Campylobacter jejuni, a foodborne pathogen, is one of the most common bacterial causes of gastroenteritis in the world. Undercooked poultry, raw (unpasteurized) dairy products, untreated water, and contaminated produce are the most common sources associated with infection. C. jejuni establishes a niche in the gut by adhering to and invading epithelial cells, which results in diarrhea with blood and mucus in the stool. The process of colonization is mediated, in part, by surface-exposed molecules (adhesins) that bind directly to host cell ligands or the extracellular matrix (ECM) surrounding cells. In this review, we introduce the known and putative adhesins of the foodborne pathogen C. jejuni. We then focus our discussion on two C. jejuni Microbial Surface Components Recognizing Adhesive Matrix Molecule(s) (MSCRAMMs), termed CadF and FlpA, which have been demonstrated to contribute to C. jejuni colonization and pathogenesis. In vitro studies have determined that these two surface-exposed proteins bind to the ECM glycoprotein fibronectin (FN). In vivo studies have shown that cadF and flpA mutants exhibit impaired colonization of chickens compared to the wildtype strain. Additional studies have revealed that CadF and FlpA stimulate epithelial cell signaling pathways necessary for cell invasion. Interestingly, CadF and FlpA have distinct FN-binding domains, suggesting that the functions of these proteins are nonredundant. In summary, the binding of FN by C. jejuni CadF and FlpA adhesins has been demonstrated to contribute to adherence, invasion, and cell signaling.

Campylobacter jejuni is a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells by C. jejuni requires cell binding as well as delivery of the Cia proteins (Campylobacter invasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization of C. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate that C. jejuni-stimulated Rac signaling is dependent on IQGAP1.

Campylobacter jejuni is a major foodborne pathogen that causes severe gastritis. We investigated the dynamics of focal adhesion structure and function in C. jejuni -infected epithelial cells.

Cannabis is the most used illicit drug in the United States. With many states passing legislation to permit its recreational use, there is concern that cannabis use among adolescents could increase dramatically in the coming years. Historically, it has been difficult to model real-world cannabis use to investigate the causal relationship between cannabis use in adolescence and behavioral and neurobiological effects in adulthood. To this end, we used a novel volitional vapor administration model to investigate long-term effects of cannabis use during adolescence on the medial prefrontal cortex (mPFC) and mPFC-dependent behaviors in male and female rats. Adolescent (35-55 day old) female rats had significantly higher rates of responding for vaporized Δ9-tetrahydrocannabinol (THC)-dominant cannabis extract (CANTHC) compared to adolescent males. In adulthood (70-110 day old), female, but not male, CANTHC rats also took more trials to reach criterion and made more regressive errors in an automated attentional set-shifting task compared to vehicle rats. Similar set-shifting deficits were observed in males when they were exposed to a non-contingent CANTHC vapor dosing regimen that approximated CANTHC self-administration rates in females. No differences were observed in effort-based decision making in either sex. In the mPFC, female (but not male) CANTHC rats displayed more reactive microglia with no significant changes in myelin basic protein expression or dendritic spine density. Together, these data reveal important sex differences in rates of cannabis vapor self-administration in adolescence that confer enduring alterations to mPFC structure and function. Importantly, female-specific deficits in behavioral flexibility appear to be driven by elevated rates of CANTHC self-administration as opposed to a sex difference in the effects of CANTHC vapor per se.

Gonadal sex steroids are important regulators of energy balance in adult rodents, and gonadectomy (GDX) has opposing effects on weight gain in sexually mature males and females. Puberty is associated with the emergence of sex differences in weight, body composition, and feeding behaviors, yet the role of gonadal hormones at puberty remains unclear. To address this, we performed GDX or sham surgery in male and female C57Bl/6 mice at postnatal day (P)25 (prepubertal) or P60 (postpubertal) timepoints and measured weight and body composition for 35 days, after which ad libitum and operant food intake was measured using Feeding Experimentation Device 3 (FED3s) in the home cage. Consistent with previous studies, postpubertal GDX caused weight gain in females and weight loss in males and increased adiposity in both sexes. However, prepubertal GDX decreased weight gain and altered body composition across the adolescent transition (P25 to P60) in males but had no effect in females. Despite the varied effects on weight, GDX decreased food intake and motivation for food as assessed in operant tasks regardless of sex or timing of surgery relative to puberty. Our findings indicate that GDX interacts with both sex and age at surgery to influence weight, body composition, and feeding behavior.