bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic Expression of the CXCL10 Gene in Response to IL-1β and IFN-γ Involves NF-κB, Phosphorylation of STAT1 at Tyr701, and Acetylation of Histones H3 and H4
Authors: Burke Susan J. , Goff Matthew R. , Lu Danhong , Proud David , Karlstad Michael D. , Collier J. Jason 
Published: June 2013

Abstract
The CXCL10 gene encodes a peptide that chemoattracts a variety of leukocytes associated with type 1 and type 2 diabetes. The present study was undertaken to determine the molecular mechanisms required for expression of the CXCL10 gene in response to IL-1β and IFN-γ using rat islets and β cell lines. IL-1β induced the expression of the CXCL10 gene and promoter activity, whereas the combination of IL-1β plus IFN-γ was synergistic. Small interfering RNA–mediated suppression of NF-κB p65 markedly inhibited the ability of cytokines to induce the expression of the CXCL10 gene, whereas targeting STAT1 only diminished the synergy provided by IFN-γ. Furthermore, we found that a JAK1 inhibitor dose dependently reduced IFN-γ–controlled CXCL10 gene expression and promoter activity, concomitant with a decrease in STAT1 phosphorylation at Tyr701. We further discovered that, although the Tyr701 phosphorylation site is inducible (within 15 min of IFN-γ exposure), the Ser727 site within STAT1 is constitutively phosphorylated. Thus, we generated single-mutant STAT1 Y701F and double-mutant STAT1 Y701F/S727A adenoviruses. Using these recombinant adenoviruses, we determined that overexpression of either the single- or double-mutant STAT1 decreased the IFN-γ–mediated potentiation of CXCL10 gene expression, promoter activity, and secretion of protein. Moreover, the Ser727 phosphorylation was neither contingent on a functional Y701 site in β cells nor was it required for cytokine-mediated expression of the CXCL10 gene. We conclude that the synergism of IL-1β and IFN-γ to induce expression of the CXCL10 gene requires NF-κB, STAT1 phosphorylated at Tyr701, recruitment of coactivators, and acetylation of histones H3 and H4.
Amino Acid Copolymers That Alleviate Experimental Autoimmune Encephalomyelitis In Vivo Interact with Heparan Sulfates and Glycoprotein 96 in APCs
Authors: Koenig Paul-Albert , Spooner Eric , Kawamoto Norio , Strominger Jack L. , Ploegh Hidde L. 
Published: June 2013

Abstract
Multiple sclerosis (MS) is an autoimmune disease that affects the CNS. One approved treatment for relapsing forms of MS is YEAK, a random copolymer of the amino acids tyrosine, glutamic acid, alanine, and lysine. YFAK, a second-generation copolymer composed of tyrosine, phenylalanine, alanine, and lysine, is more successful in treating experimental autoimmune encephalomyelitis, a mouse model of MS. Although originally designed and optimized based on the autoantigen myelin basic protein (MBP) and the MBP-derived peptide MBP85-99 presented to the MS-associated class II MHC molecule HLA-DR2, YEAK and YFAK also stimulate cytokine and chemokine production in APCs that lack class II MHC products. How YEAK and YFAK copolymers interact with APCs remains enigmatic. We used biotinylated YFAK to affinity-purify YFAK-interacting proteins from RAW264.7 cells and tested APCs from mice deficient in several of the newly identified interactors for their capacity to secrete CCL22 in response to YEAK and YFAK. We propose that initial contact of YFAK with cells is mediated mainly by electrostatic interactions, and find that interaction of YFAK with host proteins is strongly dependent on ionic strength. Cells deficient in enzymes involved in sulfation of proteins and proteoglycans showed strongly reduced binding of biotinylated YFAK. Lastly, cells stimulated with YFAK in the presence of heparin, structurally similar to heparan sulfates, failed to produce CCL22. We conclude that charge-dependent interactions of copolymers that alleviate MS/experimental autoimmune encephalomyelitis are critical for their effects exerted on APCs and may well be the main initial mediators of these therapeutically active copolymers.
Low frequency of male circumcision and unwillingness to be circumcised among MSM in Buenos Aires, Argentina: association with sexually transmitted infections
Authors: Pando María A , Balan Ivan C , Dolezal Curtis , Marone Ruben , Barreda Victoria , Carballo‐Dieguez Alex , Avila María M 
Published: June 2013

