dial procedures, completed a telephone interview assessment. Results indicated significant ethnic/racial variation across groups in reports of injurious spanking in the NSA and the NSA-R samples; however, significant differences were not observed within groups between the two samples over time. Ethnic/racial differences also were found between groups in reports of CPA in the NSA-R sample. Limitations and future directions of this research are discussed.
Local News Outlets and Political Participation
Authors: Filla Jackie , Johnson Martin
Published: May 2010

We investigate how access to local government information affects turnout in municipal elections. We hypothesize that the availability of news focused on local public affairs in an individual’s municipality affects her political participation.We anticipate that turnout will be depressed by restricted access to local government news. We test this expectation using survey data from the Los Angeles (California) Designated Market Area (DMA) collected by the Public Policy Institute of California, and the availability of weekly and daily newspapers in municipalities surrounding Los Angeles. We find that absent local news, voters are less likely to turnout. We examine reasons for this and discuss future research to investigate the influence of local news on voting.
High-performance Computing to Simulate Large-scale Industrial Flows in Multistage Compressors
Authors: Gourdain Nicolas , Montagnac Marc , Wlassow Fabien , Gazaix Michel
Published: May 2010

The aim of this study is to propose a computing method to obtain a detailed simulation of the unsteady flow that develops in multistage turbomachines. The three-dimensional unsteady Reynolds-averaged Navier—Stokes equations are solved using a structured multiblock decomposition method. Although this kind of flow solver is very popular in the turbomachine community nowadays, the complex block connectivities used in meshes of industrial configurations can be penalizing for parallel computing. The computing strategy implemented in a modern flow solver is investigated in this paper, with a particular interest in mesh partitioning, communications and load balancing. Advantages and drawbacks of different computing platforms are then discussed, ranging from vector supercomputers to massively scalar platforms. Comparisons are performed regarding criteria such as the elapsed time and the electrical power consumption. The results show that the use of a large number of computing cores (>128) is heavily penalized by communications and load balancing errors, whereas computing performance with a moderate number of computing cores (<128) is mainly driven by the peak power of the architecture. To help users estimate a priori the parallel performance of a task, a tool based on an extension of Amdahl’s law is proposed, showing satisfying results when compared with observations. Finally, an unsteady flow simulation is performed in a complete three-stage compressor at the design operating point. While still far beyond industrial resources, this numerical flow simulation shows that potential breakthroughs in the design of compression systems can be expected.
Adiponectin and Polycystic Ovary Syndrome
Authors: Groth Susan W.
Published: May 2010

Introduction. Polycystic ovary syndrome (PCOS) has a prevalence of 5—8% in women of reproductive age. Women with PCOS have an increased risk of metabolic syndrome and associated comorbidities. Adiponectin is a circulating protein produced by adipocytes. Circulating levels of adiponectin are inversely related to adipocyte mass. Low levels occur with insulin resistance, type 2 diabetes, metabolic syndrome, and obesity-related cardiovascular disease. This article reviews the literature on the link between adiponectin and PCOS and the potential use of adiponectin as a biomarker for PCOS. Method. Data-based studies on adiponectin and PCOS and adiponectin measurement were identified through the Medline (1950—2009) and ISI Web of Knowledge (1973—2009) databases. Results. Fifteen studies related to adiponectin and PCOS met inclusion criteria and were included in this review. These studies present evidence that adiponectin is linked to insulin resistance, insulin sensitivity, body mass index (BMI), and adiposity. In women with PCOS, lower levels, as opposed to higher levels, of adiponectin occur in the absence of adiposity. Conclusion. The relationships between adiponectin and insulin resistance and sensitivity, metabolic syndrome, and BMI in women with PCOS suggest that adiponectin potentially could serve as a marker for disease risk and provide opportunity for earlier intervention if knowledge is successfully translated from laboratory to clinical practice. However, further study of the relationship between adiponectin and PCOS is required before there can be direct application to clinical practice.
Culture as the Co-evolution of Psychic and Social Systems: New Perspectives on the Person—Environment Relationship
Authors: Thommen Beat , Wettstein Alexander
Published: May 2010

