A new insight into the three-dimensional architecture of the Golgi complex: Characterization of unusual structures in epididymal principal cells

PubMed Central

Martínez-Martínez, Narcisa; Martínez-Alonso, Emma; Tomás, Mónica; Neumüller, Josef; Pavelka, Margit

2017-01-01

Principal epididymal cells have one of the largest and more developed Golgi complex of mammalian cells. In the present study, we have used this cell as model for the study of the three-dimensional architecture of the Golgi complex of highly secretory and endocytic cells. Electron tomography demonstrated the presence in this cell type of some unknown or very unusual Golgi structures such as branched cisternae, pocket-like cisternal invaginations or tubular connections. In addition, we have used this methodology and immunoelectron microscopy to analyze the close relationship between this organelle and both the endoplasmic reticulum and microtubules, and to describe in detail how these elements interact with compact and non-compact regions of the ribbon. PMID:28957389

Mankind's Magnificent Milestone: Smallpox Eradication.

ERIC Educational Resources Information Center

Small, Parker A., Jr.; Small, Natalie S.

1996-01-01

Illustrates the complex interactions between disease, societal attitudes, and technology by looking at the history of smallpox. Describes one of mankind's most magnificent accomplishments--the eradication of smallpox from the earth. (JRH)

Invasive mammal eradication on islands results in substantial conservation gains

PubMed Central

Jones, Holly P.; Holmes, Nick D.; Butchart, Stuart H. M.; Tershy, Bernie R.; Kappes, Peter J.; Corkery, Ilse; Aguirre-Muñoz, Alfonso; Armstrong, Doug P.; Bonnaud, Elsa; Burbidge, Andrew A.; Campbell, Karl; Courchamp, Franck; Cowan, Philip E.; Cuthbert, Richard J.; Ebbert, Steve; Genovesi, Piero; Howald, Gregg R.; Keitt, Bradford S.; Kress, Stephen W.; Miskelly, Colin M.; Oppel, Steffen; Poncet, Sally; Rauzon, Mark J.; Rocamora, Gérard; Russell, James C.; Samaniego-Herrera, Araceli; Seddon, Philip J.; Spatz, Dena R.; Towns, David R.; Croll, Donald A.

2016-01-01

More than US$21 billion is spent annually on biodiversity conservation. Despite their importance for preventing or slowing extinctions and preserving biodiversity, conservation interventions are rarely assessed systematically for their global impact. Islands house a disproportionately higher amount of biodiversity compared with mainlands, much of which is highly threatened with extinction. Indeed, island species make up nearly two-thirds of recent extinctions. Islands therefore are critical targets of conservation. We used an extensive literature and database review paired with expert interviews to estimate the global benefits of an increasingly used conservation action to stem biodiversity loss: eradication of invasive mammals on islands. We found 236 native terrestrial insular faunal species (596 populations) that benefitted through positive demographic and/or distributional responses from 251 eradications of invasive mammals on 181 islands. Seven native species (eight populations) were negatively impacted by invasive mammal eradication. Four threatened species had their International Union for the Conservation of Nature (IUCN) Red List extinction-risk categories reduced as a direct result of invasive mammal eradication, and no species moved to a higher extinction-risk category. We predict that 107 highly threatened birds, mammals, and reptiles on the IUCN Red List—6% of all these highly threatened species—likely have benefitted from invasive mammal eradications on islands. Because monitoring of eradication outcomes is sporadic and limited, the impacts of global eradications are likely greater than we report here. Our results highlight the importance of invasive mammal eradication on islands for protecting the world's most imperiled fauna. PMID:27001852

Invasive mammal eradication on islands results in substantial conservation gains.

PubMed

Jones, Holly P; Holmes, Nick D; Butchart, Stuart H M; Tershy, Bernie R; Kappes, Peter J; Corkery, Ilse; Aguirre-Muñoz, Alfonso; Armstrong, Doug P; Bonnaud, Elsa; Burbidge, Andrew A; Campbell, Karl; Courchamp, Franck; Cowan, Philip E; Cuthbert, Richard J; Ebbert, Steve; Genovesi, Piero; Howald, Gregg R; Keitt, Bradford S; Kress, Stephen W; Miskelly, Colin M; Oppel, Steffen; Poncet, Sally; Rauzon, Mark J; Rocamora, Gérard; Russell, James C; Samaniego-Herrera, Araceli; Seddon, Philip J; Spatz, Dena R; Towns, David R; Croll, Donald A

2016-04-12

More than US$21 billion is spent annually on biodiversity conservation. Despite their importance for preventing or slowing extinctions and preserving biodiversity, conservation interventions are rarely assessed systematically for their global impact. Islands house a disproportionately higher amount of biodiversity compared with mainlands, much of which is highly threatened with extinction. Indeed, island species make up nearly two-thirds of recent extinctions. Islands therefore are critical targets of conservation. We used an extensive literature and database review paired with expert interviews to estimate the global benefits of an increasingly used conservation action to stem biodiversity loss: eradication of invasive mammals on islands. We found 236 native terrestrial insular faunal species (596 populations) that benefitted through positive demographic and/or distributional responses from 251 eradications of invasive mammals on 181 islands. Seven native species (eight populations) were negatively impacted by invasive mammal eradication. Four threatened species had their International Union for the Conservation of Nature (IUCN) Red List extinction-risk categories reduced as a direct result of invasive mammal eradication, and no species moved to a higher extinction-risk category. We predict that 107 highly threatened birds, mammals, and reptiles on the IUCN Red List-6% of all these highly threatened species-likely have benefitted from invasive mammal eradications on islands. Because monitoring of eradication outcomes is sporadic and limited, the impacts of global eradications are likely greater than we report here. Our results highlight the importance of invasive mammal eradication on islands for protecting the world's most imperiled fauna.

Restoration through eradication? Removal of an invasive bioengineer restores some habitat function for a native predator.

PubMed

Holsman, Kirstin K; McDonald, P Sean; Barreyro, Pablo A; Armstrong, David A

2010-12-01

Invasive aquatic macrophytes increase structural complexity in recipient systems and alter trophic and physical resources; thus, eradication programs that remove plant structure have potential to restore some impaired ecological functions. In this study we evaluate how an invasive ecosystem engineer, Atlantic smooth cordgrass (Spartina alterniflora), interferes with the movement and foraging activity of a mobile predator, Dungeness crab (Cancer magister), and whether removal of aboveground cordgrass structure rapidly reestablishes access to foraging habitats. By 2004, smooth cordgrass had invaded >25% of crab foraging habitat in Willapa Bay, Washington (USA), and transformed it into a highly structured landscape. However, by 2007 successful eradication efforts had eliminated most meadows of the cordgrass. In order to investigate the effect of smooth cordgrass on the habitat function of littoral areas for foraging crabs, we integrated field, laboratory, and statistical modeling approaches. We conducted trapping surveys at multiple sites and used a hierarchical model framework to examine patterns in catches prior to and following cordgrass removal (i.e., before-after control-impact design, BACI). Prior to eradication, catches of Dungeness crabs in unstructured habitats were 4-19 times higher than catches in adjacent patches of live cordgrass. In contrast, the results of post-eradication trapping in 2007 indicated similar catch rates of crabs in unstructured habitats and areas formerly invaded by the cordgrass. Subsequent laboratory experiments and video observations demonstrated that the rigid physical structure of smooth cordgrass shoots reduces the ability of Dungeness crabs to access prey resources and increases the risk of stranding. Taken together, these findings suggest that eliminating the structural complexity of invasive macrophytes may rapidly restore some ecological function (i.e., foraging area) for migratory predators like Dungeness crab. However, restoration of affected areas to a preinvasion state will also depend on long-term patterns of succession in invaded areas and the degree of persistence of physical changes that continue to alter biotic characteristics of the habitat. Our work highlights: (1) the efficacy of employing multiple methods of inquiry to evaluate causal relationships through mechanisms of interaction, and (2) the importance of targeting particular ecological functions when identifying both short- and long-term goals of restoration efforts.

Vaccine refusal and the endgame: walking the last mile first.

PubMed

Saint-Victor, Diane S; Omer, Saad B

2013-08-05

As multiple papers within this special issue illustrate, the dynamics of disease eradication are different from disease control. When it comes to disease eradication, 'the last mile is longest'. For social and ecological reasons such as vaccine refusal, further ending incidence of a disease when it has reached low levels is frequently complex. Issues of non-compliance within a target population often influence the outcome of disease eradication efforts. Past eradication efforts confronted such obstacles towards the tail end of the campaign, when disease incidence was lowest. This article provides a comparison of non-compliance within polio, measles and smallpox campaigns, demonstrating the tendency of vaccine refusal to rise as disease incidence falls. In order to overcome one of the most intractable challenges to eradication, future disease eradication efforts must prioritize vaccine refusal from the start, i.e. 'walk the last mile first'.

Vaccine refusal and the endgame: walking the last mile first

PubMed Central

Saint-Victor, Diane S.; Omer, Saad B.

2013-01-01

As multiple papers within this special issue illustrate, the dynamics of disease eradication are different from disease control. When it comes to disease eradication, ‘the last mile is longest’. For social and ecological reasons such as vaccine refusal, further ending incidence of a disease when it has reached low levels is frequently complex. Issues of non-compliance within a target population often influence the outcome of disease eradication efforts. Past eradication efforts confronted such obstacles towards the tail end of the campaign, when disease incidence was lowest. This article provides a comparison of non-compliance within polio, measles and smallpox campaigns, demonstrating the tendency of vaccine refusal to rise as disease incidence falls. In order to overcome one of the most intractable challenges to eradication, future disease eradication efforts must prioritize vaccine refusal from the start, i.e. ‘walk the last mile first’. PMID:23798696

The Florey lecture, 1983. Biological control, as exemplified by smallpox eradication and myxomatosis.

PubMed

Fenner, F

1983-06-22

Biological control is an important method of dealing with plant and insect pests. The control of rabbits by myxomatosis and the eradication of smallpox by vaccination are unusual examples of biological control, in that they involve a vertebrate and a viral pest respectively. Myxomatosis is a benign disease in Sylvilagus rabbits in South America which is transmitted mechanically by mosquitoes. In the European rabbit, Oryctolagus, which is a pest in Australia and England, the virus from Sylvilagus produces a generalized disease that is almost always lethal. Myxomatosis was deliberately introduced into Australia in 1950 and into Europe in 1952. It was at first spectacularly successful in controlling the rabbit pest, but biological adjustments occurred in the virulence of the virus and the genetic resistances of rabbits. After 30 years of interaction, natural selection has resulted in a balance at a fairly high level of viral virulence. Smallpox has been a major scourge of mankind for over 1500 years. It spread from Asia to Europe in the Middle ages and from Europe to Africa and the Americas in the 15th and 16th centuries. Jenner's cowpox vaccine provided a method of control that reduced the severity of the disease during the 19th century but failed to eliminate the disease from many countries before the 1930s. Thereafter it was eradicated from Europe and North America, but remained endemic in South America, Africa and Asia. In 1967 it was still endemic in 33 countries and W.H.O. established a programme for global eradication within 10 years. The goal was achieved in 1977. Problems of the eradication programme and reasons for its success will be described.

Challenges to global measles eradication: is it all in the timing?

PubMed

Davis, Robert; Mbabazi, William Baguma

2017-01-01

The case for global eradication of measles was first made in 1982. Since then, technical aspects of measles eradication have concluded that measles satisfied all criteria required for eradication. To date, only smallpox, among human diseases, has been eradicated, with polio, the next eradication candidate. In all previous eradication programmes, the pattern of slow implementation and missed deadlines is similar. Lessons from these past eradication programs should inform development of a time-limited measles eradication program. Notably, no measles eradication resolution is likely until member states are satisfied that polio eradication is accomplished. However, there is an impetus for measles eradication from the western hemisphere, where governments continue to pay the high costs of keeping their region measles free until global measles eradication is achieved. While previous vaccine preventable diseases eradications have depended on supplemental immunizations (SIAs), measles eradication will have to build both on SIAs and routine immunization systems strengthening. This article reviews non-technical considerations that could facilitate the delivery of a time-limited measles eradication initiative. The issues discussed are categorized as a) specificities of measles disease; b) specifics of measles vaccine/vaccination; c) special considerations for endemic countries and d) organization of international partnerships. The disease and vaccine specific issues are not insurmountable. The introduction of routine measles second dose, in the context of EPI systems strengthening, is paramount to endemic developing countries. In the international partnerships, it should be noted that i) Measles eradication will be easier and cheaper; ii) the return on investment is compelling; iii) leverage is feasible on the experiences of the Measles/Rubella initiative; iv) two disease eradication targets in one initiative are feasible and v) for the first time, an eradication investment case will inform the decisions. However, if previous eradication efforts have been marathons, measles eradication will need to be a sprint.

Challenges to global measles eradication: is it all in the timing?

PubMed Central

Davis, Robert; Mbabazi, William Baguma

2017-01-01

The case for global eradication of measles was first made in 1982. Since then, technical aspects of measles eradication have concluded that measles satisfied all criteria required for eradication. To date, only smallpox, among human diseases, has been eradicated, with polio, the next eradication candidate. In all previous eradication programmes, the pattern of slow implementation and missed deadlines is similar. Lessons from these past eradication programs should inform development of a time-limited measles eradication program. Notably, no measles eradication resolution is likely until member states are satisfied that polio eradication is accomplished. However, there is an impetus for measles eradication from the western hemisphere, where governments continue to pay the high costs of keeping their region measles free until global measles eradication is achieved. While previous vaccine preventable diseases eradications have depended on supplemental immunizations (SIAs), measles eradication will have to build both on SIAs and routine immunization systems strengthening. This article reviews non-technical considerations that could facilitate the delivery of a time-limited measles eradication initiative. The issues discussed are categorized as a) specificities of measles disease; b) specifics of measles vaccine/vaccination; c) special considerations for endemic countries and d) organization of international partnerships. The disease and vaccine specific issues are not insurmountable. The introduction of routine measles second dose, in the context of EPI systems strengthening, is paramount to endemic developing countries. In the international partnerships, it should be noted that i) Measles eradication will be easier and cheaper; ii) the return on investment is compelling; iii) leverage is feasible on the experiences of the Measles/Rubella initiative; iv) two disease eradication targets in one initiative are feasible and v) for the first time, an eradication investment case will inform the decisions. However, if previous eradication efforts have been marathons, measles eradication will need to be a sprint. PMID:29296146

Genital Autoinoculation with Vaccinia: A Look at Two Cases.

PubMed

Whittington, Julie R; Rollene, Nanette L; Gist, Richard S

2018-05-01

Smallpox, or vaccinia, has been eradicated worldwide as a disease; however, it may be weaponized and is thus a required immunization when military members deploy to certain parts of the world. We report two unusual cases of genital autoinoculation following smallpox vaccination. Both patients' lesions resolved without sequelae within 20 d. We advocate for thorough education on this potential vaccination adverse event. These cases highlight the importance of a broad differential diagnosis when dealing with vulvar lesions, particularly in our military population.

The polio endgame.

PubMed

Minor, Philip

2014-01-01

Paralytic poliomyelitis is a disease that became a public health issue at the beginning of the twentieth century and was more or less eliminated in developed countries by the early 1970s. The Global Polio Eradication Initiative of WHO has now eradicated endemic polio from all but three countries although re-introductions occur. The progress in polio eradication is striking and has accelerated over the last few years. It is likely that it will be finally eradicated from the world soon, the looming issue will then be how to stop vaccinating or modify immunization programs safely so that poliomyelitis does not re-emerge. This review article discusses the history and pathogenesis of poliomyelitis. The progress made, and challenges in sustaining the eradication of this debilitating infectious disease are considered.

The polio endgame

PubMed Central

Minor, Philip

2014-01-01

Paralytic poliomyelitis is a disease that became a public health issue at the beginning of the twentieth century and was more or less eliminated in developed countries by the early 1970s. The Global Polio Eradication Initiative of WHO has now eradicated endemic polio from all but three countries although re-introductions occur. The progress in polio eradication is striking and has accelerated over the last few years. It is likely that it will be finally eradicated from the world soon, the looming issue will then be how to stop vaccinating or modify immunization programs safely so that poliomyelitis does not re-emerge. This review article discusses the history and pathogenesis of poliomyelitis. The progress made, and challenges in sustaining the eradication of this debilitating infectious disease are considered. PMID:25608050

The contribution of vaccination to global health: past, present and future.

PubMed

Greenwood, Brian

2014-01-01

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.

Unusual chromosomal organization of telomeric sequences and expeditious karyotypic differentiation in the recently evolved Mus terricolor complex.

PubMed

Sharma, G G; Sharma, T

1998-01-01

The Mus terricolor complex displays a stable homozygous arrangement of autosomal heterochromatin variations in the form of accretion of definitive autosomal short arms among three nonoverlapping populations, in concert with an expeditious evolutionary differentiation into three chromosomal species: M. terricolor I, II, and III. In contrast to the highly conservative M. musculus-like chromosomes in the coexisting sibling species, M. booduga, reshuffling and differentiation of centric heterochromatin has occurred in harmony with a revision of centric configurations, resulting in acrocentric and submetacentric autosomes. The chromosomal distribution of the prevalent vertebrate telomeric sequence (TTAGGG)n was examined by fluorescence in situ hybridization to metaphase cells of M. terricolor I, II, and III. An unusual centric organization of internal telomeric sequences was detected in all the submetacentric and acrocentric autosomes. An auxiliary role of these presumably fragile, recombinogenic telomeric sequences in the evolutionary revision of centric configurations in the terricolor complex is hypothesized.

Japanese encephalitis virus replication is negatively regulated by autophagy and occurs on LC3-I- and EDEM1-containing membranes.

PubMed

Sharma, Manish; Bhattacharyya, Sankar; Nain, Minu; Kaur, Manpreet; Sood, Vikas; Gupta, Vishal; Khasa, Renu; Abdin, Malik Z; Vrati, Sudhanshu; Kalia, Manjula

2014-09-01

Autophagy is a lysosomal degradative pathway that has diverse physiological functions and plays crucial roles in several viral infections. Here we examine the role of autophagy in the life cycle of JEV, a neurotropic flavivirus. JEV infection leads to induction of autophagy in several cell types. JEV replication was significantly enhanced in neuronal cells where autophagy was rendered dysfunctional by ATG7 depletion, and in Atg5-deficient mouse embryonic fibroblasts (MEFs), resulting in higher viral titers. Autophagy was functional during early stages of infection however it becomes dysfunctional as infection progressed resulting in accumulation of misfolded proteins. Autophagy-deficient cells were highly susceptible to virus-induced cell death. We also observed JEV replication complexes that are marked by nonstructural protein 1 (NS1) and dsRNA colocalized with endogenous LC3 but not with GFP-LC3. Colocalization of NS1 and LC3 was also observed in Atg5 deficient MEFs, which contain only the nonlipidated form of LC3. Viral replication complexes furthermore show association with a marker of the ER-associated degradation (ERAD) pathway, EDEM1 (ER degradation enhancer, mannosidase α-like 1). Our data suggest that virus replication occurs on ERAD-derived EDEM1 and LC3-I-positive structures referred to as EDEMosomes. While silencing of ERAD regulators EDEM1 and SEL1L suppressed JEV replication, LC3 depletion exerted a profound inhibition with significantly reduced RNA levels and virus titers. Our study suggests that while autophagy is primarily antiviral for JEV and might have implications for disease progression and pathogenesis of JEV, nonlipidated LC3 plays an important autophagy independent function in the virus life cycle.

A VCP inhibitor substrate trapping approach (VISTA) enables proteomic profiling of endogenous ERAD substrates.

PubMed

Huang, Edmond Y; To, Milton; Tran, Erica; Dionisio, Lorraine T Ador; Cho, Hyejin J; Baney, Katherine L M; Pataki, Camille I; Olzmann, James A

2018-05-01

Endoplasmic reticulum (ER)-associated degradation (ERAD) mediates the proteasomal clearance of proteins from the early secretory pathway. In this process, ubiquitinated substrates are extracted from membrane-embedded dislocation complexes by the AAA ATPase VCP and targeted to the cytosolic 26S proteasome. In addition to its well-established role in the degradation of misfolded proteins, ERAD also regulates the abundance of key proteins such as enzymes involved in cholesterol synthesis. However, due to the lack of generalizable methods, our understanding of the scope of proteins targeted by ERAD remains limited. To overcome this obstacle, we developed a VCP inhibitor substrate trapping approach (VISTA) to identify endogenous ERAD substrates. VISTA exploits the small-molecule VCP inhibitor CB5083 to trap ERAD substrates in a membrane-associated, ubiquitinated form. This strategy, coupled with quantitative ubiquitin proteomics, identified previously validated (e.g., ApoB100, Insig2, and DHCR7) and novel (e.g., SCD1 and RNF5) ERAD substrates in cultured human hepatocellular carcinoma cells. Moreover, our results indicate that RNF5 autoubiquitination on multiple lysine residues targets it for ubiquitin and VCP--dependent clearance. Thus, VISTA provides a generalizable discovery method that expands the available toolbox of strategies to elucidate the ERAD substrate landscape.

Novel Cage-Like Hexanuclear Nickel(II) Silsesquioxane. Synthesis, Structure, and Catalytic Activity in Oxidations with Peroxides.

PubMed

Bilyachenko, Alexey N; Yalymov, Alexey I; Shul'pina, Lidia S; Mandelli, Dalmo; Korlyukov, Alexander A; Vologzhanina, Anna V; Es'kova, Marina A; Shubina, Elena S; Levitsky, Mikhail M; Shul'pin, Georgiy B

2016-05-19

New hexanuclear nickel(II) silsesquioxane [(PhSiO1.5)12(NiO)₆(NaCl)] (1) was synthesized as its dioxane-benzonitrile-water complex (PhSiO1,5)12(NiO)₆(NaCl)(C₄H₈O₂)13(PhCN)₂(H₂O)₂ and studied by X-ray and topological analysis. The compound exhibits cylinder-like type of molecular architecture and represents very rare case of polyhedral complexation of metallasilsesquioxane with benzonitrile. Complex 1 exhibited catalytic activity in activation of such small molecules as light alkanes and alcohols. Namely, oxidation of alcohols with tert-butylhydroperoxide and alkanes with meta-chloroperoxybenzoic acid. The oxidation of methylcyclohexane gave rise to the isomeric ketones and unusual distribution of alcohol isomers.

Recent plant eradications on the islands of Maui County, Hawai'i

USGS Publications Warehouse

Penniman, Teya M.; Buchanan, Lori; Loope, Lloyd L.; Veitch, C.R.; Clout, Mike N.; Towns, D. R.

2011-01-01

The state of Hawai'i (USA) has few regulations to limit plant introductions. A network of interagency islandbased invasive species committees has evolved over the past decade to address this vulnerability, with the aim of stopping invasions before they threaten natural areas. On Maui, Moloka‘i, and Lāna‘i, which comprise three of the four islands of Maui County, single-island eradications have been achieved for 12 plant species and eradication is likely imminent for an additional eight species. The islands vary in size, population, and land ownership. We explore the relative importance of those variables in achieving successful eradications along with target species selection, detection strategies, and public support

HLA-B27 Misfolding and Ankylosing Spondylitis

PubMed Central

Colbert, Robert A.; Tran, Tri M.; Layh-Schmitt, Gerlinde

2013-01-01

Understanding how HLA-B27 contributes to the pathogenesis of spondyloarthritis continues to be an important goal. Current efforts are aimed largely on three areas of investigation; peptide presentation to CD8 T cells, abnormal forms of the HLA-B27 heavy chain and their recognition by leukocyte immunoglobulin-like receptors on immune effector cells, and HLA-B27 heavy chain misfolding and intrinsic biological effects on affected cells. In this chapter we review our current understanding of the causes and consequences of HLA-B27 misfolding, which can be defined biochemically as a propensity to oligomerize and form complexes in the endoplasmic reticulum (ER) with the chaperone BiP (HSPA5/GRP78). HLA-B27 misfolding is linked to an unusual combination of polymorphisms that identify this allele, and cause the heavy chain to fold and load peptides inefficiently. Misfolding can result in ER-associated degradation (ERAD) of heavy chains, which is mediated in part by the E3 ubiquitin ligase HRD1 (SYVN1), and the ubiquitin conjugating enzyme UBE2JL. Upregulation of HLA-B27 and accumulation of misfolded heavy chains can activate ER stress signaling pathways that orchestrate the unfolded protein response. In transgenic rats where HLA-B27 is overexpressed, UPR activation is prominent. However, it is specific for heavy chain misfolding, since overexpression of HLA-B7, an allele that does not misfold, fails to generate ER stress. UPR activation has been linked to cytokine dysregulation, promoting lL-23, IFNβ, and lL-1α production, and may activate the IL-23/IL-17 axis in these rats. IL-1α and IFNβ are pro- and anti-osteoclastogenic cytokines, respectively, that modulate osteoclast development in HLA-B27-expressing transgenic rat monocytes. Translational studies of patient derived cells expressing HLA-B27 at physiologic levels have provided evidence that ER stress and UPR activation can occur in peripheral blood, but this has not been reported to date in isolated macrophages. Inflamed gastrointestinal tissue reveals evidence for HLA-B27 misfolding, ERAD, and autophagy, without acute UPR activation. A more complete picture of conditions that impact HLA-B27 folding and misfolding, the full spectrum and time course of consequences of ER stress, and critical cell types involved is needed to understand the role of HLA-B27 misfolding in spondyloarthritis pathogenesis. PMID:23993278

HLA-B27 misfolding and ankylosing spondylitis.

PubMed

Colbert, Robert A; Tran, Tri M; Layh-Schmitt, Gerlinde

2014-01-01

Understanding how HLA-B27 contributes to the pathogenesis of spondyloarthritis continues to be an important goal. Current efforts are aimed largely on three areas of investigation; peptide presentation to CD8T cells, abnormal forms of the HLA-B27 heavy chain and their recognition by leukocyte immunoglobulin-like receptors on immune effector cells, and HLA-B27 heavy chain misfolding and intrinsic biological effects on affected cells. In this chapter we review our current understanding of the causes and consequences of HLA-B27 misfolding, which can be defined biochemically as a propensity to oligomerize and form complexes in the endoplasmic reticulum (ER) with the chaperone BiP (HSPA5/GRP78). HLA-B27 misfolding is linked to an unusual combination of polymorphisms that identify this allele, and cause the heavy chain to fold and load peptides inefficiently. Misfolding can result in ER-associated degradation (ERAD) of heavy chains, which is mediated in part by the E3 ubiquitin ligase HRD1 (SYVN1), and the ubiquitin conjugating enzyme UBE2JL. Upregulation of HLA-B27 and accumulation of misfolded heavy chains can activate ER stress signaling pathways that orchestrate the unfolded protein response. In transgenic rats where HLA-B27 is overexpressed, UPR activation is prominent. However, it is specific for heavy chain misfolding, since overexpression of HLA-B7, an allele that does not misfold, fails to generate ER stress. UPR activation has been linked to cytokine dysregulation, promoting lL-23, IFNβ, and lL-1α production, and may activate the IL-23/IL-17 axis in these rats. IL-1α and IFNβ are pro- and anti-osteoclastogenic cytokines, respectively, that modulate osteoclast development in HLA-B27-expressing transgenic rat monocytes. Translational studies of patient derived cells expressing HLA-B27 at physiologic levels have provided evidence that ER stress and UPR activation can occur in peripheral blood, but this has not been reported to date in isolated macrophages. Inflamed gastrointestinal tissue reveals evidence for HLA-B27 misfolding, ERAD, and autophagy, without acute UPR activation. A more complete picture of conditions that impact HLA-B27 folding and misfolding, the full spectrum and time course of consequences of ER stress, and critical cell types involved is needed to understand the role of HLA-B27 misfolding in spondyloarthritis pathogenesis. Published by Elsevier Ltd.

Identification of proteins likely to be involved in morphogenesis, cell division, and signal transduction in Planctomycetes by comparative genomics.

PubMed

Jogler, Christian; Waldmann, Jost; Huang, Xiaoluo; Jogler, Mareike; Glöckner, Frank Oliver; Mascher, Thorsten; Kolter, Roberto

2012-12-01

Members of the Planctomycetes clade share many unusual features for bacteria. Their cytoplasm contains membrane-bound compartments, they lack peptidoglycan and FtsZ, they divide by polar budding, and they are capable of endocytosis. Planctomycete genomes have remained enigmatic, generally being quite large (up to 9 Mb), and on average, 55% of their predicted proteins are of unknown function. Importantly, proteins related to the unusual traits of Planctomycetes remain largely unknown. Thus, we embarked on bioinformatic analyses of these genomes in an effort to predict proteins that are likely to be involved in compartmentalization, cell division, and signal transduction. We used three complementary strategies. First, we defined the Planctomycetes core genome and subtracted genes of well-studied model organisms. Second, we analyzed the gene content and synteny of morphogenesis and cell division genes and combined both methods using a "guilt-by-association" approach. Third, we identified signal transduction systems as well as sigma factors. These analyses provide a manageable list of candidate genes for future genetic studies and provide evidence for complex signaling in the Planctomycetes akin to that observed for bacteria with complex life-styles, such as Myxococcus xanthus.

Is life most likely around Sun-like stars?

NASA Astrophysics Data System (ADS)

Lingam, Manasvi; Loeb, Abraham

2018-05-01

We consider the habitability of Earth-analogs around stars of different masses, which is regulated by the stellar lifetime, stellar wind-induced atmospheric erosion, and biologically active ultraviolet (UV) irradiance. By estimating the timescales associated with each of these processes, we show that they collectively impose limits on the habitability of Earth-analogs. We conclude that planets orbiting most M-dwarfs are not likely to host life, and that the highest probability of complex biospheres is for planets around K- and G-type stars. Our analysis suggests that the current existence of life near the Sun is slightly unusual, but not significantly anomalous.

Fun with maths: exploring implications of mathematical models for malaria eradication.

PubMed

Eckhoff, Philip A; Bever, Caitlin A; Gerardin, Jaline; Wenger, Edward A

2014-12-11

Mathematical analyses and modelling have an important role informing malaria eradication strategies. Simple mathematical approaches can answer many questions, but it is important to investigate their assumptions and to test whether simple assumptions affect the results. In this note, four examples demonstrate both the effects of model structures and assumptions and also the benefits of using a diversity of model approaches. These examples include the time to eradication, the impact of vaccine efficacy and coverage, drug programs and the effects of duration of infections and delays to treatment, and the influence of seasonality and migration coupling on disease fadeout. An excessively simple structure can miss key results, but simple mathematical approaches can still achieve key results for eradication strategy and define areas for investigation by more complex models.

Local extinction of the Asian tiger mosquito (Aedes albopictus) following rat eradication on Palmyra Atoll

PubMed Central

McLaughlin, John P.; Bogar, Taylor A.; Bui, An; Childress, Jasmine N.; Espinoza, Magaly; Forbes, Elizabeth S.; Johnston, Cora A.; Klope, Maggie; Miller-ter Kuile, Ana; Lee, Michelle; Plummer, Katherine A.; Weber, David A.; Young, Ronald T.

2018-01-01

The Asian tiger mosquito, Aedes albopictus, appears to have been extirpated from Palmyra Atoll following rat eradication. Anecdotal biting reports, collection records, and regular captures in black-light traps showed the species was present before rat eradication. Since then, there have been no biting reports and no captures over 2 years of extensive trapping (black-light and scent traps). By contrast, the southern house mosquito, Culex quinquefasciatus, was abundant before and after rat eradication. We hypothesize that mammals were a substantial and preferred blood meal for Aedes, whereas Culex feeds mostly on seabirds. Therefore, after rat eradication, humans and seabirds alone could not support positive population growth or maintenance of Aedes. This seems to be the first documented accidental secondary extinction of a mosquito. Furthermore, it suggests that preferred host abundance can limit mosquito populations, opening new directions for controlling important disease vectors that depend on introduced species like rats. PMID:29491026

The human qualities needed to complete the global eradication of polio

PubMed Central

2013-01-01

Abstract Although the 99% decrease seen in global polio incidence between 1988 and 2000 represented remarkable progress towards polio eradication, tackling the last 1% of polio has proved tantalizingly difficult. Pockets of endemic transmission currently persist both on the border between Afghanistan and Pakistan and in northern Nigeria. These pockets have permitted the reinfection of countries that were previously polio-free. Global strategic plans for polio eradication set out the activities, resources and financing needed to overcome the managerial, technical and security challenges faced by those tasked with the interruption of poliovirus transmission. However, polio eradication also depends on the less tangible but equally important human qualities of energy, realism, articulacy, determination, imagination, collaboration, adaptability, tactical awareness, innovation, openness and nimbleness (the initial letters of which give the acronym “ERADICATION”). By paying attention to these human qualities, the stakeholders involved may be more likely to achieve global polio eradication. PMID:23599552

ER-associated degradation is required for vasopressin prohormone processing and systemic water homeostasis

PubMed Central

Somlo, Diane R.M.; Kim, Geun Hyang; Prescianotto-Baschong, Cristina; Sun, Shengyi; Beuret, Nicole; Long, Qiaoming; Rutishauser, Jonas

2017-01-01

Peptide hormones are crucial regulators of many aspects of human physiology. Mutations that alter these signaling peptides are associated with physiological imbalances that underlie diseases. However, the conformational maturation of peptide hormone precursors (prohormones) in the ER remains largely unexplored. Here, we report that conformational maturation of proAVP, the precursor for the antidiuretic hormone arginine-vasopressin, within the ER requires the ER-associated degradation (ERAD) activity of the Sel1L-Hrd1 protein complex. Serum hyperosmolality induces expression of both ERAD components and proAVP in AVP-producing neurons. Mice with global or AVP neuron–specific ablation of Se1L-Hrd1 ERAD progressively developed polyuria and polydipsia, characteristics of diabetes insipidus. Mechanistically, we found that ERAD deficiency causes marked ER retention and aggregation of a large proportion of all proAVP protein. Further, we show that proAVP is an endogenous substrate of Sel1L-Hrd1 ERAD. The inability to clear misfolded proAVP with highly reactive cysteine thiols in the absence of Sel1L-Hrd1 ERAD causes proAVP to accumulate and participate in inappropriate intermolecular disulfide–bonded aggregates, promoted by the enzymatic activity of protein disulfide isomerase (PDI). This study highlights a pathway linking ERAD to prohormone conformational maturation in neuroendocrine cells, expanding the role of ERAD in providing a conducive ER environment for nascent proteins to reach proper conformation. PMID:28920920

Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity

PubMed Central

Duennwald, Martin L.; Lindquist, Susan

2008-01-01

Protein misfolding, whether caused by aging, environmental factors, or genetic mutations, is a common basis for neurodegenerative diseases. The misfolding of proteins with abnormally long polyglutamine (polyQ) expansions causes several neurodegenerative disorders, such as Huntington’s disease (HD). Although many cellular pathways have been documented to be impaired in HD, the primary triggers of polyQ toxicity remain elusive. We report that yeast cells and neuron-like PC12 cells expressing polyQ-expanded huntingtin (htt) fragments display a surprisingly specific, immediate, and drastic defect in endoplasmic reticulum (ER)-associated degradation (ERAD). We further decipher the mechanistic basis for this defect in ERAD: the entrapment of the essential ERAD proteins Npl4, Ufd1, and p97 by polyQ-expanded htt fragments. In both yeast and mammalian neuron-like cells, overexpression of Npl4 and Ufd1 ameliorates polyQ toxicity. Our results establish that impaired ER protein homeostasis is a broad and highly conserved contributor to polyQ toxicity in yeast, in PC12 cells, and, importantly, in striatal cells expressing full-length polyQ-expanded huntingtin. PMID:19015277

Techniques for characterization and eradication of potato cyst nematode: a review.

PubMed

Bairwa, Aarti; Venkatasalam, E P; Sudha, R; Umamaheswari, R; Singh, B P

2017-09-01

Correct identification of species and pathotypes is must for eradication of potato cyst nematodes (PCN). The identification of PCN species after completing the life cycle is very difficult because it is based on morphological and morphometrical characteristics. Genetically different populations of PCN are morphologically same and differentiated based on the host differential study. Later on these traditional techniques have been replaced by biochemical techniques viz, one and two dimensional gel electrophoresis, capillary gel electrophoresis, isozymes, dot blot hybridization and isoelectric focusing etc. to distinguish both the species. One and two dimensional gel electrophoresis has used to examine inter- and intra-specific differences in proteins of Globodera rostochiensis and G. pallida . Now application of PCR and DNA based characterization techniques like RAPD, AFLP and RFLP are the important tools for differentiating inter- and intra specific variation in PCN and has given opportunities to accurate identification of PCN. For managing the PCN, till now we are following integrated pest management (IPM) strategies, however these strategies are not effective to eradicate the PCN. Therefore to eradicate the PCN we need noval management practices like RNAi (RNA interference) or Gene silencing.

Unfolded protein response activation compensates endoplasmic reticulum-associated degradation deficiency in Arabidopsis.

PubMed

Li, Qingliang; Wei, Hai; Liu, Lijing; Yang, Xiaoyuan; Zhang, Xiansheng; Xie, Qi

2017-07-01

Abiotic stresses often disrupt protein folding and induce endoplasmic reticulum (ER) stress. There is a sophisticated ER quality control (ERQC) system to mitigate the effects of malfunctioning proteins and maintain ER homeostasis. The accumulation of misfolded proteins in the ER activates the unfolded protein response (UPR) to enhance ER protein folding and the degradation of misfolded proteins mediate by ER-associated degradation (ERAD). That ERQC reduces abiotic stress damage has been well studied in mammals and yeast. However, in plants, both ERAD and UPR have been studied separately and found to be critical for plant abiotic stress tolerance. In this study, we discovered that UPR-associated transcription factors AtbZIP17, AtbZIP28 and AtbZIP60 responded to tunicamycin (TM) and NaCl induced ER stress and subsequently enhanced Arabidopsis thaliana abiotic stress tolerance. They regulated the expression level of ER chaperones and the HRD1-complex components. Moreover, overexpression of AtbZIP17, AtbZIP28 and AtbZIP60 could restore stress tolerance via ERAD in the HRD1-complex mutant hrd3a-2, which suggested that UPR and ERAD have an interactive mechanism in Arabidopsis. © 2017 Institute of Botany, Chinese Academy of Sciences.

Modelling detectability of kiore (Rattus exulans) on Aguiguan, Mariana Islands, to inform possible eradication and monitoring efforts

USGS Publications Warehouse

Adams, A.A.Y.; Stanford, J.W.; Wiewel, A.S.; Rodda, G.H.

2011-01-01

Estimating the detection probability of introduced organisms during the pre-monitoring phase of an eradication effort can be extremely helpful in informing eradication and post-eradication monitoring efforts, but this step is rarely taken. We used data collected during 11 nights of mark-recapture sampling on Aguiguan, Mariana Islands, to estimate introduced kiore (Rattus exulans Peale) density and detection probability, and evaluated factors affecting detectability to help inform possible eradication efforts. Modelling of 62 captures of 48 individuals resulted in a model-averaged density estimate of 55 kiore/ha. Kiore detection probability was best explained by a model allowing neophobia to diminish linearly (i.e. capture probability increased linearly) until occasion 7, with additive effects of sex and cumulative rainfall over the prior 48 hours. Detection probability increased with increasing rainfall and females were up to three times more likely than males to be trapped. In this paper, we illustrate the type of information that can be obtained by modelling mark-recapture data collected during pre-eradication monitoring and discuss the potential of using these data to inform eradication and posteradication monitoring efforts. ?? New Zealand Ecological Society.

Can We Capitalize on the Virtues of Vaccines? Insights from the Polio Eradication Initiative

PubMed Central

Aylward, R. Bruce; Heymann, David L.

2005-01-01

Twenty-five years after the eradication of smallpox, the ongoing effort to eradicate poliomyelitis has grown into the largest international health initiative ever undertaken. By 2004, however, the polio eradication effort was threatened by a challenge regularly faced by public health policymakers everywhere—misperception about the benefits and risks of vaccines. The propagation of false rumors about oral poliovirus vaccine safety led to the reinfection of 13 previously polio-free countries and the largest polio epidemic in Africa in recent years. With deft management of such challenges by local, national, and international health authorities, poliomyelitis, a disease that threatened children everywhere just 2 generations ago, could soon be relegated to history like smallpox before it. PMID:15855451

Inhibition by stabilization: targeting the Plasmodium falciparum aldolase-TRAP complex.

PubMed

Nemetski, Sondra Maureen; Cardozo, Timothy J; Bosch, Gundula; Weltzer, Ryan; O'Malley, Kevin; Ejigiri, Ijeoma; Kumar, Kota Arun; Buscaglia, Carlos A; Nussenzweig, Victor; Sinnis, Photini; Levitskaya, Jelena; Bosch, Jürgen

2015-08-20

Emerging resistance of the malaria parasite Plasmodium to current therapies underscores the critical importance of exploring novel strategies for disease eradication. Plasmodium species are obligate intracellular protozoan parasites. They rely on an unusual form of substrate-dependent motility for their migration on and across host-cell membranes and for host cell invasion. This peculiar motility mechanism is driven by the 'glideosome', an actin-myosin associated, macromolecular complex anchored to the inner membrane complex of the parasite. Myosin A, actin, aldolase, and thrombospondin-related anonymous protein (TRAP) constitute the molecular core of the glideosome in the sporozoite, the mosquito stage that brings the infection into mammals. Virtual library screening of a large compound library against the PfAldolase-TRAP complex was used to identify candidate compounds that stabilize and prevent the disassembly of the glideosome. The mechanism of these compounds was confirmed by biochemical, biophysical and parasitological methods. A novel inhibitory effect on the parasite was achieved by stabilizing a protein-protein interaction within the glideosome components. Compound 24 disrupts the gliding and invasive capabilities of Plasmodium parasites in in vitro parasite assays. A high-resolution, ternary X-ray crystal structure of PfAldolase-TRAP in complex with compound 24 confirms the mode of interaction and serves as a platform for future ligand optimization. This proof-of-concept study presents a novel approach to anti-malarial drug discovery and design. By strengthening a protein-protein interaction within the parasite, an avenue towards inhibiting a previously "undruggable" target is revealed and the motility motor responsible for successful invasion of host cells is rendered inactive. This study provides new insights into the malaria parasite cell invasion machinery and convincingly demonstrates that liver cell invasion is dramatically reduced by 95 % in the presence of the small molecule stabilizer compound 24.

Critical behavior in graphene with Coulomb interactions.

PubMed

Wang, Jianhui; Fertig, H A; Murthy, Ganpathy

2010-05-07

We demonstrate that, in the presence of Coulomb interactions, electrons in graphene behave like a critical system, supporting power law correlations with interaction-dependent exponents. An asymptotic analysis shows that the origin of this behavior lies in particle-hole scattering, for which the Coulomb interaction induces anomalously close approaches. With increasing interaction strength the relevant power law changes from real to complex, leading to an unusual instability characterized by a complex-valued susceptibility in the thermodynamic limit. Measurable quantities, as well as the connection to classical two-dimensional systems, are discussed.

A vacuolar carboxypeptidase mutant of Arabidopsis thaliana is degraded by the ERAD pathway independently of its N-glycan

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

Yamamoto, Masaya; Kawanabe, Mitsuyoshi; Hayashi, Yoko

2010-03-12

Misfolded proteins produced in the endoplasmic reticulum (ER) are degraded by a mechanism, the ER-associated degradation (ERAD). Here we report establishment of the experimental system to analyze the ERAD in plant cells. Carboxypeptidase Y (CPY) is a vacuolar enzyme and its mutant CPY* is degraded by the ERAD in yeast. Since Arabidopsis thaliana has AtCPY, an ortholog of yeast CPY, we constructed and expressed fusion proteins consisting of AtCPY and GFP and of AtCPY*, which carries a mutation homologous to yeast CPY*, and GFP in A. thaliana cells. While AtCPY-GFP was efficiently transported to the vacuole, AtCPY*-GFP was retained inmore » the ER to be degraded in proteasome- and Cdc48-dependent manners. We also found that AtCPY*-GFP was degraded by the ERAD in yeast cells, but that its single N-glycan did not function as a degradation signal in yeast or plant cells. Therefore, AtCPY*-GFP can be used as a marker protein to analyze the ERAD pathway, likely for nonglycosylated substrates, in plant cells.« less

Mouse Mammary Tumor Virus Signal Peptide Uses a Novel p97-Dependent and Derlin-Independent Retrotranslocation Mechanism To Escape Proteasomal Degradation

PubMed Central

Byun, Hyewon; Das, Poulami; Yu, Houqing; Aleman, Alejandro; Lozano, Mary M.; Matouschek, Andreas

2017-01-01

ABSTRACT Multiple pathogens, including viruses and bacteria, manipulate endoplasmic reticulum-associated degradation (ERAD) to avoid the host immune response and promote their replication. The betaretrovirus mouse mammary tumor virus (MMTV) encodes Rem, which is a precursor protein that is cleaved into a 98-amino-acid signal peptide (SP) and a C-terminal protein (Rem-CT). SP uses retrotranslocation for ER membrane extraction and yet avoids ERAD by an unknown mechanism to enter the nucleus and function as a Rev-like protein. To determine how SP escapes ERAD, we used a ubiquitin-activated interaction trap (UBAIT) screen to trap and identify transient protein interactions with SP, including the ERAD-associated p97 ATPase, but not E3 ligases or Derlin proteins linked to retrotranslocation, polyubiquitylation, and proteasomal degradation of extracted proteins. A dominant negative p97 ATPase inhibited both Rem and SP function. Immunoprecipitation experiments indicated that Rem, but not SP, is polyubiquitylated. Using both yeast and mammalian expression systems, linkage of a ubiquitin-like domain (UbL) to SP or Rem induced degradation by the proteasome, whereas SP was stable in the absence of the UbL. ERAD-associated Derlin proteins were not required for SP activity. Together, these results suggested that Rem uses a novel p97-dependent, Derlin-independent retrotranslocation mechanism distinct from other pathogens to avoid SP ubiquitylation and proteasomal degradation. PMID:28351922

Potential Use of Antiviral Agents in Polio Eradication

PubMed Central

De Palma, Armando M.; Pürstinger, Gerhard; Wimmer, Eva; Patick, Amy K.; Andries, Koen; Rombaut, Bart; De Clercq, Erik

2008-01-01

In 1988, the World Health Assembly launched the Global Polio Eradication Initiative, which aimed to use large-scale vaccination with the oral vaccine to eradicate polio worldwide by the year 2000. Although important progress has been made, polio remains endemic in several countries. Also, the current control measures will likely be inadequate to deal with problems that may arise in the postpolio era. A panel convoked by the National Research Council concluded that the use of antiviral drugs may be essential in the polio eradication strategy. We here report on a comparative study of the antipoliovirus activity of a selection of molecules that have previously been reported to be inhibitors of picornavirus replication and discuss their potential use, alone or in combination, for the treatment or prophylaxis of poliovirus infection. PMID:18394270

Eradication versus control for poliomyelitis: an economic analysis.

PubMed

Thompson, Kimberly M; Tebbens, Radboud J Duintjer

2007-04-21

Worldwide eradication of wild polioviruses is likely to yield substantial health and financial benefits, provided we finish the job. Challenges in the four endemic areas combined with continuing demands for financial resources for eradication have led some to question the goal of eradication and to suggest switching to a policy of control. We developed a dynamic model, based on modelling of the currently endemic areas in India, to show the importance of maintaining and increasing the immunisation intensity to complete eradication and to illustrate how policies based on perception about high short-term costs or cost-effectiveness ratios without consideration of long-term benefits could undermine any eradication effort. An extended model assesses the economic implications and disease burden of a change in policy from eradication to control. Our results suggest that the intensity of immunisation must be increased to achieve eradication, and that even small decreases in intensity could lead to large outbreaks. This finding implies the need to pay even higher short-run costs than are currently being spent, which will further exacerbate concerns about continued investment in interventions with high perceived cost-effectiveness ratios. We show that a wavering commitment leads to a failure to eradicate, greater cumulative costs, and a much larger number of cases. We further show that as long as it is technically achievable, eradication offers both lower cumulative costs and cases than control, even with the costs of achieving eradication exceeding several billion dollars more. A low-cost control policy that relies only on routine immunisation for 20 years with discounted costs of more than $3500 million could lead to roughly 200 000 expected paralytic poliomyelitis cases every year in low-income countries, whereas a low-case control policy that keeps the number of cases at about 1500 per year could cost around $10 000 million discounted over the 20 years. Focusing on the large costs for poliomyelitis eradication, without assessing the even larger potential benefits of eradication and the enormous long-term costs of effective control, might inappropriately affect commitments to the goal of eradication, and thus debate should include careful consideration of the options.

The Promise of Systems Biology Approaches for Revealing Host Pathogen Interactions in Malaria

PubMed Central

Zuck, Meghan; Austin, Laura S.; Danziger, Samuel A.; Aitchison, John D.; Kaushansky, Alexis

2017-01-01

Despite global eradication efforts over the past century, malaria remains a devastating public health burden, causing almost half a million deaths annually (WHO, 2016). A detailed understanding of the mechanisms that control malaria infection has been hindered by technical challenges of studying a complex parasite life cycle in multiple hosts. While many interventions targeting the parasite have been implemented, the complex biology of Plasmodium poses a major challenge, and must be addressed to enable eradication. New approaches for elucidating key host-parasite interactions, and predicting how the parasite will respond in a variety of biological settings, could dramatically enhance the efficacy and longevity of intervention strategies. The field of systems biology has developed methodologies and principles that are well poised to meet these challenges. In this review, we focus our attention on the Liver Stage of the Plasmodium lifecycle and issue a “call to arms” for using systems biology approaches to forge a new era in malaria research. These approaches will reveal insights into the complex interplay between host and pathogen, and could ultimately lead to novel intervention strategies that contribute to malaria eradication. PMID:29201016

Local extinction of the Asian tiger mosquito (Aedes albopictus) following rat eradication on Palmyra Atoll.

PubMed

Lafferty, Kevin D; McLaughlin, John P; Gruner, Daniel S; Bogar, Taylor A; Bui, An; Childress, Jasmine N; Espinoza, Magaly; Forbes, Elizabeth S; Johnston, Cora A; Klope, Maggie; Miller-Ter Kuile, Ana; Lee, Michelle; Plummer, Katherine A; Weber, David A; Young, Ronald T; Young, Hillary S

2018-02-01

The Asian tiger mosquito, Aedes albopictus, appears to have been extirpated from Palmyra Atoll following rat eradication. Anecdotal biting reports, collection records, and regular captures in black-light traps showed the species was present before rat eradication. Since then, there have been no biting reports and no captures over 2 years of extensive trapping (black-light and scent traps). By contrast, the southern house mosquito, Culex quinquefasciatus, was abundant before and after rat eradication. We hypothesize that mammals were a substantial and preferred blood meal for Aedes , whereas Culex feeds mostly on seabirds. Therefore, after rat eradication, humans and seabirds alone could not support positive population growth or maintenance of Aedes This seems to be the first documented accidental secondary extinction of a mosquito. Furthermore, it suggests that preferred host abundance can limit mosquito populations, opening new directions for controlling important disease vectors that depend on introduced species like rats. © 2018 The Authors.

Local extinction of the Asian tiger mosquito (Aedes albopictus) following rat eradication on Palmyra Atol

USGS Publications Warehouse

Lafferty, Kevin D.; McLaughlin, John P.; Gruner, Daniel S.; Bogar, Taylor A.; Bui, An; Childress, Jasmine N.; Espinoza, Magaly; Forbes, Elizabeth S.; Johnston, Cora A.; Klope, Maggie; Kuile, Ana Miller-ter; Lee, Michelle; Plummer, Katherine A.; Weber, David A.; Young, Ronald T.; Young, Hillary S.

2018-01-01

The Asian tiger mosquito, Aedes albopictus, appears to have been extirpated from Palmyra Atoll following rat eradication. Anecdotal biting reports, collection records, and regular captures in black-light traps showed the species was present before rat eradication. Since then, there have been no biting reports and no captures over 2 years of extensive trapping (black-light and scent traps). By contrast, the southern house mosquito, Culex quinquefasciatus, was abundant before and after rat eradication. We hypothesize that mammals were a substantial and preferred blood meal for Aedes, whereas Culex feeds mostly on seabirds. Therefore, after rat eradication, humans and seabirds alone could not support positive population growth or maintenance of Aedes. This seems to be the first documented accidental secondary extinction of a mosquito. Furthermore, it suggests that preferred host abundance can limit mosquito populations, opening new directions for controlling important disease vectors that depend on introduced species like rats.

Novel approaches to SOD management in California wildlands: a case study of "eradication" and collaboration in Redwood Valley

Treesearch

Y. Valachovic; L. Quinn-Davidson; E. Goldsworthy; P. Cannon

2013-01-01

In California, sudden oak death (SOD) treatment efforts have been localized, often targeting specific trees or properties. The widespread nature of SOD establishment and spread in coastal mountains of California has mostly precluded use of broader eradication strategies, which are more applicable in isolated infestations like those in Oregon. However, the 2010...

Current practice of emergency vagotomy and Helicobacter pylori eradication for complicated peptic ulcer in the United Kingdom.

PubMed

Gilliam, A D; Speake, W J; Lobo, D N; Beckingham, I J

2003-01-01

The aim was to assess the current opinion of surgeons, by subspecialty, towards vagotomy and the practice of Helicobacter pylori testing, treatment and follow-up, in patients with bleeding or perforated duodenal ulcer. A postal questionnaire was sent to 1073 Fellows of the Association of Surgeons of Great Britain and Ireland in 2001. Some 697 valid questionnaires were analysed (65.0 per cent). Most surgeons did not perform vagotomy for perforated or bleeding duodenal ulcer. There was no statistical difference between the responses of upper gastrointestinal surgeons and those of other specialists for perforated (P = 0.35) and bleeding (P = 0.45) ulcers. Respondents were more likely to perform a vagotomy for bleeding than for a perforated ulcer (P < 0.001). Although more than 80 per cent of surgeons prescribed H. pylori eradication treatment after operation, fewer than 60 per cent routinely tested patients for H. pylori eradication. Upper gastrointestinal surgeons were more likely to prescribe H. pylori treatment and test for eradication than other specialists (P < 0.01). Most surgeons in the UK no longer perform vagotomy for duodenal ulcer complications. Copyright 2002 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd

Unusual target site disruption by the rare-cutting HNH restriction endonuclease PacI

PubMed Central

Shen, Betty; Heiter, Daniel F.; Chan, Siu-Hong; Wang, Hua; Xu, Shuang-Yong; Morgan, Richard D.; Wilson, Geoffrey G.; Stoddard, Barry L.

2010-01-01

The crystal structure of the rare-cutting HNH restriction endonuclease PacI in complex with its eight base pair target recognition sequence 5'-TTAATTAA-3' has been determined to 1.9 Å resolution. The enzyme forms an extended homodimer, with each subunit containing two zinc-bound motifs surrounding a ββα-metal catalytic site. The latter is unusual in that a tyrosine residue likely initiates strand-cleavage. PacI dramatically distorts its target sequence from Watson-Crick duplex DNA basepairing, with every base separated from its original partner. Two bases on each strand are unpaired, four are engaged in non-canonical A:A and T:T base pairs, and the remaining two bases are matched with new Watson-Crick partners. This represents a highly unusual DNA binding mechanism for a restriction endonuclease, and implies that initial recognition of the target site might involve significantly different contacts from those visualized in the DNA-bound cocrystal structures. PMID:20541511

The "Horns" of FK Comae and the Complex Structure of its Outer Atmosphere

NASA Astrophysics Data System (ADS)

Saar, Steven H.; Ayres, T. R.; Kashyap, V.

2014-01-01

As part of a large multiwavelength campaign (COCOA-PUFS*) to explore magnetic activity in the unusual, single, rapidly rotating giant FK Comae, we have taken a time series of moderate resolution FUV spectra of the star with the COS spectrograph on HST. We find that the star has unusual, time-variable emission profiles in the chromosphere and transition region which show horn-like features. We use simple spatially inhomogeneous models to explain the variable line shapes. Modeling the lower chromospheric Cl I 1351 Å line, we find evidence for a very extended, spatial inhomogeneous outer atmosphere, likely composed of many huge "sling-shot" prominences of cooler material with embedded in a rotationally distended corona. We compare these results with hotter hotter transition region lines (Si IV) and optical spectra of the chromospheric He I D3 line. We also employ the model Cl I profiles, and data-derived empirical models, to fit the complex spectral region around the coronal Fe XXI 1354.1 Å line. We place limits on the flux of this line, and show these limits are consistent with expectations from the observed X-ray spectrum. *Campaign for Observation of the Corona and Outer Atmosphere of the Fast-rotating Star, FK Comae This work was supported by HST grant GO-12376.01-A.

Is eradication of the pinewood nematode (Bursaphelenchus xylophilus) likely? An evaluation of current contingency plans.

PubMed

Okland, Bjørn; Skarpaas, Olav; Schroeder, Martin; Magnusson, Christer; Lindelöw, Ake; Thunes, Karl

2010-09-01

The pinewood nematode (PWN) is one of the worst tree-killing exotic pests in East-Asian countries. The first European record of establishment in Portugal in 1999 triggered extensive surveys and contingency plans for eradication in European countries, including immediate removal of large areas of conifer host trees. Using Norway as an example, we applied a simulation model to evaluate the chance of successful eradication of a hypothetical introduction by the current contingency plan in a northern area where wilting symptoms are not expected to occur. Despite a highly variable spread of nematode infestations in space and time, the probability of successful eradication in 20 years was consistently low (mean 0.035, SE 0.02). The low success did not change significantly by varying the biological parameters in sensitivity analyses (SA), probably due to the late detection of infestations by the survey (mean 14.3 years). SA revealed a strong influence of management parameters. However, a high probability of eradication required unrealistic measures: achieving an eradication probability of 0.99 in 20 years required 10,000 survey samples per year and a host tree removal radius of 8,000 m around each detection point. © 2010 Society for Risk Analysis.

Selenoprotein K Binds Multiprotein Complexes and Is Involved in the Regulation of Endoplasmic Reticulum Homeostasis*

PubMed Central

Shchedrina, Valentina A.; Everley, Robert A.; Zhang, Yan; Gygi, Steven P.; Hatfield, Dolph L.; Gladyshev, Vadim N.

2011-01-01

Selenoprotein K (SelK) is an 11-kDa endoplasmic reticulum (ER) protein of unknown function. Herein, we defined a new eukaryotic protein family that includes SelK, selenoprotein S (SelS), and distantly related proteins. Comparative genomics analyses indicate that this family is the most widespread eukaryotic selenoprotein family. A biochemical search for proteins that interact with SelK revealed ER-associated degradation (ERAD) components (p97 ATPase, Derlins, and SelS). In this complex, SelK showed higher affinity for Derlin-1, whereas SelS had higher affinity for Derlin-2, suggesting that these selenoproteins could determine the nature of the substrate translocated through the Derlin channel. SelK co-precipitated with soluble glycosylated ERAD substrates and was involved in their degradation. Its gene contained a functional ER stress response element, and its expression was up-regulated by conditions that induce the accumulation of misfolded proteins in the ER. Components of the oligosaccharyltransferase complex (ribophorins, OST48, and STT3A) and an ER chaperone, calnexin, were found to bind SelK. A glycosylated form of SelK was also detected, reflecting its association with the oligosaccharyltransferase complex. These data suggest that SelK is involved in the Derlin-dependent ERAD of glycosylated misfolded proteins and that the function defined by the prototypic SelK is the widespread function of selenium in eukaryotes. PMID:22016385

Lightning can strike twice: an unlucky patient of neurological interest.

PubMed

Gilbee, Ebony S

2013-06-24

Poliomyelitis, once a worldwide epidemic, is becoming increasingly rare owing to the introduction of the polio vaccine in the 1950s. It is estimated that the number of cases of polio has reduced by 99% since the Global Polio Eradication Initiative (GPEI) started in 1988. Amyotrophic lateral sclerosis (ALS) is another relatively uncommon condition which also affects anterior horn cells with debilitating neurological, and deadly, consequences. An unusual case of an aggressive form of ALS developing in a 72-year-old patient with paralytic poliomyelitis in childhood is presented. Her initial presentation was puzzling, and our approach to the diagnostic dilemma is discussed.

Lightning can strike twice: an unlucky patient of neurological interest

PubMed Central

Gilbee, Ebony S

2013-01-01

Poliomyelitis, once a worldwide epidemic, is becoming increasingly rare owing to the introduction of the polio vaccine in the 1950s. It is estimated that the number of cases of polio has reduced by 99% since the Global Polio Eradication Initiative (GPEI) started in 1988. Amyotrophic lateral sclerosis (ALS) is another relatively uncommon condition which also affects anterior horn cells with debilitating neurological, and deadly, consequences. An unusual case of an aggressive form of ALS developing in a 72-year-old patient with paralytic poliomyelitis in childhood is presented. Her initial presentation was puzzling, and our approach to the diagnostic dilemma is discussed. PMID:23814000

[Global eradication of dracunculiasis is a reality nowadays].

PubMed

Litvinov, S K; Migliorini, L; Chernikova, E A; Lutsevich, O A

2014-01-01

Global efforts to eradicate dracunculiasis have continued to progress with only 542 cases reported in 2012 versus almost 1 million cases in the 1980s when the initiative was launched. The disease is still endemic, but in only four countries: South Sudan (541 cases), Chad (10 cases), Mali (4 cases), and Ethiopia (4 cases). The International Commission for the Certification of Dracunculiasis Eradication declared that 180 countries were free of the disease by 2013. Dracunculiasis was first eradicated in the former USSR in 1931 when its last case was registered due to the successful implementation of a package of appropriate measures (case detection and management, vector control, and health education, including water filtration from open water sources and behavioral changes). These approaches were actively taken into account when developing the global strategy for dracunculiasis. The World Health Organization has set a goal to eradicate the disease by 2015. However, despite the fact that the global situation looks very optimistic, the time for completing the program will be most likely postponed due to a few operational challenges remaining in the still endemic countries, in South Sudan in particular.

Effects of gamma irradiation on the midgut ultrastructure of Glossina palpalis subspecies

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

Stiles, J.K.; Molyneux, D.H.; Wallbanks, K.R.

1989-05-01

In the sterile insect technique, insects are sterilized prior to release in areas where they are pests. The sterile males compete for and with fertile wild individuals for mates, thus reducing the population's reproductive rate. Tsetse fly (Glossina spp.) populations have been eradicated after release of laboratory-bred flies sterilized by gamma irradiation. However, no studies exist on radiation-induced damage to the midgut morphology and function of the radiation-sterilized insects. After G. palpalis palpalis and G. p. gambiensis were subjected to 130 Gy gamma radiation, their midgut damage and recovery were monitored by electron microscopy. The first sign of damage wasmore » atrophy and loss of the microvillous border from epithelial cells. The rate of cell degeneration increased, with young as well as old cells being affected and cellular debris filling the ectoperitrophic space. Muscle cells were destroyed, patches of basal lamina were left bare, intracellular virus- and rickettsia-like organisms became more frequent, and many replacement cells became unusually large. Partial recovery occurred from the 10th day postirradiation. Such changes in midgut ultrastructure and the corresponding inhibition of functions may increase the susceptibility of the fly to trypanosome infection.« less

Using Models to Inform Policy: Insights from Modeling the Complexities of Global Polio Eradication

NASA Astrophysics Data System (ADS)

Thompson, Kimberly M.

Drawing on over 20 years of experience modeling risks in complex systems, this talk will challenge SBP participants to develop models that provide timely and useful answers to critical policy questions when decision makers need them. The talk will include reflections on the opportunities and challenges associated with developing integrated models for complex problems and communicating their results effectively. Dr. Thompson will focus the talk largely on collaborative modeling related to global polio eradication and the application of system dynamics tools. After successful global eradication of wild polioviruses, live polioviruses will still present risks that could potentially lead to paralytic polio cases. This talk will present the insights of efforts to use integrated dynamic, probabilistic risk, decision, and economic models to address critical policy questions related to managing global polio risks. Using a dynamic disease transmission model combined with probabilistic model inputs that characterize uncertainty for a stratified world to account for variability, we find that global health leaders will face some difficult choices, but that they can take actions that will manage the risks effectively. The talk will emphasize the need for true collaboration between modelers and subject matter experts, and the importance of working with decision makers as partners to ensure the development of useful models that actually get used.

"Why we could not eradicate polio from pakistan and how can we?"

PubMed

Shah, Syed Zawar; Saad, Muhammad; Rahman Khattak, Mohammad Hasan; Rizwan, Muhammad; Haidari, Asma; Idrees, Fatima

2016-01-01

Polio is a major health problem and a deadly infectious disease in the developing countries. It is a viral illness caused by polio virus that can lead to paralysis, limb deformities, breathing problems or even death. Polio virus resides only in humans and passes on to the environment in the faeces of someone who is infected. Polio is still endemic in three countries, i.e., Pakistan, Nigeria and Afghanistan and is eradicated from the rest of the world. Pakistan is considered as the exporter of Wild Polio Virus (WPV) with highest number of polio outbreaks among endemic countries. With the start of World Polio Eradication Initiative in 1988, the number of polio cases has been reduced up to 99% worldwide until now. In 2015, Pakistan has shown a decrease of 70-75% in number of polio cases as compare to last year which is the result of good government's initiatives. Militant organizations such as Tehreek-e-Taliban Pakistan, Al-Qaeda and Boko haram movement of northern Nigeria are a major hurdle in the eradication of polio from these countries. The misconception of people about polio vaccine, insecurity within the country and poor health system are the reasons of failure of polio eradication campaigns in these regions. Awareness campaigns about polio for locals and development of proper health system will help in the eradication of polio. Once polio is eradicated, about 40-50 billion dollars can be saved globally. With the strong commitment, seriousness and good initiatives, polio will be eradicated from Pakistan within two years more likely.

A safety rule approach to surveillance and eradication of biological invasions

PubMed Central

Haight, Robert G.; Koch, Frank H.; Venette, Robert; Studens, Kala; Fournier, Ronald E.; Swystun, Tom; Turgeon, Jean J.

2017-01-01

Uncertainty about future spread of invasive organisms hinders planning of effective response measures. We present a two-stage scenario optimization model that accounts for uncertainty about the spread of an invader, and determines survey and eradication strategies that minimize the expected program cost subject to a safety rule for eradication success. The safety rule includes a risk standard for the desired probability of eradication in each invasion scenario. Because the risk standard may not be attainable in every scenario, the safety rule defines a minimum proportion of scenarios with successful eradication. We apply the model to the problem of allocating resources to survey and eradicate the Asian longhorned beetle (ALB, Anoplophora glabripennis) after its discovery in the Greater Toronto Area, Ontario, Canada. We use historical data on ALB spread to generate a set of plausible invasion scenarios that characterizes the uncertainty of the beetle’s extent. We use these scenarios in the model to find survey and tree removal strategies that minimize the expected program cost while satisfying the safety rule. We also identify strategies that reduce the risk of very high program costs. Our results reveal two alternative strategies: (i) delimiting surveys and subsequent tree removal based on the surveys' outcomes, or (ii) preventive host tree removal without referring to delimiting surveys. The second strategy is more likely to meet the stated objectives when the capacity to detect an invader is low or the aspirations to eradicate it are high. Our results provide practical guidelines to identify the best management strategy given aspirational targets for eradication and spending. PMID:28759584

Polio Eradication Initiative: Contribution to improved communicable diseases surveillance in WHO African region.

PubMed

Mwengee, William; Okeibunor, Joseph; Poy, Alain; Shaba, Keith; Mbulu Kinuani, Leon; Minkoulou, Etienne; Yahaya, Ali; Gaturuku, Peter; Landoh, Dadja Essoya; Nsubuga, Peter; Salla, Mbaye; Mihigo, Richard; Mkanda, Pascal

2016-10-10

Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, there has been a tremendous progress in the reduction of cases of poliomyelitis. The world is on the verge of achieving global polio eradication and in May 2013, the 66th World Health Assembly endorsed the Polio Eradication and Endgame Strategic Plan (PEESP) 2013-2018. The plan provides a timeline for the completion of the GPEI by eliminating all paralytic polio due to both wild and vaccine-related polioviruses. We reviewed how GPEI supported communicable disease surveillance in seven of the eight countries that were documented as part of World Health Organization African Region best practices documentation. Data from WHO African region was also reviewed to analyze the performance of measles cases based surveillance. All 7 countries (100%) which responded had integrated communicable diseases surveillance core functions with AFP surveillance. The difference is on the number of diseases included based on epidemiology of diseases in a particular country. The results showed that the polio eradication infrastructure has supported and improved the implementation of surveillance of other priority communicable diseases under integrated diseases surveillance and response strategy. As we approach polio eradication, polio-eradication initiative staff, financial resources, and infrastructure can be used as one strategy to build IDSR in Africa. As we are now focusing on measles and rubella elimination by the year 2020, other disease-specific programs having similar goals of eradicating and eliminating diseases like malaria, might consider investing in general infectious disease surveillance following the polio example. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Rheumatoid arthritis as a hyper-endoplasmic-reticulum-associated degradation disease.

PubMed

Yamasaki, Satoshi; Yagishita, Naoko; Tsuchimochi, Kaneyuki; Nishioka, Kusuki; Nakajima, Toshihiro

2005-01-01

We introduce Synoviolin as a novel pathogenic factor in rheumatoid arthritis (RA). Experimental studies indicate that this endoplasmic reticulum (ER)-resident E3 ubiquitin ligase has important functions in the ER-associated degradation (ERAD) system, an essential system for ER homeostasis. Overexpression of Synoviolin in mice causes arthropathy with synovial hyperplasia, whereas heterozygous knockdown results in increased apoptosis of synovial cells and resistance to collagen-induced arthritis in mice. On the basis of these experimental data, we propose that excess elimination of unfolded proteins (that is, 'hyper-ERAD') by overexpression of Synoviolin triggers synovial cell overgrowth and hence a worsening of RA. Further analysis of the hyper-ERAD system may permit the complex pathomechanisms of RA to be uncovered.

New Insights Into Roles of Ubiquitin Modification in Regulating Plastids and Other Endosymbiotic Organelles.

PubMed

Broad, W; Ling, Q; Jarvis, P

2016-01-01

Recent findings have revealed important and diverse roles for the ubiquitin modification of proteins in the regulation of endosymbiotic organelles, which include the primary plastids of plants as well as complex plastids: the secondary endosymbiotic organelles of cryptophytes, alveolates, stramenopiles, and haptophytes. Ubiquitin modifications have a variety of potential consequences, both to the modified protein itself and to cellular regulation. The ubiquitin-proteasome system (UPS) can target individual proteins for selective degradation by the cytosolic 26S proteasome. Ubiquitin modifications can also signal the removal of whole endosymbiotic organelles, for example, via autophagy as has been well characterized in mitochondria. As plastids must import over 90% of their proteins from the cytosol, the observation that the UPS selectively targets the plastid protein import machinery is particularly significant. In this way, the UPS may influence the development and interconversions of different plastid types, as well as plastid responses to stress, by reconfiguring the organellar proteome. In complex plastids, the Symbiont-derived ERAD-Like Machinery (SELMA) has coopted the protein transport capabilities of the ER-Associated Degradation (ERAD) system, whereby misfolded proteins are retrotranslocated from ER for proteasomal degradation, uncoupling them from proteolysis: SELMA components have been retargeted to the second outermost plastid membrane to mediate protein import. In spite of this wealth of new information, there still remain a large number of unanswered questions and a need to define the roles of ubiquitin modification further in the regulation of plastids. Copyright © 2016 Elsevier Inc. All rights reserved.

Hsp70 and Hsp90 Multichaperone Complexes Sequentially Regulate Thiazide-sensitive Cotransporter Endoplasmic Reticulum-associated Degradation and Biogenesis*

PubMed Central

Donnelly, Bridget F.; Needham, Patrick G.; Snyder, Avin C.; Roy, Ankita; Khadem, Shaheen; Brodsky, Jeffrey L.; Subramanya, Arohan R.

