bluuebunny/crossref_metadata_2025 huggingface dataset:
Menthol Induces Cell Death via the TRPM8 Channel in the Human Bladder Cancer Cell Line T24
Authors: Li Qin , Wang Xinghuan , Yang Zhonghua , Wang Bin , Li Shilin
Published: December 2009

Objective: Growing evidence has shown that menthol has potent anticancer activity in various human cancers via the transient receptor potential melastatin 8 (TRPM8)-dependent pathway or in a TRPM8-independent manner. However, its effect on bladder cancer remains obscure. In the present investigation, we examined the expression of TRPM8 and the role of menthol in cells of the human bladder cancer cell line T24. Methods: RT-PCR, Western blotting and immunocytochemistry were used to confirm the expression and location of TRPM8 in T24 cells. Results: TRPM8 was highly expressed in T24 cells and located in both the cell membrane and cytoplasm. With the use of small interfering RNA to silence the expression of TRPM8, we found that menthol could increase the concentration of intracellular calcium and decrease cell viability via the TRPM8 channel in T24 cells. We also found that menthol could induce cell death through TRPM8 in T24 cells, rather than cell cycle arrest or apoptosis. Moreover, the detection of mitochondrial membrane potential showed that menthol could induce mitochondrial membrane depolarization in T24 cells. Conclusions: In the present study, we demonstrated that menthol can induce mitochondrial membrane depolarization via the TRPM8 channel in cells of the human bladder cancer cell line T24, resulting in cell death. It would be helpful to explore the precise mechanism of action of menthol in bladder cancer with a view to its possible use as intravesical chemotherapy.
Prehospital 12-Lead ECG to Triage ST-Elevation Myocardial Infarction and Emergency Department Activation of the Infarct Team Significantly Improves Door-to-Balloon Times
Authors: Hutchison Adam W. , Malaiapan Yuvaraj , Jarvie Ian , Barger Bill , Watkins Edward , Braitberg George , Kambourakis Tony , Cameron James D. , Meredith Ian T.
Published: December 2009

Background—

American College of Cardiology/American Heart Association guidelines recommend >75% of patients with an ST-elevation myocardial infarction receive primary percutaneous coronary interventions (PPCI) within 90 minutes. Despite these recommendations, this goal has been difficult to achieve.

Methods and Results—

We conducted a prospective interventional study involving 349 patients undergoing PPCI at a single tertiary referral institution to determine the impact of prehospital 12-lead ECG triage and emergency department activation of the infarct team on door-to-balloon time (D2BT). The median D2BT of all patients (n=107) who underwent PPCI after field ECG and emergency department activation of the infarct team (MonashHEART Acute Myocardial Infarction [MonAMI] group) was 56 minutes (interquartile range, 36.5 to 70) compared with the median time of a contemporary group (n=122) undergoing PPCI during the same period but not receiving field triage (non-MonAMI group) of 98 minutes (73 to 126.45). The median D2BT time of 120 consecutive patients who underwent PPCI before initiation of the project (pre-MonAMI group) was 101.5 minutes (72.5 to 134;
P
<0.001). The proportion of patients who achieved a D2BT of ≤90 minutes increased from 39% in the pre-MonAMI group and 45% in the non-MonAMI group to 93% in the MonAMI group (
P
<0.001).

Conclusions—

The performance of prehospital 12-lead ECG triage and emergency department activation of the infarct team significantly improves D2BT and results in a greater proportion of patients achieving guideline recommendations.
What Makes Shabti Slave?
Authors: Silver Morris
Published: December 2009

The first part of this paper considers why small funerary figures called shabtis, were willing to slave in the Beyond for deceased Egyptians. The proposed answer is that they agreed in return for being given "life" by the craftsman. It is well understood that ancient Egyptians were willing to utilize standard legal forms to mediate between the earthly and supernatural dimensions. However, consideration of the "contract" between craftsmen and shabtis casts new light on the nature of ancient Egypt's labor market and, more specifically, on the prevalence of resorting to contractual slavery. The second part of the paper uses economic analysis to reinforce the suggestion that temple ateliers probably earned a substantial profit by marketing shabtis. La première partie de cet article envisage les raisons pour lesquelles les figurines funéraires appelées oushebtis consentaient à servir les Egyptiens comme esclaves dans l'au-delà. Nous proposons que ces figurines acceptaient ce rôle en échange de la « vie » que leur insufflaient les artisans. Il est bien connu que les anciens Egyptiens employaient des formulaires juridiques comme mode de médiation entre le domaine terrestre et celui du surnaturel. L'examen du « contrat » passé entre artisans et oushebtis éclaire néanmoins d'un jour nouveau la nature du marché du travail dans l'Egypte ancienne, notamment le recours répandu à l'esclavage contractuel. Dans la seconde partie de l'article, une analyse économique confirme que la vente des oushebtis assurait vraisemblablement des profits substantiels aux ateliers des temples.
Ascertaining Living Standards in Erstwhile Mysore, Southern India, from Francis Buchanan's Journey of 1800-01: An Empirical Contribution to the Great Divergence Debate
Authors: Sivramkrishna Sashi
Published: December 2009