In this article we contribute a new theoretical perspective to the analysis of the relationship between individual and culture, and the person and the environment. Many hotly debated issues in cultural psychology, such as reification, the discourse of personality traits, and models of part—whole hierarchies are productively addressed. Taking a systems-theoretical approach following Niklas Luhmann and others, we distinguish three different types of system and their operational processes (biotic, psychic and social) and suggest that the person—environment relationship should be conceptualized as a process of co-evolution of psychic and social systems. We discuss the critical role of communication in this process and its implications for the concept of culture. Our own research on classroom disruptions and problem behavior in educational settings provides illustrative examples for the kinds of methodological considerations generally relevant to a systems-theoretical approach in empirical research.
Commentary: Environment, Behaviour and Communication: The Definitive Answer or the Continuation of a Crisis?
Authors: Maslov Kirill
Published: May 2010

The attempt to create general theory in social sciences is not new. Reductionism is one of the main problems in this process. Here I analyze the relationship between human, environment, and culture, based on Luhmann’s systems theory and its implications for modern psychology as discussed in Thommen and Wettstein’s (2010) critique of the field. Distinguishing three types of system (biotic, psychic, and social) that function autonomously is not sufficient—what is needed is to clarify on what level any particular analysis should be done. The problem of reconstruction of the past is considered from the point of view that ‘the past’ does not exist as an objective material category and that the only way to perceive it is through sign-based reconstructions of events that have taken place.
Sympathy, Compassion, and Empathy in English and Russian: A Linguistic and Cultural Analysis
Authors: Gladkova Anna
Published: May 2010

In this corpus-based study I contribute to the description and analysis of linguistic and cultural variation in the conceptualization of sympathy , compassion, and empathy. On the basis of a contrastive semantic analysis of sympathy, compassion, and empathy in English and their Russian translational equivalents, sočuvstvie , sostradanie, and sopereživanie, I demonstrate significant differences in the conceptualization of these words, which I explain by reference to the prevalence of different models of social interaction in Anglo and Russian cultures, as well as different cultural attitudes towards emotional expression. As a methodology I apply the Natural Semantic Metalanguage (NSM), which is based on empirically established lexical and grammatical universals, and argue that it is a powerful tool in contrastive studies.
Integrative Tumor Board: A Case Report and Discussion From East-West Cancer Center
Authors: Park Hyo-Min , Kim Seo-Yeon , Jung In-Chul , Lee Yeon-Weol , Cho Chong-Kwan , Yoo Hwa-Seung
Published: May 2010

Aim. To introduce the application of wheel balance cancer therapy (WBCT) in cancer treatment through an intensive study of a representative patient. Method. A 59-year-old, female patient who was a secondhand smoker and who carried no significant medical and family history was diagnosed with T1N0M1 (stage 4) lung adenocarcinoma. Immunohistochemistry was positive for thyroid transcription factor-1, CK7, cyclin D1, p53, and Ki-67 on both lung biopsy specimens. An open lobectomy with mediastinal nodal dissection followed. The patient was transferred to East-West Cancer Center (EWCC) suffering from exertional dyspnea (NYHA [New York Heart Association] grade 2) with thoracic pain and pain in both upper limbs because of the decreased ventilatory capacity and reduced exercise capacity after a pulmonary resection. She also complained of emotional stress. EWCC provided WBCT, a multimodality alternative protocol based on the theory of traditional oriental medicine. Physicians regularly monitored whether metastasis or recurrence existed through blood and radiation tests. Observations and dialogues with the patient were used to record the changes in symptoms such as thoracic pain, dyspnea, anxiety, and fear. Results . Treatments at EWCC led to a disease-free survival of 28 months without adjuvant chemotherapy. Neither metastasis nor recurrence occurred during this period. Exertional dyspnea recovered to NYHA grade 1. Other physical and psychological symptoms were alleviated. Conclusion. This report suggests that WBCT may have the potential for extending life expectancy, controlling symptoms, and improving quality of life in cancer patients.
The anatomy of the dorsal cutaneous branch of the ulnar nerve
Authors: Puna R. , Poon P.
Published: May 2010

We investigated the anatomy of the dorsal cutaneous branch of the ulnar nerve in 32 upper limbs in cadavers. The dorsal cutaneous branch of the ulnar nerve originated on average 5.1 cm proximal to the ulnar styloid process and 1.9 cm palmar and radial to the subcutaneous border of the ulna. It crossed the subcutaneous border 0.2 cm proximal to the ulnar styloid process. In all cases it displaced further away in full pronation. We recommend cautious dissection when approaching within 2.5 cm of the ulnar styloid process. We also recommend making the initial incision in full pronation and just along the dorsal aspect of the subcutaneous border of the ulna.
Ten questions on Kienböck’s disease of the lunate
Authors: Dias Joseph J. , Lunn Peter
Published: May 2010

