WorldWideScience

Sample records for korarchaeota archaeal orphans

  1. The Korarchaeota: Archaeal orphans representing an ancestral lineage of life

    Energy Technology Data Exchange (ETDEWEB)

    Elkins, James G.; Kunin, Victor; Anderson, Iain; Barry, Kerrie; Goltsman, Eugene; Lapidus, Alla; Hedlund, Brian; Hugenholtz, Phil; Kyrpides, Nikos; Graham, David; Keller, Martin; Wanner, Gerhard; Richardson, Paul; Stetter, Karl O.

    2007-05-01

    Based on conserved cellular properties, all life on Earth can be grouped into different phyla which belong to the primary domains Bacteria, Archaea, and Eukarya. However, tracing back their evolutionary relationships has been impeded by horizontal gene transfer and gene loss. Within the Archaea, the kingdoms Crenarchaeota and Euryarchaeota exhibit a profound divergence. In order to elucidate the evolution of these two major kingdoms, representatives of more deeply diverged lineages would be required. Based on their environmental small subunit ribosomal (ss RNA) sequences, the Korarchaeota had been originally suggested to have an ancestral relationship to all known Archaea although this assessment has been refuted. Here we describe the cultivation and initial characterization of the first member of the Korarchaeota, highly unusual, ultrathin filamentous cells about 0.16 {micro}m in diameter. A complete genome sequence obtained from enrichment cultures revealed an unprecedented combination of signature genes which were thought to be characteristic of either the Crenarchaeota, Euryarchaeota, or Eukarya. Cell division appears to be mediated through a FtsZ-dependent mechanism which is highly conserved throughout the Bacteria and Euryarchaeota. An rpb8 subunit of the DNA-dependent RNA polymerase was identified which is absent from other Archaea and has been described as a eukaryotic signature gene. In addition, the representative organism possesses a ribosome structure typical for members of the Crenarchaeota. Based on its gene complement, this lineage likely diverged near the separation of the two major kingdoms of Archaea. Further investigations of these unique organisms may shed additional light onto the evolution of extant life.

  2. Geochemical Constraints on Archaeal Diversity in the Vulcano Hydrothermal System

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    Rogers, K. L.; Amend, J. P.

    2006-12-01

    The shallow marine hydrothermal system of Vulcano, Italy hosts a wide diversity of cultured thermophilic Archaea, including Palaeococcus helgesonii, Archaeoglobus fulgidus, and Pyrococcus furiosus, to name a few. However, recent studies have revealed a plethora of uncultured archaeal lineages in the Vulcano system. For example, a 16S rRNA gene survey of an onshore geothermal well identified a diverse archaeal community including deeply-branching uncultured Crenarchaeota, Korarchaeota, and Euryarchaeota. Additionally, culture-independent hybridization techniques suggested that Archaea account for nearly half of the microbial community in the Vulcano system. Furthermore, geochemical characterization of fluids revealed numerous lithotrophic and heterotrophic exergonic reactions that could support as yet uncultured organisms. Archaeal diversity throughout the Vulcano hydrothermal system was investigated using 16S rRNA gene surveys at five submarine vents and an onshore sediment seep. Overall, archaeal diversity was higher (10 groups) at submarine vents with moderate temperatures (59°C) compared with higher temperature (94°C) vents (4 groups). Archaeal communities at the moderately thermal vents were dominated by Thermococcales and also contained Archaeoglobales, Thermoproteales, and uncultured archaea among the Korarchaeota, Marine Group I, and the Deep-sea Hydrothermal Vent Euryarchaeota (DHVE). Fluid composition also affects the microbial community structure. At two high-temperature sites variations in archaeal diversity can be attributed to differences in iron and hydrogen concentrations, and pH. Comparing sites with similar temperature and pH conditions suggests that the presence of Desulfurococcales is limited to sites at which metabolic energy yields exceed 10 kJ per mole of electrons transferred. The Vulcano hydrothermal system hosts diverse archaeal communities, containing both cultured and uncultured species, whose distribution appears to be constrained by

  3. A korarchaeal genome reveals insights into the evolution of the Archaea

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Iain J; Elkins, James G.; Podar, Mircea; Graham, David E.; Makarova, Kira S.; Wolf, Yuri; Randau, Lennart; Hedlund, Brian P.; Brochier-Armanet, Celine; Kunin, Victor; Anderson, Iain; Lapidus, Alla; Goltsman, Eugene; Barry, Kerrie; Koonin, Eugene V.; Hugenholtz, Phil; Kyrpides, Nikos; Wanner, Gerhard; Richardson, Paul; Keller, Martin; Stetter, Karl O.

    2008-06-05

    The candidate division Korarchaeota comprises a group of uncultivated microorganisms that, by their small subunit rRNA phylogeny, may have diverged early from the major archaeal phyla Crenarchaeota and Euryarchaeota. Here, we report the initial characterization of a member of the Korarchaeota with the proposed name,"Candidatus Korarchaeum cryptofilum," which exhibits an ultrathin filamentous morphology. To investigate possible ancestral relationships between deep-branching Korarchaeota and other phyla, we used whole-genome shotgun sequencing to construct a complete composite korarchaeal genome from enriched cells. The genome was assembled into a single contig 1.59 Mb in length with a G + C content of 49percent. Of the 1,617 predicted protein-coding genes, 1,382 (85percent) could be assigned to a revised set of archaeal Clusters of Orthologous Groups (COGs). The predicted gene functions suggest that the organism relies on a simple mode of peptide fermentation for carbon and energy and lacks the ability to synthesize de novo purines, CoA, and several other cofactors. Phylogenetic analyses based on conserved single genes and concatenated protein sequences positioned the korarchaeote as a deep archaeal lineage with an apparent affinity to the Crenarchaeota. However, the predicted gene content revealed that several conserved cellular systems, such as cell division, DNA replication, and tRNA maturation, resemble the counterparts in the Euryarchaeota. In light of the known composition of archaeal genomes, the Korarchaeota might have retained a set of cellular features that represents the ancestral archaeal form.

  4. A Korarchael Genome Reveals Insights into the Evolution of the Archaea

    Energy Technology Data Exchange (ETDEWEB)

    Lapidus, Alla; Elkins, James G.; Podar, Mircea; Graham, David E.; Makarova, Kira S.; Wolf, Yuri; Randau, Lennart; Hedlund, Brian P.; Brochier-Armanet, Celine; Kunin, Victor; Anderson, Iain; Lapidus, Alla; Goltsman, Eugene; Barry, Kerrie; Koonin, Eugene V.; Hugenholtz, Phil; Kyrpides, Nikos; Wanner, Gerhard; Richardson, Paul; Keller, Martin; Stetter, Karl O.

    2008-01-07

    The candidate division Korarchaeota comprises a group of uncultivated microorganisms that, by their small subunit rRNA phylogeny, may have diverged early from the major archaeal phyla Crenarchaeota and Euryarchaeota. Here, we report the initial characterization of a member of the Korarchaeota with the proposed name, ?Candidatus Korarchaeum cryptofilum,? which exhibits an ultrathin filamentous morphology. To investigate possible ancestral relationships between deep-branching Korarchaeota and other phyla, we used whole-genome shotgun sequencing to construct a complete composite korarchaeal genome from enriched cells. The genome was assembled into a single contig 1.59 Mb in length with a G + C content of 49percent. Of the 1,617 predicted protein-coding genes, 1,382 (85percent) could be assigned to a revised set of archaeal Clusters of Orthologous Groups (COGs). The predicted gene functions suggest that the organism relies on a simple mode of peptide fermentation for carbon and energy and lacks the ability to synthesize de novo purines, CoA, and several other cofactors. Phylogenetic analyses based on conserved single genes and concatenated protein sequences positioned the korarchaeote as a deep archaeal lineage with an apparent affinity to the Crenarchaeota. However, the predicted gene content revealed that several conserved cellular systems, such as cell division, DNA replication, and tRNA maturation, resemble the counterparts in the Euryarchaeota. In light of the known composition of archaeal genomes, the Korarchaeota might have retained a set of cellular features that represents the ancestral archaeal form.

  5. Bacterial and archaeal diversity in two hot spring microbial mats from the geothermal region of Tengchong, China.

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    Pagaling, Eulyn; Grant, William D; Cowan, Don A; Jones, Brian E; Ma, Yanhe; Ventosa, Antonio; Heaphy, Shaun

    2012-07-01

    We investigated the bacterial and archaeal diversity in two hot spring microbial mats from the geothermal region of Tengchong in the Yunnan Province, China, using direct molecular analyses. The Langpu (LP) laminated mat was found by the side of a boiling pool with temperature of 60-65 °C and a pH of 8.5, while the Tengchong (TC) streamer mat consisted of white streamers in a slightly acidic (pH 6.5) hot pool outflow with a temperature of 72 °C. Four 16S rRNA gene clone libraries were constructed and restriction enzyme analysis of the inserts was used to identify unique sequences and clone frequencies. From almost 200 clones screened, 55 unique sequences were retrieved. Phylogenetic analysis showed that the LP mat consisted of a diverse bacterial population [Cyanobacteria, Chloroflexi, Chlorobia, Nitrospirae, 'Deinococcus-Thermus', Proteobacteria (alpha, beta and delta subdivisions), Firmicutes, Bacteroidetes and Actinobacteria], while the archaeal population was dominated by methanogenic Euryarchaeota and Crenarchaeota. In contrast, the TC streamer mat consisted of a bacterial population dominated by Aquificae, while the archaeal population also contained Korarchaeota as well as Crenarchaeota and methanogenic Euryarchaeota. These mats harboured clone sequences affiliated to unidentified lineages, suggesting that they are a potential source for discovering novel bacteria and archaea.

  6. Distribution of Archaeal Communities along the Coast of the Gulf of Finland and Their Response to Oil Contamination

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    Yan, Lijuan; Yu, Dan; Hui, Nan; Naanuri, Eve; Viggor, Signe; Gafarov, Arslan; Sokolov, Sergei L.; Heinaru, Ain; Romantschuk, Martin

    2018-01-01

    The Baltic Sea is vulnerable to environmental changes. With the increasing shipping activities, the risk of oil spills remains high. Archaea are widely distributed in many environments. However, the distribution and the response of archaeal communities to oil contamination have rarely been investigated in brackish habitats. Hence, we conducted a survey to investigate the distribution, diversity, composition, and species interactions of indigenous archaeal communities at oil-contaminated sites along the coast of the Gulf of Finland (GoF) using high-throughput sequencing. Surface water and littoral sediment samples were collected at presumably oil-contaminated (oil distribution facilities) and clean sites along the coastline of the GoF in the winter 2015 and the summer 2016. Another three samples of open sea surface water were taken as offshore references. Of Archaea, Euryarchaeota dominated in the surface water and the littoral sediment of the coast of the GoF, followed by Crenarchaeota (including Thaumarchaeota, Thermoprotei, and Korarchaeota based on the Greengenes database used). The unclassified sequences accounted for 5.62% of the total archaeal sequences. Our study revealed a strong dependence of the archaeal community composition on environmental variables (e.g., salinity, pH, oil concentration, TOM, electrical conductivity, and total DNA concentration) in both littoral sediment and coastal water in the GoF. The composition of archaeal communities was season and ecosystem dependent. Archaea was highly diverse in the three ecosystems (littoral sediment, coastal water, and open sea water). Littoral sediment harbored the highest diversity of archaea. Oil was often detected in the littoral sediment but rarely detected in water at those presumably contaminated sites. Although the composition of archaeal community in the littoral sediment was sensitive to low-input oil contamination, the unchanged putative functional profiles and increased interconnectivity of the

  7. Archaeal extrachromosomal genetic elements

    DEFF Research Database (Denmark)

    Wang, Haina; Peng, Nan; Shah, Shiraz Ali

    2015-01-01

    SUMMARY: Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes, such as spind......SUMMARY: Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes...... on archaeal ECEs has just started to unravel the molecular biology of these genetic entities and their interactions with archaeal hosts, it is expected to accelerate in the next decade....

  8. The enigmatic archaeal virosphere.

    Science.gov (United States)

    Prangishvili, David; Bamford, Dennis H; Forterre, Patrick; Iranzo, Jaime; Koonin, Eugene V; Krupovic, Mart

    2017-11-10

    One of the most prominent features of archaea is the extraordinary diversity of their DNA viruses. Many archaeal viruses differ substantially in morphology from bacterial and eukaryotic viruses and represent unique virus families. The distinct nature of archaeal viruses also extends to the gene composition and architectures of their genomes and the properties of the proteins that they encode. Environmental research has revealed prominent roles of archaeal viruses in influencing microbial communities in ocean ecosystems, and recent metagenomic studies have uncovered new groups of archaeal viruses that infect extremophiles and mesophiles in diverse habitats. In this Review, we summarize recent advances in our understanding of the genomic and morphological diversity of archaeal viruses and the molecular biology of their life cycles and virus-host interactions, including interactions with archaeal CRISPR-Cas systems. We also examine the potential origins and evolution of archaeal viruses and discuss their place in the global virosphere.

  9. Issues surrounding orphan disease and orphan drug policies in Europe.

    Science.gov (United States)

    Denis, Alain; Mergaert, Lut; Fostier, Christel; Cleemput, Irina; Simoens, Steven

    2010-01-01

    An orphan disease is a disease with a very low prevalence. Although there are 5000-7000 orphan diseases, only 50 orphan drugs (i.e. drugs developed to treat orphan diseases) were marketed in the EU by the end of 2008. In 2000, the EU implemented policies specifically designed to stimulate the development of orphan drugs. While decisions on orphan designation and the marketing authorization of orphan drugs are made at the EU level, decisions on drug reimbursement are made at the member state level. The specific features of orphan diseases and orphan drugs make them a high-priority issue for policy makers. The aim of this article is to identify and discuss several issues surrounding orphan disease and drug policies in Europe. The present system of orphan designation allows for drugs for non-orphan diseases to be designated as orphan drugs. The economic factors underlying orphan designation can be questioned in some cases, as a low prevalence of a certain indication does not equal a low return on investment for the drug across its indications. High-quality evidence about the clinical added value of orphan drugs is rarely available at the time of marketing authorization, due to the low number of patients. A balance must be struck between ethical and economic concerns. To this effect, there is a need to initiate a societal dialogue on this issue, to clarify what society wants and accepts in terms of ethical and economic consequences. The growing budgetary impact of orphan drugs puts pressure on drug expenditure. Indications can be extended for an orphan drug and the total prevalence across indications is not considered. Finally, cooperation needs to be fostered in the EU, particularly through a standardized approach to the creation and use of registries. These issues require further attention from researchers, policy makers, health professionals, patients, pharmaceutical companies and other stakeholders with a view to optimizing orphan disease and drug policies in

  10. Archaeal Viruses from High-Temperature Environments.

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    Munson-McGee, Jacob H; Snyder, Jamie C; Young, Mark J

    2018-02-27

    Archaeal viruses are some of the most enigmatic viruses known, due to the small number that have been characterized to date. The number of known archaeal viruses lags behind known bacteriophages by over an order of magnitude. Despite this, the high levels of genetic and morphological diversity that archaeal viruses display has attracted researchers for over 45 years. Extreme natural environments, such as acidic hot springs, are almost exclusively populated by Archaea and their viruses, making these attractive environments for the discovery and characterization of new viruses. The archaeal viruses from these environments have provided insights into archaeal biology, gene function, and viral evolution. This review focuses on advances from over four decades of archaeal virology, with a particular focus on archaeal viruses from high temperature environments, the existing challenges in understanding archaeal virus gene function, and approaches being taken to overcome these limitations.

  11. Archaeal Viruses from High-Temperature Environments

    Directory of Open Access Journals (Sweden)

    Jacob H. Munson-McGee

    2018-02-01

    Full Text Available Archaeal viruses are some of the most enigmatic viruses known, due to the small number that have been characterized to date. The number of known archaeal viruses lags behind known bacteriophages by over an order of magnitude. Despite this, the high levels of genetic and morphological diversity that archaeal viruses display has attracted researchers for over 45 years. Extreme natural environments, such as acidic hot springs, are almost exclusively populated by Archaea and their viruses, making these attractive environments for the discovery and characterization of new viruses. The archaeal viruses from these environments have provided insights into archaeal biology, gene function, and viral evolution. This review focuses on advances from over four decades of archaeal virology, with a particular focus on archaeal viruses from high temperature environments, the existing challenges in understanding archaeal virus gene function, and approaches being taken to overcome these limitations.

  12. A pursuit of lineage-specific and niche-specific proteome features in the world of archaea.

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    Roy Chowdhury, Anindya; Dutta, Chitra

    2012-06-12

    Archaea evoke interest among researchers for two enigmatic characteristics -a combination of bacterial and eukaryotic components in their molecular architectures and an enormous diversity in their life-style and metabolic capabilities. Despite considerable research efforts, lineage- specific/niche-specific molecular features of the whole archaeal world are yet to be fully unveiled. The study offers the first large-scale in silico proteome analysis of all archaeal species of known genome sequences with a special emphasis on methanogenic and sulphur-metabolising archaea. Overall amino acid usage in archaea is dominated by GC-bias. But the environmental factors like oxygen requirement or thermal adaptation seem to play important roles in selection of residues with no GC-bias at the codon level. All methanogens, irrespective of their thermal/salt adaptation, show higher usage of Cys and have relatively acidic proteomes, while the proteomes of sulphur-metabolisers have higher aromaticity and more positive charges. Despite of exhibiting thermophilic life-style, korarchaeota possesses an acidic proteome. Among the distinct trends prevailing in COGs (Cluster of Orthologous Groups of proteins) distribution profiles, crenarchaeal organisms display higher intra-order variations in COGs repertoire, especially in the metabolic ones, as compared to euryarchaea. All methanogens are characterised by a presence of 22 exclusive COGs. Divergences in amino acid usage, aromaticity/charge profiles and COG repertoire among methanogens and sulphur-metabolisers, aerobic and anaerobic archaea or korarchaeota and nanoarchaeota, as elucidated in the present study, point towards the presence of distinct molecular strategies for niche specialization in the archaeal world.

  13. A pursuit of lineage-specific and niche-specific proteome features in the world of archaea

    Directory of Open Access Journals (Sweden)

    Roy Chowdhury Anindya

    2012-06-01

    Full Text Available Abstract Background Archaea evoke interest among researchers for two enigmatic characteristics –a combination of bacterial and eukaryotic components in their molecular architectures and an enormous diversity in their life-style and metabolic capabilities. Despite considerable research efforts, lineage- specific/niche-specific molecular features of the whole archaeal world are yet to be fully unveiled. The study offers the first large-scale in silico proteome analysis of all archaeal species of known genome sequences with a special emphasis on methanogenic and sulphur-metabolising archaea. Results Overall amino acid usage in archaea is dominated by GC-bias. But the environmental factors like oxygen requirement or thermal adaptation seem to play important roles in selection of residues with no GC-bias at the codon level. All methanogens, irrespective of their thermal/salt adaptation, show higher usage of Cys and have relatively acidic proteomes, while the proteomes of sulphur-metabolisers have higher aromaticity and more positive charges. Despite of exhibiting thermophilic life-style, korarchaeota possesses an acidic proteome. Among the distinct trends prevailing in COGs (Cluster of Orthologous Groups of proteins distribution profiles, crenarchaeal organisms display higher intra-order variations in COGs repertoire, especially in the metabolic ones, as compared to euryarchaea. All methanogens are characterised by a presence of 22 exclusive COGs. Conclusions Divergences in amino acid usage, aromaticity/charge profiles and COG repertoire among methanogens and sulphur-metabolisers, aerobic and anaerobic archaea or korarchaeota and nanoarchaeota, as elucidated in the present study, point towards the presence of distinct molecular strategies for niche specialization in the archaeal world.

  14. Orphans and political instability.

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    Breuning, Marijke; Ishiyama, John

    2011-01-01

    This study investigates the security implications of growing orphan populations, particularly in Sub-Saharan Africa. Little has been written about the security implications of this especially vulnerable group of children. Are growing orphan populations associated with increases in political instability as has been suggested? Using data from several sources, we employ regression analysis to test whether Sub-Saharan African countries with larger proportions of orphans and those with increasing orphan populations experience higher rates of political instability. We find that the increase in the orphan population is related to an increasing incidence of civil conflict, but do not find a similar relationship for the proportion of orphans. In addition, we find that the causes of orphanhood matter. We conclude that increases in orphan populations (rather than simple proportions) are destabilizing. We suggest possible avenues for mediating the security risks posed by growing orphan populations.

  15. Orphan sources in Slovenia

    International Nuclear Information System (INIS)

    Janzekovic, H.; Cesarek, J.

    2005-01-01

    For decades the international standards and requirements postulate severe control over all lifecycle phases of radioactive sources in order to prevent risks associated with exposure of people and the environment. Despite this fact the orphan sources became a serious problem as a consequence of enlargement of economic transactions in many countries in Europe as well as in the world. The countries as well as international organisations, aware of this emerging problem, are trying to gain control over orphan sources using different approaches. These approaches include control over sources before they could become orphan sources. In addition, countries are also developing action plans in case that an orphan source could be found. The problems related to orphan sources in Slovenia is discussed based on the case studies from the last years. While in the nineties of the last century just a few cases of orphan sources were identified their number has increased substantially since 2003. The paper discusses the general reasons for the phenomena of orphan sources as well as the experience related to regaining control over orphan sources. (author)

  16. Archaeal Viruses: Diversity, Replication, and Structure.

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    Dellas, Nikki; Snyder, Jamie C; Bolduc, Benjamin; Young, Mark J

    2014-11-01

    The Archaea-and their viruses-remain the most enigmatic of life's three domains. Once thought to inhabit only extreme environments, archaea are now known to inhabit diverse environments. Even though the first archaeal virus was described over 40 years ago, only 117 archaeal viruses have been discovered to date. Despite this small number, these viruses have painted a portrait of enormous morphological and genetic diversity. For example, research centered around the various steps of the archaeal virus life cycle has led to the discovery of unique mechanisms employed by archaeal viruses during replication, maturation, and virion release. In many instances, archaeal virus proteins display very low levels of sequence homology to other proteins listed in the public database, and therefore, structural characterization of these proteins has played an integral role in functional assignment. These structural studies have not only provided insights into structure-function relationships but have also identified links between viruses across all three domains of life.

  17. Identification and functional verification of archaeal-type phosphoenolpyruvate carboxylase, a missing link in archaeal central carbohydrate metabolism.

    Science.gov (United States)

    Ettema, Thijs J G; Makarova, Kira S; Jellema, Gera L; Gierman, Hinco J; Koonin, Eugene V; Huynen, Martijn A; de Vos, Willem M; van der Oost, John

    2004-11-01

    Despite the fact that phosphoenolpyruvate carboxylase (PEPC) activity has been measured and in some cases even purified from some Archaea, the gene responsible for this activity has not been elucidated. Using sensitive sequence comparison methods, we detected a highly conserved, uncharacterized archaeal gene family that is distantly related to the catalytic core of the canonical PEPC. To verify the predicted function of this archaeal gene family, we cloned a representative from the hyperthermophilic acidophile Sulfolobus solfataricus and functionally produced the corresponding enzyme as a fusion with the Escherichia coli maltose-binding protein. The purified fusion protein indeed displayed highly thermostable PEPC activity. The structural and biochemical properties of the characterized archaeal-type PEPC (atPEPC) from S. solfataricus are in good agreement with previously reported biochemical analyses of other archaeal PEPC enzymes. The newly identified atPEPC, with its distinct properties, constitutes yet another example of the versatility of the enzymes of the central carbon metabolic pathways in the archaeal domain.

  18. ORPHANED PROTOSTARS

    International Nuclear Information System (INIS)

    Reipurth, Bo; Connelley, Michael; Mikkola, Seppo; Valtonen, Mauri

    2010-01-01

    We explore the origin of a population of distant companions (∼1000-5000 AU) to Class I protostellar sources recently found by Connelley and coworkers, who noted that the companion fraction diminished as the sources evolved. Here, we present N-body simulations of unstable triple systems embedded in dense cloud cores. Many companions are ejected into unbound orbits and quickly escape, but others are ejected with insufficient momentum to climb out of the potential well of the cloud core and associated binary. These loosely bound companions reach distances of many thousands of AU before falling back and eventually being ejected into escapes as the cloud cores gradually disappear. We use the term orphans to denote protostellar objects that are dynamically ejected from their placental cloud cores, either escaping or for a time being tenuously bound at large separations. Half of all triple systems are found to disintegrate during the protostellar stage, so if multiple systems are a frequent outcome of the collapse of a cloud core, then orphans should be common. Bound orphans are associated with embedded close protostellar binaries, but escaping orphans can travel as far as ∼0.2 pc during the protostellar phase. The steep climb out of a potential well ensures that orphans are not kinematically distinct from young stars born with a less violent pre-history. The identification of orphans outside their heavily extincted cloud cores will allow the detailed study of protostars high up on their Hayashi tracks at near-infrared and in some cases even at optical wavelengths.

  19. Orphan drugs, orphan diseases. The first decade of orphan drug legislation in the EU.

    Science.gov (United States)

    Joppi, Roberta; Bertele', Vittorio; Garattini, Silvio

    2013-04-01

    To assess the methodological quality of Orphan Medicinal Product (OMP) dossiers and discuss possible reasons for the small number of products licensed. Information about orphan drug designation, approval, refusal or withdrawal was obtained from the website of the European Medicines Agency and from the European Public Assessment Reports. From 2000 up to 2010, 80.9 % of the 845 candidate orphan drug designations received a positive opinion from the European Medicines Agency (EMA)'s Committee on Orphan Medicinal Products. Of the 108 OMP marketing authorizations applied for, 63 were granted. Randomised clinical trials were done for 38 OMPs and placebo was used as comparator for nearly half the licensed drugs. One third of the OMPs were tested in trials involving fewer than 100 patients and more than half in trials with 100-200 cases. The clinical trials lasted less than one year for 42.9 % of the approved OMPs. Although there may have been some small improvements over time in the methods for developing OMPs, in our opinion, the number of patients studied, the use of placebo as control, the type of outcome measure and the follow-up have often been inadequate. The present system should be changed to find better ways of fostering the development of effective and sustainable treatments for patients with orphan diseases. Public funds supporting independent clinical research on OMPs could bridge the gap between designation and approval. More stringent criteria to assess OMPs' efficacy and cost/effectiveness would improve the clinical value and the affordability of products allowed onto the market.

  20. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  1. Evolution of the archaeal and mammalian information processing systems: towards an archaeal model for human disease.

    Science.gov (United States)

    Lyu, Zhe; Whitman, William B

    2017-01-01

    Current evolutionary models suggest that Eukaryotes originated from within Archaea instead of being a sister lineage. To test this model of ancient evolution, we review recent studies and compare the three major information processing subsystems of replication, transcription and translation in the Archaea and Eukaryotes. Our hypothesis is that if the Eukaryotes arose within the archaeal radiation, their information processing systems will appear to be one of kind and not wholly original. Within the Eukaryotes, the mammalian or human systems are emphasized because of their importance in understanding health. Biochemical as well as genetic studies provide strong evidence for the functional similarity of archaeal homologs to the mammalian information processing system and their dissimilarity to the bacterial systems. In many independent instances, a simple archaeal system is functionally equivalent to more elaborate eukaryotic homologs, suggesting that evolution of complexity is likely an central feature of the eukaryotic information processing system. Because fewer components are often involved, biochemical characterizations of the archaeal systems are often easier to interpret. Similarly, the archaeal cell provides a genetically and metabolically simpler background, enabling convenient studies on the complex information processing system. Therefore, Archaea could serve as a parsimonious and tractable host for studying human diseases that arise in the information processing systems.

  2. Shaping the Archaeal Cell Envelope

    Directory of Open Access Journals (Sweden)

    Albert F. Ellen

    2010-01-01

    Full Text Available Although archaea have a similar cellular organization as other prokaryotes, the lipid composition of their membranes and their cell surface is unique. Here we discuss recent developments in our understanding of the archaeal protein secretion mechanisms, the assembly of macromolecular cell surface structures, and the release of S-layer-coated vesicles from the archaeal membrane.

  3. Profiling the orphan enzymes

    Science.gov (United States)

    2014-01-01

    The emergence of Next Generation Sequencing generates an incredible amount of sequence and great potential for new enzyme discovery. Despite this huge amount of data and the profusion of bioinformatic methods for function prediction, a large part of known enzyme activities is still lacking an associated protein sequence. These particular activities are called “orphan enzymes”. The present review proposes an update of previous surveys on orphan enzymes by mining the current content of public databases. While the percentage of orphan enzyme activities has decreased from 38% to 22% in ten years, there are still more than 1,000 orphans among the 5,000 entries of the Enzyme Commission (EC) classification. Taking into account all the reactions present in metabolic databases, this proportion dramatically increases to reach nearly 50% of orphans and many of them are not associated to a known pathway. We extended our survey to “local orphan enzymes” that are activities which have no representative sequence in a given clade, but have at least one in organisms belonging to other clades. We observe an important bias in Archaea and find that in general more than 30% of the EC activities have incomplete sequence information in at least one superkingdom. To estimate if candidate proteins for local orphans could be retrieved by homology search, we applied a simple strategy based on the PRIAM software and noticed that candidates may be proposed for an important fraction of local orphan enzymes. Finally, by studying relation between protein domains and catalyzed activities, it appears that newly discovered enzymes are mostly associated with already known enzyme domains. Thus, the exploration of the promiscuity and the multifunctional aspect of known enzyme families may solve part of the orphan enzyme issue. We conclude this review with a presentation of recent initiatives in finding proteins for orphan enzymes and in extending the enzyme world by the discovery of new

  4. Identification of diverse archaeal proteins with class III signal peptides cleaved by distinct archaeal prepilin peptidases

    NARCIS (Netherlands)

    Szabó, Zalán; Oliveira Stahl, Adriana; Albers, Sonja-V.; Kissinger, Jessica C.; Driessen, Arnold J.M.; Pohlschröder, Mechthild; Pohlschroder, M.

    2007-01-01

    Most secreted archaeal proteins are targeted to the membrane via a tripartite signal composed of a charged N terminus and a hydrophobic domain, followed by a signal peptidase-processing site. Signal peptides of archaeal flagellins, similar to class III signal peptides of bacterial type IV pilins,

  5. Orphan drugs: the regulatory environment.

    Science.gov (United States)

    Franco, Pedro

    2013-02-01

    The definition of a rare disease is not universal and depends on the legislation and policies adopted by each region or country. The main objective of this article is to describe and discuss the legal framework and the regulatory environment of orphan drugs worldwide. Some reflections and discussions on the need for specific orphan drug legislation or policies are described at length. Furthermore, some aspects of the history of each region in respect of the orphan drug legislation evolution are outlined. This article describes and compares the orphan drug legislation or policies of the following countries or regions: United Sates of America (US), European Union (EU), Japan, Australia, Singapore, Taiwan and Canada. The incentives described in the orphan drug legislations or policies, the criteria for designation of orphan status and the authorisation process of an orphan drug are also described and compared. The legislations and policies are to some extent similar but not the same. It is important to understand the main differences among all available legislative systems to improve the international collaboration in the field of orphan drugs and rare diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Archaeal Enzymes and Applications in Industrial Biocatalysts.

    Science.gov (United States)

    Littlechild, Jennifer A

    2015-01-01

    Archaeal enzymes are playing an important role in industrial biotechnology. Many representatives of organisms living in "extreme" conditions, the so-called Extremophiles, belong to the archaeal kingdom of life. This paper will review studies carried by the Exeter group and others regarding archaeal enzymes that have important applications in commercial biocatalysis. Some of these biocatalysts are already being used in large scale industrial processes for the production of optically pure drug intermediates and amino acids and their analogues. Other enzymes have been characterised at laboratory scale regarding their substrate specificity and properties for potential industrial application. The increasing availability of DNA sequences from new archaeal species and metagenomes will provide a continuing resource to identify new enzymes of commercial interest using both bioinformatics and screening approaches.

  7. Outcome of anti-retroviral treatment in HIV-infected orphans and non-orphans at an ART centre in North India.

    Science.gov (United States)

    Bhattacharya, Malobika; Saxena, Romit

    2012-01-01

    Few Indian studies have reported the long-term efficacy of anti-retroviral treatment (ART) in children and in orphaned, HIV-infected children in particular. To study differences in outcome of ART in HIV-infected orphans compared with non-orphans. A retrospective study of 87 HIV-infected children who commenced ART in the period January 2006 to August 2007. The main measures were orphan status, absolute CD4 count and weight-for-height (WHZ) and height-for-age (HAZ) Z-scores. Median follow-up was 33 months. Forty (45·9%) children were orphaned. Orphans and non-orphans had similar baseline median WHZ and HAZ (-2·48 vs -2·63, P = 0·65 and -2·78 vs -2·91, P = 0·77, respectively). The two groups were similar in terms of WHO clinical stage and frequency of severe immunosuppression at presentation (P = 0·88 and 0·25, respectively). After ART initiation, the median absolute CD4 count increased progressively in both groups. Median WHZ and HAZ increased throughout the study period in the orphans and reached -1 at 27 and 39 months of ART, respectively. In the non-orphans, WHZ remained below that of the orphan group, the difference becoming statistically significant from 18 months of ART. The increment in HAZ in the non-orphan group was at par with the orphan group until 12 months of follow-up, after which it fell between 18 and 30 months. Subsequently, HAZ rose but remained below that of the orphan group. Both WHZ and HAZ failed to reach -1 in the non-orphan group. In both groups, 85% reported 100% adherence to ART. The outcome of ART is not affected by orphan status with the extended family adequately supporting orphaned children. Growth of children whose parents are HIV-infected may be constrained despite ART if there is inadequate family support.

  8. Orphan drug: Development trends and strategies

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2010-01-01

    Full Text Available The growth of pharma industries has slowed in recent years because of various reasons such as patent expiries, generic competition, drying pipelines, and increasingly stringent regulatory guidelines. Many blockbuster drugs will loose their exclusivity in next 5 years. Therefore, the current economic situation plus the huge generic competition shifted the focus of pharmaceutical companies from the essential medicines to the new business model - niche busters, also called orphan drugs. Orphan drugs may help pharma companies to reduce the impact of revenue loss caused by patent expiries of blockbuster drugs. The new business model of orphan drugs could offer an integrated healthcare solution that enables pharma companies to develop newer areas of therapeutics, diagnosis, treatment, monitoring, and patient support. Incentives for drug development provided by governments, as well as support from the FDA and EU Commission in special protocols, are a further boost for the companies developing orphan drugs. Although there may still be challenges ahead for the pharmaceutical industry, orphan drugs seem to offer the key to recovery and stability within the market. In our study, we have compared the policies and orphan drug incentives worldwide alongwith the challenges faced by the pharmaceutical companies. Recent developments are seen in orphan drug approval, the various drugs in orphan drug pipeline, and the future prospectives for orphan drugs and diseases.

  9. Phylogeny and Taxonomy of Archaea: A Comparison of the Whole-Genome-Based CVTree Approach with 16S rRNA Sequence Analysis

    Directory of Open Access Journals (Sweden)

    Guanghong Zuo

    2015-03-01

    Full Text Available A tripartite comparison of Archaea phylogeny and taxonomy at and above the rank order is reported: (1 the whole-genome-based and alignment-free CVTree using 179 genomes; (2 the 16S rRNA analysis exemplified by the All-Species Living Tree with 366 archaeal sequences; and (3 the Second Edition of Bergey’s Manual of Systematic Bacteriology complemented by some current literature. A high degree of agreement is reached at these ranks. From the newly proposed archaeal phyla, Korarchaeota, Thaumarchaeota, Nanoarchaeota and Aigarchaeota, to the recent suggestion to divide the class Halobacteria into three orders, all gain substantial support from CVTree. In addition, the CVTree helped to determine the taxonomic position of some newly sequenced genomes without proper lineage information. A few discrepancies between the CVTree and the 16S rRNA approaches call for further investigation.

  10. The psychosocial well-being of orphans in Southern Africa: the perception of orphans and teachers

    Directory of Open Access Journals (Sweden)

    M W de Witt

    2010-03-01

    Full Text Available The escalation in numbers of orphans in Sub-Saharan Africa has become a human catastrophe. If governments do not deal with this phenomenon as a priority it might spiral beyond control. Very few studies have been done to investigate the psychosocial impact of orphanhood on children and communities in developing countries. Very little is known about the life world of orphans in developing countries and even less is known about factors in these children’s lives which can affect their mental health. The researchers decided to undertake research in three areas in Southern Africa to investigate the psychosocial well-being of orphans and to compare the findings with existing research findings. A survey was done in three rural areas to determine the perceptions of orphans regarding their own personal experiences and emotional feelings which may reflect on psychosocial well-being, as well as the perceptions of teachers working with these orphans. Except for depression, the findings with regard to most of the psychosocial aspects were in accordance with the literature. The most important findings were that bereavement practices and approaches fit for developed communities might be of little value in developing settings. We are, however, more than aware that orphans from developed counties or even urban settings might differ from those of developing or deep rural areas. Keywords: Orphans; psychosocial well-being; bereavement; poverty; stigmatisation

  11. From novice to expert: agroecological competences of children orphaned by AIDS compared to non-orphans in Benin

    Directory of Open Access Journals (Sweden)

    Price Lisa L

    2011-01-01

    Full Text Available Abstract Background AIDS has created new vulnerabilities for rural African households due to prime-age adult mortality and is assumed to lead to impairment of the intergenerational transfer of farming knowledge. There has been scant research to date, however, on the impacts of parental death on farming knowledge of children made orphans by AIDS. The question we investigate is if there is a difference in agricultural expertise between AIDS affected and non-affected adults and children. Methods The research was carried out in rural Benin with 77 informants randomly selected according to their AIDS status: 13 affected and 13 non-affected adults; 13 paternal, 13 maternal and 13 double orphans; and 12 non-orphan children. Informants descriptions from pile sorting exercises of maize and cowpea pests were categorized and then aggregated into descriptions based form (morphology and function (utility and used to determine whether the moving from novice to expert is impaired by children orphaned by AIDS. Differences and similarities in responses were determined using the Fischer exact test and the Cochran-Mantzel-Haenszel test. Results No significant differences were found between AIDS affected and non-affected adults. Results of the study do reveal differences in the use of form and function descriptors among the children. There is a statistically significant difference in the use of form descriptors between one-parent orphans and non-orphans and in descriptors of specific damages to maize. One-parent paternal orphans were exactly like non-affected adults in their 50/50 balanced expertise in the use of both form and function descriptors. One-parent orphans also had the highest number of descriptors used by children overall and these descriptors are spread across the various aspects of the knowledge domain relative to non-orphans. Conclusions Rather than a knowledge loss for one-parent orphans, particularly paternal orphans, we believe we are witnessing

  12. Impact of orphan drugs on Latvian budget.

    Science.gov (United States)

    Logviss, Konstantins; Krievins, Dainis; Purvina, Santa

    2016-05-11

    Number of orphan medicinal products on the market and number of rare disease patients, taking these usually expensive products, are increasing. As a result, budget impact of orphan drugs is growing. This factor, along with the cost-effectiveness of orphan drugs, is often considered in the reimbursement decisions, directly affecting accessibility of rare disease therapies. The current study aims to assess the budget impact of orphan drugs in Latvia. Our study covered a 5-year period, from 2010 to 2014. Impact of orphan drugs on Latvian budget was estimated from the National Health Service's perspective. It was calculated in absolute values and relative to total pharmaceutical market and total drug reimbursement budget. A literature review was performed for comparison with other European countries. Orphan drug annual expenditure ranged between EUR 2.065 and 3.065 million, with total 5-year expenditure EUR 12.467 million. It constituted, on average, 0.84 % of total pharmaceutical market and 2.14 % of total drug reimbursement budget, respectively. Average annual per patient expenditures varied widely, from EUR 1 534 to EUR 580 952. The most costly treatment was enzyme replacement therapy (Elaprase) for MPS II. Glivec had the highest share (34 %) of the total orphan drug expenditure. Oncological drugs represented more than a half of the total orphan drug expenditure, followed by drugs for metabolic and endocrine conditions and medicines for cardiopulmonary diseases. Three indications: Ph+ CML, MPS II, and PAH accounted for nearly 90 % of the total orphan drug expenditure. Budget impact of orphan drugs in Latvia is very small. It increased slightly over a period of five years, due to the slight increase in the number of patients and the number of orphan drugs reimbursed. Current Latvian drug reimbursement system is not sufficient for most orphan drugs.

  13. Magnetic Au Nanoparticles on Archaeal S-Layer Ghosts as Templates

    Directory of Open Access Journals (Sweden)

    Sonja Selenska-Pobell

    2011-10-01

    Full Text Available Cell‐ghosts representing empty cells of the archaeon Sulfolobus acidocaldarius, consisting only of their highly ordered and unusually stable outermost proteinaceous surface layer (S‐layer, were used as templates for Au nanoparticles fabrication. The properties of these archaeal Au nanoparticles differ significantly from those produced earlier by us onto bacterial S‐layer sheets. The archaeal Au nanoparticles, with a size of about 2.5 nm, consist exclusively of metallic Au(0, while those produced on the bacterial S‐layer had a size of about 4 nm and represented a mixture of Au(0 and Au(III in the ratio of 40 to 60 %. The most impressive feature of the archaeal Au nanoparticles is that they are strongly paramagnetic, in contrast to the bacterial ones and also to bulk gold. SQUID magnetometry and XMCD measurements demonstrated that the archaeal Au nanoparticles possess a rather large magnetic moment of about 0.1 µB/atom. HR‐ TEM‐EDX analysis revealed that the archaeal Au nanoparticles are linked to the sulfur atoms of the thiol groups of the amino acid cysteine, characteristic only for archaeal S‐layers. This is the first study demonstrating the formation of such unusually strong magnetic Au nanoparticles on a non‐modified archaeal S‐layer.

  14. Some Numbers behind Canada's Decision to Adopt an Orphan Drug Policy: US Orphan Drug Approvals in Canada, 1997-2012.

    Science.gov (United States)

    Herder, Matthew; Krahn, Timothy Mark

    2016-05-01

    We examined whether access to US-approved orphan drugs in Canada has changed between 1997 (when Canada chose not to adopt an orphan drug policy) and 2012 (when Canada reversed its policy decision). Specifically, we looked at two dimensions of access to US-approved orphan drugs in Canada: (1) regulatory access; and (2) temporal access. Whereas only 63% of US-approved orphan drugs were granted regulatory approval in 1997, we found that regulatory access to US-approved orphan drugs in Canada increased to 74% between 1997 and 2012. However, temporal access to orphan drugs is slower in Canada: in a head-on comparison of 40 matched drugs, only two were submitted and four were approved first in Canada; moreover, the mean review time in Canada (423 days) was longer than that in the US (mean = 341 days), a statistically significant difference (t[39] = 2.04, p = 0.048). These results raise questions about what motivated Canada's apparent shift in orphan drug policy. Copyright © 2016 Longwoods Publishing.

  15. Diversity and subcellular distribution of archaeal secreted proteins

    Directory of Open Access Journals (Sweden)

    Mechthild ePohlschroder

    2012-07-01

    Full Text Available Secreted proteins make up a significant percentage of a prokaryotic proteome and play critical roles in important cellular processes such as polymer degradation, nutrient uptake, signal transduction, cell wall biosynthesis and motility. The majority of archaeal proteins are believed to be secreted either in an unfolded conformation via the universally conserved Sec pathway or in a folded conformation via the Twin arginine transport (Tat pathway. Extensive in vivo and in silico analyses of N-terminal signal peptides that target proteins to these pathways have led to the development of computational tools that not only predict Sec and Tat substrates with high accuracy but also provide information about signal peptide processing and targeting. Predictions therefore include indications as to whether a substrate is a soluble secreted protein, a membrane or cell-wall anchored protein, or a surface structure subunit, and whether it is targeted for post-translational modification such as glycosylation or the addition of a lipid. The use of these in silico tools, in combination with biochemical and genetic analyses of transport pathways and their substrates, has resulted in improved predictions of the subcellular localization of archaeal secreted proteins, allowing for a more accurate annotation of archaeal proteomes, and has led to the identification of potential adaptations to extreme environments, as well as archaeal kingdom-specific pathways. A more comprehensive understanding of the transport pathways and post-translational modifications of secreted archaeal proteins will also generate invaluable insights that will facilitate the identification of commercially valuable archaeal enzymes and the development of heterologous systems in which to efficiently express them.

  16. World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients.

    Science.gov (United States)

    Kontoghiorghe, Christina N; Andreou, Nicholas; Constantinou, Katerina; Kontoghiorghes, George J

    2014-09-26

    According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The

  17. World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients

    Science.gov (United States)

    Kontoghiorghe, Christina N; Andreou, Nicholas; Constantinou, Katerina; Kontoghiorghes, George J

    2014-01-01

    According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The

  18. Optimised management of orphan wastes in the UK

    International Nuclear Information System (INIS)

    Doudou, Slimane; McTeer, Jennifer; Wickham, Stephen; Thied, Rob; Woodcock, Richard; Turner, Tom; Hamblin, Clive; Buckley, Matthew; Walsh, Ciara

    2013-01-01

    Orphan wastes have properties preventing them from being managed according to existing or currently planned management routes, or lack characterisation so that their management is uncertain. The identification of new management opportunities for orphan wastes could realise significant benefits by reducing the number of processing facilities required, reducing waste volumes, reducing hazard or leading to the development of centres of excellence for the processing of certain types of orphan wastes. Information on the characteristics of orphan waste existing at nuclear licensed sites across the UK has been collated and a database developed to act as a repository for the information gathered. The database provides a capability to analyse the data and to explore possible treatment technologies for each orphan waste type. Thirty five distinct orphan waste types have been defined and possible treatment options considered. Treatment technologies (including chemical, high temperature, immobilisation and physical technologies) that could be applied to one or more of the generic orphan waste streams have been identified. Wiring diagrams have been used to highlight the waste treatment / lifecycle management options that are available for each of the generic orphan groups as well as identifying areas for further research and development. This work has identified the potential for optimising the management of orphan wastes in a number of areas, and many potential opportunities were identified. Such opportunities could be investigated by waste managers at waste producing nuclear sites, to facilitate the development of new management routes for orphan wastes. (authors)

  19. 1997/98 Orphan Well Fund annual report

    International Nuclear Information System (INIS)

    1999-04-01

    Alberta's Orphan Well Fund (previously referred as the Abandonment Fund) is funded by the oil and gas industry with provincial government support and approval. It was created to enforce and improve regulations regarding orphan wells. 1997/98 marked the year in which Orphan Well Fund activities included pipeline abandonments, facility decommissioning, and well site reclamation. The first part of this report includes the annual report of the Orphan Fund, while the second part includes the report on the Energy and Utilities Board's (EUB's) Liability Management activities which are an important part of enforcing and improving provincial regulations in the prevention of orphan wells. The fund allows liability management to be done with industry's dollars rather than taxpayer's dollars. Highlights for the year include the successful completion on eleven downhole and surface wells. Expanded activities also included the abandonment of eleven pipelines, and facilities decommissioning work at five locations. The report also includes a financial review, and a summary of the future goals of the program. The EUB enforcement activities and operations, as well as the EUB orphan prevention activities are also reviewed. tabs

  20. Intra-household differences in health seeking behaviour for orphans ...

    African Journals Online (AJOL)

    Conclusion: There were some differences between orphans and non-orphans within each sub-county and between orphans in the two sub-counties. NGO support is critical in cultivating equity, compassion and non-discrimination. The extended family system in Africa was managing orphan care although it displayed cracks ...

  1. Orphans in the Dead Sea Scrolls

    Directory of Open Access Journals (Sweden)

    Gideon R. Kotzé

    2016-08-01

    Full Text Available This study investigates the literary references to orphans in writings amongst the Qumran texts that were written in Hebrew and can be associated with the sectarian Qumran movement. The study focuses on passages where forms of the word יתום are used. These include the Damascus Document (CD 6:16–17, Hodayot (1QHa 13:22 and Barkhi Nafshia (4Q434 1 i 2. The investigation concludes that the references to orphans in these passages do not have the same rhetorical functions. In CD 6, the wordings of authoritative scriptures are adapted to portray orphans and widows as the victims of wrongdoing. In 1QHa and 4Q434, however, orphans are mentioned in hymns that praise the Lord’s positive treatment of needy people

  2. A Survey of Protein Structures from Archaeal Viruses

    Directory of Open Access Journals (Sweden)

    Nikki Dellas

    2013-01-01

    Full Text Available Viruses that infect the third domain of life, Archaea, are a newly emerging field of interest. To date, all characterized archaeal viruses infect archaea that thrive in extreme conditions, such as halophilic, hyperthermophilic, and methanogenic environments. Viruses in general, especially those replicating in extreme environments, contain highly mosaic genomes with open reading frames (ORFs whose sequences are often dissimilar to all other known ORFs. It has been estimated that approximately 85% of virally encoded ORFs do not match known sequences in the nucleic acid databases, and this percentage is even higher for archaeal viruses (typically 90%–100%. This statistic suggests that either virus genomes represent a larger segment of sequence space and/or that viruses encode genes of novel fold and/or function. Because the overall three-dimensional fold of a protein evolves more slowly than its sequence, efforts have been geared toward structural characterization of proteins encoded by archaeal viruses in order to gain insight into their potential functions. In this short review, we provide multiple examples where structural characterization of archaeal viral proteins has indeed provided significant functional and evolutionary insight.

  3. Diversity and subcellular distribution of archaeal secreted proteins.

    Science.gov (United States)

    Szabo, Zalan; Pohlschroder, Mechthild

    2012-01-01

    Secreted proteins make up a significant percentage of a prokaryotic proteome and play critical roles in important cellular processes such as polymer degradation, nutrient uptake, signal transduction, cell wall biosynthesis, and motility. The majority of archaeal proteins are believed to be secreted either in an unfolded conformation via the universally conserved Sec pathway or in a folded conformation via the Twin arginine transport (Tat) pathway. Extensive in vivo and in silico analyses of N-terminal signal peptides that target proteins to these pathways have led to the development of computational tools that not only predict Sec and Tat substrates with high accuracy but also provide information about signal peptide processing and targeting. Predictions therefore include indications as to whether a substrate is a soluble secreted protein, a membrane or cell wall anchored protein, or a surface structure subunit, and whether it is targeted for post-translational modification such as glycosylation or the addition of a lipid. The use of these in silico tools, in combination with biochemical and genetic analyses of transport pathways and their substrates, has resulted in improved predictions of the subcellular localization of archaeal secreted proteins, allowing for a more accurate annotation of archaeal proteomes, and has led to the identification of potential adaptations to extreme environments, as well as phyla-specific pathways among the archaea. A more comprehensive understanding of the transport pathways used and post-translational modifications of secreted archaeal proteins will also facilitate the identification and heterologous expression of commercially valuable archaeal enzymes.

  4. Psychosocial and health risk outcomes among orphans and non ...

    African Journals Online (AJOL)

    The study sample comprised 134 children (61 non-orphans, 73 orphans; mean age = 14.64, SD = 1.85) from the Amajuba district in KwaZulu-Natal. Orphans were no worse off in terms of anxiety/depression (p = 0.65), affability (p = 0.11) and resilience (p = 0.29) in comparison to non-orphans in similar type households.

  5. Orphan immunotherapies for allergic diseases.

    Science.gov (United States)

    Ridolo, Erminia; Montagni, Marcello; Incorvaia, Cristoforo; Senna, Gianenrico; Passalacqua, Giovanni

    2016-03-01

    As confirmed by systematic reviews and meta-analyses, allergen immunotherapy is clinically effective in the treatment of allergic diseases. In particular, subcutaneous immunotherapy is a pivotal treatment in patients with severe reactions to Hymenoptera venom, whereas subcutaneous immunotherapy and sublingual immunotherapy are indicated in the treatment of allergic rhinitis and asthma by inhalant allergens. Other allergies related to animal dander (other than cat, which is the most studied), such as dog, molds, occupational allergens, and insects, have also been recognized. For these allergens, immunotherapy is poorly studied and often unavailable. Thus, use of the term orphan immunotherapies is appropriate. We used MEDLINE to search the medical literature for English-language articles. Randomized, controlled, masked studies for orphan immunotherapies were selected. In the remaining cases, the available reports were described. The literature on food desensitization is abundant, but for other orphan allergens, such as mosquito, Argas reflexus, dog, or occupational allergens, there are only a few studies, and most are small studies or case reports. Orphan immunotherapy is associated with insufficient evidence of efficacy from controlled trials, an erroneous belief of the limited importance of some allergen sources, and the unlikelihood for producers to have a profit in making commercially available extracts (with an expensive process for registration) to be used in few patients. It should be taken into consideration that adequate preparations should be available also for orphan allergens. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Archaeal virus-host interactions

    NARCIS (Netherlands)

    Quax, T.E.F.

    2013-01-01

    The work presented in this thesis provides novel insights in several aspects of the molecular

    biology of archaea, bacteria and their viruses.

    Three fundamentally different groups of viruses are associated with the three domains of life.

    Archaeal viruses are

  7. Cultural practices and sexual risk behaviour among adolescent orphans and non-orphans: a qualitative study on perceptions from a community in Western Kenya.

    Science.gov (United States)

    Juma, Milka; Askew, Ian; Alaii, Jane; Bartholomew, L Kay; van den Borne, Bart

    2014-01-27

    This study explored community perceptions of cultural beliefs and practices that may increase sexual risk behaviour of adolescents, to understand more about meaning they hold within the culture and how they expose adolescent orphans and non-orphans to higher risks in a high HIV and teenage pregnancy prevalence context. Using a qualitative descriptive cross-sectional design 14 focus group discussions were conducted with 78 adolescents and 68 parents/guardians purposively selected to represent their communities. Thirteen key informant interviews were also conducted with community leaders, health care and child welfare workers, and adolescents who were also selected purposively. The two methods were used to explore how cultural beliefs and practices predispose adolescent orphans and non- orphans to risky sexual behaviours. Data were analysed through line-by-line coding, grouped into families and retrieved as themes and sub-themes. Identified cultural practices that predisposed adolescents orphans and non-orphans to risky sexual behaviours included: adolescent sleeping arrangements, funeral ceremonies, replacing a deceased married daughter with her younger sister in marriage, widow inheritance among boys, early marriage among girls, and preference for boys/sons. Cultural risks perceived to equally affect both orphans and non-orphans were sleeping arrangements, funeral ceremonies, and sister replacement. Factors associated more with orphans than non-orphans were widow inheritance among boys and a preference for boy over girl children. Adolescent sexual risk reduction programs should be developed considering the specific cultural context, using strategies that empower communities to challenge the widely accepted cultural norms that may predispose young people in general to sexual risks while targeting those that unequally influence orphans.

  8. 78 FR 35117 - Orphan Drug Regulations

    Science.gov (United States)

    2013-06-12

    ..., ``This [framework] affects the plasma protein therapeutics industry significantly because various drugs... orphan designated.'' Because many plasma protein therapies lack orphan-drug designation, they are... change in delivery system from intravenous (IV) to oral may, in some cases and for some drugs, constitute...

  9. Affordable orphan drugs: a role for not-for-profit organizations.

    Science.gov (United States)

    Davies, Elin H; Fulton, Emma; Brook, Daniel; Hughes, Dyfrig A

    2017-07-01

    The success of the Regulation on Orphan Medicinal Products in the European Union is evidenced by the 127 orphan drugs that have had market authorization since 2000. However, the incentives aimed at stimulating research and development have had the unintended consequence of increasing drug cost, resulting in many orphan drugs not being cost-effective. Orphan drugs command an increasing share of the pharmaceutical market and account for a disproportionate amount of healthcare expenditure. Orphan drug ownership by socially motivated, not-for-profit organizations may facilitate access to more affordable orphan drugs, for the benefit of patients and healthcare systems alike. This study aims to describe opportunities for such organizations to become orphan drug Market Authorization Holders. We reviewed data on the ownership of EMA designated and approved orphan drugs, identified funding opportunities and business models for not-for-profit organizations, and summarised relevant legal and policy documents concerning intellectual property rights and drug regulation. Using repurposed drugs as a paradigm, this narrative review navigates the regulatory hurdles, describes the legal context and identifies funding opportunities, in a bid to facilitate and encourage not-for-profit organizations to lead on the development of affordable orphan drugs. Although the regulatory steps required to obtain an MA for an orphan drug are numerous and challenging, they are not insurmountable and can be achieved by not-for-profit organizations that are socially motivated to reduce the costs of orphan drugs to the payers of healthcare. Opportunities for orphan drug development resulting in affordable products lie mainly with repurposed drugs. © 2017 The British Pharmacological Society.

  10. Persisting mental health problems among AIDS-orphaned children in South Africa.

    Science.gov (United States)

    Cluver, Lucie D; Orkin, Mark; Gardner, Frances; Boyes, Mark E

    2012-04-01

      By 2008, 12 million children in sub-Saharan Africa were orphaned by AIDS. Cross-sectional studies show psychological problems for AIDS-orphaned children, but until now no longitudinal study has explored enduring psychological effects of AIDS-orphanhood in the developing world.   A 4-year longitudinal follow-up of AIDS-orphaned children with control groups of other-orphans and non-orphans. 1021 children (M = 13.4 years, 50% female, 98% isiXhosa-speaking) were interviewed in 2005 and followed up in 2009 with 71% retention (49% female, M = 16.9 years), in poor urban South African settlements. Children were interviewed using sociodemographic questionnaires and well-validated standardised scales for assessing depression, anxiety, and post-traumatic stress. Data were analysed using mixed-design ANOVA and backward-stepping regression.   AIDS-orphaned children showed higher depression, anxiety, and post-traumatic stress disorder (PTSD) scores in both 2005 and 2009 when compared with other-orphans and non-orphans. Backward-stepping regression, controlling for baseline mental health, and sociodemographic cofactors such as age, gender, and type of bereavement, revealed that being AIDS-orphaned in 2005 was associated with depression, anxiety, and PTSD scores in 2009. This was not the case for other-orphaned or non-orphaned children. Age interacted with orphan status, such that there was a steep rise in psychological distress in the AIDS-orphaned group, but no rise with age amongst other-orphans and non-orphans.   Negative mental health outcomes amongst AIDS-orphaned children are maintained and worsen over a 4-year period. It is important that psychosocial support programmes are sustained, and focus on youth as well as young children. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

  11. Incentives for orphan drug research and development in the United States.

    Science.gov (United States)

    Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Szeinbach, Sheryl L; Visaria, Jay

    2008-12-16

    The Orphan Drug Act (1983) established several incentives to encourage the development of orphan drugs (ODs) to treat rare diseases and conditions. This study analyzed the characteristics of OD designations, approvals, sponsors, and evaluated the effective patent and market exclusivity life of orphan new molecular entities (NMEs) approved in the US between 1983 and 2007. Primary data sources were the FDA Orange Book, the FDA Office of Orphan Drugs Development, and the US Patent and Trademark Office. Data included all orphan designations and approvals listed by the FDA and all NMEs approved by the FDA during the study period. The FDA listed 1,793 orphan designations and 322 approvals between 1983 and 2007. Cancer was the main group of diseases targeted for orphan approvals. Eighty-three companies concentrated 67.7% of the total orphan NMEs approvals. The average time from orphan designation to FDA approval was 4.0 +/- 3.3 years (mean +/- standard deviation). The average maximum effective patent and market exclusivity life was 11.7 +/- 5.0 years for orphan NME. OD market exclusivity increased the average maximum effective patent and market exclusivity life of ODs by 0.8 years. Public programs, federal regulations, and policies support orphan drugs R&D. Grants, research design support, FDA fee waivers, tax incentives, and orphan drug market exclusivity are the main incentives for orphan drug R&D. Although the 7-year orphan drug market exclusivity provision had a positive yet relatively modest overall effect on effective patent and market exclusivity life, economic incentives and public support mechanisms provide a platform for continued orphan drug development for a highly specialized market.

  12. Understanding orphan and non-orphan adolescents' sexual risks in the context of poverty: a qualitative study in Nyanza Province, Kenya.

    Science.gov (United States)

    Juma, Milka; Alaii, Jane; Bartholomew, L Kay; Askew, Ian; Van den Born, Bart

    2013-07-25

    Some studies show orphanhood to be associated with increased sexual risk-taking while others have not established this relationship, but have found factors other than orphanhood as predictors of sexual risk behaviours and outcomes among adolescents. This study examines community members' perceptions of how poverty influences adolescent sexual behaviour and outcomes in four districts of Nyanza Province, Kenya. Eight study sites within the four districts were randomly selected. Focus group discussions were conducted with a purposive sample of adolescents, parents and caregivers. Key informant interviews were undertaken with a purposive sample of community leaders, child welfare and healthcare workers, and adolescents. The two methods elicited information on factors perceived to predispose adolescent orphans and non-orphans to sexual risks. Data were analysed through line-by-line coding, grouped into families and retrieved as themes and sub-themes. Participants included 147 adolescents and parents/caregivers in 14 focus groups and 13 key informants. Poverty emerged as a key predisposing factor to sexual risk behaviour among orphans and non-orphans. Poverty was associated with lack of food, poor housing, school dropout, and engaging in income generating activities, all of which increase their vulnerability to transactional sex, early marriage, sexual experimentation, and the eventual consequences of increased risk of unintended pregnancies and STI/HIV. Poverty was perceived to contribute to increasing sexual risks among orphan and non-orphan adolescents through survival strategies adopted to be able to meet their basic needs. Policies for prevention and intervention that target adolescents in a generalized poverty and HIV epidemic should integrate economic empowerment for caregivers and life skills for adolescents to reduce vulnerabilities of orphan and non-orphan adolescents to sexual risk behaviour.

  13. Shining a light in the black box of orphan drug pricing

    Science.gov (United States)

    2014-01-01

    Background The pricing mechanism of orphan drugs appears arbitrary and has been referred to as a “black box”. Therefore, the aim of this study is to investigate how drug- and disease-specific variables relate to orphan drug prices. Additionally, we aim to explore if certain country-specific pricing and reimbursement policies affect the price level of orphan drugs. Methods Annual treatment costs per indication per patient were calculated for 59 orphan drugs with a publicly available price in Belgium, the Netherlands, Czech Republic, France, Italy and the United Kingdom. A multiple linear regression model was built with 14 drug- and disease-specific variables. A Mann-Whitney U test was used to explore whether there is a correlation between annual treatment costs of orphan drugs across countries with different pricing and reimbursement policies. Results Repurposed orphan drugs, orally administered orphan drugs or orphan drugs for which an alternative treatment is available are associated with lower annual treatment costs. Orphan drugs with multiple orphan indications, for chronic treatments or for which an improvement in overall survival or quality-of-life has been demonstrated, are associated with higher annual treatment costs. No association was found between annual treatments cost of orphan drugs across countries and the different pricing and reimbursement systems. Conclusions This study has shown that prices of orphan drugs are influenced by factors such as the availability of an alternative drug treatment, repurposing, etc. Current debate about the affordability of orphan drugs highlights the need for more transparency in orphan drug price setting. PMID:24767472

  14. Radiation Safety and Orphan Sources

    International Nuclear Information System (INIS)

    Janzekovic, H.; Krizman, M.

    2006-01-01

    The wide spread use of radioactive and particularly of nuclear materials which started in the last century very quickly also demonstrated negative sides. The external exposure and radiotoxicity of these materials could be easily used in a malevolent act. Due to the fact that these materials could not be detected without special equipment designed for that purpose, severe control over their use in all phases of a life cycle is required. An orphan source is a radioactive source which is not under regulatory control, either because it has never been under regulatory or because it has been abandoned, lost, misplaced, stolen or transferred without proper authorization. In the last ten years a few international conferences were dedicated to the improvement of the safety and security of radioactive sources. Three main tasks are focused, the maintenance of data bases related to events with orphan sources and the publications of such events, the preparation of recommendations and guidelines to national regulatory bodies in order to prevent and detect the events related to orphan sources as well as to develop the response strategies to radiological or nuclear emergency, appraisals of the national strategies of radioactive sources control. Concerning Slovenia, strengthening control over orphan sources in Slovenia started after the adoption of new legislation in 2002. It was carried out through several tasks with the aim to prevent orphan sources, as well as to identify the sources which could be potentially orphan sources. The comprehensive methodology was developed by the Slovenian nuclear safety administration (S.N.S.A.) based on international guidelines as well as on the study of national lesson learned cases. The methodology was developed and used in close cooperation with all parties involved, namely other regulatory authorities, police, customs, agency for radioactive waste management (A.R.A.O.), technical support organisations (T.S.O.), users of source, authorised

  15. Radiation Safety and Orphan Sources

    Energy Technology Data Exchange (ETDEWEB)

    Janzekovic, H.; Krizman, M. [Slovenian Nuclear Safety Administration, Ljubljana (Slovenia)

    2006-07-01

    The wide spread use of radioactive and particularly of nuclear materials which started in the last century very quickly also demonstrated negative sides. The external exposure and radiotoxicity of these materials could be easily used in a malevolent act. Due to the fact that these materials could not be detected without special equipment designed for that purpose, severe control over their use in all phases of a life cycle is required. An orphan source is a radioactive source which is not under regulatory control, either because it has never been under regulatory or because it has been abandoned, lost, misplaced, stolen or transferred without proper authorization. In the last ten years a few international conferences were dedicated to the improvement of the safety and security of radioactive sources. Three main tasks are focused, the maintenance of data bases related to events with orphan sources and the publications of such events, the preparation of recommendations and guidelines to national regulatory bodies in order to prevent and detect the events related to orphan sources as well as to develop the response strategies to radiological or nuclear emergency, appraisals of the national strategies of radioactive sources control. Concerning Slovenia, strengthening control over orphan sources in Slovenia started after the adoption of new legislation in 2002. It was carried out through several tasks with the aim to prevent orphan sources, as well as to identify the sources which could be potentially orphan sources. The comprehensive methodology was developed by the Slovenian nuclear safety administration (S.N.S.A.) based on international guidelines as well as on the study of national lesson learned cases. The methodology was developed and used in close cooperation with all parties involved, namely other regulatory authorities, police, customs, agency for radioactive waste management (A.R.A.O.), technical support organisations (T.S.O.), users of source, authorised

  16. Orphan Well Association 2007-08 annual report

    International Nuclear Information System (INIS)

    2008-06-01

    The Alberta Oil and Gas Orphan Abandonment and Reclamation Association or Orphan Well Association (OWA) is a not for profit organization which operates as a separate, financially independent organization under the legal authority delegated by the Alberta Energy Resources Conservation Board (ERCB). The OWA was established in January 2002 as a joint initiative between the upstream oil and gas industry and the provincial government. The Alberta government supports the initiative to deal with upstream oil and gas orphan wells through the ERCB and Alberta Environment (AENV). The ERCB collects funds from industry through an annual orphan fund levy and other fees which are then contributed directly to the OWA to cover the expenditures on orphan well abandonment and reclamation activities. The OWA prepares a yearly annual budget which determines the amount of the orphan fund levy. This budget is then approved by its four member organizations, notably the Canadian Association of Petroleum Producers (CAPP), Small Explorers and Producers Association of Canada, ERCB and AENV. This annual report for the OWA for 2007-2008 presented a historical summary of funding; a historical summary of expenditures; and a discussion of operating and financial highlights. These operating highlights included well abandonment; pipeline abandonment; facility decommissioning; and site reclamation. Financial statements for the OWA were also provided. It was concluded that the OWA had a year of responsible and productive operations. 8 tabs., 6 figs

  17. Estimating the budget impact of orphan medicines in Europe: 2010 - 2020

    Directory of Open Access Journals (Sweden)

    Milanova Tsveta

    2011-09-01

    Full Text Available Abstract Background Orphan drugs are a growing issue of importance to European healthcare policy makers. The success of orphan drug legislation in Europe has resulted in an increasing number of licensed medicines for rare diseases, and many more yet unlicensed products have received orphan drug designation. Increasingly the concerns amongst policy makers relate to issues of patient access and affordability, yet few studies have sought to estimate the future budget impact of orphan drugs. The aim of this study was to predict the total cost of orphan medicines in Europe between 2010 and 2020 as a percentage of total European pharmaceutical expenditure. Methods A disease-based epidemiological model was created based upon trends in the designation and approval of new orphan medicines, prevalence estimates for orphan diseases, and historical price and sales data for orphan drugs in Europe (defined as Eurozone + UK. The analysis incorporated two stages: 1 Predicting the number of diseases for which new orphan drugs will be approved over the next decade, based on an analysis of trends from the EU registry of orphan medicines; 2 Estimating the average ex-factory drug cost across an orphan disease life cycle, from the year in which the first orphan medicine is launched to the point where the first medicine loses marketing exclusivity. The two sets of information were combined to quantify the annual cost of orphan drugs from 2010 through 2020. Results The results from the model predicted a steady increase in the cumulative number of diseases for which an orphan drug is approved, averaging just over 5 new diseases per year over the next 10 years. The annual per patient cost of existing orphan drugs was seen to vary between €1,251 and €407,631, with the median cost being €32,242 per year. The share of the total pharmaceutical market represented by orphan drugs is predicted to increase from 3.3% in 2010 to a peak of 4.6% in 2016 after which it is

  18. The importance of HIV prevention messaging for orphaned youth in Zimbabwe.

    Science.gov (United States)

    Haney, Erica; Singh, Kavita

    2012-01-01

    The AIDS epidemic has contributed to a drastic increase in the number of orphans in Zimbabwe. Female adolescent orphans are particularly in jeopardy of contracting HIV due to disadvantages including extreme poverty, low education, and the absent of parental oversight which can lead to higher risk-taking sexual behaviors. By understanding where girls receive education about HIV and who they rely on for information, organizations can effectively modify existing programs to better target this at-risk population. For this study a household survey was conducted which included 216 orphans and 324 non-orphans (n=540), aged 12-17 years, in the resource-poor setting of Hwange District, Zimbabwe. The aims of this article were to examine the differences between orphans and non-orphans in HIV prevention message exposure, level of motivation for learning about HIV, and communication with caregivers about safe sex. The household survey revealed that younger orphans, aged 12-15 years, were more motivated to learn about HIV and had greater HIV messaging exposure in school than non-orphans. These exposure and differences in the levels of motivation between groups dissipated at older ages. Our research also discovered less caregiver communication among orphans than non-orphans. Our findings suggest that HIV programs targeting orphans need to do a better job at keeping older orphans interested in HIV prevention at a time when it matters most. Furthermore, intervention strategies that provide caregiver support are instrumental in effectively delivering prevention messages to girls at home.

