bluuebunny/crossref_metadata_2025 huggingface dataset:
Noradrenergic neurons of the area postrema mediate amylin's hypophagic action
Authors: Potes Catarina S. , Turek Victoria F. , Cole Rebecca L. , Vu Calvin , Roland Barbara L. , Roth Jonathan D. , Riediger Thomas , Lutz Thomas A.
Published: June 2010

Circulating amylin inhibits food intake via activation of the area postrema (AP). The aim of this study was to identify the neurochemical phenotype of the neurons mediating amylin's hypophagic action by immunohistochemical and feeding studies in rats. Expression of c-Fos protein was used as a marker for neuronal activation and dopamine-β-hydroxylase (DBH), the enzyme-catalyzing noradrenaline synthesis, as a marker for noradrenergic neurons. We found that ∼50% of amylin-activated AP neurons are noradrenergic. To clarify the functional role of these neurons in amylin's effect on eating, noradrenaline-containing neurons in the AP were lesioned using a saporin conjugated to an antibody against DBH. Amylin (5 or 20 μg/kg sc)-induced anorexia was observed in sham-lesioned rats with both amylin doses. Rats with a lesion of > 50% of the noradrenaline neurons were unresponsive to the low dose of amylin (5 μg/kg) and only displayed a reduction in food intake 60 min after injection of the high amylin dose (20 μg/kg). In a terminal experiment, the same rats received amylin (20 μg/kg) or saline. The AP and nucleus of the solitary tract (NTS) were stained for DBH to assess noradrenaline lesion success and for c-Fos expression to evaluate amylin-induced neuronal activation. In contrast to sham-lesioned animals, noradrenaline-lesioned rats did not show a significant increase in amylin-induced c-Fos expression in the AP and NTS. We conclude that the noradrenergic neurons in the AP mediate at least part of amylin's hypophagic effect.
Dopaminergic D2 receptors activate PKA to inhibit spinal pelvic-urethra reflex in rats
Authors: Wu Hsi-Chin , Chiu Chun-Hsien , Tung Kwong-Chung , Chen Gin-Den , Peng Hsien-Yu , Lin Tzer-Bin
Published: June 2010

To clarify the role of descending dopaminergic innervation in reflexive urethral closure, the impacts of dopaminergic D2 receptor (DR2)-selective agonists and antagonists on repetitive stimulation-induced pelvic-to-urethra spinal reflex potentiation (SRP) were tested using in vivo rat preparations. Pelvic afferent nerve test stimulation (TS; 1 pulse/30 s for 30 min) evoked baseline reflex activity with single spikes in the external urethral sphincter electromyogram (EUSE), whereas, repetitive stimulation (RS; 1 pulse/s for 30 min) induced SRP. Intrathecal application of quinelorane dihydrochloride (Q110; 10, 30, and 100 nM, 10 μl, a selective DR2 agonist) dose dependently inhibited the RS-induced SRP. Pretreatment with L135 (100 nM, 10 μL it, a selective DR2 antagonist) antagonized the Q110-dependent inhibition (100 nM, 10 μl it). Intrathecal AMPA (10 μM, 10 μl, a selective glutamatergic AMPA receptor agonist), and NMDA (10 μM, 10 μl, a selective glutamatergic NMDA receptor agonist) reversed the Q110-dependent inhibition. Intrathecal forskolin (100 nM, 10 μl, a PKA activator) prevented the Q110-dependent inhibition that was reversed by CNQX (10 μM, 10 μl it, a selective glutamate AMPA receptor antagonist) and APV (10 μM, 10 μl it , a selective glutamate NMDA receptor antagonist). Our results suggest that DR2 activation, which inactivates intracellular PKA, may be involved in descending dopaminergic inhibition of NMDA/AMPA receptor-dependent SRP at the lumbosacral spinal cord, which is thought to be involved in reflexive urethral closure.
The pleiotropic actions of rosuvastatin confer renal benefits in the diabetic Apo-E knockout mouse
Authors: Giunti Sara , Calkin Anna C. , Forbes Josephine M. , Allen Terri J. , Thomas Merlin C. , Cooper Mark E. , Jandeleit-Dahm Karin A.
Published: June 2010

Diabetic nephropathy is a leading cause of end-stage renal disease. Statins may exert renoprotective effects independently of lipid-lowering properties. We investigated the pleiotropic effects of rosuvastatin on renal structure and function in streptozotocin diabetic apolipoprotein-E knockout (Apo-E−/−) mice, a model of progressive nephropathy in which dyslipidemia is resistant to statin treatment. These effects were compared with those observed with conventional renin-angiotensin system blockade (candesartan) or combined treatment. Nondiabetic and diabetic Apo-E−/− mice were randomized to no treatment or treatment with candesartan (2.5 mg/kg), rosuvastatin (5 mg/kg), or their combination per gavage for 20 wk. Urine and blood samples were collected for assessment of albuminuria, creatinine clearance, plasma lipids, glucose, and glycated hemoglobin. Renal sclerosis was analyzed on paraffin-embedded kidney sections stained with periodic acid-Schiff. Renal expression of collagen IV, fibronectin and advanced glycation end products (AGEs), receptor for advanced glycation and products (RAGE), NADPH oxidase 4 (NOX4), and nitrotyrosine was assessed by real-time PCR and/or immunohistochemistry. Diabetes-induced albuminuria was not affected by rosuvastatin and combination treatment but was prevented by candesartan. Diabetes resulted in increased creatinine clearance, which was not modified by the treatments. Rosuvastatin and/or candesartan prevented diabetes-associated renal extracellular matrix accumulation. Rosuvastatin reduced accumulation of AGEs and expression of RAGE, NOX4, and nitrotyrosine. In conclusion, in the diabetic Apo-E−/− mouse, rosuvastatin confers renal benefits that are independent of lipid lowering and equivalent or greater to those observed with candesartan. The combination treatment is not superior to monotherapies.
Subtype-Specific Dendritic Ca2+Dynamics of Inhibitory Interneurons in the Rat Visual Cortex
Authors: Cho Kwang-Hyun , Jang Jin Hwa , Jang Hyun-Jong , Kim Myung-Jun , Yoon Shin Hee , Fukuda Takaichi , Tennigkeit Frank , Singer Wolf , Rhie Duck-Joo
Published: June 2010

The Ca2+increase in dendrites that is evoked by the backpropagation of somatic action potentials (APs) is involved in the activity-dependent modulation of dendritic and synaptic functions that are location dependent. In the present study, we investigated dendritic Ca2+dynamics evoked by backpropagating APs (bAPs) in four subtypes of inhibitory interneurons classified by their spiking patterns: fast spiking (FS), late spiking (LS), burst spiking (BS), and regular-spiking nonpyramidal (RSNP) cells. Cluster analysis, single-cell RT-PCR, and immunohistochemistry confirmed the least-overlapping nature of the grouped cell populations. Somatic APs evoked dendritic Ca2+transients in all subtypes of inhibitory interneurons with different spatial profiles along the tree: constantly linear in FS and LS cells, increasing to a plateau in BS cells and bell-shaped in RSNP cells. The increases in bAP-evoked dendritic Ca2+transients brought about by the blocking of A-type K+channels were similar in whole dendritic trees of each subtype of inhibitory interneurons. However, in RSNP cells, the increases in the distal dendrites were larger than those in the proximal dendrites. On cholinergic activation, nicotinic inhibition of bAP-evoked dendritic Ca2+transients was observed only in BS cells expressing cholecystokinin and vasoactive intestinal peptide mRNAs, with no muscarinic modulation in all subtypes of inhibitory interneurons. Cell subtype-specific differential spatial profiles and their modulation in bAP-evoked dendritic Ca2+transients might be important for the domain-specific modulation of segregated inputs in inhibitory interneurons and differential control between the excitatory and inhibitory networks in the visual cortex.
Inhibitory Modulation of Cortical Up States
Authors: Sanchez-Vives Maria V. , Mattia Maurizio , Compte Albert , Perez-Zabalza Maria , Winograd Milena , Descalzo Vanessa F. , Reig Ramon
Published: June 2010

The balance between excitation and inhibition is critical in the physiology of the cerebral cortex. To understand the influence of inhibitory control on the emergent activity of the cortical network, inhibition was progressively blocked in a slice preparation that generates spontaneous rhythmic up states at a similar frequency to those occurring in vivo during slow-wave sleep or anesthesia. Progressive removal of inhibition induced a parametric shortening of up state duration and elongation of the down states, the frequency of oscillations decaying. Concurrently, a gradual increase in the network firing rate during up states occurred. The slope of transitions between up and down states was quantified for different levels of inhibition. The slope of upward transitions reflects the recruitment of the local network and was progressively increased when inhibition was decreased, whereas the speed of activity propagation became faster. Removal of inhibition eventually resulted in epileptiform activity. Whereas gradual reduction of inhibition induced linear changes in up/down states and their propagation, epileptiform activity was the result of a nonlinear transformation. A computational network model showed that strong recurrence plus activity-dependent hyperpolarizing currents were sufficient to account for the observed up state modulations and predicted an increase in activity-dependent hyperpolarization following up states when inhibition was decreased, which was confirmed experimentally.
Postural Constraints on Movement Variability
Authors: Lametti Daniel R. , Ostry David J.
Published: June 2010

Movements are inherently variable. When we move to a particular point in space, a cloud of final limb positions is observed around the target. Previously we noted that patterns of variability at the end of movement to a circular target were not circular, but instead reflected patterns of limb stiffness—in directions where limb stiffness was high, variability in end position was low, and vice versa. Here we examine the determinants of variability at movement end in more detail. To do this, we have subjects move the handle of a robotic device from different starting positions into a circular target. We use position servocontrolled displacements of the robot's handle to measure limb stiffness at the end of movement and we also record patterns of end position variability. To examine the effect of change in posture on movement variability, we use a visual motor transformation in which we change the limb configuration and also the actual movement target, while holding constant the visual display. We find that, regardless of movement direction, patterns of variability at the end of movement vary systematically with limb configuration and are also related to patterns of limb stiffness, which are likewise configuration dependent. The result suggests that postural configuration determines the base level of movement variability, on top of which control mechanisms can act to further alter variability.
Loss of the Fragile X Mental Retardation Protein Decouples Metabotropic Glutamate Receptor Dependent Priming of Long-Term Potentiation From Protein Synthesis
Authors: Auerbach Benjamin D. , Bear Mark F.
Published: June 2010

Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). FMRP is a negative regulator of local mRNA translation downstream of group 1 metabotropic glutamate receptor (Gp1 mGluR) activation. In the absence of FMRP there is excessive mGluR-dependent protein synthesis, resulting in exaggerated mGluR-dependent long-term synaptic depression (LTD) in area CA1 of the hippocampus. Understanding disease pathophysiology is critical for development of therapies for FXS and the question arises of whether it is more appropriate to target excessive LTD or excessive mGluR-dependent protein synthesis. Priming of long-term potentiation (LTP) is a qualitatively different functional consequence of Gp1 mGluR-stimulated protein synthesis at the same population of CA1 synapses where LTD can be induced. Therefore we determined if LTP priming, like LTD, is also disrupted in the Fmr1 knockout (KO) mouse. We found that mGluR-dependent priming of LTP is of comparable magnitude in wild-type (WT) and Fmr1 KO mice. However, whereas LTP priming requires acute stimulation of protein synthesis in WT mice, it is no longer protein synthesis dependent in the Fmr1 KO. These experiments show that the dysregulation of mGluR-mediated protein synthesis seen in Fmr1 KO mice has multiple consequences on synaptic plasticity, even within the same population of synapses. Furthermore, it suggests that there is a bifurcation in the Gp1 mGluR signaling pathway, with one arm triggering synaptic modifications such as LTP priming and LTD and the other stimulating protein synthesis that is permissive for these modifications.
Neuronal Density Determines Network Connectivity and Spontaneous Activity in Cultured Hippocampus
Authors: Ivenshitz Miriam , Segal Menahem
Published: June 2010

The effects of neuronal density on morphological and functional attributes of the evolving networks were studied in cultured dissociated hippocampal neurons. Plating at different densities affected connectivity among the neurons, such that sparse networks exhibited stronger synaptic connections between pairs of recorded neurons. This was associated with different patterns of spontaneous network activity with enhanced burst size but reduced burst frequency in the sparse cultures. Neuronal density also affected the morphology of the dendrites and spines of these neurons, such that sparse neurons had a simpler dendritic tree and fewer dendritic spines. Additionally, analysis of neurons transfected with PSD95 revealed that in sparse cultures the synapses are formed on the dendritic shaft, whereas in dense cultures the synapses are formed primarily on spine heads. These experiments provide important clues on the role of neuronal density in population activity and should yield new insights into the rules governing neuronal network connectivity.
Canal–Otolith Interactions and Detection Thresholds of Linear and Angular Components During Curved-Path Self-Motion
Authors: MacNeilage Paul R. , Turner Amanda H. , Angelaki Dora E.
Published: June 2010

Gravitational signals arising from the otolith organs and vertical plane rotational signals arising from the semicircular canals interact extensively for accurate estimation of tilt and inertial acceleration. Here we used a classical signal detection paradigm to examine perceptual interactions between otolith and horizontal semicircular canal signals during simultaneous rotation and translation on a curved path. In a rotation detection experiment, blindfolded subjects were asked to detect the presence of angular motion in blocks where half of the trials were pure nasooccipital translation and half were simultaneous translation and yaw rotation (curved-path motion). In separate, translation detection experiments, subjects were also asked to detect either the presence or the absence of nasooccipital linear motion in blocks, in which half of the trials were pure yaw rotation and half were curved path. Rotation thresholds increased slightly, but not significantly, with concurrent linear velocity magnitude. Yaw rotation detection threshold, averaged across all conditions, was 1.45 ± 0.81°/s (3.49 ± 1.95°/s2). Translation thresholds, on the other hand, increased significantly with increasing magnitude of concurrent angular velocity. Absolute nasooccipital translation detection threshold, averaged across all conditions, was 2.93 ± 2.10 cm/s (7.07 ± 5.05 cm/s2). These findings suggest that conscious perception might not have independent access to separate estimates of linear and angular movement parameters during curved-path motion. Estimates of linear (and perhaps angular) components might instead rely on integrated information from canals and otoliths. Such interaction may underlie previously reported perceptual errors during curved-path motion and may originate from mechanisms that are specialized for tilt-translation processing during vertical plane rotation.
TAA Polyepitope DNA-Based Vaccines: A Potential Tool for Cancer Therapy
Authors: Bei Roberto , Scardino Antonio
Published: June 2010

DNA-based cancer vaccines represent an attractive strategy for inducing immunity to tumor associated antigens (TAAs) in cancer patients. The demonstration that the delivery of a recombinant plasmid encoding epitopes can lead to epitope production, processing, and presentation to CD8+ T-lymphocytes, and the advantage of using a single DNA construct encoding multiple epitopes of one or more TAAs to elicit a broad spectrum of cytotoxic T-lymphocytes has encouraged the development of a variety of strategies aimed at increasing immunogenicity of TAA polyepitope DNA-based vaccines. The polyepitope DNA-based cancer vaccine approach can (a) circumvent the variability of peptide presentation by tumor cells, (b) allow the introduction in the plasmid construct of multiple immunogenic epitopes including heteroclitic epitope versions, and (c) permit to enroll patients with different major histocompatibility complex (MHC) haplotypes. This review will discuss the rationale for using the TAA polyepitope DNA-based vaccination strategy and recent results corroborating the usefulness of DNA encoding polyepitope vaccines as a potential tool for cancer therapy.
An Atypical Etiology of Suprasphincteric Fistula: A Forgotten Surgical Material
Authors: Paksoy Melih , Ozben Volkan , Ayan Fadil , Simsek Arife
Published: June 2010

