bluuebunny/crossref_metadata_2025 huggingface dataset:
Urethral Carcinoma and Hyperplasia in Male and Female B6C3F1 Mice Treated With 3,3′,4,4′-Tetrachloroazobenzene (TCAB)
Authors: Singh B. P. , Nyska A. , Kissling G. E. , Lieuallen W. , Johansson S. L. , Malarkey D. E. , Hooth M. J.
Published: March 2010

B6C3F1 mice chronically exposed to 3,3′,4,4′-tetrachloroazobenzene (TCAB), a contaminant of dichloroaniline-derived herbicides, developed a number of neoplastic and nonneoplastic lesions, including carcinoma of the urinary tract. Groups of fifty male and fifty female B6C3F1 mice were exposed by gavage to TCAB at dose levels of 0, 3, 10, and 30 mg/kg five days a week for two years. Control animals received corn oil:acetone (99:1) vehicle. Decreased survival of male mice in the mid-dose group and of male and female mice in the high-dose groups was related mainly to the occurrence of urethral transitional cell (urothelial) carcinoma and resulting urinary obstruction. Increased urethral transitional cell carcinomas were seen in all treated male groups in a dose-related manner as well as in the females treated with 30 mg/kg TCAB. Administration of TCAB was also associated with increased transitional cell hyperplasia of the urethra. Most nonneoplastic lesions of the urogenital tract were considered secondary to local invasion and urinary obstruction by the urethral transitional cell carcinomas. The mechanism of tumor induction is uncertain, but the high frequency of tumors in the proximal urethra of male mice suggests that the neoplasms result from the exposure of a susceptible population of urothelial cells to a carcinogenic metabolite of TCAB.
Deep hypothermic total circulatory arrest for internal carotid artery aneurysm extending into the cranium: experience from a developing country
Authors: Shahabuddin Syed , Jabbar Abid , Hidayat Ijaz , Sophie Ziad , Fatimi Saulat
Published: March 2010

Cardiopulmonary bypass is commonplace for acquired and congenital cardiac procedures. It has also stretched to facilitate complicated non-cardiac operations. Carotid artery aneurysms are treated both with surgical repair without cardiopulmonary bypass (CPB) and, occasionally, by utilizing CPB perfusion techniques. We have successfully repaired an internal carotid artery aneurysm, extending into cranium in a 30-year-old woman, by establishing deep hypothermic circulatory arrest on cardiopulmonary bypass.
Intermetropolitan Comparison of Transportation Accessibility: Sorting Out Mobility and Proximity in San Francisco and Washington, D.C
Authors: Grengs Joe , Levine Jonathan , Qing Shen  , Qingyun Shen
Published: March 2010

Both mobility and proximity influence transportation accessibility, but they exist in tension with each other. To understand the region-level trade-off between mobility and proximity requires intermetropolitan comparisons of accessibility. With a focus on the two metropolitan cases of San Francisco and Washington, D.C., we first describe a method for comparing regional accessibility and then explain a method that separates out the effects of mobility and proximity on regional accessibility. We find that the San Francisco region enjoys an accessibility advantage over Washington largely because of faster highway speeds but that central Washington offers an advantage in proximity.
Efficacy of a Computer-Based Program on Acquisition of Reading Skills of Incarcerated Youth
Authors: Shippen Margaret E. , Morton Rhonda Collins , Flynt Samuel W. , Houchins David E. , Smitherman Tracy
Published: March 2010

Despite the importance of literacy skill training for incarcerated youth, a very limited number of empirically based research studies have examined reading instruction in correctional facilities. The purpose of this study was to determine whether the Fast ForWord computer-assisted reading program improved the reading and spelling abilities of incarcerated youth. A group of 51 incarcerated male youth identified by facility staff as low performers in reading composed the target group for this study. Both standardized and curriculum-based measures were employed to determine reading and spelling skill growth over an average of 24 sessions in an 11-week intervention. Results indicated no clear literacy skill improvement for the treatment group. Implications for future research are discussed.
Patterns of School Functioning Over Time Among Students Served in a System of Care
Authors: Anderson Jeffrey A.
Published: March 2010

Systems of care can be used to help coordinate and direct resources both external and internal to a school, thereby providing critical supports for students with emotional and behavioral challenges that historically have not been available to educators. In this study, hierarchical linear modeling was used to longitudinally examine school functioning change trajectories for a sample of students who participated in the Dawn Project system of care in Indianapolis, Indiana. The investigation was driven by the hypotheses that improvements in school functioning would be associated with improvements in clinical functioning over time and also that demographic characteristics would not be associated with such changes in school functioning. In general, the findings supported these hypotheses. Specifically, school functioning was found to significantly improve between the time students enrolled in the system of care and up to 36 months postenrollment. Moreover, longitudinal improvements in school functioning were significantly associated with improvements in clinical functioning, even after controlling for the influence of time. Although the relationship between school and clinical functioning is not well understood, these findings suggest that an interdependent relationship exists, highlighting the importance of simultaneously targeting school and social-emotional challenges.
Comparison of Child Self-Report and Parent Report on the Sibling Need and Involvement Profile
Authors: Senner Jill E. , Fish Thomas
Published: March 2010

Considering the needs of siblings is an important component of family-centered practice for children with developmental disabilities. A syntactically and semantically simplified version of the Sibling Need and Involvement Profile (SNIP) was developed to allow self-report. Total profile scores for the self-report version correlated well with the original (Spearman’s rho = .928, p < .01), and test–retest reliability was good (Spearman’s rho = .896, p < .01). Children who piloted the instrument demonstrated good understanding of the vocabulary and the intent of the questions; however, using the instrument with adult supervision is suggested. A comparison of children’s self-report scores to those of their parents’ resulted in low, insignificant correlations, suggesting that parents’ and children’s perspectives do not always agree. Multiple measures, including sibling self-report and parent reports, are necessary for accurate determination of sibling need and involvement.
Mentoring Special Educators
Authors: Wasburn Mara H. , Wasburn-Moses Leah , Davis Darrel R.
Published: March 2010

Although mentoring programs for novice special education teachers have been highly touted, there is scant research describing either novice needs or mentor roles. This study is based on a sample of 66 randomly selected national board certified teachers (NBCTs) in special education in an effort to determine the nature and extent of their involvement in mentoring junior colleagues, both formally and informally. A previously published instrument was modified to determine the frequency of their engagement in various mentoring roles. Results indicated that formal mentoring involved more of the 19 identified mentor activities than did informal mentoring. Implications include a need for mentor training for NBCTs and for further exploration of mentoring roles in the professional literature.
Quality of Relationships as a Predictor of Psychosocial Functioning in Patients With Dementia
Authors: Ball Valdesha , Snow A. Lynn , Steele Avila B. , Morgan Robert O. , Davila Jessica A. , Wilson Nancy , Kunik Mark E.
Published: March 2010

This prospective cohort study evaluated the quality of caregiver and care-recipient relationship, or mutuality, and its relationship to psychosocial functioning among patients with dementia. Patients older than 59 years of age with newly diagnosed dementia between 2001 and 2004 were identified from the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. Among these patients, we identified patients who were under the care of a caregiver in the community setting for at least 8 hours per week. A Mutuality Scale was used to measure the quality of relationships between family caregivers and care recipients. The effect of relationship quality on the following dependent variables was assessed: depression, psychosis, pain, caregiver burden, social stimulation, and aggression. Based on the sample of 171 patients, high mutuality scores predicted decreased patient depression and caregiver burden. Increased mutuality scores also correlated with increased number and frequency of pleasant events (social stimulation) 4 months later. There was no relationship between total mutuality scores and patients’ pain levels, psychotic symptoms, or aggression. Improvement in mutuality over 4-month periods was associated with increased social stimulation, decreased caregiver burden, and decreased aggression over time.
Using Simulation to Explore Lean Manufacturing Implementation Strategies
Authors: Shannon Patrick W. , Krumwiede Kip R. , Street Jeffrey N.
Published: March 2010

Lean manufacturing, an outgrowth of the Toyota Production System, has spread far beyond the automobile industry and is seen by many leaders as a key management philosophy in the battle to compete on an international scale. Successful implementation of lean requires that managers and employees be educated in the proper application of lean tools and the effective strategies for lean implementation. However, there is a shortage of lean teaching materials available to both corporate trainers and university educators. This article describes a computer simulation exercise that provides students with hands-on experience in developing and evaluating alternative lean implementation strategies. We also offer all ancillary teaching materials, including a demonstration case study and modifiable Excel spreadsheets.
Attachment in Romantic Couples and Perceptions of a Joint Drawing Session
Authors: Snir Sharon , Wiseman Hadas
Published: March 2010

This study examined the postsession evaluations of romantic partners that engaged in a joint drawing task, which is a commonly used technique in art therapy. The shared nonverbal interaction between partners while drawing together is assumed to elicit tensions between closeness and individuality among the partners. To examine couples’ postsession evaluations and their associations to the attachment characteristics of the partners, each of 60 romantic couples drew on one shared sheet of paper and completed the Session Evaluation Questionnaire (SEQ) and the adult romantic attachment scale. As hypothesized, both attachment-related anxiety and attachment-related avoidance were negatively correlated with perceptions of the joint drawing session as smooth and positive. Women evaluated session depth as greater than did men, with the widest gap found in the insecure—insecure couple attachment combination. The importance of evaluating the divergent experiences of participants in a joint drawing session and the interpersonal dynamics in anxious woman—avoidant man couples are discussed.
Astrocytes and Synaptic Plasticity
Authors: Barker Alison J. , Ullian Erik M.
Published: March 2010

