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1

Advances in Genetic Manipulation of Obligate Intracellular Bacterial Pathogens  

PubMed Central

Infections by obligate intracellular bacterial pathogens result in significant morbidity and mortality worldwide. These bacteria include Chlamydia spp., which causes millions of cases of sexually transmitted disease and blinding trachoma annually, and members of the ?-proteobacterial genera Anaplasma, Ehrlichia, Orientia, and Rickettsia, agents of serious human illnesses including epidemic typhus. Coxiella burnetii, the agent of human Q fever, has also been considered a prototypical obligate intracellular bacterium, but recent host cell-free (axenic) growth has rescued it from obligatism. The historic genetic intractability of obligate intracellular bacteria has severely limited molecular dissection of their unique lifestyles and virulence factors involved in pathogenesis. Host cell restricted growth is a significant barrier to genetic transformation that can make simple procedures for free-living bacteria, such as cloning, exceedingly difficult. Low transformation efficiency requiring long-term culture in host cells to expand small transformant populations is another obstacle. Despite numerous technical limitations, the last decade has witnessed significant gains in genetic manipulation of obligate intracellular bacteria including allelic exchange. Continued development of genetic tools should soon enable routine mutation and complementation strategies for virulence factor discovery and stimulate renewed interest in these refractory pathogens. In this review, we discuss the technical challenges associated with genetic transformation of obligate intracellular bacteria and highlight advances made with individual genera. PMID:21833334

Beare, Paul A.; Sandoz, Kelsi M.; Omsland, Anders; Rockey, Daniel D.; Heinzen, Robert A.

2011-01-01

2

Mobile DNA in obligate intracellular bacteria  

Microsoft Academic Search

The small genomes of obligate intracellular bacteria are often presumed to be impervious to mobile DNA and the fluid genetic processes that drive diversification in free-living bacteria. Categorized by reductive evolution and streamlining, the genomes of some obligate intracellular bacteria manifest striking degrees of stability and gene synteny. However, recent findings from complete genome sequences of obligate intracellular species and

William S. Reznikoff; Seth R. Bordenstein

2005-01-01

3

Genome degeneration affects both extracellular and intracellular bacterial endosymbionts  

PubMed Central

The obligate intracellular bacterial endosymbionts of insects are a paradigm for reductive genome evolution. A study published recently in BMC Biology demonstrates that similar evolutionary forces shaping genome structure may also apply to extracellular endosymbionts. PMID:19435469

Feldhaar, Heike; Gross, Roy

2009-01-01

4

Rickettsia Phylogenomics: Unwinding the Intricacies of Obligate Intracellular Life  

Microsoft Academic Search

BackgroundCompleted genome sequences are rapidly increasing for Rickettsia, obligate intracellular ?-proteobacteria responsible for various human diseases, including epidemic typhus and Rocky Mountain spotted fever. In light of phylogeny, the establishment of orthologous groups (OGs) of open reading frames (ORFs) will distinguish the core rickettsial genes and other group specific genes (class 1 OGs or C1OGs) from those distributed indiscriminately throughout

Joseph J. Gillespie; Kelly Williams; Maulik Shukla; Eric E. Snyder; Eric K. Nordberg; Shane M. Ceraul; Chitti Dharmanolla; Daphne Rainey; Jeetendra Soneja; Joshua M. Shallom; Nataraj Dongre Vishnubhat; Rebecca Wattam; Anjan Purkayastha; Michael Czar; Oswald Crasta; Joao C. Setubal; Abdu F. Azad; Bruno S. Sobral; Adam J. Ratner

2008-01-01

5

Autophagy in intracellular bacterial infection.  

PubMed

Numerous pathogens have developed the capacity to invade host cells to be protected from components of the systemic immune system. However, once in the host cells they utilize sophisticated strategies to avoid the powerful machinery built by the cells to kill invading pathogens. In the last few years cumulative evidence indicates that autophagy is one of the most remarkable tools of the intracellular host cell defense machinery that bacteria must confront upon cell invasion. However, several pathogens subvert the autophagic pathway and, manipulate this process at the molecular level, as a strategy to establish a persistent infection. In this review we have summarized the interaction between autophagy and different bacterial pathogens including those that take advantage of the host cell autophagy, allowing successful colonization, as well as those microorganisms which are controlled by autophagy as part of the innate surveillance mechanism. PMID:19303905

Campoy, Emanuel; Colombo, María I

2009-09-01

6

Metabolic Interdependence of Obligate Intracellular Bacteria and Their Insect Hosts†  

PubMed Central

Mutualistic associations of obligate intracellular bacteria and insects have attracted much interest in the past few years due to the evolutionary consequences for their genome structure. However, much less attention has been paid to the metabolic ramifications for these endosymbiotic microorganisms, which have to compete with but also to adapt to another metabolism—that of the host cell. This review attempts to provide insights into the complex physiological interactions and the evolution of metabolic pathways of several mutualistic bacteria of aphids, ants, and tsetse flies and their insect hosts. PMID:15590782

Zientz, Evelyn; Dandekar, Thomas; Gross, Roy

2004-01-01

7

Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth  

PubMed Central

Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungal-related parasites responsible for widespread disease, and here we address questions about microsporidia biology and evolution. We sequenced three microsporidian genomes from two species, Nematocida parisii and Nematocida sp1, which are natural pathogens of Caenorhabditis nematodes and provide model systems for studying microsporidian pathogenesis. We performed deep sequencing of transcripts from a time course of N. parisii infection. Examination of pathogen gene expression revealed compact transcripts and a dramatic takeover of host cells by Nematocida. We also performed phylogenomic analyses of Nematocida and other microsporidian genomes to refine microsporidian phylogeny and identify evolutionary events of gene loss, acquisition, and modification. In particular, we found that all microsporidia lost the tumor-suppressor gene retinoblastoma, which we speculate could accelerate the parasite cell cycle and increase the mutation rate. We also found that microsporidia acquired transporters that could import nucleosides to fuel rapid growth. In addition, microsporidian hexokinases gained secretion signal sequences, and in a functional assay these were sufficient to export proteins out of the cell; thus hexokinase may be targeted into the host cell to reprogram it toward biosynthesis. Similar molecular changes appear during formation of cancer cells and may be evolutionary strategies adopted independently by microsporidia to proliferate rapidly within host cells. Finally, analysis of genome polymorphisms revealed evidence for a sexual cycle that may provide genetic diversity to alleviate problems caused by clonal growth. Together these events may explain the emergence and success of these diverse intracellular parasites. PMID:22813931

Cuomo, Christina A.; Desjardins, Christopher A.; Bakowski, Malina A.; Goldberg, Jonathan; Ma, Amy T.; Becnel, James J.; Didier, Elizabeth S.; Fan, Lin; Heiman, David I.; Levin, Joshua Z.; Young, Sarah; Zeng, Qiandong; Troemel, Emily R.

2012-01-01

8

Rickettsia Phylogenomics: Unwinding the Intricacies of Obligate Intracellular Life  

PubMed Central

Background Completed genome sequences are rapidly increasing for Rickettsia, obligate intracellular ?-proteobacteria responsible for various human diseases, including epidemic typhus and Rocky Mountain spotted fever. In light of phylogeny, the establishment of orthologous groups (OGs) of open reading frames (ORFs) will distinguish the core rickettsial genes and other group specific genes (class 1 OGs or C1OGs) from those distributed indiscriminately throughout the rickettsial tree (class 2 OG or C2OGs). Methodology/Principal Findings We present 1823 representative (no gene duplications) and 259 non-representative (at least one gene duplication) rickettsial OGs. While the highly reductive (?1.2 MB) Rickettsia genomes range in predicted ORFs from 872 to 1512, a core of 752 OGs was identified, depicting the essential Rickettsia genes. Unsurprisingly, this core lacks many metabolic genes, reflecting the dependence on host resources for growth and survival. Additionally, we bolster our recent reclassification of Rickettsia by identifying OGs that define the AG (ancestral group), TG (typhus group), TRG (transitional group), and SFG (spotted fever group) rickettsiae. OGs for insect-associated species, tick-associated species and species that harbor plasmids were also predicted. Through superimposition of all OGs over robust phylogeny estimation, we discern between C1OGs and C2OGs, the latter depicting genes either decaying from the conserved C1OGs or acquired laterally. Finally, scrutiny of non-representative OGs revealed high levels of split genes versus gene duplications, with both phenomena confounding gene orthology assignment. Interestingly, non-representative OGs, as well as OGs comprised of several gene families typically involved in microbial pathogenicity and/or the acquisition of virulence factors, fall predominantly within C2OG distributions. Conclusion/Significance Collectively, we determined the relative conservation and distribution of 14354 predicted ORFs from 10 rickettsial genomes across robust phylogeny estimation. The data, available at PATRIC (PathoSystems Resource Integration Center), provide novel information for unwinding the intricacies associated with Rickettsia pathogenesis, expanding the range of potential diagnostic, vaccine and therapeutic targets. PMID:19194535

Gillespie, Joseph J.; Williams, Kelly; Shukla, Maulik; Snyder, Eric E.; Nordberg, Eric K.; Ceraul, Shane M.; Dharmanolla, Chitti; Rainey, Daphne; Soneja, Jeetendra; Shallom, Joshua M.; Vishnubhat, Nataraj Dongre; Wattam, Rebecca; Purkayastha, Anjan; Czar, Michael; Crasta, Oswald; Setubal, Joao C.; Azad, Abdu F.; Sobral, Bruno S.

2008-01-01

9

Autophagosome formation in response to intracellular bacterial invasion.  

PubMed

Autophagy is an intracellular bulk degradation system in which double-membrane vesicles, called autophagosomes, engulf cytoplasmic components and later fuse with lysosomes to degrade the autophagosome content. Although autophagy was initially thought a non-selective process, recent studies have clarified that it can selectively target intracellular bacteria and function as an intracellular innate immune system that suppresses bacterial survival. A key mechanism for the recognition of cytosol-invading bacteria is ubiquitination, and the recognition of the ubiquitinated target by the autophagy machinery can be accomplished multiple ways. In this review, we discuss recent findings regarding the induction of autophagosome formation in response to intracellular bacterial invasion. PMID:25180443

Shibutani, Shusaku T; Yoshimori, Tamotsu

2014-11-01

10

Laser microdissection coupled with RNA-seq analysis of porcine enterocytes infected with an obligate intracellular pathogen (Lawsonia intracellularis)  

PubMed Central

Background Lawsonia intracellularis is an obligate intracellular bacterium and the etiologic agent of proliferative enteropathy. The disease is endemic in pigs, emerging in horses and has been described in various other species including nonhuman primates. Cell proliferation is associated with bacterial replication in enterocyte cytoplasm, but the molecular basis of the host-pathogen interaction is unknown. We used laser capture microdissection coupled with RNA-seq technology to characterize the transcriptional responses of infected enterocytes and the host-pathogen interaction. Results Proliferative enterocytes was associated with activation of transcription, protein biosynthesis and genes acting on the G1 phase of the host cell cycle (Rho family). The lack of differentiation in infected enterocytes was demonstrated by the repression of membrane transporters related to nutrient acquisition. The activation of the copper uptake transporter by infected enterocytes was associated with high expression of the Zn/Cu superoxide dismutase by L. intracellularis. This suggests that the intracellular bacteria incorporate intracytoplasmic copper and express a sophisticated mechanism to cope with oxidative stress. Conclusions The feasibility of coupling microdissection and RNA-seq was demonstrated by characterizing the host-bacterial interactions from a specific cell type in a heterogeneous tissue. High expression of L. intracellularis genes encoding hypothetical proteins and activation of host Rho genes infers the role of unrecognized bacterial cyclomodulins in the pathogenesis of proliferative enteropathy. PMID:23800029

2013-01-01

11

Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens  

PubMed Central

Summary: Intracellular bacterial pathogens have evolved highly specialized mechanisms to enter and survive within their eukaryotic hosts. In order to do this, bacterial pathogens need to avoid host cell degradation and obtain nutrients and biosynthetic precursors, as well as evade detection by the host immune system. To create an intracellular niche that is favorable for replication, some intracellular pathogens inhibit the maturation of the phagosome or exit the endocytic pathway by modifying the identity of their phagosome through the exploitation of host cell trafficking pathways. In eukaryotic cells, organelle identity is determined, in part, by the composition of active Rab GTPases on the membranes of each organelle. This review describes our current understanding of how selected bacterial pathogens regulate host trafficking pathways by the selective inclusion or retention of Rab GTPases on membranes of the vacuoles that they occupy in host cells during infection. PMID:18063721

Brumell, John H.; Scidmore, Marci A.

2007-01-01

12

Exploring Anti-Bacterial Compounds against Intracellular Legionella  

PubMed Central

Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an ‘accidental’ human pathogen and cause a severe pneumonia known as Legionnaires’ disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoebacastellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the ?-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target. PMID:24058631

Harrison, Christopher F.; Kicka, Sebastien; Trofimov, Valentin; Berschl, Kathrin; Ouertatani-Sakouhi, Hajer; Ackermann, Nikolaus; Hedberg, Christian; Cosson, Pierre; Soldati, Thierry; Hilbi, Hubert

2013-01-01

13

Modulation of iron homeostasis in macrophages by bacterial intracellular pathogens  

PubMed Central

Background Intracellular bacterial pathogens depend on acquisition of iron for their success as pathogens. The host cell requires iron as an essential component for cellular functions that include innate immune defense mechanisms. The transferrin receptor TfR1 plays an important part for delivering iron to the host cell during infection. Its expression can be modulated by infection, but its essentiality for bacterial intracellular survival has not been directly investigated. Results We identified two distinct iron-handling scenarios for two different bacterial pathogens. Francisella tularensis drives an active iron acquisition program via the TfR1 pathway program with induction of ferrireductase (Steap3), iron membrane transporter Dmt1, and iron regulatory proteins IRP1 and IRP2, which is associated with a sustained increase of the labile iron pool inside the macrophage. Expression of TfR1 is critical for Francisella's intracellular proliferation. This contrasts with infection of macrophages by wild-type Salmonella typhimurium, which does not require expression of TfR1 for successful intracellular survival. Macrophages infected with Salmonella lack significant induction of Dmt1, Steap3, and IRP1, and maintain their labile iron pool at normal levels. Conclusion The distinction between two different phenotypes of iron utilization by intracellular pathogens will allow further characterization and understanding of host-cell iron metabolism and its modulation by intracellular bacteria. PMID:20184753

2010-01-01

14

Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms  

PubMed Central

Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance. PMID:24137567

Mansilla Pareja, Maria Eugenia; Colombo, Maria I.

2013-01-01

15

An Optimal Method of Iron Starvation of the Obligate Intracellular Pathogen, Chlamydia Trachomatis  

PubMed Central

Iron is an essential cofactor in a number of critical biochemical reactions, and as such, its acquisition, storage, and metabolism is highly regulated in most organisms. The obligate intracellular bacterium, Chlamydia trachomatis experiences a developmental arrest when iron within the host is depleted. The nature of the iron starvation response in Chlamydia is relatively uncharacterized because of the likely inefficient method of iron depletion, which currently relies on the compound deferoxamine mesylate (DFO). Inefficient induction of the iron starvation response precludes the identification of iron-regulated genes. This report evaluated DFO with another iron chelator, 2,2?-bipyridyl (Bpdl) and presented a systematic comparison of the two across a range of criteria. We demonstrate that the membrane permeable Bpdl was superior to DFO in the inhibition of chlamydia development, the induction of aberrant morphology, and the induction of an iron starvation transcriptional response in both host and bacteria. Furthermore, iron starvation using Bpdl identified the periplasmic iron-binding protein-encoding ytgA gene as iron-responsive. Overall, the data present a compelling argument for the use of Bpdl, rather than DFO, in future iron starvation studies of chlamydia and other intracellular bacteria. PMID:21687412

Thompson, Christopher C.; Carabeo, Rey A.

2011-01-01

16

Innovative approach for transcriptomic analysis of obligate intracellular pathogen: selective capture of transcribed sequences of Ehrlichia ruminantium  

Microsoft Academic Search

BACKGROUND: Whole genome transcriptomic analysis is a powerful approach to elucidate the molecular mechanisms controlling the pathogenesis of obligate intracellular bacteria. However, the major hurdle resides in the low quantity of prokaryotic mRNAs extracted from host cells. Our model Ehrlichia ruminantium (ER), the causative agent of heartwater, is transmitted by tick Amblyomma variegatum. This bacterium affects wild and domestic ruminants

Loïc Emboulé; France Daigle; Damien F Meyer; Bernard Mari; Valérie Pinarello; Christian Sheikboudou; Virginie Magnone; Roger Frutos; Alain Viari; Pascal Barbry; Dominique Martinez; Thierry Lefrançois; Nathalie Vachiéry

2009-01-01

17

Pathogenic Potential of Novel Chlamydiae and Diagnostic Approaches to Infections Due to These Obligate Intracellular Bacteria  

PubMed Central

Novel chlamydiae are newly recognized members of the phylum Chlamydiales that are only distantly related to the classic Chlamydiaceae, i.e., Chlamydia and Chlamydophila species. They also exibit an obligate biphasic intracellular life cycle within eukaryote host cells. Some of these new chlamydiae are currently considered potential emerging human and/or animal pathogens. Parachlamydia acanthamoebae and Simkania negevensis are both emerging respiratory human pathogens, Waddlia chondrophila could be a novel abortigenic bovine agent, and Piscichlamydia salmonis has recently been identified as an agent of the gill epitheliocystis in the Atlantic salmon. Fritschea spp. and Rhabdochlamydia spp. seem to be confined to arthropods, but some evidence for human exposure exists. In this review, we first summarize the data supporting a pathogenic potential of the novel chlamydiae for humans and other vertebrates and the interactions that most of these chlamydiae have with free-living amoebae. We then review the diagnostic approaches to infections potentially due to the novel chlamydiae, especially focusing on the currently available PCR-based protocols, mammalian cell culture, the amoebal coculture system, and serology. PMID:16614250

Corsaro, Daniele; Greub, Gilbert

2006-01-01

18

The genome of obligately intracellular Ehrlichia canis revealsthemes of complex membrane structure and immune evasion strategies  

SciTech Connect

Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, a-proteobacterium is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, and 17 putative pseudogenes, and a substantial proportion of non-coding sequence (27 percent). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences, and a unique serine-threonine bias associated with the potential for O-glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly G:C tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Proteins associated with pathogen-host interactions were identified including a small group of proteins (12) with tandem repeats and another with eukaryotic-like ankyrin domains (7).

Mavromatis, K.; Kuyler Doyle, C.; Lykidis, A.; Ivanova, N.; Francino, P.; Chain, P.; Shin, M.; Malfatti, S.; Larimer, F.; Copeland,A.; Detter, J.C.; Land, M.; Richardson, P.M.; Yu, X.J.; Walker, D.H.; McBride, J.W.; Kyrpides, N.C.

2005-09-01

19

Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection  

PubMed Central

Background Urinary tract infections (UTIs) are one of the most common bacterial infections and are predominantly caused by uropathogenic Escherichia coli (UPEC). While UTIs are typically considered extracellular infections, it has been recently demonstrated that UPEC bind to, invade, and replicate within the murine bladder urothelium to form intracellular bacterial communities (IBCs). These IBCs dissociate and bacteria flux out of bladder facet cells, some with filamentous morphology, and ultimately establish quiescent intracellular reservoirs that can seed recurrent infection. This IBC pathogenic cycle has not yet been investigated in humans. In this study we sought to determine whether evidence of an IBC pathway could be found in urine specimens from women with acute UTI. Methods and Findings We collected midstream, clean-catch urine specimens from 80 young healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a history of UTI. Investigators were blinded to culture results and clinical history. Samples were analyzed by light microscopy, immunofluorescence, and electron microscopy for evidence of exfoliated IBCs and filamentous bacteria. Evidence of IBCs was found in 14 of 80 (18%) urines from women with UTI. Filamentous bacteria were found in 33 of 80 (41%) urines from women with UTI. None of the 20 urines from the asymptomatic comparative group showed evidence of IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with IBCs compared to 19 (29%) of 66 samples with no evidence of IBCs (p < 0.001). Of 65 urines from patients with E. coli infections, 14 (22%) had evidence of IBCs and 29 (45%) had filamentous bacteria, while none of the gram-positive infections had IBCs or filamentous bacteria. Conclusions The presence of exfoliated IBCs and filamentous bacteria in the urines of women with acute cystitis suggests that the IBC pathogenic pathway characterized in the murine model may occur in humans. The findings support the occurrence of an intracellular bacterial niche in some women with cystitis that may have important implications for UTI recurrence and treatment. PMID:18092884

Rosen, David A; Hooton, Thomas M; Stamm, Walter E; Humphrey, Peter A; Hultgren, Scott J

2007-01-01

20

Metabolic host responses to infection by intracellular bacterial pathogens  

PubMed Central

The interaction of bacterial pathogens with mammalian hosts leads to a variety of physiological responses of the interacting partners aimed at an adaptation to the new situation. These responses include multiple metabolic changes in the affected host cells which are most obvious when the pathogen replicates within host cells as in case of intracellular bacterial pathogens. While the pathogen tries to deprive nutrients from the host cell, the host cell in return takes various metabolic countermeasures against the nutrient theft. During this conflicting interaction, the pathogen triggers metabolic host cell responses by means of common cell envelope components and specific virulence-associated factors. These host reactions generally promote replication of the pathogen. There is growing evidence that pathogen-specific factors may interfere in different ways with the complex regulatory network that controls the carbon and nitrogen metabolism of mammalian cells. The host cell defense answers include general metabolic reactions, like the generation of oxygen- and/or nitrogen-reactive species, and more specific measures aimed to prevent access to essential nutrients for the respective pathogen. Accurate results on metabolic host cell responses are often hampered by the use of cancer cell lines that already exhibit various de-regulated reactions in the primary carbon metabolism. Hence, there is an urgent need for cellular models that more closely reflect the in vivo infection conditions. The exact knowledge of the metabolic host cell responses may provide new interesting concepts for antibacterial therapies. PMID:23847769

Eisenreich, Wolfgang; Heesemann, Jurgen; Rudel, Thomas; Goebel, Werner

2013-01-01

21

Motor-driven intracellular transport powers bacterial gliding motility.  

PubMed

Protein-directed intracellular transport has not been observed in bacteria despite the existence of dynamic protein localization and a complex cytoskeleton. However, protein trafficking has clear potential uses for important cellular processes such as growth, development, chromosome segregation, and motility. Conflicting models have been proposed to explain Myxococcus xanthus motility on solid surfaces, some favoring secretion engines at the rear of cells and others evoking an unknown class of molecular motors distributed along the cell body. Through a combination of fluorescence imaging, force microscopy, and genetic manipulation, we show that membrane-bound cytoplasmic complexes consisting of motor and regulatory proteins are directionally transported down the axis of a cell at constant velocity. This intracellular motion is transmitted to the exterior of the cell and converted to traction forces on the substrate. Thus, this study demonstrates the existence of a conserved class of processive intracellular motors in bacteria and shows how these motors have been adapted to produce cell motility. PMID:21482768

Sun, Mingzhai; Wartel, Morgane; Cascales, Eric; Shaevitz, Joshua W; Mignot, Tâm

2011-05-01

22

Current Biology 16, 16461651, August 22, 2006 2006 Elsevier Ltd All rights reserved DOI 10.1016/j.cub.2006.06.060 The Obligate Intracellular Pathogen  

E-print Network

, the causative agent of tra- choma and many sexually transmitted diseases [2], leads to the accumulation, and signaling [1]. We report that infection with the obligate intracellular pathogen Chlamydia trachomatis and replication in infected cells. The co-option of mammalian LD function by a pathogenic bacterium represents

Valdivia, Raphael

23

Host-Directed Antimicrobial Drugs with Broad-Spectrum Efficacy against Intracellular Bacterial Pathogens  

PubMed Central

ABSTRACT We sought a new approach to treating infections by intracellular bacteria, namely, by altering host cell functions that support their growth. We screened a library of 640 Food and Drug Administration (FDA)-approved compounds for agents that render THP-1 cells resistant to infection by four intracellular pathogens. We identified numerous drugs that are not antibiotics but were highly effective in inhibiting intracellular bacterial growth with limited toxicity to host cells. These compounds are likely to target three kinds of host functions: (i) G protein-coupled receptors, (ii) intracellular calcium signals, and (iii) membrane cholesterol distribution. The compounds that targeted G protein receptor signaling and calcium fluxes broadly inhibited Coxiella burnetii, Legionella pneumophila, Brucella abortus, and Rickettsia conorii, while those directed against cholesterol traffic strongly attenuated the intracellular growth of C. burnetii and L. pneumophila. These pathways probably support intracellular pathogen growth so that drugs that perturb them may be therapeutic candidates. Combining host- and pathogen-directed treatments is a strategy to decrease the emergence of drug-resistant intracellular bacterial pathogens. PMID:25073644

Czyz, Daniel M.; Potluri, Lakshmi-Prasad; Jain-Gupta, Neeta; Riley, Sean P.; Martinez, Juan J.; Steck, Theodore L.; Crosson, Sean; Gabay, Joelle E.

2014-01-01

24

Evolution to a chronic disease niche correlates with increased sensitivity to tryptophan availability for the obligate intracellular bacterium Chlamydia pneumoniae.  

PubMed

The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge. PMID:24682324

Huston, Wilhelmina M; Barker, Christopher J; Chacko, Anu; Timms, Peter

2014-06-01

25

The Genome of the Obligately Intracellular Bacterium Ehrlichia canis Reveals Themes of Complex Membrane Structure and Immune Evasion Strategies  

SciTech Connect

Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, {alpha}-proteobacterium, is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, 17 putative pseudogenes, and a substantial proportion of noncoding sequence (27%). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences and a unique serine-threonine bias associated with the potential for O glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly(G-C) tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Genes associated with pathogen-host interactions were identified, including a small group encoding proteins (n = 12) with tandem repeats and another group encoding proteins with eukaryote-like ankyrin domains (n = 7).

Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Doyle, C Kuyler [Center for Biodenfense and Emerging Infectious Diseases; Lykidis, A [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Francino, M P [U.S. Department of Energy, Joint Genome Institute; Chain, Patrick S [ORNL; Shin, M [U.S. Department of Energy, Joint Genome Institute; Malfatti, Stephanie [Lawrence Livermore National Laboratory (LLNL); Larimer, Frank W [ORNL; Copeland, A [U.S. Department of Energy, Joint Genome Institute; Detter, J C [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Richardson, P M [U.S. Department of Energy, Joint Genome Institute; Yu, X J [Center for Biodenfense and Emerging Infectious Diseases; Walker, D H [Center for Biodenfense and Emerging Infectious Diseases; McBride, J W [Center for Biodenfense and Emerging Infectious Diseases; Kyripides, N C [U.S. Department of Energy, Joint Genome Institute

2006-01-01

26

Characterization of an Obligate Intracellular Bacterium in the Midgut Epithelium of the Bulrush Bug Chilacis typhae (Heteroptera, Lygaeidae, Artheneinae)?  

PubMed Central

Many members of the suborder Heteroptera have symbiotic bacteria, which are usually found extracellularly in specific sacs or tubular outgrowths of the midgut or intracellularly in mycetomes. In this study, we describe the second molecular characterization of a symbiotic bacterium in a monophagous, seed-sucking stink bug of the family Lygaeidae (sensu stricto). Chilacis typhae possesses at the end of the first section of the midgut a structure which is composed of circularly arranged, strongly enlarged midgut epithelial cells. It is filled with an intracellular endosymbiont. This “mycetocytic belt” might represent an evolutionarily intermediate stage of the usual symbiotic structures found in stink bugs. Phylogenetic analysis based on the 16S rRNA and the groEL genes showed that the bacterium belongs to the Gammaproteobacteria, and it revealed a phylogenetic relationship with a secondary bacterial endosymbiont of Cimex lectularius and free-living plant pathogens such as Pectobacterium and Dickeya. The distribution and ultrastructure of the rod-shaped Chilacis endosymbiont were studied in adults and nymph stages using fluorescence in situ hybridization (FISH) and electron microscopy. The detection of symbionts at the anterior poles of developing eggs indicates that endosymbionts are transmitted vertically. A new genus and species name, “Candidatus Rohrkolberia cinguli,” is proposed for this newly characterized clade of symbiotic bacteria. PMID:21378044

Kuechler, Stefan Martin; Dettner, Konrad; Kehl, Siegfried

2011-01-01

27

Exogenous myeloperoxidase enhances bacterial phagocytosis and intracellular killing by macrophages.  

PubMed Central

It is well documented that myeloperoxidase (MyPo) contributes to the bacterial activities of neutrophils and monocytes. Since mature macrophages (M phi) are devoid of this enzyme, its participation in M phi-mediated phagocytes and bacterial killing has not been completely defined. The present study demonstrates the exogenously added MyPo, at physiological levels, enhances both phagocytosis and killing of Escherichia coli. Murine peritoneal M phi were exposed to various concentrations of MyPo for different time intervals. Viable opsonized E. coli was added either prior to or after addition of MyPo. Thioglycolate-induced but not resident M pho exhibited an increase in the number of phagocytizing cells. Both resident and thioglycolate-induced M phi demonstrated increased bactericidal activity. Physiological levels of soluble MyPo also induced a significant increase in chemiluminescence. Since luminol-dependent chemiluminescence measures reactive oxygen intermediate production, studies were done to determine whether superoxide anion or H2O2 was involved in MyPo-induced M pho killing. Both superoxide dismutase and catalase ablated MyPo-induced bactericidal activity. The above data suggest that soluble MyPo, released from neutrophils at a site of infection or inflammation, can enhance both phagocytosis and killing of microorganisms. PMID:7622228

Lincoln, J A; Lefkowitz, D L; Cain, T; Castro, A; Mills, K C; Lefkowitz, S S; Moguilevsky, N; Bollen, A

1995-01-01

28

Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells.  

PubMed

MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including cancer and microbial infections. A number of different human viruses also encode microRNAs that can attenuate cellular innate immune responses and promote viral replication, and a fungal pathogen that infects plants has recently been shown to express microRNAs in infected cells that repress host cell immune responses and promote fungal pathogenesis. Here, we have used deep sequencing of total expressed small RNAs, as well as small RNAs associated with the cellular RNA-induced silencing complex RISC, to search for microRNAs that are potentially expressed by intracellular bacterial pathogens and translocated into infected animal cells. In the case of Legionella and Chlamydia and the two mycobacterial species M. smegmatis and M. tuberculosis, we failed to detect any bacterial small RNAs that had the characteristics expected for authentic microRNAs, although large numbers of small RNAs of bacterial origin could be recovered. However, a third mycobacterial species, M. marinum, did express an ? 23-nt small RNA that was bound by RISC and derived from an RNA stem-loop with the characteristics expected for a pre-microRNA. While intracellular expression of this candidate bacterial microRNA was too low to effectively repress target mRNA species in infected cultured cells in vitro, artificial overexpression of this potential bacterial pre-microRNA did result in the efficient repression of a target mRNA. This bacterial small RNA therefore represents the first candidate microRNA of bacterial origin. PMID:25184567

Furuse, Yuki; Finethy, Ryan; Saka, Hector A; Xet-Mull, Ana M; Sisk, Dana M; Smith, Kristen L Jurcic; Lee, Sunhee; Coers, Jörn; Valdivia, Raphael H; Tobin, David M; Cullen, Bryan R

2014-01-01

29

Metal-induced isomerization yields an intracellular chelator that disrupts bacterial iron homeostasis.  

PubMed

The dwindling supply of antibiotics that remain effective against drug-resistant bacterial pathogens has precipitated efforts to identify new compounds that inhibit bacterial growth using untapped mechanisms of action. Here, we report both (1) a high-throughput screening methodology designed to discover chemical perturbants of the essential, yet unexploited, process of bacterial iron homeostasis, and (2) our findings from a small-molecule screen of more than 30,000 diverse small molecules that led to the identification and characterization of two spiro-indoline-thiadiazoles that disrupt iron homeostasis in bacteria. We show that these compounds are intracellular chelators with the capacity to exist in two isomeric states. Notably, these spiroheterocyles undergo a transition to an open merocyanine chelating form with antibacterial activity that is specifically induced in the presence of its transition-metal target. PMID:24361049

Falconer, Shannon B; Wang, Wenliang; Gehrke, Sebastian S; Cuneo, Jessica D; Britten, James F; Wright, Gerard D; Brown, Eric D

2014-01-16

30

Multi-species bacterial biofilm and intracellular infection in otitis media  

PubMed Central

Background Bacteria which are metabolically active yet unable to be cultured and eradicated by antibiotic treatment are present in the middle ear effusion of children with chronic otitis media with effusion (COME) and recurrent acute otitis media (rAOM). These observations are suggestive of biofilm presence or intracellular sequestration of bacteria and may play a role in OM pathogenesis. The aim of this project is to provide evidence for the presence of otopathogenic bacteria intracellularly or within biofilm in the middle ear mucosa of children with COME or rAOM. Methods Middle ear mucosal biopsies from 20 children with COME or rAOM were examined for otopathogenic bacteria (either in biofilm or located intracellularly) using transmission electron microscopy (TEM) or species specific fluorescent in situ hybridisation (FISH) and confocal laser scanning microscopy (CLSM). One healthy control biopsy from a child undergoing cochlear implant surgery was also examined. Results No bacteria were observed in the healthy control sample. In 2 of the 3 biopsies imaged using TEM, bacteria were observed in mucus containing vacuoles within epithelial cells. Bacterial species within these could not be identified and biofilm was not observed. Using FISH with CLSM, bacteria were seen in 15 of the 17 otitis media mucosal specimens. In this group, 11 (65%) of the 17 middle ear mucosal biopsies showed evidence of bacterial biofilm and 12 demonstrated intracellular bacteria. 52% of biopsies were positive for both biofilm and intracellular bacteria. At least one otopathogen was identified in 13 of the 15 samples where bacteria were present. No differences were observed between biopsies from children with COME and those with rAOM. Conclusion Using FISH and CLSM, bacterial biofilm and intracellular infection with known otopathogens are demonstrated on/in the middle ear mucosa of children with COME and/or rAOM. While their role in disease pathogenesis remains to be determined, this previously undescribed infection pattern may help explain the ineffectiveness of current treatment strategies at preventing or resolving COME or rAOM. PMID:22018357

2011-01-01

31

An obligately photosynthetic bacterial anaerobe from a deep-sea hydrothermal vent.  

PubMed

The abundance of life on Earth is almost entirely due to biological photosynthesis, which depends on light energy. The source of light in natural habitats has heretofore been thought to be the sun, thus restricting photosynthesis to solar photic environments on the surface of the Earth. If photosynthesis could take place in geothermally illuminated environments, it would increase the diversity of photosynthetic habitats both on Earth and on other worlds that have been proposed to possibly harbor life. Green sulfur bacteria are anaerobes that require light for growth by the oxidation of sulfur compounds to reduce CO2 to organic carbon, and are capable of photosynthetic growth at extremely low light intensities. We describe the isolation and cultivation of a previously unknown green sulfur bacterial species from a deep-sea hydrothermal vent, where the only source of light is geothermal radiation that includes wavelengths absorbed by photosynthetic pigments of this organism. PMID:15967984

Beatty, J Thomas; Overmann, Jörg; Lince, Michael T; Manske, Ann K; Lang, Andrew S; Blankenship, Robert E; Van Dover, Cindy L; Martinson, Tracey A; Plumley, F Gerald

2005-06-28

32

Two apextrin-like proteins mediate extracellular and intracellular bacterial recognition in amphioxus  

PubMed Central

Animals exploit different germ-line-encoded proteins with various domain structures to detect the signature molecules of pathogenic microbes. These molecules are known as pathogen-associated molecular patterns (PAMPs), and the host proteins that react with PAMPs are called pattern recognition proteins (PRPs). Here, we present a novel type of protein domain structure capable of binding to bacterial peptidoglycan (PGN) and the minimal PGN motif muramyl dipeptide (MDP). This domain is designated as apextrin C-terminal domain (ApeC), and its presence was confirmed in several invertebrate phyla and subphyla. Two apextrin-like proteins (ALP1 and ALP2) were identified in a basal chordate, the Japanese amphioxus Branchiostoma japonicum (bj). bjALP1 is a mucosal effector secreted into the gut lumen to agglutinate the Gram-positive bacterium Staphylococcus aureus via PGN binding. Neutralization of secreted bjALP1 by anti-bjALP1 monoclonal antibodies caused serious damage to the gut epithelium and rapid death of the animals after bacterial infection. bjALP2 is an intracellular PGN sensor that binds to TNF receptor-associated factor 6 (TRAF6) and prevents TRAF6 from self-ubiquitination and hence from NF-?B activation. MDP was found to compete with TRAF6 for bjALP2, which released TRAF6 to activate the NF-?B pathway. BjALP1 and bjALP2 therefore play distinct and complementary functions in amphioxus gut mucosal immunity. In conclusion, discovery of the ApeC domain and the functional analyses of amphioxus ALP1 and ALP2 allowed us to define a previously undocumented type of PRP that is represented across different animal phyla. PMID:25187559

Huang, Guangrui; Huang, Shengfeng; Yan, Xinyu; Yang, Ping; Li, Jun; Xu, Weiya; Zhang, Lingling; Wang, Ruihua; Yu, Yingcai; Yuan, Shaochun; Chen, Shangwu; Luo, Guangbin; Xu, Anlong

2014-01-01

33

Life in an unusual intracellular niche: a bacterial symbiont infecting the nucleus of amoebae.  

PubMed

Amoebae serve as hosts for various intracellular bacteria, including human pathogens. These microbes are able to overcome amoebal defense mechanisms and successfully establish a niche for replication, which is usually the cytoplasm. Here, we report on the discovery of a bacterial symbiont that is located inside the nucleus of its Hartmannella sp. host. This symbiont, tentatively named 'Candidatus Nucleicultrix amoebiphila', is only moderately related to known bacteria (?90% 16S and 23S rRNA sequence similarity) and member of a novel clade of protist symbionts affiliated with the Rickettsiales and Rhodospirillales. Screening of 16S rRNA amplicon data sets revealed a broad distribution of these bacteria in freshwater and soil habitats. 'Candidatus Nucleicultrix amoebiphila' traffics within 6?h post infection to the host nucleus. Maximum infection levels are reached after 96-120?h, at which time point the nucleus is pronouncedly enlarged and filled with bacteria. Transmission of the symbionts occurs vertically upon host cell division but may also occur horizontally through host cell lysis. Although we observed no impact on the fitness of the original Hartmannella sp. host, the bacteria are rather lytic for Acanthamoeba castellanii. Intranuclear symbiosis is an exceptional phenomenon, and amoebae represent an ideal model system to further investigate evolution and underlying molecular mechanisms of these unique microbial associations. PMID:24500618

Schulz, Frederik; Lagkouvardos, Ilias; Wascher, Florian; Aistleitner, Karin; Kostanjšek, Rok; Horn, Matthias

2014-08-01

34

Genome sequence of Blochmannia pennsylvanicus indicates parallel evolutionary trends among bacterial mutualists of insects  

Microsoft Academic Search

The distinct lifestyle of obligately intracellular bacteria can alter fundamental forces that drive and constrain genome change. In this study, sequencing the 792-kb genome of Blochmannia pennsylvanicus, an obligate endosymbiont of Camponotus pennsylvanicus, enabled us to trace evolutionary changes that occurred in the context of a bacterial-ant association. Comparison to the genome of Blochmannia floridanus reveals differential loss of genes

Patrick H. Degnan; Adam B. Lazarus; Jennifer J. Wernegreen

2005-01-01

35

A census of membrane-bound and intracellular signal transduction proteins in bacteria: Bacterial IQ, extroverts and introverts  

PubMed Central

Background Analysis of complete microbial genomes showed that intracellular parasites and other microorganisms that inhabit stable ecological niches encode relatively primitive signaling systems, whereas environmental microorganisms typically have sophisticated systems of environmental sensing and signal transduction. Results This paper presents results of a comprehensive census of signal transduction proteins – histidine kinases, methyl-accepting chemotaxis receptors, Ser/Thr/Tyr protein kinases, adenylate and diguanylate cyclases and c-di-GMP phosphodiesterases – encoded in 167 bacterial and archaeal genomes, sequenced by the end of 2004. The data have been manually checked to avoid false-negative and false-positive hits that commonly arise during large-scale automated analyses and compared against other available resources. The census data show uneven distribution of most signaling proteins among bacterial and archaeal phyla. The total number of signal transduction proteins grows approximately as a square of genome size. While histidine kinases are found in representatives of all phyla and are distributed according to the power law, other signal transducers are abundant in certain phylogenetic groups but virtually absent in others. Conclusion The complexity of signaling systems differs even among closely related organisms. Still, it usually can be correlated with the phylogenetic position of the organism, its lifestyle, and typical environmental challenges it encounters. The number of encoded signal transducers (or their fraction in the total protein set) can be used as a measure of the organism's ability to adapt to diverse conditions, the 'bacterial IQ', while the ratio of transmembrane receptors to intracellular sensors can be used to define whether the organism is an 'extrovert', actively sensing the environmental parameters, or an 'introvert', more concerned about its internal homeostasis. Some of the microorganisms with the highest IQ, including the current leader Wolinella succinogenes, are found among the poorly studied beta-, delta- and epsilon-proteobacteria. Among all bacterial phyla, only cyanobacteria appear to be true introverts, probably due to their capacity to conduct oxygenic photosynthesis, using a complex system of intracellular membranes. The census data, available at , can be used to get an insight into metabolic and behavioral propensities of each given organism and improve prediction of the organism's properties based solely on its genome sequence. PMID:15955239

Galperin, Michael Y

2005-01-01

36

Extracellular Superoxide Dismutase Inhibits Innate Immune Responses and Clearance of an Intracellular Bacterial Infection  

PubMed Central

Reactive oxygen and nitrogen species (ROS/RNS) play important roles during immune responses to bacterial pathogens. Extracellular superoxide dismutase (ecSOD) regulates extracellular concentrations of ROS/RNS and contributes to tissue protection during inflammatory insults. The participation of ecSOD in immune responses seems therefore intuitive, yet is poorly understood. In the present study, we utilized mice with varying levels of ecSOD activity to investigate the involvement of this enzyme in immune responses against Listeria monocytogenes. Surprisingly, our data demonstrate that, despite enhanced neutrophil recruitment to the liver, ecSOD activity negatively impacted host survival and bacterial clearance. Increased ecSOD activity was accompanied by decreased co-localization of neutrophils with bacteria, as well as increased neutrophil apoptosis, which reduced overall and neutrophil-specific TNF-? production. Liver leukocytes from mice lacking ecSOD produced equivalent nitric oxide (NO·) when compared to mice expressing ecSOD. However, during infection, there were higher levels of peroxynitrite (NO3·?) in livers from mice lacking ecSOD compared to mice expressing ecSOD. Neutrophil depletion studies revealed that high levels of ecSOD activity resulted in neutrophils with limited protective capacity, whereas neutrophils from mice lacking ecSOD provided superior protection compared to neutrophils from wild-type mice. Taken together, our data demonstrate that ecSOD activity reduces innate immune responses during bacterial infection and provides a potential target for therapeutic intervention. PMID:22393157

Break, Timothy J.; Jun, Sujung; Indramohan, Mohanalaxmi; Carr, Karen D.; Sieve, Amy N.; Dory, Ladislav; Berg, Rance E.

