Publications

Activity of Tachykinin1-expressing Pet1 raphe neurons modulates the drive to breathe.

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the 5-HT system, which have borne out in functional studies, including the modulation of distinct facets of homeostatic control.

Glucagon receptor inhibition normalizes blood glucose in severe insulin-resistant mice

Inactivating mutations in the insulin receptor results in extreme insulin resistance. The resulting hyperglycemia is very difficult to treat, and patients are at risk for early morbidity and mortality from complications of diabetes. We used the insulin receptor antagonist S961 to induce severe insulin resistance, hyperglycemia, and ketonemia in mice.

Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner

Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi-a process termed 'cell shedding'.

Inhibitory suppression of heterogeneously tuned excitation enhances spatial coding in CA1 place cells

Place cells in the CA1 region of the hippocampus express location-specific firing despite receiving a steady barrage of heterogeneously tuned excitatory inputs that should compromise output dynamic range and timing. We examined the role of synaptic inhibition in countering the deleterious effects of off-target excitation.

A ROR1–HER3–lncRNA signalling axis modulates the Hippo–YAP pathway to regulate bone metastasis

Bone metastases remain a serious health concern because of limited therapeutic options. Here, we report that crosstalk between ROR1-HER3 and the Hippo-YAP pathway promotes breast cancer bone metastasis in a long noncoding RNA-dependent fashion. Mechanistically, the orphan receptor tyrosine kinase ROR1 phosphorylates HER3 at a previously unidentified site Tyr1307, following neuregulin stimulation, independently of other ErbB family members.

FZD10-Gα13 signalling axis points to a role of FZD10 in CNS angiogenesis.

Among the 10 Frizzled (FZD) isoforms belonging to the Class F of G protein-coupled receptors (GPCRs), FZD10 remains the most enigmatic.

Novel Assay to Detect RNA Polymerase I Activity in vivo.

This report develops an analytically validated chromogenic in situ hybridization (CISH) assay using branched DNA signal amplification (RNAscope) for detecting the expression of the 5' external transcribed spacer (ETS) of the 45S ribosomal (r) RNA precursor in formalin fixed and paraffin embedded (FFPE) human tissues.

Controlling multi-cycle replication of live-attenuated HIV-1 using an unnatural genetic switch

A safe and effective human immunodeficiency virus type 1 (HIV-1) vaccine is urgently needed, but remains elusive. While HIV-1 live-attenuated vaccine can provide potent protection as demonstrated in rhesus macaque-simian immunodeficiency virus model, the potential pathogenic consequences associated with the uncontrolled virus replication preclude such vaccine from clinical applications.

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