bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein kinase D1 (PKD1) activation mediates a compensatory protective response during early stages of oxidative stress-induced neuronal degeneration
Authors: Asaithambi Arunkumar , Kanthasamy Arthi , Saminathan Hariharan , Anantharam Vellareddy , Kanthasamy Anumantha G 
Published: June 2011

AbstractBackgroundOxidative stress is a key pathophysiological mechanism contributing to degenerative processes in many neurodegenerative diseases and therefore, unraveling molecular mechanisms underlying various stages of oxidative neuronal damage is critical to better understanding the diseases and developing new treatment modalities. We previously showed that protein kinase C delta (PKCδ) proteolytic activation during the late stages of oxidative stress is a key proapoptotic signaling mechanism that contributes to oxidative damage in Parkinson's disease (PD) models. The time course studies revealed that PKCδ activation precedes apoptotic cell death and that cells resisted early insults of oxidative damage, suggesting that some intrinsic compensatory response protects neurons from early oxidative insult. Therefore, the purpose of the present study was to characterize protective signaling pathways in dopaminergic neurons during early stages of oxidative stress.ResultsHerein, we identify that protein kinase D1 (PKD1) functions as a key anti-apoptotic kinase to protect neuronal cells against early stages of oxidative stress. Exposure of dopaminergic neuronal cells to H2O2or 6-OHDA induced PKD1 activation loop (PKD1S744/748) phosphorylation long before induction of neuronal cell death. Blockade of PKCδ cleavage, PKCδ knockdown or overexpression of a cleavage-resistant PKCδ mutant effectively attenuated PKD1 activation, indicating that PKCδ proteolytic activation regulates PKD1 phosphorylation. Furthermore, the PKCδ catalytic fragment, but not the regulatory fragment, increased PKD1 activation, confirming PKCδ activity modulates PKD1 activation. We also identified that phosphorylation of S916 at the C-terminal is a preceding event required for PKD1 activation loop phosphorylation. Importantly, negative modulation of PKD1 by the RNAi knockdown or overexpression of PKD1S916Aphospho-defective mutants augmented oxidative stress-induced apoptosis, while positive modulation of PKD1 by the overexpression of full length PKD1 or constitutively active PKD1 plasmids attenuated oxidative stress-induced apoptosis, suggesting an anti-apoptotic role for PKD1 during oxidative neuronal injury.ConclusionCollectively, our results demonstrate that PKCδ-dependent activation of PKD1 represents a novel intrinsic protective response in counteracting early stage oxidative damage in neuronal cells. Our results suggest that positive modulation of the PKD1-mediated compensatory protective mechanism against oxidative damage in dopaminergic neurons may provide novel neuroprotective strategies for treatment of PD.
Novel multiplex technology for diagnostic characterization of rheumatoid arthritis
Authors: Chandra Piyanka E , Sokolove Jeremy , Hipp Berthold G , Lindstrom Tamsin M , Elder James T , Reveille John D , Eberl Heike , Klause Ursula , Robinson William H 
Published: June 2011

Abstract
Introduction
The aim of this study was to develop a clinical-grade, automated, multiplex system for the differential diagnosis and molecular stratification of rheumatoid arthritis (RA).

Methods
We profiled autoantibodies, cytokines, and bone-turnover products in sera from 120 patients with a diagnosis of RA of < 6 months' duration, as well as in sera from 27 patients with ankylosing spondylitis, 28 patients with psoriatic arthritis, and 25 healthy individuals. We used a commercial bead assay to measure cytokine levels and developed an array assay based on novel multiplex technology (Immunological Multi-Parameter Chip Technology) to evaluate autoantibody reactivities and bone-turnover markers. Data were analyzed by Significance Analysis of Microarrays and hierarchical clustering software.

Results
We developed a highly reproducible, automated, multiplex biomarker assay that can reliably distinguish between RA patients and healthy individuals or patients with other inflammatory arthritides. Identification of distinct biomarker signatures enabled molecular stratification of early-stage RA into clinically relevant subtypes. In this initial study, multiplex measurement of a subset of the differentiating biomarkers provided high sensitivity and specificity in the diagnostic discrimination of RA: Use of 3 biomarkers yielded a sensitivity of 84.2% and a specificity of 93.8%, and use of 4 biomarkers a sensitivity of 59.2% and a specificity of 96.3%.

