bluuebunny/crossref_metadata_2025 huggingface dataset:
It Takes Two
Authors: Cunningham David E. , Skrede Gleditsch Kristian , Salehyan Idean
Published: May 2009

Theories of conflict emphasize dyadic interaction, yet existing empirical studies of civil war focus largely on state attributes and pay little attention to nonstate antagonists. We recast civil war in a dyadic perspective, and consider how nonstate actor attributes and their relationship to the state influence conflict dynamics. We argue that strong rebels, who pose a military challenge to the government, are likely to lead to short wars and concessions. Conflicts where rebels seem weak can become prolonged if rebels can operate in the periphery so as to defy a government victory yet are not strong enough to extract concessions. Conflicts should be shorter when potential insurgents can rely on alternative political means to violence. We examine these hypotheses in a dyadic analysis of civil war duration and outcomes, using new data on nonstate actors and conflict attributes, finding support for many of our conjectures.
Continuity and Change in Cuba at 50
Authors: Alzugaray Treto Carlos
Published: May 2009

After Fidel Castro's retirement from his main governmental positions, Cuba finds itself at a crossroads. Two main challenges emerge, one economic and one political. The economic one arises from the need to design a productive system that resolves the imbalance between workers' salaries and the actual distribution of basic goods and the imbalance between different sectors of society without destroying the revolution's social achievements. The political one must deal with the creation of a new form of governance and consensus building in the absence of the revolution's founder and leader. The changes to be introduced require the broadening of democracy. These challenges entail a national deliberation process during the Sixth Congress of the Cuban Communist Party that will identify several fundamental issues.
Cuban Internationalism, Che Guevara, and the Survival of Cuba's Socialist Regime
Authors: Harris Richard L.
Published: May 2009

Two of the most important factors that have contributed to the survival of Cuba's socialist regime are its commitment to its socialist ideals and its policies of internationalism. Cuba's socialist regime has provided substantial support for national liberation struggles against imperialism in every region of the world, humanitarian assistance to people in at least 90 countries, and solidarity with progressive governments and a wide array of progressive international movements and organizations around the globe. Cuba's socialist regime, like Che Guevara's ideas and example of socialist internationalism, will survive if the regime continues to support socialist revolutions and to struggle against imperialism. Moreover, Cuba's revolutionary example and its internationalist support for the Bolivarian Revolution in Venezuela will be a fundamental factor in determining the outcome of the current trends toward the radical left in Latin American politics.
Buying Up Nature
Authors: Horton Lynn R.
Published: May 2009

From a range of diverse political perspectives, proponents have presented ecotourism as a market-based activity that will provide income and empowerment to local communities while promoting environmental conservation. The experiences of Costa Rica's Osa Peninsula, where relative isolation has limited the presence of transnational corporate capital, suggest that the impacts of community-based ecotourism expansion are far from certain and are the outcomes of struggles over access to land and natural resources, economic benefits, and representations of the environment. Ecotourism, while potentially offering new economic opportunities to Latin America's poor majority, may also reproduce preexisting patterns of stratification, particularly where state policies have favored larger and foreign ecotourism enterprises. Ecotourism may also engender processes of ideological resistance and reconfiguration that transform existing relationships of nationality, class, and gender.
Affecting Others: Social Appraisal and Emotion Contagion in Everyday Decision Making
Authors: Parkinson Brian , Simons Gwenda
Published: May 2009

In a diary study of interpersonal affect transfer, 41 participants reported on decisions involving other people over 3 weeks. Reported anxiety and excitement were reliably related to the perceived anxiety and excitement of another person who was present during decision making. Risk and importance appraisals partially mediated effects of other's anxiety on own anxiety as predicted by social appraisal theory. However, other's emotion remained a significant independent predictor of own emotion after controlling for appraisals, supporting the additional impact of more direct forms of affect transfer such as emotion contagion. Significant affect-transfer effects remained even after controlling for participants' perceptions of the other's emotion in addition to all measured appraisals, confirming that affect transfer does not require explicit registration of someone else's feelings. This research provides some of the clearest evidence for the operation of both social appraisal and automatic affect transfer in everyday social life.
Reduction-based Control of Three-dimensional Bipedal Walking Robots
Authors: Gregg Robert D. , Spong Mark W.
Published: May 2009

In this paper we develop the concept of reduction-based control, which is founded on a controlled form of geometric reduction known as functional Routhian reduction. We prove a geometric property of general serial-chain robots termed recursive cyclicity, identifying the inherent robot symmetries that we exploit with the Subrobot Theorem. This shows that any serial-chain robot can be decomposed for arbitrarily lower-dimensional analysis and control. We apply this method to construct stable directional three-dimensional walking gaits for a four-degree-of-freedom hipped bipedal robot. The controlled reduction decouples the biped’s sagittal-plane motion from the yaw and lean modes, and on the sagittal subsystem we use passivity-based control to produce known planar limit cycles on flat ground. The unstable yaw and lean modes are separately controlled to 2-periodic orbits through their shaped momenta. We numerically verify the existence of stable 2-periodic straight-walking limit cycles and demonstrate turning capabilities for the controlled biped.
Effect of Processing Factors on Flexural Properties of Cf-HA/PMMA Composites
Authors: Zeng Liping  , Cao Liyun  , Huang Jianfeng  , Guo Shen
Published: May 2009

