Identification of the Type Eleven Secretion System (T11SS) and Characterization of T11SS-dependent Effector Proteins

Host-associated microbes live in dangerous environments as a result of host immune killing, nutrient provisioning, and physiological conditions. Bacteria have evolved a host of surface and secreted proteins to help interact with this host environment and overcome nutrient limitation. The studies included within this dissertation describe the identification of a novel bacterial secretion system which has evolved to transport these symbiosis mediating proteins. This system, termed the type eleven secretion system (T11SS), is present throughout the Gram negative phylum Proteobacteria, including many human pathogens such as Neisseria meningitidis, Acinetobacter baumanii, Haemophilus haemolyticus, and Proteus vulgaris. Furthermore, these studies describe how novel cargo proteins of this secretion system were identified and characterized using molecular biology and physicochemical techniques. Chapter 1 establishes the importance of nematode model systems in researching symbiosis, highlighting how research in entomopathogenic nematodes identified the first T11S. Chapters 2 and 3 use a T11SS-dependent hemophore named hemophilin and its transporter protein to demonstrate T11SS secretion and its mechanisms of cargo specificity. Chapter 3 also explores the role of hemophilin within the nematode symbiont X. nematophila in surviving heme starvation and facilitating nematode fitness. Chapter 4 demonstrates that the lipidated symbiosis factor NilC is surface exposed by the T11SS NilB and uses a combination of metabolomics, proteomics, and lectin library analysis to describe the role of NilC in colonization. Chapter 5 describes a protocol for bioinformatically controlling genome co-occurrence analyses and utilizes this technique to demonstrate significant co-occurrence of T11SS with metal uptake pathways, single carbon metabolism, and mobile genetic elements. Additionally, this protocol allowed prediction of 141 T11SS-dependent cargo falling into 10 distinct architectures, including never before seen T11SS-dependent adhesins and glycoproteins. Finally, Chapter 6 summarizes our findings and contextualizes how the T11SS plays essential roles in host-microbe association in mutualistic bacteria and pathogenic bacteria alike

Say A Prayer For The Boys Out There

https://digitalcommons.library.umaine.edu/mmb-vp/5332/thumbnail.jp

A Method to Measure ϕ1\phi_1 Using Bˉ0→Dh0\bar{B}^0 \to D h^0 With Multibody DD Decay

We describe a new method to measure the angle $\phi_1$ of the CKM Unitarity Triangle using amplitude analysis of the multibody decay of the neutral $D$ meson produced via $\bar{B} \to D h^0$ colour-suppressed decays. The method employs the interference between $D^0$ and $\bar{D}^0$ to directly extract the value of $2\phi_1$, and thus resolve the ambiguity between $2\phi_1$ and $\pi-2\phi_1$ in the measurement of $\sin(2\phi_1)$ using \bar{B}^0 \to J/ \psi \ks. We present a feasibility study of this method using Monte Carlo simulation.Comment: 12 pages, 7 figures, 2 tables. See also talk presented by T.G. at CKM2005 (http://ckm2005.ucsd.edu/) Submitted to Physics Letters

NPR1 Protein Regulates Pathogenic and Symbiotic Interactions between Rhizobium and Legumes and Non-Legumes

BACKGROUND:Legumes are unique in their ability to establish symbiotic interaction with rhizobacteria from Rhizobium genus, which provide them with available nitrogen. Nodulation factors (NFs) produced by Rhizobium initiate legume root hair deformation and curling that entrap the bacteria, and allow it to grow inside the plant. In contrast, legumes and non-legumes activate defense responses when inoculated with pathogenic bacteria. One major defense pathway is mediated by salicylic acid (SA). SA is sensed and transduced to downstream defense components by a redox-regulated protein called NPR1. METHODOLOGY/PRINCIPAL FINDINGS:We used Arabidopsis mutants in SA defense pathway to test the role of NPR1 in symbiotic interactions. Inoculation of Sinorhizobium meliloti or purified NF on Medicago truncatula or nim1/npr1 A. thaliana mutants induced root hair deformation and transcription of early and late nodulins. Application of S. meliloti or NF on M. truncatula or A. thaliana roots also induced a strong oxidative burst that lasted much longer than in plants inoculated with pathogenic or mutualistic bacteria. Transient overexpression of NPR1 in M. truncatula suppressed root hair curling, while inhibition of NPR1 expression by RNAi accelerated curling. CONCLUSIONS/SIGNIFICANCE:We show that, while NPR1 has a positive effect on pathogen resistance, it has a negative effect on symbiotic interactions, by inhibiting root hair deformation and nodulin expression. Our results also show that basic plant responses to Rhizobium inoculation are conserved in legumes and non-legumes

Screening for Gynecologic Conditions With Pelvic Examination US Preventive Services Task Force Recommendation Statement

