bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant placental immune parameters in the feline immunodeficiency virus (FIV)-infected cat suggest virus-induced changes in T cell function
Authors: Chumbley Lyndon Bart , Boudreaux Crystal E , Coats Karen S 
Published: July 2013

AbstractBackgroundImmune activity during pregnancy must be tightly regulated to ensure successful pregnancy. This regulation includes the suppression of inflammatory activity that could target the semi-allogeneic fetus. Tregs are immunosuppressive; Th17 cells are pro-inflammatory. A precise balance in the two cell populations is critical to pregnancy maintenance, while dysregulation in this balance accompanies compromised pregnancy in humans and mice. FIV is known to target Tregs preferentially in the infected cat. Therefore, it may be hypothesized that FIV infection alters the placental Treg/Th17 cell balance resulting in aberrant immunomodulator expression by these cells and consequent pregnancy perturbation.MethodsRNA was purified from random sections of whole placental tissues collected from both uninfected and FIV-infected queens at early pregnancy, including tissues from viable and nonviable fetuses. Real time qPCR was performed to quantify expression of intranuclear markers of Tregs (FoxP3) and Th17 cells (RORγ); cytokine products of Tregs (IL-10 and TGF-β), Th17 cells (IL-2, IL-6, and IL-17a), and macrophages (IL-1β); and the FIV gag gene. Pairwise comparisons were made to evaluate coexpression patterns between the cytokines and between the cytokines and the virus.ResultsBoth FoxP3 and RORγ were reduced in placentas of infected animals. Neither infection status nor fetal viability affected placental expression of IL-1β. However, fetal nonviability was associated with reduced levels of all other cytokines. Infection and fetal nonviability impacted coexpression of various cytokine pairs. No obvious bias toward Treg or Th17 cells was observed.ConclusionsFIV infection coupled with fetal nonviability alters expression patterns of T cell cytokines. These data suggest that functionally altered placental T cell leukocyte populations may occur in the infected queen and possibly contribute to fetal nonviability.
Engineering lentiviral vectors for modulation of dendritic cell apoptotic pathways
Authors: Wang James CM , Felizardo Tânia C , Au Bryan CY , Fowler Daniel H , Dekaban Gregory A , Medin Jeffrey A 
Published: July 2013

AbstractBackgroundDendritic cells (DCs) are promising mediators of anti-tumor immune responses due to their potent antigen-presentation capacity. Unfortunately, cancer cells can often disarm differentiated DCs by rendering them incapable of maturation or by promoting their apoptosis. DC vaccine regimens attempt to generate functional DCs and preload them with Tumor-Associated Antigens (TAAs) to target various malignancies. Despite these efforts, the efficacy of DC vaccines in clinical trials is still rather disappointing to date. In addition to undergoing cancer-induced apoptosis, it is well established that DCs are intrinsically short-lived cell types. It is likely that a significant portion of infused DCs undergo apoptosis prior to locating and activating naïve TAA-reactive T cells.MethodsIn our current study, we constructed and investigated novel bicistronic lentivectors (LVs) encoding the cDNA for the xeno-TAA,rat HER-2/neu (rHER-2), along with five candidate mouse DC survival factors (c-FLIPS, c-FLIPL, Bcl-XL, M11L, and AKT-1) that operate in both the extrinsic and intrinsic cycles of apoptosis. The murine DC cell line, DC2.4 was transduced separately with each novel LV construct. Infected cells were enriched via flow cytometric methods based on rHER-2 expression. Transduced DC2.4 cell lines were then exposed to Fetal Calf Serum (FCS) withdrawal and to specific pharmacological apoptosis-inducing agents. DC2.4 cell death was assayed based on Annexin V and PI double-positive staining via flow cytometry. The phenotype and function of transduced DC2.4 cells and primary bone marrow-derived DCs were then assessed via expression and secretion of DC markers and cytokines, respectively.ResultsDC2.4 cells transduced with LVs encoding cDNAs for c-FLIPS, c-FLIPL, Bcl-XL, and M11L were protected from apoptosis when exposed to low FCS-containing culture media. When treated with an anti-CD95 antibody, only DC2.4 cells transduced with LVs encoding c-FLIPSand c-FLIPLwere protected from apoptosis. In contrast, only DC2.4 cells transduced with LVs encoding Bcl-XLand M11L were protected from effects of staurosporine (STS) treatment. Also, LV-modified DCs maintained their original phenotype and function.ConclusionsWe present evidence that by employing novel recombinant bicistronic LVs we can simultaneously load DCs with a relevant TAA and block apoptosis; thereby confirming the usage of such LVs in the modulation of DC lifespan and function.
MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer cells
Authors: Li Jhy-Ming , Kao Kuo-Chin , Li Li-Fu , Yang Tsung-Ming , Wu Chean-Ping , Horng Yan-Ming , Jia William WG , Yang Cheng-Ta 
Published: July 2013