Conclusions
The multiplex biomarker assay described herein has the potential to diagnose RA with greater sensitivity and specificity than do current clinical tests. Its ability to stratify RA patients in an automated and reproducible manner paves the way for the development of assays that can guide RA therapy.
In vivo-transmigrated human neutrophils are resistant to antiapoptotic stimulation
Authors: Christenson Karin , Björkman Lena , Karlsson Jennie , Sundqvist Martina , Movitz Charlotta , Speert David P , Dahlgren Claes , Bylund Johan 
Published: June 2011

ABSTRACTNeutrophils respond to microbial invasion or injury by transmigration from blood to tissue. Transmigration involves cellular activation and degranulation, resulting in altered levels of surface receptors and changed responsiveness to certain stimuli. Thus, fundamental functional changes are associated with neutrophil transmigration from blood to tissue. Neutrophils isolated from peripheral blood spontaneously enter apoptosis, a process that can be accelerated or delayed by different pro- or antiapoptotic factors. How tissue neutrophils that have transmigrated in vivo regulate cell death is poorly understood. In this study, in vivo-transmigrated neutrophils (tissue neutrophils) were collected using a skin chamber technique and compared with blood neutrophils from the same donors with respect to regulation of cell death. Skin chamber fluid contained a variety of cytokines known to activate neutrophils and regulate their lifespan. Freshly prepared tissue neutrophils had elevated activity of caspase 3/7 but were fully viable; spontaneous cell death after in vitro culture was also similar between blood and tissue neutrophils. Whereas apoptosis of cultured blood neutrophils was delayed by soluble antiapoptotic factors (e.g., TLR ligands), tissue neutrophils were completely resistant to antiapoptotic stimulation, even though receptors were present and functional. In vitro transmigration of blood neutrophils into skin chamber fluid did not fully confer resistance to antiapoptotic stimulation, indicating that a block of antiapoptotic signaling occurs specifically during in vivo transmigration. We describe a novel, functional alteration that takes place during in vivo transmigration and highlights the fact that life and death of neutrophils may be regulated differently in blood and tissue.
Telomerase-Driven Expression of the Sodium Iodide Symporter (NIS) for in Vivo Radioiodide Treatment of Cancer: A New Broad-Spectrum NIS-Mediated Antitumor Approach
Authors: Riesco-Eizaguirre Garcilaso , De la Vieja Antonio , Rodríguez Irene , Miranda Soledad , Martín-Duque Pilar , Vassaux Georges , Santisteban Pilar 
Published: June 2011

Abstract

Context:
Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging.

Objective:
The aim of this study was to investigate the NIS-mediated therapeutic effect of telomerase promoters in a wide variety of human cancer cell lines.

Design and Methods:
Promoter fragments from either hTERT or hTR were used to drive the expression of NIS in cell lines derived from melanoma (M14), breast (MDA-MB-231), colon (HT-29), lung (H460), ovarian (OVCAR-3), and thyroid (TPC-1) carcinomas. Iodide uptake assays, protein immunodetection, and clonigenic assays were used to confirm NIS functional expression and the 131I-mediated cytopathic effect. Tumor xenografts in mice were infected with hTERT and hTR and then treated using radioiodide.

Results:
Both promoters were selectively active in cancer cells that were effectively killed by exposure to 131I. One single dose of 1 mCi 131I markedly suppressed tumor growth of melanoma-derived tumor xenografts compared with controls. This effect was more modest in colon cancer-derived xenografts in part due to the reduced infectivity and the tumor cystic nature. The therapeutic effect of hTR promoter was found to be stronger than that of hTERT promoter.

Conclusions:
These results demonstrate that telomerase-driven expression of NIS could potentially have applications for 131I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated 131I therapy of melanoma tumors in vivo.
Treatment of Congenital Hyperinsulinism with Lanreotide Acetate (Somatuline Autogel)
Authors: Modan-Moses Dalit , Koren Ilana , Mazor-Aronovitch Kineret , Pinhas-Hamiel Orit , Landau Heddy 
Published: June 2011

Abstract

Context:
Congenital hyperinsulinism (CH) may be treated conservatively in many children with octreotide given by multiple sc injections or via an insulin pump.

