bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vital role of protein kinase C‐related kinase in the formation and stability of neurites during hypoxia
Authors: Thauerer Bettina , Zur Nedden Stephanie , Baier‐Bitterlich Gabriele 
Published: January 2010

J. Neurochem.(2010)113, 432–446.AbstractExposure of pheochromocytoma cells to hypoxia (1% O2) favors differentiation at the expense of cell viability. Additional incubation with nerve growth factor (NGF) and guanosine, a purine nucleoside with neurotrophin characteristics, rescued cell viability and further enhanced the extension of neurites. In parallel, an increase in the activity of protein kinase C‐related kinase (PRK1), which is known to be involved in regulation of the actin cytoskeleton, was observed in hypoxic cells. NGF and guanosine further enhanced PRK1 in normoxic and hypoxic cells. To study the role of PRK1 during cellular stress response and neurotrophin‐mediated signaling, pheochromocytoma cells were transfected with small interfering RNA directed against PRK1. Loss of functional PRK1 initiated a significant loss of viability and inhibited neurite formation. SiRNA‐mediated knockdown of PRK1 also completely stalled guanosine‐mediated neuroprotective effects. Additionally, the F‐actin‐associated cytoskeleton and the expression of the plasticity protein growth associated protein‐43 were disturbed upon PRK1 knockdown. A comparable dependency of neurite formation and growth associated protein‐43 immunoreactivity on functional PRK1 expression was observed in cerebellar granule neurons. Based on these data, a putative role of PRK1 as a key‐signaling element for the successive NGF‐ and purine nucleoside‐mediated protection of hypoxic neuronal cells is hypothesized.
Elections and Discretionary Accruals: Evidence from 2004
Authors: RAMANNA KARTHIK , ROYCHOWDHURY SUGATA 
Published: January 2010

ABSTRACTWe examine the accrual choices of outsourcing firms with links to U.S. congressional candidates during the 2004 elections, when corporate outsourcing was a major campaign issue. We find that politically connected firms with more extensive outsourcing activities have more income‐decreasing discretionary accruals. Further, relative to adjacent periods, the evidence is concentrated in the two calendar quarters immediately preceding the 2004 election, consistent with heightened incentives for firms to manage earnings during the election season. The incentives can be attributed to donor firms' concerns about the potentially negative consequences of scrutiny over outsourcing for themselves and for their affiliated candidates.
SZ‐685C, a marine anthraquinone, is a potent inducer of apoptosis with anticancer activity by suppression of the Akt/FOXO pathway
Authors: Xie Gui'e , Zhu Xun , Li Qing , Gu Minghui , He Zhenjian , Wu Jueheng , Li Jun , Lin Yongcheng , Li Mengfeng , She Zhigang , Yuan Jie 
Published: January 2010

Background and purpose:  The aims of this study were to investigate the anti‐cancer activity of SZ‐685C, an anthracycline analogue isolated from marine‐derived mangrove endophytic fungi, and to explore the molecular mechanisms underlying such activity.Experimental approach:  The effect of SZ‐685C on the viability of cancer cell lines was investigated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. SZ‐685C‐induced apoptosis was assessed by Annexin V‐fluorescein isothiocyanate/propidium iodide staining, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling assay and analysis of caspase activation. The effect of SZ‐685C on the Akt/FOXO pathway was studied using Western blotting analysis, and the in vivo anti‐tumour efficacy was examined in an MDA‐MB‐435 breast cancer xenograft model.Key results:  SZ‐685C suppressed the proliferation of six cancer cell lines derived from human breast cancer, prostate cancer, glioma and hepatoma (IC50 values ranged from 3.0 to 9.6 µM) and the growth of breast cancer xenografts in mice. SZ‐685C had a direct apoptosis‐inducing effect through both the extrinsic and intrinsic apoptotic pathways, as shown by activation of caspase‐8 and 9 as well as effector caspase‐3 and poly (ADP‐ribose) polymerase. Phosphorylation of Akt and its downstream effectors, forkhead box protein O1 and forkhead box protein O3a, was down‐regulated in SZ‐685C‐treated cancer cells. Furthermore, the pro‐apoptotic protein Bim was up‐regulated by SZ‐685C treatment consistent with FOXO dephosphorylation.Conclusions and implications:  SZ‐685C could induce apoptosis through the Akt/FOXO pathway, which consequently leads to the observed anti‐tumour effect both in vitro and in vivo. Our data suggest that SZ‐685C may be a potentially promising Akt inhibitor and anti‐cancer drug candidate.
Pharmacological stimulation and inhibition of insulin secretion in mouse islets lacking ATP‐sensitive K+channels
Authors: Szollosi A , Nenquin M , Henquin JC 
Published: January 2010

Background and purpose: ATP‐sensitive potassium channels (KATPchannels) in beta cells are a major target for insulinotropic drugs. Here, we studied the effects of selected stimulatory and inhibitory pharmacological agents in islets lacking KATPchannels.Experimental approach: We compared insulin secretion (IS) and cytosolic calcium ([Ca2+]c) changes in islets isolated from control mice and mice lacking sulphonylurea receptor1 (SUR1), and thus KATPchannels in their beta cells (Sur1KO).Key results: While similarly increasing [Ca2+]cand IS in controls, agents binding to site A (tolbutamide) or site B (meglitinide) of SUR1 were ineffective inSur1KO islets. Of two non‐selective blockers of potassium channels, quinine was inactive, whereas tetraethylammonium was more active inSur1KO compared with control islets. Phentolamine, efaroxan and alinidine, three imidazolines binding to KIR6.2 (pore of KATPchannels), stimulated control islets, but only phentolamine retained weaker stimulatory effects on [Ca2+]cand IS inSur1KO islets. Neither KATPchannel opener (diazoxide, pinacidil) inhibitedSur1KO islets. Calcium channel blockers (nimodipine, verapamil) or diphenylhydantoin decreased [Ca2+]cand IS in both types of islets, verapamil and diphenylhydantoin being more efficient inSur1KO islets. Activation of α2‐adrenoceptors or dopamine receptors strongly inhibited IS while partially (clonidine > dopamine) lowering [Ca2+]c(control >Sur1KO islets).Conclusions and implications: Those drugs retaining effects on IS in islets lacking KATPchannels, also affected [Ca2+]c, indicating actions on other ionic channels. The greater effects of some inhibitors inSur1KO than in control islets might be relevant to medical treatment of congenital hyperinsulinism caused by inactivating mutations of KATPchannels.
Thrombin activation of proteinase‐activated receptor 1 potentiates the myofilament Ca2+sensitivity and induces vasoconstriction in porcine pulmonary arteries
Authors: Maki Jun , Hirano Mayumi , Hoka Sumio , Kanaide Hideo , Hirano Katsuya 
Published: January 2010

Background and purpose: Thrombus formation is commonly associated with pulmonary arterial hypertension (PAH). Thrombin may thus play an important role in the pathogenesis and pathophysiology of PAH. Hence, we investigated the contractile effects of thrombin and its mechanism in pulmonary artery.Experimental approach: The cytosolic Ca2+concentrations ([Ca2+]i), 20 kDa myosin light chain (MLC20) phosphorylation and tension development were evaluated using the isolated porcine pulmonary artery.Key results: Thrombin induced a sustained contraction in endothelium‐denuded strips obtained from different sites of a pulmonary artery, ranging from the main pulmonary artery to the intrapulmonary artery. In the presence of endothelium, thrombin induced a transient relaxation. The contractile effect of thrombin was abolished by either a protease inhibitor or a proteinase‐activated receptor 1 (PAR1) antagonist, while it was mimicked by PAR1‐activating peptide (PAR1AP), but not PAR4AP. The thrombin‐induced contraction was associated with a small elevation of [Ca2+]iand an increase in MLC20 phosphorylation. Thrombin and PAR1AP induced a greater increase in tension for a given [Ca2+]ielevation than that obtained with high K+‐depolarization. They also induced a contraction at a fixed Ca2+concentration in α‐toxin‐permeabilized preparations.Conclusions and implications: The present study revealed a unique property of the pulmonary artery. In contrast to normal arteries of the systemic circulation, thrombin induces a sustained contraction in the normal pulmonary artery, by activating PAR1and thereby increasing the sensitivity of the myofilament to Ca2+. This responsiveness of the pulmonary artery to thrombin may therefore contribute to the pathogenesis and pathophysiology of PAH.
Triptan Exposure During Pregnancy and the Risk of Major Congenital Malformations and Adverse Pregnancy Outcomes: Results From The Norwegian Mother and Child Cohort Study
Authors: Nezvalová‐Henriksen Kateřina , Spigset Olav , Nordeng Hedvig 
Published: January 2010

(Headache 2010;50:563‐575)Objective.— To evaluate the safety of triptan therapy during pregnancy.Background.— Information on the safety of triptan therapy during pregnancy is scarce and only available for sumatriptan, naratriptan, and rizatriptan. No associations with congenital malformations have been detected so far, but one study found a significant association between sumatriptan exposure during pregnancy and prematurity.Methods.— The study population consisted of 69,929 pregnant women and their newborn children for whom data on drug exposure and pregnancy outcome were available. Information on triptan therapy and potential socio‐demographic and medical confounding factors was obtained from the Norwegian Mother and Child Cohort Study. Information on congenital malformations and other adverse pregnancy outcomes was obtained from the Norwegian Medical Birth Registry. The datasets were linked via the women's personal identification number. Pearson's χ2 tests and logistic regression analyses were used to identify associations between triptan therapy and pregnancy outcome.Results.— No significant associations between triptan therapy during the first trimester and major congenital malformations (unadjusted OR: 1.0; 95% CI 0.8‐1.3, adjusted OR: 1.0; 95% CI 0.7‐1.2) or other adverse pregnancy outcomes were found. Triptan therapy during the second and/or third trimesters was significantly associated with atonic uterus (unadjusted OR: 1.5; 95% CI 1.1‐1.9, adjusted OR: 1.4; 95% CI 1.1‐1.8), and blood loss >500 mL during labor (unadjusted OR: 1.3; 95% CI 1.1‐1.5, adjusted OR: 1.3; 95% CI 1.1‐1.5).Conclusions.— Triptan therapy during pregnancy was not associated with an overall increased risk of congenital malformations. It cannot, however, be excluded that a difference in the risk between triptan use and individual or rare congenital malformations may exist. A slight increase in the risk of atonic uterus and hemorrhage was associated with triptan use during the second and/or third trimesters. Although the present findings are reassuring, confirmation in independent studies is warranted.
Outpatient Home‐Based Continuous Intravenous Dihydroergotamine Therapy for Intractable Migraine
Authors: Charles James A. , Von Dohln Patricia 
Published: January 2010

(Headache 2010;50:852‐860)Background.— Established consecutive‐day inpatient intravenous dihydroergotamine protocols administered by bolus intravenous injection or continuous infusion injection in the hospital have demonstrated efficacy and safety in modifying the course of daily intractable headache. We conducted a study to determine efficacy, tolerability, and feasibility to treat patients with daily intractable headache with continuous intravenous dihydroergotamine in an outpatient home‐based setting.Methods.— A total of 31 patients fulfilling ICHD‐II criteria for chronic daily headache, 25 with chronic migraine and 6 with medication overuse headache, were treated with outpatient home‐based continuous intravenous dihydroergotamine for 3 days. Patients were pretreated with 10 mg intravenous metoclopramide prior to the first day of infusion and administered 3 mg dihydroergotamine given continuously at a rate of 42 mL/hour on day 1 and 2, and administered 1.5 mg on day 3 at the rate of 21 mL/hour. The primary end point was a change in pain intensity, as measured by an 11‐point numeric pain intensity scale at the end of 3 days. The secondary end point was reduction in headache frequency at long‐term follow‐up.Results.— Patients reported an average of 63.4% reduction in the intensity of migraine pain by the end of the 3‐day infusion. Side effects were minimal and no serious adverse effects occurred. Approximately one‐third of patients became completely headache‐free after day 3, and 1 patient had no improvement. Long‐term follow‐up data indicated an average 86% reduction in headache frequency and almost every patient converted from chronic daily headache to episodic migraine except for 1 patient. Patients with medication overuse headache were no longer consuming the daily offending medication.Conclusions.— Efficacy and safety of our outpatient home‐based intravenous dihydroergotamine program compared favorably to that of established inpatient intravenous pulse injection and continuous infusion protocols for the treatment of intractable migraine. The use of outpatient continuous intravenous dihydroergotamine is an effective and well‐tolerated therapy for intractable migraine but without the added cost and inconvenience of hospitalization.
Reconfiguring freedom: Muslim piety and the limits of secular law and public discourse in France
Authors: FERNANDO MAYANTHI L. 
Published: January 2010

ABSTRACTThrough an analysis of the practice of veiling, I first examine how pious Muslim French women reconcile the dominant secular oppositions between personal autonomy and religious authority, and between the “true” self and religious norms, as they constitute themselves as religious subjects. I then turn to the 2004 law banning headscarves in public schools, and to the attendant public debates, exploring how this Muslim French religiosity was rendered incommensurable in secular law and unintelligible in public discourse. In so doing, I bring into focus both the underlying assumptions and exigencies of French secularity as well as some of its aporias.
The time of the interval: Historicity, modernity, and epoch in rural France
Authors: HODGES MATT 
Published: January 2010

ABSTRACTWith recognition that historical consciousness, or “historicity,” is culturally mediated comes acknowledgment that periodization of history into epochs is as much a product of cultural practice as a reflection of historical “fact.” In this article, I examine popular “modernist” invocations of epoch in rural France—those positing traditional pasts against fluid presents with uncertain futures—which scholars frequently subordinate to analyses of collective memory and identity politics. Submitting this “response” to French modernity to temporal analysis reveals an additional critique in this periodization, one that valorizes enduring social time over processual temporalities, with implications for the temporal frameworks and ideology of anthropologists.
Being neurologically human today: Life and science and adult cerebral plasticity (an ethical analysis)
Authors: REES TOBIAS 
Published: January 2010

ABSTRACTThroughout the 20th century, scientists believed that the adult human brain is fully developed, organized in fixed and immutable function‐specific neural circuits. Since the discovery of the profound plasticity of the human brain in the late 1990s, this belief has been thoroughly undermined. In this article, combining ethnographic and historical research, I develop an “ethical analysis” to show that (and in what concrete sense) the emergence of adult cerebral plasticity was a major mutation of the neurologically human—a metamorphosis of the confines within which neuroscience requires all those who live under the spell of the brain to think and live the human.
Akt mediates 17β‐estradiol and/or estrogen receptor‐α inhibition of LPS‐induced tumor necresis factor‐α expression and myocardial cell apoptosis by suppressing the JNK1/2‐NFκB pathway
Authors: Liu Chung‐Jung , Lo Jeng‐Fan , Kuo Chia‐Hua , Chu Chun‐Hsien , Chen Li‐Ming , Tsai Fuu‐Jen , Tsai Chang‐Hai , Tzang Bor‐Show , Kuo Wei‐Wen , Huang Chih‐Yang 
Published: January 2010

AbstractEvidence shows that women have lower tumour necrosis factor‐α (TNF‐α) levels and lower incidences of heart dysfunction and sepsis‐related morbidity and mortality. To identify the cardioprotective effects and precise cellular/molecular mechanisms behind estrogen and estrogen receptors (ERs), we investigated the effects of 17β‐estradiol (E2) and estrogen receptor α (ERα) on LPS‐induced apoptosis by analyzing the activation of survival and death signalling pathways in doxycycline (Dox)‐inducible Tet‐On/ERα H9c2 myocardial cells and ERα‐transfected primary cardiomyocytes overexpressing ERα. We found that LPS challenge activated JNK1/2, and then induced IκB degradation, NFκB activation, TNF‐α up‐regulation and subsequent myocardial apoptotic responses. In addition, treatments involving E2, membrane‐impermeable BSA‐E2 and/or Dox, which induces ERα overexpression, significantly inhibited LPS‐induced apoptosis by suppressing LPS‐up‐regulated JNK1/2 activity, IκB degradation, NFκB activation and pro‐apoptotic proteins (e.g. TNF‐α, active caspases‐8, t‐Bid, Bax, released cytochrome c, active caspase‐9, active caspase‐3) in myocardial cells. However, the cardioprotective properties of E2, BSA‐E2 and ERα overexpression to inhibit LPS‐induced apoptosis and promote cell survival were attenuated by applying LY294002 (PI3K inhibitor) and PI3K siRNA. These findings suggest that E2, BSA‐E2 and ERα expression exert their cardioprotective effects by inhibiting JNK1/2‐mediated LPS‐induced TNF‐α expression and cardiomyocyte apoptosis through activation of Akt.
Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases
Authors: Haan Claude , Behrmann Iris , Haan Serge 
Published: January 2010

Abstract

Introduction
Structure/function: the potential interest of the Jak domains as drug targets
The growing family of ATP‐competitive nanomolar Jak inhibitors
Analogue‐sensitive kinases and possible applications to Jaks
Structure‐based interpretation of the Jak mutations
Perspectives

Gain‐of‐function mutations in the genes encoding Janus kinases have been discovered in various haematologic diseases. Jaks are composed of a FERM domain, an SH2 domain, a pseudokinase domain and a kinase domain, and a complex interplay of the Jak domains is involved in regulation of catalytic activity and association to cytokine receptors. Most activating mutations are found in the pseudokinase domain. Here we present recently discovered mutations in the context of our structural models of the respective domains. We describe two structural hotspots in the pseudokinase domain of Jak2 that seem to be associated either to myeloproliferation or to lymphoblastic leukaemia, pointing at the involvement of distinct signalling complexes in these disease settings. The different domains of Jaks are discussed as potential drug targets. We present currently available inhibitors targeting Jaks and indicate structural differences in the kinase domains of the different Jaks that may be exploited in the development of specific inhibitors. Moreover, we discuss recent chemical genetic approaches which can be applied to Jaks to better understand the role of these kinases in their biological settings and as drug targets.
A triad of evidence for care of women with genital piercings
Authors: Young Cathy , Armstrong Myrna L. , Roberts Alden E. , Mello Inola , Angel Elayne 
Published: January 2010

Purpose: To add three further dimensions of evidence for the care of women with genital piercings (GPs). Data sources: Following a literature review, a cross‐sectional study replicated previous work, using a web‐based survey. This triad of evidence provides (a) descriptive quantitative data (N = 240) about women with GPs, (b) qualitative data about women with GPs, as well as (c) clinical observations from 60 healthcare providers (HCPs) who have cared for women with GPs. Conclusions: Three important findings about women with GPs were validated: (a) GPs were deliberate actions, sought for personal and sexual expression; (b) women with GPs treat piercings as a normal, meaningful part of their lives which produce sexual enhancement and expression; and (c) they continue to seek information about GP care from nonhealth providers. New data indicate that they have experienced depression (47%), abuse (physical 18%; emotional, 27%; sexual, 14%), and forced sexual activity (35%) in their lives. Several unsubstantiated assumptions about women with GPs are challenged with these data. Implications for practice: GPs should not delay important health care. Health‐protective, as well as health promotion, behaviors are important to reduce risks. Nurse practitioners (NPs) can become effective and resourceful advocates in three specific areas of care: (a) responsiveness to women with GPs, (b) collaborative decision making for the removal of jewelry, and (c) promotion of applicable patient education.
Hydroxyl Radical and Ferryl‐Generating Systems Promote Gel Network Formation of Myofibrillar Protein
Authors: Xiong Youling L. , Blanchard Suzanne P. , Ooizumi Tooru , Ma Yuanyuan 
Published: January 2010

ABSTRACT:  The objective of the study was to examine how oxidatively induced protein cross‐linking would influence the gelation properties of myofibrillar protein (MP) under meat processing conditions. MP suspensions in 0.6 M NaCl at pH 6 were treated with an iron‐catalyzed oxidizing system (IOS: 10 μM FeCl3, 0.1 mM ascorbic acid, 0.05 to 5 mM H2O2) or a H2O2‐activated metmyoglobin oxidizing system (MOS: 0.01 to 0.1 mM metmyoglobin/H2O2) that produced hydroxyl radical and ferryl species, respectively. Both oxidizing systems promoted MP thermal gelation, which was evidenced by rapid protein–protein interaction and the enhancement in storage modulus (elasticity) of the gel network as revealed by dynamic rheological testing in the 20 to 74 °C temperature range. This gelation‐enhancing effect was attributed to the shift of myosin aggregation in the early stage of heating from predominantly head–head association (nonoxidized control samples) to prevalently tail–tail cross‐linking through disulfide bonds. However, both hardness and water‐holding capacity of chilled gels tended to decline when MP was exposed to ≥1 mM H2O2 in IOS and to all concentrations of metmyoglobin in MOS. Microscopic examination confirmed a more porous structure in oxidized gels when compared with nonoxidized protein gels. The results demonstrated that mild oxidation altered the mode of myosin aggregation in favor of an elastic gel network formation, but it did not improve or had a negative effect on water‐binding properties of MP gels.Practical Application: Mild oxidation promotes protein network formation and enhances gelation of myofibrillar protein under normal salt and pH conditions used in meat processing. This oxidative effect, which involves disulfide linkages, is somewhat similar to that in bakery product processing where oxidants are used to improve dough performance through gluten protein interaction.
An Overview of the Victims’ Rights Movement: Historical, Legislative, and Research Developments†
Authors: Mastrocinque Jeanna M. 
Published: February 2010

AbstractThe Victims' Rights Movement has made considerable accomplishments since the 1960s, when an increasing crime rate, coupled with the underreporting of crime, inspired concerns regarding crime victims. In subsequent decades the Victims' Rights Movement evolved and gained considerable momentum. This paper examines the historical development of the Victims' Rights Movement, including the movement's focus on specific types of victimization and crimes. State and Federal responses to the movement are also presented, with attention to constitutional developments and debates. Finally, current issues are presented and future research is suggested.