bluuebunny/crossref_metadata_2025 huggingface dataset:
Legislation, Political Context, and Interest Group Behavior
Authors: Dusso Aaron
Published: October 2008

It is well documented that the number of interest groups lobbying a piece of legislation in Congress varies greatly. While most legislation generates little to no activity, the number of groups interested in a bill can grow into the hundreds. The challenge for scholars is to explain these behavioral differences. Using a population ecology approach to explain interest-group populations, it is argued that the number of groups lobbying a bill is influenced by the political context. Using data generated by the Lobbying Disclosure Act, this article demonstrates how the actions of members of Congress can both stimulate and suppress lobbying activity.
The Prevalence of Methylenetetrahydrofolate Reductase 677 C-T, Factor V 1691 G-A, and Prothrombin 20210 G-A Mutations in Healthy Populations in Sétif, Algeria
Authors: Bourouba Romyla , Houcher Bakhouche , Djabi Farida , Eğin Yonca , Akar Nejat
Published: October 2008

The polymorphic mutation 677 C-T in the methylenetetrahydrofolate reductase (MTHFR) gene presents a heterogeneous worldwide distribution and is associated with different disorders such as cardiovascular disease. Its frequency shows great ethnic and geographic variations. The aim of this work is to determine the frequency of MTHFR 677 C-T and coexistence of MTHFR 677 C-T with 2 other common, hereditary thrombophilia causes—namely, factor V 1691 G-A and prothrombin (PT) 20210 G-A mutation—in the Sétif region of Algeria. The study involved 147 apparently healthy participants (82 men and 65 women). Genotyping was carried out by a real-time polymerase chain reaction. The MTHFR 677T carrier frequency was found to be 54.4% (80/147); 59 individuals were heterozygous (40.1%), and 21 were homozygous (14.3%). The frequency of MTHFR 677T was found to be 34.3%. Among the 147 individuals, 3 (2.0%) had factor V Leiden, and 5 (3.4%) had PT 20210 A mutation. Of the 80 participants with MTHFR 677T mutation, 2 had heterozygote factor V 1691 G-A gene mutation, and 4 had heterozygote PT 20210 G-A gene mutation. The results showed that MTHFR 677T prevalence is quite high: an allelic frequency of 34.3% with a genotype frequency of 14.3%. Factor V 1691 G-A and PT 20210 G-A gene mutations are rare in the healthy population of the Sétif region of Algeria.
Successful Use of Danaparoid in Two Pregnant Women With Heart Valve Prosthesis and Heparin-Induced Thrombocytopenia Type II (HIT)
Authors: Gerhardt Andrea , Scharf Rüdiger E. , Zotz Rainer B.
Published: October 2008

Anticoagulant therapy with heparin for the prevention of thromboembolism in pregnant women with prosthetic heart valves is associated with an increased risk to the mother and/or the fetus. A life-threatening complication of the therapy with heparin is heparin-induced thrombocytopenia type II (HIT). danaparoid has not yet been reported to be safe and effective for this indication. This study reports on a 26-year-old woman with tricuspidal valve prosthesis and a 37-year-old woman with a St. Jude Medical mitral valve prosthesis who were anticoagulated with danaparoid during pregnancy because of HIT. Anti-Xa levels were between 0.6 and 1.2 IU/mL during pregnancy with target levels of 1.0 IU/mL. Cesarean section was performed at anti-Xa levels of 0.3 and 0.7 IU/mL. One woman developed a placental hematoma at the 32nd week of gestation, which did not increase over the following week. Both patients delivered healthy boys. Heparin-induced thrombocytopenia in pregnant women with prosthetic heart valve can be successfully managed with danaparoid.
Right Atrial Appendage: Forgotten Part of the Heart in Atrial Fibrillation
Authors: Ozer Orhan , Sari Ibrahim , Davutoglu Vedat
Published: October 2008

Atrial fibrillation (AF) is the most common clinically encountered arrhythmia in adults. Because it is associated with an increased risk of atrial thrombus formation and embolism, medical and/or electrical cardioversion is the preferred treatment method in the majority of clinics. Thrombus formation in the setting of AF most commonly occurs in the left atrial appendage (LAA), left atrium (LA), right atrial appendage (RAA), and right atrium in decreasing frequency. In routine transesophageal echocardiographic evaluation for AF, examination is generally limited to LA and LAA. Although relatively rare when compared with the left side, RAA thrombus has also the potential of embolism and should be screened. A case of RAA thrombus in which the LA and LAA were spared is described. The authors aimed to underline the importance of this rare but potentially dangerous complication of AF.
Effects of Antithrombin III in Patients With Disseminated Intravascular Coagulation Diagnosed by Newly Developed Diagnostic Criteria for Critical Illness
Authors: Sawamura Atsushi , Gando Satoshi , Hayakawa Mineji , Hoshino Hirokatsu , Kubota Nobuhiko , Sugano Masahiro
Published: October 2008