Abstract

Background
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and novel treatment modalities to improve the prognosis of patients with advanced disease are highly desirable. Oncolytic virotherapy is a promising approach for the treatment of advanced NSCLC. MicroRNAs (miRNAs) may be a factor in the regulation of tumor-specific viral replication. The purpose of this study was to investigate whether miRNA-145 regulated oncolytic herpes simplex virus-1 (HSV-1) can selectively kill NSCLC cells with reduced collateral damage to normal cells.

Methods
We incorporated 4 copies of miRNA-145 target sequences into the 3′-untranslated region of an HSV-1 essential viral gene, ICP27, to create AP27i145 amplicon viruses and tested their target specificity and toxicity on normal cells and lung cancer cells in vitro.

Results
miRNA-145 expression in normal cells was higher than that in NSCLC cells. AP27i145 replication was inversely correlated with the expression of miRNA-145 in infected cells. This oncolytic HSV-1 selectively reduced cell proliferation and prevented the colony formation of NSCLC cells. The combination of radiotherapy and AP27i145 infection was significantly more potent in killing cancer cells than each therapy alone.

Conclusions
miRNA-145-regulated oncolytic HSV-1 is a promising agent for the treatment of NSCLC.
Determination of five flavonoids in different parts of Fordia cauliflora by ultra performance liquid chromatography/triple-quadrupole mass spectrometry and chemical comparison with the root of Millettia pulchra var. laxior
Authors: Fan Lanlan , Zhang Yazhou , Huang Renbin , Qin Shanding , Yi Tao , Xu Feng , Tang Yina , Qu Xiaosheng , Chen Hubiao , Miao Jianhua 
Published: July 2013

Abstract

Background
The root of Fordia cauliflora Hemsl (FC) has long been used in southern China for the treatment of rheumatism, bruises, dementia in children, and valetudinarianism. However, sometimes it is mixed with other parts. And it has always been confused with the root of Millettia pulchra (Benth.) Kurz var. laxior (Dunn) Z. Wei (MP) by the local people. The chemical differences between the two ethnic drugs are not clear until now. The aim of this study is to develop a precise and accurate method to characterize and quantify multiple chemical components of FC, which is helpful for the quality evaluation and identification of FC.

Results
A method coupling ultra performance liquid chromatography (UPLC) with triple-quadrupole mass spectrometry (QqQ-MS) was first developed for simultaneous determination of five flavonoids in different parts of FC and the root of MP, based on a UPLC-diode array detection (DAD) fingerprint method. All calibration curves showed good linearity (R2>0.99) within test ranges. The overall LOD and LOQ were lower than 2.5 ng/mL and 5.0 ng/mL, respectively. The RSDs for intra- and inter-day of five analytes were less than 2.83% and 3.04%, respectively. Recovery studies for the quantified compounds were found to be within the range 93.6-99.8% with RSD less than 5.73%. The results suggest that the root, traditionally used medicinal part, yields the highest flavanoid content in FC. Pachycarin A, 3′,4′-dimethoxy(2′′,3′′:7,8) furanoflavone, karanjachromene and isoderricin A can be used to differentiate between FC and MP samples.

Conclusions
The present method is specific, precise and reliable, and is suitable for characterizing and quantifying multiple chemical components of FC.
Influence of astaxanthin, emulsifier and organic phase concentration on physicochemical properties of astaxanthin nanodispersions
Authors: Anarjan Navideh , Nehdi Imededdine Arbi , Tan Chin Ping 
Published: July 2013

AbstractBackgroundThe emulsification-evaporation method was used to prepare astaxanthin nanodispersions using a three-component emulsifier system composed of Tween 20, sodium caseinate and gum Arabic. Using Response-surface methodology (RSM), we studied the main and interaction effects of the major emulsion components, namely, astaxanthin concentration (0.02–0.38 wt %, x1), emulsifier concentration (0.2–3.8 wt %, x2) and organic phase (dichloromethane) concentration (2–38 wt %, x3) on nanodispersion characteristics. The physicochemical properties considered as response variables were: average particle size (Y1), PDI (Y2) and astaxanthin loss (Y3).ResultsThe results indicated that the response-surface models were significantly (p < 0.05) fitted for all studied response variables. The fitted polynomial regression models for the prediction of variations in the response variables showed high coefficients of determination (R2 > 0.930) for all responses. The overall optimum region resulted in a desirable astaxanthin nanodispersions obtained with the concentrations of 0.08 wt % astaxanthin, 2.5 wt % emulsifier and 11.5 wt % organic phase.ConclusionNo significant differences were found between the experimental and predicted values, thus certifying the adequacy of the Response-surface models developed for describing the changes in physicochemical properties as a function of main emulsion component concentrations.
Differences in PAR-2 activating potential by king crab (Paralithodes camtschaticus), salmon (Salmo salar), and bovine (Bos taurus) trypsin
Authors: Larsen Anett K , Kristiansen Kurt , Sylte Ingebrigt , Seternes Ole-Morten , Bang Berit E 
Published: July 2013