Short carbon fiber (Cf) reinforced nano-hydroxyapatite (HA)/poly(methyl methacrylate) (PMMA) matrix bio-composites were prepared by an in situ processing and solution co-mixing process. The influence of carbon fiber content, initiator dosage, and nano-HA mass fraction on the flexural properties of the composites were particularly investigated. The flexural strength and modulus were tested by universal testing machine. The flexural fracture surface morphologies were characterized using scanning electron microscope. Results reveal that the as-prepared Cf/HA-PMMA composites have excellent flexural properties. With the increase of carbon fiber content, benzoyl peroxide (BPO) dosage, HA mass fraction and reaction temperature, the flexural strength, and modulus of Cf-HA/PMMA composites first increase to a maximum and then decrease. The flexural strength and flexural modulus will reach the maximum value of 129.56 MPa and 4.47 GPa when carbon fiber mass content, BPO dosage, and HA mass content arrive at 4, 1.6, and 8 wt%, respectively and reaction temperature is 80°C.
Glass Fiber-reinforced Composites based on Epoxy Resin—Maleated Shellac Interacting System
Authors: Patel H.S. , Patel S.J.
Published: May 2009

Shellac, a forest product, was reacted with various proportions of maleic anhydride. The resultant maleated shellac (MS) samples were characterized by acid value. The MS samples were then reacted with commercial epoxy resin i.e., DGEBA (diglycidyl ether of bisphenol-A) according to the acid value of MS samples. The resultant MS—DGEBA systems were monitored on differential scanning calorimetry (DSC). Based on DSC data, the glass fiber-reinforced composites of MS were prepared and the resultant products were characterized by physical and mechanical properties.
Thermal Expansion Process for Manufacturing of Stitched Sandwich Structures
Authors: Zhang Zuoguang  , Hao Jijun  , Sun Zhijie  , Li Min  , Gu Yizuo
Published: May 2009

A thermal expansion process was applied to prepare stitched sandwich structures using the pressure generated by the foam core inside a closed mold. In this way, buckling of stitches was avoided. The mechanical properties of the specimens prepared by thermal expansion process were significantly improved when compared to that of specimens prepared using the hot press. In order to increase the thermal expansion pressure, the foam cores were pre-compressed, and then stitched with the face sheets. The pre-compressed foam cores underwent thermal expansion easily and their thermal expansion pressure increased with increase in pre-compressive ratio.
Self-deployable Space Structure using Partially Flexible CFRP with SMA Wires
Authors: Todoroki Akira , Kumagai Keisuke , Matsuzaki Ryosuke
Published: May 2009

This article deals with a self-deployable composite structure using a partially flexible composite (PFC) with shape memory alloy wires and reveals the fabrication process of the PFC. Two different matrices are used in the PFC: epoxy resin for the normal part, and silicone rubber for the folding line. Since the fibers are continuous, the PFC has the same strength as a normal composite. We investigate carbon fiber breakages during the folding process by considering changes in electrical resistance, and cyclic tests are performed to confirm the availability even after long-term cyclic folding. An SMA wire is embedded in the PFC to keep the folded configuration without loading and self-deployment is achieved using Joule heating. The results confirm that a flexible part of adequate length enables foldable composite structures without causing carbon fiber breakages, while the cyclic folding tests reveal that the PFC is reliable when a long flexible part is used. The embedded SMA wire realizes compactly folded composite panel structures without loading and Joule heating of the SMA wires enables self-deployable composite structures.
Promoting Evidence-based Practice
Authors: Nutley Sandra , Walter Isabel , Davies Huw T. O.
Published: May 2009

This article draws on both a cross-sector literature review of mechanisms to promote evidence-based practice and a specific review of ways of improving research use in social care. At the heart of the article is a discussion of three models of evidence-based practice: the research-based practitioner model, the embedded research model, and the organizational excellence model. The article concludes that the ideas contained within each of these models are likely to be appropriate at different times and for different service settings. There is a need to build on such models to develop a coherent framework for strategies to promote research use.
What Is Implementation Research?
Authors: Bhattacharyya Onil , Reeves Scott , Zwarenstein Merrick
Published: May 2009

Despite the growing knowledge base on evidence-based practices in social work and medicine, there is a large gap between what is known and what is consistently done. Implementation research is the study of methods to promote the uptake of research findings into routine practice. In this article, we describe the rationale for implementation research and outline the concepts and effectiveness of its practices. Despite a large number of systematic reviews of implementation interventions, many of the fundamental questions regarding what approaches should be used in which settings for which problems remain unanswered. We go on to argue that future implementation studies should assess the context of practice and key features of interventions to better inform service quality improvement efforts.
Cultural Exchange and the Implementation of Evidence-Based Practices
Authors: Palinkas Lawrence A. , Aarons Gregory A. , Chorpita Bruce F. , Hoagwood Kimberly , Landsverk John , Weisz John R.
Published: May 2009