While the majority of fistulas in ano result from infection of the anal crypts, complex, recurrent, and/or nonhealing fistulas should always raise the suspicion of a chronic underlying condition. In this paper, we present a 30-year-old male patient with a diagnosis of a complex suprasphincteric fistula caused by a surgical thread left behind after an orthopedic hip operation performed sixteen years ago. Partial fistulectomy, extraction of the foreign material, and debridement procedures were performed. Few cases of such complex fistulas in ano due to foreign materials have been described in the literature. After careful history-taking, meticulous physical examination under general anesthesia should be done in order to deal with this rare type of fistula.
Diet, Screen Time, Physical Activity, and Childhood Overweight in the General Population and in High Risk Subgroups: Prospective Analyses in the PIAMA Birth Cohort
Authors: Wijga Alet H. , Scholtens Salome , Bemelmans Wanda J. E. , Kerkhof Marjan , Koppelman Gerard H. , Brunekreef Bert , Smit Henriette A.
Published: June 2010

Objective. To prospectively identify behavioral risk factors for childhood overweight and to assess their relevance in high risk sub groups (children of mothers with overweight or low education).Methods. In the PIAMA birth cohort (), questionnaire data were obtained at ages 5 and 7 on “screen time”, walking or cycling to school, playing outside, sports club membership, fast food consumption, snack consumption and soft drink consumption. Weight and height were measured at age 8 years.Results. Screen time, but none of the other hypothesized behavioral factors, was associated with overweight (aOR 1.4 (CI: 1.2–1.6)). The adjusted population attributable risk fraction for screen time > 1 hr/day was 10% in the high risk and 17% in the low risk sub groups.Conclusion. Reduction of screen time to < 1 hr/day could result in a reduction of overweight prevalence in the order of 2 percentage points in both high and low risks sub groups.
Epidemiology, Prognosis, and Evolution of Management of Septic Shock in a French Intensive Care Unit: A Five Years Survey
Authors: Boussekey Nicolas , Cantrel Juliette , Dorchin Debrabant Lise , Langlois Joachim , Devos Patick , Meybeck Agnes , Chiche Arnaud , Georges Hugues , Leroy Olivier
Published: June 2010

Purpose. To evaluate the epidemiology, prognosis, and management of septic shock patients hospitalized in our intensive care unit (ICU).Materiel and Methods. Five-year monocenter observational study including 320 patients.Results. ICU mortality was 54.4%. Independent mortality risk factors were mechanical ventilation (), Simplify Acute Physiology Score (SAPS) II > 60 (), chronic alcoholism (), age >65 years (), prothrombin ratio <40% (), and ratio <150 (). These six mortality risk factors recovered allow screening immediately septic shock patients with a high mortality risk. Morbidity improved with time (diminution of septic shock complications, increase of the number of days alive free from mechanical ventilation and vasopressors on day 28), concomitant to an evolution of the management (earlier institution of all replacement and medical therapies and more initial volume expansion). There was no difference in mortality.Conclusion. Our study confirms a high mortality rate in septic shock patients despite a new approach of treatment.
Reduction of Ischemic and Oxidative Damage to the Hypothalamus by Hyperbaric Oxygen in Heatstroke Mice
Authors: Tai Po-An , Chang Chen-Kuei , Niu Ko-Chi , Lin Mao-Tsun , Chiu Wen-Ta , Lin Jia-Wei
Published: June 2010

The aims of the present paper were to ascertain whether the heat-induced ischemia and oxidative damage to the hypothalamus and lethality in mice could be ameliorated by hyperbaric oxygen therapy. When normobaric air-treated mice underwent heat treatment, the fractional survival and core temperature at 4 hours after heat stress were found to be 0 of 12 and34∘C±0.3∘C, respectively. In hyperbaric oxygen-treated mice, when exposed to the same treatment, both fractional survival and core temperature values were significantly increased to new values of 12/12 and37.3∘C±0.3∘C, respectively. Compared to normobaric air-treated heatstroke mice, hyperbaric oxygen-treated mice displayed lower hypothalamic values of cellular ischemia and damage markers, prooxidant enzymes, proinflammatory cytokines, inducible nitric oxide synthase-dependent nitric oxide, and neuronal damage score. The data indicate that hyperbaric oxygen may improve outcomes of heatstroke by normalization of hypothalamic and thermoregulatory function in mice.
Killing the Killer: Natural Killer Cells to Treat Ewing's Sarcoma
Authors: Ahn Yong-Oon , Weigel Brenda , Verneris Michael R.
Published: June 2010

Cho and coworkers show that Ewing's sarcoma cells are highly sensitive to expanded allogeneic natural killer (NK) cells, partially through a NKG2D– and DNAM-1–dependent mechanism. Using an orthotopic murine model, they also show that irradiation significantly enhances the NK-cell killing of these tumors. Clin Cancer Res; 16(15); 3819–21. ©2010 AACR.
Bodiless Demons and Written Gospels
Authors: Mitchell Matthew W.
Published: June 2010

This article explores some of the methodological and exegetical issues raised in a recent Novum Testamentum article by Pier Franco Beatrice, in which a new understanding of the Judaic gospel tradition in the second century was proposed, based in large part upon the contention that Ignatius of Antioch displays knowledge of the Gospel of the Hebrews. The author responds specifically to Beatrice’s treatment of Ignatius’ writings, as well as discussing other recent literature on the issue of Ignatius and his sources, arguing that great caution needs to be displayed in any discussion alleging Ignatius’ use of written sources.
Ehe als Sanatorium Plutarchs
Authors: Becker Matthias
Published: June 2010

This study examines the relevance of Plutarch’s Conjugal Precepts for the interpretation of the Pastoral Epistles’ view on marriage with special regard to 1 Tim 2:9-15. By comparing the two texts the author concludes that not only do they share a conservative marriage-ethos, which can be detected in their approval of female subordination, but they more importantly share the belief that marriage acts as a kind of sanatorium within which the wife is made free from her so-called vitium feminae. According to Plutarch, marriage helps women to be freed from a lack of logos that supposedly characterizes their nature. In the Pastoral Epistles the healing function of marriage is directed toward the Satanic deception that every woman supposedly suffers from as a result of Eve’s transgression. Through marriage the vitium feminae is transformed into the salus uxoris.
What do we really know about Women’s Rites in the Israelite Family Context?
Authors: Olyan Saul M.
Published: June 2010

What we know about the roles of women in Israelite family religion is a topic in need of reassessment. In this article, the author evaluates a number of common claims which have been made about family religion and gender. These include the idea that goddess worship was especially important to women; that Judean pillar figurines were used primarily or exclusively by women in their ritual activities; that the religious practices of ancient Israelite women overlapped little with those of men; and that birth-related ritual contexts were a special preserve of women.
Expelling the Demon of Effeminacy: Anniwiyani’s Ritual and the Question of Homosexuality in Hittite Thought
Authors: Peled Ilan
Published: June 2010

The ritual of Anniwiyani drew the attention of scholars for more than eighty years, since its earliest publications. As its aim is not self-evident, various speculations and attempts were made during the years in order to try and comprehend it. The conventional explanations focused on the masculine-feminine dichotomy characterizing the ritual, as the background for its performance. The current paper sets forth a new interpretation, according to which the ritual actually aimed at treating a passive homosexual, in order to turn him into the active party in sexual relations.In light of this new perspective, the paper also seeks to assess the broader question of homosexuality in Hittite thought, as evident from several other textual sources.
The Availability in the UAE of Liens to Secure Payment under Construction Contracts
Authors: Barrette Amy L. , Brendel Neal R. , El-Riachi Wadih
Published: June 2010

While much attention has been devoted to curbing the rise of lawsuits surrounding Dubai’s struggling construction industry, surprisingly little attention has been focused on another option available to contractors who seek payment for failed or troubled projects. Contractors, architects, and engineers may find relief under a seldom-reported UAE federal law that establishes qualified rights for contractors to secure payment for work under non-governmental contracts by filing a priority lien against the project itself. This article discusses the remedy, known in many common-law jurisdictions as ‘mechanic’s liens’ or ‘builders’ liens’, and why it is important for contractors to be familiar with the applicable Civil Code and Civil Procedure Code provisions. Those who first exercise their lien rights and seek to register liens with the Land Department will be treading new ground and will want to be well- prepared and educated on their rights provided under existing law.
A Calvinist Heritage to the “Curse of Ham”: Assessing the Accuracy of a Claim about Racial Subordination
Authors: Whitford David
Published: June 2010

This article assesses the validity of the claim that Puritan theology was “preset for racism” and that it played a preeminent role in establishing racial hatred in America. It does so by examining a number of Puritans beliefs regarding the most important theological justification for slavery, the socalled Curse of Ham.
Sulfotransferase Ndst1 is Needed for Mandibular and TMJ Development
Authors: Yasuda T. , Mundy C. , Kinumatsu T. , Shibukawa Y. , Shibutani T. , Grobe K. , Minugh-Purvis N. , Pacifici M. , Koyama E.
Published: June 2010

Heparan sulfate proteoglycans (HS-PGs) regulate several developmental processes, but their possible roles in mandibular and TMJ formation are largely unclear. To uncover such roles, we generated mice lacking Golgi-associated N-sulfotransferase 1 (Ndst1) that catalyzes sulfation of HS-PG glycosaminoglycan chains. Ndst1-null mouse embryos exhibited different degrees of phenotypic penetrance. Severely affected mutants lacked the temporomandibular joint and condyle, but had a mandibular remnant that displayed abnormal tooth germs, substandard angiogenesis, and enhanced apoptosis. In mildly affected mutants, the condylar growth plate was dysfunctional and exhibited thicker superficial and polymorphic cell zones, a much wider distribution of Indian hedgehog signaling activity, and ectopic ossification along its lateral border. Interestingly, mildly affected mutants also exhibited facial asymmetry resembling that seen in individuals with hemifacial microsomia. Our findings indicate that Ndst1-dependent HS sulfation is critical for mandibular and TMJ development and allows HS-PGs to exert their roles via regulation of Ihh signaling topography and action.
The Trustworthiness of Online Channels for Experience- and Goal-Directed Search Tasks
Authors: Dickinger Astrid
Published: June 2010