A study was conducted to test the hypotheses that antithrombin III (antithrombin) improves disseminated intravascular coagulation (DIC) when applied to DIC patients diagnosed by sensitive criteria and that the administration of high-dose antithrombin is a beneficial treatment for DIC. Twenty-three DIC patients diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC diagnostic criteria were treated with either high-dose (60 IU/kg/day) or low-dose (30 IU/kg/day) antithrombin concentrates for 3 days. The clinical conditions that cause DIC were restricted to systemic inflammatory response syndrome (SIRS) and sepsis. Data of antithrombin activity, platelet counts, coagulation and fibrinolytic markers, and DIC scores before antithrombin administration (day 0), on days 1 to 3, and on day 7 were retrospectively collected from computer-based records. Patients who met the JAAM DIC criteria were administered either high-dose (12 patients) or low-dose (11 patients) antithrombin. The patients’ backgrounds and antithrombin activity (high dose, 51.5 ± 14.5%; low dose, 62.6 ± 19.3%; P = .153) on day 0 were identical in the 2 groups. The JAAM DIC score and prothrombin time ratio on day 7 significantly improved when compared with those on day 0. However, mortality at 28 days as well as interaction within the antithrombin doses administered showed no difference. There were also no differences in the time course of the platelet counts, coagulation and fibrinolytic markers, and DIC scores in the 2 groups. The authors conclude that the effects of antithrombin on prognosis and coagulation and fibrinolytic parameters are independent of the doses administered in patients with SIRS/sepsis-associated DIC.
Relationship Between Functional Promoter Polymorphism in the XBP1 Gene (-116C/G) and Obesity
Authors: Yilmaz Erkan , Berberoglu Merih , Akar Nejat
Published: October 2008

Endoplasmic reticulum stress is a central feature of obesity, insulin resistance, and type 2 diabetes. A polymorphism of the XBP1 gene (-116C/G), a transcription factor that modulates the endoplasmic reticulum stress response, causes an impairment of its positive feedback system. The authors examined a role of the polymorphism in the development of obesity. The polymorphism was investigated in clinically obese children and compared with controls. Significant difference of genotype distribution was observed, which suggested that the -116C/G genotype may be a risk factor for at least pediatric obesity.
Thrombotic Thrombocytopenic Purpura and Sickle Cell Crisis
Authors: Shelat Suresh G.
Published: October 2008

Described is a case of acute chest syndrome in a sickle-cell patient (hemoglobin SS) who also developed signs and symptoms of thrombotic thrombocytopenic purpura, including thrombocytopenia and hemolysis (anemia, elevated lactate dehydrogenase, presence of schistocytes, dark-colored plasma, and elevations in nucleated red blood cells). The ADAMTS13 activity level was normal. Discussed are the diagnosis and therapeutic management issues and the challenges of differentiating the vasoocclusive and hemolytic complications of sickling red blood cells from the thrombotic microangiopathy of thrombotic thrombocytopenic purpura.
Use and Feasibility of Telemedicine Technology in the Dissemination of Parent-Child Interaction Therapy
Authors: Funderburk Beverly W. , Ware Lisa M. , Altshuler Elizabeth , Chaffin Mark
Published: October 2008

This brief report discusses the use and feasibility of telemedicine technology in the dissemination of Parent-Child Interaction Therapy (PCIT). PCIT is an empirically supported behavioral parent training program for reducing disruptive behavior in young children and for reducing future rates of child physical abuse. The positive impact PCIT has demonstrated in reducing child maltreatment has galvanized interest in widespread dissemination of the PCIT model into child service systems. PCIT has traditionally been taught in university-based training programs in a mentored cotherapy model. By contrast, in field settings, PCIT training typically consists of workshop training supplemented by a period of telephone consultation (PC). Given concerns with the level of practitioner competency and fidelity yielded by the PC model, PCIT training programs have begun to examine Internet-based telemedicine technology to deliver live, mentored PCIT training to trainees at remote locations (Remote Real-Time or RRT) to better approximate the university-based training model. Challenges of disseminating evidence-based practices are discussed, using PCIT as a model of how these challenges are being addressed by telemedicine technology.
Commentary on Using New Technologies in the Child Maltreatment Field
Authors: Saunders Benjamin E.
Published: October 2008

The articles in this special issue describe how different types of technology can be applied in the child maltreatment field to improve activities. This commentary suggests that though new technology does not necessarily make for better content, it does create exciting new possibilities that creative minds can use to advance the field. The projects described in this issue are examples of such creativity and give a glimpse of the future. However, advances in technology applications do not come without some cost and some loss. Technological approaches may reduce human interaction and result in the loss of its intangible benefits. The commentary suggests that the child maltreatment field appears ripe for broad-based application of technology in three areas: web-based professional training, self-directed interventions and prevention programs, and use of social networking technology. Finally, ideas are proposed for understanding the true cost of developing, implementing, and maintaining technological applications.
A Neophyte About Online Teaching
Authors: Lee Karen V.
Published: October 2008

The following autoethnography reflects a neophyte instructor's obsession with teaching an online graduate course. The experience forces her to move ethnographically forward and backward with students in a novel, and sometimes, more intimate fashion. She struggles to balance a serving of technology with a dollop of human interaction, but finds online teaching can be time consuming. Though students are physically dispersed and isolated, they sustain and bond in new and different ways in an online community. Her narrative reveals how technologies are created, apprehended, and used in everyday life. Online learning has become ubiquitous at all levels of education. Teachers and students need to question whether technology in their lives represents a force for good or evil. In the end, autoethnography becomes trans-formative as the author gains a heightened awareness of the social, cultural, and personal influences shaping her online teaching experience.
Where the Interaction Is
Authors: Tutt Dylan
Published: October 2008