ObjectiveThe aims of this study were to investigate the frequency of male circumcision among men who have sex with men (MSM) in Buenos Aires, Argentina; the association between circumcision and sexually transmitted infections (STIs); and, among those uncircumcised, the willingness to be circumcised.MethodsA cross‐sectional study was conducted among 500 MSM recruited through the respondent‐driven sampling (RDS) technique. Participants underwent a consent process, responded to a Web‐based survey that included questions on demographic information, sexual behaviour, and circumcision and provided biological samples. HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, and human papiloma virus (HPV) diagnoses were performed using standard methodologies. For all analyses, data were weighted based on participants’ network size.ResultsOnly 64 (13%) of the 500 MSM in our study reported being circumcised. Among uncircumcised men (n=418), 302 (70.4%) said that they would not be willing to get circumcised even if the procedure could reduce the risk of HIV infection. When considering all participants, circumcision status was not significantly associated with HIV, HBV, HCV, T. pallidum or HPV infections. However, when we restricted the sample to men who do not practice receptive anal intercourse (RAI) and compared circumcised to uncircumcised men, the former (N=33) had no cases of HIV infection, while 34 of 231 (14.8%) uncircumcised men were HIV positive (p=0.020). Regarding HPV, uncircumcised men had a significantly larger number of different HPV types compared with circumcised men (mean 1.83 vs. 1.09, p<0.001) and a higher frequency of high‐risk‐HPV genotypes (47.6% vs. 12.5%, p=0.012).ConclusionsConsistent with international evidence, male circumcision appears to have a partial protective effect among MSM. The efficacy of circumcision in reducing risk of HIV infection among MSM appears to be correlated with sexual practices. Given the lack of motivation among MSM with regard to circumcision, proper awareness on the risks and benefits of circumcision needs to be created, if circumcision has to be introduced as a prevention strategy.
Submaximal Heart and Pulmonary Evaluation: A Novel Noninvasive Test to Identify Pulmonary Hypertension in Patients With Systemic Sclerosis
Authors: Bernstein Elana J. , Mandl Lisa A. , Gordon Jessica K. , Spiera Robert F. , Horn Evelyn M. 
Published: June 2013

ObjectivePulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc; scleroderma). Although right‐sided heart catheterization (RHC) is the gold standard for diagnosing PH, it is an invasive test with associated risks. The submaximal heart and pulmonary evaluation (step test) is a noninvasive, submaximal stress test that could be used to identify patients with PH. The purpose of this study is to assess the correlation between change in end tidal carbon dioxide (ΔPETCO2) from rest to end‐exercise on the step test and mean pulmonary artery pressure (mPAP) on RHC in SSc patients.MethodsThis is a retrospective cohort study of patients with limited or diffuse cutaneous SSc who were evaluated in an academic cardiology practice between November 2007 and November 2011 and underwent a step test and RHC. Statistical analysis was performed using Spearman's correlation test and multivariable linear regression.ResultsA total of 679 charts were reviewed. Nineteen SSc patients who underwent a step test and RHC were included. ΔPETCO2 was negatively correlated with mPAP (r = −0.82, P < 0.0001). In a multivariable linear regression model evaluating the relationship between ΔPETCO2 and mPAP, controlling for age, sex, and time between and order of step test and RHC, ΔPETCO2 remained the only variable statistically significantly associated with mPAP (P < 0.001). The step test had a sensitivity of 100%, specificity of 75%, positive predictive value of 93.8%, and negative predictive value of 100% for the diagnosis of PH.ConclusionΔPETCO2on the step test has a strong, statistically significant negative correlation with mPAP on RHC.
Non‐Viral Co‐Delivery of the Four Yamanaka Factors for Generation of Human Induced Pluripotent Stem Cells via Calcium Phosphate Nanocomposite Particles
Authors: Cao Xia , Deng Wenwen , Qu Rui , Yu Qingtong , Li Jun , Yang Yan , Cao Yue , Gao Xiangdong , Xu Ximing , Yu Jiangnan 
Published: June 2013

