bluuebunny/crossref_metadata_2025 huggingface dataset:
Deleterious Effects of Sleep-Disordered Breathing on the Heart and Vascular System
Authors: Dincer H. Erhan , O’Neill William
Published: November 2005

Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing, affecting 5–15% of the population. It is characterized by intermittent episodes of partial or complete obstruction of the upper airway during sleep that disrupts normal ventilation and sleep architecture, and is typically associated with excessive daytime sleepiness, snoring, and witnessed apneas. Patients with obstructive sleep apnea present risk to the general public safety by causing 8-fold increase in vehicle accidents, and they may themselves also suffer from the physiologic consequences of OSA; these include hypertension, coronary artery disease, stroke, congestive heart failure, pulmonary hypertension, and cardiac arrhythmias. Of these possible cardiovascular consequences, the association between OSA and hypertension has been found to be the most convincing. Although the exact mechanism has not been understood, there is some evidence that OSA is associated with frequent apneas causing mechanical effects on intrathoracic pressure, cardiac function, and intermittent hypoxemia, which may in turn cause endothelial dysfunction and increase in sympathetic drive. Therapy with continuous positive airway pressure has been demonstrated to improve cardiopulmonary hemodynamics in patients with OSA and may reverse the endothelial cell dysfunction. Despite the availability of diagnostic measures and effective treatment, many patients with sleep-disordered breathing remain undiagnosed. Therefore, OSA continues to be a significant health risk both for affected individuals and for thegeneral public. Awareness and timely initiation of an effective treatment may prevent potential deleterious cardiovascular effects of OSA.
Successful Treatment of Sarcoidosis-Associated Pulmonary Hypertension with Bosentan
Authors: Foley Raymond J. , Metersky Mark L.
Published: November 2005

Sarcoidosis is a systemic granulomatous disease of unknown etiology, in which the lungs and intrathoracic lymph nodes are predominant sites of involvement. Pulmonary hypertension is a known complication of sarcoidosis. Treatment of sarcoidosis-associated pulmonary hypertension has traditionally focused on the initiation of systemic corticosteroids, but has had inconsistent results. We present a patient with sarcoidosis-associated pulmonary hypertension who achieved substantial clinical improvement with the dual endothelin receptor antagonist bosentan.
Asthma Control following Initial Inhaled Corticosteroid Monotherapy in Mild to Moderate Asthma: A 4- to 8-Week Observational Study
Authors: Giraud Violaine , Rogeaux Yves , Dusser Daniel
Published: November 2005

Background: There is an increasing trend for the use of combination therapy of inhaled corticosteroids (ICS) and long-acting β2-agonists as initial treatment for asthma. Objective: To assess the efficacy of initial monotherapy with ICS for achieving asthma control in steroid-naive mild to moderate asthmatics. Method: During an observational survey, steroid-naive patients received ICS in a dosage of 400–2,000 µg/day. After 4–8 weeks’ treatment, achievement of asthma control, defined according to the Global Initiative for Asthma (GINA) guidelines, was assessed and the Asthma Control Questionnaire (ACQ) was completed. Results: Among 537 selected patients, 21 were excluded because of severe asthma and 96 because of inadequate ICS daily dosage. Four hundred and twenty patients were analyzed, 396 (94%) of whom completed the survey. Mean ICS dosage, in equivalent beclomethasone, was 479 ± 62 µg/day for mild asthma (group A) and 1,115 ± 306 µg/day for moderate asthma (group B). Asthma control was achieved for 71 and 65% of the patients, mean ACQ score improved from 1.1 ± 0.6 to 0.5 ± 0.5 (p < 0.001) and from 2.0 ± 0.8 to 0.8 ± 0.7 (p < 0,001), and FEV1 (% predicted) improved from 93 ± 9 to 96 ± 13 (p < 0.05) and from 85 ± 15 to 91 ± 15 (p < 0.001) for groups A and B, respectively. Conclusion: Asthma control can be achieved by ICS monotherapy for two thirds of steroid-naive patients with mild to moderate asthma. For these patients, we suggest that ICS alone could be started as initial therapy and that additional therapy should be considered after 4–8 weeks for patients who do not achieve control.
Old female reed buntings (Emberiza schoeniclus) increase extra-pair paternity in their broods when mated to young males
Authors: Bouwman Karen M. , Komdeur Jan
Published: November 2005

In birds, females are generally assumed to determine whether extra-pair copulations occur, and thus most studies on extra-pair paternity (EPP) have focussed on female preference for male traits, whereas female traits have been largely neglected. However, the occurrence of EPP is likely to be a result of behavioural interactions (e.g., mate guarding by the social male and escaping mate guarding by the female), and may be related to individual experience, which is expected to increase with age. We investigated the effect of age on levels of EPP in reed buntings Emberiza schoeniclus, a socially monogamous passerine with extremely high levels of extra-pair young (more than 50% of offspring). In broods of older males the rate of cuckoldry declined, which is in agreement with our previous finding that older males are more successful, either through female choice or through male experience. In contrast, older females tended to increase the level of extra-pair paternity in their broods. When including the age of the partner, we found that young males, but not old males, were cuckolded more by old females than by young females. The increase in EPP with female age is not likely to be due to disassortative mating with respect to age, an increased capacity of older females to raise a brood without male help, nor a male preference for older females. With age, males nor females changed their share in parental effort. We suggest that with increase in age, females become more choosy when selecting the male that sires their offspring, or alternatively, become more experienced at circumventing paternity assurance tactics of young males.
Parental care and brood division in a songbird, the black redstart
Authors: Draganoiu Tudor I. , Nagle Laurent , Musseau Raphael , Kreutzer Michel
Published: November 2005

Sexual conflict over parental care can be mediated through differences in male and female overall feeding rates, brood division or both. At present, it is not clear whether post-fledging brood division occurs due to sexual conflict over parental investment or is due to bi-parental cooperation, e.g. increase offspring fitness. We provide evidence suggesting that brood division in the black redstart, Phoenicurus ochruros is due to sexual conflict. Males and females had similar feeding contributions during the nestling stage, which is common for most passerine species. After fledging, each parent showed long-term feeding preferences for particular chicks within the brood. In most cases (74%; 17/23) both parents provided care but males tended to feed less fledglings than females did and in about a quarter of cases (26%; 6/23) females fed the whole brood by themselves. The relative amount of male to female post-fledging feedings showed a significant negative relationship with the proportion of fledglings cared for exclusively by the male. These results suggest (1) a close link between the amount of parental care and brood division; (2) sexual conflict can be mediated through brood division; (3) female redstarts appear to loose this conflict more often than male redstarts, with in the extreme cases males showing post-fledging brood desertion. A literature review shows brood division to occur in at least a dozen of songbird species but male black redstarts have the lowest relative post-fledging parental investment, expressed either as feeding rates or number of chicks in care.
Active and passive social support in families of greylag geese (Anser anser)
Authors: Frigerio Didone , Weiß Brigitte M. , Scheiber Isabella B.R. , Kotrschal Kurt
Published: November 2005

In general, support by social allies may reduce stress, increase success in agonistic encounters and ease access to resources. Social support was mainly known from mammals, particularly primates, and has been studied in birds only recently. Basically two types are known: (i) 'active social support', which describes the participation of a social ally in agonistic encounters, and (ii) 'passive social support' in which the mere presence of a social ally reduces behavioural and physiological stress responses. In greylag geese (Anser anser) offspring stay with their parents for an entire year or even longer and therefore are a candidate avian model to study support by social allies. We investigated the effects of active and passive social support in ten families (ten males, ten females, 33 juveniles) in a free-roaming, semi-tame flock of greylag geese. Focal individuals were observed during three time periods: (i) re-establishment of the flock in the fall, (ii) stable winter flock, and (iii) disintegration of the flock and break-up of family bonds. We recorded all agonistic interactions of the members of one focal family during morning feedings for two consecutive days: a control day, in which food was distributed widely, and a social density stress situation, in which the same amount of food was spread over a much smaller area. In addition, we collected faeces of all individuals within this family for three hours from the beginning of the feeding situation for determining excreted corticosterone immuno-reactive metabolites by enzyme immuno assay. We found that the small families, i.e. pairs with one or two accompanying young, were involved in more agonistic interactions, mainly through the lack of active social support, as compared to large families in the same situation. Members of greylag goose families lost agonistic encounters significantly less often when actively supported. In addition, the excretion of corticosterone metabolites was significantly decreased in large families during a social density stress situation, probably as an effect of passive social support. Via such a socially induced decrease in hormonal stress response during challenging situations, an individual's long term energy management may benefit.
Division of labour within cooperatively breeding groups
Authors: Arnold Kathryn E. , Owens Ian P.F. , Goldizen Anne W.
Published: November 2005

Within cooperative societies, group members share in caring for offspring. Although division of labour among group members has been relatively well studied in insects, less is known about vertebrates. Most studies of avian helping focus solely on the extent to which helpers provision the offspring, however, helpers can participate in everything from nest building to predator defence. Bad provisioners may, for example, not be as 'uncooperative' as they appear, if they are good defenders. Thus, the distribution of helping tasks between group members should have important implications for our interpretation of group dynamics. Here, we compare two distinct forms of helping behaviour in the cooperatively breeding noisy miner (Manorina melanocephala): chick provisioning and mobbing nest predators. We show that the way in which individual helpers invest in these two helping behaviours varies enormously across individuals and among social groups. Good provisioners often contributed relatively little to mobbing and vice versa. Indeed, (18%) of helpers only mobbed, 22% just provisioned, whereas 60% of helpers performed both forms of helping. Across nests, provisioning was significantly negatively correlated with mobbing effort. We suggest that small differences in the costs or benefits of different aspects of helping (due to differences in age, relatedness or social status) have a big impact on the division of labour within a group. Consequently, social groups can be made up from individuals who often specialise in one helping behaviour, and/or helpers who perform a number of behaviours to differing degrees. Division of labour within social groups will, therefore, have important consequences for the maintenance of cooperatively breeding in vertebrates.
The Articulation of Religious Identities and their Boundaries in Ethiopia: Labelling Difference and Processes of Contextualization in Islam
Authors: Desplat Patrick
Published: November 2005