This article presents three ethnographic tales of interactions with living room media to help recreate the experience of significant moments in time, of affective encounters at the interface in which there is a collision or confusion of situated and virtual worlds. It draws on a year-long video ethnography of the practice and performance of everyday interactions with living room media. By studying situated activity and the lived practice of (new) media, rather than taking an exclusive focus on the virtual as a detached space, this ethnographic work demonstrates how the situated and mediated clash, or are crafted into complex emotional encounters during everyday living room life.
An Ethnography of Everyday Caring for the Living, the Dying, and the Dead
Authors: McGibbon Elizabeth , Peter Elizabeth
Published: October 2008

Technology has become synonymous with medical intervention, particularly in hospital settings in the Western world. Much money is spent on the invention, design, and implementation of biomedical technologies. Yet there is little analysis of how the implementation of these technologies unfolds in an everyday or every night context. This article illustrates how ethnographic practices may be used to study everyday caring for the living, the dying, and the dead for organ donation. The description of the social organization of technological practices includes the first author's stories and field reflections and the stories of participants in interviews and conversations in the field. Using ethnographic practice as a reference point, a biomedical technographic approach to illuminate the human—technology relationship in a world of techno-intervention is described. Emphasis is placed on the urgent need for development of a biomedical technography and for social change to address biomedical dominance.
From My Narrative Inheritance to Their Own Narratives
Authors: Goodall Harold Lloyd
Published: October 2008

These comments provide a brief introduction to and framework for this special issue honoring and commenting on the author's memoir: A Need to Know: The Clandestine History of a CIA Family. By locating his narrative within scholarship dedicated to family secrecy and to cultural histories of the cold war and war on terror, the author connects the long term consequences of growing up in a family marked by secrecy and fear to the long term consequences of a people living under conditions of an enduring war marked by a culture of secrecy and fear.
Do We Need to Know?
Authors: Ellis Carolyn
Published: October 2008

Playing off Goodall's title, A Need to Know, this author asks the question, “Do We Need to Know?” She views Goodall's book as a double spy story, one in which Buddy plays the role of an ethnographic spy who investigates his father's career as a CIA spy. Goodall's revelations about his family secrets prompt her to consider and raise issues about her own family secrets, for example, her role in contributing to and maintaining the mystery, the ramifications of the secrets her family failed to keep as well as the ones they kept, the influence of time and events on the perception of secrets, and how one decides the ethical dimensions and costs and rewards of telling and not telling.
Buddy Goodall's A Need to Know and the Long Road From the Cold War to the War on Terrorism
Authors: Hartnett Stephen John
Published: October 2008

This short article is the text of a speech offered as part of a public tribute to Buddy Goodall's A Need to Know; as the text of a speech offered before friends and colleagues, it employs colorful language not usually found in academic publications. The speech/essay pursues three arguments, one regarding questions of silence and decorum, one about the personal damage caused by state repression, and one criticizing Goodall's cavalier comments (apparently) endorsing George Bush's bungled war on terrorism.
Friend and Foe? Technology in a Collaborative Writing Group
Authors: Sakellariadis Artemi , Chromy Sam , Martin Viv , Speedy Jane , Trahar Sheila , Williams Susan , Wilson Sue
Published: October 2008

This is a partial account of the journey undertaken by a group of academic nomads in search of collaborative writing space. Never intending to permanently settle anywhere, we chose to explore writing technologies that supported collaborative forms of engagement with our task and with each other. Along the way we took up with, and discarded, a variety of writing technologies. Reflecting teamwork and collective biography practices sustained our work and our commitments towards collaboration. Although we have not found any electronic technologies helpful in creating or maintaining our sense of community, they enabled collective ways of re-presenting our work to ourselves and, later, to others. Twenty of us set out and twelve* remain on this journey. The current text includes three voices, each woven from writings and silences of many members of our group, thereby including traces of us all. The text explores our relationship with electronic technology and its role in our collaborative writing venture.
Mad Cows, Regional Governance, and Urban Sprawl
Authors: Ghitter Geoff , Smart Alan
Published: October 2008

History matters. Inspired by evolutionary approaches in economics and, more recently, economic geography, the authors present, through the lens of a slaughterhouse development on the city's fringe, a historical model of urban development in the metropolitan region of Calgary, Canada. Their analysis shows how an unanticipated system shock conditioned by strong historical differences in the political and economic aspirations of adjacent urban and rural jurisdictions manifested at multiple temporal and spatial scales. Their narrative explores the intertwined evolutionary trajectories of five key system elements whose pathways converged in 2004, resulting in unintended, and from a regional environmental perspective, undesirable, consequences.
The Interaction Between Genetic Risk and Childhood Sexual Abuse in the Prediction of Adolescent Violent Behavior
Authors: Beaver Kevin M.
Published: October 2008

