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Triose Phosphate Isomerase Deficiency Is Caused by Altered Dimerization–Not Catalytic Inactivity–of the Mutant Enzymes
Triosephosphate isomerase (TPI) deficiency is an autosomal recessive disorder caused by various mutations in the gene encoding the key glycolytic enzyme TPI. A drastic decrease in TPI activity and an increased level of its substrate, dihydroxyacetone phosphate, have been measured in unpurified cell…
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Human Resistin Is a Systemic Immune-Derived Proinflammatory Cytokine Targeting both Leukocytes and Adipocytes
The characteristics of human resistin (RETN) are unclear and controversial despite intensive adipose-focused research. Its transcriptional and functional similarity with the murine myeloid-specific and CCAAT/enhancer binding protein epsilon (Cebpe)-dependent gene, resistin-like gamma (Retnlg), is…
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A Mouse Stromal Response to Tumor Invasion Predicts Prostate and Breast Cancer Patient Survival
Primary and metastatic tumor growth induces host tissue responses that are believed to support tumor progression. Understanding the molecular changes within the tumor microenvironment during tumor progression may therefore be relevant not only for discovering potential therapeutic targets, but also…
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A Weakened Transcriptional Enhancer Yields Variegated Gene Expression
Identical genes in the same cellular environment are sometimes expressed differently. In some cases, including the immunoglobulin heavy chain (IgH) locus, this type of differential gene expression has been related to the absence of a transcriptional enhancer. To gain additional information on the…
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Electrochemically Generated Acid and Its Containment to 100 Micron Reaction Areas for the Production of DNA Microarrays
An addressable electrode array was used for the production of acid at sufficient concentration to allow deprotection of the dimethoxytrityl (DMT) protecting group from an overlaying substrate bound to a porous reaction layer. Containment of the generated acid to an active electrode of 100 micron…
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Restructuring of Pancreatic Islets and Insulin Secretion in a Postnatal Critical Window
Function and structure of adult pancreatic islets are determined by early postnatal development, which in rats corresponds to the first month of life. We analyzed changes in blood glucose and hormones during this stage and their association with morphological and functional changes of alpha and…
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Use of Confocal Laser as Light Source Reveals Stomata-Autonomous Function
In most terrestrial plants, stomata open during the day to maximize the update of CO2 for photosynthesis, but they close at night to minimize water loss. Blue light, among several environmental factors, controls this process. Stomata response to diverse stimuli seems to be dictated by the behaviour…
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Ribosomal Protein Gene Knockdown Causes Developmental Defects in Zebrafish
The ribosomal proteins (RPs) form the majority of cellular proteins and are mandatory for cellular growth. RP genes have been linked, either directly or indirectly, to various diseases in humans. Mutations in RP genes are also associated with tissue-specific phenotypes, suggesting a possible role…
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Efficient Non-Viral Ocular Gene Transfer with Compacted DNA Nanoparticles
Background: The eye is an excellent candidate for gene therapy as it is immune privileged and much of the disease-causing genetics are well understood. Towards this goal, we evaluated the efficiency of compacted DNA nanoparticles as a system for non-viral gene transfer to ocular tissues. The…
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A Virtual Reprise of the Stanley Milgram Obedience Experiments
Background: Stanley Milgram's 1960s experimental findings that people would administer apparently lethal electric shocks to a stranger at the behest of an authority figure remain critical for understanding obedience. Yet, due to the ethical controversy that his experiments ignited, it is nowadays…
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Mapping the Antigenicity of the Parasites in Leishmania donovani Infection by Proteome Serology
Background: Leishmaniasis defines a cluster of protozoal diseases with diverse clinical manifestations. The visceral form caused by Leishmania donovani is the most severe. So far, no vaccines exist for visceral leishmaniasis despite indications of naturally developing immunity, and sensitive…
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Is Adipose Tissue a Place for Mycobacterium tuberculosis Persistence?
Background: Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), has the ability to persist in its human host for exceptionally long periods of time. However, little is known about the location of the bacilli in latently infected individuals. Long-term mycobacterial persistence…
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Predator Mimicry: Metalmark Moths Mimic Their Jumping Spider Predators
Cases of mimicry provide many of the nature's most convincing examples of natural selection. Here we report evidence for a case of predator mimicry in which metalmark moths in the genus Brenthia mimic jumping spiders, one of their predators. In controlled trials, Brenthia had higher survival rates…
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Fine Tuning of Globin Gene Expression by DNA Methylation
Expression patterns in the globin gene cluster are subject to developmental regulation in vivo. While the γA and γG genes are expressed in fetal liver, both are silenced in adult erythrocytes. In order to decipher the role of DNA methylation in this process, we generated a YAC transgenic mouse…
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Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells
Background: Transcription factor Cdx4 and transcriptional coregulator menin are essential for Hoxa9 expression and normal hematopoiesis. However, the precise mechanism underlying Hoxa9 regulation is not clear. Methods and Findings: Here, we show that the expression level of Hoxa9 is correlated with…
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Does FXIII Deficiency Impair Wound Healing after Myocardial Infarction?
Inadequate healing of myocardial infarction may contribute to local expansion of the infarct, frequently leading to chamber dilation, heart failure, or myocardial rupture. Experimental evidence in mouse models suggests that Factor XIII might play a key role in wound healing, and low persistent…
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Adaptive Response of a Gene Network to Environmental Changes by Fitness-Induced Attractor Selection
Cells switch between various stable genetic programs (attractors) to accommodate environmental conditions. Signal transduction machineries efficiently convey environmental changes to the gene regulation apparatus in order to express the appropriate genetic program. However, since the number of…
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Modulation of T Cell Function by Combination of Epitope Specific and Low Dose Anticytokine Therapy Controls Autoimmune Arthritis
Innate and adaptive immunity contribute to the pathogenesis of autoimmune arthritis by generating and maintaining inflammation, which leads to tissue damage. Current biological therapies target innate immunity, eminently by interfering with single pro-inflammatory cytokine pathways. This approach…
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Probe Selection and Expression Index Computation of Affymetrix Exon Arrays
Background: There is great current interest in developing microarray platforms for measuring mRNA abundance at both gene level and exon level. The Affymetrix Exon Array is a new high-density gene expression microarray platform, with over six million probes targeting all annotated and predicted…
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Clinical Outcome of HIV-Infected Patients with Sustained Virologic Response to Antiretroviral Therapy: Long-Term Follow-Up of a Multicenter Cohort
Background: Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. Methods: Using data collected from ten…
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