Travelers have used the Internet as an information channel for years and more recently also started to produce content themselves. With an abundance of information channels competing for customers’ attention, researchers and practitioners need to better understand which online channels are trustworthy and consulted for travel-related factual information or for reports on experiences. Thus, this article compares the trustworthiness of three different online channels (personal, marketing, and editorial). The results of the experiment indicate that user-generated content appears to be highly trustworthy, showing high levels of integrity; however, it is not always regarded as the most informative. Editorial content providers, such as tourist boards, are considered to be the most able information provider. The results confirm that depending on the type of online channel, different dimensions of trustworthiness become effective as drivers of overall trust.
Direct and Indirect Effects for Neighborhood-Based Clustered and Longitudinal Data
Authors: VanderWeele Tyler J.
Published: June 2010

Definitions of direct and indirect effects are given for settings in which individuals are clustered in groups or neighborhoods and in which treatments are administered at the group level. A particular intervention may affect individual outcomes both through its effect on the individual and by changing the group or neighborhood itself. Identification conditions are given for controlled direct effects and for natural direct and indirect effects. The interpretation of these identification conditions are discussed within the context of neighborhood research and multilevel modeling. Interventions at a single point in time and time-varying interventions are both considered. The definition of direct and indirect effects requires certain stability or no-interference conditions; some discussion is given as to how these no-interference conditions can be relaxed.
Generals, Dictators, and Kings
Authors: Fjelde Hanne
Published: June 2010

Recent years have seen a surge of literature examining how political institutions influence the risk of civil conflict. A comparatively neglected aspect of this debate has been the heterogeneous impact of different forms of authoritarianism. In this article, I theoretically and empirically unpack the authoritarian regime category. I argue that authoritarian regimes differ both in their capacity to forcefully control opposition and in their ability to co-opt their rivals through offers of power positions and rents. Authoritarian regimes thus exhibit predictable differences in their ability to avoid organized violent challenges to their authority. I examine the association between four types of authoritarian regimes—military, monarchy, single-party, and multi-party electoral autocracies—and the onset of civil conflict from 1973 to 2004. I find that military regimes and multi-party electoral autocracies run a higher risk of armed conflict than single-party authoritarian regimes, which on the other hand seem to have an institutional set-up that makes them particularly resilient to armed challenges to their authority. These findings suggest that the emerging view, that political institutions are not a significant determinant of civil conflict, results from treating a heterogeneous set of authoritarian regimes as homogenous.
Territorial Issues and Recurrent Conflict
Authors: Quackenbush Stephen L.
Published: June 2010

It is well established that territorial issues are highly conflict prone. Furthermore, dyads encountering conflicts over territory should be expected to fight more frequently, with shorter durations of peace than other dyads. However, the growing literature examining factors leading to the recurrence of conflict has largely ignored the impact of territorial issues, focusing instead on factors such as the type of dispute settlement. In this article, I seek to examine the relationship between territorial issues, settlements, and conflict recurrence through survival analyses of the periods of peace following 2,974 dyadic militarized interstate disputes between 1816 and 2001.
Beyond Kantian Liberalism
Authors: Choi Seung-Whan
Published: June 2010

Although globalization has become one of the most salient issues in the study of international relations during the past few decades, its net effect on international conflict remains unexplored. I argue that although the manifold phenomena of globalization may conflict (i.e. produce both positive and negative influences), its overall consequences help foster a common peaceful disposition among national leaders who are then less likely to resort to arms in times of crisis. Based on a cross-sectional, time-series dyadic data analysis for 114 countries during the period from 1970 to 2001, this study reports that socio-economic and political globalization in its entirety generates a dampening effect on militarized interstate disputes. Even when common conflict-related control variables such as democracy, economic interdependence, joint membership in international organizations, and others are incorporated into the analysis, globalization emerges as the most powerful explanatory variable. Consequently, globalization when taken in its entirety represents an unambiguous force for interstate peace.
Cyto-genotoxicity of amphibole asbestos fibers in cultured human lung epithelial cell line: Role of surface iron
Authors: Ritesh Kumar Srivastava  , Lohani Mohtashim , Aditya Bhushan Pant  , Rahman Qamar
Published: June 2010

The present investigations correlate the potentials of the reactive oxygen species (ROS) generation and the cyto-genotoxicity of amphibole asbestos fibers (amosite, crocidolite and tremolite) with their surface iron, under in vitro controlled conditions, using A549 cells (human lung epithelial cell line). The mobilizable surface iron was measured by Atomic Absorption Spectroscopy; the production of ROS was investigated using 2, 7 dichloro-dihydrofluorescein-diacetate (DCFH-DA) dye; for cytotoxicity assessment, the intracellular organelles specific damages were measured, using 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide salt (MTT) assay; and, the genotoxic potential of amphibole fibers was determined by cytokinesis block micronucleus (CBMN) assay. In the study, highest amount of ROS was generated by crocidolite followed by tremolite and minimum with amosite. In MTT assay, the time- and concentration-dependent decrease in percent cell viability was recorded with all the three amphibole fibers, tremolite being most cytotoxic, followed by crocidolite, and then amosite. In genotoxicity assay, an increase in the frequency of micronuclei (MNi) in binucleated (BN) cells was observed, where crocidolite was most genotoxic, followed by tremolite, and amosite the least.The comparison of results depicts a clear trend of cyto-genotoxic potential paralleling the ROS generation, suggesting a definite role of oxidative stress in fiber-induced toxicity. However, amosite contains maximum surface iron (28%), followed by crocidolite (27%), and tremolite carrying least (as contaminant) or no iron, the mobilizable surface iron is maximum in crocidolite followed by amosite and is minimum in tremolite. The mobilizable iron somewhat corresponds with the ROS generation capacity of these fibers. This shows that the surface iron could be mainly responsible for amphibole asbestos-induced ROS toxicity; though it may not be the only factor responsible, other factors like shape and size etc., also play role in amphibole asbestos-induced toxicity.
The Lived Experience of Feeling Sad
Authors: Bunkers Sandra Schmidt
Published: June 2010