Objective:
We describe two children treated with a once-monthly injection of a long-acting somatostatin analog.

Patients and Methods:
Both patients presented with hypoglycemia 30 min after birth and were subsequently diagnosed with CH. Patients were initially treated with diazoxide, hydrochlorothiazide, frequent feedings, and octreotide via an insulin pump. With this therapy, they were normoglycemic with a good growth rate, normal weight gain, and excellent neurodevelopment. Treatment with the long-acting somatostatin analog lanreotide acetate (Somatuline Autogel), administered by deep sc injection of 30 mg once a month, was started at the ages of 4½ and 4 yr, respectively. Octreotide infusion was gradually weaned over 1 month. Continuous glucose monitoring after discontinuation of pump therapy showed normoglycemia. The first patient has now been treated with the lanreotide acetate for over 5 yr, and the second for 3 yr. Treatment is well-tolerated, and both the patients and their parents are satisfied with the transition from pump therapy to once-a-month injection and prefer it to pump therapy.

Conclusion:
Lanreotide acetate may be a safe and effective alternative to octreotide pump therapy in patients with CH, offering an improved quality of life. Longer follow-up of a larger patient group is needed.
Analytical evaluation of a high-sensitivity troponin T assay and its clinical assessment in acute coronary syndrome
Authors: Chenevier-Gobeaux Camille , Meune Christophe , Blanc Marie-Céline , Cynober Luc , Jaffray Patrick , Lefevre Guillaume 
Published: June 2011

Background The recently developed, highly sensitive cardiac troponin T (hs-cTnT) immunoassay improves the detection of acute myocardial infarction (AMI). However, this assay requires further analytical and clinical evaluation. Methods Imprecision, linearity, limits of quantification and interferences were evaluated; hs-cTnT was compared with a conventional cardiac troponin I assay (cTnI), performed on an X-pand®HM, in a population of patients with suspected AMI. Finally, the 99th percentile cut-off point for a reference population was explored in 213 healthy control subjects. Results Imprecision analysis demonstrated coefficients of variation (CVs) below 4%, linearity showed a 0.999 coefficient of correlation, with excellent recovery (99.9%) and a limit of quantification (10%CV) was found at 9.2 ng/L. A negative interference (>20%) with haemolysis was observed when supplemental haemoglobin was above 0.25 g/dL. Patients with suspected AMI more frequently displayed an increased hs-cTnT (83%) than an increased cTnI (55%, P < 0.01). Unstable angina was present in 63% of patients with an increased hs-cTnT associated with no increase in cTnI. The 99th percentile value for our reference population was 16.9 ng/L. In 213 healthy blood donors, hs-cTnT levels were significantly correlated with age ( P < 0.0001), and were higher in men than in women ( P < 0.0001). Conclusions The analytical performance of hs-cTnT complied with the international guidelines for AMI detection. Determining the degree of haemolysis in a sample is of paramount importance to the interpretation of hs-cTnT results. The 99th percentile value of our reference population was established.
“The Secret at the Root”: Performing African American Religious Modernity in Hall Johnson'sRun, Little Chillun
Authors: Weisenfeld Judith 
Published: June 2011

AbstractFrancis Hall Johnson's (1888–1970) work to preserve and promote Negro spirituals places him among the twentieth century's most influential interpreters of African American religious music. Johnson was most closely associated with Marc Connelly's 1930 Pulitzer Prize-winning play,The Green Pastures, for which he served as musical arranger and choral conductor. His participation in this production, which became a lightning rod for discussions about the nature of black religious thought, made him sharply aware of the complex terrain of popular culture representations of African American religious life for the consumption of white audiences. This article examines Johnson's 1933 “music-drama,”Run, Little Chillun, through which he hoped to counter the commonly deployed tropes of African Americans as a simple, naturally religious people. Moderately successful on Broadway, the production did particularly well when revived in California in 1938 and 1939 as part of the Federal Theatre and Federal Music projects.Most critics found Johnson's presentation of black Baptist music and worship to be thrillingly authentic but were confused by the theology of the drama's other religious community, the Pilgrims of the New Day. Examining Johnson's Pilgrims of the New Day in light of his interest in Christian Science and New Thought reveals a broader objective than providing a dramatic foil for the Baptists and a platform for endorsing Christianity. With his commitment to and expertise with vernacular forms of African American religious culture unassailable, Johnson presented a critique of the conservative tendencies and restrictive parochialism of some black church members and leaders and insisted on the ability of the individual religious self to range freely across a variety of spiritual possibilities. In doing so, he presented “the secret at the root” of black culture as not only revealing the spiritual genius of people of African descent but also as offering eternal and universal truths not bound by race.
Effects of Stubble Height and Cutting Frequency on Regrowth of Berseem Clover in a Mediterranean Semiarid Environment
Authors: Giambalvo Dario , Amato Gaetano , Stringi Luigi 
Published: June 2011

