LAG3 associates with TCR-CD3 complexes and suppresses signaling by driving co-receptor-Lck dissociation.

LAG3 is an inhibitory receptor that is highly expressed on exhausted T cells. Although LAG3-targeting immunotherapeutics are currently in clinical trials, how LAG3 inhibits T cell function remains unclear. Here, we show that LAG3 moved to the immunological synapse and associated with the T cell receptor (TCR)-CD3 complex in CD4 and CD8 T cells, in the absence of binding to major histocompatibility complex class II-its canonical ligand.

Enhancement of T2* Weighted MRI Imaging Sensitivity of U87MG Glioblastoma Cells Using γ-Ray Irradiated Low Molecular Weight Hyaluronic Acid-Conjugated Iron Nanoparticles.

Introduction: It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (FeO) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection.

mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation.

Cells adjust to nutrient fluctuations to restore metabolic homeostasis. The mechanistic target of rapamycin (mTOR) complex 2 responds to nutrient levels and growth signals to phosphorylate protein kinases belonging to the AGC (Protein Kinases A,G,C) family such as Akt and PKC. Phosphorylation of these AGC kinases at their conserved hydrophobic motif (HM) site by mTORC2 enhances their activation and mediates the functions of mTORC2 in cell growth and metabolism.

Physical and Biological Evaluation of Low-Molecular-Weight Hyaluronic Acid/FeO Nanoparticle for Targeting MCF7 Breast Cancer Cells.

Low-molecular-weight hyaluronic acid (LMWHA) was integrated with superparamagnetic FeO nanoparticles (FeO NPs). The size distribution, zeta potential, viscosity, thermogravimetric and paramagnetic properties of the LMWHA-FeO NPs were systematically examined. For cellular experiments, MCF7 breast cancer cell line was carried out.

mTORC2 Responds to Glutamine Catabolite Levels to Modulate the Hexosamine Biosynthesis Enzyme GFAT1.

Highly proliferating cells are particularly dependent on glucose and glutamine for bioenergetics and macromolecule biosynthesis. The signals that respond to nutrient fluctuations to maintain metabolic homeostasis remain poorly understood. Here, we found that mTORC2 is activated by nutrient deprivation due to decreasing glutamine catabolites.

Mammalian target of rapamycin complex 2 modulates αβTCR processing and surface expression during thymocyte development.

An efficient immune response relies on the presence of T cells expressing a functional TCR. Whereas the mechanisms generating TCR diversity for antigenic recognition are well defined, what controls its surface expression is less known. In this study, we found that deletion of the mammalian target of rapamycin complex (mTORC) 2 component rictor at early stages of T cell development led to aberrant maturation and increased proteasomal degradation of nascent TCRs.

Enhancement of optical adaptive sensing by using a dual-stage seesaw-swivel actuator with a tunable vibration absorber.

Technological obstacles to the use of rotary-type swing arm actuators to actuate optical pickup modules in small-form-factor (SFF) disk drives stem from a hinge's skewed actuation, subsequently inducing off-axis aberrations and deteriorating optical quality. This work describes a dual-stage seesaw-swivel actuator for optical pickup actuation. A triple-layered bimorph bender made of piezoelectric materials (PZTs) is connected to the suspension of the pickup head, while the tunable vibration absorber (TVA) unit is mounted on the seesaw swing arm to offer a balanced force to reduce vibrations in a focusing direction.

Fascin1 promotes cell migration of mature dendritic cells.

Dendritic cells (DCs) play central roles in innate and adaptive immunity. Upon maturation, DCs assemble numerous veil-like membrane protrusions, disassemble podosomes, and travel from the peripheral tissues to lymph nodes to present Ags to T cells. These alterations in morphology and motility are closely linked to the primary function of DCs, Ag presentation.

Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt.

Nijmegen breakage syndrome (NBS) is a chromosomal instability syndrome associated with cancer predisposition, radiosensitivity, microcephaly, and growth retardation. The NBS gene product, NBS1 (p95) or nibrin, is a part of the hMre11 complex, a central player associated with double strand break repair. We previously demonstrated that c-Myc directly activates NBS1 expression.

Direct activation of HSP90A transcription by c-Myc contributes to c-Myc-induced transformation.

The c-myc proto-oncogene encodes a ubiquitous transcription factor involved in the control of cell growth and differentiation and implicated in inducing tumorigenesis. Understanding the function of c-Myc and its role in cancer depends upon the identification of c-Myc target genes. Heat shock protein 90 (HSP90) is involved in the folding of proteins such as signal transduction molecules (Src, Raf1, cdk4) and steroid receptors and in enhancing the activity of telomerase and nitric-oxide synthase.