Type I interferon regulation by USP18 is a key vulnerability in cancer.

Precise regulation of Type I interferon signaling is crucial for combating infection and cancer while avoiding autoimmunity. Type I interferon signaling is negatively regulated by USP18. USP18 cleaves ISG15, an interferon-induced ubiquitin-like modification, via its canonical catalytic function, and inhibits Type I interferon receptor activity through its scaffold role.

Methods to Assess Blood and Nectar Meals in Mosquitoes.

Male and female mosquitoes survive by feeding on floral nectar for metabolic energy, but females require blood protein, obtained from biting a host, for egg development. Although males exclusively derive energy from nectar sugars, females must select the meal that best matches their present metabolic and reproductive needs. In females, blood and nectar promote independent feeding behaviors with distinct sensory appendages, meal sizes, digestive tract targets, and metabolic fates.

Size Quantification of Blood and Sugar Meals in Mosquitoes.

Both male and female mosquitoes consume sugar-rich nectar meals required for metabolic energy, but only females consume protein-rich blood meals, which are required for egg development. The size of each meal consumed has subsequent effects on behavior and reproduction; therefore, precise quantification is an important aspect of mosquito feeding behavior studies. This protocol describes a high-throughput, end-point assay to quantify meal volumes ingested by individual mosquitoes.

Feeding and Quantifying Animal-Derived Blood and Artificial Meals in Aedes aegypti Mosquitoes.

Females of certain mosquito species can spread diseases while biting vertebrate hosts to obtain protein-rich blood meals required for egg development. In the laboratory, researchers can deliver animal-derived and artificial blood meals to mosquitoes via membrane feeders, which allow for manipulation of meal composition. Here, we present methods for feeding blood and artificial blood meals to Aedes aegypti mosquitoes and quantifying the volume consumed by individual females.

Sensory Discrimination of Blood and Floral Nectar by Aedes aegypti Mosquitoes.

Blood-feeding mosquitoes survive by feeding on nectar for metabolic energy but require a blood meal to develop eggs. Aedes aegypti females must accurately discriminate blood and nectar because each meal promotes mutually exclusive feeding programs with distinct sensory appendages, meal sizes, digestive tract targets, and metabolic fates. We investigated the syringe-like blood-feeding appendage, the stylet, and discovered that sexually dimorphic stylet neurons taste blood.

Microbiota-modulated CART enteric neurons autonomously regulate blood glucose.

The gut microbiota affects tissue physiology, metabolism, and function of both the immune and nervous systems. We found that intrinsic enteric-associated neurons (iEANs) in mice are functionally adapted to the intestinal segment they occupy; ileal and colonic neurons are more responsive to microbial colonization than duodenal neurons. Specifically, a microbially responsive subset of viscerofugal CART neurons, enriched in the ileum and colon, modulated feeding and glucose metabolism.

Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.

Oral tolerance prevents pathological inflammatory responses to innocuous foreign antigens by peripheral regulatory T cells (pT(reg) cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure for the 'instruction' of naive CD4(+) T cells to differentiate into pT(reg) cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs were dispensable, while classical dendritic cells (cDCs) were critical, for pT(reg) cell induction and oral tolerance.

B cells promote tumor progression via STAT3 regulated-angiogenesis.

The role of B cells in cancer and the underlying mechanisms remain to be further explored. Here, we show that tumor-associated B cells with activated STAT3 contribute to tumor development by promoting tumor angiogenesis. B cells with or without Stat3 have opposite effects on tumor growth and tumor angiogenesis in both B16 melanoma and Lewis Lung Cancer mouse models.

Prognostic significance of B-cells and pSTAT3 in patients with ovarian cancer.

Background: Several previous studies have identified a strong association between T-cell infiltration and clinical outcome in ovarian cancer. The role of B-cells remains controversial, however.

Methods: Forty-nine paraffin-embedded omental specimens derived from patients with high grade epithelial ovarian cancer were assessed.

Sorafenib inhibits endogenous and IL-6/S1P induced JAK2-STAT3 signaling in human neuroblastoma, associated with growth suppression and apoptosis.

Neuroblastoma is the most common extracranial solid tumor in the pediatric population. Sorafenib (Nexavar), a multikinase inhibitor, blocks cell proliferation and induces apoptosis in certain types of cancers. Here, we tested antitumor effects of sorafenib (≤ 10 µM) on four human neuroblastoma cell lines, CHLA255, CHLA171, CHLA90 and SK-N-AS.

Bortezomib induces apoptosis and growth suppression in human medulloblastoma cells, associated with inhibition of AKT and NF-ĸB signaling, and synergizes with an ERK inhibitor.

Medulloblastoma is the most common brain tumor in children. Here, we report that bortezomib, a proteasome inhibitor, induced apoptosis and inhibited cell proliferation in two established cell lines and a primary culture of human medulloblastomas. Bortezomib increased the release of cytochrome c to cytosol and activated caspase-9 and caspase-3, resulting in cleavage of PARP.

Sunitinib induces apoptosis and growth arrest of medulloblastoma tumor cells by inhibiting STAT3 and AKT signaling pathways.

Medulloblastomas are the most frequent malignant brain tumors in children. Sunitinib is an oral multitargeted tyrosine kinase inhibitor used in clinical trials as an antiangiogenic agent for cancer therapy. In this report, we show that sunitinib induced apoptosis and inhibited cell proliferation of both a short-term primary culture (VC312) and an established cell line (Daoy) of human medulloblastomas.