Contents
09 September 2020
Vol 12, Issue 560
Vol 12, Issue 560
Research Articles
- Characterization of ANGPT2 mutations associated with primary lymphedema
Loss-of-function mutations in the TIE2-ligand angiopoietin 2 are associated with primary lymphedema in humans.
- Restoring the natural tropism of AAV2 vectors for human liver
AAVs isolated from human liver are tropic for human hepatocytes in vivo, but this phenotype becomes attenuated after passage in culture.
- Ultrasensitive molecular imaging of intestinal mucosal inflammation using leukocyte-mimicking particles targeted to MAdCAM-1 in mice
Molecular magnetic resonance imaging allows noninvasive evaluation of intestinal mucosal inflammation in clinically relevant mouse models.
- A patient-based model of RNA mis-splicing uncovers treatment targets in Parkinson’s disease
The genetic and pharmacological rescue of pathogenic U1-dependent exon skipping in c.192G>C PARK7 restores PD-associated cellular abnormalities in vitro.
- Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade
The bifunctional compound D18 improves checkpoint blockade efficacy by increasing KDM5A and PD-L1 abundance and inducing TLR7/8 activation.
- Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair
Roseomonas mucosa treatment in children with atopic dermatitis is associated with clinical improvements and potentially lipid-mediated TNF signaling.
Editors' Choice
- Interfering too soon: Type I interferons can dampen antiviral immunity
Short-term blockade of type I interferons at the time of viral infection or vaccine administration enhances immunological memory.
- Leaky pipes: Tau and apoE implicated in blood-brain barrier dysfunction in Alzheimer disease
Concentrations of tight junction proteins correlate with tau and apolipoprotein E in Alzheimer disease brain tissue independent of cerebral amyloid angiopathy.
- Targeting leukemia-specific mutations
T cells can recognize neoantigens derived from protein products of characteristic genetic fusions and thereby specifically target leukemia cells.
About The Cover
ONLINE COVER Complex Mutations in Primary Lymphedema. The model shows angiopoietin-2 (ANGPT2) complexed with its receptors TIE1 and TIE2, factors involved in the regulation of vascular integrity. Leppänen et al. found that inactivating mutations in human ANGPT2 associated with primary lymphedema, a condition marked by tissue swelling resulting from impaired lymphatic function. These dominant negative mutations altered oligomerization and reduced ANGPT2 secretion or its interaction with integrin α5 (at sites highlighted in purple) in lymphatic endothelial cells, and one tested mutation resulted in hyperplastic and dilated lymphatic vessels when overexpressed in mouse ear skin. This work adds to the primary genetic factors associated with lymphedema in humans. [CREDIT: LEPPÄNEN ET AL./SCIENCE TRANSLATIONAL MEDICINE]