Processes of contextualization in Islam are constantly raising questions about self-perception and the 'other', thus challenging the concept of an 'authentic' identity and its boundaries. Innovations and their appropriation or rejection currently play a significant role in Harar, an urban community in Eastern Ethiopia where local saints constitute a key element of everyday religious life. Islamic reform movements have been able to enter Ethiopia since the downfall of the socialist regime in 1991 and have been provoking disputes concerning the 'true' Islam, focusing on saints and related 'un-Islamic' practices. The majority of the Harar community has rejected this essentializing tendency, partly because of the influence of a Harari scholar who presides over the Lebanese organization Hasbashiyya. However, the contemporary role of religious networks and the quest for authenticity must be embedded in both the historical and contemporary socio-political context.
Translating the Qur'ān in Sub-Saharan Africa: Dynamics and Disputes
Authors: Loimeier Roman
Published: November 2005

In the last decades, African Muslim societies have experienced multiple processes of modernization, as, for instance, in the sphere of education. As a consequence, the number of African Muslims literate in African languages has grown tremendously and so has the number of texts, including religious texts, published in these languages. At the same time, the Qur'ān has been translated into many African languages, and these translations of the Qur'ān have triggered disputes among religious scholars on the translatability of the Qur'ān as well as the interpretative orientation of these translations. The disputes over the translation and interpretation of the Qur'ān into African languages might contribute to the emergence, in sub-Saharan Africa, of a tradition of scholarly debates that would stress contextualized interpretations of the text.
Roaming About For God's Sake: The Upsurge of the Tablīgh Jamā'at in the Gambia
Authors: Janson Marloes
Published: November 2005

The proliferation of the Tablīgh Jamā'at, an Islamic missionary movement that strictly observes the fundamentals of the faith, is a manifestation of the recent Islamic resurgence in West Africa. The movement originated in South Asia, but has expanded to Africa. Despite the Jamā'at's great influence on the lives of many West African Muslims, sub-Saharan Africa is a region that has been ignored almost completely in studies of the movement. This article focuses on The Gambia, which appears to be a booming centre of Tablīgh activities in West Africa. On the basis of the conversion stories of a male and a female Tablīgh activist, the central themes in the Gambian branch of the Tablīgh Jamā'at will be explored. These themes result from local factors such as the socio-economic crisis and gender relations. Nevertheless, they also bear similarities with recurrent subjects in other 'fundamentalist' movements throughout the world.
Two Published Hausa Translations of the Qur'ān and their Doctrinal Background
Authors: Brigaglia Andrea
Published: November 2005

This article presents an analysis of two written Hausa translations of the Qur'ān. Though emphasizing that these endeavours were strictly linked to their authors' previous careers as oral exegetes, the article argues also that a certain shift may take place in the significance of tafsīr through the importance assumed by written translation. These translations were published when a broad dogmatic conflict was taking place in Nigeria, and they feature a strong concern to de-legitimize or defend certain contended issues. The recurring object of debate in the two translations is usually Sufism, but, on a closer look, other related issues emerge as being at stake: the soundness of the local exegetical tradition, and the role of Aš'arism as a set of theological doctrines providing the conventional framework for traditional exegetes to speak about God and His attributes. Issues of language and style are also briefly explored.
Monitoring Selective Logging in Tropical Evergreen Forests Using Landsat: Multitemporal Regional Analyses in Mato Grosso, Brazil
Authors: Matricardi Eraldo A. T. , Skole David L. , Cochrane Mark A. , Qi Jiaguo , Chomentowski Walter
Published: November 2005

Selective logging degrades tropical forests. Logging operations vary in timing, location, and intensity. Evidence of this land use is rapidly obscured by forest regeneration and ongoing deforestation. A detailed study of selective logging operations was conducted near Sinop, State of Mato Grosso, Brazil, one of the key Amazonian logging centers. An 11-yr series of annual Lansdat images (1992–2002) was used to detect and track logged forests across the landscape. A semiautomated method was applied and compared to both visual interpretation and field data. Although visual detection provided precise delineation of some logged areas, it missed many areas. The semiautomated technique provided the best estimates of logging extent that are largely independent of potential user bias. Multitemporal analyses allowed the authors to analyze the annual variations in logging and deforestation, as well as the interaction between them. It is shown that, because of both rapid regrowth and deforestation, evidence of logging activities often disappeared within 1–3 yr. During the 1992–2002 interval, a total of 11 449 km2 of forest was selectively logged. Around 17% of these logged forests had been deforested by 2002. An intra-annual analysis was also conducted using four images spread over a single year. Nearly 3% of logged forests were rapidly deforested during the year in which logging occurred, indicating that even annual monitoring will underestimate logging extent. Great care will need to be taken when inferring logging rates from observations greater than a year apart because of the partial detection of previous years of logging activity.
Mariachi music as a symbol of Mexican culture in the United States
Authors: Clark Sylvia
Published: November 2005