2013-01-01

The thiazide-sensitive NaCl cotransporter (NCC) is the primary mediator of salt reabsorption in the distal convoluted tubule and is a key determinant of the blood pressure set point. Given its complex topology, NCC is inefficiently processed and prone to endoplasmic reticulum (ER)-associated degradation (ERAD), although the mechanisms governing this process remain obscure. Here, we identify factors that impact the ER quality control of NCC. Analyses of NCC immunoprecipitates revealed that the cotransporter formed complexes with the core chaperones Hsp90, Hsp70, and Hsp40. Disruption of Hsp90 function accelerated NCC degradation, suggesting that Hsp90 promotes NCC folding. In addition, two cochaperones, the C terminus of Hsp70-interacting protein (CHIP) and the Hsp70/Hsp90 organizer protein, were associated with NCC. Although CHIP, an E3 ubiquitin ligase, promoted NCC ubiquitination and ERAD, the Hsp70/Hsp90 organizer protein stabilized NCC turnover, indicating that these two proteins differentially remodel the core chaperone systems to favor cotransporter degradation and biogenesis, respectively. Adjusting the folding environment in mammalian cells via reduced temperature enhanced NCC biosynthetic trafficking, increased Hsp90-NCC interaction, and diminished binding to Hsp70. In contrast, cotransporters harboring disease-causing mutations that impair NCC biogenesis failed to escape ERAD as efficiently as the wild type protein when cells were incubated at a lower temperature. Instead, these mutants interacted more strongly with Hsp70, Hsp40, and CHIP, consistent with a role for the Hsp70/Hsp40 system in selecting misfolded NCC for ERAD. Collectively, these observations indicate that Hsp70 and Hsp90 comprise two functionally distinct ER quality control checkpoints that sequentially monitor NCC biogenesis. PMID:23482560

Role of HERP and a HERP-related protein in HRD1-dependent protein degradation at the endoplasmic reticulum.

PubMed

Huang, Chih-Hsiang; Chu, Yue-Ru; Ye, Yihong; Chen, Xin

2014-02-14

Misfolded proteins of the endoplasmic reticulum (ER) are retrotranslocated to the cytosol and degraded by the proteasome via a process termed ER-associated degradation (ERAD). The precise mechanism of retrotranslocation is unclear. Here, we use several lumenal ERAD substrates targeted for degradation by the ubiquitin ligase HRD1 including SHH (sonic hedgehog) and NHK (null Hong Kong α1-antitrypsin) to study the geometry, organization, and regulation of the HRD1-containing ERAD machinery. We report a new HRD1-associated membrane protein named HERP2, which is homologous to the previously identified HRD1 partner HERP1. Despite sequence homology, HERP2 is constitutively expressed in cells, whereas HERP1 is highly induced by ER stress. We find that these proteins are required for efficient degradation of both glycosylated and nonglycosylated SHH proteins as well as NHK. In cells depleted of HERPs, SHH proteins are largely trapped inside the ER with a fraction of the stabilized SHH protein bound to the HRD1-SEL1L ligase complex. Ubiquitination of SHH is significantly attenuated in the absence of HERPs, suggesting a defect in retrotranslocation. Both HERP proteins interact with HRD1 through a region located in the cytosol. However, unlike its homolog in Saccharomyces cerevisiae, HERPs do not regulate HRD1 stability or oligomerization status. Instead, they help recruit DERL2 to the HRD1-SEL1L complex. Additionally, the UBL domain of HERP1 also seems to have a function independent of DERL2 recruitment in ERAD. Our studies have revealed a critical scaffolding function for mammalian HERP proteins that is required for forming an active retrotranslocation complex containing HRD1, SEL1L, and DERL2.

Biofilm infections between Scylla and Charybdis: interplay of host antimicrobial peptides and antibiotics

PubMed Central

Gordya, Natalia; Tulin, Dmitry; Yakovlev, Andrey

2018-01-01

Purpose The aim of this study is to improve the anti-biofilm activity of antibiotics. We hypothesized that the antimicrobial peptide (AMP) complex of the host’s immune system can be used for this purpose and examined the assumption on model biofilms. Methods FLIP7, the AMP complex of the blowfly Calliphora vicina containing a combination of defensins, cecropins, diptericins and proline-rich peptides was isolated from the hemolymph of bacteria-challenged maggots. The complex interaction with antibiotics of various classes was studied in biofilm and planktonic cultures of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by the checkerboard method using trimethyl tetrazolium chloride cell viability and crystal violet biofilm eradication assays supplemented with microscopic analysis. Results We found that FLIP7 demonstrated: high synergy (fractional inhibitory concentration index <0.25) with meropenem, amikacin, kanamycin, ampicillin, vancomycin and cefotaxime; synergy with clindamycin, erythromycin and chloramphenicol; additive interaction with oxacillin, tetracycline, ciprofloxacin and gentamicin; and no interaction with polymyxin B. The interaction in planktonic cell models was significantly weaker than in biofilms of the same strains. The analysis of the dose–effect curves pointed to persister cells as a likely target of FLIP7 synergistic effect. The biofilm eradication assay showed that the effect also caused total destruction of S. aureus and E. coli biofilm materials. The effect allowed reducing the effective anti-biofilm concentration of the antibiotic to a level well below the one clinically achievable (2–3 orders of magnitude in the case of meropenem, ampicillin, cefotaxime and oxacillin). Conclusion FLIP7 is a highly efficient host antimicrobial system helping antibiotics to overcome biofilm barriers through persisters’ sensitization and biofilm material destruction. It is promising for the treatment of biofilm infections as an adjuvant of various small-molecule antibiotics. PMID:29674848

EBS7 is a plant-specific component of a highly conserved endoplasmic reticulum-associated degradation system in Arabidopsis

PubMed Central

Liu, Yidan; Zhang, Congcong; Wang, Dinghe; Su, Wei; Liu, Linchuan; Wang, Muyang; Li, Jianming

2015-01-01

Endoplasmic reticulum (ER)-associated degradation (ERAD) is an essential part of an ER-localized protein quality-control system for eliminating terminally misfolded proteins. Recent studies have demonstrated that the ERAD machinery is conserved among yeast, animals, and plants; however, it remains unknown if the plant ERAD system involves plant-specific components. Here we report that the Arabidopsis ethyl methanesulfonate-mutagenized brassinosteroid-insensitive 1 suppressor 7 (EBS7) gene encodes an ER membrane-localized ERAD component that is highly conserved in land plants. Loss-of-function ebs7 mutations prevent ERAD of brassinosteroid insensitive 1-9 (bri1-9) and bri1-5, two ER-retained mutant variants of the cell-surface receptor for brassinosteroids (BRs). As a result, the two mutant receptors accumulate in the ER and consequently leak to the plasma membrane, resulting in the restoration of BR sensitivity and phenotypic suppression of the bri1-9 and bri1-5 mutants. EBS7 accumulates under ER stress, and its mutations lead to hypersensitivity to ER and salt stresses. EBS7 interacts with the ER membrane-anchored ubiquitin ligase Arabidopsis thaliana HMG-CoA reductase degradation 1a (AtHrd1a), one of the central components of the Arabidopsis ERAD machinery, and an ebs7 mutation destabilizes AtHrd1a to reduce polyubiquitination of bri1-9. Taken together, our results uncover a plant-specific component of a plant ERAD pathway and also suggest its likely biochemical function. PMID:26371323

Complex of Fas-associated Factor 1 (FAF1) with Valosin-containing Protein (VCP)-Npl4-Ufd1 and Polyubiquitinated Proteins Promotes Endoplasmic Reticulum-associated Degradation (ERAD)*

PubMed Central

Lee, Jae-Jin; Park, Joon Kyu; Jeong, Jaeho; Jeon, Hyesung; Yoon, Jong-Bok; Kim, Eunice EunKyeong; Lee, Kong-Joo

2013-01-01

Fas-associated factor 1 (FAF1) is a ubiquitin receptor containing multiple ubiquitin-related domains including ubiquitin-associated (UBA), ubiquitin-like (UBL) 1, UBL2, and ubiquitin regulatory X (UBX). We previously showed that N-terminal UBA domain recognizes Lys48-ubiquitin linkage to recruit polyubiquitinated proteins and that a C-terminal UBX domain interacts with valosin-containing protein (VCP). This study shows that FAF1 interacts only with VCP complexed with Npl4-Ufd1 heterodimer, a requirement for the recruitment of polyubiquitinated proteins to UBA domain. Intriguingly, VCP association to C-terminal UBX domain regulates ubiquitin binding to N-terminal UBA domain without direct interaction between UBA and UBX domains. These interactions are well characterized by structural and biochemical analysis. VCP-Npl4-Ufd1 complex is known as the machinery required for endoplasmic reticulum-associated degradation. We demonstrate here that FAF1 binds to VCP-Npl4-Ufd1 complex via UBX domain and polyubiquitinated proteins via UBA domain to promote endoplasmic reticulum-associated degradation. PMID:23293021

Can we spend our way out of the AIDS epidemic? A world halting AIDS model

PubMed Central

2009-01-01

Background There has been a sudden increase in the amount of money donors are willing to spend on the worldwide HIV/AIDS epidemic. Present plans are to hold most of the money in reserve and spend it slowly. However, rapid spending may be the best strategy for halting this disease. Methods We develop a mathematical model that predicts eradication or persistence of HIV/AIDS on a world scale. Dividing the world into regions (continents, countries etc), we develop a linear differential equation model of infectives which has the same eradication properties as more complex models. Results We show that, even if HIV/AIDS can be eradicated in each region independently, travel/immigration of infectives could still sustain the epidemic. We use a continent-level example to demonstrate that eradication is possible if preventive intervention methods (such as condoms or education) reduced the infection rate to two fifths of what it is currently. We show that, for HIV/AIDS to be eradicated within five years, the total cost would be ≈ $63 billion, which is within the existing $60 billion (plus interest) amount raised by the donor community. However, if this action is spread over a twenty year period, as currently planned, then eradication is no longer possible, due to population growth, and the costs would exceed $90 billion. Conclusion Eradication of AIDS is feasible, using the tools that we have currently to hand, but action needs to occur immediately. If not, then HIV/AIDS will race beyond our ability to afford it. PMID:19922685

Unraveling the function of Arabidopsis thaliana OS9 in the endoplasmic reticulum-associated degradation of glycoproteins.

PubMed

Hüttner, Silvia; Veit, Christiane; Schoberer, Jennifer; Grass, Josephine; Strasser, Richard

2012-05-01

In the endoplasmic reticulum, immature polypeptides coincide with terminally misfolded proteins. Consequently, cells need a well-balanced quality control system, which decides about the fate of individual proteins and maintains protein homeostasis. Misfolded and unassembled proteins are sent for destruction via the endoplasmic reticulum-associated degradation (ERAD) machinery to prevent the accumulation of potentially toxic protein aggregates. Here, we report the identification of Arabidopsis thaliana OS9 as a component of the plant ERAD pathway. OS9 is an ER-resident glycoprotein containing a mannose-6-phosphate receptor homology domain, which is also found in yeast and mammalian lectins involved in ERAD. OS9 fused to the C-terminal domain of YOS9 can complement the ERAD defect of the corresponding yeast Δyos9 mutant. An A. thaliana OS9 loss-of-function line suppresses the severe growth phenotype of the bri1-5 and bri1-9 mutant plants, which harbour mutated forms of the brassinosteroid receptor BRI1. Co-immunoprecipitation studies demonstrated that OS9 associates with Arabidopsis SEL1L/HRD3, which is part of the plant ERAD complex and with the ERAD substrates BRI1-5 and BRI1-9, but only the binding to BRI1-5 occurs in a glycan-dependent way. OS9-deficiency results in activation of the unfolded protein response and reduces salt tolerance, highlighting the role of OS9 during ER stress. We propose that OS9 is a component of the plant ERAD machinery and may act specifically in the glycoprotein degradation pathway.

Unusual Electrical Transport Driven by the Competition between Antiferromagnetism and Ferromagnetism in Antiperovskite Mn3Zn1−xCoxN

PubMed Central

Chu, Lihua; Wang, Cong; Guo, Yanjiao; Liu, Zhuohai

2018-01-01

The magnetic, electrical transport and thermal expansion properties of Mn3Zn1−xCoxN (x = 0.2, 0.4, 0.5, 0.7, 0.9) have been systematically investigated. Co-doping in Mn3ZnN complicates the magnetic interactions, leading to a competition between antiferromagnetism and ferromagnetism. Abrupt resistivity jump phenomenon and negative thermal expansion behavior, both associated with the complex magnetic transition, are revealed in all studied cases. Furthermore, semiconductor-like transport behavior is found in sample x = 0.7, distinct from the metallic behavior in other samples. Below 50 K, resistivity minimum is observed in samples x = 0.4, 0.7, and 0.9, mainly caused by e-e scattering mechanism. We finally discussed the strong correlation among unusual electrical transport, negative thermal expansion and magnetic transition in Mn3Zn1−xCoxN, which allows us to conclude that the observed unusual electrical transport properties are attributed to the shift of the Fermi energy surface entailed by the abrupt lattice contraction. PMID:29439522

A complex baleen whale call recorded in the Mariana Trench Marine National Monument.

PubMed

Nieukirk, Sharon L; Fregosi, Selene; Mellinger, David K; Klinck, Holger

2016-09-01

In fall 2014 and spring 2015, passive acoustic data were collected via autonomous gliders east of Guam in an area that included the Mariana Trench Marine National Monument. A short (2-4 s), complex sound was recorded that features a ∼38 Hz moan with both harmonics and amplitude modulation, followed by broad-frequency metallic-sounding sweeps up to 7.5 kHz. This sound was recorded regularly during both fall and spring surveys. Aurally, the sound is quite unusual and most resembles the minke whale "Star Wars" call. It is likely this sound is biological and produced by a baleen whale.

Highly deformable bones: unusual deformation mechanisms of seahorse armor.

PubMed

Porter, Michael M; Novitskaya, Ekaterina; Castro-Ceseña, Ana Bertha; Meyers, Marc A; McKittrick, Joanna

2013-06-01

Multifunctional materials and devices found in nature serve as inspiration for advanced synthetic materials, structures and robotics. Here, we elucidate the architecture and unusual deformation mechanisms of seahorse tails that provide prehension as well as protection against predators. The seahorse tail is composed of subdermal bony plates arranged in articulating ring-like segments that overlap for controlled ventral bending and twisting. The bony plates are highly deformable materials designed to slide past one another and buckle when compressed. This complex plate and segment motion, along with the unique hardness distribution and structural hierarchy of each plate, provide seahorses with joint flexibility while shielding them against impact and crushing. Mimicking seahorse armor may lead to novel bio-inspired technologies, such as flexible armor, fracture-resistant structures or prehensile robotics. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Leprosy: eradication or cure?

PubMed

Kakar, S

1995-01-01

The National Leprosy Eradication Program (NLEP), launched in 1986, has brought medicine for leprosy to more people than ever before, covering 200 of India's 455 districts. Since 1988, the number of leprosy patients discharged as cured each year has been greater than the number of newly detected, thus moving the country closer to its goal of eradicating leprosy from India. A substantial number of the 3 million people with leprosy in India are likely to come under the coverage of the NLEP. The author, however, argues that the fight against leprosy and the NLEP should be considered in their historical context. Leprosy is therefore used to illustrate how the perhaps interchangeable terms eradication and cure are charged with history and custom. Historically, the focus on eradicating leprosy has had terrible consequences for the patient. In England, perceptions about leprosy are relevant to the situation India, for colonial policy on leprosy was largely derivative. In the 1880s, especially, leprosy excited the public imagination. Asylums adopted segregation and confinement during this period for people with leprosy and the colonial government in India supported that approach from 1882. The author concludes that while the NLEP is laudable, the program must not focus upon eradicating leprosy. It should instead focus upon the leprosy patient, who has for so long been denied and discriminated against. The individual must be placed at the center of any program. Some steps in this direction have been taken.

The Rakiura Titi Islands Restoration Project: community action to eradicate Rattus rattus and Rattus exulans for ecological restoration and cultural wellbeing

USGS Publications Warehouse

McClelland, P.J; Coote,; Trow,; Hutchins,; Nevins, HannahRose M.; Adams, Josh; Newman, J.; Moller, H.; Veitch, C.R.; Clout, Mike N.; Towns, D. R.

2011-01-01

In 2003, a non-profit group, Ka Mate Nga Kiore, was set up to oversee the restoration of four Maori-owned islands off the south coast of Stewart Island, New Zealand. The first step in the restoration was to eradicate ship rats (Rattus rattus) from three islands and Pacific rats (R. exulans) from another. The eradication was funded by the Command Oil Spill Trustee Council which managed the mitigation money from an oil spill off the Californian coast in 1998. The funding was coordinated via Oikonos Ecosystem Knowledge, a non-profit USA group primarily involved in seabird research and restoration. The project was primarily to benefit sooty shearwater (Puffinus griseus) and to sustain a culturally important customary harvest of their chicks by Rakiura Maori. However, like all island eradications, a wide range of other species also benefited from the removal of rats. The New Zealand Department of Conservation provided technical advice and assistance for the planning and implementation of the eradication programme. This paper describes how, with appropriate funding, community and technical support, rodent eradications can be achieved on private islands. In this case, a range of institutions and individuals joined to achieve a common goal that highlighted a significant international conservation action. We urge that more international and local-community-led restoration projects be initiated in the future.

Cutaneous anthrax in an unusual location: case report.

PubMed

Sari, Tugba; Koruk, Suda Tekin

2015-12-01

Cutaneous anthrax is well known, unlike anthrax of the lumbar region, which is not reported elsewhere. We present a case of anthrax of the lumbar region in a 50-year-old man. The infection was characterised by a wide, black eschar and oedema on an erythematous ground. After isolation of the Gram-positive bacilli from the skin lesions, prompt antibiotic treatment (intravenous sulbactam-ampicillin 1.5 g every six hours) was initiated. Following eradication of the bacilli after 14 days of antibiotic treatment, a split-thickness skin graft was applied. A diagnosis of anthrax depends on clinical suspicion. Early diagnosis, antibiotic and surgical treatment can facilitate the treatment and prevent development of complications.

Are We Prepared in Case of a Possible Smallpox-Like Disease Emergence?

PubMed Central

Olson, Victoria A.; Shchelkunov, Sergei N.

2017-01-01

Smallpox was the first human disease to be eradicated, through a concerted vaccination campaign led by the World Health Organization. Since its eradication, routine vaccination against smallpox has ceased, leaving the world population susceptible to disease caused by orthopoxviruses. In recent decades, reports of human disease from zoonotic orthopoxviruses have increased. Furthermore, multiple reports of newly identified poxviruses capable of causing human disease have occurred. These facts raise concerns regarding both the opportunity for these zoonotic orthopoxviruses to evolve and become a more severe public health issue, as well as the risk of Variola virus (the causative agent of smallpox) to be utilized as a bioterrorist weapon. The eradication of smallpox occurred prior to the development of the majority of modern virological and molecular biological techniques. Therefore, there is a considerable amount that is not understood regarding how this solely human pathogen interacts with its host. This paper briefly recounts the history and current status of diagnostic tools, vaccines, and anti-viral therapeutics for treatment of smallpox disease. The authors discuss the importance of further research to prepare the global community should a smallpox-like virus emerge.

Greater than 95% success with 14-day bismuth quadruple anti- Helicobacter pylori therapy: a pilot study in US Hispanics.

PubMed

Salazar, Cesar O; Cardenas, Victor M; Reddy, Rita K; Dominguez, Delfina C; Snyder, Lindsey K; Graham, David Y

2012-10-01

A combination capsule of bismuth, metronidazole, and tetracycline plus omeprazole given as 10-day therapy has an overall effectiveness of 92-93% in per-protocol analysis (Grade B) with eradication of 86-91% of metronidazole-resistant Helicobacter pylori. This study aimed to explore whether extending the duration to 14 days would improve overall effectiveness per protocol to ≥95% (Grade A) in a population in which metronidazole resistance was anticipated to exist. A one-arm, open-label pilot study of H. pylori-infected, asymptomatic/mildly dyspeptic adults, Hispanic residents of El Paso, Texas, received a 14-day course of omeprazole, plus the combination capsule. We cultured and Gram-stained specimens obtained using a minimally invasive orogastric brush. Helicobacter pylori status was determined by (13)C-urea breath test at 4 or more weeks post-therapy. Forty-seven subjects (7 men and 40 women, average age 42 years) were entered. The per-protocol effectiveness was 97.1% (33/34) (95% mid-P CI: 86.3, 99.9); 100% of metronidazole-resistant strains were eradicated. Side effects were mild and self-limited but contributed to nonadherence. Therapy taken for <10 days was more likely to result in eradication failure (p < .001). Office-based orogastric brushing was well tolerated; positive cultures were obtained in 95%. Gram staining showed H. pylori-like forms in all specimens. This pilot study supports the concept that 14-day OBMT therapy is likely to be more efficacious for H. pylori eradication (Grade A, PP basis) than a 10-day course where metronidazole resistance is suspected. If confirmed, 14 days should be recommended in populations where metronidazole resistance is common. © 2012 Blackwell Publishing Ltd.

Testing Anthropic Selection: A Climate Change Example

PubMed Central

2011-01-01

Abstract Planetary anthropic selection, the idea that Earth has unusual properties since, otherwise, we would not be here to observe it, is a controversial idea. This paper proposes a methodology by which to test anthropic proposals by comparison of Earth to synthetic populations of Earth-like planets. The paper illustrates this approach by investigating possible anthropic selection for high (or low) rates of Milankovitch-driven climate change. Three separate tests are investigated: (1) Earth-Moon properties and their effect on obliquity; (2) Individual planet locations and their effect on eccentricity variation; (3) The overall structure of the Solar System and its effect on eccentricity variation. In all three cases, the actual Earth/Solar System has unusually low Milankovitch frequencies compared to similar alternative systems. All three results are statistically significant at the 5% or better level, and the probability of all three occurring by chance is less than 10−5. It therefore appears that there has been anthropic selection for slow Milankovitch cycles. This implies possible selection for a stable climate, which, if true, undermines the Gaia hypothesis and also suggests that planets with Earth-like levels of biodiversity are likely to be very rare. Key Words: Planetary habitability and biosignatures—Intelligence—Paleoenvironment and paleoclimate—Co-evolution of Earth and life—Complex life. Astrobiology 11, 105–114. PMID:21401338

Unusual benign polypoid and papular neoplasms and tumor-like lesions of the vulva.

PubMed

AbdullGaffar, Badr; Keloth, Tasnim R; Raman, Lakshmiah G; Mahmood, Suaad; Almulla, Amal; AlMarzouqi, Mamoun; Al-Hasani, Salam

2014-04-01

We aimed to investigate the prevalence and spectrum of unusual benign neoplasms and tumor-like lesions presenting as vulvar polyps and papules, to study their clinical, pathologic, hormonal, and developmental features and whether they have important associations with other pathologic lesions or clinical diseases. We conducted a retrospective review study of 115 vulvar specimens over 7 years. Common lesions, for example, fibroepithelial polyps, skin tags, papillomas, abscesses, viral warts and common cysts, were excluded. We found 21 cases (18%) with uncommon benign vulvar lesions. They included 7 epithelial cysts, 3 vascular lesions, 3 glandular neoplasms, 3 endometrioses, 1 caruncle, 1 pilonidal sinus, 1 prolapsed urethra, 1 seborrheic keratosis, and 1 granular cell tumor. The age range was between 1 and 64 years with a mean age of 33 years. Most (86%) were 2.5 cm or less. Many were asymptomatic incidental pathologic findings that can be missed clinically. Nine cases have important clinical associations or coexisting incidental pathologic lesions. Some lesions demonstrated hormone receptors. Some were clinically confused with fibroepithelial polyps, abscesses, warts, melanocytic lesions, and tumors. In conclusion, although the vulva is a small compartment, its developmental and histologic complexity can result in a variety of unusual and rare benign polypoid and papular lesions, some unique to the vulva, which might present diagnostic challenges to the clinicians and pathologists. In addition, many bear controversy regarding their histogenesis and origin of development in the vulva. Copyright © 2014 Elsevier Inc. All rights reserved.

Protein-like fully reversible tetramerisation and super-association of an aminocellulose

NASA Astrophysics Data System (ADS)

Nikolajski, Melanie; Adams, Gary G.; Gillis, Richard B.; Besong, David Tabot; Rowe, Arthur J.; Heinze, Thomas; Harding, Stephen E.

2014-01-01

Unusual protein-like, partially reversible associative behaviour has recently been observed in solutions of the water soluble carbohydrates known as 6-deoxy-6-(ω-aminoalkyl)aminocelluloses, which produce controllable self-assembling films for enzyme immobilisation and other biotechnological applications. Now, for the first time, we have found a fully reversible self-association (tetramerisation) within this family of polysaccharides. Remarkably these carbohydrate tetramers are then seen to associate further in a regular way into supra-molecular complexes. Fully reversible oligomerisation has been hitherto completely unknown for carbohydrates and instead resembles in some respects the assembly of polypeptides and proteins like haemoglobin and its sickle cell mutation. Our traditional perceptions as to what might be considered ``protein-like'' and what might be considered as ``carbohydrate-like'' behaviour may need to be rendered more flexible, at least as far as interaction phenomena are concerned.

Comparison of the distribution of large magmatic centers on Earth, Venus, and Mars

NASA Technical Reports Server (NTRS)

Crumpler, L. S.

1993-01-01

Volcanism is widely distributed over the surfaces of the major terrestrial planets: Venus, Earth, and Mars. Anomalous centers of magmatic activity occur on each planet and are characterized by evidence for unusual concentrations of volcanic centers, long-lived activity, unusual rates of effusion, extreme size of volcanic complexes, compositionally unusual magmatism, and evidence for complex geological development. The purpose of this study is to compare the characteristics and distribution of these magmatic anomalies on Earth, Venus, and Mars in order to assess these characteristics as they may relate to global characteristics and evolution of the terrestrial planets.

Injection tube differentiation in gun cells of a haptoglossa species which infects nematodes

PubMed

Beakes; Glockling

1998-06-01

The gun cells which develop from germinating cysts in Haptoglossa produce a specialized infection apparatus, the injection tube. Upon eversion this tube fires a missile-like projectile which penetrates the host cuticle and then forms an infective sporidium within the body cavity of the nematode host. The temporal assembly of this complex cell organelle has been determined by serial-section reconstructions of maturing gun cells in a previously undescribed Haptoglossa species. The differentiation of the partially walled inverted injection tube is an unusual example of internal tube growth, in which membrane and wall assembly are temporally separated. There is no evidence that the shape of this inverted tube, which coils around the nucleus until it doubles back on itself, is dictated by the disposition of cytoplasmic microtubules. However, actin-like material was associated with the delimiting membrane of the differentiating tube, particularly in the regions of extension. From these studies it seems likely that the "head and buttress" structures previously depicted as the barbed tip of the "harpoon-like" penetration missile are part of a separate, structurally complex system which we suggest locks the "missile" into position in the invaginated injection tube. From this detailed account of cell architecture, models for the likely mechanism of infection cell firing are discussed, and unresolved questions relating to the cell biology and biochemistry of these complex organelles are highlighted. Copyright 1998 Academic Press.

Feasibility of Mating Disruption for Agricultural Pest Eradication in an Urban Environment: Light Brown Apple Moth (Lepidoptera: Tortricidae) in Perth.

PubMed

Soopaya, Rajendra; Woods, Bill; Lacey, Ian; Virdi, Amandip; Mafra-Neto, Agenor; Suckling, David Maxwell

2015-08-01

Eradication technologies are needed for urban and suburban situations, but may require different technologies from pest management in agriculture. We investigated mating disruption of a model moth species recently targeted for eradication in Californian cities, by applying dollops of SPLAT releasing a two-component sex pheromone of the light brown apple moth in 2-ha plots in low-density residential Perth, Australia. The pheromone technology was applied manually at ∼1.5 m height to street and garden trees, scrubs, and walls at 500 dollops per hectare of 0.8 g containing ∼80 mg active two-component pheromone. Catches of male moths were similar among all plots before treatment, but in treated areas (six replicates) pheromone trap catches were substantially reduced for up to 29 wk posttreatment, compared with untreated control plot catches (three replicates). The treatment with pheromone reduced catch to virgin females by 86% (P < 0.001) and reduced the occurrence of mating by 93%, compared with three equivalent untreated control plot catches (P < 0.001). Eradication programs are following an upward trend with globalization and the spread of invasive arthropods, which are often first detected in urban areas. Eradication requires a major increase in the communication distance between individuals, but this can be achieved using sex pheromone-based mating disruption technology, which is very benign and suitable for sensitive environments. The need for new socially acceptable tools for eradication in urban environments is likely to increase because of increasing need for eradications. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Driven to extinction? The ethics of eradicating mosquitoes with gene-drive technologies.

PubMed

Pugh, Jonathan

2016-09-01

Mosquito-borne diseases represent a significant global disease burden, and recent outbreaks of such diseases have led to calls to reduce mosquito populations. Furthermore, advances in 'gene-drive' technology have raised the prospect of eradicating certain species of mosquito via genetic modification. This technology has attracted a great deal of media attention, and the idea of using gene-drive technology to eradicate mosquitoes has been met with criticism in the public domain. In this paper, I shall dispel two moral objections that have been raised in the public domain against the use of gene-drive technologies to eradicate mosquitoes. The first objection invokes the concept of the 'sanctity of life' in order to claim that we should not drive an animal to extinction. In response, I follow Peter Singer in raising doubts about general appeals to the sanctity of life, and argue that neither individual mosquitoes nor mosquitoes species considered holistically are appropriately described as bearing a significant degree of moral status. The second objection claims that seeking to eradicate mosquitoes amounts to displaying unacceptable degrees of hubris. Although I argue that this objection also fails, I conclude by claiming that it raises the important point that we need to acquire more empirical data about, inter alia, the likely effects of mosquito eradication on the ecosystem, and the likelihood of gene-drive technology successfully eradicating the intended mosquito species, in order to adequately inform our moral analysis of gene-drive technologies in this context. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step

PubMed Central

Ninagawa, Satoshi; Okada, Tetsuya; Sumitomo, Yoshiki; Kamiya, Yukiko; Kato, Koichi; Horimoto, Satoshi; Ishikawa, Tokiro; Takeda, Shunichi; Sakuma, Tetsushi; Yamamoto, Takashi

2014-01-01

Glycoproteins misfolded in the endoplasmic reticulum (ER) are subjected to ER-associated glycoprotein degradation (gpERAD) in which Htm1-mediated mannose trimming from the oligosaccharide Man8GlcNAc2 to Man7GlcNAc2 is the rate-limiting step in yeast. In contrast, the roles of the three Htm1 homologues (EDEM1/2/3) in mammalian gpERAD have remained elusive, with a key controversy being whether EDEMs function as mannosidases or as lectins. We therefore conducted transcription activator-like effector nuclease–mediated gene knockout analysis in human cell line and found that all endogenous EDEMs possess mannosidase activity. Mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 is performed mainly by EDEM3 and to a lesser extent by EDEM1. Most surprisingly, the upstream mannose trimming from Man9GlcNAc2 to Man8GlcNAc2 is conducted mainly by EDEM2, which was previously considered to lack enzymatic activity. Based on the presence of two rate-limiting steps in mammalian gpERAD, we propose that mammalian cells double check gpERAD substrates before destruction by evolving EDEM2, a novel-type Htm1 homologue that catalyzes the first mannose trimming step from Man9GlcNAc2. PMID:25092655

[Role of the National Poliovirus Laboratory for the Program of eradication and poliomyelitis surveillance].

PubMed

Trallero, Gloria; Cabrerizo, María; Avellón, Ana

2013-01-01

The Spanish acute flaccid paralysis surveillance network is coordinated by the National Poliovirus Laboratory (NPL), which, since 1998, carries out polioviruses (PV) and other enteroviruses detected characterization by cell culture and molecular techniques. A total of 110,725 (70046+40679) samples were studied between 1998-2012 and enteroviruses were detected in 8% of these. Among these enteroviruses 241 PV were characterized as PV Sabin-like, except samples belong to an imported poliomyelitis case, all of which were characterised as vaccine derived PV type 2. The NPL has carried out the serotyping and the intratypic differentiation of all the isolated PV in Spain of any syndrome. It is shown that wild PV has not circulated in our country during the 15 years studied and that has led to the signing of the Act of the "eradication of poliomyelitis in Spain" by WHO in 2001, and the /"certification of the eradication of wild PV free for European countries" on 21 June 2002. Currently only 3 countries have endemic transmission of wild PV (Pakistan, Afghanistan and Nigeria). Until a complete worldwide eradication, was achieved, Spain will actively continue to participate in the maintenance of the poliomyelitis eradication infrastructure by monitoring and vaccination as well as the wild PV containment plan to avoid the spread of wild PV.

Unusual CoS2 ellipsoids with anisotropic tube-like cavities and their application in supercapacitors.

PubMed

Zhang, Lei; Wu, Hao Bin; Lou, Xiong Wen

2012-07-14

Unusual CoS(2) ellipsoids with anisotropic tube-like cavities have been synthesized from the simultaneous thermal decomposition and sulfidation of a preformed cobalt carbonate precursor. The as-prepared CoS(2) ellipsoids show interesting supercapacitive properties with high capacitance and good cycling performance.

Measles with a possible 23 day incubation period.

PubMed

Fitzgerald, Tove L; Durrheim, David N; Merritt, Tony D; Birch, Christopher; Tran, Thomas

2012-09-30

Measles virus (MV) eradication is biologically, technically and operationally feasible. An essential feature in understanding the chain of MV transmission is its incubation period, that is, the time from infection to the onset of symptoms. This period is important for determining the likely source of infection and directing public health measures to interrupt ongoing transmission. Long measles incubation periods have rarely been documented in the literature. We report on a previously healthy 11-year-old Australian boy who was confirmed with measles genotype D9 infection following travel in the Philippines. Epidemiological evidence supported an unusually long incubation period of at least 23 days and virological evidence was consistent with this finding. Although public health control measures such as post exposure prophylaxis, isolation and surveillance of susceptible individuals should continue to be based on the more common incubation period, a longer incubation period may occasionally explain an unexpected measles case. This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.

Endodontic management of an unusual maxillary first molar with a single buccal root.

PubMed

Nayak, Gurudutt; Dahiya, Surya; Singh, Inderpreet; Mohammad, Faiz Hasan

2014-05-01

The aim of this clinical article is to describe the unusual anatomy that was detected in a maxillary first molar during routine endodontic treatment. Variation in Root and Root canal morphology especially in multirooted teeth presents a constant challenge for a clinician in their detection and management. The literature is replete with cases that have extra canal or Root but cases with fused Root and fewer numbers of canals are sparse. This case report describes the endodontic management of one such unusual case of maxillary first molar presenting with a single fused buccal and a palatal Root. The confirmatory diagnosis of this morphologic aberration was done with the help of spiral computerized tomography, which revealed that the contralateral tooth also had a similar morphology. Dental practitioners should always be aware of the fact that abnormalities need not be in form of extra Roots or Root canals; anomalies can also be in form of fewer number of Roots or Root canals. A thorough knowledge of the complexities and variations of the Root canal system would help in avoiding some of the common iatrogenic access opening errors like perforations and excessive tooth removal caused during the search for the missing or extracanal.

Logistics of Guinea Worm Disease Eradication in South Sudan

PubMed Central

Jones, Alexander H.; Becknell, Steven; Withers, P. Craig; Ruiz-Tiben, Ernesto; Hopkins, Donald R.; Stobbelaar, David; Makoy, Samuel Yibi

2014-01-01

From 2006 to 2012, the South Sudan Guinea Worm Eradication Program reduced new Guinea worm disease (dracunculiasis) cases by over 90%, despite substantial programmatic challenges. Program logistics have played a key role in program achievements to date. The program uses disease surveillance and program performance data and integrated technical–logistical staffing to maintain flexible and effective logistical support for active community-based surveillance and intervention delivery in thousands of remote communities. Lessons learned from logistical design and management can resonate across similar complex surveillance and public health intervention delivery programs, such as mass drug administration for the control of neglected tropical diseases and other disease eradication programs. Logistical challenges in various public health scenarios and the pivotal contribution of logistics to Guinea worm case reductions in South Sudan underscore the need for additional inquiry into the role of logistics in public health programming in low-income countries. PMID:24445199

Logistics of Guinea worm disease eradication in South Sudan.

PubMed

Jones, Alexander H; Becknell, Steven; Withers, P Craig; Ruiz-Tiben, Ernesto; Hopkins, Donald R; Stobbelaar, David; Makoy, Samuel Yibi

2014-03-01

From 2006 to 2012, the South Sudan Guinea Worm Eradication Program reduced new Guinea worm disease (dracunculiasis) cases by over 90%, despite substantial programmatic challenges. Program logistics have played a key role in program achievements to date. The program uses disease surveillance and program performance data and integrated technical-logistical staffing to maintain flexible and effective logistical support for active community-based surveillance and intervention delivery in thousands of remote communities. Lessons learned from logistical design and management can resonate across similar complex surveillance and public health intervention delivery programs, such as mass drug administration for the control of neglected tropical diseases and other disease eradication programs. Logistical challenges in various public health scenarios and the pivotal contribution of logistics to Guinea worm case reductions in South Sudan underscore the need for additional inquiry into the role of logistics in public health programming in low-income countries.

Non-microbial approach for Helicobacter pylori as faster track to prevent gastric cancer than simple eradication

PubMed Central

Park, Sang-Ho; Kangwan, Napapan; Park, Jong-Min; Kim, Eun-Hee; Hahm, Ki Baik

2013-01-01

Although the International Agency for Research on Cancer declared Helicobacter pylori (H. pylori) as a definite human carcinogen in 1994, the Japanese Society for Helicobacter Research only recently (February 2013) adopted the position that H. pylori infection should be considered as an indication for either amelioration of chronic gastritis or for decreasing gastric cancer mortality. Japanese researchers have found that H. pylori eradication halts progressive mucosal damage and that successful eradication in patients with non-atrophic gastritis most likely prevents subsequent development of gastric cancer. However, those who have already developed atrophic gastritis/gastric atrophy retain potential risk factors for gastric cancer. Because chronic perpetuated progression of H. pylori-associated gastric inflammation is associated with increased morbidity culminating in gastric carcinogenesis, a non-microbial approach to treatment that provides long-term control of gastric inflammation through nutrients and other interventions may be an effective way to decrease this morbidity. This non-microbial approach might represent a new form of prerequisite “rescue” therapy that provides a quicker path to the prevention of gastric cancer as compared to simple eradication. PMID:24379623

The UNUSUAL FLORAL ORGANS gene of Arabidopsis thaliana is an F-box protein required for normal patterning and growth in the floral meristem.

PubMed

Samach, A; Klenz, J E; Kohalmi, S E; Risseeuw, E; Haughn, G W; Crosby, W L

1999-11-01

Genetic and molecular studies have suggested that the UNUSUAL FLORAL ORGANS (UFO) gene, from Arabidopsis thaliana, is expressed in all shoot apical meristems, and is involved in the regulation of a complex set of developmental events during floral development, including floral meristem and floral organ identity. Results from in situ hybridization using genes expressed early in floral development as probes indicate that UFO controls growth of young floral primordia. Transgenic constructs were used to provide evidence that UFO regulates floral organ identity by activating or maintaining transcription of the class B organ-identity gene APETALA 3, but not PISTILLATA. In an attempt to understand the biochemical mode of action of the UFO gene product, we show here that UFO is an F-box protein that interacts with Arabidopsis SKP1-like proteins, both in the yeast two-hybrid system and in vitro. In yeast and other organisms both F-box proteins and SKP1 homologues are subunits of specific ubiquitin E3 enzyme complexes that target specific proteins for degradation. The protein selected for degradation by the complex is specified by the F-box proteins. It is therefore possible that the role of UFO is to target for degradation specific proteins controlling normal growth patterns in the floral primordia, as well as proteins that negatively regulate APETALA 3 transcription.

Epidemiology of yaws: an update

PubMed Central

Kazadi, Walter M; Asiedu, Kingsley B; Agana, Nsiire; Mitjà, Oriol

2014-01-01

Yaws, a neglected tropical disease, is targeted for eradication by 2020 through large-scale mass-treatment programs of endemic communities. A key determinant for the success of the eradication campaign is good understanding of the disease epidemiology. We did a review of historical trends and new information from endemic countries, with the aim of assessing the state of knowledge on yaws disease burden. Transmission of yaws is now present in Africa, Asia, and the South Pacific. At least 12 countries are known to harbor yaws cases and 21 to 42 million people live in endemic areas. Between 2008 and 2012 more than 300,000 new cases were reported to the World Health Organization. Yaws presented high geographical variation within a country or region, high seasonality for incidence of active disease, and evidence that low standards of hygiene predispose to suffering of the disease. Key data issues include low levels of reporting, potential misdiagnosis, and scarce documentation on prevalence of asymptomatic infections. Currently available data most likely underestimates the magnitude of the disease burden. More effort is needed in order to refine accuracy of data currently being reported. A better characterization of the epidemiology of yaws globally is likely to positively impact on planning and implementation of yaws eradication. PMID:24729728

Magnetic vortex excitation as spin torque oscillator and its unusual trajectories

NASA Astrophysics Data System (ADS)

Natarajan, Kanimozhi; Muthuraj, Ponsudana; Rajamani, Amuda; Arumugam, Brinda

2018-05-01

We report an interesting observation of unusual trajectories of vortex core oscillations in a spin valve pillar. Micromagnetic simulation in the composite free layer spin valve nano-pillar shows magnetic vortex excitation under critical current density. When current density is slightly increased and wave vector is properly tuned, for the first time we observe a star like and square gyration. Surprisingly this star like and square gyration also leads to steady, coherent and sustained oscillations. Moreover, the frequency of gyration is also very high for this unusual trajectories. The power spectral analysis reveals that there is a marked increase in output power and frequency with less distortions. Our investigation explores the possibility of these unusual trajectories to exhibit spin torque oscillations.

Nuclear factor 90 uses an ADAR2-like binding mode to recognize specific bases in dsRNA.

PubMed

Jayachandran, Uma; Grey, Heather; Cook, Atlanta G

2016-02-29

Nuclear factors 90 and 45 (NF90 and NF45) form a protein complex involved in the post-transcriptional control of many genes in vertebrates. NF90 is a member of the dsRNA binding domain (dsRBD) family of proteins. RNA binding partners identified so far include elements in 3' untranslated regions of specific mRNAs and several non-coding RNAs. In NF90, a tandem pair of dsRBDs separated by a natively unstructured segment confers dsRNA binding activity. We determined a crystal structure of the tandem dsRBDs of NF90 in complex with a synthetic dsRNA. This complex shows surprising similarity to the tandem dsRBDs from an adenosine-to-inosine editing enzyme, ADAR2 in complex with a substrate RNA. Residues involved in unusual base-specific recognition in the minor groove of dsRNA are conserved between NF90 and ADAR2. These data suggest that, like ADAR2, underlying sequences in dsRNA may influence how NF90 recognizes its target RNAs. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Particular Oceanic Core Complex evolution in an extremely low melt supply environment

NASA Astrophysics Data System (ADS)

Maia, M.; Vincent, C.; Briais, A.; Brunelli, D.; Ligi, M.; Adrião, Á.; Sichel, S. E.

2017-12-01

Saint Paul is a major transform system in the Equatorial Mid-Atlantic Ridge. It consists of four transform faults and three short intra-transform ridge segments. This study focuses on peridotitic and gabbroic ridges and unusual Oceanic Core Complex (OCC)-related tectonics found at the St. Paul southern intra-transform segment. These structures display the same characters as the OCCs worldwide (termination, rafted blocks, corrugations, breakaway); however unusual features suggest that they have evolved in a particular way with respect to other OCCs along the Mid-Atlantic Ridge. Small ridge segments display an asymmetrical accretion through successive nucleations of detachment faults over more than 10 m.y. marked by crustal mylonitisation (Adrião et al., this session). Structural mapping and gravity models covering about 100 km on each ridge flank confirm the existence of four consecutive detachments, the more recent being still active, and provide an interpretative model of their spatiotemporal evolution. The unusual aspect is that each detachment appears to have been split on the two sides of the ridge axis. As a consequence, the breakaways are located on the American plate, while the conjugate terminations are drafted away on the African plate. We suggest that this unusual feature results from the rupture of the detachment surfaces by relocation of the ridge axis through westward small ridge jumps. This mode of expansion is somehow intermediate between the "normal" OCCs spreading and the Smooth Seafloor-type model described off-axis along the Southwest Indian Ridge (Sauter et al., 2013). It partly compensates the long-term asymmetric expansion of this ridge segment and is likely related to the extremely low melt supply and thick lithosphere inferred from other studies. Adrião et al., 2017. Mechanical mixing and metamorphism of mafic and ultramafic lithologies .... This Session Sauter et al., 2013. Continuous exhumation of mantle-derived rocks… Nat Geo, 2013

Eradication of bovine tuberculosis at a herd-level in Madrid, Spain: study of within-herd transmission dynamics over a 12 year period

PubMed Central

2012-01-01

Background Eradication of bovine tuberculosis (bTB) through the application of test-and-cull programs is a declared goal of developed countries in which the disease is still endemic. Here, longitudinal data from more than 1,700 cattle herds tested during a 12 year-period in the eradication program in the region of Madrid, Spain, were analyzed to quantify the within-herd transmission coefficient (β) depending on the herd-type (beef/dairy/bullfighting). In addition, the probability to recover the officially bTB free (OTF) status in infected herds depending on the type of herd and the diagnostic strategy implemented was assessed using Cox proportional hazard models. Results Overall, dairy herds showed higher β (median 4.7) than beef or bullfighting herds (2.3 and 2.2 respectively). Introduction of interferon-gamma (IFN-γ) as an ancillary test produced an apparent increase in the β coefficient regardless of production type, likely due to an increase in diagnostic sensitivity. Time to recover OTF status was also significantly lower in dairy herds, and length of bTB episodes was significantly reduced when the IFN-γ was implemented to manage the outbreak. Conclusions Our results suggest that bTB spreads more rapidly in dairy herds compared to other herd types, a likely cause being management and demographic-related factors. However, outbreaks in dairy herds can be controlled more rapidly than in typically extensive herd types. Finally, IFN-γ proved its usefulness to rapidly eradicate bTB at a herd-level. PMID:22748007

Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice.

PubMed

Pajic, Marina; Blatter, Sohvi; Guyader, Charlotte; Gonggrijp, Maaike; Kersbergen, Ariena; Küçükosmanoğlu, Aslι; Sol, Wendy; Drost, Rinske; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

2017-11-15

Purpose: We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse. Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53 -mutant breast cancer. Because of the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs. To characterize the cell-cycle stage from which Brca1 -/- ;p53 -/- mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell-cycle indicator (FUCCI) construct into the tumor cells. Results: Despite repeated sensitivity to the MTD of platinum drugs, the Brca1 -mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G 0 -like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA-crosslinking agent nimustine, resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our in vivo finding that the nimustine MTD, among several alkylating agents, is the most effective in eradicating Brca1 -mutated mouse mammary tumors. Conclusions: Our data show that targeting G 0 -like cells is crucial for the eradication of BRCA1/p53-deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine. Clin Cancer Res; 23(22); 7020-33. ©2017 AACR . ©2017 American Association for Cancer Research.

ABC triblock copolymer vesicles with mesh-like morphology.

PubMed

Zhao, Wei; Chen, Dian; Hu, Yunxia; Grason, Gregory M; Russell, Thomas P

2011-01-25

Polymer vesicles made from poly(isoprene-b-styrene-b-2-vinyl pyridine) (PI-b-PS-b-P2VP) triblock copolymer confined within the nanopores of an anodic aluminum oxide (AAO) membrane are studied. It was found that these vesicles have well-defined, nanoscopic size, and complex microphase-separated hydrophobic membranes, comprised of the PS and PI blocks, while the coronas are formed by the P2VP block. Vesicle formation was tracked using both transmission and scanning electron microscopy. A mesh-like morphology formed in the membrane at a well-defined composition of the three blocks that can be tuned by changing the copolymer composition. The nanoscale confinement, copolymer composition, and subtle molecular interactions contribute to the generation of these vesicles with such unusual morphologies.

The Mysteries and Curiosities of Mars: A Tour of Unusual and Unexplained Terrains

NASA Astrophysics Data System (ADS)

Kerber, L.

2017-12-01

The large amount of data available from orbiting satellites around Mars has provided a wealth of information about the Martian surface and geological history. The published literature tends to focus on regions of Mars for which there are ready explanations; however, many regions of Mars remain mysterious. In this contribution, we present some of the strangest and least explained terrains on Mars: The Taffy Terrain: This complex terrain, consisting of swirling layers with variably sized bands, is present mostly at the bottom of Hellas Basin, but versions of it can also be found on the floor of Melas Chasma and in the Medusae Fossae Formation near Apollinaris Sulci. While little has been written about the taffy terrain, hypotheses include "glacial features" and salt domes. The taffy terrain bears some resemblance to submarine salt domes in the Gulf of Mexico, glacial deposits with mixed ash and ice in Iceland, or chalk formations in Egypt's White Desert. The Fishscale Terrain: At the northern edge of Lucus Planum, the friable Medusae Fossae Formation transitions into a chaos-like terrain with hundreds of mesas forming a pattern like the scales of a fish. While chaos terrains are mysterious in general, this morphologically fresh, near-equatorial chaos is especially unusual. Polygonal Ridges in Gordii Dorsum: Also a part of the Medusae Fossae Formation, the ridges in Gordii Dorsum represent a negative image of the fishscale terrain—a intricate lattice of slender black ridges. These are thought to form via the embayment of the fishscale terrain with lava and the subsequent erosion of the original mesas. Horseshoe Features: These geomorphological features look like inverted barchan dunes, but they are actually pits eroded into the surface of the Medusae Fossae Formation. Channels surrounding Elysium Mons: These channel systems are among the most complex on Mars, but they appear on a young Amazonian lava surface. The channels cut through topography, anastomose, and create streamlined islands. Strange flows around cones: Some rootless cones in Cerberus Palus have unusual flows coming out of them. Possible hypotheses include lava or mudflows. Sinus Meridiani: This region is host to arcuate ridge lattices, circular mesas with concentric patterns, and straight, subparallel ridges, similar to other ridges found near the South Pole.

Mice deficient for ERAD machinery component Sel1L develop central diabetes insipidus.

PubMed

Bichet, Daniel G; Lussier, Yoann

2017-10-02

Deficiency of the antidiuretic hormone arginine vasopressin (AVP) underlies diabetes insipidus, which is characterized by the excretion of abnormally large volumes of dilute urine and persistent thirst. In this issue of the JCI, Shi et al. report that Sel1L-Hrd1 ER-associated degradation (ERAD) is responsible for the clearance of misfolded pro-arginine vasopressin (proAVP) in the ER. Additionally, mice with Sel1L deficiency, either globally or specifically within AVP-expressing neurons, developed central diabetes insipidus. The results of this study demonstrate a role for ERAD in neuroendocrine cells and serve as a clinical example of the effect of misfolded ER proteins retrotranslocated through the membrane into the cytosol, where they are polyubiquitinated, extracted from the ER membrane, and degraded by the proteasome. Moreover, proAVP misfolding in hereditary central diabetes insipidus likely shares common physiopathological mechanisms with proinsulin misfolding in hereditary diabetes mellitus of youth.

Crystal structure of the human 4-1BB/4-1BBL complex.

PubMed

Gilbreth, Ryan N; Oganesyan, Vaheh Y; Amdouni, Hamza; Novarra, Shabazz; Grinberg, Luba; Barnes, Arnita; Baca, Manuel

2018-05-02

4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4 Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

A rectangular Ni-Fe cluster with unusual cyanide bridges.

PubMed

Krüger, Christoph; Sato, Hiroki; Matsumoto, Takuto; Shiga, Takuya; Newton, Graham N; Renz, Franz; Oshio, Hiroki

2012-10-07

An asymmetric polycyanide iron complex, K(2)[Fe(III)(L1)(CN)(4)](MeOH) (HL1 = 2,2'-(1H-pyrazole-3,5-diyl)bis-pyridine), was synthesized and its complexation compatibility with nickel ions was examined. Two kinds of enantiomeric nickel-iron squares were obtained in the presence of a chiral bidentate capping ligand. The compounds display unusual cyanide bridge geometry and have ferromagnetic interactions between nickel and iron ions.

Steady progress toward a malaria vaccine.

PubMed

Lyke, Kirsten E

2017-10-01

Great progress has been made in reducing malaria morbidity and mortality, yet the parasite continues to cause a startling 200 million infections and 500 000 deaths annually. Malaria vaccine development is pushing new boundaries by steady advancement toward a licensed product. Despite 50 years of research, the complexity of Plasmoidum falciparum confounds all attempts to eradicate the organism. This very complexity has pushed the boundaries of vaccine development to new heights, yet it remains to be seen if an affordable vaccine can provide durable and high-level protection. Novel vaccines such as RTS,S/AS01E are on the edge of licensure, but old techniques have resurged with the ability to deliver vialed, whole organism vaccines. Novel adjuvants, multistage/multiantigen approaches and transmission blocking vaccines all contribute to a multipronged battle plan to conquer malaria. Vaccines are the most cost-effective tools to control infectious diseases, yet the complexity of malaria has frustrated all attempts to develop an effective product. This review concentrates on recent advances in malaria vaccine development that lend hope that a vaccine can be produced and malaria eradicated.

Contain or eradicate? Optimizing the management goal for Australian acacia invasions in the face of uncertainty

USGS Publications Warehouse

Moore, J.L.; Runge, M.C.; Webber, B.L.; Wilson, J.R.U.

2011-01-01

Aim To identify whether eradication or containment is expected to be the most cost-effective management goal for an isolated invasive population when knowledge about the current extent is uncertain. Location Global and South Africa. Methods We developed a decision analysis framework to analyse the best management goal for an invasive species population (eradication, containment or take no action) when knowledge about the current extent is uncertain. We used value of information analysis to identify when investment in learning about the extent will improve this decision-making and tested the sensitivity of the conclusions to different parameters (e.g. spread rate, maximum extent, and management efficacy and cost). The model was applied to Acacia paradoxa DC, an Australian shrub with an estimated invasive extent of 310ha on Table Mountain, South Africa. Results Under the parameters used, attempting eradication is cost-effective for infestations of up to 777ha. However, if the invasion extent is poorly known, then attempting eradication is only cost-effective for infestations estimated as 296ha or smaller. The value of learning is greatest (maximum of 8% saving) when infestation extent is poorly known and if it is close to the maximum extent for which attempting eradication is optimal. The optimal management action is most sensitive to the probability that the action succeeds (which depends on the extent), with the discount rate and cost of management also important, but spread rate less so. Over a 20-year time-horizon, attempting to eradicate A. paradoxa from South Africa is predicted to cost on average ZAR 8 million if the extent is known, and if our current estimate is poor, ZAR 33.6 million as opposed to ZAR 32.8 million for attempting containment. Main conclusions Our framework evaluates the cost-effectiveness of attempting eradication or containment of an invasive population that takes uncertainty in population extent into account. We show that incorporating uncertainty in the analysis avoids overly optimistic beliefs about the effectiveness of management enabling better management decisions. For A. paradoxa in South Africa, attempting to eradicate is likely to be cost-effective, particularly if resources are allocated to better understand and improve management efficacy. ?? 2011 Blackwell Publishing Ltd.

Effect on time in quarantine of the choice of program for eradication of footrot from 196 sheep flocks in southern New South Wales.

PubMed

Mills, K; McClenaughan, P; Morton, A; Alley, D; Lievaart, J; Windsor, P A; Egerton, J R

2012-01-01

To identify and compare programs for eradicating virulent footrot (VFR) chosen by owners of quarantined sheep flocks in southern New South Wales. Data from 196 sheep flocks in the Wagga Wagga and Young Rural Lands Protection Boards were used to determine the program chosen, the influence of flock size on the program chosen and the effects of the program chosen and the use of contractors on the time in quarantine. The most popular programs in flocks using a single program were: total destocking (61/173; 35.3%) and inspection and culling of affected animals (71/173; 41.0%). Treatment of known infected animals was chosen in 41 flocks and of those, 10 (5.8%) used antibiotics for treatment and 31 (17.9%) used foot-bathing. Combined programs were used in 23 flocks and in 10 flocks a change of program occurred before eradication was achieved. The choice of program was, to some extent, affected by flock size, with owners of small flocks (<500 sheep) more likely to destock. The chosen program strongly influenced the time in quarantine, the shortest time being for destocking (mean 284 days), followed by culling of infected sheep (395 days), treatment with antibiotics (433 days) and finally foot-bathing (502 days). Time in quarantine was significantly shorter when contractors were used. All the options chosen led to the eradication of VFR. However, in this sample both the choice of program and the use of contractors influenced the time taken to achieve eradication and therefore the time in quarantine. Based on time in quarantine, foot-bathing was the least desirable option for the eradication of VFR because of the significantly greater time involved, perpetuation of risk to neighbours and increased cost of inspections. These findings were derived from flocks that were quarantined, but they are relevant to all flock owners considering eradication of VFR. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

A win for the patient: Direct patient notification improves treatment rates of active Helicobacter pylori infection.

PubMed

Selvaratnam, Sriharan; Yeoh, Joey; Hsiang, John; Patrick, Alasdair B

2014-01-01

Current international guidelines recommend the commencement of effective eradication therapy as soon as active Helicobacter pylori (H. pylori) infection is confirmed. At our institution, all positive Campylobacter-like Organism (CLO) test results were automatically communicated to general practitioners (GPs) via a standardised letter, which also advised the commencement of eradication therapy. Despite this endeavour, a clinical audit conducted in 2011 demonstrated that only 66 per cent of confirmed H. pylori-positive South Auckland patients received eradication treatment and only 83 per cent of these patients received treatment within one month. Improve the timely initiation of H. pylori eradication therapy through direct patient notification. A prospective clinical audit of 109 consecutive outpatients with a positive CLO test identified at gastroscopy. In addition to standard general practitioner notification, patients were also directly notified of their positive CLO test result via a standardised letter, which provided information about H. pylori and its disease associations as well as advising patients to seek consultation with their GP to commence eradication therapy. Dispensing data was examined using Test Safe electronic records to determine the total uptake and timing of treatment compared to data from a preliminary 2011 audit. Ninety-five per cent of H. pylori-positive patients received standard triple therapy; therefore, treatment of active H. pylori infection was significantly higher when patients were directly notified in addition to standard GP notification, when compared to GP notification alone (95 per cent vs 66 per cent, p<0.001). All patients who received eradication therapy did so within one month of notification, a significant improvement compared to data from the previous audit in 2011 (100 per cent vs. 83 per cent, p<0.001). Direct patient notification using a standardised letter is a simple and economical strategy that significantly improves the timely initiation of eradication therapy for active H. pylori infection. This has since been integrated into standard practice at our District Health Board (DHB).

Identification of SNPs associated with variola virus virulence.

PubMed

Hoen, Anne Gatewood; Gardner, Shea N; Moore, Jason H

2013-02-14

Decades after the eradication of smallpox, its etiological agent, variola virus (VARV), remains a threat as a potential bioweapon. Outbreaks of smallpox around the time of the global eradication effort exhibited variable case fatality rates (CFRs), likely attributable in part to complex viral genetic determinants of smallpox virulence. We aimed to identify genome-wide single nucleotide polymorphisms associated with CFR. We evaluated unadjusted and outbreak geographic location-adjusted models of single SNPs and two- and three-way interactions between SNPs. Using the data mining approach multifactor dimensionality reduction (MDR), we identified five VARV SNPs in models significantly associated with CFR. The top performing unadjusted model and adjusted models both revealed the same two-way gene-gene interaction. We discuss the biological plausibility of the influence of the SNPs identified these and other significant models on the strain-specific virulence of VARV. We have identified genetic loci in the VARV genome that are statistically associated with VARV virulence as measured by CFR. While our ability to infer a causal relationship between the specific SNPs identified in our analysis and VARV virulence is limited, our results suggest that smallpox severity is in part associated with VARV strain variation and that VARV virulence may be determined by multiple genetic loci. This study represents the first application of MDR to the identification of pathogen gene-gene interactions for predicting infectious disease outbreak severity.

Identification of SNPs associated with variola virus virulence

PubMed Central

2013-01-01

Background Decades after the eradication of smallpox, its etiological agent, variola virus (VARV), remains a threat as a potential bioweapon. Outbreaks of smallpox around the time of the global eradication effort exhibited variable case fatality rates (CFRs), likely attributable in part to complex viral genetic determinants of smallpox virulence. We aimed to identify genome-wide single nucleotide polymorphisms associated with CFR. We evaluated unadjusted and outbreak geographic location-adjusted models of single SNPs and two- and three-way interactions between SNPs. Findings Using the data mining approach multifactor dimensionality reduction (MDR), we identified five VARV SNPs in models significantly associated with CFR. The top performing unadjusted model and adjusted models both revealed the same two-way gene-gene interaction. We discuss the biological plausibility of the influence of the SNPs identified these and other significant models on the strain-specific virulence of VARV. Conclusions We have identified genetic loci in the VARV genome that are statistically associated with VARV virulence as measured by CFR. While our ability to infer a causal relationship between the specific SNPs identified in our analysis and VARV virulence is limited, our results suggest that smallpox severity is in part associated with VARV strain variation and that VARV virulence may be determined by multiple genetic loci. This study represents the first application of MDR to the identification of pathogen gene-gene interactions for predicting infectious disease outbreak severity. PMID:23410064

Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

PubMed Central

Liu, Kai Y.; Du, Fang C.; Fu, Qiang; Zhang, Wei J.; Sun, Hong W.; Zhang, Yi; Gan, Le L.; Yue, Zhi Y.

2014-01-01

This study examined the efficacy and pharmacological mechanism of pronase-assisted low-dose antibiotics for eradication of Helicobacter pylori. Mongolian gerbils infected with H. pylori received 7-day treatment (omeprazole, different concentrations of pronase, amoxicillin, and clarithromycin), and the efficacy was assessed using the eradication rate and the colonization of H. pylori. In Mongolian gerbils orally administered pronase, the thickness of the gastric mucous layer (GML) was examined using immunohistochemical and alcian blue staining, and the concentrations of amoxicillin in gastric tissue and serum were detected using high-performance liquid chromatography (HPLC). The eradication rates were 80.0% (12/15) in the high-pronase quadruple group (HPQG) and 86.7% (13/15) in the high-antibiotic group (HAG) (P = 1.000). The antibiotic dose in the HPQG was only 1/20 that in the HAG. Thirty minutes after oral treatment with pronase, the sticky protein of the GML was hydrolyzed, and the GML became thinner. Higher amoxicillin concentrations in both the gastric tissue and serum were observed in the pronase group than in the Am10 group. The concentration of amoxicillin in the Am10-plus-Pr108 group in gastric tissue was 3.8 times higher than in the Am10 group in 5 min. Together, these data suggest that pronase significantly reduced the dose of antibiotics used in H. pylori eradication. The pharmacological mechanism is likely pronase removal of the mucus layer, promoting chemical factor (i.e., gastric acid and pepsinogen) distribution and increasing the antibiotic concentrations in the deep GML, which acted on H. pylori collectively. Thus, pronase may enhance the level of antibiotics for eradication of H. pylori in the clinic. PMID:24687504

Introduction: the goals of antimicrobial therapy.

PubMed

Song, Jae-Hoon

2003-03-01

Antimicrobial agents are generally evaluated in preclinical studies assessing in vitro activity, animal models demonstrating in vivo bacteriologic efficacy, and clinical trials primarily investigating safety and clinical efficacy. However, large sample sizes are required to detect any differences in outcomes between antimicrobials in clinical trials, and, generally, studies are powered to show only clinical equivalence. In addition, diagnosis is often based on clinical symptoms, rather than microbiological evidence of bacterial infection, and the patients most likely to have resistant pathogens are often excluded. Clinical efficacy can be achieved in some bacterial infections in which antimicrobials are suboptimal or even not prescribed. However, bacterial eradication maximizes clinical efficacy and may also reduce the development and spread of resistant organisms. The goal of antimicrobial therapy is, therefore, to eradicate bacteria at the site of infection. Bacterial eradication is not usually assessed as a primary endpoint within the limits of currently recommended clinical trial design. However, pharmacokinetic (PK) (serum concentration profiles, penetration to site of infection) and pharmacodynamic (PD) (susceptibility, concentration- versus time-dependent killing, post-antimicrobial effects) criteria can be used to predict bacteriologic efficacy. PK/PD predictions should be confirmed during all phases of antimicrobial development and throughout clinical use in response to changing patterns of resistance. A clear rationale for dose recommendations can be determined preclinically based on PK/PD parameters, and correlated with efficacy, safety and resistance endpoints in clinical trials. The duration of treatment and dose should be the shortest that will reliably eradicate the pathogen(s), and that is safe and well tolerated. Currently available agents vary significantly in their ability to achieve PK/PD parameters necessary for bacteriologic eradication. Recommendations for appropriate antimicrobial therapy should be based on PK/PD parameters, with the aim of achieving the maximum potential for eradication of both existing and emerging resistant pathogens.

Unusual thyroid carcinoma with excessive extracellular hyaline globules: a case of "hyalinizing papillary carcinoma".

PubMed

Kondo, Tetsuo; Nakazawa, Tadao; Terada, Nobuo; Nakazawa, Kumiko; Kawasaki, Tomonori; Mochizuki, Kunio; Yamane, Tetsu; Ohno, Shinichi; Katoh, Ryohei

2012-06-01

We present an unusual case of papillary thyroid carcinoma in a 47-year-old Japanese woman. The tumor, 0.8 cm in diameter, was located in the upper left lobe of the thyroid. Histologically, we observed a microfollicular-like and trabecular arrangement of the tumor cells with marked hyalinized stroma and hyaline globules. Immunohistochemically, tumor cells were positive for thyroglobulin and thyroid transcription factor 1. Hyaline stroma and globular bodies were immunopositive for laminin and type IV collagen. MIB-1 index was approximately 1% without membranous immunoreactivity. Under the electron microscope, hyaline stroma and globules showed electron-dense, complex meshwork structures composed of granular and fibrous elements similar to the structure of the lamina densa. Genetic analysis demonstrated a BRAF(V600E) mutation. Based on these findings, we diagnosed the present tumor as a rare morphological variation of papillary thyroid carcinoma with excessive hyaline globules consisting of basal membrane materials. Copyright © 2012 Elsevier Inc. All rights reserved.

Hoiamide A, a Sodium Channel Activator of Unusual Architecture from a Consortium of Two Papua New Guinea Cyanobacteria

PubMed Central

Pereira, Alban; Cao, Zhengyu; Murray, Thomas F.; Gerwick, William H.

2009-01-01

Summary Hoiamide A, a novel bioactive cyclic depsipeptide, was isolated from an environmental assemblage of the marine cyanobacteria Lyngbya majuscula and Phormidium gracile collected in Papua New Guinea. This stereochemically complex metabolite possesses a highly unusual structure which likely derives from a mixed peptide-polyketide biogenetic origin, and includes a peptidic section featuring an acetate extended and S-adenosyl methionine modified isoleucine moiety, a triheterocyclic fragment bearing two a-methylated thiazolines and one thiazole, as well as a highly oxygenated and methylated C15-polyketide substructure. Pure hoiamide A potently inhibited [3H]batrachotoxin binding to voltage-gated sodium channels (IC50 = 92.8 nM) and activated sodium influx (EC50 = 1.73 μM) in mouse neocortical neurons, as well as exhibited modest cytotoxicity to cancer cells. Further investigation revealed that hoiamide A is a partial agonist of site 2 on the voltage gated sodium channel. PMID:19716479

Nanotechnology approaches to eradicating HIV reservoirs.

PubMed

Cao, Shijie; Woodrow, Kim A

2018-06-04

The advent of combination antiretroviral therapy (cART) has transformed HIV-1 infection into a controllable chronic disease, but these therapies are incapable of eradicating the virus to bring about an HIV cure. Multiple strategies have been proposed and investigated to eradicate latent viral reservoirs from various biological sanctuaries. However, due to the complexity of HIV infection and latency maintenance, a single drug is unlikely to eliminate all HIV reservoirs and novel strategies may be needed to achieve better efficacy while limiting systemic toxicity. In this review, we describe HIV latency in cellular and anatomical reservoirs, and present an overview of current strategies for HIV cure with a focus on their challenges for clinical translation. We also provide a summary of nanotechnology solutions that have been used to address challenges in HIV cure by delivering physicochemically diverse agents for combination therapy or targeting HIV reservoir sites. We also review nanocarrier-based gene delivery and immunotherapy used in cancer treatment but may have potential applications in HIV cure. Copyright © 2018. Published by Elsevier B.V.

Current developments in bovine mastitis treatment and control.

PubMed

Wager, L A; Linquist, W E; Hayes, G L; Britten, A M; Whitehead, R G; Webster, D E; Barnes, F D

1978-01-01

Mastitis in its complexity has managed to forestall all efforts of eradication in spite of years of research, antibiotics and practical control measures. This minisymposium will touch on seven topics current to treatment and control of this economically important disease.

Hexavalent IPV-based combination vaccines for public-sector markets of low-resource countries

PubMed Central

Mahmood, Kutub; Pelkowski, Sonia; Atherly, Deborah; Sitrin, Robert; Donnelly, John J

2013-01-01

In anticipation of the successful eradication of wild polio virus, alternative vaccination strategies for public-sector markets of low-resource countries are extremely important, but are still under development. Following polio eradication, inactivated polio vaccine (IPV) would be the only polio vaccine available, and would be needed for early childhood immunization for several years, as maintenance of herd immunity will be important for sustaining polio eradication. Low-cost combination vaccines containing IPV could provide reliable and continuous immunization in the post-polio eradication period. Combination vaccines can potentially simplify complex pediatric routine immunization schedules, improve compliance, and reduce costs. Hexavalent vaccines containing Diphtheria (D), Tetanus (T), whole cell pertussis (wP), Hepatitis B (HBV), Haemophilus b (Hib) and the three IPV serotype antigens have been considered as the ultimate combination vaccine for routine immunization. This product review evaluates potential hexavalent vaccine candidates by composition, probable time to market, expected cost of goods, presentation, and technical feasibility and offers suggestions for development of low-cost hexavalent combination vaccines. Because there are significant technical challenges facing wP-based hexavalent vaccine development, this review also discusses other alternative approaches to hexavalent that could also ensure a timely and reliable supply of low-cost IPV based combination vaccines. PMID:23787559

Hexavalent IPV-based combination vaccines for public-sector markets of low-resource countries.

PubMed

Mahmood, Kutub; Pelkowski, Sonia; Atherly, Deborah; Sitrin, Robert D; Donnelly, John J

2013-09-01

In anticipation of the successful eradication of wild polio virus, alternative vaccination strategies for public-sector markets of low-resource countries are extremely important, but are still under development. Following polio eradication, inactivated polio vaccine (IPV) would be the only polio vaccine available, and would be needed for early childhood immunization for several years, as maintenance of herd immunity will be important for sustaining polio eradication. Low-cost combination vaccines containing IPV could provide reliable and continuous immunization in the post-polio eradication period. Combination vaccines can potentially simplify complex pediatric routine immunization schedules, improve compliance, and reduce costs. Hexavalent vaccines containing Diphtheria (D), Tetanus (T), whole cell pertussis (wP), Hepatitis B (HBV), Haemophilus b (Hib) and the three IPV serotype antigens have been considered as the ultimate combination vaccine for routine immunization. This product review evaluates potential hexavalent vaccine candidates by composition, probable time to market, expected cost of goods, presentation, and technical feasibility and offers suggestions for development of low-cost hexavalent combination vaccines. Because there are significant technical challenges facing wP-based hexavalent vaccine development, this review also discusses other alternative approaches to hexavalent that could also ensure a timely and reliable supply of low-cost IPV based combination vaccines.

Multiple E2 ubiquitin-conjugating enzymes regulate human cytomegalovirus US2-mediated immunoreceptor downregulation.