A rich line of empirical research has indicated that antisocial behaviors are the result of genetic factors and environmental factors working interactively. The current study uses this knowledge base as a springboard to examine the effects of childhood sexual abuse and genetic risk in the prediction of adolescent violent delinquency. To address this issue, data from the National Longitudinal Study of Adolescent Health were analyzed. The results of the analyses reveal that childhood sexual abuse interacts with genetic risk to predict involvement in violent delinquency for males. The effects of childhood sexual abuse and genetic risk as well as the interaction between the two are unrelated to violent delinquency for females. Implications of the study are discussed.
Long-Term Predictive Validity of the Risk Matrix 2000
Authors: Kingston Drew A. , Yates Pamela M. , Firestone Philip , Babchishin Kelly , Bradford John M.
Published: October 2008

The purpose of this study is to examine the predictive accuracy of the Risk Matrix 2000 on an independent sample of 351 sexual offenders, followed in the community for an average duration of 11.4 years (range 0-20 years, SD = 4.4 years). For comparison purposes, this study also examines the predictive accuracy of two other risk assessment instruments, specifically modified versions of the Static-99 and the Sex Offender Risk Appraisal Guide (SORAG). Results indicate that the Risk Matrix 2000 demonstrates convergent validity by correlating with the other risk assessment instruments. Moreover, the Risk Matrix 2000 is predictive of recidivism above chance levels, exhibiting medium to large effect sizes, although in general, the other two instruments, particularly the SORAG, are superior. Results also indicate differences in predictive validity when comparing 2-year, 5-year, and variable follow-up periods. Finally, a cumulative meta-analysis compares and integrates current findings with those obtained from the accumulation of previous studies, and new cumulative estimates are provided.
Using Critical Praxis to Understand and Teach Teamwork
Authors: Seibold David R. , Kang Paul
Published: October 2008

The authors pursue three aims in this article. The first is to underscore critical praxis as an especially valuable approach to understanding and enabling teamwork. The second is to offer four dimensions of teamwork—vision, roles, processes, and relationships— as salient areas to interrogate using critical praxis. The third aim is to consider the implications and methods for teaching teamwork in the classroom context. In the process of doing so, the authors highlight limitations of prevailing theoretical approaches and note changes in their own practice of teaching and facilitating teamwork that have occurred through a commitment to critical praxis.
The Effect of a Senior Jazz Dance Class on Static Balance in Healthy Women Over 50 Years of Age: A Pilot Study
Authors: Wallmann Harvey W. , Gillis Carrie B. , Alpert Patricia T. , Miller Sally K.
Published: October 2008

The purpose of this pilot study is to assess the impact of a senior jazz dance class on static balance for healthy women over 50 years of age using the NeuroCom Smart Balance Master System (Balance Master). A total of 12 healthy women aged 54—88 years completed a 15-week jazz dance class which they attended 1 time per week for 90 min per class. Balance data were collected using the Sensory Organization Test (SOT) at baseline (pre), at 7 weeks (mid), and after 15 weeks (post). An equilibrium score measuring postural sway was calculated for each of six different conditions. The composite equilibrium score (all six conditions integrated to 1 score) was used as an overall measure of balance. Repeated measures analyses of variance (ANOVAs) were used to compare the means of each participant's SOT composite equilibrium score in addition to the equilibrium score for each individual condition (1—6) across the 3 time points (pre, mid, post). There was a statistically significant difference among the means, p < .0005. Pairwise (Bonferroni) post hoc analyses revealed the following statistically significant findings for SOT composite equilibrium scores for the pre (67.33 + 10.43), mid (75.25 + 6.97), and post (79.00 + 4.97) measurements: premid (p = .008); prepost (p < .0005); midpost (p = .033). In addition, correlational statistics were used to determine any relationship between SOT scores and age. Results indicated that administration of a 15-week jazz dance class 1 time per week was beneficial in improving static balance as measured by the Balance Master SOT.
Institutional Economics and Human Resource Development
Authors: Wang Greg G. , Dobbs Rita L.
Published: October 2008

The problem and the solution. Institutional economics has long been associated with economic and training behaviors in organizations since the 1950s. Human resource development (HRD) scholars have not been adequately exposed to the relevant theories for its foundational role and direct applicability to HRD research and practice. In an effort to properly understand economics as a foundation of HRD, this article presents institutional economic theories and models pertinent to HRD research and practices. By examining institutional school of contemporary economics, especially the internal labor market theory, it is shown that economic theories not only provide a foundation but also have important implications to research and analytical approaches to the field of HRD.
The Role of Candidate Choice in the California Recall Election
Authors: McGhee Eric , Baldassare Mark
Published: October 2008

Many have argued that the reelection and later recall of Governor Gray Davis in California serves as a perfect example of how primaries draw politics to the extremes by nominating candidates too liberal or conservative for the general electorate. Davis defeated a conservative Republican opponent in his reelection campaign, only to lose in the recall just one year later when there were no primaries to prevent a moderate Republican from running. We test this notion with survey data from both elections. We find that the choice of candidates was important to votes in each election, but evaluations of Davis were far more significant and largely determined the outcome. We conclude with implications for the role of primaries in American politics generally.
Ethics and the Broader Rethinking/Reconceptualization of Research as Construct
Authors: Lincoln Yvonna S. , Cannella Gaile S.
Published: October 2008

