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Sample records for early browning virus

  1. Molecular insights into Cassava brown streak virus susceptibility and resistance by profiling of the early host response.

    PubMed

    Anjanappa, Ravi B; Mehta, Devang; Okoniewski, Michal J; Szabelska-Berȩsewicz, Alicja; Gruissem, Wilhelm; Vanderschuren, Hervé

    2018-02-01

    Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV) are responsible for significant cassava yield losses in eastern sub-Saharan Africa. To study the possible mechanisms of plant resistance to CBSVs, we inoculated CBSV-susceptible and CBSV-resistant cassava varieties with a mixed infection of CBSVs using top-cleft grafting. Transcriptome profiling of the two cassava varieties was performed at the earliest time point of full infection (28 days after grafting) in the susceptible scions. The expression of genes encoding proteins in RNA silencing, salicylic acid pathways and callose deposition was altered in the susceptible cassava variety, but transcriptional changes were limited in the resistant variety. In total, the expression of 585 genes was altered in the resistant variety and 1292 in the susceptible variety. Transcriptional changes led to the activation of β-1,3-glucanase enzymatic activity and a reduction in callose deposition in the susceptible cassava variety. Time course analysis also showed that CBSV replication in susceptible cassava induced a strong up-regulation of RDR1, a gene previously reported to be a susceptibility factor in other potyvirus-host pathosystems. The differences in the transcriptional responses to CBSV infection indicated that susceptibility involves the restriction of callose deposition at plasmodesmata. Aniline blue staining of callose deposits also indicated that the resistant variety displays a moderate, but significant, increase in callose deposition at the plasmodesmata. Transcriptome data suggested that resistance does not involve typical antiviral defence responses (i.e. RNA silencing and salicylic acid). A meta-analysis of the current RNA-sequencing (RNA-seq) dataset and selected potyvirus-host and virus-cassava RNA-seq datasets revealed that the conservation of the host response across pathosystems is restricted to genes involved in developmental processes. © 2017 THE AUTHORS. MOLECULAR PLANT

  2. Comparative genome and evolutionary analysis of naturally occurring Beilong virus in brown and black rats.

    PubMed

    Woo, Patrick C Y; Wong, Annette Y P; Wong, Beatrice H L; Lam, Carol S F; Fan, Rachel Y Y; Lau, Susanna K P; Yuen, Kwok-Yung

    2016-11-01

    Recently, we reported the presence of Beilong virus in spleen and kidney samples of brown rats and black rats, suggesting that these rodents could be natural reservoirs of Beilong virus. In this study, four genomes of Beilong virus from brown rats and black rats were sequenced. Similar to the Beilong virus genome sequenced from kidney mesangial cell line culture, those of J-virus from house mouse and Tailam virus from Sikkim rats, these four genomes from naturally occurring Beilong virus also contain the eight genes (3'-N-P/V/C-M-F-SH-TM-G-L-5'). In these four genomes, the attachment glycoprotein encoded by the G gene consists of 1046 amino acids; but for the original Beilong virus genome sequenced from kidney mesangial cell line, the G CDS was predicted to be prematurely terminated at position 2205 (TGG→TAG), resulting in a 734-amino-acid truncated G protein. This phenomenon of a lack of nonsense mutation in naturally occurring Beilong viruses was confirmed by sequencing this region of 15 additional rodent samples. Phylogenetic analyses showed that the cell line and naturally occurring Beilong viruses were closely clustered, without separation into subgroups. In addition, these viruses were further clustered with J-virus and Tailam virus, with high bootstrap supports of >90%, forming a distinct group in Paramyxoviridae. Brown rats and black rats are natural reservoirs of Beilong virus. Our results also supports that the recently proposed genus, Jeilongvirus, should encompass Beilong virus, J-virus and Tailam virus as members. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Deep Sequencing Reveals a Divergent Ugandan cassava brown streak virus Isolate from Malawi

    PubMed Central

    Winter, Stephan; Mukasa, Settumba; Tairo, Fred; Sseruwagi, Peter; Ndunguru, Joseph; Duffy, Siobain

    2017-01-01

    ABSTRACT Illumina sequencing of RNA from a cassava cutting from northern Malawi produced a genome of Ugandan cassava brown streak virus (UCBSV-MW-NB7_2013). Sequence comparisons revealed stronger similarity to an isolate from nearby Tanzania (93.4% pairwise nucleotide identity) than to those previously reported from Malawi (86.9 to 87.0%). PMID:28818908

  4. Worldwide occurrence of virus-infections in filamentous marine brown algae

    NASA Astrophysics Data System (ADS)

    Müller, D. G.; Stache, B.

    1992-03-01

    Virus infections were detected in Ectocarpus siliculosus and Ectocarpus fasciculatus on the coasts of Ireland, California, Peru, southern South America, Australia and New Zealand; in three Feldmannia species on the coasts of Ireland, continental Chile and Archipelago Juan Fernandez (Chile); and in Leptonematella from Antarctica. Natural populations on the Irish coast contained 3% infected plants in E. fasciculatus, and less than 1% in Feldmannia simplex. On the Californian coast, 15 to 25% of Ectocarpus isolates were infected. Virus symptoms were absent in E. siliculosus from Peru, but appeared after meiosis in laboratory cultures. The virus particles in E. fasciculatus are identical in size and capsid structure to those reported for E. siliculosus, while the virus in F. simplex is smaller and has a different envelope. Our findings suggest that virus infections are a common and worldwide phenomenon in filamentous brown algae.

  5. Molecular evolution and antigenic variation of European brown hare syndrome virus (EBHSV).

    PubMed

    Lopes, Ana M; Capucci, Lorenzo; Gavier-Widén, Dolores; Le Gall-Reculé, Ghislaine; Brocchi, Emiliana; Barbieri, Ilaria; Quéméner, Agnès; Le Pendu, Jacques; Geoghegan, Jemma L; Holmes, Edward C; Esteves, Pedro J; Abrantes, Joana

    2014-11-01

    European brown hare syndrome virus (EBHSV) is the aetiological agent of European brown hare syndrome (EBHS), a disease affecting Lepus europaeus and Lepus timidus first diagnosed in Sweden in 1980. To characterize EBHSV evolution we studied hare samples collected in Sweden between 1982 and 2008. Our molecular clock dating is compatible with EBHSV emergence in the 1970s. Phylogenetic analysis revealed two lineages: Group A persisted until 1989 when it apparently suffered extinction; Group B emerged in the mid-1980s and contains the most recent strains. Antigenic differences exist between groups, with loss of reactivity of some MAbs over time, which are associated with amino acid substitutions in recognized epitopes. A role for immune selection is also supported by the presence of positively selected codons in exposed regions of the capsid. Hence, EBHSV evolution is characterized by replacement of Group A by Group B viruses, suggesting that the latter possess a selective advantage. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS

    EPA Science Inventory

    EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS (P. Singhl, D.W. Winsett2, M.J. Daniels2,
    C.A.J. Dick', K.B. Adlerl and M.I. Gilmour2, INCSU, Raleigh, N.C., 2NHEERL/ORD/ USEPA, RTP, N.C. and 3UNC, Chapel Hill, N.C.)The interaction between ...

  7. Cassava brown streak disease in Rwanda, the associated viruses and disease phenotypes.

    PubMed

    Munganyinka, E; Ateka, E M; Kihurani, A W; Kanyange, M C; Tairo, F; Sseruwagi, P; Ndunguru, J

    2018-02-01

    Cassava brown streak disease (CBSD) was first observed on cassava ( Manihot esculenta ) in Rwanda in 2009. In 2014 eight major cassava-growing districts in the country were surveyed to determine the distribution and variability of symptom phenotypes associated with CBSD, and the genetic diversity of cassava brown streak viruses. Distribution of the CBSD symptom phenotypes and their combinations varied greatly between districts, cultivars and their associated viruses. The symptoms on leaf alone recorded the highest (32.2%) incidence, followed by roots (25.7%), leaf + stem (20.3%), leaf + root (10.4%), leaf + stem + root (5.2%), stem + root (3.7%), and stem (2.5%) symptoms. Analysis by RT-PCR showed that single infections of Ugandan cassava brown streak virus (UCBSV) were most common (74.2% of total infections) and associated with all the seven phenotypes studied. Single infections of Cassava brown streak virus (CBSV) were predominant (15.3% of total infections) in CBSD-affected plants showing symptoms on stems alone. Mixed infections (CBSV + UCBSV) comprised 10.5% of total infections and predominated in the combinations of leaf + stem + root phenotypes. Phylogenetic analysis and the estimates of evolutionary divergence, using partial sequences (210 nt) of the coat protein gene, revealed that in Rwanda there is one type of CBSV and an indication of diverse UCBSV. This study is the first to report the occurrence and distribution of both CBSV and UCBSV based on molecular techniques in Rwanda.

  8. A Virus-Derived Stacked RNAi Construct Confers Robust Resistance to Cassava Brown Streak Disease

    PubMed Central

    Beyene, Getu; Chauhan, Raj Deepika; Ilyas, Muhammad; Wagaba, Henry; Fauquet, Claude M.; Miano, Douglas; Alicai, Titus; Taylor, Nigel J.