PubMed

van de Weijer, Michael L; Schuren, Anouk B C; van den Boomen, Dick J H; Mulder, Arend; Claas, Frans H J; Lehner, Paul J; Lebbink, Robert Jan; Wiertz, Emmanuel J H J

2017-09-01

Misfolded endoplasmic reticulum (ER) proteins are dislocated towards the cytosol and degraded by the ubiquitin-proteasome system in a process called ER-associated protein degradation (ERAD). During infection with human cytomegalovirus (HCMV), the viral US2 protein targets HLA class I molecules (HLA-I) for degradation via ERAD to avoid elimination by the immune system. US2-mediated degradation of HLA-I serves as a paradigm of ERAD and has facilitated the identification of TRC8 (also known as RNF139) as an E3 ubiquitin ligase. No specific E2 enzymes had previously been described for cooperation with TRC8. In this study, we used a lentiviral CRISPR/Cas9 library targeting all known human E2 enzymes to assess their involvement in US2-mediated HLA-I downregulation. We identified multiple E2 enzymes involved in this process, of which UBE2G2 was crucial for the degradation of various immunoreceptors. UBE2J2, on the other hand, counteracted US2-induced ERAD by downregulating TRC8 expression. These findings indicate the complexity of cellular quality control mechanisms, which are elegantly exploited by HCMV to elude the immune system. © 2017. Published by The Company of Biologists Ltd.

High-spin ribbons and antiferromagnetic ordering of a Mn(II)-biradical-Mn(II) complex.

PubMed

Fatila, Elisabeth M; Clérac, Rodolphe; Rouzières, Mathieu; Soldatov, Dmitriy V; Jennings, Michael; Preuss, Kathryn E

2013-09-11

A binuclear metal coordination complex of the first thiazyl-based biradical ligand 1 is reported (1 = 4,6-bis(1,2,3,5-dithiadiazolyl)pyrimidine; hfac =1,1,1,5,5,5,-hexafluoroacetylacetonato-). The Mn(hfac)2-biradical-Mn(hfac)2 complex 2 is a rare example of a discrete, molecular species employing a neutral bridging biradical ligand. It is soluble in common organic solvents and can be easily sublimed as a crystalline solid. Complex 2 has a spin ground state of S(T) = 4 resulting from antiferromagnetic coupling between the S(birad) = 1 biradical bridging ligand and two S(Mn) = 5/2 Mn(II) ions. Electrostatic contacts between atoms with large spin density promote a ferromagnetic arrangement of the moments of neighboring complexes in ribbon-like arrays. Weak antiferromagnetic coupling between these high-spin ribbons stabilizes an ordered antiferromagnetic ground state below 4.5 K. This is an unusual example of magnetic ordering in a molecular metal-radical complex, wherein the electrostatic contacts that direct the crystal packing are also responsible for providing an efficient exchange coupling pathway between molecules.

Transport mechanisms in Schottky diodes realized on GaN

NASA Astrophysics Data System (ADS)

Amor, Sarrah; Ahaitouf, Ali; Ahaitouf, Abdelaziz; Salvestrini, Jean Paul; Ougazzaden, Abdellah

2017-03-01

This work is focused on the conducted transport mechanisms involved on devices based in gallium nitride GaN and its alloys. With considering all conduction mechanisms of current, its possible to understanded these transport phenomena. Thanks to this methodology the current-voltage characteristics of structures with unusual behaviour are further understood and explain. Actually, the barrier height (SBH) is a complex problem since it depends on several parameters like the quality of the metal-semiconductor interface. This study is particularly interesting as solar cells are made on this material and their qualification is closely linked to their transport properties.

Unusual Presentation of Central Diabetes Insipidus in a Patient With Neurosarcoidosis.

PubMed

Sanghi, Vedha; Kapoor, Aanchal

2016-01-01

Hypernatremia is a frequent cause of intensive care unit admission. The patient presented in this article had hypernatremia refractory to D5W (dextrose 5% water) therapy, which led to a complex investigation. Workup revealed central diabetes insipidus most likely secondary to flare up of neurosarcoidosis. The challenge in terms of diagnosis was a presentation with low urine output in the setting of hypernatremia resistant to treatment with desmopressin. This case unfolded the role of hypothyroidism causing secondary renal dysfunction and hence needed continued treatment with thyroxine in addition to treatment for hypernatremia.

Structural and Functional Studies of WlbA: A Dehydrogenase Involved in the Biosynthesis of 2,3-Diacetamido-2,3-dideoxy-d-mannuronic Acid

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

Thoden, James B.; Holden, Hazel M.

2010-09-08

2,3-Diacetamido-2,3-dideoxy-D-mannuronic acid (ManNAc3NAcA) is an unusual dideoxy sugar first identified nearly 30 years ago in the lipopolysaccharide of Pseudomonas aeruginosa O:3a,d. It has since been observed in other organisms, including Bordetella pertussis, the causative agent of whooping cough. Five enzymes are required for the biosynthesis of UDP-ManNAc3NAcA starting from UDP-N-acetyl-D-glucosamine. Here we describe a structural study of WlbA, the NAD-dependent dehydrogenase that catalyzes the second step in the pathway, namely, the oxidation of the C-3{prime} hydroxyl group on the UDP-linked sugar to a keto moiety and the reduction of NAD{sup +} to NADH. This enzyme has been shown to usemore » {alpha}-ketoglutarate as an oxidant to regenerate the oxidized dinucleotide. For this investigation, three different crystal structures were determined: the enzyme with bound NAD(H), the enzyme in a complex with NAD(H) and {alpha}-ketoglutarate, and the enzyme in a complex with NAD(H) and its substrate (UDP-N-acetyl-D-glucosaminuronic acid). The tetrameric enzyme assumes an unusual quaternary structure with the dinucleotides positioned quite closely to one another. Both {alpha}-ketoglutarate and the UDP-linked sugar bind in the WlbA active site with their carbon atoms (C-2 and C-3{prime}, respectively) abutting the re face of the cofactor. They are positioned {approx}3 {angstrom} from the nicotinamide C-4. The UDP-linked sugar substrate adopts a highly unusual curved conformation when bound in the WlbA active site cleft. Lys 101 and His 185 most likely play key roles in catalysis.« less

Reproductive Ecology of the Giant African Snail in South Florida: Implications for Eradication Programs.

PubMed

Roda, Amy; Nachman, Gösta; Weihman, Scott; Yong Cong, Mary; Zimmerman, Fredrick

2016-01-01

Giant African snail (Achatina fulica (Bowdich, 1822)), an important invasive snail, was recently found in South Florida, USA. An extensive eradication effort was initiated consisting of pesticide applications, debris removal and hand collections. We studied the reproduction capacity and population dynamics of snails collected from 22 populations for two years to help evaluate the likely success of the eradication program. A total of 23,890 snails, ranging from 25-131 mm, were measured, dissected and the number of eggs in each snail counted. Gravid snails ranged from 48-128 mm. Only 5% of snails had eggs, which were found year round. As the snails increased in size, they were more likely to include reproducing individuals. However, the percentage of gravid snails peaked when snails were approximately 90 mm. Although more prevalent, small (<65 mm) adults contributed fewer eggs to the population than the larger snails. We evaluated the effect of control measures on six populations having >1000 adult snails and used data from the two largest populations to investigate how environmental factors (temperature, humidity, and rainfall) interacted with population dynamics and control measures. More snails were collected in weeks with high humidity and more gravid snails were collected when the temperature was higher. The addition of metaldehyde pesticides had the greatest impact on population dynamics by reducing snail numbers. In populations with fewer snails, their numbers were already declining before the use of metaldehyde, although the new treatment accelerated the process. As a consequence of the eradication program, egg-producing snails were no longer collected from most populations by the end of the study. The aggressive and persistent control efforts apparently lead to reduced populations of egg producing snails, eventually resulting in local extinctions of this important pest.

Reproductive Ecology of the Giant African Snail in South Florida: Implications for Eradication Programs

PubMed Central

2016-01-01

Giant African snail (Achatina fulica (Bowdich, 1822)), an important invasive snail, was recently found in South Florida, USA. An extensive eradication effort was initiated consisting of pesticide applications, debris removal and hand collections. We studied the reproduction capacity and population dynamics of snails collected from 22 populations for two years to help evaluate the likely success of the eradication program. A total of 23,890 snails, ranging from 25–131 mm, were measured, dissected and the number of eggs in each snail counted. Gravid snails ranged from 48–128 mm. Only 5% of snails had eggs, which were found year round. As the snails increased in size, they were more likely to include reproducing individuals. However, the percentage of gravid snails peaked when snails were approximately 90 mm. Although more prevalent, small (<65 mm) adults contributed fewer eggs to the population than the larger snails. We evaluated the effect of control measures on six populations having >1000 adult snails and used data from the two largest populations to investigate how environmental factors (temperature, humidity, and rainfall) interacted with population dynamics and control measures. More snails were collected in weeks with high humidity and more gravid snails were collected when the temperature was higher. The addition of metaldehyde pesticides had the greatest impact on population dynamics by reducing snail numbers. In populations with fewer snails, their numbers were already declining before the use of metaldehyde, although the new treatment accelerated the process. As a consequence of the eradication program, egg-producing snails were no longer collected from most populations by the end of the study. The aggressive and persistent control efforts apparently lead to reduced populations of egg producing snails, eventually resulting in local extinctions of this important pest. PMID:27861504

The Community Collaboration Stakeholder Project

ERIC Educational Resources Information Center

Heath, Renee Guarriello

2010-01-01

Today's increasingly complex and diverse world demands 21st century communication skills to solve community and social justice problems. Interorganizational collaboration is at the heart of much community activism, such as that focused on solving environmental disputes, eradicating racially discriminating real estate practices, and bringing early…

Dysfunction in gastric myoelectric and motor activity in Helicobacter pylori positive gastritis patients with non-ulcer dyspesia.

PubMed

Thor, P; Lorens, K; Tabor, S; Herman, R; Konturek, J W; Konturek, S J

1996-09-01

Helicobacter pylori (Hp) infection has been shown to affect gastric acid secretion and the somatostatin-gastrin ratio but its effects on gastric motility have not been evaluated. This study was carried out in 12 patients (10 males and 2 females, mean age 33 +/- 6 yrs) who underwent endoscopy and Campylobacter-like Organism (CLO)-test. All patients were found initially to be Hp positive according to CLO-test. Gastric emptying was evaluated by measuring antral diameter with ultrasonography (Hitachi EUB 240) in fasted and fed patients. Electrogastrography (EGG) with antral manometry were done 5 h before and 4 h after a meal before the therapy and one month after the eradication with triple therapy (lanzoprazole 30 mg daily- 2 x 250 mg clarithromycin 500 mg t.i.d.-3 x 500 mg and metronidazole 500 mg b.i.d.-2 x 500 mg). In Hp positive patients before the triple therapy the mean fasted antral diameter was 4.3 cm2, initial EGG showed significant dysrhythmia of electrical control activity (ECA) with tachygastria up to 25% of recording time in 9 of 12 Hp positive patients without normal increase of the power of signal in any of tested subjects. In 7 Hp positive fasted antral manometry failed to exhibit gastric phases III of the migrating motor complex (MMC). Hp eradication was accomplished in 10 of 12 examined patients and this was followed by a decrease in tachygastria to 3 cpm rhythm with an increase of the ECA power after meal. Phase III of MMC was observed again in 7 Hp negative patients with a decrease of fasted antral diameter (p < 0.05). Fasted and fed antral motility pattern increased after eradication. Two patients remained Hp positive after standard therapy. We conclude that most symptomatic non ulcer dyspeptic Hp positive patients show changes in ECA and antral hypomotility that are associated with Hp infections.

The C-Terminal Amino Acid of the MHC-I Heavy Chain Is Critical for Binding to Derlin-1 in Human Cytomegalovirus US11-Induced MHC-I Degradation

PubMed Central

Cho, Sunglim; Kim, Bo Young; Ahn, Kwangseog; Jun, Youngsoo

2013-01-01

Derlin-1 plays a critical role in endoplasmic reticulum-associated protein degradation (ERAD) of a particular subset of proteins. Although it is generally accepted that Derlin-1 mediates the export of ERAD substrates from the ER to the cytosol, little is known about how Derlin-1 interacts with these substrates. Human cytomegalovirus (HCMV) US11 exploits Derlin-1-dependent ERAD to degrade major histocompatibility complex class I (MHC-I) molecules and evade immune surveillance. US11 requires the cytosolic tail of the MHC-I heavy chain to divert MHC-I molecules into the ERAD pathway for degradation; however, the underlying mechanisms remain unknown. Here, we show that the cytosolic tail of the MHC-I heavy chain, although not required for interaction with US11, is required for tight binding to Derlin-1 and thus for US11-induced dislocation of the MHC-I heavy chain to the cytosol for proteasomal degradation. Surprisingly, deletion of a single C-terminal amino acid from the cytosolic tail disrupted the interaction between MHC-I molecules and Derlin-1, rendering mutant MHC-I molecules resistant to US11-induced degradation. Consistently, deleting the C-terminal cytosolic region of Derlin-1 prevented it from binding to MHC-I molecules. Taken together, these results suggest that the cytosolic region of Derlin-1 is involved in ERAD substrate binding and that this interaction is critical for the Derlin-1-mediated dislocation of the MHC-I heavy chain to the cytosol during US11-induced MHC-I degradation. PMID:23951315

The C-terminal amino acid of the MHC-I heavy chain is critical for binding to Derlin-1 in human cytomegalovirus US11-induced MHC-I degradation.

PubMed

Cho, Sunglim; Kim, Bo Young; Ahn, Kwangseog; Jun, Youngsoo

2013-01-01

Derlin-1 plays a critical role in endoplasmic reticulum-associated protein degradation (ERAD) of a particular subset of proteins. Although it is generally accepted that Derlin-1 mediates the export of ERAD substrates from the ER to the cytosol, little is known about how Derlin-1 interacts with these substrates. Human cytomegalovirus (HCMV) US11 exploits Derlin-1-dependent ERAD to degrade major histocompatibility complex class I (MHC-I) molecules and evade immune surveillance. US11 requires the cytosolic tail of the MHC-I heavy chain to divert MHC-I molecules into the ERAD pathway for degradation; however, the underlying mechanisms remain unknown. Here, we show that the cytosolic tail of the MHC-I heavy chain, although not required for interaction with US11, is required for tight binding to Derlin-1 and thus for US11-induced dislocation of the MHC-I heavy chain to the cytosol for proteasomal degradation. Surprisingly, deletion of a single C-terminal amino acid from the cytosolic tail disrupted the interaction between MHC-I molecules and Derlin-1, rendering mutant MHC-I molecules resistant to US11-induced degradation. Consistently, deleting the C-terminal cytosolic region of Derlin-1 prevented it from binding to MHC-I molecules. Taken together, these results suggest that the cytosolic region of Derlin-1 is involved in ERAD substrate binding and that this interaction is critical for the Derlin-1-mediated dislocation of the MHC-I heavy chain to the cytosol during US11-induced MHC-I degradation.

Forced interaction of cell surface proteins with Derlin-1 in the endoplasmic reticulum is sufficient to induce their dislocation into the cytosol for degradation.

PubMed

Cho, Sunglim; Lee, Miriam; Jun, Youngsoo

2013-01-11

Aberrantly folded proteins in the endoplasmic reticulum (ER) are rapidly removed into the cytosol for degradation by the proteasome via an evolutionarily conserved process termed ER-associated protein degradation (ERAD). ERAD of a subset of proteins requires Derlin-1 for dislocation into the cytosol; however, the molecular function of Derlin-1 remains unclear. Human cytomegalovirus US11 exploits Derlin-1-dependent ERAD to degrade major histocompatibility complex class I (MHC-I) molecules for immune evasion. Because US11 binds to both MHC-I molecules and Derlin-1 via its luminal and transmembrane domains (TMDs), respectively, the major role of US11 has been proposed to simply be delivery of MHC-I molecules to Derlin-1. Here, we directly tested this proposal by generating a hybrid MHC-I molecule, which contains the US11 TMD, and thus can associate with Derlin-1 in the absence of US11. Intriguingly, this MHC-I hybrid was rapidly degraded in a Derlin-1- and proteasome-dependent manner. Similarly, the vesicular stomatitis virus G protein, otherwise expressed at the cell surface, was degraded via Derlin-1-dependent ERAD when its TMD was replaced with that of US11. Thus, forced interaction of cell surface proteins with Derlin-1 is sufficient to induce their degradation via ERAD. Taken together, these results suggest that the main role of US11 is to recruit MHC-I molecules to Derlin-1, which then mediates the dislocation of MHC-I molecules into the cytosol for degradation. Copyright © 2012 Elsevier Inc. All rights reserved.

Treatment of cancer micrometastasis using a multicomponent chain-like nanoparticle.

PubMed

Peiris, Pubudu M; Toy, Randall; Abramowski, Aaron; Vicente, Pete; Tucci, Samantha; Bauer, Lisa; Mayer, Aaron; Tam, Morgan; Doolittle, Elizabeth; Pansky, Jenna; Tran, Emily; Lin, Dishen; Schiemann, William P; Ghaghada, Ketan B; Griswold, Mark A; Karathanasis, Efstathios

2014-01-10

While potent cytotoxic agents are available to oncologists, the clinical utility of these agents is limited due to their non-specific distribution in the body and toxicity to normal tissues leading to use of suboptimal doses for eradication of metastatic disease. Furthermore, treatment of micrometastases is impeded by several biobarriers, including their small size and high dispersion to organs, making them nearly inaccessible to drugs. To circumvent these limitations in treating metastatic disease, we developed a multicomponent, flexible chain-like nanoparticle (termed nanochain) that possesses a unique ability to gain access to and be deposited at micrometastatic sites. Moreover, coupling nanochain particles to radiofrequency (RF)-triggered cargo delivery facilitated widespread delivery of drug into hard-to-reach cancer cells. Collectively, these features synergistically facilitate effective treatment and ultimately eradication of micrometastatic disease using a low dose of a cytotoxic drug. © 2013.

Unusual Circularly Polarized and Aggregation-Induced Near-Infrared Phosphorescence of Helical Platinum(II) Complexes with Tetradentate Salen Ligands.

PubMed

Song, Jintong; Wang, Man; Zhou, Xiangge; Xiang, Haifeng

2018-05-17

A series of chiral and helical Pt II -Salen complexes with 1,1'-binaphthyl linkers were synthesized and characterized. Owing to the restriction of intramolecular motions of central 1,1'-binaphthyls, the complexes exhibit unusual near-infrared aggregation-induced phosphorescence (AIP). The (R)/(S) enantiopure complexes were characterized by X-ray diffraction, circular dichroism spectra, time-dependent density functional theory calculations, and circularly polarized luminescence (CPL). The present work explores the use of tetradentate ligands that can be easily prepared from commercially available enantiopure compounds, and the subsequent preparation of stable CPL-active square planar Pt II complexes with AIP effect that may have interest in many applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

UNUSUAL BACTEROIDES-LIKE ORGANISM

PubMed Central

Goldberg, Herbert S.; Barnes, Ella M.; Charles, Anthony B.

1964-01-01

Goldberg, Herbert S. (University of Missouri, Columbia), Ella M. Barnes, and Anthony B. Charles. Unusual Bacteroides-like organism. J. Bacteriol. 87:737–742. 1964.—An organism is described which appears to be a new species of gram-negative, anaerobic, nonsporulating rod. It was isolated from poultry caeca at levels of 107 to 108 per g. It is primarily distinguished from related organisms by its unusual size (2.0 by 10.0 μ). It is biochemically differentiated from known species of Bacteroides, Fusobacterium, Sphaerophorous, and other accepted related genera. Its presence in large numbers in the gut of poultry, and its high metabolic activity would seem to indicate an important intestinal organism. Images PMID:14127590

Optimal vaccine stockpile design for an eradicated disease: application to polio.

PubMed

Tebbens, Radboud J Duintjer; Pallansch, Mark A; Alexander, James P; Thompson, Kimberly M

2010-06-11

Eradication of a disease promises significant health and financial benefits. Preserving those benefits, hopefully in perpetuity, requires preparing for the possibility that the causal agent could re-emerge (unintentionally or intentionally). In the case of a vaccine-preventable disease, creation and planning for the use of a vaccine stockpile becomes a primary concern. Doing so requires consideration of the dynamics at different levels, including the stockpile supply chain and transmission of the causal agent. This paper develops a mathematical framework for determining the optimal management of a vaccine stockpile over time. We apply the framework to the polio vaccine stockpile for the post-eradication era and present examples of solutions to one possible framing of the optimization problem. We use the framework to discuss issues relevant to the development and use of the polio vaccine stockpile, including capacity constraints, production and filling delays, risks associated with the stockpile, dynamics and uncertainty of vaccine needs, issues of funding, location, and serotype dependent behavior, and the implications of likely changes over time that might occur. This framework serves as a helpful context for discussions and analyses related to the process of designing and maintaining a stockpile for an eradicated disease. (c) 2010 Elsevier Ltd. All rights reserved.

Media and interpersonal persuasions in the polio eradication campaign in northern Nigeria.

PubMed

Ozohu-Suleiman, Yakubu

2010-09-01

This study is premised on the increasing global concerns over the widespread resistance to polio eradication campaign in northern Nigeria. It aims to determine the level of campaign acceptance and compare the influences of mass media and interpersonal communication sources in Zaria local government area, being one of the high-risk (WPV-endemic) areas in northern Nigeria, where campaign resistance is known to be high. By way of quantitative survey, the study utilized 10% sample of the populations of eight out of the thirteen Wards in Zaria local government area, with a response rate of 78.6%. Findings reveal close ranks between campaign acceptance and resistance in the local government area, thus further confirming the difficulties still faced in polio eradication campaign in the region. This study also indicates higher performance of Interpersonal than Mass Media sources in influencing campaign acceptance and resistance in the local communities. Contact with friends and relations was rated the most influential interpersonal sources in the acceptance and resistance decision of individuals, while newspapers and magazines were rated most influential media sources that influenced campaign resistance in the local communities. The study concludes that a polio eradication campaign, backed with competent and sufficient communication expertise that utilizes knowledge-based indigenous interpersonal communication strategies will likely result in greater community acceptance in northern Nigeria.

Is narrow-band imaging useful for histological evaluation of gastric mucosa-associated lymphoid tissue lymphoma after treatment?

PubMed

Nonaka, Kouichi; Ohata, Ken; Matsuhashi, Nobuyuki; Shimizu, Michio; Arai, Shin; Hiejima, Yoshimitsu; Kita, Hiroto

2014-05-01

Endoscopic diagnosis of stomach mucosa-associated lymphoid tissue (MALT) lymphoma is often difficult because few specific findings are indicated. Even when MALT lymphoma is suspected by endoscopy, it is still difficult to make a definitive diagnosis by biopsy because lymphoma cells sometimes distribute unevenly. We previously reported that a tree-like appearance (TLA) is a characteristic finding of MALT lymphoma by narrow-band imaging (NBI) magnifying endoscopy and it is valuable in the selection of an optimal biopsy site in MALT lymphoma. Here, we study the frequency of TLA and evaluate the relationship between the response to eradication therapy and TLA in MALT lymphoma. We retrospectively examined the clinical background, endoscopic findings, response to eradication therapy, and Helicobacter pylori infection status of 16 patients diagnosed with MALT lymphoma who were referred to our hospital from April 2007 to August 2012. The regimen for eradicationtherapy consisted of rabeprazole, with amoxicillin and clarithromycin, all given for 7 days. TLA was found in 75% (12/16) and H. pylori infection in 75% (12/16) of patients diagnosed with MALT lymphoma by NBI magnifying endoscopy. In all complete regression (CR) patients after eradication treatment, the TLA finding had disappeared (100%); however, in the non-CR patients, TLA remained the same as before the eradication therapy (P=0.002). These results suggest that NBI magnifying endoscopy may be useful not only in the diagnosis but also in the evaluation of the response to eradication therapy of MALT lymphoma of the stomach. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

Hypothalamic ER–associated degradation regulates POMC maturation, feeding, and age-associated obesity

PubMed Central

Kim, Geun Hyang; Somlo, Diane R.M.; Haataja, Leena; Song, Soobin; Nillni, Eduardo A.

2018-01-01

Pro-opiomelanocortin (POMC) neurons function as key regulators of metabolism and physiology by releasing prohormone-derived neuropeptides with distinct biological activities. However, our understanding of early events in prohormone maturation in the ER remains incomplete. Highlighting the significance of this gap in knowledge, a single POMC cysteine-to-phenylalanine mutation at position 28 (POMC-C28F) is defective for ER processing and causes early onset obesity in a dominant-negative manner in humans through an unclear mechanism. Here, we report a pathologically important role of Sel1L-Hrd1, the protein complex of ER-associated degradation (ERAD), within POMC neurons. Mice with POMC neuron–specific Sel1L deficiency developed age-associated obesity due, at least in part, to the ER retention of POMC that led to hyperphagia. The Sel1L-Hrd1 complex targets a fraction of nascent POMC molecules for ubiquitination and proteasomal degradation, preventing accumulation of misfolded and aggregated POMC, thereby ensuring that another fraction of POMC can undergo normal posttranslational processing and trafficking for secretion. Moreover, we found that the disease-associated POMC-C28F mutant evades ERAD and becomes aggregated due to the presence of a highly reactive unpaired cysteine thiol at position 50. Thus, this study not only identifies ERAD as an important mechanism regulating POMC maturation within the ER, but also provides insights into the pathogenesis of monogenic obesity associated with defective prohormone folding. PMID:29457782

Rheological Characterization of Unusual DWPF Slurry Samples (U)

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

Koopman, D. C.

2005-09-01

A study was undertaken to identify and clarify examples of unusual rheological behavior in Defense Waste Processing Facility (DWPF) simulant slurry samples. Identification was accomplished by reviewing sludge, Sludge Receipt and Adjustment Tank (SRAT) product, and Slurry Mix Evaporator (SME) product simulant rheological results from the prior year. Clarification of unusual rheological behavior was achieved by developing and implementing new measurement techniques. Development of these new methods is covered in a separate report, WSRC-TR-2004-00334. This report includes a review of recent literature on unusual rheological behavior, followed by a summary of the rheological measurement results obtained on a set ofmore » unusual simulant samples. Shifts in rheological behavior of slurries as the wt. % total solids changed have been observed in numerous systems. The main finding of the experimental work was that the various unusual DWPF simulant slurry samples exhibit some degree of time dependent behavior. When a given shear rate is applied to a sample, the apparent viscosity of the slurry changes with time rather than remaining constant. These unusual simulant samples are more rheologically complex than Newtonian liquids or more simple slurries, neither of which shows significant time dependence. The study concludes that the unusual rheological behavior that has been observed is being caused by time dependent rheological properties in the slurries being measured. Most of the changes are due to the effect of time under shear, but SB3 SME products were also changing properties while stored in sample bottles. The most likely source of this shear-related time dependence for sludge is in the simulant preparation. More than a single source of time dependence was inferred for the simulant SME product slurries based on the range of phenomena observed. Rheological property changes were observed on the time-scale of a single measurement (minutes) as well as on a time scale of hours to weeks. The unusual shape of the slurry flow curves was not an artifact of the rheometric measurement. Adjusting the user-specified parameters in the rheometer measurement jobs can alter the shape of the flow curve of these time dependent samples, but this was not causing the unusual behavior. Variations in the measurement parameters caused the time dependence of a given slurry to manifest at different rates. The premise of the controlled shear rate flow curve measurement is that the dynamic response of the sample to a change in shear rate is nearly instantaneous. When this is the case, the data can be fitted to a time independent rheological equation, such as the Bingham plastic model. In those cases where this does not happen, interpretation of the data is difficult. Fitting time dependent data to time independent rheological equations, such as the Bingham plastic model, is also not appropriate.« less

The Complex Shell and Pulsar-Wind Nebula in the Young Supernova Remnant Kes 75

NASA Astrophysics Data System (ADS)

Borkowski, Kazimierz

2015-09-01

Kes 75 (G29.7-0.3) may be the youngest supernova remnant/pulsar-wind nebula (SNR/PWN) in the Galaxy, 400 - 900 years old. As such, it can illuminate early stages of PWN/SNR interaction and the nature of the immediate SN environment. The pulsar is unusual with some magnetar-like properties. Spectral studies are complex and conflicting, but Chandra can provide basic dynamical information: the expansion rate of the shell since earlier observations in 2000 and 2006, information crucial to a better age determination, model discrimination, and interpretation of the very large asymmetry (only about half the SNR shell is detectable). Our 150 ks proposed observation should allow rates to be measured to 15% or better. We shall also monitor the PWN for any morphological and spectral changes.

Studies on the Himbert Intramolecular Arene/ Allene Diels – Alder Cycloaddition. Mechanistic Studies and Expansion of Scope to All-Carbon Tethers

PubMed Central

Schmidt, Yvonne; Lam, Jonathan K.; Pham, Hung V.; Houk, K. N.; Vanderwal, Christopher D.

2013-01-01

The unusual intramolecular arene/allene cycloaddition described thirty years ago by Himbert permits rapid access to strained polycyclic compounds that offer great potential for the synthesis of complex scaffolds. To more fully understand the mechanism of this cycloaddition reaction, and to guide efforts to extend its scope to new substrates, quantum mechanical computational methods were employed in concert with laboratory experiments. These studies indicated that the cycloadditions likely proceed via concerted processes; a stepwise biradical mechanism was shown to be higher in energy in the cases studied. The original Himbert cycloaddition chemistry is also extended from heterocyclic to carbocyclic systems, with computational guidance used to predict thermodynamically favorable cases. Complex polycyclic scaffolds result from the combination of the cycloaddition and subsequent ring-rearrangement metathesis reactions. PMID:23634642

Transition Planning For After Polio Eradication.

PubMed

Rutter, Paul D; Hinman, Alan R; Hegg, Lea; King, Dennis; Sosler, Stephen; Swezy, Virginia; Hussey, Ann-Lee; Cochi, Stephen L

2017-07-01

The Global Polio Eradication Initiative (GPEI) has been in operation since 1988, now spends $1 billion annually, and operates through thousands of staff and millions of volunteers in dozens of countries. It has brought polio to the brink of eradication. After eradication is achieved, what should happen to the substantial assets, capabilities, and lessons of the GPEI? To answer this question, an extensive process of transition planning is underway. There is an absolute need to maintain and mainstream some of the functions, to keep the world polio-free. There is also considerable risk-and, if seized, substantial opportunity-for other health programs and priorities. And critical lessons have been learned that can be used to address other health priorities. Planning has started in the 16 countries where GPEI's footprint is the greatest and in the program's 5 core agencies. Even though poliovirus transmission has not yet been stopped globally, this planning process is gaining momentum, and some plans are taking early shape. This is a complex area of work-with difficult technical, financial, and political elements. There is no significant precedent. There is forward motion and a willingness on many sides to understand and address the risks and to explore the opportunities. Very substantial investments have been made, over 30 years, to eradicate a human pathogen from the world for the second time ever. Transition planning represents a serious intent to responsibly bring the world's largest global health effort to a close and to protect and build upon the investment in this effort, where appropriate, to benefit other national and global priorities. Further detailed technical work is now needed, supported by broad and engaged debate, for this undertaking to achieve its full potential. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Second-line rescue therapy with levofloxacin after H. pylori treatment failure: a Spanish multicenter study of 300 patients.

PubMed

Gisbert, Javier P; Bermejo, Fernando; Castro-Fernández, Manuel; Pérez-Aisa, Angeles; Fernández-Bermejo, Miguel; Tomas, Albert; Barrio, José; Bory, Felipe; Almela, Pedro; Sánchez-Pobre, Pilar; Cosme, Angel; Ortiz, Vicente; Niño, Pilar; Khorrami, Sam; Benito, Luis-Miguel; Carneros, Jose-Antonio; Lamas, Eloisa; Modolell, Inés; Franco, Alejandro; Ortuño, Juan; Rodrigo, Luis; García-Durán, Fernando; O'Callaghan, Elena; Ponce, Julio; Valer, María-Paz; Calvet, Xavier

2008-01-01

Quadruple therapy is generally recommended as second-line therapy after Helicobacter pylori (H. pylori) eradication failure. However, this regimen requires the administration of four drugs with a complex scheme, is associated with a relatively high incidence of adverse effects, and bismuth salts are not available worldwide anymore. Our aim was to evaluate the efficacy and tolerability of a triple second-line levofloxacin-based regimen in patients with H. pylori eradication failure. Prospective multicenter study. in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin had failed. A second eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. Eradication was confirmed with (13)C-urea breath test 4-8 wk after therapy. Compliance with therapy was determined from the interview and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. Three hundred consecutive patients were included. Mean age was 48 yr, 47% were male, 38% had peptic ulcer, and 62% functional dyspepsia. Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 81% (95% CI 77-86%) and 77% (73-82%). Adverse effects were reported in 22% of the patients, mainly including nausea (8%), metallic taste (5%), abdominal pain (3%), and myalgias (3%); none of them were severe. Ten-day levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous proton pump inhibitor-clarithromycin-amoxicillin failure, being simple and safe.

Placing Human Behavior at the Center of the Fight to Eradicate Polio: Lessons Learned and Their Application to Other Life-Saving Interventions

PubMed Central

Obregon, Rafael; Coleman, Michael; Hickler, Benjamin; SteelFisher, Gillian

2017-01-01

Abstract Today, acceptance of oral polio vaccine is the highest ever. Reaching this level of acceptance has depended on decades of engaging with communities, building trust amid extraordinary social contexts, and responding to the complex variables that trigger behavioral and social change. Drawing on both the successes and setbacks in the 28 years of the Global Polio Eradication Initiative (GPEI), this article articulates what happened when the GPEI began to pay more attention to the dynamics of human and social behavior change. Three particular lessons for other health and immunization programs can be drawn from the experience of GPEI: change begins from within (ie, success needs institutional recognition of the importance of human behavior), good data are not enough for good decision-making, and health workers are important agents of behavior change. These lessons should be harnessed and put into practice to build demand and trust for the last stages of polio eradication, as well as for other life-saving health interventions. PMID:28838157

Placing Human Behavior at the Center of the Fight to Eradicate Polio: Lessons Learned and Their Application to Other Life-Saving Interventions.

PubMed

Guirguis, Sherine; Obregon, Rafael; Coleman, Michael; Hickler, Benjamin; SteelFisher, Gillian

2017-07-01

Today, acceptance of oral polio vaccine is the highest ever. Reaching this level of acceptance has depended on decades of engaging with communities, building trust amid extraordinary social contexts, and responding to the complex variables that trigger behavioral and social change. Drawing on both the successes and setbacks in the 28 years of the Global Polio Eradication Initiative (GPEI), this article articulates what happened when the GPEI began to pay more attention to the dynamics of human and social behavior change. Three particular lessons for other health and immunization programs can be drawn from the experience of GPEI: change begins from within (ie, success needs institutional recognition of the importance of human behavior), good data are not enough for good decision-making, and health workers are important agents of behavior change. These lessons should be harnessed and put into practice to build demand and trust for the last stages of polio eradication, as well as for other life-saving health interventions. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Barriers to a cure for HIV in women

PubMed Central

Gianella, Sara; Tsibris, Athe; Barr, Liz; Godfrey, Catherine

2016-01-01

Introduction Distinct biological factors exist that affect the natural history of HIV and the host immune response between women and men. These differences must be addressed to permit the optimal design of effective HIV eradication strategies for much of the HIV-positive population. Methods and results Here, we review the literature on sex-based differences in HIV pathogenesis and natural history in tissues and anatomic compartments, HIV latency and transcriptional activity, and host immunity including the role of sex hormones. We then outline the potential effects of these differences on HIV persistence, and on the safety and efficacy of HIV eradication and curative interventions. Finally, we discuss the next steps necessary to elucidate these factors to achieve a cure for HIV, taking in account the complex ethical issues and the regulatory landscape in the hopes of stimulating further research and awareness in these areas. Conclusions Targeted enrolment of women in clinical trials and careful sex-based analysis will be crucial to gain further insights into sex-based differences in HIV persistence and to design sex-specific approaches to HIV eradication, if required. PMID:26900031

Establishing an unusual cell type: How to make a dikaryon

PubMed Central

Kruzel, Emilia K.; Hull, Christina M.

2010-01-01

Summary The dikaryons of basidiomycete fungi represent an unusual cell type required for complete sexual development. Dikaryon formation occurs via the activities of cell type-specific homeodomain transcription factors, which form regulatory complexes to establish the dikaryotic state. Decades of classical genetic and cell biological studies in mushrooms have provided a foundation for more recent molecular studies in the pathogenic species Ustilago maydis and Cryptococcus neoformans. Studies in these systems have revealed novel mechanisms of regulation that function downstream of classic homeodomain complexes to ensure that dikaryons are established and propagated. Comparisons of these dikaryon-specific networks promise to reveal the nature of regulatory network evolution and the adaptations responsible for driving complex eukaryotic development. PMID:21036099

Efficacy of phase 3 trial of RTS, S/AS01 malaria vaccine: The need for an alternative development plan.

PubMed

Mahmoudi, Shima; Keshavarz, Hossein

2017-09-02

Although vaccines would be the ideal tool for control, prevention, elimination, and eradication of many infectious diseases, developing of parasites vaccines such as malaria vaccine is very complex. The most advanced malaria vaccine candidate RTS,S, a pre-erythrocytic vaccine, has been recommended for licensure by EMEA. The results of this phase III trial suggest that this candidate malaria vaccine has relatively little efficacy, and the vaccine apparently will not meet the goal of malaria eradication by itself. Since there are many vaccine candidates in the pipeline 1 that are being evaluated in vaccine trials, further study on using of alternative parasite targets and vaccination strategies are highly recommended.

Ecohealth System Dynamic Model as a Planning Tool for the Reduction of Breeding Sites

NASA Astrophysics Data System (ADS)

Respati, T.; Raksanagara, A.; Djuhaeni, H.; Sofyan, A.; Shandriasti, A.

2017-03-01

Dengue is still one of major health problem in Indonesia. Dengue transmission is influenced by dengue prevention and eradication program, community participation, housing environment and climate. The complexity of the disease coupled with limited resources necessitates different approach for prevention methods that include factors contribute to the transmission. One way to prevent the dengue transmission is by reducing the mosquito’s breeding sites. Four factors suspected to influence breeding sites are dengue prevention and eradication program, community participation, housing environment, and weather condition. In order to have an effective program in reducing the breeding site it is needed to have a model which can predict existence of the breeding sites while the four factors under study are controlled. The objective of this study is to develop an Ecohealth model using system dynamic as a planning tool for the reduction of breeding sites to prevent dengue transmission with regard to dengue prevention and eradication program, community participation, housing environment, and weather condition. The methodology is a mixed method study using sequential exploratory design. The study comprised of 3 stages: first a qualitative study to 14 respondents using in-depth interview and 6 respondents for focus group discussion. The results from the first stage was used to develop entomology and household survey questionnaires for second stage conducted in 2036 households across 12 sub districts in Bandung City. Ecohealth system dynamic model was developed using data from first and second stages. Analyses used are thematic analysis for qualitative data; spatial, generalized estimating equation (GEE) and structural equation modeling for quantitative data; also average mean error (AME) and average variance error (AVE) for dynamic system model validation. System dynamic model showed that the most effective approach to eliminate breeding places was by ensuring the availability of basic sanitation for all houses. Weather factors such as precipitation can be compensated with the eradication of breeding sites activities which is conducted as scheduled and at the same time for the whole areas. Conclusion of this study is that dengue prevention and eradication program, community participation, and housing environment contributed to breeding places elimination influenced the existence of the breeding sites. The availability of basic sanitation and breeding places eradication program done timely and collectively are the most effective approach to eradicate breeding sites. Ecohealth dynamic system model can be used as a tool for the planning of breeding sites eradication program to prevent disease transmissions at city level.

Host-parasite oscillation dynamics and evolution in a compartmentalized RNA replication system.

PubMed

Bansho, Yohsuke; Furubayashi, Taro; Ichihashi, Norikazu; Yomo, Tetsuya

2016-04-12

To date, various cellular functions have been reconstituted in vitro such as self-replication systems using DNA, RNA, and proteins. The next important challenges include the reconstitution of the interactive networks of self-replicating species and investigating how such interactions generate complex ecological behaviors observed in nature. Here, we synthesized a simple replication system composed of two self-replicating host and parasitic RNA species. We found that the parasitic RNA eradicates the host RNA under bulk conditions; however, when the system is compartmentalized, a continuous oscillation pattern in the population dynamics of the two RNAs emerges. The oscillation pattern changed as replication proceeded mainly owing to the evolution of the host RNA. These results demonstrate that a cell-like compartment plays an important role in host-parasite ecological dynamics and suggest that the origin of the host-parasite coevolution might date back to the very early stages of the evolution of life.

The rarity of "unusual" [corrected] dispositions of victim bodies: staging and posing.

PubMed

Keppel, Robert D; Weis, Joseph G

2004-11-01

The act of leaving a victim's body in an unusual position is a conscious criminal action by an offender to thwart an investigation, shock the finder and investigators of the crime scene, or give perverted pleasure to the killer. The unusual position concepts of posing and staging a murder victim have been documented thoroughly and have been accepted by the courts as a definable phenomenon. One staging case and one posing case are outlined and reveal characteristics of those homicides. From the Washington State Attorney General's Homicide Investigation and Tracking System's database on murder covering the years 1981-2000 (a total of 5,224 cases), the relative frequency of unusual body dispositions is revealed as a very rare occurrence. Only 1.3% of victims are left in an unusual position, with 0.3% being posed and 0.1% being staged. The characteristics of these types of murders also set them apart: compared to all other murders, in staged murders the victims and killers are, on average, older. All victims and offenders in the staged murders are white, with victims being disproportionately white in murders with any kind of unusual body disposition. Likewise, females stand out as victims when the body is posed, staged, or left in other unusual positions. Whereas posed bodies are more likely to include sexual assault, often in serial murders, there is no evidence of either in the staged cases. Lastly, when a body is left in an unusual position, binding is more likely, as well as the use of more "hands on" means of killing the victim, such as stabbing or cutting weapons, bludgeons, ligatures, or hands and feet.

Morphology and formation mechanism in precipitation of calcite induced by Curvibacter lanceolatus strain HJ-1

NASA Astrophysics Data System (ADS)

Zhang, Chonghong; Li, Fuchun; Lv, Jiejie

2017-11-01

Precipitation of calcium carbobate induced by microbial activities is common occurrence in controlled solution, but the formation mechanism and morphology in precipitation of calcite in solution systems is unclear, and the role of microbes is disputed. Here, culture experiment was performed for 50 days using the Curvibacter lanceolatus strain HJ-1 in a M2 culture medium, and the phase composition and morphology of the precipitates were characterized by the X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM) techniques. We show that the precipitation processes in our experiment lead to unusual morphologies of crystals corresponding to different growth stages, and the morphologies of the precipitated crystal aggregates ranging from the main rod-, cross-, star-, cauliflower-like morphologies to spherulitic structure. The complex and unusual morphologies of the precipitated calcite by strain HJ-1 may provide a reference point for better understanding the biomineralization mechanism of calcite, moreover, morphological transition of minerals revealed that the multi-ply crystals-aggregation mechanism for calcite growth in crystallisation media.

The Structure of the GM-CSF Receptor Complex Reveals a Distinct Mode of Cytokine Receptor Activation

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

Hansen, Guido; Hercus, Timothy R.; McClure, Barbara J.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that controls the production and function of blood cells, is deregulated in clinical conditions such as rheumatoid arthritis and leukemia, yet offers therapeutic value for other diseases. Its receptors are heterodimers consisting of a ligand-specific {alpha} subunit and a {beta}c subunit that is shared with the interleukin (IL)-3 and IL-5 receptors. How signaling is initiated remains an enigma. We report here the crystal structure of the human GM-CSF/GM-CSF receptor ternary complex and its assembly into an unexpected dodecamer or higher-order complex. Importantly, mutagenesis of the GM-CSF receptor at the dodecamer interface andmore » functional studies reveal that dodecamer formation is required for receptor activation and signaling. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors, providing a structural basis for understanding their mechanism of activation and for the development of therapeutics.« less

The genotype-phenotype map of an evolving digital organism.

PubMed

Fortuna, Miguel A; Zaman, Luis; Ofria, Charles; Wagner, Andreas

2017-02-01

To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences), which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable.

The genotype-phenotype map of an evolving digital organism

PubMed Central

Zaman, Luis; Wagner, Andreas

2017-01-01

To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences), which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable. PMID:28241039

Four-coordinate, 14-electron Ru(II) complexes: unusual trigonal pyramidal geometry enforced by bis(phosphino)silyl ligation.

PubMed

MacInnis, Morgan C; McDonald, Robert; Ferguson, Michael J; Tobisch, Sven; Turculet, Laura

2011-08-31

Unprecedented diamagnetic, four-coordinate, formally 14-electron (Cy-PSiP)RuX (Cy-PSiP = [κ(3)-(2-R(2)PC(6)H(4))(2)SiMe](-); X = amido, alkoxo) complexes that do not require agostic stabilization and that adopt a highly unusual trigonal pyramidal coordination geometry are reported. The tertiary silane [(2-Cy(2)PC(6)H(4))(2)SiMe]H ((Cy-PSiP)H) reacted with 0.5 [(p-cymene)RuCl(2)](2) in the presence of Et(3)N and PCy(3) to afford [(Cy-PSiP)RuCl](2) (1) in 74% yield. Treatment of 1 with KO(t)Bu led to the formation of (Cy-PSiP)RuO(t)Bu (2, 97% yield), which was crystallographically characterized and shown to adopt a trigonal pyramidal coordination geometry in the solid state. Treatment of 1 with NaN(SiMe(3))(2) led to the formation of (Cy-PSiP)RuN(SiMe(3))(2) (3, 70% yield), which was also found to adopt a trigonal pyramidal coordination geometry in the solid state. The related anilido complexes (Cy-PSiP)RuNH(2,6-R(2)C(6)H(3)) (4, R = H; 5, R = Me) were also prepared in >90% yields by treating 1 with LiNH(2,6-R(2)C(6)H(3)) (R = H, Me) reagents. The solid state structure of 5 indicates a monomeric trigonal pyramidal complex that features a C-H agostic interaction. Complexes 2 and 3 were found to react readily with 1 equiv of H(2)O to form the dimeric hydroxo-bridged complex [(Cy-PSiP)RuOH](2) (6, 94% yield), which was crystallographically characterized. Complexes 2 and 3 also reacted with 1 equiv of PhOH to form the new 18-electron η(5)-oxocyclohexadienyl complex (Cy-PSiP)Ru(η(5)-C(6)H(5)O) (7, 84% yield). Both amido and alkoxo (Cy-PSiP)RuX complexes reacted with H(3)B·NHRR' reagents to form bis(σ-B-H) complexes of the type (Cy-PSiP)RuH(η(2):η(2)-H(2)BNRR') (8, R = R' = H; 9, R = R' = Me; 10, R = H, R' = (t)Bu), which illustrates that such four-coordinate (Cy-PSiP)RuX (X = amido, alkoxo) complexes are able to undergo multiple E-H (E = main group element) bond activation steps. Computational methods were used to investigate structurally related PCP, PPP, PNP, and PSiP four-coordinate Ru complexes and confirmed the key role of the strongly σ-donating silyl group of the PSiP ligand set in enforcing the unusual trigonal pyramidal coordination geometry featured in complexes 2-5, thus substantiating a new strategy for the synthesis of low-coordinate Ru species. The mechanism of the activation of ammonia-borane by such low-coordinate (R-PSiP)RuX (X = amido, alkoxo) species was also studied computationally and was determined to proceed most likely in a stepwise fashion via intramolecular deprotonation of ammonia and subsequent borane B-H bond oxidative addition steps.

A neo-sex-chromosome that drives post-zygotic sex determiniation in the Hessian fly

USDA-ARS?s Scientific Manuscript database

Two nonoverlapping autosomal inversions defined unusual neo-sex chromosomes in the Hessian fly (Mayetiola destructor). Like other neo-sex chromosomes, these were normally heterozygous, present only in one sex, and suppressed recombination around a sex-determining master switch. Their unusual propert...

Media and interpersonal persuasions in the polio eradication campaign in northern Nigeria

PubMed Central

Ozohu-Suleiman, Yakubu

2010-01-01

This study is premised on the increasing global concerns over the widespread resistance to polio eradication campaign in northern Nigeria. It aims to determine the level of campaign acceptance and compare the influences of mass media and interpersonal communication sources in Zaria local government area, being one of the high-risk (WPV-endemic) areas in northern Nigeria, where campaign resistance is known to be high. By way of quantitative survey, the study utilized 10% sample of the populations of eight out of the thirteen Wards in Zaria local government area, with a response rate of 78.6%. Findings reveal close ranks between campaign acceptance and resistance in the local government area, thus further confirming the difficulties still faced in polio eradication campaign in the region. This study also indicates higher performance of Interpersonal than Mass Media sources in influencing campaign acceptance and resistance in the local communities. Contact with friends and relations was rated the most influential interpersonal sources in the acceptance and resistance decision of individuals, while newspapers and magazines were rated most influential media sources that influenced campaign resistance in the local communities. The study concludes that a polio eradication campaign, backed with competent and sufficient communication expertise that utilizes knowledge-based indigenous interpersonal communication strategies will likely result in greater community acceptance in northern Nigeria. PMID:28299036

Prolapsing Gastric Polyp Causing Intermittent Gastric Outlet Obstruction.

PubMed

Kosai, Nik Ritza; Gendeh, Hardip Singh; Norfaezan, Abdul Rashid; Razman, Jamin; Sutton, Paul Anthony; Das, Srijit

2015-06-01

Gastric polyps are often an incidental finding on upper gastrointestinal endoscopy, with an incidence up to 5%. The majority of gastric polyps are asymptomatic, occurring secondary to inflammation. Prior reviews discussed Helicobacter pylori (H pylori)-associated singular gastric polyposis; however, we present a rare and unusual case of recurrent multiple benign gastric polyposis post H pylori eradication resulting in intermittent gastric outlet obstruction. A 70-year-old independent male, Chinese in ethnicity, with a background of diabetes mellitus, hypertension, and a simple renal cyst presented with a combination of melena, anemia, and intermittent vomiting of partially digested food after meals. Initial gastroscopy was positive for H pylori; thus he was treated with H pylori eradication and proton pump inhibitors. Serial gastroscopy demonstrated multiple sessile gastric antral polyps, the largest measuring 4 cm. Histopathologic examination confirmed a benign hyperplastic lesion. Computed tomography identified a pyloric mass with absent surrounding infiltration or metastasis. A distal gastrectomy was performed, whereby multiple small pyloric polyps were found, the largest prolapsing into the pyloric opening, thus explaining the intermittent nature of gastric outlet obstruction. Such polyps often develop from gastric ulcers and, if left untreated, may undergo neoplasia to form malignant cells. A distal gastrectomy was an effective choice of treatment, taking into account the polyp size, quantity, and potential for malignancy as opposed to an endoscopic approach, which may not guarantee a complete removal of safer margins and depth. Therefore, surgical excision is favorable for multiple large gastric polyps with risk of malignancy.

Prolapsing Gastric Polyp Causing Intermittent Gastric Outlet Obstruction

PubMed Central

Kosai, Nik Ritza; Gendeh, Hardip Singh; Norfaezan, Abdul Rashid; Razman, Jamin; Sutton, Paul Anthony; Das, Srijit

2015-01-01

Gastric polyps are often an incidental finding on upper gastrointestinal endoscopy, with an incidence up to 5%. The majority of gastric polyps are asymptomatic, occurring secondary to inflammation. Prior reviews discussed Helicobacter pylori (H pylori)–associated singular gastric polyposis; however, we present a rare and unusual case of recurrent multiple benign gastric polyposis post H pylori eradication resulting in intermittent gastric outlet obstruction. A 70-year-old independent male, Chinese in ethnicity, with a background of diabetes mellitus, hypertension, and a simple renal cyst presented with a combination of melena, anemia, and intermittent vomiting of partially digested food after meals. Initial gastroscopy was positive for H pylori; thus he was treated with H pylori eradication and proton pump inhibitors. Serial gastroscopy demonstrated multiple sessile gastric antral polyps, the largest measuring 4 cm. Histopathologic examination confirmed a benign hyperplastic lesion. Computed tomography identified a pyloric mass with absent surrounding infiltration or metastasis. A distal gastrectomy was performed, whereby multiple small pyloric polyps were found, the largest prolapsing into the pyloric opening, thus explaining the intermittent nature of gastric outlet obstruction. Such polyps often develop from gastric ulcers and, if left untreated, may undergo neoplasia to form malignant cells. A distal gastrectomy was an effective choice of treatment, taking into account the polyp size, quantity, and potential for malignancy as opposed to an endoscopic approach, which may not guarantee a complete removal of safer margins and depth. Therefore, surgical excision is favorable for multiple large gastric polyps with risk of malignancy. PMID:25578789

Prediction of Helicobacter pylori status by conventional endoscopy, narrow-band imaging magnifying endoscopy in stomach after endoscopic resection of gastric cancer.

PubMed

Yagi, Kazuyoshi; Saka, Akiko; Nozawa, Yujiro; Nakamura, Atsuo

2014-04-01

To reduce the incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer, Helicobacter pylori eradication therapy has been endorsed. It is not unusual for such patients to be H. pylori negative after eradication or for other reasons. If it were possible to predict H. pylori status using endoscopy alone, it would be very useful in clinical practice. To clarify the accuracy of endoscopic judgment of H. pylori status, we evaluated it in the stomach after endoscopic submucosal dissection (ESD) of gastric cancer. Fifty-six patients treated by ESD were enrolled. The diagnostic criteria for H. pylori status by conventional endoscopy and narrow-band imaging (NBI)-magnifying endoscopy were decided, and H. pylori status was judged by two endoscopists. Based on the H. pylori stool antigen test as a diagnostic gold standard, conventional endoscopy and NBI-magnifying endoscopy were compared for their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Interobserver agreement was assessed in terms of κ value. Interobserver agreement was moderate (0.56) for conventional endoscopy and substantial (0.77) for NBI-magnifying endoscopy. The sensitivity, specificity, PPV, and NPV were 0.79, 0.52, 0.70, and 0.63 for conventional endoscopy and 0.91, 0.83, 0.88, and 0.86 for NBI-magnifying endoscopy, respectively. Prediction of H. pylori status using NBI-magnifying endoscopy is practical, and interobserver agreement is substantial. © 2013 John Wiley & Sons Ltd.

African swine fever virus transmission cycles in Central Europe: Evaluation of wild boar-soft tick contacts through detection of antibodies against Ornithodoros erraticus saliva antigen.

PubMed

Pietschmann, Jana; Mur, Lina; Blome, Sandra; Beer, Martin; Pérez-Sánchez, Ricardo; Oleaga, Ana; Sánchez-Vizcaíno, José Manuel

2016-01-04

African swine fever (ASF) is one of the most complex viral diseases affecting both domestic and wild pigs. It is caused by ASF virus (ASFV), the only DNA virus which can be efficiently transmitted by an arthropod vector, soft ticks of the genus Ornithodoros. These ticks can be part of ASFV-transmission cycles, and in Europe, O. erraticus was shown to be responsible for long-term maintenance of ASFV in Spain and Portugal. In 2014, the disease has been reintroduced into the European Union, affecting domestic pigs and, importantly, also the Eurasian wild boar population. In a first attempt to assess the risk of a tick-wild boar transmission cycle in Central Europe that would further complicate eradication of the disease, over 700 pre-existing serum samples from wild boar hunted in four representative German Federal States were investigated for the presence of antibodies directed against salivary antigen of Ornithodoros erraticus ticks using an indirect ELISA format. Out of these samples, 16 reacted with moderate to high optical densities that could be indicative of tick bites in sampled wild boar. However, these samples did not show a spatial clustering (they were collected from distant geographical regions) and were of bad quality (hemolysis/impurities). Furthermore, all positive samples came from areas with suboptimal climate for soft ticks. For this reason, false positive reactions are likely. In conclusion, the study did not provide stringent evidence for soft tick-wild boar contact in the investigated German Federal States and thus, a relevant involvement in the epidemiology of ASF in German wild boar is unlikely. This fact would facilitate the eradication of ASF in the area, although other complex relations (wild boar biology and interactions with domestic pigs) need to be considered.

Towards global Guinea worm eradication in 2015: the experience of South Sudan.

PubMed

Awofeso, Niyi

2013-08-01

For centuries, the Guinea worm parasite (Dracunculus medinensis) has caused disabling misery, infecting people who drink stagnant water contaminated with the worm's larvae. In 2012, there were 542 cases of Guinea worm reported globally, of which 521 (96.1%) were reported in South Sudan. Protracted civil wars, an inadequate workforce, neglect of potable water provision programs, suboptimal Guinea worm surveillance and case containment, and fragmented health systems account for many of the structural and operational factors encumbering South Sudan's Guinea worm eradication efforts. This article reviews the impacts of six established Guinea worm control strategies in South Sudan: (1) surveillance to determine actual caseload distribution and trends in response to control measures; (2) educating community members from whom worms are emerging to avoid immersing affected parts in sources of drinking water; (3) filtering potentially contaminated drinking water using cloth filters or filtered drinking straws; (4) treating potentially contaminated surface water with the copepod larvicide temephos (Abate); (5) providing safe drinking water from boreholes or hand-dug wells; and (6) containment of transmission through voluntary isolation of each patient to prevent contamination of drinking water sources, provision of first aid, and manual extraction of the worm. Surveillance, community education, potable water provision, and case containment remain weak facets of the program. Abate pesticide is not a viable option for Guinea worm control in South Sudan. In light of current case detection and containment trends, as well as capacity building efforts for Guinea worm eradication, South Sudan is more likely to eradicate Guinea worm by 2020, rather than by 2015. The author highlights areas in which substantial improvements are required in South Sudan's Guinea worm eradication program, and suggests improvement strategies. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Single-molecule spectroscopy reveals that individual low-light LH2 complexes from Rhodopseudomonas palustris 2.1.6. have a heterogeneous polypeptide composition.

PubMed

Brotosudarmo, Tatas H P; Kunz, Ralf; Böhm, Paul; Gardiner, Alastair T; Moulisová, Vladimíra; Cogdell, Richard J; Köhler, Jürgen

2009-09-02

Rhodopseudomonas palustris belongs to the group of purple bacteria that have the ability to produce LH2 complexes with unusual absorption spectra when they are grown at low-light intensity. This ability is often related to the presence of multiple genes encoding the antenna apoproteins. Here we report, for the first time to our knowledge, direct evidence that individual low-light LH2 complexes have a heterogeneous alphabeta-apoprotein composition that modulates the site energies of Bchl a molecules, producing absorption bands at 800, 820, and 850 nm. The arrangement of the Bchl a molecules in the "tightly coupled ring" can be modeled by nine alphabeta-Bchls dimers, such that the Bchls bound to six alphabeta-pairs have B820-like site energies and the remaining Bchl a molecules have B850-like site energies. Furthermore, the experimental data can only be satisfactorily modeled when these six alphabeta-pairs with B820 Bchl a molecules are distributed such that the symmetry of the assembly is reduced to C(3). It is also clear from the measured single-molecule spectra that the energies of the electronically excited states in the mixed B820/850 ring are mainly influenced by diagonal disorder.

The Sentence-Composition Effect: Processing of Complex Sentences Depends on the Configuration of Common Noun Phrases versus Unusual Noun Phrases

ERIC Educational Resources Information Center

Johnson, Marcus L.; Lowder, Matthew W.; Gordon, Peter C.

2011-01-01

In 2 experiments, the authors used an eye tracking while reading methodology to examine how different configurations of common noun phrases versus unusual noun phrases (NPs) influenced the difference in processing difficulty between sentences containing object- and subject-extracted relative clauses. Results showed that processing difficulty was…

Tracking the return of Aedes aegypti to Brazil, the major vector of the dengue, chikungunya and Zika viruses

PubMed Central

Gloria-Soria, Andrea; Caccone, Adalgisa; Evans, Benjamin; Schama, Renata; Martins, Ademir Jesus; Powell, Jeffrey R.

2017-01-01

Background Aedes aegypti, commonly known as “the yellow fever mosquito”, is of great medical concern today primarily as the major vector of dengue, chikungunya and Zika viruses, although yellow fever remains a serious health concern in some regions. The history of Ae. aegypti in Brazil is of particular interest because the country was subjected to a well-documented eradication program during 1940s-1950s. After cessation of the campaign, the mosquito quickly re-established in the early 1970s with several dengue outbreaks reported during the last 30 years. Brazil can be considered the country suffering the most from the yellow fever mosquito, given the high number of dengue, chikungunya and Zika cases reported in the country, after having once been declared “free of Ae. aegypti”. Methodology/Principal findings We used 12 microsatellite markers to infer the genetic structure of Brazilian Ae. aegypti populations, genetic variability, genetic affinities with neighboring geographic areas, and the timing of their arrival and spread. This enabled us to reconstruct their recent history and evaluate whether the reappearance in Brazil was the result of re-invasion from neighboring non-eradicated areas or re-emergence from local refugia surviving the eradication program. Our results indicate a genetic break separating the northern and southern Brazilian Ae. aegypti populations, with further genetic differentiation within each cluster, especially in southern Brazil. Conclusions/Significance Based on our results, re-invasions from non-eradicated regions are the most likely scenario for the reappearance of Ae. aegypti in Brazil. While populations in the northern cluster are likely to have descended from Venezuela populations as early as the 1970s, southern populations seem to have derived more recently from northern Brazilian areas. Possible entry points are also revealed within both southern and northern clusters that could inform strategies to control and monitor this important arbovirus vector. PMID:28742801

Tracking the return of Aedes aegypti to Brazil, the major vector of the dengue, chikungunya and Zika viruses.

PubMed

Kotsakiozi, Panayiota; Gloria-Soria, Andrea; Caccone, Adalgisa; Evans, Benjamin; Schama, Renata; Martins, Ademir Jesus; Powell, Jeffrey R

2017-07-01

Aedes aegypti, commonly known as "the yellow fever mosquito", is of great medical concern today primarily as the major vector of dengue, chikungunya and Zika viruses, although yellow fever remains a serious health concern in some regions. The history of Ae. aegypti in Brazil is of particular interest because the country was subjected to a well-documented eradication program during 1940s-1950s. After cessation of the campaign, the mosquito quickly re-established in the early 1970s with several dengue outbreaks reported during the last 30 years. Brazil can be considered the country suffering the most from the yellow fever mosquito, given the high number of dengue, chikungunya and Zika cases reported in the country, after having once been declared "free of Ae. aegypti". We used 12 microsatellite markers to infer the genetic structure of Brazilian Ae. aegypti populations, genetic variability, genetic affinities with neighboring geographic areas, and the timing of their arrival and spread. This enabled us to reconstruct their recent history and evaluate whether the reappearance in Brazil was the result of re-invasion from neighboring non-eradicated areas or re-emergence from local refugia surviving the eradication program. Our results indicate a genetic break separating the northern and southern Brazilian Ae. aegypti populations, with further genetic differentiation within each cluster, especially in southern Brazil. Based on our results, re-invasions from non-eradicated regions are the most likely scenario for the reappearance of Ae. aegypti in Brazil. While populations in the northern cluster are likely to have descended from Venezuela populations as early as the 1970s, southern populations seem to have derived more recently from northern Brazilian areas. Possible entry points are also revealed within both southern and northern clusters that could inform strategies to control and monitor this important arbovirus vector.

The Purification of the Chlamydomonas reinhardtii chloroplast ClpP complex: additional subunits and structural features

PubMed Central

Derrien, Benoît; Majeran, Wojciech; Effantin, Grégory; Ebenezer, Joseph; Friso, Giulia; van Wijk, Klaas J.; Steven, Alasdair C.; Maurizi, Michael R.; Vallon, Olivier

2012-01-01

The ClpP peptidase is a major constituent of the proteolytic machinery of bacteria and organelles. The chloroplast ClpP complex is unusual, in that it associates a large number of subunits, one of which (ClpP1) is encoded in the chloroplast, the others in the nucleus. The complexity of these large hetero-oligomeric complexes has been a major difficulty in their overproduction and biochemical characterization. In this paper, we describe the purification of native chloroplast ClpP complex from the green alga Chlamydomonas reinhardtii, using a strain that carries the Strep-tag II at the C-terminus of the ClpP1 subunit. Similar to land plants, the algal complex comprises active and inactive subunits (3 ClpP and 5 ClpR, respectively). Evidence is presented that a sub-complex can be produced by dissociation, comprising ClpP1 and ClpR1, 2, 3 and 4, similar to the ClpR-ring described in land plants. Our Chlamydomonas ClpP preparation also contains two ClpT subunits, ClpT3 and ClpT4, which like the land plant ClpT1 and ClpT2 show 2 Clp-N domains. ClpTs are believed to function in substrate binding and/or assembly of the two heptameric rings. Phylogenetic analysis indicates that ClpT subunits have appeared independently in Chlorophycean algae, in land plants and in dispersed cyanobacterial genomes. Negative staining electron microscopy shows that the Chlamydomonas complex retains the barrel-like shape of homo-oligomeric ClpPs, with 4 additional peripheral masses that we speculate represent either the additional IS1 domain of ClpP1 (a feature unique to algae) or ClpTs or extensions of ClpR subunits PMID:22772861

Complete Genome Sequence of the Complex Carbohydrate-Degrading Marine Bacterium, Saccharophagus degradans Strain 2-40T

PubMed Central

Weiner, Ronald M.; Taylor, Larry E.; Henrissat, Bernard; Hauser, Loren; Land, Miriam; Coutinho, Pedro M.; Rancurel, Corinne; Saunders, Elizabeth H.; Longmire, Atkinson G.; Zhang, Haitao; Bayer, Edward A.; Gilbert, Harry J.; Larimer, Frank; Zhulin, Igor B.; Ekborg, Nathan A.; Lamed, Raphael; Richardson, Paul M.; Borovok, Ilya; Hutcheson, Steven

2008-01-01

The marine bacterium Saccharophagus degradans strain 2-40 (Sde 2-40) is emerging as a vanguard of a recently discovered group of marine and estuarine bacteria that recycles complex polysaccharides. We report its complete genome sequence, analysis of which identifies an unusually large number of enzymes that degrade >10 complex polysaccharides. Not only is this an extraordinary range of catabolic capability, many of the enzymes exhibit unusual architecture including novel combinations of catalytic and substrate-binding modules. We hypothesize that many of these features are adaptations that facilitate depolymerization of complex polysaccharides in the marine environment. This is the first sequenced genome of a marine bacterium that can degrade plant cell walls, an important component of the carbon cycle that is not well-characterized in the marine environment. PMID:18516288

HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD).

PubMed

Zhang, Xianfeng; Zhou, Tao; Frabutt, Dylan A; Zheng, Yong-Hui

2016-09-01

Vpr enhances HIV-1 replication in macrophages and dendritic cells, as well as the human CD4(+) CEM.NKR T cell line. Recently, Vpr was reported to increase HIV-1 Env expression in macrophages. Here, we report that Vpr also increases HIV-1 Env expression in dendritic cells and CEM.NKR cells. The Vpr activity depends on its N-terminal region, which was disrupted by a single A30L mutation. Env was rapidly degraded in the absence of Vpr, which was blocked by the ERAD pathway inhibitor kifunesine or the lysosome inhibitor Bafilomycin. As2O3 or PK11195, which reportedly enhances HIV-1 Env folding, also blocked the Env degradation in CEM.NKR cells. Thus, these results not only identify Env as a primary target for Vpr to boost HIV-1 replication, but also suggest that Vpr likely promotes Env folding in the ER, which is otherwise misfolded and targeted by the ERAD pathway to lysosomes for degradation. Copyright © 2016 Elsevier Inc. All rights reserved.

Live attenuated vaccines: Historical successes and current challenges

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

Minor, Philip D., E-mail: Philip.Minor@nibsc.org

Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up inmore » clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.« less

Uniportal anatomic combined unusual segmentectomies.

PubMed

González-Rivas, Diego; Lirio, Francisco; Sesma, Julio

2017-01-01

Nowadays, sublobar anatomic resections are gaining momentum as a valid alternative for early stage lung cancer. Despite being technically demanding, anatomic segmentectomies can be performed by uniportal video-assisted thoracic surgery (VATS) approach to combine the benefits of minimally invasiveness with the maximum lung sparing. This procedure can be even more complex if a combined resection of multiple segments from different lobes has to be done. Here we report five cases of combined and unusual segmentectomies done by the same experienced surgeon in high volume institutions to show uniportal VATS is a feasible approach for these complex resections and to share an excellent educational resource.

The Importance of Challenging Hegemonic Masculinity in Preventing School Violence

ERIC Educational Resources Information Center

Dragowski, Eliza A.; Scharrón-del Río, María R.

2014-01-01

In this article we argue that efforts to eradicate school violence should include an understanding of the complex social, cultural, and historical contexts in which violence is perpetrated. Specifically, we assert that the production and perpetuation of hegemonic/dominant masculinity plays a pivotal role in various forms of aggression and violence…

Poverty, Work and Education

ERIC Educational Resources Information Center

von Kotze, Astrid

2007-01-01

This contribution suggests that if we are serious about adult education in the context of poverty eradication we require some shifts away from neo-liberal assumptions and values. Women and/in the informal economy should become the central focus, and livelihood studies would better allow us to understand the complex daily struggle for food and the…

Eeyarestatin 1 Interferes with Both Retrograde and Anterograde Intracellular Trafficking Pathways

PubMed Central

Aletrari, Mina-Olga; McKibbin, Craig; Williams, Helen; Pawar, Vidya; Pietroni, Paola; Lord, J. Michael; Flitsch, Sabine L.; Whitehead, Roger; Swanton, Eileithyia; High, Stephen; Spooner, Robert A.

2011-01-01

Background The small molecule Eeyarestatin I (ESI) inhibits the endoplasmic reticulum (ER)-cytosol dislocation and subsequent degradation of ERAD (ER associated protein degradation) substrates. Toxins such as ricin and Shiga/Shiga-like toxins (SLTx) are endocytosed and trafficked to the ER. Their catalytic subunits are thought to utilise ERAD-like mechanisms to dislocate from the ER into the cytosol, where a proportion uncouples from the ERAD process, recovers a catalytic conformation and destroys their cellular targets. We therefore investigated ESI as a potential inhibitor of toxin dislocation. Methodology and Principal Findings Using cytotoxicity measurements, we found no role for ESI as an inhibitor of toxin dislocation from the ER, but instead found that for SLTx, ESI treatment of cells was protective by reducing the rate of toxin delivery to the ER. Microscopy of the trafficking of labelled SLTx and its B chain (lacking the toxic A chain) showed a delay in its accumulation at a peri-nuclear location, confirmed to be the Golgi by examination of SLTx B chain metabolically labelled in the trans-Golgi cisternae. The drug also reduced the rate of endosomal trafficking of diphtheria toxin, which enters the cytosol from acidified endosomes, and delayed the Golgi-specific glycan modifications and eventual plasma membrane appearance of tsO45 VSV-G protein, a classical marker for anterograde trafficking. Conclusions and Significance ESI acts on one or more components that function during vesicular transport, whilst at least one retrograde trafficking pathway, that of ricin, remains unperturbed. PMID:21799938

Factors Associated with Gastric Black Spot, White Flat Elevated Mucosa, and Cobblestone-Like Mucosa: A Cross-Sectional Study.

PubMed

Hatano, Yu; Haruma, Ken; Kamada, Tomoari; Shiotani, Akiko; Takahari, Kosuke; Matsumoto, Masatoshi; Uchida, Osamu

2018-06-05

Previous studies have reported a possible relevance between proton pump inhibitor (PPI) use and 3 new gastric mucosal changes: black spots (BSs), white flat elevated mucosa (WFEM), and cobblestone-like mucosa (CLM). The aim of this study was to investigate the association between these mucosal changes and multiple factors including PPI use. All subjects who underwent a routine esophagogastroduodenoscopy (EGD) were successively enrolled. Endoscopists carried out the EGD after being blinded about -information on patient PPI usage and determined the presence of these mucosal changes. The ratio of each factor was -compared in cases with and without each gastric finding. Out of 1,214 patients, BSs were recognized in 75 (6.2%) cases, WFEM in 59 (4.9%), and CLM in 41 (3.4%). In logistic regression analysis, PPI use was significantly correlated with all of these findings (BSs: OR 2.94; 95% CI 1.66-5.21), (WFEM: OR 3.58; 95% CI 1.94-6.61), and (CLM: OR 4.57; 95% CI 2.34-9.96), and Helicobacter pylori eradication was related to BSs (OR 3.01; 95% CI 1.73-5.24) and WFEM (OR 2.11; 95% CI 1.08-4.11). Decision-tree analyses showed that H. pylori eradication was associated with all findings. All of the considered findings were correlated with PPI and H. pylori eradication. © 2018 S. Karger AG, Basel.

