Structural basis for mouse LAG3 interactions with the MHC class II molecule I-A.

The immune checkpoint protein, Lymphocyte activation gene-3 (LAG3), binds Major Histocompatibility Complex Class II (MHC-II) and suppresses T cell activation. Despite the recent FDA approval of a LAG3 inhibitor for the treatment of melanoma, how LAG3 engages MHC-II on the cell surface remains poorly understood. Here, we determine the 3.

Strong damped Lyman-α absorption in young star-forming galaxies at redshifts 9 to 11.

Primordial neutral atomic gas, mostly composed of hydrogen, is the raw material for star formation in galaxies. However, there are few direct constraints on the amount of neutral atomic hydrogen (H i) in galaxies at early cosmic times. We analyzed James Webb Space Telescope (JWST) near-infrared spectroscopy of distant galaxies, at redshifts ≳8.

Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells.

The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.

The nature of an ultra-faint galaxy in the cosmic dark ages seen with JWST.

In the first billion years after the Big Bang, sources of ultraviolet (UV) photons are believed to have ionized intergalactic hydrogen, rendering the Universe transparent to UV radiation. Galaxies brighter than the characteristic luminosity L* (refs. ) do not provide enough ionizing photons to drive this cosmic reionization.

LAG3 ectodomain structure reveals functional interfaces for ligand and antibody recognition.

The immune checkpoint receptor lymphocyte activation gene 3 protein (LAG3) inhibits T cell function upon binding to major histocompatibility complex class II (MHC class II) or fibrinogen-like protein 1 (FGL1). Despite the emergence of LAG3 as a target for next-generation immunotherapies, we have little information describing the molecular structure of the LAG3 protein or how it engages cellular ligands. Here we determined the structures of human and murine LAG3 ectodomains, revealing a dimeric assembly mediated by Ig domain 2.

DksA plays an essential role in regulating the virulence of Borrelia burgdorferi.

The RNA polymerase-binding protein DksA, together with the alarmone nucleotides (p)ppGpp, mediates the stringent response to nutrient starvation in Borrelia burgdorferi. To date, the contribution of DksA to B. burgdorferi infection remains unknown.

The Lon-1 Protease Is Required by Borrelia burgdorferi To Infect the Mammalian Host.

encodes a functional homolog of canonical Lon protease termed Lon-2. In addition, encodes a second Lon homolog called Lon-1. Recent studies suggest that Lon-1 may function differently from the prototypical Lon protease.

The Lon-2 protease of Borrelia burgdorferi is critical for infection in the mammalian host.

Borrelia burgdorferi encodes a functional homolog of canonical Lon protease termed Lon-2. To date, the contribution of Lon-2 to B. burgdorferi fitness and infection remains unexplored.

Retrospective evaluation of the association between admission blood glucose and l-lactate concentrations in ponies and horses with gastrointestinal disease (2008-2016): 545 cases.

Objectives: A recent study described increased l-lactate concentrations in ponies with gastrointestinal disease compared to horses, but blood glucose (BG) concentrations were not considered. The study tested the hypothesis that BG and l-lactate concentrations are correlated in horses and ponies with gastrointestinal disease and that BG concentrations, not equid type (pony vs horse), are an independent predictor of L-lactate concentrations. It was further hypothesized that equid type was an independent predictor of BG concentrations.

The CXXC Motifs Are Essential for the Function of BosR in .

BosR, a Fur family member, is essential for the pathogenesis of the Lyme disease pathogen, . Unlike typical Fur proteins in which DNA binding represses gene expression, binding of BosR to the promoter directly activates transcription in . However, virtually nothing is known concerning potential structural features and amino acid residues of BosR that are important for protein function and virulence regulation in .

Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging.

Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations.