bluuebunny/crossref_metadata_2025 huggingface dataset:
In our culture, in our gender: Implications of the culture/gender interface for South African psychotherapists
Authors: Eagle Gillian , Long Carol
Published: June 2011

Debates about the relationship between culture and gender, and the potential contradictions involved in simultaneously respecting both multicultural and feminist principles and values, have occupied an important place in theoretical discussion in the social sciences and humanities. This paper examines the relationship between gender and culture from the perspective of the psychotherapeutic encounter in a multicultural society, in this case contemporary South Africa. With the help of illustrative case material involving traumatically bereaved women who became subject to cultural ascriptions of maliciousness or murderousness, and where cultural beliefs potentially jeopardized gender rights, mental health and therapeutic recovery, the article argues that the relationship between gender and culture, viewed from a therapeutic perspective, can be seen to present complex conceptual and ethical challenges for the therapist. In addition, the structural, psychological and discursive positioning of the therapist and client in respect of warrants to speak and to accept or contest cultural constructions is recognized as implicated in particular kinds of therapeutic impasses. Both clinical and political concerns are discussed in order to illustrate the intersections between the intrapsychic and the social, as well as between the personal and the political. Two related lines of theory, that of intersectionality (derived primarily from feminist theory) and of psychoanalytic theory, are proposed and juxtaposed as a productive way of thinking about instances in which the interface between gender and culture presents particular kinds of problems in the consulting room for both clients and therapists. The necessity for a particular kind of critical self, group and cultural awareness is proposed.
Toes That Look Like Toes
Authors: Hussain Sofia
Published: June 2011

When designing assistive devices for people with disabilities in developing countries, product developers tend to prioritize economic and technical requirements, ignoring aesthetic and cultural issues. This can result in devices that create or reinforce social barriers, creating negative impacts on users’ self-esteem and sense of well-being. To understand the social implications of using prosthetic legs for Cambodian children, a pilot research study was conducted in Phnom Penh and surrounding provinces. I used innovative research methods to help children share their perspectives. The objective was to help product designers develop improved assistive devices that not only increase mobility for child prosthesis users but also support the sociocultural integration of these children and their families. A philosophical hermeneutics research approach was used to seek the views of three children. The findings are useful for nongovernmental organizations and product developers that focus on the needs of impoverished children in rural, predominantly Buddhist communities.
The Clinicopathologic Spectrum of Benign Mass Lesions of the Vocal Fold due to Vocal Abuse
Authors: Cipriani Nicole A. , Martin Daniel E. , Corey Jacquelynne P. , Portugal Louis , Caballero Nadieska , Lester Rosemary , Anthony Benjamin , Taxy Jerome B.
Published: June 2011

Benign masses of the vocal fold related to phonotrauma are clinically classified into polyps, nodules, Reinke’s edema, and cysts. Despite the apparent distinctiveness of the clinical nomenclature, low inter- and intraobserver diagnostic agreement has been reported. Excepting cysts, which are epithelial lined, histologic examination of the remaining lesions has shown a variety of overlapping features insufficiently specific for the clinical diagnoses. This study reviews the clinicopathologic characteristics among these benign lesions of the vocal fold. A total of 78 nonneoplastic lesions of the vocal fold were reviewed by 2 pathologists for the presence of epithelial hyperplasia, basement membrane thickening, edema, vascular proliferation, and extracellular “amyloid-like” fibrin. In 46 cases with prebiopsy stroboscopic images, 2 otolaryngologists classified each lesion as polyp, nodule, Reinke’s edema, cyst, or other. They agreed in 43% (n = 20, 13 polyps, 5 nodules, 1 Reinke’s edema, 1 other) and disagreed in 57% (n = 26). There was no histologic feature that reliably distinguished among the lesions. In addition, reactive stromal cell atypia was present in 14 cases. Cysts were distinctive, as all were epithelial lined. The clinicopathologic classification of benign laryngeal lesions is neither clinically reproducible nor histologically unique. Treatment will continue to be individualized based on clinical judgment.
Far Away in Another Land: One Immigrant’s Story of Incest, Trauma, and Healing
Authors: Sethi Bharati
Published: June 2011

This article is a collection of performance poetry pieces that provide insight into my experiences of childhood abuse. I took refuge in Canada to escape the “patriarchal and misogynistic” sickness that imprisoned girls/women in my family for generations. Recent scholarship is just beginning to address the broader issue of trauma among immigrants and refugees as a result of preimmigration stress resulting from war, natural disasters, religious persecution, and other such horrors. However, very little is known about the violence in their family life—a private domain—pre- and postimmigration. As a child I was forbidden to “write”. So, I wrote on sand and let the waves carry my secrets to the shore. I wrote on imaginary walls. I wrote in the sky. Writing these pieces is/was an expression of my resistance against the disciplinary rules of incest. The sand, walls, and sky became a site of healing and hope.
Storytelling as Research/Research as Storytelling
Authors: Lewis Patrick J.
Published: June 2011

