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Molecular Coupling of Xist Regulation and Pluripotency
Area: DNA
Pluripotency key factors bind to Xist intron 1 in undifferentiated embryonic stem cells, report research groups from the Pasteur Institute in Paris and the University of Edinburgh, UK. During murine embryogenesis, the imprinted X chromosome inactivation can be reprogrammed in the inner cell mass of a pluripotent female blastocyst. The reversion is triggered by repression of Xist from the paternal X chromosome. The three main genetic factors underlying pluripotency, Nanog, Oct3/4 and Sox2, bind to Xist intron 1.
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FBXW7 Targets mTOR for Degradation and Cooperates with PTEN in Tumor Suppression
The enzyme mTOR (mammalian target of rapamycin) is selected for ubiquitination and subsequent degradation by binding to the tumour suppressor protein FBXW7
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Activation of Aldehyde Dehydrogenase-2 Reduces Ischemic Damage to the Heart
Mitochondrial aldehyde dehydrogenase 2 (ALDH2) was identified as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models by Che-Hong Chen and colleagues from the Stanford University (USA), using an unbiased proteomic search. The research team wanted to find a drug that limits the severity of ischemia-induced cardiac damage occurring after a myocardial infarction or certain cardiac surgical procedures.
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Epigenetic Reprogramming by Adenovirus E1A
Area: Cell Cycle
Epigenetic reprogramming by Adenovirus E1A that causes transformations of the cell were discovered by Roberto Ferrari and his co-workers from the University of California (USA).
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Censoring of Autoreactive B Cell Development by the Pre-B Cell Receptor
Area: Immunology
The pre-B cell receptor appears to censor the development of certain autoantibody-secreting cells, as Rebecca A. Keenan and her team from The Babraham Institute in Cambridge, UK report. The pre-B cell receptor is composed of immunoglobulin (Ig) heavy and substitute light chains. It seems to be involved in the negative selection of cells expressing heavy chains bearing the potential to generate autoantibodies. It thus may be an important factor in multifactorial autoimmune diseases. » Read more
New publication: Detection of Bacteria in water samples
Area: Bacteria
Anne Wolter et al. utilize a polyclonal anti-E. Coli antibody from antibodies-online for detecting E. Coli bacteria in water.
Pyogenic Bacterial Infections in Humans with MyD88 Deficiency
Areas: Bacteria, Immunology
Scientists from mainly French and Spanish universities and institutes recently described an extraordinary situation within a natural setting of human infection. Nine children, carrying an autosomal recessive MyD88 deficiency, suffered from pyogenic bacterial infections. The infections were life-threatening and often recurred, among them invasive pneumococcal disease.
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Sporadic Autonomic Dysregulation and Death Associated with Excessive Serotonin Autoinhibition
Area: Neurology
Excessive serotonin autoinhibition was found to be a risk factor for autonomic dysregulation by Enrica Audero and her colleagues from the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy. It could also be a mechanism by which altered serotonin homeostasis plays a role in sudden infant death syndrome.
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Germline Allele-Specific Expression of TGFBR1 Confers an Increased Risk of Colorectal Cancer
Area: Oncology
Germline allele-specific expression of the gene encoding TGF-β type I receptor (TGFBR1) occurs more frequently in colorectal cancer patients than in healthy controls. This was shown in a study by Laura Valle and her colleagues from The Ohio State University (USA).
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Mouse embryonic stem cell–based functional assay to evaluate mutations in BRCA2
Area: Oncology
Researchers of the National Cancer Institute (USA) recently reported the establishment of a simple, versatile and reliable assay to test for the functional significance of mutations in the BRCA2 gene. Humans carrying mutations in the genes BRCA1 and BRCA2 have a risk of 80% to develop breast cancer by the age of 70. Reliable identification of mutation carriers can reduce mortality through preventive measures and early diagnosis. The tests available until now could only detect BRCA1 and BRCA2 variants that clearly disrupt the gene product.
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A tumor necrosis factor-mediated pathway promoting autosomal dominant polycystic kidney disease
Area: Cytokines
Tumor necrosis factor α (TNF-α) was discovered to disturb the connection between polycystin-2 and the plasma membrane by induction of the scaffold protein FIP2, as scientists from the Stowers Institute for Medical Research (USA) report. TNF-α is an inflammatory cytokine, found in the cystic fluid of humans suffering from autosomal dominant polycystic kidney disease (ADPKD). The disease is caused by heterozygous mutations of the polycystin-1 (PKD1) or polycystin-2 genes (PKD2).
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Amyloid- protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory
Area: Morbus Alzheimer, Receptors
Scientists of Harvard University succeeded in extracting soluble amyloid-beta protein oligomers directly from the cerebral cortex of Morbus Alzheimer patients. The amyloid-beta oligomers effectively inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus, the brain centre of long-term memory.
