bluuebunny/crossref_metadata_2025 huggingface dataset:
Statins but Not Thiazolidinediones Attenuate Albumin-Mediated Chemokine Production by Proximal Tubular Cells Independently of Endocytosis
Authors: Chana Ravinder S. , Sidaway James E. , Brunskill Nigel J.
Published: June 2008

Background: Proximal tubular epithelial cells (PTEC) secrete chemokines under proteinuric conditions. Both statins and thiazolidinediones (TZDs) possess pleiotropic anti-inflammatory effects. This study examined the ability of statins and TZDs and the natural peroxisome proliferator activated receptor-γ (PPARγ) agonist 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2) to attenuate the proteinuria-induced pro-inflammatory phenotype of PTEC. Methods: Mouse PTEC were treated with statins, TZDs and PGJ2 and effects on uptake and binding of FITC-albumin determined. PTEC were incubated with fatty acid free bovine serum albumin with or without statins/TZDs/PGJ2, and the release of MCP-1 and RANTES measured. Results: Statins and TZDs significantly inhibited PTEC albumin endocytosis. PGJ2 had no effect. Incubation of PTEC with albumin significantly stimulated production of MCP-1 and RANTES. Co-treatment with statins and PGJ2 significantly reduced albumin-stimulated chemokine production, an effect reversed by the addition of mevalonate and geranylgeranyl pyrophosphate. In contrast, TZDs had no effect on albumin-mediated chemokine production. Conclusion: Statins and PGJ2, but not TZDs, prevent the development of a PTEC pro-inflammatory phenotype in response to albumin. Albumin endocytosis is not a prerequisite for PTEC chemokine production, and inhibition of albumin endocytosis alone is insufficient to attenuate chemokine production. These studies suggest a therapeutic role for statins and some PPARγ ligands in proteinuric renal disease.
Nrf2 Regulates Antioxidant Gene Expression Evoked by Oxidized Phospholipids in Endothelial Cells and Murine Arteries In Vivo
Authors: Jyrkkänen Henna-Kaisa , Kansanen Emilia , Inkala Matias , Kivelä Annukka M. , Hurttila Hanna , Heinonen Suvi E. , Goldsteins Gundars , Jauhiainen Suvi , Tiainen Satu , Makkonen Harri , Oskolkova Olga , Afonyushkin Taras , Koistinaho Jari , Yamamoto Masayuki , Bochkov Valery N. , Ylä-Herttuala Seppo , Levonen Anna-Liisa
Published: June 2008

Besides their well-characterized proinflammatory and proatherogenic effects, oxidized phospholipids, such as oxPAPC (oxidized 1-palmitoyl-2-arachidonoyl-
sn
-glycero-phosphocholine) have been shown to have beneficial responses in vascular cells via induction of antioxidant enzymes such as heme oxygenase-1. We therefore hypothesized that oxPAPC could evoke a general cytoprotective response via activation of antioxidative transcription factor Nrf2. Here, we show that oxPAPC increases nuclear accumulation of Nrf2. Using the small interfering RNA approach, we demonstrate that Nrf2 is critical in mediating the induction of glutamate-cysteine ligase modifier subunit (GCLM) and NAD(P)H quinone oxidoreductase-1 (NQO1) by oxPAPC in human endothelial cells, whereas the contribution to the induction of heme oxygenase-1 was less significant. The induction of GCLM and NQO1 was attenuated by reduction of electrophilic groups with sodium borohydrate, as well as treatment with thiol antioxidant
N
-acetylcysteine, suggesting that the thiol reactivity of oxPAPC is largely mediating its effect on Nrf2-responsive genes. Moreover, we show that oxidized phospholipid having a highly electrophilic isoprostane ring in its
sn-2
position is a potent inducer of Nrf2 target genes. Finally, we demonstrate that the oxPAPC-inducible expression of heme oxygenase-1, GCLM, and NQO1 is lower in Nrf2-null than wild-type mouse carotid arteries in vivo. We suggest that the activation of Nrf2 by oxidized phospholipids provides a mechanism by which their deleterious effects are limited in the vasculature.
Ethnic Group Disparities in 10-Year Trends in Stroke Incidence and Vascular Risk Factors
Authors: Heuschmann Peter U. , Grieve Andy P. , Toschke Andre Michael , Rudd Anthony G. , Wolfe Charles D.A.
Published: June 2008

Background and Purpose—

Data monitoring trends in stroke risk among different ethnic groups are lacking. Thus, we investigated trends in stroke incidence and modifiable stroke risk factors over a 10-year time period between different ethnic groups.

Methods—

Changes in stroke incidence were investigated with the South London Stroke Register (SLSR). The SLSR is a population-based stroke register, covering a multiethnic population of 271 817 inhabitants in South London with 63% white, 28% black, and 9% of other ethnic group (2001 Census).

