bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent Autologous and Heterologous Neutralizing Antibody Responses Occur in HIV-2 Infection across a Broad Range of Infection Outcomes
Authors: de Silva Thushan I. , Aasa-Chapman Marlén , Cotten Matthew , Hué Stéphane , Robinson James , Bibollet-Ruche Frederic , Sarge-Njie Ramu , Berry Neil , Jaye Assan , Aaby Peter , Whittle Hilton , Rowland-Jones Sarah , Weiss Robin 
Published: November 2011

ABSTRACT

Few studies have explored the role of neutralizing antibody (NAb) responses in controlling HIV-2 viremia and disease progression. Using a TZM-bl neutralization assay, we assessed heterologous and autologous NAb responses from a community cohort of HIV-2-infected individuals with a broad range of disease outcomes in rural Guinea-Bissau. All subjects (
n
= 40) displayed exceptionally high heterologous NAb titers (50% inhibitory plasma dilution or 50% inhibitory concentration [IC
50
], 1:7,000 to 1:1,000,000) against 5 novel primary HIV-2 envelopes and HIV-2 7312A, whereas ROD A and 3 primary envelopes were relatively resistant to neutralization. Most individuals also showed high autologous NAb against contemporaneous envelopes (78% of plasma-envelope combinations in 69 envelopes from 21 subjects), with IC
50
s above 1:10,000. No association between heterologous or autologous NAb titer and greater control of HIV-2 was found. A subset of envelopes was found to be more resistant to neutralization (by plasma and HIV-2 monoclonal antibodies). These envelopes were isolated from individuals with greater intrapatient sequence diversity and were associated with changes in potential N-linked glycosylation sites but not CD4 independence or CXCR4 use. Plasma collected from up to 15 years previously was able to potently neutralize recent autologous envelopes, suggesting a lack of escape from NAb and the persistence of neutralization-sensitive variants over time, despite significant NAb pressure. We conclude that despite the presence of broad and potent NAb responses in HIV-2-infected individuals, these are not the primary forces behind the dichotomous outcomes observed but reveal a limited capacity for adaptive selection and escape from host immunity in HIV-2 infection.
Arterivirus and Nairovirus Ovarian Tumor Domain-Containing Deubiquitinases Target Activated RIG-I To Control Innate Immune Signaling
Authors: van Kasteren Puck B. , Beugeling Corrine , Ninaber Dennis K. , Frias-Staheli Natalia , van Boheemen Sander , García-Sastre Adolfo , Snijder Eric J. , Kikkert Marjolein 
Published: November 2011

ABSTRACT

The innate immune response constitutes the first line of defense against viral infection and is extensively regulated through ubiquitination. The removal of ubiquitin from innate immunity signaling factors by deubiquitinating enzymes (DUBs) therefore provides a potential opportunity for viruses to evade this host defense system. It was previously found that specific proteases encoded by the unrelated arteri- and nairoviruses resemble the ovarian tumor domain-containing (OTU) family of DUBs. In arteriviruses, this domain has been characterized before as a papain-like protease (PLP2) that is also involved in replicase polyprotein processing. In nairoviruses, the DUB resides in the polymerase protein but is not essential for RNA replication. Using both
in vitro
and cell-based assays, we now show that PLP2 DUB activity is conserved in all members of the arterivirus family and that both arteri- and nairovirus DUBs inhibit RIG-I-mediated innate immune signaling when overexpressed. The potential relevance of RIG-I-like receptor (RLR) signaling for the innate immune response against arterivirus infection is supported by our finding that in mouse embryonic fibroblasts, the production of beta interferon primarily depends on the recognition of arterivirus RNA by the pattern-recognition receptor MDA5. Interestingly, we also found that both arteri- and nairovirus DUBs inhibit RIG-I ubiquitination upon overexpression, suggesting that both MDA5 and RIG-I have a role in countering infection by arteriviruses. Taken together, our results support the hypothesis that arteri- and nairoviruses employ their deubiquitinating potential to inactivate cellular proteins involved in RLR-mediated innate immune signaling, as exemplified by the deubiquitination of RIG-I.
Dung longevity influences the fate of endozoochorically dispersed seeds in forest ecosystems
Authors: Jaroszewicz Bogdan , Pirożnikow Ewa 
Published: November 2011