AbstractGenerating of induced pluripotent stem cells (iPSCs) can be achieved by ectopic expression of defined transcription factor sets. However, most instances of iPSC induction have been achieved using viral vectors, which carry the risk of unpredictable genetic dysfunction. Here, for the first time, a non‐viral vector based on calcium phosphate nanoparticles for the generation of virus‐free iPSCs from human umbilical cord mesenchymal stem cells (HUMSCs) via co‐delivery of the four plasmids (Oct4, Sox2, Klf4, and c‐Myc) is reported. As a result, a total of 98 colonies from 200 000 cells have been obtained, with a reprogramming efficiency of 0.049%. The iPSCs shows positive expression of pluripotency markers, including OCT4, SSEA‐3, SSEA‐4, NANOG, and TRA‐1‐81. Moreover, the iPSCs are able to differentiate into all three germ layers in vitro. Subcutaneous injection of the iPSCs into immunocompromised mice results in the formation of teratomas containing a variety of tissues from all three germ layers. These findings indicate that co‐delivery of the four Yamanaka factors via plasmid‐encapsulated calcium phosphate nanoparticles can provide a simple, safe, and efficient method for the generation of virus‐free iPSCs, which is crucial for their future clinical applications in the field of regenerative medicine.
Patterned Transparent Conductive Au Films through Direct Reduction of Gold Thiocyanate
Authors: Morag Ahiud , Froumin Natalya , Mogiliansky Dimitry , Ezersky Vladimir , Beilis Edith , Richter Shachar , Jelinek Raz 
Published: June 2013

AbstractConstruction of structurally defined, patterned metal films is a fundamental objective in the emerging and active field of bottom‐up nanotechnology. A new strategy for constructing macroscopically organized Au nanostructured films is presented. The approach is based upon a novel phenomenon in which incubation of water‐soluble Au(SCN)41− complex with amine‐displaying surfaces gives rise to spontaneous crystallization and concurrent reduction, resulting in the formation of patterned metallic gold films. The Au films exhibit unique nanoribbon morphology, likely corresponding to aurophilic interactions between the complex moieties anchored to the amine groups through electrostatic attraction. Critically, no external reducing agents are needed to initiate or promote formation of the metallic Au films. In essence, the thiocyanate ligands provide the means for surface targeting of the complex, guide the Au crystallization process and, importantly, donate the reducing electrons. It is shown that the Au films exhibit electrical conductivity and high transparency over a wide spectral range, lending the new approach to possible applications in optoelectronics, catalysis, and sensing. In a broader context, a new gold chemistry route is presented in which ligand‐enabled crystallization/reduction could open the way to a wealth of innovative reaction pathways and applications.
Rhodium‐Catalyzed CH Olefination of Aryl Weinreb Amides
Authors: Wang Yan , Li Chao , Li Yan , Yin Feng , Wang Xi‐Sheng 
Published: June 2013

AbstractA rhodium(III)‐catalyzed oxidative CH olefination directed by Weinreb amides, a class of well developed versatile building blocks in organic synthesis, has been developed with air as the terminal oxidant. The reactions proceed with excellent reactivity, good functional group tolerance and high yields.
Efficacy and Safety of Ocrelizumab in Active Proliferative Lupus Nephritis: Results From a Randomized, Double‐Blind, Phase III Study
Authors: Mysler Eduardo F. , Spindler Alberto J. , Guzman Renato , Bijl Marc , Jayne David , Furie Richard A. , Houssiau Frédéric A. , Drappa Jorn , Close David , Maciuca Romeo , Rao Kajal , Shahdad Saba , Brunetta Paul 
Published: June 2013

ObjectiveTo investigate the efficacy and safety of ocrelizumab in patients with class III/IV lupus nephritis (LN).MethodsPatients were randomized 1:1:1 to receive placebo, 400 mg ocrelizumab, or 1,000 mg ocrelizumab given as an intravenous infusion on days 1 and 15, followed by a single infusion at week 16 and every 16 weeks thereafter, accompanied by background glucocorticoids plus either mycophenolate mofetil (MMF) or the Euro‐Lupus Nephritis Trial (ELNT) regimen (cyclophosphamide followed by azathioprine). The study was terminated early due to an imbalance in serious infections in ocrelizumab‐treated patients versus placebo‐treated patients. We report week 48 efficacy data for patients receiving ≥32 weeks of treatment (n = 223) and safety results for all treated patients (n = 378).ResultsThe overall renal response rate was 54.7%, 66.7%, 67.1%, and 66.9% in the placebo‐treated, 400 mg ocrelizumab–treated, 1,000 mg ocrelizumab–treated, and combined ocrelizumab‐treated groups, respectively. The associated treatment difference versus placebo for the combined ocrelizumab‐treated groups was 12.7% (95% confidence interval [95% CI] −0.8, 26.1) (P = 0.065), with similar differences observed for both ocrelizumab‐treated groups. Ocrelizumab versus placebo treatment differences were apparent in patients receiving the background ELNT regimen, but not in those receiving background MMF. A numerically greater proportion of ocrelizumab‐treated patients had a ≥50% reduction in the urinary protein:urinary creatinine ratio at 48 weeks compared with placebo‐treated patients (placebo‐treated patients, 58.7%; 400 mg ocrelizumab–treated patients, 70.7%; 1,000 mg ocrelizumab–treated patients, 68.5%). Serious adverse events occurred in 27.2% of placebo‐treated patients, 35.7% of 400 mg ocrelizumab–treated patients, and 22.0% of 1,000 mg ocrelizumab–treated patients. Corresponding serious infection rates (events/100 patient‐years) were 18.7 (95% CI 12.2, 28.7), 28.8 (95% CI 20.6, 40.3), and 25.1 (95% CI 17.4, 36.1), respectively. The imbalance in serious infections with ocrelizumab occurred with background MMF but not with the background ELNT regimen.ConclusionIn patients with active LN, overall renal response rates with ocrelizumab were numerically but not statistically significantly superior to those with placebo. Ocrelizumab treatment was associated with a higher rate of serious infections in the subgroup receiving background MMF.
Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage In Vitro and In Vivo
Authors: Chong Ka‐Wing , Chanalaris Anastasios , Burleigh Annika , Jin Huilin , Watt Fiona E. , Saklatvala Jeremy , Vincent Tonia L. 
Published: June 2013