Prosthetic Device Infections.

PubMed

Martinez, Raquel M; Bowen, Thomas R; Foltzer, Michael A

2016-08-01

The immunocompromised host is a particularly vulnerable population in whom routine and unusual infections can easily and frequently occur. Prosthetic devices are commonly used in these patients and the infections associated with those devices present a number of challenges for both the microbiologist and the clinician. Biofilms play a major role in device-related infections, which may contribute to failed attempts to recover organisms from routine culture methods. Moreover, device-related microorganisms can be difficult to eradicate by antibiotic therapy alone. Changes in clinical practice and advances in laboratory diagnostics have provided significant improvements in the detection and accurate diagnosis of device-related infections. Disruption of the bacterial biofilm plays an essential role in recovering the causative agent in culture. Various culture and nucleic acid amplification techniques are more accurate to guide directed treatment regimens. This chapter reviews the performance characteristics of currently available diagnostic assays and summarizes published guidelines, where available, for addressing suspected infected prosthetic devices.

Myxococcus xanthus Growth, Development, and Isolation.

PubMed

Vaksman, Zalman; Kaplan, Heidi B

2015-11-03

Myxobacteria are a highly social group among the delta proteobacteria that display unique multicellular behaviors during their complex life cycle and provide a rare opportunity to study the boundary between single cells and multicellularity. These organisms are also unusual as their entire life cycle is surface associated and includes a number of social behaviors: social gliding and rippling motility, 'wolf-pack'-like predation, and self-organizing complex biostructures, termed fruiting bodies, which are filled with differentiated environmentally resistant spores. Here we present methods for the growth, maintenance, and storage of Myxococcus xanthus, the most commonly studied of the myxobacteria. We also include methods to examine various developmental and social behaviors (fruiting body and spore formation, predation, and rippling motility). As the myxobacteria, similar to the streptomycetes, are excellent sources of many characterized and uncharacterized antibiotics and other natural products, we have provided a protocol for obtaining natural isolates from a variety of environmental sources. Copyright © 2015 John Wiley & Sons, Inc.

The Endoplasmic Reticulum-Associated Degradation Pathways of Budding Yeast

PubMed Central

Thibault, Guillaume; Ng, Davis T.W.

2012-01-01

Protein misfolding is a common cellular event that can produce intrinsically harmful products. To reduce the risk, quality control mechanisms are deployed to detect and eliminate misfolded, aggregated, and unassembled proteins. In the secretory pathway, it is mainly the endoplasmic reticulum-associated degradation (ERAD) pathways that perform this role. Here, specialized factors are organized to monitor and process the folded states of nascent polypeptides. Despite the complex structures, topologies, and posttranslational modifications of client molecules, the ER mechanisms are the best understood among all protein quality-control systems. This is the result of convergent and sometimes serendipitous discoveries by researchers from diverse fields. Although major advances in ER quality control and ERAD came from all model organisms, this review will focus on the discoveries culminating from the simple budding yeast. PMID:23209158

[Influence of hypocaloric diet with addition of a vitamin-mineral complex on status of patients with obesity 1st and 2nd degrees].

PubMed

Sharafetdinov, Kh Kh; Plotnikova, O A; Zykina, V V; Mal'tsev, G Iu; Sokol'nikov, A A; Kaganov, B S

2011-01-01

Addition of a vitamin-mineral complex (VMC) to a standard hypocaloric diet leads to a positive dynamics of antropometric characteristics in patients with obesity 1st and 2nd degrees which is comparable to effectiveness of standard dietotherapy (dietary treatment) traditionally used in complex treatment of obesity. Addition of 1,8 mg of vitamin B2 as part of VMC to a hypocaloric diet is shown to be inadequate in eradication of marginal provision of riboflavin when using diets reduced in calories.

The Ruthenostannylene Complex [Cp*(IXy)H2 Ru-Sn-Trip]: Providing Access to Unusual Ru-Sn Bonded Stanna-imine, Stannene, and Ketenylstannyl Complexes.

PubMed

Liu, Hsueh-Ju; Ziegler, Micah S; Tilley, T Don

2015-05-26

Reactivity studies of the thermally stable ruthenostannylene complex [Cp*(IXy)(H)2 Ru-Sn-Trip] (1; IXy=1,3-bis(2,6-dimethylphenyl)imidazol-2-ylidene; Cp*=η(5) -C5 Me5 ; Trip=2,4,6-iPr3 C6 H2 ) with a variety of organic substrates are described. Complex 1 reacts with benzoin and an α,β-unsaturated ketone to undergo [1+4] cycloaddition reactions and afford [Cp*(IXy)(H)2 RuSn(κ(2) -O,O-OCPhCPhO)Trip] (2) and [Cp*(IXy)(H)2 RuSn(κ(2) -O,C-OCPhCHCHPh)Trip] (3), respectively. The reaction of 1 with ethyl diazoacetate resulted in a tin-substituted ketene complex [Cp*(IXy)(H)2 RuSn(OC2 H5 )(CHCO)Trip] (4), which is most likely a decomposition product from the putative ruthenium-substituted stannene complex. The isolation of a ruthenium-substituted stannene [Cp*(IXy)(H)2 RuSn(=Flu)Trip] (5) and stanna-imine [Cp*(IXy)(H)2 RuSn(κ(2) -N,O-NSO2 C6 H4 Me)Trip] (6) complexes was achieved by treatment of 1 with 9-diazofluorene and tosyl azide, respectively. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Live attenuated vaccines: Historical successes and current challenges.

PubMed

Minor, Philip D

2015-05-01

Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Chronic active Epstein-Barr virus infection (CAEBV) successfully treated with allogeneic peripheral blood stem cell transplantation.

PubMed

Taketani, T; Kikuchi, A; Inatomi, J; Hanada, R; Kawaguchi, H; Ida, K; Oh-Ishi, T; Arai, T; Kishimoto, H; Yamamoto, K

2002-03-01

We report a pediatric case of CAEBV and T cell-based Hodgkin's-like disease successfully treated with allo PBSCT from an HLA-matched sibling. The diagnosis of CAEBV was made from clinical signs and the presence of the EBV genome in PBMC and tumor cells. Conditioning with busulfan (BU) + etoposide (VP16) + cyclophosphamide (CY) was effective and well tolerated. EBV was totally eradicated by 3 months after allo PBSCT. Although she suffered from chronic GVHD of the liver, she has been well and free of disease for 47 months since PBSCT. We suggest allo PBSCT for CAEBV as a potent therapeutic strategy for eradication of the EBV genome and allowing immunological reconstitution.

Male and female viewpoints on female circumcision in Ekpeye, Rivers State, Nigeria.

PubMed

Briggs, L A

2002-12-01

One hundred and ninety five male and female volunteers across the social strata were interviewed using structured questionnaire. Data were analysed using frequency tables. The study revealed that 74.7% of female respondents were circumcised. They believe that the practice would help prevent sexual promiscuity, curb sexual desires and that it is a custom they cannot do without. Most of the men would not marry an uncircumcised female, while a substantial number of the respondents would like to circumcise their daughters. Community effort to eradicate the practice is very minimal. Based on the findings, it is suggested that communities where female genital mutilation (FGM) is practiced as a social norm should be involved in eradication campaigns with support from national and international organisations.

Very unusual "needle- and pencil-like" uric acid crystals in the urine unmasked by infrared spectroscopy investigation.

PubMed

Baroni, S; Garigali, G; Primiano, A; Gervasoni, J; Fogazzi, G B

2018-04-01

In this paper we describe a case with very unusual "needle- and pencil-like" crystals, partly similar to those reported by other investigators, who considered them as due to uric acid. Quite importantly, infrared spectroscopy investigation which, to our knowledge, we have been the first to perform on this type of crystals, confirmed their nature as uric acid structures. This case demonstrates that the planet of urinary crystals still has several unknown facets and still deserves exploration. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis, X-ray characterisation and reactions of a trigonal planar palladium(0) carbonyl complex, (tbpx)PdCO.

PubMed

Bellabarba, Ronan M; Tooze, Robert P; Slawin, Alexandra M Z

2003-08-07

The novel complex (tbpx)PdCO (1), the first example of a structurally characterised sixteen electron, trigonal planar palladium(0) carbonyl complex, was prepared, characterised by NMR spectroscopy and X-ray crystallography, and some unusual aspects of its reactivity were studied.

Multisite Phosphorylation of Human Liver Cytochrome P450 3A4 Enhances Its gp78- and CHIP-mediated Ubiquitination

PubMed Central

Wang, YongQiang; Guan, Shenheng; Acharya, Poulomi; Liu, Yi; Thirumaran, Ranjit K.; Brandman, Relly; Schuetz, Erin G.; Burlingame, Alma L.; Correia, Maria Almira

2012-01-01

CYP3A4, an integral endoplasmic reticulum (ER)-anchored protein, is the major human liver cytochrome P450 enzyme responsible for the disposition of over 50% of clinically relevant drugs. Alterations of its protein turnover can influence drug metabolism, drug-drug interactions, and the bioavailability of chemotherapeutic drugs. Such CYP3A4 turnover occurs via a classical ER-associated degradation (ERAD) process involving ubiquitination by both UBC7/gp78 and UbcH5a/CHIP E2-E3 complexes for 26 S proteasomal targeting. These E3 ligases act sequentially and cooperatively in CYP3A4 ERAD because RNA interference knockdown of each in cultured hepatocytes results in the stabilization of a functionally active enzyme. We have documented that UBC7/gp78-mediated CYP3A4 ubiquitination requires protein phosphorylation by protein kinase (PK) A and PKC and identified three residues (Ser-478, Thr-264, and Ser-420) whose phosphorylation is required for intracellular CYP3A4 ERAD. We document herein that of these, Ser-478 plays a pivotal role in UBC7/gp78-mediated CYP3A4 ubiquitination, which is accelerated and enhanced on its mutation to the phosphomimetic Asp residue but attenuated on its Ala mutation. Intriguingly, CYP3A5, a polymorphically expressed human liver CYP3A4 isoform (containing Asp-478) is ubiquitinated but not degraded to a greater extent than CYP3A4 in HepG2 cells. This suggests that although Ser-478 phosphorylation is essential for UBC7/gp78-mediated CYP3A4 ubiquitination, it is not sufficient for its ERAD. Additionally, we now report that CYP3A4 protein phosphorylation by PKA and/or PKC at sites other than Ser-478, Thr-264, and Ser-420 also enhances UbcH5a/CHIP-mediated ubiquitination. Through proteomic analyses, we identify (i) 12 additional phosphorylation sites that may be involved in CHIP-CYP3A4 interactions and (ii) 8 previously unidentified CYP3A4 ubiquitination sites within spatially associated clusters of Asp/Glu and phosphorylatable Ser/Thr residues that may serve to engage each E2-E3 complex. Collectively, our findings underscore the interplay between protein phosphorylation and ubiquitination in ERAD and, to our knowledge, provide the very first example of gp78 substrate recognition via protein phosphorylation. PMID:22101235

An unusual complication of a "blind" femoral embolectomy.

PubMed

Karkos, Christos D; Karamanos, Dimitrios G; Papadimitriou, Dimitrios N; Demiropoulos, Filippos; Zambas, Neophytos; Gerassimidis, Thomas S

2010-08-01

Iatrogenic pseudoaneurysms after femoral embolectomy are unusual and have been described in the peroneal, posterior tibial, and popliteal arteries. We present an unusual case of such a pseudoaneurysm originating from a medial superior genicular collateral vessel that was coming off the proximal popliteal artery at an acute angle. It is likely that the embolectomy catheter had accidentally entered this branch, which ruptured when the balloon was inflated. Transcatheter coil embolization resulted in successful thrombosis of the pseudoaneurysm. Copyright 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Why Congo red binding is specific for amyloid proteins - model studies and a computer analysis approach.

PubMed

Roterman, I; KrUl, M; Nowak, M; Konieczny, L; Rybarska, J; Stopa, B; Piekarska, B; Zemanek, G

2001-01-01

The complexing of Congo red in two different ligand forms - unimolecular and supramolecular (seven molecules in a micelle) - with eight deca-peptides organized in a b-sheet was tested by computational analysis to identify its dye-binding preferences. Polyphenylananine and polylysine peptides were selected to represent the specific side chain interactions expected to ensure particularly the stabilization of the dye-protein complex. Polyalanine was used to verify the participation of non-specific backbone-derived interactions. The initial complexes for calculation were constructed by intercalating the dye between the peptides in the middle of the beta-sheet. The long axis of the dye molecule (in the case of unimolecular systems) or the long axis of the ribbon-like micelle (in the case of the supramolecular dye form) was oriented parallel to the peptide backbone. This positioning maximally reduced the exposure of the hydrophobic diphenyl (central dye fragment) to water. In general the complexes of supramolecular Congo red ligands appeared more stable than those formed by individual dye molecules. Specific interactions (electrostatic and/or ring stacking) dominated as binding forces in the case of the single molecule, while non-specific surface adsorption seemed decisive in complexing with the supramolecular ligand. Both the unimolecular and supramolecular versions of the dye ligand were found to be likely to form complexes of sufficient stability with peptides. The low stability of the protein and the gap accessible to penetration in the peptide sheet seem sufficient for supramolecular ligand binding, but the presence of positively charged or hydrophobic amino acids may strengthen binding significantly. The need for specific interaction makes single-molecule Congo red binding rather unusual as a general amyloid protein ligand. The structural feature of Congo red, which enables specific and common interaction with amyloid proteins, probably derives from the ribbon-like self-assembled form of the dye.

India's Research Contributions Towards Polio Eradication (1965-2015).

PubMed

John, T Jacob

2016-08-07

Pioneering research has been conducted in India during the past five decades, comprehensively covering epidemiology of poliovirus infection and of polio, efficacy and effectiveness of oral and inactivated polio vaccines (OPV, IPV) as well as pathogenesis of wild and vaccine polioviruses. It was estimated, based on epidemiology data, that India had a very heavy burden of polio, with average 500-1000 cases per day. Prevention was an urgent need, but OPV showed unacceptably low vaccine efficacy (VE) for poliovirus types 1 and 3. Having learned that response to sequential doses followed arithmetic pattern and not prime-boost principle, multiple doses were tested and found to be a simple intervention to increase VE. Eventually this knowledge became critical for polio eradication. Indian research demonstrated that monovalent OPV (mOPV) had nearly three timed higher VE than trivalent OPV (tOPV). Eventually, mOPV type 1 became essential to interrupt wild type 1 infection in many locations where the VE of tOPV was very low. Indian research pointed to the epidemiologic importance of direct person-to-person spread of wild polio viruses and the need and potential of IPV to prevent and control polio. Research on vaccine responses led to the understanding that OPV would become wild-like through back mutations and to the definition of eradication as interrupting transmission of both wild and vaccine-derived polioviruses. By asking and answering the right questions insequence, Indian polio research presaged and guided polio eradication.

The immunoglobulin-like domains 1 and 2 of the protein tyrosine phosphatase LAR adopt an unusual horseshoe-like conformation

PubMed Central

Biersmith, Bridget H.; Hammel, Michal; Geisbrecht, Erika R.; Bouyain, Samuel

2011-01-01

Neurogenesis depends on exquisitely regulated interactions between macromolecules on the cell surface and in the extracellular matrix. In particular, interactions between proteoglycans and members of the type IIa subgroup of receptor protein tyrosine phosphatases underlie critical developmental processes such as the formation of synapses at the neuromuscular junction and the migration of axons to their appropriate targets. We report here the crystal structures of the first and second immunoglobulin-like domains of the Drosophila type IIa receptor Dlar and its mouse homologue LAR. These two domains adopt an unusual antiparallel arrangement that has not been previously observed in tandem repeats of immunoglobulin-like domains and that is presumably conserved in all type IIa receptor protein tyrosine phosphatases. PMID:21402080

Uniportal anatomic combined unusual segmentectomies

PubMed Central

Lirio, Francisco; Sesma, Julio

2017-01-01

Nowadays, sublobar anatomic resections are gaining momentum as a valid alternative for early stage lung cancer. Despite being technically demanding, anatomic segmentectomies can be performed by uniportal video-assisted thoracic surgery (VATS) approach to combine the benefits of minimally invasiveness with the maximum lung sparing. This procedure can be even more complex if a combined resection of multiple segments from different lobes has to be done. Here we report five cases of combined and unusual segmentectomies done by the same experienced surgeon in high volume institutions to show uniportal VATS is a feasible approach for these complex resections and to share an excellent educational resource. PMID:29078653

Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

PubMed

Gisbert, Javier P; Pérez-Aisa, Angeles; Bermejo, Fernando; Castro-Fernández, Manuel; Almela, Pedro; Barrio, Jesús; Cosme, Angel; Modolell, Inés; Bory, Felipe; Fernández-Bermejo, Miguel; Rodrigo, Luis; Ortuño, Jesús; Sánchez-Pobre, Pilar; Khorrami, Sam; Franco, Alejandro; Tomas, Albert; Guerra, Iván; Lamas, Eloisa; Ponce, Julio; Calvet, Xavier

2013-02-01

Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. Prospective multicenter study. In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

Intracellular activation of the fibrinolytic cascade in the Quebec Platelet Disorder.

PubMed

Sheth, Prameet M; Kahr, Walter H A; Haq, M Anwar; Veljkovic, Dragoslava Kika; Rivard, Georges E; Hayward, Catherine P M

2003-08-01

The Quebec Platelet Disorder (QPD) is an unusual bleeding disorder associated with increased platelet stores of urokinase-type plasminogen activator (u-PA) and proteolysis of platelet alpha-granule proteins. The increased u-PA and proteolyzed plasminogen in QPD platelets led us to investigate possible contributions of intracellular plasmin generation to QPD alpha-granule proteolysis. ELISA indicated there were normal amounts of plasminogen and plasmin-alpha(2)-antiplasmin (PAP) complexes in QPD plasmas. Like normal platelets, QPD platelets contained only a small proportion of the blood plasminogen, however, they contained an increased amount of PAP complexes compared to normal platelets (P < 0.005). The quantities of plasminogen stored in platelets were important to induce QPD-like proteolysis of normal alpha-granule proteins by two chain u-PA (tcu-PA) in vitro. Moreover, adding supplemental plasminogen to QPD, but not to control, platelet lysates, triggered further alpha-granule protein proteolysis to forms that comigrated with plasmin degraded proteins. These data suggest the generation of increased but limiting amounts of plasmin within platelets is involved in producing the unique phenotypic changes to alpha-granule proteins in QPD platelets. The QPD is the only known bleeding disorder associated with chronic, intracellular activation of the fibrinolytic cascade.

Hepatobiliary fascioliasis: a case with unusual radiological features.

PubMed

Yeşildağ, Ahmet; Senol, Altuğ; Köroğlu, Mert; Koçkar, Cem; Oyar, Orhan; Işler, Mehmet

2010-12-01

We report a case of hepatobiliary fascioliasis presenting with unusual radiological findings that have not been reported previously. Imaging studies revealed hepatic cystic pouches communicating with intrahepatic bile ducts. Snail-like, oval shaped and conglomerated echogenic particles with no acoustic shadowing, suggesting F. hepatica, were detected in these cystic pouches. In addition, secondary sclerosing cholangitis developed after fascioliasis.

PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfide-dependent interactions in the endoplasmic reticulum.

PubMed

van Lith, Marcel; Hartigan, Nichola; Hatch, Jennifer; Benham, Adam M

2005-01-14

Protein disulfide isomerase (PDI) is the archetypal enzyme involved in the formation and reshuffling of disulfide bonds in the endoplasmic reticulum (ER). PDI achieves its redox function through two highly conserved thioredoxin domains, and PDI can also operate as an ER chaperone. The substrate specificities and the exact functions of most other PDI family proteins remain important unsolved questions in biology. Here, we characterize a new and striking member of the PDI family, which we have named protein disulfide isomerase-like protein of the testis (PDILT). PDILT is the first eukaryotic SXXC protein to be characterized in the ER. Our experiments have unveiled a novel, glycosylated PDI-like protein whose tissue-specific expression and unusual motifs have implications for the evolution, catalytic function, and substrate selection of thioredoxin family proteins. We show that PDILT is an ER resident glycoprotein that liaises with partner proteins in disulfide-dependent complexes within the testis. PDILT interacts with the oxidoreductase Ero1alpha, demonstrating that the N-terminal cysteine of the CXXC sequence is not required for binding of PDI family proteins to ER oxidoreductases. The expression of PDILT, in addition to PDI in the testis, suggests that PDILT performs a specialized chaperone function in testicular cells. PDILT is an unusual PDI relative that highlights the adaptability of chaperone and redox function in enzymes of the endoplasmic reticulum.

Endgame for polio eradication? Options for overcoming social and political factors in the progress to eradicating polio.

PubMed

Ganapathiraju, Pavan V; Morssink, Christiaan B; Plumb, James

2015-01-01

In 1988, the Global Polio Eradication Initiative (GPEI) was launched with the goal of eradicating polio by the year 2000. After 25 years, several dynamics still challenge this large public health campaign with new cases of polio being reported annually. We examine the roots of this initiative to eradicate polio, its scope, the successes and setbacks during the last 25 years and reflect on the current state of affairs. We examine the social and political factors that are barriers to polio eradication. Options are discussed for solving the current impasse of polio eradication: using force, respecting individual freedoms and gaining support from those vulnerable to fundamentalist 'propaganda'. The travails of the GPEI indicate the need for expanding the Convention on the Rights of the Child to address situations of war and civic strife. Such a cultural and structural reference will provide the basis for global stakeholders to engage belligerent local actors whose local political conflicts are barriers to the eradication of polio. Disregard for these actors will result in stagnation of polio eradication policy, delaying eradication beyond 2018.

A Metagenomics-Based Metabolic Model of Nitrate-Dependent Anaerobic Oxidation of Methane by Methanoperedens-Like Archaea

PubMed Central

Arshad, Arslan; Speth, Daan R.; de Graaf, Rob M.; Op den Camp, Huub J. M.; Jetten, Mike S. M.; Welte, Cornelia U.

2015-01-01

Methane oxidation is an important process to mitigate the emission of the greenhouse gas methane and further exacerbating of climate forcing. Both aerobic and anaerobic microorganisms have been reported to catalyze methane oxidation with only a few possible electron acceptors. Recently, new microorganisms were identified that could couple the oxidation of methane to nitrate or nitrite reduction. Here we investigated such an enrichment culture at the (meta) genomic level to establish a metabolic model of nitrate-driven anaerobic oxidation of methane (nitrate-AOM). Nitrate-AOM is catalyzed by an archaeon closely related to (reverse) methanogens that belongs to the ANME-2d clade, tentatively named Methanoperedens nitroreducens. Methane may be activated by methyl-CoM reductase and subsequently undergo full oxidation to carbon dioxide via reverse methanogenesis. All enzymes of this pathway were present and expressed in the investigated culture. The genome of the archaeal enrichment culture encoded a variety of enzymes involved in an electron transport chain similar to those found in Methanosarcina species with additional features not previously found in methane-converting archaea. Nitrate reduction to nitrite seems to be located in the pseudoperiplasm and may be catalyzed by an unusual Nar-like protein complex. A small part of the resulting nitrite is reduced to ammonium which may be catalyzed by a Nrf-type nitrite reductase. One of the key questions is how electrons from cytoplasmically located reverse methanogenesis reach the nitrate reductase in the pseudoperiplasm. Electron transport in M. nitroreducens probably involves cofactor F420 in the cytoplasm, quinones in the cytoplasmic membrane and cytochrome c in the pseudoperiplasm. The membrane-bound electron transport chain includes F420H2 dehydrogenase and an unusual Rieske/cytochrome b complex. Based on genome and transcriptome studies a tentative model of how central energy metabolism of nitrate-AOM could work is presented and discussed. PMID:26733968

Eradication of tetanus.

PubMed

Thwaites, C L; Loan, H T

2015-01-01

The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care. Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications. The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world. Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization. It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses. © The Author 2015. Published by Oxford University Press.

Chemotherapy in heterogeneous cultures of cancer cells with interconversion

NASA Astrophysics Data System (ADS)

Dilão, Rui

2015-02-01

Recently, the interconversion between differentiated and stem-like cancer cells has been observed. Here, we model the in vitro growth of heterogeneous cell cultures in the presence of interconversion from differentiated cancer cells to cancer stem cells (CSCs), showing that, by targeting only CSC with cytotoxic agents, it is not always possible to eradicate cancer. We have determined the kinetic conditions under which cytotoxic agents in in vitro heterogeneous cultures of cancer cells eradicate cancer. In particular, we have shown that the chemotherapeutic elimination of in vitro cultures of heterogeneous cancer cells is effective only if it targets all cancer cell types, and if the induced death rates for the different subpopulations of cancer cell types are large enough. The quantitative results of the model are compared and validated with experimental data.

WISE J233237.05-505643.5: A Double-Peaked Broad-Lined AGN with Spiral-Shaped Radio Morphology

NASA Technical Reports Server (NTRS)

Tsai, Chao Wei; Jarrett, Thomas H.; Stern, Daniel; Emonts, Bjorn; Barrows, R. Scott; Assef, Roberto J.; Norris, Ray P.; Eisenhardt, Peter R. M.; Lonsdale, Carol; Blain, Andrew W.;

A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life*

PubMed Central

Schoch, Angela; Larraillet, Vincent; Hilger, Maximiliane; Schlothauer, Tilman; Emrich, Thomas

2017-01-01

The success of recombinant monoclonal immunoglobulins (IgG) is rooted in their ability to target distinct antigens with high affinity combined with an extraordinarily long serum half-life, typically around 3 weeks. The pharmacokinetics of IgGs is intimately linked to the recycling mechanism of the neonatal Fc receptor (FcRn). For long serum half-life of therapeutic IgGs, the highly pH-dependent interaction with FcRn needs to be balanced to allow efficient FcRn binding and release at slightly acidic pH and physiological pH, respectively. Some IgGs, like the antibody briakinumab has an unusually short half-life of ∼8 days. Here we dissect the molecular origins of excessive FcRn binding in therapeutic IgGs using a combination of hydrogen/deuterium exchange mass spectrometry and FcRn affinity chromatography. We provide experimental evidence for a two-pronged IgG-FcRn binding mechanism involving direct FcRn interactions with both the Fc region and the Fab regions of briakinumab, and correlate the occurrence of excessive FcRn binding to an unusually strong Fab-FcRn interaction. PMID:28062799

Computer Virus Protection

ERIC Educational Resources Information Center

Rajala, Judith B.

2004-01-01

A computer virus is a program--a piece of executable code--that has the unique ability to replicate. Like biological viruses, computer viruses can spread quickly and are often difficult to eradicate. They can attach themselves to just about any type of file, and are spread by replicating and being sent from one individual to another. Simply having…

Eradication failure of newly acquired Pseudomonas aeruginosa isolates in cystic fibrosis.

PubMed

Cohen-Cymberknoh, Malena; Gilead, Noa; Gartner, Silvia; Rovira, Sandra; Blau, Hannah; Mussaffi, Huda; Rivlin, Joseph; Gur, Michal; Shteinberg, Michal; Bentur, Lea; Livnat, Galit; Aviram, Micha; Picard, Elie; Tenenbaum, Ariel; Armoni, Shoshana; Breuer, Oded; Shoseyov, David; Kerem, Eitan

2016-11-01

Eradication of Pseudomonas aeruginosa (PA) is critical in cystic fibrosis (CF) patients. To determine eradication success rate of newly acquired PA and to identify characteristics associated with eradication failure. In an observational study, data from patients with newly acquired PA infection from 2007 to 2013 were collected. Clinical variables were compared in patients with and without successful eradication for ≥1year. Of 183 patients out of 740 (25%) from 7 CF Centers that had newly acquired PA, eradication succeeded in 72%. Patients with the highest risk of failure had multi-resistant PA, fewer sputum cultures taken, were older, and were diagnosed at a later age. The risk of eradication failure increased by 1.3% with each year of delayed CF diagnosis; successful eradication increased by 17% with each additional sputum culture taken. Delayed detection of PA infection leading to delayed treatment and growth of multi-resistant organisms is associated with eradication failure. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Temporal Epidemiology of Sudden Oak Death in Oregon.

PubMed

Peterson, Ebba K; Hansen, Everett M; Kanaskie, Alan

2015-07-01

An effort to eradicate Phytophthora ramorum, causal agent of sudden oak death, has been underway since its discovery in Oregon forests. Using an information-theoretical approach, we sought to model yearly variation in the size of newly infested areas and dispersal distance. Maximum dispersal distances were best modeled by spring and winter precipitation 2 years before detection, and infestation size the year prior. Infestation size was best modeled by infestation size and spring precipitation the year prior. In our interpretation, there is a 2-year delay between the introduction of inoculum and onset of mortality for a majority of sites. The year-long gap in between allows ample time for the production of inoculum contributing to the spread of P. ramorum. This is supported by epidemic development following changes in eradication protocols precipitated by an outbreak in 2011, attributable to a 2009 treatment delay and an uncharacteristically wet spring in 2010. Posteradication, we have observed an increase in the total area of new outbreaks and increased frequency in dispersal distances greater than 4 km. Although the eradication program has not eliminated P. ramorum from Oregon forests, it has likely moderated this epidemic, emphasizing the need for prompt treatment of future invasive forest pathogens.

Use of probiotics in the fight against Helicobacter pylori

PubMed Central

Ruggiero, Paolo

2014-01-01

After the discovery of Helicobacter pylori (H. pylori), and the evidence of its relationship with gastric diseases, antibiotic-based therapies were developed, which efficacy was however limited by antibiotic resistance and lack of patient compliance. A vaccine would overcome these drawbacks, but currently there is not any H. pylori vaccine licensed. In the frame of the studies aimed at finding alternative therapies or at increasing the efficacy of the current ones and/or reducing their side effects, the investigation on the use of probiotics plays an interesting role. In vitro and preclinical studies have shown the feasibility of this approach. Several clinical trials indicated that administration of probiotics can reduce the side effects of H. pylori eradication treatment, increasing tolerability, and often increases the overall efficacy. The results of these trials vary, likely reflecting the variety of probiotics assessed and that of the eradication treatment, as well as the differences in the geographic area that imply different H. pylori strains distribution, host susceptibility, and therapy efficacy. In conclusion, the use of probiotics appears promising as an adjuvant for the current H. pylori eradication treatment, though it still requires optimization. PMID:25400981

Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation.

PubMed

Nasr, Rihab; Guillemin, Marie-Claude; Ferhi, Omar; Soilihi, Hassan; Peres, Laurent; Berthier, Caroline; Rousselot, Philippe; Robledo-Sarmiento, Macarena; Lallemand-Breitenbach, Valérie; Gourmel, Bernard; Vitoux, Dominique; Pandolfi, Pier Paolo; Rochette-Egly, Cécile; Zhu, Jun; de Thé, Hugues

2008-12-01

Retinoic acid and arsenic trioxide target the protein stability and transcriptional repression activity of the fusion oncoprotein PML-RARA, resulting in regression of acute promyelocytic leukemia (APL). Phenotypically, retinoic acid induces differentiation of APL cells. Here we show that retinoic acid also triggers growth arrest of leukemia-initiating cells (LICs) ex vivo and their clearance in PML-RARA mouse APL in vivo. Retinoic acid treatment of mouse APLs expressing the fusion protein PLZF-RARA triggers full differentiation, but not LIC loss or disease remission, establishing that differentiation and LIC loss can be uncoupled. Although retinoic acid and arsenic synergize to clear LICs through cooperative PML-RARA degradation, this combination does not enhance differentiation. A cyclic AMP (cAMP)-dependent phosphorylation site in PML-RARA is crucial for retinoic acid-induced PML-RARA degradation and LIC clearance. Moreover, activation of cAMP signaling enhances LIC loss by retinoic acid, identifying cAMP as another potential APL therapy. Thus, whereas transcriptional activation of PML-RARA is likely to control differentiation, its catabolism triggers LIC eradication and long-term remission of mouse APL. Therapy-triggered degradation of oncoproteins could be a general strategy to eradicate cancer stem cells.

The potential impact of immunization campaign budget re-allocation on global eradication of paediatric infectious diseases

PubMed Central

2011-01-01

Background The potential benefits of coordinating infectious disease eradication programs that use campaigns such as supplementary immunization activities (SIAs) should not be over-looked. One example of a coordinated approach is an adaptive "sequential strategy": first, all annual SIA budget is dedicated to the eradication of a single infectious disease; once that disease is eradicated, the annual SIA budget is re-focussed on eradicating a second disease, etc. Herd immunity suggests that a sequential strategy may eradicate several infectious diseases faster than a non-adaptive "simultaneous strategy" of dividing annual budget equally among eradication programs for those diseases. However, mathematical modeling is required to understand the potential extent of this effect. Methods Our objective was to illustrate how budget allocation strategies can interact with the nonlinear nature of disease transmission to determine time to eradication of several infectious diseases under different budget allocation strategies. Using a mathematical transmission model, we analyzed three hypothetical vaccine-preventable infectious diseases in three different countries. A central decision-maker can distribute funding among SIA programs for these three diseases according to either a sequential strategy or a simultaneous strategy. We explored the time to eradication under these two strategies under a range of scenarios. Results For a certain range of annual budgets, all three diseases can be eradicated relatively quickly under the sequential strategy, whereas eradication never occurs under the simultaneous strategy. However, moderate changes to total SIA budget, SIA frequency, order of eradication, or funding disruptions can create disproportionately large differences in the time and budget required for eradication under the sequential strategy. We find that the predicted time to eradication can be very sensitive to small differences in the rate of case importation between the countries. We also find that the time to eradication of all three diseases is not necessarily lowest when the least transmissible disease is targeted first. Conclusions Relatively modest differences in budget allocation strategies in the near-term can result in surprisingly large long-term differences in time required to eradicate, as a result of the amplifying effects of herd immunity and the nonlinearities of disease transmission. More sophisticated versions of such models may be useful to large international donors or other organizations as a planning or portfolio optimization tool, where choices must be made regarding how much funding to dedicate to different infectious disease eradication efforts. PMID:21955853

The potential impact of immunization campaign budget re-allocation on global eradication of paediatric infectious diseases.

PubMed

Fitzpatrick, Tiffany; Bauch, Chris T

2011-09-28

The potential benefits of coordinating infectious disease eradication programs that use campaigns such as supplementary immunization activities (SIAs) should not be over-looked. One example of a coordinated approach is an adaptive "sequential strategy": first, all annual SIA budget is dedicated to the eradication of a single infectious disease; once that disease is eradicated, the annual SIA budget is re-focussed on eradicating a second disease, etc. Herd immunity suggests that a sequential strategy may eradicate several infectious diseases faster than a non-adaptive "simultaneous strategy" of dividing annual budget equally among eradication programs for those diseases. However, mathematical modeling is required to understand the potential extent of this effect. Our objective was to illustrate how budget allocation strategies can interact with the nonlinear nature of disease transmission to determine time to eradication of several infectious diseases under different budget allocation strategies. Using a mathematical transmission model, we analyzed three hypothetical vaccine-preventable infectious diseases in three different countries. A central decision-maker can distribute funding among SIA programs for these three diseases according to either a sequential strategy or a simultaneous strategy. We explored the time to eradication under these two strategies under a range of scenarios. For a certain range of annual budgets, all three diseases can be eradicated relatively quickly under the sequential strategy, whereas eradication never occurs under the simultaneous strategy. However, moderate changes to total SIA budget, SIA frequency, order of eradication, or funding disruptions can create disproportionately large differences in the time and budget required for eradication under the sequential strategy. We find that the predicted time to eradication can be very sensitive to small differences in the rate of case importation between the countries. We also find that the time to eradication of all three diseases is not necessarily lowest when the least transmissible disease is targeted first. Relatively modest differences in budget allocation strategies in the near-term can result in surprisingly large long-term differences in time required to eradicate, as a result of the amplifying effects of herd immunity and the nonlinearities of disease transmission. More sophisticated versions of such models may be useful to large international donors or other organizations as a planning or portfolio optimization tool, where choices must be made regarding how much funding to dedicate to different infectious disease eradication efforts.

Length of Barrett's segment predicts failure of eradication in radiofrequency ablation for Barrett's esophagus: a retrospective cohort study.

PubMed

Luckett, Tyler; Allamneni, Chaitanya; Cowley, Kevin; Eick, John; Gullick, Allison; Peter, Shajan

2018-05-21

We aim to investigate factors that may contribute to failure of eradication of dysplastic Barrett's Esophagus among patients undergoing radiofrequency ablation treatment. A retrospective review of patients undergoing radiofrequency ablation for treatment of Barrett's Esophagus was performed. Data analyzed included patient demographics, medical history, length of Barrett's Esophagus, number of radiofrequency ablation sessions, and histopathology. Subsets of patients achieving complete eradication were compared with those not achieving complete eradication. A total of 107 patients underwent radiofrequency ablation for Barrett's Esophagus, the majority white, overweight, and male. Before treatment, 63 patients had low-grade dysplasia, and 44 patients had high-grade dysplasia or carcinoma. Complete eradication was achieved in a majority of patients (57% for metaplasia, and 76.6% for dysplasia). Failure of eradication occurred in 15.7% of patients. The median number of radiofrequency ablation treatments in patients achieving complete eradication was 3 sessions, compared to 4 sessions for failure of eradication (p = 0.06). Barrett's esophagus length of more than 5 cm was predictive of failure of eradication (p < 0.001). Radiofrequency ablation for dysplastic Barrett's Esophagus is a proven and effective treatment modality, associated with a high rate of complete eradication. Our rates of eradication from a center starting an ablation program are comparable to previously published studies. Length of Barrett's segment > 5 cm was found to be predictive of failure of eradication in patients undergoing radiofrequency ablation.

[Magnetic therapy for complex treatment of chronic periodontal disease].

PubMed

P'yanzina, A V

The aim of the study was to elaborate the methodology of magnetic therapy for complex treatment of chronic periodontal disease (CPD). The study included 60 patients aged 35 to 65 years with moderate CPD divided in 2 groups. Patients in group 1 (controls) received impulse carbonate irrigation for 12 min №10, group 2 additionally received magnetic therapy for 5 min №10 in maxillary and mandibular areas. periodontal and rheological indices proved magnetic therapy to be useful tool for eradication of inflammation, periodontal tissue functional recovery and stabilization.

Molecular And Structural Basis of Cytokine Receptor Pleiotropy in the Interleukin-4/13 System

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

LaPorte, S.L.; Juo, Z.S.; Vaclavikova, J.

2009-05-20

Interleukin-4 and Interleukin-13 are cytokines critical to the development of T cell-mediated humoral immune responses, which are associated with allergy and asthma, and exert their actions through three different combinations of shared receptors. Here we present the crystal structures of the complete set of type I (IL-4R{alpha}/{gamma}{sub c}/IL-4) and type II (IL-4R/IL-13R{alpha}1/IL-4, IL-4R{alpha}/IL-13R{alpha}1/IL-13) ternary signaling complexes. The type I complex reveals a structural basis for {gamma}{sub c}'s ability to recognize six different {gamma}{sub c}-cytokines. The two type II complexes utilize an unusual top-mounted Ig-like domain on IL-13R{alpha}1 for a novel mode of cytokine engagement that contributes to a reversal inmore » the IL-4 versus IL-13 ternary complex assembly sequences, which are mediated through substantially different recognition chemistries. We also show that the type II receptor heterodimer signals with different potencies in response to IL-4 versus IL-13 and suggest that the extracellular cytokine-receptor interactions are modulating intracellular membrane-proximal signaling events.« less

Isolation of Mycobacterium avium from waterfowl with polycystic livers

USGS Publications Warehouse

Roffe, Thomas J.

1989-01-01

An unusual gross appearance of avian tuberculosis, where fluid-filled thin-walled cysts are produced and grossly apparent in preference to granulomas, is presented. Histopathology confirmed the granulomatous nature of the lesions and the presence of intracellular acid-fast organisms. Mycobacterium avium complex was cultured from affected organs. The unusual gross presentation in these cases indicates the need to consider tuberculosis in the differential of cystic diseases of avian livers.

Eradication of Yaws: Historical Efforts and Achieving WHO's 2020 Target

PubMed Central

Asiedu, Kingsley; Fitzpatrick, Christopher; Jannin, Jean

2014-01-01

Background Yaws, one of the 17 neglected tropical diseases (NTDs), is targeted for eradication by 2020 in resolution WHA66.12 of the World Health Assembly (2013) and the WHO roadmap on NTDs (2012). The disease frequently affects children who live in poor socioeconomic conditions. Between 1952 and 1964, WHO and the United Nations Children's Fund (UNICEF) led a global eradication campaign using injectable benzathine penicillin. Recent developments using a single dose of oral azithromycin have renewed optimism that eradication can be achieved through a comprehensive large-scale treatment strategy. We review historical efforts to eradicate yaws and argue that this goal is now technically feasible using new tools and with the favorable environment for control of NTDs. We also summarize the work of WHO's Department of Control of Neglected Tropical Diseases in leading the renewed eradication initiative and call on the international community to support efforts to achieve the 2020 eradication goal. The critical factor remains access to azithromycin. Excluding medicines, the financial cost of yaws eradication could be as little as US$ 100 million. Conclusions The development of new tools has renewed interest in eradication of yaws; with modest support, the WHO eradication target of 2020 can be achieved. PMID:25254372

Economic considerations for the eradication endgame

PubMed Central

Barrett, Scott

2013-01-01

An infectious disease will be eradicated only if it is eliminated everywhere, including in the hardest-to-reach, most vaccine-wary communities. If eradication is successful, it promises a dividend in the form of avoided infections and vaccinations. However, success is never certain unless and until eradication is achieved, and claiming the dividend means bearing the possibly great risk of re-emergence. Economic analysis of eradication evaluates these risks and rewards relative to the alternative of ‘optimal control’, and also exposes the incentives for achieving and capitalizing on eradication. Eradication is a ‘game’, because some countries may be willing to eliminate the disease within their borders only if assured that all others will eliminate the disease within their borders. International financing is also a game, because each country would rather free ride than contribute. Finally, for diseases such as polio, capitalizing on eradication is a game, for should any country continue to vaccinate in the post-eradication era using the live-attenuated polio vaccine, the countries that stop vaccinating will be exposed to the risk of vaccine-derived polioviruses. In the framework developed in this paper, eradication is a seductive goal, its attainment fraught with peril. PMID:23798697

Helicobacter pylori eradication with lansoprazole, amoxycillin and clarithromycin: testing an ideal regimen in a multicultural south east Asian population and examining factors potentially influencing eradication.

PubMed

Kaushik, S P; Vu, C

2000-04-01

From European and North American data, it is recommended in the Asia Pacific consensus statement, that one week therapy with a proton pump inhibitor, amoxycillin and clarithromycin be used for Helicobacter pylori eradication, in areas of high metronidazole resistance. The efficacy of this regimen is unknown in Singapore. To assess the efficacy, safety and compliance of an H. pylori eradication regimen and examine clinical factors that potentially determine eradication. Consecutive outpatients from a multicultural, south east Asian, population with H. pylori infection, with or without peptic ulcer, were treated with lansoprazole 30 mg, amoxycillin 1 gm, clarithromycin 500 mg, twice a day for seven days. Eradication was assessed by either rapid urease, histology or urea breath test. Compliance and side effects were recorded. The eradication rate and effect of ethnicity, age, sex, usage of alcohol, smoking and non-steroidal anti-inflammatory drugs, history of ulcer and endoscopic diagnosis on eradication were examined by univariate and multivariate analysis. Of 113 patients, the eradication rate by intention to treat was 98/113 (87%) (95% confidence interval [CI] 80-93%) and per protocol was 98/106 (92%) (95% CI 87-97%). Using Fisher's exact test, eradication was more successful in Chinese (intention to treat and per protocol respectively p=0.02 and p<0.001) compared to non-Chinese. By logistic regression analysis ethnicity was an independent factor associated with eradication success (p=0.0025). Side effects occurred in five (4.4%), resulting in cessation of treatment. This one week eradication regimen is safe and effective in south east Asians. Chinese ethnicity may be associated with a higher likelihood of eradication success.

Seventeen-year effects of eradicating Helicobacter pylori on the prevention of gastric cancer in patients with peptic ulcer; a prospective cohort study.

PubMed

Take, Susumu; Mizuno, Motowo; Ishiki, Kuniharu; Hamada, Fumihiro; Yoshida, Tomowo; Yokota, Kenji; Okada, Hiroyuki; Yamamoto, Kazuhide

2015-06-01

We previously reported that eradication of Helicobacter pylori in our cohort of patients with peptic ulcer disease reduced their risk of developing gastric cancer to approximately one-third after a mean follow-up period of 3.4 years (up to 8.6 years). We have now followed these patients for a longer period. A total of 1,222 consecutive patients with peptic ulcer diseases who completed more than 1-year follow-up after receiving H. pylori eradication therapy were followed with annual endoscopic surveillance for a mean of 9.9 years (as long as 17.4 years). H. pylori infection was judged cured in 1,030 patients (eradication-success group) but persisted in 192 (eradication-failure group) after initial eradication therapy. In the eradication-failure group, 114 patients received re-treatment at a mean of 4.4 years after the start of follow-up, and 105 of these were cured of infection. Gastric cancer developed in 21 of the 1,030 patients in the eradication-success group and in nine of the 192 in the failure group (p = 0.04). The risk of developing gastric cancer in the eradication-success group (0.21 %/year) was significantly lower than that in the failure group (0.45 %, p = 0.049). The longest interval between the initial H. pylori eradication and the occurrence of gastric cancer was 14.5 years in the eradication-success group and 13.7 years in the eradication-failure group. A prophylactic effect for gastric cancer persists for more than 10 years after H. pylori eradication therapy, but we should be aware that cancer can develop even after that interval.

The Effects of Helicobacter pylori Eradication Therapy for Chronic Idiopathic Thrombocytopenic Purpura

PubMed Central

Hwang, Jae Jin; Lee, Dong Ho; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

2016-01-01

Background/Aims The aim of this study was to evaluate the ability of Helicobacter pylori eradication treatment to increase platelet counts in Korean patients with chronic idiopathic thrombocytopenic purpura (ITP). Methods A total of 102 patients were evaluated against two criteria. First, those diagnosed with H. pylori infections in whom eradication was successful were assigned to the H. pylori-positive and -eradicated group (n=39), whereas those diagnosed with H. pylori infections in whom eradication failed were assigned to the H. pylori-positive and -non-eradicated group (n=3), and those without H. pylori infections were assigned to the H. pylori-negative group (n=60). Second, patients with complete remission in whom the platelet recovery effect was maintained over the average follow-up period of 6 months after eradication therapy were defined as the responder group (n=58), whereas those with partial or no response were defined as the nonresponder group (n=44). Results The platelet counts of the H. pylori-positive and -eradicated group were significantly increased 6 months after eradication therapy compared to those of the H. pylori-positive and -non-eradicated group and the H. pylori-negative group (43.2±29.1 to 155.3±68.7×103/μL vs 42.5±28.1 to 79.8±59.7×103/μL vs 43.1±28.9 to 81.2±62.2×103/μL; p=0.041). The eradication therapy success rate in the responder group was 100.0% (39/39), in contrast to the nonresponder group (0%, 0/3) (p<0.001). Conclusions H. pylori eradication therapy was related to increased platelet count, and successful eradication affected the increased platelet count in Korean patients with chronic ITP. PMID:26347517

Profiling nonhuman intelligence: An exercise in developing unbiased tools for describing other "types" of intelligence on earth

NASA Astrophysics Data System (ADS)

Herzing, Denise L.

2014-02-01

Intelligence has historically been studied by comparing nonhuman cognitive and language abilities with human abilities. Primate-like species, which show human-like anatomy and share evolutionary lineage, have been the most studied. However, when comparing animals of non-primate origins our abilities to profile the potential for intelligence remains inadequate. Historically our measures for nonhuman intelligence have included a variety of tools: (1) physical measurements - brain to body ratio, brain structure/convolution/neural density, presence of artifacts and physical tools, (2) observational and sensory measurements - sensory signals, complexity of signals, cross-modal abilities, social complexity, (3) data mining - information theory, signal/noise, pattern recognition, (4) experimentation - memory, cognition, language comprehension/use, theory of mind, (5) direct interfaces - one way and two way interfaces with primates, dolphins, birds and (6) accidental interactions - human/animal symbiosis, cross-species enculturation. Because humans tend to focus on "human-like" attributes and measures and scientists are often unwilling to consider other "types" of intelligence that may not be human equated, our abilities to profile "types" of intelligence that differ on a variety of scales is weak. Just as biologists stretch their definitions of life to look at extremophiles in unusual conditions, so must we stretch our descriptions of types of minds and begin profiling, rather than equating, other life forms we may encounter.

Inactivated polio vaccine: time to introduce it in India's national immunization schedule.

PubMed

Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj

2012-07-01

Polio is a communicable disease caused by poliovirus that may attack nerve cells of the brain and spinal cord. The victims develop neurological complications, likes stiffness of the neck, muscular weakness, or paralysis of one or more limbs. In severe cases, it may be fatal due to respiratory paralysis. The world has seen tremendous gains in polio eradication over the past year. India and Nigeria saw a reduction in cases of almost 95% from 2009 to 2010, and cases of wild poliovirus type 3 (WPV3) fell by 92% globally over the same period. In fact, no case has been reported in India since February 2011, such that India may be on the verge of eradicating polio. Nevertheless, polio control experts are particularly worried about Vaccine-Derived Poliovirus (VDPV). Global surveillance efforts picked up 430 cases of VDPV from several countries between July 2009 and March 2011. In India, 7 cases of VDPV were reported during the year 2011. As long as OPV is used, virologists say that the world is at risk of VDPV causing polio in unprotected children. Achieving a polio-free world will require the "cessation of all OPV" and with it the elimination of the risk of vaccine-associated paralytic polio (VAPP) or VDPV infections. To this effect, in 2011 the Global Polio Eradication Initiative (GPEI) will produce and develop a new roadmap for VDPV Elimination. Several countries have shifted from all OPV to sequential OPV-IPV schedules and all-IPV schedules with elimination of live poliovirus. IPV will be indispensable in the post-eradication era when use of OPV has to stop but "vaccination against polio" cannot stop. IPV offers complete individual protection and has been considered as an additional tool at present for those who can afford the vaccine, and since we are nearing the eradication of polio, it is time to shift from OPV to sequential OPV-IPV schedule in India. Such a strategy will avoid inevitable problems with VAPP.

Effect of Lippia alba and Cymbopogon citratus essential oils on biofilms of Streptococcus mutans and cytotoxicity in CHO cells.

PubMed

Tofiño-Rivera, A; Ortega-Cuadros, M; Galvis-Pareja, D; Jiménez-Rios, H; Merini, L J; Martínez-Pabón, M C

2016-12-24

Caries is a public health problem, given that it prevails in 60 to 90% of the school-age global population. Multiple factors interact in its etiology, among them dental plaque is necessary to have lactic acid producing microorganisms like Streptococcus from he Mutans group. Existing prevention and treatment measures are not totally effective and generate adverse effects, which is why it is necessary to search for complementary strategies for their management. The study sought to evaluate the eradication capacity of Streptococcus mutans biofilms and the toxicity on eukaryotic cells of Lippia alba and Cymbopogon citratus essential oils. Essential oils were extracted from plant material through steam distillation and then its chemical composition was determined. The MBEC-high-throughput (MBEC-HTP) (Innovotech, Edmonton, Alberta, Canada) assay used to determine the eradication concentration of S. mutans ATCC 35668 strain biofilms. Cytotoxicity was evaluated on CHO cells through the MTT cell proliferation assay. The major components in both oils were Geraniol and Citral; in L. alba 18.9% and 15.9%, respectively, and in C. citratus 31.3% and 26.7%. The L. alba essential oils presented eradication activity against S. mutans biofilms of 95.8% in 0.01mg/dL concentration and C. citratus essential oils showed said eradication activity of 95.4% at 0.1, 0.01mg/dL concentrations and of 93.1% in the 0.001mg/dL concentration; none of the concentrations of both essential oils showed toxicity on CHO cells during 24h. The L. alba and C. citratus essential oils showed eradication activity against S. mutans biofilms and null cytotoxicity, evidencing the need to conduct further studies that can identify their active components and in order to guide a safe use in treating and preventing dental caries. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Eradication of tephritid fruit fly pest populations: outcomes and prospects.

PubMed

Suckling, David Maxwell; Kean, John M; Stringer, Lloyd D; Cáceres-Barrios, Carlos; Hendrichs, Jorge; Reyes-Flores, Jesus; Dominiak, Bernard C

2016-03-01

The number of insect eradication programmes is rising in response to globalisation. A database of arthropod and plant pathogen eradications covers 1050 incursion responses, with 928 eradication programmes on 299 pest and disease taxa in 104 countries (global eradication database b3.net.nz/gerda). A subset of the database was assembled with 211 eradication or response programmes against 17 species of fruit flies (Tephritidae) in 31 countries, in order to investigate factors affecting the outcome. The failure rate for fruit fly eradication programmes was about 7%, with 0% for Ceratitis capitata (n = 85 programmes) and 0% for two Anastrepha species (n = 12 programmes), but 12% for 13 Bactrocera species (n = 108 programmes). A number of intended eradication programmes against long-established populations were not initiated because of cost and other considerations, or evolved during the planning phase into suppression programmes. Cost was dependent on area, ranged from $US 0.1 million to $US 240 million and averaged about $US 12 million (normalised to $US in 2012). In addition to the routine use of surveillance networks, quarantine and fruit destruction, the key tactics used in eradication programmes were male annihilation, protein bait sprays (which can attract both sexes), fruit destruction and the sterile insect technique. Eradication success generally required the combination of several tactics applied on an area-wide basis. Because the likelihood of eradication declines with an increase in the area infested, it pays to invest in effective surveillance networks that allow early detection and delimitation while invading populations are small, thereby greatly favouring eradication success. © 2014 Society of Chemical Industry.

Changes in Metabolic Hormones in Malaysian Young Adults following Helicobacter pylori Eradication

PubMed Central

Yap, Theresa Wan-Chen; Leow, Alex Hwong-Ruey; Azmi, Ahmad Najib; Francois, Fritz; Perez-Perez, Guillermo I; Blaser, Martin J.; Poh, Bee-Hoon; Loke, Mun-Fai; Goh, Khean-Lee; Vadivelu, Jamuna

2015-01-01

Background More than half of the world’s adults carry Helicobacter pylori. The eradication of H. pylori may affect the regulation of human metabolic hormones. The aim of this study was to evaluate the effect of H. pylori eradication on meal-associated changes in appetite-controlled insulinotropic and digestive hormones, and to assess post-eradication changes in body mass index as part of a currently on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study. Methods We enrolled 29 H. pylori-positive young adult (18–30 year-old) volunteer subjects to evaluate the effect of H. pylori eradication on meal-associated changes on eight gastrointestinal hormones, using a multiplex bead assay. Changes in body mass index and anthropometric measurements were recorded, pre- and post-eradication therapy. Results Pre-prandial active amylin, total peptide YY (PYY) and pancreatic polypeptide (PP) levels were significantly elevated 12 months post-eradication compared with baseline (n = 18; Wilcoxon's signed rank test, p<0.05). Four of the post-prandial gut metabolic hormones levels (GLP-1, total PYY, active amylin, PP) were significantly higher 12 months post-eradication compared to baseline (n = 18; p<0.05). Following H. pylori eradication, the BMI and anthropometric values did not significantly change. Conclusions Our study indicates that H. pylori eradication was associated with long-term disturbance in three hormones (active amylin, PP and total PYY) both pre- and post-prandially and one hormone (GLP-1) post-prandially. Longer post-eradication monitoring is needed to investigate the long-term impact of the observed hormonal changes on metabolic homeostasis. PMID:26291794

[Comparison of Helicobacter pylori eradication rate according to different PPI-based triple therapy--omeprazole, rabeprazole, esomeprazole and lansoprazole--].

PubMed

Keum, Bora; Lee, Sang Woo; Kim, Se Yune; Kim, Jeong Min; Choung, Rok Son; Yim, Hyung Joon; Jeen, Yoon Tae; Lee, Hong Sik; Chun, Hoon Jai; Um, Soon Ho; Choi, Jai Hyun; Kim, Chang Duck; Ryu, Ho Sang; Hyun, Jin Hai

2005-12-01

Helicobacter pylori (H. pylori) is an important cause of various gastrointestinal diseases. H. pylori eradication is essential for the cure and prevention of associated diseases. Nowdays, proton pump inhibitor (PPI)-based triple therapy is the standard eradication regimen. The aims of this study were to compare the H. pylori eradication rate of different PPI-based triple therapies and to find out the factors influencing the eradication rate. From May 2002 through February 2004, H. pylori infected patients were treated with the eradication regimen based on one of the four PPIs (omeprazole, rabeprazole, esomeprazole and lansoprazole) for 1 or 2 weeks. After two weeks, drug compliance, adverse effects, and smoking history during the eradication therapy were obtained. The follow-up H. pylori test was performed 4 weeks after the completion of therapy. The data were analyzed by Chi-square test and multiple logistic regression analysis. Overall eradication rate was 83.5%. There was no significant difference in eradication rate among four PPIs (p=0.379). Odds ratio (OR) for omeprazole and rabeprazole was 1.15 (95% CI 0.50-2.68); for omeprazole and esomeprazole, OR 1.63 (95% CI 0.68-3.89); and for omeprazole and lansoprazole, OR 1.13 (95% CI 0.50-2.56). Smoking habit, site of ulcer, and the duration of therapy affected the eradication rate significantly. The efficacy of four different PPIs for H. pylori eradication is similar to each other. Smoking, site of ulcer, and the duration of treatment have significant effects on eradication rates.

ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy.

PubMed

Antonelli, Martina; Strappazzon, Flavie; Arisi, Ivan; Brandi, Rossella; D'Onofrio, Mara; Sambucci, Manolo; Manic, Gwenola; Vitale, Ilio; Barilà, Daniela; Stagni, Venturina

2017-03-28

The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels. Transcriptomic analyses revealed that, in mammospheres, ATM modulates the expression of cell cycle-, DNA repair- and autophagy-related genes. Among these, the silencing of the autophagic gene, autophagy related 4C cysteine peptidase (ATG4C), impairs mammosphere formation similarly to ATM depletion. Conversely, ATG4C ectopic expression in cells silenced for ATM expression, rescues mammospheres growth. Finally, tumor array analyses, performed using public data, identify a significant correlation between ATM and ATG4C expression levels in all human breast cancer subtypes, except for the basal-like one.Overall, we uncover a new connection between ATM kinase and autophagy regulation in breast cancer. We demonstrate that, in breast cancer cells, ATM and ATG4C are essential drivers of mammosphere formation, suggesting that their targeting may improve current approaches to eradicate breast cancer cells with a stem-like phenotype.

Fetus-in-Fetu: An Unusual Cause for Abdominal Mass in Infancy

PubMed Central

Grosfeld, Jay L.; Stepita, Donald S.; Nance, Walter E.; Palmer, Catherine G.

1974-01-01

Fetus-in-fetu is an unusual cause of retroperitoneal abdominal mass in infants, which most likely arises from inclusion of a monozygotic, diamniotic twin. This entity is distinguished from teratoma by its embryological origin, its unusual location in the retroperitoneal space, its invariable benignity, and by the presence of vertebral organization with limb buds and well-developed organ systems. Diagnosis is made radiographically by the finding of a diminutive vertebral column on a plain abdominal film. The treatment of choice is total excision with special attention being given to the fetus' blood supply which may be directly from the host's superior mesenteric vessels. A well-documented example of this unusual entity that occurred in a six-week old infant male is presented. ImagesFig. 1.Fig. 2.Fig. 3. PMID:4471720

Interactions Between Convective Storms and Their Environment

NASA Technical Reports Server (NTRS)

Maddox, R. A.; Hoxit, L. R.; Chappell, C. F.

1979-01-01

The ways in which intense convective storms interact with their environment are considered for a number of specific severe storm situations. A physical model of subcloud wind fields and vertical wind profiles was developed to explain the often observed intensification of convective storms that move along or across thermal boundaries. A number of special, unusually dense, data sets were used to substantiate features of the model. GOES imagery was used in conjunction with objectively analyzed surface wind data to develop a nowcast technique that might be used to identify specific storm cells likely to become tornadic. It was shown that circulations associated with organized meso-alpha and meso-beta scale storm complexes may, on occasion, strongly modify tropospheric thermodynamic patterns and flow fields.

An Atypical Tropomyosin in Drosophila with Intermediate Filament-like Properties.

PubMed

Cho, Aeri; Kato, Masato; Whitwam, Tess; Kim, Ji Hoon; Montell, Denise J

2016-07-26

A longstanding mystery has been the absence of cytoplasmic intermediate filaments (IFs) from Drosophila despite their importance in other organisms. In the course of characterizing the in vivo expression and functions of Drosophila Tropomyosin (Tm) isoforms, we discovered an essential but unusual product of the Tm1 locus, Tm1-I/C, which resembles an IF protein in some respects. Like IFs, Tm1-I/C spontaneously forms filaments in vitro that are intermediate in diameter between F-actin and microtubules. Like IFs but unlike canonical Tms, Tm1-I/C contains N- and C-terminal low-complexity domains flanking a central coiled coil. In vivo, Tm1-I/C forms cytoplasmic filaments that do not associate with F-actin or canonical Tms. Tm1-I/C is essential for collective border cell migration, in epithelial cells for proper cytoarchitecture, and in the germline for the formation of germ plasm. These results suggest that flies have evolved a distinctive type of cytoskeletal filament from Tm. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Eradication of common mynas Acridotheres tristis from Denis Island, Seychelles.

PubMed

Feare, Chris J; van der Woude, Jildou; Greenwell, Phill; Edwards, Hannah A; Taylor, Jenni A; Larose, Christine S; Ahlen, Per-Arne; West, Jack; Chadwick, Will; Pandey, Smita; Raines, Katherine; Garcia, Fernando; Komdeur, Jan; de Groene, Arjan

2017-02-01

In Seychelles, the common myna has been shown to have a negative impact on endangered endemic birds on Denis Island, interfering with breeding attempts and attacking adult endemic birds at their nests. This stimulated an attempt to eradicate the island's mynas. The eradication was undertaken in three phases, overall killing 1186 mynas and lasting 5 years. Decoy trapping was the most effective method for catching mynas, but the last birds were shot. Decoy trapping was compromised by catches of non-target species. Data collection from killed birds indicated that trapping did not favour either sex, and that most breeding occurred during the wetter season, November to March. Eradication of mynas from small tropical islands is feasible. The Denis Island eradication was prolonged by difficulties in management and staffing. Using volunteers, the cost of the eradication was similar to that of eradicating rodents from the island. In future eradication attempts in Seychelles, possible food stress during the drier season (May to September) might facilitate trapping at this time. Habitat management, especially the removal of short mown grass, could enhance eradication progress. Continued monitoring is needed to confirm eradication and detect any immigration, and also to record responses in the endemic birds. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Emergence of Atypical Mycoplasma agalactiae Strains Harboring a New Prophage and Associated with an Alpine Wild Ungulate Mortality Episode

PubMed Central

Tardy, Florence; Baranowski, Eric; Nouvel, Laurent-Xavier; Mick, Virginie; Manso-Silvàn, Lucía; Thiaucourt, François; Thébault, Patricia; Breton, Marc; Sirand-Pugnet, Pascal; Blanchard, Alain; Garnier, Alexandre; Gibert, Philippe; Game, Yvette; Poumarat, François

2012-01-01

The bacterium Mycoplasma agalactiae is responsible for contagious agalactia (CA) in small domestic ruminants, a syndrome listed by the World Organization for Animal Health and responsible for severe damage to the dairy industry. Recently, we frequently isolated this pathogen from lung lesions of ibexes during a mortality episode in the French Alps. This situation was unusual in terms of host specificity and tissue tropism, raising the question of M. agalactiae emergence in wildlife. To address this issue, the ibex isolates were characterized using a combination of approaches that included antigenic profiles, molecular typing, optical mapping, and whole-genome sequencing. Genome analyses showed the presence of a new, large prophage containing 35 coding sequences (CDS) that was detected in most but not all ibex strains and has a homolog in Mycoplasma conjunctivae, a species causing keratoconjunctivitis in wild ungulates. This and the presence in all strains of large integrated conjugative elements suggested highly dynamic genomes. Nevertheless, M. agalactiae strains circulating in the ibex population were shown to be highly related, most likely originating from a single parental clone that has also spread to another wild ungulate species of the same geographical area, the chamois. These strains clearly differ from strains described in Europe so far, including those found nearby, before CA eradication a few years ago. While M. agalactiae pathogenicity in ibexes remains unclear, our data showed the emergence of atypical strains in Alpine wild ungulates, raising the question of a role for the wild fauna as a potential reservoir of pathogenic mycoplasmas. PMID:22522685

Formation of heterobimetallic zirconium/cobalt diimido complexes via a four-electron transformation.

PubMed

Wu, Bing; Hernández Sánchez, Raúl; Bezpalko, Mark W; Foxman, Bruce M; Thomas, Christine M

2014-10-06

The reactivity of the reduced heterobimetallic complex Zr((i)PrNP(i)Pr2)3CoN2 (1) toward aryl azides was examined, revealing a four-electron redox transformation to afford unusual heterobimetallic zirconium/cobalt diimido complexes. In the case of p-tolyl azide, the diamagnetic C3-symmetric bis(terminal imido) complex 3 is formed, but mesityl azide instead leads to asymmetric complex 4 featuring a bridging imido fragment.

Management and treatment of hepatitis C virus in patients with HIV and hepatitis C virus coinfection: A practical guide for health care professionals.

PubMed

Côté, Pierre; Baril, Jean-Guy; Hébert, Marie-Nicole; Klein, Marina; Lalonde, Richard; Poliquin, Marc; Rouleau, Danielle; Therrien, Rachel; Vézina, Sylvie; Willems, Bernard; Dion, Harold; Junod, Patrice; Lapointe, Normand; Lévesque, Dominic; Pinault, Lyse; Tremblay, Cécile; Trottier, Benoît; Trottier, Sylvie; Tsoukas, Chris; Piché, Alain

2007-09-01

Concomitant HIV and hepatitis C virus (HCV) is a common yet complex coinfection. The present document is a practical guide for treating HCV infection in people coinfected with HIV. Effective antiretroviral therapies have prolonged survival rates for HIV-infected people over the past decade, which have made latent complications of HCV major causes of morbidity and mortality in these patients. Advances in the treatment of HCV (eg, combined pegylated interferon and ribavirin) offer the possibility of eradicating HCV infection in coinfected persons. The treatment of HCV must be considered in all cases. Intensive management of the adverse effects of HCV treatment is one of the factors for the success of these therapies. HCV eradication is predicted to decrease the mortality associated with coinfection and reduce the toxicity of HIV treatment.

Non-native fishes of the central Indian River Lagoon

USGS Publications Warehouse

Schofield, Pamela J.; Loftus, William F.; Reaver, Kristen M.

2018-01-01

We provide a comprehensive review of the status of non-native fishes in the central Indian River Lagoon (from Cape Canaveral to Grant-Valkaria, east of I-95) through literature review and field surveys. Historical records exist for 17 taxa (15 species, one hybrid, one species complex). We found historical records for one additional species, and collected one species in our field survey that had never been recorded in the region before (and which we eradicated). Thus, we evaluate 19 total taxa herein. Of these, we documented range expansion of four salt-tolerant cichlid species, extirpation of six species that were previously recorded from the area and eradication of three species. There was no noticeable change in geographic range for one widespread species and the records for one species are doubtful and may be erroneous. Currently, there is not enough information to evaluate geographic ranges for four species although at least one of those is established.

Management and treatment of hepatitis C virus in patients with HIV and hepatitis C virus coinfection: A practical guide for health care professionals

PubMed Central

Côté, Pierre; Baril, Jean-Guy; Hébert, Marie-Nicole; Klein, Marina; Lalonde, Richard; Poliquin, Marc; Rouleau, Danielle; Therrien, Rachel; Vézina, Sylvie; Willems, Bernard; Dion, Harold; Junod, Patrice; Lapointe, Normand; Lévesque, Dominic; Pinault, Lyse; Tremblay, Cécile; Trottier, Benoît; Trottier, Sylvie; Tsoukas, Chris; Piché, Alain

2007-01-01

Concomitant HIV and hepatitis C virus (HCV) is a common yet complex coinfection. The present document is a practical guide for treating HCV infection in people coinfected with HIV. Effective antiretroviral therapies have prolonged survival rates for HIV-infected people over the past decade, which have made latent complications of HCV major causes of morbidity and mortality in these patients. Advances in the treatment of HCV (eg, combined pegylated interferon and ribavirin) offer the possibility of eradicating HCV infection in coinfected persons. The treatment of HCV must be considered in all cases. Intensive management of the adverse effects of HCV treatment is one of the factors for the success of these therapies. HCV eradication is predicted to decrease the mortality associated with coinfection and reduce the toxicity of HIV treatment. PMID:18923731

Interferon γ limits the effectiveness of melanoma peptide vaccines.

PubMed

Cho, Hyun-Il; Lee, Young-Ran; Celis, Esteban

2011-01-06

The development of effective therapeutic vaccines to generate tumor-reactive cytotoxic T lymphocytes (CTLs) continues to be a top research priority. However, in spite of some promising results, there are no clear examples of vaccines that eradicate established tumors. Most vaccines are ineffective because they generate low numbers of CTLs and because numerous immunosuppressive factors abound in tumor-bearing hosts. We designed a peptide vaccine that produces large numbers of tumor-reactive CTLs in a mouse model of melanoma. Surprisingly, CTL tumor recognition and antitumor effects decreased in the presence of interferon γ (IFNγ), a cytokine that can provide therapeutic benefit. Tumors exposed to IFNγ evade CTLs by inducing large amounts of noncognate major histocompatibility complex class I molecules, which limit T-cell activation and effector function. Our results demonstrate that peptide vaccines can eradicate large, established tumors in circumstances under which the inhibitory activities of IFNγ are curtailed.

The World Health Organization and global smallpox eradication.

PubMed

Bhattacharya, S

2008-10-01

This article examines the multifaceted structures and complex operations of the World Health Organization and its regional offices; it also reassesses the form and the workings of the global smallpox eradication programme with which these bodies were closely linked in the 1960s and 1970s. Using the case study of South Asia, it seeks to highlight the importance of writing nuanced histories of international health campaigns through an assessment of differences between official rhetoric and practice. The article argues that the detailed examination of the implementation of policy in a variety of localities, within and across national borders, allows us to recognise the importance of the agency of field managers and workers. This analytical approach also helps us acknowledge that communities were able to influence the shape and the timing of completion of public health campaigns in myriad ways. This, in turn, can provide useful pointers for the design and management of health programmes in the contemporary world.

Implementing the Synchronized Global Switch from Trivalent to Bivalent Oral Polio Vaccines-Lessons Learned From the Global Perspective.

