bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice
Authors: Fazio Elena N , DiMattia Gabriel E , Chadi Sami A , Kernohan Kristin D , Pin Christopher L 
Published: May 2011

Abstract

Background
Stanniocalcin 2 (STC2) is a secreted protein activated by (PKR)-like Endoplasmic Reticulum Kinase (PERK) signalling under conditions of ER stress in vitro. Over-expression of STC2 in mice leads to a growth-restricted phenotype; however, the physiological function for STC2 has remained elusive. Given the relationship of STC2 to PERK signalling, the objective of this study was to examine the role of STC2 in PERK signalling in vivo.

Results
Since PERK signalling has both physiological and pathological roles in the pancreas, STC2 expression was assessed in mouse pancreata before and after induction of injury using a cerulein-induced pancreatitis (CIP) model. Increased Stc2 expression was identified within four hours of initiating pancreatic injury and correlated to increased activation of PERK signalling. To determine the effect of STC2 over-expression on PERK, mice systemically expressing human STC2 (STC2

Tg
) were examined. STC2

Tg
pancreatic tissue exhibited normal pancreatic morphology, but altered activation of PERK signalling, including increases in Activating Transcription Factor (ATF) 4 accumulation and autophagy. Upon induction of pancreatic injury, STC2

Tg
mice exhibited limited increases in circulating amylase levels and increased maintenance of cellular junctions.

Conclusions
This study links STC2 to the pathological activation of PERK in vivo, and suggests involvement of STC2 in responding to pancreatic acinar cell injury.
Efficient induction of CD25- iTreg by co-immunization requires strongly antigenic epitopes for T cells
Authors: Geng Shuang , Yu Yang , Kang Youmin , Pavlakis George , Jin Huali , Li Jinyao , Hu Yanxin , Hu Weibin , Wang Shuang , Wang Bin 
Published: May 2011

Abstract

Background
We previously showed that co-immunization with a protein antigen and a DNA vaccine coding for the same antigen induces CD40low IL-10high tolerogenic DCs, which in turn stimulates the expansion of antigen-specific CD4+CD25-Foxp3+ regulatory T cells (CD25- iTreg). However, it was unclear how to choose the antigen sequence to maximize tolerogenic antigen presentation and, consequently, CD25- iTreg induction.

Results
In the present study, we demonstrated the requirement of highly antigenic epitopes for CD25- iTreg induction. Firstly, we showed that the induction of CD25- iTreg by tolerogenic DC can be blocked by anti-MHC-II antibody. Next, both the number and the suppressive activity of CD25- iTreg correlated positively with the overt antigenicity of an epitope to activate T cells. Finally, in a mouse model of dermatitis, highly antigenic epitopes derived from a flea allergen not only induced more CD25- iTreg, but also more effectively prevented allergenic reaction to the allergen than did weakly antigenic epitopes.

Conclusions
Our data thus indicate that efficient induction of CD25- iTreg requires highly antigenic peptide epitopes. This finding suggests that highly antigenic epitopes should be used for efficient induction of CD25- iTreg for clinical applications such as flea allergic dermatitis.
Estimation of affinities of ligands in mixtures via magnetic recovery of target-ligand complexes and chromatographic analyses: chemometrics and an experimental model
Authors: Yang Xiaolan , Xie Yanling , Pu Jun , Zhao Hua , Liao Juan , Yuan Yonghua , Zhu Sha , Long Gaobo , Zhang Chun , Yuan Huidong , Chen Yiwen , Liao Fei 
Published: May 2011

Abstract

Background
The combinatorial library strategy of using multiple candidate ligands in mixtures as library members is ideal in terms of cost and efficiency, but needs special screening methods to estimate the affinities of candidate ligands in such mixtures. Herein, a new method to screen candidate ligands present in unknown molar quantities in mixtures was investigated.

