Structural genomics analysis of uncharacterized protein families overrepresented in human gut bacteria identifies a novel glycoside hydrolase.

BackgroundBacteroides spp. form a significant part of our gut microbiome and are well known for optimized metabolism of diverse polysaccharides. Initial analysis of the archetypal Bacteroides thetaiotaomicron genome identified 172 glycosyl hydrolases and a large number of uncharacterized proteins associated with polysaccharide metabolism.ResultsBT_1012 from Bacteroides thetaiotaomicron VPI-5482 is a protein of unknown function and a member of a large protein family consisting entirely of uncharacterized proteins. Initial sequence analysis predicted that this protein has two domains, one on the N- and one on the C-terminal. A PSI-BLAST search found over 150 full length and over 90 half size homologs consisting only of the N-terminal domain. The experimentally determined three-dimensional structure of the BT_1012 protein confirms its two-domain architecture and structural analysis of both domains suggests their specific functions. The N-terminal domain is a putative catalytic domain with significant similarity to known glycoside hydrolases, the C-terminal domain has a beta-sandwich fold typically found in C-terminal domains of other glycosyl hydrolases, however these domains are typically involved in substrate binding. We describe the structure of the BT_1012 protein and discuss its sequence-structure relationship and their possible functional implications.ConclusionsStructural and sequence analyses of the BT_1012 protein identifies it as a glycosyl hydrolase, expanding an already impressive catalog of enzymes involved in polysaccharide metabolism in Bacteroides spp. Based on this we have renamed the Pfam families representing the two domains found in the BT_1012 protein, PF13204 and PF12904, as putative glycoside hydrolase and glycoside hydrolase-associated C-terminal domain respectively

Respiration-Induced Intraorgan Deformation of the Liver: Implications for Treatment Planning in Patients Treated With Fiducial Tracking.

Stereotactic body radiation therapy is a well-tolerated modality for the treatment of primary and metastatic liver lesions, and fiducials are often used as surrogates for tumor tracking during treatment. We evaluated respiratory-induced liver deformation by measuring the rigidity of the fiducial configuration during the breathing cycle. Seventeen patients, with 18 distinct treatment courses, were treated with stereotactic body radiosurgery using multiple fiducials. Liver deformation was empirically quantified by measuring the intrafiducial distances at different phases of respiration. Data points were collected at the 0%, 50%, and 100% inspiration points, and the distance between each pair of fiducials was measured at the 3 phases. The rigid body error was calculated as the maximum difference in the intrafiducial distances. Liver disease was calculated with Child-Pugh score using laboratory values within 3 months of initiation of treatment. A peripheral fiducial was defined as within 1.5 cm of the liver edge, and all other fiducials were classified as central. For 5 patients with only peripheral fiducials, the fiducial configuration had more deformation (average maximum rigid body error 7.11 mm, range: 1.89-11.35 mm) when compared to patients with both central and peripheral and central fiducials only (average maximum rigid body error 3.36 mm, range: 0.5-9.09 mm, P = .037). The largest rigid body errors (11.3 and 10.6 mm) were in 2 patients with Child-Pugh class A liver disease and multiple peripheral fiducials. The liver experiences internal deformation, and the fiducial configuration should not be assumed to act as a static structure. We observed greater deformation at the periphery than at the center of the liver. In our small data set, we were not able to identify cirrhosis, which is associated with greater rigidity of the liver, as predictive for deformation. Treatment planning based only on fiducial localization must take potential intraorgan deformation into account

Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.

ObjectiveTo compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.DesignAdult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.ResultsThe UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5-16.4) and 7.0 (1.0-19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.ConclusionsThe present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state

Subject preferences of fifth-grade children.

Thesis (Ed.M.)--Boston University N.B.:Pages 155 and 309 are missing from original thesis

Interference effects in two-photon ATI by multiple orders high harmonics with random or locked phases

We numerically study 2-photon processes using a set of harmonics from a Ti:Sapphire laser and in particular interference effects in the Above Threshold Ionization spectra. We compare the situation where the harmonic phases are assumed locked to the case where they have a random distribution. Suggestions for possible experiments, using realistic parameters are discussed.Comment: 11 pages, 13 figures, LaTe

Healthâ Related Quality of Life Components in Children With Neonatal Brachial Plexus Palsy: A Qualitative Study

