Melanocortin-4 receptor signaling is required for weight loss after gastric bypass surgery.

Context: Roux-en-Y gastric bypass (RYGB) is one of the most effective long-term therapies for the treatment of severe obesity. Recent evidence indicates that RYGB effects weight loss through multiple physiological mechanisms, including changes in energy expenditure, food intake, food preference, and reward pathways.

Objective: Because central melanocortin signaling plays an important role in the regulation of energy homeostasis, we investigated whether genetic disruption of the melanocortin-4 receptor (MC4R) in rodents and humans affects weight loss after RYGB.

MafA and MafB regulate Pdx1 transcription through the Area II control region in pancreatic beta cells.

Pancreatic-duodenal homeobox factor-1 (Pdx1) is highly enriched in islet beta cells and integral to proper cell development and adult function. Of the four conserved 5'-flanking sequence blocks that contribute to transcription in vivo, Area II (mouse base pairs -2153/-1923) represents the only mammalian specific control domain. Here we demonstrate that regulation of beta-cell-enriched Pdx1 expression by the MafA and MafB transcription factors is exclusively through Area II.

Novel blockade of protein kinase A-mediated phosphorylation of AMPA receptors.

The phosphorylation state of the glutamate receptor subtype 1 (GluR1) subunit of the AMPA receptor (AMPAR) plays a critical role in synaptic expression of the receptor, channel properties, and synaptic plasticity. Several Gs-coupled receptors that couple to protein kinase A (PKA) readily recruit phosphorylation of GluR1 at S845. Conversely, activation of the ionotropic glutamate NMDA receptor (NMDAR) readily recruits dephosphorylation of the same GluR1 site through Ca2+-mediated recruitment of phosphatase activity.

A comparison of regional and systemic humoral immune responses to a nematode infection.

The kinetics of humoral immune response against Trichinella spiralis (TS) was characterized with immunofluorescence assay. The mesenteric lymph nodes (MLN) and the spleen of infected rats were examined for concurrent expression of multiple antibody (Ab) isotypes from day 1 to day 15 after infection. The tissues were processed and stained with either a pan-B cell marker (OX33) conjugated with rhodamine (XRITC) or combinations of dual monoclonal Ab probes plus A secondary Ab conjugated with XRITC or fluorescein (FITC).

Regulation of cAMP levels in area CA1 of hippocampus by Gi/o-coupled receptors is stimulus dependent in mice.

The cAMP signaling cascade plays a critical role in regulating synaptic efficacy and cellular excitability in hippocampus. Adenylyl cyclase (AC) activation and subsequent generation of cAMP occurs through a number of mechanisms in area CA1 of hippocampus, including Galpha(s)-mediated stimulation upon G-protein coupled receptor (GPCR) activation and Ca2+ -mediated stimulation upon NMDA receptor activation. In addition, activation of Gi/o-coupled receptor subtypes can regulate cAMP levels through modulation of AC activity.

Rapidity and multiplicity of synthesis and expression of immunoglobulin isotypes by B lymphocytes in the small intestine.

An immunofluorescence double labeling assay was used to examine the kinetics of intestinal B lymphocytes with concurrent expression of multiple antibody isotypes in the mucosal tissues of rats infected with Trichinella spiralis (TS) muscle larvae for 1 to 15 days. As compared to the uninfected controls (day 0), the non-Peyer's patch tissues of the small intestine contained a significantly increased number of dual antibody-expressing B cells as early as 3 days after infection with a maximum proliferation of these B cells on days 7 and 10. These results indicate the rapidity of B cell response in the small intestine.

NMDA and beta1-adrenergic receptors differentially signal phosphorylation of glutamate receptor type 1 in area CA1 of hippocampus.

Glutamatergic synaptic transmission is mediated primarily through the AMPA-type glutamate receptor (AMPAR); the regulation of this receptor underlies many forms of synaptic plasticity. In particular, phosphorylation of GluR1, an AMPAR subunit, by PKA at serine 845 (S845) increases peak open channel probability and is permissive for both the synaptic expression of the receptor and NMDA-receptor (NMDAR)-dependent long-term potentiation (LTP). Robust NMDAR activation activates PKA as well as other signaling enzymes; however, we find that maximal NMDAR activation dephosphorylates GluR1 at the PKA site S845.

ERK activation by G-protein-coupled receptors in mouse brain is receptor identity-specific.

In transfected cells and non-neuronal tissues many G-protein-coupled receptors activate p44/42 MAP kinase (ERK), a kinase involved in both hippocampal synaptic plasticity and learning and memory. However, it is not clear to what degree these receptors couple to ERK in brain. G(s)-coupled beta-adrenergic receptor activation of ERK in neurons is critical in the regulation of synaptic plasticity in area CA1 of the hippocampus.