Objective: The dynamics of interactions between evidence-based intervention (EBI) developers and trainers and organizations and providers that deliver the EBI was examined in two case studies, a statewide randomized effectiveness trial of an EBI to reduce child neglect and a randomized trial of EBIs for depression, anxiety, and conduct problems in children and adolescents. Methods: Data were collected using ethnographic methods of participant observation and semistructured interviews and analyzed using grounded theory analytic methods. Results: Formal and informal interactions between EBI propagators and end users provide access to resources and exchange of global and local knowledge of service delivery. Productive interactions require accessibility, mutual respect, a shared language, and a willingness to engage in negotiation and compromise to resolve differences in demands imposed by organizational culture, the need for EBI fidelity, and client characteristics. Conclusion: A cultural exchange characterized by information sharing and behavioral change through a process of negotiation and compromise is central to evidence-based practice in youth serving systems of care.
Implementation Practice and Implementation Research
Authors: Brekke John S. , Phillips Elizabeth , Pancake Laura , O Anne , Lewis Jenebah , Duke Jessica
Published: May 2009

The Interventions and Practice Research Infrastructure Program (IPRISP) funding mechanism was introduced by the National Institute of Mental Health (NIMH) to bridge the gap between the worlds of services research and the usual care practice in the community. The goal was to build infrastructure that would provide a platform for research to establish the evidence base for improving mental health care available in diverse communities. This is done by providing support for researchers and community mental health providers to establish working and sustainable partnerships to make evidence-based mental health services available and acceptable for people in need of mental health care. In this article, we (a) present the nature of one IPRISP and its attempt to foster science-to-service and service-to-science interchange; (b) discuss two models of implementation practice for human service agencies, the more common ‘‘external specialist purveyor model’’ and the ‘‘embedded generalist purveyor model’’ that is emerging from our IPRISP experience; and (c) we address our emerging practice approach to two issues that are critical in implementation practice and research: local adaptation of evidence-based interventions, and the use of client outcome data in usual care environments to inform clinical practice decisions.
Communication Channels in General Internal Medicine: A Description of Baseline Patterns for Improved Interprofessional Collaboration
Authors: Conn Lesley Gotlib , Lingard Lorelei , Reeves Scott , Miller Karen-Lee , Russell Ann , Zwarenstein Merrick
Published: May 2009

General internal medicine (GIM) is a communicatively complex specialty because of its diverse patient population and the number and diversity of health care providers working on a medicine ward. Effective interprofessional communication in such information-intensive environments is critical to achieving optimal patient care. Few empirical studies have explored the ways in which health professionals exchange patient information and the implications of their chosen communication forms. In this article, we report on an ethnographic study of health professionals' communication in two GIM wards through the lens of communication genre theory. We categorize and explore communication in GIM into two genre sets—synchronous and asynchronous—and analyze the relationship between them. Our findings reveal an essential relationship between synchronous and asynchronous modes of communication that has implications for the effectiveness of interprofessional collaboration in this and similar health care settings, and is intended to inform efforts to overcome existing interprofessional communication barriers.
Evaluation of the Nutrition Knowledge, Attitudes, and Food Consumption Behaviors of High School Students Before and After Completion of a Nutrition Course
Authors: Watson Lauren Crawford , Kwon Junehee , Nichols David , Rew Martha
Published: May 2009

Adolescents may lower their risk of becoming overweight and lead a healthier lifestyle by improving their nutrition knowledge and attitudes towards nutrition and health. A quasi‐experimental design was used to assess nutrition knowledge, attitudes, and food consumption behaviors of students 14 to 19 years old before and after a nutrition course in a North Texas high school. The intervention group (n = 45) was enrolled in elective family and consumer science courses and received nutrition and health education, whereas the control group (n = 30) received no nutrition education. Identical pre‐ and posttest questionnaires were completed at the beginning and the end of a semester by students in both groups. Descriptive statistics, cross‐tabulation with chi‐square analyses, and independent and paired‐sample t tests were calculated using SPSS. No differences in the dependent variables existed between the two groups before the intervention, but after the intervention, only the intervention group significantly improved in nutrition knowledge, some attitude scores, and milk and breakfast consumption behaviors. The findings of this study indicate that nutrition education may positively influence the knowledge, attitudes, and eating behaviors of high school students.
Real Estate Brokerage, Homebuyer Training, and Homeownership Sustainability for Housing Assistance Programs
Authors: Archer Wayne , Fitterman Stan , Smith Marc T.
Published: May 2009

This study examines a previously overlooked factor in the rate of default on home loans by marginal first‐time homebuyers; namely, the purchase transaction process. In particular, the study examines the potential for the type of initial contact in a homebuyer assistance program to affect the likelihood of default on a subsequent home loan. Using data from 41 state funded local assistance programs in Florida, the study is able to examine the relationship of program default rates to the source of applicant for assistance. Specifically, it examines the explanatory capacity of the percentage of applicants who had a contract to purchase prior to applying for assistance, indicated that the applicant already has engaged with a broker or lender. It finds that the percentage of applicants for assistance who already have engaged with a broker or lender is very significantly and positively relate to the program default rate.
Consumer Perception of Food‐Borne Illness Risks Before and After the 2006 E. Coli Events
Authors: Brady John T. , Li Peace , Brown Deborah
Published: May 2009