2012-01-01

37

The Role of Non-Cognate T Cell Stimulation during Intracellular Bacterial Infection  

PubMed Central

Intra-macrophage bacterial infections cause significant morbidity and mortality in both the developed and developing world. Protective host immune responses to these infections initially requires the activation and expansion of pathogen-specific CD4 Th1 cells within lymphoid tissues and subsequent relocation of these effector cells to sites of infection. After entering infected tissues, the elicitation of Th1 bactericidal activity can be triggered by cognate or non-cognate signals that are delivered by locally infected antigen-presenting cells and innate cells. However, the contribution of non-cognate stimulation to the resolution of bacterial infection remains poorly understood, especially in the context of a Th1 response. Here, we review the current data on Th1 cell activation and expansion in mouse models of Salmonella and Chlamydia infection and discuss the potential role of non-cognate Th1 cell stimulation in these disease models. Greater understanding of this pathway of T cell activation may lead to the design of therapeutics or vaccines to combat intra-macrophage pathogens. PMID:25071779

McSorley, Stephen J.

2014-01-01

38

Inhibition of intracellular bacterial replication in fibroblasts is dependent on the perforin-like protein (perforin-2) encoded by macrophage-expressed gene 1.  

PubMed

Fibroblasts are known to eliminate intracellular bacteria, but the lethal hit of the bactericidal mechanism has not been defined. We show that primary embryonic and established fibroblasts can be induced by interferons or by intracellular bacterial infection to express a perforin-like mRNA previously described as macrophage-expressed gene 1 (Mpeg1). The presence and level of the perforin-like mRNA correlate with the ability of primary mouse embryonic fibroblasts (MEF) to eliminate intracellular bacteria. In addition, siRNA knockdown of the perforin-like molecule abolishes bactericidal activity and allows intracellular bacterial replication. Complementation of MEF in which the endogenous perforin-like molecule has been knocked down with a red fluorescent protein-tagged version restores bactericidal activity. The perforin-like molecule has broad bactericidal specificity for pathogenic and non-pathogenic bacteria, including Gram-positive and -negative, and acid fast bacteria. The perforin-like molecule renders previously lysozyme-resistant bacteria sensitive to lysis by lysozyme suggesting physical damage of the outer cell wall by the perforin-like protein. MEF damage cell walls of intracellular bacteria by insertion, polymerization, and pore formation of the perforin-like protein, analogous to pore formers of complement and perforin-1 of cytolytic lymphocytes. We propose the name perforin-2. PMID:23257510

McCormack, Ryan; de Armas, Lesley R; Shiratsuchi, Motoaki; Ramos, Jahir E; Podack, Eckhard R

2013-01-01

39

Invasion of the Central Nervous System by Intracellular Bacteria  

PubMed Central

Infection of the central nervous system (CNS) is a severe and frequently fatal event during the course of many diseases caused by microbes with predominantly intracellular life cycles. Examples of these include the facultative intracellular bacteria Listeria monocytogenes, Mycobacterium tuberculosis, and Brucella and Salmonella spp. and obligate intracellular microbes of the Rickettsiaceae family and Tropheryma whipplei. Unfortunately, the mechanisms used by intracellular bacterial pathogens to enter the CNS are less well known than those used by bacterial pathogens with an extracellular life cycle. The goal of this review is to elaborate on the means by which intracellular bacterial pathogens establish infection within the CNS. This review encompasses the clinical and pathological findings that pertain to the CNS infection in humans and includes experimental data from animal models that illuminate how these microbes enter the CNS. Recent experimental data showing that L. monocytogenes can invade the CNS by more than one mechanism make it a useful model for discussing the various routes for neuroinvasion used by intracellular bacterial pathogens. PMID:15084504

Drevets, Douglas A.; Leenen, Pieter J. M.; Greenfield, Ronald A.

2004-01-01

40

Obliging children.  

PubMed

Children may sometimes undergo healthcare procedures that are not intended to improve their health status. Such interventions might include the use of young children as bone marrow donors or their enrolment in non-therapeutic research. One of the justifications used to legitimise these interventions is the premise that children have obligations to others; to their family in the case of related bone marrow transplantation, and to wider society in the case of non-therapeutic research. However, this 'obligation model' (the notion that children possess positive obligations to advance the health status of others) fails as a justificatory paradigm because it is based upon a confusion, identified by Hart, between two notions; that of 'being under an obligation to do something' and that of 'being obliged to do something'. Instead the 'obligation model' is a device employed to put a justificatory gloss upon a consequentialist decision-making process; removing the legitimising gloss allows for a more transparent look at the conflict between parental rights and an individual child's right to bodily integrity. PMID:21289034

Lyons, Barry

2011-01-01

41

Mechanism of Asp24 upregulation in Brucella abortus rough mutant with a disrupted O-antigen export system and effect of Asp24 in bacterial intracellular survival.  

PubMed

We previously showed that Brucella abortus rough mutant strain 2308 ?ATP (called the ?rfbE mutant in this study) exhibits reduced intracellular survival in RAW264.7 cells and attenuated persistence in BALB/c mice. In this study, we performed microarray analysis to detect genes with differential expression between the ?rfbE mutant and wild-type strain S2308. Interestingly, acid shock protein 24 gene (asp24) expression was significantly upregulated in the ?rfbE mutant compared to S2308, as confirmed by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. Further studies using additional strains indicated that the upregulation of asp24 occurred only in rough mutants with disrupted O-antigen export system components, including the ATP-binding protein gene rfbE (bab1_0542) and the permease gene rfbD (bab1_0543), while the ?wboA rough mutant (which lacks an O-antigen synthesis-related glycosyltransferase) and the RB51 strain (a vaccine strain with the rough phenotype) showed no significant changes in asp24 expression compared to S2308. In addition, abolishing the intracellular O-antigen synthesis of the ?rfbE mutant by deleting the wboA gene (thereby creating the ?rfbE ?wboA double-knockout strain) recovered asp24 expression. These results indicated that asp24 upregulation is associated with intracellular O-antigen synthesis and accumulation but not with the bacterial rough phenotype. Further studies indicated that asp24 upregulation in the ?rfbE mutant was associated neither with bacterial adherence and invasion nor with cellular necrosis on RAW264.7 macrophages. However, proper expression of the asp24 gene favors intracellular survival of Brucella in RAW264.7 cells and HeLa cells during an infection. This study reveals a novel mechanism for asp24 upregulation in B. abortus mutants. PMID:24752516

Tian, Mingxing; Qu, Jing; Han, Xiangan; Ding, Chan; Wang, Shaohui; Peng, Daxin; Yu, Shengqing

2014-07-01

42

Characterization of a Lipopolysaccharide-Targeted Monoclonal Antibody and Its Variable Fragments as Candidates for Prophylaxis against the Obligate Intracellular Bacterial Pathogen Coxiella burnetii.  

PubMed

Our previous study demonstrated that treatment of Coxiella burnetii with the phase I lipopolysaccharide (PI-LPS)-targeted monoclonal antibody (MAb) 1E4 significantly inhibited C. burnetii infection in mice, suggesting that 1E4 is a protective MAb. To determine whether passive transfer of antibodies (Abs) can provide protection against C. burnetii natural infection, we examined if passive transfer of 1E4 would protect SCID mice against C. burnetii aerosol infection. The results indicated that 1E4 conferred significant protection against aerosolized C. burnetii, suggesting that 1E4 may be useful for preventing C. burnetii natural infection. To further understand the mechanisms of 1E4-mediated protection and to test the possibility of using humanized 1E4 to prevent C. burnetii infection, we examined whether the Fab fragment of 1E4 (Fab1E4), a recombinant murine single-chain variable fragment (muscFv1E4), and a humanized single-chain variable fragment (huscFv1E4) retained the ability of 1E4 to inhibit C. burnetii infection. The results indicated that Fab1E4, muscFv1E4, and huscFv1E4 were able to inhibit C. burnetii infection in mice but that their ability to inhibit C. burnetii infection was lower than that of 1E4. In addition, treatment of C. burnetii with Fab1E4, muscFv1E4, or huscFv1E4 can block C. burnetii infection of macrophages. Interestingly, treatment of C. burnetii with huscFv1E4 can significantly reduce C. burnetii infectivity in human macrophages. This report provides the first evidence to demonstrate that the humanized variable fragments of an LPS-specific MAb can neutralize C. burnetii infection and appears to be a promising step toward the potential use of a humanized MAb as emergency prophylaxis against C. burnetii exposure. PMID:25114119

Peng, Ying; Schoenlaub, Laura; Elliott, Alexandra; Mitchell, William J; Zhang, Guoquan

2014-11-01

43

Proteolytic Pathways of Activation and Degradation of a Bacterial Phospholipase C during Intracellular Infection by Listeria monocytogenes  

Microsoft Academic Search

Listeria monocytogenes is a facultative intra- cellular bacterial pathogen that spreads cell to cell with- out exposure to the extracellular environment. Bacte- rial cell-to-cell spread is mediated in part by two secreted bacterial phospholipases C (PLC), a broad spectrum PLC (PC-PLC) and a phosphatidylinositol- specific PLC (PI-PLC). PI-PLC is secreted in an active state, whereas PC-PLC is secreted as an

Hélène Marquis; Howard Goldfine; Daniel A. Portnoy

1997-01-01

44

The Francisella pathogenicity island protein IglA localizes to the bacterial cytoplasm and is needed for intracellular growth  

PubMed Central

Background Francisella tularensis is a gram negative, facultative intracellular bacterium that is the etiological agent of tularemia. F. novicida is closely related to F. tularensis but has low virulence for humans while being highly virulent in mice. IglA is a 21 kDa protein encoded by a gene that is part of an iglABCD operon located on the Francisella pathogenicity island (FPI). Results Bioinformatics analysis of the FPI suggests that IglA and IglB are components of a newly described type VI secretion system. In this study, we showed that IglA regulation is controlled by the global regulators MglA and MglB. During intracellular growth IglA production reaches a maximum at about 10 hours post infection. Biochemical fractionation showed that IglA is a soluble cytoplasmic protein and immunoprecipitation experiments demonstrate that it interacts with the downstream-encoded IglB. When the iglB gene was disrupted IglA could not be detected in cell extracts of F. novicida, although IglC could be detected. We further demonstrated that IglA is needed for intracellular growth of F. novicida. A non-polar iglA deletion mutant was defective for growth in mouse macrophage-like cells, and in cis complementation largely restored the wild type macrophage growth phenotype. Conclusion The results of this study demonstrate that IglA and IglB are interacting cytoplasmic proteins that are required for intramacrophage growth. The significance of the interaction may be to secrete effector molecules that affect host cell processes. PMID:17233889

de Bruin, Olle M; Ludu, Jagjit S; Nano, Francis E

2007-01-01

45

High-affinity Zn2+ uptake system ZnuABC is required for bacterial zinc homeostasis in intracellular environments and contributes to the virulence of Salmonella enterica.  

PubMed

To investigate the relevance of zinc in host-pathogen interactions, we have constructed Salmonella enterica mutant strains in which the znuA gene, which encodes the periplasmic component of the ZnuABC high-affinity Zn2+ transporter, was deleted. This mutation does not alter the ability of Salmonella to grow in rich media but drastically reduces its ability to multiply in media deprived of zinc. In agreement with this phenotype, ZnuA accumulates only in bacteria cultivated in environments poor in zinc. In spite of the nearly millimolar intracellular concentration of zinc, we have found that znuA is highly expressed in intracellular salmonellae recovered either from cultivated cells or from the spleens of infected mice. We have also observed that znuA mutants are impaired in their ability to grow in Caco-2 epithelial cells and that bacteria starved for zinc display decreased ability to multiply in phagocytes. A dramatic reduction in the pathogenicity of the znuA mutants was observed in Salmonella-susceptible (BALB/c) or Salmonella-resistant (DBA-2) mice infected intraperitoneally or orally. This study shows that the amount of free metals available for bacterial growth within the infected animal is limited, despite the apparent elevated concentration of free metals within cells and in plasma and suggests that Salmonella exploits the ZnuABC zinc transporter to maximize zinc availability in such conditions. These results shed new light on the complex functions of zinc in vertebrate and bacterial physiology and pave the way for a better comprehension of pathogenic mechanisms in Salmonella infections. PMID:17923515

Ammendola, Serena; Pasquali, Paolo; Pistoia, Claudia; Petrucci, Paola; Petrarca, Patrizia; Rotilio, Giuseppe; Battistoni, Andrea

2007-12-01

46

The immunosuppressive drug azathioprine inhibits biosynthesis of the bacterial signal molecule cyclic-di-GMP by interfering with intracellular nucleotide pool availability.  

PubMed

In Gram-negative bacteria, production of the signal molecule c-di-GMP by diguanylate cyclases (DGCs) is a key trigger for biofilm formation, which, in turn, is often required for the development of chronic bacterial infections. Thus, DGCs represent interesting targets for new chemotherapeutic drugs with anti-biofilm activity. We searched for inhibitors of the WspR protein, a Pseudomonas aeruginosa DGC involved in biofilm formation and production of virulence factors, using a set of microbiological assays developed in an Escherichia coli strain expressing the wspR gene. We found that azathioprine, an immunosuppressive drug used in the treatment of Crohn's disease, was able to inhibit WspR-dependent c-di-GMP biosynthesis in bacterial cells. However, in vitro enzymatic assays ruled out direct inhibition of WspR DGC activity either by azathioprine or by its metabolic derivative 2-amino-6-mercapto-purine riboside. Azathioprine is an inhibitor of 5-aminoimidazole-4-carboxamide ribotide (AICAR) transformylase, an enzyme involved in purine biosynthesis, which suggests that inhibition of c-di-GMP biosynthesis by azathioprine may be due to perturbation of intracellular nucleotide pools. Consistent with this hypothesis, WspR activity is abolished in an E. coli purH mutant strain, unable to produce AICAR transformylase. Despite its effect on WspR, azathioprine failed to prevent biofilm formation by P. aeruginosa; however, it affected production of extracellular structures in E. coli clinical isolates, suggesting efficient inhibition of c-di-GMP biosynthesis in this bacterium. Our results indicate that azathioprine can prevent biofilm formation in E. coli through inhibition of c-di-GMP biosynthesis and suggest that such inhibition might contribute to its anti-inflammatory activity in Crohn's disease. PMID:23584245

Antoniani, Davide; Rossi, Elio; Rinaldo, Serena; Bocci, Paola; Lolicato, Marco; Paiardini, Alessandro; Raffaelli, Nadia; Cutruzzolà, Francesca; Landini, Paolo

2013-08-01

47

Ultrastructural Changes in an Obligately Barophilic Marine Bacterium after Decompression  

PubMed Central

The bacterial isolate MT-41 from 10,476 m, nearly the greatest ocean depth, is obligately barophilic. The purpose of this study was to describe the morphological changes in MT-41 due to nearly isothermal decompression followed by incubation at atmospheric pressure. Two cultures were grown at 103.5 MPa and 2°C and then decompressed to atmospheric pressure (0.101 MPa). One of the cultures was fixed just before decompression. The other culture, kept at 0°C, was sampled immediately and four more times over 168 h. The number of CFU (assayed at 103.5 MPa and 2°C) declined with incubation time at atmospheric pressure. Decompression itself did not lead to immediate morphological changes. The ultrastructure, however, was altered with increasing time at atmospheric pressure. The first aberrations were intracellular vesicles and membrane fragments in the medium. After these changes were plasmolysis, cell lysis, the formation of extracellular vesicles, and the formation of ghost cells. Intact cells in the longest incubation at atmospheric pressure had the normal cytoplasmic granularity suggestive of ribosomes but had few and poorly stained fibrils in the bacterial nucleoids. From the practical standpoint, samples of hadal deep-sea regions need to be fixed either in situ or shortly after arrival at the sea surface even when recovered in insulated sampling gear. This should prevent drastic structural degradation of sampled cells, thus allowing both accurate estimates of deep-sea benthic standing stock and realistic morphological descriptions. Images PMID:16348489

Chastain, Roger A.; Yayanos, A. Aristides

1991-01-01

48

Induction of IL8 expression by bacterial flagellin is mediated through lipid raft formation and intracellular TLR5 activation in A549 cells  

Microsoft Academic Search

We investigated the mechanism for the induction of a chemokine, IL-8, by bacterial flagellins in the human alveolar type II epithelial cell line, A549. Bacterial flagellin induced expression of IL-8 mRNA and protein in dose- and time-dependent manners. IL-8 expression was inhibited by nystatin (a lipid rafts inhibitor) but not by chlorpromazine (a clathrin-coated pits inhibitor). Interestingly, Toll-like receptor 5

Jintaek Im; Jun Ho Jeon; Min Kyung Cho; Sang Su Woo; Seok-Seong Kang; Cheol-Heui Yun; Kangseok Lee; Dae Kyun Chung; Seung Hyun Han

2009-01-01

49

Slc11a1 limits intracellular growth of Salmonella enterica sv. Typhimurium by promoting macrophage immune effector functions and impairing bacterial iron acquisition  

PubMed Central

The natural-resistance associated macrophage protein 1, Slc11a1, is a phagolysosomal transporter for protons and divalent ions including iron, that confers host protection against diverse intracellular pathogens including Salmonella. We investigated and compared the regulation of iron homeostasis and immune function in RAW264.7 murine phagocytes stably transfected with non-functional Slc11a1 and functional Slc11a1 controls in response to an infection with Salmonella enterica serovar Typhimurium (S. Typhimurium). We report that macrophages lacking functional Slc11a1 displayed an increased expression of transferrin receptor 1, resulting in enhanced acquisition of transferrin-bound iron. In contrast, cellular iron release mediated via ferroportin 1 was significantly lower in Salmonella-infected Slc11a1-negative macrophages in comparison to phagocytes bearing Slc11a1. Lack of Slc11a1 led to intracellular persistence of S. Typhimurium within macrophages which was paralleled by a reduced formation of nitric oxide, tumour necrosis factor-alpha and interleukin-6 in Slc11a1-negative macrophages following Salmonella infection, whereas interleukin-10 production was increased. Moreover, Slc11a1-negative phagocytes exhibited higher cellular iron content, resulting in increased iron acquisition by intracellular Salmonella. Our observations indicate a bifunctional role for Slc11a1 within phagocytes. Slc11a restricts iron availability, which firstly augments pro-inflammatory macrophage effector functions and secondly concomitantly limits microbial iron access. PMID:19500110

Nairz, Manfred; Fritsche, Gernot; Crouch, Marie-Laure V.; Barton, Howard C.; Fang, Ferric C.; Weiss, Gunter

2009-01-01

50

Gene Conversion Maintains Nonfunctional Transposable Elements in an Obligate Mutualistic Endosymbiont  

E-print Network

LETTER Gene Conversion Maintains Nonfunctional Transposable Elements in an Obligate Mutualistic that ISs constitute 2.4% of the genome of the obligate mutualistic endosymbiont Wolbachia wBm. AlthoughBm. Mutualistic intracellular symbiosis between bacteria and eukaryotes is a widespread phenomenon that has signif

Cordaux, Richard

51

On public obligation.  

PubMed

Poverty has a potent and provable impact on health, education, opportunity, safety, dignity, and overall quality of life for Americans. This article argues that our obligations to ameliorate poverty are not only private, religious, and charitable, they are public and governmental as well. PMID:23189436

Nichol, Gene R

2012-01-01

52

MgtC as a horizontally-acquired virulence factor of intracellular bacterial pathogens: evidence from molecular phylogeny and comparative genomics.  

PubMed

MgtC is a virulence factor required for intramacrophage survival and growth in low Mg2+ medium in two pathogens that are not phylogenetically related, Salmonella typhimurium and Mycobacterium tuberculosis. In S. typhimurium, mgtC is carried by the SPI-3 pathogenicity island and hybridization studies have suggested that the distribution of mgtC among enterobacteria is limited. In the present study, we searched for the presence of mgtC-like sequences in eubacterial genomes. Analyses of MgtC-like proteins phylogeny and mgtC-like chromosomal context support the hypothesis that mgtC has been acquired by horizontal gene transfer repeatedly throughout bacterial evolution. In addition, the phylogenetic analysis revealed the existence of a subgroup of proteins, that includes the S. typhimurium and M. tuberculosis MgtC proteins, as well as MgtC-related proteins from other pathogens that are able to survive in macrophages, B. melitensis and Y. pestis. We propose that MgtC has a similar function in all these distantly related pathogens, most likely providing the ability to grow in a low Mg2+ environment. PMID:14708580

Blanc-Potard, Anne-Béatrice; Lafay, Bénédicte

2003-10-01

53

Classification Revisions Reduce Reported Federal Development Obligations  

NSF Publications Database

... See Related Reports Classification Revisions Reduce Reported Federal Development Obligations by ... reported obligations. For example, if $1 billion previously classified and reported as "development ...

54

Obligately barophilic bacterium from the Mariana trench.  

PubMed

An amphipod (Hirondellea gigas) was retrieved with decompression in an insulated trap from an ocean depth of 10,476 m. Bacterial isolates were obtained from the dead and cold animal by using silica gel medium incubated at 1000 bars (1 bar = 10(5) Pa) and 2 degrees C. The isolate designated MT41 was found to be obligately barophilic and did not grow at a pressure close to that of 380 bars found at average depths of the sea. The optimal generation time of about 25 hr was at 2 degrees C and 690 bars. The generation time at 2 degrees C and 1,035 bars, a pressure close to that at the depth of origin, was about 33 hr. Among the conclusions are: (i) pressure is an important determinant of zonation along the water column of the sea; (ii) some obligately barophilic bacteria survive decompressions; (iii) the pressure of optimal growth at 2 degrees C appears to be less than the pressure at the depth of origin and may be diagnostic for the depth of origin; (iv) rates of reproduction are slow yet significant and an order of magnitude greater than previously thought; and (v) much of deep-sea microbiology may have been done with spurious deep-sea organisms due to warming of samples. PMID:6946468

Yayanos, A A; Dietz, A S; Van Boxtel, R

1981-08-01

55

Studies of polyamine metabolism in obligately alkalophilic Bacillus alcalophilus that grow at pH 11  

SciTech Connect

Bacillus alcalophilus, an obligately alkalophilic bacterium, grow at pH 11 with an intracellular pH greater than 9.5. Polyamines are positively charged at physiological pH, but less than 50% of polyamines will be charged at pH 9.5 and above. In view of the importance of polycationic nature of polyamines in their physiological functions, it is of interest to study the polyamine metabolism in B. alcalophilus, an unusual organism that grow at very high pH. Spermidine is the major polyamine in this organism, accounts for more than 90% of total polyamine. The level of spermidine fluctuates between 10 to 30 nmol per mg protein during growth. In contrast, putrescine and spermine levels stay constant during entire period of growth. No ornithine decarboxylase (DC) activity can be detected in B. alcalophilus under all conditions examined. When (/sup 3/H)arginine was added to the bacterial culture, the distribution of radioactivity in polyamine pool was 3% for putrescine, 94% for spermidine, and 3% for spermine, suggesting the presence of arginine pathway for polyamine biosynthesis. B. alcalophilus appears to possess a polyamine transport system that is Na/sup +/-dependent. Putrescine uptake in B. alcalophilus is sensitive to the inhibition of gramicidine S (10 ..mu..M) and valinomycin (2..mu..M).

Cheng, S.; Chen, K.Y.

1987-05-01

56

Evolution of signal transduction in intracellular symbiosis  

Microsoft Academic Search

Plant roots form intracellular symbioses with fungi and bacteria resulting in arbuscular mycorrhiza and nitrogen-fixing root nodules, respectively. A novel receptor like-kinase has been discovered that is required for the transduction of both bacterial and fungal symbiotic signals. This kinase defines an ancient signalling pathway that probably evolved in the context of arbuscular mycorrhiza and has been recruited subsequently for

Catherine Kistner; Martin Parniske

2002-01-01

57

Section III Intracellular Methods and Assays  

E-print Network

Abstract The twocomponent pathway in Escherichia coli chemotaxis has be- come a paradigm for bacterial intracellular kinase activity and thus to analyze properties of the chemotaxis signaling network. Introduction E. coli Chemotaxis Motile chemotactic bacteria are able to follow gradients of certain chemicals

Shimizu, Tom

58

45 CFR 2400.65 - Teaching obligation.  

Code of Federal Regulations, 2011 CFR

...2011-10-01 2011-10-01 false Teaching obligation. 2400.65 Section 2400... Special Conditions § 2400.65 Teaching obligation. Upon receiving...the Fellow is employed indicating the teaching activities of the Fellow during...

2011-10-01

59

45 CFR 2400.65 - Teaching obligation.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 2013-10-01 false Teaching obligation. 2400.65 Section 2400... Special Conditions § 2400.65 Teaching obligation. Upon receiving...the Fellow is employed indicating the teaching activities of the Fellow during...

2013-10-01

60

45 CFR 2400.65 - Teaching obligation.  

Code of Federal Regulations, 2012 CFR

...2012-10-01 2012-10-01 false Teaching obligation. 2400.65 Section 2400... Special Conditions § 2400.65 Teaching obligation. Upon receiving...the Fellow is employed indicating the teaching activities of the Fellow during...

2012-10-01

61

An Update Semantics for Prima Facie Obligations  

Microsoft Academic Search

The deontic logic dus is a deontic update semantics for prescriptive obligations based on the update semantics of Veltman. In dus the denition of logical validity of obligations is not based on static truth values but on dynamic action transitions. In this paper prescriptive prima facie obligations are formalized in update semantics. The logic formalizes the specicity principle, has reinstatement

Leendert W. N. Van Der Torre; Yao-hua Tan

1998-01-01

62

Contribution of genomics to bacterial pathogenesis.  

PubMed

Genomics is changing the landscape of modern biology. The impact is far-reaching because it provides both the most economical means of acquiring large amounts of information and because it has forced the creation of new technologies to exploit this information. Five of the six genomes published in the year from August 1998 to August 1999 were human pathogens, all of which are highly host-adapted. Four of these are obligate intracellular pathogens and the study of these genomes is providing novel insights into the intricacies of pathogen-host interactions and co-evolution. These genomes are also significant because they mark the beginning of an important trend in the sequencing of closely related genomes, including the sequencing of more than one strain from a single pathogenic species. As comparative genomics truly comes of age, the ability to compare the genomes of pathogenic and non-pathogenic organisms will hopefully provide insight into what makes certain bacterial strains and species pathogens. PMID:10607606

Field, D; Hood, D; Moxon, R

1999-12-01

63

Bacterial DNA sifted from the Trichoplax adhaerens (Animalia: Placozoa) genome project reveals a putative rickettsial endosymbiont.  

PubMed

Eukaryotic genome sequencing projects often yield bacterial DNA sequences, data typically considered as microbial contamination. However, these sequences may also indicate either symbiont genes or lateral gene transfer (LGT) to host genomes. These bacterial sequences can provide clues about eukaryote-microbe interactions. Here, we used the genome of the primitive animal Trichoplax adhaerens (Metazoa: Placozoa), which is known to harbor an uncharacterized Gram-negative endosymbiont, to search for the presence of bacterial DNA sequences. Bioinformatic and phylogenomic analyses of extracted data from the genome assembly (181 bacterial coding sequences [CDS]) and trace read archive (16S rDNA) revealed a dominant proteobacterial profile strongly skewed to Rickettsiales (Alphaproteobacteria) genomes. By way of phylogenetic analysis of 16S rDNA and 113 proteins conserved across proteobacterial genomes, as well as identification of 27 rickettsial signature genes, we propose a Rickettsiales endosymbiont of T. adhaerens (RETA). The majority (93%) of the identified bacterial CDS belongs to small scaffolds containing prokaryotic-like genes; however, 12 CDS were identified on large scaffolds comprised of eukaryotic-like genes, suggesting that T. adhaerens might have recently acquired bacterial genes. These putative LGTs may coincide with the placozoan's aquatic niche and symbiosis with RETA. This work underscores the rich, and relatively untapped, resource of eukaryotic genome projects for harboring data pertinent to host-microbial interactions. The nature of unknown (or poorly characterized) bacterial species may only emerge via analysis of host genome sequencing projects, particularly if these species are resistant to cell culturing, as are many obligate intracellular microbes. Our work provides methodological insight for such an approach. PMID:23475938

Driscoll, Timothy; Gillespie, Joseph J; Nordberg, Eric K; Azad, Abdu F; Sobral, Bruno W

2013-01-01

64

Real-Time Molecular Monitoring of Chemical Environment in ObligateAnaerobes during Oxygen Adaptive Response  

SciTech Connect

Determining the transient chemical properties of the intracellular environment canelucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms which enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier Transform Infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bonding in their cellular water. We observed a sequence of wellorchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses.

Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David. A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

2009-02-25

65

Real-time molecular monitoring of chemical environment in obligate anaerobes during oxygen adaptive response  

PubMed Central

Determining the transient chemical properties of the intracellular environment can elucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms that enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier transform infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bond structures in their cellular water. We observed a sequence of well orchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses. PMID:19541631

Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

2009-01-01

66

Speaking up: a moral obligation.  

PubMed

As we rush around attending to the essentials of our lives (family, friends, clients, employers), what is left? Nursing Forum invites readers to engage in thoughts and activities that may awaken an untouched place. We hope these writings will kindle your personal involvement in something that was previously avoided--because of bias, fear, or uneasiness--in order to stretch your mind and spirit. The purpose of this paper is to explore the act of speaking up as a moral obligation and its relationship to moral courage and habit. The difficulties of speaking up and the consequences of silence are examined. The benefits of speaking up are raising self-respect, gaining courage, forming good habits and passing on that legacy. PMID:8716884

Kelly, B

1996-01-01

67

Toward Intracellular Targeted Delivery of Cancer Therapeutics  

PubMed Central

A number of anti-cancer drugs have their targets localized to particular intracellular compartments. These drugs reach the targets mainly through diffusion, dependent on biophysical and biochemical forces that allow cell penetration. This means that both cancer cells and normal cells will be subjected to such diffusion; hence many of these drugs, like chemotherapeutics, are potentially toxic and the concentration achieved at the site of their action is often suboptimal. The same relates to radiation that indiscriminately affects normal and diseased cells. However, nature-designed systems enable compounds present in the extracellular environment to end up inside the cell and even travel to more specific intracellular compartments. For example, viruses and bacterial toxins can more or less specifically recognize eukaryotic cells, enter these cells, and direct some protein portions to designated intracellular areas. These phenomena have led to creative thinking, such as employing viruses or bacterial toxins for cargo delivery to cells and, more specifically, to cancer cells. Proteins can be genetically engineered in order to not only mimic what viruses and bacterial toxins can do, but also to add new functions, extending or changing the intracellular routes. It is possible to make conjugates or, more preferably, single-chain proteins that recognize cancer cells and deliver cargo inside the cells, even to the desired subcellular compartment. These findings offer new opportunities to deliver drugs/labels only to cancer cells and only to their site of action within the cells. The development of such dual-specificity vectors for targeting cancer cells is an attractive and potentially safer and more efficacious way of delivering drugs. We provide examples of this approach for delivering brain cancer therapeutics, using a specific biomarker on glioblastoma tumor cells. PMID:22671766

Pandya, Hetal; Debinski, Waldemar

2013-01-01

68

5 CFR 724.404 - Agency obligations.  

Code of Federal Regulations, 2010 CFR

...IMPLEMENTATION OF TITLE II OF THE NOTIFICATION AND FEDERAL EMPLOYEE ANTIDISCRIMINATION AND RETALIATION ACT OF 2002 Best Practices § 724.404 Agency obligations. (a) Within 30 working days of issuance of the advisory guidelines...

2010-01-01

69

21 CFR 26.62 - General obligations.  

Code of Federal Regulations, 2010 CFR

...MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE EUROPEAN COMMUNITY âFrameworkâ Provisions § 26.62 General obligations...assessment bodies (CAB's) and/or authorities. (b) The European Community (EC) and its Member States shall, as...

2010-04-01

70

7 CFR 989.37 - Obligation.  

Code of Federal Regulations, 2011 CFR

...MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN CALIFORNIA Order Regulating Handling Raisin Administrative Committee § 989.37 Obligation....

2011-01-01

71

Federal Academic Science and Engineering Obligations Decreased  

NSF Publications Database

... Obligations Decreased Slightly in FY 1996 (April 27, 1998) This data brief highlights the major ... Fiscal Year 1996. A full set of Detailed Statistical Tables covering FY 1996 and prior years will be ...

72

19 CFR 10.865 - Importer obligations.  

Code of Federal Regulations, 2012 CFR

...HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Oman Free Trade Agreement Import Requirements § 10.865 Importer obligations. (a) General. An importer who makes...

2012-04-01

73

19 CFR 10.865 - Importer obligations.  

Code of Federal Regulations, 2011 CFR

...HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Oman Free Trade Agreement Import Requirements § 10.865 Importer obligations. (a) General. An importer who makes...

2011-04-01

74

19 CFR 10.865 - Importer obligations.  

Code of Federal Regulations, 2013 CFR

...HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Oman Free Trade Agreement Import Requirements § 10.865 Importer obligations. (a) General. An importer who makes...

2013-04-01

75

19 CFR 10.865 - Importer obligations.  

...HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Oman Free Trade Agreement Import Requirements § 10.865 Importer obligations. (a) General. An importer who makes...

2014-04-01

76

Naval Engineering A National Naval Obligation  

E-print Network

As part of its national obligations, ONR must ensure US world leadership in those unique technology areas that insure naval superiority. ONR accomplishes this mission through research, recruitment and education, maintaining ...

Chryssostomidis, Chryssostomos

2000-05-16

77

46 CFR Sec. 11 - Guarantee obligations.  

Code of Federal Regulations, 2013 CFR

...REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP Sec. 11 Guarantee obligations. (a) Under the provisions of Article 10 of the NSA-LUMPSUMREP Contract the Contractor's guarantee liability...

2013-10-01

78

5 CFR 352.908 - Agency obligation.  

Code of Federal Regulations, 2010 CFR

...OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REEMPLOYMENT RIGHTS Reemployment Rights After Service With the Panama Canal Commission § 352.908 Agency obligation. (a) Time limits. An employee is to be reemployed by the...

2010-01-01

79

Bacterial Vaginosis  

MedlinePLUS

... vaginosis can increase your chance of getting an STD. What is bacterial vaginosis? Bacterial vaginosis (BV) is ... contributes to BV. BV is not considered an STD, but having BV can increase your chances of ...

80

Mechanisms of cellular invasion by intracellular parasites.  

PubMed

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality. PMID:24221133

Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

2014-04-01

81

Determining the Repertoire of Immunodominant Proteins via Whole-Genome Amplification of Intracellular Pathogens  

PubMed Central

Culturing many obligate intracellular bacteria is difficult or impossible. However, these organisms have numerous adaptations allowing for infection persistence and immune system evasion, making them some of the most interesting to study. Recent advancements in genome sequencing, pyrosequencing and Phi29 amplification, have allowed for examination of whole-genome sequences of intracellular bacteria without culture. We have applied both techniques to the model obligate intracellular pathogen Anaplasma marginale and the human pathogen Anaplasma phagocytophilum, in order to examine the ability of phi29 amplification to determine the sequence of genes allowing for immune system evasion and long-term persistence in the host. When compared to traditional pyrosequencing, phi29-mediated genome amplification had similar genome coverage, with no additional gaps in coverage. Additionally, all msp2 functional pseudogenes from two strains of A. marginale were detected and extracted from the phi29-amplified genomes, highlighting its utility in determining the full complement of genes involved in immune evasion. PMID:22558468

Dark, Michael J.; Lundgren, Anna M.; Barbet, Anthony F.

2012-01-01

82

Bacterial conjunctivitis  

PubMed Central

Clinical question What is the best treatment for bacterial conjunctivitis? Results Topical antibiotics expedite recovery from bacterial conjunctivitis. The choice of antibiotic usually does not affect outcome. Implementation Recognition of key distinguishing features of bacterial conjunctivitis Pitfalls that can be recognized in the history and physical examinationChoice of antibioticWhen to refer for specialist treatment. PMID:21188158

Hutnik, Cindy; Mohammad-Shahi, Mohammad H

2010-01-01

83

Patients' ethical obligation for their health.  

PubMed Central

In contemporary medical ethics health is rarely acknowledged to be an ethical obligation. This oversight is due to the preoccupation of most bioethicists with a rationalist, contract model for ethics in which moral obligation is limited to truth-telling and promise-keeping. Such an ethics is poorly suited to medicine because it fails to appreciate that medicine's basis as a moral enterprise is oriented towards health values. A naturalistic model for medical ethics is proposed which builds upon biological and medical values. This perspective clarifies ethical obligations to ourselves and to others for life and health. It provides a normative framework for the doctor-patient relationship within which to formulate medical advice and by which to evaluate patient choice. PMID:6502640

Sider, R C; Clements, C D

1984-01-01

84

Virulence determinants in the obligate intracellular pathogen Chlamydia trachomatis revealed by forward genetic approaches.  

PubMed

Chlamydia trachomatis, a pathogen responsible for diseases of significant clinical and public health importance, remains poorly characterized because of its intractability to routine molecular genetic manipulation. We have developed a combinatorial approach to rapidly generate a comprehensive library of genetically defined mutants. Chemical mutagenesis, coupled with whole-genome sequencing (WGS) and a system for DNA exchange within infected cells, was used to generate Chlamydia mutants with distinct phenotypes, map the underlying genetic lesions, and generate isogenic strains. As a result, we identified mutants with altered glycogen metabolism, including an attenuated strain defective for type II secretion. The coupling of chemically induced gene variation and WGS to establish genotype-phenotype associations should be broadly applicable to the large list of medically and environmentally important microorganisms currently intractable to genetic analysis. PMID:22232666

Nguyen, Bidong D; Valdivia, Raphael H

2012-01-24

85

Benefit Finding and Perceived Obligations of Victims  

E-print Network

of abuse and thought about the lesson of victimization for the perpetrator or the victim. Participants perceived the victim as more obligated to help and to not do harm when focused on the victim as compared to the perpetrator, to the extent...

Warner, Ruth

2007-12-11

86

Higher Education's Cultural Obligations: Views and Reviews.  

ERIC Educational Resources Information Center

Perspectives on the cultural obligations of higher education are presented in this collection of papers. Higher education's possible and probable cultural function is addressed from the perspective of business, the arts, education, and religion. Also discussed is the role of institutions of higher education in establishing a system of values,…

Reid, John Y., Ed.

87

Fetal Diagnosis – Obligations of the Clinician  

Microsoft Academic Search

Fetal echocardiography allows for accurate diagnosis of major heart abnormalities by 16–18 weeks. The parents have up to 22 weeks to consider possible termination. What are the obligations of the clinician once an abnormality is found? Should only information be provided or is there a role in influencing the parents’ decision? Two diverse examples are provided to discuss these questions.

Samuel Menahem; Lynn Gillam

2007-01-01

88

Bacterial Overgrowth  

Microsoft Academic Search

\\u000a The human gastrointestinal tract typically contains 300–500 bacterial species. Most bacterial species are acquired during\\u000a the birth process and although some changes to the flora may occur during later stages of life, the composition of the intestinal\\u000a microflora remains relatively constant. Small bowel bacterial overgrowth (SBBO) is defined as an excessive increase in the\\u000a number of bacteria in the upper

Rosemary J. Young; Jon A. Vanderhoof

89

28 CFR 811.3 - Notice of obligation to register.  

Code of Federal Regulations, 2012 CFR

...AGENCY FOR THE DISTRICT OF COLUMBIA SEX OFFENDER REGISTRATION § 811.3 Notice of obligation to register. (a) Sex offenders may be notified of their obligation...See sections 4, 6 and 8 of the Sex Offender Registration Act of...

2012-07-01

90

28 CFR 811.3 - Notice of obligation to register.  

Code of Federal Regulations, 2011 CFR

...AGENCY FOR THE DISTRICT OF COLUMBIA SEX OFFENDER REGISTRATION § 811.3 Notice of obligation to register. (a) Sex offenders may be notified of their obligation...See sections 4, 6 and 8 of the Sex Offender Registration Act of...

2011-07-01

91

28 CFR 811.3 - Notice of obligation to register.  

Code of Federal Regulations, 2013 CFR

...AGENCY FOR THE DISTRICT OF COLUMBIA SEX OFFENDER REGISTRATION § 811.3 Notice of obligation to register. (a) Sex offenders may be notified of their obligation...See sections 4, 6 and 8 of the Sex Offender Registration Act of...

2013-07-01

92

12 CFR 966.2 - Issuance of consolidated obligations.  

Code of Federal Regulations, 2011 CFR

...Section 966.2 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK LIABILITIES CONSOLIDATED... (a) Consolidated obligations issued by the Finance Board. The Finance Board may issue consolidated obligations...

2011-01-01

93

12 CFR 966.2 - Issuance of consolidated obligations.  

Code of Federal Regulations, 2010 CFR

...Section 966.2 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK LIABILITIES CONSOLIDATED... (a) Consolidated obligations issued by the Finance Board. The Finance Board may issue consolidated obligations...

2010-01-01

94

28 CFR 42.307 - Obligations of recipients.  

...2014-07-01 false Obligations of recipients. 42.307 Section 42.307 Judicial Administration DEPARTMENT OF JUSTICE... Equal Employment Opportunity Program Guidelines § 42.307 Obligations of recipients. The...

2014-07-01

95

24 CFR 291.565 - Continuing obligations after purchase.  

Code of Federal Regulations, 2010 CFR

... false Continuing obligations after purchase. 291.565 Section 291.565 Housing...HUD-ACQUIRED SINGLE FAMILY PROPERTY Good Neighbor Next Door Sales Program § 291.565 Continuing obligations after purchase. To remain in compliance with...

2010-04-01

96

23 CFR 230.205 - Supportive services funds obligation.  

...ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS EXTERNAL PROGRAMS Supportive Services for Minority, Disadvantaged, and Women Business Enterprises § 230.205 Supportive services funds obligation. Supportive services funds shall be obligated...

2014-04-01

97

Divine voluntarism: moral obligation supervenes on God's antecedent will  

E-print Network

undesirable implications, e.g., that moral obligation is arbitrary and that God's goodness is trivial. Also, while it avoids these undesirable implications, divine voluntarism must not imply that God is, in some way, restricted by moral obligation which exists...

Nam, Mi Young

2004-11-15

98

29 CFR 5.31 - Meeting wage determination obligations.  

Code of Federal Regulations, 2011 CFR

...subcontractor performing work subject to a Davis-Bacon wage determination may discharge his minimum wage obligations for the payment of both straight...contractor or subcontractor may discharge his minimum wage obligations for the payment of straight...

2011-07-01

99

29 CFR 5.31 - Meeting wage determination obligations.  

Code of Federal Regulations, 2012 CFR

...subcontractor performing work subject to a Davis-Bacon wage determination may discharge his minimum wage obligations for the payment of both straight...contractor or subcontractor may discharge his minimum wage obligations for the payment of straight...

2012-07-01

100

29 CFR 5.31 - Meeting wage determination obligations.  

Code of Federal Regulations, 2013 CFR

...subcontractor performing work subject to a Davis-Bacon wage determination may discharge his minimum wage obligations for the payment of both straight...contractor or subcontractor may discharge his minimum wage obligations for the payment of straight...

2013-07-01

101

29 CFR 5.31 - Meeting wage determination obligations.  

Code of Federal Regulations, 2010 CFR

...subcontractor performing work subject to a Davis-Bacon wage determination may discharge his minimum wage obligations for the payment of both straight...contractor or subcontractor may discharge his minimum wage obligations for the payment of straight...

2010-07-01

102

29 CFR 5.31 - Meeting wage determination obligations.  

...subcontractor performing work subject to a Davis-Bacon wage determination may discharge his minimum wage obligations for the payment of both straight...contractor or subcontractor may discharge his minimum wage obligations for the payment of straight...

2014-07-01

103

16 CFR 436.2 - Obligation to furnish documents.  

Code of Federal Regulations, 2010 CFR

...Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES DISCLOSURE REQUIREMENTS AND PROHIBITIONS CONCERNING FRANCHISING Franchisors' Obligations § 436.2 Obligation to furnish documents. In connection with the offer or...