The purpose of this study was to follow the development of mariachi music from its origin in the rural cultural celebrations of Mexico to its contemporary position in American music education. A dominant factor in traditional ceremonies, mariachi music emerged as the primary musical representation of Mexican nationalism in Mexico, a representation sustained and elaborated when Mexicans migrated to the United States. Incorporating mariachi training in the school curriculum ensures the continuing transmission of music that is vital to the identity of the Hispanic population. Music teachers can encourage children to explore the musical traditions of their own cultural heritage as well as those of other countries. Participation in meaningful musical performances can help students take pride in themselves and add a powerful dimension to their education.
Re-appraising ideas of musicality in intercultural contexts of music education
Authors: O’flynn John
Published: November 2005

This article examines ideas of musicality as they may apply to local, national and intercultural contexts of music education. Conceptions of multicultural music education are explored in the light of alternative approaches to musicality adapted from ethnomusicological perspectives. It is argued that while recently published music curricula in many countries appear to offer a more pluralistic view of music and music education than previously, these may fall short of providing an intercultural model for teachers and schools. Critically, an intercultural music education will draw on a variety of performing and learning practices, in addition to a range of beliefs and values that are pertinent to the musical systems in question. Ideas of bimusicalityand intermusicalitycan be adapted not only to our understanding of individual learners and performers, but also to the professional preparation of teachers, to the design of music curricula and to the development of musical infrastructures in contemporary societies.
Where is the Frame?
Authors: Van Gorp Baldwin
Published: November 2005

In this article an empirically oriented conceptualization of frames is developed, using the issue of asylum and illegal immigration in the Belgian press as a test case. The methodological focus of this study is on the question of how these frames can be detected in the coverage. How can they be defined independently of the researcher’s perspective, knowing that the naming of frames in itself already involves a kind of framing? Two frames are reconstructed and deductively ‘measured’ by a content analysis: on the one hand, ‘asylum-seekers are innocent victims’ and, on the other hand, ‘asylum-seekers are intruders’. In the second phase, this article examines to what extent eight Belgian newspapers used these two frames to cover the issue of asylum. A homogeneity analysis by means of HOMALS is introduced in the framing research. It turns out to be a fruitful way to establish the frames in the news more precisely. The construction of indices made it possible to explore the evolution of the use of frames over time. Surprisingly, the Christmas mood was a factor that caused a frame-shift and it even led to a media hype.
Explaining the Determinants of Public Support for Cuts in Unemployment Benefits Spending across OECD Countries
Authors: Fraile Marta , Ferrer Mariona
Published: November 2005

This article analyses comparative data for the last half of the 1990s to investigate the determinants of individual and cross-national variation in public support for cuts in unemployment benefits spending. The authors consider public opinion on unemployment benefits retrenchment as a product not only of individual-level characteristics but also of national-level features. With few exceptions, the latter features have been limited by previous studies to the institutional characteristics of welfare policies across countries operationalized in a superficial way: i.e. the type of welfare regime. This article proposes a more detailed operationalization of the institutional characteristics of welfare policies by considering cross-country variations in the generosity of unemployment protection. The authors also take into account a structural characteristic of the polities considered here: i.e. the seriousness of the unemployment problem. Even if the results are tentative, the authors believe they open the ‘black box of welfare types’ that until very recently has been the predominant explanation when accounting for aggregated variation in public opinion on welfare states.
The Double Dividend of Expanding Education for Development
Authors: Bornschier Volker , Herkenrath Mark , König Claudia
Published: November 2005

Education has been used in models of both econometricians and sociologists to explain differences in the speed of economic development. This important field of research is, however, theoretically underspecified, and the empirical tests have remained incomplete for they only model the direct effects of education suggested by the human capital school. This article complements this individualistic view by also considering functions of education stressed in sociology. The educational system is seen as a device to integrate society and legitimize socioeconomic inequality. Such a perspective allows one to consider both cohesion as well as socioeconomic conflict as mediating between public educational expenditure and economic achievement; this translates into a model that contains direct as well as indirect effects. The resulting proposition of a ‘double dividend’ of education in development suggests that in the short and medium term the educational efforts of governments may contribute to legitimizing society, which is reflected in tempering socioeconomic conflict. This again fosters economic growth via greater motivation of citizens and higher propensity to invest. In this article, the double-dividend thesis is corroborated in an empirical test using a sample of 83 societies.
The Demand for Volunteer Labor: A Study of Hospital Volunteers
Authors: Handy Femida , Srinivasan Narasimhan
Published: November 2005