If story is central to human meaning why, in the research world, is there not more storytelling? Walter Benjamin (1973) noted that, “a story is different. It does not expend itself. It preserves and concentrates its strength and is capable of releasing it even after a long time” (p. 90). How might research not expend itself, but preserve and concentrate its strength?
A Typology for the Case Study in Social Science Following a Review of Definition, Discourse, and Structure
Authors: Thomas Gary
Published: June 2011

The author proposes a typology for the case study following a definition wherein various layers of classificatory principle are disaggregated. First, a clear distinction is drawn between two parts: (1) the subject of the study, which is the case itself, and (2) the object, which is the analytical frame or theory through which the subject is viewed and which the subject explicates. Beyond this distinction the case study is presented as classifiable by its purposes and the approaches adopted— principally with a distinction drawn between theory-centered and illustrative study. Beyond this, there are distinctions to be drawn among various operational structures that concern comparative versus noncomparative versions of the form and the ways that the study may employ time. The typology reveals that there are numerous valid permutations of these dimensions and many trajectories, therefore, open to the case inquirer.
Validity in Dialogic Encounters With Hermeneutic Truths
Authors: Freeman Melissa
Published: June 2011

Hermeneutic theories of interpretation are at the core of qualitative methodologies and can be identified as belonging to either epistemological or ontological philosophical orientations. Concerns about validity in qualitative research have mainly been shaped by epistemological questions. What differentiates philosophical hermeneutics, an ontological perspective, from traditional hermeneutics is its radical departure from finding a “technique” of interpretation to proposing a hermeneutic ontology, where the hermeneutic task of understanding is thought to be our very way of being in the world. Unlike traditional interpretive approaches which often seek to maximize validity by eliciting a respondent’s account of an experience in a way that closely corresponds to that experience, philosophical hermeneutical approaches assert that the meaning of the experience is uniquely configured in the dialogic encounter itself. Dialogue is thought to offer a hermeneutic valence for people’s engagement with understanding and the means of encountering truth. Understanding, therefore, cannot be conceived of as a fixing of meaning but as an event in which meaning is generated and transformed. This article considers how philosophical hermeneutics might inform qualitative research when the aim is to understand.
Chicana Transborder Vivencias and Autoherteorías: Reflections From the Field
Authors: Galván Ruth Trinidad
Published: June 2011

In this self-reflexive piece, the author shares vivencias (lived realities) of growing up transborderly between the United States and Mexico and invokes that history and experience in the crafting of theories from the field. Her narrative reveals three autoherteorías of transborder existence and research: new tribalism, convivencia (coexistence), and supervivencia (survivance). In the tradition of Anzaldúa’s work, the author finds new tribalism suggests a move beyond rigid identities to that of fluid and transborder vivencias and relationships that underscore the interconnection of people, ideas, and places. In the field, she also found that convivencia transcends the objective self—other divide and promotes transborder praxis. That is, research that is committed to the collection and production of knowledge for transformative purposes across physical and symbolic borders. Last, from a very personal space, the author rediscovers her own supervivencia and the significance of a research agenda based on people’s survivance, resiliency, and commitment to change.
Working Within and In-Between Frames: An Academic Tourist/ Midnight Robber and the Academy
Authors: Fournillier Janice B.
Published: June 2011

Having assumed the role of academic tourist/midnight robber from the Caribbean island of Trinidad and Tobago, I discover that I have never fully dealt with the emotional aspect of using academic discourses that came out of a Eurocentric frame. Academic habitus, conventions, laws, shame, guilt, and fear of the repercussions because of my dual status inhibit me. In this autoethnographic text, I make a bold move to become vulnerable as I critically explore the social, political, and cultural contexts of a dissertation culture that I experienced. I use methodological tools provided by specifically chosen tour guides, Carnival midnight robber talk, and a “layered account” to move from the outside to the inside and back out again of the experience of using academic discourses in an ethnographic study of Trinidad Carnival.
You’ll Never be More of a Man: Gay Male Masculinities in Academic Women’s Studies
Authors: Murphy Michael J.
Published: June 2011

This essay analyzes the complicated gendered landscape that academic women’s studies represents for gay male students and instructors. It uses personal experience and contemporary gender theory to explore why women’s studies is perceived to be the natural province of gay males, how gay males are interpellated as ‘‘men’’ in women’s studies, and the choices gay males face between academic feminism and popular discourses of gay rights activism. It argues that Women’s studies represents both a promising and perilous discursive space for gay males, especially those attempting to embody gender constructionist, anti-essentialist, and queer subject positions.
Heterosexual Masculinity in Contemporary Vietnam
Authors: Horton Paul , Rydstrom Helle
Published: June 2011

By drawing on ethnographic data collected in two different settings in northern Vietnam, this article considers the ways in which heterosexual masculinity is configured by younger men. The intersection between heterosexuality and masculinity, the article argues, epitomizes a site of contestations between moral ideals, expectations about gendered support, and sexual pleasures disguised as protests. In introducing into a Southeast Asian context, the Latin American term machismo, understood as an expression of male-centered privileges and the ways in which they foster men’s chauvinism against women (or other men), the article explores how local assumptions about the natural quintessential drive of male sexuality as well as a wife’s obligations to comply with his sexual needs together provide men with morally legitimized explanations for the buying of various kinds of female sexual services.
Associations of Family and Peer Experiences with Masculinity Attitude Trajectories at the Individual and Group Level in Adolescent and Young Adult Males
Authors: Marcell Arik V. , Eftim Sorina E. , Sonenstein Freya L. , Pleck Joseph H.
Published: June 2011

