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Cover Image
Cover Image
ON THE COVER
Cook et al. show that combining a γ-secretase inhibitor with gemcitabine synergistically kills intratumoral endothelial cells and prolongs survival in mice with advanced pancreatic adenocarcinoma. The authors’ original image shows Meca32-expressing endothelial cells (orange) among Ki67-positive proliferating cells (green) bordering a murine pancreatic tumor.
See page 437 - PDF Icon PDF LinkTable of Contents
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Perspective
Letter
Brief Definitive Report
Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma
Blocking Notch signaling in pancreatic cancer promotes hypoxia and cell death.
Lethal myelofibrosis induced by Bmi1-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes
Polycomb group gene Bmi1 functions as a tumor suppressor in myelofibrosis.
An extra allele of Chk1 limits oncogene-induced replicative stress and promotes transformation
Protection from replicative stress conferred by Chk1 promotes transformation.
Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K
A patient with a homozygous premature stop codon in PIK3R1 showed an early developmental block in B cell development but minimal effects in other organ systems.
Primary Epstein-Barr virus infection does not erode preexisting CD8+ T cell memory in humans
Bystander activation of human CD8+ T cells specific for influenza or cytomegalovirus during primary Epstein-Barr virus infection does not result in preexisting memory T cell attrition.
Article
TGF-β synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth
Hippo and TGF-β converge on CTGF to promote malignant mesothelioma.
Ovarian cancer progression is controlled by phenotypic changes in dendritic cells
Dendritic cells are transformed to become immunosuppressive during ovarian cancer progression.
Autocrine VEGF–VEGFR2–Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth
Autocrine VEGFR2 signaling in glioma stem-like cells evades VEGF neutralization.
Stimulation of the neurotrophin receptor TrkB on astrocytes drives nitric oxide production and neurodegeneration
The neurotrophin receptor TrkB is up-regulated on astrocytes in white matter lesions from multiple sclerosis patients, and mice lacking TrkB specifically in astrocytes are more resistant to experimental autoimmune encephalomyelitis–induced neurodegeneration.
Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow
Osteoclasts promote the formation of the HSC niche by inducing the differentiation of osteoblastic cells from mesenchymal stem cells.
HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4
CXCL12 forms a complex with HMGB1 that binds to the chemokine receptor CXCR4 and increases inflammatory cell migration.
Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis
Neutropenia in mice and humans results in the generation of NK cells with an immature and hyporesponsive phenotype.
Dual regulation of IRF4 function in T and B cells is required for the coordination of T–B cell interactions and the prevention of autoimmunity
Female mice lacking DEF6 and SWAP70 develop a lupus-like syndrome through dysregulation of IRF4 in activated B cells and plasma cells.
A germinal center–independent pathway generates unswitched memory B cells early in the primary response
Early IgM+ and switched Ig+ memory B cells develop from a germinal center (GC)–independent pathway, whereas late switched memory cells are GC dependent.
Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection
The repair protein trefoil factor 2 promotes Th2 responses to helminth infection and allergens in part by inducing IL-33.
Thymic negative selection is functional in NOD mice
Erk1/2-dependent TCR decisions, but not negative selection, are impaired in NOD thymocytes, leading to preferential development of αβ CD4+CD8+ thymocytes over γδ thymocytes and saturation of selection niches in TCR tg mouse models.