The authors challenge the assumption that organizations are willing to use all the volunteer labor available to them. Rather, they are influenced by the costs incurred of utilizing volunteer labor. This article provides a modest first look at the demand for volunteers by nonprofit institutions. Specifically, the article presents an economic analysis of the demand of volunteer labor by hospitals in the Toronto area and examines some of the factors that may determine the hospitals’ willingness to use volunteer labor. Using data generated from 28 hospitals in Toronto, which use a total of more than 2 million volunteer hr per year, the authors show that the quantity of volunteer hours demanded is a decreasing function of their costs. Other factors such as productivity, output, and labor market institutions also influence the demand for volunteers.
Are They Here for the Long Haul? The Effects of Functional Motives and Personality Factors on the Psychological Contracts of Volunteers
Authors: Liao-Troth Matthew A.
Published: November 2005

In this article, the author discusses the concepts of the psychological contract, functional motivation, and the five-factor model of personality and explains how these should relate to one another when anticipating volunteer preferences. Two studies are presented: In the first he applied the psychological contract and the volunteer functional inventory to a sample of volunteer firefighters; in the second he applied the psychological contract, the volunteer functional inventory, and the five-factor model of personality to a sample of students volunteering for various student and community groups. No relationships were foundinStudy1betweenfunctional motives and psychological contract type. In Study 2, the personality dimensions of agreeableness and emotional stability were found to relate to the relational psychological contract. Career motives, and the personality factor of conscientiousness, were related to transactional psychological contracts. The implications for these findings are discussed.
Communication, global justice and the moral economy
Authors: Calabrese Andrew
Published: November 2005

The concept of a ‘moral economy,’ used famously by historian Edward Thompson in his 1971 essay, ‘The Moral Economy of the English Crowd in the Eighteenth Century,’ is sometimes invoked in discussions of struggles for social justice. Drawing from Thompson and others who have written about the idea of a ‘moral economy,’ this article shows how that concept serves as an instructive guide for thinking today about the idea of a global civil society and the global justice movement. Relying on historical work about selected struggles for social justice, this article demonstrates how the means of communication have been vital to transnational social movements for far longer than generally is acknowledged. Moreover, the means of communication have been central to sustaining the idea of a moral economy.
Tolerance induction by lentiviral gene therapy with a nonmyeloablative regimen
Authors: Mitsuhashi Noboru , Fischer-Lougheed Jacqueline , Shulkin Irina , Kleihauer Annette , Kohn Donald B. , Weinberg Kenneth I. , Starnes Vaughn A. , Kearns-Jonker Mary
Published: November 2005

Antibodies (Abs) directed at the Galα1,3Galβ1,4GlcNAc-R (αGal) carbohydrate epitope initiate xenograft rejection. Previously, we have shown that bone marrow transplantation (BMT) with lentivirus-mediated gene transfer of porcine α1,3 galactosyltransferase (GalT) is able to induce tolerance to αGal-expressing heart grafts following a lethal dose of irradiation. Here we show the first demonstration of permanent survival of αGal+ hearts following transplantation with autologous, lentivirus-transduced BM using a nonmyeloablative regimen. Autologous BM from GalT knockout (GalT–/–) mice was transduced with a lentiviral vector expressing porcine GalT and transplanted into sublethally irradiated (3 Gy) GalT–/– mice. Chimerism in the peripheral blood cells (PBCs) remained low but was higher in the BM, especially within the stromal cell population. Mice reconstituted with GalT did not produce anti-αGal Abs over time. We immunized these mice with αGal-expressing cells and assessed humoral immune responses. Anti-αGal xenoantibodies were not produced in mice reconstituted with GalT, but normal Ab responses to other xenoantigens were detected. Mice reconstituted with GalT accepted αGal+ heart grafts over 100 days. Transduction with lentiviral vectors results in chimerism at levels sufficient to induce long-term tolerance under nonmyeloablative conditions.
Apaf-1 and caspase-9 are required for cytokine withdrawal-induced apoptosis of mast cells but dispensable for their functional and clonogenic death
Authors: Marsden Vanessa S. , Kaufmann Thomas , O'Reilly Lorraine A. , Adams Jerry M. , Strasser Andreas
Published: November 2005