Data were drawn from 845 males in the National Survey of Adolescent Males who were initially aged 15-17, and followed-up 2.5 and 4.5 years later, to their early twenties. Mixed-effects regression models (MRM) and semiparametric trajectory analyses (STA) modeled patterns of change in masculinity attitudes at the individual and group levels, guided by gender intensification theory and cognitive-developmental theory. Overall, men’s masculinity attitudes became significantly less traditional between middle adolescence and early adulthood. In MRM analyses using time-varying covariates, maintaining paternal coresidence and continuing to have first sex in uncommitted heterosexual relationships were significantly associated with masculinity attitudes remaining relatively traditional. The STA modeling identified three distinct patterns of change in masculinity attitudes. A traditional-liberalizing trajectory of masculinity attitudes was most prevalent, followed by traditional-stable and nontraditional-stable trajectories. Implications for gender intensification and cognitive-developmental approaches to masculinity attitudes are discussed.
Cooking, Food, and Masculinity: Palestinian Men in Israeli Society
Authors: Gvion Liora
Published: June 2011

This article examines the relationships between food and masculinity as experienced by Palestinian men, citizens of Israel. Their preoccupation with food reveals issues of masculinity and identity via two complementary streams. By defining domestic cooking as a feminine task, Palestinian men strengthen their domination over women. Conversely, in the public sphere, men use cooking as a means of breadwinning. Their cooking intertwines with issues of identity formation and relations of domination. As restaurateurs, Palestinian men refrain from serving domestic dishes. Thus, they show respect to Palestinian women and simultaneously preserve the traditional distinctions between home food and restaurant food. They view their upholding of their culinary knowledge as a major contribution to the limited appropriation of Palestinian food into the popular Jewish culinary repertoire. Consequently, they appear as the guardians of Palestinian cuisine and culture who prevent their diffusion into Israeli culinary common knowledge.
Cognitive dysfunction and multiple sclerosis: developing a rationale for considering the efficacy of exercise training
Authors: Motl Robert W , Sandroff Brian M , Benedict Ralph HB
Published: June 2011

Cognitive impairment is a prevalent, disabling, and poorly managed consequence of multiple sclerosis (MS). This underscores the importance of considering alternative approaches, such as exercise training, for managing cognitive impairment in persons with MS. The consideration of exercise training is warranted based on evidence summarized in literature reviews and meta-analyses that (1) aerobic fitness, physical activity, and exercise training are associated with better cognitive function in older adults; and (2) exercise training has comparable effects on mobility and quality of life outcomes in older adults and persons with MS. To date, research examining aerobic fitness, physical activity, and exercise training effects on cognition in MS is nascent and mostly includes cross-sectional designs that provide preliminary evidence for a well-designed randomized controlled trial (RCT). We believe that a future RCT should adopt research methodologies and practices from gerontology when examining exercise training and cognition in MS. This will maximize the potential for successfully generating a body of knowledge on exercise training and cognition with the potential for impacting the lives of persons with MS.
Incorporation of an interferon-β neutralizing antibody assay into routine clinical practice
Authors: Farrell RA , Espasandin M , Lakdawala N , Creeke PI , Worthington V , Giovannoni G
Published: June 2011

Background: Incorporation of routine clinical testing for neutralizing antibodies (NAbs) to interferon (IFN)-β has remained problematic. With increasing treatment choice for patients, routine NAb testing should be incorporated to aid therapeutic decisions.

Objective: We sought to improve interpretation of NAb results by combining the luciferase NAb assay (luciferase gene expression assay under control of interferon-stimulated response element) and in-vivo biomarker (myxovirus A protein, MxA) induction in patients with MS.

Methods: Blood samples (serum and PAXGene® for RNA) were obtained pre-injection and 12 hours post-injection of IFN-β from 144 subjects. Sera were tested for NAbs using the luciferase assay. MxA expression was quantified by real-time polymerase chain reaction (PCR).

Results: 26% of samples were NAb positive (titre > 20 NU). There was no difference in NAb titres in the pre- or post-dose sera ( p = 0.643). MxA expression was inhibited in a dose-dependent fashion in NAb positive samples. Mean MxA level post-IFN-β: NAb negative 2330 (95% CI 1940–2719), NAb 20–99 NU 1533 (95% CI 741–2324), NAb 100–600 NU 832 (186–1478) and NAb > 600 NU 101 (95% CI 0–224). NAb titre and MxA level correlated strongly: MxA pre- (Spearman r = −0.72, p < 0.0001), MxA post- (Spearman r = −0.79, p < 0.0001) and MxA induction (Spearman r = −0.67, p = 0.0004).