  19. Factors associated with internalising problems in orphans and their ...

    African Journals Online (AJOL)

    Objectives: To compare internalising problems reported by orphans and their caregivers with that of non-orphans and their caregivers. Design: Case control study. Setting: Cahora-Bassa District of Tete, Mozambique Subjects: Seventy-six maternal or double orphans (aged 10-14 years) and their caregivers were compared ...

  20. Copper Pollution Increases the Resistance of Soil Archaeal Community to Changes in Water Regime.

    Science.gov (United States)

    Li, Jing; Liu, Yu-Rong; Cui, Li-Juan; Hu, Hang-Wei; Wang, Jun-Tao; He, Ji-Zheng

    2017-11-01

    Increasing efforts have been devoted to exploring the impact of environmental stresses on soil bacterial communities, but the work on the archaeal community is seldom. Here, we constructed microcosm experiments to investigate the responses of archaeal communities to the subsequent dry-rewetting (DW) disturbance in two contrasting soils (fluvo-aquic and red soil) after 6 years of copper pollution. Ten DW cycles were exerted on the two soils with different copper levels, followed by a 6-week recovery period. In both soils, archaeal diversity (Shannon index) in the high copper-level treatments increased over the incubation period, and archaeal community structure changed remarkably as revealed by the non-metric multidimensional scaling ordinations. In both soils, copper pollution altered the response of dominant operational taxonomic units (OTUs) to the DW disturbance. Throughout the incubation and recovery period, the resistance of archaeal abundance to the DW disturbance was higher in the copper-polluted soils than soils without pollution. Taken together, copper pollution altered the response of soil archaeal diversity and community composition to the DW disturbance and increased the resistance of the archaeal abundance. These findings have important implications for understanding soil microbial responses to ongoing environmental change.

  1. Advancements in therapeutically-targeting orphan GPCRs

    Directory of Open Access Journals (Sweden)

    Jennifer eStockert

    2015-05-01

    Full Text Available G-protein coupled receptors (GPCRs are popular biological targets for drug discovery and development. To date there are more than 140 orphan GPCRs, i.e. receptors whose endogenous ligands are unknown. Traditionally orphan GPCRs have been difficult to study and the development of therapeutic compounds targeting these receptors has been extremely slow although these GPCRs are considered important targets based on their distribution and behavioral phenotype revealed by animals lacking the receptor. Recent advances in several methods used to study orphan receptors, including protein crystallography and homology modeling are likely to be useful in the identification of therapeutics targeting these receptors. In the past 13 years, over a dozen different Class A GPCRs have been crystallized; this trend is exciting, since homology modeling of GPCRs has previously been limited by the availability of solved structures. As the number of solved GPCR structures continues to grow so does the number of templates that can be used to generate increasingly accurate models of phylogenetically-related orphan GPCRs. The availability of solved structures along with the advances in using multiple templates to build models (in combination with molecular dynamics simulations that reveal structural information not provided by crystallographic data and methods for modeling hard-to-predict flexible loop regions have improved the quality of GPCR homology models. This, in turn, has improved the success rates of virtual ligand screens that use homology models to identify potential receptor binding compounds. Experimental testing of the predicted hits and validation using traditional GPCR pharmacological approaches can be used to drive ligand-based efforts to probe orphan receptor biology as well as to define the chemotypes and chemical scaffolds important for binding. As a result of these advances, orphan GPCRs are emerging from relative obscurity as a new class of drug

  2. Orphan diseases: state of the drug discovery art.

    Science.gov (United States)

    Volmar, Claude-Henry; Wahlestedt, Claes; Brothers, Shaun P

    2017-06-01

    Since 1983 more than 300 drugs have been developed and approved for orphan diseases. However, considering the development of novel diagnosis tools, the number of rare diseases vastly outpaces therapeutic discovery. Academic centers and nonprofit institutes are now at the forefront of rare disease R&D, partnering with pharmaceutical companies when academic researchers discover novel drugs or targets for specific diseases, thus reducing the failure risk and cost for pharmaceutical companies. Considerable progress has occurred in the art of orphan drug discovery, and a symbiotic relationship now exists between pharmaceutical industry, academia, and philanthropists that provides a useful framework for orphan disease therapeutic discovery. Here, the current state-of-the-art of drug discovery for orphan diseases is reviewed. Current technological approaches and challenges for drug discovery are considered, some of which can present somewhat unique challenges and opportunities in orphan diseases, including the potential for personalized medicine, gene therapy, and phenotypic screening.

  3. Archaeal S-Layers: Overview and Current State of the Art

    Directory of Open Access Journals (Sweden)

    Thiago Rodrigues-Oliveira

    2017-12-01

    Full Text Available In contrast to bacteria, all archaea possess cell walls lacking peptidoglycan and a number of different cell envelope components have also been described. A paracrystalline protein surface layer, commonly referred to as S-layer, is present in nearly all archaea described to date. S-layers are composed of only one or two proteins and form different lattice structures. In this review, we summarize current understanding of archaeal S-layer proteins, discussing topics such as structure, lattice type distribution among archaeal phyla and glycosylation. The hexagonal lattice type is dominant within the phylum Euryarchaeota, while in the Crenarchaeota this feature is mainly associated with specific orders. S-layers exclusive to the Crenarchaeota have also been described, which are composed of two proteins. Information regarding S-layers in the remaining archaeal phyla is limited, mainly due to organism description through only culture-independent methods. Despite the numerous applied studies using bacterial S-layers, few reports have employed archaea as a study model. As such, archaeal S-layers represent an area for exploration in both basic and applied research.

  4. Psychological distress amongst AIDS-orphaned children in urban South Africa.

    Science.gov (United States)

    Cluver, Lucie; Gardner, Frances; Operario, Don

    2007-08-01

    South Africa is predicted to have 2.3 million children orphaned by Acquired Immune Deficiency Syndrome (AIDS) by 2020 (Actuarial Society of South Africa, 2005). There is little knowledge about impacts of AIDS-related bereavement on children, to aid planning of services. This study aimed to investigate psychological consequences of AIDS orphanhood in urban township areas of Cape Town, South Africa, compared to control groups of children and adolescents orphaned by other causes, and non-orphans. One thousand and twenty-five children and adolescents (aged 10-19) were interviewed using socio-demographic questionnaires and standardised scales for assessing depression, anxiety, post-traumatic stress, peer problems, delinquency and conduct problems. Controlling for socio-demographic factors such as age, gender, formal/informal dwelling and age at orphanhood, children orphaned by AIDS were more likely to report symptoms of depression, peer relationship problems, post-traumatic stress, delinquency and conduct problems than both children orphaned by other causes and non-orphaned children. Anxiety showed no differences. AIDS-orphaned children were more likely to report suicidal ideation. Compared to Western norms, AIDS-orphaned children showed higher levels of internalising problems and delinquency, but lower levels of conduct problems. Children orphaned by AIDS may be a particularly vulnerable group in terms of emotional and, to a lesser extent, behavioural problems. Intervention programs are necessary to ameliorate the psychological sequelae of losing a parent to AIDS.

  5. [A novel archaeal phylum: thaumarchaeota--a review].

    Science.gov (United States)

    Zhang, Limei; He, Jizheng

    2012-04-04

    Based on the archaeal 16S rRNA gene phylogenetic tree, the archaeal domain is divided into two major phyla, Euryarchaeota and Crenarchaeota. During the past 20 years, diverse groups of archaea have been found to be widely distributed in moderate environments with the rapid development and application of molecular techniques in microbial ecology. Increasing evidence demonstrated that these archaea, especially ammonia-oxidizing archaea, play a major role in biogeochemical cycles of nitrogen and carbon elements. These mesophilic archaea were placed initially as a sister group of the Crenarchaeota and named as "non-thermophilic Crenarchaeota". More recently, phylogenetic analyses based on more SSU and SLU rDNA sequences suggested that the non-thermophilic Crenarchaeota constituted a separate phylum of the Archaea that branched off before the separation of Crenarchaeota and Euryarchaeota. The Thaumarchaeota (the Greek "Thaumas", meaning wonder) was therefore proposed for a novel phylum, as the third archaeal phylum. More studies based on r-proteins and comparative genomics confirm that the Thaumarchaeota are distinct from Crenarchaeota. In this paper, we gave a translated Chinese name for Thaumarchaeota and reviewed the recent progress on the phylogeny position, genetics, ecology and physiology of the Thaumarchaeota.

  6. Orphan drugs: trends and issues in drug development.

    Science.gov (United States)

    Rana, Proteesh; Chawla, Shalini

    2018-04-12

    Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.

  7. Priority setting for orphan drugs: an international comparison.

    Science.gov (United States)

    Rosenberg-Yunger, Zahava R S; Daar, Abdallah S; Thorsteinsdóttir, Halla; Martin, Douglas K

    2011-04-01

    To describe the process of priority setting for two orphan drugs - Cerezyme and Fabrazyme - in Canada, Australia and Israel, in order to understand and improve the process based on stakeholder perspectives. We conducted qualitative case studies of how three independent drug advisory committees made decisions relating to the funding of Cerezyme and Fabrazyme. Interviews were conducted with 22 informants, including committee members, patient groups and industry representatives. (1) DESCRIPTION: Orphan drugs reimbursement recommendations by expert panels were based on clinical evidence, cost and cost-effectiveness analysis. (2) EVALUATION: Committee members expressed an overall preference for the current drug review process used by their own committee, but were concerned with the fairness of the process particularly for orphan drugs. Other informants suggested the inclusion of other relevant values (e.g. lack of alternative treatments) in order to improve the priority setting process. Some patient groups suggested the use of an alternative funding mechanism for orphan drugs. Priority setting for drugs is not solely a technical process (involving cost-effective analysis, evidence-based medicine, etc.). Understanding the process by which reimbursement decisions are made for orphan drugs may help improve the system for future orphan drugs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Pricing and reimbursement of orphan drugs: the need for more transparency

    Directory of Open Access Journals (Sweden)

    Simoens Steven

    2011-06-01

    Full Text Available Abstract Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement. Although orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic power of orphan drugs results in high prices: a orphan drugs benefit from a period of marketing exclusivity; b few alternative health technologies are available; c third-party payers and patients have limited negotiating power; d manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e substantial R&D costs need to be recouped from a small number of patients. Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions. Given their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care payer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social value. There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should be targeted at demonstrating the relative effectiveness

  9. Pricing and reimbursement of orphan drugs: the need for more transparency.

    Science.gov (United States)

    Simoens, Steven

    2011-06-17

    Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement. Although orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic power of orphan drugs results in high prices: a) orphan drugs benefit from a period of marketing exclusivity; b) few alternative health technologies are available; c) third-party payers and patients have limited negotiating power; d) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e) substantial R&D costs need to be recouped from a small number of patients. Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions. Given their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care payer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social value. There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and

  10. Orphan drugs expenditure in the Netherlands in the period 2006–2012

    OpenAIRE

    Kanters, Tim A; Steenhoek, Adri; Hakkaart, Leona

    2014-01-01

    textabstractBackground: The relatively low budget impact of orphan drugs is often used as an argument in reimbursement decisions. However, overall, the budget impact of orphan drugs can still be substantial. In this study, we assess the uptake and budget impact of orphan drugs in the Netherlands.Methods. We examined the number of orphan drugs, the number of patients and budget impact of orphan drugs in the Netherlands in the period 2006 to 2012, both for inpatient and outpatient orphan drugs....

  11. RNA-Based Assessment of Diversity and Composition of Active Archaeal Communities in the German Bight

    Directory of Open Access Journals (Sweden)

    Bernd Wemheuer

    2012-01-01

    Full Text Available Archaea play an important role in various biogeochemical cycles. They are known extremophiles inhabiting environments such as thermal springs or hydrothermal vents. Recent studies have revealed a significant abundance of Archaea in moderate environments, for example, temperate sea water. Nevertheless, the composition and ecosystem function of these marine archaeal communities is largely unknown. To assess diversity and composition of active archaeal communities in the German Bight, seven marine water samples were taken and studied by RNA-based analysis of ribosomal 16S rRNA. For this purpose, total RNA was extracted from the samples and converted to cDNA. Archaeal community structures were investigated by pyrosequencing-based analysis of 16S rRNA amplicons generated from cDNA. To our knowledge, this is the first study combining next-generation sequencing and metatranscriptomics to study archaeal communities in marine habitats. The pyrosequencing-derived dataset comprised 62,045 archaeal 16S rRNA sequences. We identified Halobacteria as the predominant archaeal group across all samples with increased abundance in algal blooms. Thermoplasmatales (Euryarchaeota and the Marine Group I (Thaumarchaeota were identified in minor abundances. It is indicated that archaeal community patterns were influenced by environmental conditions.

  12. A study of descriptive data for orphans and non-orphans on key criteria of economic vulnerability in two municipalities in South Africa

    Directory of Open Access Journals (Sweden)

    Donald Skinner

    2013-05-01

    Full Text Available Background: It is generally assumed that orphan status increases the risk to children of a range of negative outcomes. In South Africa, death of parents due to HIV-related illness is contributing to a rapid increase in the prevalence of orphans. This paper presents descriptive data from two South African communities, namely Kopanong, in the Free State and Kanana in the North West province, characterising the differences between orphans (double, maternal and paternal and non-orphans on key criteria of social vulnerability.Objectives: The objective was to obtain a better understanding of how different types of orphans and non-orphans may differ in these key areas as a crucial starting point for addressing the devastating consequences the AIDS epidemic has on these children’s lives. While the study focuses on two specific areas these will provide insight into the general situation of orphans in South Africa.Methods: A cross-sectional census survey was conducted in the two communities of Kopanong, comprising n = 5254 households and Kanana, comprising n = 12 984 households.Results: In Kopanong, 8.2% of children had lost both parents, 19.1% had lost their father and 6.5% their mother only, whilst in Kanana the results were 6.5%, 28.1% and 3.7% respectively. Loss of both parents appeared to have a consistent impact on material need, including access to food, clothing and essential services, whilst loss of a single parent seems to have a more variable impact. At present, there are very few child headed households, but this constitutes a risk in the longer term. Conclusions: Orphans appear to be more vulnerable in terms of material need. Children assessed in this study as being most in need were not accessing adequately many services directed at them. There is a need to extend understanding and measurement of emotional need and abuse.

  13. Characterizing Novel Archaeal Lineages in Salton Sea Sediments

    Science.gov (United States)

    Tarn, J.; Valentine, D. L.

    2016-12-01

    Biological communities in extreme environments are often dominated by microorganisms of the domain Archaea. Abundant microbial assemblages of this group are found in the hottest, saltiest, and most thermodynamically-limited ecosystems on earth. These taxing surroundings are thought to impose a state of chronic energy stress on resident organisms due to high costs of cellular maintenance relative to resource availability. Even in more temperate settings, Archaea are regularly associated with low-nutrient lifestyles, reflecting their adaptation to extreme, biologically-limiting conditions, which may be an ancestral, domain-wide trait. In this study, we seek to characterize the Archaeal community of the Salton Sea, where members of this domain are novel and highly abundant. Previous work by Swan et al. in 2010 showed that gradients in salinity, sulfate, carbon and nitrogen across sediment horizons of the Salton Sea are linked to changes in Archaeal dominance and community structure. In light of recent taxonomic revisions of the domain, I reclassified the 107 published small subunit rRNA Archaeal sequences from the 2010 study using updated reference databases. The majority of these Euryarchaeal sequences were reassigned to the so-called DPANN superphylum, with Pacearchaeota-related sequences being very abundant in shallow, organic-rich sediments. In deeper, energy-limited strata, several groups of Bathyarchaeota and one divergent DPANN clade were dominant. Ongoing metagenomic work on these sediment communities is being used to assemble genomes of these novel Archaeal groups. These results will help define genomic adaptations of Salton Sea Archaea to varying levels of energy stress as well as inform future cultivation efforts.

  14. Financing drug discovery for orphan diseases.

    Science.gov (United States)

    Fagnan, David E; Gromatzky, Austin A; Stein, Roger M; Fernandez, Jose-Maria; Lo, Andrew W

    2014-05-01

    Recently proposed 'megafund' financing methods for funding translational medicine and drug development require billions of dollars in capital per megafund to de-risk the drug discovery process enough to issue long-term bonds. Here, we demonstrate that the same financing methods can be applied to orphan drug development but, because of the unique nature of orphan diseases and therapeutics (lower development costs, faster FDA approval times, lower failure rates and lower correlation of failures among disease targets) the amount of capital needed to de-risk such portfolios is much lower in this field. Numerical simulations suggest that an orphan disease megafund of only US$575 million can yield double-digit expected rates of return with only 10-20 projects in the portfolio. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. The availability and affordability of orphan drugs for rare diseases in China.

    Science.gov (United States)

    Gong, Shiwei; Wang, Yingxiao; Pan, Xiaoyun; Zhang, Liang; Huang, Rui; Chen, Xin; Hu, Juanjuan; Xu, Yi; Jin, Si

    2016-02-27

    Orphan drugs are intended to treat, prevent or diagnose rare diseases. In recent years, China healthcare policy makers and patients have become increasingly concerned about orphan drug issues. However, very few studies have assessed the availability and affordability of orphan drugs for rare diseases in China. The aim of this study was to provide an overview of the availability and affordability of orphan drugs in China and to make suggestions to improve patient access to orphan drugs. Two components of the availability of orphan drugs were examined. Market availability was assessed by the extent to which orphan drugs were marketed in China with a comparison to orphan drugs in international markets, such as the U.S., EU and Japan. We conducted surveys and collected data from 24 tertiary public hospitals in China to measure hospital-level availability of orphan drugs. The affordability of orphan drugs was calculated using hospital dispensary prices and was expressed as days of average daily income required for the cost of a course of treatment. Affordability was also analyzed under the Chinese basic medical insurance system. Orphan drugs approved in the U.S., EU and Japan had 37.8%, 24.6% and 52.4% market availability in China, respectively. Median availability of 31 orphan drugs surveyed at the 24 tertiary public hospitals was 20.8% (very low). Within a periodic treatment course, the average treatment cost of 23 orphan drugs is approximately 4, 843. 5 USD, which equates to 505.6 days of per capita net income for an urban resident with a middle income (187.4 days for a high-income urban resident) or 1,582.8 days's income for a rural resident with a middle income (657.2 days for a high-income rural resident). Except for homoharringtonine, 22 orphan drugs for 14 rare diseases were unaffordable for the most of residents in China. With 5% out-of-pocket expenses, only three generics could be afforded by middle-income residents, whereas seven drugs for high-income urban

  16. Nutritional Issues of HIV/AIDS Orphans in Sagamu South Western ...

    African Journals Online (AJOL)

    Little is known about the health and nutrition of those HIV/AIDS orphans and inconsistent findings make it difficult to assess if orphans and other vulnerable children have specific nutritional needs. This study investigated nutritional status HIV/AIDS orphans in Sagamu. The study population consisted of fifty seronegative ...

  17. A Meta-Analysis of the Bacterial and Archaeal Diversity Observed in Wetland Soils

    Directory of Open Access Journals (Sweden)

    Xiaofei Lv

    2014-01-01

    Full Text Available This study examined the bacterial and archaeal diversity from a worldwide range of wetlands soils and sediments using a meta-analysis approach. All available 16S rRNA gene sequences recovered from wetlands in public databases were retrieved. In November 2012, a total of 12677 bacterial and 1747 archaeal sequences were collected in GenBank. All the bacterial sequences were assigned into 6383 operational taxonomic units (OTUs 0.03, representing 31 known bacterial phyla, predominant with Proteobacteria (2791 OTUs, Bacteroidetes (868 OTUs, Acidobacteria (731 OTUs, Firmicutes (540 OTUs, and Actinobacteria (418 OTUs. The genus Flavobacterium (11.6% of bacterial sequences was the dominate bacteria in wetlands, followed by Gp1, Nitrosospira, and Nitrosomonas. Archaeal sequences were assigned to 521 OTUs from phyla Euryarchaeota and Crenarchaeota. The dominating archaeal genera were Fervidicoccus and Methanosaeta. Rarefaction analysis indicated that approximately 40% of bacterial and 83% of archaeal diversity in wetland soils and sediments have been presented. Our results should be significant for well-understanding the microbial diversity involved in worldwide wetlands.

  18. Bipartite Network Analysis of the Archaeal Virosphere: Evolutionary Connections between Viruses and Capsidless Mobile Elements.

    Science.gov (United States)

    Iranzo, Jaime; Koonin, Eugene V; Prangishvili, David; Krupovic, Mart

    2016-12-15

    Archaea and particularly hyperthermophilic crenarchaea are hosts to many unusual viruses with diverse virion shapes and distinct gene compositions. As is typical of viruses in general, there are no universal genes in the archaeal virosphere. Therefore, to obtain a comprehensive picture of the evolutionary relationships between viruses, network analysis methods are more productive than traditional phylogenetic approaches. Here we present a comprehensive comparative analysis of genomes and proteomes from all currently known taxonomically classified and unclassified, cultivated and uncultivated archaeal viruses. We constructed a bipartite network of archaeal viruses that includes two classes of nodes, the genomes and gene families that connect them. Dissection of this network using formal community detection methods reveals strong modularity, with 10 distinct modules and 3 putative supermodules. However, compared to similar previously analyzed networks of eukaryotic and bacterial viruses, the archaeal virus network is sparsely connected. With the exception of the tailed viruses related to bacteriophages of the order Caudovirales and the families Turriviridae and Sphaerolipoviridae that are linked to a distinct supermodule of eukaryotic and bacterial viruses, there are few connector genes shared by different archaeal virus modules. In contrast, most of these modules include, in addition to viruses, capsidless mobile elements, emphasizing tight evolutionary connections between the two types of entities in archaea. The relative contributions of distinct evolutionary origins, in particular from nonviral elements, and insufficient sampling to the sparsity of the archaeal virus network remain to be determined by further exploration of the archaeal virosphere. Viruses infecting archaea are among the most mysterious denizens of the virosphere. Many of these viruses display no genetic or even morphological relationship to viruses of bacteria and eukaryotes, raising questions

  19. Diversity and mobility in households with children orphaned by AIDS ...

    African Journals Online (AJOL)

    An in-depth study of the orphans' lives, undertaken to complement the census, revealed that these orphans were highly mobile between households, with almost 50% of them moving homes within a six-month period. An analysis of this phenomenon found that orphan mobility was a deliberate household strategy to manage ...

  20. The socio-demographic factors of children orphaned by aids in ...

    African Journals Online (AJOL)

    Conclusion: The percentage of HIV patients that are orphans in this study is significant. The morbidities in the orphans had deprived them of early childhood education and immunization. Breastfeeding of all the orphans may have compounded the seemingly high mother to child HIV transmission. There is an urgent need for ...

  1. The Use of Social Media in Orphan Drug Development.

    Science.gov (United States)

    Milne, Christopher-Paul; Ni, Wendi

    2017-11-01

    Social media has transformed how people interact with one another through the Internet, and it has the potential to do the same for orphan drug development. Currently, social media influences the orphan drug development process in the following three ways: assisting the study of orphan diseases, increasing the awareness of orphan disease, and playing a vital role in clinical trials. However, there are some caveats to the utilization of social media, such as the need to protect patient privacy by adequately de-identifying personal health information, assuring consistent quality and representativeness of the data, and preventing the unblinding of patient group assignments. Social media has both potential for improving orphan drug development and pitfalls, but with proper oversight on the part of companies, support and participation of patients and their advocacy groups, and timely guidance from regulatory authorities, the positives outweigh the negatives for this powerful and patient-centric tool. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  2. Financing drug discovery for orphan diseases

    OpenAIRE

    Fagnan, David Erik; Gromatzky, Austin A.; Stein, Roger Mark; Fernandez, Jose-Maria; Lo, Andrew W.

    2014-01-01

    Recently proposed ‘megafund’ financing methods for funding translational medicine and drug development require billions of dollars in capital per megafund to de-risk the drug discovery process enough to issue long-term bonds. Here, we demonstrate that the same financing methods can be applied to orphan drug development but, because of the unique nature of orphan diseases and therapeutics (lower development costs, faster FDA approval times, lower failure rates and lower correlation of failures...

  3. Mechanism of Archaeal MCM Helicase Recruitment to DNA Replication Origins

    Science.gov (United States)

    Samson, Rachel Y.; Abeyrathne, Priyanka D.; Bell, Stephen D.

    2015-01-01

    Summary Cellular DNA replication origins direct the recruitment of replicative helicases via the action of initiator proteins belonging to the AAA+ superfamily of ATPases. Archaea have a simplified subset of the eukaryotic DNA replication machinery proteins and possess initiators that appear ancestral to both eukaryotic Orc1 and Cdc6. We have reconstituted origin-dependent recruitment of the homohexameric archaeal MCM in vitro with purified recombinant proteins. Using this system, we reveal that archaeal Orc1-1 fulfills both Orc1 and Cdc6 functions by binding to a replication origin and directly recruiting MCM helicase. We identify the interaction interface between these proteins and reveal how ATP binding by Orc1-1 modulates recruitment of MCM. Additionally, we provide evidence that an open-ring form of the archaeal MCM homohexamer is loaded at origins. PMID:26725007

  4. THE ORBIT OF THE ORPHAN STREAM

    International Nuclear Information System (INIS)

    Newberg, Heidi Jo; Willett, Benjamin A.; Yanny, Brian; Xu Yan

    2010-01-01

    We use recent Sloan Extension for Galactic Understanding and Exploration (SEGUE) spectroscopy and the Sloan Digital Sky Survey (SDSS) and SEGUE imaging data to measure the sky position, distance, and radial velocities of stars in the tidal debris stream that is commonly referred to as the 'Orphan Stream'. We fit orbital parameters to the data and find a prograde orbit with an apogalacticon, perigalacticon, and eccentricity of 90 kpc, 16.4 kpc, and e = 0.7, respectively. Neither the dwarf galaxy UMa II nor the Complex A gas cloud has velocities consistent with a kinematic association with the Orphan Stream. It is possible that Segue-1 is associated with the Orphan Stream, but no other known Galactic clusters or dwarf galaxies in the Milky Way lie along its orbit. The detected portion of the stream ranges from 19 to 47 kpc from the Sun and is an indicator of the mass interior to these distances. There is a marked increase in the density of Orphan Stream stars near (l, b) = (253 0 , 49 0 ), which could indicate the presence of the progenitor at the edge of the SDSS data. If this is the progenitor, then the detected portion of the Orphan Stream is a leading tidal tail. We find blue horizontal branch (BHB) stars and F turnoff stars associated with the Orphan Stream. The turnoff color is (g - r) 0 = 0.22. The BHB stars have a low metallicity of [Fe/H] WBG = -2.1. The orbit is best fit to a halo potential with a halo plus disk mass of about 2.6 x 10 11 M sun , integrated to 60 kpc from the Galactic center. Our fits are done to orbits rather than full N-body simulations; we show that if N-body simulations are used, the inferred mass of the galaxy would be slightly smaller. Our best fit is found with a logarithmic halo speed of v halo = 73 ± 24 km s -1 , a disk+bulge mass of M(R 11 M sun , and a halo mass of M(R 11 M sun . However, we can find similar fits to the data that use a Navarro-Frenk-White halo profile or that have smaller disk masses and correspondingly larger

  5. Biosynthesis of archaeal membrane ether lipids

    Directory of Open Access Journals (Sweden)

    Samta eJain

    2014-11-01

    Full Text Available A vital function of the cell membrane in all living organism is to maintain the membrane permeability barrier and fluidity. The composition of the phospholipid bilayer is distinct in archaea when compared to bacteria and eukarya. In archaea, isoprenoid hydrocarbon side chains are linked via an ether bond to the sn-glycerol-1-phosphate backbone. In bacteria and eukarya on the other hand, fatty acid side chains are linked via an ester bond to the sn-glycerol-3-phosphate backbone. The polar head groups are globally shared in the three domains of life. The unique membrane lipids of archaea have been implicated not only in the survival and adaptation of the organisms to extreme environments but also to form the basis of the membrane composition of the last universal common ancestor (LUCA. In nature, a diverse range of archaeal lipids is found, the most common are the diether (or archaeol and the tetraether (or caldarchaeol lipids that form a monolayer. Variations in chain length, cyclization and other modifications lead to diversification of these lipids. The biosynthesis of these lipids is not yet well understood however progress in the last decade has led to a comprehensive understanding of the biosynthesis of archaeol. This review describes the current knowledge of the biosynthetic pathway of archaeal ether lipids; insights on the stability and robustness of archaeal lipid membranes; and evolutionary aspects of the lipid divide and the last universal common ancestor LUCA. It examines recent advances made in the field of pathway reconstruction in bacteria.

  6. Gender Differences in Maladaptive Cognitive Schema in Orphans in Dakahlia, Egypt

    Directory of Open Access Journals (Sweden)

    Abdel-Hady El-Gilany

    2013-01-01

    Full Text Available The objective of this study was to assess the gender differences of maladaptive cognitive schema among orphans in Dakahlia governorate orphanages. A cross-sectional comparative study included 152 orphan boys and 48 orphan girls in all orphanages homes in Dakahlia governorate, Egypt. Data collection tools included a structured interview questionnaire for personal data; early maladaptive schema questionnaire-short form (EMSQ-SF. The mean score of the total YSQ and all the subscales, except self-sacrifice and unrelenting standards, are significantly higher among females than males. Attention should be given to the psychological care of the orphans especially security, trust, confidence, and autonomy with more attention to orphan girls.

  7. Phylogenomic reconstruction of archaeal fatty acid metabolism

    Science.gov (United States)

    Dibrova, Daria V.; Galperin, Michael Y.; Mulkidjanian, Armen Y.

    2014-01-01

    While certain archaea appear to synthesize and/or metabolize fatty acids, the respective pathways still remain obscure. By analyzing the genomic distribution of the key lipid-related enzymes, we were able to identify the likely components of the archaeal pathway of fatty acid metabolism, namely, a combination of the enzymes of bacterial-type β-oxidation of fatty acids (acyl-CoA-dehydrogenase, enoyl-CoA hydratase, and 3-hydroxyacyl-CoA dehydrogenase) with paralogs of the archaeal acetyl-CoA C-acetyltransferase, an enzyme of the mevalonate biosynthesis pathway. These three β-oxidation enzymes working in the reverse direction could potentially catalyze biosynthesis of fatty acids, with paralogs of acetyl-CoA C-acetyltransferase performing addition of C2 fragments. The presence in archaea of the genes for energy-transducing membrane enzyme complexes, such as cytochrome bc complex, cytochrome c oxidase, and diverse rhodopsins, was found to correlate with the presence of the proposed system of fatty acid biosynthesis. We speculate that because these membrane complexes functionally depend on fatty acid chains, their genes could have been acquired via lateral gene transfer from bacteria only by those archaea that already possessed a system of fatty acid biosynthesis. The proposed pathway of archaeal fatty acid metabolism operates in extreme conditions and therefore might be of interest in the context of biofuel production and other industrial applications. PMID:24818264

  8. Archaeal community of cattle digestive system

    Czech Academy of Sciences Publication Activity Database

    Němcová, Anna; Elhottová, Dana; Gattinger, A.

    2007-01-01

    Roč. 48, - (2007), s. 233 ISSN 0009-0646. [Kongres Československé společnosti mikrobiologické /24./. 02.10.2007-05.10.2007, Liberec] Institutional research plan: CEZ:AV0Z60660521 Keywords : archaeal community * cattle digestive system Subject RIV: EH - Ecology, Behaviour

  9. Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience

    OpenAIRE

    Casamento, K.; Laverty, A.; Wilsher, M.; Twiss, J.; Gabbay, E.; Glaspole, I.; Jaffe, A.

    2016-01-01

    Background We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. Methods A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were s...

  10. A roadmap for breeding orphan leafy vegetable species

    NARCIS (Netherlands)

    Sogbohossou, E.O.D.; Achigan-Dako, Enoch G.; Maundu, Patrick; Solberg, Svein; Deguenon, Edgar M.S.; Mumm, Rita H.; Hale, Iago; Deynze, van Allen; Schranz, M.E.

    2018-01-01

    Despite an increasing awareness of the potential of "orphan" or unimproved crops to contribute to food security and enhanced livelihoods for farmers, coordinated research agendas to facilitate production and use of orphan crops by local communities are generally lacking. We provide an overview of

  11. Orphan Strontium-87 in Abyssal Peridotites: Daddy Was a Granite

    Science.gov (United States)

    Snow, Jonathan E.; Hart, Stanley R.; Dick, Henry J. B.

    1993-12-01

    The 87Sr/86Sr ratios in some bulk abyssal and alpine peridotites are too high to be binary mixtures of depleted mantle and seawater components. The apparent excess, or "orphan," 87Sr appears to be separated from its radioactive parent. Such observations were widely held to be analytical artifacts. Study of several occurrences of orphan 87Sr shows that the orphan component in abyssal peridotite is located in the alteration products of olivine and enstatite in the peridotite. The orphan 87Sr is most likely introduced by infiltration of low-temperature (<200^circC) seawater bearing suspended detrital particulates. These particulates include grains of detrital clay that are partly derived from continental (that is, granitic) sources and thus are highly radiogenic. Orphan 87Sr and other radiogenic isotopes may provide a tracer for low-temperature seawater penetrating into the oceanic crust.

  12. Health Technology Assessment Of Orphan Drugs : The example of Pompe disease

    NARCIS (Netherlands)

    T.A. Kanters (Tim A.)

    2016-01-01

    markdownabstractIn recent decades, the development of orphan drugs, i.e. drugs for rare diseases, is stimulated by regulations in various countries. However, the generally high prices of orphan drugs confront policy makers with difficult reimbursement decisions. The orphan disease investigated in

  13. Enriching Orphans' Potentials through Interpersonal and Intrapersonal Intelligence Enrichment Activities

    Science.gov (United States)

    Azid, Nurulwahida Hj; Yaacob, Aizan

    2016-01-01

    Orphans are considered a minority and they should be given a greater emphasis so that they do not feel left out and can build their own lives without a sense of humility. This does not mean that the orphans should be pampered instead they should be given the confidence and motivation to strive for success in later life. Humility among orphans can…

  14. The Orphan Problem in Selected African Countries | Lalthapersad ...

    African Journals Online (AJOL)

    becoming more widespread in response to the emerging orphan crisis. Orphans themselves are in a diffi cult position, having to contend with conditions that are fi nancially, socially and emotionally dislocating, and experiencing hunger, homelessness, forced migration, limited or no access to healthcare and social services, ...

  15. pH dominates variation in tropical soil archaeal diversity and community structure.

    Science.gov (United States)

    Tripathi, Binu M; Kim, Mincheol; Lai-Hoe, Ang; Shukor, Nor A A; Rahim, Raha A; Go, Rusea; Adams, Jonathan M

    2013-11-01

    Little is known of the factors influencing soil archaeal community diversity and composition in the tropics. We sampled soils across a range of forest and nonforest environments in the equatorial tropics of Malaysia, covering a wide range of pH values. DNA was PCR-amplified for the V1-V3 region of the 16S rRNA gene, and 454-pyrosequenced. Soil pH was the best predictor of diversity and community composition of Archaea, being a stronger predictor than land use. Archaeal OTU richness was highest in the most acidic soils. Overall archaeal abundance in tropical soils (determined by qPCR) also decreased at higher pH. This contrasts with the opposite trend previously found in temperate soils. Thaumarcheota group 1.1b was more abundant in alkaline soils, whereas group 1.1c was only detected in acidic soils. These results parallel those found in previous studies in cooler climates, emphasizing niche conservatism among broad archaeal groups. Among the most abundant operational taxonomic units (OTUs), there was clear evidence of niche partitioning by pH. No individual OTU occurred across the entire range of pH values. Overall, the results of this study show that pH plays a major role in structuring tropical soil archaeal communities. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  16. Orphan drugs expenditure in the Netherlands in the period 2006-2012

    NARCIS (Netherlands)

    T.A. Kanters (Tim A.); A. Steenhoek (Adri); L. van Hakkaart-van Roijen (Leona)

    2014-01-01

    textabstractBackground: The relatively low budget impact of orphan drugs is often used as an argument in reimbursement decisions. However, overall, the budget impact of orphan drugs can still be substantial. In this study, we assess the uptake and budget impact of orphan drugs in the

  17. Neglect and perceived stigmatization impact psychological distress of orphans in Tanzania

    Directory of Open Access Journals (Sweden)

    Katharin Hermenau

    2015-11-01

    Full Text Available Background: Research has shown that orphans in sub-Saharan Africa are at increased risk for mental health problems. Exposure to maltreatment and HIV/AIDS-related stigmatization are related to orphans’ psychological distress. Yet, researchers stress the need for more research in low-income countries to identify which factors of being an orphan may lead to psychological distress. Objectives: The present study aims to systematically investigate orphans’ experiences of maltreatment and stigmatization to identify factors that relate to their psychological distress. Methods: In total, 89 Tanzanian children who had lost at least one parent were compared to 89 matched non-orphans (mean age: 11 years; 51% boys. We measured exposure to maltreatment and perceived stigmatization as an orphan. Mental health was assessed using the Strengths and Difficulties Questionnaire, the Children's Depression Inventory, the UCLA PTSD Index for Children, and the Reactive–Proactive Questionnaire. Results: Orphans reported significantly more experiences of neglect, but not of abuse. A group comparison revealed more depressive symptoms, posttraumatic stress symptoms, and aggressive behavior among orphans. Neglect, abuse, and stigmatization correlated with orphans’ internalizing and externalizing problems, yet only neglect and stigmatization were related to orphans’ depression severity. Perceived stigmatization moderated the relationship between neglect and depression. Conclusions: Our findings suggest that orphans in Tanzania are at increased risk of experiencing neglect. Maltreatment and perceived stigmatization may play a role in orphans’ psychological distress. Culturally appropriate and evidence-based interventions may help to prevent maltreatment and stigmatization of orphans.

  18. Unique characteristics of regulatory approval and pivotal studies of orphan anticancer drugs in Japan.

    Science.gov (United States)

    Nakayama, Hiroki; Tsukamoto, Katsura

    2018-04-17

    The approval of orphan anticancer drugs has increased, with the number exceeding that of non-orphan drugs in Japan in recent years. Although orphan anticancer drugs may have unique characteristics due to their rarity, these have not been fully characterized. We investigated anticancer drugs approved in Japan between April 2004 and November 2017 to reveal the characteristics of regulatory approval and pivotal studies on orphan anticancer drugs compared to non-orphan drugs. The median regulatory review time and number of patients in pivotal studies on orphan anticancer drugs (281.0 days [interquartile range, 263.3-336.0]; 222.5 patients [66.0-454.3]) were significantly lower than those on non-orphan drugs (353.0 days [277.0-535.5]; 521.0 patients [303.5-814.5], respectively) (P < 0.001). Phase II, non-randomized and non-controlled designs were more frequently used in pivotal studies on orphan anticancer drugs (45.9%, 41.9% and 43.2%) than non-orphan drugs (17.2%, 14.1% and 14.1%, respectively). Response rate was more commonly used as a primary endpoint in pivotal studies on orphan anticancer drugs (48.6%) than non-orphan drugs (17.2%). Indications limited by molecular features, second or later treatment line, and accelerated approval in the United States were associated with the use of response rate in orphan anticancer drug studies. In conclusion, we demonstrated that orphan anticancer drugs in Japan have unique characteristics compared to non-orphan drugs: shorter regulatory review and pivotal studies frequently using phase II, non-randomized, or non-controlled designs and response rate as a primary endpoint, with fewer patients.

  19. Insurance companies' perspectives on the orphan drug pipeline.

    Science.gov (United States)

    Handfield, Robert; Feldstein, Josh

    2013-11-01

    Rare diseases are of increasing concern to private and public healthcare insurance plans. Largely neglected by manufacturers before the 1983 passing of the Orphan Drug Act (ODA), orphan drugs have become a commercialization target of steadily increasing importance to the healthcare industry. The ODA mandates the coverage of rare diseases, which are defined in research communities as diseases that are so infrequent that there is no reasonable expectation of a drugmaker recovering the cost of developing that drug. To determine the views of leading commercial US payers regarding providing access to and coverage for orphan drugs; to assess whether and to what degree cost-effectiveness analysis (CEA) is viewed by payers as relevant to rare disease coverage. The study sample was identified through a call for action sent by America's Health Insurance Plans to its members, resulting in 4 interviews conducted and 3 completed surveys from a total of 7 companies. These 7 US health insurance companies represent approximately 75% of the US private insurance market by revenue and include approximately 157 million covered lives (using self-reported data from insurance companies). Representatives of 3 companies responded to the survey, and representatives of 4 companies were interviewed via the phone. The interviews were conducted with subject matter experts at each company and included 2 senior vice presidents of a pharmacy program, 1 chief medical director, and 1 head of pharmacoeconomics. The surveys were completed by 1 vice president of clinical pharmacy strategy, 1 chief pharmacy director, and 1 medical director. Based on the responses in this study, approximately 67% of US private insurance companies are concerned about orphan drugs, but only approximately 17% have developed meaningful strategies for addressing the cost of orphan drugs. Of the companies who do have such a strategy, 100% are unsure how to determine the best economic assessment tools to control orphan drug

  20. Bioinformatic Analysis Reveals Archaeal tRNATyr and tRNATrp Identities in Bacteria

    Directory of Open Access Journals (Sweden)

    Takahito Mukai

    2017-02-01

    Full Text Available The tRNA identity elements for some amino acids are distinct between the bacterial and archaeal domains. Searching in recent genomic and metagenomic sequence data, we found some candidate phyla radiation (CPR bacteria with archaeal tRNA identity for Tyr-tRNA and Trp-tRNA synthesis. These bacteria possess genes for tyrosyl-tRNA synthetase (TyrRS and tryptophanyl-tRNA synthetase (TrpRS predicted to be derived from DPANN superphylum archaea, while the cognate tRNATyr and tRNATrp genes reveal bacterial or archaeal origins. We identified a trace of domain fusion and swapping in the archaeal-type TyrRS gene of a bacterial lineage, suggesting that CPR bacteria may have used this mechanism to create diverse proteins. Archaeal-type TrpRS of bacteria and a few TrpRS species of DPANN archaea represent a new phylogenetic clade (named TrpRS-A. The TrpRS-A open reading frames (ORFs are always associated with another ORF (named ORF1 encoding an unknown protein without global sequence identity to any known protein. However, our protein structure prediction identified a putative HIGH-motif and KMSKS-motif as well as many α-helices that are characteristic of class I aminoacyl-tRNA synthetase (aaRS homologs. These results provide another example of the diversity of molecular components that implement the genetic code and provide a clue to the early evolution of life and the genetic code.

  1. Orphans in the Dead Sea Scrolls | Kotzé | HTS Teologiese Studies ...

    African Journals Online (AJOL)

    The investigation concludes that the references to orphans in these passages do not have the same rhetorical functions. In CD 6, the wordings of authoritative scriptures are adapted to portray orphans and widows as the victims of wrongdoing. In 1QHa and 4Q434, however, orphans are mentioned in hymns that praise the ...

  2. Orphan caribou, Rangifer tarandus, calves: A re-evaluation of overwinter survival data

    Science.gov (United States)

    Joly, Kyle

    2000-01-01

    Low sample size and high variation within populations reduce power of statistical tests. These aspects of statistical power appear to have affected an analysis comparing overwinter survival rates of non-orphan and orphan Caribou (Rangifer tarandus) calves by an earlier study for the Porcupine Caribou Herd. A re-evaluation of the data revealed that conclusions about a lack of significant difference in the overwinter survival rates between orphan and non-orphan calves were premature.

  3. Assertiveness and Attitudes of HIV/AIDS Orphaned Girls Towards Education in Kampala (Uganda).

    Science.gov (United States)

    Kitara, David Lagoro; Amongin, Hellen Christine; Oonyu, Joseph C; Baguma, Peter K

    2013-08-09

    Whereas HIV/AIDS prevalence has been declining in Uganda from 30% to less than 10% in the last 2 decades, the number of HIV/AIDS orphaned girls in secondary schools is still high and girl children have tended to carry the heaviest burdens of family responsibilities thereby adversely affecting their assertiveness and attitudes towards education. Assertiveness is a critical life skill that enables a person to state an opinion, claim a right, or establish authority and it is important to improve attitude towards education. This study examined the relationship between assertiveness and attitude towards education of HIV/AIDS orphaned and non-orphaned adolescent school girls in Kampala. The California Psychological Inventory (CPI) Dominance (Do) Assertiveness Scale and the Attitude Scale were administered to 225 students consecutively selected from 6 secondary schools in Kampala. HIV/AIDS Orphaned girls had lower levels of assertiveness and most had a negative attitude towards education compared to non-orphaned girls. Girls orphaned to HIV/AIDS were less assertive compared to those orphaned by other causes. There was a positive relationship between assertiveness and attitude towards education among orphaned adolescent secondary school girls in Kampala. Girls orphaned to HIV/AIDS were less assertive compared to other school girls and have a poor attitude towards education.

  4. Prediction of novel archaeal enzymes from sequence-derived features

    DEFF Research Database (Denmark)

    Jensen, Lars Juhl; Skovgaard, Marie; Brunak, Søren

    2002-01-01

    The completely sequenced archaeal genomes potentially encode, among their many functionally uncharacterized genes, novel enzymes of biotechnological interest. We have developed a prediction method for detection and classification of enzymes from sequence alone (available at http://www.cbs.dtu.dk/......The completely sequenced archaeal genomes potentially encode, among their many functionally uncharacterized genes, novel enzymes of biotechnological interest. We have developed a prediction method for detection and classification of enzymes from sequence alone (available at http......://www.cbs.dtu.dk/services/ArchaeaFun/). The method does not make use of sequence similarity; rather, it relies on predicted protein features like cotranslational and posttranslational modifications, secondary structure, and simple physical/chemical properties....

  5. Stratification of archaeal membrane lipids in the ocean and implications for adaptation and chemotaxonomy of planktonic archaea.

    Science.gov (United States)

    Zhu, Chun; Wakeham, Stuart G; Elling, Felix J; Basse, Andreas; Mollenhauer, Gesine; Versteegh, Gerard J M; Könneke, Martin; Hinrichs, Kai-Uwe

    2016-12-01

    Membrane lipids of marine planktonic archaea have provided unique insights into archaeal ecology and paleoceanography. However, past studies of archaeal lipids in suspended particulate matter (SPM) and sediments mainly focused on a small class of fully saturated glycerol dibiphytanyl glycerol tetraether (GDGT) homologues identified decades ago. The apparent low structural diversity of GDGTs is in strong contrast to the high diversity of metabolism and taxonomy among planktonic archaea. Furthermore, adaptation of archaeal lipids in the deep ocean remains poorly constrained. We report the archaeal lipidome in SPM from diverse oceanic regimes. We extend the known inventory of planktonic archaeal lipids to include numerous unsaturated archaeal ether lipids (uns-AELs). We further reveal (i) different thermal regulations and polar headgroup compositions of membrane lipids between the epipelagic (≤ 100 m) and deep (>100 m) populations of archaea, (ii) stratification of unsaturated GDGTs with varying redox conditions, and (iii) enrichment of tetra-unsaturated archaeol and fully saturated GDGTs in epipelagic and deep oxygenated waters, respectively. Such stratified lipid patterns are consistent with the typical distribution of archaeal phylotypes in marine environments. We, thus, provide an ecological context for GDGT-based paleoclimatology and bring about the potential use of uns-AELs as biomarkers for planktonic Euryarchaeota. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  6. Correlating Orphaned Windows Registry Data Structures

    Directory of Open Access Journals (Sweden)

    Damir Kahved

    2009-06-01

    Full Text Available Recently, it has been shown that deleted entries of the Microsoft Windows registry (keys may still reside in the system files once the entries have been deleted from the active database. Investigating the complete keys in context may be extremely important from both a Forensic Investigation point of view and a legal point of view where a lack of context can bring doubt to an argument. In this paper we formalise the registry behaviour and show how a retrieved value may not maintain a relation to the part of the registry it belonged to and hence lose that context. We define registry orphans and elaborate on how they can be created inadvertently during software uninstallation and other system processes. We analyse the orphans and attempt to reconstruct them automatically. We adopt a data mining approach and introduce a set of attributes that can be applied by the forensic investigator to match values to their parents. The heuristics are encoded in a Decision Tree that can discriminate between keys and select those which most likely owned a particular orphan value.

  7. Multiple transitions and HIV risk among orphaned Kenyan schoolgirls.

    Science.gov (United States)

    Mojola, Sanyu A

    2011-03-01

    Why are orphaned girls at particular risk of acquiring HIV infection? Using a transition-to-adulthood framework, this study employs qualitative data from Nyanza Province, Kenya, to explore pathways to HIV risk among orphaned and nonorphaned high-school girls. It shows how simultaneous processes such as leaving their parental home, negotiating financial access, and relationship transitions interact to produce disproportionate risk for orphaned girls. The role of financial provision and parental love in modifying girls' trajectories to risk are also explored. A testable theoretical model is proposed based on the qualitative findings, and policy implications are suggested.

  8. Tackling the growing number of suspended and orphan wells

    International Nuclear Information System (INIS)

    Cornford, A.

    1996-01-01

    The number of suspended and potentially orphaned wells in the three oil producing Western provinces has grown substantially in recent years. There are currently some 38,000 wells in Alberta, 2,000 in B.C., and some 5,000 in Saskatchewan that have been inactive for at least one year. Governments are now looking at proposals to deal with the issue which, if implemented, will have far reaching implications for the oil and gas and reclamation industry in Western Canada. Proposals to date have not dealt with the potential liability for sulphur-recovery gas plants and oil and gas transmission pipelines and associated facilities. It is estimated that to pay for the expanded orphaned well program in Alberta, the current Orphan Well Program would have to be increased from $2 million to $5 million in the first four years. The recommendation is to levy an annual fee on all inactive wells and facilities. This would put the burden of paying for orphan wells on those who have facilities most in risk of becoming orphans. Informed opinion is that while the cost of addressing the problem is admittedly high, however, preventing it from getting worse is much less than the alternative

  9. Archaeal Communities in a Heterogeneous Hypersaline-Alkaline Soil

    Directory of Open Access Journals (Sweden)

    Yendi E. Navarro-Noya

    2015-01-01

    Full Text Available In this study the archaeal communities in extreme saline-alkaline soils of the former lake Texcoco, Mexico, with electrolytic conductivities (EC ranging from 0.7 to 157.2 dS/m and pH from 8.5 to 10.5 were explored. Archaeal communities in the 0.7 dS/m pH 8.5 soil had the lowest alpha diversity values and were dominated by a limited number of phylotypes belonging to the mesophilic Candidatus Nitrososphaera. Diversity and species richness were higher in the soils with EC between 9.0 and 157.2 dS/m. The majority of OTUs detected in the hypersaline soil were members of the Halobacteriaceae family. Novel phylogenetic branches in the Halobacteriales class were detected in the soil, and more abundantly in soil with the higher pH (10.5, indicating that unknown and uncharacterized Archaea can be found in this soil. Thirteen different genera of the Halobacteriaceae family were identified and were distributed differently between the soils. Halobiforma, Halostagnicola, Haloterrigena, and Natronomonas were found in all soil samples. Methanogenic archaea were found only in soil with pH between 10.0 and 10.3. Retrieved methanogenic archaea belonged to the Methanosarcinales and Methanomicrobiales orders. The comparison of the archaeal community structures considering phylogenetic information (UniFrac distances clearly clustered the communities by pH.

  10. Hereditary Angioedema: The Economics of Treatment of an Orphan Disease.

    Science.gov (United States)

    Lumry, William Raymond

    2018-01-01

    This review will discuss the cost burden of hereditary angioedema on patients, healthcare systems, and society. The impact of availability of and access to novel and specific therapies on morbidity, mortality, and the overall burden of disease will be explored along with potential changes in treatment paradigms to improve effectiveness and reduce cost of treatment. The prevalence of orphan diseases, legislative incentives to encourage development of orphan disease therapies and the impact of orphan disease treatment on healthcare payment systems will be discussed.

  11. Diversity, assembly and regulation of archaeal type IV pili-like and non-type-IV pili-like surface structures.

    Science.gov (United States)

    Lassak, Kerstin; Ghosh, Abhrajyoti; Albers, Sonja-Verena

    2012-01-01

    Archaea have evolved fascinating surface structures allowing rapid adaptation to changing environments. The archaeal surface appendages display such diverse biological roles as motility, adhesion, biofilm formation, exchange of genetic material and species-specific interactions and, in turn, increase fitness of the cells. Intriguingly, despite sharing the same functions with their bacterial counterparts, the assembly mechanism of many archaeal surface structures is rather related to assembly of bacterial type IV pili. This review summarizes our state-of-the-art knowledge about unique structural and biochemical properties of archaeal surface appendages with a particular focus on archaeal type IV pili-like structures. The latter comprise not only widely distributed archaella (formerly known as archaeal flagella), but also different highly specialized archaeal pili, which are often restricted to certain species. Recent findings regarding assembly mechanisms, structural aspects and physiological roles of these type IV pili-like structures will be discussed in detail. Recently, first regulatory proteins involved in transition from both planktonic to sessile lifestyle and in assembly of archaella were identified. To conclude, we provide novel insights into regulatory mechanisms underlying the assembly of archaeal surface structures. Copyright © 2012. Published by Elsevier Masson SAS.

  12. Orphan drugs

    OpenAIRE

    Goločorbin-Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojša; Mikov, Momir

    2013-01-01

    Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of ...

  13. Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries.

    Science.gov (United States)

    Gammie, Todd; Lu, Christine Y; Babar, Zaheer Ud-Din

    2015-01-01

    To review existing regulations and policies utilised by countries to enable patient access to orphan drugs. A review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country. Fifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country's legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country's pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access. Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.

  14. Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries.

    Directory of Open Access Journals (Sweden)

    Todd Gammie

    Full Text Available To review existing regulations and policies utilised by countries to enable patient access to orphan drugs.A review of the literature (1998 to 2014 was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country.Fifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country's legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35 had in place orphan drug legislation. Access to orphan drugs depends on individual country's pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access.Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.

  15. Implementation of oral health education to orphan children

    International Nuclear Information System (INIS)

    Malik, N.

    2015-01-01

    To determine the knowledge and oral hygiene status of orphange children in apune and a changes in them after health education. Study Design: Interventional study. Place and Duration of Study: Centers for Orphan Children in Pune, India, from April to June 2014. Methodology: A specially designed questionnaire was used to assess the dental problems and existing oral hygiene maintenance practice among children between 5 - 12 years of age (n=100) in an orphanage center. Pre- and post interventional intra-oral examination was carried out to check their oral hygiene status which included DMFS (Decayed Missing Filled Tooth Surfaces index (for permanent teeth)), OHIS (Simplified Oral Hygiene Index) and gingival indices. Intervention was in the form of oral health education, demonstration of correct brushing technique, diet counselling and maintenance of overall oral hygiene. Results: Present study shows that the orphans had multiple dental problems along with improper oral hygiene practices and careless attitude towards oral health. Pre- and post-interventional DMFS was compared using Wilcoxon sign rank test, which was not significant; while OHIS and gingival indices were compared by using repeat measures ANOVA(p < 0.001) which was significant for each, respectively. Conclusion: There was considerable improvement in the oral hygiene status of orphans due to educational intervention. Oral health education at right age can help to cultivate healthy oral hygiene practices in orphans which will benefit them for lifelong. Caretakers should be educated and trained about oral hygiene practices so that they can implement it and supervise the orphan children. (author)

  16. Challenges to orphan drugs access in Eastern Europe: the case of Bulgaria.

    Science.gov (United States)

    Iskrov, Georgi; Miteva-Katrandzhieva, Tsonka; Stefanov, Rumen

    2012-11-01

    This article explores how an Eastern European country could deal with orphan drugs access, combining EU policies with its own national settings. The cross-sectional observational study takes the total number of orphan drugs (61) available on EU level by March 2011, and then consecutively filters it through the requirements and criteria of relevant Bulgarian legislation on registration, pricing and reimbursement of medicinal products, obtaining the final number of accessible orphan drugs (16) in Bulgaria. The study further evaluates the average time period from market authorisation to positive reimbursement decision by Bulgarian health authorities (43±29.1 months). Access to orphan drugs should be provided on a reasonable and justified basis. Having in mind the limited availability of resources, it is not a question whether to prioritise rarity, but to create legitimate mechanisms for properly assessing orphan drugs' value and optimally using this value, according to the society's needs and views. The analysis identifies four important challenges to orphan drugs' access in Eastern Europe: (1) elaboration of new orphan drugs pricing approaches, (2) further interaction of cost-effectiveness analysis with medical criteria, (3) active introduction of epidemiological registries for rare diseases, and (4) research of societal preferences and raising public awareness. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries

    Science.gov (United States)

    Gammie, Todd

    2015-01-01

    Objective To review existing regulations and policies utilised by countries to enable patient access to orphan drugs. Methods A review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country. Results Fifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country’s legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country’s pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access. Conclusions Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases. PMID:26451948

  18. Accounting for orphaned aftershocks in the earthquake background rate

    Science.gov (United States)

    Van Der Elst, Nicholas

    2017-01-01

    Aftershocks often occur within cascades of triggered seismicity in which each generation of aftershocks triggers an additional generation, and so on. The rate of earthquakes in any particular generation follows Omori's law, going approximately as 1/t. This function decays rapidly, but is heavy-tailed, and aftershock sequences may persist for long times at a rate that is difficult to discriminate from background. It is likely that some apparently spontaneous earthquakes in the observational catalogue are orphaned aftershocks of long-past main shocks. To assess the relative proportion of orphaned aftershocks in the apparent background rate, I develop an extension of the ETAS model that explicitly includes the expected contribution of orphaned aftershocks to the apparent background rate. Applying this model to California, I find that the apparent background rate can be almost entirely attributed to orphaned aftershocks, depending on the assumed duration of an aftershock sequence. This implies an earthquake cascade with a branching ratio (the average number of directly triggered aftershocks per main shock) of nearly unity. In physical terms, this implies that very few earthquakes are completely isolated from the perturbing effects of other earthquakes within the fault system. Accounting for orphaned aftershocks in the ETAS model gives more accurate estimates of the true background rate, and more realistic expectations for long-term seismicity patterns.

  19. Posttraumatic stress symptoms among adults caring for orphaned children in HIV-endemic South Africa.

    Science.gov (United States)

    Kuo, Caroline; Reddy, Madhavi K; Operario, Don; Cluver, Lucie; Stein, Dan J

    2013-06-01

    There is growing evidence that mental health is a significant issue among families affected by AIDS-related parental deaths. The current study examined posttraumatic stress symptoms and identified risk factors among adults caring for AIDS-orphaned and other-orphaned children in an HIV-endemic South African community. A representative community sample of adults caring for children (N = 1,599) was recruited from Umlazi Township. Of the 116 participants who reported that a traumatic event was still bothering them, 19 % reported clinically significant posttraumatic stress symptoms. Of the 116 participants, caregivers of AIDS-orphaned and other-orphaned children were significantly more likely to meet threshold criteria for PTSD (28 %) compared to caregivers of non-orphaned children (10 %). Household receipt of an old age pension was identified as a possible protective factor for PTSD symptoms among caregivers of orphaned children. Services are needed to address PTSD symptoms among caregivers of orphaned children.

  20. Seasonal effects in a lake sediment archaeal community of the Brazilian Savanna.

    Science.gov (United States)

    Rodrigues, Thiago; Catão, Elisa; Bustamante, Mercedes M C; Quirino, Betania F; Kruger, Ricardo H; Kyaw, Cynthia M

    2014-01-01

    The Cerrado is a biome that corresponds to 24% of Brazil's territory. Only recently microbial communities of this biome have been investigated. Here we describe for the first time the diversity of archaeal communities from freshwater lake sediments of the Cerrado in the dry season and in the transition period between the dry and rainy seasons, when the first rains occur. Gene libraries were constructed, using Archaea-specific primers for the 16S rRNA and amoA genes. Analysis revealed marked differences between the archaeal communities found in the two seasons. I.1a and I.1c Thaumarchaeota were found in greater numbers in the transition period, while MCG Archaea was dominant on the dry season. Methanogens were only found in the dry season. Analysis of 16S rRNA sequences revealed lower diversity on the transition period. We detected archaeal amoA sequences in both seasons, but there were more OTUs during the dry season. These sequences were within the same cluster as Nitrosotalea devanaterra's amoA gene. The principal coordinate analysis (PCoA) test revealed significant differences between samples from different seasons. These results provide information on archaeal diversity in freshwater lake sediments of the Cerrado and indicates that rain is likely a factor that impacts these communities.

  1. Turnover of microbial lipids in the deep biosphere and growth of benthic archaeal populations.

    Science.gov (United States)

    Xie, Sitan; Lipp, Julius S; Wegener, Gunter; Ferdelman, Timothy G; Hinrichs, Kai-Uwe

    2013-04-09

    Deep subseafloor sediments host a microbial biosphere with unknown impact on global biogeochemical cycles. This study tests previous evidence based on microbial intact polar lipids (IPLs) as proxies of live biomass, suggesting that Archaea dominate the marine sedimentary biosphere. We devised a sensitive radiotracer assay to measure the decay rate of ([(14)C]glucosyl)-diphytanylglyceroldiether (GlcDGD) as an analog of archaeal IPLs in continental margin sediments. The degradation kinetics were incorporated in model simulations that constrained the fossil fraction of subseafloor IPLs and rates of archaeal turnover. Simulating the top 1 km in a generic continental margin sediment column, we estimated degradation rate constants of GlcDGD being one to two orders of magnitude lower than those of bacterial IPLs, with half-lives of GlcDGD increasing with depth to 310 ky. Given estimated microbial community turnover times of 1.6-73 ky in sediments deeper than 1 m, 50-96% of archaeal IPLs represent fossil signals. Consequently, previous lipid-based estimates of global subseafloor biomass probably are too high, and the widely observed dominance of archaeal IPLs does not rule out a deep biosphere dominated by Bacteria. Reverse modeling of existing concentration profiles suggest that archaeal IPL synthesis rates decline from around 1,000 pg⋅mL(-1) sediment⋅y(-1) at the surface to 0.2 pg⋅mL(-1)⋅y(-1) at 1 km depth, equivalent to production of 7 × 10(5) to 140 archaeal cells⋅mL(-1) sediment⋅y(-1), respectively. These constraints on microbial growth are an important step toward understanding the relationship between the deep biosphere and the carbon cycle.

  2. Search and localization of orphan sources

    International Nuclear Information System (INIS)

    Gayral, J.-P.

    2001-01-01

    The control of all radioactive materials should be a major and permanent concern of every state. This paper outlines some of the steps which should be taken in order to detect and localize orphan sources. Two of them are of great importance to any state wishing to resolve the orphan source problem. The first one is to analyse the situation and the second is to establish a strategy before taking action. It is the responsibility of the state to work on the first step; but for the second one it can draw on the advice of the IAEA specialists with experience grained from a variety of situations

  3. Determinants of orphan drugs prices in France: a regression analysis.

    Science.gov (United States)

    Korchagina, Daria; Millier, Aurelie; Vataire, Anne-Lise; Aballea, Samuel; Falissard, Bruno; Toumi, Mondher

    2017-04-21

    The introduction of the orphan drug legislation led to the increase in the number of available orphan drugs, but the access to them is often limited due to the high price. Social preferences regarding funding orphan drugs as well as the criteria taken into consideration while setting the price remain unclear. The study aimed at identifying the determinant of orphan drug prices in France using a regression analysis. All drugs with a valid orphan designation at the moment of launch for which the price was available in France were included in the analysis. The selection of covariates was based on a literature review and included drug characteristics (Anatomical Therapeutic Chemical (ATC) class, treatment line, age of target population), diseases characteristics (severity, prevalence, availability of alternative therapeutic options), health technology assessment (HTA) details (actual benefit (AB) and improvement in actual benefit (IAB) scores, delay between the HTA and commercialisation), and study characteristics (type of study, comparator, type of endpoint). The main data sources were European public assessment reports, HTA reports, summaries of opinion on orphan designation of the European Medicines Agency, and the French insurance database of drugs and tariffs. A generalized regression model was developed to test the association between the annual treatment cost and selected covariates. A total of 68 drugs were included. The mean annual treatment cost was €96,518. In the univariate analysis, the ATC class (p = 0.01), availability of alternative treatment options (p = 0.02) and the prevalence (p = 0.02) showed a significant correlation with the annual cost. The multivariate analysis demonstrated significant association between the annual cost and availability of alternative treatment options, ATC class, IAB score, type of comparator in the pivotal clinical trial, as well as commercialisation date and delay between the HTA and commercialisation. The

  4. The extent of community and public support available to families caring for orphans in Malawi.

    Science.gov (United States)

    Kidman, Rachel; Heymann, S Jody

    2009-04-01

    There are an estimated 15 million AIDS orphans worldwide. Families play an important role in safeguarding orphans, but they may be increasingly compromised by the HIV/AIDS epidemic. The international aid community has recognized the need to help families continue caring for orphaned children by strengthening their safety nets. Before we build new structures, however, we need to know the extent to which community and public safety nets already provide support to families with orphans. To address this gap, we analyzed nationally representative data from 27,495 children in the 2004-2005 Malawi Integrated Household Survey. We found that communities commonly assisted orphan households through private transfers; organized responses to the orphan crisis were far less frequent. Friends and relatives provided assistance to over 75% of orphan households through private gifts, but the value of such support was relatively low. Over 40% of orphans lived in a community with support groups for the chronically ill and approximately a third of these communities provided services specifically for orphans and other vulnerable children. Public programs, which form a final safety net for vulnerable households, were more widespread. Free/subsidized agricultural inputs and food were the most commonly used public safety nets by children's households in the past year (44 and 13%, respectively), and households with orphans were more likely to be beneficiaries. Malawi is poised to drastically expand safety nets to orphans and their families, and these findings provide an important foundation for this process.

  5. Community-based capital cash transfer to support orphans in Western Kenya

    DEFF Research Database (Denmark)

    Skovdal, Morten; Mwasiaji, W.; Morrison, J.

    2008-01-01

    Various types of 'cash transfer' are currently receiving much attention as a way of helping orphans and vulnerable children in Africa. Drawing on a qualitative study conducted in Western Kenya, this paper points to the strategy of community-based capital cash transfers (CCCT) as a particularly...... promising method of supporting orphans and carers. Qualitative data were obtained from 15 orphans and 26 caregivers in Bondo District, Kenya, beneficiaries of a CCCT programme run by a partnership between the community, the government social services department and a foreign donor. Our findings suggest...... that the programme not only increased food availability, but also enhanced social capital. Further research is needed to explore the potential of CCCT in supporting orphans and vulnerable children in countries with high orphanhood rates....

  6. Access to orphan drugs in Europe: current and future issues.

    Science.gov (United States)

    Michel, Morgane; Toumi, Mondher

    2012-02-01

    Orphan drugs target small populations of patients. In order to make the field more attractive to pharmaceutical companies and encourage R&D in rare diseases, incentives were put forward by the EU, which are discussed in this article. Because they often are the only available option to treat a disease, some orphan drugs are considered to have high value and as such benefit from high prices on national markets. This has made orphan drugs an attractive market for pharmaceutical companies, with approximately 40 approved orphan drugs generating over $200 million each in yearly sales. The resulting burden this puts on national health insurances may lead to a change in regulation and will certainly lead to new national pricing and reimbursement strategies. They will need to be coherent, fair, effective and sustainable so as to be predictable for companies. Reflection on the subject needs to be initiated.

  7. Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience.

    Science.gov (United States)

    Casamento, K; Laverty, A; Wilsher, M; Twiss, J; Gabbay, E; Glaspole, I; Jaffe, A

    2016-04-18

    We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were sent regular emails between July 2009 and June 2014 requesting information on patients they had seen with any of 30 rare lung diseases. Prevalence rates were calculated using population statistics. Emails were sent to 649 Australian respiratory physicians and 65 in New Zealand. 231 (32.4%) physicians responded to emails a total of 1554 times (average 7.6 responses per physician). Prevalence rates of 30 rare lung diseases are reported. A multi-disease rare lung disease registry was implemented in the Australian and New Zealand health care settings that provided prevalence data on orphan lung diseases in this region but was limited by under reporting.

  8. Archaeal orthologs of Cdc45 and GINS form a stable complex that stimulates the helicase activity of MCM.

    Science.gov (United States)

    Xu, Yuli; Gristwood, Tamzin; Hodgson, Ben; Trinidad, Jonathan C; Albers, Sonja-Verena; Bell, Stephen D

    2016-11-22

    The regulated recruitment of Cdc45 and GINS is key to activating the eukaryotic MCM(2-7) replicative helicase. We demonstrate that the homohexameric archaeal MCM helicase associates with orthologs of GINS and Cdc45 in vivo and in vitro. Association of these factors with MCM robustly stimulates the MCM helicase activity. In contrast to the situation in eukaryotes, archaeal Cdc45 and GINS form an extremely stable complex before binding MCM. Further, the archaeal GINS•Cdc45 complex contains two copies of Cdc45. Our analyses give insight into the function and evolution of the conserved core of the archaeal/eukaryotic replisome.

