bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential functional genomic effects of anti-inflammatory phytocompounds on immune signaling
Authors: Chiu Shao-Chih , Tsao Shan-Wen , Hwang Pei-Ing , Vanisree Staniforth , Chen Yi-An , Yang Ning-Sun 
Published: October 2010

AbstractBackgroundFunctional comparative genomic analysis of the cellular immunological effects of different anti-inflammatory phytocompounds is considered as a helpful approach to distinguish the complex and specific bioactivities of candidate phytomedicines. Using LPS-stimulated THP-1 monocytes, we characterize here the immunomodulatory activities of three single phytocompounds (emodin, shikonin, and cytopiloyne) and a defined phytocompound mixture extracted fromEchinaceaplant (BF/S+L/Ep) by focused DNA microarray analysis of selected immune-related genes.ResultsShikonin and emodin significantly inhibited the early expression (within 0.5 h) of approximately 50 genes, notably cytokines TNF-α, IL-1β and IL-4, chemokines CCL4 and CCL8, and inflammatory modulators NFATC3 and PTGS2. In contrast, neither cytopiloyne nor BF/S+L/Ep inhibited the early expression of these 50 genes, but rather inhibited most late-stage expression (~12 h) of another immune gene subset. TRANSPATH database key node analysis identified the extracellular signal-regulated kinase (ERK) 1/2 activation pathway as the putative target of BF/S+L/Ep and cytopiloyne. Western blot confirmed that delayed inactivation of the ERK pathway was indeed demonstrable for these two preparations during the mid-stage (1 to 4 h) of LPS stimulation. We further identified ubiquitin pathway regulators, E6-AP and Rad23A, as possible key regulators for emodin and shikonin, respectively.ConclusionThe current focused DNA microarray approach rapidly identified important subgenomic differences in the pattern of immune cell-related gene expression in response to specific anti-inflammatory phytocompounds. These molecular targets and deduced networks may be employed as a guide for classifying, monitoring and manipulating the molecular and immunological specificities of different anti-inflammatory phytocompounds in key immune cell systems and for potential pharmacological application.
Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage
Authors: Tulsawani Rajkumar , Kelly Lorena S , Fatma Nigar , Chhunchha Bhavanaben , Kubo Eri , Kumar Anil , Singh Dhirendra P 
Published: October 2010

Abstract

Background
The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS)-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC) death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6) plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis.

Results
We have shown that RGCs exposed to hypoxia (1%) or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM), revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6.

Conclusion
Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.
Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women
Authors: Rantala Anne-Maria , Taylor Steve M , Trottman Paul A , Luntamo Mari , Mbewe Bernard , Maleta Kenneth , Kulmala Teija , Ashorn Per , Meshnick Steven R 
Published: October 2010

AbstractBackgroundNew diagnostic tools for malaria are required owing to the changing epidemiology of malaria, particularly among pregnant women in sub-Saharan Africa. Real-time PCR assays targetingPlasmodium falciparumlactate dehydrogenase (pfldh) gene may facilitate the identification of a high proportion of pregnant women with aP. falciparumparasitaemia below the threshold of microscopy. These molecular methods will enable further studies on the effects of these submicroscopic infections on maternal health and birth outcomes.MethodsThepfldhreal-time PCR assay and conventional microscopy were compared for the detection ofP. falciparumfrom dried blood spots and blood smears collected from the peripheral blood of 475 Malawian women at delivery. A cycle threshold (Ct) of the real-time PCR was determined optimizing the sensitivity and specificity of thepfldhPCR assay compared to microscopy. A real-time PCR species-specific assay was applied to identify the contribution to malaria infections of threePlasmodiumspecies (P. falciparum P. ovaleandP. malariae) in 44 discordant smear andpfldhPCR assay results.ResultsOf the 475 women,P. falciparumwas detected in 11 (2.3%) by microscopy and in 51 (10.7%) by real-time PCR; compared to microscopy, the sensitivity of real-time PCR was 90.9% and the specificity 91.2%. If a Ct value of 38 was used as a cut-off, specificity improved to 94.6% with no change in sensitivity. The real-time PCR species-specific assay detectedP. falciparumalone in all but four samples: two samples were mixed infections withP. falciparumandP. malariae, one was a pureP. malariaeinfection and one was apfldhPCR assay-positive/species-specific assay-negative sample. Of threeP. malariaeinfections detected by microscopy, only one was confirmed by the species-specific assay.ConclusionsAlthough microscopy remains the most appropriate method for clinical malaria diagnosis in field settings, molecular diagnostics such as real-time PCR offer a more reliable means to detect malaria parasites, particularly at low levels. Determination of the possible contribution of these submicroscopic infections to poor birth outcomes and maternal health is critical. For future studies to investigate these effects, thispfldhreal-time PCR assay offers a reliable detection method.
Proteomic characterization of van A-containing Enterococcu s recovered from Seagulls at the Berlengas Natural Reserve, W Portugal
Authors: Radhouani Hajer , Poeta Patrícia , Pinto Luís , Miranda Júlio , Coelho Céline , Carvalho Carlos , Rodrigues Jorge , López María , Torres Carmen , Vitorino Rui , Domingues Pedro , Igrejas Gilberto 
Published: October 2010