BackgroundCurrently, no published, validated patientâ reported outcome (PRO) measures of healthâ related quality of life (HRQOL) exist for use with neonatal brachial plexus palsy (NBPP). NBPP is a debilitating condition that occurs during the perinatal period, resulting in paralysis/paresis and loss of sensation in the affected arm. Commonly used NBPP measures are not comprehensive and do not fully account for clinically meaningful changes in function or progression of the disorder.ObjectiveTo evaluate important components of HRQOL for children with NBPP and identify where new PRO measures are needed.DesignEleven focus groups comprising children with NBPP (4), family members (6), and professional providers (1) to assess HRQOL.SettingBrachial plexus clinic.ParticipantsChildren with NBPP, their parents, and professional providers.Inclusion CriteriaChildren 7â 17 years old with NBPP; parents/caregivers at least 18 years of age; professionals with â ¥2 years’ experience providing NBPP clinical care; ability to read and speak English fluently.MethodsFocus group sessions were recorded, transcribed verbatim, and deidentified. Qualitative frequency analysis identified different aspects of HRQOL relevant to NBPP. This analysis expands on the groundedâ theory approach to qualitative analysis, including development of a domain framework, open and axial coding, selective coding, and descriptive analysis. The resulting HRQOL domain framework (and frequency analysis) was then compared to the domain framework for existing PRO measures (PROMIS and Neuroâ QoL) to identify components of HRQOL where new PRO measures are needed for NBPP.Main Outcome MeasuresNot applicable.ResultsAlthough many physical, social, and emotional health domains were captured by existing PRO measures, some significant NBPPâ specific topics emerged from qualitative analysisâ functionality, sensory, physical appearance, arm/hand compensation and preference, explaining functionality/appearance to others, and selfâ esteem and body image concerns.ConclusionsDevelopment of sensitive and specific measures capturing arm/hand function and body image would improve the clinical care of patients with NBPP.Level of EvidenceNot applicable.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146831/1/pmr2383.pd

Maize terpene synthase 1 impacts insect behavior via the production of monoterpene volatiles \u3ci\u3eβ\u3c/i\u3e-myrcene and linalool

Plant-derived volatiles are important mediators of plant-insect interactions as they can provide cues for host location and quality, or act as direct or indirect defense molecules. The volatiles produced by Zea mays (maize) include a range of terpenes, likely produced by several of the terpene synthases (TPS) present in maize. Determining the roles of specific terpene volatiles and individual TPSs in maize-insect interactions is challenging due to the promiscuous nature of TPSs in vitro and their potential for functional redundancy. In this study, we used metabolite GWAS of a sweetcorn diversity panel infested with Spodoptera frugiperda (fall armyworm) to identify genetic correlations between TPSs and individual volatiles. This analysis revealed a correlation between maize terpene synthase 1 (ZmTPS1) and emission of the monoterpene volatiles linalool and β-myrcene. Electroantennogram assays showed gravid S. frugiperda could detect both linalool and β-myrcene. Quantification of headspace volatiles in a maize tps1 loss-of-function mutant confirmed that ZmTPS1 is an important contributor to linalool and β-myrcene emission in maize. Furthermore, pairwise choice assays between tps1 mutant and wildtype plants showed that ZmTPS1, and by extension its volatile products, aid host location in the chewing insect S. frugiperda, yet repel the sap-sucking pest, Rhopalosiphum maidis (corn leaf aphid). On the other hand, ZmTPS1 had no impact on indirect defense via the recruitment of the parasitoid Cotesia marginiventris. ZmTPS1 is therefore an important mediator of the interactions between maize and its insect pests

A CD3-Specific Antibody Reduces Cytokine Production and Alters Phosphoprotein Profiles in Intestinal Tissues From Patients With Inflammatory Bowel Disease

NOTICE: this is the author’s version of a work that was accepted for publication in Gastroenterology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in GASTROENTEROLOGY, 10.1053/j.gastro.2014.03.04

Effect of bilayer coupling on tunneling conductance of double-layer high T_c cuprates

Physical effects of bilayer coupling on the tunneling spectroscopy of high T$_{c}$ cuprates are investigated. The bilayer coupling separates the bonding and antibonding bands and leads to a splitting of the coherence peaks in the tunneling differential conductance. However, the coherence peak of the bonding band is strongly suppressed and broadened by the particle-hole asymmetry in the density of states and finite quasiparticle life-time, and is difficult to resolve by experiments. This gives a qualitative account why the bilayer splitting of the coherence peaks was not clearly observed in tunneling measurements of double-layer high-T$_c$ oxides.Comment: 4 pages, 3 figures, to be published in PR