  9. A roadmap for breeding orphan leafy vegetable species

    OpenAIRE

    Sogbohossou, E.O.D.; Achigan-Dako, Enoch G.; Maundu, Patrick; Solberg, Svein; Deguenon, Edgar M.S.; Mumm, Rita H.; Hale, Iago; Deynze, van, Allen; Schranz, M.E.

    2018-01-01

    Despite an increasing awareness of the potential of "orphan" or unimproved crops to contribute to food security and enhanced livelihoods for farmers, coordinated research agendas to facilitate production and use of orphan crops by local communities are generally lacking. We provide an overview of the current knowledge on leafy vegetables with a focus on Gynandropsis gynandra, a highly nutritious species used in Africa and Asia, and highlight general and species-specific guidelines for partici...

  10. World and experiences of AIDS orphans in north central Namibia

    NARCIS (Netherlands)

    Brug, van der M.

    2007-01-01

    How do young AIDS orphans deal with the loss of their parents and their changed circumstances? This thesis discusses the social environment, experiences and perceptions of fourteen orphans in north central Namibia. The author followed the children for five months from September 2003 until March

  11. Abundance and diversity of archaeal accA gene in hot springs in Yunnan Province, China.

    Science.gov (United States)

    Song, Zhao-Qi; Wang, Li; Wang, Feng-Ping; Jiang, Hong-Chen; Chen, Jin-Quan; Zhou, En-Min; Liang, Feng; Xiao, Xiang; Li, Wen-Jun

    2013-09-01

    It has been suggested that archaea carrying the accA gene, encoding the alpha subunit of the acetyl CoA carboxylase, autotrophically fix CO2 using the 3-hydroxypropionate/4-hydroxybutyrate pathway in low-temperature environments (e.g., soils, oceans). However, little new information has come to light regarding the occurrence of archaeal accA genes in high-temperature ecosystems. In this study, we investigated the abundance and diversity of archaeal accA gene in hot springs in Yunnan Province, China, using DNA- and RNA-based phylogenetic analyses and quantitative polymerase chain reaction. The results showed that archaeal accA genes were present and expressed in the investigated Yunnan hot springs with a wide range of temperatures (66-96 °C) and pH (4.3-9.0). The majority of the amplified archaeal accA gene sequences were affiliated with the ThAOA/HWCG III [thermophilic ammonia-oxidizing archaea (AOA)/hot water crenarchaeotic group III]. The archaeal accA gene abundance was very close to that of AOA amoA gene, encoding the alpha subunit of ammonia monooxygenase. These data suggest that AOA in terrestrial hot springs might acquire energy from ammonia oxidation coupled with CO2 fixation using the 3-hydroxypropionate/4-hydroxybutyrate pathway.

  12. Salinity drives archaeal distribution patterns in high altitude lake sediments on the Tibetan Plateau.

    Science.gov (United States)

    Liu, Yongqin; Priscu, John C; Xiong, Jinbo; Conrad, Ralf; Vick-Majors, Trista; Chu, Haiyan; Hou, Juzhi

    2016-03-01

    Archaeal communities and the factors regulating their diversity in high altitude lakes are poorly understood. Here, we provide the first high-throughput sequencing study of Archaea from Tibetan Plateau lake sediments. We analyzed twenty lake sediments from the world's highest and largest plateau and found diverse archaeal assemblages that clustered into groups dominated by methanogenic Euryarchaeota, Crenarchaeota and Halobacteria/mixed euryarchaeal phylotypes. Statistical analysis inferred that salinity was the major driver of community composition, and that archaeal diversity increased with salinity. Sediments with the highest salinities were mostly dominated by Halobacteria. Crenarchaeota dominated at intermediate salinities, and methanogens were present in all lake sediments, albeit most abundant at low salinities. The distribution patterns of the three functional types of methanogens (hydrogenotrophic, acetotrophic and methylotrophic) were also related to changes in salinity. Our results show that salinity is a key factor controlling archaeal community diversity and composition in lake sediments on a spatial scale that spans nearly 2000 km on the Tibetan Plateau. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Adolescent girls orphaned by AIDS in South Africa: Approaches in ...

    African Journals Online (AJOL)

    The effects of orphaning on adolescents girls are well documented in literature. Adolescents orphaned by AIDS have particular vulnerabilities to a range of mental health difficulties and with that they face specific challenges that include stigma and discrimination, poverty, school drop-out and sexual and labour exploitation.

  14. Seasonal Effects in a Lake Sediment Archaeal Community of the Brazilian Savanna

    Directory of Open Access Journals (Sweden)

    Thiago Rodrigues

    2014-01-01

    Full Text Available The Cerrado is a biome that corresponds to 24% of Brazil’s territory. Only recently microbial communities of this biome have been investigated. Here we describe for the first time the diversity of archaeal communities from freshwater lake sediments of the Cerrado in the dry season and in the transition period between the dry and rainy seasons, when the first rains occur. Gene libraries were constructed, using Archaea-specific primers for the 16S rRNA and amoA genes. Analysis revealed marked differences between the archaeal communities found in the two seasons. I.1a and I.1c Thaumarchaeota were found in greater numbers in the transition period, while MCG Archaea was dominant on the dry season. Methanogens were only found in the dry season. Analysis of 16S rRNA sequences revealed lower diversity on the transition period. We detected archaeal amoA sequences in both seasons, but there were more OTUs during the dry season. These sequences were within the same cluster as Nitrosotalea devanaterra’s amoA gene. The principal coordinate analysis (PCoA test revealed significant differences between samples from different seasons. These results provide information on archaeal diversity in freshwater lake sediments of the Cerrado and indicates that rain is likely a factor that impacts these communities.

  15. Children, AIDS and the politics of orphan care in Ethiopia: the extended family revisited.

    Science.gov (United States)

    Abebe, Tatek; Aase, Asbjorn

    2007-05-01

    The astounding rise in the number of orphans due to the HIV/AIDS epidemic has left many Ethiopian families and communities with enormous childcare problems. Available studies on the capacity and sustainability of the extended family system, which culturally performs the role of care for children in need, suggest two competing theories. The first is grounded in the social rupture thesis and assumes that the traditional system of orphan care is stretched by the impact of the epidemic, and is actually collapsing. By contrast, the second theory counter-suggests that the flexibility and strength of the informal childcare practise, if supported by appropriate interventions, can still support a large number of orphans. Based on a seven-month period of child-focused, qualitative research fieldwork in Ethiopia involving observations; in-depth interviews with orphans (42), social workers (12) and heads of households (18); focus group discussions with orphans (8), elderly people and community leaders (6); and story-writing by children in school contexts, this article explores the trade-offs and social dynamics of orphan care within extended family structures in Ethiopia. It argues that there is a rural-urban divide in the capacity to cater for orphans that emanates from structural differences as well as the socio-cultural and economic values associated with children. The care of orphans within extended family households is also characterised by multiple and reciprocal relationships in care-giving and care-receiving practices. By calling for a contextual understanding of the 'orphan burden', the paper concludes that interventions for orphans may consider care as a continuum in the light of four profiles of extended families, namely rupturing, transient, adaptive, and capable families.

  16. Archaeal “Dark Matter” and the Origin of Eukaryotes

    Science.gov (United States)

    Williams, Tom A.; Embley, T. Martin

    2014-01-01

    Current hypotheses about the history of cellular life are mainly based on analyses of cultivated organisms, but these represent only a small fraction of extant biodiversity. The sequencing of new environmental lineages therefore provides an opportunity to test, revise, or reject existing ideas about the tree of life and the origin of eukaryotes. According to the textbook three domains hypothesis, the eukaryotes emerge as the sister group to a monophyletic Archaea. However, recent analyses incorporating better phylogenetic models and an improved sampling of the archaeal domain have generally supported the competing eocyte hypothesis, in which core genes of eukaryotic cells originated from within the Archaea, with important implications for eukaryogenesis. Given this trend, it was surprising that a recent analysis incorporating new genomes from uncultivated Archaea recovered a strongly supported three domains tree. Here, we show that this result was due in part to the use of a poorly fitting phylogenetic model and also to the inclusion by an automated pipeline of genes of putative bacterial origin rather than nucleocytosolic versions for some of the eukaryotes analyzed. When these issues were resolved, analyses including the new archaeal lineages placed core eukaryotic genes within the Archaea. These results are consistent with a number of recent studies in which improved archaeal sampling and better phylogenetic models agree in supporting the eocyte tree over the three domains hypothesis. PMID:24532674

  17. [GPCRs heterodimerization: a new way towards the discovery of function for the orphan receptors?].

    Science.gov (United States)

    Levoye, Angélique; Jockers, Ralf

    2007-01-01

    G protein-coupled receptors (GPCRs), also called seven transmembrane domain (7TM) proteins, represent the largest family of cell surface receptors. GPCRs control a variety of physiological processes, are involved in multiple diseases and are major drug targets. Despite a vast effort of academic and industrial research, more than one hundred receptors remain orphans. These orphan GPCRs offer a great potential for drug discovery, as almost 60% of currently prescribed drugs target GPCRs. Deorphenization strategies have concentrated mainly on the identification of the natural ligands of these proteins. Recent advances have shown that orphan GPCRs, similar to orphan nuclear receptors, can regulate the function of non-orphan receptors by heterodimerization. These findings not only help to better understand the extraordinary diversity of GPCRs, but also open new perspectives for the identification of the function of these orphan receptors that hold great therapeutic potential.

  18. Solution approaches of social adaptation of orphan children

    OpenAIRE

    Olga Vahrameeva

    2013-01-01

    The actual problem of social-cultural activity of boarding schools directed on process of social adaptation of orphan children and children who have remained without guardianship of parents is considered in the article. Author offers use of an individual approach during the work with orphan children. This approach includes carrying out a complex of the interconnected programs of social and pedagogical work with the use of technologies of the social-cultural activity, which main objective is a...

  19. Orphan drugs for rare diseases: is it time to revisit their special market access status?

    Science.gov (United States)

    Simoens, Steven; Cassiman, David; Dooms, Marc; Picavet, Eline

    2012-07-30

    Orphan drugs are intended for diseases with a very low prevalence, and many countries have implemented legislation to support market access of orphan drugs. We argue that it is time to revisit the special market access status of orphan drugs. Indeed, evidence suggests that there is no societal preference for treating rare diseases. Although society appears to assign a greater value to severity of disease, this criterion is equally relevant to many common diseases. Furthermore, the criterion of equity in access to treatment, which underpins orphan drug legislation, puts more value on health improvement in rare diseases than in common diseases and implies that population health is not maximized. Finally, incentives for the development, pricing and reimbursement of orphan drugs have created market failures, including monopolistic prices and the artificial creation of rare diseases. We argue that, instead of awarding special market access status to orphan drugs, there is scope to optimize research and development (R&D) of orphan drugs and to control prices of orphan drugs by means of, for example, patent auctions, advance purchase commitments, pay-as-you-go schemes and dose-modification studies. Governments should consider carefully the right incentive strategy for R&D of orphan drugs in rare diseases.

  20. Factors affecting Archaeal Lipid Compositions of the Sulfolobus Species

    Science.gov (United States)

    He, L.; Han, J.; Wei, Y.; Lin, L.; Wei, Y.; Zhang, C.

    2010-12-01

    Temperature is the best known variable affecting the distribution of the archaeal glycerol dibiphytanyl glycerol tetraethers (GDGTs) in marine and freshwater systems. Other variables such as pH, ionic strength, or bicarbonate concentration may also affect archaeal GDGTs in terrestrial systems. Studies of pure cultures can help us pinpoint the specific effects these variables may have on archaeal lipid distribution in natural environments. In this study, three Sulfolobus species (HG4, HB5-2, HB9-6) isolated from Tengchong hot springs (pH 2-3, temperature 73-90°C) in China were used to investigate the effects of temperature, pH, substrate, and type of strain on the composition of GDGTs. Results showed that increase in temperature had negative effects on the relative contents of GDGT-0 (no cyclopentyl rings), GDGT-1 (one cyclopentyl ring), GDGT-2 and GDGT-3 but positive effects on GDGT-4, GDGT-4', GDGT-5 and GDGT-5'. Increase in pH, on the other hand, had negative effects on GDGT-0, GDGT-1, GDGT-4', GDGT-5 and GDGT-5', and positive effects on GDGT-3 and GDGT-4. GDGT-2 remained relatively constant with changing pH. When the HG4 was grown on different substrates, GDGT-5 was five time more abundant in sucrose-grown cultures than in yeast extract- or sulfur- grown cultures, suggesting that carbohydrates may stimulate the production of GDGT-5. For all three species, the ring index (average number of rings) of GDGTs correlated positively with incubation temperature. In HG4, ring index was much lower at optimal pH (3.5) than at other pH values. Ring index of HB5-2 or HB9-6 is higher than that of HG4, suggesting that speciation may affect the degree of cyclization of GDGT of the Sulfolobus. These results indicate that individual archaeal lipids respond differently to changes in environmental variables, which may be also species specific.

  1. Nitrification of archaeal ammonia oxidizers in a high- temperature hot spring

    Science.gov (United States)

    Chen, Shun; Peng, Xiaotong; Xu, Hengchao; Ta, Kaiwen

    2016-04-01

    The oxidation of ammonia by microbes has been shown to occur in diverse natural environments. However, the link of in situ nitrification activity to taxonomic identities of ammonia oxidizers in high-temperature environments remains poorly understood. Here, we studied in situ ammonia oxidation rates and the diversity of ammonia-oxidizing Archaea (AOA) in surface and bottom sediments at 77 °C in the Gongxiaoshe hot spring, Tengchong, Yunnan, China. The in situ ammonia oxidation rates measured by the 15N-NO3- pool dilution technique in the surface and bottom sediments were 4.80 and 5.30 nmol N g-1 h-1, respectively. Real-time quantitative polymerase chain reaction (qPCR) indicated that the archaeal 16S rRNA genes and amoA genes were present in the range of 0.128 to 1.96 × 108 and 2.75 to 9.80 × 105 gene copies g-1 sediment, respectively, while bacterial amoA was not detected. Phylogenetic analysis of 16S rRNA genes showed high sequence similarity to thermophilic Candidatus Nitrosocaldus yellowstonii, which represented the most abundant operational taxonomic units (OTU) in both surface and bottom sediments. The archaeal predominance was further supported by fluorescence in situ hybridization (FISH) visualization. The cell-specific rate of ammonia oxidation was estimated to range from 0.410 to 0.790 fmol N archaeal cell-1 h-1, higher than those in the two US Great Basin hot springs. These results suggest the importance of archaeal rather than bacterial ammonia oxidation in driving the nitrogen cycle in terrestrial geothermal environments.

  2. Profitability and Market Value of Orphan Drug Companies: A Retrospective, Propensity-Matched Case-Control Study.

    Science.gov (United States)

    Hughes, Dyfrig A; Poletti-Hughes, Jannine

    2016-01-01

    Concerns about the high cost of orphan drugs has led to questions being asked about the generosity of the incentives for development, and associated company profits. We conducted a retrospective, propensity score matched study of publicly-listed orphan companies. Cases were defined as holders of orphan drug market authorisation in Europe or the USA between 2000-12. Control companies were selected based on their propensity for being orphan drug market authorisation holders. We applied system General Method of Moments to test whether companies with orphan drug market authorization are valued higher, as measured by the Tobin's Q and market to book value ratios, and are more profitable based on return on assets, than non-orphan drug companies. 86 companies with orphan drug approvals in European (4), USA (61) or both (21) markets were matched with 258 controls. Following adjustment, orphan drug market authorization holders have a 9.6% (95% confidence interval, 0.6% to 18.7%) higher return on assets than non-orphan drug companies; Tobin's Q was higher by 9.9% (1.0% to 19.7%); market to book value by 15.7% (3.1% to 30.0%) and operating profit by 516% (CI 19.8% to 1011%). For each additional orphan drug sold, return on assets increased by 11.1% (0.6% to 21.3%), Tobin's Q by 2.7% (0.2% to 5.2%), and market to book value ratio by 5.8% (0.7% to 10.9%). Publicly listed pharmaceutical companies that are orphan drug market authorization holders are associated with higher market value and greater profits than companies not producing treatments for rare diseases.

  3. Familial relationships in hyperthermo- and acidophilic archaeal viruses

    DEFF Research Database (Denmark)

    Happonen, Lotta Johanna; Redder, Peter; Peng, Xu

    2010-01-01

    Archaea often live in extreme, harsh environments such as acidic hot springs and hypersaline waters. To date, only two icosahedrally symmetric, membrane-containing archaeal viruses, SH1 and Sulfolobus turreted icosahedral virus (STIV), have been described in detail. We report the sequence and thr...

  4. Studies of archaeal virus-host systems in thermal environments

    DEFF Research Database (Denmark)

    Erdmann, Susanne

    Since the first organisms were isolated from hot springs, a large number of viruses were found in these geothermal active environments, most of them infecting Archaea. Archaeal viruses form a separate lineage from those of Eukarya and Bacteria often showing exceptional morphologies and genomic...... features. Most of the isolated archaeal viruses infecting members of the Crenarchaeota have been characterized regarding their genome, the structure of their virions and their influence on the host viability. Only a few, SIRV a rod-shaped and STIV an icosahedrical virus, have been subjected to more...... extensive studies. This work investigates tailed spindle-shaped viruses that we have isolated from different geographical acidothermal, terrestrial hot springs and they primarily infect members of the genus Sulfolobales. The wide distribution of these viruses was established and, moreover, genomic...

  5. Planktonic Euryarchaeota are a significant source of archaeal tetraether lipids in the ocean.

    Science.gov (United States)

    Lincoln, Sara A; Wai, Brenner; Eppley, John M; Church, Matthew J; Summons, Roger E; DeLong, Edward F

    2014-07-08

    Archaea are ubiquitous in marine plankton, and fossil forms of archaeal tetraether membrane lipids in sedimentary rocks document their participation in marine biogeochemical cycles for >100 million years. Ribosomal RNA surveys have identified four major clades of planktonic archaea but, to date, tetraether lipids have been characterized in only one, the Marine Group I Thaumarchaeota. The membrane lipid composition of the other planktonic archaeal groups--all uncultured Euryarchaeota--is currently unknown. Using integrated nucleic acid and lipid analyses, we found that Marine Group II Euryarchaeota (MG-II) contributed significantly to the tetraether lipid pool in the North Pacific Subtropical Gyre at shallow to intermediate depths. Our data strongly suggested that MG-II also synthesize crenarchaeol, a tetraether lipid previously considered to be a unique biomarker for Thaumarchaeota. Metagenomic datasets spanning 5 y indicated that depth stratification of planktonic archaeal groups was a stable feature in the North Pacific Subtropical Gyre. The consistent prevalence of MG-II at depths where the bulk of exported organic matter originates, together with their ubiquitous distribution over diverse oceanic provinces, suggests that this clade is a significant source of tetraether lipids to marine sediments. Our results are relevant to archaeal lipid biomarker applications in the modern oceans and the interpretation of these compounds in the geologic record.

  6. Clusters of orthologous genes for 41 archaeal genomes and implications for evolutionary genomics of archaea

    Directory of Open Access Journals (Sweden)

    Wolf Yuri I

    2007-11-01

    Full Text Available Abstract Background An evolutionary classification of genes from sequenced genomes that distinguishes between orthologs and paralogs is indispensable for genome annotation and evolutionary reconstruction. Shortly after multiple genome sequences of bacteria, archaea, and unicellular eukaryotes became available, an attempt on such a classification was implemented in Clusters of Orthologous Groups of proteins (COGs. Rapid accumulation of genome sequences creates opportunities for refining COGs but also represents a challenge because of error amplification. One of the practical strategies involves construction of refined COGs for phylogenetically compact subsets of genomes. Results New Archaeal Clusters of Orthologous Genes (arCOGs were constructed for 41 archaeal genomes (13 Crenarchaeota, 27 Euryarchaeota and one Nanoarchaeon using an improved procedure that employs a similarity tree between smaller, group-specific clusters, semi-automatically partitions orthology domains in multidomain proteins, and uses profile searches for identification of remote orthologs. The annotation of arCOGs is a consensus between three assignments based on the COGs, the CDD database, and the annotations of homologs in the NR database. The 7538 arCOGs, on average, cover ~88% of the genes in a genome compared to a ~76% coverage in COGs. The finer granularity of ortholog identification in the arCOGs is apparent from the fact that 4538 arCOGs correspond to 2362 COGs; ~40% of the arCOGs are new. The archaeal gene core (protein-coding genes found in all 41 genome consists of 166 arCOGs. The arCOGs were used to reconstruct gene loss and gene gain events during archaeal evolution and gene sets of ancestral forms. The Last Archaeal Common Ancestor (LACA is conservatively estimated to possess 996 genes compared to 1245 and 1335 genes for the last common ancestors of Crenarchaeota and Euryarchaeota, respectively. It is inferred that LACA was a chemoautotrophic hyperthermophile

  7. Expression, purification and crystallization of an archaeal-type phosphoenolpyruvate carboxylase

    International Nuclear Information System (INIS)

    Dharmarajan, Lakshmi; Kraszewski, Jessica L.; Mukhopadhyay, Biswarup; Dunten, Pete W.

    2009-01-01

    The expression, purification, crystallization and preliminary diffraction analysis of an archaeal-type phosphoenolpyruvate carboxylase are described. Complete highly redundant X-ray data have been measured from a crystal diffracting to 3.13 Å resolution. An archaeal-type phosphoenolpyruvate carboxylase (PepcA) from Clostridium perfringens has been expressed in Escherichia coli in a soluble form with an amino-terminal His tag. The recombinant protein is enzymatically active and two crystal forms have been obtained. Complete diffraction data extending to 3.13 Å resolution have been measured from a crystal soaked in KAu(CN) 2 , using radiation at a wavelength just above the Au L III edge. The asymmetric unit contains two tetramers of PepcA

  8. Elevational characteristics of the archaeal community in full-scale activated sludge wastewater treatment plants at a 3,660-meter elevational scale.

    Science.gov (United States)

    Niu, Lihua; Zhang, Xue; Li, Yi; Wang, Peifang; Zhang, Wenlong; Wang, Chao; Wang, Qing

    2017-07-01

    Due to the important roles of archaea in wastewater treatment processes, archaeal communities have been studied extensively in various anaerobic reactors, but the knowledge of archaeal communities in full-scale activated sludge wastewater treatment plants (WWTPs) remains quite poor. In this study, 454-pyrosequencing was for the first time employed to investigate archaeal communities from 20 full-scale activated sludge WWTPs distributed at a 3,660-meter elevational scale in China. Results showed that archaeal communities from WWTPs were dominated by Methanosarcinales (84.6%). A core archaeal population (94.5%) composed of Methanosaeta, Methanosarcina, Methanogenium and Methanobrevibacter was shared among WWTPs. The elevational pattern of archaeal communities was observed in WWTPs, with an elevational threshold associated with archaeal community richness and structures at approximately 1,500 meters above sea level (masl). A declining trend in community richness with increasing elevation was observed at higher elevations, whereas no trend was presented at lower elevations. Spearman correlation analysis indicated that the archaeal community richness at higher elevations was associated with more environmental variables than that at lower elevations. Redundancy analysis indicated that wastewater variables were the dominant contributors to the variation of community structures at higher elevations, followed by operational variables and elevation.

  9. Emerging health disparities in Botswana: examining the situation of orphans during the AIDS epidemic.

    Science.gov (United States)

    Miller, Candace Marie; Gruskin, Sofia; Subramanian, S V; Heymann, Jody

    2007-06-01

    Botswana has the second highest HIV prevalence rate and highest rate of orphanhood in the world. Although child mortality rates have doubled in 15 years, the extent to which health disparities are connected to orphan status remains unclear. We conducted an analysis of the 2000 Botswana Multiple Indicator Cluster Survey to examine whether orphan-based health disparities exist. We measured health inequalities using anthropometric data among 2723 under-five year olds, nested in 1854 households, and 208 communities. We calculated multilevel logistic regression models to estimate the child, household, and regional determinants of growth failure. We found that orphaned children aged 0-4 are 49% more likely to be underweight than nonorphans (ppoverty and other factors; and orphans disproportionately live in the poorest households. Throughout sub-Saharan Africa (SSA), Botswana is a leader in responding to the AIDS epidemic, in particular as one of the first countries to offer universal antiretroviral treatment. However, orphan-based health disparities confirm that the orphan response is still insufficient. Better data are needed to fully understand the mechanisms that lead to these disparities, and the public sector needs an increased capacity to fully implement the policies and programs designed to meet the needs of orphans. Findings from this study have important implications for countries throughout SSA, and Southern Africa in particular, where the number of orphans has doubled to tripled over the past 15 years.

  10. Inverse association of natural mentoring relationship with distress mental health in children orphaned by AIDS

    Directory of Open Access Journals (Sweden)

    Munakata Tsunetsugu

    2010-01-01

    Full Text Available Abstract Background The magnitude of the AIDS-orphaned children crisis in sub-Saharan Africa has so overstretched the resource of most families that the collapse of fostering in the sub-region seems imminent (UNICEF, 2003, fueling the need for a complementary/alternative care. This paper examines the probability of the natural mentoring care to ameliorate distress mental health in children orphaned by AIDS. Methods 952 children, mean age about 14 years, from local community schools and child-care centers in Kampala (Uganda and Mafikeng/Klerksdorp (South Africa towns participated in the study. The design has AIDS-orphaned group (n = 373 and two control groups: Other-causes orphaned (n = 287 and non-orphaned (n = 290 children. We use measures of child abuse, depression, social discrimination, anxiety, parental/foster care, self-esteem, and social support to estimate mental health. Natural mentoring care is measured with the Ragins and McFarlin (1990 Mentor Role Instrument as adapted. Results AIDS-orphaned children having a natural mentor showed significant decreased distress mental health factors. Similar evidence was not observed in the control groups. Also being in a natural mentoring relationship inversely related to distress mental health factors in the AIDS-orphaned group, in particular. AIDS-orphaned children who scored high mentoring relationship showed significant lowest distress mental health factors that did those who scored moderate and low mentoring relationship. Conclusions Natural mentoring care seems more beneficial to ameliorate distress mental health in AIDS-orphaned children (many of whom are double-orphans, having no biological parents than in children in the control groups.

  11. The Vertical Distribution of Sediment Archaeal Community in the “Black Bloom” Disturbing Zhushan Bay of Lake Taihu

    Science.gov (United States)

    Fan, Xianfang; Xing, Peng

    2016-01-01

    Using the Illumina sequencing technology, we investigated the vertical distribution of archaeal community in the sediment of Zhushan Bay of Lake Taihu, where the black bloom frequently occurred in summer. Overall, the Miscellaneous Crenarchaeotal Group (MCG), Deep Sea Hydrothermal Vent Group 6 (DHVEG-6), and Methanobacterium dominated the archaeal community. However, we observed significant difference in composition of archaeal community among different depths of the sediment. DHVEG-6 dominated in the surface layer (0–3 cm) sediment. Methanobacterium was the dominating archaeal taxa in the L2 (3–6 cm) and L3 (6–10) sediment. MCG was most abundant in the L4 (10–15 cm) and L5 (15–20 cm) sediment. Besides, DHVEG-6 was significantly affected by the concentration of total phosphorus (TP). And loss on ignition (LOI) was an important environmental factor for Methanobacterium. As the typical archaeal taxa in the surface layer sediment, DHVEG-6 and Methanobacterium might be more adapted to abundant substrate supply from cyanobacterial blooms and take active part in the biomass transformation. We propose that DHVEG-6 and Methanobacterium could be the key archaeal taxa correlated with the “black bloom” formation in Zhushan Bay. PMID:26884723

  12. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

    Science.gov (United States)

    2010-04-01

    ...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Timing of requests for orphan-drug designation..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan...

  13. The current status of orphan drug development in Europe and the US

    OpenAIRE

    Hall, Anthony K; Carlson, Marilyn R

    2014-01-01

    Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, e...

  14. The many "small COPDs": COPD should be an orphan disease

    DEFF Research Database (Denmark)

    Rennard, Stephen I; Vestbo, Jørgen

    2008-01-01

    COPD is one of the most common causes of morbidity and mortality. Perhaps paradoxically, COPD also should be an orphan disease. Importantly, this could advance the development of treatments for COPD. There are two criteria for orphan status in the United States. Most widely known is the criterion...... of COPD should qualify for the first criterion if the various conditions that comprise COPD are regarded separately. The subphenotyping of COPD into separate...... groups based on mechanism sets the stage for the rational development of therapeutics. In addition, many candidate treatments may alter the natural history of COPD. Testing them, however, will require large studies for a duration that will compromise the commercial life of any resulting product. Orphan...

  15. Spatial distribution of planktonic bacterial and archaeal communities in the upper section of the tidal reach in Yangtze River

    Science.gov (United States)

    Fan, Limin; Song, Chao; Meng, Shunlong; Qiu, Liping; Zheng, Yao; Wu, Wei; Qu, Jianhong; Li, Dandan; Zhang, Cong; Hu, Gengdong; Chen, Jiazhang

    2016-01-01

    Bacterioplankton and archaeaplankton communities play key roles in the biogeochemical processes of water, and they may be affected by many factors. In this study, we used high-throughput 16S rRNA gene sequencing to profile planktonic bacterial and archaeal community compositions in the upper section of the tidal reach in Yangtze River. We found that the predominant bacterial phyla in this river section were Proteobacteria, Firmicutes, and Actinobacteria, whereas the predominant archaeal classes were Halobacteria, Methanomicrobia, and unclassified Euryarchaeota. Additionally, the bacterial and archaeal community compositions, richnesses, functional profiles, and ordinations were affected by the spatial heterogeneity related to the concentration changes of sulphate or nitrate. Notably, the bacterial community was more sensitive than the archaeal community to changes in the spatial characteristics of this river section. These findings provide important insights into the distributions of bacterial and archaeal communities in natural water habitats. PMID:27966673

  16. Psychosocial Support for Children Orphaned by HIV/AIDS in Zimbabwe

    Science.gov (United States)

    Chitiyo, Jonathan; Chitiyo, Argnue; Chitiyo, Morgan

    2016-01-01

    Healthy psychosocial development during childhood is a key determinant to the future well-being of all individuals. In many areas of Africa, demand for psychosocial support continues to grow in response to the increasing number of children left orphaned as a result of the HIV/AIDS pandemic. These orphans face various challenges and yet, in most…

  17. Response of archaeal communities in the rhizosphere of maize and soybean to elevated atmospheric CO2 concentrations.

    Directory of Open Access Journals (Sweden)

    David M Nelson

    Full Text Available BACKGROUND: Archaea are important to the carbon and nitrogen cycles, but it remains uncertain how rising atmospheric carbon dioxide concentrations ([CO(2] will influence the structure and function of soil archaeal communities. METHODOLOGY/PRINCIPAL FINDINGS: We measured abundances of archaeal and bacterial 16S rRNA and amoA genes, phylogenies of archaeal 16S rRNA and amoA genes, concentrations of KCl-extractable soil ammonium and nitrite, and potential ammonia oxidation rates in rhizosphere soil samples from maize and soybean exposed to ambient (∼385 ppm and elevated (550 ppm [CO(2] in a replicated and field-based study. There was no influence of elevated [CO(2] on copy numbers of archaeal or bacterial 16S rRNA or amoA genes, archaeal community composition, KCl-extractable soil ammonium or nitrite, or potential ammonia oxidation rates for samples from maize, a model C(4 plant. Phylogenetic evidence indicated decreased relative abundance of crenarchaeal sequences in the rhizosphere of soybean, a model leguminous-C(3 plant, at elevated [CO(2], whereas quantitative PCR data indicated no changes in the absolute abundance of archaea. There were no changes in potential ammonia oxidation rates at elevated [CO(2] for soybean. Ammonia oxidation rates were lower in the rhizosphere of maize than soybean, likely because of lower soil pH and/or abundance of archaea. KCl-extractable ammonium and nitrite concentrations were lower at elevated than ambient [CO(2] for soybean. CONCLUSION: Plant-driven shifts in soil biogeochemical processes in response to elevated [CO(2] affected archaeal community composition, but not copy numbers of archaeal genes, in the rhizosphere of soybean. The lack of a treatment effect for maize is consistent with the fact that the photosynthesis and productivity of maize are not stimulated by elevated [CO(2] in the absence of drought.

  18. Archaeal abundance across a pH gradient in an arable soil and its relationship to bacterial and fungal growth rates.

    Science.gov (United States)

    Bengtson, Per; Sterngren, Anna E; Rousk, Johannes

    2012-08-01

    Soil pH is one of the most influential factors for the composition of bacterial and fungal communities, but the influence of soil pH on the distribution and composition of soil archaeal communities has yet to be systematically addressed. The primary aim of this study was to determine how total archaeal abundance (quantitative PCR [qPCR]-based estimates of 16S rRNA gene copy numbers) is related to soil pH across a pH gradient (pH 4.0 to 8.3). Secondarily, we wanted to assess how archaeal abundance related to bacterial and fungal growth rates across the same pH gradient. We identified two distinct and opposite effects of pH on the archaeal abundance. In the lowest pH range (pH 4.0 to 4.7), the abundance of archaea did not seem to correspond to pH. Above this pH range, there was a sharp, almost 4-fold decrease in archaeal abundance, reaching a minimum at pH 5.1 to 5.2. The low abundance of archaeal 16S rRNA gene copy numbers at this pH range then sharply increased almost 150-fold with pH, resulting in an increase in the ratio between archaeal and bacterial copy numbers from a minimum of 0.002 to more than 0.07 at pH 8. The nonuniform archaeal response to pH could reflect variation in the archaeal community composition along the gradient, with some archaea adapted to acidic conditions and others to neutral to slightly alkaline conditions. This suggestion is reinforced by observations of contrasting outcomes of the (competitive) interactions between archaea, bacteria, and fungi toward the lower and higher ends of the examined pH gradient.

  19. Legal assessment of current situation on orphan patients in Lithuania.

    Science.gov (United States)

    Spokiene, Indre

    2008-01-01

    After Lithuania joined the European Union, the Regulation (EC) No. 141/2000 on orphan medicinal products and Commission Regulation (EC) No. 847/2000 came into force as part of national legislation. Member States must adopt specific measures to increase knowledge on rare diseases and to improve their detection, diagnosis, and treatment. The aim of this article was to present and to assess the current legal situation on orphan patients and their treatment in Lithuania, to identify legislation gaps, and to propose some ideas how to facilitate the solution of the existing problems in this field. For this purpose, European Union and Lithuanian legal documents on rare medicinal products are examined using a comparative method. With reference to inventory of Member States' incentives for rare diseases in national level, the most important issues, which orphan patients face to in Lithuania, are singled out. In Lithuania, the situation of orphan patients in terms of protection of patient rights is insufficiently determined. The access to effective health care services or approved therapies in some cases is restricted. Working relationships between genetic services and various clinical specialists as well as with those in primary care are not legally determined; the number of clinical trials aimed at orphan medicinal products is low. These results suggest a need for awareness raising among Lithuanian Government, health care specialists, patient organizations about the importance to improve practical implementation of European Union legislation and progressive experience of some European countries in this field.

  20. A study of descriptive data for orphans and non-orphans on key criteria of economic vulnerability in two municipalities in South Africa

    Directory of Open Access Journals (Sweden)

    Donald Skinner

    2013-05-01

    Objectives: The objective was to obtain a better understanding of how different types of orphans and non-orphans may differ in these key areas as a crucial starting point for addressing the devastating consequences the AIDS epidemic has on these children’s lives. While the study focuses on two specific areas these will provide insight into the general situation of orphans in South Africa. Methods: A cross-sectional census survey was conducted in the two communities of Kopanong, comprising n = 5254 households and Kanana, comprising n = 12 984 households. Results: In Kopanong, 8.2% of children had lost both parents, 19.1% had lost their father and 6.5% their mother only, whilst in Kanana the results were 6.5%, 28.1% and 3.7% respectively. Loss of both parents appeared to have a consistent impact on material need, including access to food, clothing and essential services, whilst loss of a single parent seems to have a more variable impact. At present, there are very few child headed households, but this constitutes a risk in the longer term. Conclusions: Orphans appear to be more vulnerable in terms of material need. Children assessed in this study as being most in need were not accessing adequately many services directed at them. There is a need to extend understanding and measurement of emotional need and abuse.

  1. Modeling and Deorphanization of Orphan GPCRs.

    Science.gov (United States)

    Diaz, Constantino; Angelloz-Nicoud, Patricia; Pihan, Emilie

    2018-01-01

    Despite tremendous efforts, approximately 120 GPCRs remain orphan. Their physiological functions and their potential roles in diseases are poorly understood. Orphan GPCRs are extremely important because they may provide novel therapeutic targets for unmet medical needs. As a complement to experimental approaches, molecular modeling and virtual screening are efficient techniques to discover synthetic surrogate ligands which can help to elucidate the role of oGPCRs. Constitutively activated mutants and recently published active structures of GPCRs provide stimulating opportunities for building active molecular models for oGPCRs and identifying activators using virtual screening of compound libraries. We describe the molecular modeling and virtual screening process we have applied in the discovery of surrogate ligands, and provide examples for CCKA, a simulated oGPCR, and for two oGPCRs, GPR52 and GPR34.

  2. Budget impact analysis of drugs for ultra-orphan non-oncological diseases in Europe.

    Science.gov (United States)

    Schlander, Michael; Adarkwah, Charles Christian; Gandjour, Afschin

    2015-02-01

    Ultra-orphan diseases (UODs) have been defined by a prevalence of less than 1 per 50,000 persons. However, little is known about budget impact of ultra-orphan drugs. For analysis, the budget impact analysis (BIA) had a time horizon of 10 years (2012-2021) and a pan-European payer's perspective, based on prevalence data for UODs for which patented drugs are available and/or for which drugs are in clinical development. A total of 18 drugs under patent protection or orphan drug designation for non-oncological UODs were identified. Furthermore, 29 ultra-orphan drugs for non-oncological diseases under development that have the potential of reaching the market by 2021 were found. Total budget impact over 10 years was estimated to be €15,660 and €4965 million for approved and pipeline ultra-orphan drugs, respectively (total: €20,625 million). The analysis does not support concerns regarding an uncontrolled growth in expenditures for drugs for UODs.

  3. Cultural practices and sexual risk behaviour among adolescent orphans and non-orphans: a qualitative study on perceptions from a community in western Kenya

    OpenAIRE

    Juma, Milka; Askew, Ian; Alaii, Jane; Bartholomew, L Kay; van den Borne, Bart

    2014-01-01

    Background This study explored community perceptions of cultural beliefs and practices that may increase sexual risk behaviour of adolescents, to understand more about meaning they hold within the culture and how they expose adolescent orphans and non-orphans to higher risks in a high HIV and teenage pregnancy prevalence context. Methods Using a qualitative descriptive cross-sectional design 14 focus group discussions were conducted with 78 adolescents and 68 parents/guardians purposively sel...

  4. Orphan drugs and the NHS: Should we value rarity

    OpenAIRE

    Claxton, K.; McCabe, C.; Tsuchiya, A.

    2005-01-01

    Cost effectiveness plays an important part in current decisions about the funding of health technologies. Drugs for rare disease (orphan drugs) are often expensive to produce and, by definition, will benefit only small numbers of patients. Several countries have put measures in place to safeguard research and development of orphan drugs, but few get close to meeting the cost effectiveness criteria for funding by healthcare providers. We examine the justifications for special status for rare d...

  5. The current status of orphan drug development in Europe and the US.

    Science.gov (United States)

    Hall, Anthony K; Carlson, Marilyn R

    2014-02-01

    Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, explain the incentives and procedures, and touch on the role of patient organisations in the process.

  6. Archaeal CRISPR-based immune systems

    DEFF Research Database (Denmark)

    Garrett, Roger A; Vestergaard, Gisle Alberg; Shah, Shiraz Ali

    2011-01-01

    CRISPR (clustered regularly interspaced short palindromic repeats)-based immune systems are essentially modular with three primary functions: the excision and integration of new spacers, the processing of CRISPR transcripts to yield mature CRISPR RNAs (crRNAs), and the targeting and cleavage...... of foreign nucleic acid. The primary target appears to be the DNA of foreign genetic elements, but the CRISPR/Cmr system that is widespread amongst archaea also specifically targets and cleaves RNA in vitro. The archaeal CRISPR systems tend to be both diverse and complex. Here we examine evidence...... of CRISPR loci and the evidence for intergenomic exchange of CRISPR systems....

  7. Denaturing gradient gel electrophoresis and barcoded pyrosequencing reveal unprecedented archaeal diversity in mangrove sediment and rhizosphere samples.

    Science.gov (United States)

    Pires, Ana C C; Cleary, Daniel F R; Almeida, Adelaide; Cunha, Angela; Dealtry, Simone; Mendonça-Hagler, Leda C S; Smalla, Kornelia; Gomes, Newton C M

    2012-08-01

    Mangroves are complex ecosystems that regulate nutrient and sediment fluxes to the open sea. The importance of bacteria and fungi in regulating nutrient cycles has led to an interest in their diversity and composition in mangroves. However, very few studies have assessed Archaea in mangroves, and virtually nothing is known about whether mangrove rhizospheres affect archaeal diversity and composition. Here, we studied the diversity and composition of Archaea in mangrove bulk sediment and the rhizospheres of two mangrove trees, Rhizophora mangle and Laguncularia racemosa, using denaturing gradient gel electrophoresis (DGGE) and pyrosequencing of archaeal 16S rRNA genes with a nested-amplification approach. DGGE profiles revealed significant structural differences between bulk sediment and rhizosphere samples, suggesting that roots of both mangrove species influence the sediment archaeal community. Nearly all of the detected sequences obtained with pyrosequencing were identified as Archaea, but most were unclassified at the level of phylum or below. Archaeal richness was, furthermore, the highest in the L. racemosa rhizosphere, intermediate in bulk sediment, and the lowest in the R. mangle rhizosphere. This study shows that rhizosphere microhabitats of R. mangle and L. racemosa, common plants in subtropical mangroves located in Rio de Janeiro, Brazil, hosted distinct archaeal assemblages.

  8. Land-use change and soil type are drivers of fungal and archaeal communities in the Pampa biome.

    Science.gov (United States)

    Lupatini, Manoeli; Jacques, Rodrigo Josemar Seminoti; Antoniolli, Zaida Inês; Suleiman, Afnan Khalil Ahmad; Fulthorpe, Roberta R; Roesch, Luiz Fernando Würdig

    2013-02-01

    The current study aimed to test the hypothesis that both land-use change and soil type are responsible for the major changes in the fungal and archaeal community structure and functioning of the soil microbial community in Brazilian Pampa biome. Soil samples were collected at sites with different land-uses (native grassland, native forest, Eucalyptus and Acacia plantation, soybean and watermelon field) and in a typical toposequence in Pampa biome formed by Paleudult, Albaqualf and alluvial soils. The structure of soil microbial community (archaeal and fungal) was evaluated by ribosomal intergenic spacer analysis and soil functional capabilities were measured by microbial biomass carbon and metabolic quotient. We detected different patterns in microbial community driven by land-use change and soil type, showing that both factors are significant drivers of fungal and archaeal community structure and biomass and microbial activity. Fungal community structure was more affected by land-use and archaeal community was more affected by soil type. Irrespective of the land-use or soil type, a large percentage of operational taxonomic unit were shared among the soils. We accepted the hypothesis that both land-use change and soil type are drivers of archaeal and fungal community structure and soil functional capabilities. Moreover, we also suggest the existence of a soil microbial core.

  9. Archaeal RNA polymerase arrests transcription at DNA lesions.

    Science.gov (United States)

    Gehring, Alexandra M; Santangelo, Thomas J

    2017-01-01

    Transcription elongation is not uniform and transcription is often hindered by protein-bound factors or DNA lesions that limit translocation and impair catalysis. Despite the high degree of sequence and structural homology of the multi-subunit RNA polymerases (RNAP), substantial differences in response to DNA lesions have been reported. Archaea encode only a single RNAP with striking structural conservation with eukaryotic RNAP II (Pol II). Here, we demonstrate that the archaeal RNAP from Thermococcus kodakarensis is sensitive to a variety of DNA lesions that pause and arrest RNAP at or adjacent to the site of DNA damage. DNA damage only halts elongation when present in the template strand, and the damage often results in RNAP arresting such that the lesion would be encapsulated with the transcription elongation complex. The strand-specific halt to archaeal transcription elongation on modified templates is supportive of RNAP recognizing DNA damage and potentially initiating DNA repair through a process akin to the well-described transcription-coupled DNA repair (TCR) pathways in Bacteria and Eukarya.

  10. Massive activation of archaeal defense genes during viral infection

    NARCIS (Netherlands)

    Quax, T.E.F.; Voet, M.; Sismeiro, O.; Dillies, M.A.; Jagla, B.; Coppée, J.Y.; Sezonov, G.; Forterre, P.; Oost, van der J.; Lavigne, R.; Prangishvili, D.

    2013-01-01

    Archaeal viruses display unusually high genetic and morphological diversity. Studies of these viruses proved to be instrumental for the expansion of knowledge on viral diversity and evolution. The Sulfolobus islandicus rod-shaped virus 2 (SIRV2) is a model to study virus-host interactions in

  11. The use of drawings to facilitate interviews with orphaned children in ...

    African Journals Online (AJOL)

    children orphaned as a result of AIDS also need to cope with the stigma of, ... with the help of the teachers, used purposive sampling – carried out in two ... Researchers (Creswell, 2002; Denzin & Lincoln, 2000) recommend that before seeking ..... of the orphaned children who offered to share their stories had a positive self-.

  12. Persisting Mental Health Problems among AIDS-Orphaned Children in South Africa

    Science.gov (United States)

    Cluver, Lucie D.; Orkin, Mark; Gardner, Frances; Boyes, Mark E.

    2012-01-01

    Background: By 2008, 12 million children in sub-Saharan Africa were orphaned by AIDS. Cross-sectional studies show psychological problems for AIDS-orphaned children, but until now no longitudinal study has explored enduring psychological effects of AIDS-orphanhood in the developing world. Methods: A 4-year longitudinal follow-up of AIDS-orphaned…

  13. Prioritizing orphan proteins for further study using phylogenomics and gene expression profiles in Streptomyces coelicolor

    Directory of Open Access Journals (Sweden)

    Takano Eriko

    2011-09-01

    Full Text Available Abstract Background Streptomyces coelicolor, a model organism of antibiotic producing bacteria, has one of the largest genomes of the bacterial kingdom, including 7825 predicted protein coding genes. A large number of these genes, nearly 34%, are functionally orphan (hypothetical proteins with unknown function. However, in gene expression time course data, many of these functionally orphan genes show interesting expression patterns. Results In this paper, we analyzed all functionally orphan genes of Streptomyces coelicolor and identified a list of "high priority" orphans by combining gene expression analysis and additional phylogenetic information (i.e. the level of evolutionary conservation of each protein. Conclusions The prioritized orphan genes are promising candidates to be examined experimentally in the lab for further characterization of their function.

  14. Health of adults caring for orphaned children in an HIV-endemic community in South Africa.

    Science.gov (United States)

    Kuo, Caroline; Operario, Don

    2011-09-01

    In South Africa, an estimated 2.5 million children have been orphaned by AIDS and other causes of adult mortality. Although there is a growing body of research on the well-being of South African orphaned children, few research studies have examined the health of adult individuals caring for children in HIV-endemic communities. The cross-sectional survey assessed prevalence of general health and functioning (based on Short-Form 36 version 2 scale), depression (based on Center for Epidemiologic Studies-Depression scale), anxiety (using Kessler-10 scale), and post-traumatic stress (using the Harvard Trauma Questionnaire) among a representative community sample of adults caring for children in Umlazi Township, an HIV-endemic community in South Africa. Of 1599 respondents, 33% (n=530) were carers of orphaned children. Results showed that, overall, carers reported poor general health and functioning and elevated levels of depression, anxiety, and post-traumatic stress. Carers of orphaned children reported significantly poorer general health and functioning and higher rates of depression and post-traumatic stress compared with carers of non-orphaned children. In multivariate analyses, orphan carer and non-orphan carer differences in general health were accounted for by age, gender, education, economic assets, and source of income, but differences in depression were independent of these cofactors. Interventions are needed to address physical and mental health of carers in general. Greater health problems among orphan carers appeared to be fully explained by socioeconomic characteristics, which offer opportunities for targeting of programs. More research is needed to understand determinants of mental health disparities among orphan carers, which were not explained by socioeconomic characteristics.

  15. Bacterial and archaeal diversities in Yunnan and Tibetan hot springs, China.

    Science.gov (United States)

    Song, Zhao-Qi; Wang, Feng-Ping; Zhi, Xiao-Yang; Chen, Jin-Quan; Zhou, En-Min; Liang, Feng; Xiao, Xiang; Tang, Shu-Kun; Jiang, Hong-Chen; Zhang, Chuanlun L; Dong, Hailiang; Li, Wen-Jun

    2013-04-01

    Thousands of hot springs are located in the north-eastern part of the Yunnan-Tibet geothermal zone, which is one of the most active geothermal areas in the world. However, a comprehensive and detailed understanding of microbial diversity in these hot springs is still lacking. In this study, bacterial and archaeal diversities were investigated in 16 hot springs (pH 3.2-8.6; temperature 47-96°C) in Yunnan Province and Tibet, China by using a barcoded 16S rRNA gene-pyrosequencing approach. Aquificae, Proteobacteria, Firmicutes, Deinococcus-Thermus and Bacteroidetes comprised the large portion of the bacterial communities in acidic hot springs. Non-acidic hot springs harboured more and variable bacterial phyla than acidic springs. Desulfurococcales and unclassified Crenarchaeota were the dominated groups in archaeal populations from most of the non-acidic hot springs; whereas, the archaeal community structure in acidic hot springs was simpler and characterized by Sulfolobales and Thermoplasmata. The phylogenetic analyses showed that Aquificae and Crenarchaeota were predominant in the investigated springs and possessed many phylogenetic lineages that have never been detected in other hot springs in the world. Thus findings from this study significantly improve our understanding of microbial diversity in terrestrial hot springs. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  16. What makes orphans in Kigali, Rwanda, non-adherent to antiretroviral therapy? Perspectives of their caregivers.

    Science.gov (United States)

    Kikuchi, Kimiyo; Poudel, Krishna C; Muganda, John; Sato, Tomoko; Mutabazi, Vincent; Muhayimpundu, Ribakare; Majyambere, Adolphe; Nyonsenga, Simon P; Sase, Eriko; Jimba, Masamine

    2014-01-01

    Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda. We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation. The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans' caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers. Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children.

  17. Regional cooperation to reduce the safety and security risks of Orphan radioactive sources

    International Nuclear Information System (INIS)

    Howard, Geoffrey; Hacker, Celia; Murray, Allan; Romallosa, Kristine; Caseria, Estrella; Africa del Castillo, Lorena

    2008-01-01

    ANSTO's Regional Security of Radioactive Sources (RSRS) Project, in cooperation with the Philippine Nuclear Research Institute (PNRI), has initiated a program to reduce the safety and security risks of orphan radioactive sources in the Philippines. Collaborative work commenced in February 2006 during the Regional Orphan Source Search and Methods Workshop, co-hosted by ANSTO and the US National Nuclear Security Administration. Further professional development activities have occurred following requests by PNRI to ANSTO to support improvements in PNRI's capability and training programs to use a range of radiation survey equipment and on the planning and methods for conducting orphan source searches. The activities, methods and outcomes of the PNRI-ANSTO cooperative program are described, including: i.) Delivering a training workshop which incorporates use of source search and nuclide identification equipment and search methodology; and train-the-trainer techniques for effective development and delivery of custom designed training in the Philippines; ii.) Support and peer review of course work on Orphan Source Search Equipment and Methodology developed by PNRI Fellows; iii.) Supporting the delivery of the inaugural National Training Workshop on Orphan Source Search hosted by PNRI in the Philippines; iv.) Partnering in searching for orphan sources in Luzon, Philippines, in May 2007. The methods employed during these international cooperation activities are establishing a new model of regional engagement that emphasises sustainability of outcomes for safety and security of radioactive sources. (author)

  18. Characterization of an archaeal two-component system that regulates methanogenesis in Methanosaeta harundinacea.

    Directory of Open Access Journals (Sweden)

    Jie Li

    Full Text Available Two-component signal transduction systems (TCSs are a major mechanism used by bacteria in response to environmental changes. Although many sequenced archaeal genomes encode TCSs, they remain poorly understood. Previously, we reported that a methanogenic archaeon, Methanosaeta harundinacea, encodes FilI, which synthesizes carboxyl-acyl homoserine lactones, to regulate transitions of cellular morphology and carbon metabolic fluxes. Here, we report that filI, the cotranscribed filR2, and the adjacent filR1 constitute an archaeal TCS. FilI possesses a cytoplasmic kinase domain (histidine kinase A and histidine kinase-like ATPase and its cognate response regulator. FilR1 carries a receiver (REC domain coupled with an ArsR-related domain with potential DNA-binding ability, while FilR2 carries only a REC domain. In a phosphorelay assay, FilI was autophosphorylated and specifically transferred the phosphoryl group to FilR1 and FilR2, confirming that the three formed a cognate TCS. Through chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR using an anti-FilR1 antibody, FilR1 was shown to form in vivo associations with its own promoter and the promoter of the filI-filR2 operon, demonstrating a regulatory pattern common among TCSs. ChIP-qPCR also detected FilR1 associations with key genes involved in acetoclastic methanogenesis, acs4 and acs1. Electrophoretic mobility shift assays confirmed the in vitro tight binding of FilR1 to its own promoter and those of filI-filR2, acs4, and mtrABC. This also proves the DNA-binding ability of the ArsR-related domain, which is found primarily in Archaea. The archaeal promoters of acs4, filI, acs1, and mtrABC also initiated FilR1-modulated expression in an Escherichia coli lux reporter system, suggesting that FilR1 can up-regulate both archaeal and bacterial transcription. In conclusion, this work identifies an archaeal FilI/FilRs TCS that regulates the methanogenesis of M. harundinacea.

  19. Bending Elasticity Modulus of Giant Vesicles Composed of Aeropyrum Pernix K1 Archaeal Lipid

    Directory of Open Access Journals (Sweden)

    Julia Genova

    2015-03-01

    Full Text Available Thermally induced shape fluctuations were used to study elastic properties of giant vesicles composed of archaeal lipids C25,25-archetidyl (glucosyl inositol and C25,25-archetidylinositol isolated from lyophilised Aeropyrum pernix K1 cells. Giant vesicles were created by electroformation in pure water environment. Stroboscopic illumination using a xenon flash lamp was implemented to remove the blur effect due to the finite integration time of the camera and to obtain an instant picture of the fluctuating vesicle shape. The mean weighted value of the bending elasticity modulus kc of the archaeal membrane determined from the measurements meeting the entire set of qualification criteria was (1.89 ± 0.18 × 10−19 J, which is similar to the values obtained for a membrane composed of the eukaryotic phospholipids SOPC (1.88 ± 0.17 × 10−19 J and POPC (2.00 ± 0.21 ´ 10−19 J. We conclude that membranes composed of archaeal lipids isolated from Aeropyrum pernix K1 cells have similar elastic properties as membranes composed of eukaryotic lipids. This fact, together with the importance of the elastic properties for the normal circulation through blood system, provides further evidence in favor of expectations that archaeal lipids could be appropriate for the design of drug delivery systems.

  20. Thermophilic archaeal enzymes and applications in biocatalysis.

    Science.gov (United States)

    Littlechild, Jennifer A

    2011-01-01

    Thermophilic enzymes have advantages for their use in commercial applications and particularly for the production of chiral compounds to produce optically pure pharmaceuticals. They can be used as biocatalysts in the application of 'green chemistry'. The thermophilic archaea contain enzymes that have already been used in commercial applications such as the L-aminoacylase from Thermococcus litoralis for the resolution of amino acids and amino acid analogues. This enzyme differs from bacterial L-aminoacylases and has similarities to carboxypeptidases from other archaeal species. An amidase/γ-lactamase from Sulfolobus solfataricus has been used for the production of optically pure γ-lactam, the building block for antiviral carbocyclic nucleotides. This enzyme has similarities to the bacterial signature amidase family. An alcohol dehydrogenase from Aeropyrum pernix has been used for the production of optically pure alcohols and is related to the zinc-containing eukaryotic alcohol dehydrogenases. A transaminase and a dehalogenase from Sulfolobus species have also been studied. The archaeal transaminase is found in a pathway for serine synthesis which is found only in eukaryotes and not in bacteria. It can be used for the asymmetric synthesis of homochiral amines of high enantioselective purity. The L-2-haloacid dehalogenase has applications both in biocatalysis and in bioremediation. All of these enzymes have increased thermostability over their mesophilic counterparts.

  1. Orphan Drug Debate: A Cheat Sheet.

    Science.gov (United States)

    Patel, Krishna R

    2017-06-01

    In some respects, the 1983 Orphan Drug Act is a success story. But high prices and allegations that some drug companies have twisted the law to their advantage have made it controversial. Here are some of the main points in the debate.

  2. Oral lesions and dental status among institutionalized orphans in Yemen: A matched case-control study

    Directory of Open Access Journals (Sweden)

    Sadeq Ali Al-Maweri

    2014-01-01

    Full Text Available Objectives: The aim of this study was to assess the prevalence of oral mucosal lesions (OMLs and dental caries and to evaluate oral health practices among institutionalized orphan-children in Sana′a city, Yemen. Subjects and Methods: A sample of 202 institutionalized male-orphan-children in the main orphanage in Sana′a city, were matched to 202 non-orphan schoolchildren. Clinical examination included assessment of OMLs based on standard international diagnostic criteria and evaluation of dental status using the Decayed/decayed, Missed/missed and Filled/filled (DMFT/dmft index according to World Health Organization recommendations. Demographic data and oral hygiene practices were obtained by interviewing each subject using special questionnaire form. Results: Majority of children were in the 12-15 year age group. Nine types of lesions were reported among orphans; the most common lesions were fissured tongue (24.3%, herpes labialis (7.9% and traumatic ulcers (2.5%. The occurrence of herpes labialis was found to be significantly higher in orphans than in controls (P < 0.01. The prevalence of dental caries was insignificantly lower among the orphans (84.7% compared with the non-orphans (89.61%; P = 0.136. The mean dmft score was significantly lower in orphans than in controls (2.28 vs. 3.82; P = 0.001. Conclusions: The institutionalized children in this orphanage had a high prevalence of OMLs but low prevalence of dental caries, though they revealed poor oral hygiene practices. Effective oral health promotion strategies need to be implemented to improve the oral health and oral health practices of children living in orphanages.

  3. Orphan sources

    International Nuclear Information System (INIS)

    Pust, R.; Urbancik, L.

    2008-01-01

    The presentation describes how the stable detection systems (hereinafter referred to as S DS ) have contributed to reveal the uncontrolled sources of ionizing radiation on the territory of the State Office for Nuclear Safety (SONS) Brno Regional Centre (RC Brno). It also describes the emergencies which were solved by or in which the workers from the Brno. Regional Centre participated in. The contribution is divided into the following chapters: A. SDS systems installed on the territory of SONS RC Brno; B. Selected unusual emergencies; C. Comments to individual emergencies; D. Aspects of SDS operation in term of their users; E. Aspects of SDS operation and related activities in term of radiation protection; F. Current state of orphan sources. (authors)

  4. eRepo-ORP: Exploring the Opportunity Space to Combat Orphan Diseases with Existing Drugs.

    Science.gov (United States)

    Brylinski, Michal; Naderi, Misagh; Govindaraj, Rajiv Gandhi; Lemoine, Jeffrey

    2017-12-10

    About 7000 rare, or orphan, diseases affect more than 350 million people worldwide. Although these conditions collectively pose significant health care problems, drug companies seldom develop drugs for orphan diseases due to extremely limited individual markets. Consequently, developing new treatments for often life-threatening orphan diseases is primarily contingent on financial incentives from governments, special research grants, and private philanthropy. Computer-aided drug repositioning is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Here, we present eRepo-ORP, a comprehensive resource constructed by a large-scale repositioning of existing drugs to orphan diseases with a collection of structural bioinformatics tools, including eThread, eFindSite, and eMatchSite. Specifically, a systematic exploration of 320,856 possible links between known drugs in DrugBank and orphan proteins obtained from Orphanet reveals as many as 18,145 candidates for repurposing. In order to illustrate how potential therapeutics for rare diseases can be identified with eRepo-ORP, we discuss the repositioning of a kinase inhibitor for Ras-associated autoimmune leukoproliferative disease. The eRepo-ORP data set is available through the Open Science Framework at https://osf.io/qdjup/. Copyright © 2017. Published by Elsevier Ltd.

  5. Nutritional status, psychological well-being and the quality of life of AIDS orphans in rural Henan Province, China.

    Science.gov (United States)

    He, Zhonghu; Ji, Chengye

    2007-10-01

    To assess the influence of orphanhood due to AIDS on children's nutritional status, psychological well-being and life quality, and to explore appropriate intervention strategies in China. In 2005, 186 children aged 8-15 years (93 AIDS orphans and 93 non-orphans) from a rural area of Henan Province were surveyed in a cross-sectional and matched pairs study on nutritional status, psychological health and life quality. We found no compelling evidence for poorer nutritional status in orphans. The nutritional status of both orphans and non-orphans was extremely poor according to the prevalence of stunting, underweight, wasting and anaemia. Depression, low self-esteem and lower quality of life were more frequent in orphans. These differences mainly existed in boys' groups. No significant differences were found between paternal, maternal and double orphans, or orphans in orphanages or extended families. Regression analysis revealed that orphanhood leads to low self-esteem and more depression which contributes to lower quality of life and mediates the association between orphanhood and quality of life. The high prevalence of poor nutritional status indicates that basic material needs of children, including AIDS orphans, are not met in rural China. Psychological problems were prominent among orphans and had become the most important contributor of lower life quality. Boys were at least as vulnerable as girls. The living conditions of all children in rural China must be improved; school-based care and support are crucial and would be a cost-effective way to improve the overall life quality of AIDS orphans.

  6. Ammonium supply rate influences archaeal and bacterial ammonia oxidizers in a wetland soil vertical profile.

    Science.gov (United States)

    Höfferle, Špela; Nicol, Graeme W; Pal, Levin; Hacin, Janez; Prosser, James I; Mandić-Mulec, Ines

    2010-11-01

    Oxidation of ammonia, the first step in nitrification, is carried out in soil by bacterial and archaeal ammonia oxidizers and recent studies suggest possible selection for the latter in low-ammonium environments. In this study, we investigated the selection of ammonia-oxidizing archaea and bacteria in wetland soil vertical profiles at two sites differing in terms of the ammonium supply rate, but not significantly in terms of the groundwater level. One site received ammonium through decomposition of organic matter, while the second, polluted site received a greater supply, through constant leakage of an underground septic tank. Soil nitrification potential was significantly greater at the polluted site. Quantification of amoA genes demonstrated greater abundance of bacterial than archaeal amoA genes throughout the soil profile at the polluted site, whereas bacterial amoA genes at the unpolluted site were below the detection limit. At both sites, archaeal, but not the bacterial community structure was clearly stratified with depth, with regard to the soil redox potential imposed by groundwater level. However, depth-related changes in the archaeal community structure may also be associated with physiological functions other than ammonia oxidation. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  7. Identification of a conserved archaeal RNA polymerase subunit contacted by the basal transcription factor TFB.

    Science.gov (United States)

    Magill, C P; Jackson, S P; Bell, S D

    2001-12-14

    Archaea possess two general transcription factors that are required to recruit RNA polymerase (RNAP) to promoters in vitro. These are TBP, the TATA-box-binding protein and TFB, the archaeal homologue of TFIIB. Thus, the archaeal and eucaryal transcription machineries are fundamentally related. In both RNAP II and archaeal transcription systems, direct contacts between TFB/TFIIB and the RNAP have been demonstrated to mediate recruitment of the polymerase to the promoter. However the subunit(s) directly contacted by these factors has not been identified. Using systematic yeast two-hybrid and biochemical analyses we have identified an interaction between the N-terminal domain of TFB and an evolutionarily conserved subunit of the RNA polymerase, RpoK. Intriguingly, homologues of RpoK are found in all three nuclear RNA polymerases (Rpb6) and also in the bacterial RNA polymerase (omega-subunit).

  8. Between Charity and Education: Orphans and Orphanages in Early Modern Times

    Science.gov (United States)

    Jacobi, Juliane

    2009-01-01

    In early modern times orphans have been children who could not expect sufficient support from their family because of lack of at least one parent, in most cases the father. This article will clarify of whom we are talking if we talk about orphans and what have been the conditions of living in a society which was organised by a high variety of…

  9. Hyperthermophilic Archaeal Viruses as Novel Nanoplatforms

    DEFF Research Database (Denmark)

    Uldahl, Kristine Buch

    Viruses are the most abundant biological entities on earth, and with an estimated 1031 virus-like particles in the biosphere, viruses are virtually everywhere. Traditionally, the study of viruses has focused on their roles as infectious agents. However, over the last decades with the development...... presents an in depth investigation of the hyperthermophilic archaeal virus SMV. Decisive steps in the viral life-cycle are studied with focus on the early stages of infection. TEM observations suggest that SMV1 virions enter into host cells via a fusion entry mechanism, involving three distinct stages...

  10. Orphan sources control in the Republic of Korea

    International Nuclear Information System (INIS)

    Kim, C.-W.

    2001-01-01

    In this paper, the orphan source control programme in Korea will be discussed. Orphan sources are, in general, classified into three groups: 1) Illegally trafficking radioactive sources; 2) Domestic loss of radioactive sources due to the bankruptcy of licensees or authorized suppliers; and 3) Contaminated metal scrap, which has been imported. There are, currently, two approaches going on to control and manage orphan sources in Korea. First, the Korean regulatory authority (Ministry of Science and Technology: MOST) will fully run an information system on radiation safety to effectively trace and monitor all radioactive sources in the country by the year 2001. Second, the regulatory authority strongly advises steel mill companies to closely scrutinize and inspect scrap metal through a scrap monitoring system when they attempt to reutilize it in order to prevent it from being contaminated by uncontrolled sources. The Korea Institute of Nuclear Safety (KINS), a regulatory expert organization, is carrying out a three-year multiphase project to control and monitor orphan sources in Korea. The system, called the Information System on Integrated Radiation Safety (ISIRS) on the inter- and intra-net system has been developed to effectively control and accurately monitor radioactive sources on a real time basis since 1998. If the system is successfully set up as scheduled by the middle of May next year, the regulatory authority will be able to control any reutilization of uncontrolled sources efficiently. At the same time, the system can also provide, not only licensees, suppliers, or perspective end users but also the Korean general public of interests with information on radiation safety, safe radiation management tools and public services. The system has been created because of the necessity to effectively control radioactive sources safely. Also, it serves to prepare necessary protective measures in a timely manner for abnormal events of uncontrolled radiation from

  11. Bacterial and archaeal communities in the deep-sea sediments of inactive hydrothermal vents in the Southwest India Ridge

    Science.gov (United States)

    Zhang, Likui; Kang, Manyu; Xu, Jiajun; Xu, Jian; Shuai, Yinjie; Zhou, Xiaojian; Yang, Zhihui; Ma, Kesen

    2016-05-01

    Active deep-sea hydrothermal vents harbor abundant thermophilic and hyperthermophilic microorganisms. However, microbial communities in inactive hydrothermal vents have not been well documented. Here, we investigated bacterial and archaeal communities in the two deep-sea sediments (named as TVG4 and TVG11) collected from inactive hydrothermal vents in the Southwest India Ridge using the high-throughput sequencing technology of Illumina MiSeq2500 platform. Based on the V4 region of 16S rRNA gene, sequence analysis showed that bacterial communities in the two samples were dominated by Proteobacteria, followed by Bacteroidetes, Actinobacteria and Firmicutes. Furthermore, archaeal communities in the two samples were dominated by Thaumarchaeota and Euryarchaeota. Comparative analysis showed that (i) TVG4 displayed the higher bacterial richness and lower archaeal richness than TVG11; (ii) the two samples had more divergence in archaeal communities than bacterial communities. Bacteria and archaea that are potentially associated with nitrogen, sulfur metal and methane cycling were detected in the two samples. Overall, we first provided a comparative picture of bacterial and archaeal communities and revealed their potentially ecological roles in the deep-sea environments of inactive hydrothermal vents in the Southwest Indian Ridge, augmenting microbial communities in inactive hydrothermal vents.

  12. Archaeal ribonuclease P proteins have potential for biotechnological applications where precise hybridization of nucleic acids is needed.

    Science.gov (United States)

    Miyanoshita, Mitsuru; Nakashima, Takashi; Kakuta, Yoshimitsu; Kimura, Makoto

    2015-01-01

    Fluorescence resonance energy transfer-based assay showed that archaeal ribonuclease P (RNase P) proteins significantly promoted DNA annealing and strand displacement. Moreover, we found that archaeal RNase P proteins could discriminate nucleotide exchanges in DNA chains via their activity accelerating DNA strand displacement, suggesting that they have potential for biotechnological application to genetic diagnosis.

  13. The disposal of orphan wastes using the greater confinement disposal concept

    International Nuclear Information System (INIS)

    Bonano, E.J.; Chu, M.S.Y.; Price, L.L.; Conrad, S.H.; Dickman, P.T.

    1991-01-01

    In the United States, radioactive wastes are conventionally classified as high-level wastes, transuranic wastes, or low-level wastes. Each of these types of wastes, by law, has a ''home'' for their final disposal; i.e., high-level wastes are destined for disposal at the proposed repository at Yucca Mountain, transuranic waste for the proposed Waste Isolation Pilot Plant, and low-level waste for shallow-land disposal sites. However, there are some radioactive wastes within the United States Department of Energy (DOE) complex that do not meet the criteria established for disposal of either high-level waste, transuranic waste, or low-level waste. The former are called ''special-case'' or ''orphan'' wastes. This paper describes an ongoing project sponsored by the DOE's Nevada Operations Office for the disposal of orphan wastes at the Radioactive Waste Management Site at Area 5 of the Nevada Test Site using the greater confinement disposal (GCD) concept. The objectives of the GCD project are to evaluate the safety of the site for disposal of orphan wastes by assessing compliance with pertinent regulations through performance assessment, and to examine the feasibility of this disposal concept as a cost-effective, safe alternative for management of orphan wastes within the DOE complex. Decisions on the use of GCD or other alternate disposal concepts for orphan wastes be expected to be addressed in a Programmatic Environmental Impact Statement being prepared by DOE. The ultimate decision to use GCD will require a Record of Decision through the National Environmental Policy Act (NEPA) process. 20 refs., 3 figs., 2 tabs

  14. Multi-criteria decision analysis for assessment and appraisal of orphan drugs

    Directory of Open Access Journals (Sweden)

    Georgi Iskrov

    2016-09-01

    Full Text Available Background: Limited resources and expanding expectations push all countries and types of health systems to adopt new approaches in priority setting and resources allocation. Despite best efforts, it is difficult to reconcile all competing interests and trade-offs are inevitable. This is why multi-criteria decision analysis (MCDA has played a major role in recent uptake of value-based reimbursement. MCDA framework enables exploration of stakeholders’ preferences, as well as explicit organization of broad range of criteria on which real-world decisions are made.Assessment and appraisal of orphan drugs tend to be one of the most complicated health technology assessment (HTA tasks. Access to market approved orphan therapies remains an issue. Early constructive dialogue among rare disease stakeholders and elaboration of orphan drug-tailored decision support tools could set the scene for ongoing accumulation of evidence, as well as for proper reimbursement decision-making.Objective: The objective of this study was to create a MCDA value measurement model to assess and appraise orphan drugs. This was achieved by exploring the preferences on decision criteria’s weights and performance scores through a stakeholder-representative survey and a focus group discussion that were both organized in Bulgaria.Results/Conclusions: Decision criteria that describe the health technology’s characteristics were unanimously agreed as the most important group of reimbursement considerations. This outcome, combined with the high individual weight of disease severity and disease burden criteria underlined some of the fundamental principles of healthcare – equity and fairness. Our study proved that strength of evidence may be a key criterion in orphan drug assessment and appraisal. Evidence is not only used to shape reimbursement decision-making, but also to lend legitimacy to policies pursued. The need for real-world data on orphan drugs was largely stressed

  15. Psychological health of orphan bonobos and chimpanzees in African sanctuaries.

    Directory of Open Access Journals (Sweden)

    Victoria Wobber

    Full Text Available Facilities across Africa care for apes orphaned by the trade for "bushmeat." These facilities, called sanctuaries, provide housing for apes such as bonobos (Pan paniscus and chimpanzees (Pan troglodytes who have been illegally taken from the wild and sold as pets. Although these circumstances are undoubtedly stressful for the apes, most individuals arrive at the sanctuaries as infants and are subsequently provided with rich physical and social environments that can facilitate the expression of species-typical behaviors.We tested whether bonobo and chimpanzee orphans living in sanctuaries show any behavioral, physiological, or cognitive abnormalities relative to other individuals in captivity as a result of the early-life stress they experience. Orphans showed lower levels of aberrant behaviors, similar levels of average cortisol, and highly similar performances on a broad battery of cognitive tests in comparisons with individuals of the same species who were either living at a zoo or were reared by their mothers at the sanctuaries.Taken together, these results support the rehabilitation strategy used by sanctuaries in the Pan-African Sanctuary Alliance (PASA and suggest that the orphans we examined did not show long-term signs of stress as a result of their capture. Our findings also show that sanctuary apes are as psychologically healthy as apes in other captive settings and thus represent a valuable resource for non-invasive research.

  16. A generalizable pre-clinical research approach for orphan disease therapy

    Directory of Open Access Journals (Sweden)

    Beaulieu Chandree L

    2012-06-01

    Full Text Available Abstract With the advent of next-generation DNA sequencing, the pace of inherited orphan disease gene identification has increased dramatically, a situation that will continue for at least the next several years. At present, the numbers of such identified disease genes significantly outstrips the number of laboratories available to investigate a given disorder, an asymmetry that will only increase over time. The hope for any genetic disorder is, where possible and in addition to accurate diagnostic test formulation, the development of therapeutic approaches. To this end, we propose here the development of a strategic toolbox and preclinical research pathway for inherited orphan disease. Taking much of what has been learned from rare genetic disease research over the past two decades, we propose generalizable methods utilizing transcriptomic, system-wide chemical biology datasets combined with chemical informatics and, where possible, repurposing of FDA approved drugs for pre-clinical orphan disease therapies. It is hoped that this approach may be of utility for the broader orphan disease research community and provide funding organizations and patient advocacy groups with suggestions for the optimal path forward. In addition to enabling academic pre-clinical research, strategies such as this may also aid in seeding startup companies, as well as further engaging the pharmaceutical industry in the treatment of rare genetic disease.

  17. Different Diversity and Distribution of Archaeal Community in the Aqueous and Oil Phases of Production Fluid From High-Temperature Petroleum Reservoirs

    Directory of Open Access Journals (Sweden)

    Bo Liang

    2018-04-01

    Full Text Available To get a better knowledge on how archaeal communities differ between the oil and aqueous phases and whether environmental factors promote substantial differences on microbial distributions among production wells, we analyzed archaeal communities in oil and aqueous phases from four high-temperature petroleum reservoirs (55–65°C by using 16S rRNA gene based 454 pyrosequencing. Obvious dissimilarity of the archaeal composition between aqueous and oil phases in each independent production wells was observed, especially in production wells with higher water cut, and diversity in the oil phase was much higher than that in the corresponding aqueous phase. Statistical analysis further showed that archaeal communities in oil phases from different petroleum reservoirs tended to be more similar, but those in aqueous phases were the opposite. In the high-temperature ecosystems, temperature as an environmental factor could have significantly affected archaeal distribution, and archaeal diversity raised with the increase of temperature (p < 0.05. Our results suggest that to get a comprehensive understanding of petroleum reservoirs microbial information both in aqueous and oil phases should be taken into consideration. The microscopic habitats of oil phase, technically the dispersed minuscule water droplets in the oil could be a better habitat that containing the indigenous microorganisms.

  18. Archaeal Diversity and CO2 Fixers in Carbonate-/Siliciclastic-Rock Groundwater Ecosystems

    Directory of Open Access Journals (Sweden)

    Cassandre Sara Lazar

    2017-01-01

    Full Text Available Groundwater environments provide habitats for diverse microbial communities, and although Archaea usually represent a minor fraction of communities, they are involved in key biogeochemical cycles. We analysed the archaeal diversity within a mixed carbonate-rock/siliciclastic-rock aquifer system, vertically from surface soils to subsurface groundwater including aquifer and aquitard rocks. Archaeal diversity was also characterized along a monitoring well transect that spanned surface land uses from forest/woodland to grassland and cropland. Sequencing of 16S rRNA genes showed that only a few surface soil-inhabiting Archaea were present in the groundwater suggesting a restricted input from the surface. Dominant groups in the groundwater belonged to the marine group I (MG-I Thaumarchaeota and the Woesearchaeota. Most of the groups detected in the aquitard and aquifer rock samples belonged to either cultured or predicted lithoautotrophs (e.g., Thaumarchaeota or Hadesarchaea. Furthermore, to target autotrophs, a series of 13CO2 stable isotope-probing experiments were conducted using filter pieces obtained after filtration of 10,000 L of groundwater to concentrate cells. These incubations identified the SAGMCG Thaumarchaeota and Bathyarchaeota as groundwater autotrophs. Overall, the results suggest that the majority of Archaea on rocks are fixing CO2, while archaeal autotrophy seems to be limited in the groundwater.

  19. [The Euro-orphans phenomenon and the courses in therapeutic work and psychiatric treatment--a case study].

    Science.gov (United States)

    Nowak, Marta; Gaweda, Agnieszka; Janas-Kozik, Małgorzata

    2012-01-01

    Today, the phenomenon of Euro-orphan is more and more frequently reported in the literature. This term refers to children with one or both parents emigrated from the country for work purposes. In connection with the social transformations of orphan-hood types described in the literature (nature, spiritual, social), the definition has been broadened by the definition ofeuro-orphan. The Ministry of Education describes the euro-orphan as the destruction of the family structure, the disorder of the socialisation process of children and reduction of the emotional exchanges among family members, as a result of migration of their parents. It provides further that not every child whose parents are not present in the country is covered as an euro-orphan. However, this group has become an increasingly larger populations. Lack of physical proximity and accessibility of important persons may have some psychological and pedagogical implications. These in turn can be shaped over time, into pathological symptoms, which are diagnostic entities in developmental psychiatry. It is not know precisely how many children in Poland are Euro-orphans. The aim of this paper is an attempt to understand the social phenomenon of Euro-orphanhood in the light of the observed psychopathologies of children and adolescents. The case study of the psychotherapy of a patient suffering from the Euro-orphanhood syndrome. Euro-orphanhood is a social phenomenon that generates Euro-orphans with a wide range of psychopathological symptoms classified in different diagnostic categories. The type and intensification of the psychopathological symptoms depend on the quality of relationships with meaningful persons prior to the Euro-orphanhood period. The course of the psychotherapeutic work with Euro-orphans should cover an individual aspect taking into consideration the maturity of defensive mechanisms as well as the work-through of negative feelings cumulated due to becoming a Euro-orphan.

  20. Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

    Science.gov (United States)

    Talele, Sonali S; Xu, Kui; Pariser, Anne R; Braun, M Miles; Farag-El-Massah, Sheiren; Phillips, M Ian; Thompson, Barry H; Coté, Timothy R

    2010-07-01

    The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.

  1. Fertility among orphans in rural Malawi: challenging common assumptions about risk and mechanisms.

    Science.gov (United States)

    Kidman, Rachel; Anglewicz, Philip

    2014-12-01

    Although a substantial literature suggests that orphans suffer disadvantage relative to nonorphaned peers, the nature of this disadvantage and the mechanisms driving it are poorly understood. Some evidence suggests that orphans experience elevated fertility, perhaps because structural disadvantage leads them to engage in sexual risk-taking. An alternative explanation is that orphans intentionally become pregnant to achieve a sense of normality, acceptance and love. Data from the 2006 wave of the Malawi Longitudinal Study of Families and Health on 1,033 young adults aged 15-25 were used to examine the relationship of maternal and paternal orphanhood with sexual risk indicators and desired and actual fertility. Regression analyses were used to adjust for covariates, including social and demographic characteristics and elapsed time since parental death. Twenty-six percent of respondents had lost their father and 15% their mother. Orphanhood was not associated with sexual risk-taking. However, respondents whose mother had died in the past five years desired more children than did those whose mother was still alive (risk differences, 0.52 among women and 0.97 among men). Actual fertility was elevated among women whose father had died more than five years earlier (0.31) and among men whose mother had died in the past five years (1.06) or more than five years earlier (0.47). The elevations in desired and actual fertility among orphans are consistent with the hypothesis that orphans intentionally become pregnant. Strategies that address personal desires for parenthood may need to be part of prevention programs aimed at orphaned youth.

  2. Challenges of ligand identification for the second wave of orphan riboswitch candidates.

    Science.gov (United States)

    Greenlee, Etienne B; Stav, Shira; Atilho, Ruben M; Brewer, Kenneth I; Harris, Kimberly A; Malkowski, Sarah N; Mirihana Arachchilage, Gayan; Perkins, Kevin R; Sherlock, Madeline E; Breaker, Ronald R

    2018-03-04

    Orphan riboswitch candidates are noncoding RNA motifs whose representatives are believed to function as genetic regulatory elements, but whose target ligands have yet to be identified. The study of certain orphans, particularly classes that have resisted experimental validation for many years, has led to the discovery of important biological pathways and processes once their ligands were identified. Previously, we highlighted details for four of the most common and intriguing orphan riboswitch candidates. This facilitated the validation of riboswitches for the signaling molecules c-di-AMP, ZTP, and ppGpp, the metal ion Mn 2+ , and the metabolites guanidine and PRPP. Such studies also yield useful linkages between the ligands sensed by the riboswitches and numerous biochemical pathways. In the current report, we describe the known characteristics of 30 distinct classes of orphan riboswitch candidates - some of which have remained unsolved for over a decade. We also discuss the prospects for uncovering novel biological insights via focused studies on these RNAs. Lastly, we make recommendations for experimental objectives along the path to finding ligands for these mysterious RNAs.

  3. "When the obvious brother is not there": political and cultural contexts of the orphan challenge in northern Uganda.

    Science.gov (United States)

    Oleke, Christopher; Blystad, Astrid; Rekdal, Ole Bjørn

    2005-12-01

    It is estimated that two million of Uganda's children today are orphaned primarily due to AIDS. While recognising the immense impact of HIV/AIDS on the present orphan problem, this article calls for a broader historic and cultural contextualisation to reach an understanding of the vastness of the orphan challenge. The study on which the article is based was carried out among the Langi in Lira District, northern Uganda, with a prime focus on the situation of orphans within the extended family system. The data were collected through ethnographic fieldwork (8 months); in-depth interviews with community leaders (21), heads of households (45) and orphans (35); through focus group discussions (5) with adult men and women caring for orphans, community leaders and with orphans; and also through documentary review. A survey was conducted in 402 households. The findings reveal a transition over the past 30 years from a situation dominated by 'purposeful' voluntary exchange of non-orphaned children to one dominated by 'crisis fostering' of orphans. Sixty-three percent of the households caring for orphans were found to be no longer headed by resourceful paternal kin in a manner deemed culturally appropriate by the patrilineal Langi society, but rather by marginalised widows, grandmothers or other single women receiving little support from the paternal clan. This transition is partly linked to an abrupt discontinuation of the Langi 'widow inheritance' (laku) practice. It is argued that the consequential transformations in fostering practices in northern Uganda must be historically situated through a focus on the effects of armed conflicts and uprooting of the local pastoral and cotton-based economy, which have occurred since the late 1970s. These processes jointly produced dramatic economic marginalisation with highly disturbing consequences for orphans and their caretakers.

  4. Post-marketing access to orphan drugs: a critical analysis of health technology assessment and reimbursement decision-making considerations

    Directory of Open Access Journals (Sweden)

    Iskrov G

    2014-01-01

    Full Text Available Georgi Iskrov, Rumen Stefanov Department of Social Medicine and Public Health, Medical University of Plovdiv, Plovdiv, Bulgaria Abstract: This study aims to explore the current rationale of post-marketing access to orphan drugs. As access to orphan medicinal products depends on assessment and appraisal by health authorities, this article is focused on health technology assessment (HTA and reimbursement decision-making considerations for orphan drugs. A critical analysis may identify important factors that could predetermine the combined outcomes of these two processes. Following this objective, an analytical framework was developed, comprising three overlaying issues: to outline what is currently done and what needs to be done in the field of HTA of orphan drugs, to synthesize important variables relevant to the reimbursement decision-making about orphan drugs, and to unveil relationships between theory and practice. Methods for economic evaluation, cost-effectiveness threshold, budget impact, uncertainty of evidence, criteria in reimbursement decision-making, and HTA research agenda are all explored and discussed from an orphan drug perspective. Reimbursement decision-making for orphan drugs is a debate of policy priorities, health system specifics, and societal attitudes. Health authorities need to pursue a multidisciplinary analysis on a range of criteria, ensuring an explicit understanding of the trade-offs for decisions related to eligibility for reimbursement. The only reasonable way to accept a higher valuation of orphan drug benefits is if these are demonstrated empirically. Rarity means that the quality of orphan drug evidence is not the same as for conventional therapies. Closing this gap is another crucial point for the timely access to these products. The generation of evidence goes far beyond pre-market authorization trials and requires transnational cooperation and coordination. Early constructive dialogue among orphan drug

  5. Effect of soil properties and hydrology on Archaeal community composition in three temperate grasslands on peat

    DEFF Research Database (Denmark)

    Görres, Carolyn-Monika; Conrad, Ralf; Petersen, Søren O

    2013-01-01

    Grasslands established on drained peat soils are regarded as negligible methane (CH4) sources; however, they can still exhibit considerable soil CH4 dynamics. We investigated archaeal community composition in two different fen peat soils and one bog peat soil under permanent grassland in Denmark........ Overall, there seemed to be a significant coupling between peat type and archaeal community composition, with local hydrology modifying the strength of this coupling....

  6. Specificity and Function of Archaeal DNA Replication Initiator Proteins

    Directory of Open Access Journals (Sweden)

    Rachel Y. Samson

    2013-02-01

    Full Text Available Chromosomes with multiple DNA replication origins are a hallmark of Eukaryotes and some Archaea. All eukaryal nuclear replication origins are defined by the origin recognition complex (ORC that recruits the replicative helicase MCM(2-7 via Cdc6 and Cdt1. We find that the three origins in the single chromosome of the archaeon Sulfolobus islandicus are specified by distinct initiation factors. While two origins are dependent on archaeal homologs of eukaryal Orc1 and Cdc6, the third origin is instead reliant on an archaeal Cdt1 homolog. We exploit the nonessential nature of the orc1-1 gene to investigate the role of ATP binding and hydrolysis in initiator function in vivo and in vitro. We find that the ATP-bound form of Orc1-1 is proficient for replication and implicates hydrolysis of ATP in downregulation of origin activity. Finally, we reveal that ATP and DNA binding by Orc1-1 remodels the protein’s structure rather than that of the DNA template.

  7. A Regulatory Network Analysis of Orphan Genes in Arabidopsis Thaliana

    Science.gov (United States)

    Singh, Pramesh; Chen, Tianlong; Arendsee, Zebulun; Wurtele, Eve S.; Bassler, Kevin E.

    Orphan genes, which are genes unique to each particular species, have recently drawn significant attention for their potential usefulness for organismal robustness. Their origin and regulatory interaction patterns remain largely undiscovered. Recently, methods that use the context likelihood of relatedness to infer a network followed by modularity maximizing community detection algorithms on the inferred network to find the functional structure of regulatory networks were shown to be effective. We apply improved versions of these methods to gene expression data from Arabidopsis thaliana, identify groups (clusters) of interacting genes with related patterns of expression and analyze the structure within those groups. Focusing on clusters that contain orphan genes, we compare the identified clusters to gene ontology (GO) terms, regulons, and pathway designations and analyze their hierarchical structure. We predict new regulatory interactions and unravel the structure of the regulatory interaction patterns of orphan genes. Work supported by the NSF through Grants DMR-1507371 and IOS-1546858.

  8. Cellular and molecular biology of orphan G protein-coupled receptors.

    Science.gov (United States)

    Oh, Da Young; Kim, Kyungjin; Kwon, Hyuk Bang; Seong, Jae Young

    2006-01-01

    The superfamily of G protein-coupled receptors (GPCRs) is the largest and most diverse group of membrane-spanning proteins. It plays a variety of roles in pathophysiological processes by transmitting extracellular signals to cells via heterotrimeric G proteins. Completion of the human genome project revealed the presence of approximately 168 genes encoding established nonsensory GPCRs, as well as 207 genes predicted to encode novel GPCRs for which the natural ligands remained to be identified, the so-called orphan GPCRs. Eighty-six of these orphans have now been paired to novel or previously known molecules, and 121 remain to be deorphaned. A better understanding of the GPCR structures and classification; knowledge of the receptor activation mechanism, either dependent on or independent of an agonist; increased understanding of the control of GPCR-mediated signal transduction; and development of appropriate ligand screening systems may improve the probability of discovering novel ligands for the remaining orphan GPCRs.

  9. Supercritical Fluid Extraction of Bacterial and Archaeal Lipid Biomarkers from Anaerobically Digested Sludge

    Directory of Open Access Journals (Sweden)

    Koichi Fujie

    2012-03-01

    Full Text Available Supercritical fluid extraction (SFE was used in the analysis of bacterial respiratory quinone (RQ, bacterial phospholipid fatty acid (PLFA, and archaeal phospholipid ether lipid (PLEL from anaerobically digested sludge. Bacterial RQ were determined using ultra performance liquid chromatography (UPLC. Determination of bacterial PLFA and archaeal PLEL was simultaneously performed using gas chromatography-mass spectrometry (GC-MS. The effects of pressure, temperature, and modifier concentration on the total amounts of RQ, PLFA, and PLEL were investigated by 23 experiments with five settings chosen for each variable. The optimal extraction conditions that were obtained through a multiple-response optimization included a pressure of 23.6 MPa, temperature of 77.6 °C, and 10.6% (v/v of methanol as the modifier. Thirty nine components of microbial lipid biomarkers were identified in the anaerobically digested sludge. Overall, the SFE method proved to be more effective, rapid, and quantitative for simultaneously extracting bacterial and archaeal lipid biomarkers, compared to conventional organic solvent extraction. This work shows the potential application of SFE as a routine method for the comprehensive analysis of microbial community structures in environmental assessments using the lipid biomarkers profile.

  10. Rapid identification of sequences for orphan enzymes to power accurate protein annotation.

    Directory of Open Access Journals (Sweden)

    Kevin R Ramkissoon

    Full Text Available The power of genome sequencing depends on the ability to understand what those genes and their proteins products actually do. The automated methods used to assign functions to putative proteins in newly sequenced organisms are limited by the size of our library of proteins with both known function and sequence. Unfortunately this library grows slowly, lagging well behind the rapid increase in novel protein sequences produced by modern genome sequencing methods. One potential source for rapidly expanding this functional library is the "back catalog" of enzymology--"orphan enzymes," those enzymes that have been characterized and yet lack any associated sequence. There are hundreds of orphan enzymes in the Enzyme Commission (EC database alone. In this study, we demonstrate how this orphan enzyme "back catalog" is a fertile source for rapidly advancing the state of protein annotation. Starting from three orphan enzyme samples, we applied mass-spectrometry based analysis and computational methods (including sequence similarity networks, sequence and structural alignments, and operon context analysis to rapidly identify the specific sequence for each orphan while avoiding the most time- and labor-intensive aspects of typical sequence identifications. We then used these three new sequences to more accurately predict the catalytic function of 385 previously uncharacterized or misannotated proteins. We expect that this kind of rapid sequence identification could be efficiently applied on a larger scale to make enzymology's "back catalog" another powerful tool to drive accurate genome annotation.

  11. Caregiver issues and AIDS orphans: perspectives from a social worker focus group.

    Science.gov (United States)

    Paige, C Y; Johnson, M S

    1997-10-01

    This study examines social workers' perceptions of the needs of families coping with acquired immunodeficiency syndrome (AIDS). This research investigates the problems of family caregivers of children orphaned by human immunodeficiency virus (HIV)-related death of their parents. A qualitative semistructured interview format was used in a focus group of 18 social workers. Four questions were designed to assess family needs and resources, as well as to evaluate the social workers' perspectives of governmental policies affecting these families. A list of four problems and two recommendations for change evolved from the focus group. Inadequate finances to house and care for the children was the primary cause for distress in these families. The major governmental policy that hindered the social workers' ability to assist families pertained to the low financial entitlement for caregivers who are related to the orphaned child. It was noted that unrelated caregivers receive substantially more money for the care of these children than family caregivers receive. Recommendations were made to change this policy and to develop guardianship laws that facilitate families' abilities to provide care to AIDS orphans. Family caregivers of AIDS orphans are bombarded with great demands and limited resources. This analysis of their situation from the social workers' perspective is a positive step toward the improvement of support services for these families. Further research should include individual qualitative interviews assessing the needs of the caregivers and AIDS orphans.

  12. Rapid Identification of Sequences for Orphan Enzymes to Power Accurate Protein Annotation

    Science.gov (United States)

    Ojha, Sunil; Watson, Douglas S.; Bomar, Martha G.; Galande, Amit K.; Shearer, Alexander G.

    2013-01-01

    The power of genome sequencing depends on the ability to understand what those genes and their proteins products actually do. The automated methods used to assign functions to putative proteins in newly sequenced organisms are limited by the size of our library of proteins with both known function and sequence. Unfortunately this library grows slowly, lagging well behind the rapid increase in novel protein sequences produced by modern genome sequencing methods. One potential source for rapidly expanding this functional library is the “back catalog” of enzymology – “orphan enzymes,” those enzymes that have been characterized and yet lack any associated sequence. There are hundreds of orphan enzymes in the Enzyme Commission (EC) database alone. In this study, we demonstrate how this orphan enzyme “back catalog” is a fertile source for rapidly advancing the state of protein annotation. Starting from three orphan enzyme samples, we applied mass-spectrometry based analysis and computational methods (including sequence similarity networks, sequence and structural alignments, and operon context analysis) to rapidly identify the specific sequence for each orphan while avoiding the most time- and labor-intensive aspects of typical sequence identifications. We then used these three new sequences to more accurately predict the catalytic function of 385 previously uncharacterized or misannotated proteins. We expect that this kind of rapid sequence identification could be efficiently applied on a larger scale to make enzymology’s “back catalog” another powerful tool to drive accurate genome annotation. PMID:24386392

  13. Psychosocial support and parents' social life determine the self-esteem of orphan children

    Directory of Open Access Journals (Sweden)

    Erango MA

    2015-10-01

    Full Text Available Markos Abiso Erango,1 Zikie Ataro Ayka2 1School of Mathematical and Statistical Sciences, Department of Applied Statistics, Hawassa University, Hawassa, 2Department of Biology, Arba Minch University, Arba Minch, Ethiopia Abstract: Parental death affects the life of children in many ways, one of which is self-esteem problems. Providing psychosocial support and equipping orphans play a vital role in their lifes. A cross-sectional study was conducted on 7–18-year-old orphans at 17 local districts of Gamo Gofa Zone, Southern Regional State of Ethiopia. From a total of 48,270 orphans in these areas, 4,368 were selected using stratified simple random sampling technique. Data were collected with a designed questionnaire based on the Rosenberg's rating scale to measure their self-esteem levels. Self-esteem with a score less than or equal to an average score was considered to be low self-esteem in the analysis. Binary logistic regression model was used to analyze the data using the SPSS software. The results of the study revealed that the probability of orphans suffering from low self-esteem was 0.59. Several risk factors were found to be significant at the level of 5%. Psychosocial support (good guidance, counseling and treatment, physical protection and amount of love shared, financial and material support, and fellowship with other children, parents living together before death, strong relationship between parents before death, high average monthly income, voluntary support, and consideration from the society are some of the factors that decrease the risk of being low in self-esteem. There are many orphans with low self-esteem in the study areas. The factors negatively affecting the self-esteem of orphans include the lack of psychosocial support, poor social life of parents, and death of parents due to AIDS. Society and parents should be aware of the consequences of these factors which can influence their children's future self

  14. The handling with orphan sources of ionizing radiation in Belarus

    International Nuclear Information System (INIS)

    Dubrovskij, A.I.; Beresneva, V.A.; Pribylev, S.V.

    2013-01-01

    In Belarus, the emergency response actions, when detecting orphan sources, provide specific organs of government within their competence. Overall coordination and work on the collection, processing, exchange, accounting and transfer in the established order information about the sources of ionizing radiation interacting organs and relevant international organizations assigned to the Emergency Situations Ministry. Created in Belarus response system in case of detection of orphan sources can provide the level of emergency preparedness and response, and generally satisfy international best practice in this area. (authors)

  15. Compassionate use of orphan drugs.

    Science.gov (United States)

    Hyry, Hanna I; Manuel, Jeremy; Cox, Timothy M; Roos, Jonathan C P

    2015-08-21

    EU regulation 726/2004 authorises manufacturers to provide drugs to patients on a temporary basis when marketing authorisation sought centrally for the entire EU is still pending. Individual Member States retain the right to approve and implement such 'compassionate use' programmes which companies will usually provide for free. Nevertheless some companies have opted not to partake in such programmes, in effect restricting access to drugs for patients in need. Here we survey the state of compassionate use programmes in the EU with particular reference to the rare disease field, and provide legal and ethical arguments to encourage their increased compassionate use in the EU and beyond. We contend that if enacted, these recommendations will be mutually beneficial to companies as well as patients. Requests for information from the European Medicines Agency were made under the UK Freedom of Information Act 2000. Legal, ethical and economic/pragmatic analysis identified means by which provision of therapy in compassionate use programmes might be increased. More than 50 notifications of compassionate use programmes have been submitted to the EMA by Member States since 2006. About 40 % relate to orphan drugs. As there is a compulsory register of programmes but not of outcomes, their success is difficult to evaluate but, for example, the French programme expedited treatment for more than 20,000 (orphan and non-orphan) patients over a period of three years. Compelling self-interested, legal and ethical arguments can be mounted to encourage manufacturers to offer therapies on a compassionate use basis and these are often equally applicable to provision on a humanitarian aid basis. The EU's compassionate use programmes are instrumental in ensuring continuity of access to drugs until approval and reimbursement decisions are finalised. We propose the creation of a registry of drugs offered on a compassionate use basis; further transparency would allow such programmes to be

  16. Reconsidering the orphan problem: the emergence of male caregivers in Lesotho.

    Science.gov (United States)

    Block, Ellen

    2016-01-01

    Care for AIDS orphans in southern Africa is frequently characterized as a "crisis", where kin-based networks of care are thought to be on the edge of collapse. Yet these care networks, though strained by AIDS, are still the primary mechanisms for orphan care, in large part because of the essential role grandmothers play in responding to the needs of orphans. Ongoing demographic shifts as a result of HIV/AIDS and an increasingly feminized labor market continue to disrupt and alter networks of care for orphans and vulnerable children. This paper examines the emergence of a small but growing number of male caregivers who are responding to the needs of the extended family. While these men are still few in number, the strength of gendered ideologies of female care means that this group of men is socially, if not statistically significant. Men continue to be considered caregivers of last resort, but their care will close a small but growing gap that threatens to undermine kin-based networks of care in Lesotho and across the region. The adaptation of gender roles reinforces the strength and resilience of kinship networks even when working against deeply entrenched ideas about gendered division of domestic labor.

  17. An ultra-HTS process for the identification of small molecule modulators of orphan G-protein-coupled receptors.

    Science.gov (United States)

    Cacace, Angela; Banks, Martyn; Spicer, Timothy; Civoli, Francesca; Watson, John

    2003-09-01

    G-protein-coupled receptors (GPCRs) are the most successful target proteins for drug discovery research to date. More than 150 orphan GPCRs of potential therapeutic interest have been identified for which no activating ligands or biological functions are known. One of the greatest challenges in the pharmaceutical industry is to link these orphan GPCRs with human diseases. Highly automated parallel approaches that integrate ultra-high throughput and focused screening can be used to identify small molecule modulators of orphan GPCRs. These small molecules can then be employed as pharmacological tools to explore the function of orphan receptors in models of human disease. In this review, we describe methods that utilize powerful ultra-high-throughput screening technologies to identify surrogate ligands of orphan GPCRs.

  18. National strategies for improving control over orphan sources of ionising radiation

    International Nuclear Information System (INIS)

    Nizamska, M.

    2007-01-01

    Since 1989 Bulgaria started reformation of economy sector. Part of this process is the intensive privatisation, as well as in the sited using radioactive materials for different applications - industry, medicine, agriculture, etc. The quick change of property ownership results in difficulties to identify the assessor of radioactive source or material and finally led to appearance of orphan sources. A orphan source is defined as a source that poses sufficient radiological hazard to warrant regulatory control, but which is not under regulatory control because it has never been so, or because it has been abandoned, lost, misplaced, stolen or otherwise transferred without proper authorisation. A face on these problems, Bulgaria is performing a series of measure to improve the control over orphan sources and to strengthening the control over the nuclear and radioactive materials. The report presents briefly this measures. (author)

  19. Psychological Characteristics of Adolescents Orphans with Different Experience of Living in a Family

    Science.gov (United States)

    Shulga, Tatyana I.; Savchenko, Daria D.; Filinkova, Evgeniya B.

    2016-01-01

    The complexity of settling adolescents-orphans in foster families and significant number of break-downs in these families are the problems which determine the relevance of current research. Many adolescent orphans get in social institutions repeatedly, because their psychological features lead to difficulties that their foster parents are unable…

  20. Biogas production and methanogenic archaeal community in mesophilic and thermophilic anaerobic co-digestion processes.

    Science.gov (United States)

    Yu, D; Kurola, J M; Lähde, K; Kymäläinen, M; Sinkkonen, A; Romantschuk, M

    2014-10-01

    Over 258 Mt of solid waste are generated annually in Europe, a large fraction of which is biowaste. Sewage sludge is another major waste fraction. In this study, biowaste and sewage sludge were co-digested in an anaerobic digestion reactor (30% and 70% of total wet weight, respectively). The purpose was to investigate the biogas production and methanogenic archaeal community composition in the anaerobic digestion reactor under meso- (35-37 °C) and thermophilic (55-57 °C) processes and an increasing organic loading rate (OLR, 1-10 kg VS m(-3) d(-1)), and also to find a feasible compromise between waste treatment capacity and biogas production without causing process instability. In summary, more biogas was produced with all OLRs by the thermophilic process. Both processes showed a limited diversity of the methanogenic archaeal community which was dominated by Methanobacteriales and Methanosarcinales (e.g. Methanosarcina) in both meso- and thermophilic processes. Methanothermobacter was detected as an additional dominant genus in the thermophilic process. In addition to operating temperatures, the OLRs, the acetate concentration, and the presence of key substrates like propionate also affected the methanogenic archaeal community composition. A bacterial cell count 6.25 times higher than archaeal cell count was observed throughout the thermophilic process, while the cell count ratio varied between 0.2 and 8.5 in the mesophilic process. This suggests that the thermophilic process is more stable, but also that the relative abundance between bacteria and archaea can vary without seriously affecting biogas production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Stigma, marginalization and psychosocial well-being of orphans in Rwanda: exploring the mediation role of social support.

    Science.gov (United States)

    Caserta, Tehetna Alemu; Pirttilä-Backman, Anna-Maija; Punamäki, Raija-Leena

    2016-01-01

    Stigma and marginalization are one of the major challenges orphans face in their daily lives, particularly in developing countries, but little is known about their impacts on mental health. This study examines how orphan-related characteristics, stigma and marginalization are associated with psychosocial well-being. It further analyses the role of social support in mediating between stigma and marginalization and mental health, indicated by emotional well-being and mental distress. The participants in this study were 430 Rwandan orphans who were 10-25 years of age, and of whom 179 were females and 251 were males. Results showed that high levels of stigma and marginalization were associated with a lower level of emotional well-being and higher levels of mental distress. A mediation analysis indicated that low level of social support due to stigma and marginalization contributed significantly to low level of emotional well-being. Once stigma, marginalization and social support were fully accounted for, AIDS orphans exhibited higher levels of mental distress than those who were orphaned by genocide or other causes. Future interventions designed to reduce stigma and marginalization for orphans and actions that facilitate social support can significantly improve emotional well-being and reduce mental distress among orphans.

  2. Influence of land use on bacterial and archaeal diversity and community structures in three natural ecosystems and one agricultural soil.

    Science.gov (United States)

    Lynn, Tin Mar; Liu, Qiong; Hu, Yajun; Yuan, Hongzhao; Wu, Xiaohong; Khai, Aye Aye; Wu, Jinshui; Ge, Tida

    2017-07-01

    Studying shifts in microbial communities under different land use can help in determining the impact of land use on microbial diversity. In this study, we analyzed four different land-use types to determine their bacterial and archaeal diversity and abundance. Three natural ecosystems, that is, wetland (WL), grassland (GL), and forest (FR) soils, and one agricultural soil, that is, tea plantation (TP) soil, were investigated to determine how land use shapes bacterial and archaeal diversity. For this purpose, molecular analyses, such as quantitative polymerase chain reaction (Q-PCR), 16S rRNA gene sequencing, and terminal restriction fragment length polymorphism (T-RFLP), were used. Soil physicochemical properties were determined, and statistical analyses were performed to identify the key factors affecting microbial diversity in these soils. Phylogenetic affiliations determined using the Ribosomal Database Project (RDP) database and T-RFLP revealed that the soils had differing bacterial diversity. WL soil was rich in only Proteobacteria, whereas GR soil was rich in Proteobacteria, followed by Actinobacteria. FR soil had higher abundance of Chloroflexi species than these soils. TP soil was rich in Actinobacteria, followed by Chloroflexi, Acidobacteria, Proteobacteria, and Firmicutes. The archaeal diversity of GL and FR soils was similar in that most of their sequences were closely related to Nitrososphaerales (Thaumarchaeota phylum). In contrast, WL soil, followed by TP soil, had greater archaeal diversity than other soils. Eight different archaeal classes were found in WL soil, and Pacearchaeota class was the richest one. The abundance of bacterial and archaeal 16S rRNA gene copies in WL and GL soils was significantly higher than that in FR and TP soils. Redundancy analysis showed that bacterial diversity was influenced by abiotic factors, e.g., total organic carbon and pH, whereas total nitrogen, pH, and cation exchange capacity (CEC) significantly affected

  3. Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.

    Directory of Open Access Journals (Sweden)

    Adam L Martin

    Full Text Available The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1 200% elevation over baseline reporter gene expression; 2 40% inhibition of baseline expression; and 3 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1 inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176; 2 no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119; 3 elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12; 4 elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65; and 5 no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87. Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40. This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65% than stimulation of expression (15%. Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.

  4. Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.

    Science.gov (United States)

    Martin, Adam L; Steurer, Michael A; Aronstam, Robert S

    2015-01-01

    The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.

  5. Shifts in phylogenetic diversity of archaeal communities in mangrove sediments at different sites and depths in southeastern Brazil.

    Science.gov (United States)

    Mendes, Lucas William; Taketani, Rodrigo Gouvêa; Navarrete, Acácio Aparecido; Tsai, Siu Mui

    2012-06-01

    This study focused on the structure and composition of archaeal communities in sediments of tropical mangroves in order to obtain sufficient insight into two Brazilian sites from different locations (one pristine and another located in an urban area) and at different depth levels from the surface. Terminal restriction fragment length polymorphism (T-RFLP) of PCR-amplified 16S rRNA gene fragments was used to scan the archaeal community structure, and 16S rRNA gene clone libraries were used to determine the community composition. Redundancy analysis of T-RFLP patterns revealed differences in archaeal community structure according to location, depth and soil attributes. Parameters such as pH, organic matter, potassium and magnesium presented significant correlation with general community structure. Furthermore, phylogenetic analysis revealed a community composition distributed differently according to depth where, in shallow samples, 74.3% of sequences were affiliated with Euryarchaeota and 25.7% were shared between Crenarchaeota and Thaumarchaeota, while for the deeper samples, 24.3% of the sequences were affiliated with Euryarchaeota and 75.7% with Crenarchaeota and Thaumarchaeota. Archaeal diversity measurements based on 16S rRNA gene clone libraries decreased with increasing depth and there was a greater difference between depths (25% of sequences shared). Taken together, our findings indicate that mangrove ecosystems support a diverse archaeal community; it might possibly be involved in nutrient cycles and are affected by sediment properties, depth and distinct locations. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  6. A site-specific endonuclease encoded by a typical archaeal intron

    DEFF Research Database (Denmark)

    Dalgaard, Jacob; Garrett, Roger Antony; Belfort, Malene

    1993-01-01

    The protein encoded by the archaeal intron in the 23S rRNA gene of the hyperthermophile Desulfurococcus mobilis is a double-strand DNase that, like group I intron homing endonucleases, is capable of cleaving an intronless allele of the gene. This enzyme, I-Dmo I, is unusual among the intron...

  7. The role of Vinca Institute in national Orphan sources recovery program

    International Nuclear Information System (INIS)

    Orlic, Milan; Pavlovic, Snezana; Gajic-Kvascev, Maja

    2008-01-01

    Full text: According with establishing of radiation safety regulatory system of Republic of Serbia, Goverment of Republic of Serbia in cooperation with international community (IAEA, DOE), has developed a national Orphan sources recovery program. The role, possibilities the results of Vinca Institute in that program has been presented in this paper. The main goal of the program is to put all orphan sources found in Serbia in storage in Vinca Institute, and restore regulatory control. In this paper existing state of Orphan sources programe, goals of the system development, programmes for seaching of sources, plans, stuff education and training are given. Special concern was given to planning process for seaching of sources. It includes decission on location to be treated, quantity and types of expected source estimation and resources wich will be used. Plan of training includes radiation protection and quality assurance aspects. (author)

  8. Orphan Drug Pricing: An Original Exponential Model Relating Price to the Number of Patients

    Directory of Open Access Journals (Sweden)

    Andrea Messori

    2016-10-01

    Full Text Available In managing drug prices at the national level, orphan drugs represent a special case because the price of these agents is higher than that determined according to value-based principles. A common practice is to set the orphan drug price in an inverse relationship with the number of patients, so that the price increases as the number of patients decreases. Determination of prices in this context generally has a purely empirical nature, but a theoretical basis would be needed. The present paper describes an original exponential model that manages the relationship between price and number of patients for orphan drugs. Three real examples are analysed in detail (eculizumab, bosentan, and a data set of 17 orphan drugs published in 2010. These analyses have been aimed at identifying some objective criteria to rationally inform this relationship between prices and patients and at converting these criteria into explicit quantitative rules.

  9. Psychological distress and its predictors in AIDS orphan ...

    African Journals Online (AJOL)

    Structured interviewer administered questionnaire and scales including HAD, Rosenberg's and MPSS scales were used to measure the orphans' level of depression, anxiety, self-esteem and their perceived social support. Result: Among the ...

  10. Global occurrence of archaeal amoA genes in terrestrial hot springs.

    Science.gov (United States)

    Zhang, Chuanlun L; Ye, Qi; Huang, Zhiyong; Li, Wenjun; Chen, Jinquan; Song, Zhaoqi; Zhao, Weidong; Bagwell, Christopher; Inskeep, William P; Ross, Christian; Gao, Lei; Wiegel, Juergen; Romanek, Christopher S; Shock, Everett L; Hedlund, Brian P

    2008-10-01

    Despite the ubiquity of ammonium in geothermal environments and the thermodynamic favorability of aerobic ammonia oxidation, thermophilic ammonia-oxidizing microorganisms belonging to the crenarchaeota kingdom have only recently been described. In this study, we analyzed microbial mats and surface sediments from 21 hot spring samples (pH 3.4 to 9.0; temperature, 41 to 86 degrees C) from the United States, China, and Russia and obtained 846 putative archaeal ammonia monooxygenase large-subunit (amoA) gene and transcript sequences, representing a total of 41 amoA operational taxonomic units (OTUs) at 2% identity. The amoA gene sequences were highly diverse, yet they clustered within two major clades of archaeal amoA sequences known from water columns, sediments, and soils: clusters A and B. Eighty-four percent (711/846) of the sequences belonged to cluster A, which is typically found in water columns and sediments, whereas 16% (135/846) belonged to cluster B, which is typically found in soils and sediments. Although a few amoA OTUs were present in several geothermal regions, most were specific to a single region. In addition, cluster A amoA genes formed geographic groups, while cluster B sequences did not group geographically. With the exception of only one hot spring, principal-component analysis and UPGMA (unweighted-pair group method using average linkages) based on the UniFrac metric derived from cluster A grouped the springs by location, regardless of temperature or bulk water pH, suggesting that geography may play a role in structuring communities of putative ammonia-oxidizing archaea (AOA). The amoA genes were distinct from those of low-temperature environments; in particular, pair-wise comparisons between hot spring amoA genes and those from sympatric soils showed less than 85% sequence identity, underscoring the distinctness of hot spring archaeal communities from those of the surrounding soil system. Reverse transcription-PCR showed that amoA genes were

  11. Global Occurrence of Archaeal amoA Genes in Terrestrial Hot Springs▿

    Science.gov (United States)

    Zhang, Chuanlun L.; Ye, Qi; Huang, Zhiyong; Li, WenJun; Chen, Jinquan; Song, Zhaoqi; Zhao, Weidong; Bagwell, Christopher; Inskeep, William P.; Ross, Christian; Gao, Lei; Wiegel, Juergen; Romanek, Christopher S.; Shock, Everett L.; Hedlund, Brian P.

    2008-01-01

    Despite the ubiquity of ammonium in geothermal environments and the thermodynamic favorability of aerobic ammonia oxidation, thermophilic ammonia-oxidizing microorganisms belonging to the crenarchaeota kingdom have only recently been described. In this study, we analyzed microbial mats and surface sediments from 21 hot spring samples (pH 3.4 to 9.0; temperature, 41 to 86°C) from the United States, China, and Russia and obtained 846 putative archaeal ammonia monooxygenase large-subunit (amoA) gene and transcript sequences, representing a total of 41 amoA operational taxonomic units (OTUs) at 2% identity. The amoA gene sequences were highly diverse, yet they clustered within two major clades of archaeal amoA sequences known from water columns, sediments, and soils: clusters A and B. Eighty-four percent (711/846) of the sequences belonged to cluster A, which is typically found in water columns and sediments, whereas 16% (135/846) belonged to cluster B, which is typically found in soils and sediments. Although a few amoA OTUs were present in several geothermal regions, most were specific to a single region. In addition, cluster A amoA genes formed geographic groups, while cluster B sequences did not group geographically. With the exception of only one hot spring, principal-component analysis and UPGMA (unweighted-pair group method using average linkages) based on the UniFrac metric derived from cluster A grouped the springs by location, regardless of temperature or bulk water pH, suggesting that geography may play a role in structuring communities of putative ammonia-oxidizing archaea (AOA). The amoA genes were distinct from those of low-temperature environments; in particular, pair-wise comparisons between hot spring amoA genes and those from sympatric soils showed less than 85% sequence identity, underscoring the distinctness of hot spring archaeal communities from those of the surrounding soil system. Reverse transcription-PCR showed that amoA genes were

  12. Perceived social support and the psychological well-being of AIDS orphans in urban Kenya.

    Science.gov (United States)

    Okawa, Sumiyo; Yasuoka, Junko; Ishikawa, Naoko; Poudel, Krishna C; Ragi, Allan; Jimba, Masamine

    2011-09-01

    Parental deaths due to AIDS seriously affect the psychological well-being of children. Social support may provide an effective resource in the care of vulnerable children in resource-limited settings. However, few studies have examined the relationships between social support and psychological well-being among AIDS orphans. This cross-sectional study was conducted to explore associations between perceived social support (PSS) and the psychological well-being of AIDS orphans, and to identify socio-demographic factors that are associated with PSS. Data were collected from 398 pairs of AIDS orphans (aged 10-18 years) and their caregivers in Nairobi, Kenya. The participants provided information on their socio-demographic characteristics, the children's PSS, and the children's psychological status (based on measures of depressive symptoms and self-esteem). Of the 398 pairs, 327 were included in the analysis. PSS scores of AIDS orphans showed significant correlations with depressive symptoms (ρ =-0.31, psiblings (β=3.044, p=0.016), were also associated with higher PSS scores. In particular, HIV-infected children (n=37) had higher scores of PSS from a special person (β=2.208, p=0.004), and children living with biological siblings (n=269) also had higher scores of PSS from both a special person (β=1.411, p=0.029) and friends (β=1.276, p=0.039). In conclusion, this study showed that PSS is positively associated with the psychological well-being of AIDS orphans. Siblings and special persons can be effective sources of social support for AIDS orphans, which help to promote their psychological well-being.

  13. Do payers value rarity? : An analysis of the relationship between disease rarity and orphan drug prices in Europe

    NARCIS (Netherlands)

    Medic, Goran; Korchagina, Daria; Young, Katherine Eve; Toumi, Mondher; Postma, Maarten Jacobus; Wille, Micheline; Hemels, Michiel

    2017-01-01

    Background and Objective: Orphan drugs have been a highlight of discussions due to their higher prices than non-orphan drugs. There is currently no European consensus on the method of value assessment for orphan drugs. This study assessed the relationship between the prevalence of rare diseases and

  14. Psychosocial support and parents' social life determine the self-esteem of orphan children.

    Science.gov (United States)

    Erango, Markos Abiso; Ayka, Zikie Ataro

    2015-01-01

    Parental death affects the life of children in many ways, one of which is self-esteem problems. Providing psychosocial support and equipping orphans play a vital role in their lifes. A cross-sectional study was conducted on 7-18-year-old orphans at 17 local districts of Gamo Gofa Zone, Southern Regional State of Ethiopia. From a total of 48,270 orphans in these areas, 4,368 were selected using stratified simple random sampling technique. Data were collected with a designed questionnaire based on the Rosenberg's rating scale to measure their self-esteem levels. Self-esteem with a score less than or equal to an average score was considered to be low self-esteem in the analysis. Binary logistic regression model was used to analyze the data using the SPSS software. The results of the study revealed that the probability of orphans suffering from low self-esteem was 0.59. Several risk factors were found to be significant at the level of 5%. Psychosocial support (good guidance, counseling and treatment, physical protection and amount of love shared, financial and material support, and fellowship with other children), parents living together before death, strong relationship between parents before death, high average monthly income, voluntary support, and consideration from the society are some of the factors that decrease the risk of being low in self-esteem. There are many orphans with low self-esteem in the study areas. The factors negatively affecting the self-esteem of orphans include the lack of psychosocial support, poor social life of parents, and death of parents due to AIDS. Society and parents should be aware of the consequences of these factors which can influence their children's future self-esteem.

  15. orphans in mediterranean antiquity and early christianity

    African Journals Online (AJOL)

    animalium 588a8).3 Yet we must immediately qualify these studies and statements by .... of Anna in Luke 2:3637, who was married for just seven years, yet was still living as a ... has unlimited power, whereas the orphan has none. In what ...

  16. Thermal Adaptation of the Archaeal and Bacterial Lipid Membranes

    Science.gov (United States)

    Koga, Yosuke

    2012-01-01

    The physiological characteristics that distinguish archaeal and bacterial lipids, as well as those that define thermophilic lipids, are discussed from three points of view that (1) the role of the chemical stability of lipids in the heat tolerance of thermophilic organisms: (2) the relevance of the increase in the proportion of certain lipids as the growth temperature increases: (3) the lipid bilayer membrane properties that enable membranes to function at high temperatures. It is concluded that no single, chemically stable lipid by itself was responsible for the adaptation of surviving at high temperatures. Lipid membranes that function effectively require the two properties of a high permeability barrier and a liquid crystalline state. Archaeal membranes realize these two properties throughout the whole biological temperature range by means of their isoprenoid chains. Bacterial membranes meet these requirements only at or just above the phase-transition temperature, and therefore their fatty acid composition must be elaborately regulated. A recent hypothesis sketched a scenario of the evolution of lipids in which the “lipid divide” emerged concomitantly with the differentiation of archaea and bacteria. The two modes of thermal adaptation were established concurrently with the “lipid divide.” PMID:22927779

  17. Thermal Adaptation of the Archaeal and Bacterial Lipid Membranes

    Directory of Open Access Journals (Sweden)

    Yosuke Koga

    2012-01-01

    Full Text Available The physiological characteristics that distinguish archaeal and bacterial lipids, as well as those that define thermophilic lipids, are discussed from three points of view that (1 the role of the chemical stability of lipids in the heat tolerance of thermophilic organisms: (2 the relevance of the increase in the proportion of certain lipids as the growth temperature increases: (3 the lipid bilayer membrane properties that enable membranes to function at high temperatures. It is concluded that no single, chemically stable lipid by itself was responsible for the adaptation of surviving at high temperatures. Lipid membranes that function effectively require the two properties of a high permeability barrier and a liquid crystalline state. Archaeal membranes realize these two properties throughout the whole biological temperature range by means of their isoprenoid chains. Bacterial membranes meet these requirements only at or just above the phase-transition temperature, and therefore their fatty acid composition must be elaborately regulated. A recent hypothesis sketched a scenario of the evolution of lipids in which the “lipid divide” emerged concomitantly with the differentiation of archaea and bacteria. The two modes of thermal adaptation were established concurrently with the “lipid divide.”

  18. Cooperative RNP assembly: Complementary rescue of structural defects by protein and RNA subunits of archaeal RNase P

    Science.gov (United States)

    Chen, Wen-Yi; Xu, Yiren; Cho, I-Ming; Oruganti, Sri Vidya; Foster, Mark P.; Gopalan, Venkat

    2011-01-01

    RNase P is a ribonucleoprotein (RNP) complex that utilizes a Mg2+-dependent RNA catalyst to cleave the 5′-leader of precursor tRNAs (pre-tRNAs) and generate mature tRNAs. The bacterial RNase P protein (RPP) aids RNase P RNA (RPR) catalysis by promoting substrate binding, Mg2+ coordination, and product release. Archaeal RNase P comprises an RPR and at least four RPPs, which have eukaryal homologs and function as two binary complexes (POP5•RPP30 and RPP21•RPP29). In this study, we employed a previously characterized substrate-enzyme conjugate [pre-tRNATyr-Methanocaldococcus jannaschii (Mja) RPR] to investigate the functional role of a universally conserved uridine in a bulge-helix structure in archaeal RPRs. Deletion of this bulged uridine resulted in an 80-fold decrease in the self-cleavage rate of pre-tRNATyr-MjaΔU RPR compared to the wildtype, and this defect was partially ameliorated upon addition of either RPP pair. The catalytic defect in the archaeal mutant RPR mirrors that reported in a bacterial RPR and highlights a parallel in their active sites. Furthermore, an N-terminal deletion mutant of Pyrococcus furiosus (Pfu) RPP29 that is defective in assembling with its binary partner RPP21, as assessed by isothermal titration calorimetry and NMR spectroscopy, is functional when reconstituted with the cognate Pfu RPR. Collectively, these results indicate that archaeal RPPs are able to compensate for structural defects in their cognate RPR and vice-versa, and provide striking examples of the cooperative subunit interactions critical for driving archaeal RNase P towards its functional conformation. (236 words) PMID:21683084

  19. Epidemiology of health and vulnerability among children orphaned and made vulnerable by HIV/AIDS in sub-Saharan Africa.

    Science.gov (United States)

    Andrews, Gail; Skinner, Donald; Zuma, Khangelani

    2006-04-01

    The HIV/AIDS epidemic in sub-Saharan Africa has already orphaned a generation of children, and it is projected that by 2010, 18 million African children under the age of 18 are likely to be orphans from this single cause (UNICEF, 2005, The state of the Worlds Children: Childhood under threat. New York: UNICEF). Results from a Kellogg funded OVC project (Skinner et al., 2004, Definition of orphaned and vulnerable children. Cape Town: HSRC) supported the construct that the loss of either or both parents would indicate a situation of likely vulnerability of children. A key problem in the literature on the impact of orphanhood on the well-being of children, families and communities, is that the focus of assertions and predictions is often on the negative impact on 'AIDS orphans', or households. There are hardly any studies that compare the experiences of orphans with non-orphans. This paper thus attempts to fill that gap. It uses epidemiological data to explore the epidemiology of health and vulnerability of children within the context of AIDS in sub-Saharan Africa. Because of data limitations, only the following aspects are examined: (i) orphan status; (ii) household structure (in particular, grandparent headedness and female-headedness); (iii) illness of parents; (iv) poverty; and (v) access to services, especially schooling, health, social services. While recognizing the limitations of the analysis, data presented in this paper indicates that orphans in sub-Saharan Africa are more vulnerable than non-orphans. The authors conclude with some suggestions for policy makers and programme implementers, highlighting the importance of focusing on interventions that will have maximum impact on the health and well-being of children.

  20. High GC content causes orphan proteins to be intrinsically disordered.

    Directory of Open Access Journals (Sweden)

    Walter Basile

    2017-03-01

    Full Text Available De novo creation of protein coding genes involves the formation of short ORFs from noncoding regions; some of these ORFs might then become fixed in the population. These orphan proteins need to, at the bare minimum, not cause serious harm to the organism, meaning that they should for instance not aggregate. Therefore, although the creation of short ORFs could be truly random, the fixation should be subjected to some selective pressure. The selective forces acting on orphan proteins have been elusive, and contradictory results have been reported. In Drosophila young proteins are more disordered than ancient ones, while the opposite trend is present in yeast. To the best of our knowledge no valid explanation for this difference has been proposed. To solve this riddle we studied structural properties and age of proteins in 187 eukaryotic organisms. We find that, with the exception of length, there are only small differences in the properties between proteins of different ages. However, when we take the GC content into account we noted that it could explain the opposite trends observed for orphans in yeast (low GC and Drosophila (high GC. GC content is correlated with codons coding for disorder promoting amino acids. This leads us to propose that intrinsic disorder is not a strong determining factor for fixation of orphan proteins. Instead these proteins largely resemble random proteins given a particular GC level. During evolution the properties of a protein change faster than the GC level causing the relationship between disorder and GC to gradually weaken.

  1. Orphan Products: Hope for People with Rare Diseases

    Science.gov (United States)

    ... drug and biologics manufacturers, including tax credits for costs of clinical research, government grant funding, assistance for clinical research, and a seven-year period of exclusive marketing given to the first sponsor of an orphan- ...

  2. Education and nutritional status of orphans and children of HIV-infected parents in Kenya.

    Science.gov (United States)

    Mishra, Vinod; Arnold, Fred; Otieno, Fredrick; Cross, Anne; Hong, Rathavuth

    2007-10-01

    We examined whether orphaned and fostered children and children of HIV-infected parents are disadvantaged in schooling, nutrition, and health care. We analyzed data on 2,756 children aged 0-4 years and 4,172 children aged 6-14 years included in the 2003 Kenya Demographic and Health Survey, with linked anonymous HIV testing, using multivariate logistic regression. Results indicate that orphans, fostered children, and children of HIV-infected parents are significantly less likely to attend school than non-orphaned/non-fostered children of HIV-negative parents. Children of HIV-infected parents are more likely to be underweight and wasted, and less likely to receive medical care for ARI and diarrhea. Children of HIV-negative single mothers are also disadvantaged on most indicators. The findings highlight the need to expand child welfare programs to include not only orphans but also fostered children, children of single mothers, and children of HIV-infected parents, who tend to be equally, if not more, disadvantaged.

  3. What is known about the cost-effectiveness of orphan drugs? Evidence from cost-utility analyses.

    Science.gov (United States)

    Picavet, E; Cassiman, D; Simoens, S

    2015-06-01

    In times of financial and economic hardship, governments are looking to contain pharmaceutical expenditure by focusing on cost-effective drugs. Because of their high prices and difficulties in demonstrating effectiveness in small patient populations, orphan drugs are often perceived as not able to meet traditional reimbursement threshold value for money. The aim of this study was to provide an overview of the available evidence on the cost-effectiveness of orphan drugs. All orphan drugs listed as authorized on the website of the European Medicines Agency on 21 November 2013 were included in the analysis. Cost-utility analyses (CUAs) were identified by searching the Tufts Medical Center Cost-Effectiveness Analysis Registry and Embase. For each CUA, a number of variables were collected. The search identified 23 articles on the Tufts registry and 167 articles on Embase. The final analysis included 45 CUAs and 61 incremental cost-utility ratios (ICURs) for 19 orphan drugs. Of all ICURS, 16·3% were related to dominant drugs (i.e. more effective and less expensive than the comparator), 70·5% were related to drugs that are more effective, but at a higher cost, and 13·1% were related to dominated drugs (i.e. less effective and more expensive than the comparator). The median overall ICUR was €40 242 per quality-adjusted life year (QALY) with a minimum ICUR of €6311/QALY and a maximum ICUR of €974,917/QALY. This study demonstrates that orphan drugs can meet traditional reimbursement thresholds. Considering a threshold of £30,000/QALY, in this study, ten (52·6%) of a total of 19 orphan drugs for which data were available meet the threshold. As much as fifteen orphan drugs (78·9%) are eligible for reimbursement if a threshold of €80,000/QALY is considered. © 2015 John Wiley & Sons Ltd.

  4. Control of orphan sources. Import to and transport through Slovenia

    International Nuclear Information System (INIS)

    Cesarek, J.; Vokal Nemec, B.

    2007-01-01

    Orphan sources are radioactive sources which are not under regulatory control, either because they have never been under regulatory control, or because they have been abandoned, lost, misplaced, stolen or transferred without proper authorisation. The issue of orphan sources is not a new one but the situation has been highlighted more and more in the last ten years. One of the most important international milestones in this regard was the conference in Dijon, France in 1998. The orphan sources have become an international problem due to steady increase in international trade which made impossible to control every transfer of goods between countries. Shipments of metal scrap, either national or international, could comprise orphan sources which had come into metal stream. The consequences of such events vary greatly: from contaminated metal just above exemption levels to a melting of volatile radionuclides of significant activity which may cause enormous remediation costs. In addition, the phenomenon of deliberate abuse of nuclear material and radioactive material or previous accidents with found orphan sources worldwide and fatalities have made this issue even more provoking. In Slovenia, no such drastic events have occurred so far. Since 1991 there have been a few meltings of cobalt-60 sources with only economic impact. On several occasions, Italy - the country with strict import control - has detected elevated radiation and denied shipments of scrap metal. They had originated either from Slovenia or from other countries, mostly from former Yugoslav republics. The Slovenian experience shows that majority of cases is related to import of scrap metal in Slovenia or to transit of such material through Slovenia. These orphan sources have originated from past industrial activities or have been under no or weak regulatory control in their countries of origin. In order to prevent inadvertent movement and illicit trafficking of nuclear material and radioactive sources some

  5. Role of traditional healers in psychosocial support in caring for the orphans: A case of Dar-es Salaam City, Tanzania

    Directory of Open Access Journals (Sweden)

    Massila Mariam

    2005-07-01

    Full Text Available Abstract Orphans are an increasing problem in developing countries particularly in Africa; due to the HIV/AIDS pandemic; and needs collective effort in intervention processes by including all stakeholders right from the grass roots level. This paper attempts to present the role of traditional healers in psychosocial support for orphan children in Dar-es-Salaam City with special focus on those whose parents have died because of HIV/AIDS. Six traditional healers who were involved in taking care of orphans were visited at their "vilinge" (traditional clinics. In total they had 72 orphans, 31 being boys and 41 being girls with age range from 3 years to 19. It was learned that traditional healers, besides providing remedies for illnesses/diseases of orphans, they also provided other basic needs. Further, they even provided psychosocial support allowing children to cope with orphan hood life with ease. Traditional healers are living within communities at the grass roots level; and appear unnoticed hidden forces, which are involved in taking care of orphans. This role of traditional healers in taking care of orphans needs to be recognised and even scaling it up by empowering them both in financial terms and training in basic skills of psychosocial techniques in how to handle orphans, in order to reduce discrimination and stigmatisation in the communities where they live.

  6. Role of traditional healers in psychosocial support in caring for the orphans: a case of Dar-es Salaam City, Tanzania.

    Science.gov (United States)

    Kayombo, Edmund J; Mbwambo, Zakaria H; Massila, Mariam

    2005-07-29

    Orphans are an increasing problem in developing countries particularly in Africa; due to the HIV/AIDS pandemic; and needs collective effort in intervention processes by including all stakeholders right from the grass roots level. This paper attempts to present the role of traditional healers in psychosocial support for orphan children in Dar-es-Salaam City with special focus on those whose parents have died because of HIV/AIDS. Six traditional healers who were involved in taking care of orphans were visited at their "vilinge" (traditional clinics). In total they had 72 orphans, 31 being boys and 41 being girls with age range from 3 years to 19. It was learned that traditional healers, besides providing remedies for illnesses/diseases of orphans, they also provided other basic needs. Further, they even provided psychosocial support allowing children to cope with orphan hood life with ease. Traditional healers are living within communities at the grass roots level; and appear unnoticed hidden forces, which are involved in taking care of orphans. This role of traditional healers in taking care of orphans needs to be recognised and even scaling it up by empowering them both in financial terms and training in basic skills of psychosocial techniques in how to handle orphans, in order to reduce discrimination and stigmatisation in the communities where they live.

  7. Orphan Drug Regulation: A missed opportunity for children and adolescents with cancer.

    Science.gov (United States)

    Vassal, Gilles; Kearns, Pam; Blanc, Patricia; Scobie, Nicole; Heenen, Delphine; Pearson, Andy

    2017-10-01

    Oncology represents a major sector in the field of orphan drug development in Europe. The objective was to evaluate whether children and adolescents with cancer benefited from the Orphan Drug Regulation. Data on orphan drug designations (ODDs) and registered orphan drugs from 8th August 2000 to 10th September 2016 were collected from the Community Register of medicinal products for human use. Assessment history, product information and existence of paediatric investigation plans were searched and retrieved from the European Medicine Agency website. Over 16 years, 272 of 657 oncology ODDs (41%) concerned a malignant condition occurring both in adults and children. The five most common were acute myeloid leukaemia, high-grade glioma, acute lymphoblastic leukaemia, graft-versus-host disease and soft-tissue sarcomas. 74% of 31 marketing authorisations (MAs) for an indication both in adults and children (26 medicines) had no information for paediatric use in their Summary of Product Characteristics (SmPC) at the time of the first MA. Furthermore, 68% still have no paediatric information in their most recently updated SmPC, at a median of 7 years after. Only 15 ODDs (2%) pertained to a malignancy occurring specifically in children and only two drugs received an MA: Unituxin for high-risk neuroblastoma and Votubia for sub-ependymal giant-cell astrocytoma. The Orphan Drug Regulation failed to promote the development of innovative therapies for malignancies occurring in children. Major delays and waivers occurred through the application of the Paediatric Medicines Regulation. The European regulatory environment needs to be improved to accelerate innovation for children and adolescents dying of cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Affordability Challenges to Value-Based Pricing: Mass Diseases, Orphan Diseases, and Cures.

    Science.gov (United States)

    Danzon, Patricia M

    2018-03-01

    To analyze how value-based pricing (VBP), which grounds the price paid for pharmaceuticals in their value, can manage "affordability" challenges, defined as drugs that meet cost-effectiveness thresholds but are "unaffordable" within the short-run budget. Three specific contexts are examined, drawing on recent experience. First, an effective new treatment for a chronic, progressive disease, such as hepatitis C, creates a budget spike that is transitory because initial prevalence is high, relative to current incidence. Second, "cures" that potentially provide lifetime benefits may claim abnormally high VBP prices, with high immediate budget impact potentially/partially offset by deferred cost savings. Third, although orphan drugs in principle target rare diseases, in aggregate they pose affordability concerns because of the growing number of orphan indications and increasingly high prices. For mass diseases, the transitory budget impact of treating the accumulated patient stock can be managed by stratified rollout that delays treatment of stable patients and prioritizes patients at high risk of deterioration. Delay spreads the budget impact and permits potential savings from launch of competing treatments. For cures, installment payments contingent on outcomes could align payment flows and appropriately shift risk to producers. This approach, however, entails high administrative and incentive costs, especially if applied across multiple payers in the United States. For orphan drugs, the available evidence on research and development trends and returns argues against the need for a higher VBP threshold to incentivize research and development in orphan drugs, given existing statutory benefits under orphan drug legislation. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  9. The role of globalization in drug development and access to orphan drugs: orphan drug legislation in the US/EU and in Latin America.

    Science.gov (United States)

    Arnold, Renée J G; Bighash, Lida; Bryón Nieto, Alejandro; Tannus Branco de Araújo, Gabriela; Gay-Molina, Juan Gabriel; Augustovski, Federico

    2015-01-01

    Compared to a decade ago, nearly three times as many drugs for rare diseases are slated for development. This article addresses the market access issues associated with orphan drug status in Europe and the United States in contrast to the legislation in five Latin American (LA) countries that have made strides in this regard--Mexico, Brazil, Colombia, Chile and Argentina. Based on the success of orphan drug legislation in the EU and US, LA countries should strive to adopt similar strategies with regard to rare diseases and drug development. With the implementation of new targeted regulations, reimbursement strategies, and drug approvals, accessibility to treatment will be improved for people afflicted with rare diseases in these developing countries.

  10. Characterizing the metatranscriptomic profile of archaeal metabolic genes at deep-sea hydrothermal vents in the Mid-Cayman Rise

    Science.gov (United States)

    Galambos, D.; Reveillaud, J. C.; Anderson, R.; Huber, J. A.

    2017-12-01

    Deep-sea hydrothermal vent systems host a wide diversity of bacteria, archaea and viruses. Although the geochemical conditions at these vents are well-documented, the relative metabolic activity of microbial lineages, especially among archaea, remains poorly characterized. The deep, slow-spreading Mid-Cayman Rise, which hosts the mafic-influenced Piccard and ultramafic-influenced Von Damm vent fields, allows for the comparison of vent sites with different geochemical characteristics. Previous metagenomic work indicated that despite the distinct geochemistry at Von Damm and Piccard, the functional profile of microbial communities between the two sites was similar. We examined relative metabolic gene activity using a metatranscriptomic analysis and observed functional similarity between Von Damm and Piccard, which is consistent with previous results. Notably, the relative expression of the methyl-coenzyme M reductase (mcr) gene was elevated in both vent fields. Additionally, we analyzed the ratio of RNA expression to DNA abundance of fifteen archaeal metagenome-assembled genomes (MAGs) across the two fields. Previous work showed higher archaeal diversity at Von Damm; our results indicate relatively even expression among archaeal lineages at Von Damm. In contrast, we observed lower archaeal diversity at Piccard, but individual archaeal lineages were very highly expressed; Thermoprotei showed elevated transcriptional activity, which is consistent with higher temperatures and sulfur levels at Piccard. At both Von Damm and Piccard, specific Methanococcus lineages were more highly expressed than others. Future analyses will more closely examine metabolic genes in these Methanococcus MAGs to determine why some lineages are more active at a vent field than others. We will conduct further statistical analyses to determine whether significant differences exist between Von Damm and Piccard and whether there are correlations between geochemical metadata and metabolic gene or

  11. Orphans in the Dead Sea Scrolls

    African Journals Online (AJOL)

    2016-08-12

    Aug 12, 2016 ... ISSN: (Online) 2072-8050, (Print) 0259-9422 ... Orphans also feature in some non-biblical compositions of the .... (ntk ἰt n nmḥ hἰ n ḫᴈrt sn n wḏᶜt šndyt nt ἰwty mwt.f) (P.Berlin .... Collins (2010:7) defines 'sect' in the following ...... 2014, Social and economic life in second temple Judea, Westminster John.