Results—

Between 1995 and 2004, 2874 patients with first-ever stroke of all age groups were included. Total stroke incidence decreased over the 10-year study period in men (incidence rate ratio 1995 to 1996 versus 2003 to 2004 [IRR] 0.82, 95% CI 0.69 to 0.97) and in women (IRR 0.76, 95% CI 0.64 to 0.90). A similar decline in total stroke incidence could be observed in whites for men and women (IRR 0.76, 95% CI 0.62 to 0.93 versus IRR 0.73, 95% CI 0.59 to 0.89, respectively); in blacks, total stroke incidence was reducing only in women (IRR 0.48, 95% CI 0.31 to 0.75). In whites, the prevalence of prior-to-stroke hypertension (
P
=0.0017), atrial fibrillation (
P
=0.0113), and smoking (
P
=0.0177) decreased; no statistically significant changes in prior-to-stroke risk factors were observed in blacks. Total stroke incidence was higher in blacks compared to whites (IRR 1.27, 95% CI 1.10 to 1.46 in men; IRR 1.29, 95% CI 1.11 to 1.50 in women), but the black-white gap reduced during the 10-year time period (IRR 1.43, 95% CI 1.13 to 1.82 in 1995 to 1996 to 1.18, 95% CI 0.93 to 1.49 in 2003 to 2004).

Conclusions—

Stroke incidence decreased over a 10-year time period. The greatest decline in incidence was observed in black women, but ethnic group disparities still exist, indicating a higher stroke risk in black people compared to white people. Advances in risk factor reduction observed in the white population were failed transferring to the black population.
Stroke Incidence, Recurrence, and Case-Fatality in Relation to Socioeconomic Position
Authors: Li Cairu , Hedblad Bo , Rosvall Maria , Buchwald Fredrik , Khan Farhad Ali , Engström Gunnar
Published: June 2008

Background and Purpose—

Low socioeconomic status is associated with increased incidence of stroke. This study investigated stroke incidence, recurrence, and case-fatality after stroke among middle-aged Swedish men and women and whether this association differs by gender or stroke subtype.

Methods—

A total of 69 625 (49% men) citizens, aged 40 to 65 years, living in the city of Malmö in 1990 were studied in relation to total annual income and occupation class, ie, 2 indicators of socioeconomic status. Incidence of first-ever stroke, stroke recurrence, and case-fatality (death within 28 days or 1 year after stroke) were studied over 10 years of follow-up.

Results—

During the follow-up, a total of 1648 subjects developed a first-ever stroke of whom 275 also experienced a recurrent stroke. By using Cox regression model with covariate adjustments, the incidence of stroke was significantly increased (relative risk: 1.75, 95% CI:1.36 to 2.25) in women who were in the lowest quartile of income compared with the women being in the highest quartile. Corresponding relative risk in men was 1.29 (1.06 to 1.58). Both in men and women, income was significantly associated with ischemic, but not hemorrhagic, subtypes of stroke. Similar relationships were observed between occupation level and incidence of stroke. In addition, low income was associated with higher 28-day and 1-year fatality rates in men (relative risk: 3.13, 1.35 to 7.24 and 2.17, 1.18 to 4.00, respectively), but not in women. In contrast, recurrence of stroke was inversely associated with income only in women.

Conclusions—

Incidence of stroke, stroke recurrence, and case-fatality increased with decreasing socioeconomic status; however, this relationship differed by gender and subtype of events.
Large Ischemic Lesions on Diffusion-Weighted Imaging Done Before Intravenous Tissue Plasminogen Activator Thrombolysis Predicts a Poor Outcome in Patients With Acute Stroke
Authors: Kimura Kazumi , Iguchi Yasuyuki , Shibazaki Kensaku , Terasawa Yuka , Inoue Takeshi , Uemura Junichi , Aoki Junya
Published: June 2008

Background and Purpose—

MRI is useful for detecting early ischemic lesions before administration of tissue plasminogen activator in patients with hyperacute ischemic stroke. However, it is unclear whether early ischemic change seen on diffusion-weighted imaging (DWI) can be used to predict patient outcomes.

Methods—

Consecutive patients with anterior circulation ischemic stroke treated with tissue plasminogen activator within 3 hours of stroke onset were prospectively studied. The National Institutes of Health Stroke Scale score was obtained before and 7 days after tissue plasminogen activator administration. MRI, including DWI, was done before tissue plasminogen activator thrombolysis. The relationship between the DWI Alberta Stroke Programme Early CT Score (ASPECTS) and patients’ outcomes was assessed.

Results—

The subjects consisted of 49 consecutive patients with stroke (27 males; mean age, 72.9±10.3 years). The median (range) of the baseline DWI ASPECTS value was 9 (3–10). Dramatic improvement was seen in one of 8 patients with an ASPECTS ≤5 compared with 21 of 41 patients with a DWI ASPECTS >5 (
P
=0.0592). On the other hand, worsening was noted more frequently in patients with a DWI ASPECTS ≤5 (3 of 8 patients) than in patients with an ASPECTS >5 (4 of 41 patients;
P
=0.0753). Bad outcome was seen more frequently in patients with a DWI ASPECTS ≤5 (6 of 8 patients) than in patients with a DWI ASPECTS >5 (2 of 41 patients;
P
<0.0001). Multivariate logistic regression analysis demonstrated that a DWI ASPECTS ≤5 was the only independent predictor of a bad outcome (OR, 33.4; 95% CI, 2.7 to 410.8;
P
=0.0062).