ObjectiveThe articular cartilage is known to be highly mechanosensitive, and a number of mechanosensing mechanisms have been proposed as mediators of the cellular responses to altered mechanical load. These pathways are likely to be important in tissue homeostasis as well as in the pathogenesis of osteoarthritis. One important injury‐activated pathway involves the release of pericellular fibroblast growth factor 2 (FGF‐2) from the articular cartilage. Using a novel model of murine cartilage injury and surgically destabilized joints in mice, we examined the extent to which FGF‐2 contributes to the cellular gene response to injury.MethodsFemoral epiphyses from 5‐week‐old wild‐type mice were avulsed and cultured in serum‐free medium. Explant lysates were Western blotted for phospho‐JNK, phospho‐p38, and phospho‐ERK or were fixed for immunohistochemical analysis of the nuclear translocation of p65 (indicative of NF‐κB activation). RNA was extracted from injured explants, rested explants that had been stimulated with recombinant FGF‐2 or FGF‐18, or whole joints from either wild‐type mice or FGF‐2−/− mice. Reverse transcription–polymerase chain reaction was performed to examine a number of inflammatory response genes that had previously been identified in a microarray analysis.ResultsMurine cartilage avulsion injury resulted in rapid activation of the 3 MAP kinase pathways as well as NF‐κB. Almost all genes identified in murine joints following surgical destabilization were also regulated in cartilage explants upon injury. Many of these genes, including those for activin A (Inhba), tumor necrosis factor–stimulated gene 6 (Tnfaip6), matrix metalloproteinase 19 (Mmp19), tissue inhibitor of metalloproteinases 1 (Timp1), and podoplanin (Pdpn), were significantly FGF‐2 dependent following injury to cartilage in vitro and to joint tissues in vivo.ConclusionFGF‐2–dependent gene expression occurs in vitro and in vivo in response to cartilage/joint injury in mice.
Improving efficiency of human pluripotent stem cell differentiation platforms using an integrated experimental and computational approach
Authors: Selekman Joshua A. , Das Amritava , Grundl Nicholas J. , Palecek Sean P. 
Published: June 2013

ABSTRACTHuman pluripotent stem cells (hPSCs) have an unparalleled potential for tissue engineering applications including regenerative therapies and in vitro cell‐based models for studying normal and diseased tissue morphogenesis, or drug and toxicological screens. While numerous hPSC differentiation methods have been developed to generate various somatic cell types, the potential of hPSC‐based technologies is hinged on the ability to translate these established lab‐scale differentiation systems to large‐scale processes to meet the industrial and clinical demands for these somatic cell types. Here, we demonstrate a strategy for investigating the efficiency and scalability of hPSC differentiation platforms. Using two previously reported epithelial differentiation systems as models, we fit an ODE‐based kinetic model to data representing dynamics of various cell subpopulations present in our culture. This fit was performed by estimating rate constants of each cell subpopulation's cell fate decisions (self‐renewal, differentiation, death). Sensitivity analyses on predicted rate constants indicated which cell fate decisions had the greatest impact on overall epithelial cell yield in each differentiation process. In addition, we found that the final cell yield was limited by the self‐renewal rate of either the progenitor state or the final differentiated state, depending on the differentiation protocol. Also, the relative impact of these cell fate decision rates was highly dependent on the maximum capacity of the cell culture system. Overall, we outline a novel approach for quantitative analysis of established laboratory‐scale hPSC differentiation systems and this approach may ease development to produce large quantities of cells for tissue engineering applications. Biotechnol. Bioeng. 2013;110: 3024–3037. © 2013 Wiley Periodicals, Inc.
Enhanced Photocatalytic Activity: Macroporous Electrospun Mats of Mesoporous Au/TiO2 Nanofibers
Authors: Wang Xingdong , Choi Jonghyun , Mitchell David R. G. , Truong Yen B. , Kyratzis Ilias L. , Caruso Rachel A. 
Published: June 2013