Conclusion: A single, 12-hour post-injection sample should be used to test for NAbs using the luciferase assay and IFN-β bioactivity (MxA) in the clinical setting.
Party systems and human well-being
Authors: Mukherjee Nisha
Published: June 2011

This article analyses the impact of party systems on human well-being and argues that multiparty systems are associated with better welfare outcomes for two primary reasons: first, multiparty systems provide representation to multiple issue-dimensions in society, thereby indicating a more inclusive system, which ensures that diverse societal interests are taken into account during formulation of welfare policies. Second, multiparty systems also indicate a competitive party system, which provides incentives for parties to perform effectively while in office and propels parties to appeal to multiple segments of society by providing broader welfare services. The impact of party systems on human well-being is tested on a global sample of 68 democratic countries from 1975–2000. The findings show support for the hypothesized relationship between party systems and human well-being.
Multicultural citizenship within multination states
Authors: Kymlicka Will
Published: June 2011

In many western democracies today, there are calls to strengthen a sense of common citizenship as a way of building ‘social cohesion’ in increasingly diverse societies. Citizenship is to be promoted by, amongst other things, adding or strengthening citizenship education in schools, providing citizenship classes to immigrants, imposing new citizenship tests for naturalization, and holding citizenship ceremonies. In this article, I will examine this new citizenship agenda in the specific case of ‘multination’ states — that is, in states that have restructured themselves to accommodate significant sub-state nationalist movements, usually through some form of territorial devolution, consociational power-sharing, and/or official language status. What does it mean to promote a sense of common citizenship in multination states, and how does the new immigration-focused citizenship agenda relate to older debates on multinationalism? I will argue that in the particular context of multination states, these new citizenship agendas must promote a distinctly multinational conception of citizenship if they are to be fair and effective. But equally, we need to adapt familiar models of multinational citizenship to be more inclusive of immigrants. In short, if the citizenship agenda is to be effective, and to be fairly inclusive of both sub-state national groups and of immigrants, we need a more multinational conception of citizenship, and a more multicultural conception of multinationalism.
Intimate Partner Violence and Adverse Health Consequences
Authors: Black Michele C.
Published: June 2011

Nearly 1 in 4 women and 1 in 13 men experience intimate partner violence (IPV) at some time in their life. Victims of IPV suffer significant negative health consequences because of the physical, sexual, and emotional abuse they have experienced. Elevated risks have been observed for a wide range of adverse health outcomes. Research has substantially improved our understanding of the physiology that underlies the association between violence victimization and an array of adverse health outcomes. Given the high prevalence of IPV and the associated medical consequences and costs of IPV, it is critical to address this public health problem. IPV prevention and intervention can substantially decrease the public health burden of IPV and greatly improve the health of patients being seen in the medical system. Primary care and family physicians are in an ideal position to diagnose victims of IPV and provide the victims and their families the appropriate care that is needed. However, to accomplish this goal, there remains an urgent need to integrate information on IPV into medical and health care curricula, and to train future physicians and other health care providers about the pervasiveness of IPV and the far-reaching implications for patient health.
Risk and Resilience in Coping With Chronic Life Stress
Authors: Terre Lisa
Published: June 2011

This review discusses evidence-based perspectives on risk and resilience in coping with chronic life stress. Future directions for inquiry and practice also are addressed.
Sports Medicine
Authors: Saffary Roya , Chin Lawrence S. , Cantu Robert C.
Published: June 2011

An estimated 10% of head and spinal cord injuries are due to sports-related activities. As the popularity of sports increases so does the incidence of sports-related injuries. In recent years, concussion has received significant media attention as high-profile athletes have come forward to share their experiences and long-term struggles with this specific type of traumatic brain injury. Public health initiatives such as the “Heads Up: Concussion in Youth Sports” program run by the Center for Disease Control and Prevention have been developed to raise awareness regarding concussion injuries. These programs target not only athletes themselves but also include coaches, medical professionals, and parents to ensure that all individuals involved in sports, be it directly or peripherally, obtain the education required to prevent, correctly diagnose, and treat concussion. They are a testament to how elementary our understanding of concussion continues to be. They also demonstrate that misinformation and lack of awareness pose a significant obstacle to proper diagnosis and treatment. In this review, the authors discuss concussion both as a medical challenge and as a public health concern. The authors examine the definition as well as diagnostic criteria that have been agreed on during the Third International Conference on Concussion in Sport in Zurich 2008. Furthermore, current options and limitations in preventing and treating concussion are reviewed. Finally, the 2 most commonly used standardized grading systems as well as guidelines for return to play are reviewed. Overall, this article will offer health care providers and members of the general public alike the current understanding of concussion.
Nuclear factor-κB mediated lipopolysaccharide-induced mRNA expression of hepcidin in human peripheral blood leukocytes
Authors: Wu ShuiJing , Zhang Kai , Lv Chen , Wang HaiHong , Cheng BaoLi , Jin Yue , Chen QiXing , Lian QingQuan , Fang XiangMing
Published: June 2011