Conclusion—

DWI ASPECTS appears to be a reliable tool for predicting bad outcome. Patients with a DWI ASPECTS >5 should be considered eligible for tissue plasminogen activator therapy.
Novel technology for improving damping capacity of aluminium foam by interface layer
Authors: Hao G. L. , Han F. S. , Li W. D.
Published: June 2008

A novel technology of designing interface layer using macromolecule resin element, polystyrene, to enhance the damping capacity of aluminium foam is successfully attempted. The interface layer was fabricated by coating a polystyrene film on the pore surface of the aluminium foam using a similar sol–gel technology. Results of the measurements show that the introduction of interface layer not only improves the mechanical strength, but also significantly enhances the damping capacity that can be an order increase relative to the corresponding aluminium foam matrix in the temperature range of room temperature to 80°C. The involved damping mechanisms include the intrinsic damping and interface damping of the constituents. The latter should be dominant as a result of relatively easy energy dissipation through interfacial friction.
CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion
Authors: Kavanagh Brian , O'Brien Shaun , Lee David , Hou Yafei , Weinberg Vivian , Rini Brian , Allison James P. , Small Eric J. , Fong Lawrence
Published: June 2008

Cytotoxic T lymphocyte–associated antigen 4 (CTLA4) delivers inhibitory signals to activated T cells. CTLA4 is constitutively expressed on regulatory CD4+ T cells (Tregs), but its role in these cells remains unclear. CTLA4 blockade has been shown to induce antitumor immunity. In this study, we examined the effects of anti-CTLA4 antibody on the endogenous CD4+ T cells in cancer patients. We show that CTLA4 blockade induces an increase not only in the number of activated effector CD4+ T cells, but also in the number of CD4+ FoxP3+ Tregs. Although the effects were dose-dependent, CD4+ FoxP3+ regulatory T cells could be expanded at lower antibody doses. In contrast, expansion of effector T cells was seen only at the highest dose level studied. Moreover, these expanded CD4+ FoxP3+ regulatory T cells are induced to proliferate with treatment and possess suppressor function. Our results demonstrate that treatment with anti-CTLA4 antibody does not deplete human CD4+ FoxP3+ Tregs in vivo, but rather may mediate its effects through the activation of effector T cells. Our results also suggest that CTLA4 may inhibit Treg proliferation similar to its role on effector T cells. This study is registered at http://www.clinicaltrials.gov/ct2/show/NCT00064129, registry number NCT00064129.
Interferon-α2b–induced thrombocytopenia is caused by inhibition of platelet production but not proliferation and endomitosis in human megakaryocytes
Authors: Yamane Akiko , Nakamura Takanori , Suzuki Hidenori , Ito Mamoru , Ohnishi Yasuyuki , Ikeda Yasuo , Miyakawa Yoshitaka
Published: June 2008

Human interferon (IFN)–α is the standard therapy for chronic hepatitis C to prevent its progression to liver cirrhosis and hepatocellular carcinoma. Thrombocytopenia is one of the major adverse effects of IFN-α and often leads to dose reduction or treatment discontinuation. However, there is little information on how IFN-α inhibits human megakaryopoiesis. In this study, we demonstrated that IFN-α did not inhibit colony formation of megakaryocytes from human CD34+ hematopoietic stem cells. IFN-α did not inhibit endomitosis but did inhibit cytoplasmic maturation of megakaryocytes and platelet production in vitro. IFN-α suppressed the expression of transcription factors regulating late-stage megakaryopoiesis, such as GATA-1, p45NF-E2, MafG. IFN-α also significantly reduced the number of human platelets but not megakaryocytes, and did not inhibit endomitosis of human megakaryocytes in immunodeficient NOD/Shi-scid/IL-2Rγnull (NOG) mice transplanted with human CD34+ cells (hu-NOG). We also demonstrated that a novel thrombopoietin mimetic, NIP-004, was effective for treating IFN-α–induced thrombocytopenia in hu-NOG mice. From ultrastructural study, IFN-α inhibited the maturation of demarcation membranes in megakaryocytes, although NIP-004 prevented the inhibitory effects of IFN-α. These results defined the pathogenesis of IFN-α–induced thrombocytopenia and suggested possible future clinical applications for thrombopoietin mimetics.
GPR17: Molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors
Authors: Parravicini Chiara , Ranghino Graziella , Abbracchio Maria P , Fantucci Piercarlo
Published: June 2008

Background

GPR17 is a G-protein-coupled receptor located at intermediate phylogenetic position between two distinct receptor families: the P2Y and CysLT receptors for extracellular nucleotides and cysteinyl-LTs, respectively. We previously showed that GPR17 can indeed respond to both classes of endogenous ligands and to synthetic compounds active at the above receptor families, thus representing the first fully characterized non-peptide "hybrid" GPCR. In a rat brain focal ischemia model, the selective in vivo knock down of GPR17 by anti-sense technology or P2Y/CysLT antagonists reduced progression of ischemic damage, thus highlighting GPR17 as a novel therapeutic target for stroke. Elucidation of the structure of GPR17 and of ligand binding mechanisms are the necessary steps to obtain selective and potent drugs for this new potential target. On this basis, a 3-D molecular model of GPR17 embedded in a solvated phospholipid bilayer and refined by molecular dynamics simulations has been the first aim of this study. To explore the binding mode of the "purinergic" component of the receptor, the endogenous agonist UDP and two P2Y receptor antagonists demonstrated to be active on GPR17 (MRS2179 and cangrelor) were then modeled on the receptor.

Results

Molecular dynamics simulations suggest that GPR17 nucleotide binding pocket is similar to that described for the other P2Y receptors, although only one of the three basic residues that have been typically involved in ligand recognition is conserved (Arg255). The binding pocket is enclosed between the helical bundle and covered at the top by EL2. Driving interactions are H-bonds and salt bridges between the 6.55 and 6.52 residues and the phosphate moieties of the ligands. An "accessory" binding site in a region formed by the EL2, EL3 and the Nt was also found.

