The rockefeller university

IgG antibodies are secreted from B cells and bind to a variety of

We interviewed our Early Career Advisory Board to learn about their

During mammalian embryogenesis, extensive cellular remodeling is needed

PIEZO1 is a mechanosensitive channel that converts applied force into electrical signals. Partial molecular structures show that PIEZO1 is a bowl-shaped trimer with extended arms. Here we use cryo-electron microscopy to show that PIEZO1 adopts different degrees of curvature in lipid vesicles of different sizes. We also use high-speed atomic force microscopy to analyse the deformability of PIEZO1 under force in membranes on a mica surface, and show that PIEZO1 can be flattened reversibly into the membrane plane. By approximating the absolute force applied, we estimate a range of values for the mechanical spring constant of PIEZO1. Both methods of microscopy demonstrate that PIEZO1 can deform its shape towards a planar structure. This deformation could explain how lateral membrane tension can be converted into a conformation-dependent change in free energy to gate the PIEZO1 channel in response to mechanical perturbations

BACKGROUND: Previous studies identified several separate risk factors

Although fate maps of early embryos exist for nearly all model

To the Editor: We are delighted that our discovery of autoantibodies directed against LINE‐1 retroelement–encoded p40/ORF1p in SLE patients has been so rapidly replicated, and we thank Dr. Crow for her excellent summary of our findings. Her laboratory's detection of LINE‐1 messenger RNA (mRNA) and immunoreactive p40 protein in salivary gland specimens from patients with primary Sjögren's syndrome and kidney specimens from SLE patients 1 was an important impetus for our study. We also agree with Dr. Crow that anti–LINE‐1 immunity is indicative of a potential role of LINE‐1 in SLE pathogenesis. Besides the presence of autoantibodies against p40, the literature suggests at least 2 additional reasons to suspect this hypothesis: 1) LINE‐1–encoded proteins are physically associated with Ro 60 and other well‐recognized autoantigens in SLE, together with LINE‐1 mRNA or short RNA species such as Alu and YRNA transcripts and 2) the other LINE‐1–encoded protein, p145/ORF2p, is a reverse transcriptase that uses p40‐bound RNA as a template for DNA synthesis. The presence of autoantibodies against p40 therefore suggests that the autoimmune reaction in the SLE patient is targeting a protein–RNA complex that may also include DNA newly synthesized by reverse transcription, which has been shown to trigger the GMP‐AMP synthase (cGAS)/stimulator of IFN genes (STING) pathway to induce type I IFN production in senescent cells 2. Indeed, Dr. Crow's group has shown that introduction of full‐length LINE‐1 can induce type I IFN production in transfected cells 1. Furthermore, it has also been reported that activation of cGAS does occur in a subset of SLE patients 3.

The discovery of a biomolecular condensate involved in DNA replication

Vaccination against measles, mumps, and rubella (MMR) and yellow fever