    2017-01-01

    Cassava brown streak disease (CBSD) threatens food and economic security for smallholder farmers throughout East and Central Africa, and poses a threat to cassava production in West Africa. CBSD is caused by two whitefly-transmitted virus species: Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV) (Genus: Ipomovirus, Family Potyviridae). Although varying levels of tolerance have been achieved through conventional breeding, to date, effective resistance to CBSD within East African cassava germplasm has not been identified. RNAi technology was utilized to integrate CBSD resistance into the Ugandan farmer-preferred cassava cultivar TME 204. Transgenic plant lines were generated expressing an inverted repeat construct (p5001) derived from coat-protein (CP) sequences of CBSV and UCBSV fused in tandem. Northern blots using probes specific for each CP sequence were performed to characterize 169 independent transgenic lines for accumulation of CP-derived siRNAs. Transgenic plant lines accumulating low, medium and high levels of siRNAs were bud graft challenged with the virulent CBSV Naliendele isolate alone or in combination with UCBSV. Resistance to CBSD in the greenhouse directly correlated to levels of CP-derived siRNAs as determined by visual assessment of leaf and storage root symptoms, and RT-PCR diagnosis for presence of the pathogens. Low expressing lines were found to be susceptible to CBSV and UCBSV, while medium to high accumulating plant lines were resistant to both virus species. Absence of detectable virus in the best performing p5001 transgenic lines was further confirmed by back-inoculation via sap or graft challenge to CBSD susceptible Nicotiana benthamiana and cassava cultivar 60444, respectively. Data presented shows robust resistance of transgenic p5001 TME 204 lines to both CBSV and UCBSV under greenhouse conditions. Levels of resistance correlated directly with levels of transgene derived siRNA expression such that the

  9. Cassava brown streak virus has a rapidly evolving genome: implications for virus speciation, variability, diagnosis and host resistance

    PubMed Central

    Alicai, Titus; Ndunguru, Joseph; Sseruwagi, Peter; Tairo, Fred; Okao-Okuja, Geoffrey; Nanvubya, Resty; Kiiza, Lilliane; Kubatko, Laura; Kehoe, Monica A.; Boykin, Laura M.

    2016-01-01

    Cassava is a major staple food for about 800 million people in the tropics and sub-tropical regions of the world. Production of cassava is significantly hampered by cassava brown streak disease (CBSD), caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). The disease is suppressing cassava yields in eastern Africa at an alarming rate. Previous studies have documented that CBSV is more devastating than UCBSV because it more readily infects both susceptible and tolerant cassava cultivars, resulting in greater yield losses. Using whole genome sequences from NGS data, we produced the first coalescent-based species tree estimate for CBSV and UCBSV. This species framework led to the finding that CBSV has a faster rate of evolution when compared with UCBSV. Furthermore, we have discovered that in CBSV, nonsynonymous substitutions are more predominant than synonymous substitution and occur across the entire genome. All comparative analyses between CBSV and UCBSV presented here suggest that CBSV may be outsmarting the cassava immune system, thus making it more devastating and harder to control. PMID:27808114

  10. Hepatitis E virus in wild rabbits and European brown hares in Germany.

    PubMed

    Hammerschmidt, F; Schwaiger, K; Dähnert, L; Vina-Rodriguez, A; Höper, D; Gareis, M; Groschup, M H; Eiden, M

    2017-12-01

    Recently, a change of hepatitis E from being a typical travel-associated disease to an autochthonous zoonosis in Germany was observed. An increasing number of autochthonous infections with the hepatitis E Virus (HEV) have been recognized in developed countries. Venison from wild boar is already known to be a potential source of infection, if not prepared properly by the consumer. In Germany, certain wild animals are known to be a reservoir for HEV. However, current information is missing about European brown hares (Lepus europaeus) and wild rabbits (Oryctolagus cuniculus). Thus, a total of 833 hunting-harvested animals (European brown hares n = 669; wild rabbits n = 164) were tested for the occurrence of HEV RNA and HEV antibodies. For this, liver and blood specimens were taken after hunts in six German federal states. HEV antibodies were found by ELISA in 2.2% (624/14) of European brown hares, but no HEV RNA was detectable by nested real-time RT-PCR. In contrast, a seroprevalence of 37.3% (126/47) was observed for wild rabbits, and 17.1% (164/28) of the samples were HEV RNA positive. Genomic analysis revealed that these partial sequences clustered within the rabbit clade of HEV-3 genotype. In addition, one rabbit sequence segregated into subtype 3g of HEV-3. Highest seroprevalences for hares and rabbits were detected in the federal states of Bavaria and of Schleswig-Holstein, respectively. Comparing urban, rural and insular areas, the highest seroprevalence was shown for wild rabbits in rural areas and for European brown hares on the northern island Fehmarn. This study provides evidence that European brown hares and wild rabbits from Germany can be infected with HEV. The different prevalences indicate that wild rabbits are a potential reservoir for HEV in Germany, whereas European brown hares seem to be only of minor importance for the epidemiology of HEV. © 2017 Blackwell Verlag GmbH.