PubMed

Ramirez Gonzalez, Alejandro; Farrell, Margaret; Menning, Lisa; Garon, Julie; Everts, Hans; Hampton, Lee M; Dolan, Samantha B; Shendale, Stephanie; Wanyoike, Sarah; Veira, Chantal Laroche; Châtellier, Gaël Maufras du; Kurji, Feyrouz; Rubin, Jennifer; Boualam, Liliane; Chang Blanc, Diana; Patel, Manish

2017-07-01

In 2015, the Global Commission for the Certification of Polio Eradication certified the eradication of type 2 wild poliovirus, 1 of 3 wild poliovirus serotypes causing paralytic polio since the beginning of recorded history. This milestone was one of the key criteria prompting the Global Polio Eradication Initiative to begin withdrawal of oral polio vaccines (OPV), beginning with the type 2 component (OPV2), through a globally synchronized initiative in April and May 2016 that called for all OPV using countries and territories to simultaneously switch from use of trivalent OPV (tOPV; containing types 1, 2, and 3 poliovirus) to bivalent OPV (bOPV; containing types 1 and 3 poliovirus), thus withdrawing OPV2. Before the switch, immunization programs globally had been using approximately 2 billion tOPV doses per year to immunize hundreds of millions of children. Thus, the globally synchronized withdrawal of tOPV was an unprecedented achievement in immunization and was part of a crucial strategy for containment of polioviruses. Successful implementation of the switch called for intense global coordination during 2015-2016 on an unprecedented scale among global public health technical agencies and donors, vaccine manufacturers, regulatory agencies, World Health Organization (WHO) and United Nations Children's Fund (UNICEF) regional offices, and national governments. Priority activities included cessation of tOPV production and shipment, national inventories of tOPV, detailed forecasting of tOPV needs, bOPV licensing, scaling up of bOPV production and procurement, developing national operational switch plans, securing funding, establishing oversight and implementation committees and teams, training logisticians and health workers, fostering advocacy and communications, establishing monitoring and validation structures, and implementing waste management strategies. The WHO received confirmation that, by mid May 2016, all 155 countries and territories that had used OPV in 2015 had successfully withdrawn OPV2 by ceasing use of tOPV in their national immunization programs. This article provides an overview of the global efforts and challenges in successfully implementing this unprecedented global initiative, including (1) coordination and tracking of key global planning milestones, (2) guidance facilitating development of country specific plans, (3) challenges for planning and implementing the switch at the global level, and (4) best practices and lessons learned in meeting aggressive switch timelines. Lessons from this monumental public health achievement by countries and partners will likely be drawn upon when bOPV is withdrawn after polio eradication but also could be relevant for other global health initiatives with similarly complex mandates and accelerated timelines. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Safety of first-line triple therapy with a potassium-competitive acid blocker for Helicobacter pylori eradication in children.

PubMed

Kusano, Chika; Gotoda, Takuji; Suzuki, Sho; Ikehara, Hisatomo; Moriyama, Mitsuhiko

2018-06-01

Helicobacter pylori infection is a risk factor for gastric cancer, and it has been reported that eradication of H. pylori is effective for preventing such cancer. Recently, H. pylori eradication has been performed in children as first-line therapy against gastric cancer. Here, we report use of triple therapy with a potassium-competitive acid blocker (P-CAB) for H. pylori eradication in children. H. pylori infection testing and eradication therapy began in fiscal year 2015 in junior high school students located in Yurihonjo city and Nikaho city, Akita prefecture, Japan. Urine-based immunochromatography, stool antigen enzyme-linked immunosorbent assay tests, and serum antibody tests were performed as the initial screening examination. Those who tested positive on one of the three examinations then underwent a urea breath test ( 13 C-UBT). Those who tested positive on 13 C-UBT and expressed the desire to undergo H. pylori eradication then received eradication therapy comprising 20 mg P-CAB, 750 mg amoxicillin, and 200 mg clarithromycin twice a day for 7 days. At least 8 weeks after treatment, eradication success was evaluated using 13 C-UBT. A total of 118 students received eradication therapy. Eradication rates were 81.3% (95% confidence interval: 74.3-88.4, 96/118) in ITT analysis and 85.7% (95% confidence interval: 79.1-92.9 96/112) in PP analysis. Adverse effects associated with eradication therapy were observed in 25 of 118 subjects (21.1%), seven of whom required hospital treatment (rash in five, vomiting in two). All seven subjects either discontinued therapy or were administered anti-allergy drugs, which resulted in swift alleviation of symptoms. First-line triple therapy with a P-CAB for H. pylori eradication in children was found to be safe.

[Dental status and efficacy of Helicobacter pylori eradication].

PubMed

Namiot, D B; Namiot, Z; Kemona, A; Gołebiewska, M

2001-04-01

Beside stomach Helicobacter pylori can colonize the oral cavity. One may think, therefore, that if H. pylori persists the eradication therapy in the oral cavity, it could infect the stomach again. Since in the oral cavity H. pylori occurs most frequently in a dental plaque gathering on teeth, the aim of the study was to investigate whether the natural teeth status is important for the efficacy of H. pylori eradication. The study was conducted on 45 peptic ulcer patients with natural teeth. They were eradicated with one of two regimens: 1/OAT-omeprazole (2 x 20 mg), amoxicillin (2 x 1000 mg), tinidazole (2 x 500 mg) (14-day course), 2/OAC-omeprazole (2 x 20 mg), amoxicillin (2 x 1000 mg), clarithromycin (2 x 250 mg) (7-day course). Dentistry examination was performed 4-6 weeks after the end of eradication therapy and consisted of determination of the number of teeth, caries index, dental treatment index, plaque index, and periodontal index. It was found that in successfully eradicated patients with OAT regimen, the number of teeth was higher and caries index lower than in those whose eradication therapy was unsuccessful; 24.8 +/- 5.2 vs 15.5 +/- 8.6 (p < 0.01) and 31.4% vs 46.0% (p < 0.01), respectively. The number of teeth and caries index were not associated with the efficacy of H. pylori eradication in OAC treated group. Irrespectively of the eradication regimen used, OAT or OAC, dental treatment index, plaque index, and periodontal index were not associated with the efficacy of H. pylori eradication. It is concluded that the natural teeth status may have influence on the outcome of H. pylori eradication. One should remember about this prescribing drugs for H. pylori eradication.

Eradication of tetanus

PubMed Central

Thwaites, C. L.; Loan, H. T.

2015-01-01

Introduction The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care. Sources of data Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications. Areas of agreement The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world. Areas of controversy Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization. Areas timely for developing research It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses. PMID:26598719

Glanders: an overview of infection in humans.

PubMed

Van Zandt, Kristopher E; Greer, Marek T; Gelhaus, H Carl

2013-09-03

Glanders is a highly contagious and often fatal zoonotic disease, primarily of solipds. In the developed world, glanders has been eradicated. However, prior use of B. mallei as a biological weapon and its high mortality in inhalation animal studies has affirmed B. mallei as a biodefense concern. This threat requires the development of new glanders medical countermeasures (MCMs), as there is a lack of an effective vaccine and lengthy courses of multiple antibiotics needed to eradicate B. mallei. Here, we present a literature review of human glanders in which we discuss the clinical epidemiology and risk factors, potential routes of exposure, symptoms, the incubation period, and specific diagnostics. This review focuses on pulmonary glanders, as this is the most likely outcome of a biological weapons attack. Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection.

Glanders: an overview of infection in humans

PubMed Central

2013-01-01

Glanders is a highly contagious and often fatal zoonotic disease, primarily of solipds. In the developed world, glanders has been eradicated. However, prior use of B. mallei as a biological weapon and its high mortality in inhalation animal studies has affirmed B. mallei as a biodefense concern. This threat requires the development of new glanders medical countermeasures (MCMs), as there is a lack of an effective vaccine and lengthy courses of multiple antibiotics needed to eradicate B. mallei. Here, we present a literature review of human glanders in which we discuss the clinical epidemiology and risk factors, potential routes of exposure, symptoms, the incubation period, and specific diagnostics. This review focuses on pulmonary glanders, as this is the most likely outcome of a biological weapons attack. Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection. PMID:24004906

Detection of the supercycle in V4140 Sagittarii: First eclipsing ER Ursae Majoris-like object

NASA Astrophysics Data System (ADS)

Kato, Taichi; Hambsch, Franz-Josef; Cook, Lewis M.

2018-05-01

We observed the deeply eclipsing SU UMa-type dwarf nova V4140 Sgr and established the very short supercycle of 69.7(3) d. There were several short outbursts between superoutbursts. These values, together with the short orbital period (0.06143 d), were similar to, but not as extreme as, those of ER UMa-type dwarf novae. The object is thus the first, long sought, eclipsing ER UMa-like object. This ER UMa-like nature can naturally explain the high (apparent) quiescent viscosity and unusual temperature profile in quiescence, which were claimed observational features against the thermal-tidal instability model. The apparently unusual outburst behavior can be reasonably explained by a combination of this ER UMa-like nature and the high orbital inclination, and there is no need to introduce mass transfer bursts from its donor star.

Detection of the supercycle in V4140 Sagittarii: First eclipsing ER Ursae Majoris-like object

NASA Astrophysics Data System (ADS)

Kato, Taichi; Hambsch, Franz-Josef; Cook, Lewis M.

2018-06-01

We observed the deeply eclipsing SU UMa-type dwarf nova V4140 Sgr and established the very short supercycle of 69.7(3) d. There were several short outbursts between superoutbursts. These values, together with the short orbital period (0.06143 d), were similar to, but not as extreme as, those of ER UMa-type dwarf novae. The object is thus the first, long sought, eclipsing ER UMa-like object. This ER UMa-like nature can naturally explain the high (apparent) quiescent viscosity and unusual temperature profile in quiescence, which were claimed observational features against the thermal-tidal instability model. The apparently unusual outburst behavior can be reasonably explained by a combination of this ER UMa-like nature and the high orbital inclination, and there is no need to introduce mass transfer bursts from its donor star.

Unmasking the complexity of species identification in Australasian flying-foxes

PubMed Central

Danks, Melissa; Lott, Matthew J.; Dennison, Siobhan; Frankham, Greta J.; King, Andrew; Eldridge, Mark D. B.; Johnson, Rebecca N.; Divljan, Anja

2018-01-01

Pteropus (flying-foxes) are a speciose group of non-echolocating large bats, with five extant Australian species and 24 additional species distributed amongst the Pacific Islands. In 2015, an injured flying-fox with unusual facial markings was found in Sydney, Australia, following severe and widespread storms. Based on an initial assessment, the individual belonged to Pteropus but could not be readily identified to species. As a consequence, four hypotheses for its identification/origin were posited: the specimen represented (1) an undescribed Australian species; or (2) a morphological variant of a recognised Australian species; or (3) a hybrid individual; or (4) a vagrant from the nearby Southwest Pacific Islands. We used a combination of morphological and both mitochondrial- and nuclear DNA-based identification methods to assess these hypotheses. Based on the results, we propose that this morphologically unique Pteropus most likely represents an unusual P. alecto (black flying-fox) potentially resulting from introgression from another Pteropus species. Unexpectedly, this individual, and the addition of reference sequence data from newly vouchered specimens, revealed a previously unreported P. alecto mitochondrial DNA lineage. This lineage was distinct from currently available haplotypes. It also suggests long-term hybridisation commonly occurs between P. alecto and P. conspicillatus (spectacled flying-fox). This highlights the importance of extensive reference data, and the inclusion of multiple vouchered specimens for each species to encompass both intraspecific and interspecific variation to provide accurate and robust species identification. Moreover, our additional reference data further demonstrates the complexity of Pteropus species relationships, including hybridisation, and potential intraspecific biogeographical structure that may impact on their management and conservation. PMID:29634748

Tuberous sclerosis complex: neonatal deaths in three of four children of consanguineous, non-expressing parents.

PubMed Central

Ruggieri, M; Carbonara, C; Magro, G; Migone, N; Grasso, S; Tinè, A; Pavone, L; Gomez, M R

1997-01-01

We describe here four sibs, born to consanguineous, healthy, asymptomatic parents. Three of these infants had a rapidly fatal course in the neonatal period; death was attributed to congestive heart failure with radiographic evidence of cardiomegaly in all of them. Necropsy was done in only one of them and showed the typical findings of tuberous sclerosis complex (TSC) in the central nervous system (CNS), kidneys, heart, and liver. The fourth sib, currently 2 years old, also has typical signs of TSC, namely hypomelanotic skin macules and calcified subependymal nodules. Both parents and a living maternal grandmother had appropriate examination, which included skin inspection under Wood's lamp, dental examination, fundoscopy, echocardiography, abdominal and renal ultrasound, and head CT and MRI scans, and no signs of TSC were found in either parent or in the only living grandmother. By history alone there is no other relative with signs or symptoms suggestive of TSC. Linkage analysis and loss of heterozygosity (LOH) investigations on a variety of lesions obtained from postmortem and tissue or blood specimens from all available family members studied failed to identify a microdeletion in the chromosomal regions where TSC genes are located. It is very unusual that in a single TSC family there were three consecutive neonatal deaths, and very likely that all had cardiac rhabdomyomas. Moreover, to the best of our knowledge, there are no previous reports of TSC families with more than one affected sib, unusually severe manifestations of the disease, and completely normal, consanguineous parents. Images PMID:9132502

Managing breaches of containment and eradication of invasive plant populations.

PubMed

Fletcher, Cameron S; Westcott, David A; Murphy, Helen T; Grice, Anthony C; Clarkson, John R

2015-02-01

Containment can be a viable strategy for managing invasive plants, but it is not always cheaper than eradication. In many cases, converting a failed eradication programme to a containment programme is not economically justified. Despite this, many contemporary invasive plant management strategies invoke containment as a fallback for failed eradication, often without detailing how containment would be implemented.We demonstrate a generalized analysis of the costs of eradication and containment, applicable to any plant invasion for which infestation size, dispersal distance, seed bank lifetime and the economic discount rate are specified. We estimate the costs of adapting eradication and containment in response to six types of breach and calculate under what conditions containment may provide a valid fallback to a breached eradication programme.We provide simple, general formulae and plots that can be applied to any invasion and show that containment will be cheaper than eradication only when the size of the occupied zone exceeds a multiple of the dispersal distance determined by seed bank longevity and the discount rate. Containment becomes proportionally cheaper than eradication for invaders with smaller dispersal distances, longer lived seed banks, or for larger discount rates.Both containment and eradication programmes are at risk of breach. Containment is less exposed to risk from reproduction in the 'occupied zone' and three types of breach that lead to a larger 'occupied zone', but more exposed to one type of breach that leads to a larger 'buffer zone'.For a well-specified eradication programme, only the three types of breach leading to reproduction in or just outside the buffer zone can justify falling back to containment, and only if the expected costs of eradication and containment were comparable before the breach. Synthesis and applications . Weed management plans must apply a consistent definition of containment and provide sufficient implementation detail to assess its feasibility. If the infestation extent, dispersal capacity, seed bank longevity and economic discount rate are specified, the general results presented here can be used to assess whether containment can outperform eradication, and under what conditions it would provide a valid fallback to a breached eradication programme.

Managing breaches of containment and eradication of invasive plant populations

PubMed Central

Fletcher, Cameron S; Westcott, David A; Murphy, Helen T; Grice, Anthony C; Clarkson, John R

2015-01-01

Containment can be a viable strategy for managing invasive plants, but it is not always cheaper than eradication. In many cases, converting a failed eradication programme to a containment programme is not economically justified. Despite this, many contemporary invasive plant management strategies invoke containment as a fallback for failed eradication, often without detailing how containment would be implemented. We demonstrate a generalized analysis of the costs of eradication and containment, applicable to any plant invasion for which infestation size, dispersal distance, seed bank lifetime and the economic discount rate are specified. We estimate the costs of adapting eradication and containment in response to six types of breach and calculate under what conditions containment may provide a valid fallback to a breached eradication programme. We provide simple, general formulae and plots that can be applied to any invasion and show that containment will be cheaper than eradication only when the size of the occupied zone exceeds a multiple of the dispersal distance determined by seed bank longevity and the discount rate. Containment becomes proportionally cheaper than eradication for invaders with smaller dispersal distances, longer lived seed banks, or for larger discount rates. Both containment and eradication programmes are at risk of breach. Containment is less exposed to risk from reproduction in the ‘occupied zone’ and three types of breach that lead to a larger ‘occupied zone’, but more exposed to one type of breach that leads to a larger ‘buffer zone’. For a well-specified eradication programme, only the three types of breach leading to reproduction in or just outside the buffer zone can justify falling back to containment, and only if the expected costs of eradication and containment were comparable before the breach. Synthesis and applications. Weed management plans must apply a consistent definition of containment and provide sufficient implementation detail to assess its feasibility. If the infestation extent, dispersal capacity, seed bank longevity and economic discount rate are specified, the general results presented here can be used to assess whether containment can outperform eradication, and under what conditions it would provide a valid fallback to a breached eradication programme. PMID:25678718

Unusually large complex odontoma in maxillary sinus associated with unerupted tooth. Report of case and review of literature.

PubMed

Singer, Steven R; Mupparapu, Muralidhar; Milles, Maano; Rinaggio, Joseph; Pisano, Dominic; Quaranta, Patrick

2007-01-01

An unusual case of a large complex odontoma with an associated impacted tooth is presented. Odontomas are hamartomatous growths of enamel, dentin, cementum and pulp tissue. Although they are usually tooth-sized or smaller, occasionally, the complex variant can exhibit considerable growth, as was seen in the case presented here. It occupied most of the maxillary sinus and displaced the floor of the orbit and the medial and posterior walls of the left maxillary sinus. Panoramic radiographs, as well as axial and coronal CT studies, showed the extent of the lesion in various dimensions. A differential diagnosis of various calcifying tumors was formulated on the basis of these findings. The lesion was surgically excised, and histologic analysis confirmed the radiographic impression. Although odontomas of this magnitude are rare, this case demonstrates the value of imaging, radiographic histopathologic diagnosis and surgical treatment planning prior to any definitive treatment.

Tilted middle Tertiary ash-flow calderas and subjacent granitic plutons, southern Stillwater Range, Nevada: cross sections of an Oligocene igneous center

USGS Publications Warehouse

John, D.A.

1995-01-01

Steeply tilted late Oligocene caldera systems in the Stillwater caldera complex record a number of unusual features including extreme thickness of caldera-related deposits, lack of evidence for structural doming of the calderas and preservation of vertical compositional zoning in the plutonic rocks. The Stillwater caldera complex comprises three partly overlapping ash-flow calderas and subjacent plutonic rocks that were steeply tilted during early Miocene extension. The Job Canyon caldera, the oldest (ca. 29-28 Ma) caldera, consists of two structural blocks. The 25 to 23 Ma Poco Canyon and Elevenmile Canyon calderas and underlying Freeman Creek pluton overlap in time and space with each other. Caldera collapse occurred mostly along subvertical ring-fracture faults that penetrated to depths of >5 km and were repeatedly active during eruption of ash-flow tuffs. The calderas collapsed as large piston-like blocks, and there is no evidence for chaotic collapse. Preserved parts of caldera floors are relatively flat surfaces several kilometers across. -from Author

Unfolding of a ClC chloride transporter retains memory of its evolutionary history.

PubMed

Min, Duyoung; Jefferson, Robert E; Qi, Yifei; Wang, Jing Yang; Arbing, Mark A; Im, Wonpil; Bowie, James U

2018-05-01

ClC chloride channels and transporters are important for chloride homeostasis in species from bacteria to human. Mutations in ClC proteins cause genetically inherited diseases, some of which are likely to involve folding defects. The ClC proteins present a challenging and unusual biological folding problem because they are large membrane proteins possessing a complex architecture, with many reentrant helices that go only partway through membrane and loop back out. Here we were able to examine the unfolding of the Escherichia coli ClC transporter, ClC-ec1, using single-molecule forced unfolding methods. We found that the protein could be separated into two stable halves that unfolded independently. The independence of the two domains is consistent with an evolutionary model in which the two halves arose from independently folding subunits that later fused together. Maintaining smaller folding domains of lesser complexity within large membrane proteins may be an advantageous strategy to avoid misfolding traps.

Does the order of invasive species removal matter? The case of the eagle and the pig.

PubMed

Collins, Paul W; Latta, Brian C; Roemer, Gary W

2009-09-14

Invasive species are recognized as a primary driver of native species endangerment and their removal is often a key component of a conservation strategy. Removing invasive species is not always a straightforward task, however, especially when they interact with other species in complex ways to negatively influence native species. Because unintended consequences may arise if all invasive species cannot be removed simultaneously, the order of their removal is of paramount importance to ecological restoration. In the mid-1990s, three subspecies of the island fox Urocyon littoralis were driven to near extinction on the northern California Channel Islands owing to heightened predation by golden eagles Aquila chrysaetos. Eagles were lured to the islands by an abundant supply of feral pigs Sus scrofa and through the process of apparent competition pigs indirectly facilitated the decline in foxes. As a consequence, both pigs and eagles had to be removed to recover the critically endangered fox. Complete removal of pigs was problematic: removing pigs first could force eagles to concentrate on the remaining foxes, increasing their probability of extinction. Removing eagles first was difficult: eagles are not easily captured and lethal removal was politically distasteful. Using prey remains collected from eagle nests both before and after the eradication of pigs, we show that one pair of eagles that eluded capture did indeed focus more on foxes. These results support the premise that if the threat of eagle predation had not been mitigated prior to pig removal, fox extinction would have been a more likely outcome. If complete eradication of all interacting invasive species is not possible, the order in which they are removed requires careful consideration. If overlooked, unexpected consequences may result that could impede restoration.

Enhancement of magnetic anisotropy in a Mn-Bi heterobimetallic complex.

PubMed

Pearson, Tyler J; Fataftah, Majed S; Freedman, Danna E

2016-09-15

A novel Mn 2+ Bi 3+ heterobimetallic complex, featuring the closest MnBi interaction for a paramagnetic molecular species, exhibits unusually large axial zero-field splitting. We attribute this enhancement to the proximity of Mn 2+ to a heavy main group element, namely, bismuth.

Photochemistry of fac-[Re(CO)3(dcbH2)( trans-stpy)]+: New Insights on the Isomerization Mechanism of Coordinated Stilbene-like Ligands.

PubMed

Faustino, Leandro A; Hora Machado, Antonio Eduardo; Patrocinio, Antonio Otavio T

2018-03-05

In this work, a novel complex fac-[Re(CO) 3 (dcbH 2 )( trans-stpy)] + , (dcbH 2 = 4,4'-dicarboxylic acid-2,2'-bipyridine; trans-stpy = trans-4-styrylpyridine) was synthesized and characterized toward its spectroscopic, photochemical, and photophysical properties. The experimental data provide new insights on the mechanism of photochemical trans-to- cis isomerization of the stilbene-like ligand coordinated to Re(I) polypyridyl complexes. The new complex exhibits an unusual and strong dependence of the isomerization quantum yield (Φ t →c ) on the irradiation wavelength. Φ t →c was 0.81 ± 0.08 for irradiation at 365 nm and continuously decreased as the irradiation wavelength is shifted to the visible. At 405 nm irradiation Φ t →c is almost 2 orders of magnitude lower (0.010 ± 0.005) than that observed at 365 nm excitation. This behavior can be explained by the low-lying triplet metal-to-ligand charge-transfer excited state ( 3 MLCT) that hinders the triplet photoreaction mechanism under visible light absorption. Under UV irradiation, direct population of styrylpyridine-centered excited state ( 1 IL) leads to the occurrence of the photoisomerization via a singlet mechanism. Further experiments were performed with the complex immobilized on the surface of TiO 2 and Al 2 O 3 films. The nonoccurrence of isomerization at the oxide surfaces even under UV excitation evidences the role of energy gap between the 1 IL/ 1 MLCT states on the photochemical/photophysical processes. The results establish important relationships between the molecular structure and the photoelectrochemical behavior, which can further contribute to the development of solid-state molecular switches based on Re(I) polypyridyl complexes.

Investing in Justice: Ethics, Evidence, and the Eradication Investment Cases for Lymphatic Filariasis and Onchocerciasis

PubMed Central

Merritt, Maria W.; Tediosi, Fabrizio

2015-01-01

It has been suggested that initiatives to eradicate specific communicable diseases need to be informed by eradication investment cases to assess the feasibility, costs, and consequences of eradication compared with elimination or control. A methodological challenge of eradication investment cases is how to account for the ethical importance of the benefits, burdens, and distributions thereof that are salient in people’s experiences of the diseases and related interventions but are not assessed in traditional approaches to health and economic evaluation. We have offered a method of ethical analysis grounded in theories of social justice. We have described the method and its philosophical rationale and illustrated its use in application to eradication investment cases for lymphatic filariasis and onchocerciasis, 2 neglected tropical diseases that are candidates for eradication. PMID:25713967

The Efficacy of Saccharomyces boulardii CNCM I-745 in Addition to Standard Helicobacter pylori Eradication Treatment in Children.

PubMed

Bin, Zhang; Ya-Zheng, Xu; Zhao-Hui, Deng; Bo, Chu; Li-Rong, Jiang; Vandenplas, Yvan

2015-03-01

This study aims to investigate Saccharomyces boulardii CNCM I-745 during Helicobacter pylori eradication in children. One hundred ninety-four H. pylori positive children were randomized in two groups. Therapy (omeprazole+clarithromycin+amoxicillin or omeprazole+clarithromycin+metronidazole in case of penicillin allergy) was given to both groups during two weeks. In the treatment group (n: 102) S. boulardii was added to the triple therapy, while the control group (n: 92) only received triple therapy. The incidence, onset, duration and severity of diarrhea and compliance to the eradication treatment were compared. A (13)C urea breath test was done 4 weeks after the end of eradication therapy in two groups of 21 patients aged 12 years and older to test the H. pylori eradication rate. In the treatment group, diarrhea occurred in 12 cases (11.76%), starting after 6.25±1.24 days, lasting 3.17±1.08 days, and compliance to eradication treatment was 100%. In the control group, diarrhea occurred in 26 cases (28.26%), starting after 4.05±1.11 days, lasting 4.02±0.87 days, and in six cases eradication treatment was stopped prematurely (p<0.05). The (13)C urea breath test showed successful H. pylori eradication in 71.4% of the patients in the treatment and in 61.9 % in the control group (not significant). S. boulardii has a beneficial effect on the prevention and treatment of diarrhea during H. pylori eradication in children. Although S. boulardii did only slightly increase H. pylori eradication rate, compliance to eradication treatment was improved.

Catalytic Hydroamination of Alkynes and Norbornene with Neutral and Cationic Tantalum Imido Complexes

PubMed Central

Anderson, Laura L.; Arnold, John; Bergman, Robert G.

2005-01-01

Several tantalum imido complexes have been synthesized and shown to efficiently catalyze the hydroamination of internal and terminal alkynes. An unusual hydroamination/hydroarylation reaction of norbornene catalyzed by a highly electrophilic cationic tantalum imido complex is also reported. Factors affecting catalyst activity and selectivity are discussed along with mechanistic insights gained from stoichiometric reactions. PMID:15255680

Characterization of Two Related Drosophila γ-tubulin Complexes that Differ in Their Ability to Nucleate Microtubules

PubMed Central

Oegema, Karen; Wiese, Christiane; Martin, Ona C.; Milligan, Ronald A.; Iwamatsu, Akihiro; Mitchison, Timothy J.; Zheng, Yixian

1999-01-01

γ-tubulin exists in two related complexes in Drosophila embryo extracts (Moritz, M., Y. Zheng, B.M. Alberts, and K. Oegema. 1998. J. Cell Biol. 142:1– 12). Here, we report the purification and characterization of both complexes that we name γ-tubulin small complex (γTuSC; ∼280,000 D) and Drosophila γTuRC (∼2,200,000 D). In addition to γ-tubulin, the γTuSC contains Dgrip84 and Dgrip91, two proteins homologous to the Spc97/98p protein family. The γTuSC is a structural subunit of the γTuRC, a larger complex containing about six additional polypeptides. Like the γTuRC isolated from Xenopus egg extracts (Zheng, Y., M.L. Wong, B. Alberts, and T. Mitchison. 1995. Nature. 378:578–583), the Drosophila γTuRC can nucleate microtubules in vitro and has an open ring structure with a diameter of 25 nm. Cryo-electron microscopy reveals a modular structure with ∼13 radially arranged structural repeats. The γTuSC also nucleates microtubules, but much less efficiently than the γTuRC, suggesting that assembly into a larger complex enhances nucleating activity. Analysis of the nucleotide content of the γTuSC reveals that γ-tubulin binds preferentially to GDP over GTP, rendering γ-tubulin an unusual member of the tubulin superfamily. PMID:10037793

Eradication of Invading Insect Populations: From Concepts to Applications

Treesearch

Andrew M. Liebhold; Ludek Berec; Eckehard G. Brockerhoff; Rebecca S. Epanchin-Niell; Alan Hastings; Daniel A. Herms; John M. Kean; Deborah G. McCullough; David M. Suckling; Patrick C. Tobin; Takehiko Yamanaka

2016-01-01

Eradication is the deliberate elimination of a species from an area. Given that international quarantine measures can never be 100% effective, surveillance for newly arrived populations of nonnative species coupled with their eradication represents an important strategy for excluding potentially damaging insect species. Historically, eradication efforts have not always...

Lessons for Implementation from the World's Most Successful Programme: The Global Eradication of Smallpox.

ERIC Educational Resources Information Center

Pratt, David

1999-01-01

Focuses on lessons educators might learn from the Intensified Campaign for the Global Eradication of Smallpox. Outlines the history of smallpox eradication. Discusses the eradication effort's obstacles, campaign, and costs and benefits. Considers five factors relevant to the successful implementation of educational programs. (CMK)

A crack-like rupture model for the 19 September 1985 Michoacan, Mexico, earthquake

NASA Astrophysics Data System (ADS)

Ruppert, Stanley D.; Yomogida, Kiyoshi

1992-09-01

Evidence supporting a smooth crack-like rupture process of the Michoacan earthquake of 1985 is obtained from a major earthquake for the first time. Digital strong motion data from three stations (Caleta de Campos, La Villita, and La Union), recording near-field radiation from the fault, show unusually simple ramped displacements and permanent offsets previously only seen in theoretical models. The recording of low frequency (0 to 1 Hz) near-field waves together with the apparently smooth rupture favors a crack-like model to a step or Haskell-type dislocation model under the constraint of the slip distribution obtained by previous studies. A crack-like rupture, characterized by an approximated dynamic slip function and systematic decrease in slip duration away from the point of rupture nucleation, produces the best fit to the simple ramped displacements observed. Spatially varying rupture duration controls several important aspects of the synthetic seismograms, including the variation in displacement rise times between components of motion observed at Caleta de Campos. Ground motion observed at Caleta de Campos can be explained remarkably well with a smoothly propagating crack model. However, data from La Villita and La Union suggest a more complex rupture process than the simple crack-like model for the south-eastern portion of the fault.

Reproductive endocrine patterns and volatile urinary compounds of Arctictis binturong: discovering why bearcats smell like popcorn.

PubMed

Greene, Lydia K; Wallen, Timothy W; Moresco, Anneke; Goodwin, Thomas E; Drea, Christine M

2016-06-01

Members of the order Carnivora rely on urinary scent signaling, particularly for communicating about reproductive parameters. Here, we describe reproductive endocrine patterns in relation to urinary olfactory cues in a vulnerable and relatively unknown viverrid--the binturong (Arctictis binturong). Female binturongs are larger than and dominate males, and both sexes engage in glandular and urinary scent marking. Using a large (n = 33), captive population, we collected serum samples to measure circulating sex steroids via enzyme immunoassay and urine samples to assay volatile chemicals via gas chromatography-mass spectrometry. Male binturongs had expectedly greater androgen concentrations than did females but, more unusually, had equal estrogen concentrations, which may be linked to male deference. Males also expressed a significantly richer array of volatile chemical compounds than did females. A subset of these volatile chemicals resisted decay at ambient temperatures, potentially indicating their importance as long-lasting semiochemicals. Among these compounds was 2-acetyl-1-pyrroline (2-AP), which is typically produced at high temperatures by the Maillard reaction and is likely to be responsible for the binturong's characteristic popcorn aroma. 2-AP, the only compound expressed by all of the subjects, was found in greater abundance in males than females and was significantly and positively related to circulating androstenedione concentrations in both sexes. This unusual compound may have a more significant role in mammalian semiochemistry than previously appreciated. Based on these novel data, we suggest that hormonal action and potentially complex chemical reactions mediate communication of the binturong's signature scent and convey information about sex and reproductive state.

Reproductive endocrine patterns and volatile urinary compounds of Arctictis binturong: discovering why bearcats smell like popcorn

NASA Astrophysics Data System (ADS)

Greene, Lydia K.; Wallen, Timothy W.; Moresco, Anneke; Goodwin, Thomas E.; Drea, Christine M.

2016-06-01

Members of the order Carnivora rely on urinary scent signaling, particularly for communicating about reproductive parameters. Here, we describe reproductive endocrine patterns in relation to urinary olfactory cues in a vulnerable and relatively unknown viverrid—the binturong ( Arctictis binturong). Female binturongs are larger than and dominate males, and both sexes engage in glandular and urinary scent marking. Using a large ( n = 33), captive population, we collected serum samples to measure circulating sex steroids via enzyme immunoassay and urine samples to assay volatile chemicals via gas chromatography-mass spectrometry. Male binturongs had expectedly greater androgen concentrations than did females but, more unusually, had equal estrogen concentrations, which may be linked to male deference. Males also expressed a significantly richer array of volatile chemical compounds than did females. A subset of these volatile chemicals resisted decay at ambient temperatures, potentially indicating their importance as long-lasting semiochemicals. Among these compounds was 2-acetyl-1-pyrroline (2-AP), which is typically produced at high temperatures by the Maillard reaction and is likely to be responsible for the binturong's characteristic popcorn aroma. 2-AP, the only compound expressed by all of the subjects, was found in greater abundance in males than females and was significantly and positively related to circulating androstenedione concentrations in both sexes. This unusual compound may have a more significant role in mammalian semiochemistry than previously appreciated. Based on these novel data, we suggest that hormonal action and potentially complex chemical reactions mediate communication of the binturong's signature scent and convey information about sex and reproductive state.

Growing up Radical: Investigation of Benzyl-Like Radicals with Increasing Chain Lengths

NASA Astrophysics Data System (ADS)

Korn, Joseph A.; Jawad, Khadija M.; Hewett, Daniel M.; Zwier, Timothy S.

2015-06-01

Combustion processes involve complex chemistry including pathways leading to polyaromatic hydrocarbons (PAHs) from small molecule precursors. Resonance stabilized radicals (RSRs) likely play an important role in the pathways to PAHs due to their unusual stability. Benzyl radical is a prototypical RSR that is stabilized by conjugation with the phenyl ring. Earlier work on α-methyl benzyl radical showed perturbations to the spectroscopy due to a hindered methyl rotor. If the alkyl chain is lengthened then multiple conformations become possible. This talk will discuss the jet-cooled spectroscopy of α-ethyl benzyl radical and α-propyl benzyl radical produced from the discharge of 1-phenyl propanol and 1-phenyl butanol respectively. Electronic spectra were obtained via resonant two-photon ionization, and IR spectra were obtained by resonant ion-dip infrared spectroscopy. Kidwell, N. M.; Reilly, N. J.; Nebgen, B.; Mehta-Hurt, D. N.; Hoehn, R. D.; Kokkin, D. L.; McCarthy, M. C.; Slipchenko, L. V.; Zwier, T. S. The Journal of Physical Chemistry A 2013, 117, 13465.

Unusual bridging of three nitrates with two bridgehead protons in an octaprotonated azacryptand

PubMed Central

Saeed, Musabbir A.; Fronczek, Frank R.; Huang, Ming-Ju; Hossain, Md. Alamgir

2010-01-01

Structural analysis of the nitrate complex of a thiophene-based azacryptand suggests that three nitrates are bridged with two bridgehead protons which play the topological role of two transition metal ions in a classical Werner type coordination complex bridging three anions. PMID:20066306

Eradication of dracunculiasis from Pakistan.

PubMed

Hopkins, D R; Azam, M; Ruiz-Tiben, E; Kappus, K D

1995-09-02

In 1986 the World Health Organization targeted dracunculiasis (Guinea-worm disease), which seriously impairs socioeconomic development in 16 African countries, India, Pakistan, and Yemen, to be eradicated globally. The target date for eradication by the end of 1995 was established in 1991. Pakistan eradicated dracunculiasis from the country in October, 1993, after a national campaign which began in 1987 with a nationwide village-by-village search for cases. The infection, which is transmitted by drinking water from ponds containing infected water fleas, was eradicated by using health education, cloth filters, and the cyclopsicide, temephos; and in the later stages, by case containment. Methods pioneered in Pakistan's National Guinea Worm Eradication Program are now being applied in remaining endemic countries.

Biological Feasibility of Measles Eradication

PubMed Central

Strebel, Peter

2011-01-01

Recent progress in reducing global measles mortality has renewed interest in measles eradication. Three biological criteria are deemed important for disease eradication: (1) humans are the sole pathogen reservoir; (2) accurate diagnostic tests exist; and (3) an effective, practical intervention is available at reasonable cost. Interruption of transmission in large geographical areas for prolonged periods further supports the feasibility of eradication. Measles is thought by many experts to meet these criteria: no nonhuman reservoir is known to exist, accurate diagnostic tests are available, and attenuated measles vaccines are effective and immunogenic. Measles has been eliminated in large geographical areas, including the Americas. Measles eradication is biologically feasible. The challenges for measles eradication will be logistical, political, and financial. PMID:21666201

Can Land Managers Control Japanese Knotweed? Lessons from Control Tests in Belgium

NASA Astrophysics Data System (ADS)

Delbart, Emmanuel; Mahy, Grégory; Weickmans, Bernard; Henriet, François; Crémer, Sébastien; Pieret, Nora; Vanderhoeven, Sonia; Monty, Arnaud

2012-12-01

Japanese knotweed Fallopia japonica is an extremely abundant invasive plant in Belgium and surrounding countries. To date, no eradication method is available for land managers facing the invasion of this rhizomatous plant. We tested different chemical herbicides with two application methods (spraying and stem injection), as well as mechanical treatments, on knotweed clones throughout southern Belgium. The tested control methods were selected to be potentially usable by managers, e.g., using legally accepted rates for herbicides. Stem volume, height and density reduction were assessed after one or two years, depending on the control method. Labor estimations were made for each control method. No tested control method completely eradicated the clones. Stem injection with glyphosate-based herbicide (3.6 kg ha-1 of acid equivalent glyphosate) caused the most damage, i.e., no sprouting shoots were observed the year following the injection. The following year, though, stunted shoots appeared. Among the mechanical control methods, repeated cuts combined with native tree transplanting most appreciably reduced knotweed development. The most efficient methods we tested could curb knotweed invasion, but are not likely to be effective in eradicating the species. As such, they should be included in a more integrated restoration strategy, together with prevention and public awareness campaigns.

The energy blockers 3-bromopyruvate and lonidamine: effects on bioenergetics of brain mitochondria.

PubMed

Macchioni, Lara; Davidescu, Magdalena; Roberti, Rita; Corazzi, Lanfranco

2014-10-01

Tumor cells favor abnormal energy production via aerobic glycolysis and show resistance to apoptosis, suggesting the involvement of mitochondrial dysfunction. The differences between normal and cancer cells in their energy metabolism provide a biochemical basis for developing new therapeutic strategies. The energy blocker 3-bromopyruvate (3BP) can eradicate liver cancer in animals without associated toxicity, and is a potent anticancer towards glioblastoma cells. Since mitochondria are 3BP targets, in this work the effects of 3BP on the bioenergetics of normal rat brain mitochondria were investigated in vitro, in comparison with the anticancer agent lonidamine (LND). Whereas LND impaired oxygen consumption dependent on any complex of the respiratory chain, 3BP was inhibitory to malate/pyruvate and succinate (Complexes I and II), but preserved respiration from glycerol-3-phosphate and ascorbate (Complex IV). Accordingly, although electron flow along the respiratory chain and ATP levels were decreased by 3BP in malate/pyruvate- and succinate-fed mitochondria, they were not significantly influenced from glycerol-3-phosphate- or ascorbate-fed mitochondria. LND produced a decrease in electron flow from all substrates tested. No ROS were produced from any substrate, with the exception of 3BP-induced H(2)O(2) release from succinate, which suggests an antimycin-like action of 3BP as an inhibitor of Complex III. We can conclude that 3BP does not abolish completely respiration and ATP synthesis in brain mitochondria, and has a limited effect on ROS production, confirming that this drug may have limited harmful effects on normal cells.

Disease eradication and health systems development.

PubMed Central

Melgaard, B.; Creese, A.; Aylward, B.; Olivé, J. M.; Maher, C.; Okwo-Bele, J. M.; Lee, J. W.

1998-01-01

This article provides a framework for the design of future eradication programmes so that the greatest benefit accrues to health systems development from the implementation of such programmes. The framework focuses on weak and fragile health systems and assumes that eradication leads to the cessation of the intervention required to eradicate the disease. Five major components of health systems are identified and key elements which are of particular relevance to eradication initiatives are defined. The dearth of documentation which can provide "lessons learned" in this area is illustrated with a brief review of the literature. Opportunities and threats, which can be addressed during the design of eradication programmes, are described and a number of recommendations are outlined. It is emphasized that this framework pertains to eradication programmes but may be useful in attempts to coordinate vertical and horizontal disease control activities for maximum mutual benefits. PMID:10063670

Kudzu eradication and management

Treesearch

James H. Miller

1996-01-01

Kudzu patches can be eradicated with persistent treatments or they can be contained and managed with other treatment options. Herbicides, grazing, prescribed buring, and disk harrowing can be used as eradication or containment treatments. For eradication, every kudzu plant in and around a patch must be killed or the spread from any surviving plants can make all prior...

A novel role of BELL1-like homeobox genes, PENNYWISE and POUND-FOOLISH, in floral patterning.

PubMed

Yu, Lifeng; Patibanda, Varun; Smith, Harley M S

2009-02-01

Flowers are determinate shoots comprised of perianth and reproductive organs displayed in a whorled phyllotactic pattern. Floral organ identity genes display region-specific expression patterns in the developing flower. In Arabidopsis, floral organ identity genes are activated by LEAFY (LFY), which functions with region-specific co-regulators, UNUSUAL FLORAL ORGANS (UFO) and WUSCHEL (WUS), to up-regulate homeotic genes in specific whorls of the flower. PENNYWISE (PNY) and POUND-FOOLISH (PNF) are redundant functioning BELL1-like homeodomain proteins that are expressed in shoot and floral meristems. During flower development, PNY functions with a co-repressor complex to down-regulate the homeotic gene, AGAMOUS (AG), in the outer whorls of the flower. However, the function of PNY as well as PNF in regulating floral organ identity in the central whorls of the flower is not known. In this report, we show that combining mutations in PNY and PNF enhance the floral patterning phenotypes of weak and strong alleles of lfy, indicating that these BELL1-like homeodomain proteins play a role in the specification of petals, stamens and carpels during flower development. Expression studies show that PNY and PNF positively regulate the homeotic genes, APETALA3 and AG, in the inner whorls of the flower. Moreover, PNY and PNF function in parallel with LFY, UFO and WUS to regulate homeotic gene expression. Since PNY and PNF interact with the KNOTTED1-like homeodomain proteins, SHOOTMERISTEMLESS (STM) and KNOTTED-LIKE from ARABIDOPSIS THALIANA2 (KNAT2) that regulate floral development, we propose that PNY/PNF-STM and PNY/PNF-KNAT2 complexes function in the inner whorls to regulate flower patterning events.

H pylori recurrence after successful eradication.

PubMed

Niv, Yaron

2008-03-14

Recurrence of H pylori after eradication is rare in developed countries and more frequent in developing countries. Recrudescence (recolonization of the same strain within 12 mo after eradication) rather than reinfection (colonization with a new strain, more than 12 mo after eradication) is considered to be responsible for most of the cases. This observation was confirmed only in developed countries, while in developing countries a recent meta-analysis demonstrated a high rate of reinfection. The proportion of H pylori annual recurrence was 2.67% and 13.00% in developed and developing countries, respectively. Nested meta-analysis (only cases with a longer follow-up and a negative (13)CUBT a year after eradication) revealed annual recurrence rate of 1.45% [relative risk (RR), 0.54] and 12.00% (RR, 0.92) in developed and developing countries, respectively. These findings support the notion that in developed countries many cases of recurrence are due to recrudescence within the first year after eradication, with a 46% drop in the recurrence rate after the first year post eradication, while in developing countries reinfection is more pronounced, and continue at the same rate since eradication. A different approach for follow-up after H pylori eradication is probably needed in patients of developing countries, since reinfection is highly prevalent.

H pylori recurrence after successful eradication

PubMed Central

Niv, Yaron

2008-01-01

Recurrence of H pylori after eradication is rare in developed countries and more frequent in developing countries. Recrudescence (recolonization of the same strain within 12 mo after eradication) rather than reinfection (colonization with a new strain, more than 12 mo after eradication) is considered to be responsible for most of the cases. This observation was confirmed only in developed countries, while in developing countries a recent meta-analysis demonstrated a high rate of reinfection. The proportion of H pylori annual recurrence was 2.67% and 13.00% in developed and developing countries, respectively. Nested meta-analysis (only cases with a longer follow-up and a negative 13CUBT a year after eradication) revealed annual recurrence rate of 1.45% [relative risk (RR), 0.54] and 12.00% (RR, 0.92) in developed and developing countries, respectively. These findings support the notion that in developed countries many cases of recurrence are due to recrudescence within the first year after eradication, with a 46% drop in the recurrence rate after the first year post eradication, while in developing countries reinfection is more pronounced, and continue at the same rate since eradication. A different approach for follow-up after H pylori eradication is probably needed in patients of developing countries, since reinfection is highly prevalent. PMID:18330934

The Effect of Helicobacter pylori Eradication on the Levels of Essential Trace Elements

PubMed Central

Wu, Meng-Chieh; Huang, Chun-Yi; Kuo, Fu-Chen; Hsu, Wen-Hung; Wang, Sophie S. W.; Shih, Hsiang-Yao; Liu, Chung-Jung; Chen, Yen-Hsu; Wu, Deng-Chyang; Huang, Yeou-Lih; Lu, Chien-Yu

2014-01-01

Objective. This study was designed to compare the effect of Helicobacter pylori (H. pylori) infection treatment on serum zinc, copper, and selenium levels. Patients and Methods. We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. Results. Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (P = 0.06). There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (P < 0.05). The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. Conclusion. H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327). PMID:25548772

The Impact of Polio Eradication on Routine Immunization and Primary Health Care: A Mixed-Methods Study

PubMed Central

Closser, Svea; Cox, Kelly; Parris, Thomas M.; Landis, R. Matthew; Justice, Judith; Gopinath, Ranjani; Maes, Kenneth; Banteyerga Amaha, Hailom; Mohammed, Ismaila Zango; Dukku, Aminu Mohammed; Omidian, Patricia A.; Varley, Emma; Tedoff, Pauley; Koon, Adam D.; Nyirazinyoye, Laetitia; Luck, Matthew A.; Pont, W. Frank; Neergheen, Vanessa; Rosenthal, Anat; Nsubuga, Peter; Thacker, Naveen; Jooma, Rashid; Nuttall, Elizabeth

2014-01-01

Background. After 2 decades of focused efforts to eradicate polio, the impact of eradication activities on health systems continues to be controversial. This study evaluated the impact of polio eradication activities on routine immunization (RI) and primary healthcare (PHC). Methods. Quantitative analysis assessed the effects of polio eradication campaigns on RI and maternal healthcare coverage. A systematic qualitative analysis in 7 countries in South Asia and sub-Saharan Africa assessed impacts of polio eradication activities on key health system functions, using data from interviews, participant observation, and document review. Results. Our quantitative analysis did not find compelling evidence of widespread and significant effects of polio eradication campaigns, either positive or negative, on measures of RI and maternal healthcare. Our qualitative analysis revealed context-specific positive impacts of polio eradication activities in many of our case studies, particularly disease surveillance and cold chain strengthening. These impacts were dependent on the initiative of policy makers. Negative impacts, including service interruption and public dissatisfaction, were observed primarily in districts with many campaigns per year. Conclusions. Polio eradication activities can provide support for RI and PHC, but many opportunities to do so remain missed. Increased commitment to scaling up best practices could lead to significant positive impacts. PMID:24690667

Natural and experimental Helicobacter mustelae reinfection following successful antimicrobial eradication in ferrets.

PubMed

Batchelder, M; Fox, J G; Hayward, A; Yan, L; Shames, B; Murphy, J C; Palley, L

1996-03-01

Recrudescence or reinfection may occur after eradication of Helicobacter pylori in humans. We used the ferret Helicobacter mustelae model to investigate the effect of prior infection and eradication on reinfection by experimental and natural routes. Two groups of ferrets with naturally acquired H. mustelae infection were treated with an eradication protocol using amoxicillin, metronidazole, and bismuth subsalicylate. The ferrets were monitored for recrudescence by repeated cultures of endoscopic gastric mucosal biopsies. The ferrets were challenged at 17 months (group I) and 6 months (group II) after eradication with a strain of H. mustelae having a distinctive restriction endonuclease analysis pattern. The eradication protocol was repeated to eliminate the infection produced by experimental challenge. The ferrets were then cohoused intermittently with naturally infected ferrets. The original H. mustelae infection was successfully eliminated by the eradication protocol. No recrudescence was observed in group I for 12 months nor for 3 months in group II after eradication. All ferrets became persistently reinfected with the challenge strain. The infection from the challenge strain was eradicated successfully. No ferrets in group I and all ferrets in group II became infected through cohousing. These results suggest that though prior infection with H. mustelae may confer some protection against reinfection, such protection is not universal in all circumstances; that susceptibility to reinfection by contact with infected animals varies between individuals; and that age may be a factor in this individual variability. These results are applicable to studies of reinfection after eradication of H. pylori in humans.

The Efficacy of Saccharomyces boulardii CNCM I-745 in Addition to Standard Helicobacter pylori Eradication Treatment in Children

PubMed Central

Bin, Zhang; Ya-Zheng, Xu; Zhao-Hui, Deng; Bo, Chu; Li-Rong, Jiang

2015-01-01

Purpose This study aims to investigate Saccharomyces boulardii CNCM I-745 during Helicobacter pylori eradication in children. Methods One hundred ninety-four H. pylori positive children were randomized in two groups. Therapy (omeprazole+clarithromycin+amoxicillin or omeprazole+clarithromycin+metronidazole in case of penicillin allergy) was given to both groups during two weeks. In the treatment group (n: 102) S. boulardii was added to the triple therapy, while the control group (n: 92) only received triple therapy. The incidence, onset, duration and severity of diarrhea and compliance to the eradication treatment were compared. A 13C urea breath test was done 4 weeks after the end of eradication therapy in two groups of 21 patients aged 12 years and older to test the H. pylori eradication rate. Results In the treatment group, diarrhea occurred in 12 cases (11.76%), starting after 6.25±1.24 days, lasting 3.17±1.08 days, and compliance to eradication treatment was 100%. In the control group, diarrhea occurred in 26 cases (28.26%), starting after 4.05±1.11 days, lasting 4.02±0.87 days, and in six cases eradication treatment was stopped prematurely (p<0.05). The 13C urea breath test showed successful H. pylori eradication in 71.4% of the patients in the treatment and in 61.9 % in the control group (not significant). Conclusion S. boulardii has a beneficial effect on the prevention and treatment of diarrhea during H. pylori eradication in children. Although S. boulardii did only slightly increase H. pylori eradication rate, compliance to eradication treatment was improved. PMID:25866729

Randomized Controlled Trial for Helicobacter pylori Eradication in a Naive Portuguese Population: Is Sequential Treatment Superior to Triple Therapy in Real World Clinical Setting?

PubMed

Boal Carvalho, Pedro; Magalhães, Joana; Dias de Castro, Francisca; Rosa, Bruno; Cotter, José

2017-03-31

Helicobacter pylori eradication has become increasingly difficult as resistances to several antibiotics develop. We aimed to compare Helicobacter pylori eradication rates between triple therapy and sequential therapy in a naive Portuguese population. Prospective randomized trial including consecutive patients referred for first-line Helicobacter pylori eradication treatment. previous gastric surgery/neoplasia, pregnancy/lactancy, allergy to any of the drugs. The compared eradication regimens were triple therapy (pantoprazol, amoxicillin and clarithromycin 12/12 hours, 14 days) and sequential therapy (pantoprazol 12/12 hours for 10 days, amoxicillin 12/12 hours for days 1 - 5 and clarithromycin plus metronidazol 12/12 hours during days 6 - 10). Eradication success was confirmed with urea breath test. Statistical analysis was performed with SPSS v21.0 and a p-value < 0.05 was considered statistically significant. Included 60 patients, 39 (65%) female with mean age 52 years (SD ± 14.3). Treatment groups were homogeneous for gender, age, indication for treatment and smoking status. No statistical differences were encountered between sequential and triple therapy eradication rates (86.2% vs 77.4%, p = 0.379), global eradication rate was 82%. Tobacco consumption was associated with a significantly lower eradication success (54.5 vs 87.8%, p = 0.022). In this randomized controlled trial in a naive Portuguese population, we found a satisfactory global Helicobacter pylori eradication rate of 82%, with no statistical differences observed in the efficacy of the treatment between triple and sequential regimens. These results support the use of either therapy for the first-line eradication of Helicobacter pylori.

Patients with established gastro-esophageal reflux disease might benefit from Helicobacter pylori eradication

PubMed Central

Moschos, John M.; Kouklakis, George; Vradelis, Stergios; Zezos, Petros; Pitiakoudis, Michael; Chatzopoulos, Dimitrios; Zavos, Christos; Kountouras, Jannis

2014-01-01

Background The aim of this study was to investigate the effect of Helicobacter pylori (H. pylori) eradication in selected H. pylori-positive patients with a primary diagnosis of gastro-esophageal reflux disease (GERD) by using the 3-h postprandial esophageal pH monitoring. Methods We recruited patients with erosive esophagitis at endoscopy and H. pylori infection at histology, successfully cured following eradication therapy; the selected H. pylori-positive patients had weekly reflux symptoms for at least six months and endoscopically established Grade A or B esophagitis. Twenty-nine eligible patients were initially subjected to esophageal manometry and ambulatory 3-h postprandial esophageal pH monitoring. All patients received H. pylori triple eradication therapy accompanied by successful H. pylori eradication. After successful eradication of H. pylori (confirmed by 13C urea breath test), a second manometry and 3-h postprandial esophageal pH monitoring were introduced to assess the results of eradication therapy, after a 3-month post-treatment period. Results All 29 selected H. pylori-positive patients became negative due to successful H. pylori eradication, evaluated by 13C urea breath test after a 4-week post-treatment period. Post-eradication, 62.1% patients showed similar manometric pattern at baseline; 17.2% showed improvement; 17.2% normalization; and 3.4% deterioration of the manometric patterns. The DeMeester symptom scoring in the 3-h postprandial ambulatory esophageal pH monitoring was improved after eradication of H. pylori (median 47.47 vs. 22.00, Wilcoxon’s singed rank; P=0.016). On comparing the pH monitoring studies for each patient at baseline and post-eradication period, 82.8% patients showed improvement and 17.2% deterioration of the DeMeester score. Conclusion By using 3-h postprandial esophageal pH monitoring, this study showed, for the first time, that H. pylori eradication may positively influence GERD symptoms. Large-scale controlled relative studies are warranted to confirm these findings. PMID:25330805

Patients with established gastro-esophageal reflux disease might benefit from Helicobacter pylori eradication.

PubMed

Moschos, John M; Kouklakis, George; Vradelis, Stergios; Zezos, Petros; Pitiakoudis, Michael; Chatzopoulos, Dimitrios; Zavos, Christos; Kountouras, Jannis

2014-01-01

The aim of this study was to investigate the effect of Helicobacter pylori ( H. pylori ) eradication in selected H. pylori -positive patients with a primary diagnosis of gastro-esophageal reflux disease (GERD) by using the 3-h postprandial esophageal pH monitoring. We recruited patients with erosive esophagitis at endoscopy and H. pylori infection at histology, successfully cured following eradication therapy; the selected H. pylori -positive patients had weekly reflux symptoms for at least six months and endoscopically established Grade A or B esophagitis. Twenty-nine eligible patients were initially subjected to esophageal manometry and ambulatory 3-h postprandial esophageal pH monitoring. All patients received H. pylori triple eradication therapy accompanied by successful H. pylori eradication. After successful eradication of H. pylori (confirmed by 13 C urea breath test), a second manometry and 3-h postprandial esophageal pH monitoring were introduced to assess the results of eradication therapy, after a 3-month post-treatment period. All 29 selected H. pylori -positive patients became negative due to successful H. pylori eradication, evaluated by 13 C urea breath test after a 4-week post-treatment period. Post-eradication, 62.1% patients showed similar manometric pattern at baseline; 17.2% showed improvement; 17.2% normalization; and 3.4% deterioration of the manometric patterns. The DeMeester symptom scoring in the 3-h postprandial ambulatory esophageal pH monitoring was improved after eradication of H. pylori (median 47.47 vs. 22.00, Wilcoxon's singed rank; P=0.016). On comparing the pH monitoring studies for each patient at baseline and post-eradication period, 82.8% patients showed improvement and 17.2% deterioration of the DeMeester score. By using 3-h postprandial esophageal pH monitoring, this study showed, for the first time, that H. pylori eradication may positively influence GERD symptoms. Large-scale controlled relative studies are warranted to confirm these findings.

First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype

PubMed Central

Saito, Yoshimasa; Serizawa, Hiroshi; Kato, Yukako; Nakano, Masaru; Nakamura, Masahiko; Saito, Hidetsugu; Suzuki, Hidekazu; Kanai, Takanori

2015-01-01

AIM: To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication. METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or 13C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642). RESULTS: The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P < 0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population. CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs. PMID:26730167

A synthetic NO reduction cycle on a bis(pyrazolato)-bridged dinuclear ruthenium complex including photo-induced transformation.

PubMed

Arikawa, Yasuhiro; Hiura, Junko; Tsuchii, Chika; Kodama, Mika; Matsumoto, Naoki; Umakoshi, Keisuke

2018-05-17

A synthetic NO reduction cycle (2NO + 2H+ + 2e- → N2O + H2O) on a dinuclear platform {(TpRu)2(μ-pz)2} (Tp = HB(pyrazol-1-yl)3) was achieved, where an unusual N-N coupling complex was included. Moreover, an interesting photo-induced conversion of the N-N coupling complex to an oxido-bridged complex was revealed.

Preventative Disease Management and Grower Decision Making: A Case Study of California Wine-Grape Growers.

PubMed

Hillis, Vicken; Lubell, Mark; Kaplan, Jonathan; Baumgartner, Kendra

2017-06-01

Preventative disease management is challenging to farmers because it requires paying immediate costs in the hopes of returning uncertain future benefits. Understanding farmer decision making about prevention has the potential to reduce disease incidence and minimize the need for more costly postinfection practices. For example, the grapevine trunk-disease complex (esca, Botryosphaeria dieback, Eutypa dieback, and Phomopsis dieback) significantly affects vineyard productivity and longevity. Given the chronic nature of the infections and inability to eradicate the fungal pathogens, the preventative practices of delayed pruning, applications of pruning-wound protectants, and double pruning (also known as prepruning) are the most effective means of management. We surveyed wine-grape growers in six regions of California on their use of these three practices. In spite of acknowledging the yield impacts of trunk diseases, a substantial number of respondents either choose not to use preventative practices or incorrectly adopted them in mature vineyards, too late in the disease cycle to be effective. Growers with more negative perceptions of cost efficacy were less likely to adopt preventative practices or were more likely to time adoption incorrectly in mature vineyards. In general, preventative management may require strong intervention in the form of policy or extension to motivate behavioral change.

Arboviral diseases and malaria in Australia, 2007/08: annual report of the National Arbovirus and Malaria Advisory Committee.

PubMed

Fitzsimmons, Gerard J; Wright, Phil; Johansen, Cheryl A; Whelan, Peter I

2009-06-01

The National Notifiable Diseases Surveillance System (NNDSS) received 8,671 notifications of diseases transmitted by mosquitoes in Australia for the season 1 July 2007 to 30 June 2008. This represented a 39% increase from the annual average of 6,259 notifications for the previous 5 years. The alphaviruses, Barmah Forest and Ross River, accounted for 7,760 (89%) of these notifications during the 2007/08 season and represents an increase when compared with the mean of the past 5 seasons. Detection of flavivirus seroconversions in sentinel chicken flocks across Australia provides an early warning of increased levels of Murray Valley encephalitis virus (MVEV) and Kunjin virus activity. Unusual MVEV activity in mosquitoes and sentinel chicken flocks was reported in southeast Australia during the 2007/08 season. Two cases of MVEV were reported, one each from New South Wales and Western Australia. There were 365 notifications of dengue virus infection that were acquired overseas compared with an average of 164 overseas-acquired dengue cases per annum reported to NNDSS over the 5 seasons from 2002/03 to 2006/07. There were no reports of locally-acquired malaria notified in Australia and 505 notified cases of overseas-acquired malaria during the season 2007/08. The exotic dengue vector Aedes aegypti was first detected on Groote Eylandt, Northern Territory in October 2006 and led to a 2-year Ae. aegypti eradication project. The successful eradication of Ae. aegypti from Groote Eylandt was officially announced in May 2008. The success of the program was due to the selection of appropriate chemicals that were successful in treating mosquito adults, larvae and egg infested receptacles. This annual report presents information on diseases transmitted by mosquitoes in Australia and notified to NNDSS.

Sarcoptes infestation in two miniature pigs with zoonotic transmission - a case report.

PubMed

Grahofer, Alexander; Bannoehr, Jeanette; Nathues, Heiko; Roosje, Petra

2018-03-13

Scabies is a contagious skin disease rarely described in miniature pigs. To the best of the authors' knowledge, a zoonotic transfer from infected pet pigs to humans has not been reported previously. This case report describes the infestation with Sarcoptes scabiei mites in two miniature pigs presenting with unusual clinical signs, and disease transmission to a child. Two 7-month-old male castrated miniature pig siblings were examined. Both had developed skin lesions, one animal was presented for neurological signs and emaciation. They were housed together in an indoor- and outdoor enclosure. Dermatological examination revealed a dull, greasy coat with generalized hypotrichosis and multifocal erythema. Microscopic examination of skin scrapings, impression smears of affected skin and ear swabs revealed high numbers of Sarcoptes mites in both animals as well as bacterial overgrowth. A subcutaneous injection of ivermectin 0.3 mg/kg was administered to both animals and repeated after 2 weeks. Both miniature pigs received subcutaneous injections with butafosfan and cyanocobalamin, were washed with a 3% chlorhexidine shampoo and were fed on a well-balanced diet. Pig enclosures were cleaned. The infested child was examined by a physician and an antipruritic cream was prescribed. Both miniature pigs and the child went into clinical remission after treatment. Sarcoptic mange is rare or even eradicated in commercial pig farming in many countries but miniature pigs may represent a niche for Sarcoptes scabiei infections. This case report indicates that miniature pigs kept as pets can efficiently transmit zoonotic disease to humans. In addition, these animals may represent a niche for Sarcoptes scabiei infestation in countries where sarcoptic mange in commercial pig farms has been eradicated and could therefore pose, a hazard for specific pathogen free farms.

Morphology and molecular taxonomy of Evlachovaea-like fungi, and the status of this unusual conidial genus

USDA-ARS?s Scientific Manuscript database

The entomopathogenic anamorphic genus Evlachovaea was described to differ from other fungi in forming its conidia obliquely to the axis of the conidiogenous cell and with successive conidia having alternate orientations with a zipper- or chevron-like arrangement resulting in flat, ribbon-like chains...

Polycipiviridae: a proposed new family of polycistronic picorna-like RNA viruses

USDA-ARS?s Scientific Manuscript database

Solenopsis invicta virus 2 is a single-stranded positive-sense picorna-like RNA virus with an unusual genome structure. The monopartite genome of approximately 11 kb contains four short open reading frames in its 5' one third, three of which encode proteins with homology to picornavirus-like jelly-r...

Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

PubMed

Dunn, Glynis; Klapsa, Dimitra; Wilton, Thomas; Stone, Lindsay; Minor, Philip D; Martin, Javier

2015-08-01

There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era.

Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative

PubMed Central

Dunn, Glynis; Klapsa, Dimitra; Wilton, Thomas; Stone, Lindsay; Minor, Philip D.; Martin, Javier

2015-01-01

There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era. PMID:26313548

Recommendations of 2nd National Consultative Meeting of Indian Academy of Pediatrics (IAP) on polio eradication and improvement of routine immunization.

PubMed

Vashishtha, Vipin M; Kalra, Ajay; John, T Jacob; Thacker, Naveen; Agarwal, R K

2008-05-01

Persistence of intense wild poliovirus (WPV) transmission, particularly type 3 in northern India necessitated the Indian Academy of Pediatrics (IAP) to convene a National Consultative Meeting to review its earlier recommendations on polio eradication and improvement of routine immunization. More than thirty experts were invited and intense deliberations were held over two days to draw consensus statements on various issues related with polio eradication. To review the ongoing strategy, identify the existing challenges, and suggest modifications to the current strategy for eradication of poliomyelitis in India. IAP reiterates its support to ongoing efforts on polio eradication but demand some flexibility in the strategy. The immediate challenges identified include persistent WPV type 1 transmission in Uttar Pradesh (UP) and Bihar, intense type 3 transmission also in UP and Bihar, and maintaining polio-free status of all other states. Circulating vaccine derived poliovirus (cVDPV), particularly type 2, was identified as a great future threat. Neglect of routine immunization (RI), poor efficacy of oral polio vaccine (OPV), operational issues, and inadequate uptake of OPV in the 2 endemic states are the main reasons of failure to interrupt transmission of WPV 1 and 3. However, for the first time in history the intensity of WPV 1 circulation is very low in western UP. IAP suggests that high-quality, uniform and consistent performance of supplementary immunization activities (SIAs) in all districts of western UP, particularly using mOPV1(monovalent OPV1) should be maintained to avoid reestablishment of circulation of type 1 poliovirus. A judicious mix of mOPV1 and mOPV3, given sequentially or even simultaneously (after validating the efficacies) will be necessary to address the upsurge of WPV3. Re-establishing routine immunization should be the foremost priority. IAP strongly recommends to Government of India (GOI) to take urgent measures to attain coverage of a minimum of 90% against all UIP antigens in all the states by the end of 2008. In view of the need to simultaneously raise immunity levels to protect against WPVs 1, 3 and cVDPV2, IPV may be given immediate consideration as an additional tool. IPV will be essential in the postWPVeradication phase; it can play a useful role even in the current WPV eradication phase. IAP urges the GOI to urgently sort out various issues associated with implementation of the proposal to use IPV. More transparency is needed on cases of vaccine associated paralytic poliomyelitis (VAPP). Further improvement in stool collection rates is also warranted to minimize the tally of compatible cases. IAP urges the social mobilization network to address the issues of waning interest and shifting focus and negative media coverage. Alternate tactics like reduced numbers of SIAs applied in the low transmission season, along with IPVDTP combination vaccine in RI can also be considered. IAP believes it will be risky to stop vaccination against poliomyelitis in postWPV eradication phase. The best option is to gradually introduce IPV starting now, so that a switch to IPV following high-performance national immunization days (NIDs) can be made to ensure sustained high immunity against all polioviruses, wild and vaccine derived. IAP requests the global polio eradication initiative (GPEI) to continue relevant research to inform on various aspects related to polio eradication, defined as zero incidence of any poliovirus infection. IAP also urges GOI to take immediate measures for improvement of environmental sanitation.

9 CFR 72.6 - Interstate movement of cattle from quarantined areas not eradicating ticks.

Code of Federal Regulations, 2013 CFR

2013-01-01

... quarantined areas not eradicating ticks. 72.6 Section 72.6 Animals and Animal Products ANIMAL AND PLANT HEALTH... areas not eradicating ticks. Cattle in quarantined areas where tick eradication is not being conducted 3... inspector just prior to final dipping, found to be apparently free of ticks, and be certified as such by...

9 CFR 72.6 - Interstate movement of cattle from quarantined areas not eradicating ticks.

Code of Federal Regulations, 2012 CFR

2012-01-01

... quarantined areas not eradicating ticks. 72.6 Section 72.6 Animals and Animal Products ANIMAL AND PLANT HEALTH... areas not eradicating ticks. Cattle in quarantined areas where tick eradication is not being conducted 3... inspector just prior to final dipping, found to be apparently free of ticks, and be certified as such by...

9 CFR 72.6 - Interstate movement of cattle from quarantined areas not eradicating ticks.

Code of Federal Regulations, 2011 CFR

2011-01-01

... quarantined areas not eradicating ticks. 72.6 Section 72.6 Animals and Animal Products ANIMAL AND PLANT HEALTH... areas not eradicating ticks. Cattle in quarantined areas where tick eradication is not being conducted 3... inspector just prior to final dipping, found to be apparently free of ticks, and be certified as such by...

Eradication of Herpesvirus simiae from a Rhesus Monkey Breeding Colony. B-virus Eradication in Breeding Rhesus

DTIC Science & Technology

1992-10-01

Herpesvirus simiae from a Rhesus Monkey Breeding Colony B-virus Eradication in Breeding Rhesus 6. AUTHOR(S) Jerome J. Sauber , John W. Fanton, Roger C...for Laboratory Animal Science October 1992 An Attempt to Eradicate Herpesvirus simiae from a Rhesus Monkey Breeding Colony Jerome J. Sauber , John W

Polio eradication is just over the horizon: the challenges of global resource mobilization.

PubMed

Pirio, Gregory Alonso; Kaufmann, Judith

2010-01-01

This study draws lessons from the resource mobilization experiences of the Global Polio Eradication Initiative (GPEI). As the GPEI launched its eradication effort in 1988, it underestimated both the difficulty and the costs of the campaign. Advocacy for resource mobilization came as an afterthought in the late 1990s, when achieving eradication by the target date of 2000 began to look doubtful. The reality of funding shortfalls undercutting eradication leads to the conclusion that advocacy for resource mobilization is as central to operations as are scientific and technical factors.

Poliovirus Studies during the Endgame of the Polio Eradication Program.

PubMed

Arita, Minetaro

2017-01-24

Since the beginning of Global Polio Eradication Initiative in 1988, poliomyelitis cases caused by wild poliovirus (PV) have been drastically reduced, with only 74 cases reported in 2 endemic countries in 2015. The current limited PV transmission suggests that we are in the endgame of the polio eradication program. However, specific challenges have emerged in the endgame, including tight budget, switching of the vaccines, and changes in biorisk management of PV. To overcome these challenges, several PV studies have been implemented in the eradication program. Some of the responses to the emerging challenges in the polio endgame might be valuable in other infectious diseases eradication programs. Here, I will review challenges that confront the polio eradication program and current research to address these challenges.

Characterization of the Unusual Product from the Reaction between Cobalt(II) Chloride, Ethane-1,2-diamine, and Hydrochloric Acid: An Undergraduate Project Involving an Unknown Metal Complex.

ERIC Educational Resources Information Center

Curtis, Neil F.; And Others

1986-01-01

Discusses the need for student research-type chemistry projects based upon "unknown" metal complexes. Describes an experiment involving the product from the reaction between cobalt(II) chloride, ethane-1,2-diamine (en) and concentrated hydrochloric acid. Outlines the preparation of the cobalt complex, along with procedure, results and…

Bichat guidelines for the clinical management of smallpox and bioterrorism-related smallpox.

PubMed

Bossi, Philippe; Tegnell, Anders; Baka, Agoritsa; Van Loock, Frank; Hendriks, J; Werner, Albrecht; Maidhof, Heinrich; Gouvras, Georgios

2004-12-15

Smallpox is a viral infection caused by the variola virus. It was declared eradicated worldwide by the Word Health Organization in 1980 following a smallpox eradication campaign. Smallpox is seen as one of the viruses most likely to be used as a biological weapon. The variola virus exists legitimately in only two laboratories in the world. Any new case of smallpox would have to be the result of human accidental or deliberate release. The aerosol infectivity, high mortality, and stability of the variola virus make it a potential and dangerous threat in biological warfare. Early detection and diagnosis are important to limit the spread of the disease. Patients with smallpox must be isolated and managed, if possible, in a negative-pressure room until death or until all scabs have been shed. There is no established antiviral treatment for smallpox. The most effective prevention is vaccination before exposure.

Bichat guidelines for the clinical management of smallpox and bioterrorism-related smallpox.

PubMed

Bossi, P; Tegnell, A; Baka, A; van Loock, F; Werner, A; Hendriks, J; Maidhof, H; Gouvras, G

2004-12-01

Smallpox is a viral infection caused by the variola virus. It was declared eradicated worldwide by the Word Health Organization in 1980 following a smallpox eradication campaign. Smallpox is seen as one of the viruses most likely to be used as a biological weapon. The variola virus exists legitimately in only two laboratories in the world. Any new case of smallpox would have to be the result of human accidental or deliberate release. The aerosol infectivity, high mortality, and stability of the variola virus make it a potential and dangerous threat in biological warfare. Early detection and diagnosis are important to limit the spread of the disease. Patients with smallpox must be isolated and managed, if possible, in a negative-pressure room until death or until all scabs have been shed. There is no established antiviral treatment for smallpox. The most effective prevention is vaccination before exposure.

Structure of the membrane domain of respiratory complex I.

PubMed

Efremov, Rouslan G; Sazanov, Leonid A

2011-08-07

Complex I is the first and largest enzyme of the respiratory chain, coupling electron transfer between NADH and ubiquinone to the translocation of four protons across the membrane. It has a central role in cellular energy production and has been implicated in many human neurodegenerative diseases. The L-shaped enzyme consists of hydrophilic and membrane domains. Previously, we determined the structure of the hydrophilic domain. Here we report the crystal structure of the Esherichia coli complex I membrane domain at 3.0 Å resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-like subunits L, M and N is novel, with two inverted structural repeats of five transmembrane helices arranged, unusually, face-to-back. Each repeat includes a discontinuous transmembrane helix and forms half of a channel across the membrane. A network of conserved polar residues connects the two half-channels, completing the proton translocation pathway. Unexpectedly, lysines rather than carboxylate residues act as the main elements of the proton pump in these subunits. The fourth probable proton-translocation channel is at the interface of subunits N, K, J and A. The structure indicates that proton translocation in complex I, uniquely, involves coordinated conformational changes in six symmetrical structural elements.

Understanding the autistic dental patient.

PubMed

Green, Danielle; Flanagan, Dennis

2008-01-01

Autism spectrum disorder (ASD) is one of many pervasive developmental disorders (PDD); others include Rett syndrome, childhood disintegrative disorder (also known as Heller's syndrome), pervasive developmental disorder not otherwise specified (PDD-NOS), and the higher functioning Asperger's syndrome. Because ASD is the most common of the developmental disabilities, it is not unusual for dentists to have ASD patients among their patient population. As the name indicates, ASD varies widely in its clinical manifestations; however, dentists are likely to encounter difficulties with communication and socialization. Although communication may be difficult, it is not impossible. A thorough understanding of this complex neurological disorder and displaying patience are vital for the dentist. This article seeks to familiarize readers with ASD characteristics and co-morbid conditions that may affect dental treatment and provide some management strategies for this unique population.

Recent advances in pericentriolar material organization: ordered layers and scaffolding gels.

PubMed

Fry, Andrew M; Sampson, Josephina; Shak, Caroline; Shackleton, Sue

2017-01-01

The centrosome is an unusual organelle that lacks a surrounding membrane, raising the question of what limits its size and shape. Moreover, while electron microscopy (EM) has provided a detailed view of centriole architecture, there has been limited understanding of how the second major component of centrosomes, the pericentriolar material (PCM), is organized. Here, we summarize exciting recent findings from super-resolution fluorescence imaging, structural biology, and biochemical reconstitution that together reveal the presence of ordered layers and complex gel-like scaffolds in the PCM. Moreover, we discuss how this is leading to a better understanding of the process of microtubule nucleation, how alterations in PCM size are regulated in cycling and differentiated cells, and why mutations in PCM components lead to specific human pathologies.

Recent advances in pericentriolar material organization: ordered layers and scaffolding gels

PubMed Central

Fry, Andrew M.; Sampson, Josephina; Shak, Caroline; Shackleton, Sue

2017-01-01

The centrosome is an unusual organelle that lacks a surrounding membrane, raising the question of what limits its size and shape. Moreover, while electron microscopy (EM) has provided a detailed view of centriole architecture, there has been limited understanding of how the second major component of centrosomes, the pericentriolar material (PCM), is organized. Here, we summarize exciting recent findings from super-resolution fluorescence imaging, structural biology, and biochemical reconstitution that together reveal the presence of ordered layers and complex gel-like scaffolds in the PCM. Moreover, we discuss how this is leading to a better understanding of the process of microtubule nucleation, how alterations in PCM size are regulated in cycling and differentiated cells, and why mutations in PCM components lead to specific human pathologies. PMID:29026530

Crystal structures of dioxonium hexafluorotantalate and dioxonium hexafluoroniobate complexes with tetrabenzo-30-crown-10

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

Furmanova, N. G., E-mail: furm@ns.crys.ras.ru; Rabadanov, M. Kh.; Chernaya, T. S.

2008-03-15

Two isostructural complexes of dioxonium [H{sub 5}O{sub 2}]{sup +} with tetrabenzo-30-crown-10 of the compositions [(tetrabenzo-30-crown-10 . H{sub 5}O{sub 2})][TaF{sub 6}] (I) and [(tetrabenzo-30-crown-10 . H{sub 5}O{sub 2})][NbF{sub 6}] (II) are studied using X-ray diffraction. The complexes crystallize in the monoclinic crystal system (space group C2/c, Z = 4). The unit cell parameters of these compounds are as follows: a = 15.6583(12) A, b = 15.2259(13) A, c = 16.4473(13) A, and {beta} = 99.398(6) deg. for complex I and a = 15.7117(12) A, b = 15.2785(15) A, c = 16.5247(15) A, and {beta} = 99.398(7) deg. for complex II. Thesemore » complexes belong to the ionic type. The dioxonium cation [H{sub 5}O{sub 2}]{sup +} in the form of the two-unit cluster [H{sub 3}O . H{sub 2}O]{sup +} is stabilized by the strong hydrogen bond OH-O [O-O, 2.353(4) A] and encapsulated by the crown ether. Each oxygen atom of the dioxonium cation also forms two oxygen bonds O-O(crown). The crown ether adopts an unusual two-level (pocket-like) conformation, which provides a complete encapsulation of the oxonium associate. The interaction of the cationic complex with the anion in the crystal occurs through contacts of the C-H-F type.« less

Crystal structures of dioxonium hexafluorotantalate and dioxonium hexafluoroniobate complexes with tetrabenzo-30-crown-10

NASA Astrophysics Data System (ADS)

Furmanova, N. G.; Rabadanov, M. Kh.; Chernaya, T. S.; Fonari, M. S.; Simonov, Yu. A.; Ganin, É. V.; Gelmboldt, V. O.; Grigorash, R. Ya.; Kotlyar, S. A.; Kamalov, G. L.

2008-03-01

Two isostructural complexes of dioxonium [H5O2]+ with tetrabenzo-30-crown-10 of the compositions [(tetrabenzo-30-crown-10 · H5O2)][TaF6] ( I) and [(tetrabenzo-30-crown-10 · H5O2)][NbF6] ( II) are studied using X-ray diffraction. The complexes crystallize in the monoclinic crystal system (space group C2/ c, Z = 4). The unit cell parameters of these compounds are as follows: a = 15.6583(12) Å, b = 15.2259(13) Å, c = 16.4473(13) Å, and β = 99.398(6)° for complex I and a = 15.7117(12) Å, b = 15.2785(15) Å, c = 16.5247(15) Å, and β = 99.398(7)° for complex II. These complexes belong to the ionic type. The dioxonium cation [H5O2]+ in the form of the two-unit cluster [H3O · H2O]+ is stabilized by the strong hydrogen bond OH⋯O [O⋯O, 2.353(4) Å] and encapsulated by the crown ether. Each oxygen atom of the dioxonium cation also forms two oxygen bonds O⋯O(crown). The crown ether adopts an unusual two-level (pocket-like) conformation, which provides a complete encapsulation of the oxonium associate. The interaction of the cationic complex with the anion in the crystal occurs through contacts of the C-H⋯F type.

Free oligosaccharides to monitor glycoprotein endoplasmic reticulum-associated degradation in Saccharomyces cerevisiae.

PubMed

Hirayama, Hiroto; Seino, Junichi; Kitajima, Toshihiko; Jigami, Yoshifumi; Suzuki, Tadashi

2010-04-16

In eukaryotic cells, N-glycosylation has been recognized as one of the most common and functionally important co- or post-translational modifications of proteins. "Free" forms of N-glycans accumulate in the cytosol of mammalian cells, but the precise mechanism for their formation and degradation remains unknown. Here, we report a method for the isolation of yeast free oligosaccharides (fOSs) using endo-beta-1,6-glucanase digestion. fOSs were undetectable in cells lacking PNG1, coding the cytoplasmic peptide:N-glycanase gene, suggesting that almost all fOSs were formed from misfolded glycoproteins by Png1p. Structural studies revealed that the most abundant fOS was M8B, which is not recognized well by the endoplasmic reticulum-associated degradation (ERAD)-related lectin, Yos9p. In addition, we provide evidence that some of the ERAD substrates reached the Golgi apparatus prior to retrotranslocation to the cytosol. N-Glycan structures on misfolded glycoproteins in cells lacking the cytosol/vacuole alpha-mannosidase, Ams1p, was still quite diverse, indicating that processing of N-glycans on misfolded glycoproteins was more complex than currently envisaged. Under ER stress, an increase in fOSs was observed, whereas levels of M7C, a key glycan structure recognized by Yos9p, were unchanged. Our method can thus provide valuable information on the molecular mechanism of glycoprotein ERAD in Saccharomyces cerevisiae.

Free Oligosaccharides to Monitor Glycoprotein Endoplasmic Reticulum-associated Degradation in Saccharomyces cerevisiae*

PubMed Central

Hirayama, Hiroto; Seino, Junichi; Kitajima, Toshihiko; Jigami, Yoshifumi; Suzuki, Tadashi

2010-01-01

In eukaryotic cells, N-glycosylation has been recognized as one of the most common and functionally important co- or post-translational modifications of proteins. “Free” forms of N-glycans accumulate in the cytosol of mammalian cells, but the precise mechanism for their formation and degradation remains unknown. Here, we report a method for the isolation of yeast free oligosaccharides (fOSs) using endo-β-1,6-glucanase digestion. fOSs were undetectable in cells lacking PNG1, coding the cytoplasmic peptide:N-glycanase gene, suggesting that almost all fOSs were formed from misfolded glycoproteins by Png1p. Structural studies revealed that the most abundant fOS was M8B, which is not recognized well by the endoplasmic reticulum-associated degradation (ERAD)-related lectin, Yos9p. In addition, we provide evidence that some of the ERAD substrates reached the Golgi apparatus prior to retrotranslocation to the cytosol. N-Glycan structures on misfolded glycoproteins in cells lacking the cytosol/vacuole α-mannosidase, Ams1p, was still quite diverse, indicating that processing of N-glycans on misfolded glycoproteins was more complex than currently envisaged. Under ER stress, an increase in fOSs was observed, whereas levels of M7C, a key glycan structure recognized by Yos9p, were unchanged. Our method can thus provide valuable information on the molecular mechanism of glycoprotein ERAD in Saccharomyces cerevisiae. PMID:20150426

Knowledge, attitudes and practices towards yaws and yaws-like skin disease in Ghana.

PubMed

Marks, Michael; Kwakye-Maclean, Cynthia; Doherty, Rachel; Adwere, Paul; Aziz Abdulai, Abdul; Duah, Fredrick; Ohene, Sally-Ann; Mitja, Oriol; Oguti, Blanche; Solomon, Anthony W; Mabey, David C W; Adu-Sarkodie, Yaw; Asiedu, Kingsley; Ackumey, Mercy M

2017-07-01

Yaws is endemic in Ghana. The World Health Organization (WHO) has launched a new global eradication campaign based on total community mass treatment with azithromycin. Achieving high coverage of mass treatment will be fundamental to the success of this new strategy; coverage is dependent, in part, on appropriate community mobilisation. An understanding of community knowledge, attitudes and practices related to yaws in Ghana and other endemic countries will be vital in designing effective community engagement strategies. A verbally administered questionnaire was administered to residents in 3 districts in the Eastern region of Ghana where a randomised trial on the treatment of yaws was being conducted. The questionnaire combined both quantitative and qualitative questions covering perceptions of the cause and mechanisms of transmission of yaws-like lesions, the providers from which individuals would seek healthcare for yaws-like lesions, and what factors were important in reaching decisions on where to seek care. Chi-square tests and logistic regression were used to assess relationships between reported knowledge, attitudes and practices, and demographic variables. Thematic analysis of qualitative data was used to identify common themes. A total of 1,162 individuals participated. The majority of individuals (n = 895, 77%) reported that "germs" were the cause of yaws lesions. Overall 13% (n = 161) of respondents believed that the disease was caused by supernatural forces. Participants frequently mentioned lack of personal hygiene, irregular and inefficient bathing, and washing with dirty water as fundamental to both the cause and the prevention of yaws. A majority of individuals reported that they would want to take an antibiotic to prevent the development of yaws if they were asymptomatic (n = 689, 61.2%), but a substantial minority reported they would not want to do so. A majority of individuals (n = 839, 72.7%) reported that if they had a yaws-like skin lesion they would seek care from a doctor or nurse. Both direct and indirect costs of treatment were reported as key factors affecting where participants reported they would seek care. This is the first study that has explored community knowledge, attitudes and practices in relation to yaws in any endemic population. The belief that 'germs' are in some way related to disease through a variety of transmission routes including both contact and dirty water are similar to those reported for other skin diseases in Ghana. The prominent role of private healthcare providers is an important finding of this study and suggests engagement with this sector will be important in yaws eradication efforts. Strategies to address the substantial minority of individuals who reported they would not take treatment for yaws if they were currently asymptomatic will be needed to ensure the success of yaws eradication efforts. The data collected will be of value to the Ghana Health Service and also to WHO and other partners, who are currently developing community mobilisation tools to support yaws eradication efforts worldwide.

Association of helicobacter pylori dupA with the failure of primary eradication.

PubMed

Shiota, Seiji; Nguyen, Lam Tung; Murakami, Kazunari; Kuroda, Akiko; Mizukami, Kazuhiro; Okimoto, Tadayoshi; Kodama, Masaaki; Fujioka, Toshio; Yamaoka, Yoshio

2012-04-01

To determine whether the presence of dupA Helicobacter pylori (H. pylori) influences the cure rate of primary eradication therapy. Several virulence factors of H. pylori have been reported to affect the efficacy of the eradication rate. However, no study has investigated whether the presence of dupA affects eradication failure. The presence of dupA was evaluated in 142 H. pylori strains isolated from 142 patients with gastrointestinal diseases. Of these patients, 104 received primary eradication therapy for 1 week. The risk factors for eradication failure were determined using univariate and multivariate analyses. Among 142 strains, 44 (31.0%) were dupA positive. There was no association between dupA status and gastroduodenal diseases (P>0.05). The clarithromycin (CLR) resistance rate was generally lower in the dupA-positive than in the dupA-negative group (20.4% vs. 35.7%, P=0.06). However, dupA prevalence was higher in the eradication failure group than in the success group (36.3% vs. 21.9%). Among the CLR-resistant H. pylori infected group, the successful eradication rate was significantly lower in patients infected with dupA-positive H. pylori than dupA-negative H. pylori (P=0.04). In multivariate analysis adjusted for age, sex, and type of disease, not only CLR resistance but also dupA presence was independent risk factors for eradication failure (adjusted odds ratio=3.71; 95% confidence interval,1.07-12.83). Although CLR resistant was more reliable predictor, the presence of dupA may also be an independent risk factor for eradication failure.

Association of Helicobacter pylori dupA with the failure of primary eradication

PubMed Central

Shiota, Seiji; Nguyen, Lam Tung; Murakami, Kazunari; Kuroda, Akiko; Mizukami, Kazuhiro; Okimoto, Tadayoshi; Kodama, Masaaki; Fujioka, Toshio; Yamaoka, Yoshio

2012-01-01

Goals To determine whether the presence of dupA Helicobacter pylori (H. pylori) influences the cure rate of primary eradication therapy. Background Several virulence factors of H. pylori have been reported to affect the efficacy of the eradication rate. However, no study has investigated whether the presence of dupA affects eradication failure. Study The presence of dupA was evaluated in 142 H. pylori strains isolated from 142 patients with gastrointestinal diseases. Of these patients, 104 received primary eradication therapy for 1 week. The risk factors for eradication failure were determined using univariate and multivariate analyses. Results Among 142 strains, 44 (31.0%) were dupA-positive. There was no association between dupA status and gastroduodenal diseases (P > 0.05). The clarithromycin (CLR) resistance rate was generally lower in the dupA-positive than in the dupA-negative group (20.4 vs. 35.7%, P = 0.06). However, dupA prevalence was higher in the eradication failure group than in the success group (36.3 vs. 21.9%). Among the CLR-resistant H. pylori infected group, the successful eradication rate was significantly lower in patients infected with dupA-positive H. pylori than -negative H. pylori (P = 0.04). In multivariate analysis adjusted for age, gender, and type of disease, not only CLR resistance but also dupA presence was independent risk factors for eradication failure (adjusted odds ratio = 3.71, 95% confidence interval = 1.07–12.83). Conclusions Although CLR resistant was more reliable predictor, the presence of dupA may also be an independent risk factor for eradication failure. PMID:22298090

Unexpected individual clinical site variation in eradication rates of group a streptococci by penicillin in multisite clinical trials.

PubMed

Kaplan, Edward L; Oakes, J Michael; Johnson, Dwight R

2007-12-01

Previously, we reported an unexpectedly large percentage of failures by penicillin to eradicate group A streptococci (GAS) from the upper respiratory tract. Because penicillin has been the recommended therapy for the treatment of GAS pharyngitis, our report prompted controversy. Data from clinical trials in which our laboratory has participated demonstrated marked variation in GAS eradication rates among clinical sites. The reasons for such variation have never been adequately examined. We performed statistical analyses of site variation in eradication rates to assess the potential effect on reported reduced penicillin efficacy. Penicillin GAS eradication rates were compared using data from 4 large multisite pharyngitis treatment trials (75 clinical sites; 1158 subjects). Variation in eradication rates among clinical sites was statistically evaluated [chi(2) tests and generalized estimating equation (GEE) regression models]. There was significant site-to-site variation in GAS eradication rates in each of the trials (range, 17-100%; P < 0.005) as well as between separate trials (mean range, 58-69%; P < 0.033). GEE modeling indicated that GAS eradication rates were significantly higher for clinical sites participating in more than one clinical trial. The statistically significant site-to-site variation in penicillin eradication rates was related to factors (dependencies) at individual sites. Such factors may affect assessment of therapeutic efficacy and indicate a necessity for considering clinical site variation before reporting pooled efficacy data from multiple sites; combined data may result in misleading clinical implications. This is the first report documenting significant variation resulting from individual clinical site-related factors and offers a possible explanation for reduced penicillin eradication.

Disease eradication as a public health strategy: a case study of poliomyelitis eradication.

PubMed Central

Aylward, R. B.; Hull, H. F.; Cochi, S. L.; Sutter, R. W.; Olivé, J. M.; Melgaard, B.

2000-01-01

Disease eradication as a public health strategy was discussed at international meetings in 1997 and 1998. In this article, the ongoing poliomyelitis eradication initiative is examined using the criteria for evaluating candidate diseases for eradication proposed at these meetings, which covered costs and benefits, biological determinants of eradicability (technical feasibility) and societal and political considerations (operational feasibility). The benefits of poliomyelitis eradication are shown to include a substantial investment in health services delivery, the elimination of a major cause of disability, and far-reaching intangible effects, such as establishment of a "culture of prevention". The costs are found to be financial and finite, despite some disturbances to the delivery of other health services. The "technical" feasibility of poliomyelitis eradication is seen in the absence of a non-human reservoir and the presence of both an effective intervention and delivery strategy (oral poliovirus vaccine and national immunization days) and a sensitive and specific diagnostic tool (viral culture of specimens from acute flaccid paralysis cases). The certification of poliomyelitis eradication in the Americas in 1994 and interruption of endemic transmission in the Western Pacific since March 1997 confirm the operational feasibility of this goal. When the humanitarian, economic and consequent benefits of this initiative are measured against the costs, a strong argument is made for eradication as a valuable disease control strategy. PMID:10812724

An unusual case of posttrabeculectomy conjunctival granuloma.

PubMed

Choudhary, Samiksha; Sen, Swarnali; Gupta, Omprakash

2018-01-01

We report an unusual case of granulomatous inflammation that presented adjacent to bleb 3 weeks postoperatively after combined phacoemulsification and trabeculectomy surgery with mitomycin-C due to retained microfragments of methyl cellulose sponge. The commonly used antimetabolite delivery devices are made of cellulose. Methyl cellulose sponges are friable, and they are likely to leave behind microfragments in subconjunctival space. In our case, bleb integrity was maintained, unlike the earlier reported cases which presented with bleb leak. Hence, one should have high index of suspicion in unusual cases of postoperative inflammation not resolving conservatively. Although rare, retained sponge particles can be a cause of early bleb-related inflammation which can lead to bleb failure.

An unusual case of posttrabeculectomy conjunctival granuloma

PubMed Central

Choudhary, Samiksha; Sen, Swarnali; Gupta, Omprakash

2018-01-01

We report an unusual case of granulomatous inflammation that presented adjacent to bleb 3 weeks postoperatively after combined phacoemulsification and trabeculectomy surgery with mitomycin-C due to retained microfragments of methyl cellulose sponge. The commonly used antimetabolite delivery devices are made of cellulose. Methyl cellulose sponges are friable, and they are likely to leave behind microfragments in subconjunctival space. In our case, bleb integrity was maintained, unlike the earlier reported cases which presented with bleb leak. Hence, one should have high index of suspicion in unusual cases of postoperative inflammation not resolving conservatively. Although rare, retained sponge particles can be a cause of early bleb-related inflammation which can lead to bleb failure. PMID:29563697

Electronic phase separation at the LaAlO₃/SrTiO₃ interface.

PubMed

Ariando; Wang, X; Baskaran, G; Liu, Z Q; Huijben, J; Yi, J B; Annadi, A; Barman, A Roy; Rusydi, A; Dhar, S; Feng, Y P; Ding, J; Hilgenkamp, H; Venkatesan, T

2011-02-08

There are many electronic and magnetic properties exhibited by complex oxides. Electronic phase separation (EPS) is one of those, the presence of which can be linked to exotic behaviours, such as colossal magnetoresistance, metal-insulator transition and high-temperature superconductivity. A variety of new and unusual electronic phases at the interfaces between complex oxides, in particular between two non-magnetic insulators LaAlO(3) and SrTiO(3), have stimulated the oxide community. However, no EPS has been observed in this system despite a theoretical prediction. Here, we report an EPS state at the LaAlO(3)/SrTiO(3) interface, where the interface charges are separated into regions of a quasi-two-dimensional electron gas, a ferromagnetic phase, which persists above room temperature, and a (superconductor like) diamagnetic/paramagnetic phase below 60 K. The EPS is due to the selective occupancy (in the form of 2D-nanoscopic metallic droplets) of interface sub-bands of the nearly degenerate Ti orbital in the SrTiO(3). The observation of this EPS demonstrates the electronic and magnetic phenomena that can emerge at the interface between complex oxides mediated by the Ti orbital.

Mathematical Modeling of Programmatic Requirements for Yaws Eradication

PubMed Central

Mitjà, Oriol; Fitzpatrick, Christopher; Asiedu, Kingsley; Solomon, Anthony W.; Mabey, David C.W.; Funk, Sebastian

2017-01-01

Yaws is targeted for eradication by 2020. The mainstay of the eradication strategy is mass treatment followed by case finding. Modeling has been used to inform programmatic requirements for other neglected tropical diseases and could provide insights into yaws eradication. We developed a model of yaws transmission varying the coverage and number of rounds of treatment. The estimated number of cases arising from an index case (basic reproduction number [R0]) ranged from 1.08 to 3.32. To have 80% probability of achieving eradication, 8 rounds of treatment with 80% coverage were required at low estimates of R0 (1.45). This requirement increased to 95% at high estimates of R0 (2.47). Extending the treatment interval to 12 months increased requirements at all estimates of R0. At high estimates of R0 with 12 monthly rounds of treatment, no combination of variables achieved eradication. Models should be used to guide the scale-up of yaws eradication. PMID:27983500

USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase.

PubMed

Harada, Kumi; Kato, Masako; Nakamura, Nobuhiro

2016-11-02

In the endoplasmic reticulum (ER), misfolded and unfolded proteins are eliminated by a process called ER-associated protein degradation (ERAD) in order to maintain cell homeostasis. In the ERAD pathway, several ER-localized E3 ubiquitin ligases target ERAD substrate proteins for ubiquitination and subsequent proteasomal degradation. However, little is known about how the functions of the ERAD ubiquitin ligases are regulated. Recently, USP19, an ER-anchored deubiquitinating enzyme (DUB), has been suggested to be involved in the regulation of ERAD. In this study, HRD1, an ERAD ubiquitin ligase, is shown to be a novel substrate for USP19. We demonstrate that USP19 rescues HRD1 from proteasomal degradation by deubiquitination of K48-linked ubiquitin chains. In addition, the altered expression of USP19 affects the steady-state levels of HRD1. These results suggest that USP19 regulates the stability of HRD1 and provide insight into the regulatory mechanism of the ERAD ubiquitin ligases.

Descriptive Epidemiology of Bovine Tuberculosis in Michigan (1975–2010): Lessons Learned

PubMed Central

Okafor, Chika C.; Grooms, Daniel L.; Bruning-Fann, Colleen S.; Averill, James J.; Kaneene, John B.

2011-01-01

Despite ongoing eradication efforts, bovine tuberculosis (BTB) remains a challenge in Michigan livestock and wildlife. The objectives of this study were to (1) review the epidemiology of BTB in Michigan cattle, privately owned cervids, and wildlife between 1975 and 2010 and (2) identify important lessons learned from the review and eradication strategies. BTB information was accessed from the Michigan BTB Eradication Project agencies. Cattle herds (49), privately owned deer herds (4), and wild white-tailed deer (668) were found infected with BTB during the review period. BTB has occurred primarily in counties located at the northern portion of the state's Lower Peninsula. Currently used BTB eradication strategies have successfully controlled BTB spread. However additional changes in BTB surveillance, prevention, and eradication strategies could improve eradication efforts. PMID:21776355

Eradication: lessons from the past.

PubMed Central

Henderson, D. A.

1998-01-01

The declaration in 1980 that smallpox had been eradicated reawakened interest in disease eradication as a public health strategy. The smallpox programme's success derived, in part, from lessons learned from the preceding costly failure of the malaria eradication campaign. In turn, the smallpox programme offered important lessons with respect to other prospective disease control programmes, and these have been effectively applied in the two current global eradication initiatives, those against poliomyelitis and dracunculiasis. Taking this theme a step further, there are those who would now focus on the development of an inventory of diseases which might, one by one, be targeted either for eradication or elimination. This approach, while interesting, fails to recognize many of the important lessons learned and their broad implications for contemporary disease control programmes worldwide. PMID:10063668

A modelling framework for predicting the optimal balance between control and surveillance effort in the local eradication of tuberculosis in New Zealand wildlife.

PubMed

Gormley, Andrew M; Holland, E Penelope; Barron, Mandy C; Anderson, Dean P; Nugent, Graham

2016-03-01

Bovine tuberculosis (TB) impacts livestock farming in New Zealand, where the introduced marsupial brushtail possum (Trichosurus vulpecula) is the wildlife maintenance host for Mycobacterium bovis. New Zealand has implemented a campaign to control TB using a co-ordinated programme of livestock diagnostic testing and large-scale culling of possums, with the long-term aim of TB eradication. For management of the disease in wildlife, methods that can optimise the balance between control and surveillance effort will facilitate the objective of eradication on a fixed or limited budget. We modelled and compared management options to optimise the balance between the two activities necessary to achieve and verify eradication of TB from New Zealand wildlife: the number of lethal population control operations required to halt the M. bovis infection cycle in possums, and the subsequent surveillance effort needed to confidently declare TB freedom post-control. The approach considered the costs of control and surveillance, as well as the potential costs of re-control resulting from false declaration of TB freedom. The required years of surveillance decreased with increasing numbers of possum lethal control operations but the overall time to declare TB freedom depended on additional factors, such as the probability of freedom from disease after control and the probability of success of mop-up control, i.e. retroactive culling following detection of persistent disease in the residual possum population. The total expected cost was also dependent on a number of factors, many of which had wide cost ranges, suggesting that an optimal strategy is unlikely to be singular and fixed, but will likely vary for each different area being considered. Our approach provides a simple framework that considers the known and potential costs of possum control and TB surveillance, enabling managers to optimise the balance between these two activities to achieve and prove eradication of a wildlife disease, or the pest species that transmits it, in the most expedient and economic way. This cost- and risk-evaluation approach may be applicable to other wildlife disease problems where limited management funds exist. Copyright © 2016 Elsevier B.V. All rights reserved.

San Francisco Bay, California as seen from STS-59

NASA Image and Video Library

1994-04-14

STS059-213-009 (9-20 April 1994) --- San Francisco Bay. Orient with the sea up. The delta of the combined Sacramento and San Joaquin Rivers occupies the foreground, San Francisco Bay the middle distance, and the Pacific Ocean the rest. Variations in water color caused both by sediment load and by wind streaking strike the eye. Man-made features dominate this scene. The Lafayette/Concord complex is left of the bay head, Vallejo is to the right, the Berkeley/Oakland complex rims the shoreline of the main bay, and San Francisco fills the peninsula beyond. Salt-evaporation ponds contain differently-colored algae depending on salinity. The low altitude (less than 120 nautical miles) and unusually-clear air combine to provide unusually-strong green colors in this Spring scene. Hasselblad camera.

Planned complex suicide: an unusual case.

PubMed

Pélissier-Alicot, Anne-Laure; Gavaudan, Gilles; Bartoli, Christophe; Kintz, Pascal; Piercecchi-Marti, Marie-Dominique; Desfeux, Jacques; Leonetti, Georges

2008-07-01

We report an unusual case of planned complex suicide. The victim was a woman aged 67 years, who was found dead in her bath in a state of advanced putrefaction. A plugged-in hairdryer was submerged in the water and the electrical fuses in the room had short-circuited. A kitchen knife lay below the body of the victim, whose left forearm bore incisions suggestive of wrist-cutting. At autopsy, no sign suggesting electrocution could be observed because of the advanced state of putrefaction of the body. Toxicological analysis revealed massive ingestion of tianeptine (blood concentration 15.5 mg/L). Although the exact cause of death could not be determined because of the state of the corpse, meticulous examination of the scene and information obtained from the victim's relatives led to the conclusion of suicide.

San Francisco Bay, California as seen from STS-59

NASA Technical Reports Server (NTRS)

1994-01-01

San Francisco Bay as seen from STS-59. View is oriented with the sea up. The delta of the combined Sacramento and San Joaquin Rivers occupies the foreground with San Francisco Bay in the middle distance, then the Pacific Ocean. Variations in water color caused both by sediment load and by wind streaking strike the eye. Man-made features dominate this scene. The Lafayette/Concord complex is left of the bay head, Vallejo is to the right, the Berkeley/Oakland complex rims the shoreline of the main bay, and San Francisco fills the peninsula beyond. Salt-evaporation ponds contain differently-colored algae depending on salinity. The low altitude (less than 120 nautical miles) and unusually-clear air combine to provide unusually-strong green colors in this Spring scene.

Unusual Sleep Experiences, Dissociation, and Schizotypy: Evidence for a Common Domain

PubMed Central

Koffel, Erin; Watson, David

2009-01-01

This paper reviews studies that have examined associations between unusual sleep experiences (including nightmares, vivid dreaming, narcolepsy symptoms, and complex nighttime behaviors) and dissociation and schizotypy. Using correlational studies and structural analyses, evidence is provided that unusual sleep experiences, dissociation, and schizotypy belong to a common domain. It is demonstrated that unusual sleep experiences show specificity to dissociation and schizotypy compared to other daytime symptoms (e.g., anxiety, depression, substance use) and other sleep disturbances (e.g., insomnia, lassitude/fatigue). The paper also outlines the methodological limitations of the existing evidence and makes suggestions for future research. Finally, three models for the overlap of daytime and nighttime symptoms are reviewed, including biological abnormalities, trauma, and personality traits. Although further research is needed, it is suggested that daytime and nighttime symptoms result from problems with sleep-wake state boundaries, which may be precipitated by stress or trauma. In addition, association between daytime and nighttime symptoms can be attributed to the higher order personality trait of Oddity. PMID:19581031

How absolute is zero? An evaluation of historical and current definitions of malaria elimination.

PubMed

Cohen, Justin M; Moonen, Bruno; Snow, Robert W; Smith, David L

2010-07-22

Decisions to eliminate malaria from all or part of a country involve a complex set of factors, and this complexity is compounded by ambiguity surrounding some of the key terminology, most notably "control" and "elimination." It is impossible to forecast resource and operational requirements accurately if endpoints have not been defined clearly, yet even during the Global Malaria Eradication Program, debate raged over the precise definition of "eradication." Analogous deliberations regarding the meaning of "elimination" and "control" are basically nonexistent today despite these terms' core importance to programme planning. To advance the contemporary debate about these issues, this paper presents a historical review of commonly used terms, including control, elimination, and eradication, to help contextualize current understanding of these concepts. The review has been supported by analysis of the underlying mathematical concepts on which these definitions are based through simple branching process models that describe the proliferation of malaria cases following importation. Through this analysis, the importance of pragmatic definitions that are useful for providing malaria control and elimination programmes with a practical set of strategic milestones is emphasized, and it is argued that current conceptions of elimination in particular fail to achieve these requirements. To provide all countries with precise targets, new conceptual definitions are suggested to more precisely describe the old goals of "control" - here more exactly named "controlled low-endemic malaria" - and "elimination." Additionally, it is argued that a third state, called "controlled non-endemic malaria," is required to describe the epidemiological condition in which endemic transmission has been interrupted, but malaria resulting from onwards transmission from imported infections continues to occur at a sufficiently high level that elimination has not been achieved. Finally, guidelines are discussed for deriving the separate operational definitions and metrics that will be required to make these concepts relevant, measurable, and achievable for a particular environment.

Unusual genome complexity in Lactobacillus salivarius JCM1046.

PubMed

Raftis, Emma J; Forde, Brian M; Claesson, Marcus J; O'Toole, Paul W

2014-09-08

Lactobacillus salivarius strains are increasingly being exploited for their probiotic properties in humans and animals. Dissemination of antibiotic resistance genes among species with food or probiotic-association is undesirable and is often mediated by plasmids or integrative and conjugative elements. L. salivarius strains typically have multireplicon genomes including circular megaplasmids that encode strain-specific traits for intestinal survival and probiotic activity. Linear plasmids are less common in lactobacilli and show a very limited distribution in L. salivarius. Here we present experimental evidence that supports an unusually complex multireplicon genome structure in the porcine isolate L. salivarius JCM1046. JCM1046 harbours a 1.83 Mb chromosome, and four plasmids which constitute 20% of the genome. In addition to the known 219 kb repA-type megaplasmid pMP1046A, we identified and experimentally validated the topology of three additional replicons, the circular pMP1046B (129 kb), a linear plasmid pLMP1046 (101 kb) and pCTN1046 (33 kb) harbouring a conjugative transposon. pMP1046B harbours both plasmid-associated replication genes and paralogues of chromosomally encoded housekeeping and information-processing related genes, thus qualifying it as a putative chromid. pLMP1046 shares limited sequence homology or gene synteny with other L. salivarius plasmids, and its putative replication-associated protein is homologous to the RepA/E proteins found in the large circular megaplasmids of L. salivarius. Plasmid pCTN1046 harbours a single copy of an integrated conjugative transposon (Tn6224) which appears to be functionally intact and includes the tetracycline resistance gene tetM. Experimental validation of sequence assemblies and plasmid topology resolved the complex genome architecture of L. salivarius JCM1046. A high-coverage draft genome sequence would not have elucidated the genome complexity in this strain. Given the expanding use of L. salivarius as a probiotic, it is important to determine the genotypic and phenotypic organization of L. salivarius strains. The identification of Tn6224-like elements in this species has implications for strain selection for probiotic applications.

Utility of Lithium in Rare-Earth Metal Reduction Reactions to Form Nontraditional Ln2+ Complexes and Unusual [Li(2.2.2-cryptand)]1+ Cations.

PubMed

Huh, Daniel N; Darago, Lucy E; Ziller, Joseph W; Evans, William J

2018-02-19

The utility of lithium compared to other alkali metals in generating Ln 2+ rare-earth metal complexes via reduction of Ln 3+ precursors in reactions abbreviated as LnA 3 /M (Ln = rare-earth metal; A = anionic ligand; M = alkali metal) is described. Lithium reduction of Cp' 3 Ln (Cp' = C 5 H 4 SiMe 3 ; Ln = Y, Tb, Dy, Ho) under Ar in the presence of 2.2.2-cryptand (crypt) forms new examples of crystallographically characterizable Ln 2+ complexes of these metals, [Li(crypt)][Cp' 3 Ln]. In each complex, lithium is found in an N 2 O 4 donor atom coordination geometry that is unusual for the cryptand ligand. Magnetic susceptibility data on these new examples of nontraditional divalent lanthanide complexes are consistent with 4f n 5d 1 electronic configurations. The Dy and Ho complexes have exceptionally high single-ion magnetic moments, 11.35 and 11.67 μ B , respectively. Lithium reduction of Cp' 3 Y under N 2 at -35 °C forms the Y 2+ complex (Cp' 3 Y) 1- , which reduces dinitrogen upon warming to room temperature to generate the (N 2 ) 2- complex [Cp' 2 Y(THF)] 2 (μ-η 2 :η 2 -N 2 ). These results provide insight on the factors that lead to reduced dinitrogen complexes and/or stable divalent lanthanide complexes as a function of the specific reducing agent and conditions.

Localized blastomycosis-like pyoderma with good response to cotrimoxazol and cryotherapy.

PubMed

Su, Ozlem; Demirkesen, Cuyan; Onsun, Nahide

2004-05-01

Blastomycosis-like pyoderma is an unusual, exaggerated, vegetative-tissue reaction to a prolonged primary or secondary bacterial infection. It is a rare disease, usually seen in immunocompromized patients. We report a case of localized blastomycosis-like pyoderma responding poorly to classic treatments, but that gave a dramatic response to a combination treatment of cotrimoxazol and cryotherapy.

Boll weevil eradication: a model for sea lamprey control?

USGS Publications Warehouse

Smith, James W.; Swink, William D.

2003-01-01

Invasions of boll weevil (Anthonomus grandis) into the United States and sea lamprey (Petromyzon marinus) into the Great Lakes were similar in many ways. Important species (American cotton, Gossypium hirsutum, and lake trout, Salvelinus namaycush) and the industries they supported were negatively affected. Initial control efforts were unsuccessful until pesticides and application technologies were developed. For boll weevils, controls relying on pesticides evolved into an integrated program that included recommended farming practices and poisoned baits. However, the discovery of a boll weevil sex pheromone in 1964 allowed adoption of an ongoing program of eradication. Despite opposition over concept and cost, insecticides, pheromone traps, poisoned baits, and approved farming practices were used to eradicate boll weevils from Virginia, North Carolina, South Carolina, Georgia, Florida, and Alabama by 1999. Using the working back approach along the path of the original invasion, eradication was nearly completed by 2002 in Mississippi and eradication programs were underway in Arkansas, Tennessee, Oklahoma, Louisiana, and parts of Texas. Insecticide use for cotton production decreased 50 to 90%, and cotton yields and farm income increased an average of 78 kg/ha and $190 U.S./ha in areas where boll weevils were eradicated. For sea lampreys, integrated management uses lampricides, barriers to migration, trapping, and release of sterilized males. Although sea lamprey eradication is not currently feasible, recent research on larval and sex pheromones might provide the tools to make it possible. A successful eradication program for sea lampreys starting in Lake Superior and expanding to the lower Great Lakes would ultimately provide huge ecological and economic benefits by eliminating lampricide applications, removing barriers that block teleost fishes, and facilitating the recovery of lake trout. Should the opportunity arise, the concept of sea lamprey eradication should not be rejected out of hand. The successful boll weevil eradication program shows that sea lamprey eradication might be achievable.

Comparison of vonoprazan and proton pump inhibitors for eradication of Helicobacter pylori.

PubMed

Shinozaki, Satoshi; Nomoto, Hiroaki; Kondo, Yoshie; Sakamoto, Hirotsugu; Hayashi, Yoshikazu; Yamamoto, Hironori; Lefor, Alan Kawarai; Osawa, Hiroyuki

2016-05-01

Alternative eradication therapies for Helicobacter pylori infection are needed because of an increasing failure rate over the past decade. The aim of this study was to determine if vonoprazan, a new potassium-competitive acid blocker, showed superiority to existing proton pump inhibitors for primary eradication of H. pylori in routine clinical practice. Data for 573 patients who underwent primary H. pylori eradication therapy were retrospectively reviewed. Regimens included clarithromycin 200 mg, amoxicillin 750 mg, and an acid-suppressing drug [lansoprazole 30 mg (LAC), rabeprazole 10 mg (RAC), esomeprazole 20 mg (EAC), or vonoprazan 20 mg (VAC)] twice daily for 1 week. Eradication was successful in 73% (419/573) of patients using intention-to-treat (ITT) analysis and 76% (419/549) of patients in per-protocol (PP) analysis. The VAC group had a significantly superior eradication rate compared with the LAC and RAC groups in ITT (VAC 83%, LAC 66% and RAC 67%, p < 0.01) and PP analysis (VAC 85%, LAC 69% and RAC 70%, p < 0.01), and had a similarly high eradication rate to the EAC group (83% in ITT and 87% in PP). Although the eradication rate in the VAC and EAC groups was not significantly higher than in the LAC and RAC groups in patients with mild gastric atrophy with both ITT and PP analyses, it was significantly higher in patients with severe gastric atrophy (p < 0.01). The VAC group had a significantly higher H. pylori eradication rate than the LAC and RAC groups, and a > 80% eradication rate regardless of the degree of atrophy. Copyright © 2016. Published by Elsevier Taiwan.

Primary cumulus platinum minerals in the Monts de Cristal Complex, Gabon: magmatic microenvironments inferred from high-definition X-ray fluorescence microscopy

NASA Astrophysics Data System (ADS)

Barnes, Stephen J.; Fisher, Louise A.; Godel, Bélinda; Pearce, Mark A.; Maier, Wolfgang D.; Paterson, David; Howard, Daryl L.; Ryan, Christopher G.; Laird, Jamie S.

2016-03-01

An unusual occurrence of Pt-enriched pyroxenites in the Monts de Cristal igneous complex is characterized by unusually high ratios of Pt to other platinum-group elements (PGEs) and very low Cu and sulfide contents. Synchrotron X-ray fluorescence microscopy was used to identify over a hundred discrete grains of platinum minerals and relate their occurrence to textural associations in the host heteradcumulate orthopyroxenites. Element associations, backed up by FIB-SEM and PIXE probe observations, indicate that most of the Pt is associated with either As- or trace Cu-Ni-rich sulfides, or both. Some of the Pt-As grains can be identified as sperrylite, and most are likely to be Pt-Fe alloy. The relative abundances and volumes of Pt minerals to sulfide minerals are very large compared with typical magmatic sulfides. Almost all of the grains observed lie at or within a few tens of μm of cumulus orthopyroxene grain boundaries, and there is no significant difference between the populations of grains located inside or outside plagioclase oikocrysts. These oikocrysts are inferred to have crystallized either at the cumulus stage or very shortly thereafter, on the basis of their relationship to Ti enrichment in the margins of pyroxene grains not enclosed in oikocrysts. This relationship precludes a significant role of trapped intercumulus liquid in Pt deposition or mobilization and also allows a confident inference that Pt-rich and Pt-As-enriched phases precipitated directly from the magma at the cumulus stage. These observations lead to the conclusion that fractionation of Pt from other PGEs in this magmatic system is a consequence of a solubility limit for solid Pt metal and/or Pt arsenide.

Second-line bismuth-containing quadruple therapy for Helicobacter pylori eradication and impact of diabetes

PubMed Central

Kim, Sung Eun; Park, Moo In; Park, Seun Ja; Moon, Won; Kim, Jae Hyun; Jung, Kyoungwon; Kim, Hae Koo; Lee, Young Dal

2017-01-01

AIM To investigate Helicobacter pylori (H. pylori) eradication rates using second-line bismuth-containing quadruple therapy and to identify predictors of eradication failure. METHODS This study included 636 patients who failed first-line triple therapy and received 7 d of bismuth-containing quadruple therapy between January 2005 and December 2015. We retrospectively demonstrated H. pylori eradication rates with respect to the year of therapy as well as demographic and clinical factors. H. pylori eradication was confirmed by a 13C-urea breath test or a rapid urease test at least 4 wk after the completion of bismuth-based quadruple therapy: proton pump inhibitor, metronidazole, bismuth, and tetracycline. RESULTS The overall eradication rates by intention-to-treat analysis and per-protocol analysis were 73.9% (95%CI: 70.1%-77.4%) and 94.5% (95%CI: 92.4%-96.5%), respectively. Annual eradication rates from 2005 to 2015 were 100.0%, 92.9%, 100.0%, 100.0%, 100.0%, 97.4%, 100.0%, 93.8%, 84.4%, 98.9%, and 92.5%, respectively, by per-protocol analysis. A multivariate analysis showed that diabetes mellitus (OR = 3.99, 95%CI: 1.56-10.20, P = 0.004) was associated with H. pylori eradication therapy failure. CONCLUSION The second-line bismuth-containing quadruple therapy for H. pylori infection is still effective in Korea, and diabetes mellitus is suggested to be a risk factor for eradication failure. PMID:28246480

Helicobacter pylori Eradication Prevents Progression of Gastric Cancer in Hypergastrinemic INS-GAS Mice

PubMed Central

Lee, Chung-Wei; Rickman, Barry; Rogers, Arlin B.; Ge, Zhongming; Wang, Timothy C.; Fox, James G.

2009-01-01

Helicobacter pylori infection results in chronic gastritis, which may progress to gastric cancer. In this study, we investigated the efficacy of H. pylori eradication in preventing the progression of gastritis to gastric cancer in H. pylori–infected transgenic INS-GAS mice. H. pylori infection induced severe dysplasia and gastric cancer classified as high-grade and low-grade gastrointestinal intraepithelial neoplasia (GIN) in INS-GAS mice at 28 weeks postinfection (WPI). H. pylori eradication therapy using omeprazole, metronidazole, and clarithromycin was administered p.o. at 8, 12, or 22 WPI. Compared with untreated infected mice, H. pylori eradication at 8, 12, and 22 WPI significantly reduced the severity of dysplasia (P < 0.01). Moreover, H. pylori eradication at 8 WPI completely prevented the development of GIN (P < 0.001). Although not as effective as early antimicrobial treatment, prevention of progression to high-grade GIN was achieved by H. pylori eradication at 12 and 22 WPI (P < 0.05). Consistent with reduced gastric pathology, H. pylori eradication at all time points significantly down-regulated gastric Interferon-γ, tumor necrosis factor-α, inducible nitric oxide synthase, and Reg 1 mRNA levels (P < 0.05) and reduced epithelial proliferation in the corpus (P < 0.01) compared with untreated infected mice. We concluded that H. pylori eradication prevented gastric cancer to the greatest extent when antibiotics are given at an early point of infection, but that eradication therapy given at a later time point delayed the development of severe dysplastic lesions. PMID:18441088

Modern Endodontic Principles Part 4: Irrigation.

PubMed

Darcey, James; Jawad, Sarra; Taylor, Carly; Roudsari, Reza Vahid; Hunter, Mark

2016-01-01

The complex anatomy of the tooth limits the ability to eradicate pathogens by mechanical means alone. Irrigation is the key to solving this problem. This paper highlights the importance of irrigation, the key irrigants available and methods of improving the performance of irrigants within the canal. CPD/CLINICAL RELEVANCE: To provide advice on which irrigants to use, how to use them effectively and safely and what to do if irrigants are extruded beyond the apex.

Workforce Effects and the Evolution of Complex Sociality in Wild Damaraland Mole Rats.

PubMed

Young, Andrew J; Jarvis, Jennifer U M; Barnaville, James; Bennett, Nigel C

2015-08-01

Explaining the evolution of eusocial and cooperatively breeding societies demands that we understand the effects of workforce size on the reproductive success of breeders. This challenge has yet to be addressed in the family that arguably exhibits the most extreme outcomes of vertebrate social evolution, the African mole rats (Bathyergidae), leaving the ultimate causes of their many unusual adaptations open to debate. Here we report-using a 14-year field study of wild Damaraland mole rats, Fukomys damarensis-that workers appear to have strong but unusual effects on offspring. Groups with larger workforces exhibited substantially higher rates of offspring recruitment while maintaining high juvenile survival rates, relationships that may have favored the evolution of the delayed dispersal, cooperation, morphological specialization, and unusual patterns of longevity that characterize such societies. Offspring reared by larger workforces also showed slower growth, however. That reduced offspring growth in larger groups has also been documented under ad lib. food conditions in the laboratory raises the possibility that this reflects socially induced growth restraint rather than simple constraints on resource availability. Our findings shed new light on the evolution of complex sociality in this enigmatic clade and highlight further departures from the norms reported for other cooperative vertebrates.

Optical Emission Associated with the Galactic Supernova Remnant G179.0+2.6

NASA Astrophysics Data System (ADS)

How, Thomas G.; Fesen, Robert A.; Neustadt, Jack M. M.; Black, Christine S.; Outters, Nicolas

2018-04-01

Narrow passband optical images of the large Galactic supernova remnant G179.0+2.6 reveal a faint but nearly complete emission shell dominated by strong [O 3] 4959,5007 Å line emission. The remnant's optical emission, which consists of both diffuse and filamentary features, is brightest along its southern and northeastern limbs. Deep Hα images detect little coincidence emission indicating an unusually high [O 3]/Hα emission ratio for such a large and apparently old remnant. Low-dispersion optical spectra of several regions confirm large [O 3]/Hα line ratios with typical values around 10. The dominance of [O 3] emission for the majority of the remnant's optical filaments suggests shock velocities above 100 km s-1 are present throughout most of the remnant, likely reflecting a relatively low density ambient ISM. The remnant's unusually strong [O 3] emission adds to the remnant's interesting set of properties which include a thick radio emission shell, radial polarization of its radio emission like that typically seen in young supernova remnants, and an unusually slow-rotating gamma-ray pulsar with a characteristic spin-down age ≃ 50 kyr.

Measles and rubella elimination: learning from polio eradication and moving forward with a diagonal approach.

PubMed

Goodson, James L; Alexander, James P; Linkins, Robert W; Orenstein, Walter A

2017-12-01

In 1988, an estimated 350,000 children were paralyzed by polio and 125 countries reported polio cases, the World Health Assembly passed a resolution to achieve polio eradication by 2000, and the Global Polio Eradication Initiative (GPEI) was established as a partnership focused on eradication. Today, following eradication efforts, polio cases have decreased >99% and eradication of all three types of wild polioviruses is approaching. However, since polio resources substantially support disease surveillance and other health programs, losing polio assets could reverse progress toward achieving Global Vaccine Action Plan goals. Areas covered: As the end of polio approaches and GPEI funds and capacity decrease, we document knowledge, experience, and lessons learned from 30 years of polio eradication. Expert commentary: Transitioning polio assets to measles and rubella (MR) elimination efforts would accelerate progress toward global vaccination coverage and equity. MR elimination feasibility and benefits have long been established. Focusing efforts on MR elimination after achieving polio eradication would make a permanent impact on reducing child mortality but should be done through a 'diagonal approach' of using measles disease transmission to identify areas possibly susceptible to other vaccine-preventable diseases and to strengthen the overall immunization and health systems to achieve disease-specific goals.

The Barberry Eradication Program in Minnesota for Stem Rust Control: A Case Study.

PubMed

Peterson, Paul D

2018-06-11

The Barberry Eradication Program was an unprecedented federal and state cooperative plant disease control campaign between 1918 and the late 1970s to remove common barberry (Berberis vulgaris), the alternate host of Puccinia graminis f. sp. tritici, from the major centers of wheat production in the United States. Eradication of barberry has been credited with helping to reduce stem rust of wheat to a minor problem in the United States by the end of the campaign. The Barberry Eradication Program has also been viewed as a model for successful eradication based on its robust leadership, effective publicity and public cooperation, forceful quarantine laws, and adaptive eradication methods and procedures employed in its field operations. The Barberry Eradication Program was particularly successful because of its leaders' ability to adapt to changing internal and external conditions over time. The program lasted nearly a century, extending through two world wars and the Great Depression, with each period producing unique challenges. Because of its central role, barberry eradication in Minnesota offers an excellent case study to examine how the program developed over time and ultimately achieved success. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Clinical Outcome of Eradication Therapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma according to H. pylori Infection Status

PubMed Central

Kim, Ju Seok; Kang, Sun Hyung; Moon, Hee Seok; Jeong, Hyun Yong

2016-01-01

Background. To evaluate the long-term outcome of H. pylori eradication therapy for gastric MALT lymphoma according to the presence of H. pylori infection. Methods. We retrospectively reviewed the medical records of patients between January 2001 and June 2014. The clinicopathologic characteristics and clinical outcomes were compared between H. pylori-positive and H. pylori-negative gastric MALT lymphoma groups. Results. Fifty-four patients were enrolled: 12 H. pylori-negative and 42 H. pylori-positive patients. The tumor was located more frequently in both the proximal and distal parts of the stomach (P = 0.001), and the percentage of multiple lesions was significantly greater in the H. pylori-negative group (P = 0.046). Forty-seven patients received initial eradication therapy, and 85% (35/41) of H. pylori-positive patients and 50% (3/6) of H. pylori-negative patients achieved complete remission after eradication therapy. The presence of multiple lesions was a predictive factor for unresponsiveness to H. pylori eradication (P = 0.024). The efficacy of eradication therapy (P = 0.133), complete remission (CR) maintenance period, and relapse after eradication therapy were not significantly different between the two groups. Conclusions. H. pylori eradication therapy could be an effective first-line treatment for localized H. pylori-negative gastric MALT lymphoma, especially for single lesions. PMID:27034656

[Comparison of Helicobacter pylori eradication rate in patients with non-ulcer dyspepsia and peptic ulcer diseases according to proton pump inhibitors].

PubMed

Hong, Eun Jung; Park, Dong Il; Oh, Suk Joong; Song, Min Jun; Choi, Woo Hyuk; Hong, Cheul Ho; Park, Jung Ho; Kim, Hong Joo; Cho, Yong Kyun; Shon, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik

2008-08-01

Conflicting results have been reported whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H. pylori) eradication treatment compared with patients with peptic ulcer diseases (PUD). The aim of this study was to evaluate any difference in H. pylori eradication rates between patients with NUD and PUD according to each proton pump inhibitor (PPI). From September, 2004 to April, 2007, we retrospectively reviewed 2,297 patients with NUD (1,050 patients) or PUD (1,247 patients) infected with H. pylori. All patients received a standard 1 week triple therapy comprising of one of the five PPIs (pantoprazole, esomeprazole, omeprazole, lansoprazole, rabeprazole), clarithromycin and amoxicillin. The follow-up H. pylori test was performed 4 weeks after the completion of therapy. There was no significant difference in the eradication rates between the two groups. In comparison of eradication rates according to PPI, omeprazole- based triple therapy group showed higher eradication rate than other groups in patients with NUD, but not in patients with PUD. This study failed to show any difference in H. pylori eradication rate between patients with NUD and PUD. There is no convincing evidence that the eradication rate may be affected by different PPI.

Characterization of WDR20: A new regulator of the ERAD machinery.

PubMed

Ju, Lin-Gao; Lin, Xiang; Yan, Dong; Li, Qing-Lan; Wu, Min; Li, Lian-Yun

2018-07-01

ERAD is an important process of protein quality control that eliminates misfolded or unassembled proteins from ER. Before undergoing proteasome degradation, the misfolded proteins are dislocated from ER membrane into cytosol, which requires the AAA ATPase p97/VCP and its cofactor, the NPL4-UFD1 dimer. Here, we performed a CRISPR-based screen and identify many candidates for ERAD regulation. We further confirmed four proteins, FBOX2, TRIM6, UFL1 and WDR20, are novel regulators for ERAD. Then the molecular mechanism for WDR20 in ERAD is further characterized. Depletion of WDR20 inhibits the degradation of TCRα, a typical ERAD substrate, while WDR20 overexpression reduces TCRα protein level. WDR20 associates with TCRα and central regulators of the ERAD system, p97, GP78 and HRD1. A portion of WDR20 localizes to the ER-containing microsomal membrane. WDR20 expression increases TCRα ubiquitination, and HRD1 E3 ligase is essential for the process. WDR20 seems to serve as an adaptor protein to mediate the interaction between p97 and TCRα. Our study provides novel candidates and reveals an unexpected role of WDR20 in ERAD regulation. Copyright © 2018 Elsevier B.V. All rights reserved.

The evolving role of ubiquitin modification in endoplasmic reticulum-associated degradation

PubMed Central

Preston, G. Michael; Brodsky, Jeffrey L.

2017-01-01

The endoplasmic reticulum (ER) serves as a warehouse for factors that augment and control the biogenesis of nascent proteins entering the secretory pathway. In turn, this compartment also harbors the machinery that responds to the presence of misfolded proteins by targeting them for proteolysis via a process known as ER-associated degradation (ERAD). During ERAD, substrates are selected, modified with ubiquitin, removed from the ER, and then degraded by the cytoplasmic 26S proteasome. While integral membrane proteins can directly access the ubiquitination machinery that resides in the cytoplasm or on the cytoplasmic face of the ER membrane, soluble ERAD substrates within the lumen must be retrotranslocated from this compartment. In either case, nearly all ERAD substrates are tagged with a polyubiquitin chain, a modification that represents a commitment step to degrade aberrant proteins. However, increasing evidence indicates that the polyubiquitin chain on ERAD substrates can be further modified, serves to recruit ERAD-requiring factors, and may regulate the ERAD machinery. Amino acid side chains other than lysine on ERAD substrates can also be modified with ubiquitin, and post-translational modifications that affect substrate ubiquitination have been observed. Here, we summarize these data and provide an overview of questions driving this field of research. PMID:28159894

The evolving role of ubiquitin modification in endoplasmic reticulum-associated degradation.

PubMed

Preston, G Michael; Brodsky, Jeffrey L

2017-02-15

The endoplasmic reticulum (ER) serves as a warehouse for factors that augment and control the biogenesis of nascent proteins entering the secretory pathway. In turn, this compartment also harbors the machinery that responds to the presence of misfolded proteins by targeting them for proteolysis via a process known as ER-associated degradation (ERAD). During ERAD, substrates are selected, modified with ubiquitin, removed from the ER, and then degraded by the cytoplasmic 26S proteasome. While integral membrane proteins can directly access the ubiquitination machinery that resides in the cytoplasm or on the cytoplasmic face of the ER membrane, soluble ERAD substrates within the lumen must be retrotranslocated from this compartment. In either case, nearly all ERAD substrates are tagged with a polyubiquitin chain, a modification that represents a commitment step to degrade aberrant proteins. However, increasing evidence indicates that the polyubiquitin chain on ERAD substrates can be further modified, serves to recruit ERAD-requiring factors, and may regulate the ERAD machinery. Amino acid side chains other than lysine on ERAD substrates can also be modified with ubiquitin, and post-translational modifications that affect substrate ubiquitination have been observed. Here, we summarize these data and provide an overview of questions driving this field of research. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

[Possible method of eradication of poliomyelitis as an infection].

PubMed

Seĭbil', V B; Malyshkina, L P

2012-01-01

Problem of poliomyelitis eradication is examined in the review. After the eradication of wild poliovirus, vaccine poliomyelitis virus continues to circulate in the human population. In rare cases it can cause the development of the disease. The authors describe disadvantages of the use of oral and inactivated poliomyelitis vaccines and note that by using oral poliomyelitis vaccine and eradication only of wild poliovirus, eradication of poliomyelitis as an infection will not succeed. As one of the approaches to reach this goal the authors propose the use of various enterovirus interference. Use of live enterovirus vaccine is described and its advantages and disadvantages are examined.

[Child labour: a social problem that we are committed to].

PubMed

Cutri, Adrián; Hammermüller, Erica; Zubieta, Ana; Müller Opet, Beatriz; Miguelez, Lilia

2012-08-01

Child labor is a complex problem that violates the fundamental rights of children and affects their psychophysical development. Child labor affects 215 million children in the world and 115 million perform activities defined as the "worst forms of child labor". Most child labor is in agriculture (60%), where the majority are unpaid family workers, compared to 26% in services and 7% in industry. Argentina has adopted the abolitionist position, promoting prevention and eradication within an inclusive public policy aimed to all children can exercise their rights. The Sociedad Argentina de Pediatría endorses this approach and proposes a course of action: the health team training, and dissemination of the risks of child labor and occupational teenager safety standards. As pediatricians we must be involved in defending children rights, and be able to detect any situation of child labor, and protect the health of children and adolescents. The joint interaction with family, community and other sectors of society will strengthen the network needed to implement child labor eradication policies.

Antimalarial drug resistance: a review of the biology and strategies to delay emergence and spread.

PubMed

Klein, E Y

2013-04-01

The emergence of resistance to former first-line antimalarial drugs has been an unmitigated disaster. In recent years, artemisinin class drugs have become standard and they are considered an essential tool for helping to eradicate the disease. However, their ability to reduce morbidity and mortality and to slow transmission requires the maintenance of effectiveness. Recently, an artemisinin delayed-clearance phenotype was described. This is believed to be the precursor to resistance and threatens local elimination and global eradication plans. Understanding how resistance emerges and spreads is important for developing strategies to contain its spread. Resistance is the result of two processes: (i) drug selection of resistant parasites; and (ii) the spread of resistance. In this review, we examine the factors that lead to both drug selection and the spread of resistance. We then examine strategies for controlling the spread of resistance, pointing out the complexities and deficiencies in predicting how resistance will spread. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease

PubMed Central

Crompton, Peter D.; Moebius, Jacqueline; Portugal, Silvia; Waisberg, Michael; Hart, Geoffrey; Garver, Lindsey S.; Miller, Louis H.; Barillas, Carolina; Pierce, Susan K.

2014-01-01

Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa family, the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world’s most vulnerable populations, claiming the lives of nearly a million children and pregnant women each year in Africa alone. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite’s complex life cycle with a view towards developing the tools that will contribute to the prevention of disease and death and ultimately the goal of malaria eradication. In so doing we hope to inspire immunologists to participate in defeating this devastating disease. PMID:24655294

The World Health Organization and global smallpox eradication

PubMed Central

Bhattacharya, S

2008-01-01

Background: This article examines the multifaceted structures and complex operations of the World Health Organization and its regional offices; it also reassesses the form and the workings of the global smallpox eradication programme with which these bodies were closely linked in the 1960s and 1970s. Methods: Using the case study of South Asia, it seeks to highlight the importance of writing nuanced histories of international health campaigns through an assessment of differences between official rhetoric and practice. Results and conclusion: The article argues that the detailed examination of the implementation of policy in a variety of localities, within and across national borders, allows us to recognise the importance of the agency of field managers and workers. This analytical approach also helps us acknowledge that communities were able to influence the shape and the timing of completion of public health campaigns in myriad ways. This, in turn, can provide useful pointers for the design and management of health programmes in the contemporary world. PMID:18791049

Genetic basis for evolved tolerance to dioxin-like pollutants in wild Atlantic killifish: more than the aryl hydrocarbon receptor

EPA Science Inventory

Atlantic killifish (Fundulus heteroclitus) resident to some US urban and industrialized estuaries demonstrate recently evolved and extreme tolerance to toxic dioxin-like compounds (DLCs). Here we provide an unusually comprehensive accounting (69%) through Quantitative Trait Locu...

Urchin-like TiO₂@C core-shell microspheres: coupled synthesis and lithium-ion battery applications.

PubMed

Liu, Zhenyu; Liu, Jing; Liu, Junfeng; Wang, Li; Zhang, Guoxin; Sun, Xiaoming

2014-05-21

Carbon coated urchin-like TiO2 microspheres were prepared through coupled hydrolysis of titanium tetrachloride and catalyzed carbonization of glucose. Carbon coating endowed the composite with unusual structural stability at high temperature and reasonable Li-ion battery performance.

The Role of Research in Viral Disease Eradication and Elimination Programs: Lessons for Malaria Eradication

PubMed Central

Breman, Joel G.; de Quadros, Ciro A.; Dowdle, Walter R.; Foege, William H.; Henderson, Donald A.; John, T. Jacob; Levine, Myron M.

2011-01-01

By examining the role research has played in eradication or regional elimination initiatives for three viral diseases—smallpox, poliomyelitis, and measles—we derive nine cross-cutting lessons applicable to malaria eradication. In these initiatives, some types of research commenced as the programs began and proceeded in parallel. Basic laboratory, clinical, and field research all contributed notably to progress made in the viral programs. For each program, vaccine was the lynchpin intervention, but as the programs progressed, research was required to improve vaccine formulations, delivery methods, and immunization schedules. Surveillance was fundamental to all three programs, whilst polio eradication also required improved diagnostic methods to identify asymptomatic infections. Molecular characterization of pathogen isolates strengthened surveillance and allowed insights into the geographic source of infections and their spread. Anthropologic, sociologic, and behavioural research were needed to address cultural and religious beliefs to expand community acceptance. The last phases of elimination and eradication became increasingly difficult, as a nil incidence was approached. Any eradication initiative for malaria must incorporate flexible research agendas that can adapt to changing epidemiologic contingencies and allow planning for posteradication scenarios. PMID:21311582

Using spatially explicit surveillance models to provide confidence in the eradication of an invasive ant

PubMed Central

Ward, Darren F.; Anderson, Dean P.; Barron, Mandy C.

2016-01-01

Effective detection plays an important role in the surveillance and management of invasive species. Invasive ants are very difficult to eradicate and are prone to imperfect detection because of their small size and cryptic nature. Here we demonstrate the use of spatially explicit surveillance models to estimate the probability that Argentine ants (Linepithema humile) have been eradicated from an offshore island site, given their absence across four surveys and three surveillance methods, conducted since ant control was applied. The probability of eradication increased sharply as each survey was conducted. Using all surveys and surveillance methods combined, the overall median probability of eradication of Argentine ants was 0.96. There was a high level of confidence in this result, with a high Credible Interval Value of 0.87. Our results demonstrate the value of spatially explicit surveillance models for the likelihood of eradication of Argentine ants. We argue that such models are vital to give confidence in eradication programs, especially from highly valued conservation areas such as offshore islands. PMID:27721491

The principles of disease elimination and eradication.

PubMed Central

Dowdle, W. R.

1998-01-01

The Dahlem Workshop discussed the hierarchy of possible public health interventions in dealing with infectious diseases, which were defined as control, elimination of disease, elimination of infections, eradication, and extinction. The indicators of eradicability were the availability of effective interventions and practical diagnostic tools and the essential need for humans in the life-cycle of the agent. Since health resources are limited, decisions have to be made as to whether their use for an elimination or eradication programme is preferable to their use elsewhere. The costs and benefits of global eradication programmes concern direct effects on morbidity and mortality and consequent effects on the health care system. The success of any disease eradication initiative depends strongly on the level of societal and political commitment, with a key role for the World Health Assembly. Eradication and ongoing programmes constitute potentially complementary approaches to public health. Elimination and eradication are the ultimate goals of public health, evolving naturally from disease control. The basic question is whether these goals are to be achieved in the present or some future generation. PMID:10063669

Sequential (as Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter pylori Eradication in the Pediatric Population: A Meta-Analysis.

PubMed

Lau, Christine S M; Ward, Amanda; Chamberlain, Ronald S

2016-06-01

Helicobacter pylori is a common infection associated with many gastrointestinal diseases. Triple or quadruple therapy is the current recommendation for H pylori eradication in children but is associated with success rates as low as 50%. Recent studies have demonstrated that a 10-day sequential therapy regimen, rather than simultaneous antibiotic administration, achieved eradication rates of nearly 95%. This meta-analysis found that sequential therapy increased eradication rates by 14.2% (relative risk [RR] = 1.142; 95% confidence interval [CI] = 1.082-1.207; P < .001). Ten-day sequential therapy significantly improved H pylori eradication rates compared to the 7-day standard therapy (RR = 1.182; 95% CI = 1.102-1.269; p < .001) and 10-day standard therapy (RR = 1.179; 95% CI = 1.074-1.295; P = .001), but had lower eradication rates compared to 14-day standard therapy (RR = 0.926; 95% CI = 0.811-1.059; P = .261). The use of sequential therapy is associated with increased H pylori eradication rates in children compared to standard therapy of equal or shorter duration. © The Author(s) 2015.

Complex within complex: integrative taxonomy reveals hidden diversity in Cicadetta brevipennis (Hemiptera: Cicadidae) and unexpected relationships with a song divergent relative

USDA-ARS?s Scientific Manuscript database

Multiple sources of data in combination are essential for species delimitation and classification of difficult taxonomic groups. Here we investigate a cicada taxon with unusual cryptic diversity and we attempt to resolve seemingly contradictory data sets. Cicada songs act as species-specific premati...

Global health goals: lessons from the worldwide effort to eradicate poliomyelitis.

PubMed

Aylward, R Bruce; Acharya, Arnab; England, Sarah; Agocs, Mary; Linkins, Jennifer

2003-09-13

The Global Polio Eradication Initiative was launched in 1988. Assessment of the politics, production, financing, and economics of this international effort has suggested six lessons that might be pertinent to the pursuit of other global health goals. First, such goals should be based on technically sound strategies with proven operational feasibility in a large geographical area. Second, before launching an initiative, an informed collective decision must be negotiated and agreed in an appropriate international forum to keep to a minimum long-term risks in financing and implementation. Third, if substantial community engagement is envisaged, efficient deployment of sufficient resources at that level necessitates a defined, time-limited input by the community within a properly managed partnership. Fourth, although the so-called fair-share concept is arguably the best way to finance such goals, its limitations must be recognised early and alternative strategies developed for settings where it does not work. Fifth, international health goals must be designed and pursued within existing health systems if they are to secure and sustain broad support. Finally, countries, regions, or populations most likely to delay the achievement of a global health goal should be identified at the outset to ensure provision of sufficient resources and attention. The greatest threats to poliomyelitis eradication are a financing gap of US 210 million dollars and difficulties in strategy implementation in at most five countries.

Challenges and open issues in the management of acquired hemophilia A (AHA).

PubMed

Shetty, Shrimati D; Ghosh, Kanjaksha

2015-03-01

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by antibodies which neutralize the function of factor VIII (FVIII). The disease presents a complex clinical challenge to the treating Physicians and Hematologists. As the disease is associated with high mortality, prompt management is necessary. Early recognition, quick diagnosis and timely referral to a specialized center are important for better management of these patients. The different clinical manifestations, underlying pathology, inhibitor kinetics and the associated age related comorbidities do not allow extrapolation of the treatment protocols of congenital hemophilia to AHA. The basic strategies of the management of AHA patients involve maintaining hemostasis, suppression or eradication of antibodies, diagnosis and treatment of underlying pathology and avoid treatment related complications like thrombosis. The efficiency of hemostatic agents which are generally used to treat AHA is unpredictable. Due to the rarity of the disease, there are no randomized clinical trials on the management of this disorder and thus the expertise and experience of the treating Physicians' guide treatment strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

[Biofilms in otolaryngology].

PubMed

Mena Viveros, Nicolás

2014-01-01

According to the National Institute of Health of the USA, «more than 60% of all microbial infections are caused by biofilms».'This can surprise us, but it is enough to consider that common infections like those of the genito-urinary tract, infections produced by catheters, middle ear infections in children, the formation of dental plaque and gingivitis are caused by biofilms, for this statement to seem more realistic. At present this is one of the subjects of great interest within medicine, particularly in otolaryngology. Bacteria have traditionally been considered to be in a free state without evident organization, partly perhaps by the ease of studying them in this form. Nevertheless, the reality is that, in nature, the great majority of these germs form complex colonies adhered to surfaces, colonies that have received the name of biofilms. These biofilms are more common than previously thought and almost all of the people have been in contact with them in the form of infections in the teeth or humid, slippery areas. New treatments that can eradicate them are currently being investigated. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Organization of the sleep-related neural systems in the brain of the harbour porpoise (Phocoena phocoena).