2010-01-01

104

12 CFR 560.42 - State and local government obligations.  

Code of Federal Regulations, 2010 CFR

...Federal Savings Associations § 560.42 State and local government obligations. (a) What limitations apply? Pursuant to HOLA section 5(c)(1)(H), a Federal savings association (“you”) may invest in obligations issued by any state,...

2010-01-01

105

29 CFR 4043.20 - Post-Event filing obligation.  

Code of Federal Regulations, 2011 CFR

... 2011-07-01 2011-07-01 false Post-Event filing obligation. 4043.20 ...AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan...

2011-07-01

106

29 CFR 4043.20 - Post-Event filing obligation.  

Code of Federal Regulations, 2012 CFR

... 2012-07-01 2012-07-01 false Post-Event filing obligation. 4043.20 ...AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan...

2012-07-01

107

29 CFR 4043.20 - Post-Event filing obligation.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 2013-07-01 false Post-Event filing obligation. 4043.20 ...AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan...

2013-07-01

108

29 CFR 4043.20 - Post-Event filing obligation.  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 2010-07-01 false Post-Event filing obligation. 4043.20 ...AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan...

2010-07-01

109

Nanovehicular Intracellular Delivery Systems  

PubMed Central

This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood–brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list “elementary” phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach. PMID:18200527

PROKOP, ALES; DAVIDSON, JEFFREY M.

2013-01-01

110

Intracellular proliferation of S. aureus in osteoblasts and effects of rifampicin and gentamicin on S. aureus intracellular proliferation and survival.  

PubMed

Staphylococcus aureus is the most clinically relevant pathogen regarding implant-associated bone infection and its capability to invade osteoblasts is well known. The aim of this study was to investigate firstly whether S. aureus is not only able to invade but also to proliferate within osteoblasts, secondly to delineate the mechanism of invasion and thirdly to clarify whether rifampicin or gentamicin can inhibit intracellular proliferation and survival of S. aureus. The SAOS-2 osteoblast-like cell line and human primary osteoblasts were infected with S. aureus EDCC5055 and S. aureus Rosenbach 1884. Both S. aureus strains were able to invade efficiently and to proliferate within human osteoblasts. Immunofluorescence microscopy showed intracellular invasion of S. aureus and transmission electron microscopy images could demonstrate bacterial division as a sign of intracellular proliferation as well as cytosolic bacterial persistence. Cytochalasin D, the major actin depolymerisation agent, was able to significantly reduce S. aureus invasion, suggesting that invasion was enabled by promoting actin rearrangement at the cell surface. 7.5 ?g/mL of rifampicin was able to inhibit bacterial survival in SAOS-2 cells with almost complete elimination of bacteria after 4 h. Gentamicin could also kill intracellular S. aureus in a dose-dependent manner, an effect that was significantly lower than that observed using rifampicin. In conclusion, S. aureus is not only able to invade but also to proliferate in osteoblasts. Invasion seems to be associated with actin rearrangement at the cell surface. Rifampicin is effective in intracellular eradication of S. aureus whereas gentamicin only poorly eliminates intracellularly replicating bacteria. PMID:25340805

Mohamed, W; Sommer, U; Sethi, S; Domann, E; Thormann, U; Schütz, I; Lips, K S; Chakraborty, T; Schnettler, R; Alt, V

2014-01-01

111

Bacterial amyloids.  

PubMed

Many bacteria can assemble functional amyloid fibers on their cell surface. The majority of bacterial amyloids contribute to biofilm or other community behaviors where cells interact with a surface or with another cell. Bacterial amyloids, like all functional amyloids, share structural and biochemical properties with disease-associated eukaryotic amyloids. The general ability of amyloids to bind amyloid-specific dyes, such as Congo red, and their resistance to denaturation have provided useful tools for scoring and quantifying bacterial amyloid formation. Here, we present basic approaches to study bacterial amyloids by focusing on the well-studied curli amyloid fibers expressed by Enterobacteriaceae. These methods exploit the specific tinctorial and biophysical properties of amyloids. The methods described here are straightforward and can be easily applied by any modern molecular biology lab for the study of other bacterial amyloids. PMID:22528099

Zhou, Yizhou; Blanco, Luz P; Smith, Daniel R; Chapman, Matthew R

2012-01-01

112

Experimental evolution of nodule intracellular infection in legume symbionts  

PubMed Central

Soil bacteria known as rhizobia are able to establish an endosymbiosis with legumes that takes place in neoformed nodules in which intracellularly hosted bacteria fix nitrogen. Intracellular accommodation that facilitates nutrient exchange between the two partners and protects bacteria from plant defense reactions has been a major evolutionary step towards mutualism. Yet the forces that drove the selection of the late event of intracellular infection during rhizobium evolution are unknown. To address this question, we took advantage of the previous conversion of the plant pathogen Ralstonia solanacearum into a legume-nodulating bacterium that infected nodules only extracellularly. We experimentally evolved this draft rhizobium into intracellular endosymbionts using serial cycles of legume-bacterium cocultures. The three derived lineages rapidly gained intracellular infection capacity, revealing that the legume is a highly selective environment for the evolution of this trait. From genome resequencing, we identified in each lineage a mutation responsible for the extracellular–intracellular transition. All three mutations target virulence regulators, strongly suggesting that several virulence-associated functions interfere with intracellular infection. We provide evidence that the adaptive mutations were selected for their positive effect on nodulation. Moreover, we showed that inactivation of the type three secretion system of R. solanacearum that initially allowed the ancestral draft rhizobium to nodulate, was also required to permit intracellular infection, suggesting a similar checkpoint for bacterial invasion at the early nodulation/root infection and late nodule cell entry levels. We discuss our findings with respect to the spread and maintenance of intracellular infection in rhizobial lineages during evolutionary times. PMID:23426010

Guan, Su Hua; Gris, Carine; Cruveiller, Stephane; Pouzet, Cecile; Tasse, Lena; Leru, Aurelie; Maillard, Aline; Medigue, Claudine; Batut, Jacques; Masson-Boivin, Catherine; Capela, Delphine

2013-01-01

113

A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci.  

PubMed

The complement system modulates the intensity of innate and specific immunity. While it protects against infections by extracellular bacteria its role in infection with obligate intracellular bacteria, such as the avian and human pathogen Chlamydia (C.) psittaci, is still unknown. In the present study, knockout mice lacking C3 and thus all main complement effector functions were intranasally infected with C. psittaci strain DC15. Clinical parameters, lung histology, and cytokine levels were determined. A subset of infections was additionally performed with mice lacking C5 or C5a receptors. Complement activation occurred before symptoms of pneumonia appeared. Mice lacking C3 were ?100 times more susceptible to the intracellular bacteria compared to wild-type mice, with all C3(-/-) mice succumbing to infection after day 9. At a low infective dose, C3(-/-) mice became severely ill after an even longer delay, the kinetics suggesting a so far unknown link of complement to the adaptive, protective immune response against chlamydiae. The lethal phenotype of C3(-/-) mice is not based on differences in the anti-chlamydial IgG response (which is slightly delayed) as demonstrated by serum transfer experiments. In addition, during the first week of infection, the absence of C3 was associated with partial protection characterized by reduced weight loss, better clinical score and lower bacterial burden, which might be explained by a different mechanism. Lack of complement functions downstream of C5 had little effect. This study demonstrates for the first time a strong and complex influence of complement effector functions, downstream of C3 and upstream of C5, on the outcome of an infection with intracellular bacteria, such as C. psittaci. PMID:23189195

Bode, Jenny; Dutow, Pavel; Sommer, Kirsten; Janik, Katrin; Glage, Silke; Tümmler, Burkhard; Munder, Antje; Laudeley, Robert; Sachse, Konrad W; Klos, Andreas

2012-01-01

114

26 CFR 1.691(e)-1 - Installment obligations transmitted at death when prior law applied.  

... Installment obligations transmitted at death when prior law applied. 1.691(e... Installment obligations transmitted at death when prior law applied. (a) In general...transmission of installment obligations at the death of a holder of such obligations were...

2014-04-01

115

Cationic antimicrobial peptide LL-37 is effective against both extra- and intracellular Staphylococcus aureus.  

PubMed

The increasing resistance of bacteria to conventional antibiotics and the challenges posed by intracellular bacteria, which may be responsible for chronic and recurrent infections, have driven the need for advanced antimicrobial drugs for effective elimination of both extra- and intracellular pathogens. The purpose of this study was to determine the killing efficacy of cationic antimicrobial peptide LL-37 compared to conventional antibiotics against extra- and intracellular Staphylococcus aureus. Bacterial killing assays and an infection model of osteoblasts and S. aureus were studied to determine the bacterial killing efficacy of LL-37 and conventional antibiotics against extra- and intracellular S. aureus. We found that LL-37 was effective in killing extracellular S. aureus at nanomolar concentrations, while lactoferricin B was effective at micromolar concentrations and doxycycline and cefazolin at millimolar concentrations. LL-37 was surprisingly more effective in killing the clinical strain than in killing an ATCC strain of S. aureus. Moreover, LL-37 was superior to conventional antibiotics in eliminating intracellular S. aureus. The kinetic studies further revealed that LL-37 was fast in eliminating both extra- and intracellular S. aureus. Therefore, LL-37 was shown to be very potent and prompt in eliminating both extra- and intracellular S. aureus and was more effective in killing extra- and intracellular S. aureus than commonly used conventional antibiotics. LL-37 could potentially be used to treat chronic and recurrent infections due to its effectiveness in eliminating not only extracellular but also intracellular pathogens. PMID:23274662

Noore, Jabeen; Noore, Adly; Li, Bingyun

2013-03-01

116

Bacterial Vaginosis  

MedlinePLUS

... Field Search Button Advanced Search NIAID Home Health & Research Topics Labs & Scientific Resources Funding About NIAID News & Events NIAID > Health & Research Topics > Bacterial Vaginosis Skip Website Tools Website Tools Print ...

117

Ecophysiological Characteristics of Obligate Methanotrophic Bacteria and Methane Oxidation In Situ  

NASA Technical Reports Server (NTRS)

Most of the obligate methane-oxidizing bacteria (MOB) described to date are neutrophilic mesophiles that grow optimally in dilute media. Kinetic analyses generally indicate that bacterial methane uptake occurs by transport systems with a K(sub m) greater than l micronM. These and other properties of MOB are inconsistent with characteristics of methane oxidation in situ. The inconsistencies indicate a need for greater attention to the ecophysiological characteristics of isolates and the design of enrichment and isolation schemes which emphasize ecologically relevant parameters (e.g., low temperature, limited and diverse substrate availability, low water potential).

King, Gary M.

1993-01-01

118

“ Candidatus Contubernalis alkalaceticum,” an Obligately Syntrophic Alkaliphilic Bacterium Capable of Anaerobic Acetate Oxidation in a Coculture with Desulfonatronum cooperativum  

Microsoft Academic Search

From the silty sediments of the Khadyn soda lake (Tuva), a binary sulfidogenic bacterial association capable of syntrophic\\u000a acetate oxidation at pH 10.0 was isolated. An obligately syntrophic, gram-positive, spore-forming alkaliphilic rod-shaped\\u000a bacterium performs acetate oxidation in a syntrophic association with a hydrogenotrophic, alkaliphilic sulfate-reducing bacterium;\\u000a the latter organism was previously isolated and characterized as the new species Desulfonatronum cooperativum.

T. N. Zhilina; D. G. Zavarzina; T. V. Kolganova; T. P. Tourova; G. A. Zavarzin

2005-01-01

119

Intracellular microbes and haemophagocytosis.  

PubMed

Haemophagocytosis (hemophagocytosis) is the phenomenon of activated macrophage consumption of red and white blood cells, including professional phagocytes and lymphocytes. It can occur in patients with severe cases of intracellular microbial infection, including avian influenza, leishmaniasis, tuberculosis and typhoid fever. While well-known to physicians since at least the mid-1800s, haemophagocytosis has been little studied due to a paucity of tractable animal and cell culture models. Recently, haemophagocytosis has been described in a mouse model of typhoid fever, and it was noted that the infectious agent, Salmonella enterica, resides within haemophagocytic macrophages in mice. In addition, a cell culture model for haemophagocytosis revealed that S. enterica preferentially replicate in haemophagocytic macrophages. This review describes how, at the molecular and cellular levels, S. enterica may promote and take advantage of haemophagocytosis to establish long-term systemic infections in mammals. The role, relevance and possible molecular mechanisms of haemophagocytosis are discussed within the context of other microbial infections and of genetic deficiencies in which haemophagocytosis occurs and is associated with morbidity. PMID:18616693

Silva-Herzog, Eugenia; Detweiler, Corrella S

2008-11-01

120

Genome Reduction and Co-evolution between the Primary and Secondary Bacterial Symbionts of Psyllids  

PubMed Central

Genome reduction in obligately intracellular bacteria is one of the most well-established patterns in the field of molecular evolution. In the extreme, many sap-feeding insects harbor nutritional symbionts with genomes that are so reduced that it is not clear how they perform basic cellular functions. For example, the primary symbiont of psyllids (Carsonella) maintains one of the smallest and most AT-rich bacterial genomes ever identified and has surprisingly lost many genes that are thought to be essential for its role in provisioning its host with amino acids. However, our understanding of this extreme case of genome reduction is limited, as genomic data for Carsonella are available from only a single host species, and little is known about the functional role of “secondary” bacterial symbionts in psyllids. To address these limitations, we analyzed complete Carsonella genomes from pairs of congeneric hosts in three divergent genera within the Psyllidae (Ctenarytaina, Heteropsylla, and Pachypsylla) as well as complete secondary symbiont genomes from two of these host species (Ctenarytaina eucalypti and Heteropsylla cubana). Although the Carsonella genomes are generally conserved in size, structure, and GC content and exhibit genome-wide signatures of purifying selection, we found that gene loss has remained active since the divergence of the host species and had a particularly large impact on the amino acid biosynthesis pathways that define the symbiotic role of Carsonella. In some cases, the presence of additional bacterial symbionts may compensate for gene loss in Carsonella, as functional gene content indicates a high degree of metabolic complementarity between co-occurring symbionts. The genomes of the secondary symbionts also show signatures of long-term evolution as vertically transmitted, intracellular bacteria, including more extensive genome reduction than typically observed in facultative symbionts. Therefore, a history of co-evolution with secondary bacterial symbionts can partially explain the ongoing genome reduction in Carsonella. However, the absence of these secondary symbionts in other host lineages indicates that the relationships are dynamic and that other mechanisms, such as changes in host diet or functional coordination with the host genome, must also be at play. PMID:22821013

Sloan, Daniel B.; Moran, Nancy A.

2012-01-01

121

Salmonella enterica Serovar Typhimurium Response Involved in Attenuation of Pathogen Intracellular Proliferation  

PubMed Central

Salmonella enterica serovar Typhimurium proliferates within cultured epithelial and macrophage cells. Intracellular bacterial proliferation is, however, restricted within normal fibroblast cells. To characterize this phenomenon in detail, we investigated the possibility that the pathogen itself might contribute to attenuating the intracellular growth rate. S. enterica serovar Typhimurium mutants were selected in normal rat kidney fibroblasts displaying an increased intracellular proliferation rate. These mutants harbored loss-of-function mutations in the virulence-related regulatory genes phoQ, rpoS, slyA, and spvR. Lack of a functional PhoP-PhoQ system caused the most dramatic change in the intracellular growth rate. phoP- and phoQ-null mutants exhibited an intracellular growth rate 20- to 30-fold higher than that of the wild-type strain. This result showed that the PhoP-PhoQ system exerts a master regulatory function for preventing bacterial overgrowth within fibroblasts. In addition, an overgrowing clone was isolated harboring a mutation in a previously unknown serovar Typhimurium open reading frame, named igaA for intracellular growth attenuator. Mutations in other serovar Typhimurium virulence genes, such as ompR, dam, crp, cya, mviA, spiR (ssrA), spiA, and rpoE, did not result in pathogen intracellular overgrowth. Nonetheless, lack of either SpiA or the alternate sigma factor RpoE led to a substantial decrease in intracellular bacterial viability. These results prove for the first time that specific serovar Typhimurium virulence regulators are involved in a response designed to attenuate the intracellular growth rate within a nonphagocytic host cell. This growth-attenuating response is accompanied by functions that ensure the viability of intracellular bacteria. PMID:11553591

Cano, David A.; Martinez-Moya, Marina; Pucciarelli, M. Graciela; Groisman, Eduardo A.; Casadesus, Josep; Garcia-Del Portillo, Francisco

2001-01-01

122

Salmonella enterica serovar Typhimurium response involved in attenuation of pathogen intracellular proliferation.  

PubMed

Salmonella enterica serovar Typhimurium proliferates within cultured epithelial and macrophage cells. Intracellular bacterial proliferation is, however, restricted within normal fibroblast cells. To characterize this phenomenon in detail, we investigated the possibility that the pathogen itself might contribute to attenuating the intracellular growth rate. S. enterica serovar Typhimurium mutants were selected in normal rat kidney fibroblasts displaying an increased intracellular proliferation rate. These mutants harbored loss-of-function mutations in the virulence-related regulatory genes phoQ, rpoS, slyA, and spvR. Lack of a functional PhoP-PhoQ system caused the most dramatic change in the intracellular growth rate. phoP- and phoQ-null mutants exhibited an intracellular growth rate 20- to 30-fold higher than that of the wild-type strain. This result showed that the PhoP-PhoQ system exerts a master regulatory function for preventing bacterial overgrowth within fibroblasts. In addition, an overgrowing clone was isolated harboring a mutation in a previously unknown serovar Typhimurium open reading frame, named igaA for intracellular growth attenuator. Mutations in other serovar Typhimurium virulence genes, such as ompR, dam, crp, cya, mviA, spiR (ssrA), spiA, and rpoE, did not result in pathogen intracellular overgrowth. Nonetheless, lack of either SpiA or the alternate sigma factor RpoE led to a substantial decrease in intracellular bacterial viability. These results prove for the first time that specific serovar Typhimurium virulence regulators are involved in a response designed to attenuate the intracellular growth rate within a nonphagocytic host cell. This growth-attenuating response is accompanied by functions that ensure the viability of intracellular bacteria. PMID:11553591

Cano, D A; Martínez-Moya, M; Pucciarelli, M G; Groisman, E A; Casadesús, J; García-Del Portillo, F

2001-10-01

123

Metabolic Complementarity and Genomics of the Dual Bacterial Symbiosis of Sharpshooters  

PubMed Central

Mutualistic intracellular symbiosis between bacteria and insects is a widespread phenomenon that has contributed to the global success of insects. The symbionts, by provisioning nutrients lacking from diets, allow various insects to occupy or dominate ecological niches that might otherwise be unavailable. One such insect is the glassy-winged sharpshooter (Homalodisca coagulata), which feeds on xylem fluid, a diet exceptionally poor in organic nutrients. Phylogenetic studies based on rRNA have shown two types of bacterial symbionts to be coevolving with sharpshooters: the gamma-proteobacterium Baumannia cicadellinicola and the Bacteroidetes species Sulcia muelleri. We report here the sequencing and analysis of the 686,192–base pair genome of B. cicadellinicola and approximately 150 kilobase pairs of the small genome of S. muelleri, both isolated from H. coagulata. Our study, which to our knowledge is the first genomic analysis of an obligate symbiosis involving multiple partners, suggests striking complementarity in the biosynthetic capabilities of the two symbionts: B. cicadellinicola devotes a substantial portion of its genome to the biosynthesis of vitamins and cofactors required by animals and lacks most amino acid biosynthetic pathways, whereas S. muelleri apparently produces most or all of the essential amino acids needed by its host. This finding, along with other results of our genome analysis, suggests the existence of metabolic codependency among the two unrelated endosymbionts and their insect host. This dual symbiosis provides a model case for studying correlated genome evolution and genome reduction involving multiple organisms in an intimate, obligate mutualistic relationship. In addition, our analysis provides insight for the first time into the differences in symbionts between insects (e.g., aphids) that feed on phloem versus those like H. coagulata that feed on xylem. Finally, the genomes of these two symbionts provide potential targets for controlling plant pathogens such as Xylella fastidiosa, a major agroeconomic problem, for which H. coagulata and other sharpshooters serve as vectors of transmission. PMID:16729848

Wu, Dongying; Daugherty, Sean C; Van Aken, Susan E; Pai, Grace H; Watkins, Kisha L; Khouri, Hoda; Tallon, Luke J; Zaborsky, Jennifer M; Dunbar, Helen E; Tran, Phat L; Moran, Nancy A

2006-01-01

124

"Obligated aliens": recognizing sperm donors' ethical obligation to disclose genetic information.  

PubMed

Sperm donors' obligations are typically constrained to the immediate circumstances surrounding the donation and to its time frame. This paper makes the case for recognizing an ongoing ethical obligation that binds sperm donors to disclose, in a timely manner, meaningful genetic information to recipients and donor-conceived children. The paper delineates and conceptualizes the suggested (potentially reciprocal) duty and argues that it is not the genetic link between the donor and the donor-conceived child that binds donors by said duty, but rather social responsibility. Accordingly, an original perception of the donor as an obligated alien is suggested and developed. The main thesis of the paper is supported inter alia by a comparison between transmitting infectious diseases and passing faulty genes on to donor-conceived children. The paper also provides an in-depth analysis of the conflicting interests of the parties generated by such an obligation and proposes a model for embedding this ethical duty in a (legal) contractual framework. PMID:23678628

Tamir, Sivan

2013-03-01

125

Is there a moral obligation not to infect others?  

PubMed

The emergence of HIV infection and AIDS has refocused concern on the obligations surrounding the carrying and transmission of communicable diseases. This article asks three related questions: Is there a general duty not to spread contagion? Are there special obligations not to communicate disease in the workplace? And does the mode of transmission of the disease affect the ethics of transmission and, if so, how and to what extent? There seems to be a strong prima facie obligation not to harm others by making them ill where this is avoidable, and this obligation not to communicate disease applies as much to relatively trivial diseases like the common cold as it does to HIV disease. The reasonableness of expecting people to live up to this obligation, however, depends on society reciprocating the obligation in the form of providing protection and compensation. PMID:7488907

Harris, J; Holm, S

1995-11-01

126

Bacterial glycoproteomics.  

PubMed

Glycosylated proteins are ubiquitous components of eukaryote cellular surfaces, where the glycan moieties are implicated in a wide range of cell-cell recognition events. Once thought to be restricted to eukaryotes, glycosylation is now being increasingly reported in prokaryotes. Many of these discoveries have grown from advances in analytical technologies and genome sequencing. This review highlights the capabilities of high-sensitivity mass spectrometry for carbohydrate structure determination of bacterial glycoproteins and the emergence of glycoproteomic strategies that have evolved from proteomics and genomics for the functional analysis of bacterial glycosylation. PMID:16735721

Hitchen, Paul G; Dell, Anne

2006-06-01

127

7 CFR 1450.105 - Obligations of participant.  

Code of Federal Regulations, 2012 CFR

...Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM (BCAP) Matching Payments § 1450.105 Obligations of participant. (a) All...

2012-01-01

128

7 CFR 1450.105 - Obligations of participant.  

Code of Federal Regulations, 2011 CFR

...Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM (BCAP) Matching Payments § 1450.105 Obligations of participant. (a) All...

2011-01-01

129

7 CFR 1450.105 - Obligations of participant.  

Code of Federal Regulations, 2013 CFR

...Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM (BCAP) Matching Payments § 1450.105 Obligations of participant. (a) All...

2013-01-01

130

7 CFR 1450.105 - Obligations of participant.  

...Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM (BCAP) Matching Payments § 1450.105 Obligations of participant. (a) All...

2014-01-01

131

Comparative Genomics of Wolbachia and the Bacterial Species Concept  

PubMed Central

The importance of host-specialization to speciation processes in obligate host-associated bacteria is well known, as is also the ability of recombination to generate cohesion in bacterial populations. However, whether divergent strains of highly recombining intracellular bacteria, such as Wolbachia, can maintain their genetic distinctness when infecting the same host is not known. We first developed a protocol for the genome sequencing of uncultivable endosymbionts. Using this method, we have sequenced the complete genomes of the Wolbachia strains wHa and wNo, which occur as natural double infections in Drosophila simulans populations on the Seychelles and in New Caledonia. Taxonomically, wHa belong to supergroup A and wNo to supergroup B. A comparative genomics study including additional strains supported the supergroup classification scheme and revealed 24 and 33 group-specific genes, putatively involved in host-adaptation processes. Recombination frequencies were high for strains of the same supergroup despite different host-preference patterns, leading to genomic cohesion. The inferred recombination fragments for strains of different supergroups were of short sizes, and the genomes of the co-infecting Wolbachia strains wHa and wNo were not more similar to each other and did not share more genes than other A- and B-group strains that infect different hosts. We conclude that Wolbachia strains of supergroup A and B represent genetically distinct clades, and that strains of different supergroups can co-exist in the same arthropod host without converging into the same species. This suggests that the supergroups are irreversibly separated and that barriers other than host-specialization are able to maintain distinct clades in recombining endosymbiont populations. Acquiring a good knowledge of the barriers to genetic exchange in Wolbachia will advance our understanding of how endosymbiont communities are constructed from vertically and horizontally transmitted genes. PMID:23593012

Naslund, Kristina; Bourtzis, Kostas; Andersson, Siv G. E.

2013-01-01

132

Bacterial Mining  

Microsoft Academic Search

Bacterial mining (biomining) represents the use of microorganisms to leach out metals from ores or mine tailings (wastes), followed by the subsequent recovery of metals of interest from the leaching solution. This leaching of metals from ores is a natural process, which can be considerably accelerated by inducing and\\/or supporting the microbial activity of certain species with the ability to

I. G. Petrisor; I. Lazar; T. F. Yen

2007-01-01

133

Francisella tularensis Harvests Nutrients Derived via ATG5-Independent Autophagy to Support Intracellular Growth  

PubMed Central

Francisella tularensis is a highly virulent intracellular pathogen that invades and replicates within numerous host cell types including macrophages, hepatocytes and pneumocytes. By 24 hours post invasion, F. tularensis replicates up to 1000-fold in the cytoplasm of infected cells. To achieve such rapid intracellular proliferation, F. tularensis must scavenge large quantities of essential carbon and energy sources from the host cell while evading anti-microbial immune responses. We found that macroautophagy, a eukaryotic cell process that primarily degrades host cell proteins and organelles as well as intracellular pathogens, was induced in F. tularensis infected cells. F. tularensis not only survived macroautophagy, but optimal intracellular bacterial growth was found to require macroautophagy. Intracellular growth upon macroautophagy inhibition was rescued by supplying excess nonessential amino acids or pyruvate, demonstrating that autophagy derived nutrients provide carbon and energy sources that support F. tularensis proliferation. Furthermore, F. tularensis did not require canonical, ATG5-dependent autophagy pathway induction but instead induced an ATG5-independent autophagy pathway. ATG5-independent autophagy induction caused the degradation of cellular constituents resulting in the release of nutrients that the bacteria harvested to support bacterial replication. Canonical macroautophagy limits the growth of several different bacterial species. However, our data demonstrate that ATG5-independent macroautophagy may be beneficial to some cytoplasmic bacteria by supplying nutrients to support bacterial growth. PMID:23966861

Ziehr, Benjamin; Taft-Benz, Sharon; Moorman, Nathaniel; Kawula, Thomas

2013-01-01

134

Relative entropy differences in bacterial chromosomes, plasmids, phages and genomic islands  

PubMed Central

Background We sought to assess whether the concept of relative entropy (information capacity), could aid our understanding of the process of horizontal gene transfer in microbes. We analyzed the differences in information capacity between prokaryotic chromosomes, genomic islands (GI), phages, and plasmids. Relative entropy was estimated using the Kullback-Leibler measure. Results Relative entropy was highest in bacterial chromosomes and had the sequence chromosomes > GI > phage > plasmid. There was an association between relative entropy and AT content in chromosomes, phages, plasmids and GIs with the strongest association being in phages. Relative entropy was also found to be lower in the obligate intracellular Mycobacterium leprae than in the related M. tuberculosis when measured on a shared set of highly conserved genes. Conclusions We argue that relative entropy differences reflect how plasmids, phages and GIs interact with microbial host chromosomes and that all these biological entities are, or have been, subjected to different selective pressures. The rate at which amelioration of horizontally acquired DNA occurs within the chromosome is likely to account for the small differences between chromosomes and stably incorporated GIs compared to the transient or independent replicons such as phages and plasmids. PMID:22325062

2012-01-01

135

Genetic ignorance, moral obligations and social duties.  

PubMed

In a contribution to The Journal of Medicine and Philosophy, Professor Rosamond Rhodes argues that individuals sometimes have an obligation to know about their genetic disorders, because this is required by their status as autonomous persons. Her analysis, which is based on Kant's concept of autonomy and Aristotle's notion of friendship, is extended here to consequentialist concerns. These are of paramount importance if, as we believe and Professor Rhodes herself implies, the Kantian and Aristotelian doctrines can be helpful only in the sphere of private morality, not in the public realm. Better tools for assessing the right to genetic ignorance as an issue of public policy can, we contend, be found in Mill's ideas concerning liberty and the prevention of harm. Our own conclusion, based on the Millian way of thinking, is that individuals probably do have the right to remain in ignorance in the cases Professor Rhodes presents as examples of a duty to know. PMID:10732878

Takala, T; Häyry, M

2000-02-01

136

Ethical theory, "common morality," and professional obligations.  

PubMed

We have two aims in this paper. The first is negative: to demonstrate the problems in Bernard Gert's account of common morality, in particular as it applies to professional morality. The second is positive: to suggest a more satisfactory explanation of the moral basis of professional role morality, albeit one that is broadly consistent with Gert's notion of common morality, but corrects and supplements Gert's theory. The paper is in three sections. In the first, we sketch the main features of Gert's account of common morality in general. In the second, we outline Gert's explanation of the source of professional moral rules and demonstrate its inadequacy. In the third section, we provide an account of our own collectivist needs-based view of the source of the role-moral obligations of many professional roles, including those of health care professionals. PMID:19199076

Alexandra, Andrew; Miller, Seumas

2009-01-01

137

[Facultative and obligate aerobic methylobacteria synthesize cytokinins].  

PubMed

The presence and expression of genes controlling the synthesis and secretion of cytokinins by the pink-pigmented facultative methylotroph Methylobacterium mesophilicum VKM B-2143 with the serine pathway and nonpigmented obligate methylotroph Methylovorus mays VKM B-2221 with the ribulose monophosphate pathway of C1 metabolism were shown using the polymerase chain reaction (PCR) and reverse transcription-PCR methods. The presence of the corresponding mRNA in M. mesophilicum cells grown on methanol or succinate suggests that the expression of these genes is constitutive. The cytokinin activity of culture liquid and its fractions was determined by a biotest with Amarantus caudatus L. seedlings. Using enzyme-linked immunosorbent analysis, we detected zeatin (riboside) in the culture liquid of both bacteria studied. The data obtained show that the aerobic methylobacteria are phytosymbionts that are able to utilize the single- and polycarbon compounds secreted by symbiotic plants and to synthesize cytokinins. PMID:11195573

Ivanova, E G; Doronina, N V; Shepeliakovskaia, A O; Laman, A G; Brovko, F A; Trotsenko, Iu A

2000-01-01

138

Utilities` ``obligation to serve`` under deregulation  

SciTech Connect

The utility no longer has protected status, and the traditional franchise concept is under attack. Exclusive rights once conveyed to the utilities are being denied and not just in the area of gas sales. Exclusive rights once conveyed to utilities will be denied in more areas. State by state, the utilities` franchise is being examined to see which, if any, of its provisions are necessary in a deregulated environment. Can the free market provide everything that`s been provided for many years under monopolistic arrangements? Some of the most critical and difficult of these provisions concern the obligation to serve, which utilities, in most states, have assumed as part of their franchise agreement. Regulators, courts, utilities, marketers and others are busy sorting through these issues, but resolution could take years. The paper discusses deregulation, universal service fee, representation without taxation, suppliers and marketer restrictions.

Alexander, C.B.

1997-02-01

139

The Role Obligations of Students and Lecturers in Higher Education  

ERIC Educational Resources Information Center

The current discussion of consumerism in higher education focuses largely on what the providers are obliged to do for the consumers, against the background of rising tuition fees. This framework does not always sit comfortably with lecturers in the context of a learning and teaching relationship, as it appears to ignore the reciprocal obligations

Regan, Julie-Anne

2012-01-01

140

Schooling properties of an obligate and a facultative fish species  

E-print Network

Schooling properties of an obligate and a facultative fish species M. SORIA* , P. FREON § and P, Nouvelle-Calédonie, France Schooling fish species are conventionally subdivided into obligate interactions, Schooling behaviour, Polarity, Pelagic fish Running headline: Schooling properties of two fish

Paris-Sud XI, Université de

141

The Evolutionary Pathway to Obligate Scavenging in Gyps Vultures  

Microsoft Academic Search

The evolutionary pathway to obligate scavenging in Gyps vultures remains unclear. We propose that communal roosting plays a central role in setting up the information transfer network critical for obligate scavengers in ephemeral environments and that the formation of a flotilla-like foraging group is a likely strategy for foraging Gyps vultures. Using a spatial, individual-based, optimisation model we find that

Brian J. Dermody; Colby J. Tanner; Andrew L. Jackson

2011-01-01

142

Deconfounding Distance Effects in Judgments of Moral Obligation  

ERIC Educational Resources Information Center

A heavily disputed question of moral philosophy is whether spatial distance between agent and victim is normatively relevant for the degree of obligation to help strangers in need. In this research, we focus on the associated descriptive question whether increased distance does in fact reduce individuals' sense of helping obligation. One problem…

Nagel, Jonas; Waldmann, Michael R.

2013-01-01

143

Metallochaperones regulate intracellular copper levels.  

PubMed

Copper (Cu) is an important enzyme co-factor that is also extremely toxic at high intracellular concentrations, making active efflux mechanisms essential for preventing Cu accumulation. Here, we have investigated the mechanistic role of metallochaperones in regulating Cu efflux. We have constructed a computational model of Cu trafficking and efflux based on systems analysis of the Cu stress response of Halobacterium salinarum. We have validated several model predictions via assays of transcriptional dynamics and intracellular Cu levels, discovering a completely novel function for metallochaperones. We demonstrate that in addition to trafficking Cu ions, metallochaperones also function as buffers to modulate the transcriptional responsiveness and efficacy of Cu efflux. This buffering function of metallochaperones ultimately sets the upper limit for intracellular Cu levels and provides a mechanistic explanation for previously observed Cu metallochaperone mutation phenotypes. PMID:23349626

Pang, W Lee; Kaur, Amardeep; Ratushny, Alexander V; Cvetkovic, Aleksandar; Kumar, Sunil; Pan, Min; Arkin, Adam P; Aitchison, John D; Adams, Michael W W; Baliga, Nitin S

2013-01-01

144

Metallochaperones Regulate Intracellular Copper Levels  

PubMed Central

Copper (Cu) is an important enzyme co-factor that is also extremely toxic at high intracellular concentrations, making active efflux mechanisms essential for preventing Cu accumulation. Here, we have investigated the mechanistic role of metallochaperones in regulating Cu efflux. We have constructed a computational model of Cu trafficking and efflux based on systems analysis of the Cu stress response of Halobacterium salinarum. We have validated several model predictions via assays of transcriptional dynamics and intracellular Cu levels, discovering a completely novel function for metallochaperones. We demonstrate that in addition to trafficking Cu ions, metallochaperones also function as buffers to modulate the transcriptional responsiveness and efficacy of Cu efflux. This buffering function of metallochaperones ultimately sets the upper limit for intracellular Cu levels and provides a mechanistic explanation for previously observed Cu metallochaperone mutation phenotypes. PMID:23349626

Pang, W. Lee; Kaur, Amardeep; Ratushny, Alexander V.; Cvetkovic, Aleksandar; Kumar, Sunil; Pan, Min; Arkin, Adam P.; Aitchison, John D.; Adams, Michael W. W.; Baliga, Nitin S.

2013-01-01

145

Bacterial pathogen manipulation of host membrane trafficking.  

PubMed

Pathogens use a vast number of strategies to alter host membrane dynamics. Targeting the host membrane machinery is important for the survival and pathogenesis of several extracellular, vacuolar, and cytosolic bacteria. Membrane manipulation promotes bacterial replication while suppressing host responses, allowing the bacterium to thrive in a hostile environment. This review provides a comprehensive summary of various strategies used by both extracellular and intracellular bacteria to hijack host membrane trafficking machinery. We start with mechanisms used by bacteria to alter the plasma membrane, delve into the hijacking of various vesicle trafficking pathways, and conclude by summarizing bacterial adaptation to host immune responses. Understanding bacterial manipulation of host membrane trafficking provides insights into bacterial pathogenesis and uncovers the molecular mechanisms behind various processes within a eukaryotic cell. PMID:25103867

Asrat, Seblewongel; de Jesús, Dennise A; Hempstead, Andrew D; Ramabhadran, Vinay; Isberg, Ralph R

2014-10-11

146

60 FR 61700 - Schedule of Submission Dates for Statements of Net Outstanding Campaign Obligations Required from...  

Federal Register 2010, 2011, 2012, 2013

...Schedule of Submission Dates for Statements of Net Outstanding Campaign Obligations Required...Notice of submission dates for statements of net outstanding campaign obligations required...publishing submission dates for statements of net outstanding campaign obligations...

1995-12-01

147

20 CFR 726.207 - Discharge by the carrier of obligations and duties of operator.  

Code of Federal Regulations, 2010 CFR

...of obligations and duties of operator. 726...of obligations and duties of operator. Every obligation and duty in respect of payment...other treatment and care, the payment...operator by a district director,...

2010-04-01

148

A Lack of Parasitic Reduction in the Obligate Parasitic Green Alga Helicosporidium  

PubMed Central

The evolution of an obligate parasitic lifestyle is often associated with genomic reduction, in particular with the loss of functions associated with increasing host-dependence. This is evident in many parasites, but perhaps the most extreme transitions are from free-living autotrophic algae to obligate parasites. The best-known examples of this are the apicomplexans such as Plasmodium, which evolved from algae with red secondary plastids. However, an analogous transition also took place independently in the Helicosporidia, where an obligate parasite of animals with an intracellular infection mechanism evolved from algae with green primary plastids. We characterised the nuclear genome of Helicosporidium to compare its transition to parasitism with that of apicomplexans. The Helicosporidium genome is small and compact, even by comparison with the relatively small genomes of the closely related green algae Chlorella and Coccomyxa, but at the functional level we find almost no evidence for reduction. Nearly all ancestral metabolic functions are retained, with the single major exception of photosynthesis, and even here reduction is not complete. The great majority of genes for light-harvesting complexes, photosystems, and pigment biosynthesis have been lost, but those for other photosynthesis-related functions, such as Calvin cycle, are retained. Rather than loss of whole function categories, the predominant reductive force in the Helicosporidium genome is a contraction of gene family complexity, but even here most losses affect families associated with genome maintenance and expression, not functions associated with host-dependence. Other gene families appear to have expanded in response to parasitism, in particular chitinases, including those predicted to digest the chitinous barriers of the insect host or remodel the cell wall of Helicosporidium. Overall, the Helicosporidium genome presents a fascinating picture of the early stages of a transition from free-living autotroph to parasitic heterotroph where host-independence has been unexpectedly preserved. PMID:24809511

Pombert, Jean-Francois; Blouin, Nicolas Achille; Lane, Chris; Boucias, Drion; Keeling, Patrick J.

2014-01-01

149

A lack of parasitic reduction in the obligate parasitic green alga Helicosporidium.  

PubMed

The evolution of an obligate parasitic lifestyle is often associated with genomic reduction, in particular with the loss of functions associated with increasing host-dependence. This is evident in many parasites, but perhaps the most extreme transitions are from free-living autotrophic algae to obligate parasites. The best-known examples of this are the apicomplexans such as Plasmodium, which evolved from algae with red secondary plastids. However, an analogous transition also took place independently in the Helicosporidia, where an obligate parasite of animals with an intracellular infection mechanism evolved from algae with green primary plastids. We characterised the nuclear genome of Helicosporidium to compare its transition to parasitism with that of apicomplexans. The Helicosporidium genome is small and compact, even by comparison with the relatively small genomes of the closely related green algae Chlorella and Coccomyxa, but at the functional level we find almost no evidence for reduction. Nearly all ancestral metabolic functions are retained, with the single major exception of photosynthesis, and even here reduction is not complete. The great majority of genes for light-harvesting complexes, photosystems, and pigment biosynthesis have been lost, but those for other photosynthesis-related functions, such as Calvin cycle, are retained. Rather than loss of whole function categories, the predominant reductive force in the Helicosporidium genome is a contraction of gene family complexity, but even here most losses affect families associated with genome maintenance and expression, not functions associated with host-dependence. Other gene families appear to have expanded in response to parasitism, in particular chitinases, including those predicted to digest the chitinous barriers of the insect host or remodel the cell wall of Helicosporidium. Overall, the Helicosporidium genome presents a fascinating picture of the early stages of a transition from free-living autotroph to parasitic heterotroph where host-independence has been unexpectedly preserved. PMID:24809511

Pombert, Jean-François; Blouin, Nicolas Achille; Lane, Chris; Boucias, Drion; Keeling, Patrick J

2014-05-01

150

Polyamines are implicated in the emergence of the embryo from obligate diapause.  

PubMed

Embryonic diapause is a poorly understood phenomenon of reversible arrest of embryo development prior to implantation. In many carnivores, such as the mink (Neovison vison), obligate diapause characterizes each gestation. Embryo reactivation is controlled by the uterus by mechanisms that remain elusive. Because polyamines are essential regulators of cell proliferation and growth, it was hypothesized that they trigger embryo reactivation. To test this, mated mink females were treated with ?-difluoromethylornithine, an inhibitor of ornithine decarboxylase 1, the rate-limiting enzyme in polyamine biosynthesis, or saline as a control during the first 5 d of reactivation. This treatment induced polyamine deprivation with the consequence of rearrest in embryo cell proliferation. A mink trophoblast cell line in vitro subjected to ?-difluoromethylornithine treatment likewise displayed an arrest in cell proliferation, morphological changes, and intracellular translocation of ornithine decarboxylase 1 protein. The arrest in embryo development deferred implantation for a period consistent with the length of treatment. Successful implantation and parturition ensued. We conclude that polyamine deprivation brought about a reversible rearrest of embryo development, which returned the mink embryo to diapause and induced a second delay in embryo implantation. The results are the first demonstration of a factor essential to reactivation of embryos in obligate diapause. PMID:21303959

Lefèvre, Pavine L C; Palin, Marie-France; Chen, Gary; Turecki, Gustavo; Murphy, Bruce D

2011-04-01

151

The Evolution of Genomic Instability in the Obligate Endosymbionts of Whiteflies  

PubMed Central

Many insects depend on ancient associations with intracellular bacteria to perform essential metabolic functions. These endosymbionts exhibit striking examples of convergence in genome architecture, including a high degree of structural stability that is not typical of their free-living counterparts. However, the recently sequenced genome of the obligate whitefly endosymbiont Portiera revealed features that distinguish it from other ancient insect associates, such as a low gene density and the presence of perfectly duplicated sequences. Here, we report the comparative analysis of Portiera genome sequences both within and between host species. In one whitefly lineage (Bemisia tabaci), we identify large-scale structural polymorphisms in the Portiera genome that exist even within individual insects. This variation is likely mediated by recombination across identical repeats that are maintained by gene conversion. The complete Portiera genome sequence from a distantly related whitefly host (Trialeurodes vaporarium) confirms a history of extensive genome rearrangement in this ancient endosymbiont. Using gene-order-based phylogenetic analysis, we show that the majority of rearrangements have occurred in the B. tabaci lineage, coinciding with an increase in the rate of nucleotide substitutions, a proliferation of short tandem repeats (microsatellites) in intergenic regions, and the loss of many widely conserved genes involved in DNA replication, recombination, and repair. These results indicate that the loss of recombinational machinery is unlikely to be the cause of the extreme structural conservation that is generally observed in obligate endosymbiont genomes and that large, repetitive intergenic regions are an important substrate for genomic rearrangements. PMID:23542079

Sloan, Daniel B.; Moran, Nancy A.