Conclusion

Nucleotide binding to GPR17 occurs on the same receptor regions identified for already known P2Y receptors. Agonist/antagonist binding mode are similar, but not identical. An accessory external binding site could guide small ligands to the deeper principal binding site in a multi-step mechanism of activation. The nucleotide binding pocket appears to be unable to allocate the leukotrienic type ligands in the same effective way.
Induction of maturation and activation of human dendritic cells: A mechanism underlying the beneficial effect of Viscum albumas complimentary therapy in cancer
Authors: Elluru Sri Ramulu , van Huyen Jean-Paul Duong , Delignat Sandrine , Kazatchkine Michel D , Friboulet Alain , Kaveri Srini V , Bayry Jagadeesh
Published: June 2008

Background

Viscum album(VA) preparations have been used as a complimentary therapy in cancer. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. In the present study, we examine the hypothesis that the VA preparations induce activation of human DC that facilitates effective tumor regression.

Methods

Four day old monocyte-derived immature DCs were treated with VA Qu Spez at 5, 10 and 15 μg/ml for 48 hrs. The expression of surface molecules was analyzed by flow cytometry. The ability of Qu Spez-educated DC to stimulate T cells was analyzed by allogeneic mixed lymphocyte reaction and activation of Melan-A/MART-1-specific M77-80 CD8+T cells. Cytokines in cell free culture supernatant was analyzed by cytokine bead array assay.

Results

VA Qu Spez stimulated DCs presented with increased expression of antigen presenting molecule HLA-DR and of co-stimulatory molecules CD40, CD80 and CD86. The VA Qu Spez also induced the secretion of inflammatory cytokines IL-6 and IL-8. Further, Qu Spez-educated DC stimulated CD4+T cells in a allogeneic mixed lymphocyte reaction and activated melanoma antigen Melan-A/MART-1-specific M77-80 CD8+T cells as evidenced by increased secretion of TNF-α and IFNγ.

Conclusion

The VA preparations stimulate the maturation and activation of human DCs, which may facilitate anti-tumoral immune responses. These results should assist in understanding the immunostimulatory properties of VA preparations and improving the therapeutic strategies.
Soft tissue tenodesis of the long head of the biceps tendon associated to the Roman Bridge repair
Authors: Franceschi Francesco , Longo Umile Giuseppe , Ruzzini Laura , Rizzello Giacomo , Maffulli Nicola , Denaro Vincenzo
Published: June 2008

Background

Rotator cuff tears are frequently associated with pathologies of the long head of the biceps tendon (LHBT). Tenotomy and tenodesis of the LHBT are commonly used to manage disorders of the LHBT.

Methods

We present an arthroscopic soft tissue LHBT tenodesis associated with a Roman Bridge (double pulley – suture bridges) repair

Results

Two medial row 5.5-mm Bio-Corkscrew suture anchors (Arthrex, Naples, FL), double-loaded with No. 2 FiberWire sutures (Arthrex, Naples, FL), are placed in the medial aspect of the footprint. A shuttle is passed through an anterior point of the rotator cuff and through the LHBT by means of a Penetrator or a BirdBeak suture passer (Arthrex, Naples, FL). A tenotomy of the LHBT is performed. All the sutures from the anteromedial anchor are passed through a single anterior point in the rotator cuff using a shuttle technique. All the sutures from the posteromedial anchor are passed through a single posterior point in the rotator cuff. The sutures in the medial row are tied using the double pulley technique. A suture limb is retrieved from each of the medial anchors and manually tied as a six-throw surgeon's knot over a metal rod. The two free suture limbs are pulled to transport the knot over the top of the tendon bridge. The two free suture limbs are then used to produce suture bridges over the tendon, using a Pushlock (Arthrex, Naples, FL), placed 1 cm distal to the lateral edge of the footprint. The same double pulley – suture bridges technique is repeated for the other two suture limbs from the two medial anchors.

Conclusion

This technique allows to perform a double pulley – suture bridges repair for a rotator cuff tear, associated with a soft tissue tenodesis for the management of LHBT pathology. The tenodesis of the LHBT is performed just with the passage of a shuttle inside the LHBT, after passing it through the anterior portion of the rotator cuff, with successive detachment of the LHBT from the glenoid. It is a technically easy procedure which can be performed relatively quickly, and does not require additional fixation.
Cancer risk among residents of Rhineland-Palatinate winegrowing communities: a cancer-registry based ecological study
Authors: Seidler Andreas , Hammer Gaël Paul , Husmann Gabriele , König Jochem , Krtschil Anne , Schmidtmann Irene , Blettner Maria
Published: June 2008

Aim

To investigate the cancer risk among residents of Rhineland-Palatinate winegrowing communities in an ecological study.

Methods

On the basis of the Rhineland-Palatinate cancer-registry, we calculated age-adjusted incidence rate ratios for communities with a medium area under wine cultivation (>5 to 20 percent) and a large area under wine cultivation (>20 percent) in comparison with communities with a small area under wine cultivation (>0 to 5 percent). In a side analysis, standardized cancer incidence ratios (SIR) were computed separately for winegrowing communities with small, medium and large area under wine cultivation using estimated German incidence rates as reference.

Results

A statistically significant positive association with the extent of viniculture can be observed for non-melanoma skin cancer in both males and females, and additionally for prostate cancer, bladder cancer, and non-Hodgkin lymphoma in males, but not in females. Lung cancer risk is significantly reduced in communities with a large area under cultivation. In the side-analysis, elevated SIR for endocrine-related tumors of the breast, testis, prostate, and endometrium were observed.

