bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response variability to aspirin as assessed by the platelet function analyzer (PFA)-100
Authors: Castelnuovo Augusto Di , Iacoviello Licia , Vermylen Jos , Gaetano Giovanni de , Crescente Marilena , Cerletti Chiara 
Published: December 2007

SummaryIt was the aim of the present study to perform a systematic review of the published studies that estimated the prevalence of non-responders to aspirin, as assessed by the closure time of PFA-100®, a point-of-care device, and to analyse: 1) some major clinical and methodological factors that can influence it and 2) its possible association with vascular outcomes. The prevalence of non-responders to aspirin in 64 populations from 53 studies, comprising 6,450 subjects, had a median value of 0.27.A higher number of aspirin non-responders was found among older patients, those with acute vascular events, or those treated for more than one month. Aspirin non-response was more frequently associated with the use of “home-established” cut-offs or when closure time was only assessed after aspirin (rather than both before and after).Among risk factors, type 2 diabetes appeared to be associated with a higher prevalence of aspirin non-responders. The latter was also higher in less recent publications and in studies that used 3.2% rather than 3.8% Na-citrate as an anticoagulant. In eight studies comprising 847 subjects, aspirin non-responders were more likely to have vascular events than responders (relative risk: 1.63; 95% CI 1.16–2.28). In conclusion, although there appears to be heterogeneity among the studies analysed, this review indicates that about one quarter of people receiving aspirin would be identified – as an average – as aspirin non-responders by PFA-100. As this is a simple, widely available point-of-care test, efforts to better standardize it and to control for its major methodological variables might be useful to improve monitoring of platelet performance under aspirin treatment and to firmly establish the observed association with clinical vascular events.
Hegemonic Encounters: Criticism of Saints-Day Festivals and the Formation of Modern Islam in Late 19th and Early 20th-Century Egypt
Authors: Schielke Samuli 
Published: December 2007

AbstractIn late 19th century, Islamic saints-day festivals (mawlids) became the subject of strong criticism. A festive tradition that until then had been central to the religious and communal life of Egypt was now increasingly criticised for being backward and un-Islamic. Mawlids, popular festivals that combine the atmosphere of a fair with the ecstatic spirituality of Sufism, were not only problematic for the new models of nation and religion, criticising them was also functional for the demarcation of these. Constructs of this type are characteristic for the project of modernity that is defined through binary distinctions, with labels such as 'backwardness' and 'un-Islamic innovations' serving as distinctive markers of modernity and authenticity. This development was not a consequent continuation of an earlier Islamic tradition, nor was it a simple takeover of European colonial concepts and disciplining practices. It was the product of a creative and selective synthesis of the two, producing novel interpretations of both Islam and modernity that, in the course of the 20 th century, have managed to gain a hegemonic position in much of the Middle East. This emergence of Islamic reformism and modernism from a synthesis with colonial discourses compels us to rethink a currently popular endeavour in Islamic studies: the study of Islam as a discursive tradition.
Sheikh Yūsuf al-Qaradāwī in Cyberspace
Authors: Gräf Bettina 
Published: December 2007

AbstractThe article introduces and analyses the homepage of the Azhar-trained Egyptian scholar Sheikh Yūsuf al-Qaradāwī. This includes not only the analysis of the website's content but also of its context of production, i.e. Doha, a place that can be described as a hub of media-produced reality of Arabic-speaking Muslims since the mid-1990s. The author, Bettina Gräf, states that Qaradāwī was one of the first scholars to realise that the cooperation with journalists, editors, and producers of new media institutions would help to restore the influence of Muslim scholars in Muslim societies and worldwide. She identifies the techniques by which Qaradāwī's self-proclaimed position as a global Islamic authority is implemented on his website. The potential of Qaradāwī being recognised as a global authority, however, is questioned. The author argues that the relationships constitutive of his almost translocal authority were and still are negotiated in special sets of actions, namely in Qatar, Egypt, Palestine, Europe and, on the occasion of various conferences with a Sunni Islamist agenda, around the world. Although Yūsuf al-Qaradāwī's worldwide popularity, based on his activities in both the traditional and the new media, is beyond dispute, the author points to the necessity of distinguishing between popularity and authority.
Cross-Cultural Contexts of Modern Muslim Intellectualism
Authors: Feener R. Michael 
Published: December 2007