Hepcidin is a known key modulator of iron homeostasis and an innate immune molecule secreted by the liver. The transcriptional mechanism of hepcidin in hepatocytes during inflammation is mediated via the IL-6/STAT3 pathway. Recently, hepcidin demonstrated an anti-inflammatory function in endotoxic mice, and a TLR4-dependent inducible expression of hepcidin was detected in myeloid cells. In this study, we explored the expression and signaling mechanism regulating hepcidin mRNA expression in peripheral blood leukocytes. The mRNA levels of hepcidin in peripheral blood leukocytes from patients with severe sepsis (n = 14) was significantly higher than those in healthy controls (n = 16;0.286 ± 0.065 vs 0.068 ± 0.025; P < 0.05). Ex vivo studies found hepcidin mRNA can be highly induced by challenge of 100 ng/ml LPS or 20 ng/ml TNF-α in peripheral blood leukocytes rather than IL-6, IL-1 and IFN-γ. Anti-TNF-α antibody significantly decreased the levels of hepcidin mRNA induced by LPS. Inhibitor of nuclear factor (NF)-κB rather than that of STAT3 completely abolished the inducibility of hepcidin mRNA in PBMCs and neutrophils. These results indicate that hepcidin mRNA expression in peripheral blood leukocytes induced by LPS depends on NF-κB, and TNF-α may be a key mediator in this procedure.
Consumers’ Responses to Table Spacing in Restaurants
Authors: Robson Stephani K. A. , Kimes Sheryl E. , Becker Franklin D. , Evans Gary W.
Published: June 2011

Having adequate personal space is an important aspect of users’ comfort with their environment. In a restaurant, for instance, spatial intrusion by others can lead to avoidance responses such as early departure or a disinclination to spend. A web-based survey of more than 1,000 Americans elicited behavioral intentions and emotional responses to a projected restaurant experience when parallel dining tables were spaced at six, twelve, and twenty-four inches apart under three common dining scenarios. Respondents strongly objected to closely spaced tables in most circumstances, particularly in a “romantic” context. Not only did the respondents react negatively to tightly spaced tables but they were generally disdainful of banquette-style seating, regardless of table distance. The context of the dining experience (e.g., a business lunch, a family occasion) is likely to be a key factor in consumers’ preferences for table spacing and their subsequent behaviors. Gender was also a factor, as women were much less comfortable than men in tight quarters. The findings are clear but the implications for restaurateurs are not, because a tight table arrangement has been demonstrated to shorten the dining cycle without affecting spending. However, diners may be less likely to return to a restaurant with uncomfortable table spacing.
Innovation Geography and Regional Growth in European Union
Authors: Korres George M. , Tsobanoglou George O. , Kokkinou Aikaterini
Published: June 2011

There is a huge literature regarding the main determinants and sources of economic growth. Most of the recent work emphasizes on the role of knowledge and innovation activities typically produced by a specific sector of the economy, and on analyzing the implications and the importance for economic growth. Moreover, the socioeconomic and public policies aim to distinguish the determining factors of growth to enhance the regional cohesion and the convergence process. Much of the recent work on regional growth can be viewed as refining the basic economic insights of economic geography. This article attempts to analyze the European systems of innovation and the effects of European technological policy to regional growth.
Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines
Authors: Roy Debasmita , Sin Sang-Hoon , Damania Blossom , Dittmer Dirk P.
Published: June 2011

Primary effusion lymphoma (PEL) is a diffuse-large B-cell lymphoma with poor prognosis. One hundred percent of PELs carry the genome of Kaposi sarcoma–associated herpesvirus and a majority are coinfected with Epstein-Barr virus (EBV). We profiled genomic aberrations in PEL cells using the Affymetrix 6.0 SNP array. This identified for the first time individual genes that are altered in PEL cells. Eleven of 13 samples (85%) were deleted for the fragile site tumor suppressors WWOX and FHIT. Alterations were also observed in the DERL1, ETV1, RASA4, TPK1, TRIM56, and VPS41 genes, which are yet to be characterized for their roles in cancer. Coinfection with EBV was associated with significantly fewer gross genomic aberrations, and PEL could be segregated into EBV-positive and EBV-negative clusters on the basis of host chromosome alterations. This suggests a model in which both host genetic aberrations and the 2 viruses contribute to the PEL phenotype.
Plasmodium falciparum uses a key functional site in complement receptor type-1 for invasion of human erythrocytes
Authors: Tham Wai-Hong , Schmidt Christoph Q. , Hauhart Richard E. , Guariento Mara , Tetteh-Quarcoo Patience B. , Lopaticki Sash , Atkinson John P. , Barlow Paul N. , Cowman Alan F.
Published: June 2011

The Plasmodium falciparum adhesin PfRh4 binds to complement receptor type-1 (CR1) on human erythrocytes and mediates a glycophorin-independent invasion pathway. CR1 is a complement regulator and immune-adherence receptor on erythrocytes required for shuttling of C3b/C4b-opsonized particles to liver and spleen for phagocytosis. Using recombinant CR1 constructs, we mapped the recognition site for PfRh4 to complement control protein modules 1 to 3 (CCP1-3) at the membrane-distal amino terminus of CR1. This region of CR1 binds to C4b and C3b and accelerates decay of both classic pathway and alternative pathway C3 and C5 convertases. CCP1-3 competed for PfRh4 binding to erythroid CR1 and inhibited the PfRh4-CR1 invasion pathways across a wide range of P falciparum strains. PfRh4 did not bind significantly to other CR1 constructs, including CCP15-17, which is 85% identical to CCP1-3. PfRh4 binding to CR1 did not affect its C3b/C4b binding capability, and we show evidence for a ternary complex between CCP1-3, C4b, and PfRh4. PfRh4 binding specifically inhibited CR1's convertase decay-accelerating activity, whereas there was no effect on factor H-mediated decay-accelerating activity. These results increase our understanding of the functional implications of CR1 engagement with PfRh4 and highlight the interplay between complement regulation and infection.
Increase of nitrosative stress in patients with eosinophilic pneumonia
Authors: Furukawa Kanako , Sugiura Hisatoshi , Matsunaga Kazuto , Ichikawa Tomohiro , Koarai Akira , Hirano Tsunahiko , Yanagisawa Satoru , Minakata Yoshiaki , Akamatsu Keiichiro , Kanda Masae , Nishigai Manabu , Ichinose Masakazu
Published: June 2011

Background

Exhaled nitric oxide (NO) production is increased in asthma and reflects the degree of airway inflammation. The alveolar NO concentration (Calv) in interstitial pneumonia is reported to be increased. However, it remains unknown whether NO production is increased and nitrosative stress occurs in eosinophilic pneumonia (EP). We hypothesized that nitrosative stress markers including Calv, inducible type of NO synthase (iNOS), and 3-nitrotyrosine (3-NT), are upregulated in EP.

Methods

Exhaled NO including fractional exhaled NO (FENO) and Calv was measured in ten healthy subjects, 13 patients with idiopathic pulmonary fibrosis (IPF), and 13 patients with EP. iNOS expression and 3-NT formation were assessed by immunocytochemistory in BALf cells. The exhaled NO, lung function, and systemic inflammatory markers of the EP patients were investigated after corticosteroid treatment for 4 weeks.

Results

The Calv levels in the EP group (14.4 ± 2.0 ppb) were significantly higher than those in the healthy subjects (5.1 ± 0.6 ppb, p < 0.01) and the IPF groups (6.3 ± 0.6 ppb, p < 0.01) as well as the FENO and the corrected Calv levels (all p < 0.01). More iNOS and 3-NT positive cells were observed in the EP group compared to the healthy subject and IPF patient. The Calv levels had significant positive correlations with both iNOS (r = 0.858, p < 0.05) and 3-NT positive cells (r = 0.924, p < 0.01). Corticosteroid treatment significantly reduced both the FENO (p < 0.05) and the Calv levels (p < 0.01). The magnitude of reduction in the Calv levels had a significant positive correlation with the peripheral blood eosinophil counts (r = 0.802, p < 0.05).

Conclusions

These results suggested that excessive nitrosative stress occurred in EP and that Calv could be a marker of the disease activity.
Querying large read collections in main memory: a versatile data structure
Authors: Philippe Nicolas , Salson Mikaël , Lecroq Thierry , Léonard Martine , Commes Thérèse , Rivals Eric
Published: June 2011

Background

High Throughput Sequencing (HTS) is now heavily exploited for genome (re-) sequencing, metagenomics, epigenomics, and transcriptomics and requires different, but computer intensive bioinformatic analyses. When a reference genome is available, mapping reads on it is the first step of this analysis. Read mapping programs owe their efficiency to the use of involved genome indexing data structures, like the Burrows-Wheeler transform. Recent solutions index both the genome, and the k-mers of the reads using hash-tables to further increase efficiency and accuracy. In various contexts (e.g. assembly or transcriptome analysis), read processing requires to determine the sub-collection of reads that are related to a given sequence, which is done by searching for some k-mers in the reads. Currently, many developments have focused on genome indexing structures for read mapping, but the question of read indexing remains broadly unexplored. However, the increase in sequence throughput urges for new algorithmic solutions to query large read collections efficiently.

Results

Here, we present a solution, named Gk arrays, to index large collections of reads, an algorithm to build the structure, and procedures to query it. Once constructed, the index structure is kept in main memory and is repeatedly accessed to answer queries like "given a k-mer, get the reads containing this k-mer (once/at least once)". We compared our structure to other solutions that adapt uncompressed indexing structures designed for long texts and show that it processes queries fast, while requiring much less memory. Our structure can thus handle larger read collections. We provide examples where such queries are adapted to different types of read analysis (SNP detection, assembly, RNA-Seq).

