The gastrointestinal microbiome: a malleable, third genome of mammals

The nonpathogenic, mutualistic bacteria of the mammalian gastrointestinal tract provide a number of benefits to the host. Recent reports have shown how the aggregate genomes of gastrointestinal bacteria provide novel benefits by functioning as the third major genome in mammals along with the nuclear and mitochondrial genomes. Consequently, efforts are underway to elucidate the complexity of the organisms comprising the unique ecosystem of the gastrointestinal tract, as well as those associated with other epidermal surfaces. The current knowledge of the gastrointestinal microbiome, its relationship to human health and disease with a particular focus on mammalian physiology, and efforts to alter its composition as a novel therapeutic approach are reviewed

Murine models of colorectal cancer

Colorectal cancer is one of the most prevalent cancers of humans. To experimentally investigate this common disease, numerous murine models have been established. These models accurately recapitulate the molecular and pathological characteristics of human colorectal cancer including activation of MYC, which has recently been suggested to be a key mediator of colorectal cancer development. This review focuses on the variety of murine models of human colorectal cancer that are available to the research community and on their use to identify common and distinct characteristics of colorectal cancer

Assisting After Disaster: A Volunteer Management and Donations Management Training

Stakeholders in Mississippi perceived that Extension could lead volunteer management and donations management after a natural disaster. In response, Mississippi State University Extension professionals developed a training on volunteer management and donations management to supplement the existing Incident Management System/Incident Command System (ICS) curriculum. The training includes education on connecting volunteer management and donations management to local emergency planning, managing volunteers, managing goods and monetary donations, operating within ICS, and developing relationships between volunteer organizations and partners. The training has been pilot tested in Mississippi with promising preliminary results. Extension professionals elsewhere may benefit from similar trainings

Wildtype epidermal growth factor receptor (Egfr) is not required for daily locomotor or masking behavior in mice

BACKGROUND: Recent studies have implicated the epidermal growth factor receptor (EGFR) within the subparaventricular zone as being a major mediator of locomotor and masking behaviors in mice. The results were based on small cohorts of mice homozygous for the hypomorphic Egfr(wa2 )allele on a mixed, genetically uncontrolled background, and on intraventricular infusion of exogenous EGFR ligands. Subsequenlty, a larger study using the same genetically mixed background failed to replicate the original findings. Since both previous approaches were susceptible to experimental artifacts related to an uncontrolled genetic background, we analyzed the locomotor behaviors in Egfr(wa2 )mutant mice on genetically defined, congenic backgrounds. METHODS: Mice carrying the Egfr(wa2 )hypomorphic allele were bred to congenicity by backcrossing greater than ten generations onto C57BL/6J and 129S1/SvImJ genetic backgrounds. Homozygous Egfr(wa2 )mutant and wildtype littermates were evaluated for defects in locomotor and masking behaviors. RESULTS: Mice homozygous for Egfr(wa2 )showed normal daily locomotor activity and masking indistinguishable from wildtype littermates at two light intensities (200–300 lux and 400–500 lux). CONCLUSION: Our results demonstrate that reduced EGFR activity alone is insufficient to perturb locomotor and masking behaviors in mice. Our results also suggest that other uncontrolled genetic or environmental parameters confounded previous experiments linking EGFR activity to daily locomotor activity and provide a cautionary tale for genetically uncontrolled studies

ERBBs in the gastrointestinal tract: Recent progress and new perspectives

The gastrointestinal epithelium does much more than provide a physical barrier between the intestinal lumen and our internal milieu. It is actively engaged in absorption and secretion of salt and water via ion transporters, exchangers and selective ion channels. It is also a continuously self-renewing epithelium that undergoes ordered growth and differentiation along its vertical axis. From this dual perspective, we will consider the actions of the ERBB family of ligands and receptors in the maintenance of gastrointestinal homeostasis and discuss instances when the actions of this family go awry such as in cancer and Ménétrier's disease

Dietary calcium supplementation enhances efficacy but also toxicity of EGFR inhibitor therapy for colon cancer

The inverse correlation between levels of dietary calcium and colorectal cancer (CRC) incidence has been extensively investigated. However, the impact of supplemental calcium on cancer therapy remains unknown. We used four models of CRC, Caco-2 and HCT116 human cancer cell lines and ApcMin/+ and azoxymethane carcinogen-induced mouse models, to investigate the impact of a Western-style diet low in calcium (0.05%) vs. a similar diet but supplemented with calcium (5%) on therapeutic targeting of the epidermal growth factor receptor (EGFR). We found that calcium supplementation combined with pharmacologic blockade of EGFR results in an additive effect on tumor growth inhibition in all models. Unexpectedly, the combined use of dietary calcium supplementation and EGFR inhibitors also resulted in elevated toxicity suggesting that careful consideration be given when combining dietary supplements with prescribed cancer therapies

Neuronal ablation of GHSR mitigates diet-induced depression and memory impairment via AMPK-autophagy signaling-mediated inflammation

Obesity is associated with chronic inflammation in the central nervous system (CNS), and neuroinflammation has been shown to have detrimental effects on mood and cognition. The growth hormone secretagogue receptor (GHSR), the biologically relevant receptor of the orexigenic hormone ghrelin, is primarily expressed in the brain. Our previous study showed that neuronal GHSR deletion prevents high-fat diet-induced obesity (DIO). Here, we investigated the effect of neuronal GHSR deletion on emotional and cognitive functions in DIO. The neuron-specific GHSR-deficient mice exhibited reduced depression and improved spatial memory compared to littermate controls under DIO. We further examined the cortex and hippocampus, the major regions regulating cognitive and emotional behaviors, and found that the neuronal deletion of GHSR reduced DIO-induced neuroinflammation by suppressing proinflammatory chemokines/cytokines and decreasing microglial activation. Furthermore, our data showed that neuronal GHSR deletion suppresses neuroinflammation by downregulating AMPK-autophagy signaling in neurons. In conclusion, our data reveal that neuronal GHSR inhibition protects against DIO-induced depressive-like behavior and spatial cognitive dysfunction, at least in part, through AMPK-autophagy signaling-mediated neuroinflammation