To expand applications for T-cell-based immunotherapy in cancer, we designed a receptor that binds the Fc portion of human immunoglobulins and delivers activation signals. The construct included the high-affinity CD16 (FCGR3A) V158 variant, CD8a hinge, and transmembrane domains, along with signaling domains from CD3? and 4-1BB (TNFRSF9), forming a chimeric ... More
H2O2-induced endothelial NO production contributes to vascular cell apoptosis and increased permeability in rat venules.
AuthorsZhou X, Yuan D, Wang M, He P,
JournalAm J Physiol Heart Circ Physiol
PubMed ID23086988
Although elevated levels of H(2)O(2) have been implicated to play important roles in the pathogenesis of various cardiovascular diseases, the underlying mechanisms remain unclear. This study aims to examine the effect of H(2)O(2) on endothelial nitric oxide (NO) production in intact venules, and elucidate the role and mechanisms of NO ... More
Programmed reduction of ABC transporter activity in sea urchin germline progenitors.
AuthorsCampanale JP, Hamdoun A,
JournalDevelopment
PubMed ID22274698
ATP-binding cassette (ABC) transporters protect embryos and stem cells from mutagens and pump morphogens that control cell fate and migration. In this study, we measured dynamics of ABC transporter activity during formation of sea urchin embryonic cells necessary for the production of gametes, termed the small micromeres. Unexpectedly, we found ... More
Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium.
The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, ... More
The cellular mechanisms of neuronal swelling underlying cytotoxic edema.
AuthorsRungta RL, Choi HB, Tyson JR, Malik A, Dissing-Olesen L, Lin PJ, Cain SM, Cullis PR, Snutch TP, MacVicar BA,
Journal
PubMed ID25910210
Cytotoxic brain edema triggered by neuronal swelling is the chief cause of mortality following brain trauma and cerebral infarct. Using fluorescence lifetime imaging to analyze contributions of intracellular ionic changes in brain slices, we find that intense Na(+) entry triggers a secondary increase in intracellular Cl(-) that is required for ... More
VX-509 (decernotinib) is a potent and selective janus kinase 3 inhibitor that attenuates inflammation in animal models of autoimmune disease.
Cytokines, growth factors, and other chemical messengers rely on a class of intracellular nonreceptor tyrosine kinases known as Janus kinases (JAKs) to rapidly transduce intracellular signals. A number of these cytokines are critical for lymphocyte development and mediating immune responses. JAK3 is of particular interest due to its importance in ... More
Features of a spatially constrained cystine loop in the p10 FAST protein ectodomain define a new class of viral fusion peptides.
AuthorsBarry C, Key T, Haddad R, Duncan R,
JournalJ Biol Chem
PubMed ID20363742
The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral membrane fusion proteins. With ectodomains of only approximately 20-40 residues, it is unclear how such diminutive fusion proteins can mediate cell-cell fusion and syncytium formation. Contained within the 40-residue ectodomain of the p10 FAST protein resides an 11-residue ... More
Differential outgrowth of axons and their branches is regulated by localized calcium transients.
AuthorsHutchins BI, Kalil K,
JournalJ Neurosci
PubMed ID18171932
During development axon outgrowth and branching are independently regulated such that axons can stall or retract while their interstitial branches extend toward targets. Previous studies have shown that guidance cues and intracellular signaling components can promote branching of cortical axons without affecting axon outgrowth. However, the mechanisms that regulate differential ... More
Both Th1 and Th2 cells require P-selectin glycoprotein ligand-1 for optimal rolling on inflamed endothelium.
The acquisition of homing receptors that redirect lymphocyte trafficking to nonlymphoid tissues after antigen encounter is a fundamental aspect of effector T-cell development. Although a role for selectins and their ligands has been well characterized for trafficking of Th1 cells to nonlymphoid sites, mechanisms responsible for Th2 trafficking are not ... More
Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging.
AuthorsBouzigues C, Morel M, Triller A, Dahan M
JournalProc Natl Acad Sci U S A
PubMed ID17592112
During development of the nervous system, the tip of a growing axon, the growth cone (GC), must respond accurately to stimuli that direct its growth. This axonal navigation depends on extracellular concentration gradients of numerous guidance cues, including GABA. GCs can detect even weak directional signals, yet the mechanisms underlying ... More
Thrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model.
AuthorsDubois C, Panicot-Dubois L, Gainor JF, Furie BC, Furie B
JournalJ Clin Invest
PubMed ID17380206
Adhesion of platelets to an injured vessel wall and platelet activation are critical events in the formation of a thrombus. Of the agonists involved in platelet activation, thrombin, collagen, and vWF are known to induce in vitro calcium mobilization in platelets. Using a calcium-sensitive fluorochrome and digital multichannel intravital microscopy ... More