Sample records for obligate intracellular life

  1. Engineering of obligate intracellular bacteria: progress, challenges and paradigms

    USDA-ARS?s Scientific Manuscript database

    Over twenty years have passed since the first report of genetic manipulation of an obligate intracellular bacterium. Through progress interspersed by bouts of stagnation, microbiologists and geneticists have developed approaches to genetically manipulate obligates. A brief overview of the current ge...

  2. Secretome of obligate intracellular Rickettsia

    PubMed Central

    Gillespie, Joseph J.; Kaur, Simran J.; Rahman, M. Sayeedur; Rennoll-Bankert, Kristen; Sears, Khandra T.; Beier-Sexton, Magda; Azad, Abdu F.

    2014-01-01

    The genus Rickettsia (Alphaproteobacteria, Rickettsiales, Rickettsiaceae) is comprised of obligate intracellular parasites, with virulent species of interest both as causes of emerging infectious diseases and for their potential deployment as bioterrorism agents. Currently, there are no effective commercially available vaccines, with treatment limited primarily to tetracycline antibiotics, although others (e.g. josamycin, ciprofloxacin, chloramphenicol, and azithromycin) are also effective. Much of the recent research geared toward understanding mechanisms underlying rickettsial pathogenicity has centered on characterization of secreted proteins that directly engage eukaryotic cells. Herein, we review all aspects of the Rickettsia secretome, including six secretion systems, 19 characterized secretory proteins, and potential moonlighting proteins identified on surfaces of multiple Rickettsia species. Employing bioinformatics and phylogenomics, we present novel structural and functional insight on each secretion system. Unexpectedly, our investigation revealed that the majority of characterized secretory proteins have not been assigned to their cognate secretion pathways. Furthermore, for most secretion pathways, the requisite signal sequences mediating translocation are poorly understood. As a blueprint for all known routes of protein translocation into host cells, this resource will assist research aimed at uniting characterized secreted proteins with their apposite secretion pathways. Furthermore, our work will help in the identification of novel secreted proteins involved in rickettsial ‘life on the inside’. PMID:25168200

  3. Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth

    USDA-ARS?s Scientific Manuscript database

    Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungalrelated 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...

  4. Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites

    PubMed Central

    Woo, Yong H; Ansari, Hifzur; Otto, Thomas D; Klinger, Christen M; Kolisko, Martin; Michálek, Jan; Saxena, Alka; Shanmugam, Dhanasekaran; Tayyrov, Annageldi; Veluchamy, Alaguraj; Ali, Shahjahan; Bernal, Axel; del Campo, Javier; Cihlář, Jaromír; Flegontov, Pavel; Gornik, Sebastian G; Hajdušková, Eva; Horák, Aleš; Janouškovec, Jan; Katris, Nicholas J; Mast, Fred D; Miranda-Saavedra, Diego; Mourier, Tobias; Naeem, Raeece; Nair, Mridul; Panigrahi, Aswini K; Rawlings, Neil D; Padron-Regalado, Eriko; Ramaprasad, Abhinay; Samad, Nadira; Tomčala, Aleš; Wilkes, Jon; Neafsey, Daniel E; Doerig, Christian; Bowler, Chris; Keeling, Patrick J; Roos, David S; Dacks, Joel B; Templeton, Thomas J; Waller, Ross F; Lukeš, Julius; Oborník, Miroslav; Pain, Arnab

    2015-01-01

    The eukaryotic phylum Apicomplexa encompasses thousands of obligate intracellular parasites of humans and animals with immense socio-economic and health impacts. We sequenced nuclear genomes of Chromera velia and Vitrella brassicaformis, free-living non-parasitic photosynthetic algae closely related to apicomplexans. Proteins from key metabolic pathways and from the endomembrane trafficking systems associated with a free-living lifestyle have been progressively and non-randomly lost during adaptation to parasitism. The free-living ancestor contained a broad repertoire of genes many of which were repurposed for parasitic processes, such as extracellular proteins, components of a motility apparatus, and DNA- and RNA-binding protein families. Based on transcriptome analyses across 36 environmental conditions, Chromera orthologs of apicomplexan invasion-related motility genes were co-regulated with genes encoding the flagellar apparatus, supporting the functional contribution of flagella to the evolution of invasion machinery. This study provides insights into how obligate parasites with diverse life strategies arose from a once free-living phototrophic marine alga. DOI: http://dx.doi.org/10.7554/eLife.06974.001 PMID:26175406

  5. Economic Game Theory to Model the Attenuation of Virulence of an Obligate Intracellular Bacterium.

    PubMed

    Tago, Damian; Meyer, Damien F

    2016-01-01

    Diseases induced by obligate intracellular pathogens have a large burden on global human and animal health. Understanding the factors involved in the virulence and fitness of these pathogens contributes to the development of control strategies against these diseases. Based on biological observations, a theoretical model using game theory is proposed to explain how obligate intracellular bacteria interact with their host. The equilibrium in such a game shows that the virulence and fitness of the bacterium is host-triggered and by changing the host's defense system to which the bacterium is confronted, an evolutionary process leads to an attenuated strain. Although, the attenuation procedure has already been conducted in practice in order to develop an attenuated vaccine (e.g., with Ehrlichia ruminantium), there was a lack of understanding of the theoretical basis behind this process. Our work provides a model to better comprehend the existence of different phenotypes and some underlying evolutionary mechanisms for the virulence of obligate intracellular bacteria.

  6. Economic Game Theory to Model the Attenuation of Virulence of an Obligate Intracellular Bacterium

    PubMed Central

    Tago, Damian; Meyer, Damien F.

    2016-01-01

    Diseases induced by obligate intracellular pathogens have a large burden on global human and animal health. Understanding the factors involved in the virulence and fitness of these pathogens contributes to the development of control strategies against these diseases. Based on biological observations, a theoretical model using game theory is proposed to explain how obligate intracellular bacteria interact with their host. The equilibrium in such a game shows that the virulence and fitness of the bacterium is host-triggered and by changing the host's defense system to which the bacterium is confronted, an evolutionary process leads to an attenuated strain. Although, the attenuation procedure has already been conducted in practice in order to develop an attenuated vaccine (e.g., with Ehrlichia ruminantium), there was a lack of understanding of the theoretical basis behind this process. Our work provides a model to better comprehend the existence of different phenotypes and some underlying evolutionary mechanisms for the virulence of obligate intracellular bacteria. PMID:27610355

  7. Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites.

    PubMed

    Woo, Yong H; Ansari, Hifzur; Otto, Thomas D; Klinger, Christen M; Kolisko, Martin; Michálek, Jan; Saxena, Alka; Shanmugam, Dhanasekaran; Tayyrov, Annageldi; Veluchamy, Alaguraj; Ali, Shahjahan; Bernal, Axel; del Campo, Javier; Cihlář, Jaromír; Flegontov, Pavel; Gornik, Sebastian G; Hajdušková, Eva; Horák, Aleš; Janouškovec, Jan; Katris, Nicholas J; Mast, Fred D; Miranda-Saavedra, Diego; Mourier, Tobias; Naeem, Raeece; Nair, Mridul; Panigrahi, Aswini K; Rawlings, Neil D; Padron-Regalado, Eriko; Ramaprasad, Abhinay; Samad, Nadira; Tomčala, Aleš; Wilkes, Jon; Neafsey, Daniel E; Doerig, Christian; Bowler, Chris; Keeling, Patrick J; Roos, David S; Dacks, Joel B; Templeton, Thomas J; Waller, Ross F; Lukeš, Julius; Oborník, Miroslav; Pain, Arnab

    2015-07-15

    The eukaryotic phylum Apicomplexa encompasses thousands of obligate intracellular parasites of humans and animals with immense socio-economic and health impacts. We sequenced nuclear genomes of Chromera velia and Vitrella brassicaformis, free-living non-parasitic photosynthetic algae closely related to apicomplexans. Proteins from key metabolic pathways and from the endomembrane trafficking systems associated with a free-living lifestyle have been progressively and non-randomly lost during adaptation to parasitism. The free-living ancestor contained a broad repertoire of genes many of which were repurposed for parasitic processes, such as extracellular proteins, components of a motility apparatus, and DNA- and RNA-binding protein families. Based on transcriptome analyses across 36 environmental conditions, Chromera orthologs of apicomplexan invasion-related motility genes were co-regulated with genes encoding the flagellar apparatus, supporting the functional contribution of flagella to the evolution of invasion machinery. This study provides insights into how obligate parasites with diverse life strategies arose from a once free-living phototrophic marine alga.

  8. Obligate intracellular bacterium Ehrlichia inhibiting mitochondrial activity

    PubMed Central

    Liu, Yan; Zhang, Zhikai; Jiang, Yongquan; Zhang, Lihong; Popov, Vsevolod L.; Zhang, Jianzhi; Walker, David H.; Yu, Xue-jie

    2010-01-01

    Ehrlichia are obligately intracellular bacteria that reside in a vacuole in the cytoplasm of phagocytes. We determined by confocal microscopy the interaction between Ehrlichia and mitochondria in DH82 cells to investigate the mechanism of Ehrlichia survival inside the phagocyte. The most remarkable finding of our study was that Ehrlichia morulae interacted with mitochondria and inhibited mitochondrial metabolism,. We showed that in E. chaffeensis-infected DH82 cells, mitochondria did not incorporate BrdU and transcriptional level of the mitochondrial gene NADPH2 was significantly reduced, indicating the inhibition of mitochondrial metabolism. This study demonstrates that Ehrlichia are able to inhibit mitochondrial activities, and it opens up a new avenue for the study of Ehrlichia pathogenesis. PMID:21070861

  9. Rickettsia Phylogenomics: Unwinding the Intricacies of Obligate Intracellular Life

    PubMed Central

    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

    Background Completed genome sequences are rapidly increasing for Rickettsia, obligate intracellular α-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

  10. Metabolic interdependence of obligate intracellular bacteria and their insect hosts.

    PubMed

    Zientz, Evelyn; Dandekar, Thomas; Gross, Roy

    2004-12-01

    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.

  11. Use of flow cytometry and PCR analysis to detect 5-carboxyfluoroscein-stained obligate intracellular bacteria Lawsonia intracellularis invasion of McCoy cells.

    PubMed

    Obradovic, Milan; Pasternak, J Alex; Ng, Siew Hon; Wilson, Heather L

    2016-07-01

    In this study, we describe a method to quantify invasion of obligate intracellular bacteria, Lawsonia intracellularis, inside McCoy cells. In immunological research, the cell-permeable fluorescent dye 5'-carboxyfluoroscein succidyl ester (CFSE) is commonly used to quantify eukaryotic cellular proliferation. Instead of using it in this traditional way, we stained L. intracellularis with CFSE dye prior to infection of McCoy cells. Flow cytometry was performed to quantify the percentage of eukaryotic cells which had taken up or were associated with fluorescent bacteria. As obligate intracellular bacteria, they cannot replicate outside of eukaryotic cells and thus qPCR analysis was used to quantify bacterial growth. Indirectly, PCR analysis confirmed invasion rather than adherence to the McCoy cell surface. Fluorescent activated cell sorting (FACS) was used to sort the CFSE(+) (i.e. infected) McCoy cells from the CFSE(-) (i.e. non-infected) McCoy cells and confocal microscopy was used to confirm bacterial invasion and cytosolic localization of CFSE-L. intracellularis. To show that this approach could be used in conjunction with functional assays, we investigated the effect that serum antibodies had on CFSE-bacterial invasion and growth. Instead of blocking invasion, rabbit hyperimmune serum augmented invasion of the bacteria inside McCoy cells and qPCR analysis confirmed bacterial growth over the course of 5days. We conclude that CFSE-labeling of bacteria and qPCR can be used to track and quantify bacterial invasion and may be a valuable tool for studying the invasive properties of bacteria, especially if commercial antibodies are not available. This approach may be adapted for use in other obligate intracellular bacteria and intracellular pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed Central

    2009-01-01

    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 and is present in Sub-Saharan Africa and the Caribbean islands. Because of its strictly intracellular location, which constitutes a limitation for its extensive study, the molecular mechanisms involved in its pathogenicity are still poorly understood. Results We successfully adapted the SCOTS method (Selective Capture of Transcribed Sequences) on the model Rickettsiales ER to capture mRNAs. Southern Blots and RT-PCR revealed an enrichment of ER's cDNAs and a diminution of ribosomal contaminants after three rounds of capture. qRT-PCR and whole-genome ER microarrays hybridizations demonstrated that SCOTS method introduced only a limited bias on gene expression. Indeed, we confirmed the differential gene expression between poorly and highly expressed genes before and after SCOTS captures. The comparative gene expression obtained from ER microarrays data, on samples before and after SCOTS at 96 hpi was significantly correlated (R2 = 0.7). Moreover, SCOTS method is crucial for microarrays analysis of ER, especially for early time points post-infection. There was low detection of transcripts for untreated samples whereas 24% and 70.7% were revealed for SCOTS samples at 24 and 96 hpi respectively. Conclusions We conclude that this SCOTS method has a key importance for the transcriptomic analysis of ER and can be potentially used for other Rickettsiales. This study constitutes the first step for further gene expression analyses that will lead to a better understanding of both ER pathogenicity and the adaptation of obligate intracellular

  13. The Genome of the Obligate Intracellular Parasite Trachipleistophora hominis: New Insights into Microsporidian Genome Dynamics and Reductive Evolution

    PubMed Central

    Heinz, Eva; Williams, Tom A.; Nakjang, Sirintra; Noël, Christophe J.; Swan, Daniel C.; Goldberg, Alina V.; Harris, Simon R.; Weinmaier, Thomas; Markert, Stephanie; Becher, Dörte; Bernhardt, Jörg; Dagan, Tal; Hacker, Christian; Lucocq, John M.; Schweder, Thomas; Rattei, Thomas; Hall, Neil; Hirt, Robert P.; Embley, T. Martin

    2012-01-01

    The dynamics of reductive genome evolution for eukaryotes living inside other eukaryotic cells are poorly understood compared to well-studied model systems involving obligate intracellular bacteria. Here we present 8.5 Mb of sequence from the genome of the microsporidian Trachipleistophora hominis, isolated from an HIV/AIDS patient, which is an outgroup to the smaller compacted-genome species that primarily inform ideas of evolutionary mode for these enormously successful obligate intracellular parasites. Our data provide detailed information on the gene content, genome architecture and intergenic regions of a larger microsporidian genome, while comparative analyses allowed us to infer genomic features and metabolism of the common ancestor of the species investigated. Gene length reduction and massive loss of metabolic capacity in the common ancestor was accompanied by the evolution of novel microsporidian-specific protein families, whose conservation among microsporidians, against a background of reductive evolution, suggests they may have important functions in their parasitic lifestyle. The ancestor had already lost many metabolic pathways but retained glycolysis and the pentose phosphate pathway to provide cytosolic ATP and reduced coenzymes, and it had a minimal mitochondrion (mitosome) making Fe-S clusters but not ATP. It possessed bacterial-like nucleotide transport proteins as a key innovation for stealing host-generated ATP, the machinery for RNAi, key elements of the early secretory pathway, canonical eukaryotic as well as microsporidian-specific regulatory elements, a diversity of repetitive and transposable elements, and relatively low average gene density. Microsporidian genome evolution thus appears to have proceeded in at least two major steps: an ancestral remodelling of the proteome upon transition to intracellular parasitism that involved reduction but also selective expansion, followed by a secondary compaction of genome architecture in some, but

  14. 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 Central

    Manzano-Marín, Alejandro; Latorre, Amparo

    2014-01-01

    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

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mavromatis, K.; Kuyler Doyle, C.; Lykidis, A.

    2005-09-01

    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 familiesmore » 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).« less

  16. The Intracellular Life of Cryptococcus neoformans

    PubMed Central

    Coelho, Carolina; Bocca, Anamelia L.; Casadevall, Arturo

    2016-01-01

    Cryptococcus neoformans is a fungal pathogen with worldwide distribution. Serological studies of human populations show a high prevalence of human infection, which rarely progresses to disease in immunocompetent hosts. However, decreased host immunity places individuals at high risk for cryptococcal disease. The disease can result from acute infection or reactivation of latent infection, in which yeasts within granulomas and host macrophages emerge to cause disease. In this review, we summarize what is known about the cellular recognition, ingestion, and killing of C. neoformans and discuss the unique and remarkable features of its intracellular life, including the proposed mechanisms for fungal persistence and killing in phagocytic cells. PMID:24050625

  17. Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen

    PubMed Central

    Bastidas, Robert J.

    2016-01-01

    SUMMARY Chlamydia species infect millions of individuals worldwide and are important etiological agents of sexually transmitted disease, infertility, and blinding trachoma. Historically, the genetic intractability of this intracellular pathogen has hindered the molecular dissection of virulence factors contributing to its pathogenesis. The obligate intracellular life cycle of Chlamydia and restrictions on the use of antibiotics as selectable markers have impeded the development of molecular tools to genetically manipulate these pathogens. However, recent developments in the field have resulted in significant gains in our ability to alter the genome of Chlamydia, which will expedite the elucidation of virulence mechanisms. In this review, we discuss the challenges affecting the development of molecular genetic tools for Chlamydia and the work that laid the foundation for recent advancements in the genetic analysis of this recalcitrant pathogen. PMID:27030552

  18. Impact of micro-environmental changes on respiratory tract infections with intracellular bacteria.

    PubMed

    Shima, Kensuke; Coopmeiners, Jonas; Graspeuntner, Simon; Dalhoff, Klaus; Rupp, Jan

    2016-11-01

    Community-acquired pneumonia is caused by intra- and extracellular bacteria, with some of these bacteria also being linked to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease. Chlamydia pneumoniae is an obligate intracellular pathogen that is highly sensitive to micro-environmental conditions controlling both pathogen growth and host immune responses. The availability of nutrients, as well as changes in oxygen, pH and interferon-γ levels, have been shown to directly influence the chlamydial life cycle and clearance. Although the lung has been traditionally regarded as a sterile environment, sequencing approaches have enabled the identification of a large number of bacteria in healthy and diseased lungs. The influence of the lung microbiota on respiratory infections has not been extensively studied so far and data on chlamydial infections are currently unavailable. In the present study, we speculate on how lung microbiota might interfere with acute and chronic infections by focusing exemplarily on the obligate intracellular C. pneumoniae. Furthermore, we consider changes in the gut microbiota as an additional player in the control of lung infections, especially in view the increasing evidence suggesting the involvement of the gut microbiota in various immunological processes throughout the human body. © 2016 Federation of European Biochemical Societies.

  19. Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen.

    PubMed

    Bastidas, Robert J; Valdivia, Raphael H

    2016-06-01

    Chlamydia species infect millions of individuals worldwide and are important etiological agents of sexually transmitted disease, infertility, and blinding trachoma. Historically, the genetic intractability of this intracellular pathogen has hindered the molecular dissection of virulence factors contributing to its pathogenesis. The obligate intracellular life cycle of Chlamydia and restrictions on the use of antibiotics as selectable markers have impeded the development of molecular tools to genetically manipulate these pathogens. However, recent developments in the field have resulted in significant gains in our ability to alter the genome of Chlamydia, which will expedite the elucidation of virulence mechanisms. In this review, we discuss the challenges affecting the development of molecular genetic tools for Chlamydia and the work that laid the foundation for recent advancements in the genetic analysis of this recalcitrant pathogen. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  20. Monoclonal Antibodies to Intracellular Stages of Cryptosporidium parvum Define Life Cycle Progression In Vitro.

    PubMed

    Wilke, Georgia; Ravindran, Soumya; Funkhouser-Jones, Lisa; Barks, Jennifer; Wang, Qiuling; VanDussen, Kelli L; Stappenbeck, Thaddeus S; Kuhlenschmidt, Theresa B; Kuhlenschmidt, Mark S; Sibley, L David

    2018-06-27

    Among the obstacles hindering Cryptosporidium research is the lack of an in vitro culture system that supports complete life development and propagation. This major barrier has led to a shortage of widely available anti- Cryptosporidium antibodies and a lack of markers for staging developmental progression. Previously developed antibodies against Cryptosporidium were raised against extracellular stages or recombinant proteins, leading to antibodies with limited reactivity across the parasite life cycle. Here we sought to create antibodies that recognize novel epitopes that could be used to define intracellular development. We identified a mouse epithelial cell line that supported C. parvum growth, enabling immunization of mice with infected cells to create a bank of monoclonal antibodies (MAbs) against intracellular parasite stages while avoiding the development of host-specific antibodies. From this bank, we identified 12 antibodies with a range of reactivities across the parasite life cycle. Importantly, we identified specific MAbs that can distinguish different life cycle stages, such as trophozoites, merozoites, type I versus II meronts, and macrogamonts. These MAbs provide valuable tools for the Cryptosporidium research community and will facilitate future investigation into parasite biology. IMPORTANCE Cryptosporidium is a protozoan parasite that causes gastrointestinal disease in humans and animals. Currently, there is a limited array of antibodies available against the parasite, which hinders imaging studies and makes it difficult to visualize the parasite life cycle in different culture systems. In order to alleviate this reagent gap, we created a library of novel antibodies against the intracellular life cycle stages of Cryptosporidium We identified antibodies that recognize specific life cycle stages in distinctive ways, enabling unambiguous description of the parasite life cycle. These MAbs will aid future investigation into Cryptosporidium biology and

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mavromatis, K; Doyle, C Kuyler; Lykidis, A

    2006-01-01

    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 associatedmore » 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).« less

  2. Life-Long Learning and Social Responsibility Obligations

    ERIC Educational Resources Information Center

    Mayes, Robin

    2013-01-01

    The literature affirms that widespread lapses in corporate social responsibility obligations (unethical behaviors) have periodically brought about extensive forfeitures of economic wealth and countless job losses leaving the world economy in recession or depression. Put forth as a resolution to unemployment issues the academic literature champions…

  3. Discovery and Complete Genome Sequence of a Bacteriophage from an Obligate Intracellular Symbiont of a Cellulolytic Protist in the Termite Gut

    PubMed Central

    Pramono, Ajeng K.; Kuwahara, Hirokazu; Itoh, Takehiko; Toyoda, Atsushi; Yamada, Akinori; Hongoh, Yuichi

    2017-01-01

    Termites depend nutritionally on their gut microbes, and protistan, bacterial, and archaeal gut communities have been extensively studied. However, limited information is available on viruses in the termite gut. We herein report the complete genome sequence (99,517 bp) of a phage obtained during a genome analysis of “Candidatus Azobacteroides pseudotrichonymphae” phylotype ProJPt-1, which is an obligate intracellular symbiont of the cellulolytic protist Pseudotrichonympha sp. in the gut of the termite Prorhinotermes japonicus. The genome of the phage, designated ProJPt-Bp1, was circular or circularly permuted, and was not integrated into the two circular chromosomes or five circular plasmids composing the host ProJPt-1 genome. The phage was putatively affiliated with the order Caudovirales based on sequence similarities with several phage-related genes; however, most of the 52 protein-coding sequences had no significant homology to sequences in the databases. The phage genome contained a tRNA-Gln (CAG) gene, which showed the highest sequence similarity to the tRNA-Gln (CAA) gene of the host “Ca. A. pseudotrichonymphae” phylotype ProJPt-1. Since the host genome lacked a tRNA-Gln (CAG) gene, the phage tRNA gene may compensate for differences in codon usage bias between the phage and host genomes. The phage genome also contained a non-coding region with high nucleotide sequence similarity to a region in one of the host plasmids. No other phage-related sequences were found in the host ProJPt-1 genome. To the best of our knowledge, this is the first report of a phage from an obligate, mutualistic endosymbiont permanently associated with eukaryotic cells. PMID:28321010

  4. Patients' ethical obligation for their health.

    PubMed Central

    Sider, R C; Clements, C D

    1984-01-01

    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

  5. Value, obligation and the asymmetry question.

    PubMed

    Tooley, Michael

    1998-04-01

    Is there a prima facie obligation to produce additional individuals whose lives would be worth living? In his paper 'Is it good to make happy people?', Stuart Rachels argues not only that there is, but, also, that precisely as much weight should be assigned to the quality of life that would be enjoyed by such potential persons, if they were to be actualized, as to the quality of life enjoyed by actually existing persons. In response, I shall argue, first, that Rachels' view is exposed to very serious objections, and secondly, that his arguments in support of his position involve a crucial assumption, which cannot be sustained, concerning the relation between, on the one hand, propositions about good-making and bad-making properties, and, on the other, propositions about right-making and wrong-making ones. I shall then argue that there is a very plausible position concerning the conditions under which an action can be morally wrong which entails the following asymmetry: there is a prima facie obligation not to bring into existence individuals whose lives are not worth living, but there is no corresponding obligation to create additional individuals whose lives would be worth living.

  6. Felt Obligation to Help Others as a Protective Factor Against Losses in Psychological Well-being Following Functional Decline in Middle and Later Life

    PubMed Central

    2009-01-01

    This study examined felt obligation to help others in two domains (close others and society) as protective factors against losses in psychological well-being following functional decline. Lagged-dependent regression models were estimated using data from 849 respondents aged 35–74 years and without any functional limitations at baseline in the 1995–2005 National Survey of Midlife in the United States. Greater felt obligation to help close others protected against declining self-acceptance in the face of more severe functional decline, and greater felt obligation to help society protected against declining personal growth and self-acceptance. Greater felt obligation to help close others and society protected against increasing depressive symptoms at younger ages in adulthood. Findings suggest the importance for additional research on how aspects of altruism can promote psychological adaptation to declining functional health in middle and later life. PMID:19825942

  7. Biological macromolecules based targeted nanodrug delivery systems for the treatment of intracellular infections.

    PubMed

    Aparna, V; Shiva, M; Biswas, Raja; Jayakumar, R

    2018-04-15

    Intracellular infections are tricky to treat, the reason being the poor penetration of antibiotics/antimycotics into the microbial niche (host cell). Macrophages are primary targets of facultative and obligate intracellular bacteria/fungi to be abused as host cells. The need for drugs with better intracellular penetration led to the development of endocytosable drug carriers, which can cross the cell membrane of the host cells (macrophages) by imitating the entry path of the pathogens. Therefore, the drugs can be targeted to macrophages ensuring enhanced therapeutic effect. This review discusses the exploitation of various nanocarriers for targeted delivery of drugs to the macrophages in the last two decades. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Obliging children.

    PubMed

    Lyons, Barry

    2011-01-01

    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.

  9. Ethical obligations and clinical goals in end-of-life care: deriving a quality-of-life construct based on the Islamic concept of accountability before God (taklīf).

    PubMed

    Padela, Aasim; Mohiuddin, Afshan

    2015-01-01

    End-of-life medical decision making presents a major challenge to patients and physicians alike. In order to determine whether it is ethically justifiable to forgo medical treatment in such scenarios, clinical data must be interpreted alongside patient values, as well as in light of the physician's ethical commitments. Though much has been written about this ethical issue from religious perspectives (especially Christian and Jewish), little work has been done from an Islamic point of view. To fill the gap in the literature around Islamic bioethical perspectives on the matter, we derive a theologically rooted rubric for goals of care. We use the Islamic obligation for Muslims to seek medical treatment as the foundation for determining the clinical conditions under which Muslim physicians have a duty to treat. We next link the theological concept of accountability before God (taklīf) to quality-of-life assessment. Using this construct, we suggest that a Muslim physician is not obligated to maintain or continue clinical treatment when patients who were formerly of, or had the potential to be, mukallaf (the term for a person who has taklīf), are now not expected to regain that status by means of continued clinical treatment.

  10. Mi Casa es Su Casa: how an intracellular symbiont manipulates host biology.

    PubMed

    Bhattacharya, Tamanash; Newton, Irene L G

    2017-10-27

    Wolbachia pipientis, the most common intracellular infection on the planet, infects 40% of insects as well as nematodes, isopods and arachnids. Wolbachia are obligately intracellular and challenging to study; there are no genetic tools for manipulating Wolbachia nor can they be cultured outside of host cells. Despite these roadblocks, the research community has defined a set of Wolbachia loci involved in host interaction: Wolbachia effectors. Through the use of Drosophila genetics, surrogate systems and biochemistry, the field has begun to define the toolkit Wolbachia use for host manipulation. Below we review recent findings identifying these Wolbachia effectors and point to potential, as yet uncharacterized, links between known phenotypes induced by Wolbachia infection and predicted effectors. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  11. Comparative Genomics of Serratia spp.: Two Paths towards Endosymbiotic Life

    PubMed Central

    Manzano-Marín, Alejandro; Lamelas, Araceli; Moya, Andrés; Latorre, Amparo

    2012-01-01

    Symbiosis is a widespread phenomenon in nature, in which insects show a great number of these associations. Buchnera aphidicola, the obligate endosymbiont of aphids, coexists in some species with another intracellular bacterium, Serratia symbiotica. Of particular interest is the case of the cedar aphid Cinara cedri, where B. aphidicola BCc and S. symbiotica SCc need each other to fulfil their symbiotic role with the insect. Moreover, various features seem to indicate that S. symbiotica SCc is closer to an obligate endosymbiont than to other facultative S. symbiotica, such as the one described for the aphid Acirthosyphon pisum (S. symbiotica SAp). This work is based on the comparative genomics of five strains of Serratia, three free-living and two endosymbiotic ones (one facultative and one obligate) which should allow us to dissect the genome reduction taking place in the adaptive process to an intracellular life-style. Using a pan-genome approach, we have identified shared and strain-specific genes from both endosymbiotic strains and gained insight into the different genetic reduction both S. symbiotica have undergone. We have identified both retained and reduced functional categories in S. symbiotica compared to the Free-Living Serratia (FLS) that seem to be related with its endosymbiotic role in their specific host-symbiont systems. By means of a phylogenomic reconstruction we have solved the position of both endosymbionts with confidence, established the probable insect-pathogen origin of the symbiotic clade as well as the high amino-acid substitution rate in S. symbiotica SCc. Finally, we were able to quantify the minimal number of rearrangements suffered in the endosymbiotic lineages and reconstruct a minimal rearrangement phylogeny. All these findings provide important evidence for the existence of at least two distinctive S. symbiotica lineages that are characterized by different rearrangements, gene content, genome size and branch lengths. PMID:23077583

  12. Family obligation values as a protective and vulnerability factor among low-income adolescent girls.

    PubMed

    Milan, Stephanie; Wortel, Sanne

    2015-06-01

    Adolescents' beliefs about family obligation often reflect cultural variations in their family context, and thus are important for understanding development among diverse youth. In this study, we test hypotheses about the role of family obligation values in risk behavior and mental health in a sample of 194 low-income adolescent girls (mean age = 15.2; 58% Latina, 28% African-American/Black). We hypothesized that family obligation values can be both a protective and vulnerability factor, depending on the type of outcome and the presence of other risk factors. Across the sample, higher family obligation values tended to occur with indicators of positive family functioning (e.g., more frequent communication, less maternal hostility) based on mother and adolescent reports. As hypothesized, family obligation values moderated the relationship between established risk factors and adjustment in distinct ways, such that high family obligation values decreased risk in some domains (i.e., a protective factor) but increased risk in other domains (i.e., a vulnerability factor). Specifically, high family obligation values diminished the relationship between peer norms for risky behavior (sex and substance use) and individual engagement in those behaviors. At the same time, high family obligation values magnified the relationship between exposure to negative life events and poor mental health (PTSD and depressive symptoms). The results suggest that family obligation is an important but complex aspect of development among diverse adolescent girls.

  13. Mechanisms of cellular invasion by intracellular parasites.

    PubMed

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

    2014-04-01

    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.

  14. A Sense of Obligation: Cultural Differences in the Experience of Obligation.

    PubMed

    Buchtel, Emma E; Ng, Leo C Y; Norenzayan, Ara; Heine, Steven J; Biesanz, Jeremy C; Chen, Sylvia Xiaohua; Bond, Michael Harris; Peng, Qin; Su, Yanjie

    2018-05-01

    In this investigation of cultural differences in the experience of obligation, we distinguish between Confucian Role Ethics versus Relative Autonomy lay theories of motivation and illustrate them with data showing relevant cultural differences in both social judgments and intrapersonal experience. First, when judging others, Western European heritage culture (WEHC) participants (relative to Confucian heritage culture [CHC] participants) judged obligation-motivated actors more negatively than those motivated by agency (Study 1, N = 529). Second, in daily diary and situation sampling studies, CHC participants (relative to WEHC participants) perceived more congruency between their own agentic and obligated motivations, and more positive emotional associations with obligated motivations (Study 2, N = 200 and Study 3, N = 244). Agentic motivation, however, was universally associated with positive emotions. More research on a Role Ethics rather than Relative Autonomy conception of agency may improve our understanding of human motivation, especially across cultures.

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

    PubMed

    Tamir, Sivan

    2013-03-01

    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.

  16. Asset retirement obligations: a reporting concern for healthcare facilities.

    PubMed

    Berg, Gary G; Bayes, Paul E; Morgan, Robert G

    2008-11-01

    FASB statements and SEC guidelines give direction as to how healthcare organizations should account for their asset retirement obligations (AROs) where environmental issues are concerned. A key consideration is that current costs associated with environmental problems, such as encapsulating asbestos, are to be accounted for as part of an asset's cost and depreciated over the asset's remaining life.

  17. Mothers', fathers' and children's perceptions of parents' expectations about children's family obligations in nine countries.

