Human resident gut microbe Bacteroides thetaiotaomicron regulates colonic neuronal innervation and neurogenic function

BACKGROUND AND AIMS: As the importance of gut-brain interactions increases, understanding how specific gut microbes interact with the enteric nervous system (ENS), which is the first point of neuronal exposure becomes critical. Our aim was to understand how the dominant human gut bacterium Bacteroides thetaiotaomicron (Bt) regulates anatomical and functional characteristics of the ENS. METHODS: Neuronal cell populations, as well as enteroendocrine cells, were assessed in proximal colonic sections using fluorescent immunohistochemistry in specific pathogen-free (SPF), germ-free (GF) and Bt conventionalized-germ-free mice (Bt-CONV). RNA expression of tight junction proteins and toll-like receptors (TLR) were measured using qPCR. Colonic motility was analyzed using in vitro colonic manometry. RESULTS: Decreased neuronal and vagal afferent innervation observed in GF mice was normalized by Bt-CONV with increased neuronal staining in mucosa and myenteric plexus. Bt-CONV also restored expression of nitric oxide synthase expressing inhibitory neurons and of choline acetyltransferase and substance P expressing excitatory motor neurons comparable to those of SPF mice. Neurite outgrowth and glial cells were upregulated by Bt-CONV. RNA expression of tight junction protein claudin 3 was downregulated while TLR2 was upregulated by Bt-CONV. The enteroendocrine cell subtypes L-cells and enterochromaffin cells were reduced in GF mice, with Bt-CONV restoring L-cell numbers. Motility as measured by colonic migrating motor complexes (CMMCs) increased in GF and Bt-CONV. CONCLUSION: Bt, common gut bacteria, is critical in regulating enteric neuronal and enteroendocrine cell populations, and neurogenic colonic activity. This highlights the potential use of this resident gut bacteria for maintaining healthy gut function

Regulation of Enteroendocrine Cell Networks by the Major Human Gut Symbiont Bacteroides thetaiotaomicron

Gut microbes have critical roles in maintaining host physiology, but their effects on epithelial chemosensory enteroendocrine cells (EEC) remain unclear. We investigated the role that the ubiquitous commensal gut bacterium Bacteriodes thetaiotaomicron (Bt) and its major fermentation products, acetate, propionate, and succinate (APS) have in shaping EEC networks in the murine gastrointestinal tract (GIT). The distribution and numbers of EEC populations were assessed in tissues along the GIT by fluorescent immunohistochemistry in specific pathogen free (SPF), germfree (GF) mice, GF mice conventionalized by Bt or Lactobacillus reuteri (Lr), and GF mice administered APS. In parallel, we also assessed the suitability of using intestinal crypt-derived epithelial monolayer cultures for these studies. GF mice up-regulated their EEC network, in terms of a general EEC marker chromogranin A (ChrA) expression, numbers of serotonin-producing enterochromaffin cells, and both hormone-producing K- and L-cells, with a corresponding increase in serum glucagon-like peptide-1 (GLP-1) levels. Bt conventionalization restored EEC numbers to levels in SPF mice with regional specificity; the effects on ChrA and L-cells were mainly in the small intestine, the effects on K-cells and EC cells were most apparent in the colon. By contrast, Lr did not restore EEC networks in conventionalized GF mice. Analysis of secretory epithelial cell monolayer cultures from whole small intestine showed that intestinal monolayers are variable and with the possible exclusion of GIP expressing cells, did not accurately reflect the EEC cell makeup seen in vivo. Regarding the mechanism of action of Bt on EECs, colonization of GF mice with Bt led to the production and accumulation of acetate, propionate and succinate (APS) in the caecum and colon, which when administered at physiological concentrations to GF mice via their drinking water for 10 days mimicked to a large extent the effects of Bt in GF mice. After withdrawal of APS, the changes in some EEC were maintained and, in some cases, were greater than during APS treatment. This data provides evidence of microbiota influences on regulating EEC networks in different regions of the GIT, with a single microbe, Bt, recapitulating its role in a process that may be dependent upon its fermentation products

Simple synthesis of 32P-labelled inositol hexakisphosphates for study of phosphate transformations

In many soils inositol hexakisphosphate in its various forms is as abundant as inorganic phosphate. The organismal and geochemical processes that exchange phosphate between inositol hexakisphosphate and other pools of soil phosphate are poorly defined, as are the organisms and enzymes involved. We rationalized that simple enzymic synthesis of inositol hexakisphosphate labeled with 32P would greatly enable study of transformation of soil inositol phosphates when combined with robust HPLC separations of different inositol phosphates