  11. Anthropogenic roost switching and rabies virus dynamics in house-roosting big brown bats.

    PubMed

    Streicker, Daniel G; Franka, Richard; Jackson, Felix R; Rupprecht, Charles E

    2013-07-01

    Big brown bats (Eptesicus fuscus) are the most commonly encountered rabid bat in North America and represent an important source of wildlife rabies epizootics. Urban and suburban colonies of E. fuscus are often evicted from their roosts in houses, with poorly understood consequences for bat dispersal, population dynamics, and rabies virus transmission. We combined radiotelemetry and mark-recapture of E. fuscus with enhanced surveillance to understand the frequency of rabies virus exposure in house-roosting bats and to assess the potential for behavioral responses of eviction to exacerbate viral transmission. Serology demonstrated the circulation of rabies virus in nearly all sites, with an overall seroprevalence of 12%, but no bats were excreting rabies virus at the time of capture. Bats that were excluded from roosts relocated to houses <1 km from the original roost. However, behavioral responses to eviction differed, with bats switching repeatedly among new roosts in 1 site, but fusing with a neighboring colony in another. These findings confirm the circulation of rabies virus in E. fuscus that live in close contact with humans and companion animals, suggest mechanisms through which anthropogenic disturbance of bats might influence pathogen transmission, and highlight simple strategies to balance conservation and public health priorities.

  12. Infectious bronchitis virus and brown shell colour: Australian strains of infectious bronchitis virus affect brown eggshell colour in commercial laying hens differently.

    PubMed

    Samiullah, Sami; Roberts, Juliet; Chousalkar, Kapil

    2016-10-01

    The aim of the current study was to assess any effect of wild and vaccine Australian infectious bronchitis virus (IBV) strains on shell colour in brown-shelled eggs. In Experiment 1, eggs were collected from day 1 to day 13 post-inoculation (p.i.) from unvaccinated laying hens challenged with IBV wild strains T and N1/88 and from a negative control group of hens. In Experiment 2, eggs were collected from 2 to 22 days p.i. from unvaccinated and vaccinated laying hens challenged with either a wild or a vaccine strain of IBV. In Experiment 1, there was a significant effect (P < 0.05) of day p.i. and of viral strain on shell reflectivity, L* and protoporphyrin IX (PP IX) in eggshells, with and without cuticle. The mean PP IX/g of shell with and without cuticle was significantly higher on day 1 p.i. compared to day 7, after which PP IX increased with day p.i. In Experiment 2, shell reflectivity and L* increased and PP IX decreased with increased day p.i. until day 12. Shell reflectivity and L* decreased slightly after day 12 and increased again towards day 22. Shell reflectivity, L* and PP IX were not significantly different for eggshells from unvaccinated and vaccinated laying hens in the intact eggshell, but were significantly different in shells from which cuticle had been removed. In conclusion, the IBV strains reduced the intensity of brown shell colour to different extents with a lower amount of PP IX in eggshells.

  13. Early overfeed-induced obesity leads to brown adipose tissue hypoactivity in rats.

    PubMed

    de Almeida, Douglas L; Fabrício, Gabriel S; Trombini, Amanda B; Pavanello, Audrei; Tófolo, Laize P; da Silva Ribeiro, Tatiane A; de Freitas Mathias, Paulo C; Palma-Rigo, Kesia

    2013-01-01

    Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups) and small (3 pups) litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C) and dark (NL 38°C vs. SL 37.6°C) periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (p<0.01), and no difference was observed in the sympathetic nerve activity. In adulthood, the small litter rats were 11,7% heavier than the controls and presented higher glycemia 13,1%, insulinemia 70% and corticosteronemia 92,6%. Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults. © 2013 S. Karger AG, Basel.

