Learning to predict rewards based on environmental cues is essential for survival. The orbitofrontal cortex (OFC) contributes to such learning by conveying reward-related information to brain areas such as the ventral tegmental area (VTA). Despite this, how cue–reward memory representations form in individual OFC neurons and are modified based on new information is unknown. To address this, using in vivo…
Coronaviruses have caused outbreaks of deadly pneumonia in humans since the beginning of the 21st century. Currently, no specific antiviral treatments or vaccines are available to combat any human coronavirus. The authors report the first coronavirus spike glycoprotein structure in complex with a saccharide, providing an atomic description of the interactions involved in attachment to sialoside receptors at the host cell surface, and demonstrate that sialic acid binding at the site identified is required for viral infection.
We have used RNA-seq in Caenorhabditis elegans to produce transcription profiles for seven specific embryonic cell populations from gastrulation to the onset of terminal differentiation. The expression data for these seven cell populations, covering major cell lineages and tissues in the worm, reveal the complex and dynamic changes in gene expression, both spatially and temporally. Also, within genes, start sites and exon usage…
The use of monoclonal antibodies in cancer therapy is limited by their cross-reactivity to healthy tissue. Tumor targeting has been improved by generating masked antibodies that are selectively activated in the tumor microenvironment, but each such antibody necessitates a custom design. Here, we present a generalizable approach for masking the binding domains of antibodies with a heterodimeric coiled-coil domain that…
Next generation targeted sequencing of HLA-DRB1, -DRB3, -DRB4 and -DRB5 (abbreviated as DRB345) provides high resolution of functional variant positions to investigate their associations with type 1 diabetes risk and with autoantibodies against insulin (IAA), GAD65 (GADA), IA-2 (IA-2A) or ZnT8 (ZnT8A). To overcome exceptional DR sequence complexity due to high polymorphisms and extended linkage-disequilibrium among the DR loci, we…
The naturally occurring nucleotide 2-deoxy-adenosine 5′-triphosphate (dATP) can be used by cardiac muscle as an alternative energy substrate for myosin chemomechanical activity. We and others have previously shown that dATP increases contractile force in normal hearts and models of depressed systolic function, but the structural basis of these effects has remained unresolved. In this work, we combine multiple techniques to…
Protein-modified biomaterials can be used to modulate cellular function in three dimensions. However, as the dynamic heterogeneous control over complex cell physiology continues to be sought, strategies that permit a reversible and user-defined tethering of fragile proteins to materials remain in great need. Here we introduce a modular and robust semisynthetic approach to reversibly pattern cell-laden hydrogels with site-specifically modified…
Neurotoxicity remains an important and difficult to predict complication CAR T cell immunotherapy. About 40% of patients develop some evidence of brain dysfunction, such as confusion or seizures, and rarely neurotoxicity can lead to fatal cerebral edema. We studied a cohort of 43 children and young adults who received CD19-directed CAR T cells for treatment of B cell acute lymphoblastic leukemia, and found that higher levels systemic cytokines during CAR T cell proliferation...
Intracellular Salmonella use a type III secretion system (TTSS) to translocate effector proteins across the phagosome membrane and thus promote vacuole membrane tubulation, resulting in intracellular survival. This work demonstrates that the effector SseJ binds the eukaryotic lipid transporter oxysterol binding protein 1 (OSBP1). SseJ directs OSBP1 to the endosomal compartment in a manner dependent on the TTSS located on…
There is a widely-held idea that tissue macrophages are shaped mostly by the tissue in which they find themselves, and in the case of Kupffer cells this is the liver. However, the work recently published in Journal of Hepatology shows that the origin of the cells also strongly influences how they respond to stress. In our experiments the stress was radiation, and the Kupffer cells that originated from precursors in the fetus survived it much better than Kupffer cells that originated in the adult bone marrow...