2013-01-01

152

Immune responses to intracellular bacteria.  

PubMed

The multifaceted dialogue between intracellular bacteria and the mammalian host continues to be an exciting issue from both the scientific and public-health viewpoint. The recent year has witnessed some particularly impressive progress in knowledge about the two major culprits affecting the health of mankind, Mycobacterium tuberculosis and Salmonella typhi - the causative agents of tuberculosis and typhoid fever. PMID:11498297

Raupach, B; Kaufmann, S H

2001-08-01

153

Dynamics of intracellular information decoding  

Microsoft Academic Search

A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding,

Tetsuya J. Kobayashi; Atsushi Kamimura

2011-01-01

154

Physicians' strikes and the competing bases of physicians' moral obligations.  

PubMed

Many authors have addressed the morality of physicians' strikes on the assumption that medical practice is morally different from other kinds of occupations. This article analyzes three prominent theoretical accounts that attempt to ground such special moral obligations for physicians--practice-based accounts, utilitarian accounts, and social contract accounts--and assesses their applicability to the problem of the morality of strikes. After critiquing these views, it offers a fourth view grounding special moral obligations in voluntary commitments, and explains why this is a preferable basis for understanding physicians' moral obligations in general and especially as pertaining to strikes. PMID:24199524

MacDougall, D Robert

2013-09-01

155

Sulfur Production by Obligately Chemolithoautotrophic Thiobacillus Species  

PubMed Central

Transient-state experiments with the obligately autotrophic Thiobacillus sp. strain W5 revealed that sulfide oxidation proceeds in two physiological phases, (i) the sulfate-producing phase and (ii) the sulfur- and sulfate-producing phase, after which sulfide toxicity occurs. Specific sulfur-producing characteristics were independent of the growth rate. Sulfur formation was shown to occur when the maximum oxidative capacity of the culture was approached. In order to be able to oxidize increasing amounts of sulfide, the organism has to convert part of the sulfide to sulfur (HS(sup-)(symbl)S(sup0) + H(sup+) + 2e(sup-)) instead of sulfate (HS(sup-) + 4H(inf2)O(symbl)SO(inf4)(sup2-) + 9 H(sup+) + 8e(sup-)), thereby keeping the electron flux constant. Measurements of the in vivo degree of reduction of the cytochrome pool as a function of increasing sulfide supply suggested a redox-related down-regulation of the sulfur oxidation rate. Comparison of the sulfur-producing properties of Thiobacillus sp. strain W5 and Thiobacillus neapolitanus showed that the former has twice the maximum specific sulfide-oxidizing capacity of the latter (3.6 versus 1.9 (mu)mol/mg of protein/min). Their maximum specific oxygen uptake rates were very similar. Significant mechanistic differences in sulfur production between the high-sulfur-producing Thiobacillus sp. strain W5 and the moderate-sulfur-producing species T. neapolitanus were not observed. The limited sulfide-oxidizing capacity of T. neapolitanus appears to be the reason that it can convert only 50% of the incoming sulfide to elemental sulfur. PMID:16535627

Visser, J. M.; Robertson, L. A.; Van Verseveld, H. W.; Kuenen, J. G.

1997-01-01

156

7 CFR 4290.165 - Obligations of Control Persons.  

Code of Federal Regulations, 2010 CFR

...AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Qualifications for the RBIC Program Organizing A Rbic § 4290.165 Obligations of Control Persons. All Control...

2010-01-01

157

7 CFR 400.168 - Obligations of participating insurance company.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for Approval; Regulations for the 1997 and Subsequent Reinsurance Years § 400.168 Obligations of participating insurance company. The Agreement will...

2010-01-01

158

7 CFR 400.167 - Limitations on Corporation's obligations.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for Approval; Regulations for the 1997 and Subsequent Reinsurance Years § 400.167 Limitations on Corporation's obligations. The Agreement will...

2010-01-01

159

7 CFR 400.166 - Obligations of the Corporation.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for Approval; Regulations for the 1997 and Subsequent Reinsurance Years § 400.166 Obligations of the Corporation. The Agreement will include the...

2010-01-01

160

34 CFR 686.43 - Obligation to repay the grant.  

Code of Federal Regulations, 2010 CFR

...Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION TEACHER EDUCATION ASSISTANCE FOR COLLEGE AND HIGHER EDUCATION (TEACH) GRANT PROGRAM Service and Repayment Obligations § 686.43...

2010-07-01

161

34 CFR 686.40 - Documenting the service obligation.  

Code of Federal Regulations, 2010 CFR

...Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION TEACHER EDUCATION ASSISTANCE FOR COLLEGE AND HIGHER EDUCATION (TEACH) GRANT PROGRAM Service and Repayment Obligations § 686.40...

2010-07-01

162

31 CFR 223.18 - Performance of agency obligations.  

Code of Federal Regulations, 2010 CFR

...Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE UNITED STATES § 223.18 Performance of agency obligations. (a)...

2010-07-01

163

29 CFR 4.146 - Contract obligations after award, generally.  

...2014-07-01 2013-07-01 true Contract obligations after award, generally. 4.146 Section 4.146 Labor Office of the Secretary of Labor LABOR STANDARDS FOR FEDERAL SERVICE CONTRACTS Application of the...

2014-07-01

164

48 CFR 1019.202-70-14 - Obligation.  

Code of Federal Regulations, 2010 CFR

...1019.202-70-14 Section 1019.202-70-14 Federal Acquisition Regulations System DEPARTMENT OF THE TREASURY SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 1019.202-70-14 Obligation. (a) Mentor or protégé...

2010-10-01

165

23 CFR 450.332 - Annual listing of obligated projects.  

Code of Federal Regulations, 2010 CFR

...OF TRANSPORTATION PLANNING AND RESEARCH PLANNING ASSISTANCE AND STANDARDS Metropolitan Transportation Planning and Programming § 450.332 Annual listing of obligated projects. (a) In metropolitan planning areas, on an annual...

2010-04-01

166

7 CFR 760.507 - Obligations of a participant.  

Code of Federal Regulations, 2011 CFR

...PROGRAMS INDEMNITY PAYMENT PROGRAMS Tree Assistance Program § 760.507 Obligations... (a) Eligible orchardists and nursery tree growers must execute all required documents... (b) Eligible orchardist or nursery tree growers must allow representatives...

2011-01-01

167

7 CFR 1416.705 - Obligations of a participant.  

Code of Federal Regulations, 2010 CFR

...AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS 2006 EMERGENCY AGRICULTURAL DISASTER ASSISTANCE PROGRAMS 2005 Hurricane Tree Assistance Program § 1416.705 Obligations of a participant. (a) Eligible producers must execute all required...

2010-01-01

168

7 CFR 783.7 - Obligations of a participant.  

Code of Federal Regulations, 2010 CFR

...Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS TREE ASSISTANCE PROGRAM § 783.7 Obligations of a participant. (a) Eligible orchardists must execute all required...

2010-01-01

169

7 CFR 760.507 - Obligations of a participant.  

Code of Federal Regulations, 2012 CFR

...PROGRAMS INDEMNITY PAYMENT PROGRAMS Tree Assistance Program § 760.507 Obligations... (a) Eligible orchardists and nursery tree growers must execute all required documents... (b) Eligible orchardist or nursery tree growers must allow representatives...

2012-01-01

170

15 CFR 782.4 - Assistance in determining your obligations.  

Code of Federal Regulations, 2010 CFR

...false Assistance in determining your obligations. 782.4 Section 782.4 Commerce and Foreign Trade Regulations Relating...INFORMATION REGARDING REPORTING REQUIREMENTS AND PROCEDURES § 782.4 Assistance in determining your...

2010-01-01

171

21 CFR 26.75 - Suspension of recognition obligations.  

Code of Federal Regulations, 2010 CFR

...MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE EUROPEAN COMMUNITY âFrameworkâ Provisions § 26.75 Suspension of recognition obligations. Either party may suspend its...

2010-04-01

172

18 CFR 367.2300 - Account 230, Asset retirement obligations.  

...SUBJECT TO THE PROVISIONS OF THE PUBLIC UTILITY HOLDING COMPANY ACT OF 2005, FEDERAL POWER ACT AND NATURAL GAS ACT Balance Sheet Chart of Accounts Other Noncurrent Liabilities § 367.2300 Account 230, Asset retirement obligations. (a) This...

2014-04-01

173

18 CFR 367.2300 - Account 230, Asset retirement obligations.  

Code of Federal Regulations, 2010 CFR

...SUBJECT TO THE PROVISIONS OF THE PUBLIC UTILITY HOLDING COMPANY ACT OF 2005, FEDERAL POWER ACT AND NATURAL GAS ACT Balance Sheet Chart of Accounts Other Noncurrent Liabilities § 367.2300 Account 230, Asset retirement obligations. (a) This...

2010-04-01

174

18 CFR 367.2300 - Account 230, Asset retirement obligations.  

Code of Federal Regulations, 2011 CFR

...SUBJECT TO THE PROVISIONS OF THE PUBLIC UTILITY HOLDING COMPANY ACT OF 2005, FEDERAL POWER ACT AND NATURAL GAS ACT Balance Sheet Chart of Accounts Other Noncurrent Liabilities § 367.2300 Account 230, Asset retirement obligations. (a) This...

2011-04-01

175

7 CFR 982.54 - Deferment of restricted obligation.  

Code of Federal Regulations, 2010 CFR

...less than the total bonding value of the handler's deferred...restricted obligation. The bonding value shall be the deferred restricted...shall be based on the estimated value of restricted credits for the current marketing year. Until bonding...

2010-01-01

176

48 CFR 243.204-70-4 - Limitations on obligations.  

Code of Federal Regulations, 2010 CFR

...Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.204-70-4 Limitations on obligations. (a) The Government shall not...

2010-10-01

177

7 CFR 984.54 - Establishment of obligation.  

Code of Federal Regulations, 2010 CFR

...Nuts), DEPARTMENT OF AGRICULTURE WALNUTS GROWN IN CALIFORNIA Order Regulating Handling Reserve Walnuts § 984.54 Establishment of obligation...kernelweight of certified merchantable walnuts equal to a quantity derived by the...

2010-01-01

178

Influence of Fragmentation on Shrubsteppe-Obligate Passerines.  

E-print Network

??I examined reproductive success and post-fledging dispersal of shrubsteppe-obligate passerines to determine if either mechanism might contribute to the reduced abundance previously reported for these… (more)

Schoeberl, Bruce C.

2003-01-01

179

24 CFR 291.565 - Continuing obligations after purchase.  

...obligations after purchase. To remain in compliance with the GNND Sales Program, the law enforcement officer, teacher, or firefighter/emergency medical technician must, for the entire duration of the owner-occupancy term: (a) Continue to...

2014-04-01

180

22 CFR 231.07 - Fiscal Agent obligations.  

Code of Federal Regulations, 2010 CFR

...false Fiscal Agent obligations. 231.07 Section 231.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ARAB REPUBLIC OF EGYPT LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUBLIC LAW...

2010-04-01

181

Identification of transposon insertion mutants of Francisella tularensis tularensis strain Schu S4 deficient in intracellular replication in the hepatic cell line HepG2  

Microsoft Academic Search

BACKGROUND: Francisella tularensis is a zoonotic intracellular bacterial pathogen that causes tularemia. The subspecies tularensis is highly virulent and is classified as a category A agent of biological warfare because of its low infectious dose by an aerosol route, and its ability to cause severe disease. In macrophages F. tularensis exhibits a rather novel intracellular lifestyle; after invasion it remains

Aiping Qin; Barbara J Mann

2006-01-01

182

TGF-beta-Mediated Sustained ERK1\\/2 Activity Promotes the Inhibition of Intracellular Growth of Mycobacterium avium in Epithelioid Cells Surrogates  

Microsoft Academic Search

Transforming growth factor beta (TGF-?) has been implicated in the pathogenesis of several diseases including infection with intracellular pathogens such as the Mycobacterium avium complex. Infection of macrophages with M. avium induces TGF-? production and neutralization of this cytokine has been associated with decreased intracellular bacterial growth. We have previously demonstrated that epithelioid cell surrogates (ECs) derived from primary murine

Carolina L'Abbate; Ivone Cipriano; Elizabeth Cristina Pérez-Hurtado; Sylvia Cardoso Leão; Célia Regina Whitaker Carneiro; Joel Machado; Guillaume Dalmasso

2011-01-01

183

Intracellular Neutralization of Virus by Immunoglobulin A Antibodies  

NASA Astrophysics Data System (ADS)

IgA is thought to neutralize viruses at the epithelial surface of mucous membranes by preventing their attachment. Since IgA, a polymeric immunoglobulin, is transported through the lining of epithelial cells by the polymeric-immunoglobulin receptor and since viruses are obligate intracellular parasites, we hypothesized that IgA antibodies may also interfere with viral replication by binding to newly synthesized viral proteins within infected cells. Polarized monolayers of Madin-Darby canine kidney epithelial cells expressing the polymeric-immunoglobulin receptor were infected on the apical surface with Sendai virus. Anti-Sendai virus IgA monoclonal antibody delivered from the basolateral surface colocalized with viral protein within the cell, as documented by immunofluorescence. More importantly, anti-viral IgA reduced virus titers >1000-fold (P < 0.0001) in apical supernatants and >10-fold (P < 0.0001) in cell lysates from monolayers treated with anti-viral IgA compared with those treated with either anti-viral IgG or an irrelevant IgA monoclonal antibody. We believe that the differences in viral titers between cell layers treated with specific IgA, which enters the epithelial cell by binding to the polymeric-immunoglobulin receptor, and those treated with specific IgG, which does not enter the cells, or irrelevant IgA indicate that specific intracellular IgA antibodies can inhibit viral replication. Thus, in addition to the classical role of humoral antibodies in extracellular defense, IgA antibody may be able to neutralize microbial pathogens intracellularly, giving IgA a role in host defense that has traditionally been reserved for cell-mediated immunity.

Mazanec, Mary B.; Kaetzel, Charlotte S.; Lamm, Michael E.; Fletcher, David; Nedrud, John G.

1992-08-01

184

Microsporidia Are Natural Intracellular Parasites of the Nematode Caenorhabditis elegans  

PubMed Central

For decades the soil nematode Caenorhabditis elegans has been an important model system for biology, but little is known about its natural ecology. Recently, C. elegans has become the focus of studies of innate immunity and several pathogens have been shown to cause lethal intestinal infections in C. elegans. However none of these pathogens has been shown to invade nematode intestinal cells, and no pathogen has been isolated from wild-caught C. elegans. Here we describe an intracellular pathogen isolated from wild-caught C. elegans that we show is a new species of microsporidia. Microsporidia comprise a large class of eukaryotic intracellular parasites that are medically and agriculturally important, but poorly understood. We show that microsporidian infection of the C. elegans intestine proceeds through distinct stages and is transmitted horizontally. Disruption of a conserved cytoskeletal structure in the intestine called the terminal web correlates with the release of microsporidian spores from infected cells, and appears to be part of a novel mechanism by which intracellular pathogens exit from infected cells. Unlike in bacterial intestinal infections, the p38 MAPK and insulin/insulin-like growth factor (IGF) signaling pathways do not appear to play substantial roles in resistance to microsporidian infection in C. elegans. We found microsporidia in multiple wild-caught isolates of Caenorhabditis nematodes from diverse geographic locations. These results indicate that microsporidia are common parasites of C. elegans in the wild. In addition, the interaction between C. elegans and its natural microsporidian parasites provides a system in which to dissect intracellular intestinal infection in vivo and insight into the diversity of pathogenic mechanisms used by intracellular microbes. PMID:19071962

Troemel, Emily R; Felix, Marie-Anne; Whiteman, Noah K; Barriere, Antoine; Ausubel, Frederick M

2008-01-01

185

Quantification of bacterial invasion into adherent cells by flow cytometry  

Microsoft Academic Search

Quantification of invasive, intracellular bacteria is critical in many areas of cellular microbiology and immunology. We describe a novel and fast approach to determine invasion of bacterial pathogens in adherent cell types such as epithelial cells or fibroblasts based on flow cytometry. Using the CEACAM-mediated uptake of Opa-expressing Neisseria gonorrhoeae as a well-characterized model of bacterial invasion, we demonstrate that

Stefan Pils; Tim Schmitter; Florian Neske; Christof R. Hauck

2006-01-01

186

Evolutionary replacement of obligate symbionts in an ancient and diverse insect lineage.  

PubMed

Many insect groups depend on ancient obligate symbioses with bacteria that undergo long-term genomic degradation due to inactivation and loss of ancestral genes. Sap-feeding insects in the hemipteran suborder Auchenorrhyncha show complex symbioses with at least two obligate bacterial symbionts, inhabiting specialized host cells (bacteriocytes). We explored the symbiotic relationships of the spittlebugs (Auchenorrhyncha: Cercopoidea) using phylogenetic and microscopy methods. Results show that most spittlebugs contain the symbionts Sulcia muelleri (Bacteroidetes) and Zinderia insecticola (Betaproteobacteria) with each restricted to its own bacteriocyte type. However, the ancestral Zinderia symbiont has been replaced with a novel symbiont closely related to Sodalis glossinidius (Enterobacteriaceae) in members of the ecologically successful spittlebug tribe Philaenini. At least one spittlebug species retains Sulcia and Zinderia, but also has acquired a Sodalis-like symbiont, possibly representing a transitional stage in the evolutionary succession of symbioses. Phylogenetic analyses including symbionts of other Auchenorrhyncha lineages suggest that Zinderia, like Sulcia, descends from an ancestral symbiont present in the common ancestor of Auchenorrhyncha. This betaproteobacterial symbiont has been repeatedly replaced by other symbionts, such as the Sodalis-like symbiont of spittlebugs. Symbiont replacement may offer a route for hosts to escape dependence on an ancient, degraded and potentially inefficient symbiont. PMID:23574391

Koga, Ryuichi; Bennett, Gordon M; Cryan, Jason R; Moran, Nancy A

2013-07-01

187

Intense Transpositional Activity of Insertion Sequences in an Ancient Obligate Endosymbiont  

PubMed Central

The streamlined genomes of ancient obligate endosymbionts generally lack transposable elements, such as insertion sequences (IS). Yet, the genome of Wolbachia, one of the most abundant bacterial endosymbionts on Earth, is littered with IS. Such a paradox raises the question as to why there are so many ISs in the genome of this ancient endosymbiont. To address this question, we investigated IS transpositional activity in the unculturable Wolbachia by tracking the evolutionary dynamics and history of ISWpi1 elements. We show that 1) ISWpi1 is widespread in Wolbachia, being present in at least 55% of the 40 sampled strains, 2) ISWpi1 copies exhibit virtually identical nucleotide sequences both within and among Wolbachia genomes and possess an intact transposase gene, 3) individual ISWpi1 copies are differentially inserted among Wolbachia genomes, and 4) ISWpi1 occurs at variable copy numbers among Wolbachia genomes. Collectively, our results provide compelling evidence for intense ISWpi1 transpositional activity and frequent ISWpi1 horizontal transmission among strains during recent Wolbachia evolution. Thus, the genomes of ancient obligate endosymbionts can carry high loads of functional and transpositionally active transposable elements. Our results also indicate that Wolbachia genomes have experienced multiple and temporally distinct ISWpi1 invasions during their evolutionary history. Such recurrent exposition to new IS invasions may explain, at least partly, the unusually high density of transposable elements found in the genomes of Wolbachia endosymbionts. PMID:18562339

Pichon, Samuel; Ling, Alison; Perez, Philippe; Delaunay, Carine; Vavre, Fabrice; Bouchon, Didier; Greve, Pierre

2008-01-01

188

Mycoplasma hominis and Trichomonas vaginalis: a unique case of symbiotic relationship between two obligate human parasites.  

PubMed

Mollicutes are the smallest and simplest self-replicating microorganisms. Despite the minimal genome and apparent lack of complexity, mycoplasmas show a high degree of adaptation to the most diverse environments. Mycoplasma hominis is a human sexually transmitted mycoplasma which is able to establish a biological association with Trichomonas vaginalis, a pathogenic flagellated protist. M. hominis and T. vaginalis share the same specific natural niche, the human genitourinary tract. Symbiotic relationships between unicellular eukaryotes and bacteria are well known and have been extensively studied, providing interesting insights into the biology of one or both the symbionts. The relationship between T. vaginalis and M. hominis is unique in that it was the first described association of two obligated human parasites. Several aspects of this relationship have been investigated, showing how the trichomonad may be viewed not only as a new niche for M. hominis, but also as a "Trojan horse" for the transmission of the bacterial infection to the human host. PMID:16720288

Dessì, Daniele; Rappelli, Paola; Diaz, Nicia; Cappuccinelli, Piero; Fiori, Pier Luigi

2006-01-01

189

Obligate insect endosymbionts exhibit increased ortholog length variation and loss of large accessory proteins concurrent with genome shrinkage.  

PubMed

Extreme genome reduction has been observed in obligate intracellular insect mutualists and is an assumed consequence of fixed, long-term host isolation. Rapid accumulation of mutations and pseudogenization of genes no longer vital for an intracellular lifestyle, followed by deletion of many genes, are factors that lead to genome reduction. Size reductions in individual genes due to small-scale deletions have also been implicated in contributing to overall genome shrinkage. Conserved protein functional domains are expected to exhibit low tolerance for mutations and therefore remain relatively unchanged throughout protein length reduction while nondomain regions, presumably under less selective pressures, would shorten. This hypothesis was tested using orthologous protein sets from the Flavobacteriaceae (phylum: Bacteroidetes) and Enterobacteriaceae (subphylum: Gammaproteobacteria) families, each of which includes some of the smallest known genomes. Upon examination of protein, functional domain, and nondomain region lengths, we found that proteins were not uniformly shrinking with genome reduction, but instead increased length variability and variability was observed in both the functional domain and nondomain regions. Additionally, as complete gene loss also contributes to overall genome shrinkage, we found that the largest proteins in the proteomes of nonhost-restricted bacteroidetial and gammaproteobacterial species often were inferred to be involved in secondary metabolic processes, extracellular sensing, or of unknown function. These proteins were absent in the proteomes of obligate insect endosymbionts. Therefore, loss of genes encoding large proteins not required for host-restricted lifestyles in obligate endosymbiont proteomes likely contributes to extreme genome reduction to a greater degree than gene shrinkage. PMID:24671745

Kenyon, Laura J; Sabree, Zakee L

2014-04-01

190

Obligate Insect Endosymbionts Exhibit Increased Ortholog Length Variation and Loss of Large Accessory Proteins Concurrent with Genome Shrinkage  

PubMed Central

Extreme genome reduction has been observed in obligate intracellular insect mutualists and is an assumed consequence of fixed, long-term host isolation. Rapid accumulation of mutations and pseudogenization of genes no longer vital for an intracellular lifestyle, followed by deletion of many genes, are factors that lead to genome reduction. Size reductions in individual genes due to small-scale deletions have also been implicated in contributing to overall genome shrinkage. Conserved protein functional domains are expected to exhibit low tolerance for mutations and therefore remain relatively unchanged throughout protein length reduction while nondomain regions, presumably under less selective pressures, would shorten. This hypothesis was tested using orthologous protein sets from the Flavobacteriaceae (phylum: Bacteroidetes) and Enterobacteriaceae (subphylum: Gammaproteobacteria) families, each of which includes some of the smallest known genomes. Upon examination of protein, functional domain, and nondomain region lengths, we found that proteins were not uniformly shrinking with genome reduction, but instead increased length variability and variability was observed in both the functional domain and nondomain regions. Additionally, as complete gene loss also contributes to overall genome shrinkage, we found that the largest proteins in the proteomes of nonhost-restricted bacteroidetial and gammaproteobacterial species often were inferred to be involved in secondary metabolic processes, extracellular sensing, or of unknown function. These proteins were absent in the proteomes of obligate insect endosymbionts. Therefore, loss of genes encoding large proteins not required for host-restricted lifestyles in obligate endosymbiont proteomes likely contributes to extreme genome reduction to a greater degree than gene shrinkage. PMID:24671745

Kenyon, Laura J.; Sabree, Zakee L.

2014-01-01

191

Original article Mannitol enhances intracellular calcium diffusion  

E-print Network

Cedex 03, France b Department of Biostructure and Function, University of Connecticut Health Center intracellular calcium will raise the effective intracellular gradient and thereby amplify intracellular calcium]. It has been known for many years that sugars like lactose, or polyols like sorbitol or mannitol, when

Paris-Sud XI, Université de

192

Bacterial vaginosis.  

PubMed Central

Bacterial vaginosis (BV) is the most common of the vaginitides affecting women of reproductive age. It appears to be due to an alteration in the vaginal ecology by which Lactobacillus spp., the predominant organisms in the healthy vagina, are replaced by a mixed flora including Prevotella bivia, Prevotella disiens, Porphyromonas spp., Mobiluncus spp., and Peptostreptococcus spp. All of these organisms except Mobiluncus spp. are also members of the endogenous vaginal flora. While evidence from treatment trials does not support the notion that BV is sexually transmitted, recent studies have shown an increased risk associated with multiple sexual partners. It has also been suggested that the pathogenesis of BV may be similar to that of urinary tract infections, with the rectum serving as a reservoir for some BV-associated flora. The organisms associated with BV have also been recognized as agents of female upper genital tract infection, including pelvic inflammatory disease, and the syndrome BV has been associated with adverse outcome of pregnancy, including premature rupture of membranes, chorioamnionitis, and fetal loss; postpartum endometritis; cuff cellulitis; and urinary tract infections. The mechanisms by which the BV-associated flora causes the signs of BV are not well understood, but a role for H2O2-producing Lactobacillus spp. in protecting against colonization by catalase-negative anaerobic bacteria has been recognized. These and other aspects of BV are reviewed. PMID:1747864

Spiegel, C A

1991-01-01

193

Mechanisms of Obligatory Intracellular Infection with Anaplasma phagocytophilum  

PubMed Central

Summary: Anaplasma phagocytophilum persists in nature by cycling between mammals and ticks. Human infection by the bite of an infected tick leads to a potentially fatal emerging disease called human granulocytic anaplasmosis. A. phagocytophilum is an obligatory intracellular bacterium that replicates inside mammalian granulocytes and the salivary gland and midgut cells of ticks. A. phagocytophilum evolved the remarkable ability to hijack the regulatory system of host cells. A. phagocytophilum alters vesicular traffic to create an intracellular membrane-bound compartment that allows replication in seclusion from lysosomes. The bacterium downregulates or actively inhibits a number of innate immune responses of mammalian host cells, and it upregulates cellular cholesterol uptake to acquire cholesterol for survival. It also upregulates several genes critical for the infection of ticks, and it prolongs tick survival at freezing temperatures. Several host factors that exacerbate infection have been identified, including interleukin-8 (IL-8) and cholesterol. Host factors that overcome infection include IL-12 and gamma interferon (IFN-?). Two bacterial type IV secretion effectors and several bacterial proteins that associate with inclusion membranes have been identified. An understanding of the molecular mechanisms underlying A. phagocytophilum infection will foster the development of creative ideas to prevent or treat this emerging tick-borne disease. PMID:21734244

Rikihisa, Yasuko

2011-01-01

194

The Legionella effector RidL inhibits retrograde trafficking to promote intracellular replication.  

PubMed

The bacteria causing Legionnaires' disease, Legionella pneumophila, replicate intracellularly within unique Legionella-containing vacuoles (LCVs). LCV formation involves a type IV secretion system (T4SS) that translocates effector proteins into host cells. We show that the T4SS effector RidL localizes to LCVs, supports intracellular bacterial growth, and alters retrograde trafficking, in which selected proteins are transported from endosomes to the Golgi. The retromer complex that mediates retrograde trafficking localizes to LCVs independently of RidL and restricts intracellular bacterial growth. RidL binds the Vps29 retromer subunit and the lipid PtdIns(3)P, which localizes retromer components to membranes. Additionally, specific retromer cargo receptors and sorting nexins that mediate protein capture and membrane remodeling preferentially localize to LCVs in the absence of ridL. Ectopic RidL production inhibits retrograde trafficking, and L. pneumophila blocks retrograde transport at endosome exit sites in a ridL-dependent manner. Collectively, these findings suggest that RidL inhibits retromer function to promote intracellular bacterial replication. PMID:23870312

Finsel, Ivo; Ragaz, Curdin; Hoffmann, Christine; Harrison, Christopher F; Weber, Stephen; van Rahden, Vanessa A; Johannes, Ludger; Hilbi, Hubert

2013-07-17

195

Intracellular ion channels and cancer  

PubMed Central

Several types of channels play a role in the maintenance of ion homeostasis in subcellular organelles including endoplasmatic reticulum, nucleus, lysosome, endosome, and mitochondria. Here we give a brief overview of the contribution of various mitochondrial and other organellar channels to cancer cell proliferation or death. Much attention is focused on channels involved in intracellular calcium signaling and on ion fluxes in the ATP-producing organelle mitochondria. Mitochondrial K+ channels (Ca2+-dependent BKCa and IKCa, ATP-dependent KATP, Kv1.3, two-pore TWIK-related Acid-Sensitive K+ channel-3 (TASK-3)), Ca2+ uniporter MCU, Mg2+-permeable Mrs2, anion channels (voltage-dependent chloride channel VDAC, intracellular chloride channel CLIC) and the Permeability Transition Pore (MPTP) contribute importantly to the regulation of function in this organelle. Since mitochondria play a central role in apoptosis, modulation of their ion channels by pharmacological means may lead to death of cancer cells. The nuclear potassium channel Kv10.1 and the nuclear chloride channel CLIC4 as well as the endoplasmatic reticulum (ER)-located inositol 1,4,5-trisphosphate (IP3) receptor, the ER-located Ca2+ depletion sensor STIM1 (stromal interaction molecule 1), a component of the store-operated Ca2+ channel and the ER-resident TRPM8 are also mentioned. Furthermore, pharmacological tools affecting organellar channels and modulating cancer cell survival are discussed. The channels described in this review are summarized on Figure 1. Overall, the view is emerging that intracellular ion channels may represent a promising target for cancer treatment. PMID:24027528

Leanza, Luigi; Biasutto, Lucia; Manago, Antonella; Gulbins, Erich; Zoratti, Mario; Szabo, Ildiko

2013-01-01

196

Barcoding Hedgehog for Intracellular Transport  

NSDL National Science Digital Library

Hedgehog, an essential protein for the development of many vertebrate and invertebrate organs, signals at both short and long distances to control growth and patterning. The mechanism by which it moves between source and target cells is not known, but characterization of the covalent modification of its N terminus with palmitate and of its C terminus with cholesterol has led to the suggestion that the lipophilic properties of the modified protein serve to regulate movement after its secretion into the extracellular space. Another interpretation and model is that the C-terminal cholesterol acts to target Hedgehog to an intracellular trafficking pathway that prepares Hedgehog for release in an encapsulated form.

Thomas B. Kornberg (San Francisco;University of California REV)

2011-11-22

197

What are the public obligations to AIDS patients?  

PubMed

The operating assumption in most discussions of health policy is that government has some responsibility for the health of its citizens and that it may legitimately tax, subsidize, and regulate its citizens in the exercise of that responsibility. On this assumption, public obligations to HIV/AIDS patients are a function of their needs in relationship to other health needs. This paper challenges the operating assumption by arguing that it cannot be grounded in the obligations that individuals have to each other. The paper rests on its own assumption: the moral theory of individualism. On this theory, individuals are ends in themselves who have the right to choose their own actions and uses of their resources; they do not have unchosen obligations to help others. In regard to HIV/AIDS patients, consequently, individuals have no duty to help, nor any other obligation beyond that of respecting their rights; and there is no valid basis for government regulations or subsidies on their behalf. The paper argues against the two approaches commonly used to defend a more expansive view of individual obligations and the role of government. The first is the assumption of welfare rights to goods and services; the second is the assumption that distributive justice requires some redistribution of health care resources. PMID:15971567

Kelley, David

2002-01-01

198

Using Modified Bacterial Toxins To Deliver Vaccine Antigens  

E-print Network

Using Modified Bacterial Toxins To Deliver Vaccine Antigens Researchers are using toxins to deliver protect them against many elements of the im- mune response. Once inside host cells, these organisms intracellular microbes, researchers are interested in develop- ing safe and effective vaccines that specifically

Starnbach, Michael

199

The Neisseria meningitidis capsule is important for intracellular survival in human cells.  

PubMed

While much data exist in the literature about how Neisseria meningitidis adheres to and invades human cells, its behavior inside the host cell is largely unknown. One of the essential meningococcal attributes for pathogenesis is the polysaccharide capsule, which has been shown to be important for bacterial survival in extracellular fluids. To investigate the role of the meningococcal capsule in intracellular survival, we used B1940, a serogroup B strain, and its isogenic derivatives, which lack either the capsule or both the capsule and the lipooligosaccharide outer core, to infect human phagocytic and nonphagocytic cells and monitor invasion and intracellular growth. Our data indicate that the capsule, which negatively affects bacterial adhesion and, consequently, entry, is, in contrast, fundamental for the intracellular survival of this microorganism. The results of in vitro assays suggest that an increased resistance to cationic antimicrobial peptides (CAMPs), important components of the host innate defense system against microbial infections, is a possible mechanism by which the capsule protects the meningococci in the intracellular environment. Indeed, unencapsulated bacteria were more susceptible than encapsulated bacteria to defensins, cathelicidins, protegrins, and polymyxin B, which has long been used as a model compound to define the mechanism of action of CAMPs. We also demonstrate that both the capsular genes (siaD and lipA) and those encoding an efflux pump involved in resistance to CAMPs (mtrCDE) were up-regulated during the intracellular phase of the infectious cycle. PMID:17470547

Spinosa, Maria Rita; Progida, Cinzia; Talà, Adelfia; Cogli, Laura; Alifano, Pietro; Bucci, Cecilia

2007-07-01

200

Intracellular Proton Access in a Cl?/H+ Antiporter  

PubMed Central

Chloride-transporting membrane proteins of the CLC family appear in two distinct mechanistic flavors: H+-gated Cl? channels and Cl?/H+ antiporters. Transmembrane H+ movement is an essential feature of both types of CLC. X-ray crystal structures of CLC antiporters show the Cl? ion pathway through these proteins, but the H+ pathway is known only inferentially by two conserved glutamate residues that act as way-stations for H+ in its path through the protein. The extracellular-facing H+ transfer glutamate becomes directly exposed to aqueous solution during the transport cycle, but the intracellular glutamate E203, Gluin, is buried within the protein. Two regions, denoted “polar” and “interfacial,” at the intracellular surface of the bacterial antiporter CLC-ec1 are examined here as possible pathways by which intracellular aqueous protons gain access to Gluin. Mutations at multiple residues of the polar region have little effect on antiport rates. In contrast, mutation of E202, a conserved glutamate at the protein–water boundary of the interfacial region, leads to severe slowing of the Cl?/H+ antiport rate. An X-ray crystal structure of E202Y, the most strongly inhibited of these substitutions, shows an aqueous portal leading to Gluin physically blocked by cross-subunit interactions; moreover, this mutation has only minimal effect on a monomeric CLC variant, which necessarily lacks such interactions. The several lines of experiments presented argue that E202 acts as a water-organizer that creates a proton conduit connecting intracellular solvent with Gluin. PMID:23239938

Lim, Hyun-Ho; Shane, Tania; Miller, Christopher

2012-01-01

201

Environmental and safety obligations of the Chemical Weapons Convention  

SciTech Connect

Among its many unique and precedent-setting provisions, the Chemical Weapons Convention (CWC) includes important requirements for States Parties to protect the public safety and the environment in the course of carrying out the treaty. These obligations will apply to the destruction of chemical weapons, of former chemical weapons production facilities, and to other activities under the Convention such as the verification scheme. This morning, I will briefly discuss the Convention`s safety and environmental obligations, concentrating on their effects in this country as the United States chemical weapons stockpile is destroyed.

Tanzman, E.A.

1994-04-07

202

The effects of macrophage source on the mechanism of phagocytosis and intracellular survival of Leishmania  

PubMed Central

Leishmania spp. protozoa are obligate intracellular parasites that replicate in macrophages during mammalian infection. Efficient phagocytosis and survival in macrophages are important determinants of parasite virulence. Macrophage lines differ dramatically in their ability to sustain intracellular Leishmania infantum chagasi (Lic). We report that the U937 monocytic cell line supported the intracellular replication and cell-to-cell spread of Lic during 72 hours after parasite addition, whereas primary human monocyte-derived macrophages (MDMs) did not. Electron microscopy and live cell imaging illustrated that Lic promastigotes anchored to MDMs via their anterior ends and were engulfed through symmetrical pseudopods. In contrast, U937 cells bound Lic in diverse orientations, and extended membrane lamellae to reorient and internalize parasites through coiling phagocytosis. Lic associated tightly with the parasitophorous vacuole (PV) membrane in both cell types. PVs fused with LAMP-1-expressing compartments 24 hours after phagocytosis by MDMs, whereas U937 cell PVs remained LAMP-1 negative. The expression of one phagocytic receptor (CR3) was higher in MDMs than U937 cells, leading us to speculate that parasite uptake proceeds through dissimilar pathways between these cells. We hypothesize that the mechanism of phagocytosis differs between primary versus immortalized human macrophage cells, with corresponding differences in the subsequent intracellular fate of the parasite. PMID:21723411

Hsiao, Chia-Hung Christine; Ueno, Norikiyo; Shao, Jian Q.; Schroeder, Kristin R.; Moore, Kenneth C.; Donelson, John E.; Wilson, Mary E.

2011-01-01

203

Real-Time monitoring of intracellular wax ester metabolism  

PubMed Central

Background Wax esters are industrially relevant molecules exploited in several applications of oleochemistry and food industry. At the moment, the production processes mostly rely on chemical synthesis from rather expensive starting materials, and therefore solutions are sought from biotechnology. Bacterial wax esters are attractive alternatives, and especially the wax ester metabolism of Acinetobacter sp. has been extensively studied. However, the lack of suitable tools for rapid and simple monitoring of wax ester metabolism in vivo has partly restricted the screening and analyses of potential hosts and optimal conditions. Results Based on sensitive and specific detection of intracellular long-chain aldehydes, specific intermediates of wax ester synthesis, bacterial luciferase (LuxAB) was exploited in studying the wax ester metabolism in Acinetobacter baylyi ADP1. Luminescence was detected in the cultivation of the strain producing wax esters, and the changes in signal levels could be linked to corresponding cell growth and wax ester synthesis phases. Conclusions The monitoring system showed correlation between wax ester synthesis pattern and luminescent signal. The system shows potential for real-time screening purposes and studies on bacterial wax esters, revealing new aspects to dynamics and role of wax ester metabolism in bacteria. PMID:21961954

2011-01-01

204

The intracellular galactoglycome in Trichoderma reesei during growth on lactose.  

PubMed

Lactose (1,4-0-?-D-galactopyranosyl-D-glucose) is used as a soluble carbon source for the production of cellulases and hemicellulases for-among other purposes-use in biofuel and biorefinery industries. The mechanism how lactose induces cellulase formation in T. reesei is enigmatic, however. Previous results from our laboratory raised the hypothesis that intermediates from the two galactose catabolic pathway may give rise to the accumulation of intracellular oligogalactosides that could act as inducer. Here we have therefore used high-performance anion-exchange chromatography-mass spectrometry to study the intracellular galactoglycome of T. reesei during growth on lactose, in T. reesei mutants impaired in galactose catabolism, and in strains with different cellulase productivities. Lactose, allo-lactose, and lactulose were detected in the highest amounts in all strains, and two trisaccharides (Gal-?-1,6-Gal-?-1,4-Glc/Fru and Gal-?-1,4-Gal-?-1,4-Glc/Fru) also accumulated to significant levels. Glucose and galactose, as well as four further oligosaccharides (Gal-?-1,3/1,4/1,6-Gal; Gal-?-1,2-Glc) were only detected in minor amounts. In addition, one unknown disaccharide (Hex-?-1,1-Hex) and four trisaccharides were also detected. The accumulation of the unknown hexose disaccharide was shown to correlate with cellulase formation in the improved mutant strains as well as the galactose pathway mutants, and Gal-?-1,4-Gal-?-1,4-Glc/Fru and two other unknown hexose trisaccharides correlated with cellulase production only in the pathway mutants, suggesting that these compounds could be involved in cellulase induction by lactose. The nature of these oligosaccharides, however, suggests their formation by transglycosylation rather than by glycosyltransferases. Based on our results, the obligate nature of both galactose catabolic pathways for this induction must have another biochemical basis than providing substrates for inducer formation. PMID:23299458

Karaffa, Levente; Coulier, Leon; Fekete, Erzsébet; Overkamp, Karin M; Druzhinina, Irina S; Mikus, Marianna; Seiboth, Bernhard; Novák, Levente; Punt, Peter J; Kubicek, Christian P

2013-06-01

205

Intracellularly Induced Cyclophilins Play an Important Role in Stress Adaptation and Virulence of Brucella abortus  

PubMed Central

Brucella is an intracellular bacterial pathogen that causes the worldwide zoonotic disease brucellosis. Brucella virulence relies on its ability to transition to an intracellular lifestyle within host cells. Thus, this pathogen must sense its intracellular localization and then reprogram gene expression for survival within the host cell. A comparative proteomic investigation was performed to identify differentially expressed proteins potentially relevant for Brucella intracellular adaptation. Two proteins identified as cyclophilins (CypA and CypB) were overexpressed in the intracellular environment of the host cell in comparison to laboratory-grown Brucella. To define the potential role of cyclophilins in Brucella virulence, a double-deletion mutant was constructed and its resulting phenotype was characterized. The Brucella abortus ?cypAB mutant displayed increased sensitivity to environmental stressors, such as oxidative stress, pH, and detergents. In addition, the B. abortus ?cypAB mutant strain had a reduced growth rate at lower temperature, a phenotype associated with defective expression of cyclophilins in other microorganisms. The B. abortus ?cypAB mutant also displays reduced virulence in BALB/c mice and defective intracellular survival in HeLa cells. These findings suggest that cyclophilins are important for Brucella virulence and survival in the host cells. PMID:23230297

García Fernández, Lucía; DelVecchio, Vito G.; Briones, Gabriel

2013-01-01

206

CHANGING OBLIGATIONS AND THE PSYCHOLOGICAL CONTRACT: A LONGITUDINAL STUDY  

Microsoft Academic Search

In an exploratory longitudinal study of business school alumni, we investigated changes in employment obligations as perceived by em- ployees. During the first two years of employment, employees came to perceive that they owed less to their employers while seeing tbeir em- ployers as owing them more. An employer's failure to fulfill its com- mitments was found to be significantly

SANDRA L. ROBINSON; MATTHEW S. KRAATZ; DENISE M. ROUSSEAU

1994-01-01

207

47 CFR 76.56 - Signal carriage obligations.  

Code of Federal Regulations, 2010 CFR

...than 50 percent of the broadcast week. For purposes of this definition, only identical episodes of a television series are considered...must-carry obligations may do so, subject to approval by the franchising authority pursuant to Section 611 of the...