  14. Avian and human influenza virus compatible sialic acid receptors in little brown bats.

    PubMed

    Chothe, Shubhada K; Bhushan, Gitanjali; Nissly, Ruth H; Yeh, Yin-Ting; Brown, Justin; Turner, Gregory; Fisher, Jenny; Sewall, Brent J; Reeder, DeeAnn M; Terrones, Mauricio; Jayarao, Bhushan M; Kuchipudi, Suresh V

    2017-04-06

    Influenza A viruses (IAVs) continue to threaten animal and human health globally. Bats are asymptomatic reservoirs for many zoonotic viruses. Recent reports of two novel IAVs in fruit bats and serological evidence of avian influenza virus (AIV) H9 infection in frugivorous bats raise questions about the role of bats in IAV epidemiology. IAVs bind to sialic acid (SA) receptors on host cells, and it is widely believed that hosts expressing both SA α2,3-Gal and SA α2,6-Gal receptors could facilitate genetic reassortment of avian and human IAVs. We found abundant co-expression of both avian (SA α2,3-Gal) and human (SA α2,6-Gal) type SA receptors in little brown bats (LBBs) that were compatible with avian and human IAV binding. This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains.

  15. Comparing the regional epidemiology of the cassava mosaic and cassava brown streak virus pandemics in Africa.

    PubMed

    Legg, J P; Jeremiah, S C; Obiero, H M; Maruthi, M N; Ndyetabula, I; Okao-Okuja, G; Bouwmeester, H; Bigirimana, S; Tata-Hangy, W; Gashaka, G; Mkamilo, G; Alicai, T; Lava Kumar, P

    2011-08-01

    The rapid geographical expansion of the cassava mosaic disease (CMD) pandemic, caused by cassava mosaic geminiviruses, has devastated cassava crops in 12 countries of East and Central Africa since the late 1980s. Region-level surveys have revealed a continuing pattern of annual spread westward and southward along a contiguous 'front'. More recently, outbreaks of cassava brown streak disease (CBSD) were reported from Uganda and other parts of East Africa that had been hitherto unaffected by the disease. Recent survey data reveal several significant contrasts between the regional epidemiology of these two pandemics: (i) severe CMD radiates out from an initial centre of origin, whilst CBSD seems to be spreading from independent 'hot-spots'; (ii) the severe CMD pandemic has arisen from recombination and synergy between virus species, whilst the CBSD pandemic seems to be a 'new encounter' situation between host and pathogen; (iii) CMD pandemic spread has been tightly linked with the appearance of super-abundant Bemisia tabaci whitefly vector populations, in contrast to CBSD, where outbreaks have occurred 3-12 years after whitefly population increases; (iv) the CMGs causing CMD are transmitted in a persistent manner, whilst the two cassava brown streak viruses appear to be semi-persistently transmitted; and (v) different patterns of symptom expression mean that phytosanitary measures could be implemented easily for CMD but have limited effectiveness, whereas similar measures are difficult to apply for CBSD but are potentially very effective. An important similarity between the pandemics is that the viruses occurring in pandemic-affected areas are also found elsewhere, indicating that contrary to earlier published conclusions, the viruses per se are unlikely to be the key factors driving the two pandemics. A diagrammatic representation illustrates the temporal relationship between B. tabaci abundance and changing incidences of both CMD and CBSD in the Great Lakes region

  16. An analysis of correspondence between unique rabies virus variants and divergent big brown bat (Eptesicus fuscus) mitochondrial DNA lineages

    USGS Publications Warehouse

    Neubaum, M.A.; Shankar, V.; Douglas, M.R.; Douglas, M.E.; O'Shea, T.J.; Rupprecht, C.E.

    2008-01-01

    The literature supports that unique rabies virus (RABV) variants are often compartmentalized in different species of bats. In Colorado, two divergent mtDNA lineages of big brown bats (Eptesicus fuscus) co-occur. RABV associated with this species also segregates into two clades. We hypothesized that unique RABV variants might be associated with mtDNA lineages of Colorado big brown bats. DNA was extracted from brain tissue of rabid big brown bats, the ND2 gene was amplified to determine mtDNA lineage, and the lineage was compared to a previously derived phylogenetic analysis of the RABV N gene. No correspondence was found between host bat lineage and RABV variant. ?? 2008 Springer-Verlag.

  17. Transcriptional Response of Virus-Infected Cassava and Identification of Putative Sources of Resistance for Cassava Brown Streak Disease

    PubMed Central

    Maruthi, M. N.; Bouvaine, Sophie; Tufan, Hale A.; Mohammed, Ibrahim U.; Hillocks, Rory J.