Kienböck’s disease ( Kienböck, 1910 ) affects the lunate bone in patients who are usually in their twenties, and present with pain, swelling and stiffness of the wrist. Almost every treatment currently suggested for Kienböck’s disease is based on an hypothesis rather than proven knowledge. We treat it in the hope that what we are doing is logical and likely to benefit our patients. There are many questions that we should be prepared to answer and we list some we must address. A century after Kienböck’s description of this disorder a number cannot yet be answered adequately. This paper explores areas of uncertainty.
Functional analysis of the BMP9 response of ALK1 mutants from HHT2 patients: a diagnostic tool for novel ACVRL1 mutations
Authors: Ricard Nicolas , Bidart Marie , Mallet Christine , Lesca Gaetan , Giraud Sophie , Prudent Renaud , Feige Jean-Jacques , Bailly Sabine
Published: May 2010

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetically inheritable vascular dysplasia caused by mutations in genes encoding receptors of the transforming growth factor-β (TGF-β) family: ENG, encoding endoglin (HHT1), and ACVRL1, encoding activin receptor-like kinase-1 (ALK1; HHT2). Our recent discovery of bone morphogenetic protein 9 (BMP9) as the specific ligand for ALK1 allowed us to reevaluate the functional significance of ACVRL1 mutations. We generated 19 ALK1 mutants reproducing HHT2 mutations (4 were novel mutations) found throughout the protein. We show that all ALK1 mutant proteins were expressed by transfected cells; most of them were present at the cell surface and retained their ability to bind BMP9 (except for the extracellular mutants). However, most were defective in BMP9 signaling. None of the ALK1 mutants had a dominant negative effect on wild-type ALK1 activity. These data demonstrate that mutations of ACVRL1 fit with a functional haploinsufficiency model affecting BMP9 signaling. Our study also identified 4 ACVRL1 mutations (D179A, R386C, R454W, and A482V) that did not alter the BMP9 responses that are polymorphisms and 2 novel mutations that are pathogenic (L381P and I485F). This demonstrates that the analysis of BMP9 responses can be used as a diagnostic tool by geneticists confronted with novel or conflicting ACVRL1 mutations.
Characterization of the GXXXG motif in the first transmembrane segment of Japanese encephalitis virus precursor membrane (prM) protein
Authors: Lin Ying-Ju , Peng Jia-Guan , Wu Suh-Chin
Published: May 2010

The interaction between prM and E proteins in flavivirus-infected cells is a major driving force for the assembly of flavivirus particles. We used site-directed mutagenesis to study the potential role of the transmembrane domains of the prM proteins of Japanese encephalitis virus (JEV) in prM-E heterodimerization as well as subviral particle formation. Alanine insertion scanning mutagenesis within the GXXXG motif in the first transmembrane segment of JEV prM protein affected the prM-E heterodimerization; its specificity was confirmed by replacing the two glycines of the GXXXG motif with alanine, leucine and valine. The GXXXG motif was found to be conserved in the JEV serocomplex viruses but not other flavivirus groups. These mutants with alanine inserted in the two prM transmembrane segments all impaired subviral particle formation in cell cultures. The prM transmembrane domains of JEV may play importation roles in prM-E heterodimerization and viral particle assembly.
Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70 kDa U1-snRNP autoantigen
Authors: Tzang Bor-Show , Chen Der-Yuan , Tsai Chun-Chou , Chiang Szu-Yi , Lin Tsung-Ming , Hsu Tsai-Ching
Published: May 2010

Background

Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with a variety of autoimmune disorders. Although we have previously reported that B19 non-structural protein (NS1) induces mitochondrial-dependent apoptosis in COS-7 cells, the precise mechanism of B19-NS1 in developing autoimmunity is still obscure.

Methods

To further examine the effect of B19-NS1 in presence of autoantigens, COS-7 cells were transfected with pEGFP, pEGFP-B19-NS1 and pEGFP-NS1K334E, a mutant form of B19-NS1, and detected the expressions of autoantigens by various autoantibodies against Sm, U1 small nuclear ribonucleoprotein (U1-snRNP), SSA/Ro, SSB/La, Scl-70, Jo-1, Ku, and centromere protein (CENP) A/B by using Immunoblotting.