    PubMed

    Lansford, Jennifer E; Godwin, Jennifer; Alampay, Liane Peña; Uribe Tirado, Liliana Maria; Zelli, Arnaldo; Al-Hassan, Suha M; Bacchini, Dario; Bombi, Anna Silvia; Bornstein, Marc H; Chang, Lei; Deater-Deckard, Kirby; Di Giunta, Laura; Dodge, Kenneth A; Malone, Patrick S; Oburu, Paul; Pastorelli, Concetta; Skinner, Ann T; Sorbring, Emma; Tapanya, Sombat

    2016-10-01

    Children's family obligations involve assistance and respect that children are expected to provide to immediate and extended family members and reflect beliefs related to family life that may differ across cultural groups. Mothers, fathers and children (N = 1432 families) in 13 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand and United States) reported on their expectations regarding children's family obligations and parenting attitudes and behaviours. Within families, mothers and fathers had more concordant expectations regarding children's family obligations than did parents and children. Parenting behaviours that were warmer, less neglectful and more controlling as well as parenting attitudes that were more authoritarian were related to higher expectations regarding children's family obligations between families within cultures as well as between cultures. These international findings advance understanding of children's family obligations by contextualising them both within families and across a number of diverse cultural groups in 9 countries. © 2015 International Union of Psychological Science.

  18. Optimal killing for obligate killers: the evolution of life histories and virulence of semelparous parasites.

    PubMed Central

    Ebert, D; Weisser, W W

    1997-01-01

    Many viral, bacterial and protozoan parasites of invertebrates first propagate inside their host without releasing any transmission stages and then kill their host to release all transmission stages at once. Life history and the evolution of virulence of these obligately killing parasites are modelled, assuming that within-host growth is density dependent. We find that the parasite should kill the host when its per capita growth rate falls to the level of the host mortality rate. The parasite should kill its host later when the carrying capacity, K, is higher, but should kill it earlier when the parasite-independent host mortality increases or when the parasite has a higher birth rate. When K(t), for parasite growth, is not constant over the duration of an infection, but increases with time, the parasite should kill the host around the stage when the growth rate of the carrying capacity decelerates strongly. In case that K(t) relates to host body size, this deceleration in growth is around host maturation. PMID:9263465

  19. Lay obligations in professional relations.

    PubMed

    Benjamin, M

    1985-02-01

    Little has been written recently about the obligations of lay people in professional relationships. Yet the Code of Medical Ethics adopted by the American Medical Association in 1847 included an extensive statement on "Obligations of patients to their physicians'. After critically examining the philosophical foundations of this statement, I provide an alternative account of lay obligations in professional relationships. Based on a hypothetical social contract and included in a full specification of professional as well as lay obligations, this account requires lay people to honor commitments and disclose relevant information. Ethically, the account assumes that all parties in lay-professional relationships should be given equal consideration and respect in determining rights and obligations. Factually, it assumes that the treatment of many illnesses and injuries required collaboration and cooperation among lay persons and health professionals, that medical resources and personnel are limited, and that medicine, nursing, and related health professions, are, in MacIntyre's sense, practices.

  20. [Self endangerment to save life--competing Jewish legal and moral obligations].

    PubMed

    Gesundheit, Benjamin; Zlotnick, Eitan; Wygoda, Michael; Rosenzweig, Joshua P; Steinberg, Avraham

    2014-11-01

    The obligation to help others often involves personal risk. Consequently, the scope and boundaries of this obligation can present a complex dilemma, which has practical and moral implications, even in the world of medicine. In Jewish medical ethics, the dilemma stems from a confrontation between the duty to help others according to the biblical commandment: "Do not stand idly by your fellow's blood" on the one hand, and between the right and duty of man to defend himself, which is anchored in Jewish law. This article surveys the sources of this quandary in Jewish texts throughout the ages such as the Bible, Mishnah, Talmud, and responsa literature in various contexts. The discussion highlights the essential difference between the formal demands of the law, which protects human rights of self-preservation, and the moral requirement to help others even if it may include personal risk. The sources suggest distinguishing between various levels of risk ranging from high-risk to reasonable or low risk. In this way, the classic sources, provide the foundation and the tools for grappling with modern contemporary Halachic questions such as organ transplantation, and generate a Torah value-based framework to deal with new situations that may arise in the future. It is critical to assess the level of risk and the chances for success, along with other subjective considerations, in order to ensure the optimal ethical course of action.

  1. 47 CFR 7.5 - General Obligations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

  2. 47 CFR 7.5 - General Obligations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

  3. 47 CFR 7.5 - General Obligations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

  4. 47 CFR 7.5 - General Obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

  5. 47 CFR 7.5 - General Obligations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

  6. 10 CFR 600.20 - Maximum DOE obligation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the amount shown in the award as the amount of DOE funds obligated, and (2) Any designated property. (b) DOE... 10 Energy 4 2011-01-01 2011-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy...

  7. 10 CFR 600.20 - Maximum DOE obligation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the amount shown in the award as the amount of DOE funds obligated, and (2) Any designated property. (b) DOE... 10 Energy 4 2013-01-01 2013-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy...

  8. 10 CFR 600.20 - Maximum DOE obligation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the amount shown in the award as the amount of DOE funds obligated, and (2) Any designated property. (b) DOE... 10 Energy 4 2012-01-01 2012-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy...

  9. 10 CFR 600.20 - Maximum DOE obligation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the amount shown in the award as the amount of DOE funds obligated, and (2) Any designated property. (b) DOE... 10 Energy 4 2014-01-01 2014-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy...

  10. 34 CFR 108.5 - Compliance obligations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Compliance obligations. 108.5 Section 108.5 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION... § 108.5 Compliance obligations. (a) The obligation of covered entities to comply with the Act and this...

  11. Mothers’, Fathers’, and Children’s Perceptions of Parents’ Expectations about Children’s Family Obligations in Nine Countries

    PubMed Central

    Lansford, Jennifer E.; Godwin, Jennifer; Alampay, Liane Peña; Tirado, Liliana Maria Uribe; Zelli, Arnaldo; Al-Hassan, Suha M.; Bacchini, Dario; Bombi, Anna Silvia; Bornstein, Marc H.; Chang, Lei; Deater-Deckard, Kirby; Di Giunta, Laura; Dodge, Kenneth A.; Malone, Patrick S.; Oburu, Paul; Pastorelli, Concetta; Skinner, Ann T.; Sorbring, Emma; Tapanya, Sombat

    2016-01-01

    Children’s family obligations involve assistance and respect that children are expected to provide to immediate and extended family members and reflect beliefs related to family life that may differ across cultural groups. Mothers, fathers, and children (N = 1,432 families) in 13 cultural groups in nine countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and United States) reported on their expectations regarding children’s family obligations and parenting attitudes and behaviors. Within families, mothers and fathers had more concordant expectations regarding children’s family obligations than did parents and children. Parenting behaviors that were warmer, less neglectful, and more controlling as well as parenting attitudes that were more authoritarian were related to higher expectations regarding children’s family obligations between families within cultures as well as between cultures. These international findings advance understanding of children’s family obligations by contextualizing them both within families and across a number of diverse cultural groups in nine countries. PMID:26104262

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

    PubMed

    Gillon, R

    1985-06-08

    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.

  13. Antibiotic susceptibility and intracellular localization of Diplorickettsia massiliensis.

    PubMed

    Subramanian, Geetha; Barry, Abdoulaye O; Ghigo, Eric; Raoult, Didier; Mediannikov, Oleg

    2012-02-01

    Diplorickettsia massiliensis is an obligate intracellular bacterium from the Coxiellaceae family recently isolated from Ixodes ricinus ticks. The inhibitory effects of antimicrobial agents were assessed by two different methods, immunofluorescence and Gimenez staining assay. Different markers (EEA1, Lamp-1, Cathepsin D, and LysoTracker Red DND99) were used to reveal the nature of the vacuole containing the bacterium. Ciprofloxacin, levofloxacin, and rifampin had MIC values of 2 lg mL(-1). We found that 4 lg mL(-1) of Doxycycline inhibited the growth of D. massiliensis strain. Surprisingly, D. massiliensis was resistant to chloramphenicol up to the concentration of 64 lg mL(-1). We found that penicillin G, ammonium chloride, gentamycin, omeprazole, bafilomycin A1, and chloroquine were not active against D. massiliensis. Studies performed with markers EEA1, Lamp-1, Cathepsin D, and LysoTracker Red DND99 showed that D. massiliensis is localized within an acidic compartment that is not an early phagosome, but a late phagosome or a phagolysosome. Gimenez staining stays a good method that will work with a very low number of bacteria and can be used to determine the MICs of new therapeutic antibiotics precisely. The resistance profile of D. massiliensis was found to be quite unusual for intracellular Gram-negative bacterium with marked resistance to chloramphenicol. Despite of localization in acidic compartment, pH-neutralizing agents do not significantly inhibit intracellular growth of bacterium. The results of these studies prove that antibiotic resistance does not depend on pH of vacuole. This pH-related mechanism seems not to play a contributing role in the overall resistance of D. massiliensis.

  14. 29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

  15. 29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 1 2012-07-01 2012-07-01 false How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

  16. 29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

  17. 29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

  18. 29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 1 2013-07-01 2013-07-01 false How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

  19. Grandparents' entitlements and obligations.

    PubMed

    Draper, Heather

    2013-07-01

    In this article, it is argued that grandparents' obligations originate from parental obligations (i.e from the relationship they have with their children, the parents of their grandchildren) and not from the role of grandparent per se, and any entitlements flow from the extent to which these obligations are met. The position defended is, therefore, that grandparents qua grandparents are not entitled to form or continue relationships with their grandchildren. A continuation of grandparent-grandchildren relationships may be in the interests of children, but the grandparental nature of the relationship is not decisive. What counts is the extent to which relationships children have with any adults who are not their parents are is significant to them. Sometimes, however, grandparents become parents or co-parents of their grandchildren. They then gain parental rights, and as such are as entitled, ceteris parius, as any parent to expect their relationship with the child to continue. The issue of grandparents' entitlements can come to the fore when parents separate, and grandparents are unhappy with the access they have to their grandchildren. Grandparents' obligations may become a particular issue when parents die, struggle, or fail to care for their children. This article focuses particularly on these kinds of circumstances. © 2013 John Wiley & Sons Ltd.

  20. GRANDPARENTS' ENTITLEMENTS AND OBLIGATIONS

    PubMed Central

    Draper, Heather

    2013-01-01

    In this article, it is argued that grandparents' obligations originate from parental obligations (i.e from the relationship they have with their children, the parents of their grandchildren) and not from the role of grandparent per se, and any entitlements flow from the extent to which these obligations are met. The position defended is, therefore, that grandparents qua grandparents are not entitled to form or continue relationships with their grandchildren. A continuation of grandparent-grandchildren relationships may be in the interests of children, but the grandparental nature of the relationship is not decisive. What counts is the extent to which relationships children have with any adults who are not their parents are is significant to them. Sometimes, however, grandparents become parents or co-parents of their grandchildren. They then gain parental rights, and as such are as entitled, ceteris parius, as any parent to expect their relationship with the child to continue. The issue of grandparents' entitlements can come to the fore when parents separate, and grandparents are unhappy with the access they have to their grandchildren. Grandparents' obligations may become a particular issue when parents die, struggle, or fail to care for their children. This article focuses particularly on these kinds of circumstances. PMID:23718643

  1. 31 CFR 149.3 - Maximum obligation limitation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Maximum obligation limitation. 149.3 Section 149.3 Money and Finance: Treasury Regulations Relating to Money and Finance MONETARY OFFICES, DEPARTMENT OF THE TREASURY CALCULATION OF MAXIMUM OBLIGATION LIMITATION § 149.3 Maximum obligation limitation...

  2. 10 CFR 600.20 - Maximum DOE obligation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS FINANCIAL ASSISTANCE RULES General § 600.20 Maximum DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the...

  3. Free-Living Amoebae as Hosts for and Vectors of Intracellular Microorganisms with Public Health Significance.

    PubMed

    Balczun, Carsten; Scheid, Patrick L

    2017-04-01

    Free-living amoebae (FLA) are parasites within both humans and animals causing a wide range of symptoms and act as hosts of, and vehicles for phylogenetically diverse microorganisms, called endocytobionts. The interaction of the FLA with sympatric microorganisms leads to an exceptional diversity within FLA. Some of these bacteria, viruses, and even eukaryotes, can live and replicate intracellularly within the FLA. This relationship provides protection to the microorganisms from external interventions and a dispersal mechanism across various habitats. Among those intracellularly-replicating or -residing organisms there are obligate and facultative pathogenic microorganisms affecting the health of humans or animals and are therefore of interest to Public Health Authorities. Mimiviruses, Pandoraviruses, and Pithoviruses are examples for interesting viral endocytobionts within FLA. Future research is expected to reveal further endocytobionts within free-living amoebae and other protozoa through co-cultivation studies, genomic, transcriptomic, and proteomic analyses.

  4. Free-Living Amoebae as Hosts for and Vectors of Intracellular Microorganisms with Public Health Significance

    PubMed Central

    Balczun, Carsten; Scheid, Patrick L.

    2017-01-01

    Free-living amoebae (FLA) are parasites within both humans and animals causing a wide range of symptoms and act as hosts of, and vehicles for phylogenetically diverse microorganisms, called endocytobionts. The interaction of the FLA with sympatric microorganisms leads to an exceptional diversity within FLA. Some of these bacteria, viruses, and even eukaryotes, can live and replicate intracellularly within the FLA. This relationship provides protection to the microorganisms from external interventions and a dispersal mechanism across various habitats. Among those intracellularly-replicating or -residing organisms there are obligate and facultative pathogenic microorganisms affecting the health of humans or animals and are therefore of interest to Public Health Authorities. Mimiviruses, Pandoraviruses, and Pithoviruses are examples for interesting viral endocytobionts within FLA. Future research is expected to reveal further endocytobionts within free-living amoebae and other protozoa through co-cultivation studies, genomic, transcriptomic, and proteomic analyses. PMID:28368313

  5. 46 CFR 287.20 - Obligation of deposits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Obligation of deposits. 287.20 Section 287.20 Shipping... OPERATORS ESTABLISHMENT OF CONSTRUCTION RESERVE FUNDS § 287.20 Obligation of deposits. (a) Time for obligation. Within three years from the date of any deposit in a construction reserve fund, unless extension...

  6. [Exists an Obligation to be Healthy? Ethical Limits of Medical Prevention].

    PubMed

    Arntz, K

    2016-02-01

    An obligation to be healthy in the sauce of a categorical imperative "You shall change your life!" (P. Sloterdijk) does not exist. There is however a moral responsibility to shape ones own life in such a way that the resulting potentials for development can be realized within one owns possibilities (I. Kant). The example of predictive medicine illustrates, why the right not to know can be a responsible way of self governance when dealing with the knowledge of modern biomedicine. This allows the setting of limits within prevention, which preserve the quality of life of the exposed as well as enabling the individual the "acceptance of self" (R. Guardini). © Georg Thieme Verlag KG Stuttgart · New York.

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

    PubMed Central

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

    2014-01-01

    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

  8. Cancer Moonshot Funding Obligations FY 2017

    Cancer.gov

    NCI reports Cancer Moonshot obligations by funding mechanism. See obligations for Moonshot grants, intramural research, and contracts, including the number of grant awards, funding amounts, and percentages by mechanism of the total Cancer Moonshot budget.

  9. High hydrostatic pressure adaptive strategies in an obligate piezophile Pyrococcus yayanosii

    PubMed Central

    Michoud, Grégoire; Jebbar, Mohamed

    2016-01-01

    Pyrococcus yayanosii CH1, as the first and only obligate piezophilic hyperthermophilic microorganism discovered to date, extends the physical and chemical limits of life on Earth. It was isolated from the Ashadze hydrothermal vent at 4,100 m depth. Multi-omics analyses were performed to study the mechanisms used by the cell to cope with high hydrostatic pressure variations. In silico analyses showed that the P. yayanosii genome is highly adapted to its harsh environment, with a loss of aromatic amino acid biosynthesis pathways and the high constitutive expression of the energy metabolism compared with other non-obligate piezophilic Pyrococcus species. Differential proteomics and transcriptomics analyses identified key hydrostatic pressure-responsive genes involved in translation, chemotaxis, energy metabolism (hydrogenases and formate metabolism) and Clustered Regularly Interspaced Short Palindromic Repeats sequences associated with Cellular apoptosis susceptibility proteins. PMID:27250364

  10. High hydrostatic pressure adaptive strategies in an obligate piezophile Pyrococcus yayanosii

    NASA Astrophysics Data System (ADS)

    Michoud, Grégoire; Jebbar, Mohamed

    2016-06-01

    Pyrococcus yayanosii CH1, as the first and only obligate piezophilic hyperthermophilic microorganism discovered to date, extends the physical and chemical limits of life on Earth. It was isolated from the Ashadze hydrothermal vent at 4,100 m depth. Multi-omics analyses were performed to study the mechanisms used by the cell to cope with high hydrostatic pressure variations. In silico analyses showed that the P. yayanosii genome is highly adapted to its harsh environment, with a loss of aromatic amino acid biosynthesis pathways and the high constitutive expression of the energy metabolism compared with other non-obligate piezophilic Pyrococcus species. Differential proteomics and transcriptomics analyses identified key hydrostatic pressure-responsive genes involved in translation, chemotaxis, energy metabolism (hydrogenases and formate metabolism) and Clustered Regularly Interspaced Short Palindromic Repeats sequences associated with Cellular apoptosis susceptibility proteins.

  11. 46 CFR 298.30 - Nature and content of Obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Nature and content of Obligations. 298.30 Section 298.30 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VESSEL FINANCING ASSISTANCE OBLIGATION GUARANTEES Documentation § 298.30 Nature and content of Obligations. (a) Single page. An Obligation, in the...

  12. 46 CFR 298.30 - Nature and content of Obligations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Nature and content of Obligations. 298.30 Section 298.30 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VESSEL FINANCING ASSISTANCE OBLIGATION GUARANTEES Documentation § 298.30 Nature and content of Obligations. (a) Single page. An Obligation, in the...

  13. 46 CFR 298.30 - Nature and content of Obligations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 8 2012-10-01 2012-10-01 false Nature and content of Obligations. 298.30 Section 298.30 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VESSEL FINANCING ASSISTANCE OBLIGATION GUARANTEES Documentation § 298.30 Nature and content of Obligations. (a) Single page. An Obligation, in the...

  14. 46 CFR 298.30 - Nature and content of Obligations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Nature and content of Obligations. 298.30 Section 298.30 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VESSEL FINANCING ASSISTANCE OBLIGATION GUARANTEES Documentation § 298.30 Nature and content of Obligations. (a) Single page. An Obligation, in the...

  15. 46 CFR 298.30 - Nature and content of Obligations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Nature and content of Obligations. 298.30 Section 298.30 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VESSEL FINANCING ASSISTANCE OBLIGATION GUARANTEES Documentation § 298.30 Nature and content of Obligations. (a) Single page. An Obligation, in the...

  16. 7 CFR 400.167 - Limitations on Corporation's obligations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

  17. 7 CFR 400.167 - Limitations on Corporation's obligations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

  18. 7 CFR 400.167 - Limitations on Corporation's obligations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

  19. 7 CFR 400.167 - Limitations on Corporation's obligations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

  20. 7 CFR 400.167 - Limitations on Corporation's obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

  1. NCI & Division Obligations

    Cancer.gov

    Displays obligations for grants, contracts, training fellowships, intramural research, and management and support, including the number of grant awards, funding amounts, and percent of the total NCI budget.

  2. 31 CFR 1024.311 - Filing obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR MUTUAL FUNDS Reports Required To Be Made By Mutual Funds § 1024.311 Filing obligations. Refer to § 1010.311 of this chapter for reports of transactions in currency filing obligations for mutual funds. ...

  3. 43 CFR 10005.8 - Mitigation obligations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Mitigation obligations. 10005.8 Section... MITIGATION AND CONSERVATION COMMISSION POLICIES AND PROCEDURES FOR DEVELOPING AND IMPLEMENTING THE COMMISSION'S MITIGATION AND CONSERVATION PLAN § 10005.8 Mitigation obligations. While the Act authorizes the...

  4. 43 CFR 10005.8 - Mitigation obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Mitigation obligations. 10005.8 Section... MITIGATION AND CONSERVATION COMMISSION POLICIES AND PROCEDURES FOR DEVELOPING AND IMPLEMENTING THE COMMISSION'S MITIGATION AND CONSERVATION PLAN § 10005.8 Mitigation obligations. While the Act authorizes the...

  5. 43 CFR 10005.8 - Mitigation obligations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Mitigation obligations. 10005.8 Section... MITIGATION AND CONSERVATION COMMISSION POLICIES AND PROCEDURES FOR DEVELOPING AND IMPLEMENTING THE COMMISSION'S MITIGATION AND CONSERVATION PLAN § 10005.8 Mitigation obligations. While the Act authorizes the...

  6. 43 CFR 10005.8 - Mitigation obligations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Mitigation obligations. 10005.8 Section... MITIGATION AND CONSERVATION COMMISSION POLICIES AND PROCEDURES FOR DEVELOPING AND IMPLEMENTING THE COMMISSION'S MITIGATION AND CONSERVATION PLAN § 10005.8 Mitigation obligations. While the Act authorizes the...

  7. 24 CFR 891.755 - Obligations of the family.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Obligations of the family. 891.755... the Elderly and Persons with Disabilities Section 202 Projects for the Nonelderly Handicapped Families and Individuals-Section 162 Assistance § 891.755 Obligations of the family. The obligations of the...

  8. 24 CFR 891.755 - Obligations of the family.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Obligations of the family. 891.755... the Elderly and Persons with Disabilities Section 202 Projects for the Nonelderly Handicapped Families and Individuals-Section 162 Assistance § 891.755 Obligations of the family. The obligations of the...

  9. Advances in the application of genetic manipulation methods to apicomplexan parasites

    USDA-ARS?s Scientific Manuscript database

    Apicomplexan parasites such as Babesia, Theileria, Cryptosporidium, and Toxoplasma have a high negative impact on animal health globally, and improved, cost-effective measures to control them are urgently required. These parasites have complex multi-stage life cycles including obligate intracellular...

  10. 31 CFR 1026.311 - Filing obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... INTRODUCING BROKERS IN COMMODITIES Reports Required To Be Made by Futures Commission Merchants and Introducing Brokers in Commodities § 1026.311 Filing obligations. Refer to § 1010.311 of this chapter for reports of transactions in currency filing obligations for futures commission merchants and introducing brokers in...

  11. 24 CFR 891.615 - Obligations of the family.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Obligations of the family. 891.615 Section 891.615 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT... 8 Assistance § 891.615 Obligations of the family. The obligations of the family are provided in...

  12. 24 CFR 891.615 - Obligations of the family.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Obligations of the family. 891.615 Section 891.615 Housing and Urban Development Regulations Relating to Housing and Urban Development... 8 Assistance § 891.615 Obligations of the family. The obligations of the family are provided in...

  13. 12 CFR 997.5 - Termination of the obligation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Termination of the obligation. 997.5 Section 997.5 Banks and Banking FEDERAL HOUSING FINANCE BOARD NON-BANK SYSTEM ENTITIES RESOLUTION FUNDING CORPORATION OBLIGATIONS OF THE BANKS § 997.5 Termination of the obligation. (a) Generally. The Banks...

  14. 24 CFR 213.266a - Insurance fund obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Insurance fund obligations. 213... Insurance fund obligations. A mortgage endorsed for insurance under section 213 of the Act shall be the obligation either of the Cooperative Management Housing Insurance Fund or of the General Insurance Fund. The...

  15. Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease

    PubMed Central

    Haas, Laura T.; Salazar, Santiago V.; Kostylev, Mikhail A.; Um, Ji Won; Kaufman, Adam C.

    2016-01-01

    Alzheimer’s disease-related phenotypes in mice can be rescued by blockade of either cellular prion protein or metabotropic glutamate receptor 5. We sought genetic and biochemical evidence that these proteins function cooperatively as an obligate complex in the brain. We show that cellular prion protein associates via transmembrane metabotropic glutamate receptor 5 with the intracellular protein mediators Homer1b/c, calcium/calmodulin-dependent protein kinase II, and the Alzheimer’s disease risk gene product protein tyrosine kinase 2 beta. Coupling of cellular prion protein to these intracellular proteins is modified by soluble amyloid-β oligomers, by mouse brain Alzheimer’s disease transgenes or by human Alzheimer’s disease pathology. Amyloid-β oligomer-triggered phosphorylation of intracellular protein mediators and impairment of synaptic plasticity in vitro requires Prnp–Grm5 genetic interaction, being absent in transheterozygous loss-of-function, but present in either single heterozygote. Importantly, genetic coupling between Prnp and Grm5 is also responsible for signalling, for survival and for synapse loss in Alzheimer’s disease transgenic model mice. Thus, the interaction between metabotropic glutamate receptor 5 and cellular prion protein has a central role in Alzheimer’s disease pathogenesis, and the complex is a potential target for disease-modifying intervention. PMID:26667279

  16. 47 CFR 27.1239 - Reimbursement obligation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Reimbursement obligation. 27.1239 Section 27... Policies Governing the Transition of the 2500-2690 Mhz Band for Brs and Ebs § 27.1239 Reimbursement obligation. (a) A proponent may request reimbursement from BRS licensees and lessees, EBS lessees, and...

  17. 26 CFR 2.1-20 - Obligation of deposits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Obligation of deposits. 2.1-20 Section 2.1-20...) MARITIME CONSTRUCTION RESERVE FUND § 2.1-20 Obligation of deposits. (a) Time for obligation. Within three years from the date of any deposit in a construction reserve fund, unless extension is granted as...

  18. A bacteriophage endolysin that eliminates intracellular streptococci

    PubMed Central

    Shen, Yang; Barros, Marilia; Vennemann, Tarek; Gallagher, D Travis; Yin, Yizhou; Linden, Sara B; Heselpoth, Ryan D; Spencer, Dennis J; Donovan, David M; Moult, John; Fischetti, Vincent A; Heinrich, Frank; Lösche, Mathias; Nelson, Daniel C

    2016-01-01

    PlyC, a bacteriophage-encoded endolysin, lyses Streptococcus pyogenes (Spy) on contact. Here, we demonstrate that PlyC is a potent agent for controlling intracellular Spy that often underlies refractory infections. We show that the PlyC holoenzyme, mediated by its PlyCB subunit, crosses epithelial cell membranes and clears intracellular Spy in a dose-dependent manner. Quantitative studies using model membranes establish that PlyCB interacts strongly with phosphatidylserine (PS), whereas its interaction with other lipids is weak, suggesting specificity for PS as its cellular receptor. Neutron reflection further substantiates that PlyC penetrates bilayers above a PS threshold concentration. Crystallography and docking studies identify key residues that mediate PlyCB–PS interactions, which are validated by site-directed mutagenesis. This is the first report that a native endolysin can traverse epithelial membranes, thus substantiating the potential of PlyC as an antimicrobial for Spy in the extracellular and intracellular milieu and as a scaffold for engineering other functionalities. DOI: http://dx.doi.org/10.7554/eLife.13152.001 PMID:26978792

  19. Standard of care, institutional obligations, and distributive justice.

    PubMed

    MacKay, Douglas

    2015-05-01

    The problem of standard of care in clinical research concerns the level of treatment that investigators must provide to subjects in clinical trials. Commentators often formulate answers to this problem by appealing to two distinct types of obligations: professional obligations and natural duties. In this article, I investigate whether investigators also possess institutional obligations that are directly relevant to the problem of standard of care, that is, those obligations a person has because she occupies a particular institutional role. I examine two types of institutional contexts: (1) public research agencies - agencies or departments of states that fund or conduct clinical research in the public interest; and (2) private-for-profit corporations. I argue that investigators who are employed or have their research sponsored by the former have a distinctive institutional obligation to conduct their research in a way that is consistent with the state's duty of distributive justice to provide its citizens with access to basic health care, and its duty to aid citizens of lower income countries. By contrast, I argue that investigators who are employed or have their research sponsored by private-for-profit corporations do not possess this obligation nor any other institutional obligation that is directly relevant to the ethics of RCTs. My account of the institutional obligations of investigators aims to contribute to the development of a reasonable, distributive justice-based account of standard of care. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  20. 5 CFR 2635.809 - Just financial obligations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... obligations. Employees shall satisfy in good faith their obligations as citizens, including all just financial... employee or reduced to judgment by a court. In good faith means an honest intention to fulfill any just...

  1. 5 CFR 2635.809 - Just financial obligations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... obligations. Employees shall satisfy in good faith their obligations as citizens, including all just financial... employee or reduced to judgment by a court. In good faith means an honest intention to fulfill any just...

  2. 5 CFR 2635.809 - Just financial obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... obligations. Employees shall satisfy in good faith their obligations as citizens, including all just financial... employee or reduced to judgment by a court. In good faith means an honest intention to fulfill any just...

  3. Social categories as markers of intrinsic interpersonal obligations.

    PubMed

    Rhodes, Marjorie; Chalik, Lisa

    2013-06-01

    Social categorization is an early-developing feature of human social cognition, yet the role that social categories play in children's understanding of and predictions about human behavior has been unclear. In the studies reported here, we tested whether a foundational functional role of social categories is to mark people as intrinsically obligated to one another (e.g., obligated to protect rather than harm). In three studies, children (aged 3-9, N = 124) viewed only within-category harm as violating intrinsic obligations; in contrast, they viewed between-category harm as violating extrinsic obligations defined by explicit rules. These data indicate that children view social categories as marking patterns of intrinsic interpersonal obligations, suggesting that a key function of social categories is to support inferences about how people will relate to members of their own and other groups.

  4. Filial Obligation and Marital Satisfaction in Middle-aged Couples

    PubMed Central

    Seidel, Amber J.; Birditt, Kira S.; Zarit, Steven H.; Fingerman, Karen L.

    2017-01-01

    Abstract Purpose of the Study: Although prior research suggests that high filial obligation has an adverse impact on psychological well-being, little is known about the implications of these beliefs for marital quality during midlife. Therefore, the purpose of this study was to examine dyadic associations between middle-aged husbands’ and wives’ filial obligation beliefs and their marital satisfaction. Design and Methods: Using a sample of 132 middle-aged husbands (M = 51.45 years) and wives (M = 49.75 years) drawn from Wave 1 of the Family Exchanges Study, we tested actor–partner interdependence models to determine associations between husbands’ and wives’ filial obligation beliefs and marital satisfaction in both spouses. We also examined associations between spousal dissimilarity in filial obligation and marital satisfaction. Results: Wives’ greater filial obligation was associated with their own lower marital satisfaction. Conversely, husbands’ greater filial obligation was associated with their own higher marital satisfaction. Greater spousal dissimilarity in filial obligation was associated with lower levels of marital satisfaction for husbands but not for wives. Implications: Given that support provided to aging parents most often occurs within the context of marriage, findings highlight the importance of examining dyadic associations between filial obligation beliefs and marital quality among middle-aged couples. PMID:26613745

  5. Is there a moral obligation not to infect others?

    PubMed

    Harris, J; Holm, S

    1995-11-04

    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.

  6. The role of septins in infections with vacuole-dwelling intracellular bacteria.

    PubMed

    Häcker, Georg

    2017-07-29

    Septins are a relatively little understood group of GTPases that form large assemblies in cells from all eukaryotes other than plants. Septins were first identified in cell division but have also been implicated in microbial infections. Septins often associate with cytoskeletal proteins - most often described for filamentous (F-) actin - and are considered cytoskeletal components themselves. Septins have increasingly been found to partake in processes that are linked to intracellular membranes, from mitochondria to phagosomes, and evidence is accumulating that septins specifically bind to membranes. Since a number of microorganisms have specialized to live and grow inside membranous vacuoles in the cytosol of mammalian cells, this membrane-association of septins suggests that septins may also be involved in the membranous, vacuolar structures that develop around these microbes. However, data are limited on this issue: septins have been identified by proteome analysis on some microbe-bearing vacuoles, but more extensive experimental data are only available for infections with the obligate intracellular bacterium Chlamydia trachomatis. In this review article I will discuss the available data and speculate about the mechanisms of recruitment and potential functions of septins for vacuole-dwelling microorganisms, which may be peculiar to Chlamydia or may pertain more generally to this class of microbes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Population dynamics of obligate cooperators

    PubMed Central

    Courchamp, F.; Grenfell, B.; Clutton-Brock, T.

    1999-01-01

    Obligate cooperative breeding species demonstrate a high rate of group extinction, which may be due to the existence of a critical number of helpers below which the group cannot subsist. Through a simple model, we study the population dynamics of obligate cooperative breeding species, taking into account the existence of a lower threshold below which the instantaneous growth rate becomes negative. The model successively incorporates (i) a distinction between species that need helpers for reproduction, survival or both, (ii) the existence of a migration rate accounting for dispersal, and (iii) stochastic mortality to simulate the effects of random catastrophic events. Our results suggest that the need for a minimum number of helpers increases the risk of extinction for obligate cooperative breeding species. The constraint imposed by this threshold is higher when helpers are needed for reproduction only or for both reproduction and survival. By driving them below this lower threshold, stochastic mortality of lower amplitude and/or lower frequency than for non-cooperative breeders may be sufficient to cause the extinction of obligate cooperative breeding groups. Migration may have a buffering effect only for groups where immigration is higher than emigration; otherwise (when immigrants from nearby groups are not available) it lowers the difference between actual group size and critical threshold, thereby constituting a higher constraint.