The focus of this article is the conceptualization of a critical anticolonial social science that places ethics and concern for others at the forefront, while at the same time challenges the will to know others that so dominates social science research as construct. The authors propose that research examine and challenge social systems, support struggles for social justice, and construct a nonviolent revolutionary ethical consciousness.
GATA-2 regulates granulocyte-macrophage progenitor cell function
Authors: Rodrigues Neil P. , Boyd Ashleigh S. , Fugazza Cristina , May Gillian E. , Guo YanPing , Tipping Alex J. , Scadden David T. , Vyas Paresh , Enver Tariq
Published: October 2008

The zinc finger transcription factor GATA-2 has been implicated in the regulation of hematopoietic stem cells. Herein, we explored the role of GATA-2 as a candidate regulator of the hematopoietic progenitor cell compartment. We showed that bone marrow from GATA-2 heterozygote (GATA-2+/−) mice displayed attenuated granulocyte-macrophage progenitor function in colony-forming cell (CFC) and serial replating CFC assays. This defect was mapped to the Lin−CD117+Sca-1−CD34+CD16/32high granulocyte-macrophage progenitor (GMP) compartment of GATA-2+/− marrow, which was reduced in size and functionally impaired in CFC assays and competitive transplantation. Similar functional impairments were obtained using a RNA interference approach to stably knockdown GATA-2 in wild-type GMP. Although apoptosis and cell-cycle distribution remained unperturbed in GATA-2+/− GMP, quiescent cells from GATA-2+/− GMP exhibited altered functionality. Gene expression analysis showed attenuated expression of HES-1 mRNA in GATA-2–deficient GMP. Binding of GATA-2 to the HES-1 locus was detected in the myeloid progenitor cell line 32Dcl3, and enforced expression of HES-1 expression in GATA-2+/− GMP rectified the functional defect, suggesting that GATA-2 regulates myeloid progenitor function through HES-1. These data collectively point to GATA-2 as a novel, pivotal determinant of GMP cell fate.
Extracellular ligation-dependent CD45RB enzymatic activity negatively regulates lipid raft signal transduction
Authors: Parikh Kaushal , Poppema Sibrand , Peppelenbosch Maikel P. , Visser Lydia
Published: October 2008

CD45 is the most prominent membrane protein on lymphocytes. The function and regulation of this protein tyrosine phosphatase remain largely obscure, mainly because of the lack of a known ligand, and it still remains unknown whether such tyrosine phosphatases are subject to extracellular control at all. We report that an anti-CD45RB antibody (Ab) that prevents rejection and induces tolerance activates CD45RB tyrosine phosphatase enzymatic activity in T lymphocytes, allowing us to directly monitor the effects of increased CD45RB activity on signal transduction. Using both kinase substrate peptide arrays as well as conventional biochemistry, we also provide evidence of the various kinases involved in bringing about the inhibitory effect of this Ab on CD3-induced T-cell receptor signaling. Furthermore, we report that activated CD45RB translocates to lipid rafts and interferes with lipid raft localization and activation state of CD45 substrate Lck. Thus, these findings indeed prove that CD45 is subject to extracellular control and also define a novel mechanism by which receptor tyrosine phosphatases control lymphocyte biology and provide further insight into the intracellular signaling pathways effected by anti-CD45RB monoclonal Ab treatment.
Cell adhesion through αV-containing integrins is required for efficient HIV-1 infection in macrophages
Authors: Ballana Ester , Pauls Eduardo , Senserrich Jordi , Clotet Bonaventura , Perron-Sierra Françoise , Tucker Gordon C. , Esté José A.
Published: October 2008

Monocytes and macrophages are an important reservoir of human immunodeficiency virus (HIV) and may represent the largest reservoir of this virus in tissues. Differentiation of monocytes into macrophages leads to cell attachment and susceptibility to infection and replication of HIV. Among other cell-surface molecules, integrins are overexpressed during monocyte-macrophage differentiation and may play a role in the replication cycle of envelope viruses including HIV. Here, we show that inhibition of αV integrin in monocyte-derived macrophages, by RNA interference or their inhibition by a selective small heterocyclic RGD-mimetic nonpeptide compound, inhibited the replication of HIV in the absence of cytotoxicity. Interference or inhibition of αV integrins triggered a signal transduction pathway, leading to down-regulation of nuclear factor-κB–dependent HIV-1 transcription. Such inhibition was mediated by a MAP-kinase signaling cascade, probably involving ERK1/2, p38-mitogen–activated protein kinases, and HSP27. In conclusion, our results reveal a significant role of integrin αV-mediated adhesion in HIV-1 infection of macrophages.
Group IVA cytosolic phospholipase A2 (cPLA2α) and integrin αIIbβ3 reinforce each other's functions during αIIbβ3 signaling in platelets
Authors: Prévost Nicolas , Mitsios John V. , Kato Hisashi , Burke John E. , Dennis Edward A. , Shimizu Takao , Shattil Sanford J.
Published: October 2008