  12. Resource needs to support orphans and vulnerable children in sub-Saharan Africa.

    Science.gov (United States)

    Stover, John; Bollinger, Lori; Walker, Neff; Monasch, Roland

    2007-01-01

    In sub-Saharan Africa, 43 million children under the age of 18 have lost one or both parents to AIDS, conflict or other causes. This large number strains systems by which families and communities have traditionally provided care for orphans. Support for some orphans is being provided by a variety of government, community and non-governmental organizations but this assistance reaches only a small percentage of those who need it. This paper estimates the funding required for necessary support to those most in need. We estimate that US$1-4 billion will be required annually by 2010, depending on whether support is provided to all orphans living below the poverty line or just those in most need. This is at least four times current funding and should be a priority topic for donor and national government resource allocation decisions this year.

  13. Archaeal viruses of the sulfolobales

    DEFF Research Database (Denmark)

    Erdmann, Susanne; Garrett, Roger Antony

    2015-01-01

    in CRISPR loci of Sulfolobus species from a second coinfecting conjugative plasmid or virus (Erdmann and Garrett, Mol Microbiol 85:1044-1056, 2012; Erdmann et al. Mol Microbiol 91:900-917, 2014). Here we describe, firstly, the isolation of archaeal virus mixtures from terrestrial hot springs...... with an environmental virus mixture isolated from Yellowstone National Park (Erdmann and Garrett, Mol Microbiol 85:1044-1056, 2012). Experimental studies of isolated genetic elements from this mixture revealed that SMV1 (S ulfolobus Monocauda Virus 1), a tailed spindle-shaped virus, can induce spacer acquisition...... and the techniques used both to infect laboratory strains with these virus mixtures and to obtain purified virus particles. Secondly, we present the experimental conditions required for activating SMV1-induced spacer acquisition in two different Sulfolobus species....

  14. Extended family caring for children orphaned by AIDS: balancing essential work and caregiving in a high HIV prevalence nations.

    Science.gov (United States)

    Heymann, J; Earle, A; Rajaraman, D; Miller, C; Bogen, K

    2007-03-01

    While over 90 per cent of the 15 million children who have been orphaned by HIV/AIDS are cared for by family members, there is little information about whether adults can meet orphans' essential caregiving needs while working to economically survive. Using a survey we conducted in Botswana of 1033 working adults, we analyse the experience of adults who are caring for orphans. Over one-third of working adults were caring for orphans and many with few financial resources: 82% were living on household incomes below US$10 purchasing power parity adjusted per person per day. Because of their caregiving responsibilities, they were less able to supplement income with overtime, weekend, evening, or night work. At the same time caregiving responsibilities meant orphan caregivers spent fewer hours caring for their own children and other family members. Nearly half of orphan caregivers had difficulties meeting their children's needs, and nearly 75% weren't able to meet with children's teachers. Pay loss at work compounded the problems: One-quarter of orphan caregivers reported having to take unpaid leave to meet sick childcare needs and nearly half reported being absent from work for children's routine health care. This paper makes clear that if families are to provide adequate care for orphans while economically surviving there needs to be increases in social supports and improvements in working conditions.

  15. A proposal for prevention of acute radiation hazard and social panic regarding orphan sources in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Takahash, T. [Research Reactor Institute, Kyoto Univ., Osaka (Japan); Kai, M. [Oita Univ., of Nursing and Health Sciences, Oita (Japan); Yamazaki, K. [Chiyoda Technol Corporation, Tokyo (Japan); Gomi, K. [Japan Radioisotope Association, Tokyo (Japan); Nakazato, K. [School of Medicine, Keio univ., Tokyo (Japan); Iida, T. [Nagoya Univ., Nagoya (Japan)

    2002-07-01

    To respond to an increase of social problems concerning orphan sources in Japan, a working group was formed in the Japan Health Physics Society. In this working group, we investigated how to prevent acute radiation hazard or social panic regarding orphan sources in scrap metal and detection system for orphan sources brought into scrap yards before recycle. For detection system in a scrap yard we conducted an experiment on detectability of monitoring instrument using a radiation source mixed in scrap metal on a truck. The result showed that it was not easy to detect even a high-level source if it was shielded by scrap metal. We also estimated detection limits for radioactive materials in scrap metal by calculation that was validated with experimental data. We summarized present status about orphan sources in Japan and proposed a categorization of orphan sources according to dose rates to deal with unknown sources in a scrap yard. Our report includes some proposals to the government, industry and academic world for preventing acute radiation hazard and social panic.

  16. A proposal for prevention of acute radiation hazard and social panic regarding orphan sources in Japan

    International Nuclear Information System (INIS)

    Takahash, T.; Kai, M.; Yamazaki, K.; Gomi, K.; Nakazato, K.; Iida, T.

    2002-01-01

    To respond to an increase of social problems concerning orphan sources in Japan, a working group was formed in the Japan Health Physics Society. In this working group, we investigated how to prevent acute radiation hazard or social panic regarding orphan sources in scrap metal and detection system for orphan sources brought into scrap yards before recycle. For detection system in a scrap yard we conducted an experiment on detectability of monitoring instrument using a radiation source mixed in scrap metal on a truck. The result showed that it was not easy to detect even a high-level source if it was shielded by scrap metal. We also estimated detection limits for radioactive materials in scrap metal by calculation that was validated with experimental data. We summarized present status about orphan sources in Japan and proposed a categorization of orphan sources according to dose rates to deal with unknown sources in a scrap yard. Our report includes some proposals to the government, industry and academic world for preventing acute radiation hazard and social panic

  17. A review of international coverage and pricing strategies for personalized medicine and orphan drugs.

    Science.gov (United States)

    Degtiar, Irina

    2017-12-01

    Personalized medicine and orphan drugs share many characteristics-both target small patient populations, have uncertainties regarding efficacy and safety at payer submission, and frequently have high prices. Given personalized medicine's rising importance, this review summarizes international coverage and pricing strategies for personalized medicine and orphan drugs as well as their impact on therapy development incentives, payer budgets, and therapy access and utilization. PubMed, Health Policy Reference Center, EconLit, Google Scholar, and references were searched through February 2017 for articles presenting primary data. Sixty-nine articles summarizing 42 countries' strategies were included. Therapy evaluation criteria varied between countries, as did patient cost-share. Payers primarily valued clinical effectiveness; cost was only considered by some. These differences result in inequities in orphan drug access, particularly in smaller and lower-income countries. The uncertain reimbursement process hinders diagnostic testing. Payer surveys identified lack of comparative effectiveness evidence as a chief complaint, while manufacturers sought more clarity on payer evidence requirements. Despite lack of strong evidence, orphan drugs largely receive positive coverage decisions, while personalized medicine diagnostics do not. As more personalized medicine and orphan drugs enter the market, registries can provide better quality evidence on their efficacy and safety. Payers need systematic assessment strategies that are communicated with more transparency. Further studies are necessary to compare the implications of different payer approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Systematic review on the evaluation criteria of orphan medicines in Central and Eastern European countries.

    Science.gov (United States)

    Zelei, Tamás; Molnár, Mária J; Szegedi, Márta; Kaló, Zoltán

    2016-06-04

    In case of orphan drugs applicability of the standard health technology assessment (HTA) process is limited due to scarcity of good clinical and health economic evidence. Financing these premium priced drugs is more controversial in the Central and Eastern European (CEE) region where the public funding resources are more restricted, and health economic justification should be an even more important aspect of policy decisions than in higher income European countries. To explore and summarize the recent scientific evidence on value drivers related to the health technology assessment of ODs with a special focus on the perspective of third party payers in CEE countries. The review aims to list all potentially relevant value drivers in the reimbursement process of orphan drugs. A systematic literature review was performed; PubMed and Scopus databases were systematically searched for relevant publications until April 2015. Extracted data were summarized along key HTA elements. From the 2664 identified publications, 87 contained relevant information on the evaluation criteria of orphan drugs, but only 5 had direct information from the CEE region. The presentation of good clinical evidence seems to play a key role especially since this should be the basis of cost-effectiveness analyses, which have more importance in resource-constrained economies. Due to external price referencing of pharmaceuticals, the relative budget impact of orphan drugs is expected to be higher in CEE than in Western European (WE) countries unless accessibility of patients remains more limited in poorer European regions. Equity principles based on disease prevalence and non-availability of alternative treatment options may increase the price premium, however, societies must have some control on prices and a rationale based on multiple criteria in reimbursement decisions. The evaluation of orphan medicines should include multiple criteria to appropriately measure the clinical added value of orphan

  19. Respons of archaeal communities in beach sediments to spilled oil and bioremediation.

    NARCIS (Netherlands)

    Roling, W.F.M.; Couo de Brito, I.R.; Swannell, R.P.J.; Head, I.M.

    2004-01-01

    While the contribution of Bacteria to bioremediation of oil-contaminated shorelines is well established, the response of Archaea to spilled oil and bioremediation treatments is unknown. The relationship between archaeal community structure and oil spill bioremediation was examined in laboratory

  20. Factors controlling the distribution of archaeal tetraethers in terrestrial hot springs.

    Science.gov (United States)

    Pearson, Ann; Pi, Yundan; Zhao, Weidong; Li, WenJun; Li, Yiliang; Inskeep, William; Perevalova, Anna; Romanek, Christopher; Li, Shuguang; Zhang, Chuanlun L

    2008-06-01

    Glycerol dialkyl glycerol tetraethers (GDGTs) found in hot springs reflect the abundance and community structure of Archaea in these extreme environments. The relationships between GDGTs, archaeal communities, and physical or geochemical variables are underexamined to date and when reported often result in conflicting interpretations. Here, we examined profiles of GDGTs from pure cultures of Crenarchaeota and from terrestrial geothermal springs representing a wide distribution of locations, including Yellowstone National Park (United States), the Great Basin of Nevada and California (United States), Kamchatka (Russia), Tengchong thermal field (China), and Thailand. These samples had temperatures of 36.5 to 87 degrees C and pH values of 3.0 to 9.2. GDGT abundances also were determined for three soil samples adjacent to some of the hot springs. Principal component analysis identified four factors that accounted for most of the variance among nine individual GDGTs, temperature, and pH. Significant correlations were observed between pH and the GDGTs crenarchaeol and GDGT-4 (four cyclopentane rings, m/z 1,294); pH correlated positively with crenarchaeol and inversely with GDGT-4. Weaker correlations were observed between temperature and the four factors. Three of the four GDGTs used in the marine TEX(86) paleotemperature index (GDGT-1 to -3, but not crenarchaeol isomer) were associated with a single factor. No correlation was observed for GDGT-0 (acyclic caldarchaeol): it is effectively its own variable. The biosynthetic mechanisms and exact archaeal community structures leading to these relationships remain unknown. However, the data in general show promise for the continued development of GDGT lipid-based physiochemical proxies for archaeal evolution and for paleo-ecology or paleoclimate studies.

  1. Factors Controlling the Distribution of Archaeal Tetraethers in Terrestrial Hot Springs▿

    Science.gov (United States)

    Pearson, Ann; Pi, Yundan; Zhao, Weidong; Li, WenJun; Li, Yiliang; Inskeep, William; Perevalova, Anna; Romanek, Christopher; Li, Shuguang; Zhang, Chuanlun L.

    2008-01-01

    Glycerol dialkyl glycerol tetraethers (GDGTs) found in hot springs reflect the abundance and community structure of Archaea in these extreme environments. The relationships between GDGTs, archaeal communities, and physical or geochemical variables are underexamined to date and when reported often result in conflicting interpretations. Here, we examined profiles of GDGTs from pure cultures of Crenarchaeota and from terrestrial geothermal springs representing a wide distribution of locations, including Yellowstone National Park (United States), the Great Basin of Nevada and California (United States), Kamchatka (Russia), Tengchong thermal field (China), and Thailand. These samples had temperatures of 36.5 to 87°C and pH values of 3.0 to 9.2. GDGT abundances also were determined for three soil samples adjacent to some of the hot springs. Principal component analysis identified four factors that accounted for most of the variance among nine individual GDGTs, temperature, and pH. Significant correlations were observed between pH and the GDGTs crenarchaeol and GDGT-4 (four cyclopentane rings, m/z 1,294); pH correlated positively with crenarchaeol and inversely with GDGT-4. Weaker correlations were observed between temperature and the four factors. Three of the four GDGTs used in the marine TEX86 paleotemperature index (GDGT-1 to -3, but not crenarchaeol isomer) were associated with a single factor. No correlation was observed for GDGT-0 (acyclic caldarchaeol): it is effectively its own variable. The biosynthetic mechanisms and exact archaeal community structures leading to these relationships remain unknown. However, the data in general show promise for the continued development of GDGT lipid-based physiochemical proxies for archaeal evolution and for paleo-ecology or paleoclimate studies. PMID:18390673

  2. Archaeal community changes in Lateglacial lake sediments: Evidence from ancient DNA

    Science.gov (United States)

    Ahmed, Engy; Parducci, Laura; Unneberg, Per; Ågren, Rasmus; Schenk, Frederik; Rattray, Jayne E.; Han, Lu; Muschitiello, Francesco; Pedersen, Mikkel W.; Smittenberg, Rienk H.; Yamoah, Kweku Afrifa; Slotte, Tanja; Wohlfarth, Barbara

    2018-02-01

    The Lateglacial/early Holocene sediments from the ancient lake at Hässeldala Port, southern Sweden provide an important archive for the environmental and climatic shifts at the end of the last ice age and the transition into the present Interglacial. The existing multi-proxy data set highlights the complex interplay of physical and ecological changes in response to climatic shifts and lake status changes. Yet, it remains unclear how microorganisms, such as Archaea, which do not leave microscopic features in the sedimentary record, were affected by these climatic shifts. Here we present the metagenomic data set of Hässeldala Port with a special focus on the abundance and biodiversity of Archaea. This allows reconstructing for the first time the temporal succession of major Archaea groups between 13.9 and 10.8 ka BP by using ancient environmental DNA metagenomics and fossil archaeal cell membrane lipids. We then evaluate to which extent these findings reflect physical changes of the lake system, due to changes in lake-water summer temperature and seasonal lake-ice cover. We show that variations in archaeal composition and diversity were related to a variety of factors (e.g., changes in lake water temperature, duration of lake ice cover, rapid sediment infilling), which influenced bottom water conditions and the sediment-water interface. Methanogenic Archaea dominated during the Allerød and Younger Dryas pollen zones, when the ancient lake was likely stratified and anoxic for large parts of the year. The increase in archaeal diversity at the Younger Dryas/Holocene transition is explained by sediment infilling and formation of a mire/peatbog.

  3. Novel archaeal plasmid pAH1 and its interactions with the lipothrixvirus AFV1

    DEFF Research Database (Denmark)

    Basta, Tamara; Smyth, John; Forterre, Patrick

    2009-01-01

    . Although nucleotide sequence comparisons revealed extensive intergenomic exchange during the evolution of archaeal conjugative plasmids, pAH1 was shown to be stably maintained suggesting that the host system is suitable for studying plasmid-virus interactions. AFV1 infection and propagation leads to a loss...... of the circular form of pAH1 and this effect correlates positively with the increase in the intracellular quantity of AFV1 DNA. We infer that the virus inhibits plasmid replication since no pAH1 degradation was observed. This mechanism of archaeal viral inhibition of plasmid propagation is not observed...... in bacteria where relevant bacteriophages either are dependent on a conjugative plasmid for successful infection or are excluded by a resident plasmid....

  4. Orphans and at-risk children in Haiti: vulnerabilities and human rights issues postearthquake.

    Science.gov (United States)

    Nicholas, Patrice K; George, Erin K; Raymond, Nadia; Lewis-OʼConnor, Annie; Victoria, Stephanie; Lucien, Sergeline; Peters-Lewis, Angelleen; Hickey, Nancy; Corless, Inge B; Tyer-Viola, Lynda; Davis, Sheila M; Barry, Donna; Marcelin, Naomie; Valcourt, Roodeline

    2012-01-01

    The vulnerability of children in Haiti has increased dramatically since the earthquake in January 2010. Prior to the earthquake, the prevalence of orphans and at-risk children was high but since the earthquake, more than 1 million people-with more than 380,000 children remaining displaced and living in over 1200 displacement sites. These existing conditions leave orphans and at-risk children vulnerable to exploitation, abuse, and increased risk of HIV/AIDS. This article will focus on the complex issues affecting orphans and at-risk children and the intersection with HIV/AIDS and human rights. Specific recommendations by United Nations Children's Fund are discussed. Nursing in Haiti must address the policy-related and population-specific approaches for the care of children living with or affected by HIV/AIDS.

  5. Archaeal Viruses Multiply: Temporal Screening in a Solar Saltern

    Directory of Open Access Journals (Sweden)

    Nina S. Atanasova

    2015-04-01

    Full Text Available Hypersaline environments around the world are dominated by archaea and their viruses. To date, very little is known about these viruses and their interaction with the host strains when compared to bacterial and eukaryotic viruses. We performed the first culture-dependent temporal screening of haloarchaeal viruses and their hosts in the saltern of Samut Sakhon, Thailand, during two subsequent years (2009, 2010. Altogether we obtained 36 haloarchaeal virus isolates and 36 archaeal strains, significantly increasing the number of known archaeal virus isolates. Interestingly, the morphological distribution of our temporal isolates (head-tailed, pleomorphic, and icosahedral membrane-containing viruses was similar to the outcome of our previous spatial survey supporting the observations of a global resemblance of halophilic microorganisms and their viruses. Myoviruses represented the most abundant virus morphotype with strikingly broad host ranges. The other viral morphotypes (siphoviruses, as well as pleomorphic and icosahedral internal membrane-containing viruses were more host-specific. We also identified a group of Halorubrum strains highly susceptible to numerous different viruses (up to 26. This high virus sensitivity, the abundance of broad host range viruses, and the maintenance of infectivity over a period of one year suggest constant interplay of halophilic microorganisms and their viruses within an extreme environment.

  6. Archaeal viruses multiply: temporal screening in a solar saltern.

    Science.gov (United States)

    Atanasova, Nina S; Demina, Tatiana A; Buivydas, Andrius; Bamford, Dennis H; Oksanen, Hanna M

    2015-04-10

    Hypersaline environments around the world are dominated by archaea and their viruses. To date, very little is known about these viruses and their interaction with the host strains when compared to bacterial and eukaryotic viruses. We performed the first culture-dependent temporal screening of haloarchaeal viruses and their hosts in the saltern of Samut Sakhon, Thailand, during two subsequent years (2009, 2010). Altogether we obtained 36 haloarchaeal virus isolates and 36 archaeal strains, significantly increasing the number of known archaeal virus isolates. Interestingly, the morphological distribution of our temporal isolates (head-tailed, pleomorphic, and icosahedral membrane-containing viruses) was similar to the outcome of our previous spatial survey supporting the observations of a global resemblance of halophilic microorganisms and their viruses. Myoviruses represented the most abundant virus morphotype with strikingly broad host ranges. The other viral morphotypes (siphoviruses, as well as pleomorphic and icosahedral internal membrane-containing viruses) were more host-specific. We also identified a group of Halorubrum strains highly susceptible to numerous different viruses (up to 26). This high virus sensitivity, the abundance of broad host range viruses, and the maintenance of infectivity over a period of one year suggest constant interplay of halophilic microorganisms and their viruses within an extreme environment.

  7. 78 FR 5828 - Agency Information Collection Activities: Petition To Classify Orphan as an Immediate Relative...

    Science.gov (United States)

    2013-01-28

    ...-0028] Agency Information Collection Activities: Petition To Classify Orphan as an Immediate Relative, Form I-600; Application for Advance Processing of Orphan Petition, Form I-600A; Listing of Adult Member... are encouraged and will be accepted until February 27, 2013. This process is conducted in accordance...

  8. Orphan crops can turn into winners | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2010-10-06

    Oct 6, 2010 ... It is not surprising that many of the orphan crops, in particular the protein-packed pulse ... diet in India, for example, accompanying almost every Indian meal. ... Canada's niche is high-quality pulses that we sell to the emerging ...

  9. From orphan virus to pathogen: the path to the clinical lab.

    Science.gov (United States)

    Li, Linlin; Delwart, Eric

    2011-10-01

    Viral metagenomics has recently yielded numerous previously uncharacterized viral genomes from human and animal samples. We review some of the metagenomics tools and strategies to determine which orphan viruses are likely pathogens. Disease association studies compare viral prevalence in patients with unexplained symptoms versus healthy individuals but require these case and control groups to be closely matched epidemiologically. The development of an antibody response in convalescent serum can temporarily link symptoms with a recent infection. Neutralizing antibody detection require often difficult cell culture virus amplification. Antibody binding assays require proper antigen synthesis and positive control sera to set assay thresholds. High levels of viral genetic diversity within orphan viral groups, frequent co-infections, low or rare pathogenicity, and chronic virus shedding, can all complicate disease association studies. The limited availability of matched cases and controls sample sets from different age groups and geographic origins is a major block for estimating the pathogenic potential of recently characterized orphan viruses. Current limitations on the practical use of deep sequencing for viral diagnostics are listed.

  10. Teachers’ Pastoral Role in Response to the Needs of Orphaned Learners

    Directory of Open Access Journals (Sweden)

    Teresa Auma Ogina

    2010-12-01

    Full Text Available This article discusses a study that explored the way teachers perceive and describe their roles in responding to the needs of orphaned learners. The participants in the study comprised three secondary and two primary school teachers. The data on the teachers’ experiences were collected through semi-structured interviews, and the findings revealed that, although some of the teachers attempted to fulfill some of the orphaned learners’ needs, most were unable to cope with the combined roles of teaching and learning and care giving. The study identified a lack of material, social, and emotional support for grieving learners. The findings indicate that there is a need for teacher development in terms of preparing teachers to provide pastoral care for orphaned learners. For the teachers’ efforts to be more fruitful, there is also an urgent need for supportive school leadership. In addition, the study highlights the need for counsellors and social workers to be appointed to work in collaboration with the teachers in providing for the needs of the learners.

  11. Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis.

    Science.gov (United States)

    Döring, Jan Henje; Lampert, Anette; Hoffmann, Georg F; Ries, Markus

    2016-01-01

    Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria. Within the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years). Orphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation.

  12. Orphan drugs assessment in the centralised procedure.

    Science.gov (United States)

    Nisticò, Giuseppe

    2011-01-01

    On the basis of the author's experience as member of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and in order to facilitate the access of new orphan drugs to the patients, some suggestions were given. Among these the following should be taken into account by the regulatory bodies: 1) conditional approval or approval under exceptional circumstances should be granted more frequently; 2) the opinion of international societies for rare diseases should be taken into greater account by the EMA Committees; 3) the guidelines requirements should be interpreted more flexibly; 4) in comparison to the fulfilment of primary and secondary endpoints, the improvement of the quality of life should justify the approval of a new orphan drug; 5) the rigidity of guideline requirements should not prevail over the unmet medical need for severe and lethal rare disorders; 6) the statistical values of clinical data to the limit of significance should not prevail over the opinion of patients' associations and international scientific societies; 7) the current legislation should be amended.

  13. National campaign for the search and recovery of Orphan radioactive sources

    International Nuclear Information System (INIS)

    Carboneras, Pedro; Ortiz, Maria T.; Correa, Cristina; Rueda, Carmen

    2008-01-01

    This paper aims to describe the main initial approaches of the campaign for the 'Recovery of Orphan Radioactive Sources' undertaken in Spain, in addition to the steps taken, the experience gained and the partial results obtained. The campaign began on 19th February 2007 and this paper reports the findings until 31st December 2007. The paper aims to share the experience gained with others who are considering or are already involved in similar campaigns and to enable opinions to be exchanged with those responsible for such campaigns in other countries. The campaign was initiated by the Spanish Ministry of Industry, Tourism and Trade with the expert assistance of the Nuclear Security Council. The initiative came about as a result of national legislation currently in force regarding the control of highly active and orphan radioactive source, which implements a European Directive. The campaign was commissioned to ENRESA (the Spanish National Company for Radioactive Waste Management) and the work, which began in 2007, will continue into 2008. The campaign aims to seek and recover the largest possible number of orphan radioactive sources (an Orphan radioactive source is understood to be one which is detected outside the standard control system and which, when detected, has an activity level higher than the exemption levels established in national and European regulations), and involves the collaboration of various different agents and organisations where such sources are or may be found. Finally, the paper provides details regarding the number and radiological characteristics of the sources which have already been recovered in Spain during the 2007 campaign. (author)

  14. Empowering caregivers of orphans and vulnerable children in ...

    African Journals Online (AJOL)

    A comparison of orphan data between 2010 and 2014 shows a slight ... The training included the use of mobile technology to report weekly ... health, psychosocial support, protection, education, and ... Data were collected on members' demographic, socio-economic status, ... mobile technology platform for data collection.

  15. Value-based reimbursement decisions for orphan drugs: a scoping review and decision framework.

    Science.gov (United States)

    Paulden, Mike; Stafinski, Tania; Menon, Devidas; McCabe, Christopher

    2015-03-01

    The rate of development of new orphan drugs continues to grow. As a result, reimbursing orphan drugs on an exceptional basis is increasingly difficult to sustain from a health system perspective. An understanding of the value that societies attach to providing orphan drugs at the expense of other health technologies is now recognised as an important input to policy debates. The aim of this work was to scope the social value arguments that have been advanced relating to the reimbursement of orphan drugs, and to locate these within a coherent decision-making framework to aid reimbursement decisions in the presence of limited healthcare resources. A scoping review of the peer reviewed and grey literature was undertaken, consisting of seven phases: (1) identifying the research question; (2) searching for relevant studies; (3) selecting studies; (4) charting, extracting and tabulating data; (5) analyzing data; (6) consulting relevant experts; and (7) presenting results. The points within decision processes where the identified value arguments would be incorporated were then located. This mapping was used to construct a framework characterising the distinct role of each value in informing decision making. The scoping review identified 19 candidate decision factors, most of which can be characterised as either value-bearing or 'opportunity cost'-determining, and also a number of value propositions and pertinent sources of preference information. We were able to synthesize these into a coherent decision-making framework. Our framework may be used to structure policy discussions and to aid transparency about the values underlying reimbursement decisions for orphan drugs. These values ought to be consistently applied to all technologies and populations affected by the decision.

  16. A review and update on orphan drugs for the treatment of noninfectious uveitis

    Science.gov (United States)

    You, Caiyun; Sahawneh, Haitham F; Ma, Lina; Kubaisi, Buraa; Schmidt, Alexander; Foster, C Stephen

    2017-01-01

    Introduction Uveitis, a leading cause of preventable blindness around the world, is a critically underserved disease in regard to the medications approved for use. Multiple immunomodulatory therapy (IMT) drugs are appropriate for uveitis therapy but are still off-label. These IMT agents, including antimetabolites, calcineurin inhibitors, alkylating agents, and biologic agents, have been designated as “orphan drugs” and are widely used for systemic autoimmune diseases or organ transplantation. Area covered The purpose of this paper is to comprehensively review and summarize the approved orphan drugs and biologics that are being used to treat systemic diseases and to discuss drugs that have not yet received approval as an “orphan drug for treating uveitis” by the US Food and Drug Administration (FDA). Our perspective IMT, as a steroid-sparing agent for uveitis patients, has shown promising clinical results. Refractory and recurrent uveitis requires combination IMT agents. IMT is continued for a period of 2 years while the patient is in remission before considering tapering medication. Our current goals include developing further assessments regarding the efficacy, optimal dose, and safety in efforts to achieve FDA approval for “on-label” use of current IMT agents and biologics more quickly and to facilitate insurance coverage and expand access to the products for this orphan disease. PMID:28203051

  17. Archaeal and Bacterial Communities Associated with the Surface Mucus of Caribbean Corals Differ in Their Degree of Host Specificity and Community Turnover Over Reefs.

    Science.gov (United States)

    Frade, Pedro R; Roll, Katharina; Bergauer, Kristin; Herndl, Gerhard J

    2016-01-01

    Comparative studies on the distribution of archaeal versus bacterial communities associated with the surface mucus layer of corals have rarely taken place. It has therefore remained enigmatic whether mucus-associated archaeal and bacterial communities exhibit a similar specificity towards coral hosts and whether they vary in the same fashion over spatial gradients and between reef locations. We used microbial community profiling (terminal-restriction fragment length polymorphism, T-RFLP) and clone library sequencing of the 16S rRNA gene to compare the diversity and community structure of dominant archaeal and bacterial communities associating with the mucus of three common reef-building coral species (Porites astreoides, Siderastrea siderea and Orbicella annularis) over different spatial scales on a Caribbean fringing reef. Sampling locations included three reef sites, three reef patches within each site and two depths. Reference sediment samples and ambient water were also taken for each of the 18 sampling locations resulting in a total of 239 samples. While only 41% of the bacterial operational taxonomic units (OTUs) characterized by T-RFLP were shared between mucus and the ambient water or sediment, for archaeal OTUs this percentage was 2-fold higher (78%). About half of the mucus-associated OTUs (44% and 58% of bacterial and archaeal OTUs, respectively) were shared between the three coral species. Our multivariate statistical analysis (ANOSIM, PERMANOVA and CCA) showed that while the bacterial community composition was determined by habitat (mucus, sediment or seawater), host coral species, location and spatial distance, the archaeal community composition was solely determined by the habitat. This study highlights that mucus-associated archaeal and bacterial communities differ in their degree of community turnover over reefs and in their host-specificity.

  18. Rwanda’s Orphans – Care and Integration During Uncertain Times

    Directory of Open Access Journals (Sweden)

    Manuela Elisabeth Kuehr

    2015-04-01

    Full Text Available Children and youth are considered cornerstones of development in post-conflict state-building practices. In the case of Rwanda, the government has engaged in an ambitious state-initiated deinstitutionalization project that anticipates the closure of all officially registered orphanages between 2012 and 2014. As a consequence, all orphans within institutional care will return to their extended families or be placed with foster parents to be given the opportunity to grow up within a Rwandan family environment. By investigating the lived realities of orphans before their departure from the orphanage, it becomes apparent that there is no “one size fits all” approach to systems of child care as historical and psychosocial dynamics play a crucial role.

  19. The impact of the Orphan Drug Act on drug discovery.

    Science.gov (United States)

    Haffner, Marlene E; Maher, Paul D

    2006-11-01

    For nearly a quarter of a century the FDA Office of Orphan Products Development has administered the US Orphan Drug Act, which assists in bringing a wide variety of drug and biological (drug) products to treat rare diseases to market. Enthusiasm for rare disease product development has been sustained, seen throughout a wide spectrum of product types and disease conditions, and has resulted in clinically meaningful medical advances. Development of programmes for rare disease treatment worldwide, coupled with the development of drugs for diseases affecting developing countries, attests to the strength of this legislation. The marketing of almost 300 products in the US for rare diseases also testifies to the depth and intensity of scientific endeavour in this area.

  20. Mechanism and function of the chaperonin from Methanococcus maripaludis: implications for archaeal protein homeostasis and energy production

    Energy Technology Data Exchange (ETDEWEB)

    frydman, judith

    2018-03-23

    Archaea offer a potentially cost effective and renewable source of energy. The methanogen M. maripaludis, a fast growing archaea that obtains energy by sequestering H2 and reducing CO2 to methane by the methanogenic pathway, is an attractive source for biofuel production. More recently, it has also been suggested that the methanogenesis pathway could be run in reverse, to produce H2 growing the organism in formate. A multi-level understanding of archaeal protein homeostasis, should be instrumental for improving the functionality and design of the enzyme pathways and complexes involved in energy production and storage. One additional importance consequence of a better understanding of archaeal protein homeostasis will be to increase their stress resistance, since their utilization for the efficient large-scale production of methane (and eventually also of H2) requires that the organisms are resistance to a range of growth conditions. This proposal was focused on understanding how archaea achieve protein folding and assembly and maintain protein homeostasis, which are essential for function and viability. We hypothesize that the homo-oligomeric ring shaped chaperonin from M. maripaludis, Mm-Cpn, is central to achaeal protein homeostasis and assists folding of a wide spectrum of metabolic, structural and regulatory archaeal proteins. Through a combination of biochemistry, systems biology, computational and structural biology, we have been testing this hypothesis through two complementary efforts: (i) identify the archaeal substrate repertoire of Mm-Cpn, and (ii) define mechanistic and structural principles of Mm-Cpn mediated protein folding.

  1. THE CONTRIBUTION OF SOCIAL ENTREPRENEURSHIP IN MEETING THE NEEDS OF ORPHANS IN THE MBERENGWA DISTRICT, ZIMBABWE

    Directory of Open Access Journals (Sweden)

    Katungu, Wisdom

    2016-08-01

    Full Text Available Since the turn of the millennium Zimbabwe has witnessed a raft of socio-economic and political challenges, exacerbated by the devastating effects of the HIV and Aids pandemic. This diminished the government’s ability to provide safety nets to vulnerable groups. The responsibility for orphan care has been shifted to the community, which has become the core focus of intervention initiatives by devising local-level coping mechanisms to deal with the orphan care crisis. The study explored the contribution of social entrepreneurship in meeting the needs of orphans in the Mberengwa district. The study concludes that the income-generating projects based on social entrepreneurship principles in Mberengwa play an important role in poverty alleviation and social protection, and particularly in meeting the needs of orphans. However, this cannot be achieved without the supportive role of government in promoting private-public partnerships.

  2. The psychological well-being of children orphaned by AIDS in Cape Town, South Africa

    Directory of Open Access Journals (Sweden)

    Cluver Lucie

    2006-07-01

    Full Text Available Abstract Background An estimated 2 million children are parentally bereaved by AIDS in South Africa. Little is known about mental health outcomes for this group. Methods This study aimed to investigate mental health outcomes for urban children living in deprived settlements in Cape Town. 30 orphaned children and 30 matched controls were compared using standardised questionnaires (SDQ on emotional and behavioural problems, peer and attention difficulties, and prosocial behaviour. The orphan group completed a modified version of a standardised questionnaire (IES-8, measuring Post-Traumatic Stress symptoms. Group differences were tested using t-tests and Pearson's chi-square. Results Both groups scored highly for peer problems, emotional problems and total scores. However, orphans were more likely to view themselves as having no good friends (p = .002, to have marked concentration difficulties (p = .03, and to report frequent somatic symptoms (p = .05, but were less likely to display anger through loss of temper (p = .03. Orphans were more likely to have constant nightmares (p = .01, and 73% scored above the cut-off for Post-Traumatic Stress Disorder. Conclusion Findings suggest important areas for larger-scale research for parentally-bereaved children.

  3. Characterization of radioactive orphan sources by gamma spectrometry

    International Nuclear Information System (INIS)

    Cruz W, H.

    2013-01-01

    The sealed radioactive sources are widely applicable in industry. They must have a permanent control and must be registered with the Technical Office of the National Authority (OTAN). However, at times it has identified the presence of abandoned sealed sources unknown to the owner. These sources are called 'orphan sources'. Of course these sources represent a high potential risk because accidents can trigger dire consequences depending on your activity and chemical form in which it presents the radioisotope. This paper describes the process and the actions taken to characterize two orphan radioactive sources from the smelter a Aceros Arequipa. For characterization we used a gamma spectrometry system using a detector NaI(Tl) 3″ x 3″ with a multichannel analyzer Nucleus PCA-II. The radioisotope identified was cesium - 137 ( 137 Cs) in both cases. Fortunately, the sources maintained their integrity would otherwise have generated significant pollution considering the chemical form of the radioisotope and easy dispersion. (author)

  4. Evolution and dynamics of orphan penumbrae in the solar photosphere: Analysis from multi-instrument observations

    International Nuclear Information System (INIS)

    Zuccarello, Francesca; Guglielmino, Salvo L.; Romano, Paolo

    2014-01-01

    We investigate the dynamics and magnetic properties of orphan penumbrae observed in the solar photosphere to understand the formation process of such structures. We observed two orphan penumbrae in active region NOAA 11089 during a coordinated observing campaign carried out in 2010 July, involving the Hinode/Solar Optical Telescope (SOT) and Dutch Open Telescope (DOT), benefiting also from continuous observations acquired by the SDO satellite. We follow their evolution during about three days. The two structures form in different ways: one seems to break off the penumbra of a nearby sunspot, the other is formed through the emergence of new flux. Then they fragment while evolving. The SDO Helioseismic and Magnetic Imager measurements indicate the presence of strong line-of-sight motions in the regions occupied by these orphan penumbrae, lasting for several hours and decreasing with time. This is confirmed by SOT spectro-polarimetric measurements of the Fe I 630.2 nm pair. The latter also show that Stokes parameters exhibit significant asymmetries in the orphan penumbral regions, typical of an uncombed filamentary structure. The orphan penumbrae lie above polarity inversion lines, where peculiar plasma motions take place with velocities larger than ±3 km s –1 . The vector magnetic field in these regions is highly inclined, with the average magnetic field strength decreasing with time. The DOT observations in the Hα line and SDO Atmospheric Imaging Assembly measurements in the He II 30.4 nm line indicate that there is no counterpart for the orphan penumbrae at midchromospheric heights or above. Our findings suggest that in at least one of the features investigated the emerging flux may be trapped in the low atmospheric layers by the overlying pre-existing fields, forming these filamentary structures.

  5. Evolution and dynamics of orphan penumbrae in the solar photosphere: Analysis from multi-instrument observations

    Energy Technology Data Exchange (ETDEWEB)

    Zuccarello, Francesca [Dipartimento di Fisica e Astronomia, Università di Catania, Via S. Sofia 78, I-95123 Catania (Italy); Guglielmino, Salvo L.; Romano, Paolo, E-mail: fzu@oact.inaf.it [INAF-Osservatorio Astrofisico di Catania, Via S. Sofia 78, I-95123 Catania (Italy)

    2014-05-20

    We investigate the dynamics and magnetic properties of orphan penumbrae observed in the solar photosphere to understand the formation process of such structures. We observed two orphan penumbrae in active region NOAA 11089 during a coordinated observing campaign carried out in 2010 July, involving the Hinode/Solar Optical Telescope (SOT) and Dutch Open Telescope (DOT), benefiting also from continuous observations acquired by the SDO satellite. We follow their evolution during about three days. The two structures form in different ways: one seems to break off the penumbra of a nearby sunspot, the other is formed through the emergence of new flux. Then they fragment while evolving. The SDO Helioseismic and Magnetic Imager measurements indicate the presence of strong line-of-sight motions in the regions occupied by these orphan penumbrae, lasting for several hours and decreasing with time. This is confirmed by SOT spectro-polarimetric measurements of the Fe I 630.2 nm pair. The latter also show that Stokes parameters exhibit significant asymmetries in the orphan penumbral regions, typical of an uncombed filamentary structure. The orphan penumbrae lie above polarity inversion lines, where peculiar plasma motions take place with velocities larger than ±3 km s{sup –1}. The vector magnetic field in these regions is highly inclined, with the average magnetic field strength decreasing with time. The DOT observations in the Hα line and SDO Atmospheric Imaging Assembly measurements in the He II 30.4 nm line indicate that there is no counterpart for the orphan penumbrae at midchromospheric heights or above. Our findings suggest that in at least one of the features investigated the emerging flux may be trapped in the low atmospheric layers by the overlying pre-existing fields, forming these filamentary structures.

  6. Evolution and Dynamics of Orphan Penumbrae in the Solar Photosphere: Analysis from Multi-instrument Observations

    Science.gov (United States)

    Zuccarello, Francesca; Guglielmino, Salvo L.; Romano, Paolo

    2014-05-01

    We investigate the dynamics and magnetic properties of orphan penumbrae observed in the solar photosphere to understand the formation process of such structures. We observed two orphan penumbrae in active region NOAA 11089 during a coordinated observing campaign carried out in 2010 July, involving the Hinode/Solar Optical Telescope (SOT) and Dutch Open Telescope (DOT), benefiting also from continuous observations acquired by the SDO satellite. We follow their evolution during about three days. The two structures form in different ways: one seems to break off the penumbra of a nearby sunspot, the other is formed through the emergence of new flux. Then they fragment while evolving. The SDO Helioseismic and Magnetic Imager measurements indicate the presence of strong line-of-sight motions in the regions occupied by these orphan penumbrae, lasting for several hours and decreasing with time. This is confirmed by SOT spectro-polarimetric measurements of the Fe I 630.2 nm pair. The latter also show that Stokes parameters exhibit significant asymmetries in the orphan penumbral regions, typical of an uncombed filamentary structure. The orphan penumbrae lie above polarity inversion lines, where peculiar plasma motions take place with velocities larger than ±3 km s-1. The vector magnetic field in these regions is highly inclined, with the average magnetic field strength decreasing with time. The DOT observations in the Hα line and SDO Atmospheric Imaging Assembly measurements in the He II 30.4 nm line indicate that there is no counterpart for the orphan penumbrae at midchromospheric heights or above. Our findings suggest that in at least one of the features investigated the emerging flux may be trapped in the low atmospheric layers by the overlying pre-existing fields, forming these filamentary structures.

  7. A roadmap for breeding orphan leafy vegetable species: a case study of Gynandropsis gynandra (Cleomaceae).

    Science.gov (United States)

    Sogbohossou, E O Deedi; Achigan-Dako, Enoch G; Maundu, Patrick; Solberg, Svein; Deguenon, Edgar M S; Mumm, Rita H; Hale, Iago; Van Deynze, Allen; Schranz, M Eric

    2018-01-01

    Despite an increasing awareness of the potential of "orphan" or unimproved crops to contribute to food security and enhanced livelihoods for farmers, coordinated research agendas to facilitate production and use of orphan crops by local communities are generally lacking. We provide an overview of the current knowledge on leafy vegetables with a focus on Gynandropsis gynandra , a highly nutritious species used in Africa and Asia, and highlight general and species-specific guidelines for participatory, genomics-assisted breeding of orphan crops. Key steps in genome-enabled orphan leafy vegetables improvement are identified and discussed in the context of Gynandropsis gynandra breeding, including: (1) germplasm collection and management; (2) product target definition and refinement; (3) characterization of the genetic control of key traits; (4) design of the 'process' for cultivar development; (5) integration of genomic data to optimize that 'process'; (6) multi-environmental participatory testing and end-user evaluation; and (7) crop value chain development. The review discusses each step in detail, with emphasis on improving leaf yield, phytonutrient content, organoleptic quality, resistance to biotic and abiotic stresses and post-harvest management.

  8. Archaeal MCM Proteins as an Analog for the Eukaryotic Mcm2–7 Helicase to Reveal Essential Features of Structure and Function

    Science.gov (United States)

    Miller, Justin M.; Enemark, Eric J.

    2015-01-01

    In eukaryotes, the replicative helicase is the large multisubunit CMG complex consisting of the Mcm2–7 hexameric ring, Cdc45, and the tetrameric GINS complex. The Mcm2–7 ring assembles from six different, related proteins and forms the core of this complex. In archaea, a homologous MCM hexameric ring functions as the replicative helicase at the replication fork. Archaeal MCM proteins form thermostable homohexamers, facilitating their use as models of the eukaryotic Mcm2–7 helicase. Here we review archaeal MCM helicase structure and function and how the archaeal findings relate to the eukaryotic Mcm2–7 ring. PMID:26539061

  9. Challenges in the clinical development of orphan drugs

    NARCIS (Netherlands)

    Kreeftmeijer-Vegter, A.R.

    2015-01-01

    Rare diseases are characterised by a low prevalence. There are so many different rare diseases, that millions of people are affected.The vast majority of these diseases suffer from a lack of approved treatment options and orphan drugs (ODs) therefore represent a huge unmet medical need. ODs face

  10. ENERGY-TRANSDUCING PROPERTIES OF PRIMARY PROTON PUMPS RECONSTITUTED INTO ARCHAEAL BIPOLAR LIPID VESICLES

    NARCIS (Netherlands)

    ELFERINK, MGL; DEWIT, JG; DRIESSEN, AJM; KONINGS, WN; Elferink, Marieke G.L.

    1993-01-01

    Archaeal lipids differ considerably from eubacterial and eukaryotic lipids in their structure and physical properties. From the membranes of the extreme thermophilic archaea Sulfolobus acidocaldarius a tetraether lipid fraction was isolated, which can form closed and stable monolayer liposomes in

  11. A review and update on orphan drugs for the treatment of noninfectious uveitis

    Directory of Open Access Journals (Sweden)

    You C

    2017-01-01

    Full Text Available Caiyun You,1–3 Haitham F Sahawneh,1,2 Lina Ma,1,2 Buraa Kubaisi,1,2 Alexander Schmidt,1,2 C Stephen Foster1,2,4 1Massachusetts Eye Research and Surgery Institution (MERSI, Waltham, 2Ocular Immunology and Uveitis Foundation, Weston, MA, USA; 3Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 4Harvard Medical School, Boston, MA, USA Introduction: Uveitis, a leading cause of preventable blindness around the world, is a critically underserved disease in regard to the medications approved for use. Multiple immunomodulatory therapy (IMT drugs are appropriate for uveitis therapy but are still off-label. These IMT agents, including antimetabolites, calcineurin inhibitors, alkylating agents, and biologic agents, have been designated as “orphan drugs” and are widely used for systemic autoimmune diseases or organ transplantation.Area covered: The purpose of this paper is to comprehensively review and summarize the approved orphan drugs and biologics that are being used to treat systemic diseases and to discuss drugs that have not yet received approval as an “orphan drug for treating uveitis” by the US Food and Drug Administration (FDA.Our perspective: IMT, as a steroid-sparing agent for uveitis patients, has shown promising clinical results. Refractory and recurrent uveitis requires combination IMT agents. IMT is continued for a period of 2 years while the patient is in remission before considering tapering medication. Our current goals include developing further assessments regarding the efficacy, optimal dose, and safety in efforts to achieve FDA approval for “on-label” use of current IMT agents and biologics more quickly and to facilitate insurance coverage and expand access to the products for this orphan disease. Keywords: immunomodulatory, orphan drug, steroid sparing, uveitis

  12. Archaeal and Bacterial Communities Associated with the Surface Mucus of Caribbean Corals Differ in Their Degree of Host Specificity and Community Turnover Over Reefs.

    Directory of Open Access Journals (Sweden)

    Pedro R Frade

    Full Text Available Comparative studies on the distribution of archaeal versus bacterial communities associated with the surface mucus layer of corals have rarely taken place. It has therefore remained enigmatic whether mucus-associated archaeal and bacterial communities exhibit a similar specificity towards coral hosts and whether they vary in the same fashion over spatial gradients and between reef locations. We used microbial community profiling (terminal-restriction fragment length polymorphism, T-RFLP and clone library sequencing of the 16S rRNA gene to compare the diversity and community structure of dominant archaeal and bacterial communities associating with the mucus of three common reef-building coral species (Porites astreoides, Siderastrea siderea and Orbicella annularis over different spatial scales on a Caribbean fringing reef. Sampling locations included three reef sites, three reef patches within each site and two depths. Reference sediment samples and ambient water were also taken for each of the 18 sampling locations resulting in a total of 239 samples. While only 41% of the bacterial operational taxonomic units (OTUs characterized by T-RFLP were shared between mucus and the ambient water or sediment, for archaeal OTUs this percentage was 2-fold higher (78%. About half of the mucus-associated OTUs (44% and 58% of bacterial and archaeal OTUs, respectively were shared between the three coral species. Our multivariate statistical analysis (ANOSIM, PERMANOVA and CCA showed that while the bacterial community composition was determined by habitat (mucus, sediment or seawater, host coral species, location and spatial distance, the archaeal community composition was solely determined by the habitat. This study highlights that mucus-associated archaeal and bacterial communities differ in their degree of community turnover over reefs and in their host-specificity.

  13. Archaeal and Bacterial Communities Associated with the Surface Mucus of Caribbean Corals Differ in Their Degree of Host Specificity and Community Turnover Over Reefs

    NARCIS (Netherlands)

    Frade, P.R.; Roll, K.; Bergauer, K.; Herndl, G.

    2016-01-01

    Comparative studies on the distribution of archaeal versus bacterial communities associatedwith the surface mucus layer of corals have rarely taken place. It has thereforeremained enigmatic whether mucus-associated archaeal and bacterial communities exhibita similar specificity towards coral hosts

  14. Bacterial and archaeal communities in sediments of the north Chinese marginal seas.

    Science.gov (United States)

    Liu, Jiwen; Liu, Xiaoshou; Wang, Min; Qiao, Yanlu; Zheng, Yanfen; Zhang, Xiao-Hua

    2015-07-01

    Microbial communities of the Chinese marginal seas have rarely been reported. Here, bacterial and archaeal community structures and abundance in the surface sediment of four sea areas including the Bohai Sea (BS), North Yellow Sea (NYS), South Yellow Sea (SYS), and the north East China Sea (NECS) were surveyed by 16S ribosomal RNA (rRNA) gene pyrosequencing and quantitative PCR. The results showed that microbial communities of the four geographic areas were distinct from each other at the operational taxonomic unit (OTU) level, whereas the microbial communities of the BS, NYS, and SYS were more similar to each other than to the NECS at higher taxonomic levels. Across all samples, Bacteria were numerically dominant relative to Archaea, and among them, Gammaproteobacteria and Euryarchaeota were predominant in the BS, NYS, and SYS, while Deltaproteobacteria and Thaumarchaeota were prevalent in the NECS. The most abundant bacterial genera were putative sulfur oxidizer and sulfate reducer, suggesting that sulfur cycle processes might prevail in these areas, and the high abundance of dsrB (10(7)-10(8) copies g(-1)) in all sites verified the dominance of sulfate reducer in the north Chinese marginal seas. The differences in sediment sources among the sampling areas were potential explanations for the observed microbial community variations. Furthermore, temperature and dissolved oxygen of bottom water were significant environmental factors in determining both bacterial and archaeal communities, whereas chlorophyll a in sediment was significant only in structuring archaeal community. This study presented an outline of benthic microbial communities and provided insights into understanding the biogeochemical cycles in sediments of the north Chinese marginal seas.

  15. 76 FR 29183 - Exclusion of Orphan Drugs for Certain Covered Entities Under 340B Program

    Science.gov (United States)

    2011-05-20

    ... and, if they are, at what price. These covered entities do not know if they can buy these orphan drugs... DEPARTMENT OF HEALTH AND HUMAN SERVICES 42 CFR Part 10 RIN 0906-AA94 Exclusion of Orphan Drugs for... Prices of Drugs Purchased by Covered Entities.'' Section 340B implemented a drug pricing program by which...

  16. On the Archaeal Origins of Eukaryotes and the Challenges of Inferring Phenotype from Genotype.

    Science.gov (United States)

    Dey, Gautam; Thattai, Mukund; Baum, Buzz

    2016-07-01

    If eukaryotes arose through a merger between archaea and bacteria, what did the first true eukaryotic cell look like? A major step toward an answer came with the discovery of Lokiarchaeum, an archaeon whose genome encodes small GTPases related to those used by eukaryotes to regulate membrane traffic. Although 'Loki' cells have yet to be seen, their existence has prompted the suggestion that the archaeal ancestor of eukaryotes engulfed the future mitochondrion by phagocytosis. We propose instead that the archaeal ancestor was a relatively simple cell, and that eukaryotic cellular organization arose as the result of a gradual transfer of bacterial genes and membranes driven by an ever-closer symbiotic partnership between a bacterium and an archaeon. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Psychosocial attributes of orphaned youths in Ibadan Metropolis ...

    African Journals Online (AJOL)

    Methods: A total of 1850 youth from 20 schools in 3 urban and 2 rural school districts in South-western Nigeria had the self-administered instruments: Global School Health Questionnaire to assess reproductive and other health indices and the Culture Free Self Esteem Inventory. Results: The overall prevalence of orphans ...

  18. “The Impact of Community-based Capital Cash Transfers on the Schooling of Orphaned and Vulnerable Children in Kenya”

    DEFF Research Database (Denmark)

    Skovdal, Morten; Webale, A.; Mwasiaji, W.

    2013-01-01

    In this article we report on a community-based capital cash transfer initiative (CCCT) in Kenya that sought to mobilise and enable HIV-affected communities to respond to the needs of orphaned and vulnerable children. With bilateral funding, the Social Services Department in Kenya provided 80 comm...... of orphaned children, particularly amongst girls. We conclude that CCCT is a viable strategy for improving orphan schooling in sub-Saharan Africa....

  19. Methanobacterium Dominates Biocathodic Archaeal Communities in Methanogenic Microbial Electrolysis Cells

    KAUST Repository

    Siegert, Michael

    2015-07-06

    © 2015 American Chemical Society. Methane is the primary end product from cathodic current in microbial electrolysis cells (MECs) in the absence of methanogenic inhibitors, but little is known about the archaeal communities that develop in these systems. MECs containing cathodes made from different materials (carbon brushes, or plain graphite blocks or blocks coated with carbon black and platinum, stainless steel, nickel, ferrihydrite, magnetite, iron sulfide, or molybdenum disulfide) were inoculated with anaerobic digester sludge and acclimated at a set potential of -600 mV (versus a standard hydrogen electrode). The archaeal communities on all cathodes, except those coated with platinum, were predominated by Methanobacterium (median 97% of archaea). Cathodes with platinum contained mainly archaea most similar to Methanobrevibacter. Neither of these methanogens were abundant (<0.1% of archaea) in the inoculum, and therefore their high abundance on the cathode resulted from selective enrichment. In contrast, bacterial communities on the cathode were more diverse, containing primarily δ-Proteobacteria (41% of bacteria). The lack of a consistent bacterial genus on the cathodes indicated that there was no similarly selective enrichment of bacteria on the cathode. These results suggest that the genus Methanobacterium was primarily responsible for methane production in MECs when cathodes lack efficient catalysts for hydrogen gas evolution. (Figure Presented).

  20. Defense islands in bacterial and archaeal genomes and prediction of novel defense systems.

    Science.gov (United States)

    Makarova, Kira S; Wolf, Yuri I; Snir, Sagi; Koonin, Eugene V

    2011-11-01

    The arms race between cellular life forms and viruses is a major driving force of evolution. A substantial fraction of bacterial and archaeal genomes is dedicated to antivirus defense. We analyzed the distribution of defense genes and typical mobilome components (such as viral and transposon genes) in bacterial and archaeal genomes and demonstrated statistically significant clustering of antivirus defense systems and mobile genes and elements in genomic islands. The defense islands are enriched in putative operons and contain numerous overrepresented gene families. A detailed sequence analysis of the proteins encoded by genes in these families shows that many of them are diverged variants of known defense system components, whereas others show features, such as characteristic operonic organization, that are suggestive of novel defense systems. Thus, genomic islands provide abundant material for the experimental study of bacterial and archaeal antivirus defense. Except for the CRISPR-Cas systems, different classes of defense systems, in particular toxin-antitoxin and restriction-modification systems, show nonrandom clustering in defense islands. It remains unclear to what extent these associations reflect functional cooperation between different defense systems and to what extent the islands are genomic "sinks" that accumulate diverse nonessential genes, particularly those acquired via horizontal gene transfer. The characteristics of defense islands resemble those of mobilome islands. Defense and mobilome genes are nonrandomly associated in islands, suggesting nonadaptive evolution of the islands via a preferential attachment-like mechanism underpinned by the addictive properties of defense systems such as toxins-antitoxins and an important role of horizontal mobility in the evolution of these islands.

  1. "Orphan" retrogenes in the human genome.

    Science.gov (United States)

    Ciomborowska, Joanna; Rosikiewicz, Wojciech; Szklarczyk, Damian; Makałowski, Wojciech; Makałowska, Izabela

    2013-02-01

    Gene duplicates generated via retroposition were long thought to be pseudogenized and consequently decayed. However, a significant number of these genes escaped their evolutionary destiny and evolved into functional genes. Despite multiple studies, the number of functional retrogenes in human and other genomes remains unclear. We performed a comparative analysis of human, chicken, and worm genomes to identify "orphan" retrogenes, that is, retrogenes that have replaced their progenitors. We located 25 such candidates in the human genome. All of these genes were previously known, and the majority has been intensively studied. Despite this, they have never been recognized as retrogenes. Analysis revealed that the phenomenon of replacing parental genes with their retrocopies has been taking place over the entire span of animal evolution. This process was often species specific and contributed to interspecies differences. Surprisingly, these retrogenes, which should evolve in a more relaxed mode, are subject to a very strong purifying selection, which is, on average, two and a half times stronger than other human genes. Also, for retrogenes, they do not show a typical overall tendency for a testis-specific expression. Notably, seven of them are associated with human diseases. Recognizing them as "orphan" retrocopies, which have different regulatory machinery than their parents, is important for any disease studies in model organisms, especially when discoveries made in one species are transferred to humans.

  2. The new orphaned radioactive sources program in the United States

    International Nuclear Information System (INIS)

    Naraine, N.; Karhnak, J.M.

    1998-01-01

    Exposure of the public to uncontrolled radioactive sources has become an significant concern to the United States (US) Government because of the continuous increase in the number of sources that are being found, sometimes without proper radiation markings. This problem is primarily due to inadequate control, insufficient accountability, and improper disposal of radioactive materials. The US Environmental Protection Agency (EPA) has funded a cooperative 'orphaned' source initiative with the Conference of Radiation Control Program Directors (CRCPD) to bring under control unwanted sources and thus reduce the potential for unnecessary exposure to the public, workers and the environment. The program is being developed through the cooperative efforts of government agencies and industry, and will provide a quick and efficient method to bring orphaned sources under control and out of potentially dangerous situations. (author)

  3. Solution structure of an archaeal DNA binding protein with an eukaryotic zinc finger fold.

    Directory of Open Access Journals (Sweden)

    Florence Guillière

    Full Text Available While the basal transcription machinery in archaea is eukaryal-like, transcription factors in archaea and their viruses are usually related to bacterial transcription factors. Nevertheless, some of these organisms show predicted classical zinc fingers motifs of the C2H2 type, which are almost exclusively found in proteins of eukaryotes and most often associated with transcription regulators. In this work, we focused on the protein AFV1p06 from the hyperthermophilic archaeal virus AFV1. The sequence of the protein consists of the classical eukaryotic C2H2 motif with the fourth histidine coordinating zinc missing, as well as of N- and C-terminal extensions. We showed that the protein AFV1p06 binds zinc and solved its solution structure by NMR. AFV1p06 displays a zinc finger fold with a novel structure extension and disordered N- and C-termini. Structure calculations show that a glutamic acid residue that coordinates zinc replaces the fourth histidine of the C2H2 motif. Electromobility gel shift assays indicate that the protein binds to DNA with different affinities depending on the DNA sequence. AFV1p06 is the first experimentally characterised archaeal zinc finger protein with a DNA binding activity. The AFV1p06 protein family has homologues in diverse viruses of hyperthermophilic archaea. A phylogenetic analysis points out a common origin of archaeal and eukaryotic C2H2 zinc fingers.

  4. Family and Nation: Cherokee Orphan Care, 1835-1903

    Science.gov (United States)

    Reed, Julie L.

    2010-01-01

    On November 17, 1903, fifteen miles from the nearest railway station and fifty miles northwest of the capital of the Cherokee Nation in Tahlequah, a fire engulfed the Cherokee Orphan Asylum. After the fire the Cherokee Nation relocated the homeless children to the nation's Insane Asylum in Tahlequah, where Sequoyah School stands today. The…

  5. Models of care for orphaned and separated children and upholding children's rights: cross-sectional evidence from western Kenya.

    Science.gov (United States)

    Embleton, Lonnie; Ayuku, David; Kamanda, Allan; Atwoli, Lukoye; Ayaya, Samuel; Vreeman, Rachel; Nyandiko, Winstone; Gisore, Peter; Koech, Julius; Braitstein, Paula

    2014-04-01

    Sub-Saharan Africa is home to approximately 55 million orphaned children. The growing orphan crisis has overwhelmed many communities and has weakened the ability of extended families to meet traditional care-taking expectations. Other models of care and support have emerged in sub-Saharan Africa to address the growing orphan crisis, yet there is a lack of information on these models available in the literature. We applied a human rights framework using the United Nations Convention on the Rights of the Child to understand what extent children's basic human rights were being upheld in institutional vs. community- or family-based care settings in Uasin Gishu County, Kenya. The Orphaned and Separated Children's Assessments Related to their Health and Well-Being Project is a 5-year cohort of orphaned children and adolescents aged ≤18 year. This descriptive analysis was restricted to baseline data. Chi-Square test was used to test for associations between categorical /dichotomous variables. Fisher's exact test was also used if some cells had expected value of less than 5. Included in this analysis are data from 300 households, 19 Charitable Children's Institutions (CCIs) and 7 community-based organizations. In total, 2871 children were enrolled and had baseline assessments done: 1390 in CCI's and 1481 living in households in the community. We identified and described four broad models of care for orphaned and separated children, including: institutional care (sub-classified as 'Pure CCI' for those only providing residential care, 'CCI-Plus' for those providing both residential care and community-based supports to orphaned children , and 'CCI-Shelter' which are rescue, detention, or other short-term residential support), family-based care, community-based care and self-care. Children in institutional care (95%) were significantly (p children and uphold their rights. Family-based care plays an essential role; however, households require increased support to adequately

  6. Cryo-EM structure of the archaeal 50S ribosomal subunit in complex with initiation factor 6 and implications for ribosome evolution

    DEFF Research Database (Denmark)

    Greber, Basil J; Boehringer, Daniel; Godinic-Mikulcic, Vlatka

    2012-01-01

    additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter...... between this archaeal ribosome and eukaryotic ribosomes but are mostly absent in bacteria and in some archaeal lineages. Furthermore, the structure reveals that, in spite of highly divergent evolutionary trajectories of the ribosomal particle and the acquisition of novel functions of IF6 in eukaryotes......, the molecular binding of IF6 on the ribosome is conserved between eukaryotes and archaea. The structure also provides a snapshot of the reductive evolution of the archaeal ribosome and offers new insights into the evolution of the translation system in archaea....

  7. Archaeal and bacterial community analysis of several Yellowstone National Park hot springs

    Science.gov (United States)

    Colman, D. R.; Takacs-Vesbach, C. D.

    2012-12-01

    The hot springs of Yellowstone National Park (YNP) are home to a diverse assemblage of microorganisms. Culture-independent studies have significantly expanded our understanding of the diversity of both Bacteria and Archaea present in YNP springs as well as the geochemical and ecological controls on communities. While the ecological analysis of Bacteria among the physicochemically heterogenous springs of YNP has been previously conducted, less is known about the extent of diversity of Archaeal communities and the chemical and ecological controls on their populations. Here we report a culture-independent analysis of 31 hot spring archaeal and bacterial communities of YNP springs using next generation sequencing. We found the phylogenetic diversity of Archaea to be generally comparable to that of co-occurring bacterial communities although overall, in the springs we investigated, diversity was higher for Bacteria than Archaea. Chemical and physical controls were similar for both domains with pH correlating most strongly with community composition. Community differences reflected the partitioning of taxonomic groups in low or high pH springs for both domains. Results will be discussed in a geochemical and ecological context.

  8. The Vulnerabilities of Orphaned Children Participating in Research: A Critical Review and Factors for Consideration for Participation in Biomedical and Behavioral Research

    Science.gov (United States)

    Thompson, Rachel T.; Meslin, Eric M.; Braitstein, Paula K. A.; Nyandiko, Winstone M.; Ayaya, Samuel O.; Vreeman, Rachel C.

    2013-01-01

    Orphans are a subpopulation with a unique set of additional vulnerabilities. Increasing focus on children’s rights, pediatric global health, and pediatric research makes it imperative to recognize and address unique vulnerabilities of orphaned children. This paper describes the unique vulnerabilities of the orphaned pediatric population and offers a structured set of factors that require consideration when including orphans in biomedical research. Pediatric orphans are particularly vulnerable due to decreased economic resources, psychosocial instability, increased risk of abuse, and delayed/decreased access to healthcare. These vulnerabilities are significant. By carefully considering each issue in a population in a culturally specific and study-specific manner, researchers can make valuable contributions to the overall health and well-being of this uniquely vulnerable population. PMID:23086048

  9. Ror receptor tyrosine kinases: orphans no more

    OpenAIRE

    Green, Jennifer L.; Kuntz, Steven G.; Sternberg, Paul W.

    2008-01-01

    Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either act...

  10. The orphaning experience: descriptions from Ugandan youth who have lost parents to HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Ssebunnya Joshua

    2010-02-01

    Full Text Available Abstract The HIV/AIDS epidemic has continued to pose significant challenges to countries in Sub-Saharan Africa. Millions of African children and youth have lost parents to HIV/AIDS leaving a generation of orphans to be cared for within extended family systems and communities. The experiences of youth who have lost parents to the HIV/AIDS epidemic provide an important ingress into this complex, evolving, multi-dimensional phenomenon. A fundamental qualitative descriptive study was conducted to develop a culturally relevant and comprehensive description of the experiences of orphanhood from the perspectives of Ugandan youth. A purposeful sample of 13 youth who had lost one or both parents to HIV/AIDS and who were affiliated with a non-governmental organization providing support to orphans were interviewed. Youth orphaned by HIV/AIDS described the experience of orphanhood beginning with parental illness, not death. Several losses were associated with the death of a parent including lost social capitol, educational opportunities and monetary assets. Unique findings revealed that youth experienced culturally specific stigma and conflict which was distinctly related to their HIV/AIDS orphan status. Exploitation within extended cultural family systems was also reported. Results from this study suggest that there is a pressing need to identify and provide culturally appropriate services for these Ugandan youth prior to and after the loss of a parent(s.

  11. Do orphan G-protein-coupled receptors have ligand-independent functions? New insights from receptor heterodimers

    OpenAIRE

    Levoye, Angélique; Dam, Julie; Ayoub, Mohammed A; Guillaume, Jean-Luc; Jockers, Ralf

    2006-01-01

    G-protein-coupled receptors (GPCRs) are important drug targets and are involved in virtually every biological process. However, there are still more than 140 orphan GPCRs, and deciphering their function remains a priority for fundamental and clinical research. Research on orphan GPCRs has concentrated mainly on the identification of their natural ligands, whereas recent data suggest additional ligand-independent functions for these receptors. This emerging concept is connected with the observ...

  12. Analysis of the archaeal sub-seafloor community at Suiyo Seamount on the Izu-Bonin Arc.

    Science.gov (United States)

    Hara, Kurt; Kakegawa, Takeshi; Yamashiro, Kan; Maruyama, Akihiko; Ishibashi, Jun-Ichiro; Marumo, Katsumi; Urabe, Tetsuro; Yamagishi, Akihiko

    2005-01-01

    A sub-surface archaeal community at the Suiyo Seamount in the Western Pacific Ocean was investigated by 16S rRNA gene sequence and whole-cell in situ hybridization analyses. In this study, we drilled and cased holes at the hydrothermal area of the seamount to minimize contamination of the hydrothermal fluid in the sub-seafloor by penetrating seawater. PCR clone analysis of the hydrothermal fluid samples collected from a cased hole indicated the presence of chemolithoautotrophic primary biomass producers of Archaeoglobales and the Methanococcales-related archaeal HTE1 group, both of which can utilize hydrogen as an electron donor. We discuss the implication of the microbial community on the early history of life and on the search for extraterrestrial life. c2005 COSPAR. Published by Elsevier Ltd. All rights reserved.

  13. Who wants to adopt and who wants to be adopted: a sample of American families and sub-Saharan African orphans.

    Science.gov (United States)

    Balding, Christopher; Feng, Yan; Atashband, Armita

    2015-12-01

    The debate between pro- and anti-international adoption advocates relies heavily on rhetoric and little on data analysis. To better understand the state of orphans and potential adopters in this debate, we utilize the National Survey of Family Growth (NSFG) and the Demographic and Health Surveys (DHS) to study who adopts internationally and the status of orphaned children in sub-Saharan Africa. According to NSFG data adopters are church going, highly educated, stable families aware of the challenges faced by international adoption, with high rates of infertility and rates of child abuse half the population average. According to the DHS data, orphans in sub-Saharan Africa suffer from significantly higher deprivation, reduced schooling and increased levels of stunting and underweight reported than their cohort. Using this data, we estimate conservatively that that 1 50 000 orphans from our sample of sub-Saharan African countries died from their 5-year birth cohort. Given the large number of families seeking to adopt and the high number of orphan deaths, it seems counterproductive to restrict international adoptions given the significantly lower risks faced by children in adopted families compared with remaining orphaned. © The Author 2015; all rights reserved. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

  14. Challenges in orphan drug development and regulatory policy in China.

    Science.gov (United States)

    Cheng, Alice; Xie, Zhi

    2017-01-18

    While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.

  15. Psychological Challenges Affecting Primary School Going Orphans In Wanganui Community Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Mbwirire John

    2017-04-01

    Full Text Available This study sought to identify psychological challenges affecting primary school orphans in Wanganui Community in Zimbabwe. The study employed a mixed method approach combining questionnaires with teachers and care givers interview sessions with orphans and in-depth interviews with community socialdevelopment worker. The study finds that lack of love lack of attention and withdrawal were the main signs and symptoms of psychological challenge in the community. The study revealed that the term and symptoms of psychological challenges were understood differently between African context and Western context. The study recommended that action must be taken as soon as possible once the signs and symptoms which include lack of love lack of attention to rectify the psychological challenges faced by the community.