Synaptic plasticity, the ability of neurons to change the number and strength of their synapses, has long been considered the sole province of the neuron. Yet neurons do not function in isolation; they are a part of elaborate glial networks where they are intimately associated with astrocytes. Astrocytes make extensive contacts with synaptic sites where they release soluble factors that can increase synapse number, provide synaptic insulation restricting the spread of neurotransmitter to neighboring synapses, and release neuroactive compounds, gliotransmitters, that can directly influence synaptic transmission. During periods of synaptogenesis, astrocyte processes are highly mobile and may contribute to the stabilization of new synapses. As our understanding of the extent of their influence at the synapse unfolds, it is clear that astrocytes are well poised to modulate multiple aspects of synaptic plasticity.
Functions of Mature Mammalian Astrocytes: A Current View
Authors: Kimelberg Harold K.
Published: March 2010

Before the roles of normal, mature astrocytes in the mammalian CNS can be discussed, we first need to define these cells. A definition proposed here is that such a class is best defined as consisting of the protoplasmic and fibrous astrocytes of the gray and white matter, respectively, the Bergmann glia of the molecular layer of the cerebellum, and the Muller cells of the retina. It is concluded that the established properties and functions of these mature astrocytes are essential support for neuronal activity, in the sense of Claude Bernard’s principle of maintaining “la fixité du milieu intérieur.” This milieu would be the extracellular space common to astrocytes and neurons. More specialized roles, such as the recently described “light guides” for retinal Muller cells can also be viewed as support and facilitation. The ECS is also, of course, common to all other neural cells, but here, I limit the discussion to perturbations of the ECS caused only by neuronal activities and the resolution of these perturbations by astrocytes, such as control of increases in extracellular K+, uptake of excitatory amino acids, and alterations in blood vessel diameter and therefore blood flow. It is also proposed how this fits into the current morphological picture for the protoplasmic astrocytes as having small cell bodies with up to 100,000 process endings that occupy separate territories on which the processes of neighboring astrocytes scarcely intrude.
Beauty queens, machistas and street children
Authors: Acosta-Alzuru Carolina
Published: March 2010

• Consumed in over 130 countries, telenovelas are media products particularly suitable for the examination of the dialogue between media, culture and society. In 2003—4, Venezuelan telenovela Cosita Rica took the stage alongside the country’s political crisis and deep polarization around President Hugo Chávez. Cosita Rica both straddled and blurred the line between fact and fiction through its multiple plots framed by Venezuela’s political and socioeconomic crises. I focus on the production and reception of Cosita Rica’s representations of three of Venezuela’s socio-cultural issues: obsession with physical beauty, machismo, and street children. The article looks closely at the dialogue between television and country at a critical and historical time, and provides clues to the reception of entertainment media content when such content includes critical stances towards the social formation’s cultural fabric. •
Acting powerfully
Authors: Coleman Stephen
Published: March 2010

This article explores the ways in which power is made visible through mediated representations within the ‘reality TV’ show, Big Brother.
Making time stand still
Authors: Huber Alison
Published: March 2010

It’s hard to keep up with the Top 40. Popular songs quickly lose their contemporaneity, become ‘past hits’, and are replaced by the next thing … and them by the next. With its high-velocity temporality and multi-mediation, Top 40 culture is hard to ‘fix’: its content is always changing, and thus is difficult to capture for critique. Top 40 culture ‘disappears’ easily, with only selected elements being retained in cultural memory, or preserved in academic analytic discourse. Much of Top 40’s content is forgotten. This article argues that the constant supersession of the texts of Top 40 poses a challenge to academic inquiry, when such writing about them threatens to become obsolete (just like singles themselves) once the songs are no longer popular. It introduces the activities of some collectors of Top 40 data who collate and publish chart information in book form. Their practices seem to succeed in ‘fixing’ the Top 40’s transience by finding ways of keeping pace with the ever-changing charts. Their success in apprehending the momentum of Top 40 provides one way of thinking beyond the anxiety of disappearance, and suggests new possibilities for research methodology in this area of popular cultural studies.
Structural Health Monitoring in mainland China: Review and Future Trends
Authors: Jinping Ou  , Hui Li
Published: March 2010

Structural health monitoring (SHM) technology has been successfully applied to understand the loads, environment actions, and behaviors of a structure subjected to various actions through solving a reverse problem. The sensing technology is a critical part of SHM. In this article, the development of advanced sensing technology and sensors in mainland China in the past decade, such as optic fiber sensing technology, wave propagation-based piezoelectric ceramic (PZT) sensing technology, smart cement-based sensing technology, and corrosion detection technology, have been critically reviewed. In addition, the article also summarizes the application of SHM technologies in earthquake engineering, wind engineering and life-cycle performance evaluation and corresponding progress achieved in mainland China. The challenges and future trends in the development of sensing technology and SHM are put forward in this paper.
Experimental Study of Impact-Damage Detection in Composite Laminates using a Cross-Modulation Vibro-Acoustic Technique
Authors: Aymerich F. , Staszewski W.J.
Published: March 2010

The paper demonstrates the application of cross-modulation vibro-acoustic technique for impact-damage detection in composite laminates. A composite plate is monitored for damage resulting from a low-velocity impact. The plate is excited simultaneously with two harmonic signals: a slow amplitude-modulated vibration pumping wave and a constant amplitude-probing wave. The frequency of both the excitation signals coincides with the resonances of the plate. An electromagnetic shaker is used to introduce the pumping wave to the plate. Two surface-bonded, low-profile piezoceramic transducers are used for probing-wave excitation and measurement. The wave modulation is transferred from the pumping wave to the probing wave in the presence of impact damage. This effect is exhibited in a power spectrum of the probing wave by a pattern of sidebands around the carrier harmonic. The results show that the amplitude of the sidebands is related to the severity of damage. The study also investigates also the effect of boundary conditions on the results.
Psychological Problems Associated With Operation Enduring Freedom/Operation Iraqi Freedom Deployment
Authors: Scioli Erica R. , Otis John D. , Keane Terence M.
Published: March 2010

Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) are the longest sustained ground combat operations involving American forces since the Vietnam era. Our continued involvement in these conflicts has yielded an experienced fighting force; however, to meet the demands of these wars, soldiers are often being asked to complete multiple tours of duty, thus increasing the probability they will experience a combat-related physical injury or experience one or more potentially traumatic events. This article addresses the major psychological issues of concern associated with OEF/OIF deployment and combat. A central aim of this review is to focus on posttraumatic stress disorder, but the authors also address other frequently observed conditions, such as chronic pain, traumatic brain injury, substance abuse, and depression, all of which can have a negative effect on soldiers’ and veterans’ functioning and quality of life. Evidence-based assessment and treatment approaches are reviewed, and relevant resources for health care professionals are identified.
Playing with environmental stories in the news — good or bad practice?
Authors: Bednarek Monika , Caple Helen
Published: March 2010

The aim of this article is to analyse environmental reporting in the Australian broadsheet newspaper The Sydney Morning Herald. The focus is on a particular kind of new, multisemiotic news story genre that appears regularly in this newspaper, and that makes use of word-image play. Using a social semiotic framework and employing Appraisal theory, we analyse a corpus of 40 stories in terms of evaluative meanings in heading, image and caption, and interpret the significance of our findings in terms of both Critical Discourse Analysis and Positive Discourse Analysis. In particular, we question whether the playing with environmental stories in the news, and the resulting clash between the humorousness of the play and the seriousness of the reported environmental event, is good or bad practice. With its multisemiotic focus, this article aims to make a significant and innovative contribution to the emerging field of ecolinguistics, and the development of Appraisal theory.
Interdiscursivity in professional communication
Authors: Bhatia Vijay K.
Published: March 2010

In recent versions of professional genre analysis, context has assumed increasingly critical importance, thus redefining genre as a configuration of text-internal and text-external factors. The emphasis on text-external properties of genre has brought into focus the notion of interdiscursivity as distinct from intertextuality, which is primarily viewed as appropriation of text-internal resources. Drawing evidence from a number of professional contexts, this article explores the nature, function, and use of interdiscursivity in genre theory, defining interdiscursivity as a function of appropriation of generic resources across discursive, professional and cultural practices, which, it is claimed, is central to our understanding of the complexities of genres that are typically employed in professional, disciplinary, and institutional communication.
Discourse research that intervenes in the quality and safety of care practices
Authors: Iedema Rick , Carroll Katherine
Published: March 2010

