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

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...

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

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...

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

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...

Kinesin-1 tail autoregulation and microtubule-binding regions function in saltatory transport but not ooplasmic streamin...

Published in Development (Cambridge, England)

Common Polymorphisms in the Solute Carrier SLC30A10 are Associated With Blood Manganese and Neurological Function.

Published in Toxicological sciences : an official journal of the Society of Toxicology

Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes an Mn transporter, influence blood Mn concentrations ...

Electrostatic Similarity Analysis of Human β-Defensin Binding in the Melanocortin System.

Published in Biophysical journal

The β-defensins are a class of small cationic proteins that serve as components of numerous systems in vertebrate biology, including the immune and melanocortin systems. Human β-defensin 3 (HBD3), which is produced in the skin, has been found to bind to melanocortin receptors 1 and 4 through complementary electrostatics, a unique mechanism of ligan...

Genome-Directed Lead Discovery: Biosynthesis, Structure Elucidation, and Biological Evaluation of Two Families of Polyen...

Published in ACS chemical biology

Marine natural products are an important source of lead compounds against many pathogenic targets. Herein, we report the discovery of lobosamides A-C from a marine actinobacterium, Micromonospora sp., representing three new members of a small but growing family of bacterially produced polyene macrolactams. The lobosamides display growth inhibitory ...

Mammary Stem Cell Self-Renewal Is Regulated by Slit2/Robo1 Signaling through SNAI1 and mINSC.

Published in Cell reports

Tissue homeostasis requires somatic stem cell maintenance; however, mechanisms regulating this process during organogenesis are not well understood. Here, we identify asymmetrically renewing basal and luminal stem cells in the mammary end bud. We demonstrate that SLIT2/ROBO1 signaling regulates the choice between self-renewing asymmetric cell divis...

Lead Exposure Risk from Trash Ingestion by the Endangered California Condor (Gymnogyps californianus).

Published in Journal of wildlife diseases

Lead poisoning from ingestion of spent lead ammunition is one of the greatest threats to the recovery of California Condors (Gymnogyps californianus) in the wild. Trash ingestion by condors is well documented, yet the extent that trash presents a lead exposure risk is unknown. We evaluated 1,413 trash items collected from condor nest areas and nest...

The telomerase essential N-terminal domain promotes DNA synthesis by stabilizing short RNA-DNA hybrids.

Published in Nucleic acids research

Telomerase is an enzyme that adds repetitive DNA sequences to the ends of chromosomes and consists of two main subunits: the telomerase reverse transcriptase (TERT) protein and an associated telomerase RNA (TER). The telomerase essential N-terminal (TEN) domain is a conserved region of TERT proposed to mediate DNA substrate interactions. Here, we h...