POSTNATAL DEVELOPMENTAL CHANGES IN ENTERIC DOPAMINERGIC SYSTEM

The postnatal period is a key period of life, characterized by the maturation of various organs and in particular of the gut. Currently, we have a poor understanding of the development of neurological and endocrine factors that control intestinal motility. Such knowledge can provide indications about the potency, efficacy, or therapeutic range of a drug in premature infants. Dopaminegic antagonists are often used as prokinetic drugs to treat impaired GI propulsion, although the role of the enteric dopaminergic system in the control of intestinal motility in neonatal vs adult has not been adequately addressed. In this view the aim of this study, was to examine, the functionality of the dopaminergic systems in the regulation of duodenal contractility in neonatal vs adult, using a murine animal model. Transcripts for all dopaminergic receptors (D1-like family, D1 and D5 receptors, and D2-like family, D2, D3, and D4 receptors) can be detected in mouse gut at each age. Mechanical responses to dopamine (DA) were examined in vitro in duodenal longitudinal muscle from postnatal and adult mice as changes in isometric tension. In neonatal duodenum, DA evoked a TTX-insensitive muscular contraction, reduced by SCH 23390, D1-like receptor antagonist, but not by domperidone, D2-like receptor antagonist, and mimicked by a D1 receptor agonist. The contractile response to DA decreased in intensity with age and in adults, in its place, a distinct TTX-insensitive muscular relaxation was detected. Inhibitory response to DA was mimicked by D1 or D2 receptor agonists and reduced by domperidone, and, to a lesser extent, by SCH 23390. In neonatal mice the excitatory responses mediated by D1 receptor activation were antagonized by U-73122, phospholipase C (PLC) inhibitor, whilst in adults the inhibitory effects were blocked by DDA, adenylyl cyclase inhibitor. In mouse gut, dopaminergic transmission undergoes to postnatal change in the pattern of receptor functionality. In postnatal period, DA leads to muscular contraction exclusively via D1-like receptors, likely D5 receptors, linked to activation of PLC. In adults, DA is able to relax duodenum recruiting D2 receptors and shifting the effects mediated by D1-like receptors, likely D1 receptors, activating cAMP pathway

A separated vortex ring underlies the flight of the dandelion

Wind-dispersed plants have evolved ingenious ways to lift their seeds1,2. The common dandelion uses a bundle of drag-enhancing bristles (the pappus) that helps to keep their seeds aloft. This passive flight mechanism is highly effective, enabling seed dispersal over formidable distances3,4; however, the physics underpinning pappus-mediated flight remains unresolved. Here we visualized the flow around dandelion seeds, uncovering an extraordinary type of vortex. This vortex is a ring of recirculating fluid, which is detached owing to the flow passing through the pappus. We hypothesized that the circular disk-like geometry and the porosity of the pappus are the key design features that enable the formation of the separated vortex ring. The porosity gradient was surveyed using microfabricated disks, and a disk with a similar porosity was found to be able to recapitulate the flow behaviour of the pappus. The porosity of the dandelion pappus appears to be tuned precisely to stabilize the vortex, while maximizing aerodynamic loading and minimizing material requirements. The discovery of the separated vortex ring provides evidence of the existence of a new class of fluid behaviour around fluid-immersed bodies that may underlie locomotion, weight reduction and particle retention in biological and manmade structures

Metabolite Cross-Feeding Enhances Virulence in a Model Polymicrobial Infection

Microbes within polymicrobial infections often display synergistic interactions resulting in enhanced pathogenesis; however, the molecular mechanisms governing these interactions are not well understood. Development of model systems that allow detailed mechanistic studies of polymicrobial synergy is a critical step towards a comprehensive understanding of these infections in vivo. In this study, we used a model polymicrobial infection including the opportunistic pathogen Aggregatibacter actinomycetemcomitans and the commensal Streptococcus gordonii to examine the importance of metabolite cross-feeding for establishing co-culture infections. Our results reveal that co-culture with S. gordonii enhances the pathogenesis of A. actinomycetemcomitans in a murine abscess model of infection. Interestingly, the ability of A. actinomycetemcomitans to utilize L-lactate as an energy source is essential for these co-culture benefits. Surprisingly, inactivation of L-lactate catabolism had no impact on mono-culture growth in vitro and in vivo suggesting that A. actinomycetemcomitans L-lactate catabolism is only critical for establishing co-culture infections. These results demonstrate that metabolite cross-feeding is critical for A. actinomycetemcomitans to persist in a polymicrobial infection with S. gordonii supporting the idea that the metabolic properties of commensal bacteria alter the course of pathogenesis in polymicrobial communities

Juvenile Hormone (JH) Esterase of the Mosquito Culex quinquefasciatus Is Not a Target of the JH Analog Insecticide Methoprene

Juvenile hormones (JHs) are essential sesquiterpenes that control insect development and reproduction. JH analog (JHA) insecticides such as methoprene are compounds that mimic the structure and/or biological activity of JH. In this study we obtained a full-length cDNA, cqjhe, from the southern house mosquito Culex quinquefasciatus that encodes CqJHE, an esterase that selectively metabolizes JH. Unlike other recombinant esterases that have been identified from dipteran insects, CqJHE hydrolyzed JH with specificity constant (kcat/KM ratio) and Vmax values that are common among JH esterases (JHEs). CqJHE showed picomolar sensitivity to OTFP, a JHE-selective inhibitor, but more than 1000-fold lower sensitivity to DFP, a general esterase inhibitor. To our surprise, CqJHE did not metabolize the isopropyl ester of methoprene even when 25 pmol of methoprene was incubated with an amount of CqJHE that was sufficient to hydrolyze 7,200 pmol of JH to JH acid under the same assay conditions. In competition assays in which both JH and methoprene were available to CqJHE, methoprene did not show any inhibitory effects on the JH hydrolysis rate even when methoprene was present in the assay at a 10-fold higher concentration relative to JH. Our findings indicated that JHE is not a molecular target of methoprene. Our findings also do not support the hypothesis that methoprene functions in part by inhibiting the action of JHE

Models of classroom assessment for course-based research experiences

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education