IMPORTANCE Many conditions that can affect women\u27s health are often evaluated through pelvic examination. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women has a significant effect on disease morbidity and mortality. OBJECTIVE To issue a new US Preventive Services Task Force(USPSTF) recommendation on screening for gynecologic conditions with pelvic examination for conditions other than cervical cancer, gonorrhea, and chlamydia, for which the USPSTF has already made specific recommendations. EVIDENCE REVIEW The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women 18 years and older who are not at increased risk for any specific gynecologic condition. FINDINGS Overall, the USPSTF found inadequate evidence on screening pelvic examinations for the early detection and treatment of a range of gynecologic conditions in asymptomatic, nonpregnant adult women. CONCLUSIONS AND RECOMMENDATION The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women. (I statement) This statement does not apply to specific disorders for which the USPSTF already recommends screening (ie, screening for cervical cancer with a Papanicolaou smear, screening for gonorrhea and chlamydia)

Resonant behavior in heat transfer across weak molecular interfaces

Molecular dynamics (MD) simulations are used to study, in detail, the transfer of thermal (vibrational) energy between objects with discrete vibrational spectra to those with a semi-continuum of spectra. The transfer of energy is stochastic and strongly dependent on the instantaneous separation between the bodies. The insight from the MD simulations can be captured with a simple classical model that agrees well with quantum models. This model can be used to optimize systems for efficient frequency selective energy transfer, which can be used in designing a chemical sensor through nanomechanical resonance spectroscopy.Article Copyright 2013 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. This is the publisher’s final pdf. The published article can be found at: http://scitation.aip.org/content/aip/journal/jap

The Minimal Composite Higgs Model

We study the idea of a composite Higgs in the framework of a five-dimensional AdS theory. We present the minimal model of the Higgs as a pseudo-Goldstone boson in which electroweak symmetry is broken dynamically via top loop effects, all flavour problems are solved, and contributions to electroweak precision observables are below experimental bounds. Since the 5D theory is weakly coupled, we are able to fully determine the Higgs potential and other physical quantities. The lightest resonances are expected to have a mass around 2 TeV and should be discovered at the LHC. The top sector is mostly composite and deviations from Standard Model couplings are expected.Comment: 27 pages, 4 figures. v2: minor corrections, comments adde

Political Cleavages within Industry: Firm level lobbying for Trade Liberalization ∗

[Work in Progress] Existing political economy models rely on inter-industry differences such as factor endowment or factor specificity to explain the politics of trade policy-making. However, this paper finds that a large proportion of variation in U.S. applied tariff rates in fact arises within industry. I offer a theory of trade liberalization that explains how product differentiation in economic markets leads to firm-level lobbying in political markets. I argue that while high product differentiation eliminates the collective action problem exporting firms confront, political objections to product-specific liberalization will decline due to less substitutability and the possibility of serving foreign markets based on the norms of reciprocity. To test this argument, I construct a new dataset on lobbying by all publicly traded manufacturing firms after parsing all 838,588 lobbying reports filed under the Lobbying Disclosure Act of 1995. I find that productive exporting firms are more likely to lobby to reduce tariffs, especially when their products are sufficiently differentiated. I also find that highly differentiated products have lower tariff rates. The results challenge the common focus on industry-level lobbying for protection

Bulk Fields and Supersymmetry in a Slice of AdS

Five-dimensional models where the bulk is a slice of AdS have the virtue of solving the hierarchy problem. The electroweak scale is generated by a ``warp'' factor of the induced metric on the brane where the standard model fields live. However, it is not necessary to confine the standard model fields on the brane and we analyze the possibility of having the fields actually living in the slice of AdS. Specifically, we study the behaviour of fermions, gauge bosons and scalars in this geometry and their implications on electroweak physics. These scenarios can provide an explanation of the fermion mass hierarchy by warp factors. We also consider the case of supersymmetry in the bulk, and analyze the conditions on the mass spectrum. Finally, a model is proposed where the warp factor generates a small (TeV) supersymmetry-breaking scale, with the gauge interactions mediating the breaking to the scalar sector.Comment: 22 pages, 2 figures, LaTe

A Warped Supersymmetric Standard Model

We study the breaking of supersymmetry in five-dimensional (5d) warped spaces, using the Randall-Sundrum model as a prototype. In particular, we present a supersymmetry-breaking mechanism which has a geometrical origin, and consists of imposing different boundary conditions between the fermions and bosons living in the 5d bulk. The scale of supersymmetry breaking is exponentially small due to the warp factor of the AdS metric. We apply this mechanism to a supersymmetric standard model where supersymmetry breaking is transmitted through the AdS bulk to matter fields confined on the Planck-brane. This leads to a predictable superparticle mass spectrum where the gravitino mass is $10^{-3}$eV and scalar particles receive masses at the one-loop level via bulk gauge interactions. We calculate the mass spectrum in full detail using the 5d AdS propagators. The AdS/CFT correspondence suggests that our 5d warped model is dual to the ordinary 4d MSSM with a strongly coupled CFT sector responsible for the breaking of supersymmetry.Comment: 22 pages, LaTeX; v2: references and more comments on AdS/CFT correspondence adde