ABSTRACTDefoliation management of forage crops affects endogenous reserves (in the root and in the stubble), the residual leaf area, and, consequently, the regrowth and biomass yield. The aim of this study was to evaluate the effect of cutting frequency (28‐d vs. 35‐d intervals) and stubble height (3 vs. 6 cm) on forage yield, regrowth, and persistence of berseem clover (Trifolium alexandrinum L.). Neither cutting interval nor cutting height affected plant survival during the crop cycle. Frequent clipping reduced crop yield. Residual biomass and leaf area were less when plants were cut at a height of 3 cm compared with 6 cm, but stubble height did not affect the total amount of dry matter (DM) removed. However, with a cutting interval of 28 d, DM yield was greater with a stubble height of 6 cm compared with 3 cm, whereas stubble height generally had no effect with a cutting interval of 35 d. This study shows that severe defoliation, which substantially reduces residual photosynthetic area, forces berseem clover plants to mobilize reserves from the taproot. With frequent clipping, taproot reserves are depleted and regrowth is impaired, whereas less frequent clipping enables taproot reserves to be restored. In contrast, less severe defoliation, which results in a considerable residual leaf area, promotes rapid regrowth regardless of the frequency of defoliation.
Exploring and Exploiting Genetic Variation from Unadapted Sorghum Germplasm in a Breeding Program
Authors: Jordan D. R. , Mace E. S. , Cruickshank A. W. , Hunt C. H. , Henzell R. G. 
Published: June 2011

ABSTRACTLoss of genetic diversity in elite breeding populations is often identified as a potential impediment to future genetic gain. The use of diverse unadapted germplasm in breeding has been suggested as one way of combating this problem but often proves impractical, due to the poor performance of progeny produced by crosses between adapted and unadapted parent lines. This study evaluates the effectiveness of a breeding method aimed at utilizing unadapted sorghum [Sorghum bicolor (L.) Moench] germplasm. The method involves producing large BC1F1 populations, using a single elite line as the recurrent parent, and then selecting the resulting progeny for key adaptive traits (e.g., height and flowering time). Populations of 30 to 90 BC1F4 lines derived from 56 unadapted parents were then evaluated in hybrid combination in 21 trials over a 4‐yr period. The unadapted sources included lines with geographic or racial diversity, phenotypic diversity for key traits, elite lines from breeding programs in other countries, and cross‐compatible wild species. Despite strong selection for acceptable height and maturity, considerable genetic variation for grain yield was retained in the populations, with molecular marker analysis indicating an average of 22% of the genome being retained in each line as compared with a theoretical 25% in the absence of selection. In all cases progeny were identified in each population that performed significantly better than the recurrent parent hybrid for grain yield, and in some cases specific adaptation of particular populations was observed. The method we used proved to be an effective way to introduce new alleles from unadapted sorghum germplasm into elite breeding material. The potential of the populations as a resource for nested association mapping to elucidate the architecture of complex traits is discussed.
General Resistance in Maize to Southern Rust (Puccinia polysora Underw.)
Authors: Brewbaker James L. , Kim Soon Kwon , So Yoon Sup , Logroño Manuel , Moon Hyeon Gui , Ming Reiguang , Lu Xiao Wu , Josue Aleksander D. 
Published: June 2011