Conclusions

Gk arrays constitute a versatile data structure that enables fast and more accurate read analysis in various contexts. The Gk arrays provide a flexible brick to design innovative programs that mine efficiently genomics, epigenomics, metagenomics, or transcriptomics reads. The Gk arrays library is available under Cecill (GPL compliant) license from http://www.atgc-montpellier.fr/ngs/.
Histone deacetylase activity is necessary for left-right patterning during vertebrate development
Authors: Carneiro Katia , Donnet Claudia , Rejtar Tomas , Karger Barry L , Barisone Gustavo A , Díaz Elva , Kortagere Sandhya , Lemire Joan M , Levin Michael
Published: June 2011

Background

Consistent asymmetry of the left-right (LR) axis is a crucial aspect of vertebrate embryogenesis. Asymmetric gene expression of the TGFβ superfamily member Nodal related 1 (Nr1) in the left lateral mesoderm plate is a highly conserved step regulating the situs of the heart and viscera. In Xenopus, movement of maternal serotonin (5HT) through gap-junctional paths at cleavage stages dictates asymmetry upstream of Nr1. However, the mechanisms linking earlier biophysical asymmetries with this transcriptional control point are not known.

Results

To understand how an early physiological gradient is transduced into a late, stable pattern of Nr1 expression we investigated epigenetic regulation during LR patterning. Embryos injected with mRNA encoding a dominant-negative of Histone Deacetylase (HDAC) lacked Nr1 expression and exhibited randomized sidedness of the heart and viscera (heterotaxia) at stage 45. Timing analysis using pharmacological blockade of HDACs implicated cleavage stages as the active period. Inhibition during these early stages was correlated with an absence of Nr1 expression at stage 21, high levels of heterotaxia at stage 45, and the deposition of the epigenetic marker H3K4me2 on the Nr1 gene. To link the epigenetic machinery to the 5HT signaling pathway, we performed a high-throughput proteomic screen for novel cytoplasmic 5HT partners associated with the epigenetic machinery. The data identified the known HDAC partner protein Mad3 as a 5HT-binding regulator. While Mad3 overexpression led to an absence of Nr1 transcription and randomized the LR axis, a mutant form of Mad3 lacking 5HT binding sites was not able to induce heterotaxia, showing that Mad3's biological activity is dependent on 5HT binding.

Conclusion

HDAC activity is a new LR determinant controlling the epigenetic state of Nr1 from early developmental stages. The HDAC binding partner Mad3 may be a new serotonin-dependent regulator of asymmetry linking early physiological asymmetries to stable changes in gene expression during organogenesis.
Balancing selection is common in the extended MHC region but most alleles with opposite risk profile for autoimmune diseases are neutrally evolving
Authors: Cagliani Rachele , Riva Stefania , Pozzoli Uberto , Fumagalli Matteo , Comi Giacomo P , Bresolin Nereo , Clerici Mario , Sironi Manuela
Published: June 2011

Background

Several susceptibility genetic variants for autoimmune diseases have been identified. A subset of these polymorphisms displays an opposite risk profile in different autoimmune conditions. This observation open interesting questions on the evolutionary forces shaping the frequency of these alleles in human populations.

We aimed at testing the hypothesis whereby balancing selection has shaped the frequency of opposite risk alleles.

Results

Since balancing selection signatures are expected to extend over short genomic portions, we focused our analyses on 11 regions carrying putative functional polymorphisms that may represent the disease variants (and the selection targets). No exceptional nucleotide diversity was observed for ZSCAN23, HLA-DMB, VARS2, PTPN22, BAT3, C6orf47, and IL10; summary statistics were consistent with evolutionary neutrality for these gene regions. Conversely, CDSN/PSORS1C1, TRIM10/TRIM40, BTNL2, and TAP2 showed extremely high nucleotide diversity and most tests rejected neutrality, suggesting the action of balancing selection. For TAP2 and BTNL2 these signatures are not secondary to linkage disequilibrium with HLA class II genes. Nonetheless, with the exception of variants in TRIM40 and CDSN, our data suggest that opposite risk SNPs are not selection targets but rather have accumulated as neutral variants.

Conclusion

Data herein indicate that balancing selection is common within the extended MHC region and involves several non-HLA loci. Yet, the evolutionary history of most SNPs with an opposite effect for autoimmune diseases is consistent with evolutionary neutrality. We suggest that variants with an opposite effect on autoimmune diseases should not be considered a distinct class of disease alleles from the evolutionary perspective and, in a few cases, the opposite effect on distinct diseases may derive from complex haplotype structures in regions with high genetic diversity.
Implication of next-generation sequencing on association studies
Authors: Siu Hoicheong , Zhu Yun , Jin Li , Xiong Momiao
Published: June 2011

Background

Next-generation sequencing technologies can effectively detect the entire spectrum of genomic variation and provide a powerful tool for systematic exploration of the universe of common, low frequency and rare variants in the entire genome. However, the current paradigm for genome-wide association studies (GWAS) is to catalogue and genotype common variants (5% < MAF). The methods and study design for testing the association of low frequency (0.5% < MAF ≤ 5%) and rare variation (MAF ≤ 0.5%) have not been thoroughly investigated. The 1000 Genomes Project represents one such endeavour to characterize the human genetic variation pattern at the MAF = 1% level as a foundation for association studies. In this report, we explore different strategies and study designs for the near future GWAS in the post-era, based on both low coverage pilot data and exon pilot data in 1000 Genomes Project.

