The DIAPH3 linker specifies a β-actin network that maintains RhoA and Myosin-II at the cytokinetic furrow.

Cytokinesis is the final step of the cell division cycle that leads to the formation of two new cells. Successful cytokinesis requires significant remodelling of the plasma membrane by spatially distinct β- and γ-actin networks. These networks are generated by the formin family of actin nucleators, DIAPH3 and DIAPH1 respectively.

Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease.

To our knowledge, IL-10-KO mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD. We showed that a diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane and protected mice to varying degrees against disease symptoms, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet, further reducing symptoms, as well as increased gut bacterial richness, increased bacterial community similarity to each other, and more location-specific communities than older mice on the diet intervention.

Protective actions of a luminally acting 5-HT receptor agonist in mouse models of colitis.

Background: 5-hydroxytryptamine 4 receptors (5-HT Rs) are expressed in the colonic epithelium, and previous studies have demonstrated that luminal administration of agonists enhances motility, suppresses nociception, and is protective in models of inflammation. We investigated whether stimulation with a luminally acting 5-HT R agonist is comparable to previously tested absorbable compounds.

Methods: The dextran sodium sulfate (DSS), trinitrobenzene sulfonic acid (TNBS), and interleukin 10 knockout (IL-10KO) models of colitis were used to test the protective effects of the luminally acting 5-HT R agonist, 5HT4-LA1, in the absence and presence of a 5-HT R antagonist.

Tryptophan-synthesizing bacteria enhance colonic motility.

Background: An emerging strategy to treat symptoms of gastrointestinal (GI) dysmotility utilizes the administration of isolated bacteria. However, the underlying mechanisms of action of these bacterial agents are not well established. Here, we elucidate a novel approach to promote intestinal motility by exploiting the biochemical capability of specific bacteria to produce the serotonin (5-HT) precursor, tryptophan (Trp).

Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease.

Crohn's Disease (CD) is a presentation of Inflammatory Bowel Disease (IBD) that manifests in childhood and adolescence, and involves chronic and severe enterocolitis, immune and gut microbiome dysregulation, and other complications. Diet and gut-microbiota-produced metabolites are sources of anti-inflammatories which could ameliorate symptoms. However, questions remain on how IBD influences biogeographic patterns of microbial location and function in the gut, how early life transitional gut communities are affected by IBD and diet interventions, and how disruption to biogeography alters disease mediation by diet components or microbial metabolites.

Epithelial 5-HT Receptors as a Target for Treating Constipation and Intestinal Inflammation.

Because of their importance in the regulation of gut functions, several therapeutic targets involving serotonin-related proteins have been developed or repurposed to treat motility disorders, including serotonin transporter inhibitors, tryptophan hydroxylase blockers, 5-HT3 antagonists, and 5-HT4 agonists. This chapter focuses on our discovery of 5-HT4 receptors in the epithelial cells of the colon and our efforts to evaluate the effects of stimulating these receptors. 5-HT4 receptors appear to be expressed by all epithelial cells in the mouse colon, based on expression of a reporter gene driven by the 5-HT4 receptor promoter.

Monitoring Gut Epithelium Serotonin and Melatonin Overflow Provides Spatial Mapping of Inflammation.

Electrochemical arrays were used to measure the overflow of serotonin (5-HT) and melatonin (MEL) from the entire colon of healthy mice and mice with chemical-induced inflammatory bowel disease (IBD), to understand the interplay between inflammation and colonic function. We show that 5-HT overflow is increased, whilst MEL levels are reduced, in inflamed tissues. The levels of MEL are increased at the interface between healthy and inflamed regions within the colon and may limit the spread of inflammation.

Direct and indirect mechanisms by which the gut microbiota influence host serotonin systems.