Conclusion

This study points to a potentially increased risk of skin cancer, bladder cancer, and endocrine-mediated tumors in Rhineland-Palatinate winegrowing communities. However, due to the explorative ecologic study design and the problem of multiple testing, these findings are not conclusve for a causal relationship.
Jab1 is a target of EGFR signaling in ERα-negative breast cancer
Authors: Wang Jiaxu , Barnes Rebecca O , West Nathan R , Olson Melanie , Chu Jenny E , Watson Peter H
Published: June 2008

Introduction

c-Jun activation domain-binding protein-1 (Jab1) is a multifunctional signaling protein that previously has been shown to be a master regulator of a poor prognostic gene signature in invasive breast cancer and to mediate the action of S100A7. Since epidermal growth factor receptor (EGFR), like S100A7, is often expressed in estrogen receptor-alpha-negative (ERα-) breast cancer, we set out to investigate the role of Jab1 in mediating EGFR signaling, another facet of the ERα- phenotype.

Methods

MDA-MB-231 and MDA-MB-468 ERα-/EGFR+ cell lines were assessed for localization of Jab1 and levels of downstream genes by immunofluorescence and nuclear protein extract assay following treatment with epidermal growth factor (EGF) and extracellular signal-regulated kinase (ERK) pathway inhibitor. A cohort of 424 human breast tumors was also assessed by immunohistochemistry.

Results

EGF treatment of cell lines resulted in increased Jab1 nuclear expression. This effect was inhibited by the ERK pathway inhibitor, PD98059. EGF treatment was also associated with colocalization of pERK (phosphorylated ERK) and Jab1 as well as regulation of the Jab1 downstream target gene, p27. When Jab1 activity was knocked down, p27 levels were restored to pre-EGF treatment level. Analysis of EGFR and Jab1 expression in a cohort of invasive breast tumors by tissue microarray and immunohistochemistry confirmed a relationship between EGFR and increased nuclear Jab1 within the ERα- subset (n = 154, P = 0.019). The same association was also confirmed for S100A7 and Jab1 (P = 0.036), and high Jab1 nuclear expression was most frequent in tumors that were positive for both EGFR and S100A7 (P = 0.004).

Conclusion

Jab1 is a target of EGFR signaling in ERα- cell lines and breast tumors and therefore may be a common central factor and potential therapeutic target for important cell signaling pathways in ERα- breast cancer.
Differential Antagonism of Activin, Myostatin and Growth and Differentiation Factor 11 by Wild-Type and Mutant Follistatin
Authors: Schneyer Alan L. , Sidis Yisrael , Gulati Anisha , Sun Jie L. , Keutmann Henry , Krasney Philip A.
Published: June 2008

Follistatin binds and neutralizes members of the TGFβ superfamily including activin, myostatin, and growth and differentiation factor 11 (GDF11). Crystal structure analysis of the follistatin-activin complex revealed extensive contacts between follistatin domain (FSD)-2 and activin that was critical for the high-affinity interaction. However, it remained unknown whether follistatin residues involved with myostatin and GDF11 binding were distinct from those involved with activin binding. If so, this would allow development of myostatin antagonists that would not inhibit activin actions, a desirable feature for development of myostatin antagonists for treatment of muscle-wasting disorders. We tested this hypothesis with our panel of point and domain swapping follistatin mutants using competitive binding analyses and in vitro bioassays. Our results demonstrate that activin binding and neutralization are mediated primarily by FSD2, whereas myostatin binding is more dependent on FSD1, such that deletion of FSD2 or adding an extra FSD1 in place of FSD2 creates myostatin antagonists with vastly reduced activin antagonism. However, these mutants also bind GDF11, indicating that further analysis is required for creation of myostatin antagonists that will not affect GDF11 activity that could potentially elicit GDF11-induced side effects in vivo.
The Effects of the Social Structure of Digital Networks on Viral Marketing Performance
Authors: Bampo Mauro , Ewing Michael T. , Mather Dineli R. , Stewart David , Wallace Mark
Published: June 2008

Viral marketing is a form of peer-to-peer communication in which individuals are encouraged to pass on promotional messages within their social networks. Conventional wisdom holds that the viral marketing process is both random and unmanageable. In this paper, we deconstruct the process and investigate the formation of the activated digital network as distinct from the underlying social network. We then consider the impact of the social structure of digital networks (random, scale free, and small world) and of the transmission behavior of individuals on campaign performance. Specifically, we identify alternative social network models to understand the mediating effects of the social structures of these models on viral marketing campaigns. Next, we analyse an actual viral marketing campaign and use the empirical data to develop and validate a computer simulation model for viral marketing. Finally, we conduct a number of simulation experiments to predict the spread of a viral message within different types of social network structures under different assumptions and scenarios. Our findings confirm that the social structure of digital networks play a critical role in the spread of a viral message. Managers seeking to optimize campaign performance should give consideration to these findings before designing and implementing viral marketing campaigns. We also demonstrate how a simulation model is used to quantify the impact of campaign management inputs and how these learnings can support managerial decision making.
The effectiveness of arthroscopic stabilisation for failed open shoulder instability surgery
Authors: Millar N. L. , Murrell G. A. C.
Published: June 2008

We identified ten patients who underwent arthroscopic revision of anterior shoulder stabilisation between 1999 and 2005. Their results were compared with 15 patients, matched for age and gender, who had a primary arthroscopic stabilisation during the same period.

