Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system

<p>Abstract</p> <p>Background</p> <p>Tracking an ingested magnet by the Magnet Tracking System MTS-1 (Motilis, Lausanne, Switzerland) is an easy and minimally-invasive method to assess gastrointestinal transit. The aim was to test the validity of MTS-1 for assessment of gastric transit time and small intestinal transit time, and to illustrate transit patterns detected by the system.</p> <p>Methods</p> <p>A small magnet was ingested and tracked by an external matrix of 16 magnetic field sensors (4 × 4) giving a position defined by 5 coordinates (position: <b>x, y, z, and angle: θ, ϕ)</b>. Eight healthy subjects were each investigated three times: (1) with a small magnet mounted on a capsule endoscope (PillCam); (2) with the magnet alone and the small intestine in the fasting state; and (3) with the magnet alone and the small intestine in the postprandial state.</p> <p>Results</p> <p>Experiment (1) showed good agreement and no systematic differences between MTS-1 and capsule endoscopy when assessing gastric transit (median difference 1 min; range: 0-6 min) and small intestinal transit time (median difference 0.5 min; range: 0-52 min). Comparing experiments (1) and (2) there were no systematic differences in gastric transit or small intestinal transit when using the magnet-PillCam unit and the much smaller magnetic pill. In experiments (2) and (3), short bursts of very fast movements lasting less than 5% of the time accounted for more than half the distance covered during the first two hours in the small intestine, irrespective of whether the small intestine was in the fasting or postprandial state. The mean contraction frequency in the small intestine was significantly lower in the fasting state than in the postprandial state (9.90 min^-1vs. 10.53 min^-1) (p = 0.03).</p> <p>Conclusion</p> <p>MTS-1 is reliable for determination of gastric transit and small intestinal transit time. It is possible to distinguish between the mean contraction frequency of small intestine in the fasting state and in the postprandial state.</p

DNA glycosylase Neil3 regulates vascular smooth muscle cell biology during atherosclerosis development.

BACKGROUND AND AIMS: Atherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cell (VSMC) phenotype. The DNA glycosylase NEIL3 has previously been shown to have a role in atherogenesis, though whether this is due to its ability to repair DNA damage or to other non-canonical functions is not yet clear. Hereby, we investigate the role of NEIL3 in atherogenesis, specifically in VSMC phenotypic modulation, which is critical in plaque formation and stability. METHODS: Chow diet-fed atherosclerosis-prone Apoe-/- mice deficient in Neil3, and NEIL3-abrogated human primary aortic VSMCs were characterized by qPCR, and immunohistochemical and enzymatic-based assays; moreover, single-cell RNA sequencing, mRNA sequencing, and proteomics were used to map the molecular effects of Neil3/NEIL3 deficiency in the aortic VSMC phenotype. Furthermore, BrdU-based proliferation assays and Western blot were performed to elucidate the involvement of the Akt signaling pathway in the transdifferentiation of aortic VSMCs lacking Neil3/NEIL3. RESULTS: We show that Neil3 deficiency increases atherosclerotic plaque development without affecting systemic lipids. This observation was associated with a shift in VSMC phenotype towards a proliferating, lipid-accumulating and secretory macrophage-like cell phenotype, without changes in DNA damage. VSMC transdifferentiation in Neil3-deficient mice encompassed increased activity of the Akt signaling pathway, supported by cell experiments showing Akt-dependent proliferation in NEIL3-abrogated human primary aortic VSMCs. CONCLUSIONS: Our findings show that Neil3 deficiency promotes atherosclerosis development through non-canonical mechanisms affecting VSMC phenotype involving activation of the Akt signaling pathway

The RNA Helicase DHX34 Activates NMD by Promoting a Transition from the Surveillance to the Decay-Inducing Complex

SummaryNonsense-mediated decay (NMD) is a surveillance mechanism that degrades aberrant mRNAs. A complex comprising SMG1, UPF1, and the translation termination factors eRF1 and eRF3 (SURF) is assembled in the vicinity of a premature termination codon. Subsequently, an interaction with UPF2, UPF3b, and the exon junction complex induces the formation of the decay-inducing complex (DECID) and triggers NMD. We previously identified the RNA helicase DHX34 as an NMD factor in C. elegans and in vertebrates. Here, we investigate the mechanism by which DHX34 activates NMD in human cells. We show that DHX34 is recruited to the SURF complex via its preferential interaction with hypophosphorylated UPF1. A series of molecular transitions induced by DHX34 include enhanced recruitment of UPF2, increased UPF1 phosphorylation, and dissociation of eRF3 from UPF1. Thus, DHX34 promotes mRNP remodeling and triggers the conversion from the SURF complex to the DECID complex resulting in NMD activation

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]