The purpose of this study was to enhance understanding of the lived experience of feeling sad. Parse’s phenomenological-hermeneutic research method was used to answer the research question: What is the structure of the lived experience of feeling sad? Participants were 7 elders who had lost a pet. Data were collected with dialogical engagement. The major finding of the study is the structure: Feeling sad is penetrating anguish surfacing with contemplating absent-yet present intimacies, while prevailing amid misfortune. Feeling sad is discussed in relation to the principles of humanbecoming and in relation to how it can inform future nursing research and nursing practice.
Lao Lai Zi—Becoming a Mother
Authors: Yang Yu-O , Chen Chung-Hey , Chiu Hui-Lai
Published: June 2010

Becoming a mother is a culturally significant value of transition for Chinese women. The purpose of this research was to explore the experiences of first-time mothers, 1 year after giving birth. Parse’s humanbecoming theory guided the research to illuminate the role transition experience. The research was conducted in a southern medical center in Taiwan using narrative inquiry with 10 first-time mothers over the age of 35. We explored the mothers’ experiences in the following areas: the pride and obstacles related to becoming a mother, the excitement and inconvenience in taking care of a baby, the struggling for energy and time in caring for the child, the worry about the child being unsociable, feeling grateful to God for the child, and realizing the inability to have another child. The findings of this research can provide nursing staff with a new perspective on the way first-time mothers experience their world, and it could enable them to offer better care.
Why Ask Why?
Authors: Senthuran Rajamalar A.
Published: June 2010

What contributes to nursing evolution? In this paper, ideas will be presented about the evolution of nursing as a discipline. These ideas are viewed within the context of nursing today and may help nursing move forward in its own evolution.
Humanbecoming
Authors: Smith Sandra Maxwell
Published: June 2010

The author in this column describes how for one nurse working with hospice and homecare patients humanbecoming was much more than a theory; it was a way of being. Through the stories of three individuals the author explicates how honoring another by being attentively present cocreated the venue necessary for the individuals to contemplate the meaning of their situations. In doing so they identified their unique healthcare patterns and how they lived what was important to them
Failing to Do the Right Thing
Authors: Milton Constance L.
Published: June 2010

Ethical end of life decisions are increasingly viewed by the global healthcare community as complex and imbued with uncertainty in institutional healthcare settings. Each person experiences health decision-making and the concept of time differently and uniquely. In the context of end of life situations, both the recipients of healthcare and their families may experience complex decision-making in situations where profound questioning and uncertainty surfaces with a struggling of desiring to do the right thing comingling with the possibilities of failing to do the right thing according to the expectations of self and others. This column begins a discussion of possible meanings found in ethical decision-making with families as articulated with the lens of the humanbecoming family model.
Does homeopathy have anything to contribute to hormesis?
Authors: Fisher Peter
Published: June 2010

Homeopathy is the best known medical analogue of hormesis, others include hormoligosis and paradoxical pharmacology. Homeopathy is based on the concept Similia similibus curentur (‘Let like be cured by like’); the exploitation of secondary effects of drugs, the body’s reaction rather than the primary pharmacological action. The most controversial aspect of homeopathy is its use of ‘ultramolecular’ dilutions in which a single molecule of the starting substance is unlikely to be present. Classical pharmacological actions in vivo have been reported with dilutions as high as 10-22mol/L, but homeopathic medicines may be far more dilute than this. There is growing biological evidence including independent reproduction that in vivo effects may occur at such dilutions. In a systematic review, 73% of experiments showed an effect with ultramolecular dilutions including 68% of high-quality experiments. Physical and physico-chemical work suggests that homeopathic preparations contain stable ordered supramolecular structures, gas nanobubbles and dissolved silicates may be involved. Homeopathy may contribute to the generalizability and reproducibility of hormesis effects. It also raises the question of the threshold of hormesis effects.
Oxidative stress induced by urban fine particles in cultured EA.hy926 cells
Authors: Han Wei  , Dan Wei  , Shuo Yi  , Fang Zhang  , Wenjun Ding
Published: June 2010

It has been reported that vascular endothelia cell damage is an important precursor to the morbidity and mortality associated with cardiovascular disease exposed to airborne particulate matter (PM). The present study investigated the hypothesis that urban fine (PM2.5) particles could cause cytotoxicity via oxidative stress in human umbilical vein endothelial cells, EA.hy926. The concentrations of metal elements (Cr, Fe, Ni, Cu, Zn, Mo, Cd and Pb) in PM2.5 suspension, water-soluble and water-insoluble fractions of PM2.5 were determined by inductively coupled plasma - mass spectrometry (ICP-MS). Iron (Fe), Zn and Pb were highly enriched in all the samples. Exposure of the cultured EA.hy926 cells to PM2.5 suspension, water-soluble and water-insoluble fractions of PM2.5 led to cell death, reactive oxygen species (ROS) increase, mitochondrial transmembrane potential (ΔΨm) disruption and NF-κB activation, respectively. The ROS increase by exposure to PM 2.5 suspension, water-soluble and water-insoluble fractions of PM 2.5 triggered the activation of nuclear factor (NF)-κB, which means that PM2.5 particles exert cytotoxicity by an apopotic process. However, the induction of cytotoxicity by PM2.5 suspension, water-soluble and water-insoluble fractions of PM2.5 was reversed by pretreatment with superoxide dismutase (SOD). These results suggest that each fraction of PM2.5 has a potency to cause oxidative stress in endothelial cells. ROS was generated through PM2.5-mediated mitochondrial apoptotic pathway, which may induce direct interaction between metal elements and endothelia cells.
Narratives of Suffering of South Asian Immigrant Survivors of Domestic Violence
Authors: Kallivayalil Diya
Published: June 2010

This article examines the narratives of suffering expressed by a group of South Asian immigrant survivors of domestic violence who accessed a mental health clinic in New York City. These accounts illustrate women’s own perceptions of their suffering and symptoms and provide a window into the South Asian immigrant community’s ideologies and moral domains regarding gender, violence, and sickness, as well as how individuals vary in their endorsement of these ideologies. The women’s narratives illustrate how migration and culture interact with the deeply personal experience of suffering caused by domestic and sexual violence.
Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis
Authors: Wade Derick T , Collin Christine , Stott Colin , Duncombe Paul
Published: June 2010

Objective: To determine the efficacy of Sativex (USAN: nabiximols) in the alleviation of spasticity in people with multiple sclerosis.

Methods: The results from three randomized, placebo-controlled, double-blind parallel group studies were combined for analysis.

Patients: 666 patients with multiple sclerosis and spasticity.

Measures: A 0—100 mm Visual Analogue Scale (VAS, transformed to a 0—10 scale) or a 0—10 Numerical Rating Scale (0—10 NRS) was used to measure spasticity. Patients achieving a ≥30% improvement from baseline in their spasticity score were defined as ‘responders’. Global impression of change (GIC) at the end of treatment was also recorded.

Results: The patient populations were similar. The adjusted mean change of the numerical rating scale from baseline in the treated group was —1.30 compared with —0.97 for placebo. Using a linear model, the treatment difference was —0.32 (95% CI —0.61, —0.04, p = 0.026). A statistically significant greater proportion of treated patients were responders (odds ratio (OR) = 1.62, 95% CI 1.15, 2.28; p = 0.0073) and treated patients also reported greater improvement: odds ratio 1.67 (95% CI 1.05, 2.65; p = 0.030). High numbers of subjects experienced at least one adverse event, but most were mild to moderate in severity and all drug-related serious adverse events resolved.

Conclusion: The meta-analysis demonstrates that nabiximols is well tolerated and reduces spasticity.
Compliance with McDonald criteria and red flag recognition in a general neurology practice in Ireland
Authors: Albertyn Christine , O'Dowd Sean , McHugh John , Murphy Raymond
Published: June 2010

Background: The revised McDonald criteria aim to simplify and speed the diagnosis of multiple sclerosis (MS). An important principle of the criteria holds there should be no better explanation for the clinical presentation. In Miller et al.’s consensus statement on the differential diagnosis of MS, red flags are identified that may suggest a non-MS diagnosis.

Objective: All new patients with a practice diagnosis of MS were assessed for compliance with McDonald criteria. The group of patients not fulfilling criteria was followed up to assess compliance over time. At the end of the follow-up period, red flags were sought in the group of patients who remained McDonald criteria negative.

Methods: Clinical notes and paraclinical tests were examined retrospectively for compliance with McDonald criteria and for the presence of red flags.

Results: Sixty-two patients were identified, with two lost to follow-up. Twenty-six (42%) patients fulfilled criteria at diagnosis. After 53 months follow-up, 47 (78%) patients fulfilled criteria. In the 13 (22%) patients who remain McDonald criteria negative, a total of 20 red flags were identified, ranging from one to six per patient. Alternative diagnoses were considered and further investigations performed in 10 patients with no significantly abnormal results.

Conclusion: Twenty-two percent of patients still do not fulfill McDonald criteria after 53 months. Dissemination in time was not proven in the majority of patients and the lack of follow-up neuroimaging was an important factor in this. Red flags may be useful in identifying alternative diagnoses, but the yield was low in our cohort.
The logic of habit in International Relations
Authors: Hopf Ted
Published: June 2010

IR theory is dominated by the logics of consequentialism and appropriateness. But Max Weber offered four logics of choice, not just two. Beyond the instrumental rationality of Zweckrationalität and the normative rationality of Wertrationalität are affect and habit. Drawing on Weber, James, Dewey, and Bourdieu, and habit’s microfoundations in neurocognitive psychology, I explore the logic of habit and its consequences for several fundamental puzzles in IR theory. The logic of habit necessarily precludes rationality, agency, and uncertainty, and so offers a different interpretation of cooperation, security dilemmas, enduring rivalries, and security communities in international politics. The logic of habit also fills a gap in mainstream constructivism’s theorization of intersubjective structures, returning the taken-for-granted lifeworld to the center of attention.