Late in 2006 there were two well‐publicized outbreaks of Escherichia coli 0157:H7 in the United States. One is traced back to contaminated spinach and the other is connected to contaminated lettuce. By looking at the relative rankings of food‐borne illness relative to other risks (i.e., war or terrorism, accidents at home, accidents away from home, environmental disaster, natural disaster, and infectious diseases), changes that occurred following the outbreaks are examined. Risks are defined for the project participants as the chance of sudden, unexpected injury, illness, or death. Changes in consumer behavior and attitude are also examined. The ranking of risks associated with food‐borne illness increases significantly following the outbreaks, but behaviors and attitudes do not change significantly. The media play a role in increasing awareness. People who listen to news on TV or on the radio daily have significant changes in their ranking of food‐borne illness risk; however, those that do not listen to media news as often do not have significant differences in their responses. Gender, age, and the presence of children in the home also mattered in determining significant changes in the ranking of food‐borne illnesses.
Generational Theory and Home Economics1: Future Proofing the Profession
Authors: Pendergast Donna
Published: May 2009

Generational theory has much to offer the home economics profession. This article explains sociocultural generational theory, traces the evolution of home economics informed by generational theory, and considers the implications of generational theory as a mechanism to “future proof” the home economics profession. In particular, insights into the unique traits, strengths, and abilities for the key baby boomer, Generation X, and the millennial generation cohorts are investigated. It is argued that the profession must adapt strategically to harness the potentialities of each generation. Several clear imperatives emerge from the application of generational theory to the home economics profession at this moment in time—the need for (a) harnessing and retaining the professional experience of baby boomers, (b) retaining Generation X and facilitating their shift to the leadership of the profession, and (c) attracting and retaining Generation Y. Strategic initiatives to achieve these imperatives are recommended and examples provided.
Self-Reported ADHD and Adjustment in College
Authors: Blase Stacey L. , Gilbert Adrianne N. , Anastopoulos Arthur D. , Costello E. Jane , Hoyle Rick H. , Swartzwelder H. Scott , Rabiner David L.
Published: May 2009

Objective: To examine the association between self-reported ADHD and college adjustment. Participants: Study 1 included nearly 3400 undergraduates attending a public and private university. Study 2 included 846 students who participated during freshman and sophomore year. Method: Students completed a web-based survey that assessed diagnostic status and adjustment in multiple domains. Results: Relative to other students, those with self-reported ADHD had lower GPAs and reported more academic concerns, depressive symptoms, social concerns, emotional instability, and substance use. Overall, however, most were making satisfactory adjustments in these domains. Benefits of medication treatment were not found. Freshman year ADHD predicted lower GPA, increased academic concerns and alcohol use, and smoking initiation. Conclusion: Students with ADHD struggled relative to peers but most were adjusting reasonably well across multiple domains. Future research should move beyond the use of self-reported diagnosis and more carefully examine the impact of medication treatment in this population. (J. of Att. Dis. 2009; 13(3) 297-309)
The Working Space of the Hand in Rheumatoid Arthritis: Its Impact on Disability
Authors: DIAS J. J. , SMITH M. , SINGH H. P. , ULLAH A. S.
Published: May 2009

The volumes enclosed by each of 108 hands in 54 rheumatoid arthritis patients were calculated using individual joint measurements. The difference between the flexion and extension volumes is the ‘working space’ of the hand. Correlations between the working space and parameters of stiffness, pain, deformity, movement, grip and functional disability were performed. The average working space volume was 4921 cc in rheumatoid patients with no visible hand deformity and 1154 cc in the presence of combined finger deformities ( P < 0.005). The loss in volume was due mainly to loss of extension. The Patient Evaluation Measure and the Functional Disability Score were significantly related to changes in the working space ( P < 0.05). The concept of the working space of the hand may aid the assessment of the rheumatoid hand and help surgical decision-making.
Statistical study of nickel and phosphorus contents in electroless Ni–P coatings
Authors: Choudhury B. S. , Sen R. S. , Oraon B. , Majumdar G.
Published: May 2009

Electroless nickel phosphorus plating process has been studied considering pure copper (99·99%) as a substrate material. Preliminary experiments were performed to obtain the autocatalytic deposition of electroless Ni–P coatings on copper. Deposited percentages of nickel and phosphorus in electroless Ni–P coatings have been evaluated by energy dispersive X-ray analysis (EDAX) and these percentages have been considered as response variables for statistical analysis. The individual and combined effects of process parameters on deposited percentages of nickel and phosphorus have been studied. Full factorial experimental design, regression analysis and Student's t test have been used to identify the influencing process parameters. It has been observed that reducing agent (NaH2PO2.H2O) significantly affects the percentages of nickel and phosphorus contents in the Ni–P coatings. Mathematical modelling has been carried out using a second order response surface model to take into account the effect of curvature in the predicted responses. Equations for response surfaces that relate the deposited percentages of nickel and phosphorus with process parameters have been determined using MATLAB software package. The surface and contour plots have been generated and these plots give visual pictures about the effect of process parameters on the deposited percentages of nickel and phosphorus in the Ni–P coatings.
A novel human gamma-globin gene vector for genetic correction of sickle cell anemia in a humanized sickle mouse model: critical determinants for successful correction
Authors: Perumbeti Ajay , Higashimoto Tomoyasu , Urbinati Fabrizia , Franco Robert , Meiselman Herbert J. , Witte David , Malik Punam
Published: May 2009