  16. Increasing human Th17 differentiation through activation of orphan nuclear receptor retinoid acid-related orphan receptor γ (RORγ) by a class of aryl amide compounds.

    Science.gov (United States)

    Zhang, Wei; Zhang, Jing; Fang, Leiping; Zhou, Ling; Wang, Shuai; Xiang, Zhijun; Li, Yuan; Wisely, Bruce; Zhang, Guifeng; An, Gang; Wang, Yonghui; Leung, Stewart; Zhong, Zhong

    2012-10-01

    In a screen for small-molecule inhibitors of retinoid acid-related orphan receptor γ (RORγ), we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the interleukin 17 (IL-17) reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies of ∼0.1 μM measured by EC₅₀. These compounds were shown to directly bind to RORγ by circular dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγ remains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune-modulating therapies.

  17. Archaeal Clusters of Orthologous Genes (arCOGs): An Update and Application for Analysis of Shared Features between Thermococcales, Methanococcales, and Methanobacteriales

    OpenAIRE

    Makarova, Kira; Wolf, Yuri; Koonin, Eugene

    2015-01-01

    With the continuously accelerating genome sequencing from diverse groups of archaea and bacteria, accurate identification of gene orthology and availability of readily expandable clusters of orthologous genes are essential for the functional annotation of new genomes. We report an update of the collection of archaeal Clusters of Orthologous Genes (arCOGs) to cover, on average, 91% of the protein-coding genes in 168 archaeal genomes. The new arCOGs were constructed using refined algorithms for...

  18. Response of Archaeal and Bacterial Soil Communities to Changes Associated with Outdoor Cattle Overwintering.

    Science.gov (United States)

    Chroňáková, Alica; Schloter-Hai, Brigitte; Radl, Viviane; Endesfelder, David; Quince, Christopher; Elhottová, Dana; Šimek, Miloslav; Schloter, Michael

    2015-01-01

    Archaea and bacteria are important drivers for nutrient transformations in soils and catalyse the production and consumption of important greenhouse gases. In this study, we investigate changes in archaeal and bacterial communities of four Czech grassland soils affected by outdoor cattle husbandry. Two show short-term (3 years; STI) and long-term impact (17 years; LTI), one is regenerating from cattle impact (REG) and a control is unaffected by cattle (CON). Cattle manure (CMN), the source of allochthonous microbes, was collected from the same area. We used pyrosequencing of 16S rRNA genes to assess the composition of archaeal and bacterial communities in each soil type and CMN. Both short- and long- term cattle impact negatively altered archaeal and bacterial diversity, leading to increase of homogenization of microbial communities in overwintering soils over time. Moreover, strong shifts in the prokaryotic communities were observed in response to cattle overwintering, with the greatest impact on archaea. Oligotrophic and acidophilic microorganisms (e.g. Thaumarchaeota, Acidobacteria, and α-Proteobacteria) dominated in CON and expressed strong negative response to increased pH, total C and N. Whereas copiotrophic and alkalophilic microbes (e.g. methanogenic Euryarchaeota, Firmicutes, Chloroflexi, Actinobacteria, and Bacteroidetes) were common in LTI showing opposite trends. Crenarchaeota were also found in LTI, though their trophic interactions remain cryptic. Firmicutes, Bacteroidetes, Methanobacteriaceae, and Methanomicrobiaceae indicated the introduction and establishment of faecal microbes into the impacted soils, while Chloroflexi and Methanosarcinaceae suggested increased abundance of soil-borne microbes under altered environmental conditions. The observed changes in prokaryotic community composition may have driven corresponding changes in soil functioning.

  19. Review of regulatory recommendations for orphan drug submissions in the Netherlands and Scotland : focus on the underlying pharmacoeconomic evaluations

    NARCIS (Netherlands)

    Vegter, Stefan; Rozenbaum, Mark H.; Postema, Roelien; Tolley, Keith; Postma, Maarten J.

    2010-01-01

    Background: Pharmacoeconomic evaluations of new drug therapies are often required for reimbursement or guidance decisions. However, for orphan drugs, country-specific requirements exist. In the Netherlands, orphan drug developers can be exempted from providing a full pharmacoeconomic evaluation,

  20. Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors.

    Science.gov (United States)

    Khan, Muhammad Zahid; He, Ling

    2017-04-01

    In the central nervous system (CNS), G protein-coupled receptors (GPCRs) are the most fruitful targets for neuropsychopharmacological drug development. Rhodopsin (class A) is the most studied class of GPCR and includes orphan receptors for which the endogenous ligand is not known or is unclear. Characterization of orphan GPCRs has proven to be challenging, and the production pace of GPCR-based drugs has been incredibly slow. Determination of the functions of these receptors may provide unexpected insight into physiological and neuropathological processes. Advances in various methods and techniques to investigate orphan receptors including in situ hybridization and knockdown/knockout (KD/KO) showed extensive expression of these receptors in the mammalian brain and unmasked their physiological and neuropathological roles. Due to these rapid progress and development, orphan GPCRs are rising as a new and promising class of drug targets for neurodegenerative diseases and psychiatric disorders. This review presents a neuropsychopharmacological perspective of 26 orphan receptors of rhodopsin (class A) family, namely GPR3, GPR6, GPR12, GPR17, GPR26, GPR35, GPR39, GPR48, GPR49, GPR50, GPR52, GPR55, GPR61, GPR62, GPR63, GPR68, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR153, GPR162, GPR171, and TAAR6. We discussed the expression of these receptors in mammalian brain and their physiological roles. Furthermore, we have briefly highlighted their roles in neurodegenerative diseases and psychiatric disorders including Alzheimer's disease, Parkinson's disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

  1. Conceptions of mental health among Ugandan youth orphaned by ...

    African Journals Online (AJOL)

    Poor mental health was perceived as a form of madness or insanity and it was associated with a loss of basic life necessities, such as access to food, education or shelter. The youths also identified factors that promote more successful orphans. The findings of this study suggest that Western terminologies and symptom ...

  2. Orphans in Three Sahelian Countries: Exploratory Analyses from Census Data

    Directory of Open Access Journals (Sweden)

    Richard Marcoux

    2010-12-01

    Full Text Available Important investments in Africa have reduced slightly the levels child mortality but life expectancy still very low. The number of children without surviving biological parents is increasing and orphans are becoming an important social problem. Because Sahelian societies are mostly patriarchal, becoming fatherless or motherless will have different effects on the well being of the child. This paper examines the levels and trends of the survival status of the parents and then, living arrangements of orphans. We describe characteristics of these children with a special focus on education and economic activities. The paper uses the censuses from Chad, Niger and Senegal made available by the African Census Analysis Project (ACAP held at University of Pennsylvania. These countries collected information on survival status of each biological parent to estimate adult mortality but the potential of this information for research on child well-being is rarely exploited.

  3. The life experiences of AIDS orphans in Malawi : a case of Area 23, Kalolo and Tsabango village in Lilongwe district

    OpenAIRE

    Chisala, Gloria Lucy

    2005-01-01

    Mastergradsoppgave i "Comparative social work" - Høgskolen i Bodø, 2005 This thesis reports on qualitative life history interviews of orphaned children who have lost both of their parents due to death by HIV/AIDS in Malawi. The focus is on double orphans who are between the ages of 15 and 17 years. The purpose is to explore and analyse the life experiences of orphans in Lilongwe in order to understand how they construct their social world. Methodologically, the study uses b...

  4. Health of adults caring for orphaned children in an HIV endemic community in South Africa

    OpenAIRE

    Kuo, Caroline; Operario, Don

    2011-01-01

    In South Africa, an estimated 2.5 million children have been orphaned by AIDS and other causes of adult mortality. Although there is a growing body of research on the well-being of South African orphaned children, few research studies have examined the health of adult individuals caring for children in HIV endemic communities. The cross-sectional survey assessed prevalence of general health and functioning (based on Short-Form 36 version 2 scale), depression (based on Center for Epidemiologic...

  5. Recognition of extremophilic archaeal viruses by eukaryotic cells: a promising nanoplatform from the third domain of life

    Science.gov (United States)

    Uldahl, Kristine Buch; Wu, Linping; Hall, Arnaldur; Papathanasiou, Pavlos; Peng, Xu; Moghimi, Seyed Moein

    2016-01-01

    Viruses from the third domain of life, Archaea, exhibit unusual features including extreme stability that allow their survival in harsh environments. In addition, these species have never been reported to integrate into human or any other eukaryotic genomes, and could thus serve for exploration of novel medical nanoplatforms. Here, we selected two archaeal viruses Sulfolobus monocaudavirus 1 (SMV1) and Sulfolobus spindle shaped virus 2 (SSV2) owing to their unique spindle shape, hyperthermostable and acid-resistant nature and studied their interaction with mammalian cells. Accordingly, we followed viral uptake, intracellular trafficking and cell viability in human endothelial cells of brain (hCMEC/D3 cells) and umbilical vein (HUVEC) origin. Whereas SMV1 is efficiently internalized into both types of human cells, SSV2 differentiates between HUVECs and hCMEC/D3 cells, thus opening a path for selective cell targeting. On internalization, both viruses localize to the lysosomal compartments. Neither SMV1, nor SSV2 induced any detrimental effect on cell morphology, plasma membrane and mitochondrial functionality. This is the first study demonstrating recognition of archaeal viruses by eukaryotic cells which provides good basis for future exploration of archaeal viruses in bioengineering and development of multifunctional vectors. PMID:27892499

  6. Biosynthesis of ribose-5-phosphate and erythrose-4-phosphate in archaea: a phylogenetic analysis of archaeal genomes

    Directory of Open Access Journals (Sweden)

    Tim Soderberg

    2005-01-01

    Full Text Available A phylogenetic analysis of the genes encoding enzymes in the pentose phosphate pathway (PPP, the ribulose monophosphate (RuMP pathway, and the chorismate pathway of aromatic amino acid biosynthesis, employing data from 13 complete archaeal genomes, provides a potential explanation for the enigmatic phylogenetic patterns of the PPP genes in archaea. Genomic and biochemical evidence suggests that three archaeal species (Methanocaldococcus jannaschii, Thermoplasma acidophilum and Thermoplasma volcanium produce ribose-5-phosphate via the nonoxidative PPP (NOPPP, whereas nine species apparently lack an NOPPP but may employ a reverse RuMP pathway for pentose synthesis. One species (Halobacterium sp. NRC-1 lacks both the NOPPP and the RuMP pathway but may possess a modified oxidative PPP (OPPP, the details of which are not yet known. The presence of transketolase in several archaeal species that are missing the other two NOPPP genes can be explained by the existence of differing requirements for erythrose-4-phosphate (E4P among archaea: six species use transketolase to make E4P as a precursor to aromatic amino acids, six species apparently have an alternate biosynthetic pathway and may not require the ability to make E4P, and one species (Pyrococcus horikoshii probably does not synthesize aromatic amino acids at all.

  7. Excluding Orphan Drugs from the 340B Drug Discount Program: the Impact on 18 Critical Access Hospitals

    Directory of Open Access Journals (Sweden)

    Madeline Carpinelli Wallack

    2012-01-01

    Full Text Available Purpose: The 340B Drug Pricing Program is a federal program designed to reduce the amount that safety net providers spend on outpatient drugs. The Patient Protection and Affordable Health Care Act of 2010 extended eligibility for 340B to critical access hospitals (CAHs for all drugs except those designated as “orphan.” Because this policy is unprecedented, this study quantifies the gross financial impact that this exemption has on a group of CAHs. Methods: Drug spending for 2010 from 18 CAHs in Minnesota and Wisconsin are reviewed to identify the prevalence of orphan drug purchases and to calculate the price differentials between the 340B price and the hospitals’ current cost. Results: The 18 CAHs’ purchases of orphan drugs comprise an average of 44% of the total annual drug budgets, but only 5% of units purchased, thus representing a very high proportion of their expenditures. In the aggregate, the 18 hospitals would have saved $3.1 million ($171,000 average per hospital had purchases of drugs with orphan designations been made at the 340B price. Because CAH claims for Medicare are reimbursed on a cost-basis, the Federal government is losing an opportunity for savings. Conclusion: The high prevalence of orphan drug use and considerable potential for cost reduction through the 340B program demonstrate the loss of benefit to the hospitals, Federal government and the states.

  8. Long-term Fertilization Structures Bacterial and Archaeal Communities along Soil Depth Gradient in a Paddy Soil

    Directory of Open Access Journals (Sweden)

    Yunfu Gu

    2017-08-01

    Full Text Available Soil microbes provide important ecosystem services. Though the effects of changes in nutrient availability due to fertilization on the soil microbial communities in the topsoil (tilled layer, 0–20 cm have been extensively explored, the effects on communities and their associations with soil nutrients in the subsoil (below 20 cm which is rarely impacted by tillage are still unclear. 16S rRNA gene amplicon sequencing was used to investigate bacterial and archaeal communities in a Pup-Calric-Entisol soil treated for 32 years with chemical fertilizer (CF and CF combined with farmyard manure (CFM, and to reveal links between soil properties and specific bacterial and archaeal taxa in both the top- and subsoil. The results showed that both CF and CFM treatments increased soil organic carbon (SOC, soil moisture (MO and total nitrogen (TN while decreased the nitrate_N content through the profile. Fertilizer applications also increased Olsen phosphorus (OP content in most soil layers. Microbial communities in the topsoil were significantly different from those in subsoil. Compared to the CF treatment, taxa such as Nitrososphaera, Nitrospira, and several members of Acidobacteria in topsoil and Subdivision 3 genera incertae sedis, Leptolinea, and Bellilinea in subsoil were substantially more abundant in CFM. A co-occurrence based network analysis demonstrated that SOC and OP were the most important soil parameters that positively correlated with specific bacterial and archaeal taxa in topsoil and subsoil, respectively. Hydrogenophaga was identified as the keystone genus in the topsoil, while genera Phenylobacterium and Steroidobacter were identified as the keystone taxa in subsoil. The taxa identified above are involved in the decomposition of complex organic compounds and soil carbon, nitrogen, and phosphorus transformations. This study revealed that the spatial variability of soil properties due to long-term fertilization strongly shapes the bacterial

  9. Segregated Planktonic and Bottom-Dwelling Archaeal Communities in High-Temperature Acidic/Sulfuric Ponds of the Tatun Volcano Group, Northern Taiwan

    Directory of Open Access Journals (Sweden)

    Ting-Wen Cheng

    2013-01-01

    Full Text Available Geothermal environments are characterized by dynamic redox and temperature fluctuations inherited from the exposure of deeply-sourced, hot, reducing fluids to low-temperature, oxidizing ambient environments. To investigate whether microbial assemblages shifted in response to the changes of a redox state within acidic hot ponds, we collected three paired water and sediment samples from the Tatun Volcano Group, assessed metabolic roles of community members, and correlated their functional capabilities with geochemical factors along depth. Molecular analyses revealed that Sulfolobus spp., Acidianus spp. and Vulcanisaeta spp. capable of respiring elemental sulfur under oxic and/or low-oxygen conditions were the major archaeal members in planktonic communities. In contrast, obligate anaerobic Caldisphaera spp. dominated over others in bottom-dwelling communities. Bacteria were only detected in one locality wherein the majority was affiliated with microaerophilic Hydrogenobaculum spp. Cluster analyses indicated that archaeal communities associated with sediments tended to cluster together and branch off those with water. In addition, the quantities of dissolved oxygen within the water column were substantially less than those in equilibrium with atmospheric oxygen, indicating a net oxygen consumption most likely catalyzed by microbial processes. These lines of evidence suggest that the segregation of planktonic from bottom-dwelling archaeal assemblages could be accounted for by the oxygen affinities inherited in individual archaeal members. Community assemblages in geothermal ecosystems would be often underrepresented without cautious sampling of both water and sediments.

  10. Cryo-EM Structure of the Archaeal 50S Ribosomal Subunit in Complex with Initiation Factor 6 and Implications for Ribosome Evolution

    Science.gov (United States)

    Greber, Basil J.; Boehringer, Daniel; Godinic-Mikulcic, Vlatka; Crnkovic, Ana; Ibba, Michael; Weygand-Durasevic, Ivana; Ban, Nenad

    2013-01-01

    Translation of mRNA into proteins by the ribosome is universally conserved in all cellular life. The composition and complexity of the translation machinery differ markedly between the three domains of life. Organisms from the domain Archaea show an intermediate level of complexity, sharing several additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter thermautotrophicus in complex with archaeal IF6 at 6.6 Å resolution using cryo-electron microscopy (EM). The structure provides detailed architectural insights into the 50S ribosomal subunit from a methanogenic archaeon through identification of the rRNA expansion segments and ribosomal proteins that are shared between this archaeal ribosome and eukaryotic ribosomes but are mostly absent in bacteria and in some archaeal lineages. Furthermore, the structure reveals that, in spite of highly divergent evolutionary trajectories of the ribosomal particle and the acquisition of novel functions of IF6 in eukaryotes, the molecular binding of IF6 on the ribosome is conserved between eukaryotes and archaea. The structure also provides a snapshot of the reductive evolution of the archaeal ribosome and offers new insights into the evolution of the translation system in archaea. PMID:22306461

  11. Children of a lesser god? Orphans, Vulnerable Children (OVCs) and ...

    African Journals Online (AJOL)

    Orphans, Vulnerable Children (OVCs) and poverty in Zambia: implications for social work practice. ... This paper attempts to present a conceptual linkage between a model of intervention of social protection and community practice model specifically locality development in terms of planning, organizing, decision making, ...

  12. Clinical evidence for orphan medicinal products-a cause for concern?

    NARCIS (Netherlands)

    Picavet, Eline; Cassiman, David; Hollak, Carla E.; Maertens, Johan A.; Simoens, Steven

    2013-01-01

    The difficulties associated with organising clinical studies for orphan medicinal products (OMPs) are plentiful. Recent debate on the long-term effectiveness of some OMPs, led us to question whether the initial standards for clinical evidence for OMPs, set by the European Medicines Agency (EMA) at

  13. Emotional well-being of orphans and vulnerable children in Ogun ...

    African Journals Online (AJOL)

    Previous research has found strong links between the emotional well-being of children and young people to their personal, social development and academic performance. This study examined stigmatisation, sexual involvement and school enrolment as predictors of emotional well-being of orphans and vulnerable ...

  14. The number of orphans in yeast and fly is drastically reduced by using combining searches in both proteomes and genomes

    OpenAIRE

    Basile, Walter; Elofsson, Arne

    2017-01-01

    The detection of orphans, i.e. genes without homologs in other species, is important as it provides a glimpse on the evolutionary processes that create novel genes. However, for an unbiased view of such de novo gene creation the detection of orphans needs to be accurate. The estimation of orphanicity, and in general the age determination of any gene, is dependent on two factors: (i) a method to detect homologs in a genome and (ii) a set of related genomes. Here, we set out to investigate how ...

  15. Interaction of extremophilic archaeal viruses with human and mouse complement system and viral biodistribution in mice

    DEFF Research Database (Denmark)

    Wu, Linping; Uldahl, Kristine Buch; Chen, Fangfang

    2017-01-01

    -dependent manner, but C3 deficiency has no overall effect on viral clearance by organs of the reticuloendothelial system on intravenous injection. However, splenic deposition was significantly higher in C3 knockout animals compared with the corresponding wild type mice. We discuss the potential application......Archaeal viruses offer exceptional biophysical properties for modification and exploration of their potential in bionanotechnology, bioengineering and nanotherapeutic developments. However, the interaction of archaeal viruses with elements of the innate immune system has not been explored, which...... surface, but factor H deposition is purely C3-dependent. This suggests that unlike some virulent pathogens Sulfolobus monocaudavirus 1 does not acquire factor H for protection. Complement activation with Sulfolobus monocaudavirus 1 also proceeds in murine sera through MBL-A/C as well as factor D...

  16. Response of Archaeal and Bacterial Soil Communities to Changes Associated with Outdoor Cattle Overwintering.

    Directory of Open Access Journals (Sweden)

    Alica Chroňáková

    Full Text Available Archaea and bacteria are important drivers for nutrient transformations in soils and catalyse the production and consumption of important greenhouse gases. In this study, we investigate changes in archaeal and bacterial communities of four Czech grassland soils affected by outdoor cattle husbandry. Two show short-term (3 years; STI and long-term impact (17 years; LTI, one is regenerating from cattle impact (REG and a control is unaffected by cattle (CON. Cattle manure (CMN, the source of allochthonous microbes, was collected from the same area. We used pyrosequencing of 16S rRNA genes to assess the composition of archaeal and bacterial communities in each soil type and CMN. Both short- and long- term cattle impact negatively altered archaeal and bacterial diversity, leading to increase of homogenization of microbial communities in overwintering soils over time. Moreover, strong shifts in the prokaryotic communities were observed in response to cattle overwintering, with the greatest impact on archaea. Oligotrophic and acidophilic microorganisms (e.g. Thaumarchaeota, Acidobacteria, and α-Proteobacteria dominated in CON and expressed strong negative response to increased pH, total C and N. Whereas copiotrophic and alkalophilic microbes (e.g. methanogenic Euryarchaeota, Firmicutes, Chloroflexi, Actinobacteria, and Bacteroidetes were common in LTI showing opposite trends. Crenarchaeota were also found in LTI, though their trophic interactions remain cryptic. Firmicutes, Bacteroidetes, Methanobacteriaceae, and Methanomicrobiaceae indicated the introduction and establishment of faecal microbes into the impacted soils, while Chloroflexi and Methanosarcinaceae suggested increased abundance of soil-borne microbes under altered environmental conditions. The observed changes in prokaryotic community composition may have driven corresponding changes in soil functioning.

  17. Response of Archaeal and Bacterial Soil Communities to Changes Associated with Outdoor Cattle Overwintering

    Science.gov (United States)

    Chroňáková, Alica; Schloter-Hai, Brigitte; Radl, Viviane; Endesfelder, David; Quince, Christopher; Elhottová, Dana; Šimek, Miloslav; Schloter, Michael

    2015-01-01

    Archaea and bacteria are important drivers for nutrient transformations in soils and catalyse the production and consumption of important greenhouse gases. In this study, we investigate changes in archaeal and bacterial communities of four Czech grassland soils affected by outdoor cattle husbandry. Two show short-term (3 years; STI) and long-term impact (17 years; LTI), one is regenerating from cattle impact (REG) and a control is unaffected by cattle (CON). Cattle manure (CMN), the source of allochthonous microbes, was collected from the same area. We used pyrosequencing of 16S rRNA genes to assess the composition of archaeal and bacterial communities in each soil type and CMN. Both short- and long- term cattle impact negatively altered archaeal and bacterial diversity, leading to increase of homogenization of microbial communities in overwintering soils over time. Moreover, strong shifts in the prokaryotic communities were observed in response to cattle overwintering, with the greatest impact on archaea. Oligotrophic and acidophilic microorganisms (e.g. Thaumarchaeota, Acidobacteria, and α-Proteobacteria) dominated in CON and expressed strong negative response to increased pH, total C and N. Whereas copiotrophic and alkalophilic microbes (e.g. methanogenic Euryarchaeota, Firmicutes, Chloroflexi, Actinobacteria, and Bacteroidetes) were common in LTI showing opposite trends. Crenarchaeota were also found in LTI, though their trophic interactions remain cryptic. Firmicutes, Bacteroidetes, Methanobacteriaceae, and Methanomicrobiaceae indicated the introduction and establishment of faecal microbes into the impacted soils, while Chloroflexi and Methanosarcinaceae suggested increased abundance of soil-borne microbes under altered environmental conditions. The observed changes in prokaryotic community composition may have driven corresponding changes in soil functioning. PMID:26274496

  18. Bacterial and Archaeal Community Dynamics at CO2-RICH Shallow-Sea Hydrothermal Vents (panarea, Italy)

    Science.gov (United States)

    Schubotz, F.; Huang, C.; Meyerdierks, A.; Amend, J.; Price, R. E.; Amann, R.; Hinrichs, K.; Summons, R. E.

    2013-12-01

    Shallow marine hydrothermal vents are highly dynamic systems with unique habitats that can support both chemosynthetic and photosynthetic communities at steep temperature and geochemical gradients. Here, we present a combined organic geochemical and microbiological approach to describe the microbial community composition and their metabolism at the CO2-rich shallow hydrothermal vents off Panarea Island, in Sicily. We investigated two contrasting hydrothermal environments: Hot Lake, a depression filled with hydrothermal fluids diffusing gradually out of the seafloor, with temperatures ranging from 40 to 70°C, and Blackpoint, a site with vigorous venting of hydrothermal gasses and fluids with temperatures as high as 135°C. At Hot Lake, Bacteria dominate the microbial community composition in the sediments. 16S rRNA clone libraries revealed Bacteriodetes-, Epsilonproteobacteria- and Deltaproteobacteria-related sequences as the most abundant members. Bacterial intact polar membrane lipids (IPLs) were dominated by the non-phosphorous containing ornithine lipids throughout all depths, indicating an important role of this aminolipid at elevated temperatures and/or low pH. At Hot Lake, archaeal IPLs were comprised mainly of glycosidic tetraethers and increased up to 20% of total IPLs with increasing temperature and depth. At the same site, archaeal 16S rRNA clone libraries were mainly comprised of Euryarchaea-affiliated sequences; crenarchaeotal sequences were only found in deeper sediment layers with temperatures of ca. 70°C. In contrast to Hot Lake, Archaea dominated sediments at the much hotter site at Blackpoint. Here, novel methylated H-shaped archaeal tetraethers, with multiple sugars as head groups, were the most abundant membrane lipids. Reports on these lipids in cultures are very limited, but their abundant occurrence at elevated temperatures suggests an important role in membrane homeostastis in thermophilic Archaea. Stable carbon isotope values of -35‰ to

  19. A study of archaeal enzymes involved in polar lipid synthesis linking amino acid sequence information, genomic contexts and lipid composition

    Directory of Open Access Journals (Sweden)

    Hiromi Daiyasu

    2005-01-01

    Full Text Available Cellular membrane lipids, of which phospholipids are the major constituents, form one of the characteristic features that distinguish Archaea from other organisms. In this study, we focused on the steps in archaeal phospholipid synthetic pathways that generate polar lipids such as archaetidylserine, archaetidylglycerol, and archaetidylinositol. Only archaetidylserine synthase (ASS, from Methanothermobacter thermautotrophicus, has been experimentally identified. Other enzymes have not been fully examined. Through database searching, we detected many archaeal hypothetical proteins that show sequence similarity to members of the CDP alcohol phosphatidyltransferase family, such as phosphatidylserine synthase (PSS, phosphatidylglycerol synthase (PGS and phosphatidylinositol synthase (PIS derived from Bacteria and Eukarya. The archaeal hypothetical proteins were classified into two groups, based on the sequence similarity. Members of the first group, including ASS from M. thermautotrophicus, were closely related to PSS. The rough agreement between PSS homologue distribution within Archaea and the experimentally identified distribution of archaetidylserine suggested that the hypothetical proteins are ASSs. We found that an open reading frame (ORF tends to be adjacent to that of ASS in the genome, and that the order of the two ORFs is conserved. The sequence similarity of phosphatidylserine decarboxylase to the product of the ORF next to the ASS gene, together with the genomic context conservation, suggests that the ORF encodes archaetidylserine decarboxylase, which may transform archaetidylserine to archaetidylethanolamine. The second group of archaeal hypothetical proteins was related to PGS and PIS. The members of this group were subjected to molecular phylogenetic analysis, together with PGSs and PISs and it was found that they formed two distinct clusters in the molecular phylogenetic tree. The distribution of members of each cluster within Archaea

  20. Effects of cash transfers on Children's health and social protection in Sub-Saharan Africa: differences in outcomes based on orphan status and household assets.

    Science.gov (United States)

    Crea, Thomas M; Reynolds, Andrew D; Sinha, Aakanksha; Eaton, Jeffrey W; Robertson, Laura A; Mushati, Phyllis; Dumba, Lovemore; Mavise, Gideon; Makoni, J C; Schumacher, Christina M; Nyamukapa, Constance A; Gregson, Simon

    2015-05-28

    Unconditional and conditional cash transfer programmes (UCT and CCT) show potential to improve the well-being of orphans and other children made vulnerable by HIV/AIDS (OVC). We address the gap in current understanding about the extent to which household-based cash transfers differentially impact individual children's outcomes, according to risk or protective factors such as orphan status and household assets. Data were obtained from a cluster-randomised controlled trial in eastern Zimbabwe, with random assignment to three study arms - UCT, CCT or control. The sample included 5,331 children ages 6-17 from 1,697 households. Generalized linear mixed models were specified to predict OVC health vulnerability (child chronic illness and disability) and social protection (birth registration and 90% school attendance). Models included child-level risk factors (age, orphan status); household risk factors (adults with chronic illnesses and disabilities, greater household size); and household protective factors (including asset-holding). Interactions were systematically tested. Orphan status was associated with decreased likelihood for birth registration, and paternal orphans and children for whom both parents' survival status was unknown were less likely to attend school. In the UCT arm, paternal orphans fared better in likelihood of birth registration compared with non-paternal orphans. Effects of study arms on outcomes were not moderated by any other risk or protective factors. High household asset-holding was associated with decreased likelihood of child's chronic illness and increased birth registration and school attendance, but household assets did not moderate the effects of cash transfers on risk or protective factors. Orphaned children are at higher risk for poor social protection outcomes even when cared for in family-based settings. UCT and CCT each produced direct effects on children's social protection which are not moderated by other child- and household

  1. Variation in levels of anxiety to dental treatment among nonorphan and orphan children living under different systems.

    Science.gov (United States)

    Chikkala, Jayanth; Chandrabhatla, Srinivas Kumar; Vanga, Narasimha Rao V

    2015-08-01

    It is essential to understand the factors influencing the level of anxiety to dental treatment among different children as it can influence seeking dental care. Here, we assessed the impact of parental loss on dental anxiety among 6-13-year-old children. A total of 444 children within the age group 6-13 years were selected. Group 1 consisted of orphan children living in government-run orphanages, Group 2 consisted of orphan children taken care by a person with a motherly relationship, Group 3 consisted of abandoned children living in private organization and Group 4 consisted of children living with their parents. Dental anxiety was measured using children's fear survey schedule-dental subscale and modified faces version of modified child dental anxiety scale. The highest number of anxious children were observed in Group 4 and the difference in the anxiety levels among the four groups was found to be highly statistically significant. Children living in government-run orphanages had least dental anxiety. All the orphans may not have the same anxiety levels and the environment of upbringing the orphans plays a significant role in the development of the anxiety.

  2. Effectiveness of the Group Play Therapy on the Insecure Attachment and Social Skills of Orphans in Ahvaz City

    Science.gov (United States)

    Mousavi, Bahareh; Safarzadeh, Sahar

    2016-01-01

    This study aimed to determine the effectiveness of the group play therapy on the insecure attachment and social skills of orphans in Ahvaz city. Statistical population included all orphans in Ahvaz city, of whom 30 students were selected whose scores in insecure attachment and in social skills were one standard deviation higher and one standard…

  3. Aspects of dealing with orphan sources

    International Nuclear Information System (INIS)

    Lovjagina, Irina

    2008-01-01

    Full text: Since Latvia joined the European Union (EU) in 2004, State have to apply EURATOM Council Directives on 2003/122/EURATOM with provisions of IAEA Code of Conduct for the Safety and Security of Radioactive Sources to comply with the Directive before 31 December 2005, to harmonize controls within European Community Member States. It is mentioned, that State have to bring into a force the laws, regulations and administrative provisions to comply with a requirements, to ensuring that each source is kept under control. Radiation sources are used around the world for variose applications, in industries, research, medicine and nuclear issues. Instead planned risk for normal use of those, for orphane sources often at the first stage of early response we have lot of uncertainties: unknown composition of radionuclides, wide activity frames, different construction and question of possible external contamination. Taken into account importance of this issue in the last few years in Latvia the control on custom, borders, scrapt yards control of transit of goods, incl. metals, were reinforced and normative basis is the country were improved. Finding of sources in scrapt metal or metal production/processing facilities become often events. Such sources may be dangerous not only to persons dealing with source, but local environment too, cause releases, contamination of facility and production, extra high costs for monitoring, cleaning up and wide variety of decontamination procedures applying. Prevention of radiological incidents starts from planning of our work, and transparency the whole 'life cycle' of source, from producer to disposal, recorded and verified, as well as notified to the Authorities. Early warning response (24-hours duty) and consultative phone service at Radiation Protection Authority is maintained; guidelines and working procedures within Authority and other Institutions involving were developed and implemented. As a result, Co-60, Cs-137 and Sr-90

  4. Archaeal rRNA operons, intron splicing and homing endonucleases, RNA polymerase operons and phylogeny

    DEFF Research Database (Denmark)

    Garrett, Roger Antony; Aagaard, Claus Sindbjerg; Andersen, Morten

    1994-01-01

    Over the past decade our laboratory has had a strong interest in defining the phylogenetic status of the archaea. This has involved determining and analysing the sequences of operons of both rRNAs and RNA polymerases and it led to the discovery of the first archaeal rRNA intron. What follows...

  5. Models of care for orphaned and separated children and upholding children’s rights: cross-sectional evidence from western Kenya

    Science.gov (United States)

    2014-01-01

    Background Sub-Saharan Africa is home to approximately 55 million orphaned children. The growing orphan crisis has overwhelmed many communities and has weakened the ability of extended families to meet traditional care-taking expectations. Other models of care and support have emerged in sub-Saharan Africa to address the growing orphan crisis, yet there is a lack of information on these models available in the literature. We applied a human rights framework using the United Nations Convention on the Rights of the Child to understand what extent children’s basic human rights were being upheld in institutional vs. community- or family-based care settings in Uasin Gishu County, Kenya. Methods The Orphaned and Separated Children’s Assessments Related to their Health and Well-Being Project is a 5-year cohort of orphaned children and adolescents aged ≤18 year. This descriptive analysis was restricted to baseline data. Chi-Square test was used to test for associations between categorical /dichotomous variables. Fisher’s exact test was also used if some cells had expected value of less than 5. Results Included in this analysis are data from 300 households, 19 Charitable Children’s Institutions (CCIs) and 7 community-based organizations. In total, 2871 children were enrolled and had baseline assessments done: 1390 in CCI’s and 1481 living in households in the community. We identified and described four broad models of care for orphaned and separated children, including: institutional care (sub-classified as ‘Pure CCI’ for those only providing residential care, ‘CCI-Plus’ for those providing both residential care and community-based supports to orphaned children , and ‘CCI-Shelter’ which are rescue, detention, or other short-term residential support), family-based care, community-based care and self-care. Children in institutional care (95%) were significantly (p children and uphold their rights. Family-based care plays an essential role; however

  6. Orphan Sources and Fresh Fallout: Virtual Exercise in Mobile Measurement (ORPEX)

    DEFF Research Database (Denmark)

    Dowdall, M.; Smethurst, M.A.; Andersson, Kasper Grann

    In recent years carborne gamma spectrometry has expanded from its role as a geological survey platform to serving as a useful asset in the field of emergency response to radiological and nuclear situations. Its two main applications are searching for orphan sources and for surveying in the afterm......In recent years carborne gamma spectrometry has expanded from its role as a geological survey platform to serving as a useful asset in the field of emergency response to radiological and nuclear situations. Its two main applications are searching for orphan sources and for surveying...... spectral data were generated for imaginary point sources and inserted into genu-ine carborne measurements from in the Trondheim area of Norway. Participants were presented with a typical software tool and data in a range of typical formats and asked to report the source locations and isotopes within a time...

  7. Diverse archaeal community of a bat guano pile in Domica Cave (Slovak Karst, Slovakia)

    Czech Academy of Sciences Publication Activity Database

    Chroňáková, Alica; Horák, Aleš; Elhottová, Dana; Krištůfek, Václav

    2009-01-01

    Roč. 54, č. 5 (2009), s. 436-446 ISSN 0015-5632 R&D Projects: GA MŠk LC06066 Institutional research plan: CEZ:AV0Z60660521; CEZ:AV0Z60220518 Keywords : archaeal community * bat guano pile * Domica Cave Subject RIV: EH - Ecology, Behaviour Impact factor: 0.978, year: 2009

  8. Civic engagement among orphans and non-orphans in five low- and middle-income countries.

    Science.gov (United States)

    Gray, Christine L; Pence, Brian W; Messer, Lynne C; Ostermann, Jan; Whetten, Rachel A; Thielman, Nathan M; O'Donnell, Karen; Whetten, Kathryn

    2016-10-11

    Communities and nations seeking to foster social responsibility in their youth are interested in understanding factors that predict and promote youth involvement in public activities. Orphans and separated children (OSC) are a vulnerable population whose numbers are increasing, particularly in resource-poor settings. Understanding whether and how OSC are engaged in civic activities is important for community and world leaders who need to provide care for OSC and ensure their involvement in sustainable development. The Positive Outcomes for Orphans study (POFO) is a multi-country, longitudinal cohort study of OSC randomly sampled from institution-based care and from family-based care, and of non-OSC sampled from the same study regions. Participants represent six sites in five low-and middle-income countries. We examined civic engagement activities and government trust among subjects > =16 years old at 90-month follow-up (approximately 7.5 years after baseline). We calculated prevalences and estimated the association between key demographic variables and prevalence of regular volunteer work using multivariable Poisson regression, with sampling weights to accounting for the complex sampling design. Among the 1,281 POFO participants > =16 who were assessed at 90-month follow-up, 45 % participated in regular community service or volunteer work; two-thirds of those volunteers did so on a strictly voluntary basis. While government trust was fairly high, at approximately 70 % for each level of government, participation in voting was only 15 % among those who were > =18 years old. We did not observe significant associations between demographic characteristics and regular volunteer work, with the exception of large variation by study site. As the world's leaders grapple with the many competing demands of global health, economic security, and governmental stability, the participation of today's youth in community and governance is essential for

  9. Protein Adaptations in Archaeal Extremophiles

    Directory of Open Access Journals (Sweden)

    Christopher J. Reed

    2013-01-01

    Full Text Available Extremophiles, especially those in Archaea, have a myriad of adaptations that keep their cellular proteins stable and active under the extreme conditions in which they live. Rather than having one basic set of adaptations that works for all environments, Archaea have evolved separate protein features that are customized for each environment. We categorized the Archaea into three general groups to describe what is known about their protein adaptations: thermophilic, psychrophilic, and halophilic. Thermophilic proteins tend to have a prominent hydrophobic core and increased electrostatic interactions to maintain activity at high temperatures. Psychrophilic proteins have a reduced hydrophobic core and a less charged protein surface to maintain flexibility and activity under cold temperatures. Halophilic proteins are characterized by increased negative surface charge due to increased acidic amino acid content and peptide insertions, which compensates for the extreme ionic conditions. While acidophiles, alkaliphiles, and piezophiles are their own class of Archaea, their protein adaptations toward pH and pressure are less discernible. By understanding the protein adaptations used by archaeal extremophiles, we hope to be able to engineer and utilize proteins for industrial, environmental, and biotechnological applications where function in extreme conditions is required for activity.

  10. Protein Adaptations in Archaeal Extremophiles

    Science.gov (United States)

    Reed, Christopher J.; Lewis, Hunter; Trejo, Eric; Winston, Vern; Evilia, Caryn

    2013-01-01

    Extremophiles, especially those in Archaea, have a myriad of adaptations that keep their cellular proteins stable and active under the extreme conditions in which they live. Rather than having one basic set of adaptations that works for all environments, Archaea have evolved separate protein features that are customized for each environment. We categorized the Archaea into three general groups to describe what is known about their protein adaptations: thermophilic, psychrophilic, and halophilic. Thermophilic proteins tend to have a prominent hydrophobic core and increased electrostatic interactions to maintain activity at high temperatures. Psychrophilic proteins have a reduced hydrophobic core and a less charged protein surface to maintain flexibility and activity under cold temperatures. Halophilic proteins are characterized by increased negative surface charge due to increased acidic amino acid content and peptide insertions, which compensates for the extreme ionic conditions. While acidophiles, alkaliphiles, and piezophiles are their own class of Archaea, their protein adaptations toward pH and pressure are less discernible. By understanding the protein adaptations used by archaeal extremophiles, we hope to be able to engineer and utilize proteins for industrial, environmental, and biotechnological applications where function in extreme conditions is required for activity. PMID:24151449

  11. Archaeal Life on Tangkuban Perahu-Sampling and Culture Growth in Indonesian Laboratories

    Directory of Open Access Journals (Sweden)

    SRI HANDAYANI

    2012-09-01

    Full Text Available The aim of the expedition to Tangkuban Perahu, West Java was to obtain archaeal samples from the solfatara fields located in Domas crater. This was one of the places, where scientists from the University of Regensburg Germany had formerly isolated Indonesian archaea, especially Thermoplasma and Sulfolobus species but not fully characterized. We collected five samples from mud holes with temperatures from 57 to 88 °C and pH of 1.5-2. A portion of each sample was grown at the University of Regensburg in modified Allen's medium at 80 °C. From four out of five samples enrichment cultures were obtained, autotrophically on elemental sulphur and heterotrophically on sulfur and yeast extract; electron micrographs are presented. In the laboratories of Universitas Indonesia the isolates were cultured at 55-60 °C in order to grow tetraetherlipid synthesizing archaea, both Thermoplasmatales and Sulfolobales. Here, we succeeded to culture the same type of archaeal cells, which had been cultured in Regensburg, probably a Sulfolobus species and in Freundt's medium, Thermoplasma species. The harvested cells are documented by phase contrast microscope equipped with a digital camera. Our next steps will be to further characterize genetically the cultured cells from Tangkuban Perahu isolates.

  12. Archaeal Life on Tangkuban Perahu- Sampling and Culture Growth in Indonesian Laboratories

    Directory of Open Access Journals (Sweden)

    SRI HANDAYANI

    2012-09-01

    Full Text Available The aim of the expedition to Tangkuban Perahu, West Java was to obtain archaeal samples from the solfatara fields located in Domas crater. This was one of the places, where scientists from the University of Regensburg Germany had formerly isolated Indonesian archaea, especially Thermoplasma and Sulfolobus species but not fully characterized. We collected five samples from mud holes with temperatures from 57 to 88 oC and pH of 1.5-2. A portion of each sample was grown at the University of Regensburg in modified Allen’s medium at 80 oC. From four out of five samples enrichment cultures were obtained, autotrophically on elemental sulphur and heterotrophically on sulfur and yeast extract; electron micrographs are presented. In the laboratories of Universitas Indonesia the isolates were cultured at 55-60 oC in order to grow tetraetherlipid synthesizing archaea, both Thermoplasmatales and Sulfolobales. Here, we succeeded to culture the same type of archaeal cells, which had been cultured in Regensburg, probably a Sulfolobus species and in Freundt’s medium, Thermoplasma species. The harvested cells are documented by phase contrast microscope equipped with a digital camera. Our next steps will be to further characterize genetically the cultured cells from Tangkuban Perahu isolates.

  13. Land-use systems affect Archaeal community structure and functional diversity in western Amazon soils

    Directory of Open Access Journals (Sweden)

    Acácio Aparecido Navarrete

    2011-10-01

    Full Text Available The study of the ecology of soil microbial communities at relevant spatial scales is primordial in the wide Amazon region due to the current land use changes. In this study, the diversity of the Archaea domain (community structure and ammonia-oxidizing Archaea (richness and community composition were investigated using molecular biology-based techniques in different land-use systems in western Amazonia, Brazil. Soil samples were collected in two periods with high precipitation (March 2008 and January 2009 from Inceptisols under primary tropical rainforest, secondary forest (5-20 year old, agricultural systems of indigenous people and cattle pasture. Denaturing gradient gel electrophoresis of polymerase chain reaction-amplified DNA (PCR-DGGE using the 16S rRNA gene as a biomarker showed that archaeal community structures in crops and pasture soils are different from those in primary forest soil, which is more similar to the community structure in secondary forest soil. Sequence analysis of excised DGGE bands indicated the presence of crenarchaeal and euryarchaeal organisms. Based on clone library analysis of the gene coding the subunit of the enzyme ammonia monooxygenase (amoA of Archaea (306 sequences, the Shannon-Wiener function and Simpson's index showed a greater ammonia-oxidizing archaeal diversity in primary forest soils (H' = 2.1486; D = 0.1366, followed by a lower diversity in soils under pasture (H' = 1.9629; D = 0.1715, crops (H' = 1.4613; D = 0.3309 and secondary forest (H' = 0.8633; D = 0.5405. All cloned inserts were similar to the Crenarchaeota amoA gene clones (identity > 95 % previously found in soils and sediments and distributed primarily in three major phylogenetic clusters. The findings indicate that agricultural systems of indigenous people and cattle pasture affect the archaeal community structure and diversity of ammonia-oxidizing Archaea in western Amazon soils.

  14. Archaeal Genome Guardians Give Insights into Eukaryotic DNA Replication and Damage Response Proteins

    Directory of Open Access Journals (Sweden)

    David S. Shin

    2014-01-01

    Full Text Available As the third domain of life, archaea, like the eukarya and bacteria, must have robust DNA replication and repair complexes to ensure genome fidelity. Archaea moreover display a breadth of unique habitats and characteristics, and structural biologists increasingly appreciate these features. As archaea include extremophiles that can withstand diverse environmental stresses, they provide fundamental systems for understanding enzymes and pathways critical to genome integrity and stress responses. Such archaeal extremophiles provide critical data on the periodic table for life as well as on the biochemical, geochemical, and physical limitations to adaptive strategies allowing organisms to thrive under environmental stress relevant to determining the boundaries for life as we know it. Specifically, archaeal enzyme structures have informed the architecture and mechanisms of key DNA repair proteins and complexes. With added abilities to temperature-trap flexible complexes and reveal core domains of transient and dynamic complexes, these structures provide insights into mechanisms of maintaining genome integrity despite extreme environmental stress. The DNA damage response protein structures noted in this review therefore inform the basis for genome integrity in the face of environmental stress, with implications for all domains of life as well as for biomanufacturing, astrobiology, and medicine.

  15. Sexual Behavior Among Orphaned Adolescents in Western Kenya: A Comparison of Institutional- and Family-Based Care Settings.

    Science.gov (United States)

    Embleton, Lonnie; Nyandat, Joram; Ayuku, David; Sang, Edwin; Kamanda, Allan; Ayaya, Samuel; Nyandiko, Winstone; Gisore, Peter; Vreeman, Rachel; Atwoli, Lukoye; Galarraga, Omar; Ott, Mary A; Braitstein, Paula

    2017-04-01

    This study sought to assess whether risky sexual behaviors and sexual exploitation of orphaned adolescents differed between family-based and institutional care environments in Uasin Gishu County, Kenya. We analyzed baseline data from a cohort of orphaned adolescents aged 10-18 years living in 300 randomly selected households and 19 charitable children's institutions. The primary outcomes were having ever had consensual sex, number of sex partners, transactional sex, and forced sex. Multivariate logistic regression compared these between participants in institutional care and family-based care while adjusting for age, sex, orphan status, importance of religion, caregiver support and supervision, school attendance, and alcohol and drug use. This analysis included 1,365 participants aged ≥10 years: 712 (52%) living in institutional environments and 653 (48%) in family-based care. Participants in institutional care were significantly less likely to report engaging in transactional sex (adjusted odds ratio, .46; 95% confidence interval, .3-.72) or to have experienced forced sex (adjusted odds ratio, .57; 95% confidence interval, .38-.88) when controlling for age, sex, and orphan status. These associations remained when adjusting for additional variables. Orphaned adolescents living in family-based care in Uasin Gishu, Kenya, may be at increased risk of transactional sex and sexual violence compared to those in institutional care. Institutional care may reduce vulnerabilities through the provision of basic material needs and adequate standards of living that influence adolescents' sexual risk-taking behaviors. The use of single items to assess outcomes and nonexplicit definition of sex suggest the findings should be interpreted with caution. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  16. Psychological Distress amongst AIDS-Orphaned Children in Urban South Africa

    Science.gov (United States)

    Cluver, Lucie; Gardner, Frances; Operario, Don

    2007-01-01

    Background: South Africa is predicted to have 2.3 million children orphaned by Acquired Immune Deficiency Syndrome (AIDS) by 2020 (Actuarial Society of South Africa, 2005). There is little knowledge about impacts of AIDS-related bereavement on children, to aid planning of services. This study aimed to investigate psychological consequences of AIDS…

  17. Inventory of orphan oil and natural gas wells in the Dover and Gautreau Village areas of Westmorland County, New Brunswick

    International Nuclear Information System (INIS)

    Brennan, J.

    1999-01-01

    In 1997, the Government of New Brunswick conducted an inventory of orphan wells in the vicinity of Dover and Gautreau Village in Westmorland County. The term orphan wells refers to those oil and natural gas wells which have been abandoned and have no owner. An abandoned well refers to those wells that are no longer active and have been properly plugged. A total of 19 orphan wells were discovered with the help of landowners and historical maps. These wells are believed to have dated from 1860 to 1906. The locations of the wells were determined digitally using the Global Positioning System. The environmental conditions around the orphan wells were evaluated and classified according to a proposed system used by the State of Michigan. The wells were separated into three categories based on the amount of petroleum contamination of soil and water. Water contamination was further divided into contamination of groundwater and surface water. 7 refs., 34 figs

  18. Structure of Pfu Pop5, an archaeal RNase P protein.

    Science.gov (United States)

    Wilson, Ross C; Bohlen, Christopher J; Foster, Mark P; Bell, Charles E

    2006-01-24

    We have used NMR spectroscopy and x-ray crystallography to determine the three-dimensional structure of PF1378 (Pfu Pop5), one of four protein subunits of archaeal RNase P that shares a homolog in the eukaryotic enzyme. RNase P is an essential and ubiquitous ribonucleoprotein enzyme required for maturation of tRNA. In bacteria, the enzyme's RNA subunit is responsible for cleaving the single-stranded 5' leader sequence of precursor tRNA molecules (pre-tRNA), whereas the protein subunit assists in substrate binding. Although in bacteria the RNase P holoenzyme consists of one large catalytic RNA and one small protein subunit, in archaea and eukarya the enzyme contains several (> or =4) protein subunits, each of which lacks sequence similarity to the bacterial protein. The functional role of the proteins is poorly understood, as is the increased complexity in comparison to the bacterial enzyme. Pfu Pop5 has been directly implicated in catalysis by the observation that it pairs with PF1914 (Pfu Rpp30) to functionally reconstitute the catalytic domain of the RNA subunit. The protein adopts an alpha-beta sandwich fold highly homologous to the single-stranded RNA binding RRM domain. Furthermore, the three-dimensional arrangement of Pfu Pop5's structural elements is remarkably similar to that of the bacterial protein subunit. NMR spectra have been used to map the interaction of Pop5 with Pfu Rpp30. The data presented permit tantalizing hypotheses regarding the role of this protein subunit shared by archaeal and eukaryotic RNase P.

  19. Characterization of Olkiluoto bacterial and archaeal communities by 454 pyrosequencing

    Energy Technology Data Exchange (ETDEWEB)

    Bomberg, M.; Nyyssoenen, M.; Itaevaara, M. [VTT Technical Research Centre of Finland, Espoo (Finland)

    2012-06-15

    Recent advancement in sequencing technologies, 'Next Generation Sequencing', such as FLX 454 pyrosequencing has made it possible to obtain large amounts of sequence data where previously only few sequences could be obtained. This technique is especially useful for the study of community composition of uncultured microbial populations in environmental samples. In this project, the FLX 454 pyrosequencing technique was used to obtain up to 20 000 16S rRNA sequences or 10 000 mRNA sequences from each sample for identification of the microbial species composition as well as for comparison of the microbial communities between different samples. This project focused on the characterization of active microbial communities in the groundwater at the final disposal site of high radioactive wastes in Olkiluoto by FLX 454 pyrosequencing of the bacterial and archaeal ribosomal RNA as well as of the mRNA transcripts of the dsrB gene and mcrA gene of sulphate reducing bacteria and methanogenic archaea, respectively. Specific emphasis was put on studying the relationship of active and latent sulphate reducers and methanogens by qPCR due to their important roles in deep geobiochemical processes connected to copper corrosion. Seven packered boreholes were sampled anaerobically in Olkiluoto during 2009-2010. Groundwater was pumped from specific depths and the microbial cells werecollected by filtration on a membrane. Active microbial communities were studied based on RNA extracted from the membranes and translated to copy DNA, followed by sequencing by 454 Tag pyrosequencing. A total of 27 different bacterial and 17 archaeal taxonomic groups were detected.

  20. Characterization of Olkiluoto bacterial and archaeal communities by 454 pyrosequencing

    Energy Technology Data Exchange (ETDEWEB)

    Bomberg, M; Nyyssoenen, M; Itaevaara, M [VTT Technical Research Centre of Finland, Espoo (Finland)

    2012-06-15

    Recent advancement in sequencing technologies, 'Next Generation Sequencing', such as FLX 454 pyrosequencing has made it possible to obtain large amounts of sequence data where previously only few sequences could be obtained. This technique is especially useful for the study of community composition of uncultured microbial populations in environmental samples. In this project, the FLX 454 pyrosequencing technique was used to obtain up to 20 000 16S rRNA sequences or 10 000 mRNA sequences from each sample for identification of the microbial species composition as well as for comparison of the microbial communities between different samples. This project focused on the characterization of active microbial communities in the groundwater at the final disposal site of high radioactive wastes in Olkiluoto by FLX 454 pyrosequencing of the bacterial and archaeal ribosomal RNA as well as of the mRNA transcripts of the dsrB gene and mcrA gene of sulphate reducing bacteria and methanogenic archaea, respectively. Specific emphasis was put on studying the relationship of active and latent sulphate reducers and methanogens by qPCR due to their important roles in deep geobiochemical processes connected to copper corrosion. Seven packered boreholes were sampled anaerobically in Olkiluoto during 2009-2010. Groundwater was pumped from specific depths and the microbial cells werecollected by filtration on a membrane. Active microbial communities were studied based on RNA extracted from the membranes and translated to copy DNA, followed by sequencing by 454 Tag pyrosequencing. A total of 27 different bacterial and 17 archaeal taxonomic groups were detected.

  1. Characterization of Olkiluoto bacterial and archaeal communities by 454 pyrosequencing

    International Nuclear Information System (INIS)

    Bomberg, M.; Nyyssoenen, M.; Itaevaara, M.

    2012-06-01

    Recent advancement in sequencing technologies, 'Next Generation Sequencing', such as FLX 454 pyrosequencing has made it possible to obtain large amounts of sequence data where previously only few sequences could be obtained. This technique is especially useful for the study of community composition of uncultured microbial populations in environmental samples. In this project, the FLX 454 pyrosequencing technique was used to obtain up to 20 000 16S rRNA sequences or 10 000 mRNA sequences from each sample for identification of the microbial species composition as well as for comparison of the microbial communities between different samples. This project focused on the characterization of active microbial communities in the groundwater at the final disposal site of high radioactive wastes in Olkiluoto by FLX 454 pyrosequencing of the bacterial and archaeal ribosomal RNA as well as of the mRNA transcripts of the dsrB gene and mcrA gene of sulphate reducing bacteria and methanogenic archaea, respectively. Specific emphasis was put on studying the relationship of active and latent sulphate reducers and methanogens by qPCR due to their important roles in deep geobiochemical processes connected to copper corrosion. Seven packered boreholes were sampled anaerobically in Olkiluoto during 2009-2010. Groundwater was pumped from specific depths and the microbial cells werecollected by filtration on a membrane. Active microbial communities were studied based on RNA extracted from the membranes and translated to copy DNA, followed by sequencing by 454 Tag pyrosequencing. A total of 27 different bacterial and 17 archaeal taxonomic groups were detected

  2. Nonblocking and orphan free message logging protocols

    Science.gov (United States)

    Alvisi, Lorenzo; Hoppe, Bruce; Marzullo, Keith

    1992-12-01

    Currently existing message logging protocols demonstrate a classic pessimistic vs. optimistic tradeoff. We show that the optimistic-pessimistic tradeoff is not inherent to the problem of message logging. We construct a message-logging protocol that has the positive features of both optimistic and pessimistic protocol: our protocol prevents orphans and allows simple failure recovery; however, it requires no blocking in failure-free runs. Furthermore, this protocol does not introduce any additional message overhead as compared to one implemented for a system in which messages may be lost but processes do not crash.

  3. Process and outcome evaluation of a community intervention for orphan adolescents in western Kenya.

    Science.gov (United States)

    Hallfors, Denise D; Cho, Hyunsan; Mbai, Isabella; Milimo, Benson; Itindi, Janet

    2012-10-01

    We conducted a 2-year pilot randomized controlled trial (N = 105) in a high HIV-prevalence area in rural western Kenya to test whether providing young orphan adolescents with uniforms, school fees, and community visitors improves school retention and reduces HIV risk factors. The trial was a community intervention, limited to one community. In this paper, we examined intervention implementation and its association with outcomes using longitudinal data. We used both quantitative and qualitative methods to evaluate the community-based model for orphan HIV prevention, with recommendations for future studies. Despite promising effects after 1 year, GEE analyses showed null effects after 2 years. Volunteer community visitors, a key element of the intervention, showed little of the expected effect although qualitative reports documented active assistance to prevent orphans' school absence. For future research, we recommend capturing the transition to high school, a larger sample size, and biomarker data to add strength to the research design. We also recommend a school-based intervention approach to improve implementation and reduce infrastructure costs. Finally, we recommend evaluating nurses as agents for improving school attendance and preventing dropout because of their unique ability to address critical biopsychosocial problems.

  4. HUNTING THE PARENT OF THE ORPHAN STREAM: IDENTIFYING STREAM MEMBERS FROM LOW-RESOLUTION SPECTROSCOPY

    International Nuclear Information System (INIS)

    Casey, Andrew R.; Da Costa, Gary; Keller, Stefan C.; Maunder, Elizabeth

    2013-01-01

    We present candidate K-giant members in the Orphan Stream that have been identified from low-resolution data taken with the AAOmega spectrograph on the Anglo-Australian Telescope. From modest signal-to-noise spectra and independent cuts in photometry, kinematics, gravity, and metallicity we yield self-consistent, highly probable stream members. We find a revised stream distance of 22.5 ± 2.0 kpc near the celestial equator and our kinematic signature peaks at V GSR = 82.1 ± 1.4 km s –1 . The observed velocity dispersion of our most probable members is consistent with arising from the velocity uncertainties alone. This indicates that at least along this line of sight, the Orphan Stream is kinematically cold. Our data indicate an overall stream metallicity of [Fe/H] = –1.63 ± 0.19 dex which is more metal-rich than previously found and unbiased by spectral type. Furthermore, the significant metallicity dispersion displayed by our most probable members, σ([Fe/H]) = 0.56 dex, suggests that the unidentified Orphan Stream parent is a dSph satellite. We highlight likely members for high-resolution spectroscopic follow-up.

  5. Process and Outcome Evaluation of a Community Intervention for Orphan Adolescents in Western Kenya

    Science.gov (United States)

    Hallfors, Denise D.; Cho, Hyunsan; Mbai, Isabella; Milimo, Benson; Itindi, Janet

    2012-01-01

    We conducted a 2-year pilot randomized controlled trial (N = 105) in a high HIV-prevalence area in rural western Kenya to test whether providing young orphan adolescents with uniforms, school fees, and community visitors improves school retention and reduces HIV risk factors. The trial was a community intervention, limited to one community. In this paper, we examined intervention implementation and its association with outcomes using longitudinal data. We used both quantitative and qualitative methods to evaluate the community-based model for orphan HIV prevention, with recommendations for future studies. Despite promising effects after 1 year, GEE analyses showed null effects after 2 years. Volunteer community visitors, a key element of the intervention, showed little of the expected effect although qualitative reports documented active assistance to prevent orphans' school absence. For future research, we recommend capturing the transition to high school, a larger sample size, and biomarker data to add strength to the research design. We also recommend a school-based intervention approach to improve implementation and reduce infrastructure costs. Finally, we recommend evaluating nurses as agents for improving school attendance and preventing dropout because of their unique ability to address critical biopsychosocial problems. PMID:22350730

  6. Bacterial and Archaeal Diversity in the Gastrointestinal Tract of the North American Beaver (Castor canadensis.

    Directory of Open Access Journals (Sweden)

    Robert J Gruninger

    Full Text Available The North American Beaver (Castor canadensis is the second largest living rodent and an iconic symbol of Canada. The beaver is a semi-aquatic browser whose diet consists of lignocellulose from a variety of plants. The beaver is a hindgut fermenter and has an enlarged ceacum that houses a complex microbiome. There have been few studies examining the microbial diversity in gastrointestinal tract of hindgut fermenting herbivores. To examine the bacterial and archaeal communities inhabiting the gastrointestinal tract of the beaver, the microbiome of the ceacum and feaces was examined using culture-independent methods. DNA from the microbial community of the ceacum and feaces of 4 adult beavers was extracted, and the16S rRNA gene was sequenced using either bacterial or archaeal specific primers. A total of 1447 and 1435 unique bacterial OTUs were sequenced from the ceacum and feaces, respectively. On average, the majority of OTUs within the ceacum were classified as Bacteroidetes (49.2% and Firmicutes (47.6%. The feaces was also dominated by OTUs from Bacteroidetes (36.8% and Firmicutes (58.9%. The composition of bacterial community was not significantly different among animals. The composition of the ceacal and feacal microbiome differed, but this difference is due to changes in the abundance of closely related OTUs, not because of major differences in the taxonomic composition of the communities. Within these communities, known degraders of lignocellulose were identified. In contrast, to the bacterial microbiome, the archaeal community was dominated by a single species of methanogen, Methanosphaera stadtmanae. The data presented here provide the first insight into the microbial community within the hindgut of the beaver.

  7. Bacterial and Archaeal Diversity in the Gastrointestinal Tract of the North American Beaver (Castor canadensis).

    Science.gov (United States)

    Gruninger, Robert J; McAllister, Tim A; Forster, Robert J

    2016-01-01

    The North American Beaver (Castor canadensis) is the second largest living rodent and an iconic symbol of Canada. The beaver is a semi-aquatic browser whose diet consists of lignocellulose from a variety of plants. The beaver is a hindgut fermenter and has an enlarged ceacum that houses a complex microbiome. There have been few studies examining the microbial diversity in gastrointestinal tract of hindgut fermenting herbivores. To examine the bacterial and archaeal communities inhabiting the gastrointestinal tract of the beaver, the microbiome of the ceacum and feaces was examined using culture-independent methods. DNA from the microbial community of the ceacum and feaces of 4 adult beavers was extracted, and the16S rRNA gene was sequenced using either bacterial or archaeal specific primers. A total of 1447 and 1435 unique bacterial OTUs were sequenced from the ceacum and feaces, respectively. On average, the majority of OTUs within the ceacum were classified as Bacteroidetes (49.2%) and Firmicutes (47.6%). The feaces was also dominated by OTUs from Bacteroidetes (36.8%) and Firmicutes (58.9%). The composition of bacterial community was not significantly different among animals. The composition of the ceacal and feacal microbiome differed, but this difference is due to changes in the abundance of closely related OTUs, not because of major differences in the taxonomic composition of the communities. Within these communities, known degraders of lignocellulose were identified. In contrast, to the bacterial microbiome, the archaeal community was dominated by a single species of methanogen, Methanosphaera stadtmanae. The data presented here provide the first insight into the microbial community within the hindgut of the beaver.

  8. Quantitative and phylogenetic study of the Deep Sea Archaeal Group in sediments of the arctic mid-ocean spreading ridge

    Directory of Open Access Journals (Sweden)

    Steffen Leth eJørgensen

    2013-10-01

    Full Text Available In marine sediments archaea often constitute a considerable part of the microbial community, of which the Deep Sea Archaeal Group (DSAG is one of the most predominant. Despite their high abundance no members from this archaeal group have so far been characterized and thus their metabolism is unknown. Here we show that the relative abundance of DSAG marker genes can be correlated with geochemical parameters, allowing prediction of both the potential electron donors and acceptors of these organisms. We estimated the abundance of 16S rRNA genes from Archaea, Bacteria and DSAG in 52 sediment horizons from two cores collected at the slow-spreading Arctic Mid-Ocean Ridge, using qPCR. The results indicate that members of the DSAG make up the entire archaeal population in certain horizons and constitute up to ~ 50% of the total microbial community. The quantitative data were correlated to 30 different geophysical and geochemical parameters obtained from the same sediment horizons. We observed a significant correlation between the relative abundance of DSAG 16S rRNA genes and the content of organic carbon (p < 0.0001. Further, significant co-variation with iron oxide, and dissolved iron and manganese (all p < 0.0000, indicated a direct or indirect link to iron and manganese cycling. Neither of these parameters correlated with the relative abundance of archaeal or bacterial 16S rRNA genes, nor did any other major electron donor or acceptor measured. Phylogenetic analysis of DSAG 16S rRNA gene sequences reveals three monophyletic lineages with no apparent habitat-specific distribution. In this study we support the hypothesis that members of the DSAG are tightly linked to the content of organic carbon and directly or indirectly involved in the cycling of iron and/or manganese compounds. Further, we provide a molecular tool to assess their abundance in environmental samples and enrichment cultures.

  9. Motives for Taking Orphan Children into a Foster (Guardian) Family

    Science.gov (United States)

    Kozlova, T. Z.

    2013-01-01

    Research in Russia on the opinions of guardians and experts of the department of guardianship examines the motives that people have for taking orphan children into their homes. The data indicate that about 80 percent of the guardians are grandmothers taking care of their grandchildren, whose parents have been stripped of their parental rights.…

  10. Thermal conductivity and rectification in asymmetric archaeal lipid membranes

    Science.gov (United States)

    Youssefian, Sina; Rahbar, Nima; Van Dessel, Steven

    2018-05-01

    Nature employs lipids to construct nanostructured membranes that self-assemble in an aqueous environment to separate the cell interior from the exterior environment. Membrane composition changes among species and according to environmental conditions, which allows organisms to occupy a wide variety of different habitats. Lipid bilayers are phase-change materials that exhibit strong thermotropic and lyotropic phase behavior in an aqueous environment, which may also cause thermal rectification. Among different types of lipids, archaeal lipids are of great interest due to their ability to withstand extreme conditions. In this paper, nonequilibrium molecular dynamics simulations were employed to study the nanostructures and thermal properties of different archaeols and to investigate thermal rectification effects in asymmetric archaeal membranes. In particular, we are interested in understanding the role of bridged phytanyl chains and cyclopentane groups in controlling the phase transition temperature and heat flow across the membrane. Our results indicate that the bridged phytanyl chains decrease the molecular packing of lipids, whereas the existence of cyclopentane rings on the tail groups increases the molecular packing by enhancing the interactions between isoprenoid chains. We found that macrocyclic archaeols have the highest thermal conductivity, whereas macrocyclic archaeols with two cyclopentane rings have the lowest. The effect of the temperature on the variation of thermal conductivity was found to be progressive. Our results further indicate that small thermal rectification effects occur in asymmetric archaeol bilayer membranes at around 25 K temperature gradient. The calculated thermal rectification factor was around 0.09 which is in the range of rectification factor obtained experimentally for nanostructures such as carbon nanotubes (0.07). Such phenomena may be of biological significance and could also be optimized for use in various engineering

  11. Archaeal and bacterial communities respond differently to environmental gradients in anoxic sediments of a California hypersaline lake, the Salton Sea.

    Science.gov (United States)

    Swan, Brandon K; Ehrhardt, Christopher J; Reifel, Kristen M; Moreno, Lilliana I; Valentine, David L

    2010-02-01

    Sulfidic, anoxic sediments of the moderately hypersaline Salton Sea contain gradients in salinity and carbon that potentially structure the sedimentary microbial community. We investigated the abundance, community structure, and diversity of Bacteria and Archaea along these gradients to further distinguish the ecologies of these domains outside their established physiological range. Quantitative PCR was used to enumerate 16S rRNA gene abundances of Bacteria, Archaea, and Crenarchaeota. Community structure and diversity were evaluated by terminal restriction fragment length polymorphism (T-RFLP), quantitative analysis of gene (16S rRNA) frequencies of dominant microorganisms, and cloning and sequencing of 16S rRNA. Archaea were numerically dominant at all depths and exhibited a lesser response to environmental gradients than that of Bacteria. The relative abundance of Crenarchaeota was low (0.4 to 22%) at all depths but increased with decreased carbon content and increased salinity. Salinity structured the bacterial community but exerted no significant control on archaeal community structure, which was weakly correlated with total carbon. Partial sequencing of archaeal 16S rRNA genes retrieved from three sediment depths revealed diverse communities of Euryarchaeota and Crenarchaeota, many of which were affiliated with groups previously described from marine sediments. The abundance of these groups across all depths suggests that many putative marine archaeal groups can tolerate elevated salinity (5.0 to 11.8% [wt/vol]) and persist under the anaerobic conditions present in Salton Sea sediments. The differential response of archaeal and bacterial communities to salinity and carbon patterns is consistent with the hypothesis that adaptations to energy stress and availability distinguish the ecologies of these domains.

  12. Defense Islands in Bacterial and Archaeal Genomes and Prediction of Novel Defense Systems ▿†‡

    Science.gov (United States)

    Makarova, Kira S.; Wolf, Yuri I.; Snir, Sagi; Koonin, Eugene V.