Results

We investigated the linkage disequilibrium (LD) pattern among common and low frequency SNPs and its implication for association studies. We found that the LD between low frequency alleles and low frequency alleles, and low frequency alleles and common alleles are much weaker than the LD between common and common alleles. We examined various tagging designs with and without statistical imputation approaches and compare their power against de novo resequencing in mapping causal variants under various disease models. We used the low coverage pilot data which contain ~14 M SNPs as a hypothetical genotype-array platform (Pilot 14 M) to interrogate its impact on the selection of tag SNPs, mapping coverage and power of association tests. We found that even after imputation we still observed 45.4% of low frequency SNPs which were untaggable and only 67.7% of the low frequency variation was covered by the Pilot 14 M array.

Conclusions

This suggested GWAS based on SNP arrays would be ill-suited for association studies of low frequency variation.
Functional characterization of an alkaline exonuclease and single strand annealing protein from the SXT genetic element of Vibrio cholerae
Authors: Chen Wen-yang , Ho John WS , Huang Jian-dong , Watt Rory M
Published: June 2011

Background

SXT is an integrating conjugative element (ICE) originally isolated from Vibrio cholerae, the bacterial pathogen that causes cholera. It houses multiple antibiotic and heavy metal resistance genes on its ca. 100 kb circular double stranded DNA (dsDNA) genome, and functions as an effective vehicle for the horizontal transfer of resistance genes within susceptible bacterial populations. Here, we characterize the activities of an alkaline exonuclease (S066, SXT-Exo) and single strand annealing protein (S065, SXT-Bet) encoded on the SXT genetic element, which share significant sequence homology with Exo and Bet from bacteriophage lambda, respectively.

Results

SXT-Exo has the ability to degrade both linear dsDNA and single stranded DNA (ssDNA) molecules, but has no detectable endonuclease or nicking activities. Adopting a stable trimeric arrangement in solution, the exonuclease activities of SXT-Exo are optimal at pH 8.2 and essentially require Mn2+ or Mg2+ ions. Similar to lambda-Exo, SXT-Exo hydrolyzes dsDNA with 5'- to 3'-polarity in a highly processive manner, and digests DNA substrates with 5'-phosphorylated termini significantly more effectively than those lacking 5'-phosphate groups. Notably, the dsDNA exonuclease activities of both SXT-Exo and lambda-Exo are stimulated by the addition of lambda-Bet, SXT-Bet or a single strand DNA binding protein encoded on the SXT genetic element (S064, SXT-Ssb). When co-expressed in E. coli cells, SXT-Bet and SXT-Exo mediate homologous recombination between a PCR-generated dsDNA fragment and the chromosome, analogous to RecET and lambda-Bet/Exo.

Conclusions

The activities of the SXT-Exo protein are consistent with it having the ability to resect the ends of linearized dsDNA molecules, forming partially ssDNA substrates for the partnering SXT-Bet single strand annealing protein. As such, SXT-Exo and SXT-Bet may function together to repair or process SXT genetic elements within infected V. cholerae cells, through facilitating homologous DNA recombination events. The results presented here significantly extend our general understanding of the properties and activities of alkaline exonuclease and single strand annealing proteins of viral/bacteriophage origin, and will assist the rational development of bacterial recombineering systems.
Infection control in delivery care units, Gujarat state, India: A needs assessment
Authors: Mehta Rajesh , Mavalankar Dileep V , Ramani KV , Sharma Sheetal , Hussein Julia
Published: June 2011

Background

Increasingly, women in India attend health facilities for childbirth, partly due to incentives paid under government programs. Increased use of health facilities can alleviate the risks of infections contracted in unhygienic home deliveries, but poor infection control practices in labour and delivery units also cause puerperal sepsis and other infections of childbirth. A needs assessment was conducted to provide information on procedures and practices related to infection control in labour and delivery units in Gujarat state, India.

Methods

Twenty health care facilities, including private and public primary health centres and referral hospitals, were sampled from two districts in Gujarat state, India. Three pre-tested tools for interviewing and for observation were used. Data collection was based on existing infection control guidelines for clean practices, clean equipment, clean environment and availability of diagnostics and treatment. The study was carried out from April to May 2009.

Results

Seventy percent of respondents said that standard infection control procedures were followed, but a written procedure was only available in 5% of facilities. Alcohol rubs were not used for hand cleaning and surgical gloves were reused in over 70% of facilities, especially for vaginal examinations in the labour room. Most types of equipment and supplies were available but a third of facilities did not have wash basins with "hands-free" taps. Only 15% of facilities reported that wiping of surfaces was done immediately after each delivery in labour rooms. Blood culture services were available in 25% of facilities and antibiotics are widely given to women after normal delivery. A few facilities had data on infections and reported rates of 3% to 5%.

Conclusions

This study of current infection control procedures and practices during labour and delivery in health facilities in Gujarat revealed a need for improved information systems, protocols and procedures, and for training and research. Simply incentivizing the behaviour of women to use health facilities for childbirth via government schemes may not guarantee safe delivery.