Many studies show large discrepancies between the potential (studied in the greenhouse) and realized (studied in the field) effects of endozoochory. The influence of environmental conditions on the fate of endozoochorically dispersed seeds and subsequent plant establishment is still not well understood. We addressed this issue by studying the viable seed content of the dung of European bison ( Bison bonasus L.) by means of seedling germination in the greenhouse and in two forest habitats in Białowieża Primeval Forest. The number of seedlings and the number of plant species that emerged from 1 L of feces were positively correlated with dung longevity. Generative shoots were produced by plants only in coniferous forest. Their number was positively correlated with dung longevity and with light availability. Germination of seeds from bison feces was higher in coniferous forest than in deciduous forest but did not differ between open- and closed-canopy plots within the same habitat. We conclude that (i) seed germination and plant establishment after endozoochorous dispersal is influenced by dung longevity; (ii) the number of generative shoots produced by endozoochorously dispersed plants is influenced by dung longevity and light availability; (iii) seeds of some plant species, present in dung, stay viable for at least 3 years.
Radiosensitization of Human Pancreatic Cancer Cells by MLN4924, an Investigational NEDD8-Activating Enzyme Inhibitor
Authors: Wei Dongping , Li Hua , Yu Jie , Sebolt Jonathan T. , Zhao Lili , Lawrence Theodore S. , Smith Peter G. , Morgan Meredith A. , Sun Yi 
Published: November 2011

Abstract
Radiotherapy is used in locally advanced pancreatic cancers in which it can improve survival in combination with gemcitabine. However, prognosis is still poor in this setting in which more effective therapies remain needed. MLN4924 is an investigational small molecule currently in phase I clinical trials. MLN4924 inhibits NAE (NEDD8 Activating Enzyme), a pivotal regulator of the E3 ubiquitin ligase SCF (SKP1, Cullins, and F-box protein), that has been implicated recently in DNA damage and repair. In this study, we provide evidence that MLN4924 can be used as an effective radiosensitizer in pancreatic cancer. Specifically, MLN4924 (20–100 nmol/L) effectively inhibited cullin neddylation and sensitized pancreatic cancer cells to ionizing radiation in vitro with a sensitivity enhancement ratio of approximately 1.5. Mechanistically, MLN4924 treatment stimulated an accumulation of several SCF substrates, including CDT1, WEE1, and NOXA, in parallel with an enhancement of radiation-induced DNA damage, aneuploidy, G2/M phase cell-cycle arrest, and apoptosis. RNAi-mediated knockdown of CDT1 and WEE1 partially abrogated MLN4924-induced aneuploidy, G2/M arrest, and radiosensitization, indicating a causal effect. Furthermore, MLN4924 was an effective radiosensitizer in a mouse xenograft model of human pancreatic cancer. Our findings offer proof-of-concept for use of MLN4924 as a novel class of radiosensitizer for the treatment of pancreatic cancer. Cancer Res; 72(1); 282–93. ©2011 AACR.
Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non–Small Cell Lung Cancer
Authors: Juergens Rosalyn A. , Wrangle John , Vendetti Frank P. , Murphy Sara C. , Zhao Ming , Coleman Barbara , Sebree Rosa , Rodgers Kristen , Hooker Craig M. , Franco Noreli , Lee Beverly , Tsai Salina , Delgado Igor Espinoza , Rudek Michelle A. , Belinsky Steven A. , Herman James G. , Baylin Stephen B. , Brock Malcolm V. , Rudin Charles M. 
Published: November 2011