ABSTRACTSouthern corn rust (Puccinia polysora Underw.) is a major tropical disease that can lead to severe yield losses in the tropics. Occasionally it becomes of concern in temperate regions, as in 2010. We summarize 45 yr of research on the occurrence, genetic basis, and breeding of general resistance. Trials were conducted in Colombia, Hawaii, Nigeria, the Philippines, Texas, and Thailand. Temperate maize proved uniformly susceptible. No racially specific monogenes were effective. Resistance varied continuously among tropical inbreds and many of these showed stable intermediate tolerance. Two diallel populations revealed high correlations of inbred values with hybrid array means and slight heterosis for resistance. Narrow‐sense heritabilities were 51% and 66%, and mean square ratios for general to specific combining ability (GCA:SCA) were 7.8 and 10.7 to 1. Generation mean analyses were performed on six sets of families. Mean and additive effects were significant across families, while significant nonadditive effects were rare. Heritability values ranged from 19% to 49%. A set of recombinant lines segregated a primary susceptibility locus on chromosome 6. Studies of 137 near‐isogenic inbred lines (NILs) of resistant tropical inbred Hi27 revealed a dominant susceptibility quantitative trait locus (QTL) in the NIL for dwarf‐1 locus, but linkage could not be confirmed. Premature senescence was associated with rust infections in many NILs, emphasizing the ubiquity of modifying genes. No correlation existed between resistance to southern and common rusts. Resistant tropical inbreds and populations were bred to serve as sources for future improvement.
Bayesian Estimation of the Additive Main Effects and Multiplicative Interaction Model
Authors: Crossa José , Perez‐Elizalde Sergio , Jarquin Diego , Cotes José Miguel , Viele Kert , Liu Genzhou , Cornelius Paul L. 
Published: June 2011

ABSTRACTMuch research has been conducted using least squares estimates of the linear–bilinear model additive main effects and multiplicative interaction (AMMI). The main difficulty with the standard linear–bilinear models is that statistical inference on the bilinear effects of genotype × environment interaction cannot be incorporated easily into the biplot of the first two components. This research proposes a Bayesian approach for the inference on the parameters of the AMMI model using a Gibbs sampler that saves computing time and makes the algorithm stable. Data from one maize (Zea mays L.) multi‐environment trial (MET) was used for illustration. Vague but proper prior distributions were introduced. Results show that the various Markov chain Monte Carlo convergence criteria were met for all parameters. Bivariate highest posterior density (HPD) regions for the Bayesian–AMMI interactions are shown in the biplot of the first two bilinear components; these regions offer a statistical inference on the bilinear parameters and allow visualizing homogeneous groups of environments and genotypes.
Grazing Behavior and Diet Preference of Beef Steers Grazing Adjacent Monocultures of Tall Fescue and Alfalfa: II. The Role of Novelty
Authors: Boland Holly T. , Scaglia Guillermo , Notter David R. , Rook Andrew J. , Swecker William S. , Abaye Azenegashe O. 
Published: June 2011

ABSTRACTDomestic ruminants select a mixed diet when grazing heterogeneous pastures. Adjacent monocultures allow diet preference to be evaluated without certain constraints that could influence diet selection; however, few forage species have been evaluated. Adjacent monocultures of tall fescue (Festuca arundinaceaSchreb.) and alfalfa (Medicago sativaL. ssp.sativa) were used to test the theories that selection of mixed diets is influenced by a plant's “novelty,” and that regardless of forage species, cattle will have a partial preference for legumes over grasses. Cattle without previous experience eating alfalfa spent 78% of total grazing time eating alfalfa, whereas after having experience grazing alfalfa they spent less (P= 0.04) time grazing alfalfa (72%). Overall, proportion of the day spent grazing was less (P= 0.001) when alfalfa was novel (40%) than when steers were experienced with both forages (46%). Proportion of the day spent idling was greater (P< 0.001) when alfalfa was novel (35%) than when both forages were familiar (26%). The proportion of grazing time in alfalfa was greater (P= 0.02) in the afternoon (76.8%) than in the morning (72.1%), differing from previous studies that reported a decline in legume preference over the day with an increased grass preference in the afternoon. Application of adjacent monocultures in production systems would benefit from additional research on performance of cattle grazing in this paddock arrangement.