India's position in the Great Divergence debate has remained tentative due to scanty data availability for the medieval and early modern periods. In the years 1800-01, Dr. Francis Buchanan conducted one of the first agricultural surveys in the erstwhile state of Mysore and its adjoining regions. His Journey contains a wealth of information, both quantitative and qualitative, which has not been studied systematically so far. This paper brings together the information scattered throughout his report to construct an aggregate welfare ratio in order to ascertain the overall living standard in Mysore at the turn of the nineteenth century, the eve of colonial intervention in the state. The results from this study have interesting and important implications for the Great Divergence debate. La place de l'Inde dans le débat sur la Grande Divergence est encore incertaine en raison de la rareté des données disponibles pour le Moyen Âge et le début de l'époque moderne. Dans les années 1800-'01, Francis Buchanan mena l'une des premières enquêtes agricoles dans l'ancien Etat de Mysore et les contrées avoisinantes. Son Voyage contient de nombreuses données relatives à cette région, tant quantitatives que qualitatives, qui n'ont jamais fait l'objet d'études systématiques. Cet article réunit les informations disponibles dans son rapport afin de restituer un taux global de bien-être. Il s'agit de déterminer le niveau de vie moyen au Mysore au tournant du XIXe siècle, à l'aube de l'intervention coloniale dans cet Etat. Les résultats de cette étude ont des implications importantes pour le débat sur la Grande Divergence.
Pathways to Persuasion: Cognitive and Experiential Responses to Health-Promoting Mass Media Messages
Authors: Dunlop Sally M. , Wakefield Melanie , Kashima Yoshihisa
Published: December 2009

The experience of transportation—being absorbed in a narrative—and its relationship to persuasion were considered in two studies exploring responses to health-promoting mass media messages. Following Epstein’s (1994) cognitive-experiential self-theory, two pathways to persuasion were considered: cognitive and experiential. In Study 1 ( n = 121), smokers who experienced increased transportation in response to antismoking messages reported that they would make a greater effort to quit smoking, and this effect was mediated by both experiential (emotional and self-referencing) and cognitive responses to the messages. In Study 2 ( n = 110), experiential responses to magazine messages promoting skin protection were related to intentions to protect oneself, and this effect was mediated by feelings of risk.The implications of these results are discussed in terms of principles for effective health communication campaigns as well as theoretical advances in narrative persuasion in the context of health communication.
Peak and mystical experiences in intimate relationships
Authors: Woodward Anne J. , Findlay Bruce M. , Moore Susan M.
Published: December 2009

The focus of this paper is intimate relationship peak experiences arising from loving or sexual involvement. Different types of peak experiences were described and their relevance to relationship functioning explored qualitatively and quantitatively. In a convenience sample (N = 298), participants who identified having peak experiences were on average significantly older, more passionate, more sexually responsive and had less negative affect. Participants reporting peak experiences of a mystical nature tended to be significantly older and more spiritually focused. We concluded that relationship peak and mystical peak experiences represent important and memorable occasions which are personally significant to some couple members, deepening their bond. As such, therapists may strengthen partners’ senses of belonging to the relationship by discussion of peak experiences.
A qualitative analysis of on-again/off-again romantic relationships: “It’s up and down, all around”
Authors: Dailey René M. , Rossetto Kelly R. , Pfiester Abigail , Surra Catherine A.
Published: December 2009

Although relational research predominantly conceptualizes romantic relationships as either together or apart, some relationships break up and renew (i.e., on-again/off-again relationships). Partners’ accounts of on-again/off-again relational experiences were qualitatively analyzed to explore both reasons for breakups and reasons for renewals. Themes were interpreted within an interdependence framework to explain why partners dissolved as well as renewed their relationships. The themes in combination suggest renewals occurred due to dissatisfying experiences with alternative relationship partners and an increase in outcomes (i.e., rewards minus costs) after breakups. Partners’ post-dissolution contact and their uncertainty about relational status may have further facilitated renewals. More generally, the themes suggest, for on-again/ off-again partners, breakups did not indicate the end of interdependence but rather a redefinition of the relationship.
Negotiating Exclusion
Authors: Martucci Jessica
Published: December 2009

In the US, blood donors face a variety of restrictions that leave many people excluded entirely from the donor pool. This paper explores the specific circumstances and meanings surrounding the donor ban on Men-who-have-Sex-with-Men (MSM). The ban on MSM is one of the few existing donor guidelines to receive considerable criticism on grounds that it effectively prohibits any sexually active gay man from donating blood and thus discriminates against gays. Due in part to these questions of fairness, the Blood Products Advisory Committee (BPAC) of the Food and Drug Administration (FDA) met to reconsider the decades-old policy, first in 1997 and again in 2000. The FDA asked its advisory committee to address the efficacy and utility of the MSM ban in light of technological developments in blood-banking, epidemiological data on the spread of HIV, and mounting pressures from gay rights and blood-banking organizations to update the policy. Through a detailed reading of meeting and conference transcripts that took place between 1997 and 2000, I argue that ‘MSM’ became a contested definitional category during the FDA’s reappraisal of the policy. During and between the Committee’s discussions, presenters and experts debated the differences between sexual behavior and sexual identity in relation to HIV and, eventually, HHV-8, a virus known to cause Kaposi’s sarcoma in immunosuppressed individuals. I argue that the underlying flexibility in the meanings behind the term ‘MSM’ allowed Committee members, in the end, to retract their more nuanced discussions of human behavior and HIV and to uphold the contested policy. Finally, I suggest how the debates surrounding the MSM donor ban can help us to better understand the place of sexuality in discussions and claims of biopolitical citizenship in early 21st-century America.
Towards a relational comparative approach to the study of cities
Authors: Ward Kevin
Published: December 2009