Cytokines promote survival of mast cells by inhibiting apoptotic pathways regulated by the Bcl-2 protein family. We previously showed that lymphocyte apoptosis can proceed via a Bcl-2-inhibitable pathway independent of the canonical initiator caspase, caspase-9, and its adaptor, Apaf-1. Here we report that mast cells lacking caspase-9 or Apaf-1 are refractory to apoptosis after cytotoxic insults but still lose effector function and ability to proliferate. In response to cytokine deprivation or DNA damage, fetal liver-derived mast cells lacking Apaf-1 or caspase-9 failed to undergo apoptosis. Nevertheless, the cytokine-starved cells were not functionally alive, because, unlike those overexpressing Bcl-2, they could not degranulate on Fcϵ receptor stimulation or resume proliferation on re-addition of cytokine. Furthermore, mast cells lacking Apaf-1 or caspase-9 had no survival advantage over wild-type counterparts in vivo. These results indicate that the Apaf-1/caspase-9-independent apoptotic pathway observed in lymphocytes is ineffective in cytokine-deprived mast cells. However, although Apaf-1 and caspase-9 are essential for mast cell apoptosis, neither is required for the functional or clonogenic death of the cells, which may be due to mitochondrial dysfunction.
Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease
Authors: Kato Gregory J. , McGowan Vicki , Machado Roberto F. , Little Jane A. , Taylor James , Morris Claudia R. , Nichols James S. , Wang Xunde , Poljakovic Mirjana , Morris Sidney M. , Gladwin Mark T.
Published: November 2005

Pulmonary hypertension is prevalent in adult patients with sickle cell disease and is strongly associated with early mortality and markers of hemolysis, in particular, serum lactate dehydrogenase (LDH). Intravascular hemolysis leads to impaired bioavailability of nitric oxide (NO), mediated by NO scavenging by plasma oxyhemoglobin and by arginine degradation by plasma arginase. We hypothesized that serum LDH may represent a convenient biomarker of intravascular hemolysis and NO bioavailability, characterizing a clinical subphenotype of hemolysis-associated vasculopathy. In a cohort of 213 patients with sickle cell disease, we found statistically significant associations of steady-state LDH with low levels of hemoglobin and haptoglobin and high levels of reticulocytes, bilirubin, plasma hemoglobin, aspartate aminotransferase, arginase, and soluble adhesion molecules. LDH isoenzyme fractionation confirmed predominance of LD1 and LD2, the principal isoforms within erythrocytes. In a subgroup, LDH levels closely correlated with plasma cell-free hemoglobin, accelerated NO consumption by plasma, and impaired vasodilatory responses to an NO donor. Remarkably, this simple biomarker was associated with a clinical subphenotype of pulmonary hypertension, leg ulceration, priapism, and risk of death in patients with sickle cell disease. We propose that LDH elevation identifies patients with a syndrome of hemolysis-associated NO resistance, endothelial dysfunction, and end-organ vasculopathy.
The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets
Authors: Sieburg Hans B. , Cho Rebecca H. , Dykstra Brad , Uchida Naoyuki , Eaves Connie J. , Muller-Sieburg Christa E.
Published: November 2005

Hematopoietic stem cells (HSCs) display extensive heterogeneity in their behavior even when isolated as phenotypically homogeneous populations. It is not clear whether this heterogeneity reflects inherently diverse subsets of HSCs or a homogeneous population of HSCs diversified by their response to different external stimuli. To address this, we analyzed 97 individual HSCs in long-term transplantation assays. HSC clones were obtained from unseparated bone marrow (BM) through limiting dilution approaches. Following transplantation into individual hosts, donor-type cells in blood were measured bimonthly and the resulting repopulation kinetics were grouped according to overall shape. Only 16 types of repopulation kinetics were found among the HSC clones even though combinatorially 54 groups were possible. All HSC clones, regardless of their origin, could be assigned to this subset of groups, and the probability of finding new patterns is negligible. Thus, the full repertoire of repopulating HSCs was covered. These data indicate that the HSC compartment consists of a limited number of distinct HSC subsets, each with predictable behavior. Enrichment of HSCs (Lin–Rho–SP) changes the representation of HSC types by selecting for distinct subsets of HSCs. These data from the steady-state HSC repertoire could provide a basis for the diagnosis of perturbed patterns of HSCs potentially caused by disease or aging.
Role of melanotransferrin in iron metabolism: studies using targeted gene disruption in vivo
Authors: Sekyere Eric O. , Dunn Louise L. , Rahmanto Yohan Suryo , Richardson Des R.
Published: November 2005

Melanotransferrin (MTf) or tumor antigen p97 is a transferrin homolog that binds one iron (Fe) atom and has been suggested to play roles in a variety of processes, including Fe metabolism, eosinophil differentiation, and plasminogen activation. Considering the vital role of Fe in many metabolic pathways, such as DNA and heme synthesis, it is important to understand the function of MTf. To define this, a MTf knockout (MTf–/–) mouse was generated through targeted disruption of the MTf gene. The MTf–/– mice were viable and fertile and developed normally, with no morphologic or histologic abnormalities. Assessment of Fe indices, tissue Fe levels, hematology, and serum chemistry parameters demonstrated no differences between MTf–/– and wild-type (MTf+/+) mice, suggesting MTf was not essential for Fe metabolism.
Coiled-coil protein composition of 22 proteomes – differences and common themes in subcellular infrastructure and traffic control
Authors: Rose Annkatrin , Schraegle Shannon J , Stahlberg Eric A , Meier Iris
Published: November 2005

Background

Long alpha-helical coiled-coil proteins are involved in diverse organizational and regulatory processes in eukaryotic cells. They provide cables and networks in the cyto- and nucleoskeleton, molecular scaffolds that organize membrane systems and tissues, motors, levers, rotating arms, and possibly springs. Mutations in long coiled-coil proteins have been implemented in a growing number of human diseases. Using the coiled-coil prediction program MultiCoil, we have previously identified all long coiled-coil proteins from the model plant Arabidopsis thaliana and have established a searchable Arabidopsis coiled-coil protein database.

