Robert T.

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.

Tumor cells respond and adapt to environmental stresses that facilitate growth in hostile environments, including cytokine-mediated inflammation elicited by antitumor immunity and enhanced by immune checkpoint blockade (ICB). However, cytokine responses also induce transcriptional and cell-state changes that may predispose tumor cells to new vulnerabilities, which remain poorly explored. Here we performed in vitro genome-scale CRISPR loss-of-function screens in eight cancer models exposed to interferon-γ (IFNγ), interferon-β or tumor necrosis factor to map inflammation-induced genetic vulnerabilities. We identified members of the glycosylphosphatidylinositol (GPI) transamidase complex and the lipid phosphatase FITM2 as interferon-specific cancer dependencies. Tumor-specific deletion of GPI transamidase subunits or FITM2 markedly enhanced response to ICB in vivo. By integrating functional genomics, metabolomics and pharmacologic perturbation of downstream stress pathways, we found that loss of FITM2 predisposed cancer cells to IFNγ-driven endoplasmic reticulum and oxidative stress, culminating in paraptosis-like cell death. Collectively, these findings identify tumor-intrinsic dependencies governing responses to inflammatory cytokines.

T cell-invigorating cancer immunotherapies have near-curative potential. However, their clinical benefit is currently limited, as only a fraction o...

We report the complete genome sequence of the model bacterial pathogen Pseudomonas syringae pathovar tomato DC3000 (DC3000), which is pathogenic ...

Gram-positive bacteria assemble pili (fimbriae) on their surfaces to adhere to host tissues and to promote polymicrobial interactions. These hair-l...

Surface proteins of Gram-positive bacteria play important roles during the pathogenesis of human infections and require sortase for anchoring to ...

Covalently cross-linked pilus polymers displayed on the cell surface of Gram-positive bacteria are assembled by class C sortase enzymes. These pilu...