AbstractAttempts at understanding the development of Islam in the modern period through its intellectual history demand new analytical frameworks to be brought to bear on both Muslim religious thought and the academic study of religion. There is a need for innovative approaches to modern Muslim intellectualism that can build upon the traditional strengths of Islamic Studies while also taking into account contemporary realities which add new dimensions of complexity to the processes of producing and transmitting knowledge. Aside from the formal contents of legal, theological, and social texts texts, approaches to Muslim thought in the modern period also require paying attention to the dynamics of new educational and publishing structures, new forms of media, and cross-cultural contexts of discussion, all complemented by a theoretically aware methodological flexibility that self-consciously moves back and forth between text-specific and broader cultural dimensions of analysis. In this article these issues are raised in the course of reflections on recent work in mapping an intellectual history of Islam in modern Indonesia.
Intellectual Dependency: Late Ottoman Intellectuals between Fiqh and Social Science
Authors: Senturk Recep 
Published: December 2007

AbstractModernization led to the intellectual dependency of the Muslim world on the West for social theories. Human action ('amal) is the subject matter of both Islamic fiqh and Western social science (i.e. of all those sciences which attempt to apply empirical methods drawn from the natural sciences to the sphere of human society, including education and law). Though different in many aspects, both have a claim on widely overlapping intellectual territories. Social science in its different forms conquered the space traditionally occupied by fiqh, and its professional representatives (such as academicians, jurists, educationists, and writers) replaced the fuqahā'. This article thus points to a dialectic tension between fiqh and Western social science which shaped Muslim intellectual history since the 19th century. This article unearths this latent tension by using the example of late Ottoman intellectuals as Ziya Gökalp, Said Halim Pasha and İzmirli İsmail Hakkı. In the Ottoman case it brought about a new cleavage in the Muslim intellectual community between advocates of social science and advocates of fiqh. Yet many intellectuals and even some fuqahā' attempted a synthesis between both fields. After the collapse of the Ottoman Empire, the modern Turkish Republic adopted the policy of wholesale westernization, an element of which was the adoption of Western social science to replace fiqh in explaining and ordering human action. This intervention in the intellectual life increased the dependence of modern Turkish intellectuals on the state; which is another aspect of their intellectual dependency explored in this article.
Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells
Authors: Ghiaur Gabriel , Ferkowicz Michael J. , Milsom Michael D. , Bailey Jeff , Witte David , Cancelas Jose A. , Yoder Mervin C. , Williams David A. 
Published: December 2007

AbstractDefinitive hematopoietic stem and progenitor cells (HSCs/Ps) originating from the yolk sac and/or para-aorta-splanchno-pleura/aorta-gonad-mesonephros are hypothesized to colonize the fetal liver, but mechanisms involved are poorly defined. The Rac subfamily of Rho GTPases has been shown to play essential roles in HSC/P localization to the bone marrow following transplantation. Here, we study the role of Rac1 in HSC/P migration during ontogeny and seeding of fetal liver. Using a triple-transgenic approach, we have deleted Rac1 in HSCs/Ps during very early embryonic development. Without Rac1, there was a decrease in circulating HSCs/Ps in the blood of embryonic day (E) 10.5 embryos, while yolk sac definitive hematopoiesis was quantitatively normal. Intraembryonic hematopoiesis was significantly impaired in Rac1-deficient embryos, culminating with absence of intra-aortic clusters and fetal liver hematopoiesis. At E10.5, Rac1-deficient HSCs/Ps displayed decreased transwell migration and impaired inter-action with the microenvironment in migration-dependent assays. These data suggest that Rac1 plays an important role in HSC/P migration during embryonic development and is essential for the emergence of intraembryonic hematopoiesis.
Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex formation and nuclear export
Authors: Gatza Michael L , Dayaram Tajhal , Marriott Susan J 
Published: December 2007

Abstract

Background
The HTLV-I oncoprotein, Tax, is a pleiotropic protein whose activity is partially regulated by its ability to interact with, and perturb the functions of, numerous cellular proteins. Tax is predominantly a nuclear protein that localizes to nuclear foci known as Tax Speckled Structures (TSS). We recently reported that the localization of Tax and its interactions with cellular proteins are altered in response to various forms of genotoxic and cellular stress. The level of cytoplasmic Tax increases in response to stress and this relocalization depends upon the interaction of Tax with CRM1. Cellular pathways and signals that regulate the subcellular localization of Tax remain to be determined. However, post-translational modifications including sumoylation and ubiquitination are known to influence the subcellular localization of Tax and its interactions with cellular proteins. The sumoylated form of Tax exists predominantly in the nucleus while ubiquitinated Tax exists predominantly in the cytoplasm. Therefore, we hypothesized that post-translational modifications of Tax that occur in response to DNA damage regulate the localization of Tax and its interactions with cellular proteins.