Results

Here, we have identified all proteins with long coiled-coil domains from 21 additional fully sequenced genomes. Because regions predicted to form coiled-coils interfere with sequence homology determination, we have developed a sequence comparison and clustering strategy based on masking predicted coiled-coil domains. Comparing and grouping all long coiled-coil proteins from 22 genomes, the kingdom-specificity of coiled-coil protein families was determined. At the same time, a number of proteins with unknown function could be grouped with already characterized proteins from other organisms.

Conclusion

MultiCoil predicts proteins with extended coiled-coil domains (more than 250 amino acids) to be largely absent from bacterial genomes, but present in archaea and eukaryotes. The structural maintenance of chromosomes proteins and their relatives are the only long coiled-coil protein family clearly conserved throughout all kingdoms, indicating their ancient nature. Motor proteins, membrane tethering and vesicle transport proteins are the dominant eukaryote-specific long coiled-coil proteins, suggesting that coiled-coil proteins have gained functions in the increasingly complex processes of subcellular infrastructure maintenance and trafficking control of the eukaryotic cell.
Targeted oligonucleotide-mediated microsatellite identification (TOMMI) from large-insert library clones
Authors: Chen Kefei , Knorr Christoph , Bornemann-Kolatzki Kirsten , Ren Jun , Huang Lusheng , Rohrer Gary A , Brenig Bertram
Published: November 2005

Background

In the last few years, microsatellites have become the most popular molecular marker system and have intensively been applied in genome mapping, biodiversity and phylogeny studies of livestock. Compared to single nucleotide polymorphism (SNP) as another popular marker system, microsatellites reveal obvious advantages. They are multi-allelic, possibly more polymorphic and cheaper to genotype. Calculations showed that a multi-allelic marker system always has more power to detect Linkage Disequilibrium (LD) than does a di-allelic marker system [1]. Traditional isolation methods using partial genomic libraries are time-consuming and cost-intensive. In order to directly generate microsatellites from large-insert libraries a sequencing approach with repeat-containing oligonucleotides is introduced.

Results

Seventeen porcine microsatellite markers were isolated from eleven PAC clones by
t
argeted
o
ligonucleotide-
m
ediated
m
icrosatellite
i
dentification (TOMMI), an improved efficient and rapid flanking sequence-based approach for the isolation of STS-markers. With the application of TOMMI, an average of 1.55 (CA/GT) microsatellites per PAC clone was identified. The number of alleles, allele size distribution, polymorphism information content (PIC), average heterozygosity (HT), and effective allele number (NE) for the STS-markers were calculated using a sampling of 336 unrelated animals representing fifteen pig breeds (nine European and six Chinese breeds). Sixteen of the microsatellite markers proved to be polymorphic (2 to 22 alleles) in this heterogeneous sampling. Most of the publicly available (porcine) microsatellite amplicons range from approximately 80 bp to 200 bp. Here, we attempted to utilize as much sequence information as possible to develop STS-markers with larger amplicons. Indeed, fourteen of the seventeen STS-marker amplicons have minimal allele sizes of at least 200 bp. Thus, most of the generated STS-markers can easily be integrated into multilocus assays covering a broader separation spectrum. Linkage mapping results of the markers indicate their potential immediate use in QTL studies to further dissect trait associated chromosomal regions.

Conclusion

The sequencing strategy described in this study provides a targeted, inexpensive and fast method to develop microsatellites from large-insert libraries. It is well suited to generate polymorphic markers for selected chromosomal regions, contigs of overlapping clones and yields sufficient high quality sequence data to develop amplicons greater than 250 bases.
Leveraging human genomic information to identify nonhuman primate sequences for expression array development
Authors: Spindel Eliot R , Pauley Mark A , Jia Yibing , Gravett Courtney , Thompson Shaun L , Boyle Nicholas F , Ojeda Sergio R , Norgren Robert B
Published: November 2005

Background

Nonhuman primates (NHPs) are essential for biomedical research due to their similarities to humans. The utility of NHPs will be greatly increased by the application of genomics-based approaches such as gene expression profiling. Sequence information from the 3' end of genes is the key resource needed to create oligonucleotide expression arrays.