Mounting evidence highlights the pivotal role of enteric microbes as a dynamic interface with the host. Indeed, the gut microbiota, located in the lumen of the gastrointestinal (GI) tract, influence many essential physiological processes that are evident in both healthy and pathological states. A key signaling molecule throughout the body is serotonin (5-hydroxytryptamine; 5-HT), which acts in the GI tract to regulate numerous gut functions including intestinal motility and secretion.

Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study.

Background: Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT).

Methods: Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay.

Inhibition of polar actin assembly by astral microtubules is required for cytokinesis.

During cytokinesis, the actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a β-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex. Here we demonstrate that the opposing regulation of the β- and γ-actin networks is required for successful cytokinesis. While activation of the formin DIAPH3 at the cytokinetic furrow underlies β-actin filament production, we show that the γ-actin network is specifically depleted at the cell poles through the localized deactivation of the formin DIAPH1.

Prokinetic actions of luminally acting 5-HT receptor agonists.

Background: 5-HT receptor (5-HT R) agonists exert prokinetic actions in the GI tract, but non-selective actions and potential for stimulation of non-target 5-HT Rs have limited their use. Since 5-HT Rs are expressed in the colonic epithelium and their stimulation accelerates colonic propulsion in vitro, we tested whether luminally acting 5-HT R agonists promote intestinal motility.

Methods: Non-absorbed 5-HT R agonists, based on prucalopride and naronapride, were assessed for potency at the 5-HT R in vitro, and for tissue and serum distribution in vivo in mice.

Identification of novel loci controlling inflammatory bowel disease susceptibility utilizing the genetic diversity of wild-derived mice.

Inflammatory bowel disease (IBD) is a complex disorder that imposes a growing health burden. Multiple genetic associations have been identified in IBD, but the mechanisms underlying many of these associations are poorly understood. Animal models are needed to bridge this gap, but conventional laboratory mouse strains lack the genetic diversity of human populations.

The scaffold-protein IQGAP1 enhances and spatially restricts the actin-nucleating activity of Diaphanous-related formin 1 (DIAPH1).

The actin cytoskeleton is a dynamic array of filaments that undergoes rapid remodeling to drive many cellular processes. An essential feature of filament remodeling is the spatio-temporal regulation of actin filament nucleation. One family of actin filament nucleators, the Diaphanous-related formins, is activated by the binding of small G-proteins such as RhoA.

No Gastrointestinal Dysmotility in Transgenic Mouse Models of Migraine.

Objective: To determine whether transgenic mouse models of migraine exhibit upper gastrointestinal dysmotility comparable to those observed in migraine patients.

Background: There is considerable evidence supporting the comorbidity of gastrointestinal dysmotility and migraine. Gastrointestinal motility, however, has never been investigated in transgenic mouse models of migraine.

CDK11-cyclin L1β regulates abscission site assembly.

Rigorous spatiotemporal regulation of cell division is required to maintain genome stability. The final stage in cell division, when the cells physically separate (abscission), is tightly regulated to ensure that it occurs after cytokinetic events such as chromosome segregation. A key regulator of abscission timing is Aurora B kinase activity, which inhibits abscission and forms the major activity of the abscission checkpoint.

Getting better my way: Feasibility study of a self-management support tool for people with mood and anxiety disorders.

Objective: Self-management support is recognized as an important component of the management of mood and anxiety disorders. The goal of this feasibility study was to evaluate the acceptability, implementation and perceived usefulness of a new comprehensive self-management tool () in four care settings in Quebec, Canada.

Method: Care providers offered the tool to people with difficulties related to mood or anxiety disorders during a 7-month period.

Regulation of Bone Metabolism by Serotonin.

The processes of bone growth and turnover are tightly regulated by the actions of various signaling molecules, including hormones, growth factors, and cytokines. Imbalances in these processes can lead to skeletal disorders such as osteoporosis or high bone mass disease. It is becoming increasingly clear that serotonin can act through a number of mechanisms, and at different locations in the body, to influence the balance between bone formation and resorption.