Recent years have witnessed the beginnings of a renaissance in the field of comparative urban studies. The paper discusses this body of work’s history, drawing on contributions from across the social sciences. Following this it highlights some of the work’s limits, namely its weak theorization of place, scale and causality. The paper then offers a relational comparative approach to the study of cities as a means of attending to these limits. This acknowledges both the territorial and relational geographies behind the production of cities.
Idiopathic Childhood Occipital Epilepsy of Gastaut: A Review and Differentiation From Migraine and Other Epilepsies
Authors: Caraballo Roberto , Koutroumanidis Michael , Panayiotopoulos Chrysostomos P. , Fejerman Natalio
Published: December 2009

The purpose of this review is to provide guidance for appropriate diagnosis and management of idiopathic childhood occipital epilepsy of Gastaut. The typical clinical features are visual seizures that typically consist of brief elementary visual hallucinations, which are mainly multicolored and circular. Ictal blindness and deviation of the eyes are also common symptoms. The seizures are usually frequent and diurnal. The electroencephalography is the only investigation with abnormal results, showing occipital spikes and often occipital paroxysms demonstrating fixation-off sensitivity. Brain magnetic resonance imaging is used to exclude symptomatic occipital epilepsy. Patients usually respond well to antiepileptic medication and about two-thirds remit by the age of 16 years. Idiopathic childhood occipital epilepsy of Gastaut is frequently misdiagnosed as migraine with visual aura, acephalgic, or basilar migraine. Differentiation from symptomatic occipital epilepsy, particularly when children are otherwise normal, can be difficult. Most children need prophylactic antiepileptic medication.
Sphingolipid Activator Protein B Deficiency: Report of 9 Saudi Patients and Review of the Literature
Authors: Al-Hassnan Zuhair N. , Al Dhalaan Hesham , Patay Zoltan , Faqeih Eissa , Al-Owain Mohammed , Al-Duraihem Adel , Faiyaz-Ul-Haque Mohammed
Published: December 2009

Mutated PSAP gene resulting in sphingolipid activator protein B deficiency is known to cause metachromatic leukodystrophy variant in which arylsulfatase A is normal. Of 16 patients with metachromatic leukodystrophy that were evaluated in our center, 7 patients were diagnosed with arylsulfatase A—deficient metachromatic leukodystrophy, whereas 9 children from 4 unrelated Saudi families were found to have sphingolipid activator protein B deficiency. PSAP analysis found that the 4 families segregate the same homozygous mutation that was a g.722G>C transversion resulting in C241S change, which was previously reported in an Arab patient. Our work, which reports the largest series of patients with sphingolipid activator protein B deficiency, suggests that this variant is likely to be more common than arylsulfatase A—deficient metachromatic leukodystrophy in Arabs, a notion that has potential diagnostic and preventive implications.
Safety and Tolerability of Rufinamide in Children With Epilepsy: A Pooled Analysis of 7 Clinical Studies
Authors: Wheless James W. , Conry Joan , Krauss Gregory , Mann Allison , LoPresti Antonia , Narurkar Milind
Published: December 2009

Rufinamide is a novel antiepileptic agent recently approved in the United States for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. To help inform clinical decision making, the authors analyzed safety and tolerability data from the entire pediatric population in the rufinamide epilepsy clinical development program. The analysis population comprised 212 rufinamide-treated (age range 3-16 years) and 197 placebo patients (age range 4-17 years) in the double-blind studies, and 391 patients receiving rufinamide in the double-blind and/or open-label extensions. The most common adverse effects observed in rufinamide-treated patients in the double-blind studies were somnolence, vomiting, and headache. Changes in laboratory values, vital signs, and weight were generally clinically insignificant. This pooled analysis of data from pediatric patients in clinical studies of rufinamide for the treatment of seizures, mainly as adjunctive therapy, suggests a favorable safety and tolerability profile in this patient population.
Drug Use and Intimate Partner Violence Among College Students: An In-Depth Exploration
Authors: Nabors Erin L.
Published: December 2009

College students experience an extremely high level of violence among intimate partners during their college careers, with prevalence rates ranging between 20% and 50%. Because intimate partner violence (IPV) among college students is such a widespread problem, it is important to understand the factors that contribute to this type of abuse. Studies using a variety of samples demonstrate that drug use is one such factor. However, research to date fails to identify specific types of drugs linked to college students’ use of violence against intimates. In an attempt to fill this void, this exploratory study uses data from the Relationship Characteristics Study, which was conducted in 2001 and includes a sample of 1,938 college students, to provide a more comprehensive understanding of the relationship between college students’ drug use and IPV perpetration than the current literature allows.
Trees in the subalpine belt since 11 700 cal. BP: origin, expansion and alteration of the modern forest
Authors: Blarquez Olivier , Carcaillet Christopher , Bremond Laurent , Mourier Brice , Radakovitch Olivier
Published: December 2009