Group IVA cytosolic phospholipase A2 (cPLA2α) catalyzes release of arachidonic acid from glycerophospholipids, leading to thromboxane A2 (TxA2) production. Some platelet agonists stimulate cPLA2α, but others require fibrinogen binding to αIIbβ3 to elicit TxA2. Therefore, relationships between cPLA2α and αIIbβ3 were examined. cPLA2α and a cPLA2α binding partner, vimentin, coimmunoprecipitated with αIIbβ3 from platelets, independent of fibrinogen binding. Studies with purified proteins and with recombinant proteins expressed in CHO cells determined that the interaction between cPLA2α and αIIbβ3 was indirect and was dependent on the αIIb and β3 cytoplasmic tails. Fibrinogen binding to αIIbβ3 caused an increase in integrin-associated cPLA2α activity in normal platelets, but not in cPLA2α-deficient mouse platelets or in human platelets treated with pyrrophenone, a cPLA2α inhibitor. cPLA2α activation downstream of αIIbβ3 had functional consequences for platelets in that it was required for fibrinogen-dependent recruitment of activated protein kinase Cβ to the αIIbβ3 complex and for platelet spreading. Thus, cPLA2α and αIIbβ3 interact to reinforce each other's functions during αIIbβ3 signaling. This provides a plausible explanation for the role of αIIbβ3 in TxA2 formation and in the defective hemostatic function of mouse or human platelets deficient in cPLA2α.
A genome-wide scan for quantitative trait loci affecting limb bone lengths and areal bone mineral density of the distal femur in a White Duroc × Erhualian F2 population
Authors: Mao Huirong , Guo Yuanmei , Yang Guangcheng , Yang Bin , Ren Jun , Liu Sanfeng , Ai Huashui , Ma Junwu , Brenig Bertram , Huang Lusheng
Published: October 2008

Background

Limb bone lengths and bone mineral density (BMD) have been used to assess the bone growth and the risk of bone fractures in pigs, respectively. It has been suggested that limb bone lengths and BMD are under genetic control. However, the knowledge about the genetic basis of the limb bone lengths and mineralisatinon is limited in pigs. The aim of this study was to identify quantitative trait loci (QTL) affecting limb bone lengths and BMD of the distal femur in a White Duroc × Erhualian resource population.

Results

Limb bone lengths and femoral bone mineral density (fBMD) were measured in a total of 1021 and 116 F2 animals, respectively. There were strong positive correlations among the lengths of limb bones and medium positive correlations between the lengths of limb bones and fBMD. A whole-genome scan involving 183 microsatellite markers across the pig genome revealed 35 QTL for the limb bone lengths and 2 for femoral BMD. The most significant QTL for the lengths of five limb bones were mapped on two chromosomes affecting all 5 limb bones traits. One was detected around 57 cM on pig chromosome (SSC) 7 with the largest F-value of more than 26 and 95% confidence intervals of less than 5 cM, providing a crucial start point to identify the causal genes for these traits. The Erhualian alleles were associated with longer limb bones. The other was located on SSCX with a peak at 50–53 cM, whereas alleles from the White Duroc breed increased the bone length. Many QTL identified are homologous to the human genomic regions containing QTL for bone-related traits and a list of interesting candidate genes.

Conclusion

This study detected the QTL for the lengths of scapula, ulna, humerus and tibia and fBMD in the pig for the first time. Moreover, several new QTL for the pig femoral length were found. As correlated traits, QTL for the lengths of five limb bones were mainly located in the same genomic regions. The most promising QTL for the lengths of five limb bones on SSC7 merits further investigation.
Deciphering the genetic basis for polyketide variation among mycobacteria producing mycolactones
Authors: Pidot Sacha J , Hong Hui , Seemann Torsten , Porter Jessica L , Yip Marcus J , Men Artem , Johnson Matthew , Wilson Peter , Davies John K , Leadlay Peter F , Stinear Timothy P
Published: October 2008

Background

Mycolactones are immunosuppressive and cytotoxic polyketides, comprising five naturally occurring structural variants (named A/B, C, D, E and F), produced by different species of very closely related mycobacteria including the human pathogen, Mycobacterium ulcerans. In M. ulcerans strain Agy99, mycolactone A/B is produced by three highly homologous type I polyketide megasynthases (PKS), whose genes (mlsA1: 51 kb, mlsA2: 7.2 kb and mlsB: 42 kb) are found on a 174 kb plasmid, known as pMUM001.