Drawing on work done in the area of health services research, this article outlines a view of discourse analysis (DA) that approaches discourse as a co-accomplished process involving researcher and research-participant. Without losing sight of the analytical-critical-reflexive moments that have typified discourse analytical endeavours, this article explores a form of DA that moves from discourse as object to be collected and processed away from where it is practised, towards discourse as dynamically emerging reality shared by (clinical) practitioner-participants and researchers, and as flexible means to intervene in the quality and safety of care practices. The article begins with highlighting the productive potential of discourse research in health. The ethics informing this mode of DA, the article goes on to explain, is interested and trustful ‘entanglement’ with those who populate this field of practice and structure it with discourse. Elsewhere referred to as ‘experience-based enquiry’, the initiative to reframe discourse research as a mode of intervention involves keeping practitioners’ interpretations and analysts’ questions, critiques and conclusions in tension. The article argues that this approach capitalizes on the intrinsically reflexive, dialogic and emergent nature of discourse. To illustrate these issues, the article presents two case studies drawn from recent projects that have manifested these researcher and practitioner-participant dynamics. The article concludes that, as emergent practice, the analysis of discourse benefits from entanglement with the people and the contexts where discourse is produced. Here, analysis vacillates between a feedback device that enables both research participants and researchers to re-appraise their and each other’s practices, and a knowledge production device that generalizes about these practices and the changes to these practices that result from the research.
AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated Kit
Authors: Lin Tzu-Yin , Fenger Joelle , Murahari Sridhar , Bear Misty D. , Kulp Samuel K. , Wang Dasheng , Chen Ching-Shih , Kisseberth William C. , London Cheryl A.
Published: March 2010

Histone hypoacetylation occurs in many cancers and inhibition of histone deacetylation is a promising approach to modulate these epigenetic changes. Our laboratory previously demonstrated that the histone deacetylase inhibitors (HDACis) vorinostat and AR-42 reduced the viability of a canine malignant mast cell line. The purpose of this study was to further investigate the mechanisms of pan-HDAC inhibition in normal and malignant mast cells. Mouse and canine malignant mast cell lines expressing various Kit mutations, normal canine mast cells, and primary canine malignant mast cells were treated with AR-42 (a novel HDACi) and effects on cell viability, cycling, and signaling were evaluated. Treatment with AR-42 induced growth inhibition, cell- cycle arrest, apoptosis, and activation of caspases-3/7. AR-42 promoted hyperacetylation of H3, H4, and alpha-tubulin, and up-regulation of p21. Down-regulation of Kit occurred after AR-42 treatment via inhibition of Kit transcription. Disassociation between Kit and heat shock protein 90 (HSP90) and up-regulation of HSP70 were observed after AR-42 treatment, suggesting potential loss of HSP90 chaperone function. Lastly, AR-42 down-regulated the expression of p-Akt, total Akt, phosphorylated STAT3/5 (pSTAT3/5), and total STAT3/5. In summary, AR-42 exhibits in vitro and ex vivo biologic activity against malignant mast cells, representing a promising therapeutic approach for malignant mast cell disease.
Use of chromosome engineering to model a segmental deletion of chromosome band 7q22 found in myeloid malignancies
Authors: Wong Jasmine C. Y. , Zhang Yan , Lieuw Kenneth H. , Tran Mary T. , Forgo Erna , Weinfurtner Kelley , Alzamora Pilar , Kogan Scott C. , Akagi Keiko , Wolff Linda , Le Beau Michelle M. , Killeen Nigel , Shannon Kevin
Published: March 2010

Monosomy 7 and del(7q) are associated with adverse features in myeloid malignancies. A 2.5-Mb commonly deleted segment (CDS) of chromosome band 7q22 is implicated as harboring a myeloid tumor suppressor gene (TSG); however, molecular analysis of candidate TSGs has not uncovered loss of function. To determine whether haploinsufficiency for the 7q22 CDS contributes to myeloid leukemogenesis, we performed sequential gene targeting to flank a region of orthologous synteny on mouse chromosome band 5A3 with loxP sites. We then generated Mx1-Cre, 5A3fl mutant mice and deleted the targeted interval in vivo. Although excision was inefficient, we confirmed somatic deletion of the 5A3 CDS in the hematopoietic stem cell compartment. Mx1-Cre, 5A3fl mice show normal hematologic parameters and do not spontaneously develop myeloid malignancies. The 5A3fl deletion does not cooperate with oncogenic KrasG12D expression, Nf1 inactivation, or retroviral mutagenesis to accelerate leukemia development and did not modulate responsiveness to antileukemia drugs. These studies demonstrate that it is feasible to somatically delete a large chromosomal segment implicated in tumor suppression in hematopoietic cell populations in vivo; however, our data do not support the hypothesis that the 7q22/5A3 CDS interval contains a myeloid TSG.
The pan-HDAC inhibitor vorinostat potentiates the activity of the proteasome inhibitor carfilzomib in human DLBCL cells in vitro and in vivo
Authors: Dasmahapatra Girija , Lembersky Dmitry , Kramer Lora , Fisher Richard I. , Friedberg Jonathan , Dent Paul , Grant Steven
Published: March 2010

Interactions between histone deacetylase inhibitors (HDACIs) and the novel proteasome inhibitor carfilzomib (CFZ) were investigated in GC- and activated B-cell–like diffuse large B-cell lymphoma (ABC-DLBCL) cells. Coadministration of subtoxic or minimally toxic concentrations of CFZ) with marginally lethal concentrations of HDACIs (vorinostat, SNDX-275, or SBHA) synergistically increased mitochondrial injury, caspase activation, and apoptosis in both GC- and ABC-DLBCL cells. These events were associated with Jun NH2-terminal kinase (JNK) and p38MAPK activation, abrogation of HDACI-mediated nuclear factor-κB activation, AKT inactivation, Ku70 acetylation, and induction of γH2A.X. Genetic or pharmacologic JNK inhibition significantly diminished CFZ/vorinostat lethality. CFZ/vorinostat induced pronounced lethality in 3 primary DLBCL specimens but minimally affected normal CD34+ hematopoietic cells. Bortezomib-resistant GC (SUDHL16) and ABC (OCI-LY10) cells exhibited partial cross-resistance to CFZ. However, CFZ/vorinostat dramatically induced resistant cell apoptosis, accompanied by increased JNK activation and γH2A.X expression. Finally, subeffective vorinostat doses markedly increased CFZ-mediated tumor growth suppression and apoptosis in a murine xenograft OCI-LY10 model. These findings indicate that HDACIs increase CFZ activity in GC- and ABC-DLBCL cells sensitive or resistant to bortezomib through a JNK-dependent mechanism in association with DNA damage and inhibition of nuclear factor-κB activation. Together, they support further investigation of strategies combining CFZ and HDACIs in DLBCL.
The inherited diseases of hemoglobin are an emerging global health burden
Authors: Weatherall David. J.
Published: March 2010

It is estimated that in excess of 300 000 children are born each year with a severe inherited disorder of hemoglobin and that approximately 80% of these births occur in low- or middle-income countries. As these countries go through an epidemiologic transition, with a reduction in childhood and infant mortality due to improved public health measures, babies who would have previously died of these diseases before they were recognized are now surviving to present for diagnosis and treatment. Hence, they are presenting an increasing global health burden. Because of their uneven distribution in high-frequency populations, reflecting their complex population genetics, the true magnitude of this burden is still unknown. In many poor countries there are virtually no facilities for the diagnosis and management of these conditions, and even in richer countries there are limited data about their frequency, clinical course, or mortality. Without this information, it will be impossible to persuade governments about the increasing importance of these diseases. The situation will only be improved by concerted action on the part of the hematology community of the richer countries together with input from the major international health organizations and funding agencies.
eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies
Authors: Weißensteiner Hansi , Schönherr Sebastian , Specht Günther , Kronenberg Florian , Brandstätter Anita
Published: March 2010

Background

Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes.

Description

eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one.

Conclusions

The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.
Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt secretion: potential implications for opioid dependence
Authors: Jin Jay , Kittanakom Saranya , Wong Victoria , Reyes Beverly AS , Van Bockstaele Elisabeth J , Stagljar Igor , Berrettini Wade , Levenson Robert
Published: March 2010

Background

Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of opioid dependence.

Results

GPR177, the mammalian ortholog ofDrosophilaWntless/Evi/Sprinter, was identified as a MORIP in a modified split ubiquitin yeast two-hybrid screen. GPR177 is an evolutionarily conserved protein that plays a critical role in mediating Wnt protein secretion from Wnt producing cells. The MOR/GPR177 interaction was validated in pulldown, coimmunoprecipitation, and colocalization studies using mammalian tissue culture cells. The interaction was also observed in rodent brain, where MOR and GPR177 were coexpressed in close spatial proximity within striatal neurons. At the cellular level, morphine treatment caused a shift in the distribution of GPR177 from cytosol to the cell surface, leading to enhanced MOR/GPR177 complex formation at the cell periphery and the inhibition of Wnt protein secretion.

Conclusions

It is known that chronic morphine treatment decreases dendritic arborization and hippocampal neurogenesis, and Wnt proteins are essential for these processes. We therefore propose that the morphine-mediated MOR/GPR177 interaction may result in decreased Wnt secretion in the CNS, resulting in atrophy of dendritic arbors and decreased neurogenesis. Our results demonstrate a previously unrecognized role for GPR177 in regulating cellular response to opioid drugs.
E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer
Authors: Kothandaraman Narasimhan , Bajic Vladimir B , Brendan Pang NK , Huak Chan Y , Keow Peh B , Razvi Khalil , Salto-Tellez Manuel , Choolani Mahesh
Published: March 2010

Background

Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.

Methods

Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.

Results

Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity, specificity, F-measure and accuracy of 97.92%, 97.37%, 97.92% and 97.67%, respectively.