Results
The proposed method involves preparing a processed-mixture-for-screening (PMFS) with each mixture sample and an exogenous reference ligand, initiating competitive binding among ligands from the PMFS to a target immobilized on magnetic particles, recovering target-ligand complexes in equilibrium by magnetic force, extracting and concentrating bound ligands, and analyzing ligands in the PMFS and the concentrated extract by chromatography. The relative affinity of each candidate ligand to its reference ligand is estimated via an approximation equation assuming (a) the candidate ligand and its reference ligand bind to the same site(s) on the target, (b) their chromatographic peak areas are over five times their intercepts of linear response but within their linear ranges, (c) their binding ratios are below 10%. These prerequisites are met by optimizing primarily the quantity of the target used and the PMFS composition ratio.
The new method was tested using the competitive binding of biotin derivatives from mixtures to streptavidin immobilized on magnetic particles as a model. Each mixture sample containing a limited number of candidate biotin derivatives with moderate differences in their molar quantities were prepared via parallel-combinatorial-synthesis (PCS) without purification, or via the pooling of individual compounds. Some purified biotin derivatives were used as reference ligands. This method showed resistance to variations in chromatographic quantification sensitivity and concentration ratios; optimized conditions to validate the approximation equation could be applied to different mixture samples. Relative affinities of candidate biotin derivatives with unknown molar quantities in each mixture sample were consistent with those estimated by a homogenous method using their purified counterparts as samples.

Conclusions
This new method is robust and effective for each mixture possessing a limited number of candidate ligands whose molar quantities have moderate differences, and its integration with PCS has promise to routinely practice the mixture-based library strategy.
Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction
Authors: Chen Yen-Ta , Sun Cheuk-Kwan , Lin Yu-Chun , Chang Li-Teh , Chen Yung-Lung , Tsai Tzu-Hsien , Chung Sheng-Ying , Chua Sarah , Kao Ying-Hsien , Yen Chia-Hung , Shao Pei-Lin , Chang Kuan-Cheng , Leu Steve , Yip Hon-Kan 
Published: May 2011

Abstract

Background
Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury.

Methods
Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 106 autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed.

Results
Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02)

Conclusion
ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.
Metabolic syndrome: definitions and controversies
Authors: Kassi Eva , Pervanidou Panagiota , Kaltsas Gregory , Chrousos George 
Published: May 2011

AbstractMetabolic syndrome (MetS) is a complex disorder defined by a cluster of interconnected factors that increase the risk of cardiovascular atherosclerotic diseases and diabetes mellitus type 2. Currently, several different definitions of MetS exist, causing substantial confusion as to whether they identify the same individuals or represent a surrogate of risk factors. Recently, a number of other factors besides those traditionally used to define MetS that are also linked to the syndrome have been identified. In this review, we critically consider existing definitions and evolving information, and conclude that there is still a need to develop uniform criteria to define MetS, so as to enable comparisons between different studies and to better identify patients at risk. As the application of the MetS model has not been fully validated in children and adolescents as yet, and because of its alarmingly increasing prevalence in this population, we suggest that diagnosis, prevention and treatment in this age group should better focus on established risk factors rather than the diagnosis of MetS.
Positional effect of phosphorylation sites 266 and 267 in the cytoplasmic domain of the E2 protein of hepatitis C virus 3a genotype: Interferon Resistance analysis via Sequence Alignment
Authors: Rafique Shazia , Idrees Muhammad , Ilyas Muhammad , Hussain Abrar , Ali Muhammad , Ali Liaqat , Butt Sadia , Afzal Samia , Ur Rehman Irshad , Saleem Sana 
Published: May 2011

AbstractBackgroundInterferon is well thought-out as the key defence against all infections including HCV. The only treatment for HCV infection is pegylated interferon alpha (IFN-α) but unluckily more than half of the infected individuals do not act in response to the cure and become chronic HCV carriers. The mechanism how HCV induce interferon resistance is still elusive. It is recently reported that HCV envelope protein 2 interacts with PKR which is the interferon-inducible protein kinase and which in turn blocks the activity of its target molecule called eukaryotic initiation factor elF2. Sequence analysis of Envelope protein reveals it contains a domain homologous to phosphorylation sites of PKR andthe translation initiation factor eIF2alpha. Envelope protein competes for phosphorylation with PKR. Inhibition of kinase activity of PKR is postulated as a mechanism of to interferon (IFN) resistance.ResultsPresent study involves the insilico investigation of possible role of potential phosphorylation in envelope 2 protein of 3a genotype in interferon resistance. Envelope protein coding genes were isolated from local HCV isolates, cloned and sequenced. Phylogenetic analysis was done and tertiary structure of envelope gene was predicted. Visualization of phosphorylation in tertiary structure reveals that residue 266 and 267 of envelope gene 2 are surface exposed and their phosphorylation may compete with the phosphorylation of PKR protein and possibly involved in mediating Interferon Resistance.ConclusionA hybrid in-silico and wet laboratory approach of motif prediction, evolutionary and structural analysis has pointed out serine 266 and 267 of the HCV E2 gene as a hopeful claimant for the serine phosphorylation. Recognition of these nucleotide variations may assist to propose genotype precise therapy to avoid and resolve HCV infections.
The effects of linkage disequilibrium in large scale SNP datasets for MDR
Authors: Grady Benjamin J , Torstenson Eric S , Ritchie Marylyn D 
Published: May 2011

Abstract

Background
In the analysis of large-scale genomic datasets, an important consideration is the power of analytical methods to identify accurate predictive models of disease. When trying to assess sensitivity from such analytical methods, a confounding factor up to this point has been the presence of linkage disequilibrium (LD). In this study, we examined the effect of LD on the sensitivity of the Multifactor Dimensionality Reduction (MDR) software package.

Results
Four relative amounts of LD were simulated in multiple one- and two-locus scenarios for which the position of the functional SNP(s) within LD blocks varied. Simulated data was analyzed with MDR to determine the sensitivity of the method in different contexts, where the sensitivity of the method was gauged as the number of times out of 100 that the method identifies the correct one- or two-locus model as the best overall model. As the amount of LD increases, the sensitivity of MDR to detect the correct functional SNP drops but the sensitivity to detect the disease signal and find an indirect association increases.

Conclusions
Higher levels of LD begin to confound the MDR algorithm and lead to a drop in sensitivity with respect to the identification of a direct association; it does not, however, affect the ability to detect indirect association. Careful examination of the solution models generated by MDR reveals that MDR can identify loci in the correct LD block; though it is not always the functional SNP. As such, the results of MDR analysis in datasets with LD should be carefully examined to consider the underlying LD structure of the dataset.
Somatic and germline expression of piwi during development and regeneration in the marine polychaete annelid Capitella teleta
Authors: Giani Vincent C , Yamaguchi Emi , Boyle Michael J , Seaver Elaine C 
Published: May 2011

Abstract

Background
Stem cells have a critical role during adult growth and regeneration. Germline stem cells are specialized stem cells that produce gametes during sexual reproduction. Capitella teleta (formerly Capitella sp. I) is a polychaete annelid that reproduces sexually, exhibits adult growth and regeneration, and thus, is a good model to study the relationship between somatic and germline stem cells.

Results
We characterize expression of the two C. teleta orthologs of piwi, genes with roles in germline development in diverse organisms. Ct-piwi1 and Ct-piwi2 are expressed throughout the life cycle in a dynamic pattern that includes both somatic and germline cells, and show nearly identical expression patterns at all stages examined. Both genes are broadly expressed during embryonic and larval development, gradually becoming restricted to putative primordial germ cells (PGCs) and the posterior growth zone. In juveniles, Ct-piwi1 is expressed in the presumptive gonads, and in reproductive adults, it is detected in gonads and the posterior growth zone. In addition, Ct-piwi1 is expressed in a population of putative PGCs that persist in sexually mature adults, likely in a stem cell niche. Ct-piwi1 is expressed in regenerating tissue, and once segments differentiate, it becomes most prominent in the posterior growth zone and immature oocytes in regenerating ovaries of regenerating segments.

