Progenitor Populations Within the Vertebrate Enteric Nervous System

Tissue maintenance and repair depends on specialised cell types with the capacity to replenish cellular compartments lost by normal turnover or disease. Within the enteric nervous system (ENS), enteric glial cells (EGCs) play roles in: supporting enteric neurons, modulating inflammation, enhancing epithelial barrier fitness and, under certain experimental conditions, regenerating the ENS. Nevertheless, the cellular and molecular basis of the regenerative capacity and the extent of regeneration of the ENS is unknown. We use zebrafish, a model organism particularly amenable to genetic, developmental and functional studies, to study the organisation and function of EGCs, including their potential role in ENS maintenance and regeneration. Since limited studies have examined EGCs in zebrafish, we first combined transgenic reporter analysis with immunostaining to characterise the EGC population in zebrafish. Our experiments led to the identification of a population of EGCs within the ENS that are closely associated with enteric neurons and express the neural crest marker Sox10, but surprisingly lack canonical peripheral glial markers. However, these cells express the Notch effector bHLH transcription factor Her4.1, and have characteristic ultrastructural features of EGCs. Since, Her4.1 is an established marker of radial glia in the zebrafish CNS, a known progenitor cell type we used EdU chase experiments and mathematical modelling to reveal the proliferative and neurogenic potential of Her4.1 cells in the adult zebrafish ENS. Moreover, we employed Notch inhibitors to show that Notch signalling promotes EGC quiescence and maintenance of the non-neuronal cell fate. Finally, using transgenic lines we identified expression of HES5, the mammalian orthologue of Her4.1, within a subpopulation of Type I mammalian EGCs, identifying the first subtype marker of mammalian EGCs. This work provides the first characterisation of zebrafish EGCs, and identifies a novel marker of EGCs in both the zebrafish and mouse ENS with putative stem cell properties

Exchangeability of Brief and Abbreviated Intelligence Tests: Illuminating the Influence on Error Variance Components on IQs

This study examined the relations between and the exchangeability of IQs from four brief and abbreviated intelligence tests. All four tests were administered to 40 college students and scored by one set of examiners and later scored by a second examiner. All IQs were submitted to a Generalizability theory analysis to examine the relative contributions of error variance components of “test” and “examiner” and their interactions in producing variance in IQs relative to the object of measurement, individual differences in general intelligence. Despite very strong mean reliability coefficients (i.e., .91 to .96), the resulting dependability coefficient was .75, which indicated suspect dependability. The inadequate dependability coefficient from this study indicates that IQs are not as exchangeable as one might have assumed based on internal consistency reliability estimates, inter-rater reliability estimates, and convergent validity evidence

Corticospinal and reticulospinal contacts on cervical commissural and long descending propriospinal neurons in the adult rat spinal cord; evidence for powerful reticulospinal connections

Descending systems have a crucial role in the selection of motor output patterns by influencing the activity of interneuronal networks in the spinal cord. Commissural interneurons that project to the contralateral grey matter are key components of such networks as they coordinate left-right motor activity of fore and hind-limbs. The aim of this study was to determine if corticospinal (CST) and reticulospinal (RST) neurons make significant numbers of axonal contacts with cervical commissural interneurons. Two classes of commissural neurons were analysed: 1) local commissural interneurons (LCINs) in segments C4-5; 2) long descending propriospinal neurons (LDPNs) projecting from C4 to the rostral lumbar cord. Commissural interneurons were labelled with Fluorogold and CST and RST axons were labelled by injecting the b subunit of cholera toxin in the forelimb area of the primary somatosensory cortex or the medial longitudinal fasciculus respectively. The results show that LCINs and LDPNs receive few contacts from CST terminals but large numbers of contacts are formed by RST terminals. Use of vesicular glutamate and vesicular GABA transporters revealed that both types of cell received about 80% excitatory and 20% inhibitory RST contacts. Therefore the CST appears to have a minimal influence on LCINs and LDPNs but the RST has a powerful influence. This suggests that left-right activity in the rat spinal cord is not influenced directly via CST systems but is strongly controlled by the RST pathway. Many RST neurons have monosynaptic input from corticobulbar pathways therefore this pathway may provide an indirect route from the cortex to commissural systems. The cortico-reticulospinal-commissural system may also contribute to functional recovery following damage to the CST as it has the capacity to deliver information from the cortex to the spinal cord in the absence of direct CST input

Attachment styles and clinical communication performance in trainee doctors

Objective To investigate the relationship between trainee doctors’ attachment style and their performance in qualifying clinical and communication skills assessments. Methods Participants were 190 undergraduate medical students whose performance was assessed by examiners across two areas (communication and clinical skills) during their qualifying Objective Structured Clinical Examination (OSCE). Simulated patients also rated communication skills. Participants’ attachment style was rated across two dimensions, avoidance and anxiety, with the Relationship Questionnaire (RQ). Results Lower levels of attachment avoidance and anxiety were significant predictors of higher performance in both communication and clinical skills. Conclusion Trainee doctors’ attachment styles are associated with patient communication and clinical performance. Further research is needed to investigate the impact of attachment on consultations between doctors and patients within clinical settings. Practice implication Attachment theory can inform our understanding why, for some student doctors, interacting with patients may be particularly challenging and require additional support by medical educators

Residence time distributions for hydrologic systems: Mechanistic foundations and steady-state analytical solutions

International audienceThis review presents the physical mechanisms generating residence time distributions (RTDs) in hydrologic systems with a focus on steady-state analytical solutions. Steady-state approximations of the RTD in hydrologic systems have seen widespread use over the last half-century because they provide a convenient, simplified modeling framework for a wide range of problems. The concept of an RTD is useful anytime that characterization of the timescales of flow and transport in hydrologic systems is important, which includes topics like water quality, water resource management, contaminant transport, and ecosystem preservation. Analytical solutions are often adopted as a model of the RTD and a broad spectrum of models from many disciplines has been applied. Although these solutions are typically reduced in dimensionality and limited in complexity, their ease of use makes them preferred tools, specifically for the interpretation of tracer data. Our review begins with the mechanistic basis for the governing equations, highlighting the physics for generating a RTD, and a catalog of analytical solutions follows. This catalog explains the geometry, boundary conditions and physical aspects of the hydrologic systems, as well as the sampling conditions, that altogether give rise to specific RTDs. The similarities between models are noted, as are the appropriate conditions for their applicability. The presentation of simple solutions is followed by a presentation of more complicated analytical models for RTDs, including serial and parallel combinations, lagged systems, and non-Fickian models. The conditions for the appropriate use of analytical solutions are discussed, and we close with some thoughts on potential applications, alternative approaches, and future directions for modeling hydrologic residence time

Evaluation of an advisory committee as a model for patient engagement

Patient engagement (PE) is not well defined and little guidance is available to those attempting to employ PE in decision-making relevant to health system improvement. After completing a 2-year PE project, overseen by an Advisory Committee, our objectives were: 1) to evaluate how effectively the project team engaged the Advisory Committee, 2) to examine how Advisory Committee members perceived PE and their role in PE, and 3) to identify barriers and facilitators to PE in order to improve future efforts. Five members of the Advisory Committee completed semi-structured interviews post-project about their experiences. Thematic analysis identified four themes: the approach, participant contributions, participant understanding of PE, and barriers and facilitators to PE. The use of a committee approach was considered beneficial, providing an opportunity to discuss the project in depth, contributing to relationship building, and helping move the project forward. The social aspect of the committee approach was an important part of the engagement process. Participants felt they contributed primarily by participating in discussion, yet could not identify specific contributions they had made. All participants agreed that the experience was meaningful but not profound with regard to how it would impact their engagement, or their engagement of others, in the future. Although experiences were highly subjective, this study suggests that the act of participating in PE has meaning in and of itself to those involved, independent of the activities and/or outcomes of that participation, reflecting a broader public value that PE is an important component of transparent, accountable health systems

Introducing Creativity In A Design Laboratory For A Freshman Level Electrical And Computer Engineering Course

In the electrical and computer engineering (ECE) curriculum at The University of Alabama, freshmen are introduced to fundamental electrical concepts and units, DC circuit analysis techniques, operational amplifiers, circuit simulation, design, and professional ethics. The two credit course has both lecture and laboratory components that address these topics. The laboratory has been used, in this project, to provide students an experience in design. In one of the laboratory assignments, students work in teams to design and build products giving attention to both function and aesthetics. Creativity is an important attribute for engineers practicing their profession in a global society. The creative process was exercised in the design lab by progressively engaging students through various stages including: brainstorming, formation of a construction plan, producing schematic representations, and implementing their design. In a two- year period, four laboratory exercises were developed to provide design experiences in our introductory ECE course. Assessment results show that the majority of students enjoy several aspects of the laboratory on design and creativity. At the same time, they consider this lab to be one of the most difficult ones due to its open-ended nature. Students who experienced the creative lab were somewhat more likely to state they would continue in their major. Overall, the project team concluded that the creative lab was valuable and did raise awareness of the creative process.