  8. Whistleblowing and the bioethicist's public obligations.

    PubMed

    MacDougall, D Robert

    2014-10-01

    Bioethicists are sometimes thought to have heightened obligations by virtue of the fact that their professional role addresses ethics or morals. For this reason it has been argued that bioethicists ought to "whistleblow"--that is, publicly expose the wrongful or potentially harmful activities of their employer--more often than do other kinds of employees. This article argues that bioethicists do indeed have a heightened obligation to whistleblow, but not because bioethicists have heightened moral obligations in general. Rather, the special duties of bioethicists to act as whistleblowers are best understood by examining the nature of the ethical dilemma typically encountered by private employees and showing why bioethicists do not encounter this dilemma in the same way. Whistleblowing is usually understood as a moral dilemma involving conflicting duties to two parties: the public and a private employer. However, this article argues that this way of understanding whistleblowing has the implication that professions whose members identify their employer as the public-such as government employees or public servants--cannot consider whistleblowing a moral dilemma, because obligations are ultimately owed to only one party: the public. The article contends that bioethicists--even when privately employed--are similar to government employees in the sense that they do not have obligations to defer to the judgments of those with private interests. Consequently, bioethicists may be considered to have a special duty to whistleblow, although for different reasons than those usually cited.

  9. Chlamydia pneumoniae exploits adipocyte lipid chaperone FABP4 to facilitate fat mobilization and intracellular growth in murine adipocytes.

    PubMed

    Walenna, Nirwana Fitriani; Kurihara, Yusuke; Chou, Bin; Ishii, Kazunari; Soejima, Toshinori; Itoh, Ryota; Shimizu, Akinori; Ichinohe, Takeshi; Hiromatsu, Kenji

    2018-01-01

    Fatty acid-binding protein 4 (FABP4), a cytosolic lipid chaperone predominantly expressed in adipocytes and macrophages, modulates lipid fluxes, trafficking, signaling, and metabolism. Recent studies have demonstrated that FABP4 regulates metabolic and inflammatory pathways, and in mouse models its inhibition can improve type 2 diabetes mellitus and atherosclerosis. However, the role of FABP4 in bacterial infection, metabolic crosstalk between host and pathogen, and bacterial pathogenesis have not been studied. As an obligate intracellular pathogen, Chlamydia pneumoniae needs to obtain nutrients such as ATP and lipids from host cells. Here, we show that C. pneumoniae successfully infects and proliferates in murine adipocytes by inducing hormone sensitive lipase (HSL)-mediated lipolysis. Chemical inhibition or genetic manipulation of HSL significantly abrogated the intracellular growth of C. pneumoniae in adipocytes. Liberated free fatty acids were utilized to generate ATP via β-oxidation, which C. pneumoniae usurped for its replication. Strikingly, chemical inhibition or genetic silencing of FABP4 significantly abrogated C. pneumoniae infection-induced lipolysis and mobilization of liberated FFAs, resulting in reduced bacterial growth in adipocytes. Collectively, these results demonstrate that C. pneumoniae exploits host FABP4 to facilitate fat mobilization and intracellular replication in adipocytes. This work uncovers a novel strategy used by intracellular pathogens for acquiring energy via hijacking of the host lipid metabolism pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Toxoplasma

    EPA Science Inventory

    T. gondii is an obligate intracellular protozoan parasite that can infect all warm blooded animals ranging from: humans, pets, livestock, to marine aquatic animals. The definitive host is the feline species (both domestic and wild cats), where the sexual stage of the life cycle o...

  11. 24 CFR 266.415 - Mortgage lien and other obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... determine, that all contractual obligations in connection with the mortgage transaction, including the... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Mortgage lien and other obligations... Mortgage and Closing Requirements; HUD Endorsement § 266.415 Mortgage lien and other obligations. (a) Liens...

  12. Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins.

    PubMed

    Palmgren, Madelene; Hernebring, Malin; Eriksson, Stefanie; Elbing, Karin; Geijer, Cecilia; Lasič, Samo; Dahl, Peter; Hansen, Jesper S; Topgaard, Daniel; Lindkvist-Petersson, Karin

    2017-12-01

    Orthodox aquaporins are transmembrane channel proteins that facilitate rapid diffusion of water, while aquaglyceroporins facilitate the diffusion of small uncharged molecules such as glycerol and arsenic trioxide. Aquaglyceroporins play important roles in human physiology, in particular for glycerol metabolism and arsenic detoxification. We have developed a unique system applying the strain of the yeast Pichia pastoris, where the endogenous aquaporins/aquaglyceroporins have been removed and human aquaglyceroporins AQP3, AQP7, and AQP9 are recombinantly expressed enabling comparative permeability measurements between the expressed proteins. Using a newly established Nuclear Magnetic Resonance approach based on measurement of the intracellular life time of water, we propose that human aquaglyceroporins are poor facilitators of water and that the water transport efficiency is similar to that of passive diffusion across native cell membranes. This is distinctly different from glycerol and arsenic trioxide, where high glycerol transport efficiency was recorded.

  13. Is there a moral obligation not to infect others?

    PubMed Central

    Harris, J.; Holm, S.

    1995-01-01

    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. Images p1216-a p1216-b p1217-a PMID:7488907

  14. Hacker within! Ehrlichia chaffeensis Effector Driven Phagocyte Reprogramming Strategy

    PubMed Central

    Lina, Taslima T.; Farris, Tierra; Luo, Tian; Mitra, Shubhajit; Zhu, Bing; McBride, Jere W.

    2016-01-01

    Ehrlichia chaffeensis is a small, gram negative, obligately intracellular bacterium that preferentially infects mononuclear phagocytes. It is the etiologic agent of human monocytotropic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. Mechanisms by which E. chaffeensis establishes intracellular infection, and avoids host defenses are not well understood, but involve functionally relevant host-pathogen interactions associated with tandem and ankyrin repeat effector proteins. In this review, we discuss the recent advances in our understanding of the molecular and cellular mechanisms that underlie Ehrlichia host cellular reprogramming strategies that enable intracellular survival. PMID:27303657

  15. Inability and Obligation in Moral Judgment

    PubMed Central

    Buckwalter, Wesley; Turri, John

    2015-01-01

    It is often thought that judgments about what we ought to do are limited by judgments about what we can do, or that “ought implies can.” We conducted eight experiments to test the link between a range of moral requirements and abilities in ordinary moral evaluations. Moral obligations were repeatedly attributed in tandem with inability, regardless of the type (Experiments 1–3), temporal duration (Experiment 5), or scope (Experiment 6) of inability. This pattern was consistently observed using a variety of moral vocabulary to probe moral judgments and was insensitive to different levels of seriousness for the consequences of inaction (Experiment 4). Judgments about moral obligation were no different for individuals who can or cannot perform physical actions, and these judgments differed from evaluations of a non-moral obligation (Experiment 7). Together these results demonstrate that commonsense morality rejects the “ought implies can” principle for moral requirements, and that judgments about moral obligation are made independently of considerations about ability. By contrast, judgments of blame were highly sensitive to considerations about ability (Experiment 8), which suggests that commonsense morality might accept a “blame implies can” principle. PMID:26296206

  16. 47 CFR 211.7 - Obligation of carriers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

  17. 47 CFR 211.7 - Obligation of carriers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

  18. 47 CFR 211.7 - Obligation of carriers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

  19. 47 CFR 211.7 - Obligation of carriers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

  20. 47 CFR 211.7 - Obligation of carriers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

  1. 49 CFR 22.17 - Compliance with child support obligations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

  2. 49 CFR 22.17 - Compliance with child support obligations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

  3. 49 CFR 22.17 - Compliance with child support obligations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

  4. 49 CFR 22.17 - Compliance with child support obligations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

  5. 49 CFR 22.17 - Compliance with child support obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

  6. 7 CFR 1000.28 - Termination of obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... which the market administrator receives the handler's report of receipts and utilization on which such obligation is based, unless within such 2-year period, the market administrator notifies the handler in... producer(s) or such cooperative association, or if the obligation is payable to the market administrator...

  7. 10 CFR 611.112 - Termination of obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Termination of obligations. 611.112 Section 611.112 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY VEHICLES MANUFACTURER ASSISTANCE PROGRAM Direct Loan Program § 611.112 Termination of obligations. DOE, the Federal Financing Bank, and the...

  8. 5 CFR 2426.13 - Obligation to consult.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Obligation to consult. 2426.13 Section 2426.13 Administrative Personnel FEDERAL LABOR RELATIONS AUTHORITY, GENERAL COUNSEL OF THE FEDERAL... Regulations § 2426.13 Obligation to consult. (a) When a labor organization has been accorded consultation...

  9. 18 CFR 346.3 - Asset retirement obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Asset retirement obligations. 346.3 Section 346.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... to the asset retirement obligations that are included in the book balances of all accounts reflected...

  10. 18 CFR 35.18 - Asset retirement obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

  11. 18 CFR 35.18 - Asset retirement obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

  12. 18 CFR 35.18 - Asset retirement obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

  13. 18 CFR 35.18 - Asset retirement obligations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

  14. 18 CFR 35.18 - Asset retirement obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

  15. 26 CFR 1.454-1 - Obligations issued at discount.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... series E bond, at which time the stated redemption value was $674.60. A never elected under section 454(a... obligation, in which he retains his investment in a matured series E U.S. savings bond, or (iii) A nontransferable obligation (whether or not a current income obligation) of the United States for which a series E...

  16. Osmoadaptative Strategy and Its Molecular Signature in Obligately Halophilic Heterotrophic Protists

    PubMed Central

    Harding, Tommy; Brown, Matthew W.; Simpson, Alastair G.B.; Roger, Andrew J.

    2016-01-01

    Halophilic microbes living in hypersaline environments must counteract the detrimental effects of low water activity and salt interference. Some halophilic prokaryotes equilibrate their intracellular osmotic strength with the extracellular milieu by importing inorganic solutes, mainly potassium. These “salt-in” organisms characteristically have proteins that are highly enriched with acidic and hydrophilic residues. In contrast, “salt-out” halophiles accumulate large amounts of organic solutes like amino acids, sugars and polyols, and lack a strong signature of halophilicity in the amino acid composition of cytoplasmic proteins. Studies to date have examined halophilic prokaryotes, yeasts, or algae, thus virtually nothing is known about the molecular adaptations of the other eukaryotic microbes, that is, heterotrophic protists (protozoa), that also thrive in hypersaline habitats. We conducted transcriptomic investigations to unravel the molecular adaptations of two obligately halophilic protists, Halocafeteria seosinensis and Pharyngomonas kirbyi. Their predicted cytoplasmic proteomes showed increased hydrophilicity compared with marine protists. Furthermore, analysis of reconstructed ancestral sequences suggested that, relative to mesophiles, proteins in halophilic protists have undergone fewer substitutions from hydrophilic to hydrophobic residues since divergence from their closest relatives. These results suggest that these halophilic protists have a higher intracellular salt content than marine protists. However, absence of the acidic signature of salt-in microbes suggests that Haloc. seosinensis and P. kirbyi utilize organic osmolytes to maintain osmotic equilibrium. We detected increased expression of enzymes involved in synthesis and transport of organic osmolytes, namely hydroxyectoine and myo-inositol, at maximal salt concentration for growth in Haloc. seosinensis, suggesting possible candidates for these inferred organic osmolytes. PMID:27412608

  17. 18 CFR 154.315 - Asset retirement obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

  18. 18 CFR 154.315 - Asset retirement obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

  19. 18 CFR 154.315 - Asset retirement obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

  20. 18 CFR 154.315 - Asset retirement obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

  1. 18 CFR 154.315 - Asset retirement obligations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

  2. 22 CFR 221.15 - Fiscal Agent obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

  3. 22 CFR 221.15 - Fiscal Agent obligations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

  4. 22 CFR 221.15 - Fiscal Agent obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

  5. 22 CFR 221.15 - Fiscal Agent obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

  6. 22 CFR 221.15 - Fiscal Agent obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

  7. 26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 2 2012-04-01 2012-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

  8. 26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

  9. 26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

  10. 26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

  11. 26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

  12. 18 CFR 1314.6 - Obligations of TVA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Obligations of TVA. 1314.6 Section 1314.6 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY BOOK-ENTRY PROCEDURES FOR TVA POWER SECURITIES ISSUED THROUGH THE FEDERAL RESERVE BANKS § 1314.6 Obligations of TVA. (a...

  13. 12 CFR 1.100 - Indirect general obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... powers of taxation. Pursuant to § 1.2(b), an obligation issued by an obligor not possessing general powers of taxation qualifies as a general obligation of a State or political subdivision for the purposes of 12 U.S.C. 24 (Seventh), if a party possessing general powers of taxation unconditionally promises...

  14. Obligations of an academic and clinical oncologist: historical reflections.

    PubMed

    Johnson, David H

    2014-01-01

    Obligations are derived from one's core values-those fundamental, enduring, deeply held beliefs that guide one's everyday actions. Gandhi stated it more eloquently than I ever could: "Your beliefs become your thoughts, your thoughts become your words, your words become your actions, your actions become your habits, your habits become your values, your values become your destiny." So what are the obligations of the academic oncologist and clinician? I believe there are a few indubitable and fundamental obligations: professionalism, patient care, stewardship, maintenance of knowledge, productivity, and mentorship). I might add that I do not see these obligations as unique to the academician but rather applicable to all physicians.

  15. What are the limits to the obligations of the nurse?

    PubMed Central

    Edwards, S D

    1996-01-01

    This paper enquires into the nature and the extent of the obligations of nurses. It is argued that nurses appear to be obliged to undertake supererogatory acts if they take clause one of the United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) Code of Professional Conduct seriously (as, indeed, they are required to do). In the first part of the paper, the nature of nursing obligations is outlined, and then the groups and individuals to whom nurses have obligations are identified. Following a brief discussion of the moral foundation of the nurse's obligations to her/his employer, a common conflict of obligations is identified. Then a distinction is drawn between ordinary and extraordinary moral standards. Appreciation of this is necessary for an understanding of the criterion of what constitutes a supererogatory act. By the definition of supererogatory acts proposed below, it is suggested that actions such as whistleblowing satisfy that definition. PMID:8731534

  16. 12 CFR 208.111 - Obligations concerning institutional customers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... adopting sales practice rules for the government securities market, a market with a particularly broad... on their suitability obligations when making recommendations to institutional customers. (b) The... suitability obligations in making recommendations to an institutional customer are the customer's capability...

  17. 12 CFR 208.111 - Obligations concerning institutional customers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... adopting sales practice rules for the government securities market, a market with a particularly broad... on their suitability obligations when making recommendations to institutional customers. (b) The... suitability obligations in making recommendations to an institutional customer are the customer's capability...

  18. 12 CFR 208.111 - Obligations concerning institutional customers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... adopting sales practice rules for the government securities market, a market with a particularly broad... on their suitability obligations when making recommendations to institutional customers. (b) The... suitability obligations in making recommendations to an institutional customer are the customer's capability...

  19. 12 CFR 13.100 - Obligations concerning institutional customers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... market, a market with a particularly broad institutional component. Accordingly, the OCC believes it is appropriate to provide further guidance to banks on their suitability obligations when making recommendations... suitability obligations in making recommendations to an institutional customer are the customer's capability...

  20. 12 CFR 368.100 - Obligations concerning institutional customers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... securities market, a market with a particularly broad institutional component. Accordingly, the FDIC believes it is appropriate to provide further guidance to banks on their suitability obligations when making... important considerations in determining the scope of a bank's suitability obligations in making...

  1. 12 CFR 368.100 - Obligations concerning institutional customers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... securities market, a market with a particularly broad institutional component. Accordingly, the FDIC believes it is appropriate to provide further guidance to banks on their suitability obligations when making... important considerations in determining the scope of a bank's suitability obligations in making...

  2. 12 CFR 13.100 - Obligations concerning institutional customers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... market, a market with a particularly broad institutional component. Accordingly, the OCC believes it is appropriate to provide further guidance to banks on their suitability obligations when making recommendations... suitability obligations in making recommendations to an institutional customer are the customer's capability...

  3. Validation of a Medium-Throughput Method for Evaluation of Intracellular Growth of Mycobacterium tuberculosis▿

    PubMed Central

    Eklund, Daniel; Welin, Amanda; Schön, Thomas; Stendahl, Olle; Huygen, Kris; Lerm, Maria

    2010-01-01

    Intracellular pathogens such as Mycobacterium tuberculosis have adapted to a life inside host cells, in which they utilize host nutrients to replicate and spread. Ineffective methods for the evaluation of growth of intracellular pathogens in their true environment pose an obstacle for basic research and drug screening. Here we present the validation of a luminometry-based method for the analysis of intramacrophage growth of M. tuberculosis. The method, which is performed in a medium-throughput format, can easily be adapted for studies of other intracellular pathogens and cell types. The use of host cells in drug-screening assays dedicated to find antimicrobials effective against intracellular pathogens permits the discovery of not only novel antibiotics but also compounds with immunomodulatory and virulence-impairing activities, which may be future alternatives or complements to antibiotics. PMID:20107000

  4. 26 CFR 1.103-4 - Interest upon United States obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Interest upon United States obligations. 1.103-4... Interest upon United States obligations. (a) Issued before March 1, 1941. (1) Interest upon obligations of the United States issued on or before September 1, 1917, is exempt from tax. In the case of...

  5. 26 CFR 1.103-4 - Interest upon United States obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Interest upon United States obligations. 1.103-4... Interest upon United States obligations. (a) Issued before March 1, 1941. (1) Interest upon obligations of the United States issued on or before September 1, 1917, is exempt from tax. In the case of...

  6. 7 CFR 400.166 - Obligations of the Corporation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

  7. 7 CFR 400.166 - Obligations of the Corporation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

  8. 7 CFR 400.166 - Obligations of the Corporation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

  9. 7 CFR 400.166 - Obligations of the Corporation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

  10. 7 CFR 400.166 - Obligations of the Corporation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

  11. Coping with the Obligation Dilemma: Prototypes of Social Workers in the Nursing Home.

    PubMed

    Lev, Sagit; Ayalon, Liat

    2016-07-01

    We examined the ways in which the social worker is coping with obligation dilemma in an Israeli nursing home. The research was conducted using semi-structured, in-depth interviews carried out with fifteen social workers employed in nursing homes. The interviews were analysed thematically, using constant comparisons. The three themes were concerned with the social worker's place in the nursing home, her relationship with the management and staff, and her coping with the obligation dilemma. These themes highlighted the difference between the interviewees. On the background of this difference, four prototypes of nursing home's social workers were defined: the managerial, the contented, the fighter and the frustrated. From analysing the findings, the significant place of the personal and environmental factors that influence the ways in which the social worker deals with these four themes emerges. Our findings suggest that the strengthening, empowerment and support of social workers in institutions can directly enhance the health, security, emotional well-being and quality of life of nursing home residents.

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

    PubMed Central

    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

    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

  13. 7 CFR 783.7 - Obligations of a participant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Obligations of a participant. 783.7 Section 783.7 Agriculture 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...

  14. The moral status of extraterrestrial life.

    PubMed

    Persson, Erik

    2012-10-01

    If we eventually discover extraterrestrial life, do we have any moral obligations for how to treat the life-forms we find; does it matter whether they are intelligent, sentient, or just microbial-and does it matter that they are extraterrestrial? In this paper, I examine these questions by looking at two of the basic questions in moral philosophy: What does it take to be a moral object? and What has value of what kind? I will start with the first of these questions by looking at the most important attempts to answer this question on our own planet and by asking whether and how they could be applied to extraterrestrial life. The results range from a very strong protection of all extraterrestrial life and all extraterrestrial environments, whether inhabited or not, to total exclusion of extraterrestrial life. Subsequently, I also examine whether extraterrestrial life that lacks moral status can have value to human or alien life with moral status, and if that could generate any obligations for how to treat extraterrestrial life. Based on this analysis, I conclude that extraterrestrial life-forms can have both instrumental value and end value to moral objects, which has strong implications for how to treat them.

  15. Dynamic Acquisition and Loss of Dual-Obligate Symbionts in the Plant-Sap-Feeding Adelgidae (Hemiptera: Sternorrhyncha: Aphidoidea)

    Treesearch

    Carol D. von Dohlen; Usha Spaulding; Kistie B. Patch; Kathryn M. Weglarz; Robert G. Foottit; Nathan P. Havill; Gaelen R. Burke

    2017-01-01

    Sap-sucking insects typically engage in obligate relationships with symbiotic bacteria that play nutritional roles in synthesizing nutrients unavailable or in scarce supply from the plant-sap diets of their hosts. Adelgids are sap-sucking insects with complex life cycles that involve alternation between conifer tree species. While all adelgid species feed on spruce...

  16. Osmoadaptative Strategy and Its Molecular Signature in Obligately Halophilic Heterotrophic Protists.

    PubMed

    Harding, Tommy; Brown, Matthew W; Simpson, Alastair G B; Roger, Andrew J

    2016-08-03

    Halophilic microbes living in hypersaline environments must counteract the detrimental effects of low water activity and salt interference. Some halophilic prokaryotes equilibrate their intracellular osmotic strength with the extracellular milieu by importing inorganic solutes, mainly potassium. These "salt-in" organisms characteristically have proteins that are highly enriched with acidic and hydrophilic residues. In contrast, "salt-out" halophiles accumulate large amounts of organic solutes like amino acids, sugars and polyols, and lack a strong signature of halophilicity in the amino acid composition of cytoplasmic proteins. Studies to date have examined halophilic prokaryotes, yeasts, or algae, thus virtually nothing is known about the molecular adaptations of the other eukaryotic microbes, that is, heterotrophic protists (protozoa), that also thrive in hypersaline habitats. We conducted transcriptomic investigations to unravel the molecular adaptations of two obligately halophilic protists, Halocafeteria seosinensis and Pharyngomonas kirbyi Their predicted cytoplasmic proteomes showed increased hydrophilicity compared with marine protists. Furthermore, analysis of reconstructed ancestral sequences suggested that, relative to mesophiles, proteins in halophilic protists have undergone fewer substitutions from hydrophilic to hydrophobic residues since divergence from their closest relatives. These results suggest that these halophilic protists have a higher intracellular salt content than marine protists. However, absence of the acidic signature of salt-in microbes suggests that Haloc. seosinensis and P. kirbyi utilize organic osmolytes to maintain osmotic equilibrium. We detected increased expression of enzymes involved in synthesis and transport of organic osmolytes, namely hydroxyectoine and myo-inositol, at maximal salt concentration for growth in Haloc. seosinensis, suggesting possible candidates for these inferred organic osmolytes. © The Author 2016

  17. Doubly distributing special obligations: what professional practice can learn from parenting

    PubMed Central

    Tilburt, Jon; Brody, Baruch

    2018-01-01

    A traditional ethic of medicine asserts that physicians have special obligations to individual patients with whom they have a clinical relationship. Contemporary trends in US healthcare financing like bundled payments seem to threaten traditional conceptions of special obligations of individual physicians to individual patients because their population-based focus sets a tone that seems to emphasise responsibilities for groups of patients by groups of physicians in an organisation. Prior to undertaking a cogent debate about the fate and normative weight of special obligations and a traditional ethic for contemporary healthcare, we need a deeper examination of what the traditional ethic of special obligations really means. Here we offer a conception of ‘doubly distributed’ special obligations. Physicians and similarly minded healing professionals abiding by a traditional ethic have always spread their devotion and attention across multiple patients and have shared responsibilities with physician and non-physician colleagues in much the same way devoted parents have frequently distributed their special obligations across multiple children and across multiple parents. By taking up the extended analogy of parent we argue that doubly distributing special obligations need not contradict the possibility of special obligations in restructured collective forms of healthcare delivery and financing. PMID:27125989

  18. 12 CFR 612.2270 - Purchase of System obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Purchase of System obligations. 612.2270... REFERRAL OF KNOWN OR SUSPECTED CRIMINAL VIOLATIONS Standards of Conduct § 612.2270 Purchase of System... Funding Corporation, may only purchase joint, consolidated, or Systemwide obligations that are: (1) Part...

  19. Importance of Branched-Chain Amino Acid Utilization in Francisella Intracellular Adaptation

    PubMed Central

    Gesbert, Gael; Ramond, Elodie; Tros, Fabiola; Dairou, Julien; Frapy, Eric; Barel, Monique

    2014-01-01

    Intracellular bacterial pathogens have adapted their metabolism to optimally utilize the nutrients available in infected host cells. We recently reported the identification of an asparagine transporter required specifically for cytosolic multiplication of Francisella. In the present work, we characterized a new member of the major super family (MSF) of transporters, involved in isoleucine uptake. We show that this transporter (here designated IleP) plays a critical role in intracellular metabolic adaptation of Francisella. Inactivation of IleP severely impaired intracellular F. tularensis subsp. novicida multiplication in all cell types tested and reduced bacterial virulence in the mouse model. To further establish the importance of the ileP gene in F. tularensis pathogenesis, we constructed a chromosomal deletion mutant of ileP (ΔFTL_1803) in the F. tularensis subsp. holarctica live vaccine strain (LVS). Inactivation of IleP in the F. tularensis LVS provoked comparable intracellular growth defects, confirming the critical role of this transporter in isoleucine uptake. The data presented establish, for the first time, the importance of isoleucine utilization for efficient phagosomal escape and cytosolic multiplication of Francisella and suggest that virulent F. tularensis subspecies have lost their branched-chain amino acid biosynthetic pathways and rely exclusively on dedicated uptake systems. This loss of function is likely to reflect an evolution toward a predominantly intracellular life style of the pathogen. Amino acid transporters should be thus considered major players in the adaptation of intracellular pathogens. PMID:25332124

  20. Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain.

    PubMed

    Keriel, Anne; Botella, Eric; Estrach, Soline; Bragagnolo, Gabriel; Vergunst, Annette C; Feral, Chloe C; O'Callaghan, David

    2015-06-01

    Brucella are intracellular bacterial pathogens that use a type IV secretion system (T4SS) to escape host defenses and create a niche in which they can multiply. Although the importance of Brucella T4SS is clear, little is known about its interactions with host cell structures. In this study, we identified the eukaryotic protein CD98hc as a partner for Brucella T4SS subunit VirB2. This transmembrane glycoprotein is involved in amino acid transport, modulation of integrin signaling, and cell-to-cell fusion. Knockdown of CD98hc expression in HeLa cells demonstrated that it is essential for Brucella infection. Using knockout dermal fibroblasts, we confirmed its role for Brucella but found that it is not required for Salmonella infection. CD98hc transiently accumulates around the bacteria during the early phases of infection and is required for both optimal bacterial uptake and intracellular multiplication of Brucella. These results provide new insights into the complex interplay between Brucella and its host. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. 47 CFR 27.1184 - Triggering a reimbursement obligation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... reimbursement obligation. (a) The clearinghouse will apply the following test to determine when an AWS entity has triggered a cost-sharing obligation and therefore must pay an AWS relocator of a BRS system in... co-channel with the licensed AWS band(s) of the AWS entity; (2) An AWS relocator has paid the...

  2. Deconfounding Distance Effects in Judgments of Moral Obligation

    ERIC Educational Resources Information Center

    Nagel, Jonas; Waldmann, Michael R.

    2013-01-01

    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…

  3. 29 CFR 4043.20 - Post-Event filing obligation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

  4. 29 CFR 4043.20 - Post-Event filing obligation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

  5. 29 CFR 4043.20 - Post-Event filing obligation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

  6. 29 CFR 4043.20 - Post-Event filing obligation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

  7. 29 CFR 4043.20 - Post-Event filing obligation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

  8. An Extended Role-Based Access Control Model for Delegating Obligations

    NASA Astrophysics Data System (ADS)

    Ben-Ghorbel-Talbi, Meriam; Cuppens, Frédéric; Cuppens-Boulahia, Nora; Bouhoula, Adel

    The main aim of access control models is to provide means to simplify the management of the security policy, which is a fastidious and error-prone task. Supporting delegation is considered as an important mean to decentralize the administration and therefore to allow security policy to be more flexible and easier to manipulate. Our main contribution is the proposition of a unified model to the administration and delegation of obligations. Managing such delegations implies more requirements than managing traditional privileges delegation. In fact, delegating obligations may include two interpretations: the delegation of the obligation and the delegation of the responsibility related to this obligation. Therefore, it is important to deal with these two notions separately. Moreover, since delegating an obligation involves the delegation of sanctions, then the consent of the user who receives this delegation may be required in some cases. We address in this paper these requirements and we propose a formalism to deal with them.

  9. 19 CFR 4.94 - Yacht privileges and obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Yacht privileges and obligations. 4.94 Section 4... THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES General § 4.94 Yacht privileges and obligations...) A cruising license may be issued to a yacht of a foreign country only if it has been made to appear...

  10. 19 CFR 4.94 - Yacht privileges and obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Yacht privileges and obligations. 4.94 Section 4... THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES General § 4.94 Yacht privileges and obligations...) A cruising license may be issued to a yacht of a foreign country only if it has been made to appear...

  11. Obligations of low income countries in ensuring equity in global health financing.

    PubMed

    Barugahare, John; Lie, Reidar K

    2015-09-08

    Despite common recognition of joint responsibility for global health by all countries particularly to ensure justice in global health, current discussions of countries' obligations for global health largely ignore obligations of developing countries. This is especially the case with regards to obligations relating to health financing. Bearing in mind that it is not possible to achieve justice in global health without achieving equity in health financing at both domestic and global levels, our aim is to show how fulfilling the obligation we propose will make it easy to achieve equity in health financing at both domestic and international levels. Achieving equity in global health financing is a crucial step towards achieving justice in global health. Our general view is that current discussions on global health equity largely ignore obligations of Low Income Country (LIC) governments and we recommend that these obligations should be mainstreamed in current discussions. While we recognise that various obligations need to be fulfilled in order to ultimately achieve justice in global health, for lack of space we prioritise obligations for health financing. Basing on the evidence that in most LICs health is not given priority in annual budget allocations, we propose that LIC governments should bear an obligation to allocate a certain minimum percent of their annual domestic budget resources to health, while they await external resources to supplement domestic ones. We recommend and demonstrate a mechanism for coordinating this obligation so that if the resulting obligations are fulfilled by both LIC and HIC governments it will be easy to achieve equity in global health financing. Although achieving justice in global health will depend on fulfillment of different categories of obligations, ensuring inter- and intra-country equity in health financing is pivotal. This can be achieved by requiring all LIC governments to allocate a certain optimal per cent of their domestic

  12. 18 CFR 292.311 - Reinstatement of obligation to purchase.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... electric energy, a qualifying cogeneration facility, a qualifying small power production facility, a State... utility's obligation to purchase electric energy under this section. Such application shall set forth the... application reinstating the electric utility's obligation to purchase electric energy under this section if...

  13. 18 CFR 292.311 - Reinstatement of obligation to purchase.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... electric energy, a qualifying cogeneration facility, a qualifying small power production facility, a State... utility's obligation to purchase electric energy under this section. Such application shall set forth the... application reinstating the electric utility's obligation to purchase electric energy under this section if...

  14. The numbers game: quantitative analysis of Neorickettsia sp. propagation through complex life cycle of its digenean host using real-time qPCR.

    PubMed

    Greiman, Stephen E; Tkach, Vasyl V

    2016-07-01

    Bacteria of the genus Neorickettsia are obligate intracellular endosymbionts of parasitic flukes (Digenea) and are passed through the entire complex life cycle of the parasite by vertical transmission. Several species of Neorickettsia are known to cause diseases in domestic animals, wildlife, and humans. Quantitative data on the transmission of the bacteria through the digenean life cycle is almost completely lacking. This study quantified for the first time the abundance of Neorickettsia within multiple stages of the life cycle of the digenean Plagiorchis elegans. Snails Lymnaea stagnalis collected from a pond in North Dakota were screened for the presence of digenean cercariae, which were subsequently tested for the presence of Neorickettsia. Three L. stagnalis were found shedding P. elegans cercariae infected with Neorickettsia. These snails were used to initiate three separate laboratory life cycles and obtain all life cycle stages for bacterial quantification. A quantitative real-time PCR assay targeting the GroEL gene was developed to enumerate Neorickettsia sp. within different stages of the digenean life cycle. The number of bacteria significantly increased throughout all stages, from eggs to adults. The two largest increases in number of bacteria occurred during the period from eggs to cercariae and from 6-day metacercariae to 48-h juvenile worms. These two periods seem to be the most important for Neorickettsia propagation through the complex digenean life cycle and maturation in the definitive host.

