bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of galectin‐3 in primary cutaneous melanoma
Authors: Buljan M. , Šitum M. , Tomas D. , Milošević M. , Krušlin B.
Published: December 2010

Background  Galectin‐3, one of the β‐galactoside‐binding lectins, has been suggested as a marker of disease progression in melanoma patients because of its overexpression observed in recent studies. However, prognostic value of galectin‐3 in primary cutaneous melanoma (PCM) has not been clearly defined.

Objectives  The aim of the study was to analyse whether the intensity of galectin‐3 expression can predict survival in patients with PMC.

Methods  Galectin‐3 expression was evaluated using immunohistochemistry in 104 PCM samples, including 71 (68.2%) superficial spreading (SSM) and 33 (31.8%) nodular melanomas (NM).

Results  Significant difference of galectin‐3 expression between SSM and NM was determined (P < 0.001). Increased galectin‐3 expression was positively correlated with tumour thickness (P < 0.001), Clark (P < 0.001) and Breslow (P < 0.001) stage, mitotic rate (P < 0.001), presence of tumour ulceration (P < 0.001), lymphatic invasion (P = 0.018), positive sentinel lymph node (P < 0.022) and distant metastases (P < 0.001). Kaplan–Meier analysis showed an association between increased galectin‐3 expression and reduced recurrence‐free survival (RFS) (P = 0.001) and reduced disease‐specific survival (DSS) (P = 0.015). In Cox proportional hazards regression analysis, significant predictors of reduced RFS were positive sentinel lymph node (P = 0.025) and lymphovascular invasion (P = 0.021), whereas predictors of DSS were tumour thickness (P = 0.012), lymphovascular invasion (P = 0.047), Clark stage (P = 0.029) and location of tumour on upper extremities (P = 0.024).

Conclusions  Our results support the potential role of galectin‐3 in PCM development, progression and metastasis. Moreover, galectin‐3 could serve as an additional prognostic marker that might help in further stratifying the risk of disease progression and metastasis in patients with PMC.
Physical urticaria: prevalence, type and natural course in a tropical country
Authors: Silpa‐archa N. , Kulthanan K. , Pinkaew S.
Published: December 2010

Background  Physical urticarias (PU) are an urticarial response to different specific physical stimuli. PU can occur concurrently with chronic spontaneous urticaria or another type of PU.

Objective  We aimed to study the prevalence, type, clinical data and natural course of each type of PU and other inducible urticarias and also the prognostic factors for remission of patients visiting a tertiary referral hospital.

Method  We performed a retrospective study of 1200 chronic urticaria patients who visited our Urticaria Clinic during a period of 5 years.

Results  Of the 1200 chronic urticaria patients, 86 (7.2%) were diagnosed as PU and other inducible urticarias. The most common type of PU was symptomatic dermographism (n = 35, 40.7%) followed by cold urticaria (n = 20, 23.3%) and delayed pressure urticaria (n = 11, 12.8%), respectively. Twelve patients (13.9%) had associated chronic spontaneous urticaria. None of the cases had multiple types of PU. Erythrocyte sedimentary rate elevation was the most common abnormal laboratory result. Nevertheless, only 4.6% declared a related infection. For each type, the median time after onset before 50% remission showed that cholinergic urticaria took the shortest course (34 months) and delayed pressure urticaria took the longest period (110 months). After 1 year and 5 years from the onset of symptoms, 13% and 50% of PU patients were free of symptoms, respectively.

Conclusion  This study emphasized the variety of PU, other inducible urticarias and natural courses based on tertiary hospital care. PU and other inducible urticarias have tendency to have a longer course than chronic spontaneous urticaria.
Right Action and the Non‐Virtuous Agent
Authors: VAN ZYL LIEZL
Published: December 2010

abstract

According to qualified‐agent virtue ethics, an action is right if and only if it is what a virtuous agent would characteristically do in the circumstances. I discuss two closely related objections to this view, both of which concern the actions of the non‐virtuous. The first is that this criterion sometimes gives the wrong result, for in some cases a non‐virtuous agent should not do what a virtuous person would characteristically do. A second objection is it altogether fails to apply whenever the agent, through previous wrongdoing, finds herself in circumstances that a virtuous person cannot be in. I focus on Rosalind Hursthouse's account of right action, and argue that it can provide a satisfactory response to both these objections. I do so by drawing attention to the distinction between action guidance and action assessment, and arguing that while the above criterion is adequate as a means of action assessment, we should turn to the virtue‐ and vice‐rules (v‐rules) for action guidance.
Failing where others have succeeded: Medial Frontal Negativity tracks failure in a social context
Authors: Boksem Maarten A. S. , Kostermans Evelien , De Cremer David
Published: December 2010

Most of us can appreciate that it feels worse to fail when people around you are successful than when others are also failing. Indeed, comparison with other individuals is of central importance within social groups. Despite the importance of relative success or failure for human decision making and even well‐being, the underlying neurobiological substrate of this social comparison process is not well understood. In the present study, ERPs were recorded while two participants received feedback on both their own, and the other participant's performance on each trial. The results showed that medial frontal negativity, an ERP component associated with deviations from the desired outcome, is particularly enhanced when an individual's own outcomes are worse than those of others. These results indicate that the way the brain evaluates the success of our actions is crucially dependent on the success or failure of others.
NPY promotes chemokinesis and neurogenesis in the rat subventricular zone
Authors: Thiriet Nathalie , Agasse Fabienne , Nicoleau Camille , Guégan Christelle , Vallette François , Cadet Jean‐Lud , Jaber Mohamed , Malva João O. , Coronas Valérie
Published: December 2010