High altitude alpine ecosystems are likely to be highly sensitive to future climate change. Understanding long-term tree stand dynamics may be a key requirement for forecasting such changes. Here, we present a high resolution record of paleobotanical macroremains covering the last 11 700 years, from a small subalpine pond situated in the inner French Alps, at 2035 m a.s.l. The early presence of larch ( Larix decidua), arolla pine ( Pinus cembra) and birch ( Betula) at this elevation, just after the end of the Younger Dryas cold transition, suggests the occurrence of either glacial tree-refugia located nearby in the northwestern Alps, or a previously unrecorded early and rapid tree migration. The 8200 cal. BP cooling event is characterized by a rapid and limited expansion of mountain pine ( Pinus mugo/uncinata type). Mixed stands of larch, birch and arolla pine established at 8300 cal. BP and were present through the mid Holocene. After the Holocene climatic optimum, at 5600 cal. BP, recurrent fires led to the development of highly dynamic and more diversified forests, with larch, birch, arolla pine, mountain pine and fir ( Abies alba). Natural and anthropogenic disturbances, e.g., fires, avalanches, slash-and-burn and other agricultural practices, influenced subsequent vegetation until the last millennium when tree-pasture established around the lake. The data indicate that the vegetation was progressively dominated by open larch woodland from 4000 years ago, and was clearly established during the Middle Ages (1250 cal. BP) up to the nineteenth century, when land began to be abandoned. The modern vegetation, dominated by larch and arolla pine and resulting from land abandonment, tends to resemble the communities that occurred from 8300 to 4000 cal. BP, before the postulated anthropogenic alteration of subalpine forest ecosystems. The plant macroremains analysis provides a unique and precise record of stand-to-local vegetation composition and dynamics that can bridge paleoecology and forest management.
Can soil phytolith analysis and charcoal be used as indicators of historic fire in the pinyon-juniper and sagebrush steppe ecosystem types of the Great Basin Desert, USA?
Authors: Morris Lesley R. , Ryel Ronald J. , West Neil E.
Published: December 2009

Wildland fire intensity and area are increasing across the Intermountain West, USA, in a variety of ecosystem types including the pinyon-juniper woodlands and sagebrush steppe of the Great Basin Desert. Unfortunately, we do not know if there were historic analogues for these high-intensity stand-replacing fires because of the lack of fire scars that record evidence of them. Soil-charcoal and phytolith analyses have been successfully employed in other regions to garner information about fire regimes through the Holocene. We studied the utility of these methodologies and related taphonomic issues in soils in the Great Basin Desert. Our results showed that both microscopic charcoal and burned phytoliths can be found in soils with radiocarbon ages from modern to late Holocene. Microscopic charcoal abundance was more useful than size class as an indicator of recent local fire. Its abundance declined rapidly and remained low at 2.8 to 4.8 km from the edge of the fire. A Burned Phytolith Index shared a similar pattern starting at 0.4 km from the fire edge. Both proxies declined in abundance with depth in the soil at recent burn sites while remaining constant in unburned sites. We were unable to detect a signal for a known historic fire, however, this may have been a result of sample depth. Our results indicate that soil-charcoal and phytolith analysis can be used to examine questions about historical fires in these two ecosystems of the Great Basin Desert.
Efficacy and safety of cyclosporine A in patients with refractory systemic lupus erythematosus in a daily clinical practice
Authors: Ogawa H. , Kameda H. , Amano K. , Takeuchi T.
Published: December 2009

We investigated the efficacy and safety of cyclosporine A (CsA; targeted serum trough level: 80—150 ng/ml) in a daily clinical practice for treating patients with systemic lupus erythematosus (SLE), who had been, or were expected to be, refractory to glucocorticoids (GCs) and other immunosuppressants. Fifty-nine patients with SLE receiving CsA were observed for at least 6 months (21.5 months on average). A significant reduction of proteinuria was noted 2 weeks after initiation of treatment in patients with nephritis, resulting in a clinical response in five of eight patients in the GC dose-up group and 11 of 18 patients in the stable GC dose group, respectively. Notably, the mean score for disease activity on the SLE Disease Activity Index decreased significantly from 8.6 ± 5.3 to 4.4 ± 2.5 after CsA treatment in patients in the stable GC dose group (n = 40). Moreover, the mean flare rate decreased by approximately 60% with CsA. Side effects of CsA appeared in 32.2% of patients and all of them subsided through dose reduction or discontinuation (n=8) of CsA. Consequently, the cumulative 2-year survival rate of CsA was 75%. The results suggest that CsA should be considered for patients with SLE refractory to GCs. Lupus (2010) 19, 162—169.
Retrovirus gene therapy for X-linked chronic granulomatous disease can achieve stable long-term correction of oxidase activity in peripheral blood neutrophils
Authors: Kang Elizabeth M. , Choi Uimook , Theobald Narda , Linton Gilda , Long Priel Debra A. , Kuhns Doug , Malech Harry L.
Published: December 2009