We show that lentiviral delivery of human γ-globin gene under β-globin regulatory control elements in hematopoietic stem cells (HSCs) results in sufficient postnatal fetal hemoglobin (HbF) expression to correct sickle cell anemia (SCA) in the Berkeley “humanized” sickle mouse. Upon de-escalating the amount of transduced HSCs in transplant recipients, using reduced-intensity conditioning and varying gene transfer efficiency and vector copy number, we assessed critical parameters needed for correction. A systematic quantification of functional and hematologic red blood cell (RBC) indices, organ pathology, and life span was used to determine the minimal amount of HbF, F cells, HbF/F-cell, and gene-modified HSCs required for correcting the sickle phenotype. We show that long-term amelioration of disease occurred (1) when HbF exceeded 10%, F cells constituted two-thirds of the circulating RBCs, and HbF/F cell was one-third of the total hemoglobin in sickle RBCs; and (2) when approximately 20% gene-modified HSCs repopulated the marrow. Moreover, we show a novel model using reduced-intensity conditioning to determine genetically corrected HSC threshold that corrects a hematopoietic disease. These studies provide a strong preclinical model for what it would take to genetically correct SCA and are a foundation for the use of this vector in a human clinical trial.
Dll1 and Dll4: similar, but not the same
Authors: Gessler Manfred
Published: May 2009

The VEGF-Dll4-Notch1 signaling cascade has taken center stage in angiogenesis, but it now appears that Dll1 ligands have precedence in arteries and even seem to control VEGF signaling.
Are all myelomas preceded by MGUS?
Authors: Bladé Joan , Rosiñol Laura , Cibeira Ma Teresa
Published: May 2009

In this issue of Blood, 2 independent articles report for the first time that an MGUS virtually precedes all cases on multiple myeloma.
Be fruitful, multiply, and replenish
Authors: Borghans José A. M. , Tesselaar Kiki
Published: May 2009

In this issue, Bains and colleagues show that T-cell proliferation plays a major role in the establishment of the T-cell pool, even in the very young, despite their high thymus output.
RTEs: lazy T-cell teenagers
Authors: Fink Pamela J.
Published: May 2009

In this issue of Blood, Opiela and colleagues analyze the phenotype and function of the lymphoid periphery's youngest T cells, RTEs.
A team player: the disintegrin domain of ADAMTS13
Authors: Zheng X. Long
Published: May 2009

In this issue of Blood, de Groot and colleagues identify novel interactions between the disintegrin domain of ADAMTS13 and the A2 domain of VWF. This provides another piece in the puzzle of how this domain of ADAMTS13 works in concert with other domains to bind and process VWF.
RhoGDIβ-induced hypertrophic growth in H9c2 cells is negatively regulated by ZAK
Authors: Huang Chih-Yang , Yang Li-Chiu , Liu Kuan-Yu , Liao Pao-Hsin , Chou Janet Ing-Yuh , Chou Ming-Yung , Lin Wei-Wen , Yang Jaw-Ji
Published: May 2009

We found that overexpression of RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and suppressed cell cycle progression in a cultured cardiomyoblast cell line. Knockdown of RhoGDIβ expression by RNA interference blocked hypertrophic growth. We further demonstrated that RhoGDIβ physically interacts with ZAK and is phosphorylated by ZAK in vitro, and this phosphorylation negatively regulates RhoGDIβ functions. Moreover, the ZAK-RhoGDIβ interaction may maintain ZAK in an inactive hypophosphorylated form. These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIβ functions through phosphorylation and RhoGDIβ counteracts the effects of ZAK by physical interaction. Knockdown of ZAK expression in ZAK- and RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the full functions of RhoGDIβ.
Effects of human parvovirus B19 VP1 unique region protein on macrophage responses
Authors: Tzang Bor-Show , Chiu Chun-Ching , Tsai Chun-Chou , Lee Yi-Ju , Lu I-Jung , Shi Jing-Yu , Hsu Tsai-Ching
Published: May 2009

Background

Activity of secreted phospholipase A (sPLA2) has been implicated in a wide range of cellular responses. However, little is known about the function of human parvovirus B19-VP1 unique region (VP1u) with sPLA2 activity on macrophage.

Methods

To investigate the roles of B19-VP1u in response to macrophage, phospholipase A2 activity, cell migration assay, phagocytosis activity, metalloproteinase assay, RT-PCR and immunoblotting were performed.