2010-10-01

208

European air transport public service obligations: a periodic review  

Microsoft Academic Search

The ‘Third Package’ of European Union air transport liberalisation measures came into effect on 1 January 1993 and has substantially reduced the restrictions on interstate flight operations. The package of measures also includes provision for the member states to impose ‘public service obligations’ on low-density routes which were deemed necessary for the purposes of regional development. In this paper, it

Aisling Reynolds-Feighan

1995-01-01

209

Filial obligations to elderly parents: a duty to care?  

PubMed Central

A continuing need for care for elderly, combined with looser family structures prompt the question what filial obligations are. Do adult children of elderly have a duty to care? Several theories of filial obligation are reviewed. The reciprocity argument is not sensitive to the parent–child relationship after childhood. A theory of friendship does not offer a correct parallel for the relationship between adult child and elderly parent. Arguments based on need or vulnerability run the risk of being unjust to those on whom a needs-based claim is laid. To compare filial obligations with promises makes too much of parents’ expectations, however reasonable they may be. The good of being in an unchosen relationship seems the best basis for filial obligations, with an according duty to maintain the relationship when possible. We suggest this relationship should be maintained even if one of the parties is no longer capable of consciously contributing to it. We argue that this entails a duty to care about one’s parents, not for one’s parents. This implies that care for the elderly is not in the first place a task for adult children. PMID:20922568

Van Delden, Johannes J. M.

2010-01-01

210

Wild dogs, Lycaon pictus, are a social species, obligated  

E-print Network

conditions apply for the African wild dog, Lycaon pictus, and data on this species in Zimbabwe support ourWild dogs, Lycaon pictus, are a social species, obligated to breed in a group, in which only one extinctions?: The case of wild dogs Angulo et al. Angulo et al. Frontiers in Zoology 2013, 10:11 http

Courchamp, Franck

211

11 CFR 9034.5 - Net outstanding campaign obligations.  

Code of Federal Regulations, 2010 CFR

...was determined. (e) Contributions received from joint fundraising activities conducted under 11 CFR 9034.8 may be used to...obligations as of the date these funds are received by the fundraising representative committee and shall be included in the...

2010-01-01

212

11 CFR 9034.5 - Net outstanding campaign obligations.  

Code of Federal Regulations, 2011 CFR

...was determined. (e) Contributions received from joint fundraising activities conducted under 11 CFR 9034.8 may be used to...obligations as of the date these funds are received by the fundraising representative committee and shall be included in the...

2011-01-01

213

Specifying and monitoring economic environments using rights and obligations  

Microsoft Academic Search

We provide a formal scripting language to capture the semantics of economic environments. The language is based on a set of well-defined design principles and makes explicit an agent's rights, as derived from property, and an agent's obligations, as derived from restrictions placed on its actions either voluntarily or as a consequence of other actions. Coupled with the language is

Loizos Michael; David C. Parkes; Avi Pfeffer

2010-01-01

214

23 CFR 450.332 - Annual listing of obligated projects.  

Code of Federal Regulations, 2012 CFR

...Metropolitan Transportation Planning and Programming § 450.332 Annual listing of...for which funds under 23 U.S.C. or 49 U.S.C. Chapter 53 were obligated in the...available for subsequent years. (c) The listing shall be...

2012-04-01

215

23 CFR 450.332 - Annual listing of obligated projects.  

Code of Federal Regulations, 2013 CFR

...Metropolitan Transportation Planning and Programming § 450.332 Annual listing of...for which funds under 23 U.S.C. or 49 U.S.C. Chapter 53 were obligated in the...available for subsequent years. (c) The listing shall be...

2013-04-01

216

23 CFR 450.332 - Annual listing of obligated projects.  

...Metropolitan Transportation Planning and Programming § 450.332 Annual listing of...for which funds under 23 U.S.C. or 49 U.S.C. Chapter 53 were obligated in the...available for subsequent years. (c) The listing shall be...

2014-04-01

217

23 CFR 450.332 - Annual listing of obligated projects.  

Code of Federal Regulations, 2011 CFR

...Metropolitan Transportation Planning and Programming § 450.332 Annual listing of...for which funds under 23 U.S.C. or 49 U.S.C. Chapter 53 were obligated in the...available for subsequent years. (c) The listing shall be...

2011-04-01

218

Acts of Commanding and Changing Obligations Tomoyuki Yamada  

E-print Network

Acts of Commanding and Changing Obligations Tomoyuki Yamada Graduate School of Letters, Hokkaido. In what follows, I will try to model changes brought about by various acts of commanding in terms of a variant of update logic. I will combine a multi-agent variant of the language of monadic deontic logic

Amsterdam, University of

219

Apoptosis of human intestinal epithelial cells after bacterial invasion.  

PubMed Central

Epithelial cells that line the human intestinal mucosa are the initial site of host invasion by bacterial pathogens. The studies herein define apoptosis as a new category of intestinal epithelial cell response to bacterial infection. Human colon epithelial cells are shown to undergo apoptosis following infection with invasive enteric pathogens, such as Salmonella or enteroinvasive Escherichia coli. In contrast to the rapid onset of apoptosis seen after bacterial infection of mouse monocyte-macrophage cell lines, the commitment of human intestinal epithelial cell lines to undergo apoptosis is delayed for at least 6 h after bacterial infection, requires bacterial entry and replication, and the ensuing phenotypic expression of apoptosis is delayed for 12-18 h after bacterial entry. TNF-alpha and nitric oxide, which are produced as components of the intestinal epithelial cell proinflammatory program in the early period after bacterial invasion, play an important role in the later induction and regulation of the epithelial cell apoptotic program. Apoptosis in response to bacterial infection may function to delete infected and damaged epithelial cells and restore epithelial cell growth regulation and epithelial integrity that are altered during the course of enteric infection. The delay in onset of epithelial cell apoptosis after bacterial infection may be important both to the host and the invading pathogen since it provides sufficient time for epithelial cells to generate signals important for the activation of mucosal inflammation and concurrently allows invading bacteria time to adapt to the intracellular environment before invading deeper mucosal layers. PMID:9819367

Kim, J M; Eckmann, L; Savidge, T C; Lowe, D C; Witthoft, T; Kagnoff, M F

1998-01-01

220

Long-Term Evolutionary Stability of Bacterial Endosymbiosis in Curculionoidea: Additional Evidence of Symbiont Replacement in the Dryophthoridae Family  

Microsoft Academic Search

Bacterial intracellular symbiosis (endosymbiosis) is well documented in the insect world where it is believed to play a crucial role in adaptation and evolution. However, although Coleopteran insects are of huge ecological and economical interest, endosymbiont molecular analysis is limited to the Dryophthoridae family. Here, we have analyzed the intracellular symbiotic bacteria in 2 Hylobius species belonging to the Molytinae

Cyrille Conord; Laurence Despres; Agnes Vallier; Severine Balmand; Christian Miquel; Stephanie Zundel; Guy Lemperiere; Abdelaziz Heddi

2008-01-01

221

Settling down: the genome of Serratia symbiotica from the aphid Cinara tujafilina zooms in on the process of accommodation to a cooperative intracellular life.  

PubMed

Particularly interesting cases of mutualistic endosymbioses come from the establishment of co-obligate associations of more than one species of endosymbiotic bacteria. Throughout symbiotic accommodation from a free-living bacterium, passing through a facultative stage and ending as an obligate intracellular one, the symbiont experiences massive genomic losses and phenotypic adjustments. Here, we scrutinized the changes in the coevolution of Serratia symbiotica and Buchnera aphidicola endosymbionts in aphids, paying particular attention to the transformations undergone by S. symbiotica to become an obligate endosymbiont. Although it is already known that S. symbiotica is facultative in Acyrthosiphon pisum, in Cinara cedri it has established a co-obligate endosymbiotic consortium along with B. aphidicola to fulfill the aphid's nutritional requirements. The state of this association in C. tujafilina, an aphid belonging to the same subfamily (Lachninae) that C. cedri, remained unknown. Here, we report the genome of S. symbiotica strain SCt-VLC from the aphid C. tujafilina. While being phylogenetically and genomically very closely related to the facultative endosymbiont S. symbiotica from the aphid A. pisum, it shows a variety of metabolic, genetic, and architectural features, which point toward this endosymbiont being one step closer to an obligate intracellular one. We also describe in depth the process of genome rearrangements suffered by S. symbiotica and the role mobile elements play in gene inactivations. Finally, we postulate the supply to the host of the essential riboflavin (vitamin B2) as key to the establishment of S. symbiotica as a co-obligate endosymbiont in the aphids belonging to the subfamily Lachninane. PMID:24951564

Manzano-Marín, Alejandro; Latorre, Amparo

2014-07-01

222

Evolution of bacterial genomes  

Microsoft Academic Search

This review examines evolution of bacterial genomes with an emphasis on RNA based life, the transition to functional DNA and small evolving genomes (possibly plasmids) that led to larger, functional bacterial genomes.

J. T. Trevors

1997-01-01

223

Intracellular Growth of Legionella pneumophila in Dictyostelium discoideum, a System for Genetic Analysis of Host-Pathogen Interactions  

Microsoft Academic Search

Conditions were established in which Legionella pneumophila, an intracellular bacterial pathogen, could replicate within the unicellular organism Dictyostelium discoideum. By several criteria, L. pneumophila grew by the same mechanism within D. discoideum as it does in amoebae and macrophages. Bacteria grew within membrane-bound vesicles associated with rough endoplasmic reticulum, and L. pneumophila dot\\/icm mutants, blocked for growth in macrophages and

JONATHAN M. SOLOMON; ADAM RUPPER; JAMES A. CARDELLI; RALPH R. ISBERG

2000-01-01

224

The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens  

Microsoft Academic Search

The caspase-recruitment domain–containing adaptor protein CARD9 regulates the innate signaling responses to fungal infection. Here we show that CARD9 is required for innate immune responses against intracellular pathogens. We generated Card9?\\/? mice and found that CARD9-deficient macrophages had defects in activation of the kinases p38 and Jnk but not of transcription factor NF-?B after bacterial and viral infection. CARD9-deficient mice

Yen-Michael S Hsu; Yongliang Zhang; Yun You; Donghai Wang; Hongxiu Li; Omar Duramad; Xiao-Feng Qin; Chen Dong; Xin Lin

2006-01-01

225

Naip5 Affects Host Susceptibility to the Intracellular Pathogen Legionella pneumophila  

Microsoft Academic Search

Background:Legionella pneumophila is a gram-negative bacterial pathogen that is the cause of Legionnaires' Disease. Legionella produces disease because it can replicate inside a specialized compartment of host macrophages. Macrophages isolated from various inbred mice exhibit large differences in permissiveness for intracellular replication of Legionella. A locus affecting this host-resistance phenotype, Lgn1, has been mapped to chromosome 13, but the responsible

Sheryl A. Goodart; Joseph D. Growney; Vey Hadinoto; Matthew G. Endrizzi; E. Michelle Long; Keyvan Sadigh; Andrew L. Abney; Isaac Bernstein-Hanley; William F. Dietrich

2003-01-01

226

Intracellular biogenic silver nanoparticles for the generation of carbon supported antiviral and sustained bactericidal agents.  

PubMed

Intracellular silver nanoparticles produced by exposing silver ions to the fungus Aspergillus ochraceus were heat-treated in nitrogen environment to yield silver nanoparticles embedded in carbonaceous supports. This carbonaceous matrix embedded silver nanoparticles showed antimicrobial properties against both bacteria (Gram-positive and Gram-negative) and virus (M 13 phage virus). The bactericidal effects were noticed even after washing and repeated exposure of these carbon supported silver nanoparticles to fresh bacterial cultures, revealing their sustained activity. PMID:19746940

Vijayakumar, P S; Prasad, B L V

2009-10-01

227

Physical constraints on the establishment of intracellular spatial gradients in bacteria  

PubMed Central

Background Bacteria dynamically regulate their intricate intracellular organization involving proteins that facilitate cell division, motility, and numerous other processes. Consistent with this sophisticated organization, bacteria are able to create asymmetries and spatial gradients of proteins by localizing signaling pathway components. We use mathematical modeling to investigate the biochemical and physical constraints on the generation of intracellular gradients by the asymmetric localization of a source and a sink. Results We present a systematic computational analysis of the effects of other regulatory mechanisms, such as synthesis, degradation, saturation, and cell growth. We also demonstrate that gradients can be established in a variety of bacterial morphologies such as rods, crescents, spheres, branched and constricted cells. Conclusions Taken together, these results suggest that gradients are a robust and potentially common mechanism for providing intracellular spatial cues. PMID:22931750

2012-01-01

228

30 CFR 585.900 - Who must meet the decommissioning obligations in this subpart?  

Code of Federal Regulations, 2012 CFR

... Environmental and Safety Management, Inspections, and Facility Assessments for Activities Conducted Under SAPs, COPs and GAPs Decommissioning Obligations and Requirements § 585.900 Who must meet the decommissioning obligations in this...

2012-07-01

229

30 CFR 585.901 - When do I accrue decommissioning obligations?  

Code of Federal Regulations, 2012 CFR

... Environmental and Safety Management, Inspections, and Facility Assessments for Activities Conducted Under SAPs, COPs and GAPs Decommissioning Obligations and Requirements § 585.901 When do I accrue decommissioning obligations? You accrue...

2012-07-01

230

18 CFR 37.5 - Obligations of Transmission Providers and Responsible Parties.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Obligations of Transmission Providers and Responsible Parties...SYSTEMS § 37.5 Obligations of Transmission Providers and Responsible Parties. (a) Each Transmission Provider is required to provide...

2012-04-01

231

Federal Agencies' AcademicS&E Obligations Continued to Climb in FY 1995  

NSF Publications Database

Federal Agencies' Academic S&E Obligations Continued to Climb in FY 1995 (May 16, 1997) This Data ... analytic summary of Federal academic science and engineering obligations collected through the ...

232

40 CFR 152.97 - Rights and obligations of data submitters.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false Rights and obligations of data submitters. 152.97 Section 152...PROCEDURES Procedures To Ensure Protection of Data Submitters' Rights § 152.97 Rights and obligations of data submitters. (a) Right to be...

2011-07-01

233

40 CFR 152.97 - Rights and obligations of data submitters.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Rights and obligations of data submitters. 152.97 Section 152...PROCEDURES Procedures To Ensure Protection of Data Submitters' Rights § 152.97 Rights and obligations of data submitters. (a) Right to be...

2013-07-01

234

40 CFR 152.97 - Rights and obligations of data submitters.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Rights and obligations of data submitters. 152.97 Section 152...PROCEDURES Procedures To Ensure Protection of Data Submitters' Rights § 152.97 Rights and obligations of data submitters. (a) Right to be...

2012-07-01

235

28 CFR 811.5 - Commencement of the obligation to register.  

Code of Federal Regulations, 2013 CFR

...AGENCY FOR THE DISTRICT OF COLUMBIA SEX OFFENDER REGISTRATION § 811.5 Commencement...obligation to register. (a) A sex offender's obligation to register starts when the sex offender is found guilty or not...

2013-07-01

236

28 CFR 811.5 - Commencement of the obligation to register.  

Code of Federal Regulations, 2011 CFR

...AGENCY FOR THE DISTRICT OF COLUMBIA SEX OFFENDER REGISTRATION § 811.5 Commencement...obligation to register. (a) A sex offender's obligation to register starts when the sex offender is found guilty or not...

2011-07-01

237

28 CFR 811.5 - Commencement of the obligation to register.  

Code of Federal Regulations, 2012 CFR

...AGENCY FOR THE DISTRICT OF COLUMBIA SEX OFFENDER REGISTRATION § 811.5 Commencement...obligation to register. (a) A sex offender's obligation to register starts when the sex offender is found guilty or not...

2012-07-01

238

40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?  

Code of Federal Regulations, 2013 CFR

...following formulas: (1) Cellulosic biofuel. RVOCB,i = (RFStdCB,i ...Renewable Volume Obligation for cellulosic biofuel for an obligated party for calendar year...RFStdCB,i = The standard for cellulosic biofuel for calendar year i, determined by...

2013-07-01

239

40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?  

Code of Federal Regulations, 2011 CFR

...following formulas: (1) Cellulosic biofuel. RVOCB,i = (RFStdCB,i ...Renewable Volume Obligation for cellulosic biofuel for an obligated party for calendar year...RFStdCB,i = The standard for cellulosic biofuel for calendar year i, determined by...

2011-07-01

240

40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?  

Code of Federal Regulations, 2012 CFR

...following formulas: (1) Cellulosic biofuel. RVOCB,i = (RFStdCB,i ...Renewable Volume Obligation for cellulosic biofuel for an obligated party for calendar year...RFStdCB,i = The standard for cellulosic biofuel for calendar year i, determined by...

2012-07-01

241

18 CFR 37.5 - Obligations of Transmission Providers and Responsible Parties.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Obligations of Transmission Providers and Responsible Parties...SYSTEMS § 37.5 Obligations of Transmission Providers and Responsible Parties. (a) Each Transmission Provider is required to provide...

2011-04-01

242

18 CFR 37.5 - Obligations of Transmission Providers and Responsible Parties.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Obligations of Transmission Providers and Responsible Parties...SYSTEMS § 37.5 Obligations of Transmission Providers and Responsible Parties. (a) Each Transmission Provider is required to provide...

2010-04-01

243

59 FR- Statement of the Commission Regarding Disclosure Obligations of Municipal Securities Issuers and...  

Federal Register 2010, 2011, 2012, 2013

...Statement of the Commission Regarding Disclosure Obligations; Final Rule 17 CFR Part 240 Municipal Securities Disclosure and Confirmation of Transactions...Statement of the Commission Regarding Disclosure Obligations of Municipal...

1994-03-17

244

24 CFR 811.110 - Refunding of obligations issued to finance Section 8 projects.  

Code of Federal Regulations, 2012 CFR

...false Refunding of obligations issued to finance Section 8 projects. 811.110 Section...110 Refunding of obligations issued to finance Section 8 projects. (a) This...savings and, if necessary, HUD will finance in refunding bond debt service...

2012-04-01

245

24 CFR 811.110 - Refunding of obligations issued to finance Section 8 projects.  

...false Refunding of obligations issued to finance Section 8 projects. 811.110 Section...110 Refunding of obligations issued to finance Section 8 projects. (a) This...savings and, if necessary, HUD will finance in refunding bond debt service...

2014-04-01

246

24 CFR 811.110 - Refunding of obligations issued to finance Section 8 projects.  

Code of Federal Regulations, 2010 CFR

...false Refunding of obligations issued to finance Section 8 projects. 811.110 Section...110 Refunding of obligations issued to finance Section 8 projects. (a) This...savings and, if necessary, HUD will finance in refunding bond debt service...

2010-04-01

247

24 CFR 811.110 - Refunding of obligations issued to finance Section 8 projects.  

Code of Federal Regulations, 2013 CFR

...false Refunding of obligations issued to finance Section 8 projects. 811.110 Section...110 Refunding of obligations issued to finance Section 8 projects. (a) This...savings and, if necessary, HUD will finance in refunding bond debt service...

2013-04-01

248

24 CFR 811.110 - Refunding of obligations issued to finance Section 8 projects.  

Code of Federal Regulations, 2011 CFR

...false Refunding of obligations issued to finance Section 8 projects. 811.110 Section...110 Refunding of obligations issued to finance Section 8 projects. (a) This...savings and, if necessary, HUD will finance in refunding bond debt service...

2011-04-01

249

29 CFR 37.27 - What are the obligations of small recipients regarding Equal Opportunity Officers?  

Code of Federal Regulations, 2010 CFR

...obligations of small recipients regarding Equal Opportunity Officers? 37.27 Section 37...IMPLEMENTATION OF THE NONDISCRIMINATION AND EQUAL OPPORTUNITY PROVISIONS OF THE WORKFORCE INVESTMENT...obligations of small recipients regarding Equal Opportunity Officers? Although small...

2010-07-01

250

29 CFR 37.26 - What are a recipient's obligations relating to the Equal Opportunity Officer?  

Code of Federal Regulations, 2010 CFR

...recipient's obligations relating to the Equal Opportunity Officer? 37.26 Section 37.26...IMPLEMENTATION OF THE NONDISCRIMINATION AND EQUAL OPPORTUNITY PROVISIONS OF THE WORKFORCE INVESTMENT...recipient's obligations relating to the Equal Opportunity Officer? A recipient has the...

2010-07-01

251

29 CFR 37.29 - What are a recipient's obligations to disseminate its equal opportunity policy?  

Code of Federal Regulations, 2010 CFR

...obligations to disseminate its equal opportunity policy? 37.29 Section 37.29...IMPLEMENTATION OF THE NONDISCRIMINATION AND EQUAL OPPORTUNITY PROVISIONS OF THE WORKFORCE INVESTMENT...obligations to disseminate its equal opportunity policy? (a) A recipient...

2010-07-01

252

12 CFR 1511.5 - Obligations of Funding Corporation; no adverse claims.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Obligations of Funding Corporation; no adverse claims. ...DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION BOOK-ENTRY PROCEDURE § 1511.5 Obligations of Funding Corporation; no adverse...

2011-01-01

253

12 CFR 1511.5 - Obligations of Funding Corporation; no adverse claims.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Obligations of Funding Corporation; no adverse claims. ...DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION BOOK-ENTRY PROCEDURE § 1511.5 Obligations of Funding Corporation; no adverse...

2013-01-01

254

12 CFR 1511.5 - Obligations of Funding Corporation; no adverse claims.  

...2014-01-01 false Obligations of Funding Corporation; no adverse claims. ...DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION BOOK-ENTRY PROCEDURE § 1511.5 Obligations of Funding Corporation; no adverse...

2014-01-01

255

12 CFR 1511.5 - Obligations of Funding Corporation; no adverse claims.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Obligations of Funding Corporation; no adverse claims. ...DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION BOOK-ENTRY PROCEDURE § 1511.5 Obligations of Funding Corporation; no adverse...

2010-01-01

256

12 CFR 1511.5 - Obligations of Funding Corporation; no adverse claims.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 false Obligations of Funding Corporation; no adverse claims. ...DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION BOOK-ENTRY PROCEDURE § 1511.5 Obligations of Funding Corporation; no adverse...

2012-01-01

257

26 CFR 1.662(a)-4 - Amounts used in discharge of a legal obligation.  

Code of Federal Regulations, 2011 CFR

...exists whether or not the parent's earnings and resources...law. In the case of a parent's obligation to support his child, to the extent that the parent's legal obligation...it is to be determined without consideration of the...

2011-04-01

258

26 CFR 1.662(a)-4 - Amounts used in discharge of a legal obligation.  

Code of Federal Regulations, 2013 CFR

...exists whether or not the parent's earnings and resources...law. In the case of a parent's obligation to support his child, to the extent that the parent's legal obligation...it is to be determined without consideration of the...

2013-04-01

259

26 CFR 1.662(a)-4 - Amounts used in discharge of a legal obligation.  

Code of Federal Regulations, 2012 CFR

...exists whether or not the parent's earnings and resources...law. In the case of a parent's obligation to support his child, to the extent that the parent's legal obligation...it is to be determined without consideration of the...

2012-04-01

260

26 CFR 1.662(a)-4 - Amounts used in discharge of a legal obligation.  

Code of Federal Regulations, 2010 CFR

...exists whether or not the parent's earnings and resources...law. In the case of a parent's obligation to support his child, to the extent that the parent's legal obligation...it is to be determined without consideration of the...

2010-04-01

261

31 CFR 354.5 - Obligations of Sallie Mae; no adverse claims.  

Code of Federal Regulations, 2010 CFR

...false Obligations of Sallie Mae; no adverse claims. 354.5 Section 354.5 Money and Finance: Treasury Regulations Relating...STUDENT LOAN MARKETING ASSOCIATION (SALLIE MAE) § 354.5 Obligations of Sallie Mae; no adverse...

2010-07-01

262

78 FR 63276 - Interim Policy, FAA Review of Solar Energy System Projects on Federally Obligated Airports  

Federal Register 2010, 2011, 2012, 2013

...Interim Policy, FAA Review of Solar Energy System Projects on Federally Obligated...obligated airports to construct solar energy systems on airport property. FAA...measuring ocular impact of proposed solar energy systems which are effective...

2013-10-23

263

31 CFR 1010.940 - Photographic or other reproductions of Government obligations.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Photographic or other reproductions of Government obligations. 1010...1010.940 Photographic or other reproductions of Government obligations. Nothing...authorize the microfilming or other reproduction of: (a) Currency or other...

2013-07-01

264

31 CFR 1010.940 - Photographic or other reproductions of Government obligations.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false Photographic or other reproductions of Government obligations. 1010...1010.940 Photographic or other reproductions of Government obligations. Nothing...authorize the microfilming or other reproduction of: (a) Currency or other...

2011-07-01

265

31 CFR 1010.940 - Photographic or other reproductions of Government obligations.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Photographic or other reproductions of Government obligations. 1010...1010.940 Photographic or other reproductions of Government obligations. Nothing...authorize the microfilming or other reproduction of: (a) Currency or other...

2012-07-01

266

31 CFR 103.52 - Photographic or other reproductions of Government obligations.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Photographic or other reproductions of Government obligations. 103... § 103.52 Photographic or other reproductions of Government obligations. Nothing...authorize the microfilming or other reproduction of (a) Currency or other...

2010-07-01

267

43 CFR 3137.41 - What continuing development obligations must I define in a unit agreement?  

Code of Federal Regulations, 2012 CFR

...continuing development obligations must I define in a unit agreement? A unit agreement must provide for submission of supplemental...initial obligations — (a) Meets or exceeds the rate of non-unit operations in the vicinity of the unit; and...

2012-10-01

268

43 CFR 3137.41 - What continuing development obligations must I define in a unit agreement?  

Code of Federal Regulations, 2013 CFR

...continuing development obligations must I define in a unit agreement? A unit agreement must provide for submission of supplemental...initial obligations — (a) Meets or exceeds the rate of non-unit operations in the vicinity of the unit; and...

2013-10-01

269

43 CFR 3137.41 - What continuing development obligations must I define in a unit agreement?  

Code of Federal Regulations, 2011 CFR

...continuing development obligations must I define in a unit agreement? A unit agreement must provide for submission of supplemental...initial obligations — (a) Meets or exceeds the rate of non-unit operations in the vicinity of the unit; and...

2011-10-01

270

46 CFR 287.22 - Time extensions for expenditure or obligation.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 2010-10-01 false Time extensions for expenditure or obligation. 287...CONSTRUCTION RESERVE FUNDS § 287.22 Time extensions for expenditure or obligation. (a) Extensions. The Administration, upon...

2010-10-01

271

26 CFR 2.1-22 - Time extensions for expenditure or obligation.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Time extensions for expenditure or obligation. 2...CONSTRUCTION RESERVE FUND § 2.1-22 Time extensions for expenditure or obligation. (a) Extensions. The Administration, upon...

2010-04-01

272

18 CFR 292.309 - Termination of obligation to purchase from qualifying facilities.  

Code of Federal Regulations, 2013 CFR

...contract that expires by its own terms is a “new contract or obligation” without a continuing obligation...PJM Interconnection, L.L.C. (PJM), ISO New England, Inc. (ISO-NE), and New York Independent System Operator (NYISO)...

2013-04-01

273

18 CFR 292.309 - Termination of obligation to purchase from qualifying facilities.  

Code of Federal Regulations, 2011 CFR

...contract that expires by its own terms is a “new contract or obligation” without a continuing obligation...PJM Interconnection, L.L.C. (PJM), ISO New England, Inc. (ISO-NE), and New York Independent System Operator (NYISO)...

2011-04-01

274

18 CFR 292.309 - Termination of obligation to purchase from qualifying facilities.  

Code of Federal Regulations, 2012 CFR

...contract that expires by its own terms is a “new contract or obligation” without a continuing obligation...PJM Interconnection, L.L.C. (PJM), ISO New England, Inc. (ISO-NE), and New York Independent System Operator (NYISO)...

2012-04-01

275

18 CFR 292.309 - Termination of obligation to purchase from qualifying facilities.  

Code of Federal Regulations, 2010 CFR

...contract that expires by its own terms is a “new contract or obligation” without a continuing obligation...PJM Interconnection, L.L.C. (PJM), ISO New England, Inc. (ISO-NE), and New York Independent System Operator (NYISO)...

2010-04-01

276

28 CFR 43.2 - Obligations of persons receiving care and treatment.  

...false Obligations of persons receiving care and treatment. 43.2 Section 43...RECOVERY OF COST OF HOSPITAL AND MEDICAL CARE AND TREATMENT FURNISHED BY THE UNITED STATES...2 Obligations of persons receiving care and treatment. (a) In the...

2014-07-01

277

28 CFR 45.10 - Procedures to promote compliance with crime victims' rights obligations.  

Code of Federal Regulations, 2011 CFR

... Procedures to promote compliance with crime victims' rights obligations. 45.10... Procedures to promote compliance with crime victims' rights obligations. (a...that relate to protection of the rights of crime victims. See 18 U.S.C. 3771....

2011-07-01

278

40 CFR 152.97 - Rights and obligations of data submitters.  

Code of Federal Regulations, 2010 CFR

... 23 2010-07-01 2010-07-01 false Rights and obligations of data submitters. 152.97...Procedures To Ensure Protection of Data Submitters' Rights § 152.97 Rights and obligations of data submitters. (a)...

2010-07-01

279

18 CFR 292.303 - Electric utility obligations under this subpart.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Electric utility obligations under this subpart...AND COGENERATION Arrangements Between Electric Utilities and Qualifying Cogeneration...Policies Act of 1978 § 292.303 Electric utility obligations under this...

2012-04-01

280

18 CFR 292.303 - Electric utility obligations under this subpart.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Electric utility obligations under this subpart...AND COGENERATION Arrangements Between Electric Utilities and Qualifying Cogeneration...Policies Act of 1978 § 292.303 Electric utility obligations under this...

2011-04-01

281

42 CFR 68a.14 - When can a CR-LRP payment obligation be discharged in bankruptcy?  

Code of Federal Regulations, 2010 CFR

...payment obligation be discharged in bankruptcy? 68a.14 Section 68a.14...payment obligation be discharged in bankruptcy? Any payment obligation incurred...68a.12 may be discharged in bankruptcy under Title 11 of the...

2010-10-01

282

Dynamics of intracellular information decoding.  

PubMed

A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding, the crucial step is filtering out the noise inevitably added during information transmission. As a minimal and optimal implementation of such an information decoding process, the autocatalytic phosphorylation and autocatalytic dephosphorylation (aPadP) cycle was recently proposed. Here, we analyze the dynamical properties of the aPadP cycle in detail. We describe the dynamical roles of the stationary and short-term responses in determining the efficiency of information decoding and clarify the optimality of the threshold value of the stationary response and its information-theoretical meaning. Furthermore, we investigate the robustness of the aPadP cycle against the receptor inactivation time and intrinsic noise. Finally, we discuss the relationship among information decoding with information-dependent actions, bet-hedging and network modularity. PMID:21832798

Kobayashi, Tetsuya J; Kamimura, Atsushi

2011-10-01

283

29 CFR 37.20 - What is a grant applicant's obligation to provide a written assurance?  

...2014-07-01 2013-07-01 true What is a grant applicant's obligation to...Obligations of Recipients § 37.20 What is a grant applicant's obligation to...United States on the basis of race, color, religion, sex, national origin, age,...

2014-07-01

284

29 CFR 37.20 - What is a grant applicant's obligation to provide a written assurance?  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false What is a grant applicant's obligation to...Obligations of Recipients § 37.20 What is a grant applicant's obligation to...United States on the basis of race, color, religion, sex, national origin, age,...

2013-07-01

285

29 CFR 37.20 - What is a grant applicant's obligation to provide a written assurance?  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false What is a grant applicant's obligation to...Obligations of Recipients § 37.20 What is a grant applicant's obligation to...United States on the basis of race, color, religion, sex, national origin, age,...

2011-07-01

286

29 CFR 37.20 - What is a grant applicant's obligation to provide a written assurance?  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 false What is a grant applicant's obligation to...Obligations of Recipients § 37.20 What is a grant applicant's obligation to...United States on the basis of race, color, religion, sex, national origin, age,...

2012-07-01

287

29 CFR 37.20 - What is a grant applicant's obligation to provide a written assurance?  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 true What is a grant applicant's obligation to...Obligations of Recipients § 37.20 What is a grant applicant's obligation to...United States on the basis of race, color, religion, sex, national origin, age,...

2010-07-01

288

20 CFR 703.115 - Discharge by the carrier of obligations and duties of employer.  

Code of Federal Regulations, 2010 CFR

...carrier of obligations and duties of employer. 703...carrier of obligations and duties of employer. Every obligation and duty in respect of payment...and other treatment and care, the payment or...employer to the district director and to the...

2010-04-01

289

30 CFR 243.8 - When will MMS suspend my obligation to comply with an order?  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false When will MMS suspend my obligation to comply with an...General Provisions § 243.8 When will MMS suspend my obligation to comply with an...require payment of a specified amount, MMS will suspend your obligation to comply...

2010-07-01

290

Federal Obligations for Research by Agency and Detailed Field of Science and Engineering: Fiscal Years 1970-2002  

NSF Publications Database

... Federal Obligations for Research by Agency and Detailed Field of Science and Engineering: Fiscal ... Format Federal Obligations for Research by Agency and Detailed Field of Science and Engineering ...

291

Duty of care is underpinned by a range of obligations.  

PubMed

The courts have long established that nurses are in a duty situation and owe a duty of care to their patients (Kent v Griffiths [2001]). Traditionally, the profession set the standard of care and nurses were required to act in accordance with a practice accepted by a responsible body of their peers (Bolam v Friern HMC [1957]).The introduction of the Human Rights Act 1998 gave rise to a positive obligation on government to ensure that laws, policies and procedures are in place to protect violations of human rights. Nurses must now inform their practice with relevant statute law, common law and professional standards in order to properly discharge their duty of care. Richard Griffith considers the law that now underpins a nurse's duty of care and uses a recent report from the Health Service Ombudsman for England to illustrate the obligations that underpin the nurse-patient relationship. PMID:24809155

Griffith, Richard

292

To what do we have moral obligations and why? II.  

PubMed

Following up on his 1 June 1985 article on moral obligations to living human beings versus other sentient beings, Gillon focuses on arguments for and against prohuman "speciesism," the claim that "viability" is a justifiable criterion for differentiating between humans that may be killed and those that may not, and claims that "personhood" is a morally relevant differentiating concept. He discusses the positions taken by Peter Singer and Dame Mary Warnock on "speciesism," and the theories of such philosphers as John Locke, Immanuel Kant, and Michael Tooley regarding the essence of personhood. He sees no solid basis for grounding the scope of moral obligations on simple sentience, membership in the human species, or technical differentia such as viability, and concludes that medical ethics still suffers from the lack of an adequate theory on which to base a right to life. PMID:3924233

Gillon, R

1985-06-01

293

Cell extract-containing medium for culture of intracellular fastidious bacteria.  

PubMed

The culture of fastidious microorganisms is a critical step in infectious disease studies. As a proof-of-concept experiment, we evaluated an empirical medium containing eukaryotic cell extracts for its ability to support the growth of Coxiella burnetii. Here, we demonstrate the exponential growth of several bacterial strains, including the C. burnetii Nine Mile phase I and phase II strains, and C. burnetii isolates from humans and animals. Low-oxygen-tension conditions and the presence of small hydrophilic molecules and short peptides were critical for facilitating growth. Moreover, bacterial antigenicity was conserved, revealing the potential for this culture medium to be used in diagnostic tests and in the elaboration of vaccines against C. burnetii. We were also able to grow the majority of previously tested intracellular and fastidious bacterial species, including Tropheryma whipplei, Mycobacterium bovis, Leptospira spp., Borrelia spp., and most putative bioterrorism agents. However, we were unable to culture Rickettsia africae and Legionella spp. in this medium. The versatility of this medium should encourage its use as a replacement for the cell-based culture systems currently used for growing several facultative and putative intracellular bacterial species. PMID:23740722

Singh, Sudhir; Kowalczewska, Malgorzata; Edouard, Sophie; Eldin, Carole; Perreal, Céline; Weber, Pascal; Azza, Said; Raoult, Didier

2013-08-01

294

Clinical findings in obligate carriers of type I Usher syndrome  

SciTech Connect

Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal puretone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electrooculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities. 29 refs., 1 fig., 3 tabs.

Wagenaar, M.; Rahe, B. ter; Aarem, A. van; Huygen, P.; Admiraal, R. [University Hospital Nijmegen (Netherlands)] [and others

1995-11-20

295

Floral scents repel facultative flower visitors, but attract obligate ones  

PubMed Central

Background and Aims Biological mutualisms rely on communication between partners, but also require protective measures against exploitation. Animal-pollinated flowers need to attract pollinators but also to avoid conflicts with antagonistic consumers. The view of flower visitors as mutualistic and antagonistic agents considers primarily the plants' interest. A classification emphasizing the consumer's point of view, however, may be more useful when considering animal's adaptations to flower visits which may include a tolerance against defensive floral scent compounds. Methods In a meta-analysis covering 18 studies on the responses of animals to floral scents, the animals were assigned to the categories of obligate and facultative flower visitors which considers their dependency on floral resources. Their responses on floral scents were compared. Key Results On average, obligate flower visitors, often corresponding to pollinators, were attracted to floral scent compounds. In contrast, facultative and mainly antagonistic visitors were strongly repelled by floral scents. The findings confirm that floral scents have a dual function both as attractive and defensive cues. Conclusions Whether an animal depends on floral resources determines its response to these signals, suggesting that obligate flower visitors evolved a tolerance against primarily defensive compounds. Therefore, floral scent bouquets in conjunction with nutritious rewards may solve the conflicting tasks of attracting mutualists while repelling antagonists. PMID:20228087

Junker, Robert R.; Blüthgen, Nico

2010-01-01

296

Kant's assessment of motivation in the fulfillment of social obligations.  

PubMed

This paper explores the motivations of physicians who promote the health of their communities through the fulfillment of social obligations beyond the boundaries of their own patients. Based on the assumption that physicians do not have social obligations, this paper looks at the normative, motivational question, namely "How should physicians be motivated to fulfill social obligations?" The paper traces the Kantian view of morality and motivation. The distinctions between required, merely permissible, and forbidden actions is drawn. Furthermore, Kant's view that required actions done in accordance with duty are of no moral worth is critiqued from three stand points. First, it is argued that just because motivations outside of Kantian-based duty are not as good, it does not follow that these motivations are of no moral worth. Second, it is argued that there are some motivations behind required actions that are clearly better than other motivations. Third, it is argued that required actions done in accordance with duty are clearly better than those actions done without relevance to duty. The paper concludes that many required actions done in accordance with duty are performed from motivations that do have moral worth. PMID:17146908

Knupp, Jackie

2006-01-01

297

Stochastic resonance in an intracellular genetic perceptron  

NASA Astrophysics Data System (ADS)

Intracellular genetic networks are more intelligent than was first assumed due to their ability to learn. One of the manifestations of this intelligence is the ability to learn associations of two stimuli within gene-regulating circuitry: Hebbian-type learning within the cellular life. However, gene expression is an intrinsically noisy process; hence, we investigate the effect of intrinsic and extrinsic noise on this kind of intracellular intelligence. We report a stochastic resonance in an intracellular associative genetic perceptron, a noise-induced phenomenon, which manifests itself in noise-induced increase of response in efficiency after the learning event under the conditions of optimal stochasticity.

Bates, Russell; Blyuss, Oleg; Zaikin, Alexey

2014-03-01

298

Manganese (Mn) Oxidation Increases Intracellular Mn in Pseudomonas putida GB-1  

PubMed Central

Bacterial manganese (Mn) oxidation plays an important role in the global biogeochemical cycling of Mn and other compounds, and the diversity and prevalence of Mn oxidizers have been well established. Despite many hypotheses of why these bacteria may oxidize Mn, the physiological reasons remain elusive. Intracellular Mn levels were determined for Pseudomonas putida GB-1 grown in the presence or absence of Mn by inductively coupled plasma mass spectrometry (ICP-MS). Mn oxidizing wild type P. putida GB-1 had higher intracellular Mn than non Mn oxidizing mutants grown under the same conditions. P. putida GB-1 had a 5 fold increase in intracellular Mn compared to the non Mn oxidizing mutant P. putida GB-1-007 and a 59 fold increase in intracellular Mn compared to P. putida GB-1 ?2665 ?2447. The intracellular Mn is primarily associated with the less than 3 kDa fraction, suggesting it is not bound to protein. Protein oxidation levels in Mn oxidizing and non oxidizing cultures were relatively similar, yet Mn oxidation did increase survival of P. putida GB-1 when oxidatively stressed. This study is the first to link Mn oxidation to Mn homeostasis and oxidative stress protection. PMID:24147089

Banh, Andy; Chavez, Valarie; Doi, Julia; Nguyen, Allison; Hernandez, Sophia; Ha, Vu; Jimenez, Peter; Espinoza, Fernanda; Johnson, Hope A.

