Robert T.

Differentiating DCs express ALDH1A2, which produces retinoic acid and suppresses DC activity. Blocking this pathway with a new inhibitor, KyA33, enhances immune responses and boosts the effectiveness of DC cancer vaccines in mouse models.

The ssrA tag, an 11-aa peptide added to the C terminus of proteins stalled during translation, targets proteins for degradation by ClpXP and ClpAP....

CAR T cell therapies are effective but costly and difficult to manufacture. Here, authors develop a novel approach using retargeted and functionalized lentiviral vectors that selectively reprogram T cells in vivo, evade immune clearance, and generate functional CAR T cells with therapeutic efficacy.

Department of Pharmacy, Faculty of Mathematics and Natural Science, Heinrich-Heine University of Düsseldorf, University Street 1, 40225 Duesseldorf, Germany

Phases of the iron–oxygen binary system are significant to most scientific disciplines, directly affecting planetary evolution, life, and technolog...

Neurotensin (NTS) binds to the G protein-coupled receptors (GPCRs) NTSR1 and NTSR2. NTSR1 regulates transactivation of the EGFR, HER2, and HER3, but its effects on HER4 are unknown. By Western blot, NTSR1 and HER4 were present in six lung cancer cell lines examined. In NCI-H522 or NCI-H661 cells, adding NTS increased phosphorylation (P) of tyrosine (Y) 1284 on HER4. Because SR48692 antagonized NTS’s ability to increase P-HER4 or P-ERK, NTSR1 may play an important role in NSCLC. SR48692, HER4 siRNA, reactive oxygen species inhibitors, and the tyrosine kinase inhibitor ibrutinib inhibited NTS-induced P-HER4. Adding NTS to NCI-H661 cells increased the formation of HER4/HER4, HER4/ EGFR, and HER4/HER2 dimers. Adding NTS to NSCLC cells increased both P-ERK and P-AKT, which were inhibited by PD98059 and LY294002, respectively. The growth of NCI-H522 or NCI-H661 cells was stimulated by NTS or neuregulin 1 (NRG1), a HER4 ligand, but inhibited by SR48692 or ibrutinib. The results indicate that NTSR1 regulates HER4 transactivation, thereby increasing the proliferation of lung cancer cells.

Context-dependent behavior selects actions according to task demands. Using direct brain recordings in humans, Binish et al. uncover how coordinated population activity efficiently channels information from prefrontal to motor cortex.

STING agonism can promote antitumor immunity, however, mechanisms of resistance to STING activation have been described in several cancer types. Here the authors report that upregulation of PTPN2 in head and neck squamous cell carcinoma is associated with STING suppression, showing that PTPN2 inhibition restores tumor cell STING expression, and enhances response to STING agonism and antitumor immunity.

Background and Clinical Significance: CTC1-related cerebroretinal microangiopathy with calcifications and cysts (CRMCC), or Coats-plus syndrome, is an extremely rare autosomal recessive telomere-dysfunction disorder. A total of 29 cases in 15 reports have been reported in the English literature. The primary imaging characteristics include leukoencephalopathy, intracranial calcifications, and parenchymal cysts. Case Presentation: We describe a patient with CRMCC, who presented with a large intracranial cystic mass and basal ganglia calcifications, with imaging findings strongly mimicking a primary CNS tumor. The patient underwent multiple surgeries with inconclusive biopsies. Ultimately, it took five years and the collaboration of several specialists to arrive at the final diagnosis. Furthermore, we present dedicated clinical 7T orbit MRI findings on the patient’s brother, who has the same disease. Conclusions: We present a rare case of CRMCC with lack of overt leukoencephalopathy at presentation and absence of characteristic extracranial/extraocular manifestations, significantly complicating diagnosis. Furthermore, to the best of our knowledge, we share the first reported clinical 7T orbital MRI in the pediatric population.