Abstract

Background
Enterococci have emerged as the third most common cause of nosocomial infections, requiring bactericidal antimicrobial therapy. Although vancomycin resistance is a major problem in clinics and has emerged in an important extend in farm animals, few studies have examined it in wild animals. To determine the prevalence of van A-containing Enterococcus strains among faecal samples of Seagulls (Larus cachinnans) of Berlengas Natural Reserve of Portugal, we developed a proteomic approach integrated with genomic data. The purpose was to detect the maximum number of proteins that vary in different enterococci species which are thought to be connected in some, as yet unknown, way to antibiotic resistance.

Results
From the 57 seagull samples, 54 faecal samples showed the presence of Enterococcus isolates (94.7%). For the enterococci, E. faecium was the most prevalent species in seagulls (50%), followed by E. faecalis and E. durans (10.4%), and E. hirae (6.3%). VanA-containing enterococcal strains were detected in 10.5% of the 57 seagull faecal samples studied. Four of the vanA-containing enterococci were identified as E. faecium and two as E. durans. The tet(M) gene was found in all five tetracycline-resistant vanA strains. The erm(B) gene was demonstrated in all six erythromycin-resistant vanA strains. The hyl virulence gene was detected in all four van A-containing E. faecium isolates in this study, and two of them harboured the pur K1 allele. In addition these strains also showed ampicillin and ciprofoxacin resistance. The whole-cell proteomic profile of van A-containing Enterococcus strains was applied to evaluate the discriminatory power of this technique for their identification. The major differences among species-specific profiles were found in the positions corresponding to 97-45 kDa. Sixty individualized protein spots for each vanA isolate was identified and suitable for peptide mass fingerprinting measures by spectrometry measuring (MALDI/TOF MS) and their identification through bioinformatic databases query. The proteins were classified in different groups according to their biological function: protein biosynthesis, ATP synthesis, glycolysis, conjugation and antibiotic resistance. Taking into account the origin of these strains and its relation to infectious processes in humans and animals, it is important to explore the proteome of new strains which might serve as protein biomarkers for biological activity.

Conclusions
The comprehensive description of proteins isolated from vancomycin-resistant Enterococcus faecium and E. durans may provide new targets for development of antimicrobial agents. This knowledge may help to identify new biomarkers of antibiotic resistance and virulence factors.
A case of recurrent giant cell tumor of bone with malignant transformation and benign pulmonary metastases
Authors: Miller Ira J , Blank Alan , Yin Suellen M , Mcnickle Allison , Gray Robert , Gitelis Steven 
Published: October 2010

Abstract
Giant cell tumor (GCT) of bone is a locally destructive tumor that occurs predominantly in long bones of post-pubertal adolescents and young adults, where it occurs in the epiphysis. The majority are treated by aggressive curettage or resection. Vascular invasion outside the boundary of the tumor can be seen. Metastasis, with identical morphology to the primary tumor, occurs in a few percent of cases, usually to the lung. On occasion GCTs of bone undergo frank malignant transformation to undifferentiated sarcomas. Here we report a case of GCT of bone that at the time of recurrence was found to have undergone malignant transformation. Concurrent metastases were found in the lung, but these were non-transformed GCT.
Scoring function to predict solubility mutagenesis
Authors: Tian Ye , Deutsch Christopher , Krishnamoorthy Bala 
Published: October 2010

Abstract

Background
Mutagenesis is commonly used to engineer proteins with desirable properties not present in the wild type (WT) protein, such as increased or decreased stability, reactivity, or solubility. Experimentalists often have to choose a small subset of mutations from a large number of candidates to obtain the desired change, and computational techniques are invaluable to make the choices. While several such methods have been proposed to predict stability and reactivity mutagenesis, solubility has not received much attention.

Results
We use concepts from computational geometry to define a three body scoring function that predicts the change in protein solubility due to mutations. The scoring function captures both sequence and structure information. By exploring the literature, we have assembled a substantial database of 137 single- and multiple-point solubility mutations. Our database is the largest such collection with structural information known so far. We optimize the scoring function using linear programming (LP) methods to derive its weights based on training. Starting with default values of 1, we find weights in the range [0,2] so that predictions of increase or decrease in solubility are optimized. We compare the LP method to the standard machine learning techniques of support vector machines (SVM) and the Lasso. Using statistics for leave-one-out (LOO), 10-fold, and 3-fold cross validations (CV) for training and prediction, we demonstrate that the LP method performs the best overall. For the LOOCV, the LP method has an overall accuracy of 81%.