Results

Significantly increased apoptosis was detected in COS-7 cells transfected with pEGFP-B19-NS1 compared to those transfected with pEGFP. Meanwhile, the apoptotic 70 kDa U1-snRNP protein in COS-7 cells transfected with pEGFP-B19-NS1 is cleaved by caspase-3 and converted into a specific 40 kDa product, which were recognized by anti-U1-snRNP autoantibody. In contrast, significantly decreased apoptosis and cleaved 40 kDa product were observed in COS-7 cells transfected with pEGFP-NS1K334E compared to those transfected with pEGFP-B19-NS1.

Conclusions

These findings suggested crucial association of B19-NS1 in development of autoimmunity by inducing apoptosis and specific cleavage of 70 kDa U1-snRNP.
APIS: accurate prediction of hot spots in protein interfaces by combining protrusion index with solvent accessibility
Authors: Xia Jun-Feng , Zhao Xing-Ming , Song Jiangning , Huang De-Shuang
Published: May 2010

Background

It is well known that most of the binding free energy of protein interaction is contributed by a few key hot spot residues. These residues are crucial for understanding the function of proteins and studying their interactions. Experimental hot spots detection methods such as alanine scanning mutagenesis are not applicable on a large scale since they are time consuming and expensive. Therefore, reliable and efficient computational methods for identifying hot spots are greatly desired and urgently required.

Results

In this work, we introduce an efficient approach that uses support vector machine (SVM) to predict hot spot residues in protein interfaces. We systematically investigate a wide variety of 62 features from a combination of protein sequence and structure information. Then, to remove redundant and irrelevant features and improve the prediction performance, feature selection is employed using the F-score method. Based on the selected features, nine individual-feature based predictors are developed to identify hot spots using SVMs. Furthermore, a new ensemble classifier, namely APIS (A combined model based on Protrusion Index and Solvent accessibility), is developed to further improve the prediction accuracy. The results on two benchmark datasets, ASEdb and BID, show that this proposed method yields significantly better prediction accuracy than those previously published in the literature. In addition, we also demonstrate the predictive power of our proposed method by modelling two protein complexes: the calmodulin/myosin light chain kinase complex and the heat shock locus gene products U and V complex, which indicate that our method can identify more hot spots in these two complexes compared with other state-of-the-art methods.

Conclusion

We have developed an accurate prediction model for hot spot residues, given the structure of a protein complex. A major contribution of this study is to propose several new features based on the protrusion index of amino acid residues, which has been shown to significantly improve the prediction performance of hot spots. Moreover, we identify a compact and useful feature subset that has an important implication for identifying hot spot residues. Our results indicate that these features are more effective than the conventional evolutionary conservation, pairwise residue potentials and other traditional features considered previously, and that the combination of our and traditional features may support the creation of a discriminative feature set for efficient prediction of hot spot residues. The data and source code are available on web site http://home.ustc.edu.cn/~jfxia/hotspot.html.
Prediction of breast cancer prognosis using gene set statistics provides signature stability and biological context
Authors: Abraham Gad , Kowalczyk Adam , Loi Sherene , Haviv Izhak , Zobel Justin
Published: May 2010

Background

Different microarray studies have compiled gene lists for predicting outcomes of a range of treatments and diseases. These have produced gene lists that have little overlap, indicating that the results from any one study are unstable. It has been suggested that the underlying pathways are essentially identical, and that the expression of gene sets, rather than that of individual genes, may be more informative with respect to prognosis and understanding of the underlying biological process.

Results

We sought to examine the stability of prognostic signatures based on gene sets rather than individual genes. We classified breast cancer cases from five microarray studies according to the risk of metastasis, using features derived from predefined gene sets. The expression levels of genes in the sets are aggregated, using what we call a set statistic. The resulting prognostic gene sets were as predictive as the lists of individual genes, but displayed more consistent rankings via bootstrap replications within datasets, produced more stable classifiers across different datasets, and are potentially more interpretable in the biological context since they examine gene expression in the context of their neighbouring genes in the pathway. In addition, we performed this analysis in each breast cancer molecular subtype, based on ER/HER2 status. The prognostic gene sets found in each subtype were consistent with the biology based on previous analysis of individual genes.