    2011-01-01

    The arms race between cellular life forms and viruses is a major driving force of evolution. A substantial fraction of bacterial and archaeal genomes is dedicated to antivirus defense. We analyzed the distribution of defense genes and typical mobilome components (such as viral and transposon genes) in bacterial and archaeal genomes and demonstrated statistically significant clustering of antivirus defense systems and mobile genes and elements in genomic islands. The defense islands are enriched in putative operons and contain numerous overrepresented gene families. A detailed sequence analysis of the proteins encoded by genes in these families shows that many of them are diverged variants of known defense system components, whereas others show features, such as characteristic operonic organization, that are suggestive of novel defense systems. Thus, genomic islands provide abundant material for the experimental study of bacterial and archaeal antivirus defense. Except for the CRISPR-Cas systems, different classes of defense systems, in particular toxin-antitoxin and restriction-modification systems, show nonrandom clustering in defense islands. It remains unclear to what extent these associations reflect functional cooperation between different defense systems and to what extent the islands are genomic “sinks” that accumulate diverse nonessential genes, particularly those acquired via horizontal gene transfer. The characteristics of defense islands resemble those of mobilome islands. Defense and mobilome genes are nonrandomly associated in islands, suggesting nonadaptive evolution of the islands via a preferential attachment-like mechanism underpinned by the addictive properties of defense systems such as toxins-antitoxins and an important role of horizontal mobility in the evolution of these islands. PMID:21908672

  13. Insights into archaeal evolution and symbiosis from the genomes of a Nanoarchaeon and its crenarchaeal host from Yellowstone National Park

    Energy Technology Data Exchange (ETDEWEB)

    Podar, Mircea [ORNL; Graham, David E [ORNL; Reysenbach, Anna-Louise [Portland State University; Koonin, Eugene [National Center for Biotechnology Information; Wolf, Yuri [National Center for Biotechnology Information; Makarova, Kira S. [National Center for Biotechnology Information

    2013-01-01

    A hyperthemophilic member of the Nanoarchaeota from Obsidian Pool, a thermal feature in Yellowstone National Park was characterized using single cell isolation and sequencing, together with its putative host, a Sulfolobales archaeon. This first representative of a non-marine Nanoarchaeota (Nst1) resembles Nanoarchaeum equitans by lacking most biosynthetic capabilities, the two forming a deep-branching archaeal lineage. However, the Nst1 genome is over 20% larger, encodes a complete gluconeogenesis pathway and a full complement of archaeal flagellum proteins. Comparison of the two genomes suggests that the marine and terrestrial Nanoarchaeota lineages share a common ancestor that was already a symbiont of another archaeon. With a larger genome, a smaller repertoire of split protein encoding genes and no split non-contiguous tRNAs, Nst1 appears to have experienced less severe genome reduction than N. equitans. The inferred host of Nst1 is potentially autotrophic, with a streamlined genome and simplified central and energetic metabolism as compared to other Sulfolobales. The two distinct Nanoarchaeota-host genomic data sets offer insights into the evolution of archaeal symbiosis and parasitism and will further enable studies of the cellular and molecular mechanisms of these relationships.

  14. Genomic Comparison of Two Family-Level Groups of the Uncultivated NAG1 Archaeal Lineage from Chemically and Geographically Disparate Hot Springs

    Directory of Open Access Journals (Sweden)

    Eric D. Becraft

    2017-10-01

    Full Text Available Recent progress based on single-cell genomics and metagenomic investigations of archaea in a variety of extreme environments has led to significant advances in our understanding of the diversity, evolution, and metabolic potential of archaea, yet the vast majority of archaeal diversity remains undersampled. In this work, we coordinated single-cell genomics with metagenomics in order to construct a near-complete genome from a deeply branching uncultivated archaeal lineage sampled from Great Boiling Spring (GBS in the U.S. Great Basin, Nevada. This taxon is distantly related (distinct families to an archaeal genome, designated “Novel Archaeal Group 1” (NAG1, which was extracted from a metagenome recovered from an acidic iron spring in Yellowstone National Park (YNP. We compared the metabolic predictions of the NAG1 lineage to better understand how these archaea could inhabit such chemically distinct environments. Similar to the NAG1 population previously studied in YNP, the NAG1 population from GBS is predicted to utilize proteins as a primary carbon source, ferment simple carbon sources, and use oxygen as a terminal electron acceptor under oxic conditions. However, GBS NAG1 populations contained distinct genes involved in central carbon metabolism and electron transfer, including nitrite reductase, which could confer the ability to reduce nitrite under anaerobic conditions. Despite inhabiting chemically distinct environments with large variations in pH, GBS NAG1 populations shared many core genomic and metabolic features with the archaeon identified from YNP, yet were able to carve out a distinct niche at GBS.

  15. РSYCHOLOGICAL AND PSYCHOPHYSIOLOGICAL CHARACTERISTICS OF ORPHANS AND CHILDREN WITHOUT PARENTAL CARE

    Directory of Open Access Journals (Sweden)

    Н. А. Киселева

    2014-01-01

    Full Text Available The article analyzes the psychological and psychophy-siological characteristics of children living in the Children’s Village-SOS and in the Children’s Home. Particular emotional and cognitive areas, self image, creativity, mental stress and neurotic tendencies in orphans and children without parental care are characterized in the article. Age and gender differences in the parameters studied are detected.Purpose. The purpose is to discoverage and gender aspects of the psychological and psychophysiological characteristics of children of orphans and children without parental care living in the Children’s Village-SOS and in the Children’s Home.Methodology. Empirical research of gender particular features of psychic state of alarmness of adopted children with the help of testing.Results. The significant gender differences in terms of phobias and fears were revealed; the significant gender differences on the scale of the emotional content of images were revealed; the study revealed the trends toward significant difference by gender in the manifestation of sleep disorders and autonomic dysfunction;the significant age-related differences in terms of increased anxiety, autonomic dysfunction, eating disorders were revealed.Practical implications. The results are of interest to the science workers of age psychology, gender psychology, social psychology, to the workers of the children’s institutions and to the organizations occupied with medical-social-psychological-pedagogycal maintenance of orphans and children without parental care.Purchase on Elibrary.ru > Buy now

  16. Systematic review of available evidence on 11 high-priced inpatient orphan drugs

    NARCIS (Netherlands)

    T.A. Kanters (Tim A.); C. de Sonneville (Caroline); W.K. Redekop (Ken); L. van Hakkaart-van Roijen (Leona)

    2013-01-01

    markdownabstract__Abstract__ __Background__: Attention for Evidence Based Medicine (EBM) is growing, but evidence for orphan drugs is argued to be limited and inferior. This study systematically reviews the available evidence on clinical effectiveness, costeffectiveness and budget impact for

  17. Characterization of soil bacterial, archaeal and fungal communities inhabiting archaeological human-impacted layers at Monte Iato settlement (Sicily, Italy).

    Science.gov (United States)

    Siles, José A; Öhlinger, Birgit; Cajthaml, Tomas; Kistler, Erich; Margesin, Rosa

    2018-01-30

    Microbial communities in human-impacted soils of ancient settlements have been proposed to be used as ecofacts (bioindicators) of different ancient anthropogenic activities. In this study, bacterial, archaeal and fungal communities inhabiting soil of three archaic layers, excavated at the archaeological site on Monte Iato (Sicily, Italy) and believed to have been created in a chronological order in archaic times in the context of periodic cultic feasts, were investigated in terms of (i) abundance (phospholipid fatty acid (PLFA) analysis and quantitative PCR)), (ii) carbon(C)-source consumption patterns (Biolog-Ecoplates) and (iii) diversity and community composition (Illumina amplicon sequencing). PLFA analyses demonstrated the existence of living bacteria and fungi in the soil samples of all three layers. The upper layer showed increased levels of organic C, which were not concomitant with an increment in the microbial abundance. In taxonomic terms, the results indicated that bacterial, archaeal and fungal communities were highly diverse, although differences in richness or diversity among the three layers were not detected for any of the communities. However, significantly different microbial C-source utilization patterns and structures of bacterial, archaeal and fungal communities in the three layers confirmed that changing features of soil microbial communities reflect different past human activities.

  18. Bacterial and Archaeal Lipids Recovered from Subsurface Evaporites of Dalangtan Playa on the Tibetan Plateau and Their Astrobiological Implications

    Science.gov (United States)

    Cheng, Ziye; Xiao, Long; Wang, Hongmei; Yang, Huan; Li, Jingjing; Huang, Ting; Xu, Yi; Ma, Nina

    2017-11-01

    Qaidam Basin (Tibetan Plateau) is considered an applicable analogue to Mars with regard to sustained extreme aridity and abundant evaporites. To investigate the possibility of the preservation of microbial lipids under these Mars analog conditions, we conducted a mineralogical and organic geochemistry study on samples collected from two Quaternary sections in Dalangtan Playa, northwestern Qaidam Basin, which will enhance our understanding of the potential preservation of molecular biomarkers on Mars. Two sedimentary units were identified along two profiles: one salt unit characterized by a predominance of gypsum and halite, and one detrital unit with a decrease of gypsum and halite and enrichment in siliciclastic minerals. Bacterial fatty acids and archaeal acyclic diether and tetraether membrane lipids were detected, and they varied throughout the sections in concentration and abundance. Bacterial and archaeal biomolecules indicate a dominance of Gram-positive bacteria and halophilic archaea in this hypersaline ecosystem that is similar to those in other hypersaline environments. Furthermore, the abundance of bacterial lipids decreases with the increase of salinity, whereas archaeal lipids showed a reverse trend. The detection of microbial lipids in hypersaline environments would indicate, for example on Mars, a high potential for the detection of microbial biomarkers in evaporites over geological timescales.

  19. Growth status of Korean orphans raised in the affluent West: anthropometric trend, multivariate determinants, and descriptive comparison with their North and South Korean peers.

    Science.gov (United States)

    Schwekendiek, Daniel J

    2017-04-01

    This paper investigates the trend in height among adult Korean orphans who were adopted in early life into affluent Western nations. Final heights of 148 females were analyzed based on a Korean government survey conducted in 2008. Height of the orphans was descriptively compared against final heights of South and North Koreans. Furthermore, statistical determinants of orphan height were investigated in multivariate regressions. Mean height of Korean orphans was 160.44 cm (SD 5.89), which was higher than that of South Koreans at 158.83 cm (SD 5.01). Both Korean orphans and South Koreans were taller than North Koreans at 155.30 cm (SD 4.94). However, height of Korean orphans stagnated at around 160-161 cm while those of North and South Koreans improved over time. In the regression analysis, the socioeconomic status of the adoptive family was statistically significant in all models, while dummies for the adoptive nations and age at adoption were insignificant. This study shows that the mean final height of women experiencing extreme environmental improvements in early-life is capped at 160-161 cm, tentatively suggesting that social stress factors in the host nation or early-life factors in the birth nation might have offset some of the environmental enrichment effects achieved through intercountry adoption.

  20. The oral hygiene status of institution dwelling orphans in Benin City ...

    African Journals Online (AJOL)

    Introduction: Orphans like other vulnerable children face a number of challenges including limited or no access to basic health care including oral health care, which is one of their unmet health care needs. Neglected oral health care is associated with the development and progression of periodontal diseases among others.

  1. The CanOE strategy: integrating genomic and metabolic contexts across multiple prokaryote genomes to find candidate genes for orphan enzymes.

    Directory of Open Access Journals (Sweden)

    Adam Alexander Thil Smith

    2012-05-01

    Full Text Available Of all biochemically characterized metabolic reactions formalized by the IUBMB, over one out of four have yet to be associated with a nucleic or protein sequence, i.e. are sequence-orphan enzymatic activities. Few bioinformatics annotation tools are able to propose candidate genes for such activities by exploiting context-dependent rather than sequence-dependent data, and none are readily accessible and propose result integration across multiple genomes. Here, we present CanOE (Candidate genes for Orphan Enzymes, a four-step bioinformatics strategy that proposes ranked candidate genes for sequence-orphan enzymatic activities (or orphan enzymes for short. The first step locates "genomic metabolons", i.e. groups of co-localized genes coding proteins catalyzing reactions linked by shared metabolites, in one genome at a time. These metabolons can be particularly helpful for aiding bioanalysts to visualize relevant metabolic data. In the second step, they are used to generate candidate associations between un-annotated genes and gene-less reactions. The third step integrates these gene-reaction associations over several genomes using gene families, and summarizes the strength of family-reaction associations by several scores. In the final step, these scores are used to rank members of gene families which are proposed for metabolic reactions. These associations are of particular interest when the metabolic reaction is a sequence-orphan enzymatic activity. Our strategy found over 60,000 genomic metabolons in more than 1,000 prokaryote organisms from the MicroScope platform, generating candidate genes for many metabolic reactions, of which more than 70 distinct orphan reactions. A computational validation of the approach is discussed. Finally, we present a case study on the anaerobic allantoin degradation pathway in Escherichia coli K-12.

  2. Comparison of the Psychological Characteristics of Adaptation in Orphan Students of Initial Learning Stage to Adaptation Potential in Students Brought up in Families

    Directory of Open Access Journals (Sweden)

    Zamorueva V.V.,

    2014-08-01

    Full Text Available We present a study of psychological characteristics of preadult orphans, their psychological adaptation to the conditions of learning in high school compared to the norm population (students living in family. We assumed that the level of adaptation of the orphan students is significantly smaller than in other students, because of their special life circumstances (maternal deprivation, living in residential care institutions, sometimes bad heredity, lack of life skills in everyday issues, personal problems. The results of the survey of 49 orphan students (26 girls and 23 boys and 49 first-year students brought up by parents (28 girls and 21 boys, confirmed this hypothesis and allow us to tell that orphan students need special psychological help in the learning process in high school to grow at a personal and professional level.

  3. Plant genotype-specific archaeal and bacterial endophytes but similar Bacillus antagonists colonize Mediterranean olive trees

    Directory of Open Access Journals (Sweden)

    Henry eMueller

    2015-03-01

    Full Text Available Endophytes have an intimate and often symbiotic interaction with their hosts. Less is known about the composition and function of endophytes in trees. In order to evaluate our hypothesis that plant genotype and origin have a strong impact on both, endophytes of leaves from 10 Olea europaea L. cultivars from the Mediterranean basin growing at a single agricultural site in Spain and from nine wild olive trees located in natural habitats in Greece, Cyprus and on Madeira Island were studied. The composition of the bacterial endophytic communities as revealed by 16S rRNA gene amplicon sequencing and the subsequent PCoA analysis showed a strong correlation to the plant genotypes. The bacterial distribution patterns were congruent with the plant origins in Eastern and Western areas of the Mediterranean basin. Subsequently, the endophytic microbiome of wild olives was shown to be closely related to those of cultivated olives of the corresponding geographic origins. The olive leaf endosphere harbored mostly Proteobacteria, followed by Firmicutes, Actinobacteria and Bacteroidetes. The detection of a high portion of archaeal taxa belonging to the phyla Thaumarchaeota, Crenarchaeota and Euryarchaeota in the amplicon libraries was an unexpected discovery, which was confirmed by quantitative real-time PCR revealing an archaeal portion of up to 35.8%. Although the function of these Archaea for their host plant remains speculative, this finding suggests a significant relevance of archaeal endophytes for plant-microbe interactions. In addition, the antagonistic potential of culturable endophytes was determined; all isolates with antagonistic activity against the olive-pathogenic fungus Verticillium dahliae Kleb. belong to Bacillus amyloliquefaciens. In contrast to the specific global structural diversity, BOX-fingerprints of the antagonistic Bacillus isolates were highly similar and independent of the olive genotype from which they were isolated.

  4. Extension style in the Orphan Basin during the Mesozoic North Atlantic rifting

    Science.gov (United States)

    Gouiza, Mohamed; Hall, Jeremy

    2013-04-01

    The Orphan Basin, lying along the Newfoundland passive continental margin, has formed in Mesozoic time during the opening of the North Atlantic Ocean and the breakup of Iberia/Eurasia from North America. Regional deep seismic reflection profiles across the basin indicate that the Neoproterozoic basement has been affected by repeated extensional episodes between the Late Triassic/Jurassic and the Early Cretaceous. Deformation initiated in the eastern part of the Orphan basin in the Jurassic and migrated toward the west in the Early Cretaceous, resulting in numerous rift structures filled with Jurassic-Lower Cretaceous syn-rift successions and sealed by thick Upper Cretaceous-Cenozoic post-rift sediments. The seismic data show an extremely attenuated crust underneath the eastern and western part of the deep basin, forming two sub-basins associated with the development of rifting. The two sub-basins are separated by a wide structural high with a relatively thick crust and are bounded to the west by the continental shelf domain. Restoration of the Orphan Basin along a 2D crustal section (520 km long), yields a total amount of stretching of about 144 km, while the total crustal thinning indicates an extension of around 250 km, assuming mass conservation along the section and an initial crustal thickness of 28 km. Brittle deformation accommodated by normal faults is documented in the seismic profiles and affected essentially the present-day upper portion of the crust, and represents only 60% of the total extension which thinned the Orphan crust. The remaining crustal thinning must involve other deformation processes which are not (easily) recognizable in the seismic data. We propose two models that could explain discrepancies between brittle deformation and total crustal thinning during lithospheric extension. The first model assumes the reactivation of pre-rift inherited structures, which act as crustal-scale detachments during the early stages of rifting. The second

  5. An archaeal tRNA-synthetase complex that enhances aminoacylation under extreme conditions

    DEFF Research Database (Denmark)

    Godinic-Mikulcic, Vlatka; Jaric, Jelena; Hausmann, Corinne D

    2011-01-01

    Aminoacyl-tRNA synthetases (aaRSs) play an integral role in protein synthesis, functioning to attach the correct amino acid with its cognate tRNA molecule. AaRSs are known to associate into higher-order multi-aminoacyl-tRNA synthetase complexes (MSC) involved in archaeal and eukaryotic translatio...... of a complex between MtSerRS and MtArgRS provides a means by which methanogenic archaea can optimize an early step in translation under a wide range of extreme environmental conditions....

  6. Orphaned and Abused Youth Are Vulnerable to Pregnancy and Suicide Risk

    Science.gov (United States)

    Zapata, Lauren B.; Kissin, Dmitry M.; Bogoliubova, Olga; Yorick, Roman V.; Kraft, Joan Marie; Jamieson, Denise J.; Marchbanks, Polly A.; Hillis, Susan D.

    2013-01-01

    Objective: Little is known about the magnitude and consequences of violence against children for those living outside family care. We sought to estimate the frequency of childhood abuse and examine its association with lifetime pregnancy involvement (LPI) and past year suicide ideation among orphaned youth. Methods: We analyzed data collected via…

  7. Orphan Sources. Extending Radiological Protection outside the Regulatory Framework

    Energy Technology Data Exchange (ETDEWEB)

    Eugenio Gil [Deputy Director for Emergency, Spanish Nuclear Safety Council (Spain)

    2006-07-01

    Radioactive sources that are not under appropriate regulatory control-Orphan sources- can result in a number of undesirable consequences including human health impacts, socio-psychological impacts, political and economic impacts, as well as environmental impacts. Many countries are now in the process of introducing the necessary measures to regain an appropriate level of control over them. For a variety of historical and economic reasons, there could already be sources in any specific country that are not within the usual regulatory system. Some of these may be known about, others may not. Therefore a national strategy is needed to ascertain the likelihood and magnitude of the issue of radioactive source control problem within a country and the priorities necessary to address the problems identified. A well-developed plan for improving control over all relevant radioactive sources tailored to the national situation will ensure optimum use of resources such as time, money and personnel. It will allow these limited resources to be allocated appropriately to ensure that control is first regained over those sources presenting the highest risks. This lecture shows a way to develop an appropriate national strategy for regaining control over orphan sources. The methodology described in this lecture is basically based in the IAEA Recommendations. (author)

  8. Orphan Sources. Extending Radiological Protection outside the Regulatory Framework

    International Nuclear Information System (INIS)

    Eugenio Gil

    2006-01-01

    Radioactive sources that are not under appropriate regulatory control-Orphan sources- can result in a number of undesirable consequences including human health impacts, socio-psychological impacts, political and economic impacts, as well as environmental impacts. Many countries are now in the process of introducing the necessary measures to regain an appropriate level of control over them. For a variety of historical and economic reasons, there could already be sources in any specific country that are not within the usual regulatory system. Some of these may be known about, others may not. Therefore a national strategy is needed to ascertain the likelihood and magnitude of the issue of radioactive source control problem within a country and the priorities necessary to address the problems identified. A well-developed plan for improving control over all relevant radioactive sources tailored to the national situation will ensure optimum use of resources such as time, money and personnel. It will allow these limited resources to be allocated appropriately to ensure that control is first regained over those sources presenting the highest risks. This lecture shows a way to develop an appropriate national strategy for regaining control over orphan sources. The methodology described in this lecture is basically based in the IAEA Recommendations. (author)

  9. Widespread distribution of archaeal reverse gyrase in thermophilic bacteria suggests a complex history of vertical inheritance and lateral gene transfers

    Directory of Open Access Journals (Sweden)

    Céline Brochier-Armanet

    2006-01-01

    Full Text Available Reverse gyrase, an enzyme of uncertain funtion, is present in all hyperthermophilic archaea and bacteria. Previous phylogenetic studies have suggested that the gene for reverse gyrase has an archaeal origin and was transferred laterally (LGT to the ancestors of the two bacterial hyperthermophilic phyla, Thermotogales and Aquificales. Here, we performed an in-depth analysis of the evolutionary history of reverse gyrase in light of genomic progress. We found genes coding for reverse gyrase in the genomes of several thermophilic bacteria that belong to phyla other than Aquificales and Thermotogales. Several of these bacteria are not, strictly speaking, hyperthermophiles because their reported optimal growth temperatures are below 80 °C. Furthermore, we detected a reverse gyrase gene in the sequence of the large plasmid of Thermus thermophilus strain HB8, suggesting a possible mechanism of transfer to the T. thermophilus strain HB8 involving plasmids and transposases. The archaeal part of the reverse gyrase tree is congruent with recent phylogenies of the archaeal domain based on ribosomal proteins or RNA polymerase subunits. Although poorly resolved, the complete reverse gyrase phylogeny suggests an ancient acquisition of the gene by bacteria via one or two LGT events, followed by its secondary distribution by LGT within bacteria. Finally, several genes of archaeal origin located in proximity to the reverse gyrase gene in bacterial genomes have bacterial homologues mostly in thermophiles or hyperthermophiles, raising the possibility that they were co-transferred with the reverse gyrase gene. Our new analysis of the reverse gyrase history strengthens the hypothesis that the acquisition of reverse gyrase may have been a crucial evolutionary step in the adaptation of bacteria to high-temperature environments. However, it also questions the role of this enzyme in thermophilic bacteria and the selective advantage its presence could provide.

  10. Widespread distribution of archaeal reverse gyrase in thermophilic bacteria suggests a complex history of vertical inheritance and lateral gene transfers.

    Science.gov (United States)

    Brochier-Armanet, Céline; Forterre, Patrick

    2007-05-01

    Reverse gyrase, an enzyme of uncertain funtion, is present in all hyperthermophilic archaea and bacteria. Previous phylogenetic studies have suggested that the gene for reverse gyrase has an archaeal origin and was transferred laterally (LGT) to the ancestors of the two bacterial hyperthermophilic phyla, Thermotogales and Aquificales. Here, we performed an in-depth analysis of the evolutionary history of reverse gyrase in light of genomic progress. We found genes coding for reverse gyrase in the genomes of several thermophilic bacteria that belong to phyla other than Aquificales and Thermotogales. Several of these bacteria are not, strictly speaking, hyperthermophiles because their reported optimal growth temperatures are below 80 degrees C. Furthermore, we detected a reverse gyrase gene in the sequence of the large plasmid of Thermus thermophilus strain HB8, suggesting a possible mechanism of transfer to the T. thermophilus strain HB8 involving plasmids and transposases. The archaeal part of the reverse gyrase tree is congruent with recent phylogenies of the archaeal domain based on ribosomal proteins or RNA polymerase subunits. Although poorly resolved, the complete reverse gyrase phylogeny suggests an ancient acquisition of the gene by bacteria via one or two LGT events, followed by its secondary distribution by LGT within bacteria. Finally, several genes of archaeal origin located in proximity to the reverse gyrase gene in bacterial genomes have bacterial homologues mostly in thermophiles or hyperthermophiles, raising the possibility that they were co-transferred with the reverse gyrase gene. Our new analysis of the reverse gyrase history strengthens the hypothesis that the acquisition of reverse gyrase may have been a crucial evolutionary step in the adaptation of bacteria to high-temperature environments. However, it also questions the role of this enzyme in thermophilic bacteria and the selective advantage its presence could provide.

  11. [Shift of focus in the financing of Hungarian drugs. Reimbursement for orphan drugs for treating rare diseases: financing of enzyme replacement therapy in Hungary].

    Science.gov (United States)

    Szegedi, Márta; Molnár, Mária Judit; Boncz, Imre; Kosztolányi, György

    2014-11-02

    Focusing on the benefits of patients with rare disease the authors analysed the aspects of orphan medicines financed in the frame of the Hungarian social insurance system in 2012 in order to make the consumption more rational, transparent and predictable. Most of the orphan drugs were financed in the frame of compassionate use by the reimbursement system. Consequently, a great deal of crucial problems occurred in relation to the unconventional subsidized method, especially in the case of the highest cost enzyme replacement therapies. On the base of the findings, proposals of the authors are presented for access to orphan drugs, fitting to the specific professional, economical and ethical aspects of this unique field of the health care system. The primary goal is to provide a suitable subsidized method for the treatment of rare disease patients with unmet medical needs. The financial modification of orphans became indispensible in Hungary. Professionals from numerous fields dealing with rare disease patients' care expressed agreement on the issue. Transforming the orphan medicines' financial structure has been initiated according to internationally shared principles.

  12. Effects of oxytetracycline on archaeal community, and tetracycline resistance genes in anaerobic co-digestion of pig manure and wheat straw.

    Science.gov (United States)

    Wang, Xiaojuan; Pan, Hongjia; Gu, Jie; Qian, Xun; Gao, Hua; Qin, Qingjun

    2016-12-01

    In this study, the effects of different concentrations of oxytetracycline (OTC) on biogas production, archaeal community structure, and the levels of tetracycline resistance genes (TRGs) were investigated in the anaerobic co-digestion products of pig manure and wheat straw. PCR denaturing gradient gel electrophoresis analysis and real-time quantitative polymerase chain reaction (RT-qPCR) (PCR) were used to detect the archaeal community structure and the levels of four TRGs: tet(M), tet(Q), tet(W), and tet(C). The results showed that anaerobic co-digestion with OTC at concentrations of 60, 100, and 140 mg/kg (dry weight of pig manure) reduced the cumulative biogas production levels by 9.9%, 10.4%, and 14.1%, respectively, compared with that produced by the control, which lacked the antibiotic. The addition of OTC substantially modified the structure of the archaeal community. Two orders were identified by phylogenetic analysis, that is, Pseudomonadales and Methanomicrobiales, and the methanogen present during anaerobic co-digestion with OTC may have been resistant to OTC. The abundances of tet(Q) and tet(W) genes increased as the OTC concentration increased, whereas the abundances of tet(M) and tet(C) genes decreased as the OTC concentration increased.

  13. Identification of GH15 Family Thermophilic Archaeal Trehalases That Function within a Narrow Acidic-pH Range.

    Science.gov (United States)

    Sakaguchi, Masayoshi; Shimodaira, Satoru; Ishida, Shin-Nosuke; Amemiya, Miko; Honda, Shotaro; Sugahara, Yasusato; Oyama, Fumitaka; Kawakita, Masao

    2015-08-01

    Two glucoamylase-like genes, TVN1315 and Ta0286, from the archaea Thermoplasma volcanium and T. acidophilum, respectively, were expressed in Escherichia coli. The gene products, TVN1315 and Ta0286, were identified as archaeal trehalases. These trehalases belong to the CAZy database family GH15, although they have putative (α/α)6 barrel catalytic domain structures similar to those of GH37 and GH65 family trehalases from other organisms. These newly identified trehalases function within a narrow range of acidic pH values (pH 3.2 to 4.0) and at high temperatures (50 to 60°C), and these enzymes display Km values for trehalose higher than those observed for typical trehalases. These enzymes were inhibited by validamycin A; however, the inhibition constants (Ki) were higher than those of other trehalases. Three TVN1315 mutants, corresponding to E408Q, E571Q, and E408Q/E571Q mutations, showed reduced activity, suggesting that these two glutamic acid residues are involved in trehalase catalysis in a manner similar to that of glucoamylase. To date, TVN1315 and Ta0286 are the first archaeal trehalases to be identified, and this is the first report of the heterologous expression of GH15 family trehalases. The identification of these trehalases could extend our understanding of the relationships between the structure and function of GH15 family enzymes as well as glycoside hydrolase family enzymes; additionally, these enzymes provide insight into archaeal trehalose metabolism. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Structure and genome organization of AFV2, a novel archaeal lipothrixvirus with unusual terminal and core structures

    DEFF Research Database (Denmark)

    Häring, Monika; Vestergaard, Gisle Alberg; Brügger, Kim

    2005-01-01

    A novel filamentous virus, AFV2, from the hyperthermophilic archaeal genus Acidianus shows structural similarity to lipothrixviruses but differs from them in its unusual terminal and core structures. The double-stranded DNA genome contains 31,787 bp and carries eight open reading frames homologous...

  15. Inhibition of Estrogen Receptor Action by the Orphan Receptors, SHP and DAX-1

    National Research Council Canada - National Science Library

    DiRenzo, James

    2003-01-01

    .... In support of DoD grant # DAMD17-99-1-9163, we present our findings regarding the mechanisms by which two orphan nuclear receptors, SHP and DAX-1 inhibit the actions of ER-alpha and ER-beta action...

  16. Orphan disease: Cherubism, optic atrophy, and short stature.

    Science.gov (United States)

    Jeevanandham, Balaji; Ramachandran, Rajoo; Dhanapal, Vignesh; Subramanian, Ilanchezhian; Sai, Venkata

    2018-01-01

    A 12-year-old female presented with complaints of progressive visual impairment in both her eyes. On clinical examination, she was short for her age and her ophthalmoscopic examination revealed bilateral optic atrophy. Computed tomography of the patient revealed multiple expansile lytic lesions of mandible suggesting cherubism. The optic atrophy was confirmed on magnetic resonance imaging, which additionally revealed bilateral retrocerebellar arachnoid cysts. This association of cherubism with optic atrophy and short stature was grouped as orphan disease by National Institutes of Health and only one case was reported in the literature so far.

  17. Review The mental health of children orphaned by AIDS: a review of ...

    African Journals Online (AJOL)

    This paper reviews research on the mental health and psychological outcomes of children who are orphaned by AIDS. Studies are limited, scattered and often unpublished. The review focuses on research which is quantitative and based on primary research with uninfected children who are parentally bereaved by AIDS.

  18. Identity and diversity of archaeal communities during anaerobic co-digestion of chicken feathers and other animal wastes.

    Science.gov (United States)

    Xia, Yun; Massé, Daniel I; McAllister, Tim A; Kong, Yunhong; Seviour, Robert; Beaulieu, Carole

    2012-04-01

    Digestion of raw feathers in anaerobic digesters inoculated with adapted swine manure, slaughterhouse sludge or dairy manure was investigated using twelve 42-L anaerobic digesters at 25°C. After 120days 74%, 49% and 40% added feathers were converted to methane in swine manure, dairy manure and slaughterhouse sludge anaerobic digesters respectively. 16S rRNA gene clone library analyses identified twenty-one operational taxonomic units containing clone sequences from 5 genera, 5 families and 2 phyla of members of the Archaea from 158 sequenced clones. Fluorescence insitu hybridization revealed that methanogens from the Methanomicrobiales, Methanosarcinales and Methanobacteriales constituted a major fraction (>78%) of these Archaea. A high correlation was seen between the distribution of functional archaeal groups and the NH(3)-N levels of digester mixed liquors. The compositions of archaeal communities fed different substrates were statistically significantly different (P<0.05). Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  19. Shifts in bacterial and archaeal community structures during the batch biomethanation of Ulva biomass under mesophilic conditions.

    Science.gov (United States)

    Kim, Jaai; Jung, Heejung; Lee, Changsoo

    2014-10-01

    Mesophilic biomethanation of Ulva biomass was performed in a batch bioreactor, and a high organic removal of 77% was obtained on the basis of chemical oxygen demand (COD) after a month of operation. The estimated methane yield was 0.43 ± 0.02 L CH4/g COD(removed) which is close to the theoretical methane potential. Transitions of bacterial and archaeal community structures, associated with process performance data, were investigated using a combination of molecular fingerprinting and biostatistical tools. During the operation, archaeal community structure had no significant changes while bacterial community structure shifted continuously and dynamically. The reactor completely stabilized volatile fatty acids (primarily acetate and propionate) accumulated from the acidogenesis phase, with Methanosaeta- and Methanolinea-related microbes respectively being the main aceticlastic and hydrogenotrophic methanogens. Methanolinea- and Syntrophobacter-related populations were likely the key members to form a syntrophic propionate-degrading consortium. A Methanolinea-related population was likely the dominant methane producer in the experimental reactor. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Archaeal phylogeny: reexamination of the phylogenetic position of Archaeoglobus fulgidus in light of certain composition-induced artifacts

    Science.gov (United States)

    Woese, C. R.; Achenbach, L.; Rouviere, P.; Mandelco, L.

    1991-01-01

    A major and too little recognized source of artifact in phylogenetic analysis of molecular sequence data is compositional difference among sequences. The problem becomes particularly acute when alignments contain ribosomal RNAs from both mesophilic and thermophilic species. Among prokaryotes the latter are considerably higher in G + C content than the former, which often results in artificial clustering of thermophilic lineages and their being placed artificially deep in phylogenetic trees. In this communication we review archaeal phylogeny in the light of this consideration, focusing in particular on the phylogenetic position of the sulfate reducing species Archaeoglobus fulgidus, using both 16S rRNA and 23S rRNA sequences. The analysis shows clearly that the previously reported deep branching of the A. fulgidus lineage (very near the base of the euryarchaeal side of the archaeal tree) is incorrect, and that the lineage actually groups with a previously recognized unit that comprises the Methanomicrobiales and extreme halophiles.

  1. The involvement of extended families in the wellness of orphans in a primary school in Masvingo city in Zimbabwe

    OpenAIRE

    2014-01-01

    D.Phil. (Career and Life Orientation) The study focuses on how extended families are involved on the wellness of orphans at a primary school in Masvingo City in Zimbabwe. Through an ethnographic research design, the study aimed to establish the involvement of extended families and challenges they face in rendering support and care to orphans. This study draws an intensive ethnographic research interrogative approach through observations, interviews, researcher made test and document analys...

  2. The use of drawings to facilitate interviews with orphaned children in ...

    African Journals Online (AJOL)

    determine their needs. In this study an orphan is a child of under 18 who has lost one or both ... The psychological trauma experienced by the children ..... no one to take the children to the clinic/hospital, and because of a lack of funds for medicine: 'I feel sick, I ..... Adolescent resilience: A framework for understanding healthy.

  3. Inhibition of Estrogen Receptor Action by the Orphan Receptors, SHP and DAX-1

    National Research Council Canada - National Science Library

    DiRenzo, James

    2002-01-01

    In support of DoD grant # DAMD17-99-1-9163, we present our progress towards understanding the function of mechanisms of action of two orphan nuclear receptors, SHP and DAX-I as inhibitors of ER alpha and ER beta action...

  4. Orphan Stars Found in Long Galaxy Tail

    Science.gov (United States)

    2007-09-01

    Astronomers have found evidence that stars have been forming in a long tail of gas that extends well outside its parent galaxy. This discovery suggests that such "orphan" stars may be much more prevalent than previously thought. The comet-like tail was observed in X-ray light with NASA's Chandra X-ray Observatory and in optical light with the Southern Astrophysical Research (SOAR) telescope in Chile. The feature extends for more than 200,000 light years and was created as gas was stripped from a galaxy called ESO 137-001 that is plunging toward the center of Abell 3627, a giant cluster of galaxies. "This is one of the longest tails like this we have ever seen," said Ming Sun of Michigan State University, who led the study. "And, it turns out that this is a giant wake of creation, not of destruction." Chandra X-ray Image of ESO 137-001 and Tail in Abell 3627 Chandra X-ray Image of ESO 137-001 and Tail in Abell 3627 The observations indicate that the gas in the tail has formed millions of stars. Because the large amounts of gas and dust needed to form stars are typically found only within galaxies, astronomers have previously thought it unlikely that large numbers of stars would form outside a galaxy. "This isn't the first time that stars have been seen to form between galaxies," said team member Megan Donahue, also of MSU. "But the number of stars forming here is unprecedented." The evidence for star formation in this tail includes 29 regions of ionized hydrogen glowing in optical light, thought to be from newly formed stars. These regions are all downstream of the galaxy, located in or near the tail. Two Chandra X-ray sources are near these regions, another indication of star formation activity. The researchers believe the orphan stars formed within the last 10 million years or so. The stars in the tail of this fast-moving galaxy, which is some 220 million light years away, would be much more isolated than the vast majority of stars in galaxies. H-alpha Image of

  5. Path of a patient with a rare diagnosis: regulatory documents and organization of the process of treatment and diagnosis of an orphan disease in the Russian Federation

    OpenAIRE

    S. I. Kutsev

    2017-01-01

    The main legislative document of the organization of medical care in the Russian Federation “On fundamental healthcare principles in the Russian Federation” and points related to the rare (orphan) diseases are  discussed. The organization of care, rules for managing a federal  registry of orphan diseases and routing of patients with main orphan nosological forms for which treatment is known are presented.

  6. The use of rites of passage in strengthening the psychosocial wellbeing of orphaned children in Botswana.

    Science.gov (United States)

    Thamuku, Masego; Daniel, Marguerite

    2012-10-01

    Children who have been bereaved in the context of AIDS may experience many challenges to their psychosocial wellbeing. Programmes to help orphaned children are usually anchored in child rights. As the individual focus of rights-based approaches is inept in African collectivist culture, NGOs tend to make use of group approaches in psychosocial support programmes. One orphan-strengthening programme in Botswana, called the Ark for Children, uses rites of passage and rites of affirmation as part of a therapeutic retreat. This study explored how rites of passage and rites of affirmation contribute to psychosocial strengthening of orphaned children in Botswana. Ten orphaned children were involved in five rounds of data collection during a 16-day therapeutic retreat; and eight social workers answered questions on the effectiveness of the therapy. A supplementary document analysis was also completed, which included retreat reports since 2001 and correspondence from community-based support workers and graduates of the programme. Participants reported that the rites used during the retreat helped them to commit to therapeutic transformation. During a retreat, all the participants witness and support each individual going through each rite - a process reported to foster and strengthen group formation. It was documented that the symbols used as part of the themed rites of affirmation are used by participants for years afterwards as reminders of their transformation and commitment to the group. We conclude that rites of passage can provide a powerful tool to help children commit to therapeutic transformation, build the supportive group, and enable the community to recognise and affirm that the children return as changed individuals and members of the group.

  7. Orphans of the HIV epidemic: the challenges from toddlerhood to adolescence and beyond.

    Science.gov (United States)

    Lala, Mamatha M

    2014-01-01

    This presentation focuses on the challenges and practical issues faced each day by orphans of the HIV epidemic and the holistic care that can be provided, as they continue to grow from toddlerhood to adolescence and beyond. An HIV Research Trust Scholarship enabled me to spend quality time in a sub-Saharan African province worst hit by the HIV epidemic and to interact with local experts and learn from mutual clinical experience. It was an immensely useful exercise as the clinical spectra of the diseases are very similar to ours and they have ongoing active research programs very relevant to our setting. India is arguably home to the largest number of orphans of the HIV epidemic. The responsibility of caring for orphaned children overwhelms and pushes many extended families beyond their ability to cope. Many countries are experiencing large increases in the number of families headed by women and grandparents, or even young children. These households are often unable to meet basic needs, and so the number of children living on the streets is rising. Orphaned children are disadvantaged in many devastating ways. In addition to the trauma of witnessing the sickness and death of one or both parents and perhaps siblings, they lack the necessary parental guidance through crucial life-stages of identity formation and transition into adulthood. They are more likely to suffer damage to their cognitive and emotional development and be subjected to; exploitation in terms of labour, social exclusion, extreme economic uncertainty, physical and sexual abuse, illiteracy, malnutrition and illness. Education remains a distant dream. With stigma and discrimination, they lack legal protection, lose inheritance rights, access to essential services available to other community members and professional help from doctors, teachers and lawyers. The implications for these unfortunate children are extraordinarily grave but governments, international agencies, non-governmental organizations

  8. Stability of a biogas-producing bacterial, archaeal and fungal community degrading food residues.

    Science.gov (United States)

    Bengelsdorf, Frank R; Gerischer, Ulrike; Langer, Susanne; Zak, Manuel; Kazda, Marian

    2013-04-01

    The resident microbiota was analyzed in a mesophilic, continuously operating biogas plant predominantly utilizing food residues, stale bread, and other waste cosubstrates together with pig manure and maize silage. The dominating bacterial, archaeal, and eukaryotic community members were characterized by two different 16S/18S rRNA gene culture-independent approaches. Prokaryotic 16S rRNA gene and eukaryotic 18S rRNA gene clone libraries were constructed and further analyzed by restriction fragment length polymorphism (RFLP), 16S/18S rRNA gene sequencing, and phylogenetic tree reconstruction. The most dominant bacteria belonged to the phyla Bacteriodetes, Chloroflexus, and Firmicutes. On the family level, the bacterial composition confirmed high differences among biogas plants studied so fare. In contrast, the methanogenic archaeal community was similar to that of other studied biogas plants. Furthermore, it was possible to identify fungi at the genus level, namely Saccharomyces and Mucor. Both genera, which are important for microbial degradation of complex compounds, were up to now not found in biogas plants. The results revealed their long-term presence as indicated by denaturating gradient gel electrophoresis (DGGE). The DGGE method confirmed that the main members of the microbial community were constantly present over more than one-year period. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  9. Housing conditions and mental health of orphans in South Africa

    OpenAIRE

    Marais, Lochner; Sharp, Carla; Pappin, Michele; Lenka, Molefi; Cloete, Jan; Skinner, Donald; Serekoane, Joe

    2013-01-01

    Literature from the developed world suggests that poor housing conditions and housing environments contribute to poor mental health outcomes, although research results are mixed. This study investigates the relationship between housing conditions and the socio-emotional health of orphans and vulnerable children (OVC) in South Africa. The results of the study are mainly inconclusive, although it is suggested that methodological considerations play a vital role in explaining the mixed results. ...

  10. Orphaned and abused youth are vulnerable to pregnancy and suicide risk☆, ☆☆

    Science.gov (United States)

    Kissin, Dmitry M.; Bogoliubova, Olga; Yorick, Roman V.; Kraft, Joan Marie; Jamieson, Denise J.; Marchbanks, Polly A.; Hillis, Susan D.

    2015-01-01

    Objective Little is known about the magnitude and consequences of violence against children for those living outside family care. We sought to estimate the frequency of childhood abuse and examine its association with lifetime pregnancy involvement (LPI) and past year suicide ideation among orphaned youth. Methods We analyzed data collected via cross-sectional interviewer-administered surveys completed by 293 orphaned youth aged 16–23 years living outside of family care in St. Petersburg, Russia. We used multivariable logistic regression to estimate adjusted odds ratios (AORs) of LPI and past year suicide ideation associated with childhood physical and sexual abuse. Other risk factors were also examined (e.g., social vulnerability, sexual and substance use behaviors), and characteristics of orphaned youth with LPI and past year suicide ideation were described. Results The prevalence of childhood abuse was higher among females than among males (23.3% versus 15.6% for physical abuse, and 20.3% versus 5.6% for sexual abuse), as was the prevalence of LPI and past year suicide ideation among those with histories of abuse. Experiences of childhood abuse were strong risk factors for both LPI and past year suicide ideation, with significant variation by gender. While both types of abuse were significantly associated with LPI and past year suicide ideation among females, physical abuse was significantly associated with LPI and sexual abuse was associated with suicide ideation for males. Of the other characteristics examined, strong modifiable risk factors included having no one to turn to for help and no involvement in activities outside of class. Among those with LPI (n = 36), nearly 20% had been pregnant or gotten someone pregnant ≥2 times, most (61.8%) reported at least one induced abortion, and current use of effective contraception was nearly non-existent. Among those with past year suicide ideation (n = 30), nearly half (44.8%) reported attempting suicide

  11. Oral hygiene status of the orphan children in Ar-Rohman Foster Home Bandung after dental health education

    Directory of Open Access Journals (Sweden)

    Nurayni Tri Hapsari

    2017-11-01

    Full Text Available Introduction: Oral hygiene status is a condition of a person’s oral cavity. Oral hygiene status can be assessed using the Oral Hygiene Index Simplified (OHI-S by Greene & Vermillion. The education given regarding oral health is one of health promotion with the purpose to increase the ability of children in terms of maintaining and improving their oral hygiene. The purpose of this study was to determine the difference of the orphans in Ar-Rohman Foster Home Bandung oral health status before and after three times of oral health education. Methods: The type of this research was a pre-experimental study with one group of pretest-posttest design with total sampling technique. Subjects of this research were orphans aged 13-15 years old. The respondents got the clinical examination of OHI-S before and after the oral health education was given for three times. The data obtained then tested using normality test, if the data were normally distributed, then analysed with a paired t-test, and if the data was not normally distributed, then will be analysed with a Wilcoxon test. Results: The results showed a significant decrease of plaque index after oral health education was given to the orphans. The examination of the calculus index (CI-S did not show any change before and after oral health education. OHI-S of children, however, showed a significant decrease. Conclusion: There was a significant increase in the orphans in Ar-Rohman Foster Home Bandung oral health status after given three times of oral health education.

  12. Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis

    OpenAIRE

    D?ring, Jan Henje; Lampert, Anette; Hoffmann, Georg F.; Ries, Markus

    2016-01-01

    Background Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. Methods Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Repor...

  13. Path of a patient with a rare diagnosis: regulatory documents and organization of the process of treatment and diagnosis of an orphan disease in the Russian Federation

    Directory of Open Access Journals (Sweden)

    S. I. Kutsev

    2017-01-01

    Full Text Available The main legislative document of the organization of medical care in the Russian Federation “On fundamental healthcare principles in the Russian Federation” and points related to the rare (orphan diseases are  discussed. The organization of care, rules for managing a federal  registry of orphan diseases and routing of patients with main orphan nosological forms for which treatment is known are presented.

  14. Phylogenetic and functional analysis of metagenome sequence from high-temperature archaeal habitats demonstrate linkages between metabolic potential and geochemistry

    Directory of Open Access Journals (Sweden)

    William P. Inskeep

    2013-05-01

    Full Text Available Geothermal habitats in Yellowstone National Park (YNP provide an unparalled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (~40-45 Mbase Sanger sequencing per site was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G+C content and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH. These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high temperature systems of YNP.

  15. Orphan disease: Cherubism, optic atrophy, and short stature

    Directory of Open Access Journals (Sweden)

    Balaji Jeevanandham

    2018-01-01

    Full Text Available A 12-year-old female presented with complaints of progressive visual impairment in both her eyes. On clinical examination, she was short for her age and her ophthalmoscopic examination revealed bilateral optic atrophy. Computed tomography of the patient revealed multiple expansile lytic lesions of mandible suggesting cherubism. The optic atrophy was confirmed on magnetic resonance imaging, which additionally revealed bilateral retrocerebellar arachnoid cysts. This association of cherubism with optic atrophy and short stature was grouped as orphan disease by National Institutes of Health and only one case was reported in the literature so far.

  16. Willingness to care for children orphaned by HIV/AIDS: a study of ...

    African Journals Online (AJOL)

    The present study explores adoptive and foster parents' (n = 175) willingness to care for a child orphaned by HIV/AIDS. Although some differences were noted depending on the HIV status of the child and whether the respondent was an adoptive or foster parent, results indicate an overall willingness in these populations to ...

  17. Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite

    NARCIS (Netherlands)

    Kenthirapalan, S.; Waters, A.P.; Matuschewski, K.; Kooij, T.W.A.

    2016-01-01

    Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of

  18. Role of traditional healers in psychosocial support in caring for the orphans:a case of Dar es Salaam city,Tanzania

    OpenAIRE

    Kayombo, J.Edmund; Mbwambo, H.Zakaria; Massila, Mariam

    2005-01-01

    Orphans are an increasing problem in developing countries particularly in Africa; due to the HIV/AIDS pandemic; and needs collective effort in intervention processes by including all stakeholders right from the grass roots level. This paper attempts to present the role of traditional healers in psychosocial support for orphan children in Dar-es-Salaam City with special focus on those whose parents have died because of HIV/AIDS. Six traditional healers who were in...

  19. Peer mentorship program on HIV/AIDS knowledge, beliefs, and prevention attitudes among orphaned adolescents: an evidence based practice

    Science.gov (United States)

    Nabunya, Proscovia; Ssewamala, Fred M.; Mukasa, Miriam N.; Byansi, William; Nattabi, Jennifer

    2015-01-01

    Adolescents and young adults in sub-Saharan Africa (SSA) are particularly vulnerable to human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) infection. Adolescents orphaned as a direct result of HIV/AIDS are at an elevated risk of acquiring HIV/AIDS and other sexually transmitted infections. However, limited empirical evidence exists on HIV knowledge and prevention programs, especially those designed to address HIV information gaps among adolescents. This study evaluates the effect of a peer mentorship program provided in addition to other supportive services on HIV/AIDS knowledge, beliefs, and prevention attitudes, among school-going orphaned adolescents in southern Uganda. We utilize data from the Bridges to the Future Study, a 5-year longitudinal randomized experimental study funded by the National Institute of Child Health and Human Development. Out of the 1410 adolescents enrolled in the study (average age = 12.7 at study initiation), 855 of them participated in a nine-session, curriculum based peer mentorship program. We analyzed data collected at baseline and 12-months post intervention initiation. The results from bivariate and regression analysis indicate that, controlling for socioeconomic characteristics, adolescents who participated in a peer mentorship program were more likely than non-participants to report increased scores on HIV/AIDS knowledge(b = .86, 95%CI = .47 – 1.3, p ≤ .001); better scores on desired HIV/AIDS-related beliefs (b = .29, 95%CI = .06 – .52, p ≤ .01); and better scores on HIV/AIDS prevention attitudes (b = .76, 95%CI = .16 – 1.4, p ≤ .01). Overall, the study findings point to the potential role a of peer mentorship program in promoting the much-desired HIV/AIDS knowledge, beliefs, and prevention attitudes among orphaned adolescents. Future programs and policies that support AIDS-orphaned adolescents in sub-Saharan Africa should consider incorporating peer mentoring programs that provide

  20. The role of globalization in drug development and access to orphan drugs: orphan drug legislation in the US/EU and in Latin America [v1; ref status: indexed, http://f1000r.es/3ix

    Directory of Open Access Journals (Sweden)

    Renée J.G. Arnold

    2015-02-01

    Full Text Available Compared to a decade ago, nearly three times as many drugs for rare diseases are slated for development. This article addresses the market access issues associated with orphan drug status in Europe and the United States in contrast to the legislation in five Latin American (LA countries that have made strides in this regard--Mexico, Brazil, Colombia, Chile and Argentina. Based on the success of orphan drug legislation in the EU and US, LA countries should strive to adopt similar strategies with regard to rare diseases and drug development. With the implementation of new targeted regulations, reimbursement strategies, and drug approvals, accessibility to treatment will be improved for people afflicted with rare diseases in these developing countries.

  1. Algal and archaeal polyisoprenoids in a recent marine sediment

    DEFF Research Database (Denmark)

    Bian, Liangqiao; Hinrichs, Kai-Uwe; Xie, Tianmin

    2001-01-01

    Analyses of C-13 contents of individual organic molecules in a marine sediment show that crocetane, 2,6,11,15-tetramethylhexadecane, an isomer of phytane, is produced by microorganisms that use methane as their main source of carbon. The sediments lie at a water depth of 68 m in the Kattegat......, the strait between Denmark and Sweden. Crocetane appears first 185 cm below the sediment-water interface, in the zone marking the transition from sulfate reduction to methanogenesis. Its delta C-13 value is -90 +/- 10 parts per thousand versus Vienna Pee Dee Belemnite (VPDB). Its structure, which includes......-consuming member of the microbial consortium responsible for the anaerobic oxidation of methane [Hoehler et al., 1994], in which, as first demonstrated quantitatively in these sediments [Iversen and Jorgensen, 1985], electrons are transferred from methane to sulfate. The presence of archaeal biomass throughout...

  2. Vertical distribution of archaeal communities associated with anaerobic degradation of pentabromodiphenyl ether (BDE-99) in river-based groundwater recharge with reclaimed water.

    Science.gov (United States)

    Yan, Yulin; Ma, Mengsi; Liu, Xiang; Ma, Weifang; Li, Yangyao

    2018-02-01

    When groundwater is recharged with reclaimed water, the presence of trace amounts of biorefractory pentabromodiphenyl ether (PBDE, specifically BDE-99) might cause potential groundwater pollution. A laboratory-scale column was designed to investigate the distribution of the community of archaea in this scenario and the associated anaerobic degradation of BDE-99. The concentration of BDE-99 decreased significantly as soil depth increased, and fluorescence in situ hybridization (FISH) analysis suggested that archaea exerted significant effects on the biodegradation of PBDE. Through 454 pyrosequencing of 16s rRNA genes, we found that the distribution and structure of the archaeal community associated with anaerobic degradation of BDE-99 in the river-based aquifer media changed significantly between different soil depths. The primary debrominated metabolites varied with changes in the vertically distributed archaeal community. The archaea in the surface layer were dominated by Methanomethylovorans, and the middle layer was mainly composed of Nitrososphaera. Nitrosopumilus and Nitrososphaera were equally abundant in the bottom layer. In addition, Methanomethylovorans abundance depended on the depth of soil, and the relative abundance of Nitrosopumilus increased with increasing depth, which was associated with the oxidation-reduction potential and the content of intermediate metabolites. We propose that Nitrososphaera and Nitrosopumilus might be the key archaeal taxa mediating the biodegradation of BDE-99.

  3. Response of Archaeal and Bacterial Soil Communities to Changes Associated with Outdoor Cattle Overwintering

    OpenAIRE

    Chro??kov?, Alica; Schloter-Hai, Brigitte; Radl, Viviane; Endesfelder, David; Quince, Christopher; Elhottov?, Dana; ?imek, Miloslav; Schloter, Michael

    2015-01-01

    Archaea and bacteria are important drivers for nutrient transformations in soils and catalyse the production and consumption of important greenhouse gases. In this study, we investigate changes in archaeal and bacterial communities of four Czech grassland soils affected by outdoor cattle husbandry. Two show short-term (3 years; STI) and long-term impact (17 years; LTI), one is regenerating from cattle impact (REG) and a control is unaffected by cattle (CON). Cattle manure (CMN), the source of...

  4. The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children.

    Science.gov (United States)

    Kreeftmeijer-Vegter, Annemarie Rosan; de Boer, Anthonius; van der Vlugt-Meijer, Roselinda H; de Vries, Peter J

    2014-08-05

    Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment of Paediatric Investigation Plans (PIPs). The effect of the EU Paediatric Drug Regulation on the marketing authorisation (MA) of drugs for children with rare diseases was studied. Data on all designated orphan drugs, their indication, MA, PIPs and indication group (adult or child) were obtained from the European Medicines Agency (EMA). The outcome and duration of the process from orphan drug designation (ODD) to MA, was compared, per indication, by age group. The effect of the Paediatric Drug Regulation, implemented in 2007, on the application process was assessed with survival analysis. Eighty-one orphan drugs obtained MA since 2000 and half are authorised for (a subgroup of) children; another 34 are currently undergoing further investigations in children through agreed PIPs. The Paediatric Drug Regulation did not significantly increase the number of ODDs with potential paediatric indications (58% before vs 64% after 2007 of ODDs, p = 0.1) and did not lead to more MAs for ODs with paediatric indications (60% vs 43%, p = 0.22). ODs authorised after 2007 had a longer time to MA than those authorised before 2007 (Hazard ratio (95% CI) 2.80 (1.84-4.28), p < 0.001); potential paediatric use did not influence the time to MA (Hazard ratio (95% CI) 1.14 (0.77-1.70), p = 0.52). The EU Paediatric Drug Regulation had a minor impact on development and availability of ODs for children, was associated with a longer time to MA, but ensured the further paediatric development of drugs still off-label to children. The impact of the Paediatric Drug Regulation on research quantity and quality in children through PIPs is not yet clear.

  5. Development and implementation of a peer-based mental health support programme for adolescents orphaned by HIV/AIDS in South Africa.

    Science.gov (United States)

    Thupayagale-Tshweneagae, Gloria

    2011-12-01

    The article describes a framework and the process for the development of the peer-based mental health support programme and its implementation. The development of a peer-based mental health support programme is based on Erikson's theory on the adolescent phase of development, the psycho-educational processes; the peer approach and the orphaned adolescents lived experiences as conceptual framework. A triangulation of five qualitative methods of photography, reflective diaries, focus groups, event history calendar and field notes were used to capture the lived experiences of adolescents orphaned to HIV and AIDS. Analysis of data followed Colaizzi's method of data analysis. The combination of psycho-education, Erikson's stages of development and peer support assisted the participants to gain knowledge and skills to overcome adversity and to assist them to become to more resilient. The peer based mental health support programme if used would enhance the mental health of adolescent orphans.

  6. Rates of trauma spectrum disorders and risks of posttraumatic stress disorder in a sample of orphaned and widowed genocide survivors

    Directory of Open Access Journals (Sweden)

    Susanne Schaal

    2011-06-01

    Full Text Available During the Rwandan genocide of 1994, nearly one million people were killed within a period of 3 months.The objectives of this study were to investigate the levels of trauma exposure and the rates of mental health disorders and to describe risk factors of posttraumatic stress reactions in Rwandan widows and orphans who had been exposed to the genocide.Trained local psychologists interviewed orphans (n=206 and widows (n=194. We used the PSS-I to assess posttraumatic stress disorder (PTSD, the Hopkins Symptom Checklist to assess depression and anxiety symptoms, and the M.I.N.I. to assess risk of suicidality.Subjects reported having been exposed to a high number of different types of traumatic events with a mean of 11 for both groups. Widows displayed more severe mental health problems than orphans: 41% of the widows (compared to 29% of the orphans met symptom criteria for PTSD and a substantial proportion of widows suffered from clinically significant depression (48% versus 34% and anxiety symptoms (59% versus 42% even 13 years after the genocide. Over one-third of respondents of both groups were classified as suicidal (38% versus 39%. Regression analysis indicated that PTSD severity was predicted mainly by cumulative exposure to traumatic stressors and by poor physical health status. In contrast, the importance given to religious/spiritual beliefs and economic variables did not correlate with symptoms of PTSD.While a significant portion of widows and orphans continues to display severe posttraumatic stress reactions, widows seem to constitute a particularly vulnerable survivor group. Our results point to the chronicity of mental health problems in this population and show that PTSD may endure over time if not addressed by clinical intervention. Possible implications of poor mental health and the need for psychological intervention are discussed.

  7. Paying for the Orphan Drug System: break or bend? Is it time for a new evaluation system for payers in Europe to take account of new rare disease treatments?

    Directory of Open Access Journals (Sweden)

    Hughes-Wilson Wills

    2012-09-01

    Full Text Available Abstract Since its enactment in 2000, the European Orphan Medicinal Products Regulation has allowed the review and approval of approaching 70 treatments for some 55 different conditions in Europe. Success does not come without a price, however. Many of these so-called “orphan drugs” have higher price points than treatments for more common diseases. This has been raising debate as to whether the treatments are worth it, which, in turn risks blocking patient access to treatment. To date, orphan drugs have only accounted for a small percentage of the overall drug budget. It would appear that, with increasing numbers of orphan drugs, governments are concerned about the future budget impact and their cost-effectiveness in comparison with other healthcare interventions. Orphan drugs are under the spotlight, something that is likely to continue as the economic crisis in Europe takes hold and governments respond with austerity measures that include cuts to healthcare expenditures. Formally and informally, governments are looking at how they are going to handle orphan drugs in the future. Collaborative proposals between EU governments to better understand the value of orphan drugs are under consideration. In recent years there has been increasing criticism of behaviours in the orphan drug field, mainly centring on two key perceptions of the system: the high prices of orphan drugs and their inability to meet standard cost-effectiveness thresholds; and the construct of the system itself, which allows companies to gain the benefits that accrue from being badged as an orphan drug. The authors hypothesise that, by examining these criticisms individually, one might be able to turn these different “behaviours” into criteria for the creation of a system to evaluate new orphan drugs coming onto the market. It has been acknowledged that standard methodologies for Health Technology Assessments (HTA will need to be tailored to take into account the

  8. The human orphan nuclear receptor tailless (TLX, NR2E1 is druggable.

    Directory of Open Access Journals (Sweden)

    Cindy Benod

    Full Text Available Nuclear receptors (NRs are an important group of ligand-dependent transcriptional factors. Presently, no natural or synthetic ligand has been identified for a large group of orphan NRs. Small molecules to target these orphan NRs will provide unique resources for uncovering regulatory systems that impact human health and to modulate these pathways with drugs. The orphan NR tailless (TLX, NR2E1, a transcriptional repressor, is a major player in neurogenesis and Neural Stem Cell (NSC derived brain tumors. No chemical probes that modulate TLX activity are available, and it is not clear whether TLX is druggable. To assess TLX ligand binding capacity, we created homology models of the TLX ligand binding domain (LBD. Results suggest that TLX belongs to an emerging class of NRs that lack LBD helices α1 and α2 and that it has potential to form a large open ligand binding pocket (LBP. Using a medium throughput screening strategy, we investigated direct binding of 20,000 compounds to purified human TLX protein and verified interactions with a secondary (orthogonal assay. We then assessed effects of verified binders on TLX activity using luciferase assays. As a result, we report identification of three compounds (ccrp1, ccrp2 and ccrp3 that bind to recombinant TLX protein with affinities in the high nanomolar to low micromolar range and enhance TLX transcriptional repressive activity. We conclude that TLX is druggable and propose that our lead compounds could serve as scaffolds to derive more potent ligands. While our ligands potentiate TLX repressive activity, the question of whether it is possible to develop ligands to de-repress TLX activity remains open.

  9. The human orphan nuclear receptor tailless (TLX, NR2E1) is druggable.

    Science.gov (United States)

    Benod, Cindy; Villagomez, Rosa; Filgueira, Carly S; Hwang, Peter K; Leonard, Paul G; Poncet-Montange, Guillaume; Rajagopalan, Senapathy; Fletterick, Robert J; Gustafsson, Jan-Åke; Webb, Paul

    2014-01-01

    Nuclear receptors (NRs) are an important group of ligand-dependent transcriptional factors. Presently, no natural or synthetic ligand has been identified for a large group of orphan NRs. Small molecules to target these orphan NRs will provide unique resources for uncovering regulatory systems that impact human health and to modulate these pathways with drugs. The orphan NR tailless (TLX, NR2E1), a transcriptional repressor, is a major player in neurogenesis and Neural Stem Cell (NSC) derived brain tumors. No chemical probes that modulate TLX activity are available, and it is not clear whether TLX is druggable. To assess TLX ligand binding capacity, we created homology models of the TLX ligand binding domain (LBD). Results suggest that TLX belongs to an emerging class of NRs that lack LBD helices α1 and α2 and that it has potential to form a large open ligand binding pocket (LBP). Using a medium throughput screening strategy, we investigated direct binding of 20,000 compounds to purified human TLX protein and verified interactions with a secondary (orthogonal) assay. We then assessed effects of verified binders on TLX activity using luciferase assays. As a result, we report identification of three compounds (ccrp1, ccrp2 and ccrp3) that bind to recombinant TLX protein with affinities in the high nanomolar to low micromolar range and enhance TLX transcriptional repressive activity. We conclude that TLX is druggable and propose that our lead compounds could serve as scaffolds to derive more potent ligands. While our ligands potentiate TLX repressive activity, the question of whether it is possible to develop ligands to de-repress TLX activity remains open.

  10. Conserved TRAM Domain Functions as an Archaeal Cold Shock Protein via RNA Chaperone Activity

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2017-08-01

    Full Text Available Cold shock proteins (Csps enable organisms to acclimate to and survive in cold environments and the bacterial CspA family exerts the cold protection via its RNA chaperone activity. However, most Archaea do not contain orthologs to the bacterial csp. TRAM, a conserved domain among RNA modification proteins ubiquitously distributed in organisms, occurs as an individual protein in most archaeal phyla and has a structural similarity to Csp proteins, yet its biological functions remain unknown. Through physiological and biochemical studies on four TRAM proteins from a cold adaptive archaeon Methanolobus psychrophilus R15, this work demonstrated that TRAM is an archaeal Csp and exhibits RNA chaperone activity. Three TRAM encoding genes (Mpsy_0643, Mpsy_3043, and Mpsy_3066 exhibited remarkable cold-shock induced transcription and were preferentially translated at lower temperature (18°C, while the fourth (Mpsy_2002 was constitutively expressed. They were all able to complement the cspABGE mutant of Escherichia coli BX04 that does not grow in cold temperatures and showed transcriptional antitermination. TRAM3066 (gene product of Mpsy_3066 and TRAM2002 (gene product of Mpsy_2002 displayed sequence-non-specific RNA but not DNA binding activity, and TRAM3066 assisted RNases in degradation of structured RNA, thus validating the RNA chaperone activity of TRAMs. Given the chaperone activity, TRAM is predicted to function beyond a Csp.

  11. 78 FR 51732 - The Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant...

    Science.gov (United States)

    2013-08-21

    ..., and the FDA Orphan Products Grant program to participants representing pharmaceutical, biotechnology... treatment of a rare disease or condition in order to discuss the processes for putting together an...

  12. The Helicase Activity of Hyperthermophilic Archaeal MCM is Enhanced at High Temperatures by Lysine Methylation.

    Science.gov (United States)

    Xia, Yisui; Niu, Yanling; Cui, Jiamin; Fu, Yang; Chen, Xiaojiang S; Lou, Huiqiang; Cao, Qinhong

    2015-01-01

    Lysine methylation and methyltransferases are widespread in the third domain of life, archaea. Nevertheless, the effects of methylation on archaeal proteins wait to be defined. Here, we report that recombinant sisMCM, an archaeal homolog of Mcm2-7 eukaryotic replicative helicase, is methylated by aKMT4 in vitro. Mono-methylation of these lysine residues occurs coincidently in the endogenous sisMCM protein purified from the hyperthermophilic Sulfolobus islandicus cells as indicated by mass spectra. The helicase activity of mini-chromosome maintenance (MCM) is stimulated by methylation, particularly at temperatures over 70°C. The methylated MCM shows optimal DNA unwinding activity after heat-treatment between 76 and 82°C, which correlates well with the typical growth temperatures of hyperthermophilic Sulfolobus. After methylation, the half life of MCM helicase is dramatically extended at 80°C. The methylated sites are located on the accessible protein surface, which might modulate the intra- and inter- molecular interactions through changing the hydrophobicity and surface charge. Furthermore, the methylation-mimic mutants of MCM show heat resistance helicase activity comparable to the methylated MCM. These data provide the biochemical evidence that posttranslational modifications such as methylation may enhance kinetic stability of proteins under the elevated growth temperatures of hyperthermophilic archaea.

  13. Linking the composition of bacterial and archaeal communities to characteristics of soil and flora composition in the Atlantic rainforest

    NARCIS (Netherlands)

    Lima-Perim, Julia Elidia; Romagnoli, Emiliana Manesco; Dini-Andreote, Francisco; Durrer, Ademir; Dias, Armando Cavalcante Franco; Andreote, Fernando Dini

    2016-01-01

    The description of microbiomes as intrinsic fractions of any given ecosystem is an important issue, for instance, by linking their compositions and functions with other biotic and abiotic components of natural systems and hosts. Here we describe the archaeal and bacterial communities from soils of

  14. A nested PCR approach for improved recovery of archaeal 16S rRNA gene fragments from freshwater samples

    NARCIS (Netherlands)

    Vissers, E.W.; Bodelier, P.L.E.; Muyzer, G.; Laanbroek, R.

    2009-01-01

    In a survey on the presence of archaea in a number of European lakes, it was found that known archaeal primer sets for PCR were not suited for use in freshwater environment, as some lack selectivity, while others were too selective. A nested PCR was developed for denaturing gradient gel

  15. Ror receptor tyrosine kinases: orphans no more.

    Science.gov (United States)

    Green, Jennifer L; Kuntz, Steven G; Sternberg, Paul W

    2008-11-01

    Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either activate or repress transcription of Wnt target genes and can modulate Wnt signaling by sequestering Wnt ligands. New evidence implicates Ror proteins in planar cell polarity, an alternative Wnt pathway. Here, we review the progress made in understanding these mysterious proteins and, in particular, we focus on their function as Wnt receptors.

  16. From orphan virus to pathogen: the path to the clinical lab

    OpenAIRE

    Li, Linlin; Delwart, Eric

    2011-01-01

    Viral metagenomics has recently yielded numerous previously uncharacterized viral genomes from human and animal samples. We review some of the metagenomics tools and strategies to determine which orphan viruses are likely pathogens. Disease association studies compare viral prevalence in patients with unexplained symptoms versus healthy individuals but require these case and control groups to be closely matched epidemiologically. The development of an antibody response in convalescent serum c...

