bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral choroidopathy in systemic lupus erythematosus
Authors: Edouard S , Douat J , Sailler L , Arlet P , Astudillo L
Published: April 2011

We report a case of bilateral choroidopathy in a 35-year-old woman with systemic lupus erythematosus (SLE) diagnosed 3 years previously, and treated with hydroxychloroquine and steroids that ceased 6 months before ocular signs. She complained about rapid bilateral blurred vision with a severe loss of visual acuity. Fluorescein angiography found multiple leakage points in the posterior pole of the pigment epithelium. Ocular coherence tomography (OCT) and fundoscopy showed bilateral retinal detachments. Lupus choroidopathy was diagnosed and high steroids were given intravenously and allowed a rapid improvement. Visual acuity, fundoscopy, retinal angiography and OCT were normalized at 2 months. Choroidopathy is rarely reported in lupus and only about 30 patients are found in the literature.
Critical Issues in International Education
Authors: Teshome Yalem , Osei-Kofi Nana
Published: April 2011

This study examines the day-to-day experiences of female spouses of international students living in the United States as legal dependents of their male student spouses. Although these women are well-educated professionals, as legal dependents, they are prohibited from engaging in educational and professional endeavors during their sojourn. As a result of these limitations placed on their day-to-day activities, this study reveals that these women frequently experience social isolation, economic challenges, and emotional struggles. Given the economic, cultural, and intellectual benefits of international students and their families to campus communities, these findings suggest that it is imperative for colleges and universities to provide spouses of international students with access to programs and services that meet their educational, professional, and social needs. As universities compete to attract international students, the existence of services and programs for accompanying spouses could become a key factor in where international students choose to pursue their education.
Collaborative Dual-Degree Programs and Value Added for Students
Authors: Culver Steven M. , Puri Ishwar K. , Spinelli Giancarlo , DePauw Karen P. K. , Dooley John E.
Published: April 2011

Dual-degree programs are intended to prepare graduates to work in a global job market by providing more extensive international experiences, thus enhancing their employability. These programs typically take longer to complete and cost more, yet there is little documentation regarding their effectiveness. This study was designed to examine strengths and weakness of a sample of existing formalized programs at the graduate level in engineering through surveys and focus groups with four key stakeholder groups: students currently enrolled in dual- or joint-degree programs, faculty teaching in those programs, alumni who have recently graduated from those programs, and employers who have either hired alumni from these programs or are in a position to hire future graduates. Results indicate that all stakeholder groups were positive about these programs, and there is demand for them among students though gains were indicated in personal dimensions (e.g., self-reliance) rather than professional ones. In addition, employers were unclear about what dual-degree programs were and did not tend to view graduates as more marketable. Further study with more diverse groups is indicated.
Promoting Intercultural Contact on Campus
Authors: Campbell Nittaya
Published: April 2011

International students’ adjustment to living in an unfamiliar cultural environment and studying in a different educational system and language has been a topic of much research. Literature has shown that support from the host community could be the difference between a smooth transition and one fraught with problems and difficulties. This article describes a “buddy project” used in an intercultural communication class in which each student was a buddy for a newly arrived international student for a semester. The purpose of the project was to give social support to international students in the crucial first few months of their sojourn while at the same time complementing host students’ class-based theoretical learning with practical, meaningful experience with peers from another culture. The article discusses the outcomes, challenges, and students’ evaluations of the experiential learning exercise. Recommendations for future projects are outlined.
The Effect of Adhesive Layers on the Dynamic Behavior of Surface-bonded Piezoelectric Sensors with Debonding
Authors: Congrui Jin  , Xiaodong Wang
Published: April 2011

The behavior of a piezoelectric sensor is strongly affected by the bonding condition along the interface between the sensor and the host structure. This article presents an analytical study of the effect of the mechanical and geometrical properties of the adhesive layer on the coupled dynamic electromechanical behavior of a thin piezoceramic sensor bonded to an elastic medium. A sensor model with an imperfect adhesive bonding layer is proposed to simulate the two dimensional electromechanical behavior of the integrated system. The analytical solution of the problem is provided by solving the resulting integral equations in terms of the interfacial stress. Numerical simulation is conducted to study the effect of the bonding layer upon the dynamic response of the sensor under different loading frequencies. The interfacial debonding and its effect on the interlaminar strain and stress transfer mechanisms are discussed in detail.
Making Voting Easier
Authors: Alvarez R. Michael , Levin Ines , Sinclair J. Andrew
Published: April 2011