Abstract
Epigenetic alterations are strongly associated with the development of cancer. We conducted a phase I/II trial of combined epigenetic therapy with azacitidine and entinostat, inhibitors of DNA methylation and histone deacetylation, respectively, in extensively pretreated patients with recurrent metastatic non–small cell lung cancer. This therapy is well tolerated, and objective responses were observed, including a complete response and a partial response in a patient who remains alive and without disease progression approximately 2 years after completing protocol therapy. Median survival in the entire cohort was 6.4 months (95% CI 3.8–9.2), comparing favorably with existing therapeutic options. Demethylation of a set of 4 epigenetically silenced genes known to be associated with lung cancer was detectable in serial blood samples in these patients and was associated with improved progression-free (P = 0.034) and overall survival (P = 0.035). Four of 19 patients had major objective responses to subsequent anticancer therapies given immediately after epigenetic therapy.
Significance: This study demonstrates that combined epigenetic therapy with low-dose azacitidine and entinostat results in objective, durable responses in patients with solid tumors and defines a blood-based biomarker that correlates with clinical benefit. Cancer Discovery; 1(7); 598–607. ©2011 AACR.
Read the Commentary on this article by Rodríguez-Paredes and Esteller, p. 557
This article is highlighted in the In This Issue feature, p. 539
Mild kidney disease as a risk factor for major bleeding in patients with atrial fibrillation undergoing percutaneous coronary stenting
Authors: Cambronero Francisco , Caro-Martínez Cesar , Hurtado-Martínez Jose A. , Marín Francisco , Pastor-Pérez Francisco J. , Mateo-Martínez Alicia , Sánchez-Martínez Marianela , Pinar-Bermúdez Eduardo , Valdés Mariano , Manzano-Fernández Sergio 
Published: November 2011

SummaryBleeding risk is increased in patients with atrial fibrillation (AF) and moderate to severe kidney disease (KD); however, the implication of mild KD on bleeding remains unclear. The aim of this study was to determine whether the presence of mild KD increases risk for major bleeding (MB) in patients with AF undergoing percutaneous coronary intervention with stent implantation (PCI-S). Two hundred eighty-five patients were included. Patients were classified into three kidney function groups: moderate to severe KD (n=91; <60 ml/min/1.73 m2), mild KD (n=139; 60–89 ml/min/1.73 m2) and non-KD (n=55; ≥90 ml/min/1.73 m2). Estimated glomerular filtration rate was calculated using the simplified Modification of Diet in Renal Disease equation. Patients were followed for one year, and the occurrence of MB was obtained in all. A total of 28 patients (9.8%) presented MB. MB complications examined as a function of KD groups revealed that there was a graded increase in MB with worsening renal function (non KD=1.8%, mild KD=7.9%, moderate to severe KD=17.6%; p <0.001). Multivariable Cox regression analysis showed that mild KD was associated with nearly a 2.5-fold (2.43 95% confidence interval 1.11–5.34, p=0.039) increase in the risk of MB as compared with non-KD patients. Other independent predictors of MB were moderate-severe KD, anaemia and triple antithrombotic therapy after PCI-S (C-index=0.76). In this population, mild KD confers a significantly increase in the risk for MB complications. Future studies should assess the potential role of incorporating mild KD into the bleeding risk scales to improve the stratification of these patients.
Short-Term Performance of the Transcatheter Melody Valve in High-Pressure Hemodynamic Environments in the Pulmonary and Systemic Circulations
Authors: Hasan Babar S. , McElhinney Doff B. , Brown David W. , Cheatham John P. , Vincent Julie A. , Hellenbrand William E. , Jones Thomas K. , Zahn Evan M. , Lock James E. 
Published: November 2011

Background—
The Melody valve is approved for percutaneous pulmonary valve replacement in dysfunctional right ventricular outflow tracts. The function of this valve when subjected to high-pressure loads in humans is unknown. The aim of this study was to describe the immediate and short-term results of Melody valves implanted in a high-pressure environment.

Methods and Results—
Definitions of a high-pressure system were established for Melody valves implanted in the systemic (ie, aortic or mitral position) and pulmonary (ie, right ventricular outflow tract conduit or tricuspid valve annulus) circulations. Implants in these environments were ascertained from databases of the 5 centers that participated in the US Investigational Device Exemption trial. Thirty implants met the inclusion criteria: 23 pulmonary circulation implants (all in the pulmonary position) systemic circulation implants (5 in the native aortic position, 1 in a left ventricle-to-descending aorta conduit, and 1 in the mitral annulus). All pulmonary circulation implants were performed percutaneously in the catheterization laboratory. A hybrid approach (surgical exposure for transcatheter implant) was used for 4 of the aortic implants. There were no procedure-related deaths. Three patients died of nonprocedure- and nonvalve-related causes. At 1 year, freedom from moderate to severe regurgitation was 100%, and freedom from mild regurgitation was 90%. Freedom from moderate to severe stenosis was 86% at 1 year.