Conclusions

Overall, our findings, in addition to opening a realistic possibility for improved OEC diagnosis, provide an indirect evidence that a cell-cycle regulatory protein E2F5 might play a significant role in OEC pathogenesis.
Prevalence of the Metabolic Syndrome among rural original adults in NingXia, China
Authors: Yi Zhao , Jing Jin , Xiu-ying Liu , Hongxia Xu , Jianjun Yang , Yuhong Zhang
Published: March 2010

Background

Metabolic syndrome (MS) is combination of medical disorders that increase people's risk for cardiovascular disease and diabetes mellitus. Little data exists on the prevalence of MS of rural original adults in Ningxia of China.

Methods

A cross-sectional survey method was used and the participants were interviewed by trained health workers under a structured questionnaire in rural of Ningxia in 2008. The number of research subjects was 1612. MS was defined by International Diabetes Federation IDF (2005).

Results

The age-adjusted prevalence of the metabolic syndrome was 11.8%, whereas ethnic-specific prevalence was 10.3% in Han ethnic group and 13.7% in Hui ethnic group. Components of MS and MS were more common in Hui ethnic group than Han ethnic group. The mean levels and prevalence of abnormal value increased with increasing age in both ethnic groups (Cochran-Artimage test for trend, Hui ethnic group P < 0.05, Han ethnic group P < 0.01).

Conclusions

The prevalence of MS was high in rural residents' adults in Ningxia. Clustering of MS components and MS was increased with age. The components of MS have big differences among different ethnic groups.
The prevalence of anemia and its association with 90-day mortality in hospitalized community-acquired pneumonia
Authors: Reade Michael C , Weissfeld Lisa , Angus Derek C , Kellum John A , Milbrandt Eric B
Published: March 2010

Background

The prevalence of anemia in the intensive care unit is well-described. Less is known, however, of the prevalence of anemia in hospitalized patients with lesser illness severity or without organ dysfunction. Community-acquired pneumonia (CAP) is one of the most frequent reasons for hospitalization in the United States (US), affecting both healthy patients and those with comorbid illness, and is typically not associated with acute blood loss. Our objective was to examine the development and progression of anemia and its association with 90d mortality in 1893 subjects with CAP presenting to the emergency departments of 28 US academic and community hospitals.

Methods

We utilized hemoglobin values obtained for clinical purposes, classifying subjects into categories consisting of no anemia (hemoglobin >13 g/dL), at least borderline (≤ 13 g/dL), at least mild (≤ 12 g/dL), at least moderate (≤ 10 g/dL), and severe (≤ 8 g/dL) anemia. We stratified our results by gender, comorbidity, ICU admission, and development of severe sepsis. We used multivariable logistic regression to determine factors independently associated with the development of moderate to severe anemia and to examine the relationship between anemia and 90d mortality.

Results

A total of 8240 daily hemoglobin values were measured in 1893 subjects. Mean (SD) number of hemoglobin values per patient was 4.4 (4.0). One in three subjects (33.9%) had at least mild anemia at presentation, 3 in 5 (62.1%) were anemic at some point during their hospital stay, and 1 in 2 (54.5%) survivors were discharged from the hospital anemic. Anemia increased with illness severity and was more common in those with comorbid illnesses, female gender, and poor outcomes. Yet, even among men and in those with no comorbidity or only mild illness, anemia during hospitalization was common (~55% of subjects). When anemia was moderate to severe (≤ 10 g/dL), its development was independently associated with increased 90d mortality, even among hospital survivors.

Conclusions

Anemia was common in hospitalized CAP and independently associated with 90d mortality when hemoglobin values were 10 g/dL or less. Whether prevention or treatment of CAP-associated anemia would improve clinical outcomes remains to be seen.
In vitro antifungal activity of hydroxychavicol isolated from Piper betle L
Authors: Ali Intzar , Khan Farrah G , Suri Krishan A , Gupta Bishan D , Satti Naresh K , Dutt Prabhu , Afrin Farhat , Qazi Ghulam N , Khan Inshad A
Published: March 2010

Background

Hydroxychavicol, isolated from the chloroform extraction of the aqueous leaf extract of Piper betle L., (Piperaceae) was investigated for its antifungal activity against 124 strains of selected fungi. The leaves of this plant have been long in use tropical countries for the preparation of traditional herbal remedies.

Methods

The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of hydroxychavicol were determined by using broth microdilution method following CLSI guidelines. Time kill curve studies, post-antifungal effects and mutation prevention concentrations were determined against Candida species and Aspergillus species "respectively". Hydroxychavicol was also tested for its potential to inhibit and reduce the formation of Candida albicans biofilms. The membrane permeability was measured by the uptake of propidium iodide.

