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Introduction of d-Glutamate at a Critical Residue of Aβ42 Stabilizes a Prefibrillary Aggregate with Enhanced Toxicity.

Warner, Christopher J A Dutta, Subrata Foley, Alejandro R Raskatov, Jevgenij A

Published in Chemistry (Weinheim an der Bergstrasse, Germany)

The amyloid beta peptide 42 (Aβ42) is an aggregation-prone peptide that plays a pivotal role in Alzheimer's disease. We report that a subtle perturbation to the peptide through a single chirality change at glutamate 22 leads to a pronounced delay in the β-sheet adoption of the peptide. This was accompanied by an attenuated propensity of the peptide...

Hematopoietic stem cell-specific GFP-expressing transgenic mice generated by genetic excision of a pan-hematopoietic rep...

Perez-Cunningham, Jessica Boyer, Scott W Landon, Mark Forsberg, E Camilla

Published in Experimental hematology

Selective labeling of specific cell types by expression of green fluorescent protein (GFP) within the hematopoietic system would have great utility in identifying, localizing, and tracking different cell populations in flow cytometry, microscopy, lineage tracing, and transplantation assays. In this report, we describe the generation and characteriz...

Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injur...

Zhang, Ling-Juan Sen, George L Ward, Nicole L Johnston, Andrew Chun, Kimberly Chen, Yifang Adase, Christopher Sanford, James A Gao, Nina Chensee, Melanie ...

Published in Immunity

Type 1 interferons (IFNs) promote inflammation in the skin but the mechanisms responsible for inducing these cytokines are not well understood. We found that IFN-β was abundantly produced by epidermal keratinocytes (KCs) in psoriasis and during wound repair. KC IFN-β production depended on stimulation of mitochondrial antiviral-signaling protein (M...

Phosphono Bisbenzguanidines as Irreversible Dipeptidomimetic Inhibitors and Activity-Based Probes of Matriptase-2.

Häußler, Daniela Mangold, Martin Furtmann, Norbert Braune, Annett Blaut, Michael Bajorath, Jürgen Stirnberg, Marit Gütschow, Michael

Published in Chemistry (Weinheim an der Bergstrasse, Germany)

Matriptase-2, a type II transmembrane serine protease, plays a key role in human iron homeostasis. Inhibition of matriptase-2 is considered as an attractive strategy for the treatment of iron-overload diseases, such as hemochromatosis and β-thalassemia. In the present study, synthetic routes to nine dipeptidomimetic inactivators were developed. Fiv...

IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.

Ennajdaoui, Hanane Howard, Jonathan M Sterne-Weiler, Timothy Jahanbani, Fereshteh Coyne, Doyle J Uren, Philip J Dargyte, Marija Katzman, Sol Draper, Jolene M Wallace, Andrew ...

Published in Cell reports

Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF...

Facilitating a culture of responsible and effective sharing of cancer genome data.

Siu, Lillian L Lawler, Mark Haussler, David Knoppers, Bartha Maria Lewin, Jeremy Vis, Daniel J Liao, Rachel G Andre, Fabrice Banks, Ian Barrett, J Carl ...

Published in Nature medicine

Rapid and affordable tumor molecular profiling has led to an explosion of clinical and genomic data poised to enhance the diagnosis, prognostication and treatment of cancer. A critical point has now been reached at which the analysis and storage of annotated clinical and genomic information in unconnected silos will stall the advancement of precisi...

TNF-α modulates genome-wide redistribution of ΔNp63α/TAp73 and NF-κB cREL interactive binding on TP53 and AP-1 motifs to...

Si, H Lu, H Yang, X Mattox, A Jang, M Bian, Y Sano, E Viadiu, H Yan, B Yau, C ...

Published in Oncogene

The Cancer Genome Atlas (TCGA) network study of 12 cancer types (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of related TP63 isoform ΔNp63 in squamous cancers. Further, aberrant expression of inflammatory genes and TP53/p63/p73 targets were detected in the PanCancer 12 project, reminiscent of gene programs com...

Sedentary lifestyle in middle-aged women is associated with severe menopausal symptoms and obesity.

Blümel, Juan E Fica, Juan Chedraui, Peter Mezones-Holguín, Edward Zuñiga, María C Witis, Silvina Vallejo, María S Tserotas, Konstantinos Sánchez, Hugo Onatra, William ...

Published in Menopause (New York, N.Y.)

There was a high prevalence of sedentary lifestyle in this middle-aged Latin American female sample which was associated with more severe menopausal symptoms and obesity.

UCSC Data Integrator and Variant Annotation Integrator.

Hinrichs, Angie S Raney, Brian J Speir, Matthew L Rhead, Brooke Casper, Jonathan Karolchik, Donna Kuhn, Robert M Rosenbloom, Kate R Zweig, Ann S Haussler, David ...

Published in Bioinformatics (Oxford, England)

Two new tools on the UCSC Genome Browser web site provide improved ways of combining information from multiple datasets, optionally including the user's own custom track data and/or data from track hubs. The Data Integrator combines columns from multiple data tracks, showing all items from the first track along with overlapping items from the other...

N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

Lee, John K Phillips, John W Smith, Bryan A Park, Jung Wook Stoyanova, Tanya McCaffrey, Erin F Baertsch, Robert Sokolov, Artem Meyerowitz, Justin G Mathis, Colleen ...

Published in Cancer cell

MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostat...

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