Health-Promoting Home and Workplace Neighborhoods: Associations With Multiple Facets of Men's Health.

Despite the importance of healthy settings for health promotion, little is known about how neighborhood characteristics affect men's health. The present study aims to explore the associations between perceptions of home and workplace neighborhoods with diverse health outcomes, and to examine mediating mechanisms. A sample of 669 men members of labor unions in Quebec, Canada, completed a questionnaire assessing social and physical aspects of their work and home neighborhoods (the Health-Promoting Neighborhood Questionnaire) as well as subjective and objective health outcomes (perceived health, positive mental health, body mass index) and potential mediators (health behaviors, self-efficacy).

Peer Positive Social Control and Men's Health-Promoting Behaviors.

Men are generally thought to be less inclined to take care of their health. To date, most studies about men's health have focused on deficits in self-care and difficulties in dealing with this sphere of their life. The present study reframes this perspective, using a salutogenic strengths-based approach and seeking to identify variables that influence men to take care of their health, rather than neglect it.

Glucagon-like peptide-2 promotes gallbladder refilling via a TGR5-independent, GLP-2R-dependent pathway.

Objective: Glucagon-like peptides (GLPs) are secreted from enteroendocrine cells in response to nutrients and bile acids and control metabolism via actions on structurally-related yet distinct G protein coupled receptors. GLP-1 regulates gut motility, appetite, islet function, and glucose homeostasis, whereas GLP-2 enhances intestinal nutrient absorption. GLP-1R agonists are used to treat diabetes and obesity, and a GLP-2R agonist is approved to treat short bowel syndrome.

Association between weight status and men's positive mental health: The influence of marital status.

The purpose of this study was to (1) examine the association between weight status and men's positive mental health, defined as the presence of symptoms of emotional, psychological, and social well-being, and (2) evaluate the moderating effect of marital status. A total of 645 men aged between 19 and 71 years self-reported their height and weight and answered a questionnaire measuring their emotional, psychological, and social well-being. Analysis of variance revealed that mean levels of emotional, psychological, and social well-being did not significantly differ according to men's weight status.

Protective Actions of Epithelial 5-Hydroxytryptamine 4 Receptors in Normal and Inflamed Colon.

Background & Aims: The 5-hydroxytryptamine receptor 4 (5-HTR or HTR) is expressed in the colonic epithelium but little is known about its functions there. We examined whether activation of colonic epithelial 5-HTR protects colons of mice from inflammation.

Methods: The 5-HTR agonist tegaserod (1 mg/kg), the 5-HTR antagonist GR113808 (1 mg/kg), or vehicle (control) were delivered by enema to wild-type or 5-HTR knockout mice at the onset of, or during, active colitis, induced by administration of dextran sodium sulfate or trinitrobenzene sulfonic acid.

Importin β2 Mediates the Spatio-temporal Regulation of Anillin through a Noncanonical Nuclear Localization Signal.

The compartmentalization of cell cycle regulators is a common mechanism to ensure the precise temporal control of key cell cycle events. For instance, many mitotic spindle assembly factors are known to be sequestered in the nucleus prior to mitotic onset. Similarly, the essential cytokinetic factor anillin, which functions at the cell membrane to promote the physical separation of daughter cells at the end of mitosis, is sequestered in the nucleus during interphase.

Impaired cholecystokinin-induced gallbladder emptying incriminated in spontaneous "black" pigment gallstone formation in germfree Swiss Webster mice.

"Black" pigment gallstones form in sterile gallbladder bile in the presence of excess bilirubin conjugates ("hyperbilirubinbilia") from ineffective erythropoiesis, hemolysis, or induced enterohepatic cycling (EHC) of unconjugated bilirubin. Impaired gallbladder motility is a less well-studied risk factor. We evaluated the spontaneous occurrence of gallstones in adult germfree (GF) and conventionally housed specific pathogen-free (SPF) Swiss Webster (SW) mice.