2013-01-01

299

A bacterial genome in transition - an exceptional enrichment of IS elements but lack of evidence for recent transposition in the symbiont Amoebophilus asiaticus  

PubMed Central

Background Insertion sequence (IS) elements are important mediators of genome plasticity and are widespread among bacterial and archaeal genomes. The 1.88 Mbp genome of the obligate intracellular amoeba symbiont Amoebophilus asiaticus contains an unusually large number of transposase genes (n = 354; 23% of all genes). Results The transposase genes in the A. asiaticus genome can be assigned to 16 different IS elements termed ISCaa1 to ISCaa16, which are represented by 2 to 24 full-length copies, respectively. Despite this high IS element load, the A. asiaticus genome displays a GC skew pattern typical for most bacterial genomes, indicating that no major rearrangements have occurred recently. Additionally, the high sequence divergence of some IS elements, the high number of truncated IS element copies (n = 143), as well as the absence of direct repeats in most IS elements suggest that the IS elements of A. asiaticus are transpositionally inactive. Although we could show transcription of 13 IS elements, we did not find experimental evidence for transpositional activity, corroborating our results from sequence analyses. However, we detected contiguous transcripts between IS elements and their downstream genes at nine loci in the A. asiaticus genome, indicating that some IS elements influence the transcription of downstream genes, some of which might be important for host cell interaction. Conclusions Taken together, the IS elements in the A. asiaticus genome are currently in the process of degradation and largely represent reflections of the evolutionary past of A. asiaticus in which its genome was shaped by their activity. PMID:21943072

2011-01-01

300

A Method for Functional Trans-Complementation of Intracellular Francisella tularensis  

PubMed Central

Francisella tularensis is a highly infectious bacterial pathogen that invades and replicates within numerous host cell types. After uptake, F. tularensis bacteria escape the phagosome, replicate within the cytosol, and suppress cytokine responses. However, the mechanisms employed by F. tularensis to thrive within host cells are mostly unknown. Potential F. tularensis mutants involved in host-pathogen interactions are typically discovered by negative selection screens for intracellular replication or virulence. Mutants that fulfill these criteria fall into two categories: mutants with intrinsic intracellular growth defects and mutants that fail to modify detrimental host cell processes. It is often difficult and time consuming to discriminate between these two possibilities. We devised a method to functionally trans-complement and thus identify mutants that fail to modify the host response. In this assay, host cells are consistently and reproducibly infected with two different F. tularensis strains by physically tethering the bacteria to antibody-coated beads. To examine the efficacy of this protocol, we tested phagosomal escape, cytokine suppression, and intracellular replication for F. tularensis ?ripA and ?pdpC. ?ripA has an intracellular growth defect that is likely due to an intrinsic defect and fails to suppress IL-1? secretion. In the co-infection model, ?ripA was unable to replicate in the host cell when wild-type bacteria infected the same cell, but cytokine suppression was rescued. Therefore, ?ripA intracellular growth is due to an intrinsic bacterial defect while cytokine secretion results from a failed host-pathogen interaction. Likewise, ?pdpC is deficient for phagosomal escape, intracellular survival and suppression of IL-1? secretion. Wild-type bacteria that entered through the same phagosome as ?pdpC rescued all of these phenotypes, indicating that ?pdpC failed to properly manipulate the host. In summary, functional trans-complementation using bead-bound bacteria co-infections is a method to rapidly identify mutants that fail to modify a host response. Francisella tularensis is a facultative intracellular bacterial pathogen and is the causative agent of the disease tularemia. F. tularensis enters host cells through phagocytosis, escapes the phagosome, and replicates in the host cell cytosol while suppressing cytokine secretion [1]–[4]. Although substantial progress has been made in understanding the intracellular life cycle of F. tularensis, the F. tularensis proteins responsible for manipulating many host cell pathways are unknown. Identifying novel host-pathogen effector proteins is difficult because there is no rapid method to reliably distinguish between bacterial proteins that modify host processes and proteins that are involved in bacterial processes that are required for the bacteria to survive or replicate in the intracellular environment. The ability to identify mutants that are deficient for host-pathogen interactions is important because it can aid in prioritizing the investigation of genes of interest and in downstream experimental design. Moreover, certain mutant phenotypes, such as decreased phagosomal escape, hinder investigation of other potential phenotypes. A method to specifically complement these phenotypes would allow for further characterizations of certain F. tularensis mutants. Thus we sought to develop a method to easily identify and functionally complement mutants that are deficient for interactions with the host. PMID:24505427

Steele, Shaun; Taft-Benz, Sharon; Kawula, Thomas

2014-01-01

301

Desulfurispira natronophila gen. nov. sp. nov.: an obligately anaerobic dissimilatory sulfur-reducing bacterium from soda lakes  

PubMed Central

Anaerobic enrichment cultures with elemental sulfur as electron acceptor and either acetate or propionate as electron donor and carbon source at pH 10 and moderate salinity inoculated with sediments from soda lakes in Kulunda Steppe (Altai, Russia) resulted in the isolation of two novel members of the bacterial phylum Chrysiogenetes. The isolates, AHT11 and AHT19, represent the first specialized obligate anaerobic dissimilatory sulfur respirers from soda lakes. They use either elemental sulfur/polysulfide or arsenate as electron acceptor and a few simple organic compounds as electron donor and carbon source. Elemental sulfur is reduced to sulfide through intermediate polysulfide, while arsenate is reduced to arsenite. The bacteria belong to the obligate haloalkaliphiles, with a pH growth optimum from 10 to 10.2 and a salt range from 0.2 to 3.0 M Na+ (optimum 0.4–0.6 M). According to the phylogenetic analysis, the two strains were close to each other, but distinct from the nearest relative, the haloalkaliphilic sulfur-reducing bacterium Desulfurispirillum alkaliphilum, which was isolated from a bioreactor. On the basis of distinct phenotype and phylogeny, the soda lake isolates are proposed as a new genus and species, Desulfurispira natronophila (type strain AHT11T = DSM22071T = UNIQEM U758T). Electronic supplementary material The online version of this article (doi:10.1007/s00792-010-0314-7) contains supplementary material, which is available to authorized users. PMID:20407798

Muyzer, G.

2010-01-01

302

Demonstrating Bacterial Flagella.  

ERIC Educational Resources Information Center

Describes an effective laboratory method for demonstrating bacterial flagella that utilizes the Proteus mirabilis organism and a special harvesting technique. Includes safety considerations for the laboratory exercise. (MDH)

Porter, John R.; And Others

1992-01-01

303

Polymer-Ag Nanocomposites with Enhanced Antimicrobial Activity against Bacterial Infection.  

PubMed

Herein, a nontoxic nanocomposite is synthesized by reduction of silver nitrate in the presence of a cationic polymer displaying strong antimicrobial activity against bacterial infection. These nanocomposites with a large concentration of positive charge promote their adsorption to bacterial membranes through electrostatic interaction. Moreover, the synthesized nanocomposites with polyvalent and synergistic antimicrobial effects can effectively kill both Gram-positive and Gram-negative bacteria without the emergence of bacterial resistance. Morphological changes obtained by transmission electron microscope observation show that these nanocomposites can cause leakage and chaos of intracellular contents. Analysis of the antimicrobial mechanism confirms that the lethal action of nanocomposites against the bacteria started with disruption of the bacterial membrane, subsequent cellular internalization of the nanoparticles, and inhibition of intracellular enzymatic activity. This novel antimicrobial material with good cytocompatibility promotes healing of infected wounds in diabetic rats, and has a promising future in the treatment of other infectious diseases. PMID:25170799

Mei, Lin; Lu, Zhentan; Zhang, Xinge; Li, Chaoxing; Jia, Yanxia

2014-09-24

304

Bacterial cell shape  

Microsoft Academic Search

Bacterial species have long been classified on the basis of their characteristic cell shapes. Despite intensive research, the molecular mechanisms underlying the generation and maintenance of bacterial cell shape remain largely unresolved. The field has recently taken an important step forward with the discovery that eukaryotic cytoskeletal proteins have homologues in bacteria that affect cell shape. Here, we discuss how

Matthew T. Cabeen; Christine Jacobs-Wagner

2005-01-01

305

Studying Biomolecule Localization by Engineering Bacterial Cell Wall Curvature  

PubMed Central

In this article we describe two techniques for exploring the relationship between bacterial cell shape and the intracellular organization of proteins. First, we created microchannels in a layer of agarose to reshape live bacterial cells and predictably control their mean cell wall curvature, and quantified the influence of curvature on the localization and distribution of proteins in vivo. Second, we used agarose microchambers to reshape bacteria whose cell wall had been chemically and enzymatically removed. By combining microstructures with different geometries and fluorescence microscopy, we determined the relationship between bacterial shape and the localization for two different membrane-associated proteins: i) the cell-shape related protein MreB of Escherichia coli, which is positioned along the long axis of the rod-shaped cell; and ii) the negative curvature-sensing cell division protein DivIVA of Bacillus subtilis, which is positioned primarily at cell division sites. Our studies of intracellular organization in live cells of E. coli and B. subtilis demonstrate that MreB is largely excluded from areas of high negative curvature, whereas DivIVA localizes preferentially to regions of high negative curvature. These studies highlight a unique approach for studying the relationship between cell shape and intracellular organization in intact, live bacteria. PMID:24391905

Renner, Lars D.; Eswaramoorthy, Prahathees; Ramamurthi, Kumaran S.; Weibel, Douglas B.

2013-01-01

306

Effect of glucocorticosteroids on the phagocytosis and intracellular killing by peritoneal macrophages.  

PubMed Central

The effect of hydrocortisone on the phagocytosis and intracellular killing by mouse peritoneal macrophages in vitro was studied by a method making it possible to measure these processes separately. The results showed that in vivo treatment with 15 mg of hydrocortisone acetate did not significantly decrease the phagocytosis of several bacterial species such as Staphylococcus albus, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa. The killing indexes of normal macrophages for the various microorganisms were found to be significantly different. This may indicate that the bactericidal mechanisms are not uniform for these bacteria. The effect of hydrocortisone on the intracellular killing was also variable. For Staphylococcus albus a normal killing index was found. For the other species of bacterial and for Candida albicans some decrease was found, but this was only significant for Salmonella typhimurium. It is concluded that a decrease host resistance due to glucocorticosterioid treatment is not caused by a direct effect of these drugs on the phagocytosis and intracellular killing by mononuclear phagocytes. PMID:811557

Zwet, T L; Thompson, J; Furth, R

1975-01-01

307

GABAAergic stimulation modulates intracellular protein arginine methylation.  

PubMed

Changes in cytoplasmic pH are known to regulate diverse cellular processes and influence neuronal activities. In neurons, the intracellular alkalization is shown to occur after stimulating several channels and receptors. For example, it has previously demonstrated in P19 neurons that a sustained intracellular alkalinization can be mediated by the Na(+)/H(+) antiporter. In addition, the benzodiazepine binding subtypes of the ?-amino butyric acid type A (GABAA) receptor mediate a transient intracellular alkalinization when they are stimulated. Because the activities of many enzymes are sensitive to pH shift, here we investigate the effects of intracellular pH modulation resulted from stimulating GABAA receptor on the protein arginine methyltransferases (PRMT) activities. We show that the major benzodiazepine subtype (2?1, 2?2, 1?2) is constitutively expressed in both undifferentiated P19 cells and retinoic acid (RA) differentiated P19 neurons. Furthermore stimulation with diazepam and, diazepam plus muscimol produce an intracellular alkalinization that can be detected ex vivo with the fluorescence dye. The alkalinization results in significant perturbation in protein arginine methylation activity as measured in methylation assays with specific protein substrates. Altered protein arginine methylation is also observed when cells are treated with the GABAA agonist muscimol but not an antagonist, bicuculline. These data suggest that pH-dependent and pH-independent methylation pathways can be activated by GABAAergic stimulation, which we verified using hippocampal slice preparations from a mouse model of fragile X syndrome. PMID:24793772

Denman, Robert B; Xie, Wen; Merz, George; Sung, Ying-Ju

2014-06-20

308

Bacterial Community Affects Toxin Production by Gymnodinium catenatum  

PubMed Central

The paralytic shellfish toxin (PST)-producing dinoflagellate Gymnodinium catenatum grows in association with a complex marine bacterial community that is both essential for growth and can alter culture growth dynamics. Using a bacterial community replacement approach, we examined the intracellular PST content, production rate, and profile of G. catenatum cultures grown with bacterial communities of differing complexity and composition. Clonal offspring were established from surface-sterilized resting cysts (produced by sexual crosses of strain GCDE06 and strain GCLV01) and grown with: 1) complex bacterial communities derived from each of the two parent cultures; 2) simplified bacterial communities composed of the G. catenatum-associated bacteria Marinobacter sp. strain DG879 or Alcanivorax sp. strain DG881; 3) a complex bacterial community associated with an untreated, unsterilized sexual cross of the parents. Toxin content (STX-equivalent per cell) of clonal offspring (134–197 fmol STX cell?1) was similar to the parent cultures (169–206 fmol STX cell?1), however cultures grown with single bacterial types contained less toxin (134–146 fmol STX cell?1) than offspring or parent cultures grown with more complex mixed bacterial communities (152–176 fmol STX cell?1). Specific toxin production rate (fmol STX day?1) was strongly correlated with culture growth rate. Net toxin production rate (fmol STX cell?1 day?1) did not differ among treatments, however, mean net toxin production rate of offspring was 8-fold lower than the parent cultures, suggesting that completion of the sexual lifecycle in laboratory cultures leads to reduced toxin production. The PST profiles of offspring cultures were most similar to parent GCDE06 with the exception of cultures grown with Marinobacter sp. DG879 which produced higher proportions of dcGTX2+3 and GC1+2, and lower proportions of C1+2 and C3+4. Our data demonstrate that the bacterial community can alter intracellular STX production of dinoflagellates. In G. catenatum the mechanism appears likely to be due to bacterial effects on dinoflagellate physiology rather than bacterial biotransformation of PST toxins. PMID:25117053

Albinsson, Maria E.; Negri, Andrew P.; Blackburn, Susan I.; Bolch, Christopher J. S.

2014-01-01

309

The evolutionary pathway to obligate scavenging in Gyps vultures.  

PubMed

The evolutionary pathway to obligate scavenging in Gyps vultures remains unclear. We propose that communal roosting plays a central role in setting up the information transfer network critical for obligate scavengers in ephemeral environments and that the formation of a flotilla-like foraging group is a likely strategy for foraging Gyps vultures. Using a spatial, individual-based, optimisation model we find that the communal roost is critical for establishing the information network that enables information transfer owing to the spatial-concentration of foragers close to the roost. There is also strong selection pressure for grouping behaviour owing to the importance of maintaining network integrity and hence information transfer during foraging. We present a simple mechanism for grouping, common in many animal species, which has the added implication that it negates the requirement for roost-centric information transfer. The formation of a flotilla-like foraging group also improves foraging efficiency through the reduction of overlapping search paths. Finally, we highlight the importance of consideration of information transfer mechanisms in order to maximise the success of vulture reintroduction programmes. PMID:21931786

Dermody, Brian J; Tanner, Colby J; Jackson, Andrew L

2011-01-01

310

The Evolutionary Pathway to Obligate Scavenging in Gyps Vultures  

PubMed Central

The evolutionary pathway to obligate scavenging in Gyps vultures remains unclear. We propose that communal roosting plays a central role in setting up the information transfer network critical for obligate scavengers in ephemeral environments and that the formation of a flotilla-like foraging group is a likely strategy for foraging Gyps vultures. Using a spatial, individual-based, optimisation model we find that the communal roost is critical for establishing the information network that enables information transfer owing to the spatial-concentration of foragers close to the roost. There is also strong selection pressure for grouping behaviour owing to the importance of maintaining network integrity and hence information transfer during foraging. We present a simple mechanism for grouping, common in many animal species, which has the added implication that it negates the requirement for roost-centric information transfer. The formation of a flotilla-like foraging group also improves foraging efficiency through the reduction of overlapping search paths. Finally, we highlight the importance of consideration of information transfer mechanisms in order to maximise the success of vulture reintroduction programmes. PMID:21931786

Dermody, Brian J.; Tanner, Colby J.; Jackson, Andrew L.

2011-01-01

311

Obligate symbionts activate immune system development in the tsetse fly  

PubMed Central

Many insects rely on the presence of symbiotic bacteria for proper immune system function. However, the molecular mechanisms that underlie this phenomenon are poorly understood. Adult tsetse flies (Glossina spp.) house 3 symbiotic bacteria that are vertically transmitted from mother to offspring during this insect's unique viviparous mode of reproduction. Larval tsetse that undergo intrauterine development in the absence of their obligate mutualist, Wigglesworthia, exhibit a compromised immune system during adulthood. In this study we characterize the immune phenotype of tsetse that develop in the absence of all of their endogenous symbiotic microbes. Aposymbiotic tsetse (GmmApo) present a severely compromised immune system that is characterized by the absence of phagocytic hemocytes and atypical expression of immunity-related genes. Correspondingly, these flies quickly succumb to infection with normally non-pathogenic E. coli. The susceptible phenotype exhibited by GmmApo adults can be reversed when they receive hemocytes transplanted from wild-type donor flies prior to infection. Furthermore, the process of immune system development can be restored in intrauterine GmmApo larvae when their moms are fed a diet supplemented with Wigglesworthia cell extracts. Our finding that molecular components of Wigglesworthia exhibit immunostimulatory activity within tsetse is representative of a novel evolutionary adaptation that steadfastly links an obligate symbiont with it's host. PMID:22368278

Weiss, Brian L.; Maltz, Michele; Aksoy, Serap

2012-01-01

312

Intracellular trafficking of P-glycoprotein.  

PubMed

Overexpression of P-glycoprotein (P-gp) is a major cause of multidrug resistance in cancer. P-gp is mainly localized in the plasma membrane and can efflux structurally and chemically unrelated substrates, including anticancer drugs. P-gp is also localized in intracellular compartments, such as endoplasmic reticulum (ER), Golgi, endosomes and lysosomes, and cycles between endosomal compartments and the plasma membrane in a microtubular-actin dependent manner. Intracellular trafficking pathways for P-gp and participation of different Rab proteins depend on cellular polarization and choice of primary culture, cell line or neoplasm. Interruption of P-gp trafficking to the plasma membrane increases intracellular P-gp accumulation and anticancer drug levels, suggesting a potential approach to overcome P-gp-mediated multidrug resistance in cancer. PMID:22212176

Fu, Dong; Arias, Irwin M

2012-03-01

313

Tumor-targeting bacterial therapy: A potential treatment for oral cancer (Review)  

PubMed Central

Certain obligate or facultative anaerobic bacteria, which exhibit an inherent ability to colonize solid tumors in vivo, may be used in tumor targeting. As genetically manipulated bacteria may actively and specifically penetrate into the tumor tissue, bacterial therapy is becoming a promising approach in the treatment of tumors. However, to the best of our knowledge, no reports have been published thus far regarding the bacterial treatment of oral cancer, one of the most common types of cancer worldwide. In this review, the progress in the understanding of bacterial strategies used in tumor-targeted therapy is discussed and particular bacterial strains that may have great therapeutic potential in oral squamous cell carcinoma (OSCC) tumor-targeted therapy are predicted as determined by previous studies. PMID:25364397

LIU, SAI; XU, XIAOPING; ZENG, XIN; LI, LONGJIANG; CHEN, QIANMING; LI, JING

2014-01-01

314

Brucella abortus siderophore 2,3-dihydroxybenzoic acid (DHBA) facilitates intracellular survival of the bacteria.  

PubMed

Siderophores are low molecular weight molecules that allow bacteria to acquire iron from host cell proteins. 2,3-dihydroxybenzoic acid (DHBA) is the only known siderophore produced by the intracellular pathogen Brucella abortus. Here its role in virulence was assessed by evaluating the ability of a mutant with a disruption of the entC gene to survive and replicate in vitro in murine and bovine cells and in vivo in resistant and susceptible murine hosts. It was hypothesized that DHBA is vital for bacterial virulence by its ability to chelate intracellular iron thereby preventing generation of anti-bacterial hydroxyl radicals via the Haber-Weiss reaction, to scavenge reactive oxygen intermediates and for acquisition of iron needed for nutritional purposes. The data showed DHBA played a significant role for bacterial survival in host cells after infection including in murine macrophages cultured in the presence and absence of exogenous interferon-gamma (IFN-gamma) and in bovine trophoblasts supplemented with erythritol. In severely iron-depleted conditions, DHBA was also found to be essential for growth in murine macrophages. Despite these deficiencies, the absence of DHBA had no long-term significant effect on the number of CFU recovered in vivo from either the Brucella-resistant C57BL/6 mice or Brucella-susceptible IFN-gamma knock-out C57BL/6 mice. PMID:12071680

Parent, Michelle A; Bellaire, Bryan H; Murphy, Erin A; Roop, R Martin; Elzer, Phillip H; Baldwin, Cynthia L

2002-05-01

315

Endosomal escape: a bottleneck in intracellular delivery.  

PubMed

With advances in therapeutic science, apart from drugs, newer bioactive moieties like oligonucleotides, proteins, peptides, enzymes and antibodies are constantly being introduced for the betterment of therapeutic efficacy. These moieties have intracellular components of the cells like cytoplasm and nucleus as one of their pharmacological sites for exhibiting therapeutic activity. Despite their promising efficacy, their intracellular bioavailability has been critically hampered leading to failure in the treatment of numerous diseases and disorders. The endosomal uptake pathway is known to be a rate-limiting barrier for such systems. Bioactive molecules get trapped in the endosomal vesicles and degraded in the lysosomal compartment, necessitating the need for effective strategies that facilitate the endosomal escape and enhance the cytosolic bioavailability of bioactives. Microbes like viruses and bacteria have developed their innate mechanistic tactics to translocate their genome and toxins by efficiently penetrating the host cell membrane. Understanding this mechanism and exploring it further for intracellular delivery has opened new avenues to surmount the endosomal barrier. These strategies include membrane fusion, pore formation and proton sponge effects. On the other hand, progress in designing a novel smart polymeric carrier system that triggers endosomal escape by undergoing modulations in the intracellular milieu has further led to an improvement in intracellular delivery. These comprise pH, enzyme and temperature-induced modulators, synthetic cationic lipids and photo-induced physical disruption. Each of the aforementioned strategies has its own unique mechanism to escape the endosome. This review recapitulates the numerous strategies designed to surmount the bottleneck of endosomal escape and thereby achieve successful intracellular uptake of bioactives. PMID:24730275

Shete, Harshad K; Prabhu, Rashmi H; Patravale, Vandana B

2014-01-01

316

NMR measurements of intracellular ions in hypertension  

NASA Astrophysics Data System (ADS)

The NMR methods for the measurement of intracellular free Na+, K+, Mg2+, Ca2+, and H+ are introduced. The recent literature is then presented showing applications of these methods to cells and tissues from hypertensive animal model systems, and humans with essential hypertension. The results support the hypothesis of consistent derangement of the intracellular ionic environment in hypertension. The theory that this derangement may be a common link in the disease states of high blood pressure and abnormal insulin and glucose metabolism, which are often associated clinically, is discussed.

Veniero, Joseph C.; Gupta, R. K.

1993-08-01

317

Intracellular Calcium Receptors: Calmodulin and Related Proteins  

NASA Technical Reports Server (NTRS)

Studies on intracellular calcium receptors, calmodulin and related proteins were carried out. Calcium binding proteins, like calmodulin fall into a class of proteins that are predominantly intracellular and reversibly bind calcium with dissociation constants in the micromolar to nanomolar range. Calcium regulation of these proteins appears to be due to localized increases in calcium concentrations in the cytoplasm. The main thrust of the research is concerned with purifying and characterizing the calcium receptors and trying to elucidate mechanistically how they are involved in cellular responses.

Watterson, D. M.

1983-01-01

318

48 CFR 49.108-2 - Prime contractor's rights and obligations.  

Code of Federal Regulations, 2010 CFR

...108-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT TERMINATION OF CONTRACTS General Principles 49.108-2 Prime contractor's rights and obligations. (a) Termination...

2010-10-01

319

25 CFR 163.42 - Obligated service and breach of contract.  

Code of Federal Regulations, 2011 CFR

...DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Forestry Education, Education Assistance, Recruitment...Obligated service. (1) Individuals completing forestry education programs with an...

2011-04-01

320

25 CFR 163.42 - Obligated service and breach of contract.  

Code of Federal Regulations, 2012 CFR

...DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Forestry Education, Education Assistance, Recruitment...Obligated service. (1) Individuals completing forestry education programs with an...

2012-04-01

321

25 CFR 163.42 - Obligated service and breach of contract.  

Code of Federal Regulations, 2013 CFR

...DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Forestry Education, Education Assistance, Recruitment...Obligated service. (1) Individuals completing forestry education programs with an...

2013-04-01

322

Federal Science And Engineering Obligations To Academic And Nonprofit Institutions Reached Record Highs In FY 2003  

NSF Publications Database

... Record Highs In FY 2003 by Richard Bennof Statistics from the National Science Foundation (NSF ... The National Science Foundation collects statistics on federal obligations to independent nonprofit ...

323

Autophagy Enhances Bacterial Clearance during P. aeruginosa Lung Infection  

PubMed Central

Pseudomonas aeruginosa is an opportunistic bacterial pathogen which is the leading cause of morbidity and mortality among cystic fibrosis patients. Although P. aeruginosa is primarily considered an extacellular pathogen, recent reports have demonstrated that throughout the course of infection the bacterium acquires the ability to enter and reside within host cells. Normally intracellular pathogens are cleared through a process called autophagy which sequesters and degrades portions of the cytosol, including invading bacteria. However the role of autophagy in host defense against P. aeruginosa in vivo remains unknown. Understanding the role of autophagy during P. aeruginosa infection is of particular importance as mutations leading to cystic fibrosis have recently been shown to cause a blockade in the autophagy pathway, which could increase susceptibility to infection. Here we demonstrate that P. aeruginosa induces autophagy in mast cells, which have been recognized as sentinels in the host defense against bacterial infection. We further demonstrate that inhibition of autophagy through pharmacological means or protein knockdown inhibits clearance of intracellular P. aeruginosa in vitro, while pharmacologic induction of autophagy significantly increased bacterial clearance. Finally we find that pharmacological manipulation of autophagy in vivo effectively regulates bacterial clearance of P. aeruginosa from the lung. Together our results demonstrate that autophagy is required for an effective immune response against P. aeruginosa infection in vivo, and suggest that pharmacological interventions targeting the autophagy pathway could have considerable therapeutic potential in the treatment of P. aeruginosa lung infection. PMID:24015228

Junkins, Robert D.; Shen, Ann; Rosen, Kirill; McCormick, Craig; Lin, Tong-Jun

2013-01-01

324

Interaction of Bartonella henselae with endothelial cells results in rapid bacterial rRNA synthesis and replication.  

PubMed

Bartonella henselae is a slow-growing microorganism and the causative pathogen of bacillary angiomatosis in man. Here, we analysed how interaction of B. henselae with endothelial cells might affect bacterial growth. For this purpose, bacterial rRNA production and ribosome content was determined by fluorescence in situ hybridization (FISH) using rRNA-targeted fluorescence-labelled oligonucleotide probes. B. henselae grown on agar plates showed no detectable rRNA content by means of FISH, whereas B. henselae co-cultured with endothelial cells showed a rapid increase of rRNA production within the first 18 h after inoculation. The increased rRNA synthesis was paralleled by a approximately 1000-fold intracellular bacterial replication, whereas bacteria grown on agar base showed only a approximately 10-fold replication within the first 48 h of culture. Pretreatment of host cells with paraformaldehyde prevented adhesion, invasion, intracellular replication and bacterial rRNA synthesis of B. henselae. In contrast, inhibition of host cell protein synthesis by cycloheximide did not affect bacterial adhesion and invasion, but prevented intracellular replication although bacterial rRNA content was increased. Inhibition of actin polymerization by cytochalasin D did not affect adhesion, invasion, increased rRNA content or intracellular replication of B. henselae. These results demonstrate that rRNA synthesis and replication of B. henselae is promoted by viable host cells with intact de novo protein synthesis. PMID:11207598

Kempf, V A; Schaller, M; Behrendt, S; Volkmann, B; Aepfelbacher, M; Cakman, I; Autenrieth, I B

2000-10-01

325

Microfluidics for bacterial chemotaxis  

E-print Network

Bacterial chemotaxis, a remarkable behavioral trait which allows bacteria to sense and respond to chemical gradients in the environment, has implications in a broad range of fields including but not limited to disease ...

Ahmed, Tanvir, Ph. D. Massachusetts Institute of Technology

2011-01-01

326

Intracellular regulation of neuronal nicotinic cholinoreceptors.  

PubMed

Experiments on isolated superior cervical ganglia from rats were used to study the effects of substances affecting intracellular second messengers on membrane currents evoked by iontophoretic application of acetylcholine (ACh currents) and on excitatory postsynaptic currents (EPSC) induced by single discharges of preganglionic nerve fibers. These studies showed that the adenylate cyclase activator forskolin, the phosphodiesterase inhibitor isobutylmethylxanthine (IMBX), and the protein kinase C activator phorbol ester decreased the amplitude of the ACh current. Neither IMBX nor phorbol ester had any effect on the amplitude or decay time constant of EPSC, while forskolin increased the amplitude of EPSC without altering its decay time constant. Thapsigargin, which liberates intracellular calcium, not only decreased the amplitude of the ACh current, but also decreased EPSC amplitude without affecting its decay time constant. These results suggest that intracellular signaling via protein kinases A and C may affect neuronal nicotinic cholinoceptors (nAChR) only by altering receptor desensitization and not affecting receptor sensitivity to transmitters released from nerves or the kinetics of receptor ion channels. At the same time, neuronal nAChR are influenced by intracellular calcium, which decreases their ability to be activated by exogenous (perhaps acting via desensitization) and nerve-released acetylcholine without affecting the kinetics of ion channel function. PMID:10768368

Voitenko, S V; Bobryshev, A Y; Skok, V I

2000-01-01

327

Bistability and Bacterial Infections  

PubMed Central

Bacterial infections occur when the natural host defenses are overwhelmed by invading bacteria. The main component of the host defense is impaired when neutrophil count or function is too low, putting the host at great risk of developing an acute infection. In people with intact immune systems, neutrophil count increases during bacterial infection. However, there are two important clinical cases in which they remain constant: a) in patients with neutropenic-associated conditions, such as those undergoing chemotherapy at the nadir (the minimum clinically observable neutrophil level); b) in ex vivo examination of the patient's neutrophil bactericidal activity. Here we study bacterial population dynamics under fixed neutrophil levels by mathematical modelling. We show that under reasonable biological assumptions, there are only two possible scenarios: 1) Bacterial behavior is monostable: it always converges to a stable equilibrium of bacterial concentration which only depends, in a gradual manner, on the neutrophil level (and not on the initial bacterial level). We call such a behavior type I dynamics. 2) The bacterial dynamics is bistable for some range of neutrophil levels. We call such a behavior type II dynamics. In the bistable case (type II), one equilibrium corresponds to a healthy state whereas the other corresponds to a fulminant bacterial infection. We demonstrate that published data of in vitro Staphylococcus epidermidis bactericidal experiments are inconsistent with both the type I dynamics and the commonly used linear model and are consistent with type II dynamics. We argue that type II dynamics is a plausible mechanism for the development of a fulminant infection. PMID:20463954

Malka, Roy; Shochat, Eliezer; Rom-Kedar, Vered

2010-01-01

328

Bistability and bacterial infections.  

PubMed

Bacterial infections occur when the natural host defenses are overwhelmed by invading bacteria. The main component of the host defense is impaired when neutrophil count or function is too low, putting the host at great risk of developing an acute infection. In people with intact immune systems, neutrophil count increases during bacterial infection. However, there are two important clinical cases in which they remain constant: a) in patients with neutropenic-associated conditions, such as those undergoing chemotherapy at the nadir (the minimum clinically observable neutrophil level); b) in ex vivo examination of the patient's neutrophil bactericidal activity. Here we study bacterial population dynamics under fixed neutrophil levels by mathematical modelling. We show that under reasonable biological assumptions, there are only two possible scenarios: 1) Bacterial behavior is monostable: it always converges to a stable equilibrium of bacterial concentration which only depends, in a gradual manner, on the neutrophil level (and not on the initial bacterial level). We call such a behavior type I dynamics. 2) The bacterial dynamics is bistable for some range of neutrophil levels. We call such a behavior type II dynamics. In the bistable case (type II), one equilibrium corresponds to a healthy state whereas the other corresponds to a fulminant bacterial infection. We demonstrate that published data of in vitro Staphylococcus epidermidis bactericidal experiments are inconsistent with both the type I dynamics and the commonly used linear model and are consistent with type II dynamics. We argue that type II dynamics is a plausible mechanism for the development of a fulminant infection. PMID:20463954

Malka, Roy; Shochat, Eliezer; Rom-Kedar, Vered

2010-01-01

329

Rapid assessment of cell viability of Lactobacillus delbrueckii subsp. bulgaricus by measurement of intracellular pH in individual cells using fluorescence ratio imaging microscopy  

Microsoft Academic Search

The aim of this study was to investigate if the measurement of intracellular pH (pHi) of individual cells by fluorescence ratio imaging microscopy (FRIM) could be utilized as a rapid method for determining the bacterial viability, using Lactobacillus delbrueckii subsp. bulgaricus as a model organism. Five different standardized cultures with equal cell densities but varying viability were prepared on a

K. Björn Rechinger; Henrik Siegumfeldt

2002-01-01

330

Ehrlichia chaffeensis TRP32 Interacts with Host Cell Targets That Influence Intracellular Survival  

PubMed Central

Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits tropism for mononuclear phagocytes and survives by evading host cell defense mechanisms. Recently, molecular interactions of E. chaffeensis tandem repeat proteins 47 and 120 (TRP47 and -120) and the eukaryotic host cell have been described. In this investigation, yeast two-hybrid analysis demonstrated that an E. chaffeensis type 1 secretion system substrate, TRP32, interacts with a diverse group of human proteins associated with major biological processes of the host cell, including protein synthesis, trafficking, degradation, immune signaling, cell signaling, iron metabolism, and apoptosis. Eight target proteins, including translation elongation factor 1 alpha 1 (EF1A1), deleted in azoospermia (DAZ)-associated protein 2 (DAZAP2), ferritin light polypeptide (FTL), CD63, CD14, proteasome subunit beta type 1 (PSMB1), ring finger and CCCH-type domain 1 (RC3H1), and tumor protein p53-inducible protein 11 (TP53I11) interacted with TRP32 as determined by coimmunoprecipitation assays, colocalization with TRP32 in HeLa and THP-1 cells, and/or RNA interference. Interactions between TRP32 and host targets localized to the E. chaffeensis morulae or in the host cell cytoplasm adjacent to morulae. Common or closely related interacting partners of E. chaffeensis TRP32, TRP47, and TRP120 demonstrate a molecular convergence on common cellular processes and molecular cross talk between Ehrlichia TRPs and host targets. These findings further support the role of TRPs as effectors that promote intracellular survival. PMID:22547548

Luo, Tian

2012-01-01

331

Mutual obligation, shared responsibility agreements & indigenous health strategy  

PubMed Central

Since 2004 the Howard Coalition government has implemented a new policy framework and administrative arrangements as part of its program of reform in Indigenous affairs. In this paper I will describe both the parameters of this reform program and review the processes established to support the implementation of national Indigenous health strategy. In particular, I will consider both the shift from a policy framework based on 'self-determination' to one based on 'mutual obligation', and the implementation of Shared Responsibility Agreements (SRAs) that are based on the latter principle. I will use the example of the Mulan SRA to illustrate the difficulties in articulating the 'new arrangements' with current approaches to Indigenous health planning and strategy implementation. I conclude that 'new arrangements' pose a number of problems for Indigenous health planning and strategy that need to be addressed. PMID:16999873

Anderson, Ian PS

2006-01-01

332

[Solitary pulmonary nodule due to Mycobacterium intracellulare showing intense uptake on 18F-fluorodeoxyglucose-positron emission tomography].  

PubMed

A 71-year-old woman with no respiratory symptoms, was admitted because of a solitary pulmonary nodule on a chest radiograph. Computed tomography revealed a 2.0 cm nodule with pleural indentation in the right S2. 18F-fluorodeoxyglucose-positron emission (18F-FDG-PET) showed positive tumor uptake (maximum standardized uptake value = 4.8). Bronchoscopy yielded no specific histological or bacterial findings. Lung biopsy using video-associated thoracoscopy revealed an epithelial granuloma with caseation, but no acid-fast bacilli were detected. PCR revealed Mycobacterium intracellulare (M. intracellulare). A solitary nodule caused by M. intracellulare is rare, but it should be considered in the differential diagnosis even with intense uptake on 18F-FDG-PET. PMID:19260535

Nakagawa, Naoko; Tanino, Yoshinori; Inokoshi, Yayoi; Sato, Suguru; Ishii, Taeko; Saito, Kazue; Fukuhara, Atsuro; Kanazawa, Kenya; Saito, Junpei; Ishida, Takashi; Munakata, Mitsuru

2009-02-01

333

Identification of Bacterial Populations in Drinking Water Using 16S rRNA-Based Sequence Analyses  

EPA Science Inventory

Intracellular RNA is rapidly degraded in stressed cells and is more unstable outside of the cell than DNA. As a result, RNA-based methods have been suggested to study the active microbial fraction in environmental matrices. The aim of this study was to identify bacterial populati...

334

Sequence conservation and functional constraint on intergenic spacers in reduced genomes of the obligate symbiont Buchnera.  

PubMed

Analyses of genome reduction in obligate bacterial symbionts typically focus on the removal and retention of protein-coding regions, which are subject to ongoing inactivation and deletion. However, these same forces operate on intergenic spacers (IGSs) and affect their contents, maintenance, and rates of evolution. IGSs comprise both non-coding, non-functional regions, including decaying pseudogenes at varying stages of recognizability, as well as functional elements, such as genes for sRNAs and regulatory control elements. The genomes of Buchnera and other small genome symbionts display biased nucleotide compositions and high rates of sequence evolution and contain few recognizable regulatory elements. However, IGS lengths are highly correlated across divergent Buchnera genomes, suggesting the presence of functional elements. To identify functional regions within the IGSs, we sequenced two Buchnera genomes (from aphid species Uroleucon ambrosiae and Acyrthosiphon kondoi) and applied a phylogenetic footprinting approach to alignments of orthologous IGSs from a total of eight Buchnera genomes corresponding to six aphid species. Inclusion of these new genomes allowed comparative analyses at intermediate levels of divergence, enabling the detection of both conserved elements and previously unrecognized pseudogenes. Analyses of these genomes revealed that 232 of 336 IGS alignments over 50 nucleotides in length displayed substantial sequence conservation. Conserved alignment blocks within these IGSs encompassed 88 Shine-Dalgarno sequences, 55 transcriptional terminators, 5 Sigma-32 binding sites, and 12 novel small RNAs. Although pseudogene formation, and thus IGS formation, are ongoing processes in these genomes, a large proportion of intergenic spacers contain functional sequences. PMID:21912528

Degnan, Patrick H; Ochman, Howard; Moran, Nancy A

2011-09-01

335

Parabacteroides chartae sp. nov., an obligately anaerobic species from wastewater of a paper mill.  

PubMed

A bacterial strain, designated NS31-3(T), was isolated from the wastewater of a paper mill. Cells of the isolate were obligately anaerobic, non-pigmented, non-motile, Gram-negative, short rods (0.7-1.0 × 1.4-2.5 µm). The isolate was able to grow on media containing 20% bile salts. API 20A tests showed that acid was produced from glucose, lactose, sucrose, maltose, D-xylose, L-arabinose, cellobiose, D-mannose, D-melezitose, D-raffinose, D-trehalose, D-mannitol, salicin and D-sorbitol. The main fermentation products from PYG broth were lactic acid, propionic acid, formic acid and acetic acid. Chemotaxonomic analysis showed that the major fatty acids were anteiso-C(15:0), C(15:0) and iso-C(17:0) 3-OH and the predominant respiratory quinones were MK-9 and MK-10. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain NS31-3(T) was related to members of genus Parabacteroides (91.2-93.2% sequence similarity); the isolate had the closest affinity with Parabacteroides merdae JCM 9497(T). The G+C content of the genomic DNA was 37.2 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analysis, strain NS31-3(T) represents a novel species of the genus Parabacteroides, for which the name Parabacteroides chartae sp. nov. is proposed. The type strain is NS31-3(T) (=JCM 17797(T) =DSM 24967(T)). PMID:22199215

Tan, Hai-Qin; Li, Tian-Tian; Zhu, Chu; Zhang, Xin-Qi; Wu, Min; Zhu, Xu-Fen

2012-11-01

336

The Role of Family Obligations and School Adjustment in Explaining the Immigrant Paradox  

ERIC Educational Resources Information Center

This study examined the role of family obligations and school adjustment in explaining immigrant adolescents' adaptation. Despite a relatively low socio-economic status, immigrant adolescents have been found to have a pattern of adaptation superior to that of national adolescents. Immigrant adolescents' strong sense of family obligations and…

van Geel, Mitch; Vedder, Paul

2011-01-01

337

The Lived Experience of How Adult Nursing Students Blend Lifestyle Obligations with Nursing School Expectations  

ERIC Educational Resources Information Center

Many adult nursing students have lifestyle obligations that require integration with nursing school programs in order to graduate and fulfill their dreams of becoming a nurse. Fourteen participants shared their stories of how they were able to blend their lifestyles commitments with nursing school. Student interaction between lifestyle obligations

Coutrier, Karen A.

2011-01-01

338

Cognitive Representations of Obligation and Prohibition Signs when They Provide the Same Amount of Semantic Information  

ERIC Educational Resources Information Center

The aim of this research was to test whether there is an inherent difficulty in understanding prohibition signs rather than obligation signs. In the experiment conducted, participants decided whether simple car movements presented on a computer screen were allowed or not according to either obligation or prohibition traffic signs. The information…

Castro, C.; Moreno-Rios, S.; Tornay, F. J.

2012-01-01

339

Conceptualising Hy-Bivalent Subjectivities to Facilitate an Examination of Australian Government Mutual Obligations Policies  

ERIC Educational Resources Information Center

This paper illustrates how the work of feminist theorists Valerie Walkerdine, Helen Lucey and June Melody, Beverly Skeggs, and Nancy Fraser were used together to examine the lived effects of Australian government Mutual Obligations policies. As "active" welfare policies, Mutual Obligations construct particular relations between themselves and…

Edwards, Jan

2006-01-01

340

40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?  

...cellulosic biofuel, in gallons. (2) Biomass-based diesel. RVOBBD,i = (RFStdBBD... = The Renewable Volume Obligation for biomass-based diesel for an obligated party... RFStdBBD,i = The standard for biomass-based diesel for calendar year i,...

2014-07-01

341

40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?  

Code of Federal Regulations, 2010 CFR

...cellulosic biofuel, in gallons. (2) Biomass-based diesel. RVOBBD,i = (RFStdBBD... = The Renewable Volume Obligation for biomass-based diesel for an obligated party... RFStdBBD,i = The standard for biomass-based diesel for calendar year i,...

2010-07-01

342

34 CFR 370.47 - When must grant funds be obligated?  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false When must grant funds be obligated? 370.47 Section 370.47...PROGRAM What Post-Award Conditions Must Be Met by a Designated Agency? § 370.47 When must grant funds be obligated? (a) Any funds...

2010-07-01

343

17 CFR 240.17Ad-17 - Transfer agents' obligation to search for lost securityholders.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Transfer agents' obligation to search for lost securityholders...Company Rules § 240.17Ad-17 Transfer agents' obligation to search for lost securityholders...a)(1) Every recordkeeping transfer agent whose master securityholder...

2011-04-01

344

Felt obligation and the family life cycle: a study on intergenerational relationships.  

PubMed

Since the 1990s researchers have considered as the dominant view on family obligation a set of responsibilities, duties, and obligation of care and assistance,that adult children should assume when parents are old or infirm. This concept is limited, because it assumes that family obligation is salient only in one period of life: when parents reach old age and are infirm. In contrast, a relational approach to family obligation considers family relationships as central to understanding children's duties and responsibilities. Following Stein, family obligation can be defined as felt obligation: expectations for appropriate and negotiated behaviour, perceived within the context of specific personal relationships with kin across life course. Felt obligation is conceptualized in five dimensions: a duty to maintain contact, assistance, avoidance of conflict, personal sharing, and self-sufficiency. The purpose of the present study was to analyze perceptions of felt obligation in intergenerational relationships (parent-child and family of origin) in different phases of the family life cycle in a specific cultural context (Italy). The sample was composed of 92 parents with children of different ages (infants, school-aged children, and young adults).The measure addressed the five dimensions of felt obligation, all assessed in various phases of family life. Results indicated differences in dimensions of felt obligation between intergenerational relationships (both parent-child and with family of origin). Some of these differences, such as self-sufficiency and personal sharing, assumed more importance and salience in some periods of the life cycle than in others. PMID:23016537

Del Corso, Annalisa Rossi; Lanz, Margherita

2013-01-01

345

The Complete Genome of Teredinibacter turnerae T7901: An Intracellular Endosymbiont of Marine Wood-Boring Bivalves (Shipworms)  

PubMed Central

Here we report the complete genome sequence of Teredinibacter turnerae T7901. T. turnerae is a marine gamma proteobacterium that occurs as an intracellular endosymbiont in the gills of wood-boring marine bivalves of the family Teredinidae (shipworms). This species is the sole cultivated member of an endosymbiotic consortium thought to provide the host with enzymes, including cellulases and nitrogenase, critical for digestion of wood and supplementation of the host's nitrogen-deficient diet. T. turnerae is closely related to the free-living marine polysaccharide degrading bacterium Saccharophagus degradans str. 2–40 and to as yet uncultivated endosymbionts with which it coexists in shipworm cells. Like S. degradans, the T. turnerae genome encodes a large number of enzymes predicted to be involved in complex polysaccharide degradation (>100). However, unlike S. degradans, which degrades a broad spectrum (>10 classes) of complex plant, fungal and algal polysaccharides, T. turnerae primarily encodes enzymes associated with deconstruction of terrestrial woody plant material. Also unlike S. degradans and many other eubacteria, T. turnerae dedicates a large proportion of its genome to genes predicted to function in secondary metabolism. Despite its intracellular niche, the T. turnerae genome lacks many features associated with obligate intracellular existence (e.g. reduced genome size, reduced %G+C, loss of genes of core metabolism) and displays evidence of adaptations common to free-living bacteria (e.g. defense against bacteriophage infection). These results suggest that T. turnerae is likely a facultative intracellular ensosymbiont whose niche presently includes, or recently included, free-living existence. As such, the T. turnerae genome provides insights into the range of genomic adaptations associated with intracellular endosymbiosis as well as enzymatic mechanisms relevant to the recycling of plant materials in marine environments and the production of cellulose-derived biofuels. PMID:19568419

Yang, Joyce C.; Madupu, Ramana; Durkin, A. Scott; Ekborg, Nathan A.; Pedamallu, Chandra S.; Hostetler, Jessica B.; Radune, Diana; Toms, Bradley S.; Henrissat, Bernard; Coutinho, Pedro M.; Schwarz, Sandra; Field, Lauren; Trindade-Silva, Amaro E.; Soares, Carlos A. G.; Elshahawi, Sherif; Hanora, Amro; Schmidt, Eric W.; Haygood, Margo G.; Posfai, Janos; Benner, Jack; Madinger, Catherine; Nove, John; Anton, Brian; Chaudhary, Kshitiz; Foster, Jeremy; Holman, Alex; Kumar, Sanjay; Lessard, Philip A.; Luyten, Yvette A.; Slatko, Barton; Wood, Nicole; Wu, Bo; Teplitski, Max; Mougous, Joseph D.; Ward, Naomi; Eisen, Jonathan A.; Badger, Jonathan H.; Distel, Daniel L.