PubMed

Dell, Leigh-Anne; Patzke, Nina; Spocter, Muhammad A; Siegel, Jerome M; Manger, Paul R

2016-07-01

The present study provides the first systematic immunohistochemical neuroanatomical investigation of the systems involved in the control and regulation of sleep in an odontocete cetacean, the harbor porpoise (Phocoena phocoena). The odontocete cetaceans show an unusual form of mammalian sleep, with unihemispheric slow waves, suppressed REM sleep, and continuous bodily movement. All the neural elements involved in sleep regulation and control found in bihemispheric sleeping mammals were present in the harbor porpoise, with no specific nuclei being absent, and no novel nuclei being present. This qualitative similarity of nuclear organization relates to the cholinergic, noradrenergic, serotonergic, and orexinergic systems and is extended to the γ-aminobutyric acid (GABA)ergic elements involved with these nuclei. Quantitative analysis of the cholinergic and noradrenergic nuclei of the pontine region revealed that in comparison with other mammals, the numbers of pontine cholinergic (126,776) and noradrenergic (122,878) neurons are markedly higher than in other large-brained bihemispheric sleeping mammals. The diminutive telencephalic commissures (anterior commissure, corpus callosum, and hippocampal commissure) along with an enlarged posterior commissure and supernumerary pontine cholinergic and noradrenergic neurons indicate that the control of unihemispheric slow-wave sleep is likely to be a function of interpontine competition, facilitated through the posterior commissure, in response to unilateral telencephalic input related to the drive for sleep. In addition, an expanded peripheral division of the dorsal raphe nuclear complex appears likely to play a role in the suppression of REM sleep in odontocete cetaceans. Thus, the current study provides several clues to the understanding of the neural control of the unusual sleep phenomenology present in odontocete cetaceans. J. Comp. Neurol. 524:1999-2017, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Incorporation of a Theranostic "Two-Tone" Luminescent Silver Complex into Biocompatible Agar Hydrogel Composite for the Eradication of ESKAPE Pathogens in a Skin and Soft Tissue Infection Model.

PubMed

Pinto, Miguel N; Martinez-Gonzalez, Jorge; Chakraborty, Indranil; Mascharak, Pradip K

2018-06-04

Microbial invasion and colonization of the skin and underlying soft tissues are among the most common types of infections, becoming increasingly prevalent in hospital settings. Systemic antibiotic chemotherapies are now extremely limited due to emergence of drug-resistant Gram-positive and multidrug-resistant Gram-negative bacterial strains. Topical administration of antimicrobials provides an effective route for the treatment of skin and soft tissue infections (SSTIs). Therefore, the development of new and effective materials for the delivery of these agents is of paramount importance. Silver is a broad-spectrum antibiotic used for the treatment and prevention of infections since ancient times. However, the high reactivity of silver cation (Ag + ) makes its incorporation into delivery materials quite challenging. Herein we report a novel soft agar hydrogel composite for the delivery of Ag + into infected wound sites. This material incorporates a Ag(I) complex [Ag 2 (DSX) 2 (NO 3 ) 2 ] (1; DSX = 5-(dimethylamino)- N, N-bis(pyridin-2-ylmethyl) naphthalene-1-sulfonamide) that exhibits a change in fluorescence upon Ag + release and qualitatively indicates the end point of silver delivery. The antibacterial efficacy of the material was tested against several bacterial strains in an SSTI model. The complex 1-agar composite proved effective at eradicating the pathogens responsible for the majority of SSTIs. The theranostic (therapeutic/diagnostic) properties coupled with its stability, softness, ease of application, and removal make this material an attractive silver-delivery vehicle for the treatment and prevention of SSTIs.

Antibacterial Potential of an Antimicrobial Agent Inspired by Peroxidase-Catalyzed Systems

PubMed Central

Tonoyan, Lilit; Fleming, Gerard T. A.; Mc Cay, Paul H.; Friel, Ruairi; O'Flaherty, Vincent

2017-01-01

Antibiotic resistance is an increasingly serious threat to global health. Consequently, the development of non-antibiotic based therapies and disinfectants, which avoid induction of resistance, or cross-resistance, is of high priority. We report the synthesis of a biocidal complex, which is produced by the reaction between ionic oxidizable salts—iodide and thiocyanate—in the presence of hydrogen peroxide as an oxidation source. The reaction generates bactericidal reactive oxygen and iodine species. In this study, we report that the iodo-thiocyanate complex (ITC) is an effective bactericidal agent with activity against planktonic and biofilm cells of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and methicillin-resistant S. aureus) bacteria. The minimum bactericidal concentrations and the minimum biofilm eradication concentrations of the biocidal composite were in the range of 7.8–31.3 and 31.3–250 μg ml−1, respectively. As a result, the complex was capable to cause a rapid cell death of planktonic test cultures at between 0.5 and 2 h, and complete eradication of dual and mono-species biofilms between 30 s and 10 min. Furthermore, the test bacteria, including a MRSA strain, exposed to the cocktail failed to develop resistance after serial passages. The antimicrobial activity of the ITC appears to derive from the combinational effect of the powerful species capable of oxidizing the essential biomolecules of bacteria. The use of this composition may provide an effective and efficient method for killing potential pathogens, as well as for disinfecting and removing biofilm contamination. PMID:28512449

Operation Ghost Dancer: The Use of Active Duty Army Forces in Marijuana Eradication.

DTIC Science & Technology

1991-03-11

NO. NO. ACCESSION NO. 11. TITLE (Include Security Classification) OPERATION GHOST DANCER: The Use of Active Duty Army Forces in Marijuana Eradication...The Use of Active Duty Army Forces in Marijuana Eradication An Individual Study Project by Lieutenant Colonel Henry J. Richter United States Army...Dancer: The Use of Active Duty Army Forces in Marijuana Eradication Format: Individual Study Project Date: 11 March 1991 Pages: 70 Classification

Daytime encopresis associated with gland mal epileptic seizures: case report.

PubMed

Oyatsi, D P

2005-08-01

Sphincteric incontinence of stool and urine are not unusual features of generalised epileptic seizures. Isolated secondary encopresis as a manifestation of an epileptic seizure is unusual. This report is of, a four year old boy, with daytime secondary non-retentive encopresis. The onset of encopresis was preceded by several episodes of nocturnal generalised tonic clonic epileptic seizures. An electroencephalogram showed features consistent with complex partial seizures. He was commenced on anti-epileptic treatment with phenytoin sodium, and by the third day of treatment, the patient had achieved stool control.

Investigating the Origin of the Supernova Remnant W49B

NASA Astrophysics Data System (ADS)

Crum, Ryan Matthew; Frank, Kari A.; Dwarkadas, Vikram; Burrows, David N.

2018-01-01

W49B is a Galactic supernova remnant whose origin is still debated. Is it the remains of an unusual asymmetric Type 1a supernova or of a jet-driven core collapse supernova? Using the X-ray analysis method, Smoothed Particle Inference (SPI), we dig deeper into understanding the complex properties of SNR W49B. We do this by characterizing the temperatures and abundance ratios throughout the remnant. We will compare the results with a wide variety of supernova nucleosynthesis models in order to constrain the mechanism behind this unusual supernova remnant.

Array-CGH in patients with Kabuki-like phenotype: Identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration

PubMed Central

Cuscó, Ivon; del Campo, Miguel; Vilardell, Mireia; González, Eva; Gener, Blanca; Galán, Enrique; Toledo, Laura; Pérez-Jurado, Luis A

2008-01-01

Background Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. Methods We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. Results No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Conclusion Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered. PMID:18405349

Array-CGH in patients with Kabuki-like phenotype: identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration.

PubMed

Cuscó, Ivon; del Campo, Miguel; Vilardell, Mireia; González, Eva; Gener, Blanca; Galán, Enrique; Toledo, Laura; Pérez-Jurado, Luis A

2008-04-11

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.

Global Polio Eradication - Way Ahead.

PubMed

Bahl, Sunil; Bhatnagar, Pankaj; Sutter, Roland W; Roesel, Sigrun; Zaffran, Michel

2018-02-01

In 1988, the World Health Assembly resolved to eradicate poliomyelitis by the year 2000. Although substantial progress was achieved by 2000, global polio eradication proved elusive. In India, the goal was accomplished in 2011, and the entire South-East Asia Region was certified as polio-free in 2014. The year 2016 marks the lowest wild poliovirus type 1 case count ever, the lowest number of polio-endemic countries (Afghanistan, Nigeria and Pakistan), the maintenance of wild poliovirus type 2 eradication, and the continued absence of wild poliovirus type 3 detection since 2012. The year also marks the Global Polio Eradication Initiative (GPEI) moving into the post-cessation of Sabin type 2, after the effort of globally synchronized withdrawal of Sabin type 2 poliovirus in April 2016. Sustained efforts will be needed to ensure polio eradication is accomplished, to overcome the access and security issues, and continue to improve the quality and reach of field operations. After that, surveillance (the "eyes and ears") will move further to the center stage. Sensitive surveillance will monitor the withdrawal of all Sabin polioviruses, and with facility containment, constitute the cornerstones for eventual global certification of wild poliovirus eradication. An emergency response capacity is essential to institute timely control measures should polio still re-emerge. Simultaneously, the public health community needs to determine whether and how to apply the polio-funded infrastructure to other priorities (after the GPEI funding has stopped). Eradication is the primary goal, but securing eradication will require continued efforts, dedicated resources, and a firm commitment by the global public health community.

Probiotics in Helicobacter pylori eradication therapy: Systematic review and network meta-analysis.

PubMed

Wang, Fan; Feng, Juerong; Chen, Pengfei; Liu, Xiaoping; Ma, Minxing; Zhou, Rui; Chang, Ying; Liu, Jing; Li, Jin; Zhao, Qiu

2017-09-01

Several probiotics were effective in the eradication treatment for Helicobacter pylori (Hp), but their comparative efficacy was unknown. To compare the efficacy of different probiotics when supplemented in Hp eradication therapy. A comprehensive search was conducted to identify all relevant studies in multiple databases and previous meta-analyses. Bayesian network meta-analysis was performed to combine direct and indirect evidence and estimate the relative effects. One hundred and forty studies (44 English and 96 Chinese) were identified with a total of 20,215 patients, and more than 10 probiotic strategies were supplemented in Hp eradication therapy. The rates of eradication and adverse events were 84.1 and 14.4% in probiotic group, while 70.5 and 30.1% in the control group. In general, supplementary probiotics were effective in improving the efficacy of Hp eradication and decreasing the incidence of adverse events, despite of few ineffective subtypes. In triple eradication therapy, there was no significant difference among the effective probiotics, and combined probiotics did not show a better efficacy and tolerance than single use. In triple therapy of 7 days and 14 days, Lactobacillus acidopilus was a slightly better choice, while Saccharomyces boulardii was more applicable for 10-day triple therapy. Compared to placebo, most probiotic strategies were effective when supplemented in Hp eradication therapy. In triple eradication therapy, no probiotic showed a superior efficacy to the others. Compared to single use, combined probiotics could not improve the efficacy or tolerance significantly. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction

PubMed Central

Nishizawa, Toshihiro; Suzuki, Hidekazu; Maekawa, Takama; Harada, Naohiko; Toyokawa, Tatsuya; Kuwai, Toshio; Ohara, Masanori; Suzuki, Takahiro; Kawanishi, Masahiro; Noguchi, Kenji; Yoshio, Toshiyuki; Katsushima, Shinji; Tsuruta, Hideo; Masuda, Eiji; Tanaka, Munehiro; Katayama, Shunsuke; Kawamura, Norio; Nishizawa, Yuko; Hibi, Toshifumi; Takahashi, Masahiko

2012-01-01

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT. PMID:22690086

Mars Life? - Microscopic Tube-like Structures

NASA Image and Video Library

1996-08-09

This high-resolution scanning electron microscope image shows an unusual tube-like structural form that is less than 1/100th the width of a human hair in size found in meteorite ALH84001, a meteorite believed to be of Martian origin. http://photojournal.jpl.nasa.gov/catalog/PIA00288

Genetic basis for evolved tolerance to dioxin-like pollutants in wild Atlantic killifish: more than the aryl hydrocarbon receptor

USDA-ARS?s Scientific Manuscript database

Atlantic killifish (Fundulus heteroclitus) resident to some US urban and industrialized estuaries demonstrate recently evolved and extreme tolerance to toxic dioxin-like compounds (DLCs). Here we provide an unusually comprehensive accounting (69%) through Quantitative Trait Locus (QTL) analysis of ...

Genetic basis for evolved tolerance to dioxin-like pollutants in wild atlantic killifish: more than the aryl hydrocarbon receptor

USDA-ARS?s Scientific Manuscript database

Atlantic killifish (Fundulus heteroclitus) resident to some US urban and industrialized estuaries demonstrate recently evolved and extreme tolerance to toxic dioxin-like compounds (DLCs). Here we provide an unusually comprehensive accounting (69%) through Quantitative Trait Locus (QTL) analysis of ...

Can Economic Analysis Contribute to Disease Elimination and Eradication? A Systematic Review.

PubMed

Sicuri, Elisa; Evans, David B; Tediosi, Fabrizio

2015-01-01

Infectious diseases elimination and eradication have become important areas of focus for global health and countries. Due to the substantial up-front investments required to eliminate and eradicate, and the overall shortage of resources for health, economic analysis can inform decision making on whether elimination/eradication makes economic sense and on the costs and benefits of alternative strategies. In order to draw lessons for current and future initiatives, we review the economic literature that has addressed questions related to the elimination and eradication of infectious diseases focusing on: why, how and for whom? A systematic review was performed by searching economic literature (cost-benefit, cost-effectiveness and economic impact analyses) on elimination/eradication of infectious diseases published from 1980 to 2013 from three large bibliographic databases: one general (SCOPUS), one bio-medical (MEDLINE/PUBMED) and one economic (IDEAS/REPEC). A total of 690 non-duplicate papers were identified from which only 43 met the inclusion criteria. In addition, only one paper focusing on equity issues, the "for whom?" question, was found. The literature relating to "why?" is the largest, much of it focusing on how much it would cost. A more limited literature estimates the benefits in terms of impact on economic growth with mixed results. The question of how to eradicate or eliminate was informed by an economic literature highlighting that there will be opportunities for individuals and countries to free-ride and that forms of incentives and/or disincentives will be needed. This requires government involvement at country level and global coordination. While there is little doubt that eliminating infectious diseases will eventually improve equity, it will only happen if active steps to promote equity are followed on the path to elimination and eradication. The largest part of the literature has focused on costs and economic benefits of elimination/eradication. To a lesser extent, challenges associated with achieving elimination/eradication and ensuring equity have also been explored. Although elimination and eradication are, for some diseases, good investments compared with control, countries' incentives to eliminate do not always align with the global good and the most efficient elimination strategies may not prioritize the poorest populations. For any infectious disease, policy-makers will need to consider realigning contrasting incentives between the individual countries and the global community and to assure that the process towards elimination/eradication considers equity.

Unusual structural transition of antimicrobial VP1 peptide.

PubMed

Shanmugam, Ganesh; Phambu, Nsoki; Polavarapu, Prasad L

2011-05-01

VP1 peptide, an active domain of m-calpain enzyme with antimicrobial activity is found to undergo an unusual conformational transition in trifluoroethanol (TFE) solvent. The nature of, and time dependent variations in, circular dichroism associated with the amide I vibrations, suggest that VP1 undergoes self-aggregation forming anti-parallel β-sheet structure in TFE. Transmission electron micrograph (TEM) images revealed that β-sheet aggregates formed by VP1 possess fibril-like assemblies. Copyright © 2011 Elsevier B.V. All rights reserved.

Compact autonomous navigation system (CANS)

NASA Astrophysics Data System (ADS)

Hao, Y. C.; Ying, L.; Xiong, K.; Cheng, H. Y.; Qiao, G. D.

2017-11-01

Autonomous navigation of Satellite and constellation has series of benefits, such as to reduce operation cost and ground station workload, to avoid the event of crises of war and natural disaster, to increase spacecraft autonomy, and so on. Autonomous navigation satellite is independent of ground station support. Many systems are developed for autonomous navigation of satellite in the past 20 years. Along them American MANS (Microcosm Autonomous Navigation System) [1] of Microcosm Inc. and ERADS [2] [3] (Earth Reference Attitude Determination System) of Honeywell Inc. are well known. The systems anticipate a series of good features of autonomous navigation and aim low cost, integrated structure, low power consumption and compact layout. The ERADS is an integrated small 3-axis attitude sensor system with low cost and small volume. It has the Earth center measurement accuracy higher than the common IR sensor because the detected ultraviolet radiation zone of the atmosphere has a brightness gradient larger than that of the IR zone. But the ERADS is still a complex system because it has to eliminate many problems such as making of the sapphire sphere lens, birefringence effect of sapphire, high precision image transfer optical fiber flattener, ultraviolet intensifier noise, and so on. The marginal sphere FOV of the sphere lens of the ERADS is used to star imaging that may be bring some disadvantages., i.e. , the image energy and attitude measurements accuracy may be reduced due to the tilt image acceptance end of the fiber flattener in the FOV. Besides Japan, Germany and Russia developed visible earth sensor for GEO [4] [5]. Do we have a way to develop a cheaper/easier and more accurate autonomous navigation system that can be used to all LEO spacecraft, especially, to LEO small and micro satellites? To return this problem we provide a new type of the system—CANS (Compact Autonomous Navigation System) [6].

Eradication of schistosomiasis in Guangxi, China. Part 2: Political economy, management strategy and costs, 1953-92.

PubMed Central

Sleigh, A.; Jackson, S.; Li, X.; Huang, K.

1998-01-01

Reported are the results of a study of the political economy, management, and costs of the successful Guangxi schistosomiasis eradication programme, spanning 40 years from 1953 to 1992. For this purpose we analysed all government data and memoranda on the policy, management, technical support, finance, and the control strategy of the programme. We also interviewed many local staff involved in the programme over the 40-year period and obtained cost data from annual county-level records on seven major categories of variable costs. Schistosomiasis control in Guangxi began with one of the first examples of community participation and rapid assessment in public health history--the use of pre-franked envelopes to return disease questionnaires and suspect snails from rural areas. This approach quickly and accurately delineated the endemic area. This was Mao Zedong's "mass line", incorporating ideas and knowledge from peasants directly into services run for and by them, here the schistosomiasis control programme. Recognition by China's leaders that schistosomiasis was a great economic burden, steadfast prioritizing of the programme over 40 years, local innovative scientific study, agricultural and environmental focus on eradicating the snail hosts and boosting rural production, and mass community education and support were all key factors in the final success. Local leaders motivated programme staff and everyone involved knew the objectives. The programme was always multisectoral, with policy developed centrally, and strategy and collaboration encouraged and rewarded at the grass-roots. These features explain how a very poor autonomous region such as Guangxi finally eradicated schistosomiasis, spending less than US$ 0.50 per protected citizen per year; it is remarkable that the disease and snails were initially found across a large area of complex environments and modern drugs such as praziquantel were not available for most of the 40-year period. The lessons from Guangxi can be adapted elsewhere and should encourage other areas to control endemic schistosomiasis using methods devised to suit the local culture and geography. Images Fig. 2 PMID:9868841

Polio vaccination: past, present and future.

PubMed

Bandyopadhyay, Ananda S; Garon, Julie; Seib, Katherine; Orenstein, Walter A

2015-01-01

Live attenuated oral polio vaccine (OPV) and inactivated polio vaccine (IPV) are the tools being used to achieve eradication of wild polio virus. Because OPV can rarely cause paralysis and generate revertant polio strains, IPV will have to replace OPV after eradication of wild polio virus is certified to sustain eradication of all polioviruses. However, uncertainties remain related to IPV's ability to induce intestinal immunity in populations where fecal-oral transmission is predominant. Although substantial effectiveness and safety data exist on the use and delivery of OPV and IPV, several new research initiatives are currently underway to fill specific knowledge gaps to inform future vaccination policies that would assure polio is eradicated and eradication is maintained.

Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.

PubMed

Sangiolo, Dario; Mesiano, Giulia; Gammaitoni, Loretta; Leuci, Valeria; Todorovic, Maja; Giraudo, Lidia; Cammarata, Cristina; Dell'Aglio, Carmine; D'Ambrosio, Lorenzo; Pisacane, Alberto; Sarotto, Ivana; Miano, Sara; Ferrero, Ivana; Carnevale-Schianca, Fabrizio; Pignochino, Ymera; Sassi, Francesco; Bertotti, Andrea; Piacibello, Wanda; Fagioli, Franca; Aglietta, Massimo; Grignani, Giovanni

2014-01-01

Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability to eradicate chemoresistant cancer stem-like cells (sCSC) that are likely responsible for relapses and drug resistance. In this study, we investigated the preclinical activity of patient-derived cytokine-induced killer (CIK) cells against autologous bone sarcoma and STS, including against putative sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP under the control of the human promoter for OCT4, a stem cell gene activated in putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK cells efficiently killed allogeneic and autologous sarcoma cells in vitro. Intravenous infusion of CIK cells delayed autologous tumor growth in immunodeficient mice. Further in vivo analyses established that CIK cells could infiltrate tumors and that tumor growth inhibition occurred without an enrichment of sCSCs relative to control-treated animals. These results provide preclinical proof-of-concept for an effective strategy to attack autologous sarcomas, including putative sCSCs, supporting the clinical development of CIK cells as a novel class of immunotherapy for use in settings of untreatable metastatic disease.

A Distinct Class of Genome Rearrangements Driven by Heterologous Recombination.

PubMed

León-Ortiz, Ana María; Panier, Stephanie; Sarek, Grzegorz; Vannier, Jean-Baptiste; Patel, Harshil; Campbell, Peter J; Boulton, Simon J

2018-01-18

Erroneous DNA repair by heterologous recombination (Ht-REC) is a potential threat to genome stability, but evidence supporting its prevalence is lacking. Here we demonstrate that recombination is possible between heterologous sequences and that it is a source of chromosomal alterations in mitotic and meiotic cells. Mechanistically, we find that the RTEL1 and HIM-6/BLM helicases and the BRCA1 homolog BRC-1 counteract Ht-REC in Caenorhabditis elegans, whereas mismatch repair does not. Instead, MSH-2/6 drives Ht-REC events in rtel-1 and brc-1 mutants and excessive crossovers in rtel-1 mutant meioses. Loss of vertebrate Rtel1 also causes a variety of unusually large and complex structural variations, including chromothripsis, breakage-fusion-bridge events, and tandem duplications with distant intra-chromosomal insertions, whose structure are consistent with a role for RTEL1 in preventing Ht-REC during break-induced replication. Our data establish Ht-REC as an unappreciated source of genome instability that underpins a novel class of complex genome rearrangements that likely arise during replication stress. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical Properties of Elements 99 and 100 [Einsteinium and Fermium

DOE R&D Accomplishments Database

Seaborg, G. T.; Thompson, S. G.; Harvey, B. G.; Choppin, G. R.

1954-07-23

A description of some of the chemical properties and of the methods used in the separations of elements 99 [Einsteinium] and 100 [Fermium] are given. The new elements exhibit the properties expected for the tenth and eleventh actinide elements. Attempts to produce an oxidation state greater than III of element 99 have been unsuccessful. In normal aqueous media only the III state of element 100 appears to exist. The relative spacings of the elution peaks of the new elements in some separations with ion exchange resin columns are the same as the relative spacings of the homologous lanthanide elements. The results of experiments involving cation exchange resins with very concentrated hydrochloric acid eluant show that the new elements, like the earlier actinides, are more strongly complexed than the lanthanides. The new elements also exist partially as anions in concentrated hydrochloric acid, as do earlier actinide elements, and they may be partially separated from each other by means of ion exchange resins. With some eluants interesting reversals of elution positions are observed in the region Bk-Cf-99-100, indicating complex ion formation involving unusual factors.

Different Antibiotic No Culture Eradicating (DANCE) strategy: an easy way to manage H. pylori eradication.

PubMed

Roccarina, Davide; Franceschi, Francesco; Zocco, Maria Assunta; Garcovich, Matteo; Gasbarrini, Giovanni; Gasbarrini, Antonio

2012-11-01

Treatment of Helicobacter pylori infection is becoming a very relevant problem especially in industrialized Countries. Although different therapeutic regimens are currently available, treatment failure remains a growing problem in daily medical practice. Several factors could play a role in the eradication failure, but the most relevant are antibiotic resistance and patient's compliance. While Helicobacter pylori resistance to amoxicillin is rare, clarithromycin and metronidazole resistance varies significantly from close to zero up to 25%. However, metronidazole in vitro resistance exhibits a lower impact on eradication success because resistance in vitro does not reflect that in vivo. Specific guidelines have then been published, mostly based on antibiotic resistance among different geographic areas. Basically, first-line and second-line regimens have been well defined; concerning third-line treatment Maastricht III guidelines suggest to adopt a culture-based approach. Culture is, however, expensive, invasive and available only in few specialized centres. An alternative approach may be to use an empirical strategy, based on the avoidance of repeating similar eradicating schemes in the same patients during the course of different eradicating regimens. For this approach we propose the acronym DANCE (Different Antibiotic No Culture Eradicating) strategy. When correctly applied, this approach showed to reach successful eradication in up to 99.5% of Helicobacter pylori-positive patients. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Eradication of Helicobacter pylori for prevention of ulcer recurrence after simple closure of perforated peptic ulcer: a meta-analysis of randomized controlled trials.

PubMed

Wong, Chung-Shun; Chia, Chee-Fah; Lee, Hung-Chia; Wei, Po-Li; Ma, Hon-Ping; Tsai, Shin-Han; Wu, Chih-Hsiung; Tam, Ka-Wai

2013-06-15

Eradication of Helicobacter pylori has become part of the standard therapy for peptic ulcer. However, the role of H pylori eradication in perforation of peptic ulcers remains controversial. It is unclear whether eradication of the bacterium confers prolonged ulcer remission after simple repair of perforated peptic ulcer. A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the effects of H pylori eradication on prevention of ulcer recurrence after simple closure of perforated peptic ulcers. The primary outcome to evaluate these effects was the incidence of postoperative ulcers; the secondary outcome was the rate of H pylori elimination. The meta-analysis included five randomized controlled trials and 401 patients. A high prevalence of H pylori infection occurred in patients with perforated peptic ulcers. Eradication of H pylori significantly reduced the incidence of ulcer recurrence at 8 wk (risk ratio 2.97; 95% confidence interval: 1.06-8.29) and 1 y (risk ratio 1.49; 95% confidence interval: 1.10-2.03) postoperation. The rate of H pylori eradication was significantly higher in the treatment group than in the nontreatment group. Eradication therapy should be provided to patients with H pylori infection after simple closure of perforated gastroduodenal ulcers. Copyright © 2013 Elsevier Inc. All rights reserved.

Malaria eradication: the economic, financial and institutional challenge.

PubMed

Mills, Anne; Lubell, Yoel; Hanson, Kara

2008-12-11

Malaria eradication raises many economic, financial and institutional challenges. This paper reviews these challenges, drawing on evidence from previous efforts to eradicate malaria, with a special focus on resource-poor settings; summarizes more recent evidence on the challenges, drawing on the literature on the difficulties of scaling-up malaria control and strengthening health systems more broadly; and explores the implications of these bodies of evidence for the current call for elimination and intensified control. Economic analyses dating from the eradication era, and more recent analyses, suggest that, in general, the benefits of malaria control outweigh the costs, though few studies have looked at the relative returns to eradication versus long-term control. Estimates of financial costs are scanty and difficult to compare. In the 1960s, the consolidation phase appeared to cost less than $1 per capita and, in 1988, was estimated to be $2.31 per capita (both in 2006 prices). More recent estimates for high coverage of control measures suggest a per capita cost of several dollars. Institutional challenges faced by malaria eradication included limits to the rule of law (a major problem where malaria was concentrated in border areas with movement of people associated with illegal activities), the existence and performance of local implementing structures, and political sustainability at national and global levels. Recent analyses of the constraints to scaling-up malaria control, together with the historical evidence, are used to discuss the economic, financial and institutional challenges that face the renewed call for eradication and intensified control. The paper concludes by identifying a research agenda covering: issues of the allocative efficiency of malaria eradication, especially using macro-economic modelling to estimate the benefits and costs of malaria eradication and intensified control, and studies of the links between malaria control and economic development, the costs and consequences of the various tools and mixes of tools employed in control and eradication, issues concerning the extension of coverage of interventions and service delivery approaches, especially those that can reach the poorest, research on the processes of formulating and implementing malaria control and eradication policies, at both international and national levels, research on financing issues, at global and national levels.

Differential Effect of Helicobacter pylori Eradication on Time-Trends in Brady/Hypokinesia and Rigidity in Idiopathic Parkinsonism

PubMed Central

Dobbs, Sylvia M; Dobbs, R John; Weller, Clive; Charlett, André; Bjarnason, Ingvar T; Lawson, Andrew J; Letley, Darren; Harbin, Lucy; Price, Ashley B; Ibrahim, Mohammad A A; Oxlade, Norman L; Bowthorpe, James; Leckstroem, Daniel; Smee, Cori; Plant, J Malcolm; Peterson, Dale W

2010-01-01

Background: We examine the effect of eradicating Helicobacter in idiopathic parkinsonism (IP). Marked deterioration, where eradication-therapy failed, prompted an interim report in the first 20 probands to reach de-blinding. The null-hypothesis, “eradication has no effect on principal outcome, mean stride length at free-walking speed,” was rejected. We report on study completion in all 30 who had commenced post-treatment assessments. Methods: This is a randomized, placebo-controlled, parallel-group efficacy study of eradicating biopsy-proven (culture and/or organism on histopathology) Helicobacter pylori infection on the time course of facets of IP, in probands taking no, or stable long-t½, anti-parkinsonian medication. Persistent infection at de-blinding (scheduled 1-year post-treatment) led to open active eradication-treatment. Results: Stride length improved (73 (95% CI 14–131) mm/year, p = .01) in favor of “successful” blinded active over placebo, irrespective of anti-parkinsonian medication, and despite worsening upper limb flexor rigidity (237 (57–416) Nm × 10−3/year, p = .01). This differential effect was echoed following open active, post-placebo. Gait did not deteriorate in year 2 and 3 post-eradication. Anti-nuclear antibody was present in all four proven (two by molecular microbiology only) eradication failures. In the remainder, it marked poorer response during the year after eradication therapy, possibly indicating residual “low-density” infection. We illustrate the importance of eradicating low-density infection, detected only by molecular microbiology, in a proband not receiving anti-parkinsonian medication. Stride length improved (424 (379–468) mm for 15 months post-eradication, p = .001), correction of deficit continuing to 3.4 years. Flexor rigidity increased before hydrogen-breath-test positivity for small intestinal bacterial overgrowth (208 (28–388) Nm × 10−3, p = .02), increased further during (171 (67–274), p = .001) (15–31 months), and decreased (136 (6–267), p = .04) after restoration of negativity (32–41 months). Conclusion: Helicobacter is an arbiter of progression, independent of infection-load. PMID:20633189

Malaria eradication: the economic, financial and institutional challenge

PubMed Central

Mills, Anne; Lubell, Yoel; Hanson, Kara

2008-01-01

Malaria eradication raises many economic, financial and institutional challenges. This paper reviews these challenges, drawing on evidence from previous efforts to eradicate malaria, with a special focus on resource-poor settings; summarizes more recent evidence on the challenges, drawing on the literature on the difficulties of scaling-up malaria control and strengthening health systems more broadly; and explores the implications of these bodies of evidence for the current call for elimination and intensified control. Economic analyses dating from the eradication era, and more recent analyses, suggest that, in general, the benefits of malaria control outweigh the costs, though few studies have looked at the relative returns to eradication versus long-term control. Estimates of financial costs are scanty and difficult to compare. In the 1960s, the consolidation phase appeared to cost less than $1 per capita and, in 1988, was estimated to be $2.31 per capita (both in 2006 prices). More recent estimates for high coverage of control measures suggest a per capita cost of several dollars. Institutional challenges faced by malaria eradication included limits to the rule of law (a major problem where malaria was concentrated in border areas with movement of people associated with illegal activities), the existence and performance of local implementing structures, and political sustainability at national and global levels. Recent analyses of the constraints to scaling-up malaria control, together with the historical evidence, are used to discuss the economic, financial and institutional challenges that face the renewed call for eradication and intensified control. The paper concludes by identifying a research agenda covering: ∘ issues of the allocative efficiency of malaria eradication, especially using macro-economic modelling to estimate the benefits and costs of malaria eradication and intensified control, and studies of the links between malaria control and economic development ∘ the costs and consequences of the various tools and mixes of tools employed in control and eradication ∘ issues concerning the extension of coverage of interventions and service delivery approaches, especially those that can reach the poorest ∘ research on the processes of formulating and implementing malaria control and eradication policies, at both international and national levels ∘ research on financing issues, at global and national levels. PMID:19091035

Rheology of Active Fluids

NASA Astrophysics Data System (ADS)

Saintillan, David

2018-01-01

An active fluid denotes a viscous suspension of particles, cells, or macromolecules able to convert chemical energy into mechanical work by generating stresses on the microscale. By virtue of this internal energy conversion, these systems display unusual macroscopic rheological signatures, including a curious transition to an apparent superfluid-like state where internal activity exactly compensates viscous dissipation. These behaviors are unlike those of classical complex fluids and result from the coupling of particle configurations with both externally applied flows and internally generated fluid disturbances. Focusing on the well-studied example of a suspension of microswimmers, this review summarizes recent experiments, models, and simulations in this area and highlights the critical role played by the rheological response of these active materials in a multitude of phenomena, from the enhanced transport of passive suspended objects to the emergence of spontaneous flows and collective motion.

Farmer and Veterinarian Attitudes towards the Bovine Tuberculosis Eradication Programme in Spain: What Is Going on in the Field?

PubMed

Ciaravino, Giovanna; Ibarra, Patricia; Casal, Ester; Lopez, Sergi; Espluga, Josep; Casal, Jordi; Napp, Sebastian; Allepuz, Alberto

2017-01-01

The effectiveness of health interventions against bovine tuberculosis (bTB) is influenced by several " non-biological " factors that may hamper bTB detection and control. Although the engagement of stakeholders is a key factor for the eradication programme's success, social factors have been often ignored in the control programmes of animal diseases, especially in developed countries. In this study, we used a qualitative approach to investigate perceptions, opinions, attitudes, and beliefs of farmers, and veterinarians who may influence the effectiveness of the Spanish bTB eradication programme. The study was carried out in two phases. First, 13 key representatives of different groups involved in the programme were interviewed through exploratory interviews to identify most relevant themes circulating in the population. Interviews focused on strong and weak points of the programme; reasons for failure to achieve eradication; benefits of being disease free; future perspectives, and proposed changes to the programme. Based on these results, a thematic guide was developed and detailed information was gained through face-to-face in-depth interviews conducted on a purposive sample of 39 farmers and veterinarians. Data were analysed following an ethnographic methodology. Main results suggested that the bTB programme is perceived as a law enforcement duty without an adequate motivation of some stakeholders and a general feeling of distrust arose. The complexity of bTB epidemiology combined with gaps in knowledge and weak communication throughout stakeholders contributed to causing disbeliefs, which in turn generated different kinds of guesses and interpretations. Low reliability in the routine skin test for bTB screening was expressed and the level of confidence on test results interpretation was linked with skills and experience of public and private veterinarians in the field. Lack of training for farmers and pressure faced by veterinarians during field activities also emerged. Few benefits of being bTB free were perceived and comparative grievances referred to wildlife and other domestic reservoirs, sector-specific legislation for bullfighting farms, and the absence of specific health legislation for game hunting farms were reported. Understanding reasons for demotivation and scepticism may help institutions to ensure stakeholders' collaboration and increase the acceptability of control measures leading to an earlier achievement of eradication.

Trends in the eradication rates of Helicobacter pylori infection for eleven years

PubMed Central

Yoon, Jai Hoon; Baik, Gwang Ho; Sohn, Kyoung Min; Kim, Dae Yong; Kim, Yeon Soo; Suk, Ki Tae; Kim, Jin Bong; Kim, Dong Joon; Kim, Jin Bae; Shin, Woon Geon; Kim, Hak Yang; Baik, Il Hyun; Jang, Hyun Joo

2012-01-01

AIM: To evaluate the trends in the eradication rate of Helicobacter pylori (H. pylori) over the past 11 years in a single center. METHODS: This retrospective study covered the period from January 2000 to December 2010. We evaluated 5746 patients diagnosed with gastric ulcers (GU), duodenal ulcers (DU), GU + DU, or nonpeptic ulcers associated with an H. pylori infection. We treated them annually with the 2 wk standard first-line triple regimen, proton pump inhibitor (PPI) + amoxicilin + clarithromycin (PAC; PPI, clarithromycin 500 mg, and amoxicillin 1 g, all twice a day). The follow-up test was performed at least 4 wk after the completion of the 2 wk standard H. pylori eradication using the PAC regimen. We also assessed the eradication rates of 1 wk second-line therapy with a quadruple standard regimen (PPI b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.) after the failure of the first-line therapy. Statistical analysis was performed with 95%CI for the differences in the annual eradication rates. RESULTS: A total of 5746 patients [2333 males (58.8%), 1636 females (41.2%); mean age of males vs females 51.31 ± 13.1 years vs 52.76 ± 13.6 years, P < 0.05, total mean age 51.9 ± 13.3 years (mean ± SD)] were investigated. Among these patients, 1674 patients were excluded: 35 patients refused treatment; 18 patients ceased H. pylori eradication due to side effects; 1211 patients had inappropriate indications for H. pylori eradication, having undergone stomach cancer operation or chemotherapy; and 410 patients did not undergo the follow-up. We also excluded 103 patients who wanted to stop eradication treatment after only 1 wk due to poor compliance or the side effects mentioned above. Finally, we evaluated the annual eradication success rates in a total of 3969 patients who received 2 wk first-line PAC therapy. The endoscopic and clinical findings in patients who received the 2 wk PAC were as follows: gastric ulcer in 855 (21.5%); duodenal ulcer in 878 (22.1%); gastric and duodenal ulcer in 124 (3.1%), erosive, atrophic gastritis and functional dyspepsia in 2055 (51.8%); and other findings (e.g., MALToma, patients who wanted to receive the therapy even though they had no abnormal endoscopic finding) in 57 (0.5%). The overall eradication rate of the 2 wk standard first-line triple regimen was 86.5%. The annual eradication rates from 2000 to 2010 were 86.7%, 85.4%, 86.5%, 83.3%, 89.9%, 90.5%, 88.4%, 84.5%, 89.1%, 85.8%, and 88.3%, sequentially (P = 0.06). No definite evidence of a significant change in the eradication rate was seen during the past eleven years. The eradication rates of second-line therapy were 88.9%, 82.4%, 85%, 83.9%, 77.3%, 85.7%, 84.4%, 87.3%, 83.3%, 88.9%, and 84% (P = 0.77). The overall eradication rate of 1 wk quadruple second-line therapy was 84.7%. There was no significant difference in the eradication rate according to the H. pylori associated diseases. CONCLUSION: This study showed that there was no trend change in the H. pylori eradication rate over the most recent 11 years in our institution. PMID:23236238

Use of 'eradication' in HIV cure-related research: a public health debate.

PubMed

Dubé, Karine; Luter, Stuart; Lesnar, Breanne; Newton, Luke; Galea, Jerome; Brown, Brandon; Gianella, Sara

2018-02-13

The landscape of Human Immunodeficiency Virus (HIV) research has changed drastically over the past three decades. With the remarkable success of antiretroviral treatment (ART) in decreasing AIDS-related mortality, some researchers have shifted their HIV research focus from treatment to cure research. The HIV cure research community often uses the term eradication to describe the science, and talks about eradicating the virus from the body. In public discourse, the term eradication could be conflated with disease eradication at the population level. In this paper, we call for a reframing of HIV cure research as control, as it is a more accurate descriptor and achievable goal in the foreseeable future. The properties of HIV are discordant with eradicability standards at both the individual level (as a clinical concept), and at the population level (as a public health concept). At the individual level, true eradication would necessitate absolute elimination of all latent HIV reservoirs from the body. Current HIV cure-related research strategies have proven unsuccessful at accurately quantifying, let alone eliminating these reservoirs. At the population level, eradication implies the permanent global reduction of HIV to zero new cases and to zero risk for future cases. Given the absence of an efficacious HIV vaccine and the impracticality and unethicality of eliminating animal reservoirs, global eradication of HIV is highly implausible. From a public health perspective, HIV eradication remains an elusive goal. The term 'eradication' is a misleading description of current HIV cure-related research. Instead, we call for the use of more realistic expressions such as 'sustained virologic HIV suppression (or control)' or 'management of HIV persistence' to describe HIV cure-related research. Using these terms reorients what HIV cure science can potentially achieve in the near future and avoids creating unrealistic expectations, particularly among the millions of people globally who live with HIV.

Comparison of Pathogen Eradication Rate and Safety of Anti-Bacterial Agents for Bronchitis: A Network Meta-Analysis.

PubMed

Wang, Jinghua; Xu, Haiyang; Wang, Dunwei; Li, Mingxian

2017-10-01

A large number of population in both developing and developed countries are affected by bronchitis, among all the factors, bacterial infection was considered as a critical cause of acute exacerbations of chronic bronchitis. Although several anti-bacterial agents were proved to have the effect of alleviating bronchitis, their relative efficacies and potential side effects remained not clear. We are keen to compare the pathogen eradication rate and safety of anti-bacterial agents for bronchitis. Relevant studies were searched in multiple sources and data were extracted from eligible studies. Then conventional meta-analysis and network meta-analysis (NMA) were conducted to determine the relative efficacy and safety of bronchitis medications. The efficacy of bronchitis medications was determined by using the outcome of pathogen eradication, including total pathogen eradication, pathogen eradication of Haemophilus influenzae, pathogen eradication of Moraxella catarrhalis, and pathogen eradication of Streptococcus pneumoniae. In addition, safety was assessed by using the outcome of adverse effects and diarrhoea. A 27 RCTs with 9,414 participants were included in the study. Among the medications, gatifloxacin and moxifloxacin exhibited better performance than clarithromycin with respect to pathogen eradication of H. influenzae (OR = 21.37, CI: 1.22-541.28; OR = 7.43, CI: 1.79-30.50). Clarithromycin, gemifloxacin, levofloxacin, moxifloxacin, and telithromycin appeared to be more preferable than amoxicillin + clavulanate and azithromycin with respect to diarrhoea (all OR <1). The surface under the cumulative ranking curve (SUCRA) results suggested that gemifloxacin and levofloxacin had a relatively high ranking in total pathogen eradication, whereas amoxicillin + clavulanate and azithromycin exhibited relatively lower ranking with respect to adverse effects and diarrhoea. Gemifloxacin and levofloxacin are more preferable than others for lowering respiratory tract inflammation and infections considering their balanced performance between pathogen eradication and adverse effects. J. Cell. Biochem. 118: 3171-3183, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Regression of gastric intestinal metaplasia after the eradication of Helicobacter pylori infection in a hospital in Mexico.

PubMed

Sánchez Cuén, Jaime Alberto; Irineo Cabrales, Ana Bertha; Bernal Magaña, Gregorio; Peraza Garay, Felipe

2016-12-01

Intestinal metaplasia is a precursor lesion of gastric cancer. Infection by Helicobacter pylori is the principal cause of metaplasia. While evidence of the regression of metaplasia after treatment to eradicate this infection has been demonstrated, controversy remains with regard to this subject. The objective of this study was to determine the frequency of the regression of gastric intestinal metaplasia one year after the eradication of Helicobacter pylori. A prospective longitudinal designed study was carried out. The population studied in this research consisted of patients attending the Endoscopy Unit to undergo an upper endoscopy, in whom various symptoms indicated intestinal metaplasia associated with Helicobacter pylori, and who received standard empiric triple therapy to eradicate the bacteria. An upper endoscopy was performed in which four gastric biopsy samples were taken (two from the antrum and two from the body) before and after the eradicating treatment, with the endoscopic and histological findings studied after one year of monitoring. The statistical analysis was conducted using the Fisher's exact test and the McNemar's test. Forty-six patients were studied, of whom 20 (43.5%) were men and 26 (56.5%) were women, with an average age of 58.9 (DE 11.2). Intestinal metaplasia was found in 46 (100%) patients before treatment and in 21 (45.7%) patients post-eradication. Complete intestinal metaplasia (type I) was found in 35 patients (76.1%) before treatment and in 11 (23.9%) patients post-eradication (p = 0.000), while incomplete intestinal metaplasia (type II) was found in 10 (21.7%) patients before treatment and in 10 (21.7%) patients post-eradication. Non-atrophic chronic gastritis was found in 35 (76.1%) patients before treatment and in 32 (69.6%) patients post-eradication. In this study, gastric intestinal metaplasia associated with Helicobacter pylori infection showed a regression of 54.3% one year after the eradication of this microorganism. This treatment could modify the natural history of the development of gastric cancer.

Varying efficacy of Helicobacter pylori eradication regimens: cost effectiveness study using a decision analysis model.

PubMed

Duggan, A E; Tolley, K; Hawkey, C J; Logan, R F

1998-05-30

To determine how small differences in the efficacy and cost of two antibiotic regimens to eradicate Helicobacter pylori can affect the overall cost effectiveness of H pylori eradication in duodenal ulcer disease. A decision analysis to examine the cost effectiveness of eight H pylori eradication strategies for duodenal ulcer disease with and without 13C-urea breath testing to confirm eradication. Cumulative direct treatment costs per 100 patients with duodenal ulcer disease who were positive for H pylori. In model 1 the strategy of omeprazole, clarithromycin, and metronidazole alone was the most cost effective of the four strategies assessed. The addition of the 13C-urea breath test and a second course of omeprazole, clarithromycin, and metronidazole achieved the highest eradication rate (97%) but was the most expensive (62.63 pounds per patient). The cost of each additional effective eradication was 589.00 pounds (incremental cost per case) when compared with the cost of treating once only with omeprazole, clarithromycin, and metronidazole; equivalent to the cost of a patient receiving ranitidine for duodenal ulcer relapse for more than 15 years. Eradication strategies of omeprazole, amoxycillin, and metronidazole were less cost effective than omeprazole, clarithromycin, and metronidazole alone. In model 2 the addition of the 13C-urea breath test after treatment, and maintenance treatment, increased the cost of all the strategies and reduced the cost advantage of omeprazole, clarithromycin, and metronidazole alone. Small differences in efficacy can influence the comparative cost effectiveness of strategies for eradicating H pylori. Of the strategies tested the most cost effective (omeprazole, clarithromycin, and metronidazole alone) was neither the least expensive (omeprazole, amoxycillin, and metronidazole alone) nor the most effective (omeprazole, clarithromycin, and metronidazole with further treatment for patients found positive for H pylori on 13C-urea breath testing). Cost effectiveness should be an important part of choosing an eradication strategy for H pylori.

Lipid disequilibrium disrupts ER proteostasis by impairing ERAD substrate glycan trimming and dislocation

PubMed Central

To, Milton; Peterson, Clark W. H.; Roberts, Melissa A.; Counihan, Jessica L.; Wu, Tiffany T.; Forster, Mercedes S.; Nomura, Daniel K.; Olzmann, James A.

2017-01-01

The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment of the secretory proteome. Proteins that fail to achieve their native conformation are retained in the ER and targeted for clearance by ER-associated degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent delivery of substrates to the 26S proteasome for proteolysis. Recent findings indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a fatty acid analogue, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a role for LDs in ERAD. However, whether LDs are involved in the ERAD process remains an outstanding question. Using chemical and genetic approaches to disrupt diacylglycerol acyltransferase (DGAT)–dependent LD biogenesis, we provide evidence that LDs are dispensable for ERAD in mammalian cells. Instead, our results suggest that triacsin C causes global alterations in the cellular lipid landscape that disrupt ER proteostasis by interfering with the glycan trimming and dislocation steps of ERAD. Prolonged triacsin C treatment activates both the IRE1 and PERK branches of the unfolded protein response and ultimately leads to IRE1-dependent cell death. These findings identify an intimate relationship between fatty acid metabolism and ER proteostasis that influences cell viability. PMID:27881664

Normalization of pH level and gastric mucosa after eradication of H. pylori in the remnant stomach.

PubMed

Kato, Shunji; Matsukura, Norio; Matsuda, Noriko; Tsuchiya, Shinichi; Naito, Zenya; Tajiri, Takashi

2008-12-01

The Updated Sydney System (USS) is used to evaluate chronic gastritis and chronic atrophic gastritis (CAG) due to H. pylori infection. Here, we investigated USS scores and gastric juice pH levels in H. pylori infection-positive or -eradicated patients with remnant stomach after surgery. Gastric juice pH levels were measured using pH test-tape in 197 patients (112 H. pylori-positive and 85 H. pylori-negative after eradication) who had undergone distal gastrectomy and conventional H. pylori eradication therapy. In H. pylori infection-positive remnant stomach cases, gastric juice pH showed a reverse correlation with pepsinogen I/II ratio, and H. pylori infection-negative patients following eradication showed associations with the degree of atrophy and intestinal metaplasia at both the anastomosis and in the corpus. Further, pH levels in these patients were normalized time depending after the eradication in the remnant stomach. Eradication therapy for the remnant stomach contributes to the possible improvement of stomach conditions by controlling the pH level of gastric juice. This effect will be protective against the risk of secondary stomach carcinogenesis in the remnant stomach.

An unusual case of severe primary molar infraocclusion.

PubMed

Gondim, Juliana Oliveira; Neto, José Jeová Siebra Moreira; de Carvalho, Fernanda Matias; da Costa, Raquel Campelo Ferreira; Monteiro, Aline Levi Baratta; Giro, Elisa Maria Aparecida

2013-01-01

Dentoalveolar ankylosis is described as the direct union between root cementum/dentin and alveolar bone. Its etiology is unknown, and conflicting opinions have been presented to explain it. Late detection of ankylosed primary teeth may cause serious problems to the occlusion and generally demands a more complex treatment approach. The purpose of this report is to present an unusual case of severe infraocclusion of the primary maxillary right second molar associated with a posterior crossbite in a 6-year-old child. The initial treatment option was tooth extraction, but the tooth resumed eruption spontaneously. After correction of the posterior crossbite and a 1-year follow-up, the tooth remained in occlusion and the permanent successor was developing without problems. From this unusual outcome, it may be concluded that further investigation of this anomaly of eruption is needed.

Asenapine

MedlinePlus

Asenapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

Risperidone

MedlinePlus

Risperidone is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

Iloperidone

MedlinePlus

Iloperidone is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

Ziprasidone

MedlinePlus

Ziprasidone is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

Olanzapine

MedlinePlus

Olanzapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

Modelling the expected rate of laboratory biosafety breakdowns involving rinderpest virus in the post-eradication era.

PubMed

Beauvais, W; Fournié, G; Jones, B A; Cameron, A; Njeumi, F; Lubroth, J; Pfeiffer, D U

2013-11-01

Now that we are in the rinderpest post-eradication era, attention is focused on the risk of re-introduction. A semi-quantitative risk assessment identified accidental use of rinderpest virus in laboratories as the most likely cause of re-introduction. However there is little data available on the rates of laboratory biosafety breakdowns in general. In addition, any predictions based on past events are subject to various uncertainties. The aims of this study were therefore to investigate the potential usefulness of historical data for predicting the future risk of rinderpest release via laboratory biosafety breakdowns, and to investigate the impacts of the various uncertainties on these predictions. Data were collected using a worldwide online survey of laboratories, a structured search of ProMED reports and discussion with experts. A stochastic model was constructed to predict the number of laboratory biosafety breakdowns involving rinderpest that will occur over the next 10 years, based on: (1) the historical rate of biosafety breakdowns; and (2) the change in the number of laboratories that will have rinderpest virus in the next 10 years compared to historically. The search identified five breakdowns, all of which occurred during 1970-2000 and all of which were identified via discussions with experts. Assuming that our search for historical events had a sensitivity of over 60% and there has been at least a 40% reduction in the underlying risk (attributable to decreased laboratory activity post eradication) the most likely number of biosafety events worldwide was estimated to be zero over a 10 year period. However, the risk of at least one biosafety breakdown remains greater than 1 in 10,000 unless the sensitivity was at least 99% or the number of laboratories has decreased by at least 99% (based on 2000-2010 during which there were no biosafety breakdowns). Copyright © 2013 Elsevier B.V. All rights reserved.

Community Learning Campus: It Takes a Simple Message to Build a Complex Project

ERIC Educational Resources Information Center

Pearson, George

2012-01-01

Education Canada asked Tom Thompson, president of Olds College and a prime mover behind the Community Learning Campus (CLC): What were the lessons learned from this unusually ambitious education project? Thompson mentions six lessons he learned from this complex project which include: (1) Dream big, build small, act now; (2) Keep a low profile at…

First-line Helicobacter pylori eradication among patients with chronic liver diseases in Taiwan.

PubMed

Tsai, Cheng-En; Liang, Chih-Ming; Lee, Chen-Hsiang; Kuo, Yuan-Hung; Wu, Keng-Liang; Chiu, Yi-Chun; Tai, Wei-Chen; Chuah, Seng-Kee

2016-08-01

Helicobacter pylori eradication in patients with chronic liver diseases (CLDs) and liver cirrhosis is seldom reported. This study aimed to assess the efficacy of 7-day standard triple therapy in patients with CLD including cirrhosis and to investigate the clinical factors influencing the success of eradication. A total of 592 H. pylori-infected patients, who received 7-day standard first-line triple therapy between January 1, 2014, and December 31, 2014, were recruited. Patients were divided into two groups: CLD group (N=136) and non-CLD group (N=456). The eradication rates attained by the CLD and non-CLD groups were 86.0% and 84.2%, respectively, in the per-protocol analysis (p=0.606). The eradication rates of liver cirrhosis and noncirrhosis CLD were 88.5% and 84.3%, respectively (p=0.783). The adverse events were similar between the two groups (8.8% vs. 9.2%, p=0.891). Compliance between the two groups was good (99.3% vs. 99.6%, p=0.670). The univariate analysis showed male sex to be the significant clinical factor in the non-CLD group (p=0.001) and alcohol consumption to be the significant clinical factor influencing H. pylori eradication rate in patients with CLD (p=0.022). Alcohol consumption was the only significant factor influencing H. pylori eradication in multivariate analysis (odds ratio=3.786, p=0.031). The results of this study suggest that H. pylori eradication rates in patients with CLD may be comparable with non-CLD patients. Alcohol consumption was the significant factor influencing H. pylori eradication in patients with CLD. Copyright © 2016. Published by Elsevier Taiwan.

A Novel Toll-Like Receptor 9 Agonist, MGN1703, Enhances HIV-1 Transcription and NK Cell-Mediated Inhibition of HIV-1-Infected Autologous CD4+ T Cells.

PubMed

Offersen, Rasmus; Nissen, Sara Konstantin; Rasmussen, Thomas A; Østergaard, Lars; Denton, Paul W; Søgaard, Ole Schmeltz; Tolstrup, Martin

2016-05-01

Toll-like receptor (TLR) agonists are potent enhancers of innate antiviral immunity and may also reverse HIV-1 latency. Therefore, TLR agonists have a potential role in the context of a "shock-and-kill" approach to eradicate HIV-1. Our extensive preclinical evaluation suggests that a novel TLR9 agonist, MGN1703, may indeed perform both functions in an HIV-1 eradication trial. Peripheral blood mononuclear cells (PBMCs) from aviremic HIV-1-infected donors on antiretroviral therapy (ART) that were incubated with MGN1703 ex vivo exhibited increased secretion of interferon alpha (IFN-α) (P= 0.005) and CXCL10 (P= 0.0005) in culture supernatants. Within the incubated PBMC pool, there were higher proportions of CD69-positive CD56(dim)CD16(+)NK cells (P= 0.001) as well as higher proportions of CD107a-positive (P= 0.002) and IFN-γ-producing (P= 0.038) NK cells. Incubation with MGN1703 also increased the proportions of CD69-expressing CD4(+)and CD8(+)T cells. Furthermore, CD4(+)T cells within the pool of MGN1703-incubated PBMCs showed enhanced levels of unspliced HIV-1 RNA (P= 0.036). Importantly, MGN1703 increased the capacity of NK cells to inhibit virus spread within a culture of autologous CD4(+)T cells assessed by using an HIV-1 p24 enzyme-linked immunosorbent assay (ELISA) (P= 0.03). In conclusion, we show that MGN1703 induced strong antiviral innate immune responses, enhanced HIV-1 transcription, and boosted NK cell-mediated suppression of HIV-1 infection in autologous CD4(+)T cells. These findings support clinical testing of MGN1703 in HIV-1 eradication trials. We demonstrate that MGN1703 (a TLR9 agonist currently undergoing phase 3 clinical testing for the treatment of metastatic colorectal cancer) induces potent antiviral responses in immune effector cells from HIV-1-infected individuals on suppressive antiretroviral therapy. The significantly improved safety and tolerability profiles of MGN1703 versus TLR9 agonists of the CpG-oligodeoxynucleotide (CpG-ODN) family are due to its novel "dumbbell-shape" structure made of covalently closed, natural DNA. In our study, we found that incubation of peripheral blood mononuclear cells with MGN1703 results in natural killer cell activation and increased natural killer cell function, which significantly inhibited the spread of HIV in a culture of autologous CD4(+)T cells. Furthermore, we discovered that MGN1703-mediated activation can enhance HIV-1 transcription in CD4(+)T cells, suggesting that this molecule may serve a dual purpose in HIV-1 eradication therapy: enhanced immune function and latency reversal. These findings provide a strong preclinical basis for the inclusion of MGN1703 in an HIV eradication clinical trial. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Are osseous artefacts a window to perishable material culture? Implications of an unusually complex bone tool from the Late Pleistocene of East Timor.

PubMed

O'Connor, S; Robertson, G; Aplin, K P

2014-02-01

We report the discovery of an unusually complex and regionally unique bone artefact in a Late Pleistocene archaeological assemblage (c. 35 ka [thousands of years ago]) from the site of Matja Kuru 2 on the island of Timor, in Wallacea. The artefact is interpreted as the broken butt of a formerly hafted projectile point, and it preserves evidence of a complex hafting mechanism including insertion into a shaped or split shaft, a complex pattern of binding including lateral stabilization of the cordage within a bilateral series of notches, and the application of mastic at several stages in the hafting process. The artefact provides the earliest direct evidence for the use of this combination of hafting technologies in the wider region of Southeast Asia, Wallacea, Melanesia and Australasia, and is morphologically unparallelled in deposits of any age. By contrast, it bears a close morphological resemblance to certain bone artefacts from the Middle Stone Age of Africa and South Asia. Examination of ethnographic projectile technology from the region of Melanesia and Australasia shows that all of the technological elements observed in the Matja Kuru 2 artefact were in use historically in the region, including the unusual feature of bilateral notching to stabilize a hafted point. This artefact challenges the notion that complex bone-working and hafting technologies were a relatively late innovation in this part of the world. Moreover, its regional uniqueness encourages us to abandon the perception of bone artefacts as a discrete class of material culture, and to adopt a new interpretative framework in which they are treated as manifestations of a more general class of artefacts that more typically were produced on perishable raw materials including wood. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

The FMRFamide-Like Peptide Family in Nematodes

PubMed Central

Peymen, Katleen; Watteyne, Jan; Frooninckx, Lotte; Schoofs, Liliane; Beets, Isabel

2014-01-01

In the three decades since the FMRFamide peptide was isolated from the mollusk Macrocallista nimbosa, structurally similar peptides sharing a C-terminal RFamide motif have been identified across the animal kingdom. FMRFamide-like peptides (FLPs) represent the largest known family of neuropeptides in invertebrates. In the phylum Nematoda, at least 32 flp-genes are classified, making the FLP system of nematodes unusually complex. The diversity of the nematode FLP complement is most extensively mapped in Caenorhabditis elegans, where over 70 FLPs have been predicted. FLPs have shown to be expressed in the majority of the 302 C. elegans neurons including interneurons, sensory neurons, and motor neurons. The vast expression of FLPs is reflected in the broad functional repertoire of nematode FLP signaling, including neuroendocrine and neuromodulatory effects on locomotory activity, reproduction, feeding, and behavior. In contrast to the many identified nematode FLPs, only few peptides have been assigned a receptor and there is the need to clarify the pathway components and working mechanisms of the FLP signaling network. Here, we review the diversity, distribution, and functions of FLPs in nematodes. PMID:24982652

Pressure Induced Phase Transformations of Silica Polymorphs and Glasses

NASA Astrophysics Data System (ADS)

Cagin, Tahir; Demiralp, Ersan; Goddard, William A., III

1998-03-01

Silica, SiO_2, is one of the most widely studied substance, and it has some complex and unusual properties. We have used a recently developed 2-body interaction force field (E. Demiralp, T. Cagin, W.A. Goddard, III, unpublished.) to study the structural phase transformations in silica under various pressure loading conditions. The specific transformations we studied are α-quartz to stishovite, coesite to stishovite and fused glass to stishovite-like dense, a dominantly six-coordinated glassy phase. Molecular dynamics simulations are performed under the constant loading rates ranging from 0.1 GPa/ps to 2.0 GPa/ps, pressures upto 100 GPa and at temperatures 300, 500, 700 and 900 K. We observe the crystal to crystal transformations to occur reconstructively, whereas it occurs in a smooth and displacive manner from glass to a stishovite-like phase confirming earlier conjectures. (E.M. Stolper and T.J. Ahrens, Geophys. Res. Let.) 14, 1231 (1987). To elucidate the shock loading experiments, we studied the dependence of transition pressure on the loading rate and the temperature. To assess the hysterisis effect we also studied the unloading behavior of each transformation.

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

Kasuga, Toshihiro; Usui, Fumihiko; Hasegawa, Sunao

Primitive, outer-belt asteroids are generally of low albedo, reflecting carbonaceous compositions like those of CI and CM meteorites. However, a few outer-belt asteroids having high albedos are known, suggesting the presence of unusually reflective surface minerals or, conceivably, even exposed water ice. Here, we present near-infrared (1.1-2.5 {mu}m) spectra of four outer-belt C-complex asteroids with albedos {>=}0.1. We find no absorption features characteristic of water ice (near 1.5 and 2.0 {mu}m) in the objects. Intimate mixture models set limits to the water ice by weight {<=}2%. Asteroids (723) Hammonia and (936) Kunigunde are featureless and have (60%-95%) amorphous Mg pyroxenesmore » that might explain the high albedos. Asteroid (1276) Ucclia also shows a featureless reflection spectrum with (50%-60%) amorphous Mg pyroxenes. Asteroid (1576) Fabiola shows a possible weak, broad absorption band (1.5-2.1 {mu}m). The feature can be reproduced by (80%) amorphous Mg pyroxenes or orthopyroxene (crystalline silicate), either of which is likely to cause its high albedo. We discuss the origin of high-albedo components in primitive asteroids.« less

How whales used to filter: exceptionally preserved baleen in a Miocene cetotheriid.

PubMed

Marx, Felix G; Collareta, Alberto; Gioncada, Anna; Post, Klaas; Lambert, Olivier; Bonaccorsi, Elena; Urbina, Mario; Bianucci, Giovanni

2017-08-01

Baleen is a comb-like structure that enables mysticete whales to bulk feed on vast quantities of small prey, and ultimately allowed them to become the largest animals on Earth. Because baleen rarely fossilises, extremely little is known about its evolution, structure and function outside the living families. Here we describe, for the first time, the exceptionally preserved baleen apparatus of an entirely extinct mysticete morphotype: the Late Miocene cetotheriid, Piscobalaena nana, from the Pisco Formation of Peru. The baleen plates of P. nana are closely spaced and built around relatively dense, fine tubules, as in the enigmatic pygmy right whale, Caperea marginata. Phosphatisation of the intertubular horn, but not the tubules themselves, suggests in vivo intertubular calcification. The size of the rack matches the distribution of nutrient foramina on the palate, and implies the presence of an unusually large subrostral gap. Overall, the baleen morphology of Piscobalaena likely reflects the interacting effects of size, function and phylogeny, and reveals a previously unknown degree of complexity in modern mysticete feeding evolution. © 2017 Anatomical Society.

[The role of Sabin inactivated poliovirus vaccine in the final phase of global polio eradication].

PubMed

Dong, S Z; Zhu, W B

2016-12-06

Global polio eradication has entered its final phase, but still faces enormous challenges. The Polio Eradication and Endgame Strategic Plan (2013-2018) set the target for making the world polio-free by 2018. Meanwhile, the World Heath Organization Global Action Plan (GAP Ⅲ) recommended that polioviruses be stored under strict conditions after eradication of the wild poliovirus. At least one dose of inactivated poliovirus vaccine (IPV) would be required for each newborn baby in the world to ensure successful completion of the final strategy and GAP Ⅲ. The Sabin IPV has a high production safety and low production cost, compared with the wild-virus IPV and, therefore, can play an important role in the final stage of global polio eradication.

The First Seven-Coordinated Triiodo Complex of Rhenium(III)

NASA Astrophysics Data System (ADS)

Schoultz, X.; Gerber, T. I. A.; Betz, R.; Hosten, E. C.

2017-12-01

The reaction of cis-[ReO2I(P Ph 3)2] with tert-butyl isocyanide in benzene led to the isolation of the complex [ReI3(CN- t-Bu)3(P Ph 3)] ( 1). The complex is unusual since it contains bulky ligands with large cone angles, i.e. three iodides, three isocyanides with tert-butyl groups and a triphenylphosphine as ligands in a seven-coordinate geometry around the rhenium(III) metal ion.

Wherever I may roam: protein and membrane trafficking in P. falciparum-infected red blood cells.

PubMed

Deponte, Marcel; Hoppe, Heinrich C; Lee, Marcus C S; Maier, Alexander G; Richard, Dave; Rug, Melanie; Spielmann, Tobias; Przyborski, Jude M

2012-12-01

Quite aside from its immense importance as a human pathogen, studies in recent years have brought to light the fact that the malaria parasite Plasmodium falciparum is an interesting eukaryotic model system to study protein trafficking. Studying parasite cell biology often reveals an overrepresentation of atypical cell biological features, possibly driven by the parasites' need to survive in an unusual biological niche. Malaria parasites possess uncommon cellular compartments to which protein traffic must be directed, including secretory organelles such as rhoptries and micronemes, a lysosome-like compartment referred to as the digestive vacuole and a complex (four membrane-bound) plastid, the apicoplast. In addition, the parasite must provide proteins to extracellular compartments and structures including the parasitophorous vacuole, the parasitophorous vacuolar membrane, the Maurer's clefts and both cytosol and plasma membrane of the host cell, the mature human red blood cell. Although some of these unusual destinations are possessed by other cell types, only Plasmodium parasites contain them all within one cell. Here we review what is known about protein and membrane transport in the P. falciparum-infected cell, highlighting novel features of these processes. A growing body of evidence suggests that this parasite is a real "box of tricks" with regards to protein traffic. Possibly, these tricks may be turned against the parasite by exploiting them as novel therapeutic targets. Copyright © 2012 Elsevier B.V. All rights reserved.

Can Hardwoods Be Eradicated From Pine Sites?

Treesearch

Michael D. Cain; D.A. Yaussy

1984-01-01

Intensive mechanical and chemical treatments were used annually for 12 years to eradicate hardwoods from a selectively managed loblolly (pinus taeda L.) shortleaf (P. echinata Mill.) pine stand in south Arkansas.Although temporarily effective, a succession of indigenous shrubs and trees followed the cessation of eradication...

Polio eradication initiative in India: deconstructing the GPEI.

PubMed

Sathyamala, C; Mittal, Onkar; Dasgupta, Rajib; Priya, Ritu

2005-01-01

The Global Polio Eradication Initiative (GPEI) promised eradication of polio by the year 2000 and certification of eradication by 2005. The first deadline is already a matter of history. With the reporting of polio cases in 2004, the new deadline for polio eradication by 2004 is postponed further. This article seeks to argue that the scientific and technical bodies spear-heading the GPEI, including the WHO, UNICEF, and the U.S. Centers for Disease Control, have formulated a conceptually flawed strategy and that it is not weak political will that is the central obstacle in this final push for global eradication. The validity of the claims of "near success" by the proponents of the GPEI is also examined in detail. By taking India as a case study, the authors examine the achievements of the GPEI in nine years of intense effort since 1995. They conclude that the GPEI is yet another exercise in mismanaging the health priorities and programs in developing countries in the era of globalization.

Malaria eradication in Mexico: Some historico-parasitological views oncold war, deadly fevers by Marcos Cueto, Ph.D

PubMed Central

Malagón, Filiberto

2008-01-01

This review of Professor Marcos Cueto's Cold War Deadly Fevers: Malaria Eradication in Mexico, 1955–1975 discusses some of the historical, sociological, political and parasitological topics included in Dr. Cueto's superbly well-informed volume. The reviewer, a parasitologist, follows the trail illuminated by Dr. Cueto through the foundations of the malaria eradication campaign; the release in Mexico of the first postage stamp in the world dedicated to malaria control; epidemiological facts on malarial morbidity and mortality in Mexico when the campaign began; the emergence of problem areas that impeded eradication; considerations on mosquitoes and malaria transmission in Mexico; the role of business and society in malaria eradication; the results of the campaign; the relationship between malaria and poverty; and the parasitological lessons to be learned from the history of malaria eradication campaigns. Dr. Cueto's excellent and well-informed exploration of malaria – not merely as a disease but as a social, economic and human problem – makes this book required reading.

Impact of Targeted Programs on Health Systems: A Case Study of the Polio Eradication Initiative

PubMed Central

Loevinsohn, Benjamin; Aylward, Bruce; Steinglass, Robert; Ogden, Ellyn; Goodman, Tracey; Melgaard, Bjorn

2002-01-01

The results of 2 large field studies on the impact of the polio eradication initiative on health systems and 3 supplementary reports were presented at a December 1999 meeting convened by the World Health Organization. All of these studies concluded that positive synergies exist between polio eradication and health systems but that these synergies have not been vigorously exploited. The eradication of polio has probably improved health systems worldwide by broadening distribution of vitamin A supplements, improving cooperation among enterovirus laboratories, and facilitating linkages between health workers and their communities. The results of these studies also show that eliminating polio did not cause a diminution of funding for immunization against other illnesses. Relatively little is known about the opportunity costs of polio eradication. Improved planning in disease eradication initiatives can minimize disruptions in the delivery of other services. Future initiatives should include indicators and baseline data for monitoring effects on health systems development. PMID:11772750

Addressing the Challenges and Opportunities of the Polio Endgame: Lessons for the Future.

PubMed

Patel, Manish; Cochi, Stephen

2017-07-01

The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in September 2015, making type 2 poliovirus the first human pathogen to be eradicated since smallpox. The eradication of type 2 poliovirus, the absence of detection of type 3 poliovirus worldwide since November 2012, and cornering type 1 poliovirus to only a few geographic areas of 3 countries has enabled implementation of the endgame of polio eradication which calls for a phased withdrawal of oral polio vaccine beginning with the type 2 component, introduction of inactivated poliovirus vaccine, strengthening of routine immunization in countries with extensive polio resources, and initiating activities to transition polio resources, program experience, and lessons learned to other global health initiatives. This supplement focuses on efforts by global partners to successfully launch polio endgame activities to permanently secure and sustain the enormous gains of polio eradication forever. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units

NASA Astrophysics Data System (ADS)

Ray, Lauren; Valentic, Timothy R.; Miyazawa, Takeshi; Withall, David M.; Song, Lijiang; Milligan, Jacob C.; Osada, Hiroyuki; Takahashi, Shunji; Tsai, Shiou-Chuan; Challis, Gregory L.

2016-12-01

Type I modular polyketide synthases assemble diverse bioactive natural products. Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain assembly. However, in several cases more exotic alkylmalonyl-CoA extender units are also known to be incorporated. In all examples studied to date, such unusual extender units are biosynthesized via reductive carboxylation of α, β-unsaturated thioesters catalysed by crotonyl-CoA reductase/carboxylase (CCRC) homologues. Here we show using a chemically-synthesized deuterium-labelled mechanistic probe, and heterologous gene expression experiments that the unusual alkylmalonyl-CoA extender units incorporated into the stambomycin family of polyketide antibiotics are assembled by direct carboxylation of medium chain acyl-CoA thioesters. X-ray crystal structures of the unusual β-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction, alone and in complex with hexanoyl-CoA, reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues.