Conclusions
In C. teleta, piwi genes may have retained an ancestral role as genetic regulators of both somatic and germline stem cells. It is likely that piwi genes, and associated stem cell co-regulators, became restricted to the germline in some taxa during the course of evolution.
Interleukin-12 treatment down-regulates STAT4 and induces apoptosis with increasing ROS production in human natural killer cells
Authors: Huang Yong , Lei YingFeng , Zhang Hai , Zhang Mingjie , Dayton Andrew 
Published: May 2011

ABSTRACTNK cells are prominent mediators of the immunomodulating and antiangiogenic activity of IL-12. However, the effect of prolonged IL-12 treatment on NK cells is unclear. In this study, we observed that IL-12 initially activates NK cells, but prolonged IL-12 treatment specifically down-regulates IL-12 signaling and induces NK cell apoptosis associated with a significant reduction in cytolytic activity and IFN-γ production in response to further IL-12 stimulation. Further results demonstrate that prolonged IL-12 stimulation of NK cells specifically decreases the level of activated STAT4 protein, a critical IL-12 signaling component, through decreasing STAT4 mRNA and protein levels rather than inducing STAT4 protein degradation. IL-12 treatment induces NK cell activation as well as levels of ROS, but prolonged IL-12 treatment causes ROS accumulation, which in turn, results in the loss of Δψm, the release of cytochrome c, and the activation of caspase-3, resulting in NK cell apoptosis. These findings provide new insights into IL-12 regulation in human NK cells, where IL-12 initially promotes NK cell activation but subsequently limits this response through a negative-feedback mechanism.
Estrogen Sulfotransferase Is Expressed in Subcutaneous Adipose Tissue of Obese Humans in Association with TNF-α and SOCS3
Authors: Ahima Rexford S. , Stanley Takara L. , Khor Victor K. , Zanni Markella V. , Grinspoon Steven K. 
Published: May 2011

Abstract

Context and Objective:
Estrogen sulfotransferase (EST) catalyzes the inactivation of estrone and estradiol in numerous tissues. Animal studies suggest that EST modulates glucose and lipid metabolism in adipose tissue, but it is unknown whether EST is expressed in human adipose tissue and, if so, how its expression relates to features of the metabolic syndrome.

Design and Participants:
Cross-sectional data from 16 obese men and women with metabolic dysregulation were collected as part of a larger randomized trial at an academic medical center.

Outcome Measures:
Participants underwent assessment of body composition, oral glucose tolerance testing, measurement of serum hormones and inflammatory markers, and sc fat biopsy to assess adipose expression of TNF-α, suppressor of cytokine signaling 3 (SOCS3), leptin, adiponectin, and EST.

Results:
EST expression was detectable in sc adipose tissue from both men and women. Log10 EST mRNA was not significantly associated with age, race, sex or menopausal status, or circulating levels of estrogen or testosterone. In univariate analysis, log10 EST mRNA was significantly associated with visceral adipose tissue area (r = 0.57, P = 0.02) as well as adipose tissue expression of TNF-α (r = 0.94, P &lt; 0.0001) and SOCS3 mRNA (r = 0.93, P &lt; 0.0001). The associations between EST expression and TNF-α and SOCS3 held in multivariate modeling controlling for age, race, sex and menopausal status, and visceral adiposity. EST expression was not significantly associated with the adipose tissue levels of leptin or adiponectin expression.

Conclusions:
EST is expressed in abdominal sc adipose tissue of both obese males and females in association with expression of TNF-α and SOCS3, suggesting potential roles in inflammation. Further studies are needed to determine the specific metabolic roles of EST expression in human adipose tissue.
Single-crystal Copper–Phthalocyanine Nanorods Self-assembled by a Solvent Evaporation Method
Authors: Xiao Yan , Li Yan , Zhang Meng , Wang Feng-Xia , Pan Ge-Bo 
Published: May 2011