Results

We report here comparative genomic analysis of pMUM001, the complete DNA sequence of a 190 kb megaplasmid (pMUM002) from Mycobacterium liflandii 128FXT and partial sequence of two additional pMUM replicons, combined with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. These data reveal how PKS module and domain differences affecting MlsB correlate with the production of mycolactones E and F. For mycolactone E these differences from MlsB in M. ulcerans Agy99 include replacement of the AT domain of the loading module (acetate to propionate) and the absence of an entire extension module. For mycolactone F there is also a reduction of one extension module but also a swap of ketoreductase domains that explains the characteristic stereochemistry of the two terminal side-chain hydroxyls, an arrangement unique to mycolactone F

Conclusion

The mycolactone PKS locus on pMUM002 revealed the same large, three-gene structure and extraordinary pattern of near-identical PKS domain sequence repetition as observed in pMUM001 with greater than 98.5% nucleotide identity among domains of the same function. Intra- and inter-strain comparisons suggest that the extreme sequence homogeneity seen among the mls PKS genes is caused by frequent recombination-mediated domain replacement. This work has shed light on the evolution of mycolactone biosynthesis among an unusual group of mycobacteria and highlights the potential of the mls locus to become a toolbox for combinatorial PKS biochemistry.
Development of a real-time multiplex PCR assay for the detection of multiple Salmonella serotypes in chicken samples
Authors: O'Regan Edel , McCabe Evonne , Burgess Catherine , McGuinness Sheila , Barry Thomas , Duffy Geraldine , Whyte Paul , Fanning Séamus
Published: October 2008

Background

A real-time multiplex PCR assay was developed for the detection of multiple Salmonella serotypes in chicken samples. Poultry-associated serotypes detected in the assay include Enteritidis, Gallinarum, Typhimurium, Kentucky and Dublin. The traditional cultural method according to EN ISO 6579:2002 for the detection of Salmonella in food was performed in parallel. The real-time PCR based method comprised a pre-enrichment step in Buffered Peptone Water (BPW) overnight, followed by a shortened selective enrichment in Rappaport Vasilliadis Soya Broth (RVS) for 6 hours and subsequent DNA extraction.

Results

The real-time multiplex PCR assay and traditional cultural method showed 100% inclusivity and 100% exclusivity on all strains tested. The real-time multiplex PCR assay was as sensitive as the traditional cultural method in detecting Salmonella in artificially contaminated chicken samples and correctly identified the serotype. Artificially contaminated chicken samples resulted in a detection limit of between 1 and 10 CFU per 25 g sample for both methods. A total of sixty-three naturally contaminated chicken samples were investigated by both methods and relative accuracy, relative sensitivity and relative specificity of the real-time PCR method were determined to be 89, 94 and 87%, respectively. Thirty cultures blind tested were correctly identified by the real-time multiplex PCR method.

Conclusion

Real-time PCR methodology can contribute to meet the need for rapid identification and detection methods in food testing laboratories.
Global transcriptional response to mammalian temperature provides new insight into Francisella tularensis pathogenesis
Authors: Horzempa Joseph , Carlson Paul E , O'Dee Dawn M , Shanks Robert MQ , Nau Gerard J
Published: October 2008

Background

After infecting a mammalian host, the facultative intracellular bacterium, Francisella tularensis, encounters an elevated environmental temperature. We hypothesized that this temperature change may regulate genes essential for infection.

Results

Microarray analysis of F. tularensis LVS shifted from 26°C (environmental) to 37°C (mammalian) showed ~11% of this bacterium's genes were differentially-regulated. Importantly, 40% of the protein-coding genes that were induced at 37°C have been previously implicated in virulence or intracellular growth of Francisella in other studies, associating the bacterial response to this temperature shift with pathogenesis. Forty-four percent of the genes induced at 37°C encode proteins of unknown function, suggesting novel Francisella virulence traits are regulated by mammalian temperature. To explore this possibility, we generated two mutants of loci induced at 37°C [FTL_1581 and FTL_1664 (deoB)]. The FTL_1581 mutant was attenuated in a chicken embryo infection model, which was likely attributable to a defect in survival within macrophages. FTL_1581 encodes a novel hypothetical protein that we suggest naming temperature-induced, virulence-associated locus A, tivA. Interestingly, the deoB mutant showed diminished entry into mammalian cells compared to wild-type LVS, including primary human macrophages and dendritic cells, the macrophage-like RAW 264.7 line, and non-phagocytic HEK-293 cells. This is the first study identifying a Francisella gene that contributes to uptake into both phagocytic and non-phagocytic host cells.

Conclusion

Our results provide new insight into mechanisms of Francisella virulence regulation and pathogenesis. F. tularensis LVS undergoes considerable gene expression changes in response to mammalian body temperature. This temperature shift is important for the regulation of genes that are critical for the pathogenesis of Francisella. Importantly, the compilation of temperature-regulated genes also defines a rich collection of novel candidate virulence determinants, including tivA (FTL_1581). An analysis of tivA and deoB (FTL_1664) revealed that these genes contribute to intracellular survival and entry into mammalian cells, respectively.
The transcription factor ATF3 acts as an oncogene in mouse mammary tumorigenesis
Authors: Wang Aijin , Arantes Stacey , Yan Leqin , Kiguchi Kaoru , McArthur Mark J , Sahin Aysegul , Thames Howard D , Aldaz C Marcelo , MacLeod Michael C
Published: October 2008

Background

Overexpression of the bZip transcription factor, ATF3, in basal epithelial cells of transgenic mice under the control of the bovine cytokeratin-5 (CK5) promoter has previously been shown to induce epidermal hyperplasia, hair follicle anomalies and neoplastic lesions of the oral mucosa including squamous cell carcinomas. CK5 is known to be expressed in myoepithelial cells of the mammary gland, suggesting the possibility that transgenic BK5.ATF3 mice may exhibit mammary gland phenotypes.