The authors analyze the choice of voting mode in the 2008 presidential election using a large-sample survey with national coverage that allows a new perspective of convenience voting. Most importantly, they make clear distinctions among the major forms of convenience voting and demonstrate that not all “convenience voters” share the same attributes. In addition, the authors find little support for the hypothesis that convenience voting methods have partisan implications, despite the differences among mail, early, and election-day voters. Results like these have important implications for future moves toward convenience voting and the design of new outreach campaigns.
“You Have to Hunt for the Fruits, the Vegetables”: Environmental Barriers and Adaptive Strategies to Acquire Food in a Low-Income African American Neighborhood
Authors: Zenk Shannon N. , Odoms-Young Angela M. , Dallas Constance , Hardy Elaine , Watkins April , Hoskins-Wroten Jacqueline , Holland Loys
Published: April 2011

This qualitative study sought to understand food acquisition behaviors and environmental factors that influence those behaviors among women in a low-income African American community with limited food resources. We drew on in-depth interviews with 30 women ages 21 to 45 years recruited from a community health center in Chicago, Illinois. Data were analyzed using qualitative content analysis. Emergent themes revealed that women identified multiple environmental barriers—material, economic, and social-interactional—to acquiring food in an acceptable setting. In response, they engaged in several adaptive strategies to manage or alter these challenges, including optimizing, settling, being proactive, and advocating. These findings indicate that efforts to improve neighborhood food environments should address not only food availability and prices but also the physical and social environments of stores.
A tentative consensus-based model for priority setting: An example from elderly patients with myocardial infarction and multi-morbidity
Authors: Ekerstad Niklas , Löfmark Rurik , Andersson David , Carlsson Per
Published: April 2011

Background: In most Western countries the growing gap between available resources and greater potential for medical treatment has brought evidence-based guidelines into focus. However, such guidelines are difficult to use when the evidence base is weak. Priority setting for frail elderly patients with heart disease illustrates this problem. We have outlined a tentative model for priority setting regarding frail elderly heart patients. The model takes cardiovascular risk, frailty, and comorbidity into account. Objective: Our aim is to validate the model’s components. We want to evaluate the inter-rater reliability of the study experts’ rankings regarding each of the model’s categories. Methods: A confidential questionnaire study consisting of 15 authentic and validated cases was conducted to assess the views of purposefully selected cardiology experts (n = 58). They were asked to rank the cases regarding the need for coronary angiography using their individual clinical experience. The response rate was 71%. Responses were analysed with frequencies and descriptive statistics. The inter-rater reliability regarding the experts’ rankings of the cases was estimated via an intra-class correlation test (ICC). Results: The cardiologists considered the clinical cases to be realistic. The intra-class correlation (two-way random, consistency, average measure) was 0.978 (95% CI 0.958—0.991), which denotes a very good inter-rater reliability on the group level. The model’s components were considered relevant regarding complex cases of non-ST elevation myocardial infarction. Comorbidity was considered to be the most relevant component, frailty the second most relevant, followed by cardiovascular risk. Conclusions: A framework taking comorbidity, frailty, and cardiovascular risk into account could constitute a foundation for consensus-based guidelines for frail elderly heart patients. From a priority setting perspective, it is reasonable to believe that the framework is applicable to other groups of elderly patients with acute disease and complex needs.
Precautions taken by mothers to prevent burn and scald injuries to young children at home: An intervention study
Authors: Carlsson Anna , Bramhagen Ann-Cathrine , Jansson Annkristin , Dykes Anna-Karin
Published: April 2011

Aim: The aim of this study was to investigate to what extent individual-based extended information given to mothers from city parts of low education can improve precautions taken by them to prevent burn and scald injuries involving young children in the home and further to compare the results with a group of mothers who had not received extended information. Methods: This intervention study, with a comparison group, has a quasi-experimental design. Individual-based information, with an empowerment approach, was given to a group of mothers living in two separate areas of a city in southern Sweden with a low level of education. In total, 99 mothers of children under the age of 7 months participated. The mothers were selected through the local child healthcare authorities. Observations were made and bivariate analyses were established. Results: The results showed that the intervention had a significant impact on improving the precautions the participating mothers introduced to protect their children against burn and scald injuries in the home and further, in relation to a comparison group. Conclusions: Through empowerment, workshops, and home visits aimed to increase their consciousness and knowledge, the participating mothers’ precautions taken against child injuries in the home improved. It is of great importance that a framework for considering the problem of burn and scald injuries to children is presented from a preventive perspective which, in combination with evidence-based interventions, may enable the creation of injury prevention programmes for implementation by the community health care.
Early education teachers’ conceptualizations and strategies for managing closeness in child care: The personal domain
Authors: Quan-McGimpsey Sharon , Kuczynski Leon , Brophy Kathleen
Published: April 2011