Chronic granulomatous disease (CGD) is associated with significant morbidity and mortality from infection. The first CGD gene therapy trial resulted in only short-term marking of 0.01% to 0.1% of neutrophils. A recent study, using busulfan conditioning and an SFFV retrovirus vector, achieved more than 20% marking in 2 patients with X-linked CGD. However, oxidase correction per marked neutrophil was less than normal and not sustained. Despite this, patients clearly benefited in that severe infections resolved. As such, we initiated a gene therapy trial for X-CGD to treat severe infections unresponsive to conventional therapy. We treated 3 adult patients using busulfan conditioning and an MFGS retroviral vector encoding gp91phox, achieving early marking of 26%, 5%, and 4% of neutrophils, respectively, with sustained long-term marking of 1.1% and 0.03% of neutrophils in 2 of the patients. Gene-marked neutrophils have sustained full correction of oxidase activity for 34 and 11 months, respectively, with full or partial resolution of infection in those 2 patients. Gene marking is polyclonal with no clonal dominance. We conclude that busulfan conditioning together with an MFGS vector is capable of achieving long-term correction of neutrophil oxidase function sufficient to provide benefit in management of severe infection. This study was registered at www.clinicaltrials.gov as #NCT00394316.
CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus
Authors: Zlotoff Daniel A. , Sambandam Arivazhagan , Logan Theodore D. , Bell J. Jeremiah , Schwarz Benjamin A. , Bhandoola Avinash
Published: December 2009

T lymphopoiesis requires settling of the thymus by bone marrow–derived precursors throughout adult life. Progenitor entry into the thymus is selective, but the molecular basis of this selectivity is incompletely understood. The chemokine receptor CCR9 has been demonstrated to be important in this process. However, progenitors lacking CCR9 can still enter the thymus, suggesting a role for additional molecules. Here we report that the chemokine receptor CCR7 is also required for efficient thymic settling. CCR7 is selectively expressed on bone marrow progenitors previously shown to have the capacity to settle the thymus, and CCR7−/− progenitors are defective in settling the thymus. We further demonstrate that CCR7 sustains thymic settling in the absence of CCR9. Mice deficient for both CCR7 and CCR9 have severe reductions in the number of early thymic progenitors, and in competitive assays CCR7−/−CCR9−/− double knockout progenitors are almost completely restricted from thymic settling. However, these mice possess near-normal thymic cellularity. Compensatory expansion of intrathymic populations can account for at least a part of this recovery. Together our results illustrate the critical role of chemokine receptor signaling in thymic settling and help to clarify the cellular identity of the physiologic thymic settling progenitors.
Regulation of human NK-cell cytokine and chemokine production by target cell recognition
Authors: Fauriat Cyril , Long Eric O. , Ljunggren Hans-Gustaf , Bryceson Yenan T.
Published: December 2009

Natural killer (NK)–cell recognition of infected or neoplastic cells can induce cytotoxicity and cytokine secretion. So far, it has been difficult to assess the relative contribution of multiple NK-cell activation receptors to cytokine and chemokine production upon target cell recognition. Using Drosophila cells expressing ligands for the NK-cell receptors LFA-1, NKG2D, DNAM-1, 2B4, and CD16, we studied the minimal requirements for secretion by freshly isolated, human NK cells. Target cell stimulation induced secretion of predominately proinflammatory cytokines and chemokines. Release of chemokines MIP-1α, MIP-1β, and RANTES was induced within 1 hour of stimulation, whereas release of TNF-α and IFN-γ occurred later. Engagement of CD16, 2B4, or NKG2D sufficed for chemokine release, whereas induction of TNF-α and IFN-γ required engagement of additional receptors. Remarkably, our results revealed that, upon target cell recognition, CD56dim NK cells were more prominent cytokine and chemokine producers than CD56bright NK cells. The present data demonstrate how specific target cell ligands dictate qualitative and temporal aspects of NK-cell cytokine and chemokine responses. Conceptually, the results point to CD56dim NK cells as an important source of cytokines and chemokines upon recognition of aberrant cells, producing graded responses depending on the multiplicity of activating receptors engaged.
The origin of bmp16, a novel Bmp2/4relative, retained in teleost fish genomes
Authors: Feiner Nathalie , Begemann Gerrit , Renz Adina J , Meyer Axel , Kuraku Shigehiro
Published: December 2009

Background

Whole genome sequences have allowed us to have an overview of the evolution of gene repertoires. The target of the present study, the TGFβ superfamily, contains many genes involved in vertebrate development, and provides an ideal system to explore the relationships between evolution of gene repertoires and that of developmental programs.

Results

As a result of a bioinformatic survey of sequenced vertebrate genomes, we identified an uncharacterized member of the TGFβ superfamily, designatedbmp16, which is confined to teleost fish species. Our molecular phylogenetic study revealed a high affinity ofbmp16to theBmp2/4subfamily. Importantly, further analyses based on the maximum-likelihood method unambiguously ruled out the possibility that this teleost-specific gene is a product of teleost-specific genome duplication. This suggests that the absence of abmp16ortholog in tetrapods is due to a secondary loss.In situhybridization showed embryonic expression of the zebrafishbmp16in the developing swim bladder, heart, tail bud, and ectoderm of pectoral and median fin folds in pharyngula stages, as well as gut-associated expression in 5-day embryos.