The demography of free-roaming dog populations and applications to disease and population control

Understanding the demography of domestic dog populations is essential for effective disease control, particularly of canine-mediated rabies. Demographic data are also needed to plan effective population management. However, no study has comprehensively evaluated the contribution of demographic processes (i.e. births, deaths and movement) to variations in dog population size or density, or determined the factors that regulate these processes, including human factors. We report the results of a 3-year cohort study of domestic dogs, which is the first to generate detailed data on the temporal variation of these demographic characteristics. The study was undertaken in two communities in each of Bali, Indonesia and Johannesburg, South Africa, in rabies-endemic areas and where the majority of dogs were free-roaming. None of the four communities had been engaged in any dog population management interventions by local authorities or animal welfare organizations. All identified dogs in the four communities were monitored individually throughout the study. We observed either no population growth or a progressive decline in population size during the study period. There was no clear evidence that population size was regulated through environmental resource constraints. Rather, almost all of the identified dogs were owned and fed regularly by their owners, consistent with population size regulated by human demand. Finally, a substantial fraction of the dogs originated from outside the population, entirely through the translocation of dogs by people, rather than from local births. These findings demonstrate that previously reported growth of dog populations is not a general phenomenon and challenge the widely held view that free-roaming dogs are unowned and form closed populations. Synthesis and applications. These observations have broad implications for disease and population control. The accessibility of dogs for vaccination and evaluation through owners and the movement of dogs (some of them infected) by people will determine the viable options for disease control strategies. The impact of human factors on population dynamics will also influence the feasibility of annual vaccination campaigns to control rabies and population control through culling or sterilization. The complex relationship between dogs and people is critically important in the transmission and control of canine-mediated rabies. For effective management, human factors must be considered in the development of disease and population control programmes

Nonstationary recharge responses to a drying climate in the Gnangara groundwater system, Western Australia

The response of groundwater recharge to climate change needs to be understood to enable sustainable management of groundwater systems today and in the future, yet observations of recharge over long-enough time periods to reveal responses to climate trends are scarce. Here we present a meta-analysis of 60 years of recharge studies over the Gnangara Groundwater System of South-West Western Australia, covering a period of sustained drying consistent with climate change projections. The recharge process in the area is defined by a wet winter during which rain saturates a deep, highly permeable soil profile with very low water storage capacity. Measurements of recharge since the 1960s show near-linear reductions in potential recharge of 50%, in response to a 20% reduction in rainfall. For the best-represented land cover in the dataset (Banksia woodland), the reduction in potential recharge was closer to 70%. A simple analytical model suggests that reductions in the duration of winter, coupled with a decreased frequency of winter storms, were most responsible for these declines, and reveals the potential for nonlinear relationships between the recharge fraction (recharge/precipitation) and climatic variables such as mean storm frequency, mean storm depth, and the length of the winter wet season. Overall, results suggest that recharge declines in drying Mediterranean groundwater systems are likely to outstrip the declines in rainfall, and that leveraging existing observation networks worldwide to characterise recharge responses to changing climate is needed to overcome existing interpretation challenges created by inconsistent sites, methods and durations of recharge estimation

Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts

The gut microbiota is a reservoir for antimicrobial resistance genes (ARGs). With current sequencing methods, it is difficult to assign ARGs to their microbial hosts, particularly if these ARGs are located on plasmids. Metagenomic chromosome conformation capture approaches (meta3C and Hi-C) have recently been developed to link bacterial genes to phylogenetic markers, thus potentially allowing the assignment of ARGs to their hosts on a microbiome-wide scale. Here, we generated a meta3C dataset of a human stool sample and used previously published meta3C and Hi-C datasets to investigate bacterial hosts of ARGs in the human gut microbiome. Sequence reads mapping to repetitive elements were found to cause problematic noise in, and may importantly skew interpretation of, meta3C and Hi-C data. We provide a strategy to improve the signal-to-noise ratio by discarding reads that map to insertion sequence elements and to the end of contigs. We also show the importance of using spike-in controls to quantify whether the cross-linking step in meta3C and Hi-C protocols has been successful. After filtering to remove artefactual links, 87 ARGs were assigned to their bacterial hosts across all datasets, including 27 ARGs in the meta3C dataset we generated. We show that commensal gut bacteria are an important reservoir for ARGs, with genes coding for aminoglycoside and tetracycline resistance being widespread in anaerobic commensals of the human gut