  15. 47 CFR 64.3001 - Obligation to transmit 911 calls.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

  16. 47 CFR 64.3001 - Obligation to transmit 911 calls.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

  17. 47 CFR 64.3001 - Obligation to transmit 911 calls.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

  18. 47 CFR 64.3001 - Obligation to transmit 911 calls.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

  19. 47 CFR 64.3001 - Obligation to transmit 911 calls.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

  20. Nature, nomenclature and taxonomy of obligate methanol utilizing strains.

    PubMed

    Cercel, M

    1999-01-01

    In a screening program, a number of different bacterial strains with the ability to utilize methanol as a sole carbon and energy source were isolated and described. They are well known methanol utilizing genera Pseudomonas, Klebsiella, Micrococcus, Methylomonas or, on the contrary, the new, unknown genera and species of methylotrophic bacteria. In the last category, Acinetobacter and Alcaligenes are the new reported genera of organisms able to use methanol as a sole carbon and energy source. The present paper reports the very complex physiological and biochemical modifications when very versatile bacteria such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus are cultured on methanol and when the obligate methylotrophic state is compared with the facultative methylotrophic state of the same bacterial strain. Based on experiments and comparisons with literature data, it seems that Methylomonas methanica is the obligate methylotrophic state of Pseudomonas aeruginosa and that Acinetobacter calcoaceticus is the facultative methylotrophic state of Methylococcus capsulatus, an obligate methylotroph. The relationship of the obligate to the facultative and of the facultative to the obligate methylotrophy were established. These new methylotrophic genera and species, the profound physiological and biochemical modifications as well as the new data concerning nature, nomenclature and taxonomy of methanol utilizing bateria were reported for the first time in 1983.

  1. Coping with the Obligation Dilemma: Prototypes of Social Workers in the Nursing Home

    PubMed Central

    Lev, Sagit; Ayalon, Liat

    2016-01-01

    We examined the ways in which the social worker is coping with obligation dilemma in an Israeli nursing home. The research was conducted using semi-structured, in-depth interviews carried out with fifteen social workers employed in nursing homes. The interviews were analysed thematically, using constant comparisons. The three themes were concerned with the social worker's place in the nursing home, her relationship with the management and staff, and her coping with the obligation dilemma. These themes highlighted the difference between the interviewees. On the background of this difference, four prototypes of nursing home's social workers were defined: the managerial, the contented, the fighter and the frustrated. From analysing the findings, the significant place of the personal and environmental factors that influence the ways in which the social worker deals with these four themes emerges. Our findings suggest that the strengthening, empowerment and support of social workers in institutions can directly enhance the health, security, emotional well-being and quality of life of nursing home residents. PMID:27559230

  2. Neisseria gonorrhoeae–Induced Inflammatory Pyroptosis in Human Macrophages is Dependent on Intracellular Gonococci and Lipooligosaccharide

    PubMed Central

    Ritter, Jessica Leigh; Genco, Caroline Attardo

    2018-01-01

    Neisseria gonorrhoeae, the human obligate pathogen responsible for the sexually transmitted disease gonorrhea, has evolved several mechanisms to evade the host immune response. One such mechanism is the modulation of host cell death pathways. In this study, we defined cell death pathways induced by N gonorrhoeae in human monocyte-derived macrophages (MDMs). In a dose-dependent manner, N gonorrhoeae stimulation of MDMs resulted in caspase 1 and 4–dependent cell deaths, indicative of canonical and noncanonical pyroptosis, respectively. Internalization of bacteria or stimulation with lipooligosaccharide (LOS) specifically induced pyroptosis in MDMs and increased secretion of IL-1β. Collectively, our results demonstrate that N gonorrhoeae induces inflammatory pyroptosis in human macrophages due in part to intracellular LOS. We propose that this in turn may exacerbate inflammatory outcomes observed during mucosal infection. PMID:29434478

  3. 7 CFR 400.168 - Obligations of participating insurance company.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Obligations of participating insurance company. 400... participating insurance company. The Agreement will include the following among the obligations of the Company... insurance policies reinsured. (b) The Company shall make available to all eligible producers in the areas...

  4. 7 CFR 400.168 - Obligations of participating insurance company.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Obligations of participating insurance company. 400... participating insurance company. The Agreement will include the following among the obligations of the Company... insurance policies reinsured. (b) The Company shall make available to all eligible producers in the areas...

  5. 7 CFR 400.168 - Obligations of participating insurance company.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Obligations of participating insurance company. 400... participating insurance company. The Agreement will include the following among the obligations of the Company... insurance policies reinsured. (b) The Company shall make available to all eligible producers in the areas...

  6. 7 CFR 400.168 - Obligations of participating insurance company.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Obligations of participating insurance company. 400... participating insurance company. The Agreement will include the following among the obligations of the Company... insurance policies reinsured. (b) The Company shall make available to all eligible producers in the areas...

  7. 7 CFR 400.168 - Obligations of participating insurance company.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Obligations of participating insurance company. 400... participating insurance company. The Agreement will include the following among the obligations of the Company... insurance policies reinsured. (b) The Company shall make available to all eligible producers in the areas...

  8. 15 CFR 711.4 - Assistance in determining your obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Assistance in determining your obligations. 711.4 Section 711.4 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade... ELECTRONIC FILING OF DECLARATIONS AND REPORTS § 711.4 Assistance in determining your obligations. (a...

  9. 18 CFR 367.22 - Accounting for asset retirement obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Accounting for asset... GAS ACT General Instructions § 367.22 Accounting for asset retirement obligations. (a) An asset... measurement changes to the initial liability for the legal obligation recorded in account 230, Asset...

  10. 48 CFR 252.239-7013 - Obligation of the Government.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Government. 252.239-7013 Section 252.239-7013 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.239-7013 Obligation of the Government. As prescribed in 239.7411(c), use the following clause: Obligation of the Government (JUL 2006) (a) This basic agreement is not a...

  11. 48 CFR 252.239-7013 - Obligation of the Government.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Government. 252.239-7013 Section 252.239-7013 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.239-7013 Obligation of the Government. As prescribed in 239.7411(c), use the following clause: Obligation of the Government (JUL 2006) (a) This basic agreement is not a...

  12. 18 CFR 292.313 - Reinstatement of obligation to sell.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... finding under § 292.312 relieving an electric utility of its obligation to sell electric energy, a... purchase electric energy under this section. Such application shall set forth the factual basis upon which... application reinstating the electric utility's obligation to sell electric energy under this section if the...

  13. 18 CFR 292.313 - Reinstatement of obligation to sell.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... finding under § 292.312 relieving an electric utility of its obligation to sell electric energy, a... purchase electric energy under this section. Such application shall set forth the factual basis upon which... application reinstating the electric utility's obligation to sell electric energy under this section if the...

  14. Phenotypic effects of an allele causing obligate parthenogenesis in a rotifer.

    PubMed

    Scheuerl, Thomas; Riss, Simone; Stelzer, Claus-Peter

    2011-01-01

    Transitions to obligate asexuality have been documented in almost all metazoan taxa, yet the conditions favoring such transitions remained largely unexplored. We address this problem in the rotifer Brachionus calyciflorus. In this species, a polymorphism at a single locus, op, can result in transitions to obligate parthenogenesis. Homozygotes for the op allele reproduce strictly by asexual reproduction, whereas heterozygous clones (+/op) and wild-type clones (+/+) are cyclical parthenogens that undergo sexual reproduction at high population densities. Here, we examine dosage effects of the op allele by analyzing various life-history characteristics and population traits in 10 clones for each of the 3 possible genotypes (op/op, +/op, and +/+). For most traits, we found that op/op clones differed significantly (P < 0.05) from the 2 cyclical parthenogenetic genotypes (+/+ and +/op). By contrast, the 2 cyclical parthenogenetic genotypes were almost indistinguishable, except that heterozygote individuals were slightly but significantly smaller in body size compared with wild-type individuals. Overall, this indicates that the op allele is selectively neutral in the heterozygous state. Thus, selective sweeps of this allele in natural populations would first require conditions favoring the generation of homozygotes. This may be given by inbreeding in very small populations or by double mutants in very large populations.

  15. Phenotypic Effects of an Allele Causing Obligate Parthenogenesis in a Rotifer

    PubMed Central

    Scheuerl, Thomas; Riss, Simone

    2011-01-01

    Transitions to obligate asexuality have been documented in almost all metazoan taxa, yet the conditions favoring such transitions remained largely unexplored. We address this problem in the rotifer Brachionus calyciflorus. In this species, a polymorphism at a single locus, op, can result in transitions to obligate parthenogenesis. Homozygotes for the op allele reproduce strictly by asexual reproduction, whereas heterozygous clones (+/op) and wild-type clones (+/+) are cyclical parthenogens that undergo sexual reproduction at high population densities. Here, we examine dosage effects of the op allele by analyzing various life-history characteristics and population traits in 10 clones for each of the 3 possible genotypes (op/op, +/op, and +/+). For most traits, we found that op/op clones differed significantly (P < 0.05) from the 2 cyclical parthenogenetic genotypes (+/+ and +/op). By contrast, the 2 cyclical parthenogenetic genotypes were almost indistinguishable, except that heterozygote individuals were slightly but significantly smaller in body size compared with wild-type individuals. Overall, this indicates that the op allele is selectively neutral in the heterozygous state. Thus, selective sweeps of this allele in natural populations would first require conditions favoring the generation of homozygotes. This may be given by inbreeding in very small populations or by double mutants in very large populations. PMID:21576287

  16. 43 CFR 3162.2-1 - Drilling and producing obligations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Drilling and producing obligations. 3162.2... Requirements for Operating Rights Owners and Operators § 3162.2-1 Drilling and producing obligations. (a) The operator, at its election, may drill and produce other wells in conformity with any system of well spacing...

  17. 43 CFR 3162.2-1 - Drilling and producing obligations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Drilling and producing obligations. 3162.2... Requirements for Operating Rights Owners and Operators § 3162.2-1 Drilling and producing obligations. (a) The operator, at its election, may drill and produce other wells in conformity with any system of well spacing...

  18. 43 CFR 3162.2-1 - Drilling and producing obligations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Drilling and producing obligations. 3162.2... Requirements for Operating Rights Owners and Operators § 3162.2-1 Drilling and producing obligations. (a) The operator, at its election, may drill and produce other wells in conformity with any system of well spacing...

  19. 43 CFR 3162.2-1 - Drilling and producing obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Drilling and producing obligations. 3162.2... Requirements for Operating Rights Owners and Operators § 3162.2-1 Drilling and producing obligations. (a) The operator, at its election, may drill and produce other wells in conformity with any system of well spacing...

  20. Transience after disturbance: Obligate species recovery dynamics depend on disturbance duration.

    PubMed

    Singer, Alexander; Johst, Karin

    2017-06-01

    After a disturbance event, population recovery becomes an important species response that drives ecosystem dynamics. Yet, it is unclear how interspecific interactions impact species recovery from a disturbance and which role the disturbance duration (pulse or press) plays. Here, we analytically derive conditions that govern the transient recovery dynamics from disturbance of a host and its obligately dependent partner in a two-species metapopulation model. We find that, after disturbance, species recovery dynamics depend on the species' role (i.e. host or obligately dependent species) as well as the duration of disturbance. Host recovery starts immediately after the disturbance. In contrast, for obligate species, recovery depends on disturbance duration. After press disturbance, which allows dynamics to equilibrate during disturbance, obligate species immediately start to recover. Yet, after pulse disturbance, obligate species continue declining although their hosts have already begun to increase. Effectively, obligate species recovery is delayed until a necessary host threshold occupancy is reached. Obligates' delayed recovery arises solely from interspecific interactions independent of dispersal limitations, which contests previous explanations. Delayed recovery exerts a two-fold negative effect, because populations continue declining to even smaller population sizes and the phase of increased risk from demographic stochastic extinction in small populations is prolonged. We argue that delayed recovery and its determinants -species interactions and disturbance duration - have to be considered in biodiversity management. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Do we have a moral obligation to synthesize organisms to increase biodiversity? On kinship, awe, and the value of life's diversity.

    PubMed

    Boldt, Joachim

    2013-10-01

    Synthetic biology can be understood as expanding the abilities and aspirations of genetic engineering. Nonetheless, whereas genetic engineering has been subject to criticism due to its endangering biodiversity, synthetic biology may actually appear to prove advantageous for biodiversity. After all, one might claim, synthesizing novel forms of life increases the numbers of species present in nature and thus ought to be ethically recommended. Two perspectives on how to spell out the conception of intrinsic value of biodiversity are examined in order to assess this line of thought. At the cost of introducing two separate capacities of human knowledge acquisition, the 'admiration stance' turns out to reject outright the assumption of a synthetic species' intrinsic value and of an imperative to create novel species. The 'kinship stance' by contrast does ascribe value to both synthetic and natural species and organisms. Nonetheless, while from this perspective creating novel species may become an ethical demand under certain conditions, it favours changing organisms by getting in contact with them rather than synthesizing them. It is concluded that neither the admiration nor the kinship stance warrants a supposed general moral obligation to create novel species to increase biodiversity. © 2013 John Wiley & Sons Ltd.

  2. Biosorption of heavy metals by obligate halophilic fungi.

    PubMed

    Bano, Amna; Hussain, Javaid; Akbar, Ali; Mehmood, Khalid; Anwar, Muhammad; Hasni, Muhammad Sharif; Ullah, Sami; Sajid, Sumbal; Ali, Imran

    2018-05-01

    The presence of heavy metals in the environment poses a serious threat to human health. Remediation of this problem using microorganisms has been widely researched to find a sustainable solution. Obligate halophilic fungi comprising Aspergillus flavus, Aspergillus gracilis, Aspergillus penicillioides (sp. 1), Aspergillus penicillioides (sp. 2), Aspergillus restrictus and Sterigmatomyces halophilus were used for the biosorption of cadmium, copper, ferrous, manganese, lead and zinc. The metals were supplemented as salts in potato dextrose broth for the growth of obligate halophilic fungi and incubated for 14 days. The supernatant and biomass were obtained by the acid digestion method. The biosorption was screened by atomic absorption spectroscopy. All tested fungi showed moderate to high adsorption of heavy metals, amongst which A. flavus and S. halophilus showed the best average adsorption of all heavy metals studied, with an average of 86 and 83%, respectively. On average, Fe and Zn are best removed from the liquid media of obligate halophilic fungi, with an average of 85 and 84%, respectively. This pioneering study of biosorption by obligate halophilic fungi using inexpensive media in stagnant conditions provides a cost-effective environmental solution for the removal of heavy metals. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. 21 CFR 312.52 - Transfer of obligations to a contract research organization.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Transfer of obligations to a contract research... and Investigators § 312.52 Transfer of obligations to a contract research organization. (a) A sponsor... research organization. Any such transfer shall be described in writing. If not all obligations are...

  4. 47 CFR 27.1174 - Termination of Cost-Sharing Obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... § 27.1174 Termination of Cost-Sharing Obligations. The cost-sharing plan will sunset for all AWS and... AWS band (i.e., 2110-2150 MHz, 2160-2175 MHz, or 2175-2180 MHz) in which the relocated FMS link was located terminates. AWS or MSS (including MSS/ATC) entrants that trigger a cost-sharing obligation prior...

  5. 47 CFR 27.1174 - Termination of Cost-Sharing Obligations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... § 27.1174 Termination of Cost-Sharing Obligations. The cost-sharing plan will sunset for all AWS and... AWS band (i.e., 2110-2150 MHz, 2160-2175 MHz, or 2175-2180 MHz) in which the relocated FMS link was located terminates. AWS or MSS (including MSS/ATC) entrants that trigger a cost-sharing obligation prior...

  6. Is conscientious objection incompatible with a physician's professional obligations?

    PubMed

    Wicclair, Mark R

    2008-01-01

    In response to physicians who refuse to provide medical services that are contrary to their ethical and/or religious beliefs, it is sometimes asserted that anyone who is not willing to provide legally and professionally permitted medical services should choose another profession. This article critically examines the underlying assumption that conscientious objection is incompatible with a physician's professional obligations (the "incompatibility thesis"). Several accounts of the professional obligations of physicians are explored: general ethical theories (consequentialism, contractarianism, and rights-based theories), internal morality (essentialist and non-essentialist conceptions), reciprocal justice, social contract, and promising. It is argued that none of these accounts of a physician's professional obligations unequivocally supports the incompatibility thesis.

  7. Filial anxiety and sense of obligation among offspring of Holocaust survivors.

    PubMed

    Shrira, Amit; Menashe, Ravit; Bensimon, Moshe

    2018-03-13

    Much is known about adult children caring for their aging parents, yet the potentially unique experience of offspring caring for traumatized parents is underexplored. Therefore, the current studies assessed filial anxiety and sense of obligation among offspring of Holocaust survivors (OHS) in caring for their parents. In Study 1, we interviewed 10 OHS (mean age = 61.0) in order to extract themes of filial anxiety. Based on Study 1's data, a newly constructed scale of filial anxiety was administered in Study 2 to 59 adult offspring (mean age = 56.4): 28 OHS and 31 comparisons. Study 3 included 143 dyads of parents and offspring (mean age = 55.4 and 81.7, respectively): 86 Holocaust dyads and 57 comparison dyads. Parents reported posttraumatic stress disorder (PTSD) symptoms and offspring reported filial anxiety and sense of obligation. In Study 1, interviewees referred to concerns about parent experiencing decline alongside caregiving difficulties. In Study 2, OHS reported higher filial anxiety and sense of obligation relative to comparisons. This group difference was mediated by sense of obligation. In Study 3, OHS with parental PTSD reported higher filial anxiety and sense of obligation relative to comparisons. Once more, filial sense of obligation served as a mediator. In Studies 2-3, results remained significant after adjusting for offspring symptoms. Parental exposure to the Holocaust, and especially parental PTSD, related to higher filial obligation, which in turn was related to higher filial anxiety. These findings bear important implications for practitioners working with survivors' families.

  8. From cytoplasm to environment: the inorganic ingredients for the origin of life.

    PubMed

    Novoselov, Alexey A; Serrano, Paloma; Pacheco, Mírian Liza Alves Forancelli; Chaffin, Michael Scott; O'Malley-James, Jack Thomas; Moreno, Susan Carla; Ribeiro, Filipe Batista

    2013-03-01

    Early in its history, Earth's surface developed from an uninhabitable magma ocean to a place where life could emerge. The first organisms, lacking ion transporters, fixed the composition of their cradle environment in their intracellular fluid. Later, though life adapted and spread, it preserved some qualities of its initial environment within. Modern prokaryotes could thus provide insights into the conditions of early Earth and the requirements for the emergence of life. In this work, we constrain Earth's life-forming environment through detailed analysis of prokaryotic intracellular fluid. Rigorous assessment of the constraints placed on the early Earth environment by intracellular liquid will provide insight into the conditions of abiogenesis, with implications not only for our understanding of early Earth but also the formation of life elsewhere in the Universe.

  9. 25 CFR 163.42 - Obligated service and breach of contract.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... REGULATIONS Forestry Education, Education Assistance, Recruitment and Training § 163.42 Obligated service and breach of contract. (a) Obligated service. (1) Individuals completing forestry education programs with an... 90 days of the date all program education requirements have been completed. If such employment is not...

  10. 25 CFR 163.42 - Obligated service and breach of contract.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... REGULATIONS Forestry Education, Education Assistance, Recruitment and Training § 163.42 Obligated service and breach of contract. (a) Obligated service. (1) Individuals completing forestry education programs with an... 90 days of the date all program education requirements have been completed. If such employment is not...

  11. 25 CFR 163.42 - Obligated service and breach of contract.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... REGULATIONS Forestry Education, Education Assistance, Recruitment and Training § 163.42 Obligated service and breach of contract. (a) Obligated service. (1) Individuals completing forestry education programs with an... 90 days of the date all program education requirements have been completed. If such employment is not...

  12. 25 CFR 163.42 - Obligated service and breach of contract.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... REGULATIONS Forestry Education, Education Assistance, Recruitment and Training § 163.42 Obligated service and breach of contract. (a) Obligated service. (1) Individuals completing forestry education programs with an... 90 days of the date all program education requirements have been completed. If such employment is not...

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

    PubMed

    MacDougall, D Robert

    2013-09-01

    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.

  14. Observer perceptions of moral obligations in groups with a history of victimization.

    PubMed

    Warner, Ruth H; Branscombe, Nyla R

    2012-07-01

    The authors investigated when observers assign contemporary group members moral obligations based on their group's victimization history. In Experiment 1, Americans perceived Israelis as obligated to help Sudanese genocide victims and as guiltworthy for not helping if reminded of the Holocaust and its descendants were linked to this history. In Experiment 2, participants perceived Israelis as more obligated to help and guiltworthy for not helping when the Holocaust was presented as a unique victimization event compared with when genocide was presented as pervasive. Experiments 3 and 4 replicated the effects of Experiment 1 with Cambodians as the victimized group. Experiment 5 demonstrated that participants perceived Cambodians as having more obligations under high just world threat compared with low just world threat. Perceiving victimized groups as incurring obligations is one just world restoration method of providing meaning to collective injustice.

  15. 46 CFR Sec. 11 - Guarantee obligations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ACCOMPLISHMENT OF VESSEL 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...

  16. 46 CFR Sec. 11 - Guarantee obligations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ACCOMPLISHMENT OF VESSEL 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...

  17. 46 CFR Sec. 11 - Guarantee obligations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ACCOMPLISHMENT OF VESSEL 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...

  18. 46 CFR Sec. 11 - Guarantee obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ACCOMPLISHMENT OF VESSEL 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...

  19. The moral obligation to be vaccinated: utilitarianism, contractualism, and collective easy rescue.

    PubMed

    Giubilini, Alberto; Douglas, Thomas; Savulescu, Julian

    2018-02-10

    We argue that individuals who have access to vaccines and for whom vaccination is not medically contraindicated have a moral obligation to contribute to the realisation of herd immunity by being vaccinated. Contrary to what some have claimed, we argue that this individual moral obligation exists in spite of the fact that each individual vaccination does not significantly affect vaccination coverage rates and therefore does not significantly contribute to herd immunity. Establishing the existence of a moral obligation to be vaccinated (both for adults and for children) despite the negligible contribution each vaccination can make to the realisation of herd immunity is important because such moral obligation would strengthen the justification for coercive vaccination policies. We show that two types of arguments-namely a utilitarian argument based on Parfit's Principle of Group Beneficence and a contractualist argument-can ground an individual moral obligation to be vaccinated, in spite of the imperceptible contribution that any single vaccination makes to vaccine coverage rates. We add a further argument for a moral obligation to be vaccinated that does not require embracing problematic comprehensive moral theories such as utilitarianism or contractualism. The argument is based on a "duty of easy rescue" applied to collectives, which grounds a collective moral obligation to realise herd immunity, and on a principle of fairness in the distribution of the burdens that must be borne to realise herd immunity.

  20. The fiduciary obligation of the physician-researcher in phase IV trials

    PubMed Central

    2014-01-01

    Background In this manuscript, we argue that within the context of phase IV, physician-researchers retain their fiduciary obligation to treat the patient-participants. Discussion We first clarify why the perspective that research ethics ought to be differentiated from clinical ethics is not applicable in phase IV, and therefore, why therapeutic orientation is most convivial in this phase. Next, assuming that ethics guidelines may be representative of common morality, we show that ethics guidelines see physician-researchers primarily as physicians and only secondarily as researchers. We then elaborate on what a fiduciary obligation is and how some of the obligations are default duties. Lastly, we look at the fiduciary obligation of the physician-researcher in phase IV interventional trials. Conclusion The fiduciary obligation to treat is not as easily waived as in earlier trials. Assuming the entwinement of research and practice in phase IV, physician-researchers, in collaboration with other researchers, investigators, and research ethics committees, should ensure that in terms of study design, methodology, and research practice, the therapeutic value of the research to the patient-participants is not diminished. PMID:24507449

  1. Should Social Value Obligations be Local or Global?

    PubMed

    Nayak, Rahul; Shah, Seema K

    2017-02-01

    According to prominent bioethics scholars and international guidelines, researchers and sponsors have obligations to ensure that the products of their research are reasonably available to research participants and their communities. In other words, the claim is that research is unethical unless it has local social value. In this article, we argue that the existing conception of reasonable availability should be replaced with a social value obligation that extends to the global poor (and not just research participants and host communities). To the extent the social value requirement has been understood as geographically constrained to the communities that host research and the countries that can afford the products of research, it has neglected to include the global poor as members of the relevant society. We argue that a new conception of social value obligations is needed for two reasons. First, duties of global beneficence give reason for researchers, sponsors, and institutions to take steps to make their products more widely accessible. Second, public commitments made by many institutions acknowledge and engender responsibilities to make the products of research more accessible to the global poor. Future research is needed to help researchers and sponsors discharge these obligations in ways that unlock their full potential. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  2. Revisiting the Life Cycle of Dung Fungi, Including Sordaria fimicola.

    PubMed

    Newcombe, George; Campbell, Jason; Griffith, David; Baynes, Melissa; Launchbaugh, Karen; Pendleton, Rosemary

    2016-01-01

    Dung fungi, such as Sordaria fimicola, generally reproduce sexually with ascospores discharged from mammalian dung after passage through herbivores. Their life cycle is thought to be obligate to dung, and thus their ascospores in Quaternary sediments have been interpreted as evidence of past mammalian herbivore activity. Reports of dung fungi as endophytes would seem to challenge the view that they are obligate to dung. However, endophyte status is controversial because surface-sterilization protocols could fail to kill dung fungus ascospores stuck to the plant surface. Thus, we first tested the ability of representative isolates of three common genera of dung fungi to affect plant growth and fecundity given that significant effects on plant fitness could not result from ascospores merely stuck to the plant surface. Isolates of S. fimicola, Preussia sp., and Sporormiella sp. reduced growth and fecundity of two of three populations of Bromus tectorum, the host from which they had been isolated. In further work with S. fimicola we showed that inoculations of roots of B. tectorum led to some colonization of aboveground tissues. The same isolate of S. fimicola reproduced sexually on inoculated host plant tissues as well as in dung after passage through sheep, thus demonstrating a facultative rather than an obligate life cycle. Finally, plants inoculated with S. fimicola were not preferred by sheep; preference had been expected if the fungus were obligate to dung. Overall, these findings make us question the assumption that these fungi are obligate to dung.

  3. Revisiting the Life Cycle of Dung Fungi, Including Sordaria fimicola

    PubMed Central

    Newcombe, George; Campbell, Jason; Griffith, David; Baynes, Melissa; Launchbaugh, Karen; Pendleton, Rosemary

    2016-01-01

    Dung fungi, such as Sordaria fimicola, generally reproduce sexually with ascospores discharged from mammalian dung after passage through herbivores. Their life cycle is thought to be obligate to dung, and thus their ascospores in Quaternary sediments have been interpreted as evidence of past mammalian herbivore activity. Reports of dung fungi as endophytes would seem to challenge the view that they are obligate to dung. However, endophyte status is controversial because surface-sterilization protocols could fail to kill dung fungus ascospores stuck to the plant surface. Thus, we first tested the ability of representative isolates of three common genera of dung fungi to affect plant growth and fecundity given that significant effects on plant fitness could not result from ascospores merely stuck to the plant surface. Isolates of S. fimicola, Preussia sp., and Sporormiella sp. reduced growth and fecundity of two of three populations of Bromus tectorum, the host from which they had been isolated. In further work with S. fimicola we showed that inoculations of roots of B. tectorum led to some colonization of aboveground tissues. The same isolate of S. fimicola reproduced sexually on inoculated host plant tissues as well as in dung after passage through sheep, thus demonstrating a facultative rather than an obligate life cycle. Finally, plants inoculated with S. fimicola were not preferred by sheep; preference had been expected if the fungus were obligate to dung. Overall, these findings make us question the assumption that these fungi are obligate to dung. PMID:26839959

  4. Medical Researchers' Ancillary Care Obligations: The Relationship-Based Approach.

    PubMed

    Olson, Nate W

    2016-06-01

    In this article, I provide a new account of the basis of medical researchers' ancillary care obligations. Ancillary care in medical research, or medical care that research participants need but that is not required for the validity or safety of a study or to redress research injuries, is a topic that has drawn increasing attention in research ethics over the last ten years. My view, the relationship-based approach, improves on the main existing theory, Richardson and Belsky's 'partial-entrustment model', by avoiding its problematic restriction on the scope of health needs for which researchers could be obligated to provide ancillary care. Instead, it grounds ancillary care obligations in a wide range of morally relevant features of the researcher-participant relationship, including the level of engagement between researchers and participants, and weighs these factors against each other. I argue that the level of engagement, that is, the duration and intensity of interactions, between researchers and participants matters for ancillary care because of its connection to the meaningfulness of a relationship, and I suggest that other morally relevant features can be grounded in researchers' role obligations. © 2015 John Wiley & Sons Ltd.

  5. Misleading by Omission: Rethinking the Obligation to Inform Research Subjects about Funding Sources.

    PubMed

    Manson, Neil C

    2017-11-15

    Informed consent requirements for medical research have expanded over the past half-century. The Declaration of Helsinki now includes an explicit positive obligation to inform subjects about funding sources. This is problematic in a number of ways and seems to oblige researchers to disclose information irrelevant to most consent decisions. It is argued here that such a problematic obligation involves an "informational fallacy." The aim in the second part of the paper is to provide a better approach to making sense of how a failure to inform about funding sources wrongs subjects: by making appeals to obligations to refrain from misleading by omission. This alternative approach-grounded in a general obligation to refrain from misleading, an obligation that is independent of informed consent-provides a basis for a norm that protects subjects' interests, without the informational fallacy. The approach developed here avoids the problems identified with the currently specified general obligation to inform about funding sources. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. 17 CFR 200.54 - Constitutional obligations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... obligations. The members of this Commission have undertaken in their oaths of office to support the Federal Constitution. Insofar as the enactments of the Congress impose executive duties upon the members, they must...

  7. 17 CFR 200.54 - Constitutional obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... obligations. The members of this Commission have undertaken in their oaths of office to support the Federal Constitution. Insofar as the enactments of the Congress impose executive duties upon the members, they must...

  8. 17 CFR 200.54 - Constitutional obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... obligations. The members of this Commission have undertaken in their oaths of office to support the Federal Constitution. Insofar as the enactments of the Congress impose executive duties upon the members, they must...

  9. 17 CFR 200.54 - Constitutional obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... obligations. The members of this Commission have undertaken in their oaths of office to support the Federal Constitution. Insofar as the enactments of the Congress impose executive duties upon the members, they must...

  10. 17 CFR 200.54 - Constitutional obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... obligations. The members of this Commission have undertaken in their oaths of office to support the Federal Constitution. Insofar as the enactments of the Congress impose executive duties upon the members, they must...

  11. 25 CFR 163.42 - Obligated service and breach of contract.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Obligated service and breach of contract. 163.42 Section... breach of contract. (a) Obligated service. (1) Individuals completing forestry education programs with an... request for waiver. (b) Breach of contract. Any individual who has participated in and accepted financial...

  12. Informed consent: Enforcing pharmaceutical companies' obligations abroad.

    PubMed

    Lee, Stacey B

    2010-06-15

    The past several years have seen an evolution in the obligations of pharmaceutical companies conducting clinical trials abroad. Key players, such as international human rights organizations, multinational pharmaceutical companies, the United States government and courts, and the media, have played a significant role in defining these obligations. This article examines how such obligations have developed through the lens of past, present, and future recommendations for informed consent protections. In doing so, this article suggests that, no matter how robust obligations appear, they will continue to fall short of providing meaningful protection until they are accompanied by a substantive enforcement mechanism that holds multinational pharmaceutical companies accountable for their conduct. Issues of national sovereignty, particularly in the United States, will continue to prevent meaningful enforcement by an international tribunal or through one universally adopted code of ethics. This article argues that, rather than continuing to pursue an untenable international approach, the Alien Torts Statute (ATS) offers a viable enforcement mechanism, at least for US-based pharmaceutical companies. Recent federal appellate court precedent interpreting the ATS provides the mechanism for granting victims redress and enforcing accountability of sponsors (usually pharmaceutical companies and research and academic institutions) for informed consent misconduct. Substantive human rights protections are vital in order to ensure that every person can realize the "right to health." This article concludes that by building on the federal appellate court's ATS analysis, which grants foreign trial participants the right to pursue claims of human rights violations in US courts, a mechanism can be created for enforcing not only substantive informed consent, but also human rights protections.

  13. [The right to self-determination versus the obligation to protect one's health].

    PubMed

    Höfling, Wolfram

    2009-01-01

    "Individual responsibility" and the abidance by any "health-related obligations" are key words of the present political and legal German healthcare debate. In the process of adjusting the German welfare state by focussing the ideal allocation of common health resources patients who do not meet their "health-related obligations" are thus expected to accept cutbacks in medical care services. However, from the perspective of constitutional law there is no "health-related obligation" deriving from the German constitution - the right to self-determination guaranteed in Art. 2 Sect. 2 Sent. 1 of the German constitution has not been amended to impose a corresponding duty. Hence, health-related obligations may only refer to indirect ways of exercising individual responsibility, no more and no less. The present article highlights the few possibilities which the German constitution provides for the implementation of "health-related obligations" and reminds us of the conceptual aspects which have to be considered by the legislator.

  14. Potent Inhibition of Human Immunodeficiency Virus Type 1 Replication by an Intracellular Anti-Rev Single-Chain Antibody

    NASA Astrophysics Data System (ADS)

    Duan, Lingxun; Bagasra, Omar; Laughlin, Mark A.; Oakes, Joseph W.; Pomerantz, Roger J.

    1994-05-01

    Human immunodeficiency virus type 1 (HIV-1) has a complex life cycle, which has made it a difficult target for conventional therapeutic modalities. A single-chain antibody moiety, directed against the HIV-1 regulatory protein Rev, which rescues unspliced viral RNA from the nucleus of infected cells, has now been developed. This anti-Rev single-chain construct (SFv) consists of both light and heavy chain variable regions of an anti-Rev monoclonal antibody, which, when expressed intracellularly within human cells, potently inhibits HIV-1 replication. This intracellular SFv molecule is demonstrated to specifically antagonize Rev function. Thus, intracellular SFv expression, against a retroviral regulatory protein, may be useful as a gene therapeutic approach to combat HIV-1 infections.

  15. 40 CFR 152.97 - Rights and obligations of data submitters.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... is an original data submitter; (iii) For each such active ingredient, the type(s) of study he has... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Rights and obligations of data... Data Submitters' Rights § 152.97 Rights and obligations of data submitters. (a) Right to be listed on...

  16. 40 CFR 152.97 - Rights and obligations of data submitters.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... is an original data submitter; (iii) For each such active ingredient, the type(s) of study he has... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Rights and obligations of data... Data Submitters' Rights § 152.97 Rights and obligations of data submitters. (a) Right to be listed on...

  17. 40 CFR 152.97 - Rights and obligations of data submitters.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... is an original data submitter; (iii) For each such active ingredient, the type(s) of study he has... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Rights and obligations of data... Data Submitters' Rights § 152.97 Rights and obligations of data submitters. (a) Right to be listed on...

  18. 40 CFR 152.97 - Rights and obligations of data submitters.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... is an original data submitter; (iii) For each such active ingredient, the type(s) of study he has... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Rights and obligations of data... Data Submitters' Rights § 152.97 Rights and obligations of data submitters. (a) Right to be listed on...

  19. Cultural Generality of the Integration of Obligation and Other Motives

    ERIC Educational Resources Information Center

    Yang, Jen-Shou

    2012-01-01

    The purpose of the present study is twofold. One is to assess the cultural generality of the information integration rule for moral obligation. The other is to examine how people integrate moral obligation and self-interest. Two studies were implemented following the functional measurement methodology with Chinese samples. Study 1 replicated the…

  20. 31 CFR 225.9 - Return of Government obligations to obligor.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... event of an obligor's default on any term, condition, or stipulation of a bond. (d) Return of definitive Government obligations; risk of loss. Definitive Government obligations to be returned to the obligor will be forwarded at the obligor's risk and expense, either by the bond official, or by a custodian upon receipt of...

  1. 7 CFR 25.603 - Grant approval and obligation of funds.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Grant approval and obligation of funds. 25.603 Section 25.603 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Round II and Round IIS Grants § 25.603 Grant approval and obligation of funds. Grants may be made...

  2. Adolescent emotional distress: the role of family obligations and school connectedness.

    PubMed

    Wilkinson-Lee, Ada M; Zhang, Qionghui; Nuno, Velia Leybas; Wilhelm, Mari S

    2011-02-01

    The current study draws upon ecodevelopmental theory to identify protective and risk factors that may influence emotional distress during adolescence. Hierarchical regression analyses were used to examine the relationship among family obligations, school connectedness and emotional distress of 4,198 (51% female) middle and high school students who were primarily (59%) European American. The overall model explained 21.1% of the variance in student emotional distress. A significant interaction effect was found indicating that school connectedness moderated the relationship between family obligations and emotional distress. Specifically, for students with low to moderate levels of family obligations, a stronger sense of school connectedness was associated with lower emotional distress. The buffering effect of school connectedness was weakened as the level of family obligations increased and completely disappeared for students who experienced high levels of family obligations. The creation of a program that takes a holistic approach, in order to curtail the levels of highly emotionally distressed adolescents, must continue to address the ever changing demands that adolescents encounter and prepare youth to deal with functioning within multiple contexts and do so while maintaining emotional well-being.

  3. 31 CFR 1023.311 - Filing obligations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR BROKERS OR DEALERS IN SECURITIES Reports Required To Be Made By Brokers or Dealers in Securities § 1023.311 Filing obligations. Refer to § 1010.311... securities. ...

  4. 31 CFR 1023.311 - Filing obligations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR BROKERS OR DEALERS IN SECURITIES Reports Required To Be Made By Brokers or Dealers in Securities § 1023.311 Filing obligations. Refer to § 1010.311... securities. ...

  5. 31 CFR 1023.311 - Filing obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR BROKERS OR DEALERS IN SECURITIES Reports Required To Be Made By Brokers or Dealers in Securities § 1023.311 Filing obligations. Refer to § 1010.311... securities. ...

  6. 31 CFR 1023.311 - Filing obligations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR BROKERS OR DEALERS IN SECURITIES Reports Required To Be Made By Brokers or Dealers in Securities § 1023.311 Filing obligations. Refer to § 1010.311... securities. ...

  7. 26 CFR 1.381(c)(16)-1 - Obligations of distributor or transferor corporation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... obligation of a distributor or transferor corporation which gives rise to a liability after the date of... shall govern: (i) If the obligation gave rise to a liability before the date of distribution or transfer, see section 381(c)(4) and the regulations thereunder. (ii) If the obligation gives rise to a liability...

  8. 26 CFR 1.691(e)-1 - Installment obligations transmitted at death when prior law applied.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Installment obligations transmitted at death... Decedents § 1.691(e)-1 Installment obligations transmitted at death when prior law applied. (a) In general... obligations at the death of a holder of such obligations were required to be reported in the return of the...

  9. Genome Evolution in the Obligate but Environmentally Active Luminous Symbionts of Flashlight Fish

    PubMed Central

    Hendry, Tory A.; de Wet, Jeffrey R.; Dougan, Katherine E.; Dunlap, Paul V.

    2016-01-01

    The luminous bacterial symbionts of anomalopid flashlight fish are thought to be obligately dependent on their hosts for growth and share several aspects of genome evolution with unrelated obligate symbionts, including genome reduction. However, in contrast to most obligate bacteria, anomalopid symbionts have an active environmental phase that may be important for symbiont transmission. Here we investigated patterns of evolution between anomalopid symbionts compared with patterns in free-living relatives and unrelated obligate symbionts to determine if trends common to obligate symbionts are also found in anomalopid symbionts. Two symbionts, “Candidatus Photodesmus katoptron” and “Candidatus Photodesmus blepharus,” have genomes that are highly similar in gene content and order, suggesting genome stasis similar to ancient obligate symbionts present in insect lineages. This genome stasis exists in spite of the symbiont’s inferred ability to recombine, which is frequently lacking in obligate symbionts with stable genomes. Additionally, we used genome comparisons and tests of selection to infer which genes may be particularly important for the symbiont’s ecology compared with relatives. In keeping with obligate dependence, substitution patterns suggest that most symbiont genes are experiencing relaxed purifying selection compared with relatives. However, genes involved in motility and carbon storage, which are likely to be used outside the host, appear to be under increased purifying selection. Two chemoreceptor chemotaxis genes are retained by both species and show high conservation with amino acid sensing genes, suggesting that the bacteria may actively seek out hosts using chemotaxis toward amino acids, which the symbionts are not able to synthesize. PMID:27389687

  10. Targeting of a chlamydial protease impedes intracellular bacterial growth.

    PubMed

    Christian, Jan G; Heymann, Julia; Paschen, Stefan A; Vier, Juliane; Schauenburg, Linda; Rupp, Jan; Meyer, Thomas F; Häcker, Georg; Heuer, Dagmar

    2011-09-01

    Chlamydiae are obligate intracellular bacteria that propagate in a cytosolic vacuole. Recent work has shown that growth of Chlamydia induces the fragmentation of the Golgi apparatus (GA) into ministacks, which facilitates the acquisition of host lipids into the growing inclusion. GA fragmentation results from infection-associated cleavage of the integral GA protein, golgin-84. Golgin-84-cleavage, GA fragmentation and growth of Chlamydia trachomatis can be blocked by the peptide inhibitor WEHD-fmk. Here we identify the bacterial protease chlamydial protease-like activity factor (CPAF) as the factor mediating cleavage of golgin-84 and as the target of WEHD-fmk-inhibition. WEHD-fmk blocked cleavage of golgin-84 as well as cleavage of known CPAF targets during infection with C. trachomatis and C. pneumoniae. The same effect was seen when active CPAF was expressed in non-infected cells and in a cell-free system. Ectopic expression of active CPAF in non-infected cells was sufficient for GA fragmentation. GA fragmentation required the small GTPases Rab6 and Rab11 downstream of CPAF-activity. These results define CPAF as the first protein that is essential for replication of Chlamydia. We suggest that this role makes CPAF a potential anti-infective therapeutic target.

  11. The genome of the obligate endobacterium of an AM fungus reveals an interphylum network of nutritional interactions.

    PubMed

    Ghignone, Stefano; Salvioli, Alessandra; Anca, Iulia; Lumini, Erica; Ortu, Giuseppe; Petiti, Luca; Cruveiller, Stéphane; Bianciotto, Valeria; Piffanelli, Pietro; Lanfranco, Luisa; Bonfante, Paola

    2012-01-01

    As obligate symbionts of most land plants, arbuscular mycorrhizal fungi (AMF) have a crucial role in ecosystems, but to date, in the absence of genomic data, their adaptive biology remains elusive. In addition, endobacteria are found in their cytoplasm, the role of which is unknown. In order to investigate the function of the Gram-negative Candidatus Glomeribacter gigasporarum, an endobacterium of the AMF Gigaspora margarita, we sequenced its genome, leading to an ∼1.72-Mb assembly. Phylogenetic analyses placed Ca. G. gigasporarum in the Burkholderiaceae whereas metabolic network analyses clustered it with insect endobacteria. This positioning of Ca. G. gigasporarum among different bacterial classes reveals that it has undergone convergent evolution to adapt itself to intracellular lifestyle. The genome annotation of this mycorrhizal-fungal endobacterium has revealed an unexpected genetic mosaic where typical determinants of symbiotic, pathogenic and free-living bacteria are integrated in a reduced genome. Ca. G. gigasporarum is an aerobic microbe that depends on its host for carbon, phosphorus and nitrogen supply; it also expresses type II and type III secretion systems and synthesizes vitamin B12, antibiotics- and toxin-resistance molecules, which may contribute to the fungal host's ecological fitness. Ca. G. gigasporarum has an extreme dependence on its host for nutrients and energy, whereas the fungal host is itself an obligate biotroph that relies on a photosynthetic plant. Our work represents the first step towards unraveling a complex network of interphylum interactions, which is expected to have a previously unrecognized ecological impact.

  12. 42 CFR 408.4 - Payment obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... kidney donors. (1) No premiums are required for SMI benefits related to the donation of a kidney if the donor is not an enrollee. (2) A kidney donor who is an enrollee is not relieved of the obligation for...

  13. 42 CFR 408.4 - Payment obligations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... kidney donors. (1) No premiums are required for SMI benefits related to the donation of a kidney if the donor is not an enrollee. (2) A kidney donor who is an enrollee is not relieved of the obligation for...

  14. 12 CFR 1270.18 - Additional requirements; notice of attachment for Book-entry consolidated obligations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... for Book-entry consolidated obligations. 1270.18 Section 1270.18 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS LIABILITIES Book-Entry Procedure for Consolidated Obligations § 1270.18 Additional requirements; notice of attachment for Book-entry consolidated obligations. (a...

  15. 12 CFR 1270.18 - Additional requirements; notice of attachment for Book-entry consolidated obligations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... for Book-entry consolidated obligations. 1270.18 Section 1270.18 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS LIABILITIES Book-Entry Procedure for Consolidated Obligations § 1270.18 Additional requirements; notice of attachment for Book-entry consolidated obligations. (a...

  16. 12 CFR 1270.18 - Additional requirements; notice of attachment for Book-entry consolidated obligations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... for Book-entry consolidated obligations. 1270.18 Section 1270.18 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS LIABILITIES Book-Entry Procedure for Consolidated Obligations § 1270.18 Additional requirements; notice of attachment for Book-entry consolidated obligations. (a...

  17. 47 CFR 51.703 - Non-Access reciprocal compensation obligation of LECs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Non-Access reciprocal compensation obligation... Telecommunications Traffic § 51.703 Non-Access reciprocal compensation obligation of LECs. (a) Each LEC shall establish Non-Access Reciprocal Compensation arrangements for transport and termination of Non-Access...

  18. 47 CFR 51.703 - Non-Access reciprocal compensation obligation of LECs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Non-Access reciprocal compensation obligation... Telecommunications Traffic § 51.703 Non-Access reciprocal compensation obligation of LECs. (a) Each LEC shall establish Non-Access Reciprocal Compensation arrangements for transport and termination of Non-Access...

  19. 47 CFR 51.703 - Non-Access reciprocal compensation obligation of LECs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Non-Access reciprocal compensation obligation... Telecommunications Traffic § 51.703 Non-Access reciprocal compensation obligation of LECs. (a) Each LEC shall establish Non-Access Reciprocal Compensation arrangements for transport and termination of Non-Access...

  20. 12 CFR 987.8 - Additional requirements; notice of attachment for Book-entry consolidated obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... for Book-entry consolidated obligations. 987.8 Section 987.8 Banks and Banking FEDERAL HOUSING FINANCE BOARD OFFICE OF FINANCE BOOK-ENTRY PROCEDURE FOR CONSOLIDATED OBLIGATIONS § 987.8 Additional requirements; notice of attachment for Book-entry consolidated obligations. (a) Additional requirements. In any...

  1. Review: Intracardiac intracellular angiotensin system in diabetes

    PubMed Central

    Kumar, Rajesh; Yong, Qian Chen; Thomas, Candice M.

    2012-01-01

    The renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appears to differ from the circulating and the local RAS, in terms of components and the mechanism of action. These differences may alter treatment strategies that target the RAS in several pathological conditions. Recent work from our laboratory has demonstrated significant upregulation of the cardiac, intracellular RAS in diabetes, which is associated with cardiac dysfunction. Here, we have reviewed evidence supporting an intracellular RAS in different cell types, ANG II's actions in cardiac cells, and its mechanism of action, focusing on the intracellular cardiac RAS in diabetes. We have discussed the significance of an intracellular RAS in cardiac pathophysiology and implications for potential therapies. PMID:22170614

  2. Promotion and Rescue of Intracellular Brucella neotomae Replication during Coinfection with Legionella pneumophila.

    PubMed

    Kang, Yoon-Suk; Kirby, James E

    2017-05-01

    We established a new Brucella neotomae in vitro model system for study of type IV secretion system-dependent (T4SS) pathogenesis in the Brucella genus. Importantly, B. neotomae is a rodent pathogen, and unlike B. abortus , B. melitensis , and B. suis , B. neotomae has not been observed to infect humans. It therefore can be handled more facilely using biosafety level 2 practices. More particularly, using a series of novel fluorescent protein and lux operon reporter systems to differentially label pathogens and track intracellular replication, we confirmed T4SS-dependent intracellular growth of B. neotomae in macrophage cell lines. Furthermore, B. neotomae exhibited early endosomal (LAMP-1) and late endoplasmic reticulum (calreticulin)-associated phagosome maturation. These findings recapitulate prior observations for human-pathogenic Brucella spp. In addition, during coinfection experiments with Legionella pneumophila , we found that defective intracellular replication of a B. neotomae T4SS virB4 mutant was rescued and baseline levels of intracellular replication of wild-type B. neotomae were significantly stimulated by coinfection with wild-type but not T4SS mutant L. pneumophila Using confocal microscopy, it was determined that intracellular colocalization of B. neotomae and L. pneumophila was required for rescue and that colocalization came at a cost to L. pneumophila fitness. These findings were not completely expected based on known temporal and qualitative differences in the intracellular life cycles of these two pathogens. Taken together, we have developed a new system for studying in vitro Brucella pathogenesis and found a remarkable T4SS-dependent interplay between Brucella and Legionella during macrophage coinfection. Copyright © 2017 American Society for Microbiology.

  3. Insecticide resistance and intracellular proteases.

    PubMed

    Wilkins, Richard M

    2017-12-01

    Pesticide resistance is an example of evolution in action with mechanisms of resistance arising from mutations or increased expression of intrinsic genes. Intracellular proteases have a key role in maintaining healthy cells and in responding to stressors such as pesticides. Insecticide-resistant insects have constitutively elevated intracellular protease activity compared to corresponding susceptible strains. This increase was shown for some cases originally through biochemical enzyme studies and subsequently putatively by transcriptomics and proteomics methods. Upregulation and expression of proteases have been characterised in resistant strains of some insect species, including mosquitoes. This increase in proteolysis results in more degradation products (amino acids) of intracellular proteins. These may be utilised in the resistant strain to better protect the cell from stress. There are changes in insect intracellular proteases shortly after insecticide exposure, suggesting a role in stress response. The use of protease and proteasome inhibitors or peptide mimetics as synergists with improved application techniques and through protease gene knockdown using RNA interference (possibly expressed in crop plants) may be potential pest management strategies, in situations where elevated intracellular proteases are relevant. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  4. [Analysis of DNA-DNA homologies in obligate methylotrophic bacteria].

    PubMed

    Doronina, N V; Govorukhina, N I; Lysenko, A M; Trotsenko, Iu A

    1988-01-01

    The genotypic affinity of 19 bacterial strains obligately dependent on methanol or methylamine as carbon and energy sources was studied by techniques of molecular DNA hybridization. The high homology level (35-88%) between motile strain Methylophilus methanolovorus V-1447D and nonmotile strain Methylobacillus sp. VSB-792 as well as other motile strains (Pseudomonas methanolica ATCC 21704, Methylomonas methanolica NRRL 5458, Pseudomonas sp. W6, strain A3) indicates that all of them belong to one genus. Rather high level of homology (62-63%) was found between Methylobacillus glycogenes ATCC 29475 and Pseudomonas insueta ATCC 21276 and strain G-10. The motile strain Methylophilus methylotrophus NCIB 10515 has a low homology (below 20%) to other of the studied obligate methylobacteria. Therefore, at least two genetically different genera of obligate methylobacteria can be distinguished, namely Methylophilus and Methylobacillus, the latter being represented by both motile and nonmotile forms.

  5. Balancing obligations: should written information about life-sustaining treatment be neutral?

    PubMed Central

    Xafis, Vicki; Wilkinson, Dominic; Gillam, Lynn; Sullivan, Jane

    2015-01-01

    Parents who are facing decisions about life-sustaining treatment for their seriously ill or dying child are supported by their child's doctors and nurses. They also frequently seek other information sources to help them deal with the medical and ethical questions that arise. This might include written or web-based information. As part of a project involving the development of such a resource to support parents facing difficult decisions, some ethical questions emerged. Should this information be presented in a strictly neutral fashion? Is it problematic if narratives, arguments or perspectives appear to favour stopping over continuing life-sustaining treatment? Similar questions might arise with written materials about decisions for adults, or for other ethically contentious decisions. This paper explores the meaning of ‘balance’ in information provision, focusing particularly on written information about life-sustaining treatment for children. We contrast the norm of non-directiveness in genetic counselling with the shared decision-making model often endorsed in end-of-life care. We review evidence that parents do not find neutrality from medical professionals helpful in discussions. We argue that balance in written information must be understood in the light of the aim of the document, the most common situation in which it will be used, and any existing biases. We conclude with four important strategies for ensuring that non-neutral information is nevertheless ethically appropriate. PMID:24763219

  6. 47 CFR 51.605 - Additional obligations of incumbent local exchange carriers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Additional obligations of incumbent local exchange carriers. 51.605 Section 51.605 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERCONNECTION Resale § 51.605 Additional obligations of incumbent local exchange carriers. (a) An incumbent LEC...

  7. 31 CFR 1010.940 - Photographic or other reproductions of Government obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY GENERAL... other obligation or security of the United States as defined in 18 U.S.C. 8, or (b) Any obligation or other security of any foreign government, the reproduction of which is prohibited by law. ...

  8. 31 CFR 1010.940 - Photographic or other reproductions of Government obligations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY GENERAL... other obligation or security of the United States as defined in 18 U.S.C. 8, or (b) Any obligation or other security of any foreign government, the reproduction of which is prohibited by law. ...

  9. 31 CFR 1010.940 - Photographic or other reproductions of Government obligations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY GENERAL... other obligation or security of the United States as defined in 18 U.S.C. 8, or (b) Any obligation or other security of any foreign government, the reproduction of which is prohibited by law. ...

  10. 33 CFR 137.5 - Disclosure obligations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Disclosure obligations. 137.5 Section 137.5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY: STANDARDS FOR CONDUCTING...

  11. 33 CFR 137.5 - Disclosure obligations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Disclosure obligations. 137.5 Section 137.5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY: STANDARDS FOR CONDUCTING...

  12. 33 CFR 137.5 - Disclosure obligations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Disclosure obligations. 137.5 Section 137.5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY: STANDARDS FOR CONDUCTING...

  13. 33 CFR 137.5 - Disclosure obligations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Disclosure obligations. 137.5 Section 137.5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY: STANDARDS FOR CONDUCTING...

  14. 33 CFR 137.5 - Disclosure obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Disclosure obligations. 137.5 Section 137.5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY: STANDARDS FOR CONDUCTING...

  15. 47 CFR 27.1340 - Reporting obligations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 700 MHz Public/Private Partnership § 27.1340 Reporting obligations. (a) The Upper 700 MHz D Block licensee and the Public Safety Broadband Licensee shall jointly file quarterly reports with...

  16. 47 CFR 27.1340 - Reporting obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 700 MHz Public/Private Partnership § 27.1340 Reporting obligations. (a) The Upper 700 MHz D Block licensee and the Public Safety Broadband Licensee shall jointly file quarterly reports with...

  17. 47 CFR 27.1340 - Reporting obligations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 700 MHz Public/Private Partnership § 27.1340 Reporting obligations. (a) The Upper 700 MHz D Block licensee and the Public Safety Broadband Licensee shall jointly file quarterly reports with...

  18. Do researchers have an obligation to actively look for genetic incidental findings?

    PubMed

    Gliwa, Catherine; Berkman, Benjamin E

    2013-01-01

    The rapid growth of next-generation genetic sequencing has prompted debate about the responsibilities of researchers toward genetic incidental findings. Assuming there is a duty to disclose significant incidental findings, might there be an obligation for researchers to actively look for these findings? We present an ethical framework for analyzing whether there is a positive duty to look for genetic incidental findings. Using the ancillary care framework as a guide, we identify three main criteria that must be present to give rise to an obligation to look: high benefit to participants, lack of alternative access for participants, and reasonable burden on researchers. Our analysis indicates that there is no obligation to look for incidental findings today, but during the ongoing translation of genomic analysis from research to clinical care, this obligation may arise.

  19. Do Researchers Have an Obligation to Actively Look for Genetic Incidental Findings?

    PubMed Central

    Gliwa, Catherine; Berkman, Benjamin E.

    2014-01-01

    The rapid growth of next-generation genetic sequencing has prompted debate about the responsibilities of researchers toward genetic incidental findings. Assuming there is a duty to disclose significant incidental findings, might there be an obligation for researchers to actively look for these findings? We present an ethical framework for analyzing whether there is a positive duty to look for genetic incidental findings. Using the ancillary care framework as a guide, we identify three main criteria that must be present to give rise to an obligation to look: high benefit to participants, lack of alternative access for participants, and reasonable burden on researchers. Our analysis indicates that there is no obligation to look for incidental findings today, but during the ongoing translation of genomic analysis from research to clinical care, this obligation may arise. PMID:23391059

  20. Mapping intracellular mechanics on micropatterned substrates

    PubMed Central

    Mandal, Kalpana; Asnacios, Atef; Goud, Bruno; Manneville, Jean-Baptiste

    2016-01-01

    The mechanical properties of cells impact on their architecture, their migration, intracellular trafficking, and many other cellular functions and have been shown to be modified during cancer progression. We have developed an approach to map the intracellular mechanical properties of living cells by combining micropatterning and optical tweezers-based active microrheology. We optically trap micrometer-sized beads internalized in cells plated on crossbow-shaped adhesive micropatterns and track their displacement following a step displacement of the cell. The local intracellular complex shear modulus is measured from the relaxation of the bead position assuming that the intracellular microenvironment of the bead obeys power-law rheology. We also analyze the data with a standard viscoelastic model and compare with the power-law approach. We show that the shear modulus decreases from the cell center to the periphery and from the cell rear to the front along the polarity axis of the micropattern. We use a variety of inhibitors to quantify the spatial contribution of the cytoskeleton, intracellular membranes, and ATP-dependent active forces to intracellular mechanics and apply our technique to differentiate normal and cancer cells. PMID:27799529

  1. Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.

    PubMed

    Kumari, Anjali; Singh, Krishn Pratap; Mandal, Abhishek; Paswan, Ranjeet Kumar; Sinha, Preeti; Das, Pradeep; Ali, Vahab; Bimal, Sanjiva; Lal, Chandra Shekhar

    2017-01-01

    Leishmaniasis caused by Leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. Therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. Leishmania is an obligate intracellular parasite that alternates between sand fly and human host. To survive and establish infections, Leishmania parasites scavenge and internalize nutrients from the host. Nevertheless, host cells presents mechanism like nutrient restriction to inhibit microbial growth and control infection. Zinc is crucial for cellular growth and disruption in its homeostasis hinders growth and survival in many cells. However, little is known about the role of zinc in Leishmania growth and survival. In this study, the effect of zinc on the growth and survival of L.donovani was analyzed by both Zinc-depletion and Zinc-supplementation using Zinc-specific chelator N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) and Zinc Sulfate (ZnSO4). Treatment of parasites with TPEN rather than ZnSO4 had significantly affected the growth in a dose- and time-dependent manner. The pre-treatment of promastigotes with TPEN resulted into reduced host-parasite interaction as indicated by decreased association index. Zn depletion resulted into flux in intracellular labile Zn pool and increased in ROS generation correlated with decreased intracellular total thiol and retention of plasma membrane integrity without phosphatidylserine exposure in TPEN treated promastigotes. We also observed that TPEN-induced Zn depletion resulted into collapse of mitochondrial membrane potential which is associated with increase in cytosolic calcium and cytochrome-c. DNA fragmentation analysis showed increased DNA fragments in Zn-depleted cells. In summary, intracellular Zn depletion in the L. donovani promastigotes led to ROS-mediated caspase-independent mitochondrial dysfunction resulting into apoptosis-like cell death. Therefore, cellular

  2. EphrinA2 Receptor (EphA2) Is an Invasion and Intracellular Signaling Receptor for Chlamydia trachomatis

    PubMed Central

    Subbarayal, Prema; Karunakaran, Karthika; Winkler, Ann-Cathrin; Rother, Marion; Gonzalez, Erik; Meyer, Thomas F.; Rudel, Thomas

    2015-01-01

    The obligate intracellular bacterium Chlamydia trachomatis invades into host cells to replicate inside a membrane-bound vacuole called inclusion. Multiple different host proteins are recruited to the inclusion and are functionally modulated to support chlamydial development. Invaded and replicating Chlamydia induces a long-lasting activation of the PI3 kinase signaling pathway that is required for efficient replication. We identified the cell surface tyrosine kinase EphrinA2 receptor (EphA2) as a chlamydial adherence and invasion receptor that induces PI3 kinase (PI3K) activation, promoting chlamydial replication. Interfering with binding of C. trachomatis serovar L2 (Ctr) to EphA2, downregulation of EphA2 expression or inhibition of EphA2 activity significantly reduced Ctr infection. Ctr interacts with and activates EphA2 on the cell surface resulting in Ctr and receptor internalization. During chlamydial replication, EphA2 remains active accumulating around the inclusion and interacts with the p85 regulatory subunit of PI3K to support the activation of the PI3K/Akt signaling pathway that is required for normal chlamydial development. Overexpression of full length EphA2, but not the mutant form lacking the intracellular cytoplasmic domain, enhanced PI3K activation and Ctr infection. Despite the depletion of EphA2 from the cell surface, Ctr infection induces upregulation of EphA2 through the activation of the ERK pathway, which keeps the infected cell in an apoptosis-resistant state. The significance of EphA2 as an entry and intracellular signaling receptor was also observed with the urogenital C. trachomatis-serovar D. Our findings provide the first evidence for a host cell surface receptor that is exploited for invasion as well as for receptor-mediated intracellular signaling to facilitate chlamydial replication. In addition, the engagement of a cell surface receptor at the inclusion membrane is a new mechanism by which Chlamydia subverts the host cell and

  3. EphrinA2 receptor (EphA2) is an invasion and intracellular signaling receptor for Chlamydia trachomatis.

    PubMed

    Subbarayal, Prema; Karunakaran, Karthika; Winkler, Ann-Cathrin; Rother, Marion; Gonzalez, Erik; Meyer, Thomas F; Rudel, Thomas

    2015-04-01

    The obligate intracellular bacterium Chlamydia trachomatis invades into host cells to replicate inside a membrane-bound vacuole called inclusion. Multiple different host proteins are recruited to the inclusion and are functionally modulated to support chlamydial development. Invaded and replicating Chlamydia induces a long-lasting activation of the PI3 kinase signaling pathway that is required for efficient replication. We identified the cell surface tyrosine kinase EphrinA2 receptor (EphA2) as a chlamydial adherence and invasion receptor that induces PI3 kinase (PI3K) activation, promoting chlamydial replication. Interfering with binding of C. trachomatis serovar L2 (Ctr) to EphA2, downregulation of EphA2 expression or inhibition of EphA2 activity significantly reduced Ctr infection. Ctr interacts with and activates EphA2 on the cell surface resulting in Ctr and receptor internalization. During chlamydial replication, EphA2 remains active accumulating around the inclusion and interacts with the p85 regulatory subunit of PI3K to support the activation of the PI3K/Akt signaling pathway that is required for normal chlamydial development. Overexpression of full length EphA2, but not the mutant form lacking the intracellular cytoplasmic domain, enhanced PI3K activation and Ctr infection. Despite the depletion of EphA2 from the cell surface, Ctr infection induces upregulation of EphA2 through the activation of the ERK pathway, which keeps the infected cell in an apoptosis-resistant state. The significance of EphA2 as an entry and intracellular signaling receptor was also observed with the urogenital C. trachomatis-serovar D. Our findings provide the first evidence for a host cell surface receptor that is exploited for invasion as well as for receptor-mediated intracellular signaling to facilitate chlamydial replication. In addition, the engagement of a cell surface receptor at the inclusion membrane is a new mechanism by which Chlamydia subverts the host cell and

  4. 31 CFR 1026.311 - Filing obligations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Filing obligations. 1026.311 Section 1026.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR FUTURES COMMISSION MERCHANTS AND...

  5. 31 CFR 1026.311 - Filing obligations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Filing obligations. 1026.311 Section 1026.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR FUTURES COMMISSION MERCHANTS AND...

  6. 31 CFR 1026.311 - Filing obligations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Filing obligations. 1026.311 Section 1026.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR FUTURES COMMISSION MERCHANTS AND...

  7. 31 CFR 1022.311 - Filing obligations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Filing obligations. 1022.311 Section 1022.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR MONEY SERVICES BUSINESSES Reports...

  8. 31 CFR 1022.311 - Filing obligations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Filing obligations. 1022.311 Section 1022.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR MONEY SERVICES BUSINESSES Reports...

  9. 31 CFR 1022.311 - Filing obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Filing obligations. 1022.311 Section 1022.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR MONEY SERVICES BUSINESSES Reports...

  10. 31 CFR 1022.311 - Filing obligations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Filing obligations. 1022.311 Section 1022.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR MONEY SERVICES BUSINESSES Reports...

  11. 47 CFR 51.603 - Resale obligation of all local exchange carriers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Resale obligation of all local exchange carriers. 51.603 Section 51.603 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERCONNECTION Resale § 51.603 Resale obligation of all local exchange carriers. (a) A LEC shall make its telecommunication...

  12. 40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... obligated party are determined according to the following formulas: (1) Cellulosic biofuel. RVOCB,i = (RFStdCB,i * (GVi + DVi)) + DCB,i-1 Where: RVOCB,i = The Renewable Volume Obligation for cellulosic biofuel... biofuel for calendar year i, determined by EPA pursuant to § 80.1405, in percent. GVi = The non-renewable...

  13. 40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... obligated party are determined according to the following formulas: (1) Cellulosic biofuel. RVOCB,i = (RFStdCB,i * (GVi + DVi)) + DCB,i-1 Where: RVOCB,i = The Renewable Volume Obligation for cellulosic biofuel... biofuel for calendar year i, determined by EPA pursuant to § 80.1405, in percent. GVi = The non-renewable...

  14. 40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... obligated party are determined according to the following formulas: (1) Cellulosic biofuel. RVOCB,i = (RFStdCB,i * (GVi + DVi)) + DCB,i-1 Where: RVOCB,i = The Renewable Volume Obligation for cellulosic biofuel... biofuel for calendar year i, determined by EPA pursuant to § 80.1405, in percent. GVi = The non-renewable...

  15. 40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... obligated party are determined according to the following formulas: (1) Cellulosic biofuel. RVOCB,i = (RFStdCB,i * (GVi + DVi)) + DCB,i-1 Where: RVOCB,i = The Renewable Volume Obligation for cellulosic biofuel... biofuel for calendar year i, determined by EPA pursuant to § 80.1405, in percent. GVi = The non-renewable...