Results

Hydroxychavicol exhibited inhibitory effect on fungal species of clinical significance, with the MICs ranging from 15.62 to 500 μg/ml for yeasts, 125 to 500 μg/ml for Aspergillus species, and 7.81 to 62.5 μg/ml for dermatophytes where as the MFCs were found to be similar or two fold greater than the MICs. There was concentration-dependent killing of Candida albicans and Candida glabrata up to 8 × MIC. Hydroxychavicol also exhibited an extended post antifungal effect of 6.25 to 8.70 h at 4 × MIC for Candida species and suppressed the emergence of mutants of the fungal species tested at 2 × to 8 × MIC concentration. Furthermore, it also inhibited the growth of biofilm generated by C. albicans and reduced the preformed biofilms. There was increased uptake of propidium iodide by C. albicans cells when exposed to hydroxychavicol thus indicating that the membrane disruption could be the probable mode of action of hydroxychavicol.

Conclusions

The antifungal activity exhibited by this compound warrants its use as an antifungal agent particularly for treating topical infections, as well as gargle mouthwash against oral Candida infections.
MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment
Authors: Spinola Monica , Falvella Felicia S. , Colombo Francesca , Sullivan James P. , Shames David S. , Girard Luc , Spessotto Paola , Minna John D. , Dragani Tommaso A.
Published: March 2010

Background

MFSD2A (major facilitator superfamily domain containing 2) gene maps on chromosome 1p34 within a linkage disequilibrium block containing genetic elements associated with progression of lung cancer.

Results

Here we show that MFSD2A expression is strongly downregulated in non-small cell lung cancer cell lines of different histotypes and in primary lung adenocarcinomas. Experimental modulation of MFSD2A in lung cancer cells is associated with alteration of mRNA levels of genes involved in cell cycle control and interaction with the extracellular matrix. Exogenous expression of MFSD2A in lung cancer cells induced a G1 block, impaired adhesion and migration in vitro, and significantly reduced tumor colony number in vitro (4- to 27-fold, P < 0.0001) and tumor volume in vivo (~3-fold, P < 0.0001). siRNA knockdown studies in normal human bronchial epithelial cells confirmed the role of MFSD2A in G1 regulation.

Conclusion

Together these data suggest that MFSD2A is a novel lung cancer tumor suppressor gene that regulates cell cycle progression and matrix attachment.
Comparison of heterologous xylose transporters in recombinant Saccharomyces cerevisiae
Authors: Runquist David , Hahn-Hägerdal Bärbel , Rådström Peter
Published: March 2010

Background

Baker's yeast (Saccharomyces cerevisiae) has been engineered for xylose utilization to enable production of fuel ethanol from lignocellulose raw material. One unresolved challenge is that S. cerevisiae lacks a dedicated transport system for pentose sugars, which means that xylose is transported by non-specific Hxt transporters with comparatively low transport rate and affinity for xylose.

Results

In this study, we compared three heterologous xylose transporters that have recently been shown to improve xylose uptake under different experimental conditions. The transporters Gxf1, Sut1 and At5g59250 from Candida intermedia, Pichia stipitis and Arabidopsis thaliana, respectively, were expressed in isogenic strains of S. cerevisiae and the transport kinetics and utilization of xylose was evaluated. Expression of the Gxf1 and Sut1 transporters led to significantly increased affinity and transport rates of xylose. In batch cultivation at 4 g/L xylose concentration, improved transport kinetics led to a corresponding increase in xylose utilization, whereas no correlation could be demonstrated at xylose concentrations greater than 15 g/L. The relative contribution of native sugar transporters to the overall xylose transport capacity was also estimated during growth on glucose and xylose.

Conclusions

Kinetic characterization and aerobic batch cultivation of strains expressing the Gxf1, Sut1 and At5g59250 transporters showed a direct relationship between transport kinetics and xylose growth. The Gxf1 transporter had the highest transport capacity and the highest xylose growth rate, followed by the Sut1 transporter. The range in which transport controlled the growth rate was determined to between 0 and 15 g/L xylose. The role of catabolite repression in regulation of native transporters was also confirmed by the observation that xylose transport by native S. cerevisiae transporters increased significantly during cultivation in xylose and at low glucose concentration.
Finite-difference modeling of Biot’s poroelastic equations across all frequencies
Authors: Masson Y. J. , Pride S. R.
Published: March 2010

An explicit time-stepping finite-difference scheme is presented for solving Biot’s equations of poroelasticity across the entire band of frequencies. In the general case for which viscous boundary layers in the pores must be accounted for, the time-domain version of Darcy’s law contains a convolution integral. It is shown how to efficiently and directly perform the convolution so that the Darcy velocity can be properly updated at each time step. At frequencies that are low enough compared to the onset of viscous boundary layers, no memory terms are required. At higher frequencies, the number of memory terms required is the same as the number of time points it takes to sample accurately the wavelet being used. In practice, we never use more than 20 memory terms and often considerably fewer. Allowing for the convolution makes the scheme even more stable (even larger time steps might be used) than it is when the convolution is entirely neglected. The accuracy of the scheme is confirmed by comparing numerical examples to exact analytic results.