Conclusions

To date, most analyses of gene expression data have focused at the level of the individual genes. We show that a complementary approach of examining the data using predefined gene sets can reduce the noise and could provide increased insight into the underlying biological pathways.
Signals of recent spatial expansions in the grey mouse lemur (Microcebus murinus)
Authors: Schneider Nicole , Chikhi Lounès , Currat Mathias , Radespiel Ute
Published: May 2010

Background

Pleistocene events have shaped the phylogeography of many taxa worldwide. Their genetic signatures in tropical species have been much less explored than in those living in temperate regions. We analysed the genetic structure of a Malagasy primate species, a mouse lemur with a wide distribution (M. murinus), in order to investigate such phylogeographic processes on a large tropical island. We also evaluated the effects of anthropogenic pressures (fragmentation/deforestation) and natural features (geographic distance, rivers) on genetic structure in order to complement our understanding of past and present processes of genetic differentiation.

Results

The analysis of the mitochondrial D-loop sequences of 195 samples from 15 study sites (10 from a continuous forest and five from isolated forest fragments) from two adjacent Inter-River-Systems (IRSs) revealed that forest fragmentation and the river restrict gene flow, thereby leading to an increased genetic differentiation between populations beyond the effect of isolation-by-distance. Demographic simulations detected signals of two successive spatial expansions that could be preliminarily dated to the late Pleistocene and early Holocene. The haplotype network revealed geographic structure and showed deep molecular divergences within and between the IRSs that would be congruent with a two-step colonization scenario.

Conclusions

This study supports the hypothesis of a relatively recent spatial expansion of the grey mouse lemur in northwestern Madagascar, which may also explain why this taxon, in contrast to its congeners, has not yet undergone allopatric speciation in the studied area and possibly across its presently wide range.
Evolution of AANAT: expansion of the gene family in the cephalochordate amphioxus
Authors: Pavlicek Jiri , Sauzet Sandrine , Besseau Laurence , Coon Steven L , Weller Joan L , Boeuf Gilles , Gaildrat Pascaline , Omelchenko Marina V , Koonin Eugene V , Falcón Jack , Klein David C
Published: May 2010

Background

The arylalkylamine N-acetyltransferase (AANAT) family is divided into structurally distinct vertebrate and non-vertebrate groups. Expression of vertebrate AANATs is limited primarily to the pineal gland and retina, where it plays a role in controlling the circadian rhythm in melatonin synthesis. Based on the role melatonin plays in biological timing, AANAT has been given the moniker "the Timezyme". Non-vertebrate AANATs, which occur in fungi and protists, are thought to play a role in detoxification and are not known to be associated with a specific tissue.

Results

We have found that the amphioxus genome contains seven AANATs, all having non-vertebrate type features. This and the absence of AANATs from the genomes of Hemichordates and Urochordates support the view that a major transition in the evolution of the AANATs may have occurred at the onset of vertebrate evolution. Analysis of the expression pattern of the two most structurally divergent AANATs in Branchiostoma lanceolatum (bl) revealed that they are expressed early in development and also in the adult at low levels throughout the body, possibly associated with the neural tube. Expression is clearly not exclusively associated with the proposed analogs of the pineal gland and retina. blAANAT activity is influenced by environmental lighting, but light/dark differences do not persist under constant light or constant dark conditions, indicating they are not circadian in nature. bfAANATα and bfAANATδ' have unusually alkaline (> 9.0) optimal pH, more than two pH units higher than that of vertebrate AANATs.

Conclusions

The substrate selectivity profiles of bfAANATα and δ' are relatively broad, including alkylamines, arylalkylamines and diamines, in contrast to vertebrate forms, which selectively acetylate serotonin and other arylalkylamines. Based on these features, it appears that amphioxus AANATs could play several roles, including detoxification and biogenic amine inactivation. The presence of seven AANATs in amphioxus genome supports the view that arylalkylamine and polyamine acetylation is important to the biology of this organism and that these genes evolved in response to specific pressures related to requirements for amine acetylation.
Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia
Authors: Samuels Amy L , Peeva Violet K , Papa Rachael A , Firth Marin J , Francis Richard W , Beesley Alex H , Lock Richard B , Kees Ursula R
Published: May 2010

Background

Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL). However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential.

Results

Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation.