Conclusions—
Short-term performance of the Melody valve in high-pressure environments is encouraging, with good valve function in all patients.
The Stability of Short Symmetric Internal Waves on Sloping Fronts: Beyond the Traditional Approximation
Authors: Colin de Verdière Alain 
Published: November 2011

AbstractThe interaction of internal waves with geostrophic flows is found to be strongly dependent upon the background stratification. Under the traditional approximation of neglecting the horizontal component of the earth’s rotation vector, the well-known inertial and symmetric instabilities highlight the asymmetry between positive and negative vertical components of relative vorticity (horizontal shear) of the mean flow, the former being stable. This is a strong stratification limit but, if it becomes too low, the traditional approximation cannot be made and the Coriolis terms caused by the earth’s rotation vector must be kept in full. A new asymmetry then appears between positive and negative horizontal components of relative vorticity (vertical shear) of the mean flow, the latter becoming more unstable. Particularly conspicuous at low latitudes, this new asymmetry does not require vanishing stratification to occur as it operates readily for rotation/stratification ratios 2Ω/N as small as 0.25 (the stratification still dominates over rotation) for realistic vertical shears. Given that such ratios are easily found in ocean–atmosphere boundary layers or in the deep ocean, such ageostrophic instabilities may be important for the routes to dissipation of the energy of the large-scale motions. The energetics show that, depending on the orientation of the internal wave crests with respect to the mean isopycnal surfaces, the unstable motions can draw their energy either from the kinetic energy or from the available potential energy of the mean flow. The kinetic energy source is usually the leading contribution when the growth rates reach their maxima.
Exploring the Cost and Clinical Outcomes of Integrating the Registered Nurse–Certified Diabetes Educator Into the Patient-Centered Medical Home
Authors: Moran Katherine , Burson Rosanne , Critchett John , Olla Phillip 
Published: November 2011

Purpose The purpose of this study was to implement and evaluate a care delivery model integrating the registered nurse–certified diabetes educator into the patient-centered medical home to assist in achieving positive clinical and cost outcomes in diabetes care. Methods A 1-group pretest-posttest research design was used. Patients were recruited from 2 patient-centered medical home designated/nominated primary care offices. Inclusion criteria were as follows: diagnosis of type 1 or type 2 diabetes, aged 18 to 80 years, A1C ≥ 8%, English speaking, and no diabetes education within 6 months. There were 34 participants (men, n = 22; women, n = 12) with a mean age of 53.24. The intervention incorporated an assessment, 4 patient-centered monthly group sessions, and 4 individual follow-up sessions. Study measures included program surveys, participation and satisfaction rates, Healthcare Effectiveness Data and Information Set attainment rates, and the following physiologic measures obtained from the medical record: A1C, fasting blood glucose, LDL, urine microalbumin, blood pressure, retinal eye exam, and body mass index. Cost-effectiveness measures included program costs, performance incentives, revenue, provider time saved, and patient health care utilization. Results Paired-samples t tests identified significant improvements in A1C, fasting blood glucose, and LDL. Patients and providers were highly satisfied with the program. Cost-benefit analysis revealed a net pretax program benefit. Conclusions Results of the study indicated that integrating the registered nurse–certified diabetes educator in the patient-centered medical home improves clinical outcomes and is cost-effective. Diabetes education and support are integral components of diabetes management.
Fabrication and biocompatibility of novel bilayer scaffold for skin tissue engineering applications
Authors: Franco Rose Ann , Min Young-Ki , Yang Hun-Mo , Lee Byong-Taek 
Published: November 2011