Diffractive Dijet Production in Antiproton-Proton Collisions at s\sqrt{s}=1.96 TeV

We report on a study of diffractive dijet production in $\bar{p}p$ collisions at $\sqrt{s}=1.96$ TeV using the CDF II detector at the Fermilab Tevatron $\bar{p}p$ collider. A data sample from 310 pb$^{-1}$ of integrated luminosity collected by triggering on a high transverse energy jet, $E_T^{jet}$, in coincidence with a recoil antiproton detected in a Roman pot spectrometer is used to measure the ratio of single-diffractive to inclusive-dijet event rates as a function of $x^{\bar p}$ of the interacting parton in the antiproton, the Bjorken-$x$, $x^{\bar p}_{Bj}$, and a $Q^2\approx (E_T^{jet})^2$ in the ranges $10^{-3}<x^{\bar p}_{Bj}<10^{-1}$ and $10^2<Q^2 <10^4$ GeV$^2$, respectively. Results are presented for the region of $\bar p$-momentum-loss fraction $0.03-4$ GeV$^2$. The $t_{\bar p}$ dependence is measured as a function of $Q^2$ and $x_{Bj}^{\bar p}$ and compared with that of inclusive single diffraction dissociation. We find weak $x^{\bar p}_{Bj}$ and $Q^2$ dependencies in the ratio of single diffractive to inclusive event rates, and no significant $Q^2$ dependence in the diffractive $t_{\bar p}$ distributions.Comment: 22 pages, 23 figures; published versio

Essential Readings in Problem-Based Learning: Exploring and Extending the Legacy of Howard S. Barrows

Essential Readings in Problem-Based Learning represents an ambitious goal to include influential articles and chapters regarding the theories and research central to ill-structured problem solving. The book is unique because it goes beyond being a traditional handbook of research by also including previously written articles germane to foundations of problem- based learning (PBL). In doing so, the chapters provide an overview of the current debates in light of established writings. Collectively, the book serves as a great resource by synthesizing various articles relevant to learning theories, practical instructional strategies, and research

Medial Temporal Lobe Does Not Tell The Whole Story: Episodic Memory In ‘atypical’ Variants Of Alzheimer’s Disease

Alzheimer’s disease is the most common form of dementia, which is globally epidemic and well-known by the general public. Episodic memory, a conscious recollection of a particular event in spatial and temporal context, is the most prominent deficit in the early stage of clinical amnestic AD, and reflected by the shrinkage of structures in medial temporal lobe (MTL), including the hippocampus. According to Braak staging, tangles begin in the transentorhinal cortex of the MTL, which then spreads to hippocampal subfields, and later to neocortical areas. Cases that are less recognized by the general public are patients with the atypical variants of AD. Interestingly, many of the atypical cases of AD appear to share the same histopathological features with clinical amnestic AD. According to the diagnostic criteria for these atypical variants of AD, episodic memory should be relatively preserved. However, inconsistent reports on the episodic memory performance and the hippocampal involvement in these atypical cases pose challenges for accurately diagnosing these patients. The two kinds of atypical variants of AD that I focused here are logopenic variant of Primary Progressive Aphasia (lvPPA) and posterior cortical atrophy (PCA). The overarching theme of my thesis is to examine 1) whether the atypical cases of AD have episodic memory difficulty, and if so, 2) what brain areas are responsible for this difficulty. Chapter 2 and 3 of the current thesis show that 1) episodic memory difficulty is observed in lvPPA and PCA cases and 2) this impairment is modulated by deficit in other cognitive domains and associated with disease in non-MTL brain regions. This would be consistent with the ‘hippocampal-sparing’ hypothesis that not all AD histopathology begins in the MTL, and these hippocampal-sparing conditions suggest that additional mechanisms must be considered in the genesis of spreading pathology in AD

Bandit-Based Online Candidate Selection for Adjustable Autonomy

Abstract In many robot navigation scenarios, the robot is able to choose between some number of operating modes. One such scenario is when a robot must decide how to trade-off online between autonomous and human tele-operation control. When little prior knowledge about the performance of each operator is known, the robot must learn online to model their abilities and be able to take advantage of the strengths of each. We present a bandit-based online candidate selection algorithm that operates in this adjustable autonomy setting and makes choices to optimize overall navigational performance. We justify this technique through such a scenario on logged data and demonstrate how the same technique can be used to optimize the use of high-resolution overhead data when its availability is limited 1.