Conclusions

We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.
Fine definition of the pedigree haplotypes of closely related rice cultivars by means of genome-wide discovery of single-nucleotide polymorphisms
Authors: Yamamoto Toshio , Nagasaki Hideki , Yonemaru Jun-ichi , Ebana Kaworu , Nakajima Maiko , Shibaya Taeko , Yano Masahiro
Published: May 2010

Background

To create useful gene combinations in crop breeding, it is necessary to clarify the dynamics of the genome composition created by breeding practices. A large quantity of single-nucleotide polymorphism (SNP) data is required to permit discrimination of chromosome segments among modern cultivars, which are genetically related. Here, we used a high-throughput sequencer to conduct whole-genome sequencing of an elite Japanese rice cultivar, Koshihikari, which is closely related to Nipponbare, whose genome sequencing has been completed. Then we designed a high-throughput typing array based on the SNP information by comparison of the two sequences. Finally, we applied this array to analyze historical representative rice cultivars to understand the dynamics of their genome composition.

Results

The total 5.89-Gb sequence for Koshihikari, equivalent to 15.7× the entire rice genome, was mapped using the Pseudomolecules 4.0 database for Nipponbare. The resultant Koshihikari genome sequence corresponded to 80.1% of the Nipponbare sequence and led to the identification of 67 051 SNPs. A high-throughput typing array consisting of 1917 SNP sites distributed throughout the genome was designed to genotype 151 representative Japanese cultivars that have been grown during the past 150 years. We could identify the ancestral origin of the pedigree haplotypes in 60.9% of the Koshihikari genome and 18 consensus haplotype blocks which are inherited from traditional landraces to current improved varieties. Moreover, it was predicted that modern breeding practices have generally decreased genetic diversity

Conclusions

Detection of genome-wide SNPs by both high-throughput sequencer and typing array made it possible to evaluate genomic composition of genetically related rice varieties. With the aid of their pedigree information, we clarified the dynamics of chromosome recombination during the historical rice breeding process. We also found several genomic regions decreasing genetic diversity which might be caused by a recent human selection in rice breeding. The definition of pedigree haplotypes by means of genome-wide SNPs will facilitate next-generation breeding of rice and other crops.
A deep investigation into the adipogenesis mechanism: Profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/β-catenin signaling pathway
Authors: Qin Limei , Chen Yaosheng , Niu Yuna , Chen Weiquan , Wang Qiwei , Xiao Shuqi , Li Anning , Xie Ying , Li Jing , Zhao Xiao , He Zuyong , Mo Delin
Published: May 2010

Background

MicroRNAs (miRNAs) are a large class of tiny non-coding RNAs (~22-24 nt) that regulate diverse biological processes at the posttranscriptional level by controlling mRNA stability or translation. As a molecular switch, the canonical Wnt/β-catenin signaling pathway should be suppressed during the adipogenesis; However, activation of this pathway leads to the inhibition of lipid depots formation. The aim of our studies was to identify miRNAs that might be involved in adipogenesis by modulating WNT signaling pathway. Here we established two types of cell model, activation and repression of WNT signaling, and investigated the expression profile of microRNAs using microarray assay.

Results

The high throughput microarray data revealed 18 miRNAs that might promote adipogenesis by repressing WNT signaling: miR-210, miR-148a, miR-194, miR-322 etc. Meanwhile, we also identified 29 miRNAs that might have negative effect on adipogenesis by activating WNT signaling: miR-344, miR-27 and miR-181 etc. The targets of these miRNAs were also analysed by bioinformatics. To validate the predicted targets and the potential functions of these identified miRNAs, the mimics of miR-210 were transfected into 3T3-L1 cells and enlarged cells with distinct lipid droplets were observed; Meanwhile, transfection with the inhibitor of miR-210 could markedly decrease differentiation-specific factors at the transcription level, which suggested the specific role of miR-210 in promoting adipogenesis. Tcf7l2, the predicted target of miR-210, is a transcription factor triggering the downstream responsive genes of WNT signaling, was blocked at transcription level. Furthermore, the activity of luciferase reporter bearing Tcf7l2 mRNA 3' UTR was decreased after co-transfection with miR-210 in HEK-293FT cells. Last but not least, the protein expression level of β-catenin was increased in the lithium (LiCl) treated 3T3-L1 cells after transfection with miR-210. These findings suggested that miR-210 could promote adipogenesis by repressing WNT signaling through targeting Tcf7l2.

Conclusions

The results suggest the presence of miRNAs in two cell models, providing insights into WNT pathway-specific miRNAs that can be further characterized for their potential roles in adipogenesis. To our knowledge, present study represents the first attempt to unveil the profile of miRNAs involed in adipogenesis by modulating WNT signaling pathway, which contributed to deeper investigation of the mechanism of adipogenesis.