AbstractAn electrospinning technique coupled with sol–gel chemistry is applied for the one‐pot preparation of macroporous–mesoporous titanium dioxide nanofibrous mats embedded with Au nanoparticles. This facile approach produces nanofibers that are thermally treated to simultaneously 1) remove the organics, 2) reduce AuIII to Au0 to form Au nanoparticles, and 3) crystallize titania to the anatase phase. This methodology allows high‐temperature treatment (650 °C) for well‐crystallized titania without agglomeration of the nanoparticulate Au (13±3 nm), which thereby significantly advances the existing methods for the synthesis of Au/TiO2 materials for which multiple steps are required. Additionally, high Au yields (≈100 %) were achieved in the final structure, which demonstrates another merit of this technique. The X‐ray diffraction patterns of the nanofibers were monitored by using a synchrotron beamline as the sample was heated to determine the optimum calcination temperature required to maximize the anatase phase and minimize the formation of rutile. Both the material properties (which include morphology, pore size distribution, surface area, Au particle size, and TiO2 crystal phase and size) and photocatalytic activity can be readily tuned as a function of the calcination temperature and Au content. The material calcined at 550 °C with 2.0 wt % Au shows the highest photocatalytic activity. This material is anatase in phase (which maximizes the electron‐transfer activity) and has the highest loading of small Au nanoparticles (which act as electron sinks to decrease the recombination of photo‐excited electrons and holes). These Au/TiO2 nanofibrous mats have the advantage of easy recovery and, therefore, reuse after the photocatalytic reaction, which addresses the issue of photocatalyst separation when using nanoparticulate powders as photocatalysts.
Increased coexpression of c‐KIT and FLT3 receptors on myeloblasts: Independent predictor of poor outcome in pediatric acute myeloid leukemia
Authors: Sharawat Surender Kumar , Gupta Ritu , Raina Vinod , Kumar Lalit , Sharma Atul , Iqbal Sobuhi , Bakhshi Radhika , Vishnubhatla Sreenivas , Bakhshi Sameer 
Published: June 2013

BackgroundSignificance of mutations in FLT3 and c‐KIT genes in AML has been well established, but role of their coexpression has not been evaluated. The aim of this study was to evaluate clinical significance of FLT3 (CD135) and c‐KIT (CD117) coexpression on myeloblasts in AML.MethodsUsing flow‐cytometry, we prospectively observed in 115 AML patients that CD135, CD117, and CD135+CD117 coexpression was expressed in 95 (82%), 104 (90%), and 81 (70%) patients respectively. Median expression of CD135, CD117, and their co expression was used as cut off for high and low expression.ResultsFLT3 ITD (internal tandem duplication) was present in 20 (17%) patients. High coexpression did not correlate with FLT3 ITD (P = 0.432) and cytogenetics (P = 0.244). Out of 115 patients, 86 (74.7%) achieved remission. At median followup of 15.5 months, EFS and OS was 29% and 35%, respectively for the entire cohort. Patients with high coexpression of CD135 and CD117 in comparison to those with low coexpression had significantly inferior EFS (20% vs 38% P < 0.001) and OS (27% vs 44% P = 0.001). In step wise Cox regression multivariable analysis, hazard ratio for high hemoglobin, WBC count, and coexpression of CD135 and CD117 was 0.63, 1.73, and 2.46 respectively for EFS, and for OS only CD135+CD117 coexpression emerged as an independent predictor (hazard ratio 2.25).ConclusionsThis is the first study to show that high coexpression of CD135+CD117 is an independent predictor of poor outcome in AML and is easily measurable by routine diagnostic flow‐cytometry. © 2013 International Clinical Cytometry Society