Global Lithium Availability

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87046/1/j.1530-9290.2011.00359.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/87046/2/JIEC_359_sm_SuppMatS1.pd

Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression in patients with functional abdominal pain - a randomised clinical study

In a recent double-blinded clinical trial the probiotic combination of L-NCFM and B-LBi07 reduced bloating symptoms in patients with functional bowel disorder; an effect more evident in those who reported abdominal pain. In mice, L-NCFM but not B-LBi07 induced colonic MOR and CB2 expression and reduced visceral sensitivity

The Innate Immune Receptor NLRX1 Functions as a Tumor Suppressor by Reducing Colon Tumorigenesis and Key Tumor-Promoting Signals

NOD-like receptor (NLR) proteins are intracellular innate immune sensors/receptors that regulate immunity. This work shows that NLRX1 serves as a tumor suppressor in colitis-associated cancer (CAC) and sporadic colon cancer by keeping key tumor promoting pathways in check. Nlrx1(-/-) mice were highly susceptible to CAC, showing increases in key cancer-promoting pathways including nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), and interleukin 6 (IL-6). The tumor-suppressive function of NLRX1 originated primarily from the non-hematopoietic compartment. This prompted an analysis of NLRX1 function in the Apc(min/+) genetic model of sporadic gastrointestinal cancer. NLRX1 attenuated Apc(min/+) colon tumorigenesis, cellular proliferation, NF-κB, MAPK, STAT3 activation, and IL-6 levels. Application of anti-interleukin 6 receptor (IL6R) antibody therapy reduced tumor burden, increased survival, and reduced STAT3 activation in Nlrx1(-/-)Apc(min/+) mice. As an important clinical correlate, human colon cancer samples expressed lower levels of NLRX1 than healthy controls in multiple patient cohorts. These data implicate anti-IL6R as a potential personalized therapy for colon cancers with reduced NLRX1

ELSA in industrial robotics

Purpose of ReviewIndustry is changing; converging technologies allow a fourth Industrial Revolution, where it is envisaged that robots will work alongside humans. We investigate how the research community is responding to the ethical, legal, and social aspects of industrial robots, with a primary focus on manufacturing industry.Recent FindingsThe literature shows considerable interest in the impact of robotics and automation on industry. This interest spans many disciplines, which is to be expected given that the ELS impacts of industrial robotics may be profound in their depth and far-reaching in their scope.SummaryWe suggest that the increasing importance of human-robot interaction (HRI) reduces the differentiation between industrial robotics and other robotic domains and that the main challenges to successful adoption for the benefit of human life are above all political and economic. Emerging standards and legal frameworks may scaffold this success, but it is apparent that getting it wrong might have repercussions that last for generations

The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer

Colitis-associated cancer (CAC) is a major complication of inflammatory bowel diseases. We show that components of the inflammasome are protective during acute and recurring colitis and CAC in the dextran sulfate sodium (DSS) and azoxymethane + DSS models. Mice lacking the inflammasome adaptor protein PYCARD (ASC) and caspase-1 demonstrate increased disease outcome, morbidity, histopathology, and polyp formation. The increased tumor burden is correlated with attenuated levels of IL-1β and IL-18 at the tumor site. To decipher the nucleotide-binding domain, leucine-rich-repeat-containing (NLR) component that is involved in colitis and CAC, we assessed Nlrp3 and Nlrc4 deficient mice. Nlrp3−/− mice showed an increase in acute and recurring colitis and CAC, although the disease outcome was less severe in Nlrp3−/− mice than in Pycard−/− or Casp1−/− animals. No significant differences were observed in disease progression or outcome in Nlrc4−/− mice compared with similarly treated wild-type animals. Bone marrow reconstitution experiments show that Nlrp3 gene expression and function in hematopoietic cells, rather than intestinal epithelial cells or stromal cells, is responsible for protection against increased tumorigenesis. These data suggest that the inflammasome functions as an attenuator of colitis and CAC

The Mass Distribution and Rotation Curve in the Galaxy

The mass distribution in the Galaxy is determined by dynamical and photometric methods. Rotation curves are the major tool for determining the dynamical mass distribution in the Milky Way and spiral galaxies. The photometric (statistical) method utilizes luminosity profiles from optical and infrared observations, and assumes empirical values of the mass-to-luminosity (M/L) ratio to convert the luminosity to mass. In this chapter the dynamical method is described in detail, and rotation curves and mass distribution in the Milky Way and nearby spiral galaxies are presented. The dynamical method is categorized into two methods: the decomposition method and direct method. The former fits the rotation curve by calculated curve assuming several mass components such as a bulge, disk and halo, and adjust the dynamical parameters of each component. Explanations are given of the mass profiles as the de Vaucouleurs law, exponential disk, and dark halo profiles inferred from numerical simulations. Another method is the direct method, with which the mass distribution can be directly calculated from the data of rotation velocities without employing any mass models. Some results from both methods are presented, and the Galactic structure is discussed in terms of the mass. Rotation curves and mass distributions in external galaxies are also discussed, and the fundamental mass structures are shown to be universal.Comment: 54 pages, 25 figures, in 'Planets, Stars and Stellar Systems', Springer, Vol. 5, ed. G. Gilmore, Chap. 19. Note: Preprint with full figures is available from http://www.ioa.s.u-tokyo.ac.jp/~sofue/htdocs/2013psss

Gnotobiotic IL-10−/−; NF-κBEGFP Mice Develop Rapid and Severe Colitis Following Campylobacter jejuni Infection

Limited information is available on the molecular mechanisms associated with Campylobacter jejuni (C. jejuni) induced food-borne diarrheal illnesses. In this study, we investigated the function of TLR/NF-κB signaling in C. jejuni induced pathogenesis using gnotobiotic IL-10−/−; NF-κBEGFP mice. In vitro analysis showed that C. jejuni induced IκB phosphorylation, followed by enhanced NF-κB transcriptional activity and increased IL-6, MIP-2α and NOD2 mRNA accumulation in infected-mouse colonic epithelial cells CMT93. Importantly, these events were blocked by molecular delivery of an IκB inhibitor (Ad5IκBAA). NF-κB signalling was also important for C.jejuni-induced cytokine gene expression in bone marrow-derived dendritic cells. Importantly, C. jejuni associated IL-10−/−; NF-κBEGFP mice developed mild (day 5) and severe (day 14) ulcerating colonic inflammation and bloody diarrhea as assessed by colonoscopy and histological analysis. Macroscopic analysis showed elevated EGFP expression indicating NF-κB activation throughout the colon of C. jejuni associated IL-10−/−; NF-κBEGFP mice, while fluorescence microscopy revealed EGFP positive cells to be exclusively located in lamina propria mononuclear cells. Pharmacological NF-κB inhibition using Bay 11-7085 did not ameliorate C. jejuni induced colonic inflammation. Our findings indicate that C. jejuni induces rapid and severe intestinal inflammation in a susceptible host that correlates with enhanced NF-κB activity from lamina propria immune cells

Mouse Background Strain Profoundly Influences Paneth Cell Function and Intestinal Microbial Composition

Increasing evidence supports the central role of Paneth cells in maintaining intestinal host-microbial homeostasis. However, the direct impact of host genotype on Paneth cell function remains unclear. Here, we characterize key differences in Paneth cell function and intestinal microbial composition in two widely utilized, genetically distinct mouse strains (C57BL/6 and 129/SvEv). In doing so, we demonstrate critical influences of host genotype on Paneth cell activity and the enteric microbiota.Paneth cell numbers were determined by flow cytometry. Antimicrobial peptide (AMP) expression was evaluated using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), acid urea-polyacrylamide gel electrophoresis, and mass spectrometry. Effects of mouse background on microbial composition were assessed by reciprocal colonization of germ-free mice from both background strains, followed by compositional analysis of resultant gut bacterial communities using terminal restriction fragment length polymorphism analysis and 16 S qPCR. Our results revealed that 129/SvEv mice possessed fewer Paneth cells and a divergent AMP profile relative to C57BL/6 counterparts. Novel 129/SvEv á-defensin peptides were identified, including Defa2/18v, Defa11, Defa16, and Defa18. Host genotype profoundly affected the global profile of the intestinal microbiota, while both source and host factors were found to influence specific bacterial groups. Interestingly, ileal α-defensins from 129/SvEv mice displayed attenuated antimicrobial activity against pro-inflammatory E. coli strains, a bacterial species found to be expanded in these animals.This work establishes the important impact of host genotype on Paneth cell function and the composition of the intestinal microbiota. It further identifies specific AMP and microbial alterations in two commonly used inbred mouse strains that have varying susceptibilities to a variety of disorders, ranging from obesity to intestinal inflammation. This will be critical for future studies utilizing these murine backgrounds to study the effects of Paneth cells and the intestinal microbiota on host health and disease