Conclusion

Comparisons of expression patterns revealed (1) the redundancy ofbmp16expression with its homologs in presumably plesiomorphic expression domains, such as the fin fold, heart, and tail bud, which might have permitted its loss in the tetrapod lineage, and (2) the loss of craniofacial expression and gain of swim bladder expression ofbmp16after the gene duplication betweenBmp2,-4and-16. Our findings highlight the importance of documenting secondary changes of gene repertoires and expression patterns in other gene families.
Multiple invasions of Gypsy and Micropia retroelements in genus Zaprionus and melanogaster subgroup of the genus Drosophila
Authors: de Setta Nathalia , Van Sluys Marie-Anne , Capy Pierre , Carareto Claudia MA
Published: December 2009

Background

The Zaprionus genus shares evolutionary features with the melanogaster subgroup, such as space and time of origin. Although little information about the transposable element content in the Zaprionus genus had been accumulated, some of their elements appear to be more closely related with those of the melanogaster subgroup, indicating that these two groups of species were involved in horizontal transfer events during their evolution. Among these elements, the Gypsy and the Micropia retroelements were chosen for screening in seven species of the two Zaprionus subgenera, Anaprionus and Zaprionus.

Results

Screening allowed the identification of diverse Gypsy and Micropia retroelements only in species of the Zaprionus subgenus, showing that they are transcriptionally active in the sampled species. The sequences of each retroelement were closely related to those of the melanogaster species subgroup, and the most parsimonious hypothesis would be that 15 horizontal transfer events shaped their evolution. The Gypsy retroelement of the melanogaster subgroup probably invaded the Zaprionus genomes about 11 MYA. In contrast, the Micropia retroelement may have been introduced into the Zaprionus subgenus and the melanogaster subgroup from an unknown donor more recently (~3 MYA).

Conclusion

Gypsy and Micropia of Zaprionus and melanogaster species share similar evolutionary patterns. The sharing of evolutionary, ecological and ethological features probably allowed these species to pass through a permissive period of transposable element invasion, explaining the proposed waves of horizontal transfers.
Correcting for cryptic relatedness by a regression-based genomic control method
Authors: Yan Ting , Hou Bo , Yang Yaning
Published: December 2009

Background

Genomic control (GC) method is a useful tool to correct for the cryptic relatedness in population-based association studies. It was originally proposed for correcting for the variance inflation of Cochran-Armitage's additive trend test by using information from unlinked null markers, and was later generalized to be applicable to other tests with the additional requirement that the null markers are matched with the candidate marker in allele frequencies. However, matching allele frequencies limits the number of available null markers and thus limits the applicability of the GC method. On the other hand, errors in genotype/allele frequencies may cause further bias and variance inflation and thereby aggravate the effect of GC correction.

Results

In this paper, we propose a regression-based GC method using null markers that are not necessarily matched in allele frequencies with the candidate marker. Variation of allele frequencies of the null markers is adjusted by a regression method.

Conclusion

The proposed method can be readily applied to the Cochran-Armitage's trend tests other than the additive trend test, the Pearson's chi-square test and other robust efficiency tests. Simulation results show that the proposed method is effective in controlling type I error in the presence of population substructure.
RNA profiles of rat olfactory epithelia: individual and age related variations
Authors: Rimbault Maud , Robin Stéphanie , Vaysse Amaury , Galibert Francis
Published: December 2009

Background

Mammalian genomes contain a large number (~1000) of olfactory receptor (OR) genes, many of which (20 to 50%) are pseudogenes. OR gene transcription is not restricted to the olfactory epithelium, but is found in numerous tissues. Using microarray hybridization and RTqPCR, we analyzed the mRNA profiles of the olfactory epithelium of male and female Brown Norway rats of different origins and ages (newborn, adult and old).

Results

(1) We observed very little difference between males and females and between rats from two different suppliers. (2) Different OR genes were expressed at varying levels, rather than uniformly across the four endoturbinates. (3) A large proportion of the gene transcripts (2/3 of all probes) were detected in all three age groups. Adult and older rats expressed similar numbers of OR genes, both expressing more OR genes than newborns. (4) Comparisons of whole transcriptomes or transcription profiles of expressed OR genes only showed a clear clustering of the samples as a function of age. (5) Most OR genes were expressed at lower levels at birth than in older animals, but a small number of OR genes were expressed specifically or were overexpressed in newborns.

Conclusion

Not all OR genes are expressed at a detectable level. Pups expressed fewer OR genes than adult rats, and generally at a lower level; however, a small subset of OR genes were more strongly expressed in these newborn rats. The reasons for these differences are not understood. However, the specific expression of some OR genes in newborn olfactory epithelia may be related to the blindness and deafness of pups at birth, when these pups are heavily reliant on olfaction and their mother.
Using transcriptome profiling to characterize QTL regions on chicken chromosome 5
Authors: Le Mignon Guillaume , Désert Colette , Pitel Frédérique , Leroux Sophie , Demeure Olivier , Guernec Gregory , Abasht Behnam , Douaire Madeleine , Le Roy Pascale , Lagarrigue Sandrine
Published: December 2009

Background

Although many QTL for various traits have been mapped in livestock, location confidence intervals remain wide that makes difficult the identification of causative mutations. The aim of this study was to test the contribution of microarray data to QTL detection in livestock species. Three different but complementary approaches are proposed to improve characterization of a chicken QTL region for abdominal fatness (AF) previously detected on chromosome 5 (GGA5).