    2014-01-01

    Cassava (Manihot esculenta) is a major food staple in sub-Saharan Africa, which is severely affected by cassava brown streak disease (CBSD). The aim of this study was to identify resistance for CBSD as well as to understand the mechanism of putative resistance for providing effective control for the disease. Three cassava varieties; Kaleso, Kiroba and Albert were inoculated with cassava brown streak viruses by grafting and also using the natural insect vector the whitefly, Bemisia tabaci. Kaleso expressed mild or no disease symptoms and supported low concentrations of viruses, which is a characteristic of resistant plants. In comparison, Kiroba expressed severe leaf but milder root symptoms, while Albert was susceptible with severe symptoms both on leaves and roots. Real-time PCR was used to estimate virus concentrations in cassava varieties. Virus quantities were higher in Kiroba and Albert compared to Kaleso. The Illumina RNA-sequencing was used to further understand the genetic basis of resistance. More than 700 genes were uniquely overexpressed in Kaleso in response to virus infection compared to Albert. Surprisingly, none of them were similar to known resistant gene orthologs. Some of the overexpressed genes, however, belonged to the hormone signalling pathways and secondary metabolites, both of which are linked to plant resistance. These genes should be further characterised before confirming their role in resistance to CBSD. PMID:24846209

  18. Unusual occurrence of a DAG motif in the Ipomovirus Cassava brown streak virus and implications for its vector transmission.

    PubMed

    Ateka, Elijah; Alicai, Titus; Ndunguru, Joseph; Tairo, Fred; Sseruwagi, Peter; Kiarie, Samuel; Makori, Timothy; Kehoe, Monica A; Boykin, Laura M

    2017-01-01

    Cassava is the main staple food for over 800 million people globally. Its production in eastern Africa is being constrained by two devastating Ipomoviruses that cause cassava brown streak disease (CBSD); Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV), with up to 100% yield loss for smallholder farmers in the region. To date, vector studies have not resulted in reproducible and highly efficient transmission of CBSV and UCBSV. Most virus transmission studies have used Bemisia tabaci (whitefly), but a maximum of 41% U/CBSV transmission efficiency has been documented for this vector. With the advent of next generation sequencing, researchers are generating whole genome sequences for both CBSV and UCBSV from throughout eastern Africa. Our initial goal for this study was to characterize U/CBSV whole genomes from CBSD symptomatic cassava plants sampled in Kenya. We have generated 8 new whole genomes (3 CBSV and 5 UCBSV) from Kenya, and in the process of analyzing these genomes together with 26 previously published sequences, we uncovered the aphid transmission associated DAG motif within coat protein genes of all CBSV whole genomes at amino acid positions 52-54, but not in UCBSV. Upon further investigation, the DAG motif was also found at the same positions in two other Ipomoviruses: Squash vein yellowing virus (SqVYV), Coccinia mottle virus (CocMoV). Until this study, the highly-conserved DAG motif, which is associated with aphid transmission was only noticed once, in SqVYV but discounted as being of minimal importance. This study represents the first comprehensive look at Ipomovirus genomes to determine the extent of DAG motif presence and significance for vector relations. The presence of this motif suggests that aphids could potentially be a vector of CBSV, SqVYV and CocMov. Further transmission and ipomoviral protein evolutionary studies are needed to confirm this hypothesis.

  19. Determinants of lifetime reproduction in female brown bears: early body mass, longevity, and hunting regulations.

    PubMed

    Zedrosser, Andreas; Pelletier, Fanie; Bischof, Richard; Festa-Bianchet, Marco; Swenson, Jon E

    2013-01-01

    In iteroparous mammals, conditions experienced early in life may have long-lasting effects on lifetime reproductive success. Human-induced mortality is also an important demographic factor in many populations of large mammals and may influence lifetime reproductive success. Here, we explore the effects of early development, population density, and human hunting on survival and lifetime reproductive success in brown bear (Ursus arctos) females, using a 25-year database of individually marked bears in two populations in Sweden. Survival of yearlings to 2 years was not affected by population density or body mass. Yearlings that remained with their mother had higher survival than independent yearlings, partly because regulations prohibit the harvest of bears in family groups. Although mass as a yearling did not affect juvenile survival, it was positively associated with measures of lifetime reproductive success and individual fitness. The majority of adult female brown bear mortality (72%) in our study was due to human causes, mainly hunting, and many females were killed before they reproduced. Therefore, factors allowing females to survive several hunting seasons had a strong positive effect on lifetime reproductive success. We suggest that, in many hunted populations of large mammals, sport harvest is an important influence on both population dynamics and life histories.