In this study, a novel bilayer scaffold composed of electrospun polycaprolactone and poly(lacto-co-glycolic acid) (PCL/PLGA) membrane and glutaraldehyde (3.5% v/v) cross-linked chitosan/gelatin hydrogel was fabricated using two methods: electrospinning of the membrane onto the lyophilized hydrogel (BS-1) and membrane underlaying and casting method (BS-2). The morphology of the fabricated scaffolds was examined by scanning electron microscope (SEM). Mechanical strength, porosity, swelling capacity, and biodegradation rates of the scaffolds were also characterized. The in vitro biocompatibility of the materials was investigated by assessing cytotoxicity and cell proliferation on the material was measured using MTT assay. In addition, cell adhesion on the material was investigated by SEM. The BS-2 was grafted in Sprague-Dawley rats to determine its in vivo behavior and biocompatibility. The experimental results showed that the addition of the membrane layer to the hydrogel decreased swelling and degradation rates and provided ease of handling during implantation. Grafted BS-2 showed normal wound healing and no major inflammatory reaction was observed.
Cytotoxicity of release products from magnetic nanocomposites in targeted drug delivery
Authors: Wamocha HL , Misak HE , Song Z , Chu HY , Chen YY , Asmatulu R , Yang S-Y , Ho JC 
Published: November 2011

The efficacy of chemotherapy can be significantly improved if the therapeutic agent remains localized at the afflicted area and released at controlled rates. Such a targeted drug delivery can be achieved using magnetic nanocomposite (MNC), which incorporates drug and magnetic nanoparticles in biodegradable polymer microspheres. Reported here are results from an in vitro study on drug release rate and cytotoxicity of other release products from MNC. The model system contains an anti-cancer chemotherapy agent 5-flurouracil (5-FU) and (Co0.5Zn0.5)Fe2O4 in poly(lactic-co-glycolic acid) (PLGA) matrix produced by an oil/oil emulsion technique. Cell proliferation data indicate a sustained release of 5-FU for mouse macrophage cell eradication, whereas other microsphere components of magnetic nanoparticles and PLGA have little cytotoxic effects.
Decreased serum levels of TGF-β1 are associated with renal damage in female patients with systemic lupus erythematosus
Authors: Jin T , Almehed K , Carlsten H , Forsblad-d’Elia H 
Published: November 2011

Introduction: Transforming growth factor β1 (TGF-β1) has a large role in the control of autoimmunity. TGF-β1 production by lymphocytes is reduced in systemic lupus erythematosus (SLE). Decreased levels of TGF-β1 might associate to disease susceptibility, activity and organ damage in SLE. However, the correlation between TGF-β1 levels and severity of renal damage in SLE has not been examined. Methods: The present study was undertaken to assess the serum levels of total and active TGF-β1 in 150 female patients with SLE and 31 healthy women. Simple and multiple regression analyses between TGF-β1 levels and the diseases-related variables were performed in patients with SLE. Results: Serum levels of both total and active TGF-β1 were significantly reduced in patients with SLE compared with levels in healthy controls ( p < 0.01). Total TGF-β1 levels correlated positively with white blood cell, platelet counts, calculated glomerular filtration rate (GFR), and active TGF-β1 level, and inversely with erythrocyte sedimentation rate (ESR). In multiple regression analysis, ESR and platelet counts remained determinants of total TGF-β1. Total TGF-β1 levels were lower in patients with high disease activity (SLEDAI > 10) and severe organ damage (SLICC > 3). Significantly lower levels of total TGF-β1 were found in patients with severe renal damage, i.e. lower TGF-β1 in patients with 24-h urine protein over 3.5 g than in those with below 3.5 g ( p < 0.05); lower TGF-β1 in patients with GFR less than 50 ml/min than in those with over 50 ml/min ( p < 0.05). In contrast, active TGF-β1 only correlated with platelet counts. There was no association between renal damage and the levels of active TGF-β1. Conclusion: This study demonstrates significantly reduced serum levels of both total and active TGF-β1 in women with SLE compared with healthy women. Total TGF-β1 levels are correlated negatively with ESR and positively with blood platelets. Total TGF-β1 levels were lower in SLE patients with high disease activity and severe organ damage. Importantly, the severity of the renal damage was associated with decreased serum levels of total TGF-β1, suggesting that TGF-β1 might be involved in pathogenesis of renal damage caused by lupus nephritis.