Risperidone Injection

MedlinePlus

... release (long-acting) injection is used to treat schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

Ziprasidone Injection

MedlinePlus

... treat episodes of agitation in people who have schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

Paliperidone Injection

MedlinePlus

... Invega Sustenna, Invega Trinza) are used to treat schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

Anterior urethral valves without diverticulae: a report of two cases and a review of the literature.

PubMed

Singh, Dig Vijay; Taneja, Rajesh

2014-05-01

Two unusual cases of anterior urethral valves (AUV) without diverticulae are presented. The first case is a male child born with prenatal diagnosis of bilateral hydronephrosis. On cystoscopy, iris-like diaphragm valves were encountered about 3 mm distal to the skeletal sphincter. In the second case, an 18-month-old male child was investigated for recurrent febrile urinary tract infections and obstructed urinary symptoms. Cystoscopy confirmed the presence of slit-like valves 5 mm distal to the skeletal sphincter. Fulguration of the AUVs was performed in both cases. It may be worthwhile to review all cases of anterior urethral obstruction collectively and re-categorize them appropriately to include the unusual AUVs without diverticulum in that classification. © 2013 Japanese Teratology Society.

Predicting the Benefits of Banana Bunchy Top Virus Exclusion from Commercial Plantations in Australia

PubMed Central

Cook, David C.; Liu, Shuang; Edwards, Jacqueline; Villalta, Oscar N.; Aurambout, Jean-Philippe; Kriticos, Darren J.; Drenth, Andre; De Barro, Paul J.

2012-01-01

Benefit cost analysis is a tried and tested analytical framework that can clearly communicate likely net changes in producer welfare from investment decisions to diverse stakeholder audiences. However, in a plant biosecurity context, it is often difficult to predict policy benefits over time due to complex biophysical interactions between invasive species, their hosts, and the environment. In this paper, we demonstrate how a break-even style benefit cost analysis remains highly relevant to biosecurity decision-makers using the example of banana bunchy top virus, a plant pathogen targeted for eradication from banana growing regions of Australia. We develop an analytical approach using a stratified diffusion spread model to simulate the likely benefits of exclusion of this virus from commercial banana plantations over time relative to a nil management scenario in which no surveillance or containment activities take place. Using Monte Carlo simulation to generate a range of possible future incursion scenarios, we predict the exclusion benefits of the disease will avoid Aus$15.9-27.0 million in annual losses for the banana industry. For these exclusion benefits to be reduced to zero would require a bunchy top re-establishment event in commercial banana plantations three years in every four. Sensitivity analysis indicates that exclusion benefits can be greatly enhanced through improvements in disease surveillance and incursion response. PMID:22879960

Acute vulvar pain in a lady with post circumcision inclusion cyst of the vulva containing stones: a case report.

PubMed

Gudu, Wondimu

2014-01-06

Despite global eradication efforts, female genital cutting is still deep routed practice in some parts of Asia and East Africa. The crude and unscientific natures of the practice lead to many complications. Epidermoid inclusion cysts of the vulva are one of the late complications of female genital cutting and typically present as painless cystic swellings. But clinical presentation as 'stone' containing, hard vulvar mass is reported only once in the literature and presentation with acute vulvar pain has never been documented. A 21 yrs old, Ethiopian, unmarried, lady presented with sever acute vulvar pain, discharge, and a stony hard vulvar swelling 13 years after type-III female genital cutting (infibulation). Surgical excision of the cyst, which contained two 'stones' inside it, and defibulation were done. Histopathology confirmed calcified, keratinizing epidermoid inclusion cyst of the vulva. Clinicians, in areas where female genital cutting is prevalent, should be aware of such unusual late vulvar complication of the practice which might be misdiagnosed for other solid vulvar swellings and be familiar with the appropriate management.

Prioritizing islands for the eradication of invasive vertebrates in the United Kingdom overseas territories.

PubMed

Dawson, Jeffrey; Oppel, Steffen; Cuthbert, Richard J; Holmes, Nick; Bird, Jeremy P; Butchart, Stuart H M; Spatz, Dena R; Tershy, Bernie

2015-02-01

Invasive alien species are one of the primary threats to native biodiversity on islands worldwide. Consequently, eradicating invasive species from islands has become a mainstream conservation practice. Deciding which islands have the highest priority for eradication is of strategic importance to allocate limited resources to achieve maximum conservation benefit. Previous island prioritizations focused either on a narrow set of native species or on a small geographic area. We devised a prioritization approach that incorporates all threatened native terrestrial vertebrates and all invasive terrestrial vertebrates occurring on 11 U.K. overseas territories, which comprise over 2000 islands ranging from the sub-Antarctic to the tropics. Our approach includes eradication feasibility and distinguishes between the potential and realistic conservation value of an eradication, which reflects the benefit that would accrue following eradication of either all invasive species or only those species for which eradication techniques currently exist. We identified the top 25 priority islands for invasive species eradication that together would benefit extant populations of 155 native species including 45 globally threatened species. The 5 most valuable islands included the 2 World Heritage islands Gough (South Atlantic) and Henderson (South Pacific) that feature unique seabird colonies, and Anegada, Little Cayman, and Guana Island in the Caribbean that feature a unique reptile fauna. This prioritization can be rapidly repeated if new information or techniques become available, and the approach could be replicated elsewhere in the world. © 2014 Crown copyright. Conservation Biology © 2014 Society for Conservation Biology.

Severe gastritis decreases success rate of Helicobacter pylori eradication.

PubMed

Kalkan, Ismail Hakki; Sapmaz, Ferdane; Güliter, Sefa; Atasoy, Pınar

2016-05-01

In several studies, different risk factors other than antibiotic resistance have been documented with Helicobacter pylori eradication failure. We aimed in this study to investigate the relationship of gastric density of H. pylori, the occurrence/degree of gastric atrophy, and intestinal metaplasia (IM) with success rate of H. pylori eradication. Two hundred consecutive treatment naive patients who received bismuth containing standart quadruple treatment due to H. pylori infection documented by histopathological examination of two antral or two corpal biopsies entered this retrospective study. The updated Sydney system was used to grade the activity of gastritis, density of H. pylori colonization, atrophy, and IM. Stages III and IV of operative link for gastritis assessment (OLGA) or the operative link on gastric intestinal metaplasia assessment (OLGIM) stages was considered as severe gastritis. H. pylori eradication was determined via stool H. pylori antigen test performed 4 weeks after the end of therapy. The presence of gastric atrophy and IM was significantly higher in patients with eradication failure (p = 0.001 and 0.01, respectively). Severe gastritis (OLGA III-IV and OLGIM III-IV) rates were higher in eradication failure group. A multiple linear regression analysis showed that OLGA and OLGIM stages were to be independent risk factors for eradication failure (p = 0.03 and 0.01, respectively). Our results suggested that histopathologically severe gastritis may cause H. pylori eradication failure. In addition, we found that H. pylori density was not a risk factor for treatment failure in patients who receive quadruple treatment.

Economic evaluation of Helicobacter pylori eradication in the CADET-Hp randomized controlled trial of H. pylori-positive primary care patients with uninvestigated dyspepsia.

PubMed

Chiba, N; Veldhuyzen Van Zanten, S J O; Escobedo, S; Grace, E; Lee, J; Sinclair, P; Barkun, A; Armstrong, D; Thomson, A B R

2004-02-01

Adult Helicobacter pylori-positive patients by 13C-urea breath test with uninvestigated dyspepsia symptoms were randomized to 1-week eradication treatment with omeprazole, metronidazole and clarithromycin (OMC) vs. omeprazole and placebo antimicrobials (OPP) in the Canadian Adult Dyspepsia Empiric Treatment-H. pylori-positive (CADET-Hp) study. To perform an economic evaluation of this 1-year study. Following blind eradication treatment, family practitioners managed patients according to their usual practices. Health resource utilization information was collected prospectively. From the mean costs of the health resources consumed and the treatment outcomes, the incremental cost-effectiveness ratios and incremental net benefits of eradication treatment vs. OPP were determined. Eradication therapy significantly improved dyspepsia symptoms (treatment success: OMC, 50%; OPP, 36%; P = 0.02). The incremental cost-effectiveness ratio of OMC vs. OPP was - 387 Canadian dollars (CAD$) per treatment success (90% CI, - CAD$1707, CAD$607), indicating a lower cost with treatment success. The incremental net benefit analysis showed that H. pylori eradication was cost-effective if the willingness-to-pay value exceeded a nominal figure of CAD$100 from a health service perspective or CAD$607 from the societal perspective. In uninvestigated patients presenting with dyspepsia at the primary care level, eradication of H. pylori in those who are H. pylori positive leads to a cost-effective improvement in dyspepsia symptoms compared with a strategy of not eradicating H. pylori in these patients.

Combined effects of photodynamic therapy and irrigants in disinfection of root canals.

PubMed

Susila, Anand V; Sugumar, R; Chandana, C S; Subbarao, C V

2016-06-01

In this study, the combined effects of photodynamic therapy and irrigants in eradicating common endodontic pathogens are evaluated. Roots of 80 extracted single rooted teeth are divided into 2 groups (1) mechanical flushing; (2) antibacterial irrigation. After cleaning and shaping, they are inoculated with either (A) Streptococcus mutans or (B) Enterococcus faecalis and incubated. They are again subdivided and either only irrigated or irrigated and lased. Dentin shavings are taken from root canal walls and cultured. Statistical analysis using One-Way ANOVA and Post-hoc tests are done. The combination eradicated both bacteria. Antibacterial irrigants controlled S. mutans better than PDT (p = 0.041). The combination of PDT and antibacterial irrigation proposed in this study can be used in all primary cases for thorough and reliable disinfection of root canals but may be highly effective in resistant cases like endodontic failures, as E. faecalis is prevalent in such cases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Smallpox vaccination: an early start of modern medicine in America.

PubMed

Liebowitz, Dan

2017-01-01

Smallpox was eradicated by the World Health Organization in 1980. Before its eradication thedisease had a mortality rate upwards of 50% and had a significant impact on society. During theAmerican Revolutionary war, smallpox outbreaks were impeding the American war effort until1777 when George Washington carried out a mass inoculation campaign in the ContinentalArmy that reduced the mortality from smallpox to less than 2%. Inoculation was an early formof vaccination that used live virus from active pustules to induce a milder, but still sometimesdeadly, case of disease. Washington has been credited with helping to ease the burden ofsmallpox on the Army which improved the odds of success against the British. When EdwardJenner's vaccine reached America it was more readily accepted by political and medical leadersdue the success of Washington's inoculation campaign. The Founding Fathers argued thatsmallpox vaccination was the greatest discovery in modern medicine and they were likely correctthat it helped to usher in the modern era of vaccinology.

Targeted DNA Mutagenesis for the Cure of Chronic Viral Infections

PubMed Central

Schiffer, Joshua T.; Aubert, Martine; Weber, Nicholas D.; Mintzer, Esther; Stone, Daniel

2012-01-01

Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and herpes simplex virus (HSV) have been incurable to date because effective antiviral therapies target only replicating viruses and do not eradicate latently integrated or nonreplicating episomal viral genomes. Endonucleases that can target and cleave critical regions within latent viral genomes are currently in development. These enzymes are being engineered with high specificity such that off-target binding of cellular DNA will be absent or minimal. Imprecise nonhomologous-end-joining (NHEJ) DNA repair following repeated cleavage at the same critical site may permanently disrupt translation of essential viral proteins. We discuss the benefits and drawbacks of three types of DNA cleavage enzymes (zinc finger endonucleases, transcription activator-like [TAL] effector nucleases [TALENs], and homing endonucleases [also called meganucleases]), the development of delivery vectors for these enzymes, and potential obstacles for successful treatment of chronic viral infections. We then review issues regarding persistence of HIV-1, HBV, and HSV that are relevant to eradication with genome-altering approaches. PMID:22718830

Determinants of Health Disparities: The Perennial Struggle against Polio in Nigeria

PubMed Central

Osazuwa-Peters, Nosayaba

2011-01-01

Polio remains a global public health issue, and even though it has been eradicated from most countries of the world, countries like Nigeria, the largest black nation on earth, threatens the dream of total eradication of polio from the surface of the earth. Transmission of wild polio virus has never been eliminated in Nigeria, but even worse is the number of countries, both in Sub-Saharan Africa and all over the world that has become re-infected by polio virus strains from Northern Nigeria in recent past. Although a lot has been documented about the Nigerian polio struggle, one aspect that has received little attention on this issue is ethnic and geographic disparities between the Southern and the Northern parts of Nigeria. Understanding these disparities involved in polio virus transmission in Nigeria, as well as the social determinants of health prevalent in Northern Nigeria will help government and other stakeholders and policy makers to synergize their efforts in the fight against this perennial scourge. PMID:21811651

Legacy of Polio—Use of India’s Social Mobilization Network for Strengthening of the Universal Immunization Program in India

PubMed Central

Deutsch, Nicole; Singh, Vivek; Curtis, Rod; Siddique, Anisur Rahman

2017-01-01

Abstract The Social Mobilization Network (SMNet) has been lauded as one of the most successsful community engagement strategies in public health for its role in polio elimination in India. The UNICEF-managed SMNet was created as a strategy to eradicate polio by engaging >7000 frontline social mobilizers to advocate for vaccination in some of the most underserved, marginalized, and at-risk communities in India. This network focused initially on generating demand for polio vaccination but later expanded its messaging to promote routine immunization and other health and sanitation interventions related to maternal and children’s health. As an impact of the network’s interventions, in collaboration with other eradication efforts, these high-risk pockets witnessed an increase in full routine immunization coverage. The experience of the SMNet offers lessons for health-system strengthening for social mobilization and promoting positive health behaviors for other priority health programs like the Universal Immunization Program. PMID:28838190

System development of the Screwworm Eradication Data System (SEDS) algorithm

NASA Technical Reports Server (NTRS)

Arp, G.; Forsberg, F.; Giddings, L.; Phinney, D.

1976-01-01

The use of remotely sensed data is reported in the eradication of the screwworm and in the study of the role of the weather in the activity and development of the screwworm fly. As a result, the Screwworm Eradication Data System (SEDS) algorithm was developed.

Can Economic Analysis Contribute to Disease Elimination and Eradication? A Systematic Review

PubMed Central

Sicuri, Elisa; Evans, David B.; Tediosi, Fabrizio

2015-01-01

Background Infectious diseases elimination and eradication have become important areas of focus for global health and countries. Due to the substantial up-front investments required to eliminate and eradicate, and the overall shortage of resources for health, economic analysis can inform decision making on whether elimination/eradication makes economic sense and on the costs and benefits of alternative strategies. In order to draw lessons for current and future initiatives, we review the economic literature that has addressed questions related to the elimination and eradication of infectious diseases focusing on: why, how and for whom? Methods A systematic review was performed by searching economic literature (cost-benefit, cost-effectiveness and economic impact analyses) on elimination/eradication of infectious diseases published from 1980 to 2013 from three large bibliographic databases: one general (SCOPUS), one bio-medical (MEDLINE/PUBMED) and one economic (IDEAS/REPEC). Results A total of 690 non-duplicate papers were identified from which only 43 met the inclusion criteria. In addition, only one paper focusing on equity issues, the “for whom?” question, was found. The literature relating to “why?” is the largest, much of it focusing on how much it would cost. A more limited literature estimates the benefits in terms of impact on economic growth with mixed results. The question of how to eradicate or eliminate was informed by an economic literature highlighting that there will be opportunities for individuals and countries to free-ride and that forms of incentives and/or disincentives will be needed. This requires government involvement at country level and global coordination. While there is little doubt that eliminating infectious diseases will eventually improve equity, it will only happen if active steps to promote equity are followed on the path to elimination and eradication. Conclusion The largest part of the literature has focused on costs and economic benefits of elimination/eradication. To a lesser extent, challenges associated with achieving elimination/eradication and ensuring equity have also been explored. Although elimination and eradication are, for some diseases, good investments compared with control, countries’ incentives to eliminate do not always align with the global good and the most efficient elimination strategies may not prioritize the poorest populations. For any infectious disease, policy-makers will need to consider realigning contrasting incentives between the individual countries and the global community and to assure that the process towards elimination/eradication considers equity. PMID:26070135

A novel tridentate coordination mode for the carbonatonickel system exhibited in an unusual hexanuclear nickel(II) mu3-carbonato-bridged complex.

PubMed

Anderson, James C; Blake, Alexander J; Moreno, Rafael Bou; Raynel, Guillaume; van Slageren, Joris

2009-11-14

The fixation of CO(2) at ambient temperature has been achieved by the reaction of Ni(cod)(2) and TMEDA in CO(2) saturated THF that yields a novel hexanuclear nickel(II) mu(3)-carbonato bridged complex [Ni(6)(mu(3)-CO(3))(4)(TMEDA)(6)(H(2)O)(12)](OH)(4) in 59% yield. The complex was characterised by MS analysis and the structure corroborated by single-crystal X-ray crystallography. The complex exhibits a rare carbonato binding mode for Ni(II) complexes and moderately strong antiferromagnetic interactions.

Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible new twist on smallpox therapy.

PubMed

Osheroff, Neil

2006-10-01

Smallpox is a serious and highly contagious disease that is caused by the variola virus. It is one of the most severe infectious human diseases known, with mortality rates as high as 30%. A successful worldwide vaccination program led to the eradication of smallpox in 1980. However, the high transmission rate of variola virus, coupled with the deadly nature of smallpox, makes this virus a potentially devastating weapon for bioterrorism. Currently, there is no specific treatment for smallpox. However, a recent article on the structure of a variola topoisomerase IB-DNA complex provides an intriguing starting point for the rational design of drugs with potential activity against smallpox.

Helicobacter pylori eradication treatment does not benefit patients with nonulcer dyspepsia.

PubMed

Froehlich, F; Gonvers, J J; Wietlisbach, V; Burnand, B; Hildebrand, P; Schneider, C; Saraga, E; Beglinger, C; Vader, J P

2001-08-01

The aim of this study was to assess the still controversial role of treatment of Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia. We conducted a double-blind, randomized, placebo-controlled, multicenter trial comparing the efficacy of 7 days of eradication treatment (lansoprazole 15 mg b.i.d., amoxicillin I g b.i.d., and clarithromycin 500 mg b.i.d.) with a control treatment (lansoprazole 15 mg b.i.d. and placebo) in H. pylori-infected patients with nonulcer dyspepsia. 13C breath tests were performed at baseline and during follow-up. We assessed patient symptoms, health status (based on the SF-12 questionnaire), patient satisfaction, drug consumption, health care consultation behavior, and absenteeism related to dyspepsia over a 1-yr period. A total of 74 patients randomized to eradication treatment and 70 patients randomized to placebo were compared. The rate of eradication of H. pylori infection was 75% in the active treatment group and 4% in the placebo group (p < 0.005). The symptom score improved to a similar extent in the group receiving active treatment (-4.0; 95% CI = -5.0 to -3.0) and placebo (-3.6; 95% CI = -4.5 to -2.7). Treatment response was not related to the severity or duration of initial symptoms or to the severity of gastritis on histology. Quality of life scores were comparable at 12 months. There was no significant difference in dyspepsia-related absenteeism or satisfaction with management of NUD. Patients receiving active treatment were more likely not to have had to use any dyspepsia treatment over the 12 months (60.8% vs 44.3%; p = 0.047). This study did not demonstrate any substantial benefit of curing H. pylori infection in patients with nonulcer dyspepsia. The study adds further evidence that H. pylori is not the main pathogenetic or therapeutic target in these patients.

Coordination as a best practice from the polio eradication initiative: Experiences from five member states in the African region of the World Health Organization.

PubMed

Okeibunor, Joseph; Nsubuga, Peter; Salla, Mbaye; Mihigo, Richard; Mkanda, Pascal

2016-10-10

As part of the efforts to eradicate polioviruses in the African Region, structures were put in place to ensure coordinated mobilization and deployment of resources within the framework of the global polio eradication initiative (PEI). The successes of these structures made them not only attractive to other public health interventions, but also caused them to be deployed to the response efforts of other diseases interventions, without any systematic documentation. This article documents the contributions of PEI coordination units to other public health interventions in the African Region of World Health Organization METHODS: We reviewed the contributions of PEI coordination units to other public health interventions in five countries in the African Region. The analysis identified significant involvement of PEI coordination structures in the implementation of routine immunization programs in all the countries analyzed. Similarly, maternal and child health programs were planned, implemented, monitored and evaluation the Inter-Agency Coordination Committees of the PEI programs in the different countries. The hubs system used in PEI in Chad facilitated the efficient coordination of resources for immunization and other public health interventions in Chad. Similarly, in the Democratic Republic of Congo PEI led coordination activities benefited other public health programs like disease control and the national nutrition program, the national malaria control program, and the tuberculosis control program. In Nigeria, the polio Expert Review Committee effectively deployed the Emergency Operation Center for the implementation of prioritized strategies and activities of the National Polio Eradication Emergency Plan, and it was utilized in the response to Ebola Virus Disease outbreak in the country. The PEI-led coordination systems are thus recognized as having made significant contribution to the coordination and delivery of other public health interventions in the African Region. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A nationwide database linking information on the hosts with sequence data of their virus strains: A useful tool for the eradication of bovine viral diarrhea (BVD) in Switzerland.

PubMed

Stalder, Hanspeter; Hug, Corinne; Zanoni, Reto; Vogt, Hans-Rudolf; Peterhans, Ernst; Schweizer, Matthias; Bachofen, Claudia

2016-06-15

Pestiviruses infect a wide variety of animals of the order Artiodactyla, with bovine viral diarrhea virus (BVDV) being an economically important pathogen of livestock globally. BVDV is maintained in the cattle population by infecting fetuses early in gestation and, thus, by generating persistently infected (PI) animals that efficiently transmit the virus throughout their lifetime. In 2008, Switzerland started a national control campaign with the aim to eradicate BVDV from all bovines in the country by searching for and eliminating every PI cattle. Different from previous eradication programs, all animals of the entire population were tested for virus within one year, followed by testing each newborn calf in the subsequent four years. Overall, 3,855,814 animals were tested from 2008 through 2011, 20,553 of which returned an initial BVDV-positive result. We were able to obtain samples from at least 36% of all initially positive tested animals. We sequenced the 5' untranslated region (UTR) of more than 7400 pestiviral strains and compiled the sequence data in a database together with an array of information on the PI animals, among others, the location of the farm in which they were born, their dams, and the locations where the animals had lived. To our knowledge, this is the largest database combining viral sequences with animal data of an endemic viral disease. Using unique identification tags, the different datasets within the database were connected to run diverse molecular epidemiological analyses. The large sets of animal and sequence data made it possible to run analyses in both directions, i.e., starting from a likely epidemiological link, or starting from related sequences. We present the results of three epidemiological investigations in detail and a compilation of 122 individual investigations that show the usefulness of such a database in a country-wide BVD eradication program. Copyright © 2015 Elsevier B.V. All rights reserved.

Airman Scholar Journal. Volume 17, Fall 2011

DTIC Science & Technology

2011-01-01

and epidemics can wreak on weak governments. Age-old diseases such as cholera , tuberculosis, and malaria, coupled with emerging diseases like...six to three (yellow fever, plague and cholera ) and to mark the global eradication of smallpox.”30 The 2005 revisions to the IHR, which entered...crucial issue for international security are the resur- gence of the some of the human race’s oldest nemeses in the forms of cholera , malaria, and

A Complex Endomembrane System in the Archaeon Ignicoccus hospitalis Tapped by Nanoarchaeum equitans

DOE PAGES

Heimerl, Thomas; Flechsler, Jennifer; Pickl, Carolin; ...

2017-06-13

Based on serial sectioning, focused ion beam scanning electron microscopy (FIB/SEM), and electron tomography, we depict in detail the highly unusual anatomy of the marine hyperthermophilic crenarchaeon, Ignicoccus hospitalis. Our data support a complex and dynamic endomembrane system consisting of cytoplasmic protrusions, and with secretory function. Moreover, we reveal that the cytoplasm of the putative archaeal ectoparasite Nanoarchaeum equitans can get in direct contact with this endomembrane system, complementing and explaining recent proteomic, transcriptomic and metabolomic data on this inter-archaeal relationship. In addition, we identified a matrix of filamentous structures and/or tethers in the voluminous inter-membrane compartment (IMC) of I.more » hospitalis, which might be responsible for membrane dynamics. Overall, this unusual cellular compartmentalization, ultrastructure and dynamics in an archaeon that belongs to the recently proposed TACK superphylum prompts speculation that the eukaryotic endomembrane system might originate from Archaea.« less

Unusual planned complex suicide committed with a muzzle-loading pistol in combination with subsequent hanging.

PubMed

Ondruschka, Benjamin; Morgenthal, Sylvia; Dreβler, Jan; Bayer, Ronny

2016-11-01

In Germany, suicides by firearms are not very common in contrast to deaths by hanging and intoxications. The use of historical muzzle-loading firearms in the context of suicides is a rarity. Contact shots from muzzle loaders cause an unusual wound morphology with extensive soot soiling. We report the case of a 59-year-old man, who committed a planned complex suicide by shooting into his mouth with a replica percussion gun in combination with hanging. The gunshot injury showed strong explosive effects in the oral cavity with fractures of the facial bones and the skull associated with cerebral evisceration (so-called Krönlein shot). Due to the special constellation of the case with hanging immediately after the shot, external bleeding from the head injuries was only moderate. Therefore, the head injuries could be assessed and partially reconstructed already at the scene.

Unusual strains of Microsporum audouinii causing tinea in Europe.

PubMed

Brasch, J; Müller, S; Gräser, Y

2015-10-01

We comment on an unusual strain of Microsporum (M.) audouinii. It was isolated from tinea corporis of a boy who lived in Germany and most likely had acquired his infection during a stay on a farm with animal husbandry in Poland. The strain showed features of M. canis (plenty of markedly rough-walled macroconidia, growth on rice, positive hair perforation) as well as of M. audouinii (white thallus, long macroconidia with central constriction) and in vitro it degraded hair of various mammals. Because its ribosomal internal transcribed spacer region showed 99.9% homology to a M. audouinii reference strain it was finally identified as M. audouinii. We relate these findings with recent observations of M. audouinii causing tinea in Europe. This appraisal suggests that irrespective of an identical ribosomal ITS region distinct M. audouinii strains can display a spectrum of morphological and physiological features that is broader than currently outlined in mycological textbooks. Certain unusual characteristics like an enhanced capacity to utilise keratins may even be associated with unexpected transmission routes. Above all sporadic M. audouinii infections in Europe that bear no relation to an endemic area should be analysed from this perspective. © 2015 Blackwell Verlag GmbH.

Eradicating a Disease: Lessons from Mathematical Epidemiology

ERIC Educational Resources Information Center

Glomski, Matthew; Ohanian, Edward

2012-01-01

Smallpox remains the only human disease ever eradicated. In this paper, we consider the mathematics behind control strategies used in the effort to eradicate smallpox, from the life tables of Daniel Bernoulli, to the more modern susceptible-infected-removed (SIR)-type compartmental models. In addition, we examine the mathematical feasibility of…

An overview of the development of remote sensing techniques for the screwworm eradication program

NASA Technical Reports Server (NTRS)

Barnes, C. M.; Forsberg, F. C.

1975-01-01

The current status of remote sensing techniques developed for the screwworm eradication program of the Mexican-American Screwworm Eradication Commission was reported. A review of the type of data and equipment used in the program is presented. Future applications of remote sensing techniques are considered.

28 CFR Appendix B to Part 61 - Drug Enforcement Administration Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2011 CFR

2011-07-01

... substances Chemical eradication of plant species from which controlled substances may be extracted... substances Storage and destruction of controlled substances Manual eradication of plant species from which... consider environmental documents Eradication of plant species from which controlled substances may be...

Measles and rubella eradication.

PubMed

Hinman, Alan R

2018-01-02

This article discusses concepts of eradication, some issues relating to vertical and horizontal public health programs, some current issues relating to measles and rubella, and what we need to do about them. It concludes that measles and rubella/CRS can and should be eradicated. A target date should be established in 2020 (or before). Eradication can only be accomplished in the context of strengthening ongoing immunization services and strengthening surveillance so it can guide activities. Additional resources will be required to achieve the goal. Copyright © 2017 Elsevier Ltd. All rights reserved.

The final stages of the global eradication of poliomyelitis.

PubMed

Grassly, Nicholas C

2013-08-05

The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI's response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis.

Vacated niches, competitive release and the community ecology of pathogen eradication

PubMed Central

Lloyd-Smith, James O.

2013-01-01

A recurring theme in the epidemiological literature on disease eradication is that each pathogen occupies an ecological niche, and eradication of one pathogen leaves a vacant niche that favours the emergence of new pathogens to replace it. However, eminent figures have rejected this view unequivocally, stating that there is no basis to fear pathogen replacement and even that pathogen niches do not exist. After exploring the roots of this controversy, I propose resolutions to disputed issues by drawing on broader ecological theory, and advance a new consensus based on robust mechanistic principles. I argue that pathogen eradication (and cessation of vaccination) leads to a ‘vacated niche’, which could be re-invaded by the original pathogen if introduced. Consequences for other pathogens will vary, with the crucial mechanisms being competitive release, whereby the decline of one species allows its competitors to perform better, and evolutionary adaptation. Hence, eradication can cause a quantitative rise in the incidence of another infection, but whether this leads to emergence as an endemic pathogen depends on additional factors. I focus on the case study of human monkeypox and its rise following smallpox eradication, but also survey how these ideas apply to other pathogens and discuss implications for eradication policy. PMID:23798698

Successes and shortcomings of polio eradication: a transmission modeling analysis.

PubMed

Mayer, Bryan T; Eisenberg, Joseph N S; Henry, Christopher J; Gomes, M Gabriela M; Ionides, Edward L; Koopman, James S

2013-06-01

Polio eradication is on the cusp of success, with only a few regions still maintaining transmission. Improving our understanding of why some regions have been successful and others have not will help with both global eradication of polio and development of more effective vaccination strategies for other pathogens. To examine the past 25 years of eradication efforts, we constructed a transmission model for wild poliovirus that incorporates waning immunity (which affects both infection risk and transmissibility of any resulting infection), age-mediated vaccination rates, and transmission of oral polio vaccine. The model produces results consistent with the 4 country categories defined by the Global Polio Eradication Program: elimination with no subsequent outbreaks; elimination with subsequent transient outbreaks; elimination with subsequent outbreaks and transmission detected for more than 12 months; and endemic polio transmission. Analysis of waning immunity rates and oral polio vaccine transmissibility reveals that higher waning immunity rates make eradication more difficult because of increasing numbers of infectious adults, and that higher oral polio vaccine transmission rates make eradication easier as adults become reimmunized. Given these dynamic properties, attention should be given to intervention strategies that complement childhood vaccination. For example, improvement in sanitation can reduce the reproduction number in problematic regions, and adult vaccination can lower adult transmission.

Helicobacter pylori eradication and reflux disease onset: did gastric acid get "crazy"?

PubMed

Zullo, Angelo; Hassan, Cesare; Repici, Alessandro; Bruzzese, Vincenzo

2013-02-14

Gastroesophageal reflux disease (GORD) is highly prevalent in the general population. In the last decade, a potential relationship between Helicobacter pylori (H. pylori) eradication and GORD onset has been claimed. The main putative mechanism is the gastric acid hypersecretion that develops after bacterial cure in those patients with corpus-predominant gastritis. We performed a critical reappraisal of the intricate pathogenesis and clinical data available in this field. Oesophagitis onset after H. pylori eradication in duodenal ulcer patients has been ascribed to a gastric acid hypersecretion, which could develop following body gastritis healing. However, the absence of an acid hypersecretive status in these patients is documented by both pathophysiology and clinical studies. Indeed, duodenal ulcer recurrence is virtually abolished following H. pylori eradication. In addition, intra-oesophageal pH recording studies failed to demonstrated increased acid reflux following bacterial eradication. Moreover, oesophageal manometric studies suggest that H. pylori eradication would reduce--rather than favor--acid reflux into the oesophagus. Finally, data of clinical studies would suggest that H. pylori eradication is not significantly associated with either reflux symptoms or erosive oesophagitis onset, some data suggesting also an advantage in curing the infection when oesophagitis is already present. Therefore, the legend of "crazy acid" remains--as all the others--a fascinating, but imaginary tale.

Helicobacter pylori and Gastric Mucosa-associated Lymphoid Tissue (MALT) Lymphoma: Updated Review of Clinical Outcomes and the Molecular Pathogenesis.

PubMed

Suzuki, Hidekazu; Saito, Yoshimasa; Hibi, Toshifumi

2009-06-01

In most H. pylori-positive patients, gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress both endoscopically and histopathologically after H. pylori eradication, but no factors that can be predictive of the response to the eradication have been definitively identified, and there is little information on how to determine the optimal observation period before additional treatment can be started. Here, clinical studies dealing with the diagnosis and treatment of gastric MALT lymphomas and H. pylori published during the last 5 years were systematically reviewed, and studies identifying the molecular approaches involved in the pathogenesis were summarized. Most of the clinical studies indicate a favorable effect of H. pylori eradication on the clinical outcome of gastric MALT lymphomas. Some studies suggest the necessity of additional treatment in nonresponders to H. pylori eradication, while others suggest the adoption of a watch-and-wait strategy. The molecular characteristics of MALT lymphomas could play an important role in prognostic prediction and the selection of further therapeutic intervention after the eradication. This updated review of gastric MALT lymphomas illustrates the potential efficacy of H. pylori eradication in tumor remission, but further molecular characterization is necessary to establish the most suitable therapeutic strategy for patients who do not respond to eradication.

Cytoplasmic peptide:N-glycanase cleaves N-glycans on a carboxypeptidase Y mutant during ERAD in Saccharomyces cerevisiae.

PubMed

Hosomi, Akira; Suzuki, Tadashi

2015-04-01

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a pathway by which misfolded or improperly assembled proteins in the ER are directed to degradation. The cytoplasmic peptide:N-glycanase (PNGase) is a deglycosylating enzyme that cleaves N-glycans from misfolded glycoproteins during the ERAD process. The mutant form of yeast carboxypeptidase Y (CPY*) is an ERAD model substrate that has been extensively studied in yeast. While a delay in the degradation of CPY* in yeast cells lacking the cytoplasmic PNGase (Png1 in yeast) was evident, the in vivo action of PNGase on CPY* has not been detected. We constructed new ERAD substrates derived from CPY*, bearing epitope tags at both N- and C-termini and examined the degradation intermediates observed in yeast cells with compromised proteasome activity. The occurrence of the PNGase-mediated deglycosylation of intact CPY* and its degradation intermediates was evident. A major endoproteolytic reaction on CPY* appears to occur between amino acid 400 and 404. The findings reported herein clearly indicate that PNGase indeed releases N-glycans from CPY* during the ERAD process in vivo. This report implies that the PNGase-mediated deglycosylation during the ERAD process may occur more abundantly than currently envisaged. Copyright © 2014 Elsevier B.V. All rights reserved.

The final stages of the global eradication of poliomyelitis

PubMed Central

Grassly, Nicholas C.

2013-01-01

The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI's response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis. PMID:23798688

Elimination of Guinea Worm Disease in Ethiopia; Current Status of the Disease's, Eradication Strategies and Challenges to the End Game.

PubMed

Beyene, Habtamu Bedimo; Bekele, Abyot; Shifara, Amanu; Ebstie, Yehenew A; Desalegn, Zelalem; Kebede, Zeyede; Mulugeta, Abate; Deribe, Kebede; Tadesse, Zerihun; Abebe, Tamrat; Kebede, Biruck; Abrha, Getaneh; Jima, Daddi

2017-01-01

Dracunculiasis, also named Guinea Worm Disease (GWD), is one of the Neglected Tropical Diseases (NTDs) caused by a parasitic nematode known as Dracunculus medinensis and has been known since antiquity as 'fiery serpent' from Israelites. It is transmitted to humans via drinking contaminated water containing infective copepods. Given, its feasibility for eradication, the Guinea Worm Eradication Program (GWEP) was launched in 1980 with the aim of eradicating the disease. Since its inception, GWEP has made an extraordinary progress in interrupting transmission. Globally, the number of reported cases reduced from 3.5 million in 20 countries in 1986 to only 22 cases in 2015 from only four countries namely South Sudan, Mali, Chad and Ethiopia. Since Mali has interrupted transmission of GWD in 2016, currently, the disease remains endemic in only three sub-Saharan African countries namely, South Sudan, Chad and Ethiopia. Each endemic country has its own national Guinea Worm Eradication Program. In Ethiopia, the Ethiopian Dracunculiasis Eradication Program (EDEP) which was established in 1993 has made remarkable move towards interruption of disease transmission and now the endgame is fast approaching. The EDEP with support mainly from The Carter Center, WHO, and UNICEF has reduced GWD by more than 99% from 1994 to 2015. In 2015, only 3 indigenous cases in humans and 14 in animals (13 in dogs and 1 in baboon) were reported. In 2016, 3 human cases, 14 dogs and 2 baboon infections were reported.. Refugee influx from the Republic of South Sudan (RSS), increased animal infections with unknown role in transmission of Dracunculiasis, the presence of hard to reach communities and lack of safe water sources in remote non-village areas remain among important challenges at this final stage of GWD eradication in Ethiopia. This paper reviews progress made towards Guinea Worm Eradication with a focus on the experience of the Ethiopian Dracunculiasis Eradication Program (EDEP), and intervention strategies that need further intensification to realize the endgame. Eradication strategies encompassing community education for behavioral change including raising awareness towards cash reward for reporting Guniea Worm Disease (GWD) and animal infection, case containment, surveillance systems, provision of safe water supply, and ABATE chemical application are discussed. It also summarizes challenges the end game faces and recommendations to strengthen the eradication effort.

Elimination of Guinea Worm Disease in Ethiopia; Current Status of the Disease’s, Eradication Strategies and Challenges to the End Game

PubMed Central

Beyene, Habtamu Bedimo; Bekele, Abyot; Shifara, Amanu; Ebstie, Yehenew A.; Desalegn, Zelalem; Kebede, Zeyede; Mulugeta, Abate; Deribe, Kebede; Tadesse, Zerihun; Abebe, Tamrat; Kebede, Biruck; Abrha, Getaneh; Jima, Daddi

2017-01-01

Dracunculiasis, also named Guinea Worm Disease (GWD), is one of the Neglected Tropical Diseases (NTDs) caused by a parasitic nematode known as Dracunculus medinensis and has been known since antiquity as ‘fiery serpent’ from Israelites. It is transmitted to humans via drinking contaminated water containing infective copepods. Given, its feasibility for eradication, the Guinea Worm Eradication Program (GWEP) was launched in 1980 with the aim of eradicating the disease. Since its inception, GWEP has made an extraordinary progress in interrupting transmission. Globally, the number of reported cases reduced from 3.5 million in 20 countries in 1986 to only 22 cases in 2015 from only four countries namely South Sudan, Mali, Chad and Ethiopia. Since Mali has interrupted transmission of GWD in 2016, currently, the disease remains endemic in only three sub-Saharan African countries namely, South Sudan, Chad and Ethiopia. Each endemic country has its own national Guinea Worm Eradication Program. In Ethiopia, the Ethiopian Dracunculiasis Eradication Program (EDEP) which was established in 1993 has made remarkable move towards interruption of disease transmission and now the endgame is fast approaching. The EDEP with support mainly from The Carter Center, WHO, and UNICEF has reduced GWD by more than 99% from 1994 to 2015. In 2015, only 3 indigenous cases in humans and 14 in animals (13 in dogs and 1 in baboon) were reported. In 2016, 3 human cases, 14 dogs and 2 baboon infections were reported.. Refugee influx from the Republic of South Sudan (RSS), increased animal infections with unknown role in transmission of Dracunculiasis, the presence of hard to reach communities and lack of safe water sources in remote non-village areas remain among important challenges at this final stage of GWD eradication in Ethiopia. This paper reviews progress made towards Guinea Worm Eradication with a focus on the experience of the Ethiopian Dracunculiasis Eradication Program (EDEP), and intervention strategies that need further intensification to realize the endgame. Eradication strategies encompassing community education for behavioral change including raising awareness towards cash reward for reporting Guniea Worm Disease (GWD) and animal infection, case containment, surveillance systems, provision of safe water supply, and ABATE chemical application are discussed. It also summarizes challenges the end game faces and recommendations to strengthen the eradication effort. PMID:28878428

Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people.

PubMed

Ford, Alexander C; Gurusamy, Kurinchi Selvan; Delaney, Brendan; Forman, David; Moayyedi, Paul

2016-04-19

Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4. To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved. In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards. We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible. A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy. Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out.

The remarkable frequency of human immunodeficiency virus type 1 genetic recombination.

PubMed

Onafuwa-Nuga, Adewunmi; Telesnitsky, Alice

2009-09-01

The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination--a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates--occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication.

Impact of environment on dynamics of exciton complexes in a WS2 monolayer

NASA Astrophysics Data System (ADS)

Jakubczyk, Tomasz; Nogajewski, Karol; Molas, Maciej R.; Bartos, Miroslav; Langbein, Wolfgang; Potemski, Marek; Kasprzak, Jacek

2018-07-01

Scientific curiosity to uncover original optical properties and functionalities of atomically thin semiconductors, stemming from unusual Coulomb interactions in the two-dimensional geometry and multi-valley band structure, drives the research on monolayers of transition metal dichalcogenides (TMDs). While recent works ascertained the exotic energetic schemes of exciton complexes in TMDs, we here infer their unusual coherent dynamics occurring on subpicosecond time scale. The dynamics is largely affected by the disorder landscape on the submicron scale, thus can be uncovered using four-wave mixing in the frequency domain, which enables microscopic investigations and imaging. Focusing on a WS2 monolayer, we observe that exciton coherence is lost primarily due to interaction with phonons and relaxation processes towards optically dark excitonic states. Notably, when temperature is low and disorder weak, excitons large coherence volume results in enhanced oscillator strength, allowing to reach the regime of radiatively limited dephasing. Additionally, we observe long valley coherence for the negatively charged exciton complex. We therefore elucidate the crucial role of exciton environment in the TMDs on its dynamics and show that revealed mechanisms are ubiquitous within this family.

Cardiac Paraganglioma Arising From the Right Atrioventricular Groove in a Paraganglioma-Pheochromocytoma Family Syndrome With Evidence of SDHB Gene Mutation: An Unusual Presentation.

PubMed

Del Forno, Benedetto; Zingaro, Carlo; Di Palma, Enza; Capestro, Filippo; Rescigno, Giuseppe; Torracca, Lucia

2016-09-01

Primary cardiac paragangliomas are extremely rare. Recently this neoplasm has been associated with a familiar syndrome as a result of mutation of genes that encode proteins in the mitochondrial complex II. We report a case of a 46-year-old woman having cases of vertebral paraganglioma in her family showing an unusual anatomic and clinical presentation of cardiac paraganglioma and expressing a genetic mutation never associated before with cardiac localization of this neoplasm. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Mechanical and thermal properties of planetologically important ices

NASA Technical Reports Server (NTRS)

Croft, Steven K.

1987-01-01

Two squences of ice composition were proposed for the icy satellites: a dense nebula model and a solar nebula model. Careful modeling of the structure, composition, and thermal history of satellites composed of these various ices requires quantitative information on the density, compressibility, thermal expansion, heat capacity, and thermal conductivity. Equations of state were fitted to the density data of the molecular ices. The unusual thermal and mechanical properties of the molecular and binary ices suggest a larger range of phenomena than previously anticipated, sufficiently complex perhaps to account for many of the unusual geologic phenomena found on the icy satellites.

mTOR at the Transmitting and Receiving Ends in Tumor Immunity

PubMed Central

Guri, Yakir; Nordmann, Thierry M.; Roszik, Jason

2018-01-01

Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis. PMID:29662490

mTOR at the Transmitting and Receiving Ends in Tumor Immunity.

PubMed

Guri, Yakir; Nordmann, Thierry M; Roszik, Jason

2018-01-01

Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

Killing of tumor cells: a drama in two acts.

PubMed

Giansanti, Vincenzo; Tillhon, Micol; Mazzini, Giuliano; Prosperi, Ennio; Lombardi, Paolo; Scovassi, A Ivana

2011-11-15

Cancer still represents a major health problem worldwide, which urges the development of more effective strategies. Resistance to chemotherapy, a major obstacle for cancer eradication, is mainly related to an intrinsic failure to activate the apoptotic pathways. However, a protective effect of autophagy toward cancer cells has been recently observed, thus adding further complexity to the development of an effective approach counteracting cancer cell growth and improving the response to therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

How much will it cost to eradicate lymphatic filariasis? An analysis of the financial and economic costs of intensified efforts against lymphatic filariasis.

PubMed

Kastner, Randee J; Sicuri, Elisa; Stone, Christopher M; Matwale, Gabriel; Onapa, Ambrose; Tediosi, Fabrizio

2017-09-01

Lymphatic filariasis (LF), a neglected tropical disease (NTD) preventable through mass drug administration (MDA), is one of six diseases deemed possibly eradicable. Previously we developed one LF elimination scenario, which assumes MDA scale-up to continue in all countries that have previously undertaken MDA. In contrast, our three previously developed eradication scenarios assume all LF endemic countries will undertake MDA at an average (eradication I), fast (eradication II), or instantaneous (eradication III) rate of scale-up. In this analysis we use a micro-costing model to project the financial and economic costs of each of these scenarios in order to provide evidence to decision makers about the investment required to eliminate and eradicate LF. Costing was undertaken from a health system perspective, with all results expressed in 2012 US dollars (USD). A discount rate of 3% was applied to calculate the net present value of future costs. Prospective NTD budgets from LF endemic countries were reviewed to preliminarily determine activities and resources necessary to undertake a program to eliminate LF at a country level. In consultation with LF program experts, activities and resources were further reviewed and a refined list of activities and necessary resources, along with their associated quantities and costs, were determined and grouped into the following activities: advocacy and communication, capacity strengthening, coordination and strengthening partnerships, data management, ongoing surveillance, monitoring and supervision, drug delivery, and administration. The costs of mapping and undertaking transmission assessment surveys and the value of donated drugs and volunteer time were also accounted for. Using previously developed scenarios and deterministic estimates of MDA duration, the financial and economic costs of interrupting LF transmission under varying rates of MDA scale-up were then modelled using a micro-costing approach. The elimination scenario, which includes countries that previously undertook MDA, is estimated to cost 929 million USD (95% Credible Interval: 884m-972m). Proceeding to eradication is anticipated to require a higher financial investment, estimated at 1.24 billion USD (1.17bn-1.30bn) in the eradication III scenario (immediate scale-up), with eradication II (intensified scale-up) projected at 1.27 billion USD (1.21bn-1.33bn), and eradication I (slow scale-up) estimated at 1.29 billion USD (1.23bn-1.34bn). The economic costs of the eradication III scenario are estimated at approximately 7.57 billion USD (7.12bn-7.94bn), while the elimination scenario is projected to have an economic cost of 5.21 billion USD (4.91bn-5.45bn). Countries in the AFRO region will require the greatest investment to reach elimination or eradication, but also stand to gain the most in cost savings. Across all scenarios, capacity strengthening and advocacy and communication represent the greatest financial costs, whereas mapping, post-MDA surveillance, and administration comprise the least. Though challenging to implement, our results indicate that financial and economic savings are greatest under the eradication III scenario. Thus, if eradication for LF is the objective, accelerated scale-up is projected to be the best investment.

Pseudo-enantiomeric chiral components and formation of the helical micro- and nanostructures in charge-transfer complexes

NASA Astrophysics Data System (ADS)

Langer, Jerzy J.; Hreczycho, Grzegorz

2018-03-01

Helical organic micro- and nanostructures are formed by a charge-transfer complex, cinchonidine-TCNQ. These unusual forms result from the chirality, the steric structure and specific interactions of cinchonidine molecules. These materials are semiconductors (10-4 S cm-1), with the typical absorption spectra in IR and UV-vis, but also have a characteristic of CD spectrum. Surprisingly, conductive micro and nano helices are not formed in pseudo-enantiomeric cinchonine, i.e. the complex of cinchonine and TCNQ.

Silver Complexes of Dihalogen Molecules.

PubMed

Malinowski, Przemysław J; Himmel, Daniel; Krossing, Ingo

2016-08-01

The perfluorohexane-soluble and donor-free silver compound Ag(A) (A=Al(OR(F) )4 ; R(F) =C(CF3 )3 ) prepared using a facile novel route has unprecedented capabilities to form unusual and weakly bound complexes. Here, we report on the three dihalogen-silver complexes Ag(Cl2 )A, Ag(Br2 )A, and Ag(I2 )A derived from the soluble silver compound Ag(A) (characterized by single-crystal/powder XRD, Raman spectra, and quantum-mechanical calculations). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Purtscher-like retinopathy: A rare complication of peribulbar anesthesia.

PubMed

Narendran, Siddharth; Saravanan, V R; Pereira, Merlyn

2016-06-01

Purtscher and Purtscher-like retinopathy is a distinctive retinal syndrome characterized by ischemic retinal whitening in a peripapillary pattern. We report a case of Purtscher-like retinopathy in a healthy 64-year-old man after a routine peribulbar anesthetic injection for cataract surgery. Although peribulbar anesthesia is considered to be a safer alternative to retrobulbar anesthesia, it has been associated with unusual but grave complications including central retinal artery occlusion.

Point-of-care controls for nosocomial legionellosis combined with chlorine dioxide potable water decontamination: a two-year survey at a Welsh teaching hospital.

PubMed

Hosein, I K; Hill, D W; Tan, T Y; Butchart, E G; Wilson, K; Finlay, G; Burge, S; Ribeiro, C D

2005-10-01

This study reports a two-year programme of attempted eradication of Legionella colonization in the potable water supply of a 1000-bed tertiary care teaching hospital in Wales. There was a simultaneous, point-of-care, sterile-water-only policy for all intensive care units (ICU) and bone marrow and renal transplant units in order to prevent acquisition of nosocomial Legionnaires' disease. The programme was initiated following a case of nosocomial pneumonia caused by Legionella pneumophila serogroup 1-Bellingham-like genotype A on the cardiac ICU. The case occurred 14 days after mitral and aortic valve replacement surgery. Clinical and epidemiological investigations implicated aspiration of hospital potable water as the mechanism of infection. Despite interventions with chlorine dioxide costing over 25000 UK pounds per annum, Legionella has remained persistently present in significant numbers (up to 20000 colony forming units/L) and with little reduction in the number of positive sites. Two further cases of nosocomial disease occurred over the following two-year period; in one case, aspiration of tap water was implicated again, and in the other case, instillation of contaminated water into the right main bronchus via a misplaced nasogastric tube was implicated. These cases arose because of inadvertent non-compliance with the sterile-water-only policy in high-risk locations. Enhanced clinical surveillance over the same two-year period detected no other cases of nosocomial disease. This study suggests that attempts at eradication of Legionella spp. from complex water systems may not be a cost-effective measure for prevention of nosocomial infections, and to the best of our knowledge is the first study from the UK to suggest that the introduction of a sterile-water-only policy for ICUs and other high-risk units may be a more cost-effective approach.

Roadmap to eliminate gastric cancer with Helicobacter pylori eradication and consecutive surveillance in Japan.

PubMed

Asaka, Masahiro; Kato, Mototsugu; Sakamoto, Naoya

2014-01-01

In Japan, the annual number of deaths from gastric cancer is approximately 50,000 and there has been no change over the last 50 years. So far, all efforts have been directed toward improving the detection of early gastric cancer by barium X-ray and endoscopy, since early cancer has a good prognosis, resulting in Japan having the best diagnostic capability for early gastric cancer worldwide. The 5-year survival rate of gastric cancer patients exceeds 60 % in Japan and is much higher than that in Europe and the US (20 %) because of this superior diagnosis of early gastric cancer. In February 2013, national health insurance coverage for Helicobacter pylori eradication therapy to treat H. pylori-associated chronic gastritis became available in Japan. H. pylori-associated gastritis leads to development of gastric and duodenal ulcers and gastric polyps. Therefore, providing treatment for gastritis is likely to substantially decrease the prevalence of both gastric and duodenal ulcers and polyps. Because treatment for H. pylori-associated gastritis, which leads to atrophic gastritis and gastric cancer, is now covered by health insurance in Japan, a strategy to eliminate gastric cancer-related deaths by taking advantage of this innovation was planned. According to this strategy, patients with gastritis will be investigated for H. pylori infection and those who are positive will receive eradication therapy followed by periodic surveillance. If this strategy is implemented, deaths from gastric cancer in Japan will decrease dramatically after 10-20 years.

Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory

PubMed Central

Díaz-Montero, C Marcela; Naga, Osama; Zidan, Abdel-Aziz A; Salem, Mohamed L; Pallin, Maria; Parmigiani, Anita; Walker, Gail; Wieder, Eric; Komanduri, Krishna; Cole, David J; Montero, Alberto J; Lichtenheld, Mathias G

2011-01-01

Adoptive T-cell therapy holds great promise for the treatment of metastatic melanoma. However, prohibitive costs associated with current technology required for culture and expansion of tumor-reactive T-cells, the need for intense preconditioning regimens to induce lymphopenia, and the unpredictable anti-tumor effect of adoptively transferred T-cells remain significant impediments for its clinical implementation. Here we report a simplified combinatorial approach that involves short activation of CD8+ T cells in the presence of IL-12 followed by adoptive transfer into tumor bearing animals after a single injection of cyclophosphamide. This approach resulted in complete eradication of B16 melanoma, and the establishment of long term immunological memory capable of fully protecting mice after a second B16 melanoma challenge. The activated donor cells were unique because they simultaneously exhibited traits for cytotoxic effector function, central memory-like, homing, and senescence. After tumor eradication and within three months after transfer, CD8+ cells exhibited a conventional memory CTL phenotype. Moreover, these memory CTLs acquired functional attributes characteristic of memory stem cells, including the ability to resist chemotherapy-induced toxicity. Our results suggest that short-term T-cell receptor signaling in the presence of IL-12 promotes promiscuous qualities in naïve CTL which - upon transfer into lymphopenic hosts- are sufficient to eradicate tumors and generate life-long tumor-specific memory. PMID:21915391

Unraveling the Transmission Ecology of Polio.

PubMed

Martinez-Bakker, Micaela; King, Aaron A; Rohani, Pejman

2015-06-01

Sustained and coordinated vaccination efforts have brought polio eradication within reach. Anticipating the eradication of wild poliovirus (WPV) and the subsequent challenges in preventing its re-emergence, we look to the past to identify why polio rose to epidemic levels in the mid-20th century, and how WPV persisted over large geographic scales. We analyzed an extensive epidemiological dataset, spanning the 1930s to the 1950s and spatially replicated across each state in the United States, to glean insight into the drivers of polio's historical expansion and the ecological mode of its persistence prior to vaccine introduction. We document a latitudinal gradient in polio's seasonality. Additionally, we fitted and validated mechanistic transmission models to data from each US state independently. The fitted models revealed that: (1) polio persistence was the product of a dynamic mosaic of source and sink populations; (2) geographic heterogeneity of seasonal transmission conditions account for the latitudinal structure of polio epidemics; (3) contrary to the prevailing "disease of development" hypothesis, our analyses demonstrate that polio's historical expansion was straightforwardly explained by demographic trends rather than improvements in sanitation and hygiene; and (4) the absence of clinical disease is not a reliable indicator of polio transmission, because widespread polio transmission was likely in the multiyear absence of clinical disease. As the world edges closer to global polio eradication and continues the strategic withdrawal of the Oral Polio Vaccine (OPV), the regular identification of, and rapid response to, these silent chains of transmission is of the utmost importance.

Contribution of polio eradication initiative to effective new vaccine introduction in Africa, 2010-2015.

PubMed

Carole Tevi-Benissan, Mable; Moturi, Edna; Anya, Blanche-Philomene Melanga; Aschalew, Teka; Dicky, Akanmori Barthlomew; Nyembo, Poy Alain; Mbulu, Leon Kinuam; Okeibunor, Joseph; Mihigo, Richard; Zawaira, Felicitas

2016-10-10

Significant progress has been made to increase access to vaccines in Africa since the 1974 launch of the Expanded Programme on Immunization (EPI). Successes include the introduction of several new vaccines across the continent and likely eradication of polio. We examined the contribution of polio eradication activities (PEI) on new vaccine introduction in the countries of the African Region. We reviewed country specific PEI reports to identify best practices relevant to new vaccine introduction (NVI), and analyzed trends in vaccine coverage during 2010-2015 from immunization estimates provided by WHO/UNICEF. Of the 47 countries in African Region 35 (74%) have introduced PCV, 27 (57%) have introduced rotavirus, and 14 (30%) have introduced IPV. National introductions for HPV vaccine have been done in 5 countries, while 15 countries have held demonstration and pilot projects. In 2014, the regional coverage for the third dose of PCV (PCV3) and rotavirus vaccines was 50% and 30% respectively. By end of 2015, all countries within the meningitis belt will have introduced MenAfriVac™ vaccine. PEI activities had a positive effect in strengthening the process of new vaccine introduction in the African Region. The major contribution was in availing immunization funding and providing trained and experienced technical staff to introduce vaccines. More investment is needed to advocate and sustain funding levels to maintain the momentum gained in introducing new vaccines in the region. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Four-times-daily Dosing of Rabeprazole with Sitafloxacin, High-Dose Amoxicillin, or Both for Metronidazole-Resistant Infection with Helicobacter pylori in Japan.

PubMed

Sugimoto, Mitsushige; Sahara, Shu; Ichikawa, Hitomi; Kagami, Takuma; Ban, Hiromitsu; Otsuka, Taketo; Andoh, Akira; Furuta, Takahisa

2017-02-01

The bacterial resistance of Helicobacter pylori to antimicrobial agents such as clarithromycin and metronidazole has been increasing worldwide, leading to the failure of eradication treatment. Here, we present an eradication regimen consisting of four-times-daily dosing (q.i.d.) of rabeprazole with potent acid inhibition. To investigate the efficacy of eradication therapy with rabeprazole q.i.d. and amoxicillin or sitafloxacin in Japanese infected with a metronidazole-resistant strain. We retrospectively investigated the efficacy of eradication regimens with rabeprazole q.i.d. for 7 days in 111 Japanese pooled patients infected with a metronidazole-resistant strain of H. pylori at Hamamatsu University School of Medicine Hospital or the Shiga University of Medical Science Hospital: 1, with sitafloxacin 100 mg twice daily (b.i.d.) (n = 82); 2, with amoxicillin 500 mg q.i.d. (n = 15); and 3, with amoxicillin q.i.d. and sitafloxacin b.i.d.-combined regimen (n = 14). Eradication status was assessed at 8 weeks via a 13 C-urea breath test. Eradication rate on intention-to-treat analysis was 93.7% (95% confidence interval: 87.4-97.4%, 104/111), irrespective of the high prevalence of strains resistant to clarithromycin (81.1%, 90/111) and levofloxacin (42.3%, 47/111). No significant differences in eradication rates were observed among the different treatment regimens (p = .408), eradication history (p = .096) and different CYP2C19 genotypes (p = .789). On multivariate analysis, no significant risk factor for eradication failure by therapy with potent acid inhibition was seen. In Japanese patients infected with metronidazole-resistant strains of H. pylori, eradication rates exceeding 90% can be achieved using appropriate dosing of antibiotic agents with strain susceptibility (amoxicillin q.i.d. and/or sitafloxacin b.i.d.) together with acid inhibition for a full 24 h and rabeprazole 10 mg q.i.d. These findings may be further evidence for dual therapy with rabeprazole q.i.d. and an antibiotic agent (amoxicillin q.i.d. or sitafloxacin b.i.d.) in Japanese patients with metronidazole-resistant strains. © 2016 John Wiley & Sons Ltd.

Carbohydrate Metabolism in Archaea: Current Insights into Unusual Enzymes and Pathways and Their Regulation

PubMed Central

Esser, Dominik; Rauch, Bernadette

2014-01-01

SUMMARY The metabolism of Archaea, the third domain of life, resembles in its complexity those of Bacteria and lower Eukarya. However, this metabolic complexity in Archaea is accompanied by the absence of many “classical” pathways, particularly in central carbohydrate metabolism. Instead, Archaea are characterized by the presence of unique, modified variants of classical pathways such as the Embden-Meyerhof-Parnas (EMP) pathway and the Entner-Doudoroff (ED) pathway. The pentose phosphate pathway is only partly present (if at all), and pentose degradation also significantly differs from that known for bacterial model organisms. These modifications are accompanied by the invention of “new,” unusual enzymes which cause fundamental consequences for the underlying regulatory principles, and classical allosteric regulation sites well established in Bacteria and Eukarya are lost. The aim of this review is to present the current understanding of central carbohydrate metabolic pathways and their regulation in Archaea. In order to give an overview of their complexity, pathway modifications are discussed with respect to unusual archaeal biocatalysts, their structural and mechanistic characteristics, and their regulatory properties in comparison to their classic counterparts from Bacteria and Eukarya. Furthermore, an overview focusing on hexose metabolic, i.e., glycolytic as well as gluconeogenic, pathways identified in archaeal model organisms is given. Their energy gain is discussed, and new insights into different levels of regulation that have been observed so far, including the transcript and protein levels (e.g., gene regulation, known transcription regulators, and posttranslational modification via reversible protein phosphorylation), are presented. PMID:24600042

Efficient plasmid DNA cleavage by a mononuclear copper(II) complex.

PubMed

Sissi, Claudia; Mancin, Fabrizio; Gatos, Maddalena; Palumbo, Manlio; Tecilla, Paolo; Tonellato, Umberto

2005-04-04

The Cu(II) complex of the ligand all-cis-2,4,6-triamino-1,3,5-trihydroxycyclohexane (TACI) is a very efficient catalyst of the cleavage of plasmid DNA in the absence of any added cofactor. The maximum rate of degradation of the supercoiled plasmid DNA form, obtained at pH 8.1 and 37 degrees C, in the presence of 48 microM TACI.Cu(II), is 2.3 x 10(-3) s(-1), corresponding to a half-life time of only 5 min for the cleavage of form I (supercoiled) to form II (relaxed circular). The dependence of the rate of plasmid DNA cleavage from the TACI.Cu(II) complex concentration follows an unusual and very narrow bell-like profile, which suggests an high DNA affinity of the complexes but also a great tendency to form unreactive dimers. The reactivity of the TACI.Cu(II) complexes is not affected by the presence of several scavengers for reactive oxygen species or when measured under anaerobic conditions. Moreover, no degradation of the radical reporter Rhodamine B is observed in the presence of such complexes. These results are consistent with the operation of a prevailing hydrolytic pathway under the normal conditions used, although the failure to obtain enzymatic religation of the linearized DNA does not allow one to rule out the occurrence of a nonhydrolytic oxygen-independent cleavage. A concurrent oxidative mechanism becomes competitive upon addition of reductants or in the presence of high levels of molecular oxygen: under such conditions, in fact, a remarkable increase in the rate of DNA cleavage is observed.

The topology and dynamics of complex networks

NASA Astrophysics Data System (ADS)

Dezso, Zoltan

We start with a brief introduction about the topological properties of real networks. Most real networks are scale-free, being characterized by a power-law degree distribution. The scale-free nature of real networks leads to unexpected properties such as the vanishing epidemic threshold. Traditional methods aiming to reduce the spreading rate of viruses cannot succeed on eradicating the epidemic on a scale-free network. We demonstrate that policies that discriminate between the nodes, curing mostly the highly connected nodes, can restore a finite epidemic threshold and potentially eradicate the virus. We find that the more biased a policy is towards the hubs, the more chance it has to bring the epidemic threshold above the virus' spreading rate. We continue by studying a large Web portal as a model system for a rapidly evolving network. We find that the visitation pattern of a news document decays as a power law, in contrast with the exponential prediction provided by simple models of site visitation. This is rooted in the inhomogeneous nature of the browsing pattern characterizing individual users: the time interval between consecutive visits by the same user to the site follows a power law distribution, in contrast with the exponential expected for Poisson processes. We show that the exponent characterizing the individual user's browsing patterns determines the power-law decay in a document's visitation. Finally, we turn our attention to biological networks and demonstrate quantitatively that protein complexes in the yeast, Saccharomyces cerevisiae, are comprised of a core in which subunits are highly coexpressed, display the same deletion phenotype (essential or non-essential) and share identical functional classification and cellular localization. The results allow us to define the deletion phenotype and cellular task of most known complexes, and to identify with high confidence the biochemical role of hundreds of proteins with yet unassigned functionality.

Doxycycline in Eradication Therapy of Helicobacter pylori--a Systematic Review and Meta-Analysis.

PubMed

Niv, Yaron

2016-01-01

Since resistance of Helicobacter pylori is developing very fast all over the world, new treatment regimens for eradication are urgently needed. To compare eradication success rate of H. pylori treatment regimens with and without doxycycline. English medical literature searches were conducted for regimens including doxycycline for eradication of H. pylori. Searches were performed up to August 31, 2015, using MEDLINE, PubMed, EMBASE, Scopus and CENTRAL. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled ORs and 95% CIs were calculated comparing treatment regimens for eradication of H. pylori infection with and without doxycycline. The OR for eradication success rate in a fixed model was in favor for treatment regimens with doxycycline: 1.292, 95% CI 1.048-1.594, p = 0.016. There was no significant heterogeneity in the included studies: Q = 15.130, d.f. (Q) = 8, I2 = 47.126, p > 0.10. When treatment regimens with doxycycline were compared only with treatment regimens with tetracycline, no significant difference was found in eradication success rate: OR 0.95, 95% CI 0.68-1.32, p = 0.77. But when treatment regimens with doxycycline were compared with treatment regimens without tetracycline, the OR in favor of doxycycline was even higher: OR 1.59, 95% CI 1.21-2.09, p < 0.001. In this meta-analysis, we confirmed doxycycline efficiency in the eradication of H. pylori. Thus, triple, quadruple or even high dose dual therapy with regimens containing doxycycline should be considered. © 2016 S. Karger AG, Basel.

Stable isotope analysis as an early monitoring tool for community-scale effects of rat eradication

USGS Publications Warehouse

Nigro, Katherine M.; Hathaway, Stacie A.; Wegmann, Alex; Miller-ter Kuile, Ana; Fisher, Robert N.; Young, Hillary S.

2017-01-01

Invasive rats have colonized most of the islands of the world, resulting in strong negative impacts on native biodiversity and on ecosystem functions. As prolific omnivores, invasive rats can cause local extirpation of a wide range of native species, with cascading consequences that can reshape communities and ecosystems. Eradication of rats on islands is now becoming a widespread approach to restore ecosystems, and many native island species show strong numerical responses to rat eradication. However, the effect of rat eradication on other consumers can extend beyond direct numerical effects, to changes in behavior, dietary composition, and other ecological parameters. These behavioral and trophic effects may have strong cascading impacts on the ecology of restored ecosystems, but they have rarely been examined. In this study, we explore how rat eradication has affected the trophic ecology of native land crab communities. Using stable isotope analysis of rats and crabs, we demonstrate that the diet or trophic position of most crabs changed subsequent to rat eradication. Combined with the numerical recovery of two carnivorous land crab species (Geograpsus spp.), this led to a dramatic widening of the crab trophic niche following rat eradication. Given the established importance of land crabs in structuring island communities, particularly plants, this suggests an unappreciated mechanism by which rat eradication may alter island ecology. This study also demonstrates the potential for stable isotope analysis as a complementary monitoring tool to traditional techniques, with the potential to provide more nuanced assessments of the community- and ecosystem-wide effects of restoration.

Immunization of complex networks

NASA Astrophysics Data System (ADS)

Pastor-Satorras, Romualdo; Vespignani, Alessandro

2002-03-01

Complex networks such as the sexual partnership web or the Internet often show a high degree of redundancy and heterogeneity in their connectivity properties. This peculiar connectivity provides an ideal environment for the spreading of infective agents. Here we show that the random uniform immunization of individuals does not lead to the eradication of infections in all complex networks. Namely, networks with scale-free properties do not acquire global immunity from major epidemic outbreaks even in the presence of unrealistically high densities of randomly immunized individuals. The absence of any critical immunization threshold is due to the unbounded connectivity fluctuations of scale-free networks. Successful immunization strategies can be developed only by taking into account the inhomogeneous connectivity properties of scale-free networks. In particular, targeted immunization schemes, based on the nodes' connectivity hierarchy, sharply lower the network's vulnerability to epidemic attacks.

Eradicating Illiteracy in the USSR. Literacy Lessons.

ERIC Educational Resources Information Center

Kabatchenko, M. V.; Yasnikova, L. D.

The eradication of illiteracy in Russia has a lengthy history but a systematic literacy campaign began only after the revolution of 1917. The literacy problem was considered to be solved two decades later. Success was due to the following factors: (1) illiterate people were eager to learn; (2) the eradication of illiteracy and preparation for…

78 FR 64002 - South Farallon Islands Invasive House Mouse Eradication Project; Farallon National Wildlife...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

...-FF08RSFC00] South Farallon Islands Invasive House Mouse Eradication Project; Farallon National Wildlife... Statement (revised DEIS) for the South Farallon Islands Invasive House Mouse Eradication Project on the... non-native invasive house mice from the South Farallon Islands, part of the Farallon National Wildlife...

Integration of ecologically-based approaches to re-eradicate cattle fever ticks from the U.S.

USDA-ARS?s Scientific Manuscript database

Here we summarize highlights of research conducted as part of a NIFA-AFRI funded grant. Cattle fever ticks, Rhipicephalus (Boophilus) microplus and R. (B.) annulatus, have been found on white-tailed deer (Odocoileus virginianus) complicating eradication efforts of the USDA’s Cattle Fever Tick Eradic...

Eradication of poliomyelitis in countries affected by conflict.

PubMed Central

Tangermann, R. H.; Hull, H. F.; Jafari, H.; Nkowane, B.; Everts, H.; Aylward, R. B.

2000-01-01

The global initiative to eradicate poliomyelitis is focusing on a small number of countries in Africa (Angola, Democratic Republic of the Congo, Liberia, Sierra Leone, Somalia, Sudan) and Asia (Afghanistan, Tajikistan), where progress has been hindered by armed conflict. In these countries the disintegration of health systems and difficulties of access are major obstacles to the immunization and surveillance strategies necessary for polio eradication. In such circumstances, eradication requires special endeavours, such as the negotiation of ceasefires and truces and the winning of increased direct involvement by communities. Transmission of poliovirus was interrupted during conflicts in Cambodia, Colombia, El Salvador, Peru, the Philippines, and Sri Lanka. Efforts to achieve eradication in areas of conflict have led to extra health benefits: equity in access to immunization, brought about because every child has to be reached; the revitalization and strengthening of routine immunization services through additional externally provided resources; and the establishment of disease surveillance systems. The goal of polio eradication by the end of 2000 remains attainable if supplementary immunization and surveillance can be accelerated in countries affected by conflict. PMID:10812729

Poverty eradication in a carbon constrained world.

PubMed

Hubacek, Klaus; Baiocchi, Giovanni; Feng, Kuishuang; Patwardhan, Anand

2017-10-24

The UN Framework Convention on Climate Change aims to keep warming below 2 °C while recognizing developing countries' right to eradicate extreme poverty. Poverty eradication is also the first of the Sustainable Development Goals. This paper investigates potential consequences for climate targets of achieving poverty eradication. We find that eradicating extreme poverty, i.e., moving people to an income above $1.9 purchasing power parity (PPP) a day, does not jeopardize the climate target even in the absence of climate policies and with current technologies. On the other hand, bringing everybody to a still modest expenditure level of at least $2.97 PPP would have long-term consequences on achieving emission targets. Compared to the reference mitigation pathway, eradicating extreme poverty increases the effort by 2.8% whereas bringing everybody to at least $2.97 PPP would increase the required mitigation rate by 27%. Given that the top 10% global income earners are responsible for 36% of the current carbon footprint of households; the discourse should address income distribution and the carbon intensity of lifestyles.