This study investigated teachers’ experiences of closeness during interactions with children in child care. Structured interviews were conducted with 24 female teachers who were teaching children between the ages of three and five (mean age = 3.9) regarding their conceptions of closeness, and their perceptions of their own and the child’s contributions to close interactions. Qualitative analyses of the interviews revealed a relational model of teacher—child relationships that included a professional domain, an attachment domain and a personal domain, with the personal domain as most dominant in teachers’ perceptions. The personal domain was interpreted as consistent with Weingarten’s (1991) theory of intimate interactions and adds a new perspective on affective dimensions of caring (Goldstein, 1999). Teachers viewed relationships with particular children as a personal two-way relationship where both contributed either solely or mutually in their desire to be close. Teachers described intentional strategies for managing the close relationship that made use of the past history and the anticipated future of the relationship.
Cultural models in communication with infants: Lessons from Kikaikelaki, Cameroon and Muenster, Germany
Authors: Demuth Carolin , Keller Heidi , Yovsi Relindis D
Published: April 2011

Child rearing is a universal task, yet there are differing solutions according to the dynamics of socio-cultural milieu in which children are raised. Cultural models of what is considered good or bad parenting become explicit in everyday routine practices. Focusing on early mother–infant interactions in this article we examine the discursive practices and strategies that foster cultural values such as autonomy and relatedness. Drawing on micro-analysis of videotaped mother–infant interactions from middle-class families in Muenster, Germany and farming Nso families in Kikaikelaki, Cameroon, we aim at illustrating how diverse discursive strategies construct alternative versions of the child’s experience of self and self-in-relation-to-others. In each case, mothers draw on discursive practices that convey cultural norms and values that fit the relevant cultural context.
Ultra-violet emissions from HMI daylight luminaires
Authors: O'Hagan JB , Khazova M. , Jones CW
Published: April 2011

The European Union Directive 2006/25/EC lays down the minimum safety requirements regarding the exposure of workers to risks arising from artificial optical radiation, including ultra-violet radiation (UVR). It places a responsibility on employers to assess exposure levels, adopt preventative measures and arrange for the provision of information and training for their workers. This is particularly important in entertainment where intentional exposure of the actors and presenters to very intense light sources may be required for extended periods of time. This study presents the results of the assessment of the optical radiation safety of six portable hydrargyrum medium-arc-length iodide daylight luminaires regularly used for film and television production at news locations. The study shows that if UVR is not adequately filtered, by UV blocking additives in the lamp envelope, output optics or safety glass of the luminaire, an accessible emission may present a significant risk of UVR overexposure to the skin and the eye.
Developing Culturally Competent Evaluation Tools With Tobacco Control Program Practitioners
Authors: Treiber Jeanette
Published: April 2011

Aiming to develop a utilization-focused evaluation approach, this article presents the process of developing culturally competent evaluation guidelines for Tobacco Control programs with American Indian/Alaska Natives, African Americans, Asian/Pacific Islanders, Hispanic/Latinos, LGBT, low–socioeconomic status populations, and rural populations. Through literature reviews and an interactive process that engages tobacco control program practitioners throughout the state of California, a UC Davis evaluation center developed a series of culture-specific guidelines for use in process and outcome evaluations. The norm change approach of the California Department of Public Health is contrasted with the norms of the priority populations it serves to determine why these populations are less responsive to the strategy than mainstream populations and points to ways in which evaluation activities can contribute to achieving greater inclusion of minority populations in tobacco control program efforts.
Evaluating Leadership Training in African American HIV Prevention Organizations
Authors: Coleman Jason D. , Dauner Kim Nichols , Richter Donna L. , Annang Lucy , Sellers Denethia B. , Lindley Lisa L.
Published: April 2011

This article aimed to examine changes in the HIV prevention capacity of HIV prevention program managers who completed the Institute for HIV Prevention Leadership (“Institute”) between 2002 and 2004, and who worked in community-based organizations that primarily served African Americans. Participants completed a survey at three points in time, in which they rated the frequency with which they conducted activities related to HIV prevention practice. Participants also rated their confidence in performing activities. Repeated measures ANOVA was conducted to detect differences at three time points (baseline, immediate posttest, and 6 months posttest). A significant overall positive trend was found in the frequency and confidence of participants to perform specific HIV prevention practices and an overall positive trend in the frequency of processes that support HIV prevention practice. Investment in long-term, intensive, capacity-building programs like the Institute is critical to address the increasing incidence of HIV in many African American communities.
Design of a Faith-Based HIV Intervention
Authors: Wingood Gina M. , Simpson-Robinson LaShun , Braxton Nikia D. , Raiford Jerris L.
Published: April 2011