  20. Low ambient temperature during early postnatal development fails to cause a permanent induction of brown adipocytes

    PubMed Central

    Chabowska-Kita, Agnieszka; Trabczynska, Anna; Korytko, Agnieszka; Kaczmarek, Monika M.; Kozak, Leslie P.

    2015-01-01

    The brown adipocyte phenotype (BAP) in white adipose tissue (WAT) is transiently induced in adult mammals in response to reduced ambient temperature. Since it is unknown whether a cold challenge can permanently induce brown adipocytes (BAs), we reared C57BL/6J (B6) and AxB8/PgJ (AxB8) mice at 17 or 29°C from birth to weaning, to assess the BAP in young and adult mice. Energy balance measurements showed that 17°C reduced fat mass in the preweaning mice by increasing energy expenditure and suppressed diet-induced obesity in adults. Microarray analysis of global gene expression of inguinal fat (ING) from 10-day-old (D) mice indicates that expression at 17°C vs. 29°C was not different. Between 10 and 21 days of age, the BAP was induced coincident with morphologic remodeling of ING and marked changes in expression of neural development genes (e.g., Akap 12 and Ngfr). Analyses of Ucp1 mRNA and protein showed that 17°C transiently increased the BAP in ING from 21D mice; however, BAs were unexpectedly present in mice reared at 29°C. The involution of the BAP in WAT occurred after weaning in mice reared at 23°C. Therefore, the capacity to stimulate thermogenically competent BAs in WAT is set by a temperature-independent, genetically controlled program between birth and weaning.—Chabowska-Kita, A., Trabczynska, A., Korytko, A., Kaczmarek, M. M., Kozak, L. P. Low ambient temperature during early postnatal development fails to cause a permanent induction of brown adipocytes. PMID:25896784

  1. Telomere dynamics in wild brown trout: effects of compensatory growth and early growth investment.

    PubMed

    Näslund, Joacim; Pauliny, Angela; Blomqvist, Donald; Johnsson, Jörgen I

    2015-04-01

    After a period of food deprivation, animals often respond with a period of faster than normal growth. Such responses have been suggested to result in decreased chromosomal maintenance, which in turn may affect the future fitness of an individual. Here, we present a field experiment in which a food deprivation period of 24 days was enforced on fish from a natural population of juvenile brown trout (Salmo trutta) at the start of the high-growth season in spring. The growth of the food-deprived fish and a non-deprived control group was then monitored in the wild during 1 year. Fin tissue samples were taken at the start of the experiment and 1 year after food deprivation to monitor the telomere dynamics, using reduced telomere length as an indicator of maintenance cost. The food-deprived fish showed partial compensatory growth in both mass and length relative to the control group. However, we found no treatment effects on telomere dynamics, suggesting that growth-compensating brown trout juveniles are able to maintain their telomeres during their second year in the stream. However, body size at the start of the experiment, reflecting growth rate during their first year of life, was negatively correlated with change in telomere length over the following year. This result raises the possibility that rapid growth early in life induces delayed costs in cellular maintenance.

  2. Detection of Pathogenic Viruses in Sewage Provided Early Warnings of Hepatitis A Virus and Norovirus Outbreaks

    PubMed Central

    Hellmér, Maria; Paxéus, Nicklas; Magnius, Lars; Enache, Lucica; Arnholm, Birgitta; Johansson, Annette; Bergström, Tomas

    2014-01-01

    Most persons infected with enterically transmitted viruses shed large amounts of virus in feces for days or weeks, both before and after onset of symptoms. Therefore, viruses causing gastroenteritis may be detected in wastewater, even if only a few persons are infected. In this study, the presence of eight pathogenic viruses (norovirus, astrovirus, rotavirus, adenovirus, Aichi virus, parechovirus, hepatitis A virus [HAV], and hepatitis E virus) was investigated in sewage to explore whether their identification could be used as an early warning of outbreaks. Samples of the untreated sewage were collected in proportion to flow at Ryaverket, Gothenburg, Sweden. Daily samples collected during every second week between January and May 2013 were pooled and analyzed for detection of viruses by concentration through adsorption to milk proteins and PCR. The largest amount of noroviruses was detected in sewage 2 to 3 weeks before most patients were diagnosed with this infection in Gothenburg. The other viruses were detected at lower levels. HAV was detected between weeks 5 and 13, and partial sequencing of the structural VP1protein identified three different strains. Two strains were involved in an ongoing outbreak in Scandinavia and were also identified in samples from patients with acute hepatitis A in Gothenburg during spring of 2013. The third strain was unique and was not detected in any patient sample. The method used may thus be a tool to detect incipient outbreaks of these viruses and provide early warning before the causative pathogens have been recognized in health care. PMID:25172863

