487 research outputs found
Portrait of John W. McCormack, Speaker of the House of Representatives.
No full textHandwritten inscription: \u27To Felton M. Johnston, my dearly valued friend with the respect and friendship of [John W. McCormack]\u27https://egrove.olemiss.edu/fmjohnston/1113/thumbnail.jp
Author response
No full textPerforin-2 (MPEG1) is an effector of the innate immune system that limits the proliferation and spread of medically relevant Gram-negative, -positive, and acid fast bacteria. We show here that a cullin-RING E3 ubiquitin ligase (CRL) complex containing cullin-1 and βTrCP monoubiquitylates Perforin-2 in response to pathogen associated molecular patterns such as LPS. Ubiquitylation triggers a rapid redistribution of Perforin-2 and is essential for its bactericidal activity. Enteric pathogens such as
Yersinia pseudotuberculosis
and enteropathogenic
Escherichia coli
disarm host cells by injecting cell cycle inhibiting factors (Cifs) into mammalian cells to deamidate the ubiquitin-like protein NEDD8. Because CRL activity is dependent upon NEDD8, Cif blocks ubiquitin dependent trafficking of Perforin-2 and thus, its bactericidal activity. Collectively, these studies further underscore the biological significance of Perforin-2 and elucidate critical molecular events that culminate in Perforin-2-dependent killing of both intracellular and extracellular, cell-adherent bacteria.
DOI:
http://dx.doi.org/10.7554/eLife.06505.001
A wide range of bacteria and other microbes can infect animals and cause disease. Throughout evolution, these microbes and their hosts have been fighting never ending arms races in which the microbes deploy ever more elaborate weapons, while the hosts adapt to defend themselves. An animal's first line of defense is provided by its ‘innate’ immune system. This system is activated by the general features of microbial cells; for example, the molecules that make up the walls surrounding most bacteria. Microbes must defeat the innate immune system in order to cause disease, and ultimately to spread from one host to the next.
One component of innate immunity is a protein called Perforin-2 that is present in most, if not all, animal cells. This protein forms pores on bacterial cells, causing them to split open and die. However, it was not clear how Perforin-2 is switched on and what, if anything, bacteria do to counteract it. To address these questions, McCormack et al. infected human and mice cells with bacteria that cause serious diseases of the digestive tract.
The experiments show that when animal cells detect bacteria, or merely a fragment of their cell wall, a specific group of proteins, called the CRL complex, attaches a molecule called ubiquitin to Perforin-2. Ubiquitin works much like the shipping label of a package, enabling the efficient targeting of Perforin-2 to the invading bacteria. McCormack et al. also show that some bacteria use a protein called a cell cycle inhibiting factor (or Cif for short) to inhibit the CRL complex. This blocks the ubiquitin labeling of Perforin-2, which renders it a useless weapon that can no longer be directed towards bacteria.
Mice that are infected with a bacterium called
Yersinia pseudotuberculosis
become seriously unwell and often die. However, McCormack et al. found that mice infected with mutant
Y. pseudotuberculosis
that lacked Cif remained healthy. Also, mice that lacked Perforin-2 are highly susceptible to infectious diseases. McCormack et al.'s findings reveal how Perforin-2 is activated during the innate immune response and how some bacteria can defeat this pivotal defense. In the current age of antibiotic resistant bacteria, these studies may spur the development of new drugs that restore or increase the activity of Perforin-2.