Results

In the present study, we report that migration, phagocytosis, IL-6, IL-1β mRNA, and MMP9 activity are significantly increased in RAW264.7 cells by B19-VP1u protein with sPLA2 activity, but not by B19-VP1uD175A protein that is mutated and lacks sPLA2 activity. Additionally, significant increases of phosphorylated ERK1/2 and JNK proteins were detected in macrophages that were treated with B19-VP1u protein, but not when they were treated with B19-VP1uD175A protein.

Conclusion

Taken together, our experimental results suggest that B19-VP1u with sPLA2 activity affects production of IL-6, IL-1β mRNA, and MMP9 activity, possibly through the involvement of ERK1/2 and JNK signaling pathways. These findings could provide clues in understanding the role of B19-VP1u and its sPLA2 enzymatic activity in B19 infection and B19-related diseases.
Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells
Authors: Lu Ying-Ying , Chen Tong-Sheng , Qu Jun-Le , Pan Wen-Liang , Sun Lei , Wei Xun-Bin
Published: May 2009

Background

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, isolated from the traditional Chinese herb Artemisia annua, is recommended as the first-line anti-malarial drug with low toxicity. DHA has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathways, although the molecular mechanisms are not well understood.

Methods

In this study, cell counting kit (CCK-8) assay was employed to evaluate the survival of DHA-treated ASTC-a-1 cells. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. Collapse of mitochondrial transmembrane potential (ΔΨm) was measured by dynamic detection under a laser scanning confocal microscope and flow cytometry analysis using Rhodamine123. Caspase-3 activities measured with or without Z-VAD-fmk (a broad spectrum caspase inhibitor) pretreatment by FRET techniques, caspase-3 activity measurement, and western blotting analysis.

Results

Our results indicated that DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of ΔΨm and the activation of caspase-3.

Conclusion

These results show for the first time that DHA can inhibit proliferation and induce apoptosis via caspase-3-dependent mitochondrial death pathway in ASTC-a-1 cells. Our work may provide evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of lung adenocarcinoma.
Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat
Authors: Wu Hsing-Hui , Hsiao Tzu-Yu , Chien Chiang-Ting , Lai Ming-Kuen
Published: May 2009

Prolonged ischemia amplified iscehemia/reperfusion (IR) induced renal apoptosis and autophagy. We hypothesize that ischemic conditioning (IC) by a briefly intermittent reperfusion during a prolonged ischemic phase may ameliorate IR induced renal dysfunction. We evaluated the antioxidant/oxidant mechanism, autophagy and apoptosis in the uninephrectomized Wistar rats subjected to sham control, 4 stages of 15-min IC (I15 × 4), 2 stages of 30-min IC (I30 × 2), and total 60-min ischema (I60) in the kidney followed by 4 or 24 hours of reperfusion. By use of ATP assay, monitoring O2
-. amounts, autophagy and apoptosis analysis of rat kidneys, I60 followed by 4 hours of reperfusion decreased renal ATP and enhanced reactive oxygen species (ROS) level and proapoptotic and autophagic mechanisms, including enhanced Bax/Bcl-2 ratio, cytochrome C release, active caspase 3, poly-(ADP-ribose)-polymerase (PARP) degradation fragments, microtubule-associated protein light chain 3 (LC3) and Beclin-1 expression and subsequently tubular apoptosis and autophagy associated with elevated blood urea nitrogen and creatinine level. I30 × 2, not I15 × 4 decreased ROS production and cytochrome C release, increased Manganese superoxide dismutase (MnSOD), Copper-Zn superoxide dismutase (CuZnSOD) and catalase expression and provided a more efficient protection than I60 against IR induced tubular apoptosis and autophagy and blood urea nitrogen and creatinine level. We conclude that 60-min renal ischemia enhanced renal tubular oxidative stress, proapoptosis and autophagy in the rat kidneys. Two stages of 30-min ischemia with 3-min reperfusion significantly preserved renal ATP content, increased antioxidant defense mechanisms and decreased ischemia/reperfusion enhanced renal tubular oxidative stress, cytosolic cytochrome C release, proapoptosis and autophagy in rat kidneys.
STAT2 hypomorphic mutant mice display impaired dendritic cell development and antiviral response
Authors: Chen Lan-Sun , Wei Pei-Chi , Liu Taming , Kao Chung-Hsuan , Pai Li-Mei , Lee Chien-Kuo
Published: May 2009