  16. 31 CFR 543.407 - Payments from blocked accounts to satisfy obligations prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY CôTE D... obligations prohibited. Pursuant to § 543.201, no debits may be made to a blocked account to pay obligations...

  17. 31 CFR 543.407 - Payments from blocked accounts to satisfy obligations prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY CôTE D... obligations prohibited. Pursuant to § 543.201, no debits may be made to a blocked account to pay obligations...

  18. 48 CFR 519.7013 - Obligation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7013 Obligation. (a) The mentor or protégé may terminate the Agreement in accordance with 519.7010. The mentor will notify the Mentor-Protégé Program Manager and the contracting officer, in writing, at least 30 days in advance of the mentor firm's...

  19. 40 CFR 80.1407 - How are the Renewable Volume Obligations calculated?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... cellulosic biofuel, in gallons. (2) Biomass-based diesel. RVOBBD,i = (RFStdBBD,i * (GVi + DVi)) + DBBD,i-1 Where: RVOBBD,i = The Renewable Volume Obligation for biomass-based diesel for an obligated party for calendar year i, in gallons. RFStdBBD,i = The standard for biomass-based diesel for calendar year i...

  20. Notification: Audit of Region 5 Unliquidated Obligations

    EPA Pesticide Factsheets

    Project #OA-FY12-0306, June 4, 2012. The U.S. Environmental Protection Agency (EPA) Office of Inspector General (OIG) is beginning the fieldwork phase of our Audit of Region 5 Unliquidated Obligations.

  1. The author’s opportunity and obligation

    USDA-ARS?s Scientific Manuscript database

    Peer review is a critical component of the scientific method and therefore should be an obligation for everyone who desires to publish their research results in refereed journals. This editorial is written to address a specific problem being encountered by editors of Soil & Tillage Research, but the...

  2. 21 CFR 26.62 - General obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false General obligations. 26.62 Section 26.62 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS...

  3. 5 CFR 724.202 - Notice obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... within your agency (e.g., EEO/civil rights office, human resources office or legal office). Additional... RETALIATION ACT OF 2002 Notification of Rights and Protections and Training § 724.202 Notice obligations. (a... employment about the rights and remedies available under the Antidiscrimination Laws and Whistleblower...

  4. 19 CFR 10.585 - Importer obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE...-United States Free Trade Agreement Import Requirements § 10.585 Importer obligations. (a) General. An... civil or administrative penalties under 19 U.S.C. 1592 for making an incorrect claim for preferential...

  5. 19 CFR 10.585 - Importer obligations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Importer obligations. 10.585 Section 10.585 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. Dominican Republic-Central America...

  6. 19 CFR 10.585 - Importer obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Importer obligations. 10.585 Section 10.585 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. Dominican Republic-Central America...

  7. 19 CFR 10.585 - Importer obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Importer obligations. 10.585 Section 10.585 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. Dominican Republic-Central America...

  8. 19 CFR 10.585 - Importer obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Importer obligations. 10.585 Section 10.585 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. Dominican Republic-Central America...

  9. The 'special obligations' of the modern Hippocratic Oath for 21st century medicine.

    PubMed

    Holmboe, Eric; Bernabeo, Elizabeth

    2014-01-01

    Profound advances and discoveries in medicine have markedly improved the lives of many over the 50 years since the modern Hippocratic Oath was written. Regrettably, these advances were and continue to be implemented suboptimally and inequitably across the globe. 'Special obligations to all my fellow humans' is an important theme of the modern Oath. From this perspective, we reflect on the special obligations of the medical profession, and examine how these obligations have changed over the past 50 years. We draw from perspectives of the social contract, professionalism, quality improvement, patient safety and a group of 31 international colleagues involved in medical education as we examine these obligations for individual doctors, health care institutions and medical education systems. The perspectives of the 31 clinician-educators helped us to situate the meaning of the theme of 'special obligations' in the context of challenges facing medical education and health care in the 21st century. Improving the quality of care and patient safety, and reducing health care disparities are now paramount as 'special obligations' for doctors, health care systems and medical education organisations, and require us to work collectively and collaboratively in an increasingly interconnected world. In our view, traditions such as the Hippocratic Oath will be worthy of public support only when the medical profession demonstrates in meaningful and transparent ways that it is meeting its social and civic obligations to make the world, not just health care, a better place. © 2013 John Wiley & Sons Ltd.

  10. 47 CFR 76.56 - Signal carriage obligations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... qualified local NCE station affiliated with a State public television network shall not be required to carry... stations in fulfillment of these must-carry obligations may do so, subject to approval by the franchising...

  11. Why patients have a moral obligation to give care to clinicians.

    PubMed

    Buetow, Stephen

    2014-12-01

    Progress is being made in transitioning from clinicians who are torn between caring for patients and populations, to clinicians who are partnering with patients to care for patients as people. However, the focus is still on what patients and others can do for patients, however defined. For clinicians whose interests must be similarly respected for their own sake and because they are integrally related to those of patients, what can and should patients do? Patients can be exempted from some normal social roles but are generally recognized to have moral obligations in health care. One of these obligations is caregiving to clinicians within the limits of each patient's capability. My paper moves this obligation beyond the ceremonial order of etiquette characterizing public statements on how patients should relate to others. It goes beyond a patient-centred ethic that is consumerist in nature, to a person-centred one that recognizes patients typically as moral agents who are dignified by recognizing the obligation to give as well as receive care as sincere benevolence. This obligation derives objective justification from divine command. It is also consistent, however, both with what people, if ignorant of their social role, would objectively produce for a hypothetical social contract, and with virtues constitutive of human nature and a relational and communitarian understanding of what it is to be a person. Including sentiment (intuition) and personal conscience, this relational identity makes caregiving intrinsically meaningful, yet caregiving also has an instrumental value to patients and clinicians. Its self-enforcement by patients will depend on their moral code and on society making caregiving achievable for them. A moral obligation for patient caregiving may then be specified to require patients to reflect on and invest in relationships in which they can feel and show care for others sincerely and respectfully. © 2014 John Wiley & Sons, Ltd.

  12. 29 CFR 4.177 - Discharging fringe benefit obligations by equivalent means.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... number of non-overtime hours in a year of work, to arrive at the hourly cash equivalent. This principle... 29 Labor 1 2012-07-01 2012-07-01 false Discharging fringe benefit obligations by equivalent means... obligations by equivalent means. (a) In general. (1) Section 2(a)(2) of the Act, which provides for fringe...

  13. 29 CFR 4.177 - Discharging fringe benefit obligations by equivalent means.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... number of non-overtime hours in a year of work, to arrive at the hourly cash equivalent. This principle... 29 Labor 1 2014-07-01 2013-07-01 true Discharging fringe benefit obligations by equivalent means... obligations by equivalent means. (a) In general. (1) Section 2(a)(2) of the Act, which provides for fringe...

  14. 29 CFR 4.177 - Discharging fringe benefit obligations by equivalent means.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... number of non-overtime hours in a year of work, to arrive at the hourly cash equivalent. This principle... 29 Labor 1 2011-07-01 2011-07-01 false Discharging fringe benefit obligations by equivalent means... obligations by equivalent means. (a) In general. (1) Section 2(a)(2) of the Act, which provides for fringe...

  15. 29 CFR 4.177 - Discharging fringe benefit obligations by equivalent means.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... number of non-overtime hours in a year of work, to arrive at the hourly cash equivalent. This principle... 29 Labor 1 2010-07-01 2010-07-01 true Discharging fringe benefit obligations by equivalent means... obligations by equivalent means. (a) In general. (1) Section 2(a)(2) of the Act, which provides for fringe...

  16. 29 CFR 4.177 - Discharging fringe benefit obligations by equivalent means.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... number of non-overtime hours in a year of work, to arrive at the hourly cash equivalent. This principle... 29 Labor 1 2013-07-01 2013-07-01 false Discharging fringe benefit obligations by equivalent means... obligations by equivalent means. (a) In general. (1) Section 2(a)(2) of the Act, which provides for fringe...

  17. Comparative Phylogeography in a Specific and Obligate Pollination Antagonism

    PubMed Central

    Espíndola, Anahí; Alvarez, Nadir

    2011-01-01

    In specific and obligate interactions the nature and abundance of a given species can have important effects on the survival and population dynamics of associated organisms. In a phylogeographic framework, we therefore expect that the fates of organisms interacting specifically are also tightly interrelated. Here we investigate such a scenario by analyzing the genetic structures of species interacting in an obligate plant-insect pollination lure-and-trap antagonism, involving Arum maculatum (Araceae) and its specific psychodid (Diptera) visitors Psychoda phalaenoides and Psycha grisescens. Because the interaction is asymmetric (i.e., only the plant depends on the insect), we expect the genetic structure of the plant to be related with the historical pollinator availability, yielding incongruent phylogeographic patterns between the interacting organisms. Using insect mtDNA sequences and plant AFLP genome fingerprinting, we inferred the large-scale phylogeographies of each species and the distribution of genetic diversities throughout the sampled range, and evaluated the congruence in their respective genetic structures using hierarchical analyses of molecular variances (AMOVA). Because the composition of pollinator species varies in Europe, we also examined its association with the spatial genetic structure of the plant. Our findings indicate that while the plant presents a spatially well-defined genetic structure, this is not the case in the insects. Patterns of genetic diversities also show dissimilar distributions among the three interacting species. Phylogeographic histories of the plant and its pollinating insects are thus not congruent, a result that would indicate that plant and insect lineages do not share the same glacial and postglacial histories. However, the genetic structure of the plant can, at least partially, be explained by the type of pollinators available at a regional scale. Differences in life-history traits of available pollinators might

  18. 19 CFR 10.765 - Importer obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Importer obligations. 10.765 Section 10.765 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Morocco Free Trade...

  19. 19 CFR 10.512 - Importer obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Importer obligations. 10.512 Section 10.512 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Singapore Free Trade...

  20. 7 CFR 987.145 - Withholding obligation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... obligation for any variety of dates for which free and restricted percentages have been established by having an adequate quantity of that variety inspected and certified as meeting the applicable grade, size... to reflect any increase in weight. (d) Dates for deferment of withholding. Any handler may defer his...

  1. 28 CFR 42.204 - Applicants' obligations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) of the Justice System Improvement Act of 1979 § 42.204 Applicants' obligations. (a) Every application... grant of $500,000 or more under the JSIA or the Juvenile Justice Act, must submit a copy of its current... 42.204 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL EMPLOYMENT OPPORTUNITY...

  2. 28 CFR 42.204 - Applicants' obligations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) of the Justice System Improvement Act of 1979 § 42.204 Applicants' obligations. (a) Every application... grant of $500,000 or more under the JSIA or the Juvenile Justice Act, must submit a copy of its current... 42.204 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL EMPLOYMENT OPPORTUNITY...

  3. 28 CFR 42.204 - Applicants' obligations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) of the Justice System Improvement Act of 1979 § 42.204 Applicants' obligations. (a) Every application... grant of $500,000 or more under the JSIA or the Juvenile Justice Act, must submit a copy of its current... 42.204 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL EMPLOYMENT OPPORTUNITY...

  4. 28 CFR 42.204 - Applicants' obligations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) of the Justice System Improvement Act of 1979 § 42.204 Applicants' obligations. (a) Every application... grant of $500,000 or more under the JSIA or the Juvenile Justice Act, must submit a copy of its current... 42.204 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL EMPLOYMENT OPPORTUNITY...

  5. 28 CFR 42.204 - Applicants' obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) of the Justice System Improvement Act of 1979 § 42.204 Applicants' obligations. (a) Every application... grant of $500,000 or more under the JSIA or the Juvenile Justice Act, must submit a copy of its current... 42.204 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL EMPLOYMENT OPPORTUNITY...

  6. 19 CFR 10.865 - Importer obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Importer obligations. 10.865 Section 10.865 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Oman Free Trade...

  7. 19 CFR 10.865 - Importer obligations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Importer obligations. 10.865 Section 10.865 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Oman Free Trade...

  8. 19 CFR 10.865 - Importer obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Importer obligations. 10.865 Section 10.865 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Oman Free Trade...

  9. 19 CFR 10.865 - Importer obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Importer obligations. 10.865 Section 10.865 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Oman Free Trade...

  10. 29 CFR 500.60 - Farm labor contractors' recruitment, contractual and general obligations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Farm labor contractors' recruitment, contractual and... labor contractors' recruitment, contractual and general obligations. The Act imposes certain specific recruitment, contractual and general obligations on farm labor contractors and farm labor contractor employees...

  11. Nanomedicine as an emerging approach against intracellular pathogens

    PubMed Central

    Armstead, Andrea L; Li, Bingyun

    2011-01-01

    Diseases such as tuberculosis, hepatitis, and HIV/AIDS are caused by intracellular pathogens and are a major burden to the global medical community. Conventional treatments for these diseases typically consist of long-term therapy with a combination of drugs, which may lead to side effects and contribute to low patient compliance. The pathogens reside within intracellular compartments of the cell, which provide additional barriers to effective treatment. Therefore, there is a need for improved and more effective therapies for such intracellular diseases. This review will summarize, for the first time, the intracellular compartments in which pathogens can reside and discuss how nanomedicine has the potential to improve intracellular disease therapy by offering properties such as targeting, sustained drug release, and drug delivery to the pathogen’s intracellular location. The characteristics of nanomedicine may prove advantageous in developing improved or alternative therapies for intracellular diseases. PMID:22228996

  12. 5 CFR 724.302 - Reporting obligations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... RETALIATION ACT OF 2002 Annual Report § 724.302 Reporting obligations. (a) Except as provided in paragraph (b) of this section, each agency must report no later than 180 calendar days after the end of each fiscal... must include: (i) An examination of trends; (ii) Causal analysis; (iii) Practical knowledge gained...

  13. 5 CFR 724.302 - Reporting obligations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... RETALIATION ACT OF 2002 Annual Report § 724.302 Reporting obligations. (a) Except as provided in paragraph (b) of this section, each agency must report no later than 180 calendar days after the end of each fiscal... must include: (i) An examination of trends; (ii) Causal analysis; (iii) Practical knowledge gained...

  14. 5 CFR 724.302 - Reporting obligations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... RETALIATION ACT OF 2002 Annual Report § 724.302 Reporting obligations. (a) Except as provided in paragraph (b) of this section, each agency must report no later than 180 calendar days after the end of each fiscal... must include: (i) An examination of trends; (ii) Causal analysis; (iii) Practical knowledge gained...

  15. 5 CFR 724.302 - Reporting obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... RETALIATION ACT OF 2002 Annual Report § 724.302 Reporting obligations. (a) Except as provided in paragraph (b) of this section, each agency must report no later than 180 calendar days after the end of each fiscal... must include: (i) An examination of trends; (ii) Causal analysis; (iii) Practical knowledge gained...

  16. 5 CFR 724.302 - Reporting obligations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... RETALIATION ACT OF 2002 Annual Report § 724.302 Reporting obligations. (a) Except as provided in paragraph (b) of this section, each agency must report no later than 180 calendar days after the end of each fiscal... must include: (i) An examination of trends; (ii) Causal analysis; (iii) Practical knowledge gained...

  17. 34 CFR 108.5 - Compliance obligations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Compliance obligations. 108.5 Section 108.5 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION EQUAL ACCESS TO PUBLIC SCHOOL FACILITIES FOR THE BOY SCOUTS OF AMERICA AND OTHER DESIGNATED YOUTH GROUPS...

  18. 34 CFR 108.5 - Compliance obligations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Compliance obligations. 108.5 Section 108.5 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION EQUAL ACCESS TO PUBLIC SCHOOL FACILITIES FOR THE BOY SCOUTS OF AMERICA AND OTHER DESIGNATED YOUTH GROUPS...

  19. 34 CFR 108.5 - Compliance obligations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Compliance obligations. 108.5 Section 108.5 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION EQUAL ACCESS TO PUBLIC SCHOOL FACILITIES FOR THE BOY SCOUTS OF AMERICA AND OTHER DESIGNATED YOUTH GROUPS...

  20. 34 CFR 108.5 - Compliance obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Compliance obligations. 108.5 Section 108.5 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION EQUAL ACCESS TO PUBLIC SCHOOL FACILITIES FOR THE BOY SCOUTS OF AMERICA AND OTHER DESIGNATED YOUTH GROUPS...

  1. What Do Core Obligations under the Right to Health Bring to Universal Health Coverage?

    PubMed

    Forman, Lisa; Beiersmann, Claudia; Brolan, Claire E; Mckee, Martin; Hammonds, Rachel; Ooms, Gorik

    2016-12-01

    Can the right to health, and particularly the core obligations of states specified under this right, assist in formulating and implementing universal health coverage (UHC), now included in the post-2015 Sustainable Development Goals? In this paper, we examine how core obligations under the right to health could lead to a version of UHC that is likely to advance equity and rights. We first address the affinity between the right to health and UHC as evinced through changing definitions of UHC and the health domains that UHC explicitly covers. We then engage with relevant interpretations of the right to health, including core obligations. We turn to analyze what core obligations might bring to UHC, particularly in defining what and who is covered. Finally, we acknowledge some of the risks associated with both UHC and core obligations and consider potential avenues for mitigating these risks.

  2. Imaging and controlling intracellular reactions: Lysosome transport as a function of diameter and the intracellular synthesis of conducting polymers

    NASA Astrophysics Data System (ADS)

    Payne, Christine

    2014-03-01

    Eukaryotic cells are the ultimate complex environment with intracellular chemical reactions regulated by the local cellular environment. For example, reactants are sequestered into specific organelles to control local concentration and pH, motor proteins transport reactants within the cell, and intracellular vesicles undergo fusion to bring reactants together. Current research in the Payne Lab in the School of Chemistry and Biochemistry at Georgia Tech is aimed at understanding and utilizing this complex environment to control intracellular chemical reactions. This will be illustrated using two examples, intracellular transport as a function of organelle diameter and the intracellular synthesis of conducting polymers. Using single particle tracking fluorescence microscopy, we measured the intracellular transport of lysosomes, membrane-bound organelles, as a function of diameter as they underwent transport in living cells. Both ATP-dependent active transport and diffusion were examined. As expected, diffusion scales with the diameter of the lysosome. However, active transport is unaffected suggesting that motor proteins are insensitive to cytosolic drag. In a second example, we utilize intracellular complexity, specifically the distinct micro-environments of different organelles, to carry out chemical reactions. We show that catalase, found in the peroxisomes of cells, can be used to catalyze the polymerization of the conducting polymer PEDOT:PSS. More importantly, we have found that a range of iron-containing biomolecules are suitable catalysts with different iron-containing biomolecules leading to different polymer properties. These experiments illustrate the advantage of intracellular complexity for the synthesis of novel materials.

  3. 47 CFR 54.802 - Obligations of local exchange carriers and the Administrator.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Obligations of local exchange carriers and the Administrator. 54.802 Section 54.802 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Interstate Access Universal Service Support Mechanism § 54.802 Obligations of local exchange...

  4. 10 CFR 1005.11 - What are the Secretary's obligations in interstate situations?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false What are the Secretary's obligations in interstate situations? 1005.11 Section 1005.11 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) INTERGOVERNMENTAL REVIEW OF DEPARTMENT OF ENERGY PROGRAMS AND ACTIVITIES § 1005.11 What are the Secretary's obligations in...

  5. 47 CFR 54.309 - Connect America Fund Phase II Public Interest Obligations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Connect America Fund Phase II Public Interest Obligations. 54.309 Section 54.309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... Connect America Fund Phase II Public Interest Obligations. (a) A price cap carrier electing Phase II model...

  6. Plasma Membrane-Located Purine Nucleotide Transport Proteins Are Key Components for Host Exploitation by Microsporidian Intracellular Parasites

    PubMed Central

    Heinz, Eva; Hacker, Christian; Dean, Paul; Mifsud, John; Goldberg, Alina V.; Williams, Tom A.; Nakjang, Sirintra; Gregory, Alison; Hirt, Robert P.; Lucocq, John M.; Kunji, Edmund R. S.; Embley, T. Martin

    2014-01-01

    Microsporidia are obligate intracellular parasites of most animal groups including humans, but despite their significant economic and medical importance there are major gaps in our understanding of how they exploit infected host cells. We have investigated the evolution, cellular locations and substrate specificities of a family of nucleotide transport (NTT) proteins from Trachipleistophora hominis, a microsporidian isolated from an HIV/AIDS patient. Transport proteins are critical to microsporidian success because they compensate for the dramatic loss of metabolic pathways that is a hallmark of the group. Our data demonstrate that the use of plasma membrane-located nucleotide transport proteins (NTT) is a key strategy adopted by microsporidians to exploit host cells. Acquisition of an ancestral transporter gene at the base of the microsporidian radiation was followed by lineage-specific events of gene duplication, which in the case of T. hominis has generated four paralogous NTT transporters. All four T. hominis NTT proteins are located predominantly to the plasma membrane of replicating intracellular cells where they can mediate transport at the host-parasite interface. In contrast to published data for Encephalitozoon cuniculi, we found no evidence for the location for any of the T. hominis NTT transporters to its minimal mitochondria (mitosomes), consistent with lineage-specific differences in transporter and mitosome evolution. All of the T. hominis NTTs transported radiolabelled purine nucleotides (ATP, ADP, GTP and GDP) when expressed in Escherichia coli, but did not transport radiolabelled pyrimidine nucleotides. Genome analysis suggests that imported purine nucleotides could be used by T. hominis to make all of the critical purine-based building-blocks for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis. PMID:25474405

  7. Biodegradable nanoparticles for intracellular delivery of antimicrobial agents.

    PubMed

    Xie, Shuyu; Tao, Yanfei; Pan, Yuanhu; Qu, Wei; Cheng, Guyue; Huang, Lingli; Chen, Dongmei; Wang, Xu; Liu, Zhenli; Yuan, Zonghui

    2014-08-10

    Biodegradable nanoparticles have emerged as a promising strategy for ferrying antimicrobial agents into specific cells due to their unique properties. This review discusses the current progress and challenges of biodegradable nanoparticles for intracellular antimicrobial delivery to understand design principles for the development of ideal nanocarriers. The intracellular delivery performances of biodegradable nanoparticles for diverse antimicrobial agents are first summarized. Second, the cellular internalization and intracellular trafficking, degradation and release kinetics of nanoparticles as well as their relation with intracellular delivery of encapsulated antimicrobial agents are provided. Third, the influences of nanoparticle properties on the cellular internalization and intracellular fate of nanoparticles and their payload antimicrobial agents are discussed. Finally, the challenges and perspectives of nanoparticles for intracellular delivery of antimicrobial agents are addressed. The review will be helpful to the scientists who are interested in searching for more efficient nanosystem strategies for intracellular delivery of antimicrobial agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. A cross-cultural study of noblesse oblige in economic decision-making.

    PubMed

    Fiddick, Laurence; Cummins, Denise Dellarosa; Janicki, Maria; Lee, Sean; Erlich, Nicole

    2013-09-01

    A cornerstone of economic theory is that rational agents are self-interested, yet a decade of research in experimental economics has shown that economic decisions are frequently driven by concerns for fairness, equity, and reciprocity. One aspect of other-regarding behavior that has garnered attention is noblesse oblige, a social norm that obligates those of higher status to be generous in their dealings with those of lower status. The results of a cross-cultural study are reported in which marked noblesse oblige was observed on a reciprocal-contract decision-making task. Participants from seven countries that vary along hierarchical and individualist/collectivist social dimensions were more tolerant of non-reciprocation when they adopted a high-ranking perspective compared with a low-ranking perspective.

  9. A Toxoplasma gondii protein with homology to intracellular type Na{sup +}/H{sup +} exchangers is important for osmoregulation and invasion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Francia, Maria E.; Wicher, Sarah; Pace, Douglas A.

    2011-06-10

    The obligate intracellular parasite Toxoplasma gondii is exposed to a variety of physiological conditions while propagating in an infected organism. The mechanisms by which Toxoplasma overcomes these dramatic changes in its environment are not known. In yeast and plants, ion detoxification and osmotic regulation are controlled by vacuolar compartments. A novel compartment named the plant-like vacuole or vacuolar compartment (PLV/VAC) has recently been described in T.gondii, which could potentially protect extracellular tachyzoites against salt and other ionic stresses. Here, we report the molecular characterization of the vacuolar type Na{sup +}/H{sup +} exchanger in T. gondii, TgNHE3, and its co-localization withmore » the PLV/VAC proton-pyrophosphatase (TgVP1). We have created a TgNHE3 knockout strain, which is more sensitive to hyperosmotic shock and toxic levels of sodium, possesses a higher intracellular Ca{sup 2+} concentration [Ca{sup 2+}]{sub i}, and exhibits a reduced host invasion efficiency. The defect in invasion correlates with a measurable reduction in the secretion of the adhesin TgMIC2. Overall, our results suggest that the PLV/VAC has functions analogous to those of the vacuolar compartments of plants and yeasts, providing the parasite with a mechanism to resist ionic fluctuations and, potentially, regulate protein trafficking.« less

  10. 26 CFR 1.691(e)-1 - Installment obligations transmitted at death when prior law applied.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Installment obligations transmitted at death....691(e)-1 Installment obligations transmitted at death when prior law applied. (a) In general—(1... death of a holder of such obligations were required to be reported in the return of the decedent for the...

  11. Support Seeking or Familial Obligation: An Investigation of Motives for Disclosing Genetic Test Results.

    PubMed

    Greenberg, Marisa; Smith, Rachel A

    2016-01-01

    Genetic test results reveal not only personal information about a person's likelihood of certain medical conditions but also information about the person's genetic relatives. Given the familial nature of genetic information, one's obligation to protect family members may be a motive for disclosing genetic test results, but this claim has not been methodically tested. Existing models of disclosure decision making presume self-interested motives, such as seeking social support, instead of other-interested motives, like familial obligation. This study investigated young adults' (N = 173) motives to share a genetic-based health condition, alpha-1 antitrypsin deficiency, after reading a hypothetical vignette. Results show that social support and familial obligation were both reported as motives for disclosure. In fact, some participants reported familial obligation as their primary motivator for disclosure. Finally, stronger familial obligation predicted increased likelihood of disclosing hypothetical genetic test results. Implications of these results were discussed in reference to theories of disclosure decision-making models and the practice of genetic disclosures.

  12. Butyl Rubber Stoppers Increase the Shelf Life of Prereduced, Anaerobically Sterilized Media

    PubMed Central

    Fulghum, Robert S.; Worthington, John M.

    1977-01-01

    Butyl rubber stoppers as compared with neoprene or black rubber stoppers significantly increased the shelf life of prereduced, anaerobically sterilized media for growth of obligately anaerobic bacteria. PMID:879778

  13. 47 CFR 76.309 - Customer service obligations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Customer service obligations. 76.309 Section 76.309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE General Operating Requirements § 76.309 Customer service...

  14. 47 CFR 76.309 - Customer service obligations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Customer service obligations. 76.309 Section 76.309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE General Operating Requirements § 76.309 Customer service...

  15. 47 CFR 76.309 - Customer service obligations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Customer service obligations. 76.309 Section 76.309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE General Operating Requirements § 76.309 Customer service...

  16. The interactions of intracellular Protista and their host cells, with special reference to heterotrophic organisms.

    PubMed

    Bannister, L H

    1979-04-11

    Intracellular genera are found in all the major groups of Protista, but are particularly common among the dinoflagellates, trypanosomatid zooflagellates and suctorian ciliates; the Sporozoa are nearly all intracellular at some stage of their life, and the Microspora entirely so. Intracellular forms can dwell in the nucleus, within phagosomal or other vacuoles or may lie free in the hyaloplasm of their host cells. Organisms tend to select their hosts from a restricted taxonomic range although there are some notable exceptions. There is also great variation in the types of host cell inhabited. There are various reasons for both host and cell selectivity including recognition phenomena at the cell surfaces. Invasion of host cells is usually preceded by surface interactions with the invader. Some organisms depend upon phagocytosis for entry, but others induce host cells to engulf them by non-phagocytic means or invade by microinjection through the host plasma membrane. Protista avoid lysosomal destruction by their resistance to enzyme attack, by surrounding themselves with lysosome-inhibiting vacuoles, by escaping from the phagosomal system into the hyaloplasm and by choosing host cells which lack lysosomes. Nutrition of intracellular heterotrophic organisms involves some degree of competition with the host cell's metabolism as well as erosion of host cell cytoplasm. In Plasmodium infections, red cells are made more permeable to required nutrients by the action of the parasite on the host cell membrane. The parasite is often dependent upon the host cell for complex nutrients which it cannot synthesize for itself. Intracellular forms often profoundly modify the structure and metabolism of the host cell or interfere with its growth and multiplication. This may result in the final lysis of the host cell at the end of the intracellular phase or before the infection of other cells. Certain types of intracellular organisms may have arisen initially as forms attached to the

  17. Efficient intracellular delivery and improved biocompatibility of colloidal silver nanoparticles towards intracellular SERS immuno-sensing.

    PubMed

    Bhardwaj, Vinay; Srinivasan, Supriya; McGoron, Anthony J

    2015-06-21

    High throughput intracellular delivery strategies, electroporation, passive and TATHA2 facilitated diffusion of colloidal silver nanoparticles (AgNPs) are investigated for cellular toxicity and uptake using state-of-art analytical techniques. The TATHA2 facilitated approach efficiently delivered high payload with no toxicity, pre-requisites for intracellular applications of plasmonic metal nanoparticles (PMNPs) in sensing and therapeutics.

  18. Evolutionary transition from blood feeding to obligate nonbiting in a mosquito.

    PubMed

    Bradshaw, William E; Burkhart, Joshua; Colbourne, John K; Borowczak, Rudyard; Lopez, Jacqueline; Denlinger, David L; Reynolds, Julie A; Pfrender, Michael E; Holzapfel, Christina M

    2018-01-30

    The spread of blood-borne pathogens by mosquitoes relies on their taking a blood meal; if there is no bite, there is no disease transmission. Although many species of mosquitoes never take a blood meal, identifying genes that distinguish blood feeding from obligate nonbiting is hampered by the fact that these different lifestyles occur in separate, genetically incompatible species. There is, however, one unique extant species with populations that share a common genetic background but blood feed in one region and are obligate nonbiters in the rest of their range: Wyeomyia smithii Contemporary blood-feeding and obligate nonbiting populations represent end points of divergence between fully interfertile southern and northern populations. This divergence has undoubtedly resulted in genetic changes that are unrelated to blood feeding, and the challenge is to winnow out the unrelated genetic factors to identify those related specifically to the evolutionary transition from blood feeding to obligate nonbiting. Herein, we determine differential gene expression resulting from directional selection on blood feeding within a polymorphic population to isolate genetic differences between blood feeding and obligate nonbiting. We show that the evolution of nonbiting has resulted in a greatly reduced metabolic investment compared with biting populations, a greater reliance on opportunistic metabolic pathways, and greater reliance on visual rather than olfactory sensory input. W. smithii provides a unique starting point to determine if there are universal nonbiting genes in mosquitoes that could be manipulated as a means to control vector-borne disease. Copyright © 2018 the Author(s). Published by PNAS.

  19. A De Novo-Assembly Based Data Analysis Pipeline for Plant Obligate Parasite Metatranscriptomic Studies.

    PubMed

    Guo, Li; Allen, Kelly S; Deiulio, Greg; Zhang, Yong; Madeiras, Angela M; Wick, Robert L; Ma, Li-Jun

    2016-01-01

    Current and emerging plant diseases caused by obligate parasitic microbes such as rusts, downy mildews, and powdery mildews threaten worldwide crop production and food safety. These obligate parasites are typically unculturable in the laboratory, posing technical challenges to characterize them at the genetic and genomic level. Here we have developed a data analysis pipeline integrating several bioinformatic software programs. This pipeline facilitates rapid gene discovery and expression analysis of a plant host and its obligate parasite simultaneously by next generation sequencing of mixed host and pathogen RNA (i.e., metatranscriptomics). We applied this pipeline to metatranscriptomic sequencing data of sweet basil (Ocimum basilicum) and its obligate downy mildew parasite Peronospora belbahrii, both lacking a sequenced genome. Even with a single data point, we were able to identify both candidate host defense genes and pathogen virulence genes that are highly expressed during infection. This demonstrates the power of this pipeline for identifying genes important in host-pathogen interactions without prior genomic information for either the plant host or the obligate biotrophic pathogen. The simplicity of this pipeline makes it accessible to researchers with limited computational skills and applicable to metatranscriptomic data analysis in a wide range of plant-obligate-parasite systems.

  20. A De Novo-Assembly Based Data Analysis Pipeline for Plant Obligate Parasite Metatranscriptomic Studies

    PubMed Central

    Guo, Li; Allen, Kelly S.; Deiulio, Greg; Zhang, Yong; Madeiras, Angela M.; Wick, Robert L.; Ma, Li-Jun

    2016-01-01

    Current and emerging plant diseases caused by obligate parasitic microbes such as rusts, downy mildews, and powdery mildews threaten worldwide crop production and food safety. These obligate parasites are typically unculturable in the laboratory, posing technical challenges to characterize them at the genetic and genomic level. Here we have developed a data analysis pipeline integrating several bioinformatic software programs. This pipeline facilitates rapid gene discovery and expression analysis of a plant host and its obligate parasite simultaneously by next generation sequencing of mixed host and pathogen RNA (i.e., metatranscriptomics). We applied this pipeline to metatranscriptomic sequencing data of sweet basil (Ocimum basilicum) and its obligate downy mildew parasite Peronospora belbahrii, both lacking a sequenced genome. Even with a single data point, we were able to identify both candidate host defense genes and pathogen virulence genes that are highly expressed during infection. This demonstrates the power of this pipeline for identifying genes important in host–pathogen interactions without prior genomic information for either the plant host or the obligate biotrophic pathogen. The simplicity of this pipeline makes it accessible to researchers with limited computational skills and applicable to metatranscriptomic data analysis in a wide range of plant-obligate-parasite systems. PMID:27462318

  1. Long-read whole genome sequencing and comparative analysis of six strains of the human pathogen Orientia tsutsugamushi.