At a mean follow-up of 37 and 36 months, respectively, the scores for pain and shoulder function improved significantly between the pre-operative and follow-up visits in both groups (p = 0.002), with no significant difference between them (p = 0.4). The UCLA and Rowe shoulder scores improved significantly (p = 0.004 and p = 0.002, respectively), with no statistically significant differences between groups (p = 0.6). Kaplan-Meier analysis for time to recurrent instability showed no differences between the groups (p = 0.2).

These results suggest that arthroscopic revision anterior shoulder stabilisation is as reliable as primary arthroscopic stabilisation for patients who have had previous open surgery for recurrent anterior instability.
The in vitro effects of bupivacaine on articular chondrocytes
Authors: Chu C. R. , Izzo N. J. , Coyle C. H. , Papas N. E. , Logar A.
Published: June 2008

We have studied the effects of bupivacaine on human and bovine articular chondrocytes in vitro. Time-lapse confocal microscopy of human articular chondrocytes showed > 95% cellular death after exposure to 0.5% bupivacaine for 30 minutes. Human and bovine chondrocytes exposed to 0.25% bupivacaine had a time-dependent reduction in viability, with longer exposure times resulting in higher cytotoxicity. Cellular death continued even after removal of 0.25% bupivacaine. After exposure to 0.25% bupivacaine for 15 minutes, flow cytometry showed bovine chondrocyte viability to be 41% of saline control after seven days. After exposure to 0.125% bupivacaine for up to 60 minutes, the viability of both bovine and human chondrocytes was similar to that of control groups.

These data show that prolonged exposure 0.5% and 0.25% bupivacaine solutions are potentially chondrotoxic.
Twice Upon a Time: The Importance of Rereading "The Devoted Friend"
Authors: Marsh Sarah
Published: June 2008

Readers frequently have wondered if Oscar Wilde's fairy tales were intended for adults or for children. Through its analysis of "The Devoted Friend" (1888), this essay describes Wilde's promotion of a moral code consistent with his developing socialist politics to both children and adults in Victorian England.
Sitting Shivah: Holocaust Mourning in Judy Blume's Starring Sally J. Freedman as Herself
Authors: Ulanowicz Anastasia
Published: June 2008

While it received dismal reviews from its critics, Judy Blume's novel, Starring Sally J. Freedman as Herself (1977), may be considered one of the most compelling representations of how young people approach an ultimately ineffable historical event and attempt to mourn the traumatic loss it has incurred.
Wise Gnomes, Nervous Astronauts, and a Very Bad General: The Children's Books of Umberto Eco and Eugenio Carmi
Authors: Truglio Maria
Published: June 2008

This essay examines three critically neglected picturebooks of Umberto Eco and Eugenio Carmi produced between the 60s and 90s. It adopts a semiotic approach to show how these books resist dominant ideologies, arguing that the interanimation of words and images promotes the ideals of disobedience, the collectivity, and active interpretive engagement.
Transporting Nostalgia: The Little Golden Books as Souvenirs of Childhood
Authors: Cassidy Julie Sinn
Published: June 2008

This essay analyzes the intersecting influences of nostalgia and the Little Golden Books in current American popular culture through the marketing, collecting, and recycling of the books' idealized images of the 1940s and '50s.
History Girls: Eighteenth- and Nineteenth-Century Historiography and the Case of Mary, Queen of Scots
Authors: Vallone Lynne
Published: June 2008

This essay argues that the compelling figure of Mary, Queen of Scots represented in conventional schoolroom textbooks inspired Jane Austen, Queen Victoria and Marjory Fleming to write counter-narratives about her life. These examples of private writing both absorb and resist the ideologies of nation, gender and causation that official histories promote.
What, Then, Does Beatrice Mean?: Hermaphroditic Gender, Predatory Sexuality, and Promiscuous Allusion in Daniel Handler/Lemony Snicket's
A Series of Unfortunate Events
Authors: Pugh Tison
Published: June 2008

A Series of Unfortunate Events depicts a virtually genderless society, in that characters express themselves in ways largely free of male/female stereotypes; nonetheless, predatory forms of male sexuality circumscribe female agency. Intriguingly, Handler opens a space for feminine resistance to male desire through promiscuous deployments of literary allusions, which highlight female agency in subverting male desire.
Centering the Home-Garden: The Arbor, Wall, and Gate in Moral Tales for Children
Authors: Smith Elise L.
Published: June 2008

The cultivated garden, centered on the arbor and bordered by fences, was seen as a training ground for children in moral tales written in late 18th and early 19th century England, and through the lessons learned in that safe space their unruly temperaments could be transformed into the moral order of a virtuous life.
Homosexuality at the Online Hogwarts: Harry Potter Slash Fanfiction
Authors: Tosenberger Catherine
Published: June 2008

Fans of J.K. Rowling's Harry Potter series have written new stories featuring the characters; many of these stories, called "slash," are homoerotic. This article examines a number of online slash stories, and discusses the potential for fans, especially teens, to experiment with non-heteronormative discourses through the medium of Potter fanfiction.
"A Highly Satisfactory Chinaman": Orientalism and American Girlhood in Louisa May Alcott's Eight Cousins
Authors: Cohoon Lorinda B.
Published: June 2008

Discussing "orientalism" in Eight Cousins , this essay investigates how Rose's encounters with foreign objects and others condition Rose to understand herself as both exoticized and superior. Linking the transition from girlhood to womanhood to the movement from excluded immigrant to American citizen, Eight Cousins explores female citizenship as a negotiation between assimilation and defiance of convention.
From Kiddie Lit to Kiddie Porn: The Sexualization of Children's Literature
Authors: Tribunella Eric L.
Published: June 2008