Interferons (IFNs) are key regulators for both innate and adaptive immune responses. By screening ENU-mutagenized mice, we identified a pedigree- P117 which displayed impaired response to type I, but not type II, IFNs. Through inheritance test, genetic mapping and sequencing, we found a T to A point mutation in the 5' splice site of STAT2 intron 4–5, leading to cryptic splicing and frame shifting. As a result, the expression of STAT2 protein was greatly diminished in the mutant mice. Nonetheless, a trace amount of functional STAT2 protein was still detectable and was capable of inducing, though to a lesser extent, IFNα-downstream gene expressions, suggesting that P117 is a STAT2 hypomorphic mutant. The restoration of mouse or human STAT2 gene in P117 MEFs rescued the response to IFNα, suggesting that the mutation in STAT2 is most likely the cause of the phenotypes seen in the pedigree. Development of different subsets of lymphocytes appeared to be normal in the mutant mice except that the percentage and basal expression of CD86 in splenic pDC and cDC were reduced. In addition,in vitroFlt3L-dependent DC development and TLR ligand-mediated DC differentiationwerealso defective in mutant cells. These results suggest that STAT2 positively regulates DC development and differentiation. Interestingly, a severe impairment of antiviral state and increased susceptibility to EMCV infection were observed in the mutant MEFs and mice, respectively, suggesting that the remaining STAT2 is not sufficient to confer antiviral response. In sum, the new allele of STAT2 mutant reported here reveals a role of STAT2 for DC development and a threshold requirement for full functions of type I IFNs.
Spatiotemporal expression of histone acetyltransferases, p300 and CBP, in developing embryonic hearts
Authors: Chen Guozhen , Zhu Jing , Lv Tiewei , Wu Gang , Sun Huichao , Huang Xupei , Tian Jie
Published: May 2009

Histone acetyltransferases (HATs), p300 and cAMP response element binding protein (CREB)-binding protein (CBP) are two structurally related transcriptional co-activators that activate expression of many eukaryotic genes involved in cellular growth and signaling, muscle differentiation and embryogenesis. However, whether these proteins play important and different roles in mouse cardiogenesis is not clear. Here, we investigate the protein distributions and mRNA expression of the two HATs in embryonic and adult mouse heart during normal heart development by using immunohistochemical and RT-PCR techniques. The data from immunohistochemical experiments revealed that p300 was extensively present in nearly every region of the hearts from embryonic stages to the adulthood. However, no CBP expression was detected in embryonic hearts at day E7.5. CBP expression appeared at the later stages, and the distribution of CBP was less than that of p300. In the developmental hearts after E10.5, both for p300 and CBP, the mRNA expression levels reached a peak on day E10.5, and then were gradually decreased afterwards. These results reveal that both p300 and CBP are related to embryonic heart development. The dynamic expression patterns of these two enzymes during mouse heart development indicate that they may play an important role on heart development. However, there is a difference in spatiotemporal expression patterns between these two enzymes during heart development. The expression of p300 is earlier and more predominate, suggesting that p300 may play a more important role in embryonic heart development especially during cardiac precursor cell induction and interventricular septum formation.
Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway
Authors: Jakóbkiewicz-Banecka Joanna , Piotrowska Ewa , Narajczyk Magdalena , Barańska Sylwia , Węgrzyn Grzegorz
Published: May 2009

Background

Mucopolysaccharidoses (MPS) are inherited metabolic disorders caused by mutations leading to dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs). Due to their impaired degradation, GAGs accumulate in cells of patients, which results in dysfunction of tissues and organs. Substrate reduction therapy is one of potential treatment of these diseases. It was demonstrated previously that genistein (4', 5, 7-trihydroxyisoflavone) inhibits synthesis and reduces levels of GAGs in cultures of fibroblasts of MPS patients. Recent pilot clinical study indicated that such a therapy may be effective in MPS III (Sanfilippo syndrome).

Methods

To learn on details of the molecular mechanism of genistein-mediated inhibition of GAG synthesis, efficiency of this process was studied by measuring of incorporation of labeled sulfate, storage of GAGs in lysosomes was estimated by using electron microscopic techniques, and efficiency of phosphorylation of epidermal growth factor (EGF) receptor was determined by using an ELISA-based assay with fluorogenic substrates.

Results

Effects of genistein on inhibition of GAG synthesis and accumulation in fibroblasts from patients suffering from various MPS types were abolished in the presence of an excess of EGF, and were partially reversed by an increased concentration of genistein. No such effects were observed when an excess of 17β-estradiol was used instead of EGF. Moreover, EGF-mediated stimulation of phsophorylation of the EGF receptor was impaired in the presence of genistein in both wild-type and MPS fibroblasts.

Conclusion

The results presented in this report indicate that the mechanism of genistein-mediated inhibition of GAG synthesis operates through epidermal growth factor (EGF)-dependent pathway.
In vitro study of the tocolytic effect of oroxylin A from Scutellaria baicalensis root
Authors: Shih Huey-Chuan , Hsu Chun-Sen , Yang Ling-Ling
Published: May 2009