Availability
Executables of programs, tables of weights, and datasets of mutants are available from the following web page: http://www.wsu.edu/~kbala/OptSolMut.html.
Signaling network of dendritic cells in response to pathogens: a community-input supported knowledgebase
Authors: Patil Sonali , Pincas Hanna , Seto Jeremy , Nudelman German , Nudelman Irina , Sealfon Stuart C 
Published: October 2010

AbstractBackgroundDendritic cells are antigen-presenting cells that play an essential role in linking the innate and adaptive immune systems. Much research has focused on the signaling pathways triggered upon infection of dendritic cells by various pathogens. The high level of activity in the field makes it desirable to have a pathway-based resource to access the information in the literature. Current pathway diagrams lack either comprehensiveness, or an open-access editorial interface. Hence, there is a need for a dependable, expertly curated knowledgebase that integrates this information into a map of signaling networks.DescriptionWe have built a detailed diagram of the dendritic cell signaling network, with the goal of providing researchers with a valuable resource and a facile method for community input. Network construction has relied on comprehensive review of the literature and regular updates. The diagram includes detailed depictions of pathways activated downstream of different pathogen recognition receptors such as Toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors and nucleotide-binding oligomerization domain-like receptors. Initially assembled using CellDesigner software, it provides an annotated graphical representation of interactions stored in Systems Biology Mark-up Language. The network, which comprises 249 nodes and 213 edges, has been web-published through the Biological Pathway Publisher software suite. Nodes are annotated with PubMed references and gene-related information, and linked to a public wiki, providing a discussion forum for updates and corrections. To gain more insight into regulatory patterns of dendritic cell signaling, we analyzed the network using graph-theory methods: bifan, feedforward and multi-input convergence motifs were enriched. This emphasis on activating control mechanisms is consonant with a network that subserves persistent and coordinated responses to pathogen detection.ConclusionsThis map represents a navigable aid for presenting a consensus view of the current knowledge on dendritic cell signaling that can be continuously improved through contributions of research community experts. Because the map is available in a machine readable format, it can be edited and may assist researchers in data analysis. Furthermore, the availability of a comprehensive knowledgebase might help further research in this area such as vaccine development. The dendritic cell signaling knowledgebase is accessible athttp://tsb.mssm.edu/pathwayPublisher/DC_pathway/DC_pathway_index.html.
Differential interleukin-6/Stat3 signaling as a function of cellular context mediates Ras-induced transformation
Authors: Leslie Kenneth , Gao Sizhi P , Berishaj Marjan , Podsypanina Katrina , Ho Hao , Ivashkiv Lionel , Bromberg Jacqueline 
Published: October 2010

Abstract
Introduction
Tyrosine phosphorylated signal transducer and activator of transcription 3 (pStat3) is expressed in numerous cancers and is required for mediating tumorigenesis. Autocrine and paracrine interleukin (IL)-6 signaling is the principal mechanism by which Stat3 is persistently phosphorylated in epithelial tumors including breast, lung, colon and gastric cancer. The Ras oncogene mediates cellular transformation without evidence of pStat3 in cultured cells. However, non-tyrosine phosphorylated Stat3 was shown to function as a transcriptional activator, localize to the mitochondria and regulate ATP synthesis and mediate cell migration. Here we examined the role of Stat3 in Ras mediated transformation.

Methods
Ha-rasV12 transformed mammary epithelial cells (MCF10A-Ras) cells were transduced with a Stat3shRNA, IL-6shRNA and/or treated with inhibitors of Janus kinases (JAKs) to examine the role of the IL-6 signaling pathway in Ras mediated migration, invasion and tumorigenesis.

Results
Cellular migration, invasion, anchorage independent growth and tumorigenesis were largely abrogated in the Stat3-reduced cells compared to control cells. Analysis of MCF10A-Ras tumors revealed high levels of pStat3 and interleukin-6. Tumors derived from transgenic MMTV-K-Ras mice were also found to express pStat3 and IL-6. MCF10A-Ras cells, when grown in a three-dimensional Matrigel culture system revealed the appearance of the junctional protein E-Cadherin as a consequence of reducing Stat3 levels or inhibiting Stat3 activity. Decreasing IL-6 levels in the MCF10A-Ras cells abrogated tumorigenesis and reduced cell migration. By isolating Ras-expressing primary tumors and serially passaging these cells in two-dimensional culture led to a decrease in IL-6 and pStat3 levels with the reappearance of E-Cadherin.