  3. Brown midrib corn silage and Tifton 85 bermudagrass in rations for early-lactation cows.

    PubMed

    Castro, J J; Bernard, J K; Mullis, N A; Eggleston, R B

    2010-05-01

    Forty Holstein cows were used in an 8-wk randomized trial to evaluate the effects of feeding combinations of forages with improved fiber digestibility on performance during early lactation. Treatments were arranged as a 2 x 2 factorial to include silage from normal (NCS) or brown midrib (BMR) corn silage with or without 10% Tifton 85 bermudagrass hay (T85). In a simultaneous digestion trial, degradation and passage kinetics and ruminal fermentation parameters were evaluated in a 4 x 4 Latin square design trial using late-lactation Holstein cows fitted with ruminal cannulas. Dry matter intake (DMI) and neutral detergent fiber (NDF) intake were greater with BMR than with NCS; however, milk yield and composition were similar among corn silage types. Inclusion of T85 reduced milk yield but supported higher milk fat percentage, resulting in similar yields of energy-corrected milk. Blood glucose concentrations were higher for BMR compared with NCS, and inclusion of T85 increased blood urea N concentrations. Treatments did not alter liquid or solid phase passage rates or rumen turnover. Corn silage type did not affect ruminal pH or volatile fatty acid concentrations, but inclusion of T85 increased pH and molar proportion of acetate but decreased butyrate. Molar proportions of propionate were greater for NCS and T85 compared with BMR and T85, resulting in an interaction. Results of this trial indicate that combinations of forages with improved fiber digestibility can be used to support intake and performance of cows during early lactation. Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    PubMed Central

    Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency. PMID:25918478

  5. Detection of pathogenic viruses in sewage provided early warnings of hepatitis A virus and norovirus outbreaks.

    PubMed

    Hellmér, Maria; Paxéus, Nicklas; Magnius, Lars; Enache, Lucica; Arnholm, Birgitta; Johansson, Annette; Bergström, Tomas; Norder, Heléne

    2014-11-01

    Most persons infected with enterically transmitted viruses shed large amounts of virus in feces for days or weeks, both before and after onset of symptoms. Therefore, viruses causing gastroenteritis may be detected in wastewater, even if only a few persons are infected. In this study, the presence of eight pathogenic viruses (norovirus, astrovirus, rotavirus, adenovirus, Aichi virus, parechovirus, hepatitis A virus [HAV], and hepatitis E virus) was investigated in sewage to explore whether their identification could be used as an early warning of outbreaks. Samples of the untreated sewage were collected in proportion to flow at Ryaverket, Gothenburg, Sweden. Daily samples collected during every second week between January and May 2013 were pooled and analyzed for detection of viruses by concentration through adsorption to milk proteins and PCR. The largest amount of noroviruses was detected in sewage 2 to 3 weeks before most patients were diagnosed with this infection in Gothenburg. The other viruses were detected at lower levels. HAV was detected between weeks 5 and 13, and partial sequencing of the structural VP1protein identified three different strains. Two strains were involved in an ongoing outbreak in Scandinavia and were also identified in samples from patients with acute hepatitis A in Gothenburg during spring of 2013. The third strain was unique and was not detected in any patient sample. The method used may thus be a tool to detect incipient outbreaks of these viruses and provide early warning before the causative pathogens have been recognized in health care. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Calcium-Dependent Rubella Virus Fusion Occurs in Early Endosomes.

    PubMed

    Dubé, Mathieu; Etienne, Loïc; Fels, Maximilian; Kielian, Margaret

    2016-07-15

    The E1 membrane protein of rubella virus (RuV) is a class II membrane fusion protein structurally related to the fusion proteins of the alphaviruses, flaviviruses, and phleboviruses. Virus entry is mediated by a low pH-dependent fusion reaction through E1's insertion into the cell membrane and refolding to a stable homotrimer. Unlike the other described class II proteins, RuV E1 contains 2 fusion loops, which complex a metal ion between them by interactions with residues N88 and D136. Insertion of the E1 protein into the target membrane, fusion, and infection require calcium and are blocked by alanine substitution of N88 or D136. Here we addressed the requirements of E1 for calcium binding and the intracellular location of the calcium requirement during virus entry. Our results demonstrated that N88 and D136 are optimally configured to support RuV fusion and are strongly selected for during the virus life cycle. While E1 has some similarities with cellular proteins that bind calcium and anionic lipids, RuV binding to the membrane was independent of anionic lipids. Virus fusion occurred within early endosomes, and chelation of intