Structural Basis for Assembly and Function of a Heterodimeric Plant Immune Receptor

Williams, Simon J.,Sohn, Kee Hoon,Wan, Li,Bernoux, Maud,Sarris, Panagiotis F.,Segonzac, Cecile,Ve, Thomas,Ma, Yan,Saucet, Simon B.,Ericsson, Daniel J.,Casey, Lachlan W.,Lonhienne, Thierry,Winzor, Dona American Association for the Advancement of Scienc 2014 Science Vol.344 No.6181

<P><B>Universal Immune Function</B></P><P>Certain pathogen effectors are detected in plants by cytoplasmic receptors. First solving the crystal structures of <I>Arabidopsis</I> receptors, <B>Williams <I>et al.</I></B> (p. 299; see the Perspective by <B>Nishimura and Dangl</B>) discovered that in the resting state, the structures form a heterodimer that readies the complex for effector binding and keeps the signaling domains from firing too early. Once the pathogen effector binds, the structure of the complex shifts such that the signaling domains can form a homodimer to initiate downstream signaling. Similarities between these plant-pathogen receptors and Toll-like receptors in animals suggest the molecular mechanisms may translate broadly.</P>

Theories and Research for the Study of Phenomena in the Client Domain of Nursing : Medical Sociology, Chronic Illness and the Body: A Rejoinder to Michael Kelly and David Field

( Simon J. Williams ),( Michael P. Kelly ),( David Field ) 서울대학교 간호과학연구소 1999 서울대학교 간호과학연구소 학술대회 자료집 Vol.1999 No.2

Dynamic causal modelling on infant fNIRS data: A validation study on a simultaneously recorded fNIRS-fMRI dataset

Bulgarelli, Chiara,Blasi, Anna,Arridge, Simon,Powell, Samuel,de Klerk, Carina C.J.M.,Southgate, Victoria,Brigadoi, Sabrina,Penny, William,Tak, Sungho,Hamilton, Antonia Elsevier 2018 NeuroImage Vol.175 No.-

<P><B>Abstract</B></P> <P>Tracking the connectivity of the developing brain from infancy through childhood is an area of increasing research interest, and fNIRS provides an ideal method for studying the infant brain as it is compact, safe and robust to motion. However, data analysis methods for fNIRS are still underdeveloped compared to those available for fMRI. Dynamic causal modelling (DCM) is an advanced connectivity technique developed for fMRI data, that aims to estimate the coupling between brain regions and how this might be modulated by changes in experimental conditions. DCM has recently been applied to adult fNIRS, but not to infants. The present paper provides a proof-of-principle for the application of this method to infant fNIRS data and a demonstration of the robustness of this method using a simultaneously recorded fMRI-fNIRS single case study, thereby allowing the use of this technique in future infant studies.</P> <P>fMRI and fNIRS were simultaneously recorded from a 6-month-old sleeping infant, who was presented with auditory stimuli in a block design. Both fMRI and fNIRS data were preprocessed using SPM, and analysed using a general linear model approach. The main challenges that adapting DCM for fNIRS infant data posed included: (i) the import of the structural image of the participant for spatial pre-processing, (ii) the spatial registration of the optodes on the structural image of the infant, (iii) calculation of an accurate 3-layer segmentation of the structural image, (iv) creation of a high-density mesh as well as (v) the estimation of the NIRS optical sensitivity functions. To assess our results, we compared the values obtained for variational Free Energy (F), Bayesian Model Selection (BMS) and Bayesian Model Average (BMA) with the same set of possible models applied to both the fMRI and fNIRS datasets. We found high correspondence in F, BMS, and BMA between fMRI and fNIRS data, therefore showing for the first time high reliability of DCM applied to infant fNIRS data. This work opens new avenues for future research on effective connectivity in infancy by contributing a data analysis pipeline and guidance for applying DCM to infant fNIRS data.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Connectivity studies give important insights into infant brain development. </LI> <LI> fNIRS is a valuable method for infancy studies, but can we analyse connectivity? </LI> <LI> On fMRI-fNIRS acquired simultaneously, we estimate effective connectivity with DCM. </LI> <LI> We showed high correspondence of DCM values between fMRI and fNIRS data. </LI> <LI> We validated DCM on fNIRS infant data, providing guidance for future projects. </LI> </UL> </P>

Detecting Facet Joint and Lateral Mass Injuries of the Subaxial Cervical Spine in Major Trauma Patients

Joost Johannes van Middendorp,Ian Cheung,Kristian Dalzell,Hamish Deverall,Brian J.C. Freeman,Stephen A.C. Morris,Simon J.I. Sandler,Richard Williams,Y.H. Yau,Ben Goss 대한척추외과학회 2015 Asian Spine Journal Vol.9 No.3

Study Design: Radiologic imaging measurement study. Purpose: To assess the accuracy of detecting lateral mass and facet joint injuries of the subaxial cervical spine on plain radiographs using computed tomography (CT) scan images as a reference standard; and the integrity of morphological landmarks of the lateral mass and facet joints of the subaxial cervical spine. Overview of Literature: Injuries of lateral mass and facet joints potentially lead to an unstable subaxial cervical spine and concomitant neurological sequelae. However, no study has evaluated the accuracy of detecting specific facet joint injuries. Methods: Eight spinal surgeons scored four sets of the same, randomly re-ordered, 30 cases with and without facet joint injuries of the subaxial cervical spine. Two surveys included conventional plain radiographs series (test) and another two surveys included CT scan images (reference). Facet joint injury characteristics were assessed for accuracy and reliability. Raw agreement, Fleiss kappa, Cohen’s kappa and intraclass correlation coefficient statistics were used for reliability analysis. Majority rules were used for accuracy analysis. Results: Of the 21 facet joint injuries discerned on CT scan images, 10 were detected in both plain radiograph surveys (sensitivity, 0.48; 95% confidence interval [CI], 0.26–0.70). There were no false positive facet joint injuries in either of the first two X-ray surveys (specificity, 1.0; 95% CI, 0.63–1.0). Five of the 11 cases with missed injuries had an injury below the lowest visible articulating level on radiographs. CT scan images resulted in superior inter- and intra-rater agreement values for assessing morphologic injury characteristics of facet joint injuries. Conclusions: Plain radiographs are not accurate, nor reliable for the assessment of facet joint injuries of the subaxial cervical spine. CT scans offer reliable diagnostic information required for the detection and treatment planning of facet joint injuries.

The Nuclear Immune Receptor <i>RPS4</i> Is Required for <i>RRS1^SLH1</i> -Dependent Constitutive Defense Activation in <i>Arabidopsis thaliana</i>

Sohn, Kee Hoon,Segonzac, Cé,cile,Rallapalli, Ghanasyam,Sarris, Panagiotis F.,Woo, Joo Yong,Williams, Simon J.,Newman, Toby E.,Paek, Kyung Hee,Kobe, Bostjan,Jones, Jonathan D. G. Public Library of Science 2014 PLoS genetics Vol.10 No.10

<▼1><P>Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific “avirulent” pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis <I>R</I> genes, <I>RPS4</I> (resistance to <I>Pseudomonas syringae</I> 4) and <I>RRS1</I> (resistance to <I>Ralstonia solanacearum</I> 1), function together to confer recognition of <I>Pseudomonas</I> AvrRps4 and <I>Ralstonia</I> PopP2. <I>RRS1</I> is the only known recessive NB-LRR <I>R</I> gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 <I>via Pseudomonas</I> type III secretion. The Arabidopsis <I>slh1</I> (<I>sensitive to low humidity 1</I>) mutant encodes an RRS1 allele (RRS1<SUP>SLH1</SUP>) with a single amino acid (leucine) insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1<SUP>SLH1</SUP>-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify <I><U>su</U>ppressor of</I><U>s</U>l<U>h</U>1 <I><U>i</U>mmunity</I> (<I>sushi</I>) mutants. We show that many <I>sushi</I> mutants carry mutations in <I>RPS4</I>, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an <I>Agrobacterium</I>-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1<SUP>SLH1</SUP> is required for RRS1<SUP>SLH1</SUP> function. We also recapitulate the dominant suppression of RRS1<SUP>SLH1</SUP> defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1<SUP>SLH1</SUP> shed new light on mechanisms by which NB-LRR protein pairs activate defense signaling, or are held inactive in the absence of a pathogen effector.</P></▼1><▼2><P><B>Author Summary</B></P><P>How plant NB-LRR resistance proteins and the related mammalian Nod-like receptors (NLRs) activate defense is poorly understood. Plant and animal immune receptors can function in pairs. Two Arabidopsis nuclear immune receptors, RPS4 and RRS1, confer recognition of the unrelated bacterial effectors, AvrRps4 and PopP2, and activate defense. Using delivery of PopP2 into Arabidopsis leaf cells <I>via Pseudomonas</I> type III secretion, we define early transcriptional changes upon RPS4/RRS1-dependent PopP2 recognition. We show an auto-active allele of RRS1, RRS1<SUP>SLH1</SUP>, triggers transcriptional reprogramming of defense genes that are also reprogrammed by AvrRps4 or PopP2 in an RPS4/RRS1-dependent manner. To discover genetic requirements for RRS1<SUP>SLH1</SUP> auto-activation, we conducted a suppressor screen. Many <I>suppressor of</I> slh1 <I>immunity</I> (<I>sushi</I>) mutants that are impaired in RRS1<SUP>SLH1</SUP>-mediated auto-activation carry loss-of-function mutations in RPS4. This suggests that RPS4 functions as a signaling component together with or downstream of RRS1-activated immunity, in contrast to earlier hypotheses, significantly advancing our understanding of how immune receptors activate defense in plants.</P></▼2>