DOI:
http://dx.doi.org/10.7554/eLife.06505.00
‘…a tiny part of that greater circum-terrestrial grid’: A Conversation with Mike McCormack
No full textThis is the author accepted manuscript. The final version is available from Edinburgh University Press via the DOI in this recor
Platinum carboxylato-pendant-arm macrocycles: structure, redox properties and anti-cancer potential
No full textIn an attempt to generate new platinum compounds that may be effective in the treatment of cancer, as well as having a lower toxicity than traditional platins and being orally viable, we are studing the synthesis and reactivity of platinum complexes of tetraazamacrocycles bearing carboxylato pendant arms. We have synthesized adducts of meso- and rac-5,5,7,12,12, 14-hexamethyl-1,4,8,11-tetraazacyclotetradecane-1,7-diacetic acid ((LH2)-H-1). The meso-(PtL1)-L-II complex is unstable with respect to disproportionation, forming platinum metal and [meso-(PtL1)-L-IV](2+). The rac-isomer shows less tendency to disproportionate. Cyclic voltammetry suggests that the rac-(PtL1)-L-II complex undergoes two one-electron oxidations. Using bis-triazacyclononanenickel(III), [Ni-III(tacn)(2)](3+) as an outer-sphere oxidant, the self-exchange rate for the [Pt-II/L-III](0/+) couple has been estimated at 0.034 M-1 s(-1). (C) 2001 Elsevier Science B.V. All rights reserved.PT: J; CR: ALBERTS DS, 1992, J CLIN ONCOL, V10, P706 BURGESS J, 1999, TRANSIT METAL CHEM, V24, P355 CHEN LQ, 1993, CAN J CHEM, V71, P1805 CHRISTIAN MC, 1992, SEMIN ONCOL, V19, P720 CLEARE MJ, 1974, COORDIN CHEM REV, V12, P349 CONNORS TA, 1972, CHEM-BIOL INTERACT, V5, P415 DODSON RW, 1953, J AM CHEM SOC, V75, P1795 HAINES RI, 1981, COORDIN CHEM REV, V39, P77 HAINES RI, 1992, CAN J CHEM, V70, P2785 HAINES RI, 1993, CAN J CHEM, V71, P976 HAINES RI, 1993, J COORD CHEM, V29, P307 HAMBLEY TW, 1997, COORDIN CHEM REV, V166, P181 HARRAP KR, 1985, CANCER TREAT REV, V12, P21 LAPPIN G, 1994, REDOX MECH INORGANIC, CH2 LOEHRER PJ, 1984, ANN INTERN MED, V100, P704 MACARTNEY DH, 1983, INORG CHEM, V22, P3530 MARCUS RA, 1985, BIOCHIM BIOPHYS ACTA, V811, P265 MCAULEY A, 1984, INORG CHEM, V23, P1938 MCAULEY A, 1984, J CHEM SOC DA, P1501 MOSMANN T, 1983, J IMMUNOL METHODS, V65, P55 ROSENBERG B, 1965, NATURE, V205, P698 ROSENBERG B, 1969, NATURE, V222, P385 ROSENBERG B, 1970, CANCER RES, V30, P1799 SHERMAN SE, 1987, CHEM REV, V87, P1153 TAIT M, 1978, INORG SYNTH, V18, P4 WONG E, 1999, CHEM REV, V99, P2451 XU JD, 1986, INORG CHIM ACTA, V111, P61; NR: 27; TC: 8; J9: J INORG BIOCHEM; PG: 7; GA: 440YYSource type: Electronic(1
Phase equilibria, thermal expansion and symmetry relations within the HfO2-Ta2O5-TiO2-temperature system
No full textMost material applications rely on a foundation of knowledge of phase equilibria. In this dissertation, a systematic approach to the rapid production of the high temperature HfO2-Ta2O5-TiO2 phase diagrams is presented that highlights the combined use of: (i) in-situ high temperature X-ray diffraction (up to 3000 ˚C), (ii) Thermal expansion measurements (iii) extraction of atomic motifs with associated material symmetry analysis and (iv) calorimetry. The tools and methodologies developed herein are essential for the development of next generation high temperature materials.
The extreme temperatures were achieved by utilizing a quadrupole lamp furnace (QLF) (200 – 2000 ± 4 ˚C) and a conical nozzle levitator system equipped with a CO2 laser (CNL) (700 – 3000 ± 100 ˚C) in conjunction with synchrotron X-ray powder diffraction. These devices allow for (i) phase identification as a function of temperature, (ii) crystal structure determination using the charge flipping algorithm, (iii) extraction of anisotropic co-efficients of thermal expansion from Rietveld analysis, (iv) measurement of lattice variant deformation during phase transformations and finally (v) identification of atomic motifs within material systems that relate the observed the observed crystal structures.
Comprehensive energetic studies were performed to accurately determine the stability of compounds and determine critical temperatures for phase transitions. The calorimetry experiments include: (i) thermal arrest measurements utilizing the CNL system to determine solidus and liquidus temperatures, (ii) high temperature oxide solution calorimetry to determine enthalpies of formation and (iii) high temperature differential thermal analysis. More low temperature calorimetry work is required for a complete energetic description.
This intersection of phase equilibria and crystallographic symmetry analysis is an innovation methodology that aims to extend our fundamental understanding of material systems. In addition, this methodology has enabled the rapid production of the HfO2-Ta2O5 phase diagram and the solidification pathways within the HfO2-Ta2O5-TiO2 ternary. The dissertation describes in detail how each of these steps were performed, and how all the data was brought together to build innovative atomic and symmetry relationships within the traditional representation of phase equilibria for the HfO2-Ta2O5-TiO2 system.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-08-01The student, Scott McCormack, accepted the attached license on 2019-05-29 at 17:13.The student, Scott McCormack, submitted this Dissertation for approval on 2019-05-29 at 18:47.This Dissertation was approved for publication on 2019-06-12 at 11:01.DSpace SAF Submission Ingestion Package generated from Vireo submission #14004 on 2019-11-26 at 13:01:06Made available in DSpace on 2019-11-26T20:49:02Z (GMT). No. of bitstreams: 4
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The declining significance of homohysteria for male students in three sixth forms in the south of England
No full text© 2011, published by Wiley. This is an author produced version of a paper, uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link below. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it
Hierarchy without Hegemony: Locating Boys in an Inclusive School Setting
No full text In this article, the author details how 16–18-year-old boys ascribe to the tenets of inclusive masculinity in a U.K. secondary school that the author calls “Standard High.” Drawing on five months of participant observation and twelve in-depth interviews, this article demonstrates that the boys' masculinities are predicated in opposition to the orthodox values of homophobia, misogyny, and aggressiveness. Accordingly, the practices of subordination and marginalization described in hegemonic masculinity theory are not used to regulate masculine behaviors or obtain dominance in this setting. At Standard High, boys ascribing to different masculine archetypes can each maintain high social status. Nonetheless, a social hierarchy still exists. Here, boys are stratified in accordance to a popularity ranking, which is determined by the possession of a matrix of variables: Namely, charisma, authenticity, emotional support, and social fluidity. </jats:p
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Displacement and shifting geographies in the noir fiction by Cesare Battisti
No full textCesare Battisti - an Italian author and former member of the ultra-left guerrilla group called Armed Proletarians for Communism, which was active in Italy in the 1970s and 1980s - writes his novels and short stories from the vantage point of a ventennial exilic experience in Mexico and France. By looking closely at Battisti's fiction, published in French and Italian,2 this paper examines displacement and exile in the current Italian and European socio-political context
Innovative sampling and participant recruitment in sexuality research.
No full text© 2014, published by Sage. This is an author produced version of a paper published in the Journal of Social and Personal Relationships, uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link below. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it
Can introgression in M-lineage honey bees be detected by abdominal colour patterns?
No full textHoney bee abdominal pigmentation is one of the most recognisable traits and it is often used by
beekeepers as an indicator of M-lineage subspecies purity. However, this approach may negatively impact
population diversity and is futile if there is no association between tergite colour patterns and the genetic
background. To assess whether this trait can be used as a proxy for introgression proportions in M-lineage
subspecies, we genotyped, with highly informative SNP assays, A. m. mellifera and A. m. iberiensis individuals
displaying four different colour phenotypes. The SNP data detected highly introgressed bees exhibiting a black
phenotype and, at the same time, pure or marginally introgressed bees with yellow banding patterns, in both
subspecies. Despite these observations, contrary to A. m. iberiensis , in A. m. mellifera , introgression proportions
revealed to be a significant predictor of abdominal pigmentation. Therefore, abdominal pigmentation could be used
by A. m. mellifera conservationists to guide colony selection when genetic tools are unavailable.KAB was funded by Dr. Tony Ryan research
scholarship and an Irish Research Council scholarship.
This work was financed by the Native Irish
Honeybee Society (NIHBS), Federation of Irish
Beekeeping Associations (FIBKA) and FEDER
(Fundo Europeu de Desenvolvimento Regional)
through the program COMPETE 2020–POCI
(Programa Operacional para a Competividade e
Internacionalização) and by the Portuguese funds
through FCT (Fundação para a Ciência e a
Tecnologia) in the framework of the project
BeeHappy (POCI-01-0145-FEDER-029871).info:eu-repo/semantics/publishedVersio
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