Results

Hepatic transcriptome profiles for 45 offspring of a sire known to be heterozygous for the distal GGA5 AF QTL were obtained using a 20 K chicken oligochip. mRNA levels of 660 genes were correlated with the AF trait. The first approach was to dissect the AF phenotype by identifying animal subgroups according to their 660 transcript profiles. Linkage analysis using some of these subgroups revealed another QTL in the middle of GGA5 and increased the significance of the distal GGA5 AF QTL, thereby refining its localization. The second approach targeted the genes correlated with the AF trait and regulated by the GGA5 AF QTL region. Five of the 660 genes were considered as being controlled either by the AF QTL mutation itself or by a mutation close to it; one having a function related to lipid metabolism (HMGCS1). In addition, a QTL analysis with a multiple trait model combining this 5 gene-set and AF allowed us to refine the QTL region. The third approach was to use these 5 transcriptome profiles to predict the paternal Q versus q AF QTL mutation for each recombinant offspring and then refine the localization of the QTL from 31 cM (100 genes) at a most probable location confidence interval of 7 cM (12 genes) after determining the recombination breakpoints, an interval consistent with the reductions obtained by the two other approaches.

Conclusion

The results showed the feasibility and efficacy of the three strategies used, the first revealing a QTL undetected using the whole population, the second providing functional information about a QTL region through genes related to the trait and controlled by this region (HMGCS1), the third could drastically refine a QTL region.
Plasmodium chabaudi limits early Nippostrongylus brasiliensis-induced pulmonary immune activation and Th2 polarization in co-infected mice
Authors: Hoeve Marieke A , Mylonas Katie J , Fairlie-Clarke Karen J , Mahajan Simmi M , Allen Judith E , Graham Andrea L
Published: December 2009

Background

Larvae of several common species of parasitic nematodes obligately migrate through, and often damage, host lungs. The larvae induce strong pulmonary Type 2 immune responses, including T-helper (Th)2 cells as well as alternatively activated macrophages (AAMφ) and associated chitinase and Fizz/resistin family members (ChaFFs), which are thought to promote tissue repair processes. Given the prevalence of systemic or lung-resident Type 1-inducing pathogens in geographical areas in which nematodes are endemic, we wished to investigate the impact of concurrent Type 1 responses on the development of these Type 2 responses to nematode larval migration. We therefore infected BALB/c mice with the nematodeNippostrongylus brasiliensis, in the presence or absence ofPlasmodium chabaudi chabaudimalaria parasites. Co-infected animals received both infections on the same day, and disease was assessed daily before immunological measurements were taken at 3, 5, 7 or 20 days post-infection.

Results

We observed that the nematodes themselves caused transient loss of body mass and red blood cell density, but co-infection then slightly ameliorated the severity of malarial anaemia. We also tracked the development of immune responses in the lung and thoracic lymph node. By the time of onset of the adaptive immune response around 7 days post-infection, malaria co-infection had reduced pulmonary expression of ChaFFs. Assessment of the T cell response demonstrated that the Th2 response to the nematode was also significantly impaired by malaria co-infection.

Conclusion

P. c. chabaudico-infection altered both local and lymph node Type 2 immune activation due to migration ofN. brasiliensislarvae. Given recent work from other laboratories showing thatN. brasiliensis-induced ChaFFs correlate to the extent of long-term lung damage, our results raise the possibility that co-infection with malaria might alter pulmonary repair processes following nematode migration. Further experimentation in the co-infection model developed here will reveal the longer-term consequences of the presence of both malaria and helminths in the lung.
High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial
Authors: Amadi Beatrice , Mwiya Mwiya , Sianongo Sandie , Payne Lara , Watuka Angela , Katubulushi Max , Kelly Paul
Published: December 2009

Background

Treatment of cryptosporidiosis in HIV infected children has proved difficult and unsatisfactory with no drugs having demonstrable efficacy in controlled trials except nitazoxanide. We hypothesised that a prolonged course of treatment with high dose nitazoxanide would be effective in treating cryptosporidiosis in HIV positive Zambian children.

Methods

We performed a double-blind, randomised, placebo controlled trial in paediatric patients in the UTH in Lusaka. The study included HIV positive children between one and eleven years of age if 2 out of 3 stool samples were positive for oocysts of Cryptosporidium spp. Children were given nitazoxanide suspension in a dose of 200 mg twice daily (bid) for 28 days (if 1-3 years old) or 400 mg bid for 28 days (if 4-11 years old), or matching placebo.