Methods

Mammary glands from nulliparous mice in our BK5.ATF3 colony, both non-transgenic and transgenic, were examined for anomalies by histopathology and immunohistochemistry. Nulliparous and biparous female mice were observed for possible mammary tumor development, and suspicious masses were analyzed by histopathology and immunohistochemistry. Human breast tumor samples, as well as normal breast tissue, were similarly analyzed for ATF3 expression.

Results

Transgenic BK5.ATF3 mice expressed nuclear ATF3 in the basal layer of the mammary ductal epithelium, and often developed squamous metaplastic lesions in one or more mammary glands by 25 weeks of age. No progression to malignancy was seen in nulliparous BK5.ATF3 or non-transgenic mice held for 16 months. However, biparous BK5.ATF3 mice developed mammary carcinomas with squamous metaplasia between 6 months and one year of age, reaching an incidence of 67%. Cytokeratin expression in the tumors was profoundly disturbed, including expression of CK5 and CK8 (characteristic of basal and luminal cells, respectively) throughout the epithelial component of the tumors, CK6 (potentially a stem cell marker), CK10 (a marker of interfollicular epidermal differentiation), and mIRSa2 and mIRSa3.1 (markers of the inner root sheath of hair follicles). Immunohistochemical studies indicated that a subset of human breast tumors exhibit high levels of nuclear ATF3 expression.

Conclusion

Overexpression of ATF3 in CK5-expressing cells of the murine mammary gland results in the development of squamous metaplastic lesions in nulliparous females, and in mammary tumors in biparous mice, suggesting that ATF3 acts as a mammary oncogene. A subset of human breast tumors expresses high levels of ATF3, suggesting that ATF3 may play an oncogenic role in human breast tumorigenesis, and therefore may be useful as either a biomarker or therapeutic target.
Gender difference in knowledge of tuberculosis and associated health-care seeking behaviors: a cross-sectional study in a rural area of China
Authors: Wang Jianming , Fei Yang , Shen Hongbing , Xu Biao
Published: October 2008

Background

Tuberculosis (TB) detection under the national TB control program in China follows passive case-finding guidelines, which could be influenced by the accessibility of health service and patient's health-care seeking behaviors. One intriguing topic is the correlation between men and women's knowledge on TB and their health-care seeking behaviors.

Methods

Two cross-sectional studies were separately carried out in Yangzhong County, a rural area of China. One study, by using systematic sampling method, including 1,200 subjects, was conducted to investigate the TB knowledge among general population. Another study in the same source population screened 33,549 people aged 15 years or over among 20 stratified cluster-sampled villages for identifying prolonged cough patients at households and individual interviews were then carried out. Gender difference in the knowledge of TB and health-care seeking behaviors was analyzed particularly.

Results

Among general population, only 16.0% (men 17.1% vs. women 15.0%) knew the prolonged cough with the duration of 3 weeks or longer was a symptom for suspicious TB. Fewer women than men knew the local appointed health facility for TB diagnosis and treatment as well as the current free TB service policy. Moreover, women were less likely to learn information about TB and share it with others on their own initiatives. On the contrary, after the onset of the prolonged cough, women (79.2%) were more likely to seek health-care than men (58.6%) did. However, a large part of women preferred to visit the lower level non-hospital health facilities at first such as village clinics and drugstores.

Conclusion

TB and DOTS program were not well known by rural Chinese. Gender issues should be considered to reduce diagnostic delay of TB and improve both men and women's access to qualified health facility for TB care. Strengthening awareness of TB and improving the accessibility of health-care service is essential in TB control strategy, especially under the current vertical TB control system.
Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure
Authors: Lenaerts Tom , Ferkinghoff-Borg Jesper , Stricher Francois , Serrano Luis , Schymkowitz Joost WH , Rousseau Frederic
Published: October 2008

Background

Efficient communication between distant sites within a protein is essential for cooperative biological response. Although often associated with large allosteric movements, more subtle changes in protein dynamics can also induce long-range correlations. However, an appropriate formalism that directly relates protein structural dynamics to information exchange between functional sites is still lacking.

Results

Here we introduce a method to analyze protein dynamics within the framework of information theory and show that signal transduction within proteins can be considered as a particular instance of communication over a noisy channel. In particular, we analyze the conformational correlations between protein residues and apply the concept of mutual information to quantify information exchange. Mapping out changes of mutual information on the protein structure then allows visualizing how distal communication is achieved. We illustrate the approach by analyzing information transfer by the SH2 domain of Fyn tyrosine kinase, obtained from Monte Carlo dynamics simulations. Our analysis reveals that the Fyn SH2 domain forms a noisy communication channel that couples residues located in the phosphopeptide and specificity binding sites and a number of residues at the other side of the domain near the linkers that connect the SH2 domain to the SH3 and kinase domains. We find that for this particular domain, communication is affected by a series of contiguous residues that connect distal sites by crossing the core of the SH2 domain.

Conclusion

As a result, our method provides a means to directly map the exchange of biological information on the structure of protein domains, making it clear how binding triggers conformational changes in the protein structure. As such it provides a structural road, next to the existing attempts at sequence level, to predict long-range interactions within protein structures.