Results
We found a significant increase in mono-ubiquitination of Tax in response to UV irradiation. Mutation of specific lysine residues (K280 and K284) within Tax inhibited DNA damage-induced ubiquitination. In contrast to wild-type Tax, which undergoes transient nucleocytoplasmic shuttling in response to DNA damage, the K280 and K284 mutants were retained in nuclear foci following UV irradiation and remained co-localized with the cellular TSS protein, sc35.

Conclusion
This study demonstrates that the localization of Tax, and its interactions with cellular proteins, are dynamic following DNA damage and depend on the post-translational modification status of Tax. Specifically, DNA damage induces the ubiquitination of Tax at K280 and K284. Ubiquitination of these residues facilitates the dissociation of Tax from sc35-containing nuclear foci, and stimulates nuclear export of Tax through the CRM1 pathway.
Selective mobilization of fatty acids from adipose tissue in migratory birds
Authors: Price Edwin R. , Krokfors Anna , Guglielmo Christopher G. 
Published: December 2007

SUMMARYDuring times of high energy demand, stored fatty acids are mobilized from adipocytes. This mobilization has previously been shown to be a non-random process, with more hydrophilic fatty acids being mobilized most readily. The objectives of this study were to characterize the relative mobilization of fatty acids from adipocytes in two migratory bird species and to investigate possible changes in selective fatty acid mobilization associated with the migratory period. Captive ruffs (Philomachus pugnax) and white-crowned sparrows (Zonotrichia leucophrys) were studied. The sparrows were divided into two treatments: `winter' (photoperiod 8 h:16 h L:D)and `migrant' (in which migratory condition was induced with a photoperiodic manipulation of 8 h:16 h L:D, followed by 16 h:8 h L:D). Adipose tissue was removed from ruffs and sparrows and incubated for 90 min after stimulation with epinephrine. The proportions of individual fatty acid species released into the incubation medium were compared with their proportions in the adipocytes to determine relative mobilizations. We found that patterns of relative mobilization in ruffs and sparrows are similar to those of mammals,with shorter chain lengths and more double bonds leading to higher relative mobilization. Seasonal condition in sparrows did not alter this pattern. This pattern of relative mobilization from adipocytes seems to be a general rule amongst birds and mammals and should be considered before inferring functionality about selective retention or mobilization of certain fatty acids. The composition of adipose stores in birds may affect migratory performance; however, our results indicate that patterns of relative mobilization at the adipocytes do not vary with season in migratory birds.
Acute Metformin Therapy Confers Cardioprotection Against Myocardial Infarction Via AMPK-eNOS–Mediated Signaling
Authors: Calvert John W. , Gundewar Susheel , Jha Saurabh , Greer James J.M. , Bestermann William H. , Tian Rong , Lefer David J. 
Published: December 2007

OBJECTIVE—Clinical studies have reported that metformin reduces cardiovascular end points of type 2 diabetic subjects by actions that cannot solely be attributed to glucose-lowering effects. The therapeutic effects of metformin have been reported to be mediated by its activation of AMP-activated protein kinase (AMPK), a metabolite sensing protein kinase whose activation following myocardial ischemia has been suggested to be an endogenous protective signaling mechanism. We investigated the potential cardioprotective effects of a single, low-dose metformin treatment (i.e., 286-fold less than the maximum antihyperglycemic dose) in a murine model of myocardial ischemia-reperfusion (I/R) injury.RESEARCH DESIGN AND METHODS—Nondiabetic and diabetic (db/db) mice were subjected to transient myocardial ischemia for a period of 30 min followed by reperfusion. Metformin (125 μg/kg) or vehicle (saline) was administered either before ischemia or at the time of reperfusion.RESULTS—Administration of metformin before ischemia or at reperfusion decreased myocardial injury in both nondiabetic and diabetic mice. Importantly, metformin did not alter blood glucose levels. During early reperfusion, treatment with metformin augmented I/R-induced AMPK activation and significantly increased endothelial nitric oxide (eNOS) phosphorylation at residue serine 1177.CONCLUSIONS—These findings provide important information that myocardial AMPK activation by metformin following I/R sets into motion events, including eNOS activation, which ultimately lead to cardioprotection.
The Effect of Cyclooxygenase-2 Inhibition on Renal Hemodynamic Function in Humans With Type 1 Diabetes
Authors: Cherney David Z.I. , Miller Judith A. , Scholey James W. , Bradley Timothy J. , Slorach Cameron , Curtis Jaqueline R. , Dekker Maria G. , Nasrallah Rania , Hébert Richard L. , Sochett Etienne B. 
Published: December 2007

OBJECTIVE—Studies in animal models suggest that cyclooxygenase-2 (COX2) plays a role in the regulation of the renal microcirculation in diabetes. Accordingly, we examined the role of COX2 in the control of renal hemodynamic function and in the renal response to hyperglycemia in humans with uncomplicated type 1 diabetes. We hypothesized that COX2 inhibition would alleviate the hyperfiltration state and would abrogate the hyperglycemia-mediated rise in glomerular filtration rate (GFR).RESEARCH DESIGN AND METHODS—Renal function was assessed during clamped euglycemia and hyperglycemia on 2 consecutive days before and then again after 14 days of COX2 inhibition using 200 mg celecoxib once daily by mouth. For analysis, the cohort was then divided into two groups based on the baseline GFR: 9 subjects exhibited hyperfiltration (GFR ≥135 ml/min per 1.73 m2), and 12 subjects exhibited normofiltration (GFR &lt;135 ml/min per 1.73 m2).RESULTS—Under euglycemic conditions, COX2 inhibition resulted in a significant decline in GFR in the hyperfiltration group (150 ± 5 to 139 ± 5 ml/min per 1.73 m2) but increased GFR in the normofiltration group (118 ± 5 to 138 ± 5 ml/min per 1.73 m2). COX2 inhibition did not blunt the hyperglycemia-associated rise in GFR in the normofiltration group and was instead associated with an augmented rise in GFR.CONCLUSIONS—In summary, our results support the hypothesis that COX2 is an important determinant of renal hemodynamic function in subjects with type 1 diabetes. The renal response to COX2 inhibition emphasizes that hyperfiltration and normofiltration are distinct physiological states.
Targeting of RhoA/ROCK Signaling Ameliorates Progression of Diabetic Nephropathy Independent of Glucose Control
Authors: Kolavennu Vasantha , Zeng Lixia , Peng Hui , Wang Yin , Danesh Farhad R. 
Published: December 2007

OBJECTIVE—RhoA, a small GTPase protein, and its immediate downstream target, Rho kinase (ROCK), control a wide variety of signal transduction pathways. Recent studies have shown that fasudil, a selective ROCK inhibitor, may play a pivotal role in a number of pathological conditions, ranging from cardiovascular diseases to pulmonary hypertension and erectile dysfunction. Considerable evidence suggests that some of the beneficial effects of statins may also stem from their modulatory effects on RhoA/ROCK signaling. In the current study, we hypothesized that pharmacological blockade of the RhoA/ROCK pathway with either fasudil or simvastatin would ameliorate progression of diabetic nephropathy.
RESEARCH DESIGN AND METHODS—In two separate experiments, diabetic db/db mice received fasudil (10 mg · kg− · day− i.p.) or simvastatin (40 mg · kg− · day− p.o.) for 16 weeks. Untreated db/db and db/m mice served as controls.
RESULTS—The kidney cortices of untreated db/db mice displayed increased ROCK activity compared with db/m mice. The fasudil-treated mice exhibited a significant reduction in ROCK activity, albuminuria, glomerular collagen IV accumulation, and urinary collagen IV excretion compared with untreated db/db mice. Interestingly, blood glucose was unaffected by fasudil administration. Treatment with simvastatin significantly attenuated RhoA activation in the kidney cortices of db/db mice and resulted in a significant reduction of albuminuria and mesangial matrix expansion.
CONCLUSIONS—Based on these results, we propose that RhoA/ROCK blockade constitutes a novel approach to the treatment of diabetic nephropathy. Our data also suggest a critical role for RhoA/ROCK activation in the pathogenesis of diabetic nephropathy.
Increased Skeletal Muscle Tumor Necrosis Factor-α and Impaired Insulin Signaling Persist in Obese Women With Gestational Diabetes Mellitus 1 Year Postpartum
Authors: Friedman Jacob E. , Kirwan John P. , Jing Ming , Presley Larraine , Catalano Patrick M. 
Published: December 2007