Retellings of children’s literature constitute a booming literary phenomenon, and among those retellings are sexualized versions that recast children’s books as adult erotica. Focusing on Chris Kent’s retellings of The Coral Island and Tom Brown’s Schooldays , this essay examines the sexualization of children’s literature and argues that it represents an adult wish to (re)experience or (re)imagine a fantasized childhood that combines the virtues of “childhood innocence” and naiveté with the possibilities of adult empowerment and sexual agency. This suggests a broader understanding of children’s literature as reflecting a desire to improve upon the limitations of childhood in its quotidian forms.
Sexual Fantasy: The Queer Utopia of David Levithan's Boy Meets Boy
Authors: Pattee Amy S.
Published: June 2008

By re-casting the young adult romance with a same-sex couple at its center and by setting his novel in a utopian town in which gay and transgendered students are accepted and even celebrated, David Levithan’s Boy Meets Boy effectively subverts the paradigm of compulsory heterosexuality in young adult fiction while creating a new template for the gay young adult novel. Boy Meets Boy is a utopian novel: it functions effectively as a romance novel, a genre critics have called utopian, and also draws upon and extends conventions of homosexual representation found in “traditional” gay-themed young adult literature and gay pornography to depict a distinctly utopian world of sexual liberation.
"We Go to Europe to Be Americanized": European Travel and National Identity in Betsy and the Great World and My Heart's in the Highlands
Authors: Mills Claudia
Published: June 2008

Two young-adult novels of the 1950s, Betsy and the Great World by Maud Hart Lovelace (1952) and My Heart's in the Highlands by Ann Durell (1958), use travel as a lens to interrogate and construct American national identity. Lovelace’s novel, borrowing from the disappearing cultural ritual of the "grand tour,” looks backward in time to portray America as a confident, classless New World of democratic inspiration; Durrell’s novel, focusing on the emerging cultural ritual of the junior year abroad, uncovers emerging postwar sources of (justified) American self-criticism.
Reconfiguring Nurture in Philip Pullman's His Dark Materials
Authors: Rutledge Amelia A.
Published: June 2008

"Reconfiguring Nurture in Philip Pullman's His Dark Materials " argues that effective nurture cannot be circumscribed by biological bonds, nor accomplished by isolated individuals. The novels present nurturing relationships grounded in the willing assumption of responsibility for Lyra Belacqua and Will Parry by surrogates in both stable and temporary relationships, providing alternate structures to compensate for those that have failed. At the same time, the novels do not deny the need for nurture grounded in a mature wisdom. Pullman's critique of parental and institutional failures stops short of a radical subversion of adult authority.
Interns at an International, Humanitarian Organization: Career Pathways and Meaning Making
Authors: Mather Peter C.
Published: June 2008

This qualitative study examined the career shaping experiences and related meaning making processes of 12 interns at The Carter Center, an international, humanitarian organization. Experiences shaping participants' careers were grouped into the following themes—academics and intellectual curiosity; travel abroad; religion; relationships—family, friends, and mentors; and transformative life events. The following themes illustrated the meaning making processes of the participants: Diversity and privilege, interconnectedness, meaningful work, and sense of home. This study suggests that student affairs educators can play an important role in fostering the complex meaning making required of international, humanitarian work.
Are They Not All the Same?: Racial Heterogeneity Among Black Male Undergraduates
Authors: Harper Shaun R. , Nichols Andrew H.
Published: June 2008

An erroneous assumption is often made that Black men, one of the most stereotyped groups on college and university campuses, all share common experiences and backgrounds. Using Celious and Oyserman's (2001) Heterogeneous Race Model as a conceptual framework, we explored within-group differences among Black male undergraduates at three private institutions. Data collected from 39 participants reveal insights into the origins and characterizations of diversity among Black men, as well as the stereotypes, competition, and social distance associated with racial heterogeneity. Implications for Black male solidarity on campuses where few are enrolled and expanding conceptualizations of interacting "across difference" are offered at the end of this article.
Mapping the Intricacies of Young Adults' Developmental Journey from Socially Prescribed to Internally Defined Identities, Relationships, and Beliefs
Authors: Taylor Kari B.
Published: June 2008

Recent research has called for complex holistic models of college student development, but traditionally, scholars have focused heavily if not exclusively on creating models that emphasize only psychological explanations and probe only one dimension or aspect of development. This article synthesizes a wide range of theories and models to construct an integrated map of both the psychological and sociological factors that influence young adults' learning and development. Moreover, the synthesis discusses the conditions that foster cognitive, interpersonal, and intrapersonal growth.
"Principles of Good Practice" for Academic and Student Affairs Partnership Programs
Authors: Whitt Elizabeth J. , Nesheim Becki Elkins , Guentzel Melanie J. , Kellogg Angela H. , McDonald William M. , Wells Cynthia A.
Published: June 2008

While academic and student affairs partnership programs have been championed as a means to enhance undergraduate education, research documenting the characteristics of effective partnership programs is sparse. The Boyer Partnership Assessment Project is a qualitative examination of academic and student affairs partnership programs at 18, diverse institutions. This article identifies seven principles of good practice for creating and sustaining effective partnerships, and discusses the implications of these principles for higher education research and practice.
Factors Influencing the Ethnic Identity Development of Latino Fraternity Members at a Hispanic Serving Institution
Authors: Guardia Juan R. , Evans Nancy J.
Published: June 2008

Higher education scholars have examined Latino/a student experiences and ethnic identity, yet there is no research describing the ethnic identity development of Latino fraternity members at a Hispanic Serving Institution (HSI). The purpose of this phenomenological study was to understand how membership in a Latino fraternity at an HSI enhanced members' ethnic identity development. Using Bronfenbrenner's (2005a) bioecological theory of human development as the guiding framework, six themes emerged that enhanced members' ethnic identity development. Implications for student affairs and higher education administrators at HSIs and non-HSIs are discussed.
Child Labor and Education for All: An Issue Paper
Authors: Guarcello Lorenzo , Lyon Scott , Rosati Furio Camillo
Published: June 2008

Education is a key element in the prevention of child labor; at the same time, child labor is one of the main obstacles to Education For All (EFA). Understanding the interplay between education and child labor is therefore critical to achieving both EFA and child labor elimination goals. This study largely confirms the conventional wisdom that child labor harms children's ability to enter and survive in the school system, and makes it more difficult for children to derive educational benefit from schooling once in the system. The evidence also suggests that these negative effects are not limited to economic activity but also extend to household chores, and that the intensity of work (in economic activity or household chores) is particularly important in determining the impact of work on schooling. This evidence indicates that both the school quality and school access can play an important role in household decisions concerning whether children study or work.
Memories of Tomorrow: Children, Labor, and the Panacea of Formal Schooling
Authors: Balagopalan Sarada
Published: June 2008

This article provides a critical reading of current efforts in India to enroll in school all children between six and fourteen years of age. These efforts usually gain moral certitude through their being constructed within a binary frame of reference i.e. formal schooling as the space that "saves" child laborers. Neither exhaustive in its review of existing literature nor in its attempt to address the working of this binary worldwide, this article largely draws on different narratives to reveal the ways in which international policy discourse relies on a particular construction of children, childhood, and family in the non-Western world. The framing of the issue that the binary sets in place and its subsequent impact on policies is discussed through an interrogation of its underlying assumptions as well as its influence on the local. To transcend a culturally relativistic reading of these narratives as local examples, incapable of exercising larger analytic weight, the article utilizes these to discuss three dominant constructions that underlie this binary, namely constructions of the child, of school, and of labor.
Practicing For Print: The Hale Children's Manuscript Libraries
Authors: Sánchez-Eppler Karen
Published: June 2008

As a home amusement and a form of literary apprenticeship, two generations of children in the same elite Boston family created their own lending libraries of hand-made books. The institutional procedures the Hale children invented for their libraries, and the contents of the books they illustrated and wrote, offer astute commentary on adult literary practices, and provide a rare vantage onto children's own attitudes towards books and reading. The Hale libraries give evidence not only of how books socialize child readers, but also of the many ways in which print culture can be modified and re-imagined by children's play.
Children as the Youthful Hope of an Old Empire: Race, Nationalism, and Elementary Education in China, 1895–1915
Authors: Bai Limin
Published: June 2008

In his writings Liang Qichao (1873–1929) used children as the symbolic representation of a new China. His vision of a young China and his key to the survival of China" provided the context for the production of new elementary textbooks on history, Chinese language, geography, and ethics. The content of these textbooks reflected the intellectual milieu of the time: social Darwinism and race theory combined to highlight China's own humiliations and her perilous position in an imperialist world, and to stimulate patriotism and nationalism among young students.
Blood Ties and Tongue Ties: The Role of Children in Shifting the Boundaries of Namibia's German-Speaking Community
Authors: Owens Jason
Published: June 2008

Germany colonized South West Africa in 1884, then lost the country (present-day Namibia) after World War I. In order to escape the apartheid perpetuated by subsequent occupier South Africa, many black Namibians fled to support the SWAPO liberation movement, based in neighboring Angola. After South Africa bombed a camp that was home to many SWAPO supporters in 1978, SWAPO sent the first of a series of 428 Namibian three-to-five-year-olds to East Germany (a.k.a. the GDR) for protection, education, and socialist training. A decade later, they were unexpectedly "returned" after Namibia's first all-race elections fell the same week as the Berlin Wall. Placing them with surviving relatives in the rural North seldom succeeded for more than a short period because the children no longer spoke their native language competently and frequently felt allegiance primarily to their other returning "siblings." Members of SWAPO and of Namibia's 30,000 ethnic Germans laid claims to these "GDR Kids," but most children who had spent over eight years in Germany were enrolled in Namibia's German-speaking schools. This article concludes that by integrating these and other Namibian German institutions, the GDR Kids altered the margins of what is considered German in this most German of former German colonies.
The Equal Rights Amendment Reconsidered: Politics, Policy, and Social Mobilization in a Democracy
Authors: Critchlow Donald T. , Stachecki Cynthia L.
Published: June 2008

In the early 1970s, fifty years after its first appearance in the U.S. Congress, the Equal Rights Amendment came the closest it ever would to ratification. The ERA declared: “Equality of rights under the law shall not be denied or abridged by the United States or by any State on account of sex.” After sailing through Congress in 1972 with bipartisan support, the amendment went to the states for ratification. The response was positive and immediate: Hawaii approved the ERA the same day, twenty-one other states approved it before the end of the year, and eight more states the following year. Yet, by 1982 the amendment lay dead, having fallen three states short of the thirty-eight states needed for ratification.