2009-01-01

346

The complete genome of Teredinibacter turnerae T7901: an intracellular endosymbiont of marine wood-boring bivalves (shipworms).  

PubMed

Here we report the complete genome sequence of Teredinibacter turnerae T7901. T. turnerae is a marine gamma proteobacterium that occurs as an intracellular endosymbiont in the gills of wood-boring marine bivalves of the family Teredinidae (shipworms). This species is the sole cultivated member of an endosymbiotic consortium thought to provide the host with enzymes, including cellulases and nitrogenase, critical for digestion of wood and supplementation of the host's nitrogen-deficient diet. T. turnerae is closely related to the free-living marine polysaccharide degrading bacterium Saccharophagus degradans str. 2-40 and to as yet uncultivated endosymbionts with which it coexists in shipworm cells. Like S. degradans, the T. turnerae genome encodes a large number of enzymes predicted to be involved in complex polysaccharide degradation (>100). However, unlike S. degradans, which degrades a broad spectrum (>10 classes) of complex plant, fungal and algal polysaccharides, T. turnerae primarily encodes enzymes associated with deconstruction of terrestrial woody plant material. Also unlike S. degradans and many other eubacteria, T. turnerae dedicates a large proportion of its genome to genes predicted to function in secondary metabolism. Despite its intracellular niche, the T. turnerae genome lacks many features associated with obligate intracellular existence (e.g. reduced genome size, reduced %G+C, loss of genes of core metabolism) and displays evidence of adaptations common to free-living bacteria (e.g. defense against bacteriophage infection). These results suggest that T. turnerae is likely a facultative intracellular ensosymbiont whose niche presently includes, or recently included, free-living existence. As such, the T. turnerae genome provides insights into the range of genomic adaptations associated with intracellular endosymbiosis as well as enzymatic mechanisms relevant to the recycling of plant materials in marine environments and the production of cellulose-derived biofuels. PMID:19568419

Yang, Joyce C; Madupu, Ramana; Durkin, A Scott; Ekborg, Nathan A; Pedamallu, Chandra S; Hostetler, Jessica B; Radune, Diana; Toms, Bradley S; Henrissat, Bernard; Coutinho, Pedro M; Schwarz, Sandra; Field, Lauren; Trindade-Silva, Amaro E; Soares, Carlos A G; Elshahawi, Sherif; Hanora, Amro; Schmidt, Eric W; Haygood, Margo G; Posfai, Janos; Benner, Jack; Madinger, Catherine; Nove, John; Anton, Brian; Chaudhary, Kshitiz; Foster, Jeremy; Holman, Alex; Kumar, Sanjay; Lessard, Philip A; Luyten, Yvette A; Slatko, Barton; Wood, Nicole; Wu, Bo; Teplitski, Max; Mougous, Joseph D; Ward, Naomi; Eisen, Jonathan A; Badger, Jonathan H; Distel, Daniel L

2009-01-01

347

Urticaria and bacterial infections.  

PubMed

The association between urticaria and infectious diseases has been discussed for >100 years. However, a causal relationship with underlying or precipitating infection is difficult to establish. The purpose of this work was to perform a systematic analysis of the published cases of urticaria associated with bacterial infections. We give an umbrella breakdown of up-to-date systematic reviews and other important publications on the complex association of urticaria and bacterial infections. We did a Medline search, for English language articles published until January 2014, using the key words "urticaria" and "bacteria/bacterial disease"; a second analysis was performed in groups of bacteria and using each germ name as a key word. Many bacterial infections have been associated with urticaria manifestation, such as Helicobacter pylori, Streptococcus, Staphylococcus, Mycoplasma pneumonia, Salmonella, Brucella, Mycobacterium leprae, Borrelia, Chlamydia pneumonia, and Yersinia enterocolitica. In some cases the skin manifestations, described as urticaria, could be caused by the presence of the microorganism in the skin, or for the action of their toxins, or to the complement activation mediated by circulating immune complexes. Although only a weak association with urticaria of unclear pathogenesis exists, clinicians should consider these bacterial agents in the workup of the patients with urticaria. The eradication of the infection could, in fact, lead to the resolution of urticaria. Prospective studies and well-structured research are obviously needed to better clarify the real role of bacteria in the pathogenesis of urticaria and their relative prevalence. PMID:24857191

Minciullo, Paola L; Cascio, Antonio; Barberi, Giuseppina; Gangemi, Sebastiano

2014-01-01

348

Adaptor protein complexes and intracellular transport  

PubMed Central

The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers that mediate transport from a donor membrane to a target organellar membrane. AP complexes play important roles in maintaining the normal physiological function of eukaryotic cells. Dysfunction of AP complexes has been implicated in a variety of inherited disorders, including: MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratodermia) syndrome, Fried syndrome, HPS (Hermansky–Pudlak syndrome) and HSP (hereditary spastic paraplegia). PMID:24975939

Park, Sang Yoon; Guo, Xiaoli

2014-01-01

349

Adaptor protein complexes and intracellular transport.  

PubMed

The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers that mediate transport from a donor membrane to a target organellar membrane. AP complexes play important roles in maintaining the normal physiological function of eukaryotic cells. Dysfunction of AP complexes has been implicated in a variety of inherited disorders, including: MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratodermia) syndrome, Fried syndrome, HPS (Hermansky-Pudlak syndrome) and HSP (hereditary spastic paraplegia). PMID:24975939

Park, Sang Yoon; Guo, Xiaoli

2014-01-01

350

Intracellular regulation of neuronal nicotinic cholinorceptors  

Microsoft Academic Search

Experiments on isolated superior cervical ganglia from rats were used to study the effects of substances affecting intracellular\\u000a second messengers on membrane currents evoked by iontophoretic application of acetylcholine (ACh currents) and on excitatory\\u000a postsynaptic currents (EPSC) induced by single discharges of preganglionic nerve fibers. These studies showed that the adenylate\\u000a cyclase activator forskolin, the phosphodiesterase inhibitor isobutylmethylxanthine (IMBX), and

S. V. Voitenko; A. Yu. Bobryshev; V. I. Skok

2000-01-01

351

Intracellular Calcium Handling and Inherited Arrhythmogenic Diseases  

Microsoft Academic Search

\\u000a Inherited arrhythmogenic diseases occur in the absence of morphological abnormalities of the heart, and common symptoms are\\u000a syncope and sudden death due to ventricular tachycardia\\/fibrillation. In this chapter, we discuss genetic abnormalities that\\u000a lead to altered intracellular calcium handling and susceptibility to ventricular tachyarrhythmias. The three diseases that\\u000a we will discuss are as follows: (1) catecholaminergic polymorphic ventricular tachycardia (CPVT)

Nicola Monteforte; Carlo Napolitano; Raffaella Bloise; Silvia G. Priori

352

Genetic regulation of resistance to intracellular pathogens  

Microsoft Academic Search

Natural resistance of mice to infections with Salmonella typhimurium and Leishmania donovani is regulated by chromosome 1 gene(s) designated Ity and Lsh, respectively1,2. Given the fact that these two microorganisms are taxonomically and antigenically distinct, and yet the host response to them is regulated by the same locus or complex3,4, one might expect that the resistance to other intracellular pathogens

Emil Skamene; Philippe Gros; Adrien Forget; Patricia A. L. Kongshavn; Carole St Charles; Benjamin A. Taylor

1982-01-01

353

Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of Legionella pneumophila  

E-print Network

Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of Legionella pneumophila Assaf, and virulence. The role of cyclic diguanylate signaling in the lifestyle of Legionella pneumophila of Legionnaires' disease, Legionella pneumophila, is an intracellular pathogen that grows inside environmental

354

24 CFR 350.4 - Law governing rights and obligations of United States, and Federal Reserve Banks as Depositories...  

Code of Federal Regulations, 2010 CFR

...obligations of United States, and Federal Reserve Banks as Depositories; Rights...Person against United States, and Federal Reserve Banks as Depositories; Law Governing...obligations of United States, and Federal Reserve Banks as Depositories;...

2010-04-01

355

24 CFR 81.92 - Law governing rights and obligations of United States, Federal Reserve Banks, and GSEs; rights of...  

Code of Federal Regulations, 2010 CFR

...obligations of United States, Federal Reserve Banks, and GSEs; rights of any Person against United States, Federal Reserve Banks, and GSEs; Law governing...obligations of United States, Federal Reserve Banks, and GSEs; rights...

2010-04-01

356

12 CFR 1.130 - Type II securities; guidelines for obligations issued for university and housing purposes.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Type II securities; guidelines for obligations issued for university...Interpretations § 1.130 Type II securities; guidelines for obligations issued for university...the hospital staff, and training of medical students, interns, residents,...

2011-01-01

357

45 CFR 309.135 - What requirements apply to funding, obligating and liquidating Federal title IV-D grant funds?  

Code of Federal Regulations, 2012 CFR

...2012-10-01 false What requirements apply to funding, obligating and liquidating Federal title...IV-D) PROGRAM Tribal IV-D Program Funding § 309.135 What requirements apply to funding, obligating and liquidating Federal...

2012-10-01

358

45 CFR 309.135 - What requirements apply to funding, obligating and liquidating Federal title IV-D grant funds?  

Code of Federal Regulations, 2011 CFR

...2011-10-01 false What requirements apply to funding, obligating and liquidating Federal title...IV-D) PROGRAM Tribal IV-D Program Funding § 309.135 What requirements apply to funding, obligating and liquidating Federal...

2011-10-01

359

45 CFR 309.135 - What requirements apply to funding, obligating and liquidating Federal title IV-D grant funds?  

Code of Federal Regulations, 2010 CFR

...2010-10-01 false What requirements apply to funding, obligating and liquidating Federal title...IV-D) PROGRAM Tribal IV-D Program Funding § 309.135 What requirements apply to funding, obligating and liquidating Federal...

2010-10-01

360

45 CFR 309.135 - What requirements apply to funding, obligating and liquidating Federal title IV-D grant funds?  

Code of Federal Regulations, 2013 CFR

...2012-10-01 true What requirements apply to funding, obligating and liquidating Federal title...IV-D) PROGRAM Tribal IV-D Program Funding § 309.135 What requirements apply to funding, obligating and liquidating Federal...

2013-10-01

361

42 CFR 411.22 - Reimbursement obligations of primary payers and entities that received payment from primary payers.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 false Reimbursement obligations of primary payers and entities that received payment from primary payers. 411.22 Section 411.22...411.22 Reimbursement obligations of primary payers and entities that received...

2010-10-01

362

45 CFR 309.135 - What requirements apply to funding, obligating and liquidating Federal title IV-D grant funds?  

...2012-10-01 true What requirements apply to funding, obligating and liquidating Federal title...IV-D) PROGRAM Tribal IV-D Program Funding § 309.135 What requirements apply to funding, obligating and liquidating Federal...

2014-10-01

363

26 CFR 46.4701-1 - Tax on issuer of registration-required obligation not in registered form.  

Code of Federal Regulations, 2011 CFR

...DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES EXCISE TAX ON POLICIES ISSUED BY FOREIGN INSURERS AND OBLIGATIONS NOT IN REGISTERED FORM Excise Tax on Obligations Not in Registered Form §...

2011-04-01

364

26 CFR 46.4701-1 - Tax on issuer of registration-required obligation not in registered form.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES EXCISE TAX ON POLICIES ISSUED BY FOREIGN INSURERS AND OBLIGATIONS NOT IN REGISTERED FORM Excise Tax on Obligations Not in Registered Form §...

2010-04-01

365

42 CFR 137.251. - What obligation does the retroceding Self-Governance Tribe have with respect to returning...  

Code of Federal Regulations, 2010 CFR

...obligation does the retroceding Self-Governance Tribe have with respect to...HUMAN SERVICES TRIBAL SELF-GOVERNANCE Retrocession § 137.251...obligation does the retroceding Self-Governance Tribe have with respect...

2010-10-01

366

[Intracellular regulation of neuronal nicotinic cholinergic receptors].  

PubMed

Effects of substances affecting intracellular secondary messengers on the membrane currents evoked by ionophoretic application of acetylcholine (ACh currents) and on the excitatory postsynaptic currents (EPSC) evoked by single stimuli applied to preganglionic nerve fibres, were studied in neurones of the rat isolated superior cervical ganglion. Forskolin, the protein kinase A activator, and isobutyl-methyxanthine, the phosphodiesterase inhibitor, decreased the ACh currents. Neither forskolin nor isobutyl-methylxanthine affected the EPSC amplitude or the EPSC decay time constant. Phorbol ester, the protein kinase C activator, decreased the ACh current but did not affect either EPSC amplitude or the EPSC decay time constant. Thapsigargin, the intracellular calcium releaser, decreased the ACh current and the EPSC amplitude but did not affect the EPSC decay time constant. The data obtained suggest that nicotinic acetylcholine receptors (nAChRs) of ganglion neurones are not modulated through the pathways involving protein kinase A or protein kinase C. The nAChRs sensitivity to both exogenous and nerve-released acetylcholine is reduced by intracellular calcium without affecting kinetics of their ionic channels. PMID:10097266

Vo?tenko, S V; Bobryshev, A Iu; Skok, V I

1998-10-01

367

Invasion and Intracellular Survival by Protozoan Parasites  

PubMed Central

Summary Intracellular parasitism has arisen only a few times during the long ancestry of protozoan parasites including in diverse groups such as microsporidians, kinetoplastids, and apicomplexans. Strategies used to gain entry differ widely from injection (e.g. microsporidians), active penetration of the host cell (e.g. Toxoplasma), recruitment of lysosomes to a plasma membrane wound (e.g. Trypanosoma cruzi), to host cell-mediated phagocytosis (e.g. Leishmania). The resulting range of intracellular niches is equally diverse ranging from cytosolic (e.g. T. cruzi) to residing within a nonfusigenic vacuole (e.g. Toxoplasma, Encephalitizoon) or a modified phagolysosome (e.g. Leishmania). These lifestyle choices influence access to nutrients, interaction with host cell signaling pathways, and detection by pathogen recognition systems. As such, intracellular life requires a repertoire of adaptations to assure entry-exit from the cell, as well as to thwart innate immune mechanisms and prevent clearance. Elucidating these pathways at the cellular and molecular level may identify key steps that can be targeted to reduce parasite survival or augment immunological responses and thereby prevent disease. PMID:21349087

Sibley, L. David

2013-01-01

368

Error Propagation Analysis for Quantitative Intracellular Metabolomics  

PubMed Central

Model-based analyses have become an integral part of modern metabolic engineering and systems biology in order to gain knowledge about complex and not directly observable cellular processes. For quantitative analyses, not only experimental data, but also measurement errors, play a crucial role. The total measurement error of any analytical protocol is the result of an accumulation of single errors introduced by several processing steps. Here, we present a framework for the quantification of intracellular metabolites, including error propagation during metabolome sample processing. Focusing on one specific protocol, we comprehensively investigate all currently known and accessible factors that ultimately impact the accuracy of intracellular metabolite concentration data. All intermediate steps are modeled, and their uncertainty with respect to the final concentration data is rigorously quantified. Finally, on the basis of a comprehensive metabolome dataset of Corynebacterium glutamicum, an integrated error propagation analysis for all parts of the model is conducted, and the most critical steps for intracellular metabolite quantification are detected. PMID:24957773

Tillack, Jana; Paczia, Nicole; Noh, Katharina; Wiechert, Wolfgang; Noack, Stephan

2012-01-01

369

Bacterial vaginosis in pregnancy.  

PubMed

Bacterial vaginosis is a clinical condition caused by replacement of the normal hydrogen peroxide producing Lactobacillus sp. in the vagina with high concentrations of characteristic sets of aerobic and anaerobic bacteria. Bacterial vaginosis is the most prevalent cause of vaginal discharge or malodor, although 50 percent of women who meet the criteria for this condition are asymptomatic. Bacterial vaginosis is reported in 10 to 41 percent of women, and new evidence has shown association with maternal and fetal morbidity. Studies have shown that spontaneous abortion, preterm labor, premature birth, preterm premature rupture of the membranes, amniotic fluid infection, postpartum endometritis, and postcesarean wound infections are increased because of infection with bacterial vaginosis during pregnancy. Clinical trials demonstrated important reductions in many of these adverse events with appropriate screening and antimicrobial treatment protocols. New low-cost, diagnostic, point-of-care screening tools are available for rapid screening of patients, affording the physician the opportunity to potentially make a dramatic clinical and cost impact in preventing preterm birth and the costly sequelae of prematurity. Practicing physicians need to be aware of current guidelines for screening and treating pregnant patients for bacterial vaginosis. The authors recommend that all pregnant women be screened and treated with the Centers for Disease Control and Prevention (CDC-P) recommended oral regimens early in pregnancy. Each treated women should be evaluated for "test of cure" 1 month after treatment. Mothers likely to benefit from "screen and treat" approaches include 1) those with the highest concentrations of genital anaerobes and mycoplasmas, 2) women with prior preterm birth or who have low body mass (BMI < 19.8 kg/m2), 3) those with evidence of endometritis before pregnancy, and 4) those who are treated with oral agents effective for both presumed intrauterine mycoplasmas and other bacterial vaginosis flora (i.e., oral clindamycin or erythromycin and metronidazole). PMID:10804540

McGregor, J A; French, J I

2000-05-01

370

Assembling the bacterial segrosome.  

PubMed

Genome segregation in prokaryotes is a highly ordered process that integrates with DNA replication, cytokinesis and other fundamental facets of the bacterial cell cycle. The segrosome is the nucleoprotein complex that mediates DNA segregation in bacteria, its assembly and organization is best understood for plasmid partition. The recent elucidation of structures of the ParB plasmid segregation protein bound to centromeric DNA, and of the tertiary structures of other segregation proteins, are key milestones in the path to deciphering the molecular basis of bacterial DNA segregation. PMID:16584885

Hayes, Finbarr; Barillà, Daniela

2006-05-01

371

Protein toxins: intracellular trafficking for targeted therapy  

Microsoft Academic Search

The immunotoxin approach is based on the use of tumor-targeting ligands or antibodies that are linked to the catalytic (toxic) moieties of bacterial or plant protein toxins. In this review, we first discuss the current state of clinical development of immunotoxin approaches describing the results obtained with the two toxins most frequently used: diphtheria and Pseudomonas toxin-derived proteins. In the

L Johannes; D Decaudin

2005-01-01

372

Intracellular diffusion restrictions in isolated cardiomyocytes from rainbow trout  

Microsoft Academic Search

BACKGROUND: Restriction of intracellular diffusion of adenine nucleotides has been studied intensively on adult rat cardiomyocytes. However, their cause and role in vivo is still uncertain. Intracellular membrane structures have been suggested to play a role. We therefore chose to study cardiomyocytes from rainbow trout (Oncorhynchus mykiss), which are thinner and have fewer intracellular membrane structures than adult rat cardiomyocytes.

Niina Sokolova; Marko Vendelin; Rikke Birkedal

2009-01-01

373

42 CFR 62.29 - Under what circumstances can the Loan Repayment Program obligation be discharged in bankruptcy?  

Code of Federal Regulations, 2010 CFR

...Repayment Program obligation be discharged in bankruptcy? 62.29 Section 62.29 Public...Repayment Program obligation be discharged in bankruptcy? Any payment obligation incurred...subpart may be released by a discharge in bankruptcy under title 11 of the United...

2010-10-01

374

66 FR 20659 - Notice of New Exposure Draft Change in Certain Requirements for Reconciling Obligations and Net...  

Federal Register 2010, 2011, 2012, 2013

...Requirements for Reconciling Obligations and Net Cost of Operations--Amendment of SFFAS...Requirements for Reconciling Obligations and Net Cost of Operations--Amendment to SFFAS...the reconciliation of obligations and the net cost of operations in the statement of...

2001-04-24

375

The ``Domino Theory'' of Gene Death: Gradual and Mass Gene Extinction Events in Three Lineages of Obligate Symbiotic Bacterial Pathogens  

E-print Network

extensive genome reduction: Mycobacterium leprae, Shigella flexneri, and Salmonella typhi. We infer additional examples of extensive reductive evolution are Shigella flexneri, a pathogen responsible for many between S. flexneri and Escherichia coli genomes revealed that at least 254 genes have become

Graur, Dan

376

The ?-Hemolysin and Intracellular Survival of Streptococcus agalactiae in Human Macrophages  

PubMed Central

S. agalactiae (group B streptococci, GBS) is a major microbial pathogen in human neonates and causes invasive infections in pregnant women and immunocompromised individuals. The S. agalactiae ?-hemolysin is regarded as an important virulence factor for the development of invasive disease. To examine the role of ?-hemolysin in the interaction with professional phagocytes, the THP-1 monocytic cell line and human granulocytes were infected with a serotype Ia S. agalactiae wild type strain and its isogenic nonhemolytic mutant. We could show that the nonhemolytic mutants were able to survive in significantly higher numbers than the hemolytic wild type strain, in THP-1 macrophage-like cells and in assays with human granulocytes. Intracellular bacterial multiplication, however, could not be observed. The hemolytic wild type strain stimulated a significantly higher release of Tumor Necrosis Factor-? than the nonhemolytic mutant in THP-1 cells, while similar levels of the chemokine Interleukin-8 were induced. In order to investigate bacterial mediators of IL-8 release in this setting, purified cell wall preparations from both strains were tested and found to exert a potent proinflammatory stimulus on THP-1 cells. In conclusion, our results indicate that the ?-hemolysin has a strong influence on the intracellular survival of S. agalactiae and that a tightly controlled regulation of ?-hemolysin expression is required for the successful establishment of S. agalactiae in different host niches. PMID:23593170

Sagar, Anubha; Klemm, Carolin; Hartjes, Lara; Mauerer, Stefanie; van Zandbergen, Ger; Spellerberg, Barbara

2013-01-01

377

The Action of Bismuth against Helicobacter pylori Mimics but Is Not Caused by Intracellular Iron Deprivation  

PubMed Central

Helicobacter pylori is highly susceptible to bismuth, a heavy metal with antimicrobial activity linked to its effect on bacterial iron uptake. Three strains of H. pylori were analyzed for indicators of iron limitation following exposure to the MIC of colloidal bismuth subcitrate (MICCBS). Similar morphologic and outer membrane changes were observed following growth in iron-limiting medium and at the MICCBS that inhibited the growth of all three strains. These changes, which were also observed for iron-limited bacteria, were alleviated by the addition of iron to the cultures. H. pylori ATP levels, reduced in iron-limiting medium, were below the limits of detection in two of the three strains following exposure to bismuth. The addition of iron partially restored bacterial ATP levels in these two strains, although not to normal concentrations. In contrast, exposure of the same strains to the MICCBS failed to deplete intracellular levels of iron, which were significantly reduced by culturing in iron-limiting medium. Thus, the antimicrobial effect of bismuth and of iron limitation on H. pylori may be similar. However, the respective mechanisms of intracellular action would appear to be mediated by different pathways within the cell. PMID:15155188

Bland, Michael V.; Ismail, Salim; Heinemann, Jack A.; Keenan, Jacqueline I.

2004-01-01

378

Methylophilus quaylei sp. nov., a new aerobic obligately methylotrophic bacterium.  

PubMed

A new obligately methylotrophic bacterium (strain MTT) with the ribulose monophosphate pathway of carbon assimilation is described. The isolate, utilizing only methanol, is an aerobic, Gram-negative, asporogenous, non-motile short rod multiplying by binary fission. Its cellular fatty acids profile consists primarily of straight-chain saturated C16:0 and unsaturated C16:l acids. The major ubiquinone is Q-8. The dominant phospholipids are phosphatidylethanolamine and phosphatidylglycerol. Diphosphatidylglycerol (cardiolipin) is absent. Optimal growth conditions are 25-29 degree C, pH 6.5 - 7.5, 0.5% CH3OH and 0.05% NaCl. Strain MTT lacks alpha-ketoglutarate dehydrogenase, the glyoxylate shunt enzymes, and glutamate dehydrogenase. Ammonium is assimilated by the operation of the glutamate cycle enzymes: glutamine synthetase and glutamate synthase. An exopolysaccharide consisting of rhamnose, glucose and galactose is formed under nitrogen limitation. The G + C content of the DNA is 54.0 mol%. Based on 16S rDNA sequence analysis and DNA-DNA relatedness (29-34%) with type strains of the genus Methylophilus, the novel isolate was classified as a new species of this genus and named Methylophilus quaylei MTT (VKM B-2338T, DSMZ, etc.). PMID:15997702

Doronina, Nina; Ivanova, Ekaterina; Trotsenko, Yuri; Pshenichnikova, Anna; Kalinina, Ekaterina; Shvets, Vitaly

2005-06-01

379

Health facilities' obligations when a patient refuses treatment.  

PubMed

Recent cases involving the decisions of Elizabeth Bouvia and G. Ross Henninger to starve themselves to death highlight the ethical obligations of patients, health care facilities, and the courts. When a patient seeks the hospital's cooperation in his or her attempt to commit suicide, society's responsibility is not merely to restrain the patient from suicide but to offer physical care, financial aid, and personal support. The hospital's duty is to intervene, and the court's responsibility is to allow such intervention. The most compassionate way in which the hospital can help is to force-feed the patient. If a patient is mentally competent, the refusal to eat is morally wrong. The patient is morally not permitted to commit suicide, though the avoidance of treatment may be justified in cases when force-feeding would be considered an extraordinary means, because of the patient's age or physical condition, for example. If a patient is incompetent, the refusal to eat is not a fully rational act; for the hospital to refrain from force-feeding would not be considered cooperation in suicide, since the incompetent patient cannot commit suicide. To avoid court rulings that order compliance with a patient's wishes, health care facilities in the future may have to require patients or their families to agree in writing to treatment by ordinary means. PMID:10268324

Gallagher, J

1984-09-01

380

Obligate symbiont involved in pest status of host insect.  

PubMed

The origin of specific insect genotypes that enable efficient use of agricultural plants is an important subject not only in applied fields like pest control and management but also in basic disciplines like evolutionary biology. Conventionally, it has been presupposed that such pest-related ecological traits are attributed to genes encoded in the insect genomes. Here, however, we report that pest status of an insect is principally determined by symbiont genotype rather than by insect genotype. A pest stinkbug species, Megacopta punctatissima, performed well on crop legumes, while a closely related non-pest species, Megacopta cribraria, suffered low egg hatch rate on the plants. When their obligate gut symbiotic bacteria were experimentally exchanged between the species, their performance on the crop legumes was, strikingly, completely reversed: the pest species suffered low egg hatch rate, whereas the non-pest species restored normal egg hatch rate and showed good performance. The low egg hatch rates were attributed to nymphal mortality before or upon hatching, which were associated with the symbiont from the non-pest stinkbug irrespective of the host insect species. Our finding sheds new light on the evolutionary origin of insect pests, potentially leading to novel approaches to pest control and management. PMID:17567556

Hosokawa, Takahiro; Kikuchi, Yoshitomo; Shimada, Masakazu; Fukatsu, Takema

2007-08-22

381

Genetic transformation of the obligate parasite Plasmodiophora brassicae.  

PubMed

A protocol for genetic transformation of the obligate parasite Plasmodiophora brassicae, causal agent of clubroot of crucifers, was developed. In this protocol, protoplast preparation was superseded with lithium acetate treatment and the selection step was omitted. In two independent experiments, germinating resting spores of P. brassicae were transformed by two fungal expression vectors containing either a green fluorescent protein (gfp) gene or a hygromycin resistance (hph) gene. Putative transformants were produced from both transformations, with ?50% of the obtained galls containing resting spores from which transforming DNA could be detected by polymerase chain reaction (PCR). PCR, quantitative PCR (qPCR), and genome walking conducted on selected transformants indicated that the transforming DNA was intergraded into the P. brassicae genome. Transcript of hph but not gfp was detected by reverse-transcription qPCR from selected transformants. From all galls produced by transformants, no GFP activity could be identified. Verified transformants were inoculated on canola and new galls were generated. PCR and qPCR analyses based on these galls indicated that transforming DNA was still resident in P. brassicae. This is the first report on genetic transformation of P. brassicae. The information and data generated from this study will facilitate research in multiple areas of the clubroot pathosystem. PMID:23550973

Feng, J; Hwang, Sheau-Fang; Strelkov, S E

2013-10-01

382

BACTERIAL WATERBORNE PATHOGENS  

EPA Science Inventory

Bacterial pathogens are examples of classical etiological agents of waterborne disease. While these agents no longer serve as major threats to U.S. water supplies, they are still important pathogens in areas with substandard sanitation and poor water treatment facilities. In th...

383

Bacterial extracellular lignin peroxidase  

DOEpatents

A newly discovered lignin peroxidase enzyme is provided. The enzyme is obtained from a bacterial source and is capable of degrading the lignin portion of lignocellulose in the presence of hydrogen peroxide. The enzyme is extracellular, oxidative, inducible by lignin, larch wood xylan, or related substrates and capable of attacking certain lignin substructure chemical bonds that are not degradable by fungal lignin peroxidases.

Crawford, Donald L. (Moscow, ID); Ramachandra, Muralidhara (Moscow, ID)

1993-01-01

384

Bacterial Transformation Lab  

NSDL National Science Digital Library

The "glowing genes" activity on this engaging website shows students the process of bacterial transformation, a specific type of genetic engineering. This online activity supplements a hands-on lab at the Dolan DNA Learning Center's Harlem DNA Lab, in which plasmids, or tiny loops of DNA that contain genes, are inserted into a harmless strain of E.coli.

Dolan DNA Learning Center * (Dolan DNA Learning Center;)

2010-05-27

385

Federal Funds for Research and Development: Federal Obligations for Research by Agency and Detailed Field of S&E: Fiscal Years 1970-2000  

NSF Publications Database

... Federal Funds for Research and Development: Federal Obligations for Research by Agency and Detailed ... Federal Funds for Research and Development: Federal Obligations for Research by Agency and Detailed ...

386

Federal Funds for Research and Development: Federal Obligations for Research to Universities and Colleges by Agency and Detailed Field of S&E: Fiscal Years 1973-2000  

NSF Publications Database

... Federal Funds for Research and Development: Federal Obligations for Research to Universities and ... Federal Funds for Research and Development: Federal Obligations for Research to Universities and ...

387

Novel Bacterial Artificial Chromosome Vector pUvBBAC for Use in Studies of the Functional Genomics of Listeria spp  

Microsoft Academic Search

Bacterial artificial chromosome (BAC) vectors are important tools for microbial genome research. We con- structed a novel BAC vector, pUvBBAC, for replication in both gram-negative and gram-positive bacterial hosts. The pUvBBAC vector was used to generate a BAC library for the facultative intracellular pathogen Listeria monocytogenes EGD-e. The library had insert sizes ranging from 68 to 178 kb. We identified

Torsten Hain; Sonja Otten; U. von Both; S. S. Chatterjee; U. Technow; A. Billion; R. Ghai; W. Mohamed; E. Domann; T. Chakraborty

2008-01-01

388

Differential modulation of intracellular survival of cytosolic and vacuolar pathogens by curcumin.  

PubMed

Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of Helicobacter pylori infection and exacerbate that of Leishmania infection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused by Shigella flexneri (clinical isolates) and Listeria monocytogenes and aggravates those caused by Salmonella enterica serovar Typhi CT18 (a clinical isolate), Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Yersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneri and L. monocytogenes) and vacuolar (Salmonella spp., Y. enterocolitica, and S. aureus) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter- and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria. PMID:22890770

Marathe, Sandhya A; Sen, Minakshi; Dasgupta, Ishani; Chakravortty, Dipshikha

2012-11-01

389

Recent developments in copper and zinc homeostasis in bacterial pathogens.  

PubMed

Copper and zinc homeostasis systems in pathogenic bacteria are required to resist host efforts to manipulate the availability and toxicity of these metal ions. Central to this microbial adaptive response is the involvement of metal-trafficking and metal-sensing proteins that ultimately exercise control of metal speciation in the cell. Cu-specific and Zn-specific metalloregulatory proteins regulate the transcription of metal-responsive genes while metallochaperones and related proteins ensure that these metals are appropriately buffered by the intracellular milieu and delivered to correct intracellular targets. In this review, we summarize recent findings on how bacterial pathogens mount a metal-specific response to derail host efforts to win the 'fight over metals.' PMID:24463765

Braymer, Joseph J; Giedroc, David P

2014-04-01

390

Intracellular Screen To Identify Metagenomic Clones That Induce or Inhibit a Quorum-Sensing Biosensor  

PubMed Central

The goal of this study was to design and evaluate a rapid screen to identify metagenomic clones that produce biologically active small molecules. We built metagenomic libraries with DNA from soil on the floodplain of the Tanana River in Alaska. We extracted DNA directly from the soil and cloned it into fosmid and bacterial artificial chromosome vectors, constructing eight metagenomic libraries that contain 53,000 clones with inserts ranging from 1 to 190 kb. To identify clones of interest, we designed a high throughput “intracellular” screen, designated METREX, in which metagenomic DNA is in a host cell containing a biosensor for compounds that induce bacterial quorum sensing. If the metagenomic clone produces a quorum-sensing inducer, the cell produces green fluorescent protein (GFP) and can be identified by fluorescence microscopy or captured by fluorescence-activated cell sorting. Our initial screen identified 11 clones that induce and two that inhibit expression of GFP. The intracellular screen detected quorum-sensing inducers among metagenomic clones that a traditional overlay screen would not. One inducing clone carries a LuxI homologue that directs the synthesis of an N-acyl homoserine lactone quorum-sensing signal molecule. The LuxI homologue has 62% amino acid sequence identity to its closest match in GenBank, AmfI from Pseudomonas fluorescens, and is on a 78-kb insert that contains 67 open reading frames. Another inducing clone carries a gene with homology to homocitrate synthase. Our results demonstrate the power of an intracellular screen to identify functionally active clones and biologically active small molecules in metagenomic libraries. PMID:16204555

Williamson, Lynn L.; Borlee, Bradley R.; Schloss, Patrick D.; Guan, Changhui; Allen, Heather K.; Handelsman, Jo

2005-01-01

391

Intracellular Bacteria Interfere with Dendritic Cell Functions: Role of the Type I Interferon Pathway  

PubMed Central

Dendritic cells (DCs) orchestrate host defenses against microorganisms. In infectious diseases due to intracellular bacteria, the inefficiency of the immune system to eradicate microorganisms has been attributed to the hijacking of DC functions. In this study, we selected intracellular bacterial pathogens with distinct lifestyles and explored the responses of monocyte-derived DCs (moDCs). Using lipopolysaccharide as a control, we found that Orientia tsutsugamushi, the causative agent of scrub typhus that survives in the cytosol of target cells, induced moDC maturation, as assessed by decreased endocytosis activity, the ability to induce lymphocyte proliferation and the membrane expression of phenotypic markers. In contrast, Coxiella burnetii, the agent of Q fever, and Brucella abortus, the agent of brucellosis, both of which reside in vacuolar compartments, only partly induced the maturation of moDCs, as demonstrated by a phenotypic analysis. To analyze the mechanisms used by C. burnetii and B. abortus to alter moDC activation, we performed microarray and found that C. burnetii and B. abortus induced a specific signature consisting of TLR4, TLR3, STAT1 and interferon response genes. These genes were down-modulated in response to C. burnetii and B. abortus but up-modulated in moDCs activated by lipopolysaccharide and O. tsutsugamushi. This transcriptional alteration was associated with the defective interferon-? production. This study demonstrates that intracellular bacteria specifically affect moDC responses and emphasizes how C. burnetii and B. abortus interfere with moDC activation and the antimicrobial immune response. We believe that comparing infection by several bacterial species may be useful for defining new pathways and biomarkers and for developing new treatment strategies. PMID:24915541

Gorvel, Laurent; Textoris, Julien; Banchereau, Romain; Ben Amara, Amira; Tantibhedhyangkul, Wiwit; von Bargen, Kristin; Ka, Mignane B.; Capo, Christian; Ghigo, Eric; Gorvel, Jean-Pierre; Mege, Jean-Louis

2014-01-01

392

Intracellular bacteria interfere with dendritic cell functions: role of the type I interferon pathway.  

PubMed

Dendritic cells (DCs) orchestrate host defenses against microorganisms. In infectious diseases due to intracellular bacteria, the inefficiency of the immune system to eradicate microorganisms has been attributed to the hijacking of DC functions. In this study, we selected intracellular bacterial pathogens with distinct lifestyles and explored the responses of monocyte-derived DCs (moDCs). Using lipopolysaccharide as a control, we found that Orientia tsutsugamushi, the causative agent of scrub typhus that survives in the cytosol of target cells, induced moDC maturation, as assessed by decreased endocytosis activity, the ability to induce lymphocyte proliferation and the membrane expression of phenotypic markers. In contrast, Coxiella burnetii, the agent of Q fever, and Brucella abortus, the agent of brucellosis, both of which reside in vacuolar compartments, only partly induced the maturation of moDCs, as demonstrated by a phenotypic analysis. To analyze the mechanisms used by C. burnetii and B. abortus to alter moDC activation, we performed microarray and found that C. burnetii and B. abortus induced a specific signature consisting of TLR4, TLR3, STAT1 and interferon response genes. These genes were down-modulated in response to C. burnetii and B. abortus but up-modulated in moDCs activated by lipopolysaccharide and O. tsutsugamushi. This transcriptional alteration was associated with the defective interferon-? production. This study demonstrates that intracellular bacteria specifically affect moDC responses and emphasizes how C. burnetii and B. abortus interfere with moDC activation and the antimicrobial immune response. We believe that comparing infection by several bacterial species may be useful for defining new pathways and biomarkers and for developing new treatment strategies. PMID:24915541

Gorvel, Laurent; Textoris, Julien; Banchereau, Romain; Ben Amara, Amira; Tantibhedhyangkul, Wiwit; von Bargen, Kristin; Ka, Mignane B; Capo, Christian; Ghigo, Eric; Gorvel, Jean-Pierre; Mege, Jean-Louis

2014-01-01

393

Identification of Host-Targeted Small Molecules That Restrict Intracellular Mycobacterium tuberculosis Growth  

PubMed Central

Mycobacterium tuberculosis remains a significant threat to global health. Macrophages are the host cell for M. tuberculosis infection, and although bacteria are able to replicate intracellularly under certain conditions, it is also clear that macrophages are capable of killing M. tuberculosis if appropriately activated. The outcome of infection is determined at least in part by the host-pathogen interaction within the macrophage; however, we lack a complete understanding of which host pathways are critical for bacterial survival and replication. To add to our understanding of the molecular processes involved in intracellular infection, we performed a chemical screen using a high-content microscopic assay to identify small molecules that restrict mycobacterial growth in macrophages by targeting host functions and pathways. The identified host-targeted inhibitors restrict bacterial growth exclusively in the context of macrophage infection and predominantly fall into five categories: G-protein coupled receptor modulators, ion channel inhibitors, membrane transport proteins, anti-inflammatories, and kinase modulators. We found that fluoxetine, a selective serotonin reuptake inhibitor, enhances secretion of pro-inflammatory cytokine TNF-? and induces autophagy in infected macrophages, and gefitinib, an inhibitor of the Epidermal Growth Factor Receptor (EGFR), also activates autophagy and restricts growth. We demonstrate that during infection signaling through EGFR activates a p38 MAPK signaling pathway that prevents macrophages from effectively responding to infection. Inhibition of this pathway using gefitinib during in vivo infection reduces growth of M. tuberculosis in the lungs of infected mice. Our results support the concept that screening for inhibitors using intracellular models results in the identification of tool compounds for probing pathways during in vivo infection and may also result in the identification of new anti-tuberculosis agents that work by modulating host pathways. Given the existing experience with some of our identified compounds for other therapeutic indications, further clinically-directed study of these compounds is merited. PMID:24586159

Silvis, Melanie R.; Luo, Samantha S.; Sogi, Kimberly; Vokes, Martha; Bray, Mark-Anthony; Carpenter, Anne E.; Moore, Christopher B.; Siddiqi, Noman; Rubin, Eric J.; Hung, Deborah T.

2014-01-01

394

Bacterial programming of host responses: coordination between type I interferon and cell death  

PubMed Central

During mammalian infection, bacteria induce cell death from an extracellular or intracellular niche that can protect or hurt the host. Data is accumulating that associate type I interferon (IFN) signaling activated by intracellular bacteria with programmed death of immune effector cells and enhanced virulence. Multiple pathways leading to IFN-dependent host cell death have been described, and in some cases it is becoming clear how these mechanisms contribute to virulence. Yet common mechanisms of IFN-enhanced bacterial pathogenesis are not obvious and no specific interferon stimulated genes have yet been identified that cause sensitivity to pathogen-induced cell death. In this review, we will summarize some bacterial infections caused by facultative intracellular pathogens and what is known about how type I IFN signaling may promote the replication of extracellular bacteria rather than stimulate protection. Each of these pathogens can survive phagocytosis but their intracellular life cycles are very different, they express distinct virulence factors and trigger different pathways of immune activation and crosstalk. These differences likely lead to widely varying amounts of type I IFN expression and a different inflammatory environment, but these may not be important to the pathologic effects on the host. Instead, each pathogen induces programmed cell death of key immune cells that have been sensitized by the activation of the type I IFN response. We will discuss how IFN-dependent host cell death may increase host susceptibility and try to understand common pathways of pathogenesis that lead to IFN-enhanced bacterial virulence. PMID:25389418

Dhariwala, Miqdad O.; Anderson, Deborah M.

2014-01-01

395

TGF-?-mediated sustained ERK1/2 activity promotes the inhibition of intracellular growth of Mycobacterium avium in epithelioid cells surrogates.  