Results

Sixty children were randomised and 52 were fully evaluated. Only five children were 4 years of age or over and received the higher dose. In the primary efficacy analysis, 11 out of 26 (42%) in the active treatment group achieved a 'Well' clinical response compared to 8 out of 26 (35%) in the placebo group. Parasitological response was declared as 'Eradicated' in 27% in the active group and 35% in the placebo group. Mortality (16/52, 31%) did not differ by treatment allocation.

Conclusion

We found no significant benefit in children with cryptosporidiosis despite high dose and longer treatment duration. This is the second randomised controlled trial to suggest that in Zambian children with HIV-related immunosuppression nitazoxanide does not eradicate this infection nor provide clinical symptom reduction.

Trial Registration

The trial was registered as ISRCTN41089957.
Identification of colorectal cancer patients with tumors carrying the TP53mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy
Authors: Godai Ten-i , Suda Tetsuji , Sugano Nobuhiro , Tsuchida Kazuhito , Shiozawa Manabu , Sekiguchi Hironobu , Sekiyama Akiko , Yoshihara Mitsuyo , Matsukuma Shoichi , Sakuma Yuji , Tsuchiya Eiju , Kameda Yoichi , Akaike Makoto , Miyagi Yohei
Published: December 2009

Background

Although postoperative chemotherapy is widely accepted as the standard modality for Dukes' stage C or earlier stage colorectal cancer (CRC) patients, biomarkers to predict those who may benefit from the therapy have not been identified. Previous in vitro and clinical investigations reported that CRC patients with wild-type p53 gene (TP53)-tumors benefit from 5-fluorouracil (5-FU) based chemotherapy, while those with mutated TP53-tumors do not. However, these studies evaluated the mutation-status of TP53 by immunohistochemistry with or without single-strand conformation polymorphism, and the mutation frequency was different from study to study. In addition, the polymorphic status at p53 codon 72, which results in arginine or proline residues (R72P) and is thought to influence the function of the protein significantly, was not examined.

Methods

To evaluate the significance of the TP53 mutation as a molecular marker to predict the prognosis of CRC patients, especially those who received postoperative chemotherapy, we examined the mutation by direct sequencing from fresh CRC tumors and evaluated the R72P polymorphism of the mutated TP53 by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR).

Results

The TP53 mutation occurred in 147 (70%) of 211 Japanese CRC tumors. The mutation was observed in 93 (63%) tumors on the R72 allele and in 54 (37%) tumors on the P72 allele. Although the alterations to TP53 have no prognostic significance for CRC patients overall, we found that Dukes' stage C CRC patients who did not receive postoperative chemotherapy and carried the mutated TP53-R72 showed significantly longer survival times than those with the mutated TP53-P72 when evaluated by overall survival (p = 0.012).

Conclusion

Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the TP53 mutated allele in Japanese CRC patients. We raised a possibility that Dukes' stage C colorectal cancer patients with tumors carrying TP53 mutation, especially the P72 allele, benefited from 5-FU based postoperative chemotherapy.
Integrated, multidisciplinary care for hand eczema: design of a randomized controlled trial and cost-effectiveness study
Authors: van Gils Robin F , van der Valk Pieter GM , Bruynzeel Derk , Coenraads Pieter J , Boot Cécile RL , van Mechelen Willem , Anema Johannes R
Published: December 2009

Background

The individual and societal burden of hand eczema is high. Literature indicates that moderate to severe hand eczema is a disease with a poor prognosis. Many patients are hampered in their daily activities, including work. High costs are related to high medical consumption, productivity loss and sick leave. Usual care is suboptimal, due to a lack of optimal instruction and coordination of care, and communication with the general practitioner/occupational physician and people involved at the workplace. Therefore, an integrated, multidisciplinary intervention involving a dermatologist, a care manager, a specialized nurse and a clinical occupational physician was developed. This paper describes the design of a study to investigate the effectiveness and cost-effectiveness of integrated care for hand eczema by a multidisciplinary team, coordinated by a care manager, consisting of instruction on avoiding relevant contact factors, both in the occupational and in the private environment, optimal skin care and treatment, compared to usual, dermatologist-led care.

Methods

The study is a multicentre, randomized, controlled trial with an economic evaluation alongside. The study population consists of patients with chronic, moderate to severe hand eczema, who visit an outpatient clinic of one of the participating 5 (three university and two general) hospitals. Integrated, multidisciplinary care, coordinated by a care manager, including allergo-dermatological evaluation by a dermatologist, occupational intervention by a clinical occupational physician, and counselling by a specialized nurse on optimizing topical treatment and skin care will be compared with usual care by a dermatologist. The primary outcome measure is the cumulative difference in reduction of the clinical severity score HECSI between the groups. Secondary outcome measures are the patient's global assessment, specific quality of life with regard to the hands, generic quality of life, sick leave and patient satisfaction. An economic evaluation will be conducted alongside the RCT. Direct and indirect costs will be measured. Outcome measures will be assessed at baseline and after 4, 12, 26 and 52 weeks. All statistical analyses will be performed on the intention-to-treat principle. In addition, per protocol analyses will be carried out.

Discussion

To improve societal participation of patients with moderate to severe hand eczema, an integrated care intervention was developed involving both person-related and environmental factors. Such integrated care is expected to improve the patients' clinical signs, quality of life and to reduce sick leave and medical costs. Results will become available in 2011.