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Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress
Areas: Transcription factors
The winged helix transcription factor Foxa2 is required for normal bile acid homeostasis, as a study conducted by Irina M. Bochkis and colleagues from the University of Pennsylvania (USA). The bile production in the liver is essential for the absorption of lipophilic nutrients. If the bile acid homeostasis is disrupted, cholestatic liver disease and endoplasmic reticulum (ER) stress can be the results.
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Effective induction of high-titer antibodies by viral vector vaccines
Areas: Immunology, Virology
A lab group from the University of Oxford discovered that a recombinant adenovirus–poxvirus prime-boost immunisation regime which induces strong T-cell immunogenicity is able to cause fulminant antigen-specific antibody responses. The scientists found a simple, complement-based adjuvant to support immunogenicity even more.
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Y-box-1 protein (Yb-1) and breast cancer: Prognostic factor and target for therapy
Area: Oncology
A research group at the University of British Columbia (Vancouver) led by Sandy Dunn underlined the potential of Y-box-1 (YB-1) for the prognosis and therapy of breast cancer in two recent publications.
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NALP3 inflammasome is involved in the innate immune response to amyloid-beta
The inflammasome of cytoplasmic receptor NALP3 was identified by Annett Halle and her colleagues from the University of Massachusetts (USA) as a sensor of amyloid-β in a process in which amyloid-β is phagocytosed, followed by lysosomal damage and the release of cathepsin B.
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Adenovirus Small e1a Alters Global Patterns of Histone Modification
A research team from the University of California recently showed that adenovirus small early region 1a (e1a) protein interaction with p300 and CBP result in a threefold reduction of total cellular histone H3 lysine 18 acetylation (H3K18). CBP and p300 seem to be essential for the reaction at this position because a specific hypoacetylation occurs at H3K18 upon knockdown of their genes. The SV40 T antigen was also observed to trigger H3K18 hypoacetylation.
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Plant Immunity Requires Conformational Charges of NPR1 via S-Nitrosylation and Thioredoxins
NPR1 is regulated by the opposing action of S-nitrosoglutathione and thioredoxins, as Yasuomi Tada and colleagues from the Duke University (USA) report.
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The Spread of Ras Activity Triggered by Activation of a Single Dendritic Spine
Area: Neurology
As scientists from the Watson School of Biological Sciences discovered, calcium ion-dependent synaptic signals in neurons can spread to couple multiple synapses on short stretches of dendrites. Individual dendritic spines segregate calcium ion accumulations from the dendrite and other spines. The accumulations were mediated by the N-methyl-D-aspartate (NMDA) receptor.
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Autophagy Is Essential for Preimplantation Development of Mouse Embryos
Areas: Autophagy, Metabolism
Autophagic degradation within early embryos seems to be essential for preimplantation development in mammals. A research group from the Tokyo Medical and Dental University, Japan analysed the degradation of maternal proteins in oocytes upon fertilisation.
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Modulation of Gene Expression via Disruption of NF-kappa-B Signaling by a Bacterial Small Molecule
Areas: Bacteria, Immunology
The bacterial N-3-oxo-dodecanoyl homoserine lactone (C12) selectively impairs the regulation of NF-κ-B functions in activated mammalian cells, according to the data of a research group from The Scripps Research Institute (USA). The nuclear transcription factor NF-κ-B is indispensable for the defence of the body against invading microbial pathogens. Activation of NF-κ-B controls the innate immune response, thus eradicating harmful pathogens.
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Anomalous Type 17 Response to Viral Infection by CD8+ T Cells Lacking T-bet and Eomesodermin
CD8+ T cells that have defective transcription factors T-bet and eomesodermin (Eomes) were shown to be unable to defend the body against lymphocytic choriomeningitis viral infection, as a study conducted by the University of Pennsylvania demonstrates.
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Eco1-Dependent Cohesin Acetylation During Establishment of Sister Chromatid Cohesion
Area: Cell Cycle
Eco1 modifies cohesin to stabilise sister chromatid cohesion. This has been observed by scientists from the Cancer Research UK London Research Institute. Sister chromosomes are bound to each other by chromosomal cohesin complexes ever since their synthesis in the S phase of mitosis. This is dependent on the acetyl transferase Eco1. Eco1 is associated with the replication fork but its way of function is yet unknown.
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Identifying Autism Loci and Genes by Tracing Recent Shared Ancestry
Area: Neurology
Subject of the study were families in which the parents were blood-related, which stresses the importance of heredity. The scientists analysed loci with large inherited homozygous deletions that were probably mutations. Among the genes affected by those deletions were PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58). The expression intensity of these genes changed according to neuronal activity, attributing thus to synaptic changes that underlie learning. Some other genes, like NHE9 (Na+/H+ exchanger 9), were also observed to carry possible mutations in patients with unrelated parents.
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Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons
Areas: Neurology, Signalling
Vascular-derived endothelins seem to be essential to axonal pathfinding and thus for the developing nervous system.
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