Results

We have developed the algorithms and procedures necessary to quickly acquire sequence information from the 3' end of nonhuman primate orthologs of human genes. To accomplish this, we identified terminal exons of over 15,000 human genes by aligning mRNA sequences with genomic sequence. We found the mean length of complete last exons to be approximately 1,400 bp, significantly longer than previous estimates. We designed primers to amplify genomic DNA, which included at least 300 bp of the terminal exon. We cloned and sequenced the PCR products representing over 5,500 Macaca mulatta (rhesus monkey) orthologs of human genes. This sequence information has been used to select probes for rhesus gene expression profiling. We have also tested 10 sets of primers with genomic DNA from Macaca fascicularis (Cynomolgus monkey), Papio hamadryas (Baboon), and Chlorocebus aethiops (African green monkey, vervet). The results indicate that the primers developed for this study will be useful for acquiring sequence from the 3' end of genes for other nonhuman primate species.

Conclusion

This study demonstrates that human genomic DNA sequence can be leveraged to obtain sequence from the 3' end of NHP orthologs and that this sequence can then be used to generate NHP oligonucleotide microarrays. Affymetrix and Agilent used sequences obtained with this approach in the design of their rhesus macaque oligonucleotide microarrays.
Construction and characterization of a genomic BAC library for the Mus m. musculus mouse subspecies (PWD/Ph inbred strain)
Authors: Jansa Petr , Divina Petr , Forejt Jiří
Published: November 2005

Background

The genome of classical laboratory strains of mice is an artificial mosaic of genomes originated from several mouse subspecies with predominant representation (>90%) of the Mus m. domesticus component. Mice of another subspecies, East European/Asian Mus m. musculus, can interbreed with the classical laboratory strains to generate hybrids with unprecedented phenotypic and genotypic variations. To study these variations in depth we prepared the first genomic large insert BAC library from an inbred strain derived purely from the Mus m. musculus-subspecies. The library will be used to seek and characterize genomic sequences controlling specific monogenic and polygenic complex traits, including modifiers of dominant and recessive mutations.

Results

A representative mouse genomic BAC library was derived from a female mouse of the PWD/Ph inbred strain of Mus m. musculus subspecies. The library consists of 144 768 primary clones from which 97% contain an insert of 120 kb average size. The library represents an equivalent of 6.7 × mouse haploid genome, as estimated from the total number of clones carrying genomic DNA inserts and from the average insert size. The clones were arrayed in duplicates onto eight high-density membranes that were screened with seven single-copy gene probes. The individual probes identified four to eleven positive clones, corresponding to 6.9-fold coverage of the mouse genome. Eighty-seven BAC-ends of PWD/Ph clones were sequenced, edited, and aligned with mouse C57BL/6J (B6) genome. Seventy-three BAC-ends displayed unique hits on B6 genome and their alignment revealed 0.92 single nucleotide polymorphisms (SNPs) per 100 bp. Insertions and deletions represented 0.3% of the BAC end sequences.

Conclusion

Analysis of the novel genomic library for the PWD/Ph inbred strain demonstrated coverage of almost seven mouse genome equivalents and a capability to recover clones for specific regions of PWD/Ph genome. The single nucleotide polymorphism between the strains PWD/Ph and C57BL/6J was 0.92/100 bp, a value significantly higher than between classical laboratory strains. The library will serve as a resource for dissecting the phenotypic and genotypic variations between mice of the Mus m. musculus subspecies and classical laboratory mouse strains.
Pscroph, a parasitic plant EST database enriched for parasite associated transcripts
Authors: Torres Manuel J , Tomilov Alexey A , Tomilova Natalya , Reagan Russell L , Yoder John I
Published: November 2005

Background

Parasitic plants in the Orobanchaceae develop invasive root haustoria upon contact with host roots or root factors. The development of haustoria can be visually monitored and is rapid, highly synchronous, and strongly dependent on host factor exposure; therefore it provides a tractable system for studying chemical communications between roots of different plants.

Description

Triphysariais a facultative parasitic plant that initiates haustorium development within minutes after contact with host plant roots, root exudates, or purified haustorium-inducing phenolics. In order to identify genes associated with host root identification and early haustorium development, we sequenced suppression subtractive libraries (SSH) enriched for transcripts regulated inTriphysariaroots within five hours of exposure toArabidopsisroots or the purified haustorium-inducing factor 2,6 dimethoxybenzoquinone. The sequences of over nine thousand ESTs from three SSH libraries and their subsequent assemblies are available at the Pscroph databasehttp://pscroph.ucdavis.edu. The web site also provides BLAST functions and allows keyword searches of functional annotations.

Conclusion

Libraries prepared fromTriphysariaroots treated with host roots or haustorium inducing factors were enriched for transcripts predicted to function in stress responses, electron transport or protein metabolism. In addition to parasitic plant investigations, the Pscroph database provides a useful resource for investigations in rhizosphere interactions, chemical signaling between organisms, and plant development and evolution.