Abstract

Background
Salmon trypsin is shown to increase secretion of the pro-inflammatory cytokine interleukin (IL)-8 from human airway epithelial cells through activation of PAR-2. Secretion of IL-8 induced by king crab trypsin is observed in a different concentration range compared to salmon trypsin, and seems to be only partially related to PAR-2 activation. This report aim to identify differences in the molecular structure of king crab trypsin (Paralithodes camtschaticus) compared to salmon (Salmo salar) and bovine trypsin (Bos taurus) that might influence the ability to activate protease-activated receptor-2 (PAR-2).

Results
During purification king crab trypsin displayed stronger binding capacity to the anionic column used in fast protein liquid chromatography compared to fish trypsins, and was identified as a slightly bigger molecule. Measurements of enzymatic activity yielded no obvious differences between the trypsins tested. Molecular modelling showed that king crab trypsin has a large area with strong negative electrostatic potential compared to the smaller negative areas in bovine and salmon trypsins. Bovine and salmon trypsins also displayed areas with strong positive electrostatic potential, a feature lacking in the king crab trypsin. Furthermore we have identified 3 divergent positions (Asp196, Arg244, and Tyr247) located near the substrate binding pocket of king crab trypsin that might affect the binding and cleavage of PAR-2.

Conclusion
These preliminary results indicate that electrostatic interactions could be of importance in binding, cleavage and subsequent activation of PAR-2.
RETRACTED ARTICLE: Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3
Authors: Patel Hiren , Bhartiya Deepa , Parte Seema , Gunjal Pranesh , Yedurkar Snehal , Bhatt Mithun 
Published: July 2013

Abstract
Background
We have earlier reported that follicle stimulating hormone (FSH) modulates ovarian stem cells which include pluripotent, very small embryonic-like stem cells (VSELs) and their immediate descendants ‘progenitors’ termed ovarian germ stem cells (OGSCs), lodged in adult mammalian ovarian surface epithelium (OSE). FSH may exert pleiotropic actions through its alternatively spliced receptor isoforms. Four isoforms of FSH receptors (FSHR) are reported in literature of which FSH-R1 and FSH-R3 have biological activity. Present study was undertaken to identify FSHR isoforms mediating FSH action on ovarian stem cells, using sheep OSE cells culture as the study model.

Methods
Cultures of sheep OSE cells (a mix of epithelial cells, VSELs, OGSCs and few contaminating red blood cells) were established with and without FSH 5IU/ml treatment. Effect of FSH treatment on self-renewal of VSELs and their differentiation into OGSCs was studied after 15 hrs by qRT-PCR using markers specific for VSELs (Oct-4A, Sox-2) and OGSCs (Oct-4). FSH receptors and its specific transcripts (R1 and R3) were studied after 3 and 15 hrs of FSH treatment by immunolocalization, in situ hybridization and qRT-PCR. FSHR and OCT-4 were also immuno-localized on sheep ovarian sections, in vitro matured follicles and early embryos.

Results
FSH treatment resulted in increased stem cells self-renewal and clonal expansion evident by the appearance of stem cell clusters. FSH receptors were expressed on ovarian stem cells whereas the epithelial cells were distinctly negative. An increase in R3 mRNA transcripts was noted after 3 hrs of FSH treatment and was reduced to basal levels by 15 hrs, whereas R1 transcript expression remained unaffected. Both FSHR and OCT-4 were immuno-localized in nuclei of stem cells, showed nuclear or ooplasmic localization in oocytes of primordial follicles and in cytoplasm of granulosa cells in growing follicles.

Conclusions
FSH modulates ovarian stem cells via FSH-R3 to undergo potential self-renewal, clonal expansion as ‘cysts’ and differentiation into oocytes. OCT-4 and FSHR proteins (required initially to maintain pluripotent state of VSELs and for FSH action respectively) gradually shift from nuclei to cytoplasm of developing oocytes and are later possibly removed by surrounding granulosa cells as the oocyte prepares itself for fertilization.
Effect of conjugated linoleic acid and vitamin E on glycemic control, body composition, and inflammatory markers in overweight type2 diabetics
Authors: Shadman Zhaleh , Taleban Forough Azam , Saadat Navid , Hedayati Mehdi 
Published: July 2013

Abstract
Background
The healthy properties of conjugated linoleic acid (CLA) such as weight loss, reducing cardiovascular risk factors and inflammation have been reported. The trans-10, cis-12 CLA isomer is related to increasing insulin resistance, but the effects of cis-9, trans-11 isomer is not clear. The aim of this study was to investigate the effects of CLA with and without Vitamin E on body weight, body composition, glycemic index, inflammatory and coagulation factors, lipid profile, serum leptin and adiponectin, malondialdehyde (MDA), and blood pressure in type2 diabetes.

Methods
56 patients with type2 diabetes were included in 8 week double-blind control trial that used metformin. They randomly divided into three groups: CLA + VitE, CLA + VitE placebo, CLA placebo + VitE placebo. All variables, anthropometric measurements, and body composition were evaluated at the beginning and the end of study. Statistical analysis and analysis of dietary data were performed using SPSS and nutritionist IV software, respectively.

Results
There were not any significant differences in variable changes among three groups. However, there was a trend to increase in MDA and decrease in apoB100 among CLA consumers.

Conclusion
The results of this study showed that administration of CLA supplementation for 8 weeks does not affect any indicators of metabolic control in overweight type2 diabetic patients.
Molecular targeting of hepatocyte growth factor by an antagonist, NK4, in the treatment of rheumatoid arthritis
Authors: Tsunemi Sachi , Iwasaki Tsuyoshi , Kitano Sachie , Matsumoto Kunio , Takagi-Kimura Misato , Kubo Shuji , Tamaoki Tomoko , Sano Hajime 
Published: July 2013

Abstract
Introduction
Hepatocyte growth factor (HGF) is a potent proangiogenic molecule that induces neovascularization. The HGF antagonist, NK4, competitively antagonizes HGF binding to its receptor. In the present study, we determined the inhibitory effect of NK4 in a rheumatoid arthritis (RA) model using SKG mice.

Methods
Arthritis was induced in SKG mice by a single intraperitoneal injection of β-glucan. Recombinant adenovirus containing NK4 cDNA (AdCMV.NK4) was also injected intravenously at the time of or 1 month after β-glucan injection. Ankle bone destruction was examined radiographically. The histopathologic features of joints were examined using hematoxylin and eosin and immunohistochemical staining. Enzyme-linked immunosorbent assays were used to determine the serum levels of HGF, interferon γ (IFN-γ, interleukin 4 (IL-4) and IL-17 production by CD4+ T cells stimulated with allogeneic spleen cells.

Results
The intravenous injection of AdCMV.NK4 into SKG mice suppressed the progression of β-glucan-induced arthritis. Bone destruction was also inhibited by NK4 treatment. The histopathologic findings of the ankles revealed that angiogenesis, inflammatory cytokines and RANKL expression in synovial tissues were significantly inhibited by NK4 treatment. Recombinant NK4 (rNK4) proteins inhibited IFN-γ, IL-4 and IL-17 production by CD4+ T cells stimulated with allogeneic spleen cells.

Conclusions
These results indicate that NK4 inhibits arthritis by inhibition of angiogenesis and inflammatory cytokine production by CD4+ T cells. Therefore, molecular targeting of angiogenic inducers by NK4 can potentially be used as a novel therapeutic approach for the treatment of RA.
Resolution of Fatty Liver and Risk of Incident Diabetes
Authors: Sung Ki-Chul , Wild Sarah H. , Byrne Christopher D. 
Published: July 2013

Context:
Fatty liver is associated with an increased risk of type 2 diabetes, but whether an increased risk remains in people in whom fatty liver resolves over time is not known.

Objective:
The objective of the study was to assess the risk of incident diabetes at a 5-year follow-up in people in whom: 1) new fatty liver developed; 2) existing fatty liver resolved, and 3) fatty liver severity worsened over 5 years.

Design and Methods:
A total of 13 218 people without diabetes at baseline from a Korean occupational cohort were examined at baseline and after 5 years, using a retrospective study design. Fatty liver status was assessed at baseline and follow-up as absent, mild, or moderate/severe using standard ultrasound criteria. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for incident diabetes at follow-up were estimated after controlling for multiple potential confounders.