J. Neurochem. (2011) 116, 1018–1027.

The subventricular zone (SVZ) is a major reservoir for stem cells in the adult mammalian brain. Neural stem cells supply the olfactory bulb with new interneurons and provide cells that migrate towards lesioned brain areas. Neuropeptide Y (NPY), one of the most abundant neuropeptides in the brain, was previously shown to induce neuroproliferation on mice SVZ cells. In the present study, performed in rats, we demonstrate the endogenous synthesis of NPY by cells in the SVZ that suggests that NPY could act as an autocrine/paracrine factor within the SVZ area. We observed that NPY promotes SVZ cell proliferation as previously reported in mice, but does not affect self‐renewal of SVZ stem cells. Additionally, this study provides the first direct evidence of a chemokinetic activity of NPY on SVZ cells. Using pharmacological approaches, we demonstrate that both the mitogenic and chemokinetic properties of NPY involve Y1 receptor‐mediated activation of the ERK1/2 MAP kinase pathway. Altogether, our data establish that NPY through Y1 receptors activation controls chemokinetic activity and, as for mice, is a major neuroproliferative regulator of rat SVZ cells.
Women’s experience of a myocardial infarction: 5 years later
Authors: Sjöström‐Strand Annica , Ivarsson Bodil , Sjöberg Trygve
Published: December 2010

Scand J Caring Sci; 2011; 25; 459–466
 
Women’s experience of a myocardial infarction: 5 years later

Background:  Myocardial infarction (MI) has long been seen as a male disease despite the fact that it is also a health problem for women. Factors that may influence their recovery, such as co‐morbidity and requirements for support, have received less scientific attention.

Aim:  To explore and describe how women conceived their health and daily life 5 years after an MI.

Method:  An explorative and descriptive approach inspired by phenomenography was chosen as the design. The present study includes 12 women who have been described in earlier short‐term studies.

Findings:  The women described how the MI caused limitations in their lives even 5 years after the MI. They experienced physical restrictions, fatigue and also other health complaints. Furthermore, the older women suffered from various co‐morbidities such as diabetes, kidney disease, high blood pressure, and stroke. Some women did not perceive their heart disease to interfere in daily life. Many of the women had thoughts about having a new MI. Furthermore, some women were grateful and described it as having a second opportunity.

Conclusion:  The present study indicates how women in the recovery process 5 years after an MI still need support to continue with lifestyle changes. The women continue to struggle with different kinds of issues, such as financial stress, co‐morbidity and side effects of medication. Support from the health care only in the first year after the MI is not enough. The women should benefit from the possibility to visit or consult professionals in primary care with knowledge of CHD.
Hot topics in aging research: protein translation and TOR signaling, 2010
Authors: Kaeberlein Matt , Kennedy Brian K.
Published: December 2010

In this, the fourth installment of our annual Hot Topics review on mRNA translation and aging, we have decided to expand our scope to include recent findings related to the role of TOR signaling in aging. As new data emerge, it is clear that TOR signaling acts upstream of mRNA translation, as well as a variety of other cellular processes, to modulate longevity and healthspan in evolutionarily diverse species. This Hot Topics review will cover important new findings in this area that have occurred over the past year. These include the demonstration that the TOR substrate ribosomal S6 kinase modulates longevity in mammals, the potential for TOR inhibitors as therapeutic treatments for Alzheimer’s disease, and further studies emphasizing the importance of differential translation of specific mRNAs for healthy aging and enhanced longevity.
Effaced preservation in the Ediacara biota and its implications for the early macrofossil record
Authors: LIU ALEXANDER G. , MCILROY DUNCAN , ANTCLIFFE JONATHAN B. , BRASIER MARTIN D.
Published: December 2010

Abstract: Ediacaran structures known as ‘pizza discs’ orIvesheadiahave long been considered enigmatic. They are amongst the oldest known members of the Ediacara biota, apparently restricted to the Avalonian successions of Newfoundland and the UK,c. 579–560 Ma. Here, we suggest that these impressions are taphomorphs, resulting from the post‐mortem decay of the frondose Ediacaran biota. Ediacaran fossils range from well‐preserved, high‐fidelity variants to almost completely effaced specimens. The effaced specimens are inferred to have undergone modification of their original morphology by post‐mortem microbial decay on the sea floor, combined with sediment trapping and binding. In this style of preservation, morphological details within the organism became variously subdued as a function of the extent of organic decay prior to casting by overlying sediments. Decay and effacement were progressive in nature, producing a continuum of grades of preservation on Ediacaran bedding planes. Fossils preserved by such ‘effaced preservation’ are those that have suffered these processes to the extent that only their gross form can be determined. We suggest that the lack of detailed morphology in effaced specimens renders such fossils unsuitable for use as type material, as it is possible that several taxa may, upon degradation and burial, generate similar morphological taphomorphs. We here reinterpret the genusIvesheadiaas a taphomorph resulting from extensive post‐mortem decay of frondose organisms.Blackbrookia,PseudovendiaandShepshediafrom beds of comparable age in England are likewise regarded as taphomorphs broadly related toCharniaorCharniodiscusspp. To reflect the suggestion that such impressions are likely to be taphomorphs, and not taxonomically discrete, we propose the term ivesheadiomorphs to incorporate all such effaced taphonomic expressions of Ediacaran macrofossil taxa in Avalonian assemblages. Our recognition of effaced preservation has significant implications for Ediacaran taxonomy, and consequently for measures of Ediacaran diversity and disparity. It is implied that Avalonian assemblages preserve both organisms that were alive and organisms that were already dead at the time of burial. As such, the fossil assemblages cannot be taken to represent census populations of living organisms, as in prior interpretations.
Public Policy towards Food Consumption*
Authors: Griffith Rachel , O'Connell Martin
Published: December 2010

Governments around the world are increasingly concerned about the rise in diet‐related chronic disease and there has been increased interest in policy interventions targeted at changing eating habits. In this paper, we discuss the ways in which food markets might fail to deliver the optimal outcome and how this may justify government intervention. We consider how well different types of policies – information campaigns, taxes and regulations – are able to counteract these market failures and we consider some of the implementation issues associated with targeting different consumers and anticipating firms' strategic responses.
The UK National Minimum Wage in Retrospect*
Authors: Dolton Peter , Bondibene Chiara Rosazza , Wadsworth Jonathan
Published: December 2010

This paper provides a retrospective summary of the effects of the UK national minimum wage (NMW) on labour market performance since its introduction in 1999. We use an ‘incremental differences‐in‐differences’ (IDiD) estimator to look at the effects of the NMW in each year through its differential impact across local labour markets. We find that the NMW is associated with a significant fall in wage inequality in the bottom half of the distribution. This suggests that geographical areas where the NMW ‘bites’ more have experienced larger declines in wage inequality than elsewhere. While the overall effect of the NMW on employment rates averaged over its existence is neutral, we do find small positive employment effects from 2003 onwards. Likewise, the association of the NMW with unemployment has been negative in recent years. NMW effects on hours have been mixed, but overall there is no compelling evidence to indicate that the NMW upratings have had an adverse effect on full‐time total hours of work. Notwithstanding the clarity of these results, any causal interpretation of them might be compromised by the presence of concomitant policies that might have been correlated with the ‘bite’ of the NMW.
The influence of social networks on romantic relationships: Through the lens of the social network
Authors: SPRECHER SUSAN
Published: December 2010

Past research indicates that social network support is linked to relationship development and continuation. This study fills a gap in the literature by examining social network influence from the perspective of network members. University students completed a survey about a relationship in their network of which they had a strong reaction, either positive or negative. Participants' social reactions to the targeted relationship were associated with the likelihood that they engaged in behaviors to try to influence the relationship. About two thirds of the participants believed that their behaviors had an influence on the outcome of the relationship, and those who reported more influence attempts also reported that they had a greater effect on the relationship. The findings help paint a picture of social network reactions, perceptions, and influence directed toward relationships, from the perspective of the social network.
The C‐terminal fragment of parathyroid hormone‐related peptide promotes bone formation in diabetic mice with low‐turnover osteopaenia
Authors: Lozano D , Fernández‐de‐Castro L , Portal‐Núñez S , López‐Herradón A , Dapía S , Gómez‐Barrena E , Esbrit P
Published: December 2010

BACKGROUND AND PURPOSE Current data suggest that parathyroid hormone (PTH)‐related peptide (PTHrP) domains other than the N‐terminal PTH‐like domain contribute to its role as an endogenous bone anabolic factor. PTHrP‐107‐139 inhibits bone resorption, a fact which has precluded an unequivocal demonstration of its possible anabolic action in vivo. We thus sought to characterize the osteogenic effects of this peptide using a mouse model of diabetic low‐turnover osteopaenia.

EXPERIMENTAL APPROACH PTHrP‐107‐139 was administered to streptozotocin‐induced diabetic mice, with or without bone marrow ablation, for 13 days. Osteopaenia was confirmed by dual‐energy X‐ray absorptiometry and microcomputed tomography analysis. Histological analysis was performed on paraffin‐embedded bone tissue sections by haematoxylin/eosin and Masson's staining, and tartrate‐resistent acid phosphatase immunohistochemistry. Mouse bone marrow stromal cells and osteoblastic MC3T3‐E1 cells were cultured in normal and/or high glucose (HG) medium. Osteogenic and adipogenic markers were assessed by real‐time PCR, and PTHrP and the PTH1 receptor protein expression by Western blot analysis.

KEY RESULTS PTHrP‐107‐139 reversed the alterations in bone structure and osteoblast function, and also promoted bone healing after marrow ablation without affecting the number of osteoclast‐like cells in diabetic mice. This peptide also reversed the high‐glucose‐induced changes in osteogenic differentiation in both bone marrow stromal cells and the more differentiated MC3T3‐E1 cells.

CONCLUSIONS AND IMPLICATIONS These findings demonstrate that PTHrP‐107‐139 promotes bone formation in diabetic mice. This mouse model and in vitro cell cultures allowed us to identify various anabolic effects of this peptide in this scenario.
Ligand‐induced internalization of the orexin OX1 and cannabinoid CB1 receptors assessed via N‐terminal SNAP and CLIP‐tagging
Authors: Ward Richard J , Pediani John D , Milligan Graeme
Published: December 2010

BACKGROUND AND PURPOSE Many G protein‐coupled receptors internalize following agonist binding. The studies were designed to identify novel means to effectively quantify this process using the orexin OX1 receptor and the cannabinoid CB1 receptor as exemplars.

EXPERIMENTAL APPROACH The human OX1 and CB1 receptors were modified to incorporate both epitope tags and variants (SNAP and CLIP) of the enzyme O6‐alkylguanine‐DNA‐alkyltransferase within their extracellular, N‐terminal domain. Cells able to regulate expression of differing amounts of these constructs upon addition of an antibiotic were developed and analysed.

KEY RESULTS Cell surface forms of each receptor construct were detected by both antibody recognition of the epitope tags and covalent binding of fluorophores to the O6‐alkylguanine‐DNA‐alkyltransferase variants. Receptor internalization in response to agonists but not antagonists could be monitored by each approach but sensitivity was up to six‐ to 10‐fold greater than other approaches when employing a novel, time‐resolved fluorescence probe for the SNAP tag. Sensitivity was not enhanced, however, for the CLIP tag, possibly due to higher levels of nonspecific binding.

CONCLUSIONS AND IMPLICATIONS These studies demonstrate that highly sensitive and quantitative assays that monitor cell surface CB1 and OX1 receptors and their internalization by agonists can be developed based on introduction of variants of O6‐alkylguanine‐DNA‐alkyltransferase into the N‐terminal domain of the receptor. This should be equally suitable for other G protein‐coupled receptors.
Chronic administration of BMS309403 improves endothelial function in apolipoprotein E‐deficient mice and in cultured human endothelial cells
Authors: Lee Mary YK , Li Huiying , Xiao Yang , Zhou Zhiguang , Xu Aimin , Vanhoutte Paul M
Published: December 2010

BACKGROUND AND PURPOSE

Adipocyte fatty acid‐binding protein (A‐FABP) is up‐regulated in regenerated endothelial cells and modulates inflammatory responses in macrophages. Endothelial dysfunction accompanying regeneration is accelerated by hyperlipidaemia. Here, we investigate the contribution of A‐FABP to the pathogenesis of endothelial dysfunction in the aorta of apolipoprotein E‐deficient (ApoE−/−) mice and in cultured human endothelial cells.

EXPERIMENTAL APPROACH

A‐FABP was measured in aortae of ApoE−/−mice and human endothelial cells by RT‐PCR, immunostaining and immunoblotting. Total and phosphorylated forms of endothelial nitric oxide synthase (eNOS) were measured by immunoblotting. Changes in isometric tension were measured in rings of mice aortae

KEY RESULTS

A‐FABP was expressed in aortic endothelium of ApoE−/− mice aged 12 weeks and older, but not at 8 weeks or in C57 wild‐type mice. Reduced endothelium‐dependent relaxations to acetylcholine, UK14304 (selective α2‐adrenoceptor agonist) and A23187 (calcium ionophore) and decreased protein presence of phosphorylated and total eNOS were observed in aortae of 18 week‐old ApoE−/− mice compared with age‐matched controls. A 6 week treatment with the A‐FABP inhibitor, BMS309403, started in 12 week‐old mice, improved endothelial function, phosphorylated and total eNOS and reduced plasma triglyceride levels but did not affect endothelium‐independent relaxations. The beneficial effect of BMS309403 on UK14304‐induced relaxations was attenuated by Pertussis toxin. In cultured human microvascular endothelial cells, lipid‐induced A‐FABP expression was associated with reduced phosphorylated eNOS and NO production and was reversed by BMS309403.

CONCLUSIONS AND IMPLICATIONS

Elevated expression of A‐FABP in endothelial cells contributes to their dysfunction both in vivo and in vitro.
The novel phospho‐non‐steroidal anti‐inflammatory drugs, OXT‐328, MDC‐22 and MDC‐917, inhibit adjuvant‐induced arthritis in rats
Authors: Huang L , Mackenzie GG , Ouyang N , Sun Y , Xie G , Johnson F , Komninou D , Rigas B
Published: December 2010

BACKGROUND AND PURPOSEThe use of non‐steroidal anti‐inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis (RA) is limited by their toxicity. We evaluated the anti‐inflammatory efficacy and safety of three novel modified NSAIDs, phospho‐aspirin, phospho‐ibuprofen and phospho‐sulindac.

EXPERIMENTAL APPROACHWe determined the anti‐inflammatory effects and gastrointestinal safety of the phospho‐NSAIDs in the rat adjuvant arthritis model and studied their mechanism of action in cultured cells, Cytokines were measured withelisaand activation of nuclear factor‐κB (NF‐κB) by immunohistochemistry.

KEY RESULTSAll three phospho‐NSAIDs showed less gastrointestinal toxicity than their parent compounds and demonstrated strong anti‐inflammatory effects, essentially reversing joint inflammation and oedema. They have a broad but not uniform effect on the expression of relevant cytokines, in general decreasing IL‐6 and IL‐1β and increasing IL‐10 levels in rat plasma and cultured cells. Phospho‐sulindac and phospho‐ibuprofen but not phospho‐aspirin suppressed PGE2productionin vitro, whereas phospho‐aspirin (in contrast to aspirin) showed the same effectin vivo. In joint tissues, phospho‐aspirin inhibited NF‐κB activation, and suppressed inflammation and bone resorption. Phospho‐aspirin also inhibited Jurkat T cell proliferation. In general, phospho‐aspirin had greater efficacy but different effects upon inflammatory mediators compared with aspirin. The chemical modification of the parent NSAIDs seems crucial for their safety and efficacy.

CONCLUSIONS AND IMPLICATIONSPhospho‐aspirin, phospho‐ibuprofen and phospho‐sulindac were safer than their parent NSAIDs, were highly effective in rat adjuvant arthritis and inhibited many key mediators in the pathophysiology of RA. These novel compounds are promising candidate drugs for the treatment of RA and merit further evaluation.
Biochemical characterization of a novel high‐affinity and specific plasma kallikrein inhibitor
Authors: Kolte D , Bryant JW , Holsworth D , Wang J , Akbari P , Gibson GW , Shariat‐Madar Z
Published: December 2010

BACKGROUND AND PURPOSE Kallikrein acts on high molecular weight kininogen (HK) to generate HKa (cleaved HK) and bradykinin (BK). BK exerts its effects by binding to B2 receptors. The activation of B2 receptors leads to the formation of tissue plasminogen activator, nitric oxide (NO) and prostacyclin (PGI2). An elevated kallikrein‐dependent pathway has been linked to cardiovascular disease risk. The aim of this study was to investigate whether our novel plasma kallikrein inhibitor abolishes kallikrein‐mediated generation of BK from HK and subsequent BK‐induced NO and PGI2 formation, thereby influencing endothelial pathophysiology during chronic inflammatory diseases.

EXPERIMENTAL APPROACH Kinetic analysis was initially used to determine the potency of PF‐04886847. Biochemical ligand binding assays, immunological methods and calcium flux studies were used to determine the selectivity of the kallikrein inhibitor. In addition, the effect of PF‐04886847 on BK‐induced relaxation of the rat aortic ring was determined in a model of lipopolysaccharide‐induced tissue inflammation.

KEY RESULTS Evidence was obtained in vitro and in situ, indicating that PF‐04886847 is a potent and specific inhibitor of plasma kallikrein. PF‐04886847 efficiently blocked calcium influx as well as NO and PGI2 formation mediated through the BK‐stimulated B2 receptor signalling pathway. PF‐04886847 blocked kallikrein‐induced endothelial‐dependent relaxation of isolated rat aortic rings pre‐contracted with phenylephrine.

CONCLUSIONS AND IMPLICATIONS PF‐04886847 was shown to be the most potent small molecule inhibitor of plasma kallikrein yet described; it inhibited kallikrein in isolated aortic rings and cultured endothelial cells. Overall, our results indicate that PF‐04886847 would be useful for the treatment of kallikrein‐mediated inflammatory disorders.
The protective effect of tianeptine on Gp120‐induced apoptosis in astroglial cells: role of GS and NOS, and NF‐κB suppression
Authors: Janda Elzbieta , Visalli Valeria , Colica Carmela , Aprigliano Serafina , Musolino Vincenzo , Vadalà Nuria , Muscoli Carolina , Sacco Iolanda , Iannone Michelangelo , Rotiroti Domenicantonio , Spedding Michael , Mollace Vincenzo
Published: December 2010

BACKGROUND AND PURPOSE Tianeptine is an antidepressant affecting the glutamatergic system. In spite of its proven clinical efficacy, molecular effects of tianeptine are not entirely clear. Tianeptine modulates cytokine expression in the CNS and protects the hippocampus from chronic stress effects. HIV infection is associated with inflammation and neuronal loss, causing HIV‐associated dementia (HAD). The human immunodeficiency virus type‐1 glycoprotein gp120 has been proposed as a likely aetiological agent of HAD. In this study, we determined whether tianeptine protects astroglial cells from the neurodegenerative effects of gp120.

EXPERIMENTAL APPROACH Human astroglial cells were treated with gp120 and tianeptine, and viability and apoptosis was monitored by TUNEL, annexin V, and activated caspase‐3 staining and flow cytometry. Protein levels of glutamine synthase (GS), inducible and constitutive nitric oxide synthases (iNOS, cNOS) and nuclear factor κB (NF‐κB) pathway were determined by Western blot analysis. The respective activities were assessed indirectly by measuring glutamine and nitrite concentrations or by luciferase reporter assays.

KEY RESULTS Tianeptine showed an anti‐apoptotic effect and prevented caspase‐3 activation by gp120. The mechanism of tianeptine's action involved GS and cNOS stabilization and iNOS suppression. Moreover, tianeptine increased IκB‐α levels in the absence of gp120 and blocked its degradation in response to gp120. This correlated with the suppression of basal and gp120‐induced NF‐κB transcriptional activity.

CONCLUSIONS AND IMPLICATIONS Tianeptine clearly exerts neuroprotective effects in vitro by suppressing the molecular pro‐inflammatory effects of gp120. Studies in animal models should be performed to evaluate the potential of tianeptine as a treatment for HAD.
Mitochondrial genome depletion dysregulates bile acid‐ and paracetamol‐induced expression of the transporters Mdr1, Mrp1 and Mrp4 in liver cells
Authors: Perez MJ , Gonzalez‐Sanchez E , Gonzalez‐Loyola A , Gonzalez‐Buitrago JM , Marin JJG
Published: December 2010

BACKGROUND AND PURPOSE Mitochondria are involved in the toxicity of several compounds, retro‐control of gene expression and apoptosis activation. The effect of mitochondrial genome (mtDNA) depletion on changes in ABC transporter protein expression in response to bile acids and paracetamol was investigated.

EXPERIMENTAL APPROACH Hepa 1‐6 mouse hepatoma cells with 70% decrease in 16S/18S rRNA ratio (Rho cells) were obtained by long‐term treatment with ethidium bromide.

KEY RESULTS Spontaneous apoptosis and reactive oxygen species (ROS) generation were decreased in Rho cells. Following glycochenodeoxycholic acid (GCDCA) or paracetamol, Rho cells generated less ROS and were more resistant to cell death. Apoptosis induced by GCDCA and Fas was also reduced. The basal expression of Mdr1 was significantly enhanced, but this was not further stimulated by GCDCA or paracetamol, as observed in wild‐type (WT) cells. Basal expression of Mrp1 and Mrp4 was similar in WT and Rho cells, whereas they were up‐regulated only in WT cells after GCDCA or paracetamol, along with the transcription factors Shp and Nrf2, but not Fxr or Pxr. Increased expression of Nrf2 was accompanied by its enhanced nuclear translocation. Glycoursodeoxycholic acid failed to cause any of the effects observed for GCDCA or paracetamol.

CONCLUSIONS AND IMPLICATIONS The Nrf2‐mediated pathway is partly independent of ROS production. Nuclear translocation of Nrf2 is insufficient to up‐regulate Mdr1, Mrp1 and Mrp4, which requires the participation of other regulatory element(s) whose activation in response to GCDCA and paracetamol is impaired in Rho cells and hence probably sensitive to ROS.
Regulation of nausea and vomiting by cannabinoids
Authors: Parker Linda A , Rock Erin M , Limebeer Cheryl L
Published: December 2010

Considerable evidence demonstrates that manipulation of the endocannabinoid system regulates nausea and vomiting in humans and other animals. The anti‐emetic effect of cannabinoids has been shown across a wide variety of animals that are capable of vomiting in response to a toxic challenge. CB1agonism suppresses vomiting, which is reversed by CB1antagonism, and CB1inverse agonism promotes vomiting. Recently, evidence from animal experiments suggests that cannabinoids may be especially useful in treating the more difficult to control symptoms of nausea and anticipatory nausea in chemotherapy patients, which are less well controlled by the currently available conventional pharmaceutical agents. Although rats and mice are incapable of vomiting, they display a distinctive conditioned gaping response when re‐exposed to cues (flavours or contexts) paired with a nauseating treatment. Cannabinoid agonists (Δ9‐THC, HU‐210) and the fatty acid amide hydrolase (FAAH) inhibitor, URB‐597, suppress conditioned gaping reactions (nausea) in rats as they suppress vomiting in emetic species. Inverse agonists, but not neutral antagonists, of the CB1receptor promote nausea, and at subthreshold doses potentiate nausea produced by other toxins (LiCl). The primary non‐psychoactive compound in cannabis, cannabidiol (CBD), also suppresses nausea and vomiting within a limited dose range. The anti‐nausea/anti‐emetic effects of CBD may be mediated by indirect activation of somatodendritic 5‐HT1Areceptors in the dorsal raphe nucleus; activation of these autoreceptors reduces the release of 5‐HT in terminal forebrain regions. Preclinical research indicates that cannabinioids, including CBD, may be effective clinically for treating both nausea and vomiting produced by chemotherapy or other therapeutic treatments.

LINKED ARTICLESThis article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visithttp://dx.doi.org/10.1111/bph.2011.163.issue‐7
The ABCG family of membrane‐associated transporters: you don't have to be big to be mighty
Authors: Kerr Ian D , Haider Ameena J , Gelissen Ingrid C
Published: December 2010

Along with many other mammalian ATP‐binding cassette (ABC) transporters, members of the ABCG group are involved in the regulated transport of hydrophobic compounds across cellular membranes. In humans, five ABCG family members have been identified, encoding proteins ranging from 638 to 678 amino acids in length. All five have been the subject of intensive investigation to better understand their physiological roles, expression patterns, interactions with substrates and inhibitors, and regulation at both the transcript and protein level. The principal substrates for at least four of the ABCG proteins are endogenous and dietary lipids, with ABCG1 implicated in particular in the export of cholesterol, and ABCG5 and G8 forming a functional heterodimer responsible for plant sterol elimination from the body. ABCG2 has a much broader substrate specificity and its ability to transport numerous diverse pharmaceuticals has implications for the absorption, distribution, metabolism, excretion and toxicity (ADMETOx) profile of these compounds. ABCG2 is one of at least three so‐called multidrug resistant ABC transporters expressed in humans, and its activity is associated with decreased efficacy of anti‐cancer agents in several carcinomas. In addition to its role in cancer, ABCG2 also plays a role in the normal physiological transport of urate and haem, the implications of which are described. We summarize here data on all five human ABCG transporters and provide a current perspective on their roles in human health and disease.

LINKED ARTICLES This article is part of a themed section on Transporters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2011.164.issue‐7
Sodium Balance in Maintenance Hemodialysis
Authors: Santos Sergio F. F. , Peixoto Aldo J.
Published: December 2010

Maintenance of extracellular fluid volume balance is an essential role of chronic maintenance hemodialysis (HD). In this population, this balance is determined by salt intake during the interdialytic period and sodium removal in HD sessions. Most of the sodium in a HD session is removed by ultrafiltration of plasma water, and the diffusion process becomes responsible for the fine tuning of sodium balance. The observation of little variation in pre‐HD serum sodium denotes that HD patients have an individual, stable osmolar set point. A positive dialysate‐to‐plasma sodium gradient is associated with increased thirst, interdialytic weight gain, and hypertension. To achieve an isonatric HD session, dialysate sodium concentration should approximately match patient’s serum sodium, and all sodium gained in the interdialytic period must be removed by convection. The pre‐HD serum sodium concentration may be used as a reference for dialysate sodium prescription in chronic HD. In this article, we also discuss new aspects of sodium balance, with particular attention to new observations on nonosmolar interstitial sodium storage.
Is Longino's Conception of Objectivity Feminist?
Authors: Hicks Daniel
Published: December 2010

Helen Longino's account of objectivity has been highly regarded by both feminist and mainstream philosophers of science. However, I have encountered three feminist philosophers who have all offered one especially compelling feminist critique of Longino's view: far from vindicating or privileging the work of feminist scientists, Longino's account actually requires the active cultivation of anti-feminist and misogynist scientists to balance out the possibility of feminist bias. I call this objection the Nazi problem, for the particular version that claims that her view requires even the active cultivation of Nazi scientists in objective inquiry. In this paper I consider one response to the Nazi problem, which I call the good faith argument. I show that the good faith argument itself is just as objectionable, on feminist grounds, as the Nazi problem it is meant to address.
Transfusion‐transmitted human immunodeficiency virus (HIV) from seroconverting donors is rare in England and Wales: results from HIV lookback, October 1995 through December 2008
Authors: Byrne Lisa , Brant Lisa J. , Davison Katy , Hewitt Patricia
Published: December 2010

BACKGROUND: Lookback is considered when human immunodeficiency virus (HIV) is detected in a repeat blood donor in case the immediately previous negative donation was donated in the infectious window period (IWP) or the assay(s) produced a false‐negative result. HIV lookback investigations undertaken by NHS Blood and Transplant and the Welsh Blood Service between October 1995 and December 2008 are described.

STUDY DESIGN AND METHODS: Investigations were undertaken into the previous negative donations of 113 HIV‐infected donors, including retrospective testing of archive samples, tracing of components, and identification of recipients who were offered HIV testing when appropriate. Data were collated on HIV seroconverters and outcome of the lookback was summarized.

RESULTS: Two previous negative donations given before the introduction of minipool nucleic acid testing (MP‐NAT) screening were confirmed positive by individual retrospective polymerase chain reaction (PCR) testing of the archive specimen. Red blood cell components had been transfused from both donations. One recipient died after transfusion, and the other was alive and tested HIV positive. All 23 (20%) donations previously testing negative by MP‐NAT were confirmed to be PCR negative on individual testing of an archive specimen and none of the tested recipients of these donations had evidence of transfusion‐transmitted HIV.

CONCLUSION: The yield of lookback was low with one positive recipient identified over 13 years of surveillance: HIV transmission occurred from a window period donation given before the introduction of MP‐NAT screening and would have been detected using current testing methods. Current residual risk estimates for the United Kingdom predict that HIV lookback will be of limited benefit, as demonstrated by our data.
How People Perceive and Will Cope with Risks from the Diffusion of Ubiquitous Information and Communication Technologies
Authors: Moser Stephanie , Bruppacher Susanne Elisabeth , Mosler Hans‐Joachim
Published: December 2010

Information and communication technologies (ICTs) are increasingly pervasive and continue to reshape our environment. This trend carries different risks. Therefore, the early sensitization of people to these risks, as well as improving their capacity for protective coping behavior, is essential. Based on the protection motivation theory (PMT), we examined with structural equation modeling the relationships between different components of threat and coping appraisal to explain protective and nonprotective responses. Calculations were performed with data from a representative survey on perception and use of ICT among German residents (N= 5,030). Our findings largely supported the proposed model: an increased perceived threat was positively related to the intentions to react protectively and nonprotectively. Perceived coping efficacy increased the protective and decreased the nonprotective responses. Negative affect enhanced the perceived threat and the nonprotective response, but inhibited protective intentions. The implications of these findings on how to sensitize people to the risks of these new technologies are outlined.
Vulnerability, Risk Perception, and Health Profile of Marginalized People Exposed to Multiple Built‐Environment Stressors in Worcester, Massachusetts: A Pilot Project
Authors: Downs Timothy J. , Ross Laurie , Goble Robert , Subedi Rajendra , Greenberg Sara , Taylor Octavia
Published: December 2010

Millions of low‐income people of diverse ethnicities inhabit stressful old urban industrial neighborhoods. Yet we know little about the health impacts of built‐environment stressors and risk perceptions in such settings; we lack even basic health profiles. Difficult access is one reason (it took us 30 months to survey 80 households); the lack of multifaceted survey tools is another. We designed and implemented a pilot vulnerability assessment tool in Worcester, Massachusetts. We answer: (1) How can we assess vulnerability to multiple stressors? (2) What is the nature of complex vulnerability—including risk perceptions and health profiles? (3) How can findings be used by our wider community, and what lessons did we learn? (4) What implications arise for science and policy? We sought a holistic picture of neighborhood life. A reasonably representative sample of 80 respondents captured data for 254 people about: demographics, community concerns and resources, time‐activity patterns, health information, risk/stress perceptions, and resources/capacities for coping. Our key findings derive partly from the survey data and partly from our experience in obtaining those data. Data strongly suggest complex vulnerability dominated by psychosocial stress. Unexpected significant gender and ethnic disease disparities emerged: notably, females have twice the disease burden of males, and white females twice the burden of females of color (p < 0.01). Self‐reported depression differentiated by gender and age is illustrative. Community based participatory research (CBPR) approaches require active engagement with marginalized populations, including representatives as funded partners. Complex vulnerability necessitates holistic, participatory approaches to improve scientific understanding and societal responses.
Which are the phenologically flexible species? A case study with common passerine birds
Authors: Moussus Jean‐Pierre , Clavel Joanne , Jiguet Frédéric , Julliard Romain
Published: December 2010

One of the most consensual ecological effects of the current climate warming is the alteration of the environmental timing of ecosystems. Phenological shifts, at different levels of food webs, are predicted to have major effects on species assemblages. Indeed it is unlikely that all species should be able to respond to the phenological shifts of their environment evenly. Yet questions remain about the specific traits that predict the ability of a species to track the temporal fluctuations of its environment. In this study, we use data from the French Constant Effort Site ringing program over a 20 years period (1989–2008) to estimate the ability of 20 common passerine species to adjust their breeding phenology to spring temperature variations. We show that the sensitivity of species breeding phenology to climate relates to species mean migration distance, species’ thermal and habitat niche breadth and brain mass. Species with the broadest ecological and thermal niches, the shortest mean migration distances and the largest brains were most able to adjust their breeding phenology to temperature variations. Our results thus identify long distance migrants and ecological specialists as species that could most suffer from the future expected climate change and suggests phenological adjustment as one possible mechanism underlying the replacement of specialist species by more generalist ones, the so called functional biotic homogenization.
Size and genetic composition of the colonizing propagules in a butterfly metapopulation
Authors: Austin Alia , Ovaskainen Otso , Hanski Ilkka
Published: December 2010

The amount and spatial distribution of genetic variation that is maintained in a metapopulation depends critically on the colonization process. Here, we use molecular markers to determine the number and genetic relatedness of individuals establishing new local populations in a large metapopulation of the Glanville fritillary butterflyMelitaea cinxia. The empirical results are compared with the predictions of a dispersal model based on a diffusion approximation of correlated random walk, which serves as a base‐line hypothesis about the rate and pattern of colonization. The results show that half of the new local populations consisted of a single larval group of full sibs and hence necessarily of the offspring of a single female. If the colonization involved two or more larval groups, these were usually oviposited by two different females that were unrelated to each other. The pattern of colonizations is thus intermediate between the propagule pool and the migrant pool models. These results elucidate the generation of genetic stochasticity, which may influence the dynamics of small populations. The dispersal model predicted well the pattern of habitat occupancy and the pattern of colonizations in relation to landscape structure, though which particular habitat patches became colonized was influenced also by measures of habitat quality not included in the model.
Tomographic, Histological, and Immunohistochemical Evidences on the Use of N‐Butyl‐2‐Cyanoacrilate for Onlay Graft Fixation in Rabbits
Authors: de Oliveira Neto Patricio José , Cricchio Giovanni , Hawthorne Ana Carolina , Okamoto Roberta , Sennerby Lars , Lungren Stefan , Salata Luiz Antonio
Published: December 2010

Background: The bone tissue responses to Cyanoacrylate have been described in the literature, but none used N‐butyl‐2‐cyanoacrilate (NB‐Cn) for bone graft fixation.

Purpose: The aims of the study were: (a) to analyze the bone grafts volume maintenance fixed either with NB‐Cn or titanium screw; (b) to assess the incorporation of onlay grafts on perforated recipient bed; and (c) the differences of expression level of tartrate‐resistant acid phosphatase (TRAP) protein involved in bone resorption.

Materials and Methods: Eighteen New Zealand White rabbits were submitted to calvaria onlay grafting on both sides of the mandible. On one side, the graft was fixed with NB‐Cn, while on the other hand the bone graft was secured with an osteosynthesis screw. The computed tomography (CT) was performed just after surgery and at animals sacrifice, after 1 (n = 9) and 6 weeks (n = 9), in order to estimate the bone grafts volume along the experiments. Histological sections of the grafted areas were prepared to evaluate the healing of bone grafts and to assess the expression of TRAP protein.

Results: The CT scan showed better volume maintenance of bone grafts fixed with NB‐Cn (p ≤ 0.05) compared with those fixed with screws, in both experimental times (analysis of variance). The immunohistochemical evaluation showed that the TRAP expression in a 6‐week period was significantly higher compared with the 1‐week period, without showing significant difference between the groups (Wilcoxon and Mann–Whitney). Histological analysis revealed that the NB‐Cn caused periosteum damage, but provided bone graft stabilization and incorporation similar to the control group.

Conclusion: The perforation provided by screw insertion into the graft during fixation may have triggered early revascularization and remodeling to render increased volume loss compared with the experimental group. These results indicate that the NB‐Cn possesses equivalent properties to titanium screw to be used as bone fixation material in osteosynthesis.