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( Jonna Jalanka ),( Ching Lam ),( Andrew Bennett ),( Anna Hartikainen ),( Fiona Crispie ),( Laura A Finnegan ),( Paul D Cotter ),( Robin Spiller ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.2
Background/Aims Diarrhea-predominant irritable bowel syndrome (IBS-D) has been previously associated with evidence of immune activation and altered microbiota. Our aim is to assess the effect of the anti-inflammatory agent, mesalazine, on inflammatory gene expression and microbiota composition in IBS-D. Methods We studied a subset of patients (n = 43) from a previously published 12-week radomized placebo-controlled trial of mesalazine. Mucosal biopsies were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction for a range of markers of inflammation, altered permeability, and sensory receptors including Toll-like receptors (TLRs) at randomization after treatment. All biopsy data were compared to 21 healthy controls. Patient’s stool microbiota composition was analysed through 16S ribosomal RNA sequencing. Results We found no evidence of increased immune activation compared to healthy controls. However, we did find increased expression of receptors in both sensory pathways and innate immune response including TLR4. Higher TLR4 expression was associated with greater urgency. TLR4 expression correlated strongly with the expression of the receptors bradykinin receptor B2, chemerin chemokine-like receptor 1, and transient receptor potential cation channel, subfamily A, member 1 as well as TLR4’s downstream adaptor myeloid differentiation factor 88. Mesalazine had minimal effect on either gene expression or microbiota composition. Conclusions Biopsies from a well-characterized IBS-D cohort showed no substantial inflammation. Mesalazine has little effect on gene expression and its previous reported effect on fecal microbiota associated with much greater inflammation found in inflammatory bowel diseases is likely secondary to reduced inflammation. Increased expression of TLR4 and correlated receptors in IBS may mediate a general increase in sensitivity to external stimuli, particularly those that signal via the TLR system. (J Neurogastroenterol Motil 2021;27:279-291)
Emergent genetic oscillations in a synthetic microbial consortium
Chen, Ye,Kim, Jae Kyoung,Hirning, Andrew J.,Josić,, Kreš,imir,Bennett, Matthew R. American Association for the Advancement of Scienc 2015 Science Vol.349 No.6251
<P><B>Engineering cell population behavior</B></P><P>Attaining the full promise of synthetic biology will require designing population-level behaviors of multiple interacting cell types. As a start, Chen et al. engineered two strains of the bacterium <I>Escherichia coli</I> to produce signaling molecules that regulate transcription in the complementary strain (see the Perspective by Teague and Weiss). The signaling circuit was successfully designed to produce feedback loops that produce synchronous oscillations in transcription between the two strains. A mathematical model helped determine how to modulate the oscillations and control their robustness to perturbations.</P><P><I>Science</I>, this issue p. 986; see also p. 924</P><P>A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types—an “activator” strain and a “repressor” strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types.</P>
Taxonomy of the order Mononegavirales: update 2018
Amarasinghe, Gaya K.,Aré,chiga Ceballos, Nidia G.,Banyard, Ashley C.,Basler, Christopher F.,Bavari, Sina,Bennett, Andrew J.,Blasdell, Kim R.,Briese, Thomas,Bukreyev, Alexander,Caì,, Y&iacu Springer-Verlag 2018 Archives of virology Vol.163 No.8