Conclusions
The cellular and environmental context can lead to differential IL-6/pStat3 signaling and a dependency on this cytokine and transcription factor for migration, invasion and tumorigenesis.
Metformin Versus Placebo from First Trimester to Delivery in Polycystic Ovary Syndrome: A Randomized, Controlled Multicenter Study
Authors: Vanky Eszter , Stridsklev Solhild , Heimstad Runa , Romundstad Pål , Skogøy Kristin , Kleggetveit Odrun , Hjelle Sissel , von Brandis Philip , Eikeland Torunn , Flo Karin , Berg Kristin Flaten , Bunford Gabor , Lund Agnethe , Bjerke Cecilie , Almås Ingunn , Berg Ann Hilde , Danielson Anna , Lahmami Gulim , Carlsen Sven Magnus 
Published: October 2010

Context: Metformin is widely prescribed to pregnant women with polycystic ovary syndrome (PCOS) in an attempt to reduce pregnancy complications. Metformin is not approved for this indication, and evidence for this practice is lacking.
Objectives: Our objective was to test the hypothesis that metformin, from first trimester to delivery, reduces pregnancy complications in women with PCOS.
Design and Setting: We conducted a randomized, placebo-controlled, double-blind, multicenter study at 11 secondary care centers.
Participants: The participants were 257 women with PCOS, in the first trimester of pregnancy, aged 18–42 yr.
Intervention: We randomly assigned 274 singleton pregnancies (in 257 women) to receive metformin or placebo, from first trimester to delivery.
Main Outcome Measures: The prevalence of preeclampsia, gestational diabetes mellitus, preterm delivery, and a composite of these three outcomes is reported.
Results: Preeclampsia prevalence was 7.4% in the metformin group and 3.7% in the placebo group (3.7%; 95% CI, −1.7–9.2) (P = 0.18). Preterm delivery prevalence was 3.7% in the metformin group and 8.2% in the placebo group (−4.4%; 95%, CI, −10.1–1.2) (P = 0.12). Gestational diabetes mellitus prevalence was 17.6% in the metformin group and 16.9% in the placebo group (0.8%; 95% CI, −8.6–10.2) (P = 0.87). The composite primary endpoint prevalence was 25.9 and 24.4%, respectively (1.5%; 95% CI, −8.9–11.3) (P = 0.78). Women in the metformin group gained less weight during pregnancy compared with those in the placebo group. There was no difference in fetal birth weight between the groups.
Conclusions: Metformin treatment from first trimester to delivery did not reduce pregnancy complications in PCOS.
Commutability of National Institute of Standards and Technology standard reference material 1955 homocysteine and folate in frozen human serum for total folate with automated assays
Authors: Ihara Hiroshi , Watanabe Toshiaki , Hashizume Naotaka , Totani Masayuki , Kamioka Kazuyuki , Onda Kimiko , Sunahara Satoshi , Suzuki Tomoko , Itabashi Mitsuharu , Aoki Yoshikazu , Ishibashi Midori , Ito Shozo , Ohashi Koji , Enomoto Tsuyoshi , Saito Kensuke , Saeki Kayoko , Nagamura Yoichi , Nobori Tsutomu , Hirota Kouichi , Fujishiro Kinya , Maekawa Masato , Miura Masakazu , Ohta Yoshiji 
Published: October 2010

Background The aim of the present study was to evaluate standard reference material (SRM) 1955 commutability as a reference material for serum folate using automated methods. We also designed so as to reduce the intermethod variability present in different automated methods. Methods Using a microbiological assay related to the ‘information value’ of SRM 1955 as a comparison method, we investigated the possibility of standardization for the assay values of serum folate as measured by the automated methods (Access, Centaur and Elecsys). In the assay of 50 patient sera by these automated methods, we corrected observed values by the SRM 1955 and compared with comparison values. Results The observed values of SRM 1955 Levels I, II and III were within or outside (but near) a 95% prediction interval obtained from patient sera by the automated methods. The normalized residuals obtained from SRM 1955 were within ±3.0 (in SD units), which enabled us to conclude that the SRM 1955 had a physicochemical characterization similar to native serum. Twelve patients were assessed as hypofolataemia (<6.0 ng/mL) and 38 patients as normal (≥6.0 ng/mL). Before correction, folate levels in six of 12 patients were lower than 6.0 ng/mL, and those in seven of 38 patients were higher than 6.0 ng/mL with the automated methods. After correction, low levels were found in four of 12 patients, and normal levels were found in 33 of 38 patients. Conclusions The use of SRM 1955 would help to reduce the intermethod variability present in different automated methods for serum folate measurement.
Denosumab
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E. 
Published: October 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The October 2010 monograph topics are on dapagliflozin, glyco-pyrrolate oral solution, alcaftadine 0.25% ophthalmic solution, fidaxomicin, and cladribine tablets. The DUE/MUE is on memantine.