OBJECTIVE—Women with gestational diabetes mellitus (GDM) demonstrate chronic and progressive insulin resistance and a markedly increased risk of converting to type 2 diabetes after pregnancy. However, the cellular mechanisms underlying this insulin resistance are unknown.
RESEARCH DESIGN AND METHODS—We investigated the progression of insulin resistance in nine obese women with GDM during late pregnancy (30–36 weeks) and 1 year postpartum. Skeletal muscle biopsies were obtained at each visit, and insulin resistance was determined by the hyperinsulinemic-euglycemic clamp technique.
RESULTS—Insulin resistance was not significantly improved in GDM women (4.1 ± 0.4 vs. 5.8 ± 1.1 10−2 mg · kg FFM · min−1/μU · ml−1). Subjects did not experience significant weight loss postpartum. Body weight, fat mass, fasting glucose, and plasma tumor necrosis factor (TNF)-α remained higher 1 year postpartum than seen in previously studied normal glucose-tolerant women. Skeletal muscle TNF-α mRNA was elevated five- to sixfold in GDM women and remained higher 1 year postpartum. While levels of insulin receptor (IR), IR substrate (IRS)-1, and p85α improved postpartum, insulin-stimulated IR tyrosine phosphorylation and receptor tyrosine kinase activity did not significantly improve postpartum in GDM. The levels of 312Ser-IRS-1 also did not improve postpartum and correlated with TNF-α mRNA (r2 = 0.19, P &lt; 0.03), consistent with a state of subclinical inflammation and chronic skeletal muscle insulin resistance.
CONCLUSIONS—These results suggest the mechanisms underlying chronic insulin resistance in GDM women may be driven by increased inflammation that impinges on the IR and IRS-1 signaling cascade in skeletal muscle. These findings have important implications for the health of GDM women during subsequent pregnancies and their risk for progression to type 2 diabetes.
Different Brain Responses to Hypoglycemia Induced by Equipotent Doses of the Long-Acting Insulin Analog Detemir and Human Regular Insulin in Humans
Authors: Rossetti Paolo , Porcellati Francesca , Ricci Natalia Busciantella , Candeloro Paola , Cioli Patrizia , Bolli Geremia B. , Fanelli Carmine G. 
Published: December 2007

OBJECTIVE—The acylated long-acting insulin analog detemir is more lipophilic than human insulin and likely crosses the blood-to-brain barrier more easily than does human insulin. The aim of these studies was to assess the brain/hypothalamus responses to euglycemia and hypoglycemia in humans during intravenous infusion of equipotent doses of detemir and human insulin.
RESEARCH DESIGN AND METHODS—Ten normal, nondiabetic subjects (six men, age 36±7 years, and BMI 22.9±2.6 kg/m2) were studied on four occasions at random during intravenous infusion of either detemir or human insulin in euglycemia (plasma glucose 90 mg/dl) or during stepped hypoglycemia (plasma glucose 90, 78, 66, 54, and 42 mg/dl steps).
RESULTS—Plasma counterregulatory hormone response to hypoglycemia did not differ between detemir and human insulin. The glycemic thresholds for adrenergic symptoms were higher with detemir (51 ± 7.7 mg/dl) versus human insulin (56 ± 7.8 mg/dl) (P = 0.029). However, maximal responses were greater with detemir versus human insulin for adrenergic (3 ± 2.5 vs. 2.4 ± 1.8) and neuroglycopenic (4 ± 3.9 vs. 2.7±2.5) symptoms (score, P &lt; 0.05). Glycemic thresholds for onset of cognitive dysfunction were lower with detemir versus human insulin (51 ± 8.1 vs. 47 ± 3.6 mg/dl, P = 0.031), and cognitive function was more deteriorated with detemir versus human insulin (P &lt; 0.05).
CONCLUSIONS—Compared with human insulin, responses to hypoglycemia with detemir resulted in higher glycemic thresholds for adrenergic symptoms and greater maximal responses for adrenergic and neuroglycopenic symptoms, with an earlier and greater impairment of cognitive function. Additional studies are needed to establish the effects of detemir on responses to hypoglycemia in subjects with diabetes.