PubMed

Transforming growth factor beta (TGF-?) has been implicated in the pathogenesis of several diseases including infection with intracellular pathogens such as the Mycobacterium avium complex. Infection of macrophages with M. avium induces TGF-? production and neutralization of this cytokine has been associated with decreased intracellular bacterial growth. We have previously demonstrated that epithelioid cell surrogates (ECs) derived from primary murine peritoneal macrophages through a process of differentiation induced by IL-4 overlap several features of epithelioid cells found in granulomas. In contrast to undifferentiated macrophages, ECs produce larger amounts of TGF-? and inhibit the intracellular growth of M. avium. Here we asked whether the levels of TGF-? produced by ECs are sufficient to induce a self-sustaining autocrine TGF-? signaling controlling mycobacterial replication in infected-cells. We showed that while exogenous addition of increased concentration of TGF-? to infected-macrophages counteracted M. avium replication, pharmacological blockage of TGF-? receptor kinase activity with SB-431542 augmented bacterial load in infected-ECs. Moreover, the levels of TGF-? produced by ECs correlated with high and sustained levels of ERK1/2 activity. Inhibition of ERK1/2 activity with U0126 increased M. avium replication in infected-cells, suggesting that modulation of intracellular bacterial growth is dependent on the activation of ERK1/2. Interestingly, blockage of TGF-? receptor kinase activity with SB-431542 in infected-ECs inhibited ERK1/2 activity, enhanced intracellular M. avium burden and these effects were followed by a severe decrease in TGF-? production. In summary, our findings indicate that the amplitude of TGF-? signaling coordinates the strength and duration of ERK1/2 activity that is determinant for the control of intracellular mycobacterial growth. PMID:21731758

L'Abbate, Carolina; Cipriano, Ivone; Pérez-Hurtado, Elizabeth Cristina; Leão, Sylvia Cardoso; Carneiro, Célia Regina Whitaker; Machado, Joel

2011-01-01

396

31 CFR 223.13 - Full penalty of the obligation regarded as the liability; exceptions.  

Code of Federal Regulations, 2010 CFR

...Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE UNITED STATES § 223.13 Full penalty of the obligation regarded as the...

2010-07-01

397

31 CFR 588.407 - Payments from blocked accounts to satisfy obligations prohibited.  

... Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WESTERN BALKANS STABILIZATION REGULATIONS Interpretations § 588.407 Payments from blocked accounts to satisfy obligations...

2014-07-01

398

An experimental test of preferences for nest contents in an obligate brood parasite,  

E-print Network

An experimental test of preferences for nest contents in an obligate brood parasite, Molothrus ater to examine the stimuli to which female brown-headed cowbirds (Molothrus ater) attend when selecting a nest

White, David J.

399

17 CFR 285.3 - Reports with respect to proposed distribution of primary obligations.  

...Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS PURSUANT TO SECTION 15(a) OF THE BRETTON WOODS AGREEMENTS ACT § 285.3 Reports with respect to proposed distribution of primary obligations. The Bank shall...

2014-04-01

400

75 FR 52266 - Qualified Zone Academy Bonds; Obligations of States and Political Subdivisions; Correction  

Federal Register 2010, 2011, 2012, 2013

...RIN 1545-BC61 Qualified Zone Academy Bonds; Obligations of States and Political...governments that issue qualified zone academy bonds and to banks, insurance companies, and other taxpayers that hold those bonds on the program requirements for...

2010-08-25

401

75 FR 52267 - Qualified Zone Academy Bonds; Obligations of States and Political Subdivisions; Correction  

Federal Register 2010, 2011, 2012, 2013

...RIN 1545-BC61 Qualified Zone Academy Bonds; Obligations of States and Political...governments that issue qualified zone academy bonds and to banks, insurance companies, and other taxpayers that hold those bonds on the program requirements for...

2010-08-25

402

The obligation nation : America's involvement in the affairs of the World  

E-print Network

Does America have an obligation, whether through foreign aid, military involvement, or by spreading democracy, to change the world? This thesis answers these above questions in intimate detail through the moral framework ...

Francel, Leif (Leif G.)

2012-01-01

403

31 CFR 403.1 - Delivery of counterfeit obligations and other securities and coins authorized.  

Code of Federal Regulations, 2012 CFR

... Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY AUTHORIZATION OF...possession of and deliver to the Treasury Department through the Secret Service all counterfeit obligations and other securities...

2012-07-01

404

31 CFR 403.1 - Delivery of counterfeit obligations and other securities and coins authorized.  

Code of Federal Regulations, 2011 CFR

... Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY AUTHORIZATION OF...possession of and deliver to the Treasury Department through the Secret Service all counterfeit obligations and other securities...

2011-07-01

405

31 CFR 403.1 - Delivery of counterfeit obligations and other securities and coins authorized.  

Code of Federal Regulations, 2013 CFR

... Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY AUTHORIZATION OF...possession of and deliver to the Treasury Department through the Secret Service all counterfeit obligations and other securities...

2013-07-01

406

31 CFR 403.1 - Delivery of counterfeit obligations and other securities and coins authorized.  

Code of Federal Regulations, 2010 CFR

... Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY AUTHORIZATION OF...possession of and deliver to the Treasury Department through the Secret Service all counterfeit obligations and other securities...

2010-07-01

407

17 CFR 290.3 - Reports with respect to proposed distribution of obligations.  

Code of Federal Regulations, 2010 CFR

...EXCHANGE COMMISSION (CONTINUED) Schedule A to Part 285 GENERAL RULES AND REGULATIONS PURSUANT TO SECTION 9(a) OF THE EUROPEAN BANK FOR RECONSTRUCTION AND DEVELOPMENT ACT § 290.3 Reports with respect to proposed distribution of obligations....

2010-04-01

408

76 FR 49477 - Termination of Federal Home Loan Bank Resolution Funding Corporation Obligation  

Federal Register 2010, 2011, 2012, 2013

...FEDERAL HOUSING FINANCE AGENCY [No. 2011-N-08] Termination...Corporation Obligation AGENCY: Federal Housing Finance Agency. ACTION: Notice...SUMMARY: The Federal Housing Finance Agency (FHFA) has determined...

2011-08-10

409

26 CFR 31.3406(a)-2 - Definition of payors obligated to backup withhold.  

Code of Federal Regulations, 2010 CFR

...EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Collection of Income Tax at Source § 31.3406(a)-2 Definition of payors obligated to backup withhold. (a) In general....

2010-04-01

410

76 FR 74721 - Reexamination of Roaming Obligations of Commercial Mobile Radio Service Providers and Other...  

Federal Register 2010, 2011, 2012, 2013

...Reexamination of Roaming Obligations of Commercial Mobile Radio Service Providers and Other Providers of Mobile Data Services AGENCY: Federal Communications...facilities-based providers of commercial mobile data services to offer data roaming...

2011-12-01

411

18 CFR 367.2430 - Account 243, Obligations under capital leases-Current.  

...SUBJECT TO THE PROVISIONS OF THE PUBLIC UTILITY HOLDING COMPANY ACT OF 2005, FEDERAL POWER ACT AND NATURAL GAS ACT Balance Sheet Chart of Accounts Current and Accrued Liabilities § 367.2430 Account 243, Obligations under capital leases—Current....

2014-04-01

412

18 CFR 367.2270 - Account 227, Obligations under capital lease-Non-current.  

...SUBJECT TO THE PROVISIONS OF THE PUBLIC UTILITY HOLDING COMPANY ACT OF 2005, FEDERAL POWER ACT AND NATURAL GAS ACT Balance Sheet Chart of Accounts Other Noncurrent Liabilities § 367.2270 Account 227, Obligations under capital...

2014-04-01

413

18 CFR 367.2430 - Account 243, Obligations under capital leases-Current.  

Code of Federal Regulations, 2013 CFR

...SUBJECT TO THE PROVISIONS OF THE PUBLIC UTILITY HOLDING COMPANY ACT OF 2005, FEDERAL POWER ACT AND NATURAL GAS ACT Balance Sheet Chart of Accounts Current and Accrued Liabilities § 367.2430 Account 243, Obligations under capital leases—Current....

2013-04-01

414

18 CFR 367.2430 - Account 243, Obligations under capital leases-Current.  

Code of Federal Regulations, 2012 CFR

...SUBJECT TO THE PROVISIONS OF THE PUBLIC UTILITY HOLDING COMPANY ACT OF 2005, FEDERAL POWER ACT AND NATURAL GAS ACT Balance Sheet Chart of Accounts Current and Accrued Liabilities § 367.2430 Account 243, Obligations under capital leases—Current....

2012-04-01

415

12 CFR 615.5102 - Issuance of debt obligations through the Funding Corporation.  

...Issuance of debt obligations through the Funding Corporation. 615.5102 Section 615...ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Issuance of Bonds,...

2014-01-01

416

12 CFR 615.5102 - Issuance of debt obligations through the Funding Corporation.  

Code of Federal Regulations, 2010 CFR

...Issuance of debt obligations through the Funding Corporation. 615.5102 Section 615...ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Issuance of Bonds,...

2010-01-01

417

12 CFR 1510.5 - How does the Funding Corporation make interest payments on its obligations?  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false How does the Funding Corporation make interest payments on its obligations...Banking DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION RESOLUTION FUNDING CORPORATION OPERATIONS § 1510.5 How...

2010-01-01

418

12 CFR 1510.5 - How does the Funding Corporation make interest payments on its obligations?  

Code of Federal Regulations, 2012 CFR

...2012-01-01 2012-01-01 false How does the Funding Corporation make interest payments on its obligations...Banking DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION RESOLUTION FUNDING CORPORATION OPERATIONS § 1510.5 How...

2012-01-01

419

12 CFR 1510.5 - How does the Funding Corporation make interest payments on its obligations?  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false How does the Funding Corporation make interest payments on its obligations...Banking DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION RESOLUTION FUNDING CORPORATION OPERATIONS § 1510.5 How...

2013-01-01

420

12 CFR 615.5102 - Issuance of debt obligations through the Funding Corporation.  

Code of Federal Regulations, 2011 CFR

...Issuance of debt obligations through the Funding Corporation. 615.5102 Section 615...ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Issuance of Bonds,...

2011-01-01

421

12 CFR 615.5102 - Issuance of debt obligations through the Funding Corporation.  

Code of Federal Regulations, 2012 CFR

...Issuance of debt obligations through the Funding Corporation. 615.5102 Section 615...ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Issuance of Bonds,...

2012-01-01

422

12 CFR 1510.5 - How does the Funding Corporation make interest payments on its obligations?  

...2014-01-01 2014-01-01 false How does the Funding Corporation make interest payments on its obligations...Banking DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION RESOLUTION FUNDING CORPORATION OPERATIONS § 1510.5 How...

2014-01-01

423

12 CFR 1510.5 - How does the Funding Corporation make interest payments on its obligations?  

Code of Federal Regulations, 2011 CFR

...2011-01-01 2011-01-01 false How does the Funding Corporation make interest payments on its obligations...Banking DEPARTMENT OF THE TREASURY RESOLUTION FUNDING CORPORATION RESOLUTION FUNDING CORPORATION OPERATIONS § 1510.5 How...

2011-01-01

424

12 CFR 615.5102 - Issuance of debt obligations through the Funding Corporation.  

Code of Federal Regulations, 2013 CFR

...Issuance of debt obligations through the Funding Corporation. 615.5102 Section 615...ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Issuance of Bonds,...

2013-01-01

425

Federal Academic Science and Engineering Obligations Up More Than 6 Percent in FY 1998  

NSF Publications Database

... This Data Brief presents Federal academic science and engineering obligations data from 19 agencies ... Nonprofit Institutions. In this annual survey, data are collected on Federal S&E support by funding ...

426

Moral obligation and the human germ-line gene therapy debate  

E-print Network

genetic engineering, there are few arguments made for a positive moral obligation to genetic intervention. This is especially so with respect to human germ-line gene therapy. Burke. K. Zimmerman makes one of the few arguments that society...

Clark, Alan B

2012-06-07

427

47 CFR 54.903 - Obligations of rate-of-return carriers and the Administrator.  

Code of Federal Regulations, 2010 CFR

...COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Interstate Common Line Support Mechanism for Rate-of-Return Carriers § 54.903 Obligations of rate-of-return carriers and the Administrator....

2010-10-01

428

20 CFR 243.2 - Legal process for the enforcement of child support and alimony obligations.  

... Legal process for the enforcement of child support and alimony... Legal process for the enforcement of child support and alimony...process brought for the enforcement of legal obligations to provide child support or to make...

2014-04-01

429

20 CFR 243.2 - Legal process for the enforcement of child support and alimony obligations.  

Code of Federal Regulations, 2013 CFR

... Legal process for the enforcement of child support and alimony... Legal process for the enforcement of child support and alimony...process brought for the enforcement of legal obligations to provide child support or to make...

2013-04-01

430

31 CFR 800.701 - Obligation of parties to provide information.  

...Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS, AND TAKEOVERS BY FOREIGN PERSONS Provision and Handling of Information § 800.701 Obligation of...

2014-07-01

431

31 CFR 800.701 - Obligation of parties to provide information.  

Code of Federal Regulations, 2012 CFR

...Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS, AND TAKEOVERS BY FOREIGN PERSONS Provision and Handling of Information § 800.701 Obligation of...

2012-07-01

432

31 CFR 800.701 - Obligation of parties to provide information.  

Code of Federal Regulations, 2013 CFR

...Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS, AND TAKEOVERS BY FOREIGN PERSONS Provision and Handling of Information § 800.701 Obligation of...

2013-07-01

433

31 CFR 800.701 - Obligation of parties to provide information.  

Code of Federal Regulations, 2011 CFR

...Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS, AND TAKEOVERS BY FOREIGN PERSONS Provision and Handling of Information § 800.701 Obligation of...

2011-07-01

434

18 CFR 292.303 - Electric utility obligations under this subpart.  

Code of Federal Regulations, 2010 CFR

...292.310, any energy and capacity which...292.312, energy and capacity requested...of the Federal Power Act. (d) Transmission to other electric...obligated to purchase energy or capacity from...down to reflect line losses...

2010-04-01

435

45 CFR 402.26 - Time period for obligation and expenditure of grant funds.  

Code of Federal Regulations, 2010 CFR

... OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES STATE LEGALIZATION IMPACT ASSISTANCE GRANTS Administration of Grants § 402.26 Time period for obligation and...

2010-10-01

436

45 CFR 402.26 - Time period for obligation and expenditure of grant funds.  

Code of Federal Regulations, 2011 CFR

... OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES STATE LEGALIZATION IMPACT ASSISTANCE GRANTS Administration of Grants § 402.26 Time period for obligation and...

2011-10-01

437

26 CFR 1.453-11 - Installment obligations received from a liquidating corporation.  

Code of Federal Regulations, 2010 CFR

...c) and (d). (B) Variable rate debt instrument. If the qualifying...installment obligation is a variable rate debt instrument (as defined in...1275-5), the shareholder uses the equivalent fixed rate debt instrument (within the...

2010-04-01

438

26 CFR 1.453-11 - Installment obligations received from a liquidating corporation.  

Code of Federal Regulations, 2011 CFR

...c) and (d). (B) Variable rate debt instrument. If the qualifying...installment obligation is a variable rate debt instrument (as defined in...1275-5), the shareholder uses the equivalent fixed rate debt instrument (within the...

2011-04-01

439

26 CFR 1.453-11 - Installment obligations received from a liquidating corporation.  

...c) and (d). (B) Variable rate debt instrument. If the qualifying...installment obligation is a variable rate debt instrument (as defined in...1275-5), the shareholder uses the equivalent fixed rate debt instrument (within the...

2014-04-01

440

26 CFR 1.453-11 - Installment obligations received from a liquidating corporation.  

Code of Federal Regulations, 2013 CFR

...c) and (d). (B) Variable rate debt instrument. If the qualifying...installment obligation is a variable rate debt instrument (as defined in...1275-5), the shareholder uses the equivalent fixed rate debt instrument (within the...

2013-04-01

441

26 CFR 1.453-11 - Installment obligations received from a liquidating corporation.  

Code of Federal Regulations, 2012 CFR

...c) and (d). (B) Variable rate debt instrument. If the qualifying...installment obligation is a variable rate debt instrument (as defined in...1275-5), the shareholder uses the equivalent fixed rate debt instrument (within the...

2012-04-01

442

16 CFR 240.11 - Wholesaler or third party performance of seller's obligations.  

Code of Federal Regulations, 2010 CFR

...Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES FOR ADVERTISING ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.11 Wholesaler or third party performance of seller's obligations. A seller may...

2010-01-01

443

16 CFR 240.11 - Wholesaler or third party performance of seller's obligations.  

Code of Federal Regulations, 2011 CFR

...Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES FOR ADVERTISING ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.11 Wholesaler or third party performance of seller's obligations. A seller may...

2011-01-01

444

16 CFR 240.11 - Wholesaler or third party performance of seller's obligations.  

Code of Federal Regulations, 2012 CFR

...Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES FOR ADVERTISING ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.11 Wholesaler or third party performance of seller's obligations. A seller may...

2012-01-01

445

16 CFR 240.11 - Wholesaler or third party performance of seller's obligations.  

...Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES FOR ADVERTISING ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.11 Wholesaler or third party performance of seller's obligations. A seller may...

2014-01-01

446

16 CFR 240.11 - Wholesaler or third party performance of seller's obligations.  

Code of Federal Regulations, 2013 CFR

...Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES FOR ADVERTISING ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.11 Wholesaler or third party performance of seller's obligations. A seller may...

2013-01-01

447

26 CFR 1.662(a)-4 - Amounts used in discharge of a legal obligation.  

...Internal Revenue 8 2014-04-01 2014-04-01 false Amounts used in discharge of a legal obligation. 1.662(a)-4 Section 1.662(a)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY...

2014-04-01

448

47 CFR 24.253 - Termination of cost-sharing obligations.  

Code of Federal Regulations, 2011 CFR

...COMMISSION (CONTINUED) COMMON CARRIER SERVICES PERSONAL COMMUNICATIONS SERVICES Broadband PCS Policies Governing Microwave Relocation from the 1850-1990 Mhz Band § 24.253 Termination of cost-sharing obligations. The...

2011-10-01

449

7 CFR 984.66 - Assistance of the Board in meeting reserve obligation.  

Code of Federal Regulations, 2010 CFR

...Nuts), DEPARTMENT OF AGRICULTURE WALNUTS GROWN IN CALIFORNIA Order Regulating Handling Reserve Walnuts § 984.66 Assistance of the Board...obligation and may aid any handler in acquiring walnuts to meet any deficiency in his...

2010-01-01

450

49 CFR 374.109 - Carriers not relieved of existing obligations.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 2010-10-01 false Carriers not relieved of existing obligations...Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS PASSENGER...

2010-10-01

451

49 CFR 199.239 - Operator obligation to promulgate a policy on the misuse of alcohol.  

Code of Federal Regulations, 2010 CFR

...obligation to promulgate a policy on the misuse of alcohol. 199.239 Section 199.239 Transportation...TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.239...

2010-10-01

452

49 CFR 199.239 - Operator obligation to promulgate a policy on the misuse of alcohol.  

Code of Federal Regulations, 2012 CFR

...obligation to promulgate a policy on the misuse of alcohol. 199.239 Section 199.239 Transportation...TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.239...

2012-10-01

453

49 CFR 199.239 - Operator obligation to promulgate a policy on the misuse of alcohol.  

Code of Federal Regulations, 2011 CFR

...obligation to promulgate a policy on the misuse of alcohol. 199.239 Section 199.239 Transportation...TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.239...

2011-10-01

454

49 CFR 199.239 - Operator obligation to promulgate a policy on the misuse of alcohol.  

Code of Federal Regulations, 2013 CFR

...obligation to promulgate a policy on the misuse of alcohol. 199.239 Section 199.239 Transportation...TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.239...

2013-10-01

455

24 CFR 81.94 - Obligations of GSEs; no adverse claims.  

Code of Federal Regulations, 2011 CFR

...REGULATION OF THE FEDERAL NATIONAL MORTGAGE ASSOCIATION (FANNIE MAE) AND THE FEDERAL HOME LOAN MORTGAGE CORPORATION (FREDDIE MAC) Book-Entry Procedures § 81.94 Obligations of GSEs; no adverse claims. (a) Except in the case...

2011-04-01

456

24 CFR 81.94 - Obligations of GSEs; no adverse claims.  

Code of Federal Regulations, 2010 CFR

...REGULATION OF THE FEDERAL NATIONAL MORTGAGE ASSOCIATION (FANNIE MAE) AND THE FEDERAL HOME LOAN MORTGAGE CORPORATION (FREDDIE MAC) Book-Entry Procedures § 81.94 Obligations of GSEs; no adverse claims. (a) Except in the case...

2010-04-01

457

42 CFR 64a.105 - What are the conditions of obligated service?  

Code of Federal Regulations, 2011 CFR

...obligated service in accordance with the requirements...to repay the United States an amount equal...Secretary extends the repayment period as provided in paragraph...this section, the individual shall pay to the United States the total...

2011-10-01

458

42 CFR 64a.105 - What are the conditions of obligated service?  

Code of Federal Regulations, 2010 CFR

...obligated service in accordance with the requirements...to repay the United States an amount equal...Secretary extends the repayment period as provided in paragraph...this section, the individual shall pay to the United States the total...

2010-10-01

459

42 CFR 64a.105 - What are the conditions of obligated service?  

Code of Federal Regulations, 2012 CFR

...obligated service in accordance with the requirements...to repay the United States an amount equal...Secretary extends the repayment period as provided in paragraph...this section, the individual shall pay to the United States the total...

2012-10-01

460

42 CFR 64a.105 - What are the conditions of obligated service?  

Code of Federal Regulations, 2013 CFR

...obligated service in accordance with the requirements...to repay the United States an amount equal...Secretary extends the repayment period as provided in paragraph...this section, the individual shall pay to the United States the total...

2013-10-01

461

31 CFR 800.701 - Obligation of parties to provide information.  

Code of Federal Regulations, 2010 CFR

...Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS, AND TAKEOVERS BY FOREIGN PERSONS Provision and Handling of Information § 800.701 Obligation of...

2010-07-01

462

24 CFR 891.415 - Obligations of the household or family.  

Code of Federal Regulations, 2010 CFR

...HOUSING FOR THE ELDERLY AND PERSONS WITH DISABILITIES Project Management § 891.415 Obligations of the household or family...section 8 program. (Approved by the Office of Management and Budget under control number...

2010-04-01

463

Intracellular BKCa (iBKCa) channels  

PubMed Central

The large conductance calcium- and voltage-activated potassium channel (BKCa) is widely expressed at the plasma membrane. This channel is involved in a variety of fundamental cellular functions including excitability, smooth muscle contractility, and Ca2+ homeostasis, as well as in pathological situations like proinflammatory responses in rheumatoid arthritis, and cancer cell proliferation. Immunochemical, biochemical and pharmacological studies from over a decade have intermittently shown the presence of BKCa in intracellular organelles. To date, intracellular BKCa (iBKCa) has been localized in the mitochondria, endoplasmic reticulum, nucleus and Golgi apparatus but its functional role remains largely unknown except for the mitochondrial BKCa whose opening is thought to play a role in protecting the heart from ischaemic injury. In the nucleus, pharmacology suggests a role in regulating nuclear Ca2+, membrane potential and eNOS expression. Establishing the molecular correlates of iBKCa, the mechanisms defining iBKCa organelle-specific targeting, and their modulation are challenging questions. This review summarizes iBKCa channels, their possible functions, and efforts to identify their molecular correlates. PMID:22930268

Singh, Harpreet; Stefani, Enrico; Toro, Ligia

2012-01-01

464

Agent-based modeling of intracellular transport  

NASA Astrophysics Data System (ADS)

We develop an agent-based model of the motion and pattern formation of vesicles. These intracellular particles can be found in four different modes of (undirected and directed) motion and can fuse with other vesicles. While the size of vesicles follows a log-normal distribution that changes over time due to fusion processes, their spatial distribution gives rise to distinct patterns. Their occurrence depends on the concentration of proteins which are synthesized based on the transcriptional activities of some genes. Hence, differences in these spatio-temporal vesicle patterns allow indirect conclusions about the (unknown) impact of these genes. By means of agent-based computer simulations we are able to reproduce such patterns on real temporal and spatial scales. Our modeling approach is based on Brownian agents with an internal degree of freedom, ?, that represents the different modes of motion. Conditions inside the cell are modeled by an effective potential that differs for agents dependent on their value ?. Agent's motion in this effective potential is modeled by an overdampted Langevin equation, changes of ? are modeled as stochastic transitions with values obtained from experiments, and fusion events are modeled as space-dependent stochastic transitions. Our results for the spatio-temporal vesicle patterns can be used for a statistical comparison with experiments. We also derive hypotheses of how the silencing of some genes may affect the intracellular transport, and point to generalizations of the model.

Birbaumer, M.; Schweitzer, F.

2011-08-01

465

Stochastic models of intracellular calcium signals  

NASA Astrophysics Data System (ADS)

Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels-one of the most important cellular signaling mechanisms-feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction-diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker-Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed.

Rüdiger, Sten

2014-01-01

466

Bacterial Leaf Symbiosis in Angiosperms: Host Specificity without Co-Speciation  

PubMed Central

Bacterial leaf symbiosis is a unique and intimate interaction between bacteria and flowering plants, in which endosymbionts are organized in specialized leaf structures. Previously, bacterial leaf symbiosis has been described as a cyclic and obligate interaction in which the endosymbionts are vertically transmitted between plant generations and lack autonomous growth. Theoretically this allows for co-speciation between leaf nodulated plants and their endosymbionts. We sequenced the nodulated Burkholderia endosymbionts of 54 plant species from known leaf nodulated angiosperm genera, i.e. Ardisia, Pavetta, Psychotria and Sericanthe. Phylogenetic reconstruction of bacterial leaf symbionts and closely related free-living bacteria indicates the occurrence of multiple horizontal transfers of bacteria from the environment to leaf nodulated plant species. This rejects the hypothesis of a long co-speciation process between the bacterial endosymbionts and their host plants. Our results indicate a recent evolutionary process towards a stable and host specific interaction confirming the proposed maternal transmission mode of the endosymbionts through the seeds. Divergence estimates provide evidence for a relatively recent origin of bacterial leaf symbiosis, dating back to the Miocene (5–23 Mya). This geological epoch was characterized by cool and arid conditions, which may have triggered the origin of bacterial leaf symbiosis. PMID:21915326

Lemaire, Benny; Vandamme, Peter; Merckx, Vincent; Smets, Erik; Dessein, Steven

2011-01-01

467

[Bacterial diseases of rape].  

PubMed

Bacterial destruction of the culture was described and its agents identified in the spring and winter rape crops. Typical symptoms are the following: browning of stem tissue and its mucilagization, chlorosis of leaves, yellowing and beginning of soft rot in the place of leaf stalks affixion to stems, loss of pigmentation (violet). Pathogenic properties of the collection strains and morphological, cultural, physiological, and biochemical properties of the agents of rape's bacterial diseases isolated by the authors have been investigated. It was found that all the isolates selected by the authors are highly or moderately aggressive towards different varieties of rape. According to the complex of phenotypic properties 44% of the total number of isolates selected by the authors are related to representatives of the genus Pseudomonas, 37% - to Xanthomonas and 19% - to Pectobacterium. PMID:23293826

Zakharova, O M; Mel'nychuk, M D; Dankevych, L A; Patyka, V P

2012-01-01

468

Physics of Bacterial Morphogenesis  

PubMed Central

Summary: Bacterial cells utilize three-dimensional (3D) protein assemblies to perform important cellular functions such as growth, division, chemoreception, and motility. These assemblies are composed of mechanoproteins that can mechanically deform and exert force. Sometimes, small-nucleotide hydrolysis is coupled to mechanical deformations. In this review, we describe the general principle for an understanding of the coupling of mechanics with chemistry in mechanochemical systems. We apply this principle to understand bacterial cell shape and morphogenesis and how mechanical forces can influence peptidoglycan cell wall growth. We review a model that can potentially reconcile the growth dynamics of the cell wall with the role of cytoskeletal proteins such as MreB and crescentin. We also review the application of mechanochemical principles to understand the assembly and constriction of the FtsZ ring. A number of potential mechanisms are proposed, and important questions are discussed. PMID:22126993

Sun, Sean X.; Jiang, Hongyuan

2011-01-01

469

Local evolution of obligate autogamy in Epipactis helleborine subsp. neerlandica (Orchidaceae)  

Microsoft Academic Search

Isozyme analysis was used to assess the origin of the DanishEpipactis renzii, a local endemic of open coastal dunes. It seems to have evolved recently in several local populations of the more or less allogamousE. helleborine subsp.neerlandica. The obligately autogamousE. renzii is restricted to the easternmost part of the Danish range ofE. helleborine subsp.neerlandica, indicating that transition to obligate autogamy

H. Æ. Pedersen; B. K. Ehlers

2000-01-01

470

Immunoprophylaxis Against Bacterial Sepsis  

Microsoft Academic Search

Sepsis can be viewed as toxigenic illness resulting from the release of excess quantities of microbial-derived inflammatory mediators into the systemic circulation. Principal among these microbial mediators is bacterial endotoxin. Endotoxin is an essential component of the outer membrane of gram-negative bacteria. Humans are exquisitely susceptible to endotoxin-induced systemic inflammatory reactions that may prove to be rapidly fatal. Many gram-positive

Steven M. Opal; Alan S. Cross; Apurba K. Bhattacharjee; Kumar Visvanathan; John B. Zabriskie

1999-01-01

471

Analysis of Ten Brucella Genomes Reveals Evidence for Horizontal Gene Transfer Despite a Preferred Intracellular Lifestyle? §  

PubMed Central

The facultative intracellular bacterial pathogen Brucella infects a wide range of warm-blooded land and marine vertebrates and causes brucellosis. Currently, there are nine recognized Brucella species based on host preferences and phenotypic differences. The availability of 10 different genomes consisting of two chromosomes and representing six of the species allowed for a detailed comparison among themselves and relatives in the order Rhizobiales. Phylogenomic analysis of ortholog families shows limited divergence but distinct radiations, producing four clades as follows: Brucella abortus-Brucella melitensis, Brucella suis-Brucella canis, Brucella ovis, and Brucella ceti. In addition, Brucella phylogeny does not appear to reflect the phylogeny of Brucella species' preferred hosts. About 4.6% of protein-coding genes seem to be pseudogenes, which is a relatively large fraction. Only B. suis 1330 appears to have an intact ?-ketoadipate pathway, responsible for utilization of plant-derived compounds. In contrast, this pathway in the other species is highly pseudogenized and consistent with the “domino theory” of gene death. There are distinct shared anomalous regions (SARs) found in both chromosomes as the result of horizontal gene transfer unique to Brucella and not shared with its closest relative Ochrobactrum, a soil bacterium, suggesting their acquisition occurred in spite of a predominantly intracellular lifestyle. In particular, SAR 2-5 appears to have been acquired by Brucella after it became intracellular. The SARs contain many genes, including those involved in O-polysaccharide synthesis and type IV secretion, which if mutated or absent significantly affect the ability of Brucella to survive intracellularly in the infected host. PMID:19346311

Wattam, Alice R.; Williams, Kelly P.; Snyder, Eric E.; Almeida, Nalvo F.; Shukla, Maulik; Dickerman, A. W.; Crasta, O. R.; Kenyon, R.; Lu, J.; Shallom, J. M.; Yoo, H.; Ficht, T. A.; Tsolis, R. M.; Munk, C.; Tapia, R.; Han, C. S.; Detter, J. C.; Bruce, D.; Brettin, T. S.; Sobral, Bruno W.; Boyle, Stephen M.; Setubal, Joao C.

2009-01-01

472

Bacterial-Modulated Signaling Pathways in Gut Homeostasis  

NSDL National Science Digital Library

Symbiotic mutualism with gut microbes occurs in all metazoans, and it is well established that commensal bacteria influence multiple aspects of host gut physiology such as innate immunity and development. However, our understanding of these coevolved interactions between prokaryotes and eukaryotes remains unclear. One mechanism by which commensal bacteria modulate host intracellular signaling pathways in order to avoid excess inflammation has now been determined. In this process, bacterial-induced reactive oxygen species in gut epithelial cells act as key messengers that inhibit the cullin-1–dependent protein degradation machinery, which in turn results in the stabilization of a master negative regulator of inflammation, inhibitor of nuclear factor-κB (IκB). Furthermore, this bacterial-mediated system also appears to be involved in the stabilization of a key developmental regulator, β-catenin. These findings provide new insights into the molecular mechanisms by which commensal microbes shape host cellular physiology.

Won-Jae Lee (Seoul;Ewha Woman's University and National Creative Research Initiative Center for Symbiosystem REV)

2008-05-27

473

Extracellular and intracellular anti-mutagenic effects of bile pigments in the Salmonella typhimurium reverse mutation assay.  

PubMed

In vitro anti-genotoxic properties of bile pigments have been explored and confirmed recently. Despite these reports mechanisms to explain DNA protection by endogenous bile pigments remain unclear. Surprisingly, the quantification of cellular pigment absorption which could represent a fundamental prerequisite for intracellular (e.g., anti-mutagenic) effects, has not been explored. Therefore, we aimed to measure the amounts of un-/conjugated bilirubin as well as biliverdin absorbed into colonies of Salmonella typhimurium, utilising HPLC analyses, and to observe whether intracellular compound concentrations could predict anti-genotoxic effects. HPLC analyses confirmed that bacterial bile pigment absorption was concentration-dependent. Plate bile pigment concentrations were inversely associated with genotoxicity of all tested mutagens, irrespective of strain and test conditions. However, protection against frame-shift mutation in strain TA98 most strongly depended on the bacterial absorption of bilirubin and biliverdin, which indicates that bile pigments can protect by intercepting mutations extracellularly and specifically inhibit frame-shift mutations intracellularly. PMID:22906569

Mölzer, C; Huber, H; Diem, K; Wallner, M; Bulmer, A C; Wagner, K-H

2013-02-01

474

Extracellular and intracellular anti-mutagenic effects of bile pigments in the Salmonella typhimurium reverse mutation assay  

PubMed Central

In vitro anti-genotoxic properties of bile pigments have been explored and confirmed recently. Despite these reports mechanisms to explain DNA protection by endogenous bile pigments remain unclear. Surprisingly, the quantification of cellular pigment absorption which could represent a fundamental prerequisite for intracellular (e.g., anti-mutagenic) effects, has not been explored. Therefore, we aimed to measure the amounts of un-/conjugated bilirubin as well as biliverdin absorbed into colonies of Salmonella typhimurium, utilising HPLC analyses, and to observe whether intracellular compound concentrations could predict anti-genotoxic effects. HPLC analyses confirmed that bacterial bile pigment absorption was concentration-dependent. Plate bile pigment concentrations were inversely associated with genotoxicity of all tested mutagens, irrespective of strain and test conditions. However, protection against frame-shift mutation in strain TA98 most strongly depended on the bacterial absorption of bilirubin and biliverdin, which indicates that bile pigments can protect by intercepting mutations extracellularly and specifically inhibit frame-shift mutations intracellularly. PMID:22906569

Molzer, C.; Huber, H.; Diem, K.; Wallner, M.; Bulmer, A.C.; Wagner, K.-H.

2013-01-01

475

The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity  

PubMed Central

SUMMARY The physical nature of the bacterial cytoplasm is poorly understood even though it determines cytoplasmic dynamics and hence cellular physiology and behavior. Through single-particle tracking of protein filaments, plasmids, storage granules and foreign particles of different sizes, we find that the bacterial cytoplasm displays properties characteristic of glass-forming liquids and changes from liquid-like to solid-like in a component size-dependent fashion. As a result, the motion of cytoplasmic components becomes disproportionally constrained with increasing size. Remarkably, cellular metabolism fluidizes the cytoplasm, allowing larger components to escape their local environment and explore larger regions of the cytoplasm. Consequently, cytoplasmic fluidity and dynamics dramatically change as cells shift between metabolically active and dormant states in response to fluctuating environments. Our findings provide insight into bacterial dormancy and have broad implications to our understanding of bacterial physiology as the glassy behavior of the cytoplasm impacts all intracellular processes involving large components. PMID:24361104

Parry, Bradley R.; Surovtsev, Ivan V.; Cabeen, Matthew T.; O'Hern, Corey S.; Dufresne, Eric R.; Jacobs-Wagner, Christine

2014-01-01

476

Tracking bacterial pathogens with genetically-encoded reporters.  

PubMed

During the infectious process, bacterial pathogens are subject to changes in environmental conditions such as nutrient availability, immune response challenges, bacterial density and physical contacts with targeted host cells. These conditions occur in the colonized organs, in diverse regions within infected tissues or even at the subcellular level for intracellular pathogens. Integration of environmental cues leads to measurable biological responses in the bacterium required for adaptation. Recent progress in technology enabled the study of bacterial adaptation in situ using genetically encoded reporters that allow single cell analysis or whole body imaging based on fluorescent proteins, alternative fluorescent assays or luciferases. This review presents a historical perspective and technical details on the methods used to develop transcriptional reporters, protein-protein interaction assays and secretion detection assays to study pathogenic bacteria adaptation in situ. Finally, studies published in the last 5 years on gram positive and gram negative bacterial adaptation to the host during infection are discussed. However, the methods described here could easily be extended to study complex microbial communities within host tissue and in the environment. PMID:24859085

Campbell-Valois, F-X; Sansonetti, Philippe J

2014-08-01

477

Stomatobaculum longum gen. nov., sp. nov., an obligately anaerobic bacterium from the human oral cavity  

PubMed Central

A strictly anaerobic Gram-stain-variable but positive by structure, non-spore-forming bacterium designated Lachnospiraceae bacterium ACC2 strain DSM 24645T was isolated from human subgingival dental plaque. Bacterial cells were 4–40 µm long non-motile rods, often swollen and forming curved filaments up to 200 µm. Cells contained intracellular, poorly crystalline, nanometre-sized iron- and sulfur-rich particles. The micro-organism was able to grow on yeast extract, trypticase peptone, milk, some sugars and organic acids. The major metabolic end-products of glucose fermentation were butyrate, lactate, isovalerate and acetate. The growth temperature and pH ranges were 30–42 °C and 4.9–7.5, respectively. Major fatty acids were C14?:?0, C14?:?0 DMA (dimethyl aldehyde), C16?:?0, C16?:?1?7c DMA. The whole-cell hydrolysate contained meso-diaminopimelic acid, indicating peptidoglycan type A1?. The DNA G+C content was calculated to be 55.05 mol% from the whole-genome sequence and 55.3 mol% as determined by HPLC. There were no predicted genes responsible for biosynthesis of respiratory lipoquinones, mycolic acids and lipopolysaccharides. Genes associated with synthesis of teichoic and lipoteichoic acids, diaminopimelic acid, polar lipids and polyamines were present. According to the 16S rRNA gene sequence phylogeny, strain DSM 24645T formed, together with several uncultured oral clones, a separate branch within the family Lachnospiraceae, with the highest sequence similarity to the type strain of Moryella indoligenes at 94.2?%. Based on distinct phenotypic and genotypic characteristics, we suggest that strain DSM 24645T represents a novel species in a new genus, for which the name Stomatobaculum longum gen. nov., sp. nov. is proposed. The type strain of Stomatobaculum longum is DSM 24645T (?=?HM-480T; deposited in BEI Resources, an NIH collection managed by the ATCC). PMID:22843721

Muller, Paul; Panikov, Nicolai; Mandalakis, Manolis; Hohmann, Tine; Hazen, Amanda; Fowle, William; Prozorov, Tanya; Bazylinski, Dennis A.

2013-01-01

478

Intracellular light-activation of riboswitch activity.  

PubMed

By combining a riboswitch with a cell-permeable photocaged small-molecule ligand, an optochemical gene control element was constructed that enabled spatial and temporal control of gene expression in bacterial cells. The simplicity of this strategy, coupled with the ability to create synthetic riboswitches with tailored ligand specificities and output in a variety of microorganisms, plants, and fungi might afford a general strategy to photocontrol gene expression in vivo. The ability to activate riboswitches by using light enables the interrogation and manipulation of a wide range of biological processes with high precision, and will have broad utility in the regulation of artificial genetic circuits. PMID:24861567

Walsh, Steven; Gardner, Laura; Deiters, Alexander; Williams, Gavin J

2014-06-16

479

Hijacking of host cellular functions by an intracellular parasite, the microsporidian Anncaliia algerae.  

PubMed

Intracellular pathogens including bacteria, viruses and protozoa hijack host cell functions to access nutrients and to bypass cellular defenses and immune responses. These strategies have been acquired through selective pressure and allowed pathogens to reach an appropriate cellular niche for their survival and growth. To get new insights on how parasites hijack host cellular functions, we developed a SILAC (Stable Isotope Labeling by Amino Acids in Cell culture) quantitative proteomics workflow. Our study focused on deciphering the cross-talk in a host-parasite association, involving human foreskin fibroblasts (HFF) and the microsporidia Anncaliia algerae, a fungus related parasite with an obligate intracellular lifestyle and a strong host dependency. The host-parasite cross-talk was analyzed at five post-infection times 1, 6, 12 and 24 hours post-infection (hpi) and 8 days post-infection (dpi). A significant up-regulation of four interferon-induced proteins with tetratricopeptide repeats IFIT1, IFIT2, IFIT3 and MX1 was observed at 8 dpi suggesting a type 1 interferon (IFN) host response. Quantitative alteration of host proteins involved in biological functions such as signaling (STAT1, Ras) and reduction of the translation activity (EIF3) confirmed a host type 1 IFN response. Interestingly, the SILAC approach also allowed the detection of 148 A. algerae proteins during the kinetics of infection. Among these proteins many are involved in parasite proliferation, and an over-representation of putative secreted effectors proteins was observed. Finally our survey also suggests that A. algerae could use a transposable element as a lure strategy to escape the host innate immune system. PMID:24967735

Panek, Johan; El Alaoui, Hicham; Mone, Anne; Urbach, Serge; Demettre, Edith; Texier, Catherine; Brun, Christine; Zanzoni, Andreas; Peyretaillade, Eric; Parisot, Nicolas; Lerat, Emmanuelle; Peyret, Pierre; Delbac, Frederic; Biron, David G

2014-01-01

480

Hijacking of Host Cellular Functions by an Intracellular Parasite, the Microsporidian Anncaliia algerae  

PubMed Central

Intracellular pathogens including bacteria, viruses and protozoa hijack host cell functions to access nutrients and to bypass cellular defenses and immune responses. These strategies have been acquired through selective pressure and allowed pathogens to reach an appropriate cellular niche for their survival and growth. To get new insights on how parasites hijack host cellular functions, we developed a SILAC (Stable Isotope Labeling by Amino Acids in Cell culture) quantitative proteomics workflow. Our study focused on deciphering the cross-talk in a host-parasite association, involving human foreskin fibroblasts (HFF) and the microsporidia Anncaliia algerae, a fungus related parasite with an obligate intracellular lifestyle and a strong host dependency. The host-parasite cross-talk was analyzed at five post-infection times 1, 6, 12 and 24 hours post-infection (hpi) and 8 days post-infection (dpi). A significant up-regulation of four interferon-induced proteins with tetratricopeptide repeats IFIT1, IFIT2, IFIT3 and MX1 was observed at 8 dpi suggesting a type 1 interferon (IFN) host response. Quantitative alteration of host proteins involved in biological functions such as signaling (STAT1, Ras) and reduction of the translation activity (EIF3) confirmed a host type 1 IFN response. Interestingly, the SILAC approach also allowed the detection of 148 A. algerae proteins during the kinetics of infection. Among these proteins many are involved in parasite proliferation, and an over-representation of putative secreted effectors proteins was observed. Finally our survey also suggests that A. algerae could use a transposable element as a lure strategy to escape the host innate immune system. PMID:24967735

Panek, Johan; El Alaoui, Hicham; Mone, Anne; Urbach, Serge; Demettre, Edith; Texier, Catherine; Brun, Christine; Zanzoni, Andreas; Peyretaillade, Eric; Parisot, Nicolas; Lerat, Emmanuelle; Peyret, Pierre; Delbac, Frederic; Biron, David G.

2014-01-01