    PubMed

    Batty, Elizabeth M; Chaemchuen, Suwittra; Blacksell, Stuart; Richards, Allen L; Paris, Daniel; Bowden, Rory; Chan, Caroline; Lachumanan, Ramkumar; Day, Nicholas; Donnelly, Peter; Chen, Swaine; Salje, Jeanne

    2018-06-01

    Orientia tsutsugamushi is a clinically important but neglected obligate intracellular bacterial pathogen of the Rickettsiaceae family that causes the potentially life-threatening human disease scrub typhus. In contrast to the genome reduction seen in many obligate intracellular bacteria, early genetic studies of Orientia have revealed one of the most repetitive bacterial genomes sequenced to date. The dramatic expansion of mobile elements has hampered efforts to generate complete genome sequences using short read sequencing methodologies, and consequently there have been few studies of the comparative genomics of this neglected species. We report new high-quality genomes of O. tsutsugamushi, generated using PacBio single molecule long read sequencing, for six strains: Karp, Kato, Gilliam, TA686, UT76 and UT176. In comparative genomics analyses of these strains together with existing reference genomes from Ikeda and Boryong strains, we identify a relatively small core genome of 657 genes, grouped into core gene islands and separated by repeat regions, and use the core genes to infer the first whole-genome phylogeny of Orientia. Complete assemblies of multiple Orientia genomes verify initial suggestions that these are remarkable organisms. They have larger genomes compared with most other Rickettsiaceae, with widespread amplification of repeat elements and massive chromosomal rearrangements between strains. At the gene level, Orientia has a relatively small set of universally conserved genes, similar to other obligate intracellular bacteria, and the relative expansion in genome size can be accounted for by gene duplication and repeat amplification. Our study demonstrates the utility of long read sequencing to investigate complex bacterial genomes and characterise genomic variation.

  2. 78 FR 46418 - Proposed Information Collection (Obligation To Report Factors Affecting Entitlement) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ... (Obligation To Report Factors Affecting Entitlement) Activity; Comment Request AGENCY: Veterans Benefits... use of other forms of information technology. Title: Obligation to Report Factors Affecting... entitlement factors. Individual factors such as income, marital status, and the beneficiary's number of...

  3. 75 FR 62634 - Proposed Information Collection (Obligation to Report Factors Affecting Entitlement) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... (Obligation to Report Factors Affecting Entitlement) Activity: Comment Request AGENCY: Veterans Benefits... use of other forms of information technology. Title: Obligation to Report Factors Affecting... entitlement factors. Individual factors such as income, marital status, and the beneficiary's number of...

  4. 7 CFR 623.11 - Obligations of the landowner.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE WATER RESOURCES EMERGENCY WETLANDS RESERVE PROGRAM § 623.11 Obligations of the... commencing restoration of the designated area. (b) In addition, program participants and their successors of...

  5. 7 CFR 623.11 - Obligations of the landowner.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., DEPARTMENT OF AGRICULTURE WATER RESOURCES EMERGENCY WETLANDS RESERVE PROGRAM § 623.11 Obligations of the... commencing restoration of the designated area. (b) In addition, program participants and their successors of...

  6. 7 CFR 1450.105 - Obligations of participant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Obligations of participant. 1450.105 Section 1450.105 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM (BCAP) Matching...

  7. 7 CFR 1450.105 - Obligations of participant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Obligations of participant. 1450.105 Section 1450.105 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM (BCAP) Matching...

  8. 7 CFR 1450.105 - Obligations of participant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Obligations of participant. 1450.105 Section 1450.105 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM (BCAP) Matching...

  9. 7 CFR 1450.105 - Obligations of participant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Obligations of participant. 1450.105 Section 1450.105 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM (BCAP) Matching...

  10. 21 CFR 312.52 - Transfer of obligations to a contract research organization.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Transfer of obligations to a contract research organization. 312.52 Section 312.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... and Investigators § 312.52 Transfer of obligations to a contract research organization. (a) A sponsor...

  11. 34 CFR 611.45 - Under what circumstances does the Secretary discharge a scholarship recipient's obligation to...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... scholarship recipient's obligation to repay for failure to meet the service obligation? 611.45 Section 611.45... EDUCATION, DEPARTMENT OF EDUCATION TEACHER QUALITY ENHANCEMENT GRANTS PROGRAM Scholarships § 611.45 Under what circumstances does the Secretary discharge a scholarship recipient's obligation to repay for...

  12. 34 CFR 611.45 - Under what circumstances does the Secretary discharge a scholarship recipient's obligation to...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... scholarship recipient's obligation to repay for failure to meet the service obligation? 611.45 Section 611.45... EDUCATION, DEPARTMENT OF EDUCATION TEACHER QUALITY ENHANCEMENT GRANTS PROGRAM Scholarships § 611.45 Under what circumstances does the Secretary discharge a scholarship recipient's obligation to repay for...

  13. 34 CFR 611.45 - Under what circumstances does the Secretary discharge a scholarship recipient's obligation to...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... scholarship recipient's obligation to repay for failure to meet the service obligation? 611.45 Section 611.45... EDUCATION, DEPARTMENT OF EDUCATION TEACHER QUALITY ENHANCEMENT GRANTS PROGRAM Scholarships § 611.45 Under what circumstances does the Secretary discharge a scholarship recipient's obligation to repay for...

  14. 77 FR 7108 - Affirmative Action and Nondiscrimination Obligations of Contractors and Subcontractors Regarding...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ...-AA02 Affirmative Action and Nondiscrimination Obligations of Contractors and Subcontractors Regarding... affirmative action regulations of section 503 of the Rehabilitation Act of 1973, as amended. This document..., OFCCP published a proposed rule entitled, ``Affirmative Action and Nondiscrimination Obligations of...

  15. 76 FR 36482 - Affirmative Action and Nondiscrimination Obligations of Contractors and Subcontractors Regarding...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ... DEPARTMENT OF LABOR Office of Federal Contract Compliance Programs 41 CFR Parts 60-250 and 60-300 RIN 1250-AA00 Affirmative Action and Nondiscrimination Obligations of Contractors and Subcontractors... Nondiscrimination Obligations of Contractors and Subcontractors Regarding Protected Veterans'' (76 FR 23358). OFCCP...

  16. 7 CFR 2201.32 - Termination of obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Termination of obligations. 2201.32 Section 2201.32 Agriculture Regulations of the Department of Agriculture (Continued) LOCAL TELEVISION LOAN GUARANTEE BOARD LOCAL TELEVISION LOAN GUARANTEE PROGRAM-PROGRAM REGULATIONS Loan Guarantees § 2201.32 Termination of...

  17. 45 CFR 1226.13 - Obligations of sponsors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Obligations of sponsors. 1226.13 Section 1226.13 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE PROHIBITIONS ON ELECTORAL AND LOBBYING ACTIVITIES Sponsor Employee Activities § 1226.13...

  18. 14 CFR 1300.22 - Termination of obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Termination of obligations. 1300.22 Section 1300.22 Aeronautics and Space AIR TRANSPORTATION SYSTEM STABILIZATION OFFICE OF MANAGEMENT AND BUDGET AVIATION DISASTER RELIEF-AIR CARRIER GUARANTEE LOAN PROGRAM Minimum Requirements and Application Procedures...

  19. 7 CFR 1755.27 - Borrower contractual obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE TELECOMMUNICATIONS POLICIES ON SPECIFICATIONS, ACCEPTABLE MATERIALS, AND STANDARD CONTRACT FORMS § 1755.27 Borrower contractual obligations. (a) Loan agreement. As a condition of a loan or... pursuant to which the borrowers agree to use RUS standard contract forms for construction, procurement...

  20. 6 CFR 25.5 - Obligations of seller.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...-TERRORISM BY FOSTERING EFFECTIVE TECHNOLOGIES § 25.5 Obligations of seller. (a) Liability Insurance Required... Terrorism when Qualified Anti-Terrorism Technologies have been deployed in defense against, response to, or...-Terrorism Technology submit any information that would: (1) Assist in determining the amount of liability...

  1. The relationship between family obligation and religiosity on caregiving.

    PubMed

    Epps, Fayron

    2014-01-01

    The purpose of this study was to examine the relationship between family obligation and religiosity on the positive appraisal of caregiving among African-American, Hispanic and non-Hispanic Caucasian family caregivers of older adults. Roy's adaptation model guided formulation of the aims and study design. A cross-sectional, correlational study design was employed to examine the relationship amongst variables for the family caregiver participants. Study participants (N = 69) completed a demographic tool and four instruments the: (1) Katz index, (2) obligation scale, (3) Duke University religion index, and (4) positive appraisal of care scale. There was a significant correlation between family obligation and positive appraisal of caregiving. However, there was no relationship between the family caregiver's religiosity and positive appraisal of caregiving overall. Demographic variables were also examined to show a higher marginal mean for Hispanic primary caregivers in relation to the positive appraisal of caregiving. Future studies should consider replicating these findings in a larger sample to provide health care professionals with substantial evidence to incorporate culturally sensitive interventions aimed at promoting positive outcomes and healthy family behaviors. Copyright © 2014 Mosby, Inc. All rights reserved.

  2. Understanding the futility of countries' obligations for health rights: realising justice for the global poor.

    PubMed

    Barugahare, John; Lie, Reidar K

    2016-06-03

    Although health is a right of all individuals without any distinction, the realisation of this right has remained very difficult for the marginalised populations of poor countries. Inequitable distribution of health opportunities globally is a major factor in explaining why this is the case. Whereas the Protection, Promotion and Fulfilment of the health rights of poor country citizens are a joint responsibility of both domestic and external governments, most governments flout their obligations. So far disproportionate effort has been dedicated to reaffirming and interpreting these obligations as opposed to investigating the fundamental question regarding why these obligations have nevertheless remained largely unfulfilled. Further the normative question regarding what ought to be done about the shortcomings of current obligations has been largely ignored. We conduct a critical content analysis of existing literature on efforts towards the realisation of the health rights of marginalised populations in our attempt to ascertain their capacity to guarantee basic health opportunities to marginalised populations. In our analysis we treat issues of 'health rights' and 'justice in global health' as having unity of purpose - guaranteeing basic health opportunities to the marginalised populations. We identify two sets of reasons for the failure of present obligations for global distributive justice in general: a set of 'superficial reasons' and a set of 'fundamental reasons' which account for the superficial reasons. In order to overcome these reasons we propose a strategy which consists in specifying a number of minimum and less-demanding obligations for both external and domestic governments to guarantee to all individuals a certain threshold of health goods and services. We argue that these minimum obligations can be freely accepted and fully complied with or enforced with "a thin system of enforcement" without significant threat to national sovereignty and autonomy. The

  3. Support Seeking or Familial Obligation: An Investigation of Motives for Disclosing Genetic Test Results

    PubMed Central

    Greenberg, Marisa; Smith, Rachel A.

    2016-01-01

    Genetic test results reveal not only personal information about a person’s likelihood of certain medical conditions but also information about their genetic relatives (Annas, Glantz, & Roche, 1995). Given the familial nature of genetic information, one’s obligation to protect family members may be a motive for disclosing genetic test results, but this claim has not been methodically tested. Existing models of disclosure decision-making presume self-interested motives, such as seeking social support, instead of other-interested motives, like familial obligation. This study investigated young adults’ (N = 173) motives to share a genetic-based health condition, alpha-1 antitrypsin deficiency, after reading a hypothetical vignette. Results show that social support and familial obligation were both reported as motives for disclosure. In fact, some participants reported familial obligation as their primary motivator for disclosure. Finally, stronger familial obligation predicted increased likelihood of disclosing hypothetical genetic test results. Implications of these results were discussed in reference to theories of disclosure decision-making models and the practice of genetic disclosures. PMID:26507777

  4. The Essential Role of Cholesterol Metabolism in the Intracellular Survival of Mycobacterium leprae Is Not Coupled to Central Carbon Metabolism and Energy Production.

    PubMed

    Marques, Maria Angela M; Berrêdo-Pinho, Marcia; Rosa, Thabatta L S A; Pujari, Venugopal; Lemes, Robertha M R; Lery, Leticia M S; Silva, Carlos Adriano M; Guimarães, Ana Carolina R; Atella, Georgia C; Wheat, William H; Brennan, Patrick J; Crick, Dean C; Belisle, John T; Pessolani, Maria Cristina V

    2015-12-01

    Mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and Schwann cells. Cholesterol is among the lipids with increased abundance in M. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. The present study investigated the capacity of M. leprae to acquire and metabolize cholesterol. In silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), the first step of cholesterol degradation catalyzed by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), is apparently the only portion of the cholesterol catabolic pathway seen in Mycobacterium tuberculosis preserved by M. leprae. Incubation of bacteria with radiolabeled cholesterol confirmed the in silico predictions. Radiorespirometry and lipid analyses performed after incubating M. leprae with [4-(14)C]cholesterol or [26-(14)C]cholesterol showed the inability of this pathogen to metabolize the sterol rings or the side chain of cholesterol as a source of energy and carbon. However, the bacteria avidly incorporated cholesterol and, as expected, converted it to cholestenone both in vitro and in vivo. Our data indicate that M. leprae has lost the capacity to degrade and utilize cholesterol as a nutritional source but retains the enzyme responsible for its oxidation to cholestenone. Thus, the essential role of cholesterol metabolism in the intracellular survival of M. leprae is uncoupled from central carbon metabolism and energy production. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies. Our study focused on the obligate intracellular pathogen Mycobacterium leprae and its capacity to metabolize cholesterol. The data make an important contribution for those interested in understanding the

  5. The Essential Role of Cholesterol Metabolism in the Intracellular Survival of Mycobacterium leprae Is Not Coupled to Central Carbon Metabolism and Energy Production

    PubMed Central

    Marques, Maria Angela M.; Berrêdo-Pinho, Marcia; Rosa, Thabatta L. S. A.; Pujari, Venugopal; Lemes, Robertha M. R.; Lery, Leticia M. S.; Silva, Carlos Adriano M.; Guimarães, Ana Carolina R.; Atella, Georgia C.; Wheat, William H.; Brennan, Patrick J.; Crick, Dean C.; Belisle, John T.

    2015-01-01

    ABSTRACT Mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and Schwann cells. Cholesterol is among the lipids with increased abundance in M. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. The present study investigated the capacity of M. leprae to acquire and metabolize cholesterol. In silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), the first step of cholesterol degradation catalyzed by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), is apparently the only portion of the cholesterol catabolic pathway seen in Mycobacterium tuberculosis preserved by M. leprae. Incubation of bacteria with radiolabeled cholesterol confirmed the in silico predictions. Radiorespirometry and lipid analyses performed after incubating M. leprae with [4-14C]cholesterol or [26-14C]cholesterol showed the inability of this pathogen to metabolize the sterol rings or the side chain of cholesterol as a source of energy and carbon. However, the bacteria avidly incorporated cholesterol and, as expected, converted it to cholestenone both in vitro and in vivo. Our data indicate that M. leprae has lost the capacity to degrade and utilize cholesterol as a nutritional source but retains the enzyme responsible for its oxidation to cholestenone. Thus, the essential role of cholesterol metabolism in the intracellular survival of M. leprae is uncoupled from central carbon metabolism and energy production. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies. IMPORTANCE Our study focused on the obligate intracellular pathogen Mycobacterium leprae and its capacity to metabolize cholesterol. The data make an important contribution for those interested in

  6. 20 CFR 655.1305 - Assurances and obligations of H-2A employers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Assurances and obligations of H-2A employers... Temporary Agricultural Employment in the United States (H-2A Workers) § 655.1305 Assurances and obligations of H-2A employers. An employer seeking to employ H-2A workers must attest as part of the Application...

  7. 24 CFR 206.131 - Contract rights and obligations for mortgages on individual dwelling units in a condominium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Contract rights and obligations for... MORTGAGE INSURANCE Contract Rights and Obligations Condominiums § 206.131 Contract rights and obligations...] Termination of Insurance Contract ...

  8. Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism.

    PubMed

    Smith, Desirée E C; Hornstra, Jacqueline M; Kok, Robert M; Blom, Henk J; Smulders, Yvo M

    2013-08-01

    In randomized trails, folic acid (FA) lowered plasma homocysteine, but failed to reduce cardiovascular risk. We hypothesize this is due to a discrepancy between plasma and intracellular effects of FA. In a double-blind trial, 50 volunteers were randomized to received 500 µg FA daily for 8 weeks, or placebo. Plasma and peripheral blood mononuclear cell (PBMC) concentrations of homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, methionine, cystathionine and 5-methyltetrahydrofolate (bioactive folate) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PBMCs were used as a cellular model since they display the full spectrum of one-carbon (1C) enzymes and reactions. At baseline, plasma concentrations were a poor reflection of intracellular concentrations for most 1C metabolites, except 5-methyltetrahydrofolate (R=0.33, p=0.02), homocysteine (Hcy) (R=0.35, p=0.01), and cystathionine (R=0.45, p=0.001). FA significantly lowered plasma homocysteine (p=0.00), but failed to lower intracellular homocysteine or change the concentrations of any of the other PBMC 1C metabolites. At baseline, PBMC homocysteine concentrations correlated to PBMC SAM. After FA supplementation, PBMC homocysteine no longer correlated with PBMC SAM, suggesting a loss of SAM's regulatory function. In vitro experiments in lymphoblasts confirmed that at higher folate substrate concentrations, physiological concentrations of SAM no longer effectively inhibit the key regulatory enzyme methylenetetrahydrofolate reductase (MTHFR). FA supplementation does not reduce intracellular concentrations of Hcy or any of its closely related substances. Rather, FA may disturb physiological regulation of intracellular 1C metabolism by interfering with SAM's inhibitory effect on MTHFR activity.

  9. Self-organization principles of intracellular pattern formation.

    PubMed

    Halatek, J; Brauns, F; Frey, E

    2018-05-26

    Dynamic patterning of specific proteins is essential for the spatio-temporal regulation of many important intracellular processes in prokaryotes, eukaryotes and multicellular organisms. The emergence of patterns generated by interactions of diffusing proteins is a paradigmatic example for self-organization. In this article, we review quantitative models for intracellular Min protein patterns in Escherichia coli , Cdc42 polarization in Saccharomyces cerevisiae and the bipolar PAR protein patterns found in Caenorhabditis elegans By analysing the molecular processes driving these systems we derive a theoretical perspective on general principles underlying self-organized pattern formation. We argue that intracellular pattern formation is not captured by concepts such as 'activators', 'inhibitors' or 'substrate depletion'. Instead, intracellular pattern formation is based on the redistribution of proteins by cytosolic diffusion, and the cycling of proteins between distinct conformational states. Therefore, mass-conserving reaction-diffusion equations provide the most appropriate framework to study intracellular pattern formation. We conclude that directed transport, e.g. cytosolic diffusion along an actively maintained cytosolic gradient, is the key process underlying pattern formation. Thus the basic principle of self-organization is the establishment and maintenance of directed transport by intracellular protein dynamics.This article is part of the theme issue 'Self-organization in cell biology'. © 2018 The Authors.

  10. 45 CFR 2551.113 - What financial obligation does the Corporation incur for non-Corporation funded projects?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Non-Corporation Funded SCP Projects § 2551.113 What financial obligation does the Corporation incur... to a sponsor of a non-Corporation funded project, does not create a financial obligation on the part... 45 Public Welfare 4 2010-10-01 2010-10-01 false What financial obligation does the Corporation...

  11. 45 CFR 2553.83 - What financial obligation does the Corporation incur for non-Corporation funded projects?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... VOLUNTEER PROGRAM Non-Corporation Funded Projects § 2553.83 What financial obligation does the Corporation... NGA to a sponsor of a non-Corporation funded project does not create a financial obligation on the... 45 Public Welfare 4 2010-10-01 2010-10-01 false What financial obligation does the Corporation...

  12. 26 CFR 46.4701-1 - Tax on issuer of registration-required obligation not in registered form.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... obligation not in registered form. 46.4701-1 Section 46.4701-1 Internal Revenue INTERNAL REVENUE SERVICE, 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 § 46.4701...

  13. 22 CFR 232.07 - Fiscal agent obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Fiscal agent obligations. 232.07 Section 232.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT REPUBLIC OF TUNISIA LOAN GUARANTEES ISSUED UNDER THE DEPARTMENT OF STATE, FOREIGN OPERATIONS, AND RELATED PROGRAMS APPROPRIATIONS ACT, 2012, DIV. I...

  14. 22 CFR 232.07 - Fiscal agent obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Fiscal agent obligations. 232.07 Section 232.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT REPUBLIC OF TUNISIA LOAN GUARANTEES ISSUED UNDER THE DEPARTMENT OF STATE, FOREIGN OPERATIONS, AND RELATED PROGRAMS APPROPRIATIONS ACT, 2012, DIV. I...

  15. 29 CFR 500.100 - Vehicle safety obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Vehicle safety obligations. 500.100 Section 500.100 Labor... SEASONAL AGRICULTURAL WORKER PROTECTION Motor Vehicle Safety and Insurance for Transportation of Migrant and Seasonal Agricultural Workers, Housing Safety and Health for Migrant Workers Motor Vehicle Safety...

  16. 29 CFR 500.100 - Vehicle safety obligations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Vehicle safety obligations. 500.100 Section 500.100 Labor... SEASONAL AGRICULTURAL WORKER PROTECTION Motor Vehicle Safety and Insurance for Transportation of Migrant and Seasonal Agricultural Workers, Housing Safety and Health for Migrant Workers Motor Vehicle Safety...

  17. 29 CFR 500.100 - Vehicle safety obligations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Vehicle safety obligations. 500.100 Section 500.100 Labor... SEASONAL AGRICULTURAL WORKER PROTECTION Motor Vehicle Safety and Insurance for Transportation of Migrant and Seasonal Agricultural Workers, Housing Safety and Health for Migrant Workers Motor Vehicle Safety...

  18. 7 CFR 984.54 - Establishment of obligation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... free and reserve percentages are in effect for a marketing year, each handler shall withhold a... 7 Agriculture 8 2010-01-01 2010-01-01 false Establishment of obligation. 984.54 Section 984.54 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing...

  19. 47 CFR 76.309 - Customer service obligations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... obligations. (a) A cable franchise authority may enforce the customer service standards set forth in paragraph (c) of this section against cable operators. The franchise authority must provide affected cable... section; (2) A franchising authority from enforcing, through the end of the franchise term, pre-existing...

  20. 10 CFR 40.56 - Restrictions on the use of Australian-obligated source material.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Restrictions on the use of Australian-obligated source material. 40.56 Section 40.56 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL... United States of America Concerning Peaceful Uses of Nuclear Energy, dated 2010, Australian-obligated...

  1. 10 CFR 40.56 - Restrictions on the use of Australian-obligated source material.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Restrictions on the use of Australian-obligated source material. 40.56 Section 40.56 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL... United States of America Concerning Peaceful Uses of Nuclear Energy, dated 2010, Australian-obligated...

  2. 10 CFR 40.56 - Restrictions on the use of Australian-obligated source material.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Restrictions on the use of Australian-obligated source material. 40.56 Section 40.56 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL... United States of America Concerning Peaceful Uses of Nuclear Energy, dated 2010, Australian-obligated...

  3. 2 CFR 376.370 - What are the obligations of Medicare carriers and intermediaries?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... responsibilities on behalf of the Medicare program (Title XVIII of the Social Security Act), these entities assume the same obligations and responsibilities as the HHS Medicare officials responsible for the Medicare... Responsibilities of Participants Regarding Transactions § 376.370 What are the obligations of Medicare carriers and...

  4. Viral Infection at High Magnification: 3D Electron Microscopy Methods to Analyze the Architecture of Infected Cells

    PubMed Central

    Romero-Brey, Inés; Bartenschlager, Ralf

    2015-01-01

    As obligate intracellular parasites, viruses need to hijack their cellular hosts and reprogram their machineries in order to replicate their genomes and produce new virions. For the direct visualization of the different steps of a viral life cycle (attachment, entry, replication, assembly and egress) electron microscopy (EM) methods are extremely helpful. While conventional EM has given important information about virus-host cell interactions, the development of three-dimensional EM (3D-EM) approaches provides unprecedented insights into how viruses remodel the intracellular architecture of the host cell. During the last years several 3D-EM methods have been developed. Here we will provide a description of the main approaches and examples of innovative applications. PMID:26633469

  5. Viral Infection at High Magnification: 3D Electron Microscopy Methods to Analyze the Architecture of Infected Cells.

    PubMed

    Romero-Brey, Inés; Bartenschlager, Ralf

    2015-12-03

    As obligate intracellular parasites, viruses need to hijack their cellular hosts and reprogram their machineries in order to replicate their genomes and produce new virions. For the direct visualization of the different steps of a viral life cycle (attachment, entry, replication, assembly and egress) electron microscopy (EM) methods are extremely helpful. While conventional EM has given important information about virus-host cell interactions, the development of three-dimensional EM (3D-EM) approaches provides unprecedented insights into how viruses remodel the intracellular architecture of the host cell. During the last years several 3D-EM methods have been developed. Here we will provide a description of the main approaches and examples of innovative applications.

  6. From surface to intracellular non-invasive nanoscale study of living cells impairments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ewald, Dr. Maxime; Tetard, Laurene; Elie-Caille, Dr. Cecile

    Among the enduring challenges in nanoscience, subsurface characterization of live cells holds major stakes. Developments in nanometrology for soft matter thriving on the sensitivity and high resolution benefits of atomic force microscopy have enabled detection of subsurface structures at the nanoscale (1,2,3). However, measurements in liquid environments remain complex (4,5,6,7), in particular in the subsurface domain. Here we introduce liquid-Mode Synthesizing Atomic Force Microscopy (l-MSAFM) to study both the inner structures and the chemically induced intracellular impairments of living cells. Specifically, we visualize the intracellular stress effects of glyphosate on living keratinocytes skin cells. This new approach for living cellmore » nanoscale imaging, l-MSAFM, in their physiological environment or in presence of a chemical stress agent confirmed the loss of inner structures induced by glyphosate. The ability to monitor the cell's inner response to external stimuli, non-destructively and in real time, has the potential to unveil critical nanoscale mechanisms of life science.« less

  7. From surface to intracellular non-invasive nanoscale study of living cells impairments

    NASA Astrophysics Data System (ADS)

    Ewald, M.; Tetard, L.; Elie-Caille, C.; Nicod, L.; Passian, A.; Bourillot, E.; Lesniewska, E.

    2014-07-01

    Among the enduring challenges in nanoscience, subsurface characterization of living cells holds major stakes. Developments in nanometrology for soft matter thriving on the sensitivity and high resolution benefits of atomic force microscopy have enabled detection of subsurface structures at the nanoscale. However, measurements in liquid environments remain complex, in particular in the subsurface domain. Here we introduce liquid-mode synthesizing atomic force microscopy (l-MSAFM) to study both the inner structures and the chemically induced intracellular impairments of living cells. Specifically, we visualize the intracellular stress effects of glyphosate on living keratinocytes skin cells. This new approach, l-MSAFM, for nanoscale imaging of living cell in their physiological environment or in presence of a chemical stress agent could resolve the loss of inner structures induced by glyphosate, the main component of a well-known pesticide (RoundUp™). This firsthand ability to monitor the cell’s inner response to external stimuli non-destructively and in liquid, has the potential to unveil critical nanoscale mechanisms of life science.

  8. Parental Cultural Socialization of Mexican American Adolescents’ Family Obligation Values and Behaviors

    PubMed Central

    Tsai, Kim M.; Telzer, Eva H.; Gonzales, Nancy A.; Fuligni, Andrew J.

    2015-01-01

    The current study examined how parents’ cultural socialization efforts contribute to adolescents’ family obligation values and behaviors and how these processes may depend upon the relational climate at home. Utilizing survey and daily diary methodologies, 428 Mexican American adolescents (50% males; MAge=15 years) and their parents (83% mothers; MAge=42 years) participated in the study. Adolescents reported on their family obligation values and engagement in family assistance tasks across 14 days. Parents reported on their cultural socialization practices. Results indicated that parental cultural socialization was associated with adolescents’ family obligation values and behaviors when parent-child relationships were low in conflict and high in support. Findings suggest that the transmission of cultural values and practices is best facilitated through positive parent-child relationships. PMID:25726966

  9. 22 CFR 233.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Fiscal Agent obligations. 233.07 Section 233.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HASHEMITE KINGDOM OF JORDAN LOAN GUARANTEES ISSUED UNDER THE FURTHER CONTINUING APPROPRIATIONS ACT, 2013, DIV. F, PUB. L. 113-6-STANDARD TERMS AND...

  10. 22 CFR 231.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 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 108-11-STANDARD TERMS AND...

  11. 22 CFR 231.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 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 108-11-STANDARD TERMS AND...

  12. 22 CFR 230.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Fiscal Agent obligations. 230.07 Section 230.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUB. L. 108-11-STANDARD TERMS AND CONDITIONS § 230.07...

  13. 22 CFR 231.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 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 108-11-STANDARD TERMS AND...

  14. 22 CFR 230.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Fiscal Agent obligations. 230.07 Section 230.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUB. L. 108-11-STANDARD TERMS AND CONDITIONS § 230.07...

  15. 22 CFR 230.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Fiscal Agent obligations. 230.07 Section 230.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUB. L. 108-11-STANDARD TERMS AND CONDITIONS § 230.07...

  16. 22 CFR 231.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 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 108-11-STANDARD TERMS AND...

  17. 22 CFR 230.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Fiscal Agent obligations. 230.07 Section 230.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUB. L. 108-11-STANDARD TERMS AND CONDITIONS § 230.07...

  18. 22 CFR 230.07 - Fiscal Agent obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Fiscal Agent obligations. 230.07 Section 230.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUB. L. 108-11-STANDARD TERMS AND CONDITIONS § 230.07...

  19. Intracellular GPCRs Play Key Roles in Synaptic Plasticity.

    PubMed

    Jong, Yuh-Jiin I; Harmon, Steven K; O'Malley, Karen L

    2018-02-16

    The trillions of synaptic connections within the human brain are shaped by experience and neuronal activity, both of which underlie synaptic plasticity and ultimately learning and memory. G protein-coupled receptors (GPCRs) play key roles in synaptic plasticity by strengthening or weakening synapses and/or shaping dendritic spines. While most studies of synaptic plasticity have focused on cell surface receptors and their downstream signaling partners, emerging data point to a critical new role for the very same receptors to signal from inside the cell. Intracellular receptors have been localized to the nucleus, endoplasmic reticulum, lysosome, and mitochondria. From these intracellular positions, such receptors may couple to different signaling systems, display unique desensitization patterns, and/or show distinct patterns of subcellular distribution. Intracellular GPCRs can be activated at the cell surface, endocytosed, and transported to an intracellular site or simply activated in situ by de novo ligand synthesis, diffusion of permeable ligands, or active transport of non-permeable ligands. Current findings reinforce the notion that intracellular GPCRs play a dynamic role in synaptic plasticity and learning and memory. As new intracellular GPCR roles are defined, the need to selectively tailor agonists and/or antagonists to both intracellular and cell surface receptors may lead to the development of more effective therapeutic tools.