Results:
Two hundred thirty-four people developed incident diabetes. Over 5 years, fatty liver resolved in 828, developed in 1640, and progressed from mild to moderate/severe in 324 people. Resolution of fatty liver was not associated with a risk of incident diabetes [aOR 0.95 (95% CIs 0.46, 1.96), P = .89]. Development of new fatty liver was associated with incident diabetes [aOR 2.49 (95% CI 1.49, 4.14), P &lt; .001]. In individuals in whom severity of fatty liver worsened over 5 years (from mild to moderate/severe), there was a marked increase in the risk of incident diabetes [aOR 6.13 (2.56, 95% CI 14.68) P &lt; .001 (compared with the risk in people with resolution of fatty liver)].

Conclusion:
Change in fatty liver status over time is associated with markedly variable risks of incident diabetes.
Calcium-Sensing Receptor Autoantibodies and Idiopathic Hypoparathyroidism
Authors: Tomar Neeraj , Gupta Nandita , Goswami Ravinder 
Published: July 2013

Context:Data on calcium-sensing receptor autoantibodies (CaSRAbs) in hypoparathyroidism are variable.Objective:We assessed the prevalence and significance of CaSRAbs in idiopathic hypoparathyroidism.Design:This was a case-control study.Subjects:One hundred forty-seven patients with idiopathic hypoparathyroidism treated during 1998–2011 in a tertiary care setting and 348 controls [healthy, n = 199; type 1 diabetes mellitus (T1DM), n = 99; and chronic lymphocytic thyroiditis (CLT), n = 50] participated in the study.Methods:CaSRAb assays included Western blot with CaSR protein expressed in Escherichia coli or human embryonic kidney (HEK)-293 cells, immunoprecipitation (IP) using in vitro-transcribed/translated protein, and indirect immunofluorescence on HEK293-CaSR. Functional significance was assessed by ERK1/2 phosphorylation. PTH and CaSR genes were sequenced for mutations.Results:E coli-Western blot assay revealed 16.3% CaSRAb positivity in idiopathic hypoparathyroidism, which was comparable with healthy subjects and CLT but significantly less than the T1DM controls. The prevalence of CaSRAbs on HEK293-Western blot (24.5%) against 150 kDa and/or 168 kDa protein in hypoparathyroidism was significantly higher than the healthy subjects, T1DM, and CLT. IP assay showed CaSRAbs in 12.9% of the hypoparathyroid patients but not in controls. The sensitivity and specificity of CaSRAbs in E coli and HEK-293-CaSR Western blot and IP assays were 16.3% and 83.1%, 24.5% and 88.9%, and 12.9% and 100%, respectively, and 42.1% of the cases detected were common in the IP assay and HEK293-Western blot. Duration of illness and coexistent autoimmunity were similar in patients with and without CaSRAbs. The CaSRAb-positive sera showed no immunofluorescence and phosphorylated ERK1/2 activity. The CaSR gene sequence was normal in all patients. One of the patients showed a novel p.Met1_Asp6del mutation in the signal peptide region of the PTH gene.Conclusion:IP performed the best in detecting CaSRAbs in 12.9% of hypoparathyroid patients. Although CaSRAbs were functionally inert, its clinical relevance remains due to 100% specificity. Limited prevalence of CaSRAb suggests heterogeneity in the etiology of idiopathic hypoparathyroidism or the presence of CaSR epitopes other than those measured in the current study.
Which U.S. Market Interactions Affect CEO Pay? Evidence from UK Companies
Authors: Gerakos Joseph J. , Piotroski Joseph D. , Srinivasan Suraj 
Published: July 2013

This paper examines how different types of interactions with U.S. markets by non-U.S. firms are associated with higher levels of CEO pay, greater emphasis on incentive-based compensation, and smaller pay gaps with U.S. firms. Using a sample of CEOs of UK firms and using both broad cross-sectional and narrow event-window tests, we find that capital market relationship in the form of a U.S. exchange listing is related to higher UK CEO pay; however, the effect is similar when UK firms have a listing in any foreign country, implying a foreign listing effect not unique to the United States. Product market relationships measured by the extent of sales in the United States by UK companies are associated with higher pay, greater use of U.S.-style pay arrangements, and a reduction in the U.S.–UK pay gap. The product market effect is incremental to the effect of a U.S. exchange listing, the extent of the firm's non-U.S. foreign market interactions, and the characteristics of the executive. The U.S.–UK CEO pay gap reduces in UK firms that make U.S. acquisitions. Furthermore, the firm's use of a U.S. compensation consultant increases the sensitivity of UK pay practices to U.S. product market relationships. This paper was accepted by Gérard P. Cachon, accounting.