Abstract
Copper–phthalocyanine (CuPc) nanorods were prepared on a Si substrate by a solvent evaporation method. The results of XRD indicate that the CuPc nanorods were β-phase single crystals and grown along the [010] direction. The diameters of CuPc nanorods depend on the solution concentration, and the formation of CuPc nanorods is insensitive to the solvents and substrates. This implies that the growth of CuPc nanorods is dominated by the intrinsic π–π stacking between Pc rings. In addition, a p–n junction was formed between CuPc nanorod and Si substrate.
Assessing the Suitability of Fractional Polynomial Methods in Health Services Research: A Perspective on the Categorization Epidemic
Authors: Williams Jennifer Stewart 
Published: May 2011

Objective To show how fractional polynomial methods can usefully replace the practice of arbitrarily categorizing data in epidemiology and health services research. Methods A health service setting is used to illustrate a structured and transparent way of representing nonlinear data without arbitrary grouping. Results When age is a regressor its effects on an outcome will be interpreted differently depending upon the placing of cutpoints or the use of a polynomial transformation. Conclusions Although it is common practice, categorization comes at a cost. Information is lost, and accuracy and statistical power reduced, leading to spurious statistical interpretation of the data. The fractional polynomial method is widely supported by statistical software programs, and deserves greater attention and use.
New Experiments for an Undivided Genetics
Authors: Rose Michael R , Mueller Laurence D , Burke Molly K 
Published: May 2011

Abstract
There used to be a broad split within the experimental genetics research community between those who did mechanistic research using homozygous laboratory strains and those who studied patterns of genetic variation in wild populations. The former benefited from the advantage of reproducible experiments, but faced difficulties of interpretation given possible genomic and evolutionary complexities. The latter research approach featured readily interpreted evolutionary and genomic contexts, particularly phylogeny, but was poor at determining functional significance. Such burgeoning experimental strategies as genome-wide analysis of quantitative trait loci, genotype–phenotype associations, and the products of experimental evolution are now fostering a unification of experimental genetic research that strengthens its scientific power.
Lacan et le processus de deuil dans la cure
Authors: Sauze Thierry 
Published: May 2011

Après avoir abordé l’essentiel des conceptions freudiennes quant à l’orientation du procès de la cure et examiné ce qui faisait question dans les théories qui prévalaient avant l’apport de Lacan, l’auteur dégage le sens à donner aux termes de « direction de la cure » dans l’article éponyme qui fit date dans les Écrits. À partir de ses articulations essentielles, il montre en quoi le chemin logique et éthique de la cure conduit à un processus de deuil de toute substantialisation de l’être. Il décrit ensuite comment, selon lui, la théorie dernière de Lacan du nouage borroméen des trois dimensions constitutives du « parlêtre » permet, au-delà de la complexité de son élaboration et contrairement à ce qui a pu en être dit ici ou là, une simplification et une efficacité renouvelée de la pratique analytique.
Le déclin de l'interprétation : de l'analyste interprète à l'émergence de la perlaboration
Authors: Sédat Jacques 
Published: May 2011

Alors que Freud avait méthodologiquement mis en place les premiers éléments de la direction de la cure, en 1985, avec les Études sur l’hystérie , il revient, en particulier avec l’analyse de Dora, à une position de théoricien qui veut vérifier la validité de son Interprétation du rêve . Ces approches divergentes amènent à réfléchir à l’exigible déclin de l’interprétation dans la cure : renoncer à une position hégémonique de savoir sur les pensées de l’autre, qui nous sont inaccessibles ; rester dans une neutralité axiologique face à chaque patient singulier.
Les théories kleiniennes de la cure
Authors: Parmentier Sabine 
Published: May 2011

La technique kleinienne issue du jeu avec l’enfant accorde une grande importance à tout ce qui fait partie du « champ » relationnel : jeux, gestes, postures, position des objets les uns par rapport aux autres, mais aussi aux communications verbales de l’enfant. C’est de là que découle l’attention portée au cadre psychanalytique, au transfert aussi bien positif que négatif, aux interprétations qui visent le point d’urgence où l’angoisse atteint son acmé. Cela explique aussi la façon de voir la fin de l’analyse, comme un moment dans la tâche de dépasser tout le long d’une vie la position dépressive. Mais aussi par l’élargissement des intérêts de l’enfant, par une plus grande capacité d’élaboration et une plus grande stabilité psychique.