  20. US arms control obligations under the Non-Proliferation Treaty

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1986-06-27

    Article VI of the 1968 Non-Proliferation Treaty (NPT) obligates the nuclear weapon states parties to the Treaty ''to pursue negotiations in good faith on effective measures relating to cessation of the nuclear arms race, ... to nuclear disarmament, and on a treaty on general and complete disarmament under strict and effective international control.'' The preamble to the NPT recalls the 1963 Limited Test Ban Treaty ''determination ... to achieve the discontinuance of ... explosions.'' These provisions are interpreted by a majority of the non-nuclear weapon states parties to the Treaty as an obligation of the nuclear weapon states parties tomore » the Treaty to pursue a comprehensive test ban (CTB). However, a review of the history of the NPT negotiations and US ratification proceedings makes clear that the NPT imposes no legal obligation on the US to pursue a CTB. The US did not make a one-to-one correspondence between Article VI and any specific arms control measure; to the contrary, the US argued successfully that such a connection (to any specific measure) would be pernicious to the attempt to achieve agreement on the NPT. This interpretation, which was sustained through the negotiations and the ratification proceedings, still reflects the limits of the legal obligations the US has accepted. But, in the absence of progress on other arms control measures, which would relieve the pressure for a CTB, the majority interpretation creates political difficulties for the US and could threaten the NPT regime in the future. These problems highlight the need for the US to better defend its compliance with Article VI and to develop a long-term strategy that will permit necessary testing while assuring the survival of the NPT regime in effective form.« less

  1. Long-Term Survival and Intracellular Replication of Mycoplasma hominis in Trichomonas vaginalis Cells: Potential Role of the Protozoon in Transmitting Bacterial Infection

    PubMed Central

    Dessì, Daniele; Delogu, Giuseppe; Emonte, Eleonora; Catania, Maria Rosaria; Fiori, Pier Luigi; Rappelli, Paola

    2005-01-01

    The existence of a symbiotic relationship between Trichomonas vaginalis and Mycoplasma hominis, which is the first reported example of symbiosis between two obligate human pathogens, has been recently reported by our research group. In this work, we examined the cellular location of M. hominis in respect to T. vaginalis. By using gentamicin protection assays, double immunofluorescence, and confocal microscopy, we obtained strong evidence that M. hominis is located within protozoan cells. 5-Bromodeoxyuridine incorporation assays showed that intracellularly located mycoplasmas actively synthesize DNA. Our results demonstrate that M. hominis has the capability of entering trichomonad cells and of replicating inside the protozoon. These findings suggest that symbiosis might provide the bacteria, during human infection, with the capability to resist to environmental stresses, such as host defense mechanisms and pharmacological therapies. PMID:15664961

  2. An obligation to provide abortion services: what happens when physicians refuse?

    PubMed

    Meyers, C; Woods, R D

    1996-04-01

    Access to abortion services in the United States continues to decline. It does so not because of significant changes in legislation or court rulings but because fewer and fewer physicians wish to perform abortions and because most states now have "conscientious objection" legislation that makes it easy for physicians to refuse to do so. We argue in this paper that physicians have an obligation to perform all socially sanctioned medical services, including abortions, and thus that the burden of justification lies upon those who wish to be excused from that obligation. That is, such persons should have to show how requiring them to perform abortions would represent a serious threat to their fundamental moral or religious beliefs. We use current California law as an example of legislation that does not take physicians' obligations into account and thus allows them too easily to declare conscientious objection.

  3. An obligation to provide abortion services: what happens when physicians refuse?

    PubMed Central

    Meyers, C; Woods, R D

    1996-01-01

    Access to abortion services in the United States continues to decline. It does so not because of significant changes in legislation or court rulings but because fewer and fewer physicians wish to perform abortions and because most states now have "conscientious objection" legislation that makes it easy for physicians to refuse to do so. We argue in this paper that physicians have an obligation to perform all socially sanctioned medical services, including abortions, and thus that the burden of justification lies upon those who wish to be excused from that obligation. That is, such persons should have to show how requiring them to perform abortions would represent a serious threat to their fundamental moral or religious beliefs. We use current California law as an example of legislation that does not take physicians' obligations into account and thus allows them too easily to declare conscientious objection. PMID:8731539

  4. 45 CFR 96.14 - Time period for obligation and expenditure of grant funds.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Time period for obligation and expenditure of grant funds. 96.14 Section 96.14 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS General Procedures § 96.14 Time period for obligation and expenditure of grant funds...

  5. 45 CFR 96.14 - Time period for obligation and expenditure of grant funds.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Time period for obligation and expenditure of grant funds. 96.14 Section 96.14 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION BLOCK GRANTS General Procedures § 96.14 Time period for obligation and expenditure of grant funds...

  6. 45 CFR 96.14 - Time period for obligation and expenditure of grant funds.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Time period for obligation and expenditure of grant funds. 96.14 Section 96.14 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS General Procedures § 96.14 Time period for obligation and expenditure of grant funds...

  7. 45 CFR 96.14 - Time period for obligation and expenditure of grant funds.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Time period for obligation and expenditure of grant funds. 96.14 Section 96.14 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS General Procedures § 96.14 Time period for obligation and expenditure of grant funds...

  8. 45 CFR 96.14 - Time period for obligation and expenditure of grant funds.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Time period for obligation and expenditure of grant funds. 96.14 Section 96.14 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS General Procedures § 96.14 Time period for obligation and expenditure of grant funds...

  9. Newcomer Psychological Contracts and Employee Socialization Activities: Does Perceived Balance in Obligations Matter?

    ERIC Educational Resources Information Center

    Payne, Stephanie C.; Culbertson, Satoris S.; Boswell, Wendy R.; Barger, Eric J.

    2008-01-01

    We sought to determine the extent to which one's beliefs about the relationship between an employee and an organization at the start of employment influence subsequent socialization activities. The balance of employee exchange relationships, employee perceptions of both their own obligations and the employers' obligations, were collected from 120…

  10. 13 CFR 500.213 - Termination of obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Termination of obligations. 500.213 Section 500.213 Business Credit and Assistance EMERGENCY OIL AND GAS GUARANTEED LOAN BOARD... the Application, the Guarantee or the Loan Documents; (5) A Lender fails to make a demand for payment...

  11. 48 CFR 1019.202-70-14 - Obligation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Obligation. 1019.202-70-14 Section 1019.202-70-14 Federal Acquisition Regulations System DEPARTMENT OF THE TREASURY SOCIOECONOMIC... voluntarily withdraw from the Mentor-Protégé Program. However, such withdrawal will not impact the program...

  12. Higher Education's Cultural Obligations: Views and Reviews.

    ERIC Educational Resources Information Center

    Reid, John Y., Ed.

    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,…

  13. Changes in Perceived Filial Obligation Norms Among Coresident Family Caregivers in Japan

    PubMed Central

    Tsutsui, Takako; Muramatsu, Naoko; Higashino, Sadanori

    2014-01-01

    Purpose of the Study: Japan introduced a nationwide long-term care insurance (LTCI) system in 2000, making long-term care (LTC) a right for older adults regardless of income and family availability. To shed light on its implications for family caregiving, we investigated perceived filial obligation norms among coresident primary family caregivers before and after the policy change. Design and Methods: Descriptive and multiple regression analyses were conducted to examine changes in perceived filial obligation norms and its subdimensions (financial, physical, and emotional support), using 2-wave panel survey data of coresident primary family caregivers (N = 611) in 1 city. The baseline survey was conducted in 1999, and a follow-up survey 2 years later. Results: On average, perceived filial obligation norms declined (p < .05). Daughters-in-law had the most significant declines (global and physical: p < .01, emotional: p < .05) among family caregivers. In particular, physical support, which Japan’s LTC reform targeted, declined significantly among daughters and daughters-in-law (p < .01). Multiple regression analysis indicated that daughters-in-law had significantly lower perceived filial obligation norms after the policy introduction than sons and daughters (p < .01 and p < .05, respectively), controlling for the baseline filial obligation and situational factors. Implications: Our research indicates declining roles of daughters-in-law in elder care during Japan’s LTCI system implementation period. Further international efforts are needed to design and implement longitudinal studies that help promote understanding of the interplay among national LTC policies, social changes, and caregiving norms and behaviors. PMID:24009170

  14. Changes in perceived filial obligation norms among coresident family caregivers in Japan.

    PubMed

    Tsutsui, Takako; Muramatsu, Naoko; Higashino, Sadanori

    2014-10-01

    Japan introduced a nationwide long-term care insurance (LTCI) system in 2000, making long-term care (LTC) a right for older adults regardless of income and family availability. To shed light on its implications for family caregiving, we investigated perceived filial obligation norms among coresident primary family caregivers before and after the policy change. Descriptive and multiple regression analyses were conducted to examine changes in perceived filial obligation norms and its subdimensions (financial, physical, and emotional support), using 2-wave panel survey data of coresident primary family caregivers (N = 611) in 1 city. The baseline survey was conducted in 1999, and a follow-up survey 2 years later. On average, perceived filial obligation norms declined (p < .05). Daughters-in-law had the most significant declines (global and physical: p < .01, emotional: p < .05) among family caregivers. In particular, physical support, which Japan's LTC reform targeted, declined significantly among daughters and daughters-in-law (p < .01). Multiple regression analysis indicated that daughters-in-law had significantly lower perceived filial obligation norms after the policy introduction than sons and daughters (p < .01 and p < .05, respectively), controlling for the baseline filial obligation and situational factors. Our research indicates declining roles of daughters-in-law in elder care during Japan's LTCI system implementation period. Further international efforts are needed to design and implement longitudinal studies that help promote understanding of the interplay among national LTC policies, social changes, and caregiving norms and behaviors. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America.

  15. Macrophage defense mechanisms against intracellular bacteria

    PubMed Central

    Weiss, Günter; Schaible, Ulrich E

    2015-01-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

  16. 76 FR 16707 - Rule 17Ad-17; Transfer Agents', Brokers', and Dealers' Obligation To Search for Lost...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... 3235-AL11 Rule 17Ad-17; Transfer Agents', Brokers', and Dealers' Obligation To Search for Lost Securityholders; Paying Agents' Obligation To Search for Missing Securityholders AGENCY: Securities and Exchange... Rule 17Ad-17, ``Transfer Agents' Obligation to Search for Lost Securityholders'' to: extend to brokers...

  17. 12 CFR 987.5 - Obligations of the Banks and the Office of Finance; no Adverse Claims.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Obligations of the Banks and the Office of Finance; no Adverse Claims. 987.5 Section 987.5 Banks and Banking FEDERAL HOUSING FINANCE BOARD OFFICE OF FINANCE BOOK-ENTRY PROCEDURE FOR CONSOLIDATED OBLIGATIONS § 987.5 Obligations of the Banks and the Office of Finance; no Adverse Claims. (a) Except...

  18. Intracellular Drug Bioavailability: Effect of Neutral Lipids and Phospholipids.

    PubMed

    Treyer, Andrea; Mateus, André; Wiśniewski, Jacek R; Boriss, Hinnerk; Matsson, Pär; Artursson, Per

    2018-06-04

    Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F ic ) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F ic . The induction of NL did not further increase drug binding but led to altered F ic due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.

  19. Requirement for Chloride Channel Function during the Hepatitis C Virus Life Cycle

    PubMed Central

    Igloi, Zsofia; Mohl, Bjorn-Patrick; Lippiat, Jonathan D.; Harris, Mark

    2015-01-01

    Hepatocytes express an array of plasma membrane and intracellular ion channels, yet their role during the hepatitis C virus (HCV) life cycle remains largely undefined. Here, we show that HCV increases intracellular hepatic chloride (Cl−) influx that can be inhibited by selective Cl− channel blockers. Through pharmacological and small interfering RNA (siRNA)-mediated silencing, we demonstrate that Cl− channel inhibition is detrimental to HCV replication. This represents the first observation of the involvement of Cl− channels during the HCV life cycle. PMID:25609806

  20. 18 CFR 1314.6 - Obligations of TVA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... PROCEDURES FOR TVA POWER SECURITIES ISSUED THROUGH THE FEDERAL RESERVE BANKS § 1314.6 Obligations of TVA. (a... or disposition of a Book-entry TVA Power Security by a Reserve Bank pursuant to a transfer message... Participant. (2) Book-entry TVA Power Securities are redeemed in accordance with their terms by a Reserve Bank...

  1. Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella.

    PubMed

    Xie, Shuyu; Yang, Fei; Tao, Yanfei; Chen, Dongmei; Qu, Wei; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Yuan, Zonghui

    2017-01-23

    Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06-37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from -8.1 to -24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment.

  2. 23 CFR 230.205 - Supportive services funds obligation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Supportive services funds obligation. 230.205 Section 230.205 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS EXTERNAL PROGRAMS Supportive Services for Minority, Disadvantaged, and Women Business Enterprises § 230.205...

  3. 23 CFR 230.205 - Supportive services funds obligation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Supportive services funds obligation. 230.205 Section 230.205 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS EXTERNAL PROGRAMS Supportive Services for Minority, Disadvantaged, and Women Business Enterprises § 230.205...

  4. 23 CFR 230.205 - Supportive services funds obligation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Supportive services funds obligation. 230.205 Section 230.205 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS EXTERNAL PROGRAMS Supportive Services for Minority, Disadvantaged, and Women Business Enterprises § 230.205...

  5. 23 CFR 230.205 - Supportive services funds obligation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Supportive services funds obligation. 230.205 Section 230.205 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS EXTERNAL PROGRAMS Supportive Services for Minority, Disadvantaged, and Women Business Enterprises § 230.205...

  6. 23 CFR 230.205 - Supportive services funds obligation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Supportive services funds obligation. 230.205 Section 230.205 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS EXTERNAL PROGRAMS Supportive Services for Minority, Disadvantaged, and Women Business Enterprises § 230.205...

  7. 24 CFR 236.755 - Housing owner's obligation under contract to report tenant income increase.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... FOR RENTAL PROJECTS Rental Assistance Payments § 236.755 Housing owner's obligation under contract to... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Housing owner's obligation under contract to report tenant income increase. 236.755 Section 236.755 Housing and Urban Development...

  8. 5 CFR 353.104 - Notification of rights and obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... employee of his or her rights, obligations, and benefits relating to Government employment, including any... exercise due diligence in ascertaining his or her rights, and to seek reemployment within the time limits...

  9. The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells.

    PubMed

    Jin, Song-Hyo; An, Sung-Kwan; Lee, Seong-Beom

    2017-06-01

    Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M.leprae-infected Schwann cells in the nerve biopsies of lepromatous leprosy patients. M.leprae-induced LD formation favors intracellular M.leprae survival in primary Schwann cells and in a myelinating Schwann cell line referred to as ST88-14. In the current study, we initially characterized SW-10 cells and investigated the effects of LDs on M.leprae-infected SW-10 cells, which are non-myelinating Schwann cells. SW-10 cells express S100, a marker for cells from the neural crest, and NGFR p75, a marker for immature or non-myelinating Schwann cells. SW-10 cells, however, do not express myelin basic protein (MBP), a marker for myelinating Schwann cells, and myelin protein zero (MPZ), a marker for precursor, immature, or myelinating Schwann cells, all of which suggests that SW-10 cells are non-myelinating Schwann cells. In addition, SW-10 cells have phagocytic activity and can be infected with M. leprae. Infection with M. leprae induces the formation of LDs. Furthermore, inhibiting the formation of M. leprae-induced LD enhances the maturation of phagosomes containing live M.leprae and decreases the ATP content in the M. leprae found in SW-10 cells. These facts suggest that LD formation by M. leprae favors intracellular M. leprae survival in SW-10 cells, which leads to the logical conclusion that M.leprae-infected SW-10 cells can be a new model for investigating the interaction of M.leprae with non-myelinating Schwann cells.

  10. The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells

    PubMed Central

    Jin, Song-Hyo; An, Sung-Kwan

    2017-01-01

    Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M.leprae-infected Schwann cells in the nerve biopsies of lepromatous leprosy patients. M.leprae-induced LD formation favors intracellular M.leprae survival in primary Schwann cells and in a myelinating Schwann cell line referred to as ST88-14. In the current study, we initially characterized SW-10 cells and investigated the effects of LDs on M.leprae-infected SW-10 cells, which are non-myelinating Schwann cells. SW-10 cells express S100, a marker for cells from the neural crest, and NGFR p75, a marker for immature or non-myelinating Schwann cells. SW-10 cells, however, do not express myelin basic protein (MBP), a marker for myelinating Schwann cells, and myelin protein zero (MPZ), a marker for precursor, immature, or myelinating Schwann cells, all of which suggests that SW-10 cells are non-myelinating Schwann cells. In addition, SW-10 cells have phagocytic activity and can be infected with M. leprae. Infection with M. leprae induces the formation of LDs. Furthermore, inhibiting the formation of M. leprae-induced LD enhances the maturation of phagosomes containing live M.leprae and decreases the ATP content in the M. leprae found in SW-10 cells. These facts suggest that LD formation by M. leprae favors intracellular M. leprae survival in SW-10 cells, which leads to the logical conclusion that M.leprae-infected SW-10 cells can be a new model for investigating the interaction of M.leprae with non-myelinating Schwann cells. PMID:28636650

  11. Therapeutic drug monitoring of intracellular anti-infective agents.

    PubMed

    D'Avolio, Antonio; Pensi, Debora; Baietto, Lorena; Di Perri, Giovanni

    2014-12-01

    Many microorganisms, including viruses, some bacteria and fungi, replicate within the cells. Therefore, the efficacy of therapy and the selection of resistances could be related to intracellular concentration of the drugs and to their ability to cross biological membranes and penetrate into various tissue compartments. The efficacy of treatment may be limited by pharmacological factors. Dose-response relationship exists for many agents, and failure to maintain adequate concentrations may allow the development of viral or bacterial resistance, thereby decreasing the probability of response of current and subsequent therapies. The major target of antivirals and many other anti-infective agents is within infected cells. Therefore, clinical outcome ultimately should be related to intracellular drug concentrations. Intracellular pharmacokinetics provides information regarding drug disposition in a compartment where microorganism replication occurs and combined with plasma data may be useful in understanding therapeutic failure in relation to cellular resistance. With a focus on possible methodological biases, this review reports the current state of the art in intracellular, particularly in peripheral blood mononuclear cells, therapeutic drug monitoring of the following anti-infective drugs: antivirals, antifungals and antibiotics. Although measurement of intracellular concentrations needs to be still standardized focusing on each single drug, this review showed some relationships between intracellular concentrations of few anti-infective drugs and their efficacy and/or toxicity. Such relationships should be interpreted with caution, as intracellular concentrations reflect the total amount of drug within the cell and not the effective unbound fraction. The number of clinical studies in that area is, however, rather limited, and not always adequately designed. Then, intracellular drug determination has to be considered a test for research only and not to be carried out

  12. 47 CFR 27.1168 - Triggering a Reimbursement Obligation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Triggering a Reimbursement Obligation. 27.1168 Section 27.1168 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1710-1755 MHz, 2110-2155 MHz, 2000-2020 MHz, and 2180-2200 MHz...

  13. 47 CFR 27.1184 - Triggering a reimbursement obligation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Triggering a reimbursement obligation. 27.1184 Section 27.1184 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1710-1755 MHz, 2110-2155 MHz, 2000-2020 MHz, and 2180-2200 MHz...

  14. 7 CFR 760.507 - Obligations of a participant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS Tree Assistance Program § 760.507 Obligations of a participant. (a) Eligible orchardists and nursery tree growers must execute all required documents and complete the TAP-funded practice within 12 months of application approval. (b) Eligible orchardist or...

  15. 7 CFR 760.507 - Obligations of a participant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS Tree Assistance Program § 760.507 Obligations of a participant. (a) Eligible orchardists and nursery tree growers must execute all required documents and complete the TAP-funded practice within 12 months of application approval. (b) Eligible orchardist or...

  16. 7 CFR 760.507 - Obligations of a participant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS Tree Assistance Program § 760.507 Obligations of a participant. (a) Eligible orchardists and nursery tree growers must execute all required documents and complete the TAP-funded practice within 12 months of application approval. (b) Eligible orchardist or...

  17. 7 CFR 760.507 - Obligations of a participant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS Tree Assistance Program § 760.507 Obligations of a participant. (a) Eligible orchardists and nursery tree growers must execute all required documents and complete the TAP-funded practice within 12 months of application approval. (b) Eligible orchardist or...

  18. Obama states obligation to act on climate change

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2012-11-01

    Obama states obligation to act on climate change Noting increased global temperatures, Arctic ice melt, and severe weather events, President Barack Obama said that climate change is real and called for a conversation across the country to determine what can be done about it.

  19. 29 CFR 1987.102 - Obligations and prohibited acts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Obligations and prohibited acts. 1987.102 Section 1987.102 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) PROCEDURES FOR HANDLING RETALIATION COMPLAINTS UNDER SECTION 402 OF THE FDA...

  20. Metabolic Cooperation of Glucose and Glutamine Is Essential for the Lytic Cycle of Obligate Intracellular Parasite Toxoplasma gondii*

    PubMed Central

    Nitzsche, Richard; Zagoriy, Vyacheslav; Lucius, Richard; Gupta, Nishith

    2016-01-01

    Toxoplasma gondii is a widespread protozoan parasite infecting nearly all warm-blooded organisms. Asexual reproduction of the parasite within its host cells is achieved by consecutive lytic cycles, which necessitates biogenesis of significant energy and biomass. Here we show that glucose and glutamine are the two major physiologically important nutrients used for the synthesis of macromolecules (ATP, nucleic acid, proteins, and lipids) in T. gondii, and either of them is sufficient to ensure the parasite survival. The parasite can counteract genetic ablation of its glucose transporter by increasing the flux of glutamine-derived carbon through the tricarboxylic acid cycle and by concurrently activating gluconeogenesis, which guarantee a continued biogenesis of ATP and biomass for host-cell invasion and parasite replication, respectively. In accord, a pharmacological inhibition of glutaminolysis or oxidative phosphorylation arrests the lytic cycle of the glycolysis-deficient mutant, which is primarily a consequence of impaired invasion due to depletion of ATP. Unexpectedly, however, intracellular parasites continue to proliferate, albeit slower, notwithstanding a simultaneous deprivation of glucose and glutamine. A growth defect in the glycolysis-impaired mutant is caused by a compromised synthesis of lipids, which cannot be counterbalanced by glutamine but can be restored by acetate. Consistently, supplementation of parasite cultures with exogenous acetate can amend the lytic cycle of the glucose transport mutant. Such plasticity in the parasite's carbon flux enables a growth-and-survival trade-off in assorted nutrient milieus, which may underlie the promiscuous survival of T. gondii tachyzoites in diverse host cells. Our results also indicate a convergence of parasite metabolism with cancer cells. PMID:26518878

  1. Hospital/Health Facilities and the Hill-Burton Obligations: A Secret from the Black Community.

    ERIC Educational Resources Information Center

    Rice, Mitchell F.

    1986-01-01

    Uncompensated/free care and community service obligations under the Hill-Burton Act can assist substantially in providing needed health care services to the Black community. Blacks, however, must become knowledgeable about these obligations, develop monitoring projects, and be prepared to take legal steps to bring Hill-Burton facilities into…

  2. 45 CFR 63.21 - Obligation and liquidation by grantee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... utilities, for travel, and for the rental of facilities, shall be considered to have been obligated as of the time such services were rendered, such travel was performed, and such rented facilities were used...

  3. The intracellular carboxyl tail of the PAR-2 receptor controls intracellular signaling and cell death.

    PubMed

    Zhu, Zhihui; Stricker, Rolf; Li, Rong yu; Zündorf, Gregor; Reiser, Georg

    2015-03-01

    The protease-activated receptors are a group of unique G protein-coupled receptors, including PAR-1, PAR-2, PAR-3 and PAR-4. PAR-2 is activated by multiple trypsin-like serine proteases, including trypsin, tryptase and coagulation proteases. The clusters of phosphorylation sites in the PAR-2 carboxyl tail are suggested to be important for the binding of adaptor proteins to initiate intracellular signaling to Ca(2+) and mitogen-activated protein kinases. To explore the functional role of PAR-2 carboxyl tail in controlling intracellular Ca(2+), ERK and AKT signaling, a series of truncated mutants containing different clusters of serines/threonines were generated and expressed in HEK293 cells. Firstly, we observed that lack of the complete C-terminus of PAR-2 in a mutated receptor gave a relatively low level of localization on the cell plasma membrane. Secondly, the shortened carboxyl tail containing 13 amino acids was sufficient for receptor internalization. Thirdly, the cells expressing truncation mutants showed deficits in their capacity to couple to intracellular Ca(2+) and ERK and AKT signaling upon trypsin challenge. In addition, HEK293 cells carrying different PAR-2 truncation mutants displayed decreased levels of cell survival after long-lasting trypsin stimulation. In summary, the PAR-2 carboxyl tail was found to control the receptor localization, internalization, intracellular Ca(2+) responses and signaling to ERK and AKT. The latter can be considered to be important for cell death control.

  4. Should We Provide Life-Sustaining Treatments to Patients with Permanent Loss of Cognitive Capacities?

    PubMed Central

    Golan, Ofra G.; Marcus, Esther-Lee

    2012-01-01

    A very troubling issue for health care systems today is that of life-sustaining treatment for patients who have permanently lost their cognitive capacities. These include patients in persistent vegetative state (PVS), or minimally conscious state (MCS), as well as a growing population of patients at the very end stage of dementia. These patients are totally dependent on life-sustaining treatments and are, actually, kept alive “artificially.” This phenomenon raises doubts as to the ethics of sustaining the life of patients who have lost their consciousness and cognitive capacities, and whether there is a moral obligation to do so. The problem is that the main facts concerning the experiences and well-being of such patients and their wishes are unknown. Hence the framework of the four principles—beneficence, non-maleficence, autonomy, and justice—is not applicable in these cases; therefore we examined solidarity as another moral value to which we may resort in dealing with this dilemma. This article shows that the source of the dilemma is the social attitudes towards loss of cognitive capacities, and the perception of this state as loss of personhood. Consequently, it is suggested that the principle of solidarity—which both sets an obligation to care for the worst-off, and can be used to identify obligations that appeal to an ethos of behavior—can serve as a guiding principle for resolving the dilemma. The value of solidarity can lead society to care for these patients and not deny them basic care and life-sustaining treatment when appropriate. PMID:23908842

  5. 33 CFR 384.11 - What are the Corps of Engineers obligations in interstate situations?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false What are the Corps of Engineers obligations in interstate situations? 384.11 Section 384.11 Navigation and Navigable Waters CORPS OF ENGINEERS... ENGINEERS PROGRAMS AND ACTIVITIES § 384.11 What are the Corps of Engineers obligations in interstate...

  6. 33 CFR 384.11 - What are the Corps of Engineers obligations in interstate situations?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false What are the Corps of Engineers obligations in interstate situations? 384.11 Section 384.11 Navigation and Navigable Waters CORPS OF ENGINEERS... ENGINEERS PROGRAMS AND ACTIVITIES § 384.11 What are the Corps of Engineers obligations in interstate...

  7. 33 CFR 384.11 - What are the Corps of Engineers obligations in interstate situations?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false What are the Corps of Engineers obligations in interstate situations? 384.11 Section 384.11 Navigation and Navigable Waters CORPS OF ENGINEERS... ENGINEERS PROGRAMS AND ACTIVITIES § 384.11 What are the Corps of Engineers obligations in interstate...

  8. Public health agencies' obligations and the case of Zika.

    PubMed

    Luna, Florencia

    2017-10-01

    This article focuses on the initial reactions to the Zika epidemic by national and international public health agencies. It presents and analyzes some responses public officials made about sexual and reproductive health at the inception of the epidemic. It also describes the different challenges and obligations faced by local and international public health agencies, as these have not been clearly outlined. The article argues that these agencies have different obligations and should fulfill them despite existing obstacles. While international agencies should honor their leadership role and make recommendations at a meta-level, local agencies should provide, in the case of Zika, a framework for empowerment and grant women the freedom to achieve sexual and reproductive health so that they can avoid the consequences of this epidemic. © 2017 John Wiley & Sons Ltd.

  9. 42 CFR 62.28 - Under what circumstances can the service or payment obligation be canceled, waived or suspended?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... obligation be canceled, waived or suspended? 62.28 Section 62.28 Public Health PUBLIC HEALTH SERVICE... what circumstances can the service or payment obligation be canceled, waived or suspended? A service or payment obligation under the Loan Repayment Program will be canceled or may be waived or suspended as...

  10. 31 CFR 223.18 - Performance of agency obligations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Performance of agency obligations. 223.18 Section 223.18 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS...

  11. 31 CFR 223.18 - Performance of agency obligations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Performance of agency obligations. 223.18 Section 223.18 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS...

  12. 31 CFR 223.18 - Performance of agency obligations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Performance of agency obligations. 223.18 Section 223.18 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS...

  13. 31 CFR 223.18 - Performance of agency obligations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false Performance of agency obligations. 223.18 Section 223.18 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS...

  14. 31 CFR 203.6 - Obligations of TT&L depositaries.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... TREASURY TAX AND LOAN PROGRAM General Information § 203.6 Obligations of TT&L depositaries. A TT&L depositary must: (a) Administer a TIP main account balance, SDI account balance, or TIO account balance, as...

  15. Climate warming and the potential extinction of fig wasps, the obligate pollinators of figs.

    PubMed

    Jevanandam, Nanthinee; Goh, Alexander G R; Corlett, Richard T

    2013-06-23

    Figs (Ficus) have a reciprocally obligate mutualism with tiny, short-lived (1-2 days) fig wasps (Agaonidae). The small size and short life of these pollinators is expected to make them more vulnerable to climate change than their larger and longer-lived hosts. We experimentally tested the thermal tolerances of four species of adult female fig wasp from equatorial Singapore. The results suggest that an increase of 3°C or more above the current temperatures experienced across much of the equatorial tropics would markedly decrease the active adult lifespan of all four species. Fig plants are the centre of an intricate web of specialist and generalist animals. Unless fig wasps can acclimate or adapt to warmer temperatures in time, these responses may disrupt the mutualism, potentially affecting multiple trophic levels.

  16. Impact of Photosensitizers Activation on Intracellular Trafficking and Viscosity

    PubMed Central

    Aubertin, Kelly; Bonneau, Stéphanie; Silva, Amanda K. A.; Bacri, Jean-Claude; Gallet, François; Wilhelm, Claire

    2013-01-01

    The intracellular microenvironment is essential for the efficiency of photo-induced therapies, as short-lived reactive oxygen species generated must diffuse through their intracellular surrounding medium to reach their cellular target. Here, by combining measurements of local cytoplasmic dissipation and active trafficking, we found that photosensitizers activation induced small changes in surrounding viscosity but a massive decrease in diffusion. These effects are the signature of a return to thermodynamic equilibrium of the system after photo-activation and correlated with depolymerization of the microtubule network, as shown in a reconstituted system. These mechanical measurements were performed with two intracellular photosensitizing chlorins having similar quantum yield of singlet oxygen production but different intracellular localizations (cytoplasmic for mTHPC, endosomal for TPCS2a). These two agents demonstrated different intracellular impact. PMID:24386423

  17. 12 CFR 611.1270 - Repayment of obligations-terminating bank.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...-wide obligations in a method that we deem acceptable. Before we make a final decision on your proposal... respect to financing and disclosure. (2) If you and the other Farm Credit banks are unable to reach...

  18. Motivation Counts: Autonomous But Not Obligated Sharing Promotes Happiness in Preschoolers.

    PubMed

    Wu, Zhen; Zhang, Zhen; Guo, Rui; Gros-Louis, Julie

    2017-01-01

    Research has demonstrated that prosocial sharing is emotionally rewarding, which leads to further prosocial actions; such a positive feedback loop suggests a proximal mechanism of human's tendency to act prosocially. However, it leaves open a question as to how the emotional benefits from sharing develop in young children and whether sharing under pressure promotes happiness as well. The current study directly compared 3- and 5-year-old Chinese children's happiness when sharing was autonomous (the recipient did not contribute to getting the reward) with when sharing was obligated (the recipient and the actor jointly earned the reward). We found that children shared more items overall when sharing was obligated than autonomous, demonstrating their conformity to social norms of merit-based sharing. In children who eventually shared with others, 5-year-olds gave out more stickers in the obligated sharing condition than in the autonomous sharing condition, but 3-year-olds shared the same amount between the conditions, suggesting that 5-year-olds adhered to the merit-based sharing norm more strictly than 3-year-olds. Moreover, in the autonomous sharing condition, children displayed greater happiness when they shared with the recipient than when they kept stickers for themselves, suggesting that costly prosocial giving benefited children with positive mood; however, children did not gain happiness when they shared with the recipient in the obligated sharing condition. These findings demonstrate that children's affective benefits depend on the motivation underlying their prosocial behavior, and further imply that normative force and emotional gains may independently drive preschoolers' prosocial behaviors.

  19. Motivation Counts: Autonomous But Not Obligated Sharing Promotes Happiness in Preschoolers

    PubMed Central

    Wu, Zhen; Zhang, Zhen; Guo, Rui; Gros-Louis, Julie

    2017-01-01

    Research has demonstrated that prosocial sharing is emotionally rewarding, which leads to further prosocial actions; such a positive feedback loop suggests a proximal mechanism of human’s tendency to act prosocially. However, it leaves open a question as to how the emotional benefits from sharing develop in young children and whether sharing under pressure promotes happiness as well. The current study directly compared 3- and 5-year-old Chinese children’s happiness when sharing was autonomous (the recipient did not contribute to getting the reward) with when sharing was obligated (the recipient and the actor jointly earned the reward). We found that children shared more items overall when sharing was obligated than autonomous, demonstrating their conformity to social norms of merit-based sharing. In children who eventually shared with others, 5-year-olds gave out more stickers in the obligated sharing condition than in the autonomous sharing condition, but 3-year-olds shared the same amount between the conditions, suggesting that 5-year-olds adhered to the merit-based sharing norm more strictly than 3-year-olds. Moreover, in the autonomous sharing condition, children displayed greater happiness when they shared with the recipient than when they kept stickers for themselves, suggesting that costly prosocial giving benefited children with positive mood; however, children did not gain happiness when they shared with the recipient in the obligated sharing condition. These findings demonstrate that children’s affective benefits depend on the motivation underlying their prosocial behavior, and further imply that normative force and emotional gains may independently drive preschoolers’ prosocial behaviors. PMID:28620328

  20. 14 CFR 272.8 - Obligation to continue service.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... PROCEEDINGS) ECONOMIC REGULATIONS ESSENTIAL AIR SERVICE TO THE FREELY ASSOCIATED STATES § 272.8 Obligation to... eligible Freely Associated State place below the level of essential air service to such place, whether or not the Department has previously determined the level of essential air service to such place, the...