Scutellariae Radix is one of the well-known tocolytic Chinese herbs. Oroxylin A is isolated from the root of Scutellaria baicalensis. The main syndrome of preterm birth is caused by uterus contractions from excitatory factors. Administration of tocolytic agents is a strategy to prevent the occurrence of preterm births. The aim of this study was to investigate the effects of oroxylin A on contractions of uterine strips isolated from non-pregnant female Wistar rats (250~350 g). Contractions of the uterus were induced with acetylcholine (Ach) (1 μM), PGF2α (0.1 μM), oxytocin (10-3 U/ml), KCl (56.3 mM), tetraethylammonium (TEA; 1 and 10 mM), 4-aminopyridine (4-AP; 5 mM), glipizide (30 μM), a nitric oxide synthase (NOS) inhibitor (LNNA; 10-3M), a β-receptor blocker (propranolol; 10 μM), and a cyclooxygenase inhibitor (indomethacin; 60 μM). The inhibitory effects of the amplitude and frequency of spontaneous contractions by oroxylin A were antagonized with Ach (IC50 22.85 μM), PGF2α (IC5027.28 μM), oxytocin (IC50 12.34 μM), TEA; 1 and 10 mM (IC50 52.73 and 76.43 μM), 4-AP (IC50 67.16 μM), and glipizide (IC5027.53 μM), but oroxylin A was not influenced by Ca2+-free medium, LNNA, propranolol, or indomethacin. Otherwise, oroxylin A-mediated relaxation of the rat uterus might occur through opening of uterine calcium-dependent potassium channels or adenosine triphosphate potassium channel activation. This suggests that oroxylin A is the tocolytic principle constituent of Scutellariae Radix, and oroxylin A may provide a lead compound for new tocolytic drug development in the future.
Antigen-driven bystander effect accelerates epicutaneous sensitization with a new protein allergen
Authors: Wang Li-Fang , Chen Jau-Shiuh , Hsu Chih-Jung , Liu Ching-Yi , Yu Jhang-Sian , Miaw Shi-Chuen
Published: May 2009

Exposure to protein allergen epicutaneously, inducing a Th2-dominant immune response, sensitizes the host to the development of atopic disease. Antigen-driven bystander effect demonstrates that polarized T cells could instruct naïve T cells to differentiate into T cells with similar phenotype. In this study, we aimed to determine the contribution of antigen-driven bystander effect on epicutaneous sensitization with a newly introduced protein allergen. BALB/c mice were immunized intraperitoneally with BSA emulsified in alum, known to induce a Th2 response, three weeks before given BSA and OVA epicutaneously. Lymph node cells from these mice restimulated with OVA secreted higher levels IL-4, IL-5 and IL-13 as compared with cells from mice without BSA immunization. In addition, BALB/c mice immunized subcutaneously with BSA emulsified in complete Freund's adjuvant, known to induce a Th1-predominant response, also induced higher Th1 as well as Th2 cytokine response when restimulated with OVA as compared with mice without immunization. We demonstrated that subcutaneous immunization with BSA in CFA induced Th2 as well as Th1 response. The threshold of epicutaneous sensitization to OVA was also reduced, possibly due to increased expressions of IL-4 and IL-10 in the draining lymph nodes during the early phase of sensitization. In conclusion, antigen-driven bystander effect, whether it is of Th1- or Th2-predominant nature, can accelerate epicutaneous sensitization by a newly introduced protein allergen. These results provide a possible explanation for mono- to poly-sensitization spread commonly observed in atopic children.
Immunotherapy for liver tumors: present status and future prospects
Authors: Matar Pablo , Alaniz Laura , Rozados Viviana , Aquino Jorge B , Malvicini Mariana , Atorrasagasti Catalina , Gidekel Manuel , Silva Marcelo , Scharovsky O Graciela , Mazzolini Guillermo
Published: May 2009

Increasing evidence suggests that immune responses are involved in the control of cancer and that the immune system can be manipulated in different ways to recognize and attack tumors. Progress in immune-based strategies has opened new therapeutic avenues using a number of techniques destined to eliminate malignant cells. In the present review, we overview current knowledge on the importance, successes and difficulties of immunotherapy in liver tumors, including preclinical data available in animal models and information from clinical trials carried out during the lasts years. This review shows that new options for the treatment of advanced liver tumors are urgently needed and that there is a ground for future advances in the field.
Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling
Authors: Lin Bor-Ru , Yu Chia-Jung , Chen Wang-Chuan , Lee Hsuan-Shu , Chang Huei-Min , Lee Yen-Chih , Chien Chiang-Ting , Chen Chau-Fong
Published: May 2009

Oxidative stress and inflammation contributed to the propagation of acute liver injury (ALI). The present study was undertaken to determine whether D-galactosamine (D-GalN) induces ALI via the mitochondrial apoptosis- and proinflammatory cytokine-signaling pathways, and possible mechanism(s) by which green tea (GT) extract modulates the apoptotic and proinflammatory signaling in rat. D-GalN induced hepatic hypoxia/hypoperfusion and triggered reactive oxygen species (ROS) production from affected hepatocytes, infiltrated leukocytes, and activated Kupffer cells. D-GalN evoked cytosolic Bax and mitochondrial cytochrome C translocation and activated proinflammatory nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) translocation, contributing to the increase of intercellular adhesion molecule-1 expression, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive hepatocytes, multiple plasma cytokines and chemokines release, and alanine aminotransferase (ALT) activity. An altered biliary secretion profile of several acute phase proteins directly indicates oxidative stress affecting intracellular trafficking in the hepatocyte. GT pretreatment attenuated ROS production, mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms. In conclusion, D-GalN induced ALI via hypoxia/hypoperfusion-enhanced mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver. GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.