This article describes the development of a gender-specific and culturally tailored, theoretically derived, faith-based HIV intervention created to reduce HIV vulnerability among African American women. This innovative culturally congruent approach to HIV prevention involves one of the most influential social structures in the African American community—the African American church. Using the ADAPT-ITT model, and principles of community-based participatory research, this faith-based HIV intervention was adapted from a CDC-defined evidence-based HIV prevention intervention for young African American women. Results of data assessing the feasibility of implementing this faith-based HIV intervention suggests that young African American women are receptive and willing to participate in a faith-based HIV intervention. Results show that fidelity to intervention implementation (97%) and participant attendance to both sessions (92%) was high, and the HIV risk behaviors targeted in the faith-based intervention matched the participants’ HIV behavioral risk profile. Given the vulnerability of young African American women to HIV sustainable efforts, in particular, the institutionalization of this intervention within the church structure could halt the persistent increase in HIV infections within this community.
Effect of filament fineness on comfort characteristics of moisture management finished polyester knitted fabrics
Authors: Sampath MB , Mani Senthilkumar , Nalankilli G
Published: April 2011

Clothing comfort is an important aspect for any garment used for sportswear and leisurewear. Every human being sweats during different kinds of activities. An important feature of any fabric is how it transports this water out of the body surface so as to make the wearer feel comfortable. Hence, wetting and wicking properties are critical aspects during wearing of clothes. Polyester micro-fibers have twin characteristics of durability and comfort. The usage of continuous filament micro-denier polyester yarn for sportswear and leisurewear clothing has a practical significance in clothing comfort. In this study, polyester filament yarn were taken and made into single jersey knitted fabrics. Five different fabrics were made from 150 denier polyester yarns constituting different number of filaments, namely, 34 filaments, 48 filaments, 108 filaments, 144 filaments, and 288 filaments. Moisture management finish was applied to the five types of single jersey knitted fabrics and the effect of filament fineness on comfort characteristics of moisture management finished polyester knitted fabrics was analyzed to achieve suitability for making sportswear. From the tests, it was observed that the fabric containing 108 filaments in yarn gives better wetting, higher wicking, and optimum moisture vapor transmission. A new test method was introduced to find out the transverse wicking behavior of the fabrics. Filament fineness and surface area of yarn play a vital role in deciding the comfort characteristics of the fabric, as also moisture management finish treatment which enhances it.
Text Messages as Mobilization Tools: The Conditional Effect of Habitual Voting and Election Salience
Authors: Malhotra Neil , Michelson Melissa R. , Rogers Todd , Valenzuela Ali Adam
Published: April 2011

Dale and Strauss’s (DS) noticeable reminder theory (NRT) of voter mobilization posits that mobilization efforts that are highly noticeable and salient to potential voters, even if impersonal, can be successful. In an innovative experimental design, DS show that text messages substantially boost turnout, challenging previous claims that social connectedness is the key to increasing participation. We replicate DS’s research design and extend it in two key ways. First, whereas the treatment in DS’s experiment was a “warm” text message combined with contact, we test NRT more cleanly by examining the effect of “cold” text messages that are completely devoid of auxiliary interaction. Second, we test an implication of NRT that habitual voters should exhibit the largest treatment effects in lower salience elections whereas casual voters should exhibit the largest treatment effects in higher salience elections. Via these two extensions, we find support for NRT.
Revisiting the Parent–Child Analogy: Implications for Law and Judgment
Authors: Lee Susanna
Published: April 2011

In order to explore the overlap between individual judgment and legal judgment, I turn to the parent–child analogy (the state is to the subject as the parent is to the child), historically much used to support the validity and basic rightness of the state’s judgment. In this commentary, I examine how the very dynamic and contested nature of the modern parent–child relationship makes the state–subject relationship, its contemporary and correlative, particularly problematic. Specifically, I argue, it destabilizes the idea of judgment and the supposed distinction between state judgment and human subject judgment; and in so doing, it undermines the notion of “the law” as a distinct and independent entity.
Democracy or Your Life! Knowledge, Ignorance and the Politics of Atheism in Saramago’s Blindness and Seeing
Authors: Aristodemou Maria
Published: April 2011

In western philosophy, the terms “gnosis” (knowledge) and “agnosia” (ignorance) are linked to seeing and to blindness: to see is to know while not to see is to be ignorant. In contrast to this genealogy, the anti-philosopher Lacan maintains that seeing does not guarantee knowledge, at least not knowledge of the “truth,” because there is always one point from which we can never see, that is, the blind spot. In a parallel way, however much we talk or write, we never manage to represent the whole truth or what Lacan terms the Real. The experience of analysis, the shattering impact of trauma, or, at times, a work of art, can enable us, however, to lift the veil covering truth. This article addresses Saramago’s twin dystopian fiction Blindness and Seeing and suggests that by pushing the limits of the possible and portraying the possibility of the impossible, Saramago enables us to catch a glimpse of the Real. The trauma depicted in Blindness leads to Saramago’s characters reassessing their relationship to knowledge and in particular their knowledge of the Big Other. Following this trauma, they cease making demands of the Other and in the process vanish him out of existence. The repercussions for our political system, and in particular for democracy, are fleshed out in the sequel Seeing where the State is impotent in the face of a silent protest by a sea of what I call atheist citizens; in other words, citizens who no longer believe in the city state. Saramago’s anti-politics, or politics of atheism, I suggest, are the natural companion to Lacan’s anti-philosophy and ethics of atheism.
Galectin-1–expressing stromal cells constitute a specific niche for pre-BII cell development in mouse bone marrow
Authors: Mourcin Frédéric , Breton Caroline , Tellier Julie , Narang Priyanka , Chasson Lionel , Jorquera Audrey , Coles Mark , Schiff Claudine , Mancini Stéphane J. C.
Published: April 2011

In the bone marrow (BM), stromal cells constitute a supportive tissue indispensable for the generation of pro-B/pre-BI, pre-BII, and immature B lymphocytes. IL-7–producing stromal cells constitute a cellular niche for pro-B/pre-BI cells, but no specific stromal cell microenvironment was identified for pre-BII cells expressing a functional pre-B cell receptor (pre-BCR). However expression of the pre-BCR represents a crucial checkpoint during B-cell development. We recently demonstrated that the stromal cell derived-galectin1 (GAL1) is a ligand for the pre-BCR, involved in the proliferation and differentiation of normal mouse pre-BII cells. Here we show that nonhematopoietic osteoblasts and reticular cells in the BM express GAL1. We observed that pre-BII cells, unlike the other B-cell subsets, were specifically localized in close contact with GAL1+ reticular cells. We also determined that IL-7+ and GAL1+ cells represent 2 distinct mesenchymal populations with different BM localization. These results demonstrate the existence of a pre-BII specific stromal cell niche and indicate that early B cells move from IL-7+ to GAL1+ supportive BM niches during their development.
New sources of drugs for hematologic malignancies
Authors: Sukhai Mahadeo A. , Spagnuolo Paul A. , Weir Scott , Kasper James , Patton Lavonne , Schimmer Aaron D.
Published: April 2011

Advancing novel therapeutic agents for the treatment of malignancy into the marketplace is an increasingly costly and lengthy process. As such, new strategies for drug discovery are needed. Drug repurposing represents an opportunity to rapidly advance new therapeutic strategies into clinical trials at a relatively low cost. Known on-patent or off-patent drugs with unrecognized anticancer activity can be rapidly advanced into clinical testing for this new indication by leveraging their known pharmacology, pharmacokinetics, and toxicology. Using this approach, academic groups can participate in the drug discovery field and smaller biotechnology companies can “de-risk” early-stage drug discovery projects. Here, several scientific approaches used to identify drug repurposing opportunities are highlighted, with a focus on hematologic malignancies. In addition, a discussion of the regulatory issues that are unique to drug repurposing and how they impact developing old drugs for new indications is included. Finally, the mechanisms to enhance drug repurposing through increased collaborations between academia, industry, and nonprofit charitable organizations are discussed.
Organogenesis during budding and lophophoral morphology of Hislopia malayensis Annandale, 1916 (Bryozoa, Ctenostomata)
Authors: Schwaha Thomas , Wood Timothy S
Published: April 2011

Background

Bryozoans represent a large lophotrochozoan phylum with controversially discussed phylogenetic position and in group relationships. Developmental processes during the budding of bryozoans are in need for revision. Just recently a study on a phylactolaemate bryozoan gave a comprehensive basis for further comparisons among bryozoans. The aim of this study is to gain more insight into developmental patterns during polypide formation in the budding process of bryozoans. Particular focus is laid upon the lophophore, also its condition in adults. For this purpose we studied organogenesis during budding and lophophoral morphology of the ctenostome bryozoan Hislopia malayensis.

Results

Polypide buds develop on the frontal side of the developing cystid as proliferation of the epidermal and peritoneal layer. Early buds develop a lumen bordered by the inner budding layer resulting in the shape of a two-layered sac or vesicle. The hind- and midgut anlagen are first to develop as outpocketing of the prospective anal area. These grow towards the prospective mouth area where a comparatively small invagination marks the formation of the foregut. In between the prospective mouth and anus the ganglion develops as an invagination protruding in between the developing gut loop. Lophophore development starts with two lateral ridges which form tentacles very early. At the lophophoral base, intertentacular pits, previously unknown for ctenostomes, develop. The ganglion develops a circum-oral nerve ring from which the tentacle nerves branch off in adult zooids. Tentacles are innervated by medio-frontal nerves arising directly from the nerve ring, and medio-frontal and abfrontal nerves which originate both from an intertentacular fork.

Conclusions

We are able to show distinct similarities among bryozoans in the formation of the different organ systems: a two-layered vesicle-like early bud, the ganglion forming as an invagination of the epidermal layer in between the prospective mouth and anal area, the digestive tract mainly forming as an outpocketing of the prospective anal area, and the lophophore forming from two lateral anlagen that first fuse on the oral and afterwards on the anal side. Future studies will concentrate on cyclostome budding to complement our knowledge on developmental patterns of bryozoans.
Do agreements between adolescent and parent reports on family socioeconomic status vary with household financial stress?
Authors: Pu Christy , Huang Nicole , Chou Yiing-Jenq
Published: April 2011

Background

Many studies compared the degree of concordance between adolescents' and parents' reports on family socioeconomic status (SES). However, none of these studies analyzed whether the degree of concordance varies by different levels of household financial stress. This research examines whether the degree of concordance between adolescents' and parent reports for the three traditional SES measures (parental education, parental occupation and household income) varied with parent-reported household financial stress and relative standard of living.

Methods

2,593 adolescents with a mean age of 13 years, and one of their corresponding parents from the Taiwan Longitudinal Youth Project conducted in 2000 were analyzed. Consistency of adolescents' and parents' reports on parental educational attainment, parental occupation and household income were examined by parent-reported household financial stress and relative standard of living.

Results

Parent-reported SES variables are closely associated with family financial stress. For all levels of household financial stress, the degree of concordance between adolescent's and parent's reports are highest for parental education (κ ranging from 0.87 to 0.71) followed by parental occupation (κ ranging from 0.50 to 0.34) and household income (κ ranging from 0.43 to 0.31). Concordance for father's education and parental occupation decreases with higher parent-reported financial stress. This phenomenon was less significant for parent-reported relative standard of living.

Conclusions

Though the agreement between adolescents' and parents' reports on the three SES measures is generally judged to be good in most cases, using adolescents reports for family SES may still be biased if analysis is not stratified by family financial stress.
Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin
Authors: Ryan Ali J , Chung Chun-wa , Curry Stephen
Published: April 2011

Background

Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA). It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA.

Results

We have determined the co-crystal structure of HSA in complex with iophenoxic acid at 2.75 Å resolution, revealing a total of four binding sites, two of which - in drugs sites 1 and 2 on the protein - are likely to be occupied at clinical doses. High-affinity binding of iophenoxic acid occurs at drug site 1. The structure reveals that polar and apolar groups on the compound are involved in its interactions with drug site 1. In particular, the 3-hydroxyl group makes three hydrogen bonds with the side-chains of Tyr 150 and Arg 257. The mode of binding to drug site 2 is similar except for the absence of a binding partner for the hydroxyl group on the benzyl ring of the compound.

Conclusions

The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin.
Daily Plasmodium yoelii infective mosquito bites do not generate protection or suppress previous immunity against the liver stage
Authors: Pollock Tzvi , Leitao Ricardo , Galan-Rodriguez Cristina , Wong Kurt A , Rodriguez Ana
Published: April 2011

Background

Human populations that are naturally subjected to Plasmodium infection do not acquire complete protection against the liver stage of this parasite despite prolonged and frequent exposure. However, sterile immunity against Plasmodium liver stage can be achieved after repeated exposure to radiation attenuated sporozoites. The reasons for this different response remain largely unknown, but a suppressive effect of blood stage Plasmodium infection has been proposed as a cause for the lack of liver stage protection.

Methods

Using Plasmodium yoelii 17XNL, the response generated in mice subjected to daily infective bites from normal or irradiated mosquitoes was compared. The effect of daily-infected mosquito bites on mice that were previously immunized against P. yoelii liver stage was also studied.

Results

It was observed that while the bites of normal infected mosquitoes do not generate strong antibody responses and protection, the bites of irradiated mosquitoes result in high levels of anti-sporozoite antibodies and protection against liver stage Plasmodium infection. Exposure to daily infected mosquito bites did not eliminate the protection acquired previously with a experimental liver stage vaccine.

Conclusions

Liver stage immunity generated by irradiated versus normal P. yoelii infected mosquitoes is essentially different, probably because of the blood stage infection that follows normal mosquito bites, but not irradiated. While infective mosquito bites do not induce a protective liver stage response, they also do not interfere with previously acquired liver stage protective responses, even if they induce a complete blood stage infection. Considering that the recently generated anti-malaria vaccines induce only partial protection against infection, it is encouraging that, at least in mouse models, immunity is not negatively affected by subsequent exposure and infection with the parasite.
A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases
Authors: Xie Chong , Kim Hyun J , Haw Jonathan G , Kalbasi Anusha , Gardner Brian K , Li Gang , Rao Jianyu , Chia David , Liong Monty , Punzalan Rubio R , Marks Leonard S , Pantuck Allan J , de la Taille Alexandre , Wang Guomin , Mukouyama Hideki , Zeng Gang
Published: April 2011

Background

The lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA).

Methods

To circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. Moreover, simultaneous quantification of autoAb plus total PSA was achieved in one reaction, and termed the "A+PSA" assay.

Results

Peptide epitopes from the above 6 PCAA were identified and confirmed that autoAb against these peptide epitopes reacted specifically with the full-length protein. A pilot study was conducted with the A+PSA assay using pre-surgery sera from 131 biopsy-confirmed prostate cancer patients and 121 benign prostatic hyperplasia and/or prostatitis patients. A logistic regression-based A+PSA index was found to enhance sensitivities and specificities over PSA alone in distinguishing prostate cancer from nonmalignant cases. The A+PSA index also reduced false positive rate and improved the area under a receiver operating characteristic curve.

Conclusions

The A+PSA assay represents a novel platform that integrates autoAb signatures with a conventional cancer biomarker, which may aid in the diagnosis and prognosis of prostate cancer and others.
"Boom" and "Bust" cycles in virus growth suggest multiple selective forces in influenza a evolution
Authors: Thangavel Rajagowthamee R , Reed Aisha , Norcross Erin W , Dixon Sherrina N , Marquart Mary E , Stray Stephen J
Published: April 2011

Background

Influenza A virus evolution in humans is driven at least in part by mutations allowing the virus to escape antibody neutralization. Little is known about the evolution of influenza in birds, a major reservoir of influenza A.

Methods

Neutralizing polyclonal antiserum was raised in chicken against reassortant influenza virus, CalX, bearing the hemagglutinin (HA) and neuraminidase (NA) of A/California/7/2004 [H3N2]. CalX was serially passaged in the presence of anti-CalX polyclonal IgY to derive viruses capable of growth in the presence of antibody.

Results

Polyclonal chicken antibody neutralized both HA activity and infection by CalX, but had no effect on a strain bearing an earlier human H3 and an irrelevant neuraminidase (A/Memphis/71-Bellamy/42 [H3N1]). Surprisingly, most of the antibody-resistant viruses were still at least partially sensitive to neutralization of HA activity and viral infection. Although mutant HA genes bearing changes that might affect antibody neutralization were identified, the vast majority of HA sequences obtained were identical to wild type, and no individual mutant sequence was found in more than one passage, suggesting that those mutations that were observed did not confer sufficient selective advantage to come to dominate the population. Different passages yielded infectious foci of varying size and plaques of varying size and morphology. Yields of infectious virus and relative frequency of different morphologies changed markedly from passage to passage. Sequences of bulk, uncloned PCR products from antibody-resistant passages indicated changes in the PB2 and PA proteins with respect to the wild type virus.

Conclusions

Each antibody-selected passage consisted of a variety of different cocirculating populations, rather than pure populations of virus able to escape antibody by changes in antibody epitopes. The ability to escape antibody is apparently due to changes in genes encoding the viral polymerase complex, probably resulting in more robust viral replication, allowing the few virus particles not completely neutralized by antibody to rapidly produce large numbers of progeny. Our data suggest that the relative success of an individual variant may depend on both its own gain and loss of fitness, as well as that of its cocirculating variants.
Melatonin reduces the severity of experimental amoebiasis
Authors: França-Botelho Aline C , França Juliana L , Oliveira Fabrício MS , Franca Eduardo L , Honório-França Adenilda C , Caliari Marcelo V , Gomes Maria A
Published: April 2011

Background

Melatonin has immunomodulatory effects but very little is known about its influence in protozoan infections, such asEntamoeba histolytica, which causes amoebiasis, a disease with significant morbidity and mortality. In this study, we evaluated the effects of exogenous melatonin interference in experimental amoebiasis and on interactions between human blood cells andE. histolyticatrophozoites.

Methods

The effect of melatonin was investigated in models of experimental amoebiasis in hamsters and rats by evaluating the area of necrosis induced byE. histolytica. The activity of melatonin on the interactions between leukocytes and amoebae was determined by examining leukophagocytosis. Forin vitrotests, polymorphonuclear and mononuclear human blood leucocytes were incubated withE. histolyticatrophozoites.

Results

The areas of amoebic necrosis were significantly reduced in animals treated with melatonin. Melatonin treatment increased leukophagocytosis but was associated with a greater number of dead amoebae.

Conclusions

These results suggest that melatonin may play a beneficial role in the control of amoebic lesions, raising the possibility that this drug may be used as an adjuvant in anti-amoebic therapy.
Silibinin induces apoptosis via calpain-dependent AIF nuclear translocation in U87MG human glioma cell death
Authors: Jeong Ji C , Shin Won Y , Kim Thae H , Kwon Chae H , Kim Jae H , Kim Yong K , Kim Ki H
Published: April 2011

Background

Silibinin, a natural polyphenolic flavonoid, has been reported to induce cell death in various cancer cell types. However, the molecular mechanism is not clearly defined. Our previous study showed that silibinin induces glioma cell death and its effect was effectively prevented by calpain inhibitor. The present study was therefore undertaken to examine the role of calpain in the silibinin-induced glioma cell death.

Methods

U87MG cells were grown on well tissue culture plates and cell viability was measured by MTT assay. ROS generation and △ψm were estimated using the fluorescence dyes. PKC activation and Bax expression were measured by Western blot analysis. AIF nuclear translocation was determined by Western blot and immunocytochemistry.

Results

Silibinin induced activation of calpain, which was blocked by EGTA and the calpain inhibitor Z-Leu-Leu-CHO. Silibinin caused ROS generation and its effect was inhibited by calpain inhibitor, the general PKC inhibitor GF 109203X, the specific PKCδ inhibitor rottlerin, and catalase. Silibinin-induce cell death was blocked by calpain inhibitor and PKC inhibitors. Silibinin-induced PKCδ activation and disruption of △ψm were prevented by the calpain inhibitor. Silibinin induced AIF nuclear translocation and its effect was prevented by calpain inhibitor. Transfection of vector expressing microRNA of AIF prevented the silibinin-induced cell death.

Conclusions

Silibinin induces apoptotic cell death through a calpain-dependent mechanism involving PKC, ROS, and AIF nuclear translocation in U87MG human glioma cells.
Comparative genome sequence analysis underscores mycoparasitism as the ancestral life style of Trichoderma
Authors: Kubicek Christian P , Herrera-Estrella Alfredo , Seidl-Seiboth Verena , Martinez Diego A , Druzhinina Irina S , Thon Michael , Zeilinger Susanne , Casas-Flores Sergio , Horwitz Benjamin A , Mukherjee Prasun K , Mukherjee Mala , Kredics László , Alcaraz Luis D , Aerts Andrea , Antal Zsuzsanna , Atanasova Lea , Cervantes-Badillo Mayte G , Challacombe Jean , Chertkov Olga , McCluskey Kevin , Coulpier Fanny , Deshpande Nandan , von Döhren Hans , Ebbole Daniel J , Esquivel-Naranjo Edgardo U , Fekete Erzsébet , Flipphi Michel , Glaser Fabian , Gómez-Rodríguez Elida Y , Gruber Sabine , Han Cliff , Henrissat Bernard , Hermosa Rosa , Hernández-Oñate Miguel , Karaffa Levente , Kosti Idit , Le Crom Stéphane , Lindquist Erika , Lucas Susan , Lübeck Mette , Lübeck Peter S , Margeot Antoine , Metz Benjamin , Misra Monica , Nevalainen Helena , Omann Markus , Packer Nicolle , Perrone Giancarlo , Uresti-Rivera Edith E , Salamov Asaf , Schmoll Monika , Seiboth Bernhard , Shapiro Harris , Sukno Serenella , Tamayo-Ramos Juan Antonio , Tisch Doris , Wiest Aric , Wilkinson Heather H , Zhang Michael , Coutinho Pedro M , Kenerley Charles M , Monte Enrique , Baker Scott E , Grigoriev Igor V
Published: April 2011

Background

Mycoparasitism, a lifestyle where one fungus is parasitic on another fungus, has special relevance when the prey is a plant pathogen, providing a strategy for biological control of pests for plant protection. Probably, the most studied biocontrol agents are species of the genusHypocrea/Trichoderma.

Results

Here we report an analysis of the genome sequences of the two biocontrol speciesTrichoderma atroviride(teleomorphHypocrea atroviridis) andTrichoderma virens(formerlyGliocladium virens, teleomorphHypocrea virens), and a comparison withTrichoderma reesei(teleomorphHypocrea jecorina). These threeTrichodermaspecies display a remarkable conservation of gene order (78 to 96%), and a lack of active mobile elements probably due to repeat-induced point mutation. Several gene families are expanded in the two mycoparasitic species relative toT. reeseior other ascomycetes, and are overrepresented in non-syntenic genome regions. A phylogenetic analysis shows thatT. reeseiandT. virensare derived relative toT. atroviride. The mycoparasitism-specific genes thus arose in a commonTrichodermaancestor but were subsequently lost inT. reesei.

Conclusions

The data offer a better understanding of mycoparasitism, and thus enforce the development of improved biocontrol strains for efficient and environmentally friendly protection of plants.