  17. Impact of protective factors on resilience of grandparent carers fostering orphans and non-orphans in Zimbabwe.

    Science.gov (United States)

    Mhaka-Mutepfa, Magen; Mpofu, Elias; Cumming, Robert

    2015-04-01

    This study sought to explore the impact of protective factors, health, and well-being on resilience of grandparents fostering orphans. Data were collected from grandparents (N = 327; M age = 62.4; SD = 11.2) in Zimbabwe using a survey instrument comprising the Resilience Scale and World Health Organization Quality of Life Questionnaire (WHOQOL-BREF). Data were analyzed using hierarchical regression, predicting resilience from demographics, personal and social assets, health, and well-being. Protective factors associated with resilience were personal assets (high self-esteem, problem-solving skills, and mastery) and social assets (social networks and spirituality). Grandparents with higher coping skills, younger age, and high socioeconomic status (SES) had superior personal competences for resilience than peers with lower self-rated personal attributes. Grandparents with good physical and mental health had higher resilience profiles. Positive emotions and good health experienced by resilient grandparent carers function as protective factors to reduce the magnitude of adversity to individuals and assist them to cope well with caregiving. © The Author(s) 2014.

  18. Structural basis for corepressor assembly by the orphan nuclear receptor TLX.

    Science.gov (United States)

    Zhi, Xiaoyong; Zhou, X Edward; He, Yuanzheng; Searose-Xu, Kelvin; Zhang, Chun-Li; Tsai, Chih-Cheng; Melcher, Karsten; Xu, H Eric

    2015-02-15

    The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX-Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression. © 2015 Zhi et al.; Published by Cold Spring Harbor Laboratory Press.

  19. Evaluation of the Relevance of Piaget's Cognitive Principles among Parented and Orphan Children in Belagavi City, Karnataka, India: A Comparative Study.

    Science.gov (United States)

    M Badakar, Chandrashekhar; J Thakkar, Prachi; M Hugar, Shivayogi; Kukreja, Pratibha; G Assudani, Harsha; Gokhale, Niraj

    2017-01-01

    To determine and compare the relevance of Piaget's cognitive principles among 4- to 7-year-old parented and orphan children in Belagavi City, Karnataka, India. This study was conducted on 240 children between the ages of 4 to 7 years who were equally divided into two groups of 120 parented and 120 orphan children. These were subdivided into four groups of 30 children each. Various characteristics like egocentrism, concept of cardinal numbers based on centration, lack of conservation, and reversibility were assessed, using experiments and comparison of their prevalence between two groups was carried out. There is a statistically significant difference in the cognitive development among parented and orphan children age 4 to 7 years. There is a significantly better cognitive development among parented children as compared with orphan children in Belagavi city. A child is not a miniature adult but rather can think and perceive the world differently from an adult. Understanding a child's intellectual level can enable a pedodontist to deliver improved quality care to children. According to Jean Piaget, in the preoperational period, children think symbolically and their reasoning is based more on appearance rather than logic. It is often rightly said that a child's behavior is a reflection of his parents. However, Piaget did not consider the effect of social setting and culture on the cognitive development. This study was carried out as there is not much literature available to describe the cognitive development of children in the Indian scenario and the influence of parental presence on the same. How to cite this article: Badakar CM, Thakkar PJ, Hugar SM, Kukreja P, Assudani HG, Gokhale N. Evaluation of the Relevance of Piaget's Cognitive Principles among Parented and Orphan Children in Belagavi City, Karnataka, India: A Comparative Study. Int J Clin Pediatr Dent 2017;10(4):346-350.

  20. Growing up without parents: socialisation and gender relations in orphaned-child-headed households in rural Zimbabwe.

    Science.gov (United States)

    Francis-Chizororo, Monica

    2010-01-01

    The most distressing consequences of the HIV/AIDS pandemic's impact on children has been the development of child-headed households (CHHs). Child 'only' households challenge notions of the ideal home, family, and 'normal' childhood, as well as undermining international attempts to institute children's rights. The development of these households raises practical questions about how the children will cope without parental guidance during their childhood and how this experience will affect their adulthood. Drawing on ethnographic research with five child heads and their siblings, this article explores how orphaned children living in 'child only' households organise themselves in terms of household domestic and paid work roles, explores the socialisation of children by children and the negotiation of teenage girls' movement. Further, it examines whether the orphaned children are in some way attempting to 'mimic' previously existing family/household gender relations after parental death. The study showed that all members in the CHHs irrespective of age and gender are an integral part of household labour including food production. Although there is masculinisation of domestic chores in boys 'only' households, roles are distributed by age. On the other hand, households with a gender mix tended to follow traditional gender norms. Conflict often arose when boys controlled teenage girls' movement and sexuality. There is a need for further research on CHHs to better understand orphans' experiences, and to inform policy interventions.

  1. Stripper, shut-in and orphan wells in joint operations

    International Nuclear Information System (INIS)

    Nixon, R.

    1999-01-01

    Low productivity wells, stripper wells, can be an excellent source of income to independent operators or small companies, but a serious financial burden for larger companies. Shut-in wells, for most companies, are either waiting on a market and production facilities, or represent deferred abandonment liabilities. Orphan wells also reflect financial distress. The firm, Cord Oil and Gas Management Ltd., was formed in 1986 to specifically assist oil and gas companies, sophisticated investors and financial institutions with the management, enhancement and disposition of non-core or low productivity assets. This type of production, depending on the number of wells and cumulative production, can be the life blood of a small organization or a serious drain on the administrative personnel and financial resources of larger organizations. Philosophically, industry and/or government needs to manage the eventuality of abandonments by establishing financial criteria. Some suggestions for industry include: (1) establish provisions within joint operating agreements to set aside an abandonment and environmental cleanup fund; (2) minimize the inventory of abandonment candidates by an ongoing program of reclamation; (3) offset abandonment costs with salvage value of tangible equipment under AFE approval; and (4) voluntarily restrict transfer abandonment liabilities with producing assets on a selective basis. Some suggestions for governments include: (1) fund the orphan well by a deposit for every well drilled; (2) restrict the transfer of liabilities for abandoned and inactive wells by ensuring that the transferee is financially capable; and (3) access the chain of title to ensure non-operators remain responsible for the proportionate shares of abandonment and cleanup costs

  2. Archaeal and bacterial H-GDGTs are abundant in peat and their relative abundance is positively correlated with temperature

    Science.gov (United States)

    Naafs, B. D. A.; McCormick, D.; Inglis, G. N.; Pancost, R. D.; T-GRES Peat Database Collaborators

    2018-04-01

    Glycerol monoalkyl glycerol tetraether lipids (GMGTs; also called 'H-GDGTs') differ from the more commonly studied glycerol dialkyl glycerol tetraether (GDGTs) in that they have an additional covalent bond that links the two alkyl chains. Six different archaeal isoprenoidal H-GDGTs (H-isoGDGTs) and one branched H-GDGT (H-brGDGT), presumably produced by bacteria, have previously been found. However, the function of H-GDGTs in both domains of life is unknown. It is thought that the formation of this additional covalent bond results in enhanced membrane stability, accounting for the high abundance of H-GDGTs in extreme environments such as geothermal settings, but so far there has been little evidence to support this hypothesis. Here we report the distribution of H-GDGTs in a global peat database (n = 471) with a broad range in mean annual air temperature (MAAT) and pH. This is the first finding of H-GDGTs in soils (specifically, peat), highlighting that H-GDGTs are widespread in mesophilic settings. In addition, we report the presence of two new H-brGDGTs with one (H-1034) and two (H-1048) additional methyl groups, respectively. Our results suggest that the relative abundance of both bacterial and archaeal H-GDGTs compared to regular GDGTs is related to temperature with the highest relative abundance of H-GDGTs in tropical peats. Although other factors besides temperature likely also play a role, these results do support the hypothesis that H-GDGTs are an adaptation to temperature to maintain membrane stability. The observation that both bacterial and archaeal membrane lipids respond to temperature indicates the same adaption across the lipid divide between these two domains of life, suggesting parallel or convergent evolution (potentially facilitated by lateral gene transfer).

  3. Controls on bacterial and archaeal community structure and greenhouse gas production in natural, mined, and restored Canadian peatlands

    Directory of Open Access Journals (Sweden)

    Nathan eBasiliko

    2013-07-01

    Full Text Available Northern peatlands are important global C reservoirs, largely because of their slow rates of microbial C mineralization. Particularly in sites that are heavily influenced by anthropogenic disturbances, there is scant information about microbial ecology and whether or not microbial community structure influences greenhouse gas production. This work characterized communities of bacteria and archaea using terminal restriction fragment length polymorphism and sequence analysis of 16S rRNA and functional genes across eight natural, mined, or restored peatlands in two locations in eastern Canada. Correlations were explored among chemical properties of peat, bacterial and archaeal community structure, and carbon dioxide and methane production rates under oxic and anoxic conditions. Bacteria and archaea similar to those found in other peat soil environments were detected. In contrast to other reports, methanogen diversity was low in our study, with only 2 groups of known or suspected methanogens. Although mining and restoration affected substrate availability and microbial activity, these land-uses did not consistently affect bacterial or archaeal community composition. In fact, larger differences were observed between the two locations and between oxic and anoxic peat samples than between mined and restored sites, with anoxic samples characterized by less detectable bacterial diversity and stronger dominance by members of the phylum Acidobacteria. There were also no apparent strong linkages between prokaryote community structure and methane or carbon dioxide production, suggesting that different organisms exhibit functional redundancy and/or that the same taxa function at very different rates when exposed to different peat substrates. In contrast to other earlier work focusing on fungal communities across similar mined and restored peatlands, bacterial and archaeal communities appeared to be more resistant or resilient to peat substrate changes brought

  4. An Initial Exploration of the Therapeutic Impact of Music on Genocide Orphans in Rwanda

    Science.gov (United States)

    d'Ardenne, Patricia; Kiyendeye, Moses

    2015-01-01

    The 1994 Rwandan Genocide murdered over a million and brought on incalculable distress to survivors. An non-governmental organisation, "Network for Africa," has a music programme to rehabilitate orphans in Kigali, now entering adulthood. This naturalistic study investigated whether music had transformational meaning for participants.…

  5. Dealing with Uncertainty and Accounting for Social Value Judgments in Assessments of Orphan Drugs: Evidence from Four European Countries.

    Science.gov (United States)

    Nicod, Elena; Berg Brigham, Karen; Durand-Zaleski, Isabelle; Kanavos, Panos

    To better understand the reasons for differences in reimbursement decisions for orphan drugs in four European countries that were not readily apparent from health technology assessment (HTA) reports and operating procedures. Semistructured interviews with representatives of HTA bodies in England, Scotland, Sweden, and France were conducted. An interview topic guide was developed on the basis of findings from a systematic comparison of HTA decisions for 10 orphan drugs. Qualitative thematic data analysis was applied to the interview transcripts using the framework approach. Eight representatives from the four HTA bodies were interviewed between March and June 2015. Evidentiary requirements and approaches to dealing with imperfect or incomplete evidence were explored, including trial design and duration, study population and subgroups, comparators, and end points. Interviewees agreed that decisions regarding orphan drugs are made in a context of lower quality evidence, and the threshold of acceptable uncertainty varied by country. Some countries imposed higher evidentiary standards for greater clinical claims, which may be more challenging for orphan diseases. The acceptability of surrogate end points was not consistent across countries nor were the validation requirements. The most common social value judgments identified related to innovation, disease severity, and unmet need. Differences were seen in the way these concepts were defined and accounted for across countries. Although agreement was seen in evidentiary requirements or preferences, there were subtle differences in the circumstances in which uncertain evidence may be considered acceptable, possibly explaining differences in HTA recommendations across countries. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  6. Orphan Basin crustal structure from a dense wide-angle seismic profile - Tomographic inversion

    Science.gov (United States)

    Watremez, Louise; Lau, K. W. Helen; Nedimović, Mladen R.; Louden, Keith E.; Karner, Garry D.

    2014-05-01

    Orphan Basin is located on the eastern margin of Canada, offshore of Newfoundland and East of Flemish Cap. It is an aborted continental rift formed by multiple episodes of rifting. The crustal structure across the basin has been determined by an earlier refraction study using 15 instruments on a 550 km long line. It shows that the continental crust was extended over an unusually wide region but did not break apart. The crustal structure of the basin thus documents stages in the formation of a magma-poor rifted margin up to crustal breakup. The OBWAVE (Orphan Basin Wide-Angle Velocity Experiment) survey was carried out to image crustal structures across the basin and better understand the processes of formation of this margin. The spacing of the 89 recording stations varies from 3 to 5 km along this 500-km-long line, which was acquired along a pre-existing reflection line. The highest resolution section corresponds to the part of the profile where the crust was expected to be the thinnest. We present the results from a joint tomography inversion of first and Moho reflected arrival times. The high data density allows us to define crustal structures with greater detail than for typical studies and to improve the understanding of the processes leading to the extreme stretching of continental crust. The final model was computed following a detailed parametric study to determine the optimal parameters controlling the ray-tracing and the inversion processes. The final model shows very good resolution. In particular, Monte Carlo standard deviations of crustal velocities and Moho depths are generally Orphan Basin is the result of rifting of a non-homogeneous Avalon terrane where the lower crust is primarily ductile.

  7. Management of 'orphan' sources

    International Nuclear Information System (INIS)

    Telleria, D.; Spano, F.; Rudelli, M.D.

    1998-01-01

    The experience has shown that most of the accidents with severe radiological consequences take place when radioactive sources were beyond the control system. In Argentina, the primary framework in radiological safety was established in the late fifties, with a non-prescriptive regulatory approach. For any application involving radioactive material, users must be authorised by the Authority, unless the application has demonstrated to be exempted. The licensees are responsible for ensuring protection against the risk associated with exposure to radiation, and for safety of radioactive sources. To obtain an authorisation, the applicant has to prove to the Authority knowledge and capability to carry on an application. Not only normal operation circumstances are considered, but every conceivable accidental situation. It has been shown the existence of radioactive sources not attributed to an authorised user or installation, and therefore outside of the primary control structure described above. These sources, from here on called 'orphans' recognise several origins. The regulatory authority should necessary foresee mechanisms to afford early detection and management of these sources, before an undesired consequence arises. Up to some extent, the deployment of multiple and varied organisations or procedures, could be understood as a 'defence in depth' concept, applied to the control. (author)

  8. Orphan therapies: making best use of postmarket data.

    Science.gov (United States)

    Maro, Judith C; Brown, Jeffrey S; Dal Pan, Gerald J; Li, Lingling

    2014-08-01

    Postmarket surveillance of the comparative safety and efficacy of orphan therapeutics is challenging, particularly when multiple therapeutics are licensed for the same orphan indication. To make best use of product-specific registry data collected to fulfill regulatory requirements, we propose the creation of a distributed electronic health data network among registries. Such a network could support sequential statistical analyses designed to detect early warnings of excess risks. We use a simulated example to explore the circumstances under which a distributed network may prove advantageous. We perform sample size calculations for sequential and non-sequential statistical studies aimed at comparing the incidence of hepatotoxicity following initiation of two newly licensed therapies for homozygous familial hypercholesterolemia. We calculate the sample size savings ratio, or the proportion of sample size saved if one conducted a sequential study as compared to a non-sequential study. Then, using models to describe the adoption and utilization of these therapies, we simulate when these sample sizes are attainable in calendar years. We then calculate the analytic calendar time savings ratio, analogous to the sample size savings ratio. We repeat these analyses for numerous scenarios. Sequential analyses detect effect sizes earlier or at the same time as non-sequential analyses. The most substantial potential savings occur when the market share is more imbalanced (i.e., 90% for therapy A) and the effect size is closest to the null hypothesis. However, due to low exposure prevalence, these savings are difficult to realize within the 30-year time frame of this simulation for scenarios in which the outcome of interest occurs at or more frequently than one event/100 person-years. We illustrate a process to assess whether sequential statistical analyses of registry data performed via distributed networks may prove a worthwhile infrastructure investment for pharmacovigilance.

  9. Microbial Diversity and Biochemical Potential Encoded by Thermal Spring Metagenomes Derived from the Kamchatka Peninsula

    Directory of Open Access Journals (Sweden)

    Bernd Wemheuer

    2013-01-01

    Full Text Available Volcanic regions contain a variety of environments suitable for extremophiles. This study was focused on assessing and exploiting the prokaryotic diversity of two microbial communities derived from different Kamchatkian thermal springs by metagenomic approaches. Samples were taken from a thermoacidophilic spring near the Mutnovsky Volcano and from a thermophilic spring in the Uzon Caldera. Environmental DNA for metagenomic analysis was isolated from collected sediment samples by direct cell lysis. The prokaryotic community composition was examined by analysis of archaeal and bacterial 16S rRNA genes. A total number of 1235 16S rRNA gene sequences were obtained and used for taxonomic classification. Most abundant in the samples were members of Thaumarchaeota, Thermotogae, and Proteobacteria. The Mutnovsky hot spring was dominated by the Terrestrial Hot Spring Group, Kosmotoga, and Acidithiobacillus. The Uzon Caldera was dominated by uncultured members of the Miscellaneous Crenarchaeotic Group and Enterobacteriaceae. The remaining 16S rRNA gene sequences belonged to the Aquificae, Dictyoglomi, Euryarchaeota, Korarchaeota, Thermodesulfobacteria, Firmicutes, and some potential new phyla. In addition, the recovered DNA was used for generation of metagenomic libraries, which were subsequently mined for genes encoding lipolytic and proteolytic enzymes. Three novel genes conferring lipolytic and one gene conferring proteolytic activity were identified.

  10. Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Benned-Jensen, Tau; Holst, Peter J

    2006-01-01

    Epstein-Barr virus (EBV)-induced receptor 2 (EBI2) is an orphan seven-transmembrane (7TM) receptor originally identified as the most up-regulated gene (>200-fold) in EBV-infected cells. Here we show that EBI2 signals with constitutive activity through Galpha(i) as determined by a receptor...

  11. The orphan G protein-coupled receptor GPR139 is activated by the peptides

    DEFF Research Database (Denmark)

    Jensen, Anne Cathrine Nøhr; Shehata, Mohamed A; Hauser, Alexander S

    2017-01-01

    GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well...

  12. The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children

    NARCIS (Netherlands)

    Kreeftmeijer-Vegter, Annemarie Rosan; de Boer, Anthonius; van der Vlugt-Meijer, Roselinda H.; de Vries, Peter J.

    2014-01-01

    Background: Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment

  13. The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children

    NARCIS (Netherlands)

    Kreeftmeijer-Vegter, Annemarie Rosan; de Boer, Anthonius; van der Vlugt-Meijer, Roselinda H; de Vries, Peter J

    2014-01-01

    BACKGROUND: Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment

  14. Structural basis for corepressor assembly by the orphan nuclear receptor TLX

    OpenAIRE

    Zhi, Xiaoyong; Zhou, X. Edward; He, Yuanzheng; Searose-Xu, Kelvin; Zhang, Chun-Li; Tsai, Chih-Cheng; Melcher, Karsten; Xu, H. Eric

    2015-01-01

    The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Zhi et al. report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. Mutations that weaken the TLX–Atrophin interaction compromise the repressive activity of TLX. In addition, mutations...

  15. Orphan chemokine receptors in neuroimmunology : functional and pharmacological analysis of L-CCR and HCR

    NARCIS (Netherlands)

    Zuurman, Michael Wilhelmer

    2003-01-01

    In this thesis we have investigated the expression and biological activity of the orphan chemokine receptors L-CCR/HCR in astrocytes and microglia. Several lines of evidence indicate that the chemokines CCL2, CCL5, CCL7 and CCL8 are agonists for these receptors. Although a variety of biological

  16. The perverse impact of external reference pricing (ERP): a comparison of orphan drugs affordability in 12 European countries. A call for policy change

    Science.gov (United States)

    Young, K. E.; Soussi, I.; Toumi, M.

    2017-01-01

    ABSTRACT Objective: The study compared the relative cost differences of similar orphan drugs among high and low GDP countries in Europe: Bulgaria, France, Germany, Greece, Hungary, Italy, Norway, Poland, Romania, Spain, Sweden, UK. Methods: Annual treatment costs per patient were calculated. Relative costs were computed by dividing the costs by each economic parameter: nominal GDP per capita, GDP in PPP per capita, % GDP contributed by the government, government budget per inhabitant, % GDP spent on healthcare, % GDP spent on pharmaceuticals, and average annual salary. An international comparison of the relative costs was done using UK as the reference country and results were analysed descriptively. Results: 120 orphan drugs were included. The median annual costs of orphan drugs in all countries varied minimally (cost ratios: 0.87 to 1.08). When the costs were adjusted using GDP per capita, the EU-5 and Nordic countries maintained minimal difference in median cost. However, the lower GDP countries showed three to six times higher relative costs. The same pattern was evident when costs were adjusted using the other economic parameters. Conclusion: When the country’s ability to pay is taken into consideration, lower GDP countries pay relatively higher costs for similarly available orphan drugs in Europe. PMID:29081920

  17. [Abundances of ammonia-oxidizing archaeal accA and amoA genes in response to NO2 - and NO3 - of hot springs in Yunnan province].

    Science.gov (United States)

    Song, Zhaoqi; Wang, Li; Zhou, Enmin; Wang, Fengping; Xiao, Xiang; Zhang, Chuanlun; Li, Wenjun

    2014-12-04

    Yunnan hot springs have highly diverseammonia-oxidizing archaea (AOA), which are autotrophic and can fix CO2 using the 3-hydroxypropionate/ 4-hydroxybutyrate (HP/HD) pathway. In this study, we investigated the abundances of prokaryotic 16S rRNA gene and archaeal accA and amoA genes in the sediments of hot springs of Yunnan Province, and analysed the correlations between the above gene abundances and environmental factors. We selected the sediments of twenty representative hot springs, and detected the gene abundances by quantitative polymerase chain reaction (qPCR). The principal component analysis (PCA) and the Mantel test in the R software package were performed for the correlations of gene abundance and environmental variables. The bacterial and archaeal 16S rRNA gene abundances were from 6.6 x 10(7) to 4.19 x 10(11) and from 1.27 x 10(6) to 1.51 x 10(11) copies/g sediment, respectively; Archaeal accA and amoA genes were from 8.89 x 10(3) to 6.49 x 10(5) and from 7.64 x 10(3) to 4.36 x 10(5) copies/g sediment, respectively. The results of mantel test showed that accA gene was significantly (R = 0.98, P < 0.001) correlated with amoA gene; Both of them also were correlated significantly with NO2- and NO3 -, but not with pH. The abundances of bacterial and archaeal 16S rRNA genes and the ratio between them varied significantly among Yunnan hot springs. The archaealaccA and amoA genes showed significant correlation with each other, validating our previous finding that AOA in terrestrial hot springs might acquire energy from ammonia oxidation coupled with CO2 fixation using the 3-hydroxypropionate/4-hydroxybutyrate pathway.

  18. A sensitive, support-vector-machine method for the detection of horizontal gene transfers in viral, archaeal and bacterial genomes.

    Science.gov (United States)

    Tsirigos, Aristotelis; Rigoutsos, Isidore

    2005-01-01

    In earlier work, we introduced and discussed a generalized computational framework for identifying horizontal transfers. This framework relied on a gene's nucleotide composition, obviated the need for knowledge of codon boundaries and database searches, and was shown to perform very well across a wide range of archaeal and bacterial genomes when compared with previously published approaches, such as Codon Adaptation Index and C + G content. Nonetheless, two considerations remained outstanding: we wanted to further increase the sensitivity of detecting horizontal transfers and also to be able to apply the method to increasingly smaller genomes. In the discussion that follows, we present such a method, Wn-SVM, and show that it exhibits a very significant improvement in sensitivity compared with earlier approaches. Wn-SVM uses a one-class support-vector machine and can learn using rather small training sets. This property makes Wn-SVM particularly suitable for studying small-size genomes, similar to those of viruses, as well as the typically larger archaeal and bacterial genomes. We show experimentally that the new method results in a superior performance across a wide range of organisms and that it improves even upon our own earlier method by an average of 10% across all examined genomes. As a small-genome case study, we analyze the genome of the human cytomegalovirus and demonstrate that Wn-SVM correctly identifies regions that are known to be conserved and prototypical of all beta-herpesvirinae, regions that are known to have been acquired horizontally from the human host and, finally, regions that had not up to now been suspected to be horizontally transferred. Atypical region predictions for many eukaryotic viruses, including the alpha-, beta- and gamma-herpesvirinae, and 123 archaeal and bacterial genomes, have been made available online at http://cbcsrv.watson.ibm.com/HGT_SVM/.

  19. GPR101 orphan GPCR: a novel cause of growth hormone deregulation

    OpenAIRE

    Abboud, Dayana; Daly, Adrian; Dupuis, Nadine; Laschet, Céline; Geubelle, Pierre; Pirotte, Bernard; BECKERS, Albert; Hanson, Julien

    2017-01-01

    GPR101 is an orphan G-protein coupled receptor with unknown ligand. In 2014, an international study clearly pointed to a strong association between this receptor and the X-linked acrogigantism (X-LAG) syndrome, which begins in childhood and causes the “tallest giants”. The children (carriers of the GPR101 duplication on the X chromosome) grow abnormally even before they are one year old, secrete phenomenal quantities of growth hormone, and develop pituitary adenomas that do not respond to cur...

  20. Effect of Pre-weaning Diet on the Ruminal Archaeal, Bacterial, and Fungal Communities of Dairy Calves.

    Science.gov (United States)

    Dias, Juliana; Marcondes, Marcos I; Noronha, Melline F; Resende, Rafael T; Machado, Fernanda S; Mantovani, Hilário C; Dill-McFarland, Kimberly A; Suen, Garret

    2017-01-01

    At birth, calves display an underdeveloped rumen that eventually matures into a fully functional rumen as a result of solid food intake and microbial activity. However, little is known regarding the gradual impact of pre-weaning diet on the establishment of the rumen microbiota. Here, we employed next-generation sequencing to investigate the effects of the inclusion of starter concentrate (M: milk-fed vs. MC: milk plus starter concentrate fed) on archaeal, bacterial and anaerobic fungal communities in the rumens of 45 crossbred dairy calves across pre-weaning development (7, 28, 49, and 63 days). Our results show that archaeal, bacterial, and fungal taxa commonly found in the mature rumen were already established in the rumens of calves at 7 days old, regardless of diet. This confirms that microbiota colonization occurs in the absence of solid substrate. However, diet did significantly impact some microbial taxa. In the bacterial community, feeding starter concentrate promoted greater diversity of bacterial taxa known to degrade readily fermentable carbohydrates in the rumen (e.g., Megasphaera, Sharpea , and Succinivribrio ). Shifts in the ruminal bacterial community also correlated to changes in fermentation patterns that favored the colonization of Methanosphaera sp. A4 in the rumen of MC calves. In contrast, M calves displayed a bacterial community dominated by taxa able to utilize milk nutrients (e.g., Lactobacillus, Bacteroides , and Parabacteroides ). In both diet groups, the dominance of these milk-associated taxa decreased with age, suggesting that diet and age simultaneously drive changes in the structure and abundance of bacterial communities in the developing rumen. Changes in the composition and abundance of archaeal communities were attributed exclusively to diet, with more highly abundant Methanosphaera and less abundant Methanobrevibacter in MC calves. Finally, the fungal community was dominated by members of the genus SK3 and Caecomyces . Relative

  1. Effect of Pre-weaning Diet on the Ruminal Archaeal, Bacterial, and Fungal Communities of Dairy Calves

    Science.gov (United States)

    Dias, Juliana; Marcondes, Marcos I.; Noronha, Melline F.; Resende, Rafael T.; Machado, Fernanda S.; Mantovani, Hilário C.; Dill-McFarland, Kimberly A.; Suen, Garret

    2017-01-01

    At birth, calves display an underdeveloped rumen that eventually matures into a fully functional rumen as a result of solid food intake and microbial activity. However, little is known regarding the gradual impact of pre-weaning diet on the establishment of the rumen microbiota. Here, we employed next-generation sequencing to investigate the effects of the inclusion of starter concentrate (M: milk-fed vs. MC: milk plus starter concentrate fed) on archaeal, bacterial and anaerobic fungal communities in the rumens of 45 crossbred dairy calves across pre-weaning development (7, 28, 49, and 63 days). Our results show that archaeal, bacterial, and fungal taxa commonly found in the mature rumen were already established in the rumens of calves at 7 days old, regardless of diet. This confirms that microbiota colonization occurs in the absence of solid substrate. However, diet did significantly impact some microbial taxa. In the bacterial community, feeding starter concentrate promoted greater diversity of bacterial taxa known to degrade readily fermentable carbohydrates in the rumen (e.g., Megasphaera, Sharpea, and Succinivribrio). Shifts in the ruminal bacterial community also correlated to changes in fermentation patterns that favored the colonization of Methanosphaera sp. A4 in the rumen of MC calves. In contrast, M calves displayed a bacterial community dominated by taxa able to utilize milk nutrients (e.g., Lactobacillus, Bacteroides, and Parabacteroides). In both diet groups, the dominance of these milk-associated taxa decreased with age, suggesting that diet and age simultaneously drive changes in the structure and abundance of bacterial communities in the developing rumen. Changes in the composition and abundance of archaeal communities were attributed exclusively to diet, with more highly abundant Methanosphaera and less abundant Methanobrevibacter in MC calves. Finally, the fungal community was dominated by members of the genus SK3 and Caecomyces. Relative

  2. Effect of Pre-weaning Diet on the Ruminal Archaeal, Bacterial, and Fungal Communities of Dairy Calves

    Directory of Open Access Journals (Sweden)

    Juliana Dias

    2017-08-01

    Full Text Available At birth, calves display an underdeveloped rumen that eventually matures into a fully functional rumen as a result of solid food intake and microbial activity. However, little is known regarding the gradual impact of pre-weaning diet on the establishment of the rumen microbiota. Here, we employed next-generation sequencing to investigate the effects of the inclusion of starter concentrate (M: milk-fed vs. MC: milk plus starter concentrate fed on archaeal, bacterial and anaerobic fungal communities in the rumens of 45 crossbred dairy calves across pre-weaning development (7, 28, 49, and 63 days. Our results show that archaeal, bacterial, and fungal taxa commonly found in the mature rumen were already established in the rumens of calves at 7 days old, regardless of diet. This confirms that microbiota colonization occurs in the absence of solid substrate. However, diet did significantly impact some microbial taxa. In the bacterial community, feeding starter concentrate promoted greater diversity of bacterial taxa known to degrade readily fermentable carbohydrates in the rumen (e.g., Megasphaera, Sharpea, and Succinivribrio. Shifts in the ruminal bacterial community also correlated to changes in fermentation patterns that favored the colonization of Methanosphaera sp. A4 in the rumen of MC calves. In contrast, M calves displayed a bacterial community dominated by taxa able to utilize milk nutrients (e.g., Lactobacillus, Bacteroides, and Parabacteroides. In both diet groups, the dominance of these milk-associated taxa decreased with age, suggesting that diet and age simultaneously drive changes in the structure and abundance of bacterial communities in the developing rumen. Changes in the composition and abundance of archaeal communities were attributed exclusively to diet, with more highly abundant Methanosphaera and less abundant Methanobrevibacter in MC calves. Finally, the fungal community was dominated by members of the genus SK3 and Caecomyces

  3. Limitations of drug registries to evaluate orphan medicinal products for the treatment of lysosomal storage disorders

    NARCIS (Netherlands)

    Hollak, Carla E. M.; Aerts, Johannes M. F. G.; Aymé, Ségolène; Manuel, Jeremy

    2011-01-01

    Orphan drugs are often approved under exceptional circumstances, requiring submission of additional data on safety and effectiveness through registries. These registries are mainly focused on one drug only and data is frequently incomplete. Some registries also address phenotypic heterogeneity and

  4. Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene expression

    International Nuclear Information System (INIS)

    Song, Kwang-Hoon

    2010-01-01

    The orphan nuclear receptor Nur77 (NR4A1) has been reported to play a crucial role in the modulation of diverse metabolic processes in liver. Here, we reported the identification of human apolipoprotein A5 (ApoA5), which implicated in lowering plasma triglyceride levels, as a novel target gene of Nur77. Nur77 induced the human ApoA5 promoter activity. Using 5'-deletion and mutagenesis of human ApoA5 promoter analysis and chromatin immunoprecipitation assays, it was shown that Nur77 directly regulated human ApoA5 gene expression by binding to a Nur77 response element (AAAGGTCA) located in the proximal human ApoA5 promoter region. In addition, we demonstrated that blocking of Nur77 transcriptional activity via overexpression of dominant negative Nur77 suppressed human ApoA5 promoter activity and mRNA expression in human hepatoma cells, HepG2. Taken together, our results demonstrated that Nur77 is a novel regulator of human ApoA5 gene expression and provide a new insight into the role of this orphan nuclear receptor in lipoprotein metabolism and triglyceride homeostasis.

  5. The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, X. Edward; Suino-Powell, Kelly M.; Xu, Yong; Chan, Cee-Wah; Tanabe, Osamu; Kruse, Schoen W.; Reynolds, Ross; Engel, James Douglas; Xu, H. Eric (Michigan-Med); (Van Andel)

    2015-11-30

    Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibits constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.

  6. Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kwang-Hoon, E-mail: ksong@kiom.re.kr [Korea Institute of Oriental Medicine, Daejeon 305-811 (Korea, Republic of)

    2010-01-29

    The orphan nuclear receptor Nur77 (NR4A1) has been reported to play a crucial role in the modulation of diverse metabolic processes in liver. Here, we reported the identification of human apolipoprotein A5 (ApoA5), which implicated in lowering plasma triglyceride levels, as a novel target gene of Nur77. Nur77 induced the human ApoA5 promoter activity. Using 5'-deletion and mutagenesis of human ApoA5 promoter analysis and chromatin immunoprecipitation assays, it was shown that Nur77 directly regulated human ApoA5 gene expression by binding to a Nur77 response element (AAAGGTCA) located in the proximal human ApoA5 promoter region. In addition, we demonstrated that blocking of Nur77 transcriptional activity via overexpression of dominant negative Nur77 suppressed human ApoA5 promoter activity and mRNA expression in human hepatoma cells, HepG2. Taken together, our results demonstrated that Nur77 is a novel regulator of human ApoA5 gene expression and provide a new insight into the role of this orphan nuclear receptor in lipoprotein metabolism and triglyceride homeostasis.

  7. 78 FR 44016 - Exclusion of Orphan Drugs for Certain Covered Entities Under 340B Program

    Science.gov (United States)

    2013-07-23

    ... used. Once a hospital is enrolled in 340B, it may change its decision to purchase all orphan drugs... alternative system to tracking each discounted drug through the purchasing and dispensing process. (59 FR... the purchasing and dispensing process, to prove compliance. If an alternate system of tracking is...

  8. Psychosocial Support for Orphans and Vulnerable Children in Public Primary Schools: Challenges and Intervention Strategies

    Science.gov (United States)

    Mwoma, Teresa; Pillay, Jace

    2015-01-01

    Much has been written about orphans and vulnerable children (OVC) with regard to their education and living. However, relatively few studies have documented the psychosocial support provided for OVC in public primary schools to enhance their psychosocial well-being. This study therefore contributes to the understanding of the challenges…

  9. Reimbursed Price of Orphan Drugs: Current Strategies and Potential Improvements.

    Science.gov (United States)

    Mincarone, Pierpaolo; Leo, Carlo Giacomo; Sabina, Saverio; Sarriá-Santamera, Antonio; Taruscio, Domenica; Serrano-Aguilar, Pedro Guillermo; Kanavos, Panos

    2017-01-01

    The pricing and reimbursement policies for pharmaceuticals are relevant to balance timely and equitable access for all patients, financial sustainability, and reward for valuable innovation. The proliferation of high-cost specialty medicines is particularly true in rare diseases (RDs) where the pricing mechanism is characterised by a lack of transparency. This work provides an overall picture of current strategies for the definition of the reimbursed prices of orphan drugs (ODs) and highlights some potential improvements. Current strategies and suggestions are presented along 4 dimensions: (1) comprehensive value assessment, (2) early dialogs among relevant stakeholders, (3) innovative reimbursement approaches, and (4) societal participation in producing ODs. Comprehensive value assessment could be achieved by clarifying the approach of distributive justice to adopt, ensuring a representative participation of stakeholders, and with a broad consideration of value-bearing factors. With respect to early dialogs, cross-border cooperation can be determinant to companies and agencies. The cost-benefit ratio of early dialogs needs to be demonstrated and the "regulatory capture" effect should be monitored. Innovative reimbursement approaches were developed to balance the need for evidence-based decisions with the timely access to innovative drugs. The societal participation in producing ODs needs to be recognised in a collaborating framework where adaptive agreements can be developed with mutual satisfaction. Such agreements could also impact on coverage and reimbursement decisions as additional elements for the determination of a comprehensive societal value of ODs. Further research is needed to investigate the highlighted open challenges so that RDs will not remain, in practical terms, orphan diseases. © 2017 S. Karger AG, Basel.

  10. Phylogenetic diversity of archaeal 16S rRNA and ammonia monooxygenase genes from tropical estuarine sediments on the central west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Singh, S.K.; Verma, P.; Ramaiah, N.; Anil, A.C.; Shouche, Y.S.

    of Euryarchaeota. Our results indicate that archaeal diversity in tropical estuarine sediments is influenced by the mangrove vegetation bordering the lower stretches of both estuaries. Higher diversity may be related to elevated land drainage during the monsoon...

  11. Combining native MS approaches to decipher archaeal box H/ACA ribonucleoprotein particle structure and activity.

    Science.gov (United States)

    Saliou, Jean-Michel; Manival, Xavier; Tillault, Anne-Sophie; Atmanene, Cédric; Bobo, Claude; Branlant, Christiane; Van Dorsselaer, Alain; Charpentier, Bruno; Cianférani, Sarah

    2015-08-01

    Site-specific isomerization of uridines into pseudouridines in RNAs is catalyzed either by stand-alone enzymes or by box H/ACA ribonucleoprotein particles (sno/sRNPs). The archaeal box H/ACA sRNPs are five-component complexes that consist of a guide RNA and the aCBF5, aNOP10, L7Ae, and aGAR1 proteins. In this study, we performed pairwise incubations of individual constituents of archaeal box H/ACA sRNPs and analyzed their interactions by native MS to build a 2D-connectivity map of direct binders. We describe the use of native MS in combination with ion mobility-MS to monitor the in vitro assembly of the active H/ACA sRNP particle. Real-time native MS was used to monitor how box H/ACA particle functions in multiple-turnover conditions. Native MS also unambiguously revealed that a substrate RNA containing 5-fluorouridine (f(5) U) was hydrolyzed into 5-fluoro-6-hydroxy-pseudouridine (f(5) ho(6) Ψ). In terms of enzymatic mechanism, box H/ACA sRNP was shown to catalyze the pseudouridylation of a first RNA substrate, then to release the RNA product (S22 f(5) ho(6) ψ) from the RNP enzyme and reload a new substrate RNA molecule. Altogether, our native MS-based approaches provide relevant new information about the potential assembly process and catalytic mechanism of box H/ACA RNPs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. HIV-Related Cognitive Impairment of Orphans in Myanmar With Vertically Transmitted HIV Taking Antiretroviral Therapy.

    Science.gov (United States)

    Linn, Kyaw; Fay, Alexander; Meddles, Katherine; Isbell, Sara; Lin, Phyo Nay; Thair, Cho; Heaps, Jodi; Paul, Robert; Mar, Soe Soe

    2015-12-01

    We determined the effect of perinatally acquired HIV on neurocognition in Myanmar children treated with antiretroviral therapy by comparison to demographically matched seronegative children. Myanmar has one of the highest HIV-1 prevalence rates in Southeast Asia. Studies from other resource-poor countries have shown that HIV-infected children differ in socioeconomic, nutritional and caregiver status compared to normal controls. Some vertically infected orphans in Myanmar reside separately from HIV-uninfected children in separate orphanages, thus the demographic variables of interest are naturally controlled. This study provides a unique evaluation of the neurocognitive effects of HIV in children, with control over key demographic variables. We hypothesized that HIV-infected orphans would perform significantly worse on cognitive indices compared with HIV-negative orphans. A battery of cognitive tests sensitive to HIV-associated impairments in children was administered to 28 perinatally acquired HIV-positive children and 31 HIV-negative children from two orphanages in Myanmar; 21 children from each cohort underwent testing at baseline and again after 12 months. Baseline comparison of the two groups indicated that the HIV-infected children performed poorly across all tests, with significant group differences in executive function, visuospatial reasoning, fine motor dexterity, and visual motor integration. On subsequent testing, both cohorts of children showed improvements across multiple domains, with no significant effect of age at treatment initiation. Our results demonstrate a strong effect of HIV infection on specific neurocognitive deficits in vertically infected children. Understanding viral and host determinants and timing and choice of antiretroviral therapy on cognition will be critical to preventing cognitive impairment of children with HIV. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours

    DEFF Research Database (Denmark)

    Yamada, Takuji; Waller, Alison S.; Raes, Jeroen

    2012-01-01

    Despite the current wealth of sequencing data, one-third of all biochemically characterized metabolic enzymes lack a corresponding gene or protein sequence, and as such can be considered orphan enzymes. They represent a major gap between our molecular and biochemical knowledge, and consequently a...... Systems Biology 8: 581; published online 8 May 2012; doi:10.1038/msb.2012.13...

  14. The Socioemotional Development of Orphans in Orphanages and Traditional Foster Care in Iraqi Kurdistan.

    Science.gov (United States)

    Ahmad, Abdulbaghi; Mohamad, Kirmanj

    1996-01-01

    A one-year follow-up study of children who had lost both parents and were placed in orphanages (n=19) or foster homes (n=18) in Iraqi Kurdistan investigated the orphans' situation and development. The children in orphanages were found to have higher frequency of post-traumatic stress disorder than the foster care children. (Author/CR)

  15. Archaeal Nitrification in Hot Springs

    Science.gov (United States)

    Richter, A.; Daims, H.; Reigstad, L.; Wanek, W.; Wagner, M.; Schleper, C.

    2006-12-01

    Biological nitrification, i.e. the aerobic conversion of ammonia to nitrate via nitrite, is a major component of the global nitrogen cycle. Until recently, it was thought that the ability to aerobically oxidize ammonia was confined to bacteria of the phylum Proteobacteria. However, it has recently been shown that Archaea of the phylum Crenarchaeota are also capable of ammonia oxidation. As many Crenarchaeota are thermophilic or hyperthermophilic, and at least some of them are capable of ammonia oxidation we speculated on the existence of (hyper)thermophilic ammonia-oxidizing archaea (AOA). Using PCR primers specifically targeting the archaeal ammonia monooxygenase (amoA) gene, we were indeed able to confirm the presence of such organisms in several hot springs in Reykjadalur, Iceland. These hot springs exhibited temperatures well above 80 °C and pH values ranging from 2.0 to 4.5. To proof that nitrification actually took place under these extreme conditions, we measured gross nitrification rates by the isotope pool dilution method; we added 15N-labelled nitrate to the mud and followed the dilution of the label by nitrate production from ammonium either in situ (incubation in the hot spring) or under controlled conditions in the laboratory (at 80 °C). The nitrification rates in the hot springs ranged from 0.79 to 2.22 mg nitrate-N per L of mud and day. Controls, in which microorganisms were killed before the incubations, demonstrated that the nitrification was of biological origin. Addition of ammonium increased the gross nitrification rate approximately 3-fold, indicating that the nitrification was ammonium limited under the conditions used. Collectively, our study provides evidence that (1) AOA are present in hot springs and (2) that they are actively nitrifying. These findings have major implications for our understanding of nitrogen cycling of hot environments.

  16. Adopted orphans as regulators of inflammation, immunity and skeletal homeostasis.

    Science.gov (United States)

    Ipseiz, Natacha; Scholtysek, Carina; Culemann, Stephan; Krönke, Gerhard

    2014-01-01

    Adopted orphan nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs), have emerged as key regulators of inflammation and immunity and likewise control skeletal homeostasis. These properties render them attractive targets for the therapy of various inflammatory and autoimmune diseases affecting the musculoskeletal system. This review summarises the current knowledge on the role of these families of receptors during innate and adaptive immunity as well as during the control of bone turnover and discuss the potential use of targeting these molecules during the treatment of chronic diseases such as osteoarthritis, rheumatoid arthritis and osteoporosis.

  17. Temporal change of composition and potential activity of the thermophilic archaeal community during the composting of organic material.

    Science.gov (United States)

    Thummes, Kathrin; Kämpfer, Peter; Jäckel, Udo

    2007-07-01

    To date, composting has been regarded as an aerobic process but it has been shown that composting piles are often sources of atmospheric methane. In order to gain a more comprehensive view on the diversity of methanogenic Archaea in compost, gas chromatographical methods and molecular cloning were used to study relationships of thermophilic archaeal communities and changes in methane production potential during compost maturation. According to the thermophilic methane production potential, wide differences could be detected between differently aged compost materials. In material derived from 3- and 4-week-old piles, low and no thermophilic methane production potential, respectively, was observed at 50 degrees C. Material from a 6-week-old pile showed the maximum methane production. With compost maturation, the production slowly decreased again with 6 weeks, 8 weeks, and mature compost showing an optimum methane production potential at 60 degrees C. At 70 degrees C, only 6-week-old material showed a comparable high production of methane. The 16S rRNA-based phylogenetic surveys revealed an increase of archaeal diversity with compost maturation. In the 6-week-old material, 86% of the sequences in the archaeal 16S rRNA library had the highest sequence similarities to Methanothermobacter spp. and the remaining 14% of the clones were related to Methanosarcina thermophila. Quantification of methanogens in 6-week-old material, on the basis of the methane production rate, resulted in values of about 2x10(7) cells per gram fresh weight. In 8-week-old and mature compost material, the proportion of sequences similar to Methanothermobacter spp. decreased to 34% and 0%, respectively. The mature compost material showed the highest variation in identified sequences, although 33% could be assigned to as yet uncultured Archaea (e.g. Rice cluster I, III, and IV). Our results indicate that compost harbours a diverse community of thermophilic methanogens, with changing composition

  18. Impact of domestic care environment on trauma and posttraumatic stress disorder among orphans in western Kenya.

    Directory of Open Access Journals (Sweden)

    Lukoye Atwoli

    Full Text Available The aim of this study was to determine the impact of the domestic care environment on the prevalence of potentially traumatic events (PTEs and posttraumatic stress disorder (PTSD among orphaned and separated children in Uasin Gishu County, western Kenya.A total of 1565 (55.5% male orphaned and separated adolescents aged 10-18 years (mean 13.8 years, sd 2.2, were assessed for PTSD and PTEs including bullying, physical abuse and sexual abuse. In this sample, 746 lived in extended family households, 746 in Charitable Children's Institutions (CCIs, and 73 on the street. Posttraumatic stress symptom (PTSS scores and PTSD were assessed using the Child PTSD Checklist.Bullying was the commonest PTE in all domestic care environments, followed by physical and sexual abuse. All PTEs were commonest among the street youth followed by CCIs. However, sexual abuse was more prevalent in households than in CCIs. Prevalence of PTSD was highest among street youth (28.8%, then households (15.0% and CCIs (11.5%. PTSS scores were also highest among street youth, followed by CCIs and households. Bullying was associated with higher PTSS scores and PTSD odds than either sexual or physical abuse.This study demonstrated differences in distribution of trauma and PTSD among orphaned and separated children in different domestic care environments, with street youth suffering more than those in CCIs or households. Interventions are needed to address bullying and sexual abuse, especially in extended family households. Street youth, a heretofore neglected population, are urgently in need of dedicated mental health services and support.

  19. Orphan Sources and Fresh Fallout: Virtual Exercise in Mobile Measurement (ORPEX)

    International Nuclear Information System (INIS)

    Dowdall, M.; Smethurst, M.A.; Andersson, K.; Aage, H.K.; Palsson, S.E.

    2011-10-01

    In recent years carborne gamma spectrometry has expanded from its role as a geological survey platform to serving as a useful asset in the field of emergency response to radiological and nuclear situations. Its two main applications are searching for orphan sources and for surveying in the aftermath of an accident involving the release of radioactive materials. Despite this expansion, the opportunities for gaining practical experience in the field are limited by cost considerations and practicability. These limitations are exacerbated by the fact that data generated and displayed in the field differ significantly from gamma spectral data generated in a laboratory environment. As a means of exercising existing emergency measuring/surveying capability and introducing carborne measurements to a larger group, a virtual exercise was devised. The exercise ORPEX (Orphan Sources and Fresh Fallout Virtual Exercise in Mobile Measurement) featured two typical emergency scenarios in which carborne measuring systems might be deployed: firstly a search for multiple orphan sources and secondly surveying to delineate patchy fallout from a local release point. In the first scenario, synthetic spectral data were generated for imaginary point sources and inserted into genuine carborne measurements from in the Trondheim area of Norway. Participants were presented with a typical software tool and data in a range of typical formats and asked to report the source locations and isotopes within a time limit. In the second scenario, synthetic spectral data representing fallout from a local fire involving radioactive material were added to real carborne data from the Trondheim area. Participants were asked to produce maps that identify and characterise the regions of contamination within the same time limit. Fourteen individual organisations from seven different countries supplied results. Results from participants indicate that for strong sources of isotopes with simple spectra featuring

  20. Orphan Sources and Fresh Fallout: Virtual Exercise in Mobile Measurement (ORPEX)

    Energy Technology Data Exchange (ETDEWEB)

    Dowdall, M. (Norwegian Radiation Protection Authority, OEsteraas (Norway)); Smethurst, M.A. (Univ. of Exeter and Avalonia Geophysics, Cornwall Campus, Penryn (United Kingdom)); Andersson, K. (Technical Univ. of Denmark. Risoe National Lab. for Sustainable Energy, Roskilde (Denmark)); Aage, H.K. (Danish Emergency Management Agency, Birkeroed (Denmark)); Palsson, S.E. (Icelandic Radiation Protection Institute, Reykjavik (Iceland))

    2011-10-15

    In recent years carborne gamma spectrometry has expanded from its role as a geological survey platform to serving as a useful asset in the field of emergency response to radiological and nuclear situations. Its two main applications are searching for orphan sources and for surveying in the aftermath of an accident involving the release of radioactive materials. Despite this expansion, the opportunities for gaining practical experience in the field are limited by cost considerations and practicability. These limitations are exacerbated by the fact that data generated and displayed in the field differ significantly from gamma spectral data generated in a laboratory environment. As a means of exercising existing emergency measuring/surveying capability and introducing carborne measurements to a larger group, a virtual exercise was devised. The exercise ORPEX (Orphan Sources and Fresh Fallout Virtual Exercise in Mobile Measurement) featured two typical emergency scenarios in which carborne measuring systems might be deployed: firstly a search for multiple orphan sources and secondly surveying to delineate patchy fallout from a local release point. In the first scenario, synthetic spectral data were generated for imaginary point sources and inserted into genuine carborne measurements from in the Trondheim area of Norway. Participants were presented with a typical software tool and data in a range of typical formats and asked to report the source locations and isotopes within a time limit. In the second scenario, synthetic spectral data representing fallout from a local fire involving radioactive material were added to real carborne data from the Trondheim area. Participants were asked to produce maps that identify and characterise the regions of contamination within the same time limit. Fourteen individual organisations from seven different countries supplied results. Results from participants indicate that for strong sources of isotopes with simple spectra featuring

  1. HER2 Deregulation in Lung Cancer: Right Time to Adopt an Orphan?

    Science.gov (United States)

    Cappuzzo, Federico; Landi, Lorenza

    2018-06-01

    HER2 -deregulated non-small cell lung cancer is an orphan of any specific therapy, probably because of lack of both accurate patient selection and effective drugs. Recent evidence suggests that osimertinib could be effective in HER2 -amplified or mutated lung cancer as a single agent or in combination. Clin Cancer Res; 24(11); 2470-2. ©2018 AACR See related article by Liu et al., p. 2594 . ©2018 American Association for Cancer Research.

  2. MED: a new non-supervised gene prediction algorithm for bacterial and archaeal genomes

    Directory of Open Access Journals (Sweden)

    Yang Yi-Fan

    2007-03-01

    Full Text Available Abstract Background Despite a remarkable success in the computational prediction of genes in Bacteria and Archaea, a lack of comprehensive understanding of prokaryotic gene structures prevents from further elucidation of differences among genomes. It continues to be interesting to develop new ab initio algorithms which not only accurately predict genes, but also facilitate comparative studies of prokaryotic genomes. Results This paper describes a new prokaryotic genefinding algorithm based on a comprehensive statistical model of protein coding Open Reading Frames (ORFs and Translation Initiation Sites (TISs. The former is based on a linguistic "Entropy Density Profile" (EDP model of coding DNA sequence and the latter comprises several relevant features related to the translation initiation. They are combined to form a so-called Multivariate Entropy Distance (MED algorithm, MED 2.0, that incorporates several strategies in the iterative program. The iterations enable us to develop a non-supervised learning process and to obtain a set of genome-specific parameters for the gene structure, before making the prediction of genes. Conclusion Results of extensive tests show that MED 2.0 achieves a competitive high performance in the gene prediction for both 5' and 3' end matches, compared to the current best prokaryotic gene finders. The advantage of the MED 2.0 is particularly evident for GC-rich genomes and archaeal genomes. Furthermore, the genome-specific parameters given by MED 2.0 match with the current understanding of prokaryotic genomes and may serve as tools for comparative genomic studies. In particular, MED 2.0 is shown to reveal divergent translation initiation mechanisms in archaeal genomes while making a more accurate prediction of TISs compared to the existing gene finders and the current GenBank annotation.

  3. Using constitutive activity to define appropriate high-throughput screening assays for orphan g protein-coupled receptors.

    Science.gov (United States)

    Ngo, Tony; Coleman, James L J; Smith, Nicola J

    2015-01-01

    Orphan G protein-coupled receptors represent an underexploited resource for drug discovery but pose a considerable challenge for assay development because their cognate G protein signaling pathways are often unknown. In this methodological chapter, we describe the use of constitutive activity, that is, the inherent ability of receptors to couple to their cognate G proteins in the absence of ligand, to inform the development of high-throughput screening assays for a particular orphan receptor. We specifically focus on a two-step process, whereby constitutive G protein coupling is first determined using yeast Gpa1/human G protein chimeras linked to growth and β-galactosidase generation. Coupling selectivity is then confirmed in mammalian cells expressing endogenous G proteins and driving accumulation of transcription factor-fused luciferase reporters specific to each of the classes of G protein. Based on these findings, high-throughput screening campaigns can be performed on the already miniaturized mammalian reporter system.

  4. Characterization of radioactive orphan sources by gamma spectrometry; Caracterizacion de fuentes huerfanas radiactivas por espectrometria gamma

    Energy Technology Data Exchange (ETDEWEB)

    Cruz W, H., E-mail: wcruz@ipen.gob.pe [Instituto Peruano de Energia Nuclear (PGRR/IPEN), Lima (Peru). Planta de Gestion de Residuos Radiactivos

    2013-07-01

    The sealed radioactive sources are widely applicable in industry. They must have a permanent control and must be registered with the Technical Office of the National Authority (OTAN). However, at times it has identified the presence of abandoned sealed sources unknown to the owner. These sources are called 'orphan sources'. Of course these sources represent a high potential risk because accidents can trigger dire consequences depending on your activity and chemical form in which it presents the radioisotope. This paper describes the process and the actions taken to characterize two orphan radioactive sources from the smelter a Aceros Arequipa. For characterization we used a gamma spectrometry system using a detector NaI(Tl) 3″ x 3″ with a multichannel analyzer Nucleus PCA-II. The radioisotope identified was cesium - 137 ({sup 137}Cs) in both cases. Fortunately, the sources maintained their integrity would otherwise have generated significant pollution considering the chemical form of the radioisotope and easy dispersion. (author)

  5. Making Good on a Promise: The Education of Civil War Orphans in Pennsylvania, 1863-1893

    Science.gov (United States)

    Bair, Sarah D.

    2011-01-01

    During and after the American Civil War, individual state governments, faced with numerous economic demands, struggled to meet the needs of soldiers and their families. Among other pressing questions, they had to decide what to do with the massive number of dependent children orphaned by the war. In order to protect children, it became more…

  6. Next generation DNA sequencing technology delivers valuable genetic markers for the genomic orphan legume species, Bituminaria bituminosa

    Directory of Open Access Journals (Sweden)

    Pazos-Navarro María

    2011-12-01

    Full Text Available Abstract Background Bituminaria bituminosa is a perennial legume species from the Canary Islands and Mediterranean region that has potential as a drought-tolerant pasture species and as a source of pharmaceutical compounds. Three botanical varieties have previously been identified in this species: albomarginata, bituminosa and crassiuscula. B. bituminosa can be considered a genomic 'orphan' species with very few genomic resources available. New DNA sequencing technologies provide an opportunity to develop high quality molecular markers for such orphan species. Results 432,306 mRNA molecules were sampled from a leaf transcriptome of a single B. bituminosa plant using Roche 454 pyrosequencing, resulting in an average read length of 345 bp (149.1 Mbp in total. Sequences were assembled into 3,838 isotigs/contigs representing putatively unique gene transcripts. Gene ontology descriptors were identified for 3,419 sequences. Raw sequence reads containing simple sequence repeat (SSR motifs were identified, and 240 primer pairs flanking these motifs were designed. Of 87 primer pairs developed this way, 75 (86.2% successfully amplified primarily single fragments by PCR. Fragment analysis using 20 primer pairs in 79 accessions of B. bituminosa detected 130 alleles at 21 SSR loci. Genetic diversity analyses confirmed that variation at these SSR loci accurately reflected known taxonomic relationships in original collections of B. bituminosa and provided additional evidence that a division of the botanical variety bituminosa into two according to geographical origin (Mediterranean region and Canary Islands may be appropriate. Evidence of cross-pollination was also found between botanical varieties within a B. bituminosa breeding programme. Conclusions B. bituminosa can no longer be considered a genomic orphan species, having now a large (albeit incomplete repertoire of expressed gene sequences that can serve as a resource for future genetic studies. This

  7. Care and support of orphaned and vulnerable children at school: helping teachers to respond

    Directory of Open Access Journals (Sweden)

    Lesley Wood

    2011-01-01

    Full Text Available It is acknowledged that teacher training programmes around HIV in most of sub-Saharan Africa appear not to have been very effective in assisting teachers to respond to the demands placed on them by the pandemic. In response to the need identified by international development agencies, for research into teacher education and HIV in sub-Saharan Africa, this study investigated teacher perceptions of the effectiveness of training programmes offered in a specific school district in South Africa to equip them to deal with issues arising from having orphans and vulnerable children in their classrooms. A qualitative research design was followed to purposively select teachers who had attended the departmental training to participate in focus groups to explore the phenomenon of teaching orphaned and vulnerable children. The findings that emerged from the thematic data analysis provided supporting evidence that current teacher education approaches in this regard are not perceived to be effective. The results are used to suggest guidelines for an alternative approach to the current forms of HIV and AIDS training for teachers that is more likely to be sustainable, culturally appropriate and suited to the context.

  8. Availability of and access to orphan drugs: an international comparison of pharmaceutical treatments for pulmonary arterial hypertension, Fabry disease, hereditary angioedema and chronic myeloid leukaemia.

    Science.gov (United States)

    Blankart, Carl Rudolf; Stargardt, Tom; Schreyögg, Jonas

    2011-01-01

    Market authorization does not guarantee patient access to any given drug. This is particularly true for costly orphan drugs because access depends primarily on co-payments, reimbursement policies and prices. The objective of this article is to identify differences in the availability of orphan drugs and in patient access to them in 11 pharmaceutical markets: Australia, Canada, England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland and the US. Four rare diseases were selected for analysis: pulmonary arterial hypertension (PAH), Fabry disease (FD), hereditary angioedema (HAE) and chronic myeloid leukaemia (CML). Indicators for availability were defined as (i) the indications for which orphan drugs had been authorized in the treatment of these diseases; (ii) the application date; and (iii) the date upon which these drugs received market authorization in each country. Indicators of patient access were defined as (i) the outcomes of technology appraisals; (ii) the extent of coverage provided by healthcare payers; and (iii) the price of the drugs in each country. For PAH we analysed bosentan, iloprost, sildenafil, treprostinil (intravenous and inhaled) as well as sitaxentan and ambrisentan; for FD we analysed agalsidase alfa and agalsidase beta; for HAE we analysed icatibant, ecallantide and two complement C1s inhibitors; for CML we analysed imatinib, dasatinib and nilotinib. Most drugs included in this study had received market authorization in all countries, but the range of indications for which they had been authorized differed by country. The broadest range of indications was found in Australia, and the largest variations in indications were found for PAH drugs. Authorization process speed (the time between application and market authorization) was fastest in the US, with an average of 362 days, followed by the EU (394 days). The highest prices for the included drugs were found in Germany and the US, and the lowest in Canada, Australia and

  9. Elucidation of primary metabolic pathways in Aspergillus species: orphaned research in characterizing orphan genes.

    Science.gov (United States)

    Andersen, Mikael Rørdam

    2014-11-01

    Primary metabolism affects all phenotypical traits of filamentous fungi. Particular examples include reacting to extracellular stimuli, producing precursor molecules required for cell division and morphological changes as well as providing monomer building blocks for production of secondary metabolites and extracellular enzymes. In this review, all annotated genes from four Aspergillus species have been examined. In this process, it becomes evident that 80-96% of the genes (depending on the species) are still without verified function. A significant proportion of the genes with verified metabolic functions are assigned to secondary or extracellular metabolism, leaving only 2-4% of the annotated genes within primary metabolism. It is clear that primary metabolism has not received the same attention in the post-genomic area as many other research areas--despite its role at the very centre of cellular function. However, several methods can be employed to use the metabolic networks in tandem with comparative genomics to accelerate functional assignment of genes in primary metabolism. In particular, gaps in metabolic pathways can be used to assign functions to orphan genes. In this review, applications of this from the Aspergillus genes will be examined, and it is proposed that, where feasible, this should be a standard part of functional annotation of fungal genomes. © The Author 2014. Published by Oxford University Press.

  10. Tide as steering factor in structuring archaeal and bacterial ammonia-oxidizing communities in mangrove forest soils dominated by Avicennia germinans and Rhizophora mangle

    NARCIS (Netherlands)

    Marcos, Magali S.; Barboza, A.D.H.; Keijzer, R.M.; Laanbroek, H.J.

    2018-01-01

    Mangrove species are adapted to grow at specific zones in a tidal gradient. Here we tested the hypothesis that the archaeal and bacterial ammonia-oxidizing microbial communities differ in soils dominated by the mangrove species Avicennia germinans and Rhizophora mangle. Two of the sampling locations

  11. [Archaeal diversity in permafrost deposits of Bunger Hills Oasis and King George Island (Antarctica) according to the 16S rRNA gene sequencing].

    Science.gov (United States)

    Karaevskaia, E S; Demchenko, L S; Demidov, N É; Rivkina, E M; Bulat, S A; Gilichinskiĭ, D A

    2014-01-01

    Archaeal communities of permafrost deposits of King George Island and Bunger Hills Oasis (Antarctica) differing in the content of biogenic methane were analyzed using clone libraries of two 16S rRNA gene regions. Phylotypes belonging to methanogenic archaea were identified in all horizons.

  12. Orphan sources: Consequences, regaining control and learning the lessons

    International Nuclear Information System (INIS)

    Croft, J.R.

    2001-01-01

    The safety and security record of technologies that use radiation sources is adequate in most cases, but on occasions there has been a lack of appropriate controls or circumvention of those that exist, leading to radiological accidents. Particular concern rise those radiation sources that have become orphans i.e. sources that were never subject to regulatory control, or were abandoned, lost or misplaced, stolen, or removed without authorisation. These sources are likely to be found in the public domain; examples include sources that used in radiotherapy units which have been unintentionally sold as scrap metal and melted thereafter, or which have been found by unsuspecting individuals or stolen, causing serious radiation exposure of people and contamination of the human habitat

  13. Non-extremophilic 'extremophiles' - Archaeal dominance in the subsurface and their implication for life

    Science.gov (United States)

    Reitschuler, Christoph; Lins, Philipp; Illmer, Paul

    2014-05-01

    Archaea - besides bacteria and eukaryota constituting the third big domain of life - were so far regarded as typical inhabitants of extreme environments, as indicated by the name (Archaeon, Greek: 'original', 'primal'). Previous research and cultivation successes were basically carried out in habitats characterized by extreme temperature, pH and salinity regimes. Such extreme conditions, as expected at the beginning of the Earth's evolution, are occasionally also prevalent on extraterrestrial planets and moons and make the Archaeal domain a key group to be studied concerning life's evolution and the most likely pioneer organisms to colonize environments that are regarded as hostile. However, in recent years it became obvious that Archaea, in particular non-extremophilic species, can be found almost ubiquitously in marine, freshwater, terrestrial and also subsurface habitats and occasionally outnumber other microbial domains and hold key positions in globally relevant energy and nutrient cycles. Besides extreme environments - the big question remains how to define a parameter as extreme - subsurface and cave environments present a window to the past, where adaptions to early life's conditions can be studied and how microbiomes may be structured in a habitat that represents a refugium on extraterrestrial celestial bodies, were surface conditions might be at first sight too extreme for life. The lower part of the alpine Hundsalm cave in Tyrol (Austria) offered a unique opportunity to study an almost pristine cave habitat, which is separated from the touristic part of the ice cave. The main focus of our research was laid on the microbial communities that were supposed to be in connection with secondary carbonate precipitations ('moonmilk'). For the ascertainment of these so far poorly evaluated structures a multiple approach assessment was chosen to generate a virtually complete picture of these subsurface microbiomes. Thereby, a combination of different cultivation

  14. 75 FR 53701 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01...

    Science.gov (United States)

    2010-09-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0394] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01); Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug...

  15. Quaternary Sedimentary Processes and Budgets in Orphan Basin, Southwestern Labrador Sea

    Science.gov (United States)

    Hiscott, Richard N.; Aksu, Ali E.

    1996-03-01

    The continental slope in Orphan Basin, northeast of Newfoundland, is underlain by several seaward-thinning debris-flow wedges alternating with acoustically stratified, regionally extensive, mainly hemipelagic sediments. δ 18O stratigraphy and volcanic ash layers in a 11.67-m core indicate that the uppermost debris-flow wedge formed during the last of several sea-level lowstands in isotopic stages 2-4. Similarly, seismic reflection correlation of dated levels at DSDP Site 111 with the Orphan Basin succession suggests that two deeper debris-flow wedges were deposited during oxygen isotopic stages 6 and 8. The oldest of the debris-flow deposits in at least three of the wedges formed well into the corresponding glacial cycle, after ice sheets had reached the edge of the continental shelf. Slower deposition by hemipelagic processes and ice rafting formed the acoustically stratified units, including Heinrich layers. The youngest three debris-flow wedges each have volumes of 1300-1650 km 3. Approximately two-thirds of this material is attributed to glacial erosion of Mesozoic and Tertiary strata beneath the Northeast Newfoundland Shelf. The remainder is believed to have been derived by glacial erosion of older bedrock that now forms the island of Newfoundland. The observed sediment volumes and the inferred basal and upper ages of the debris-flow wedges imply an average glacial denudation rate of about 0.13 mm/yr for this older bedrock, and an average of about 60 m of glacial bedrock erosion since oxygen isotope stage 22. This denudation rate is similar to estimates from the Barents Sea region off Norway.

  16. Protein phosphorylation and its role in archaeal signal transduction

    Science.gov (United States)

    Esser, Dominik; Hoffmann, Lena; Pham, Trong Khoa; Bräsen, Christopher; Qiu, Wen; Wright, Phillip C.; Albers, Sonja-Verena; Siebers, Bettina

    2016-01-01

    Reversible protein phosphorylation is the main mechanism of signal transduction that enables cells to rapidly respond to environmental changes by controlling the functional properties of proteins in response to external stimuli. However, whereas signal transduction is well studied in Eukaryotes and Bacteria, the knowledge in Archaea is still rather scarce. Archaea are special with regard to protein phosphorylation, due to the fact that the two best studied phyla, the Euryarchaeota and Crenarchaeaota, seem to exhibit fundamental differences in regulatory systems. Euryarchaeota (e.g. halophiles, methanogens, thermophiles), like Bacteria and Eukaryotes, rely on bacterial-type two-component signal transduction systems (phosphorylation on His and Asp), as well as on the protein phosphorylation on Ser, Thr and Tyr by Hanks-type protein kinases. Instead, Crenarchaeota (e.g. acidophiles and (hyper)thermophiles) only depend on Hanks-type protein phosphorylation. In this review, the current knowledge of reversible protein phosphorylation in Archaea is presented. It combines results from identified phosphoproteins, biochemical characterization of protein kinases and protein phosphatases as well as target enzymes and first insights into archaeal signal transduction by biochemical, genetic and polyomic studies. PMID:27476079

  17. Archaea, Bacteria, and Sulfur-Cycling in a Shallow-Sea Hydrothermal Ecosystem

    Science.gov (United States)

    Amend, J. P.; Huang, C.; Amann, R.; Bach, W.; Meyerdierks, A.; Price, R. E.; Schubotz, F.; Summons, R. E.; Wenzhoefer, F.

    2009-12-01

    Deep-sea hydrothermal systems are windows to the marine subsurface biosphere. It often is overlooked, however, that their far more accessible shallow-sea counterparts can serve the same purpose. To characterize the extent, diversity, and activity of the subsurface microbial community in the shallow vent ecosystem near Panarea Island (Italy), sediment cores were analyzed with a broad array of analytical techniques. Vent fluid and sediment temperatures reached up to 135 °C, with pHs in porewaters generally measuring 5-6. Microsensor profiles marked a very sharp oxic-anoxic transition, and when coupled to pH and H2S profiles, pointed to aerobic sulfide oxidation. With increasing depth from the sediment-water interface, porewater analyses showed a decrease in sulfate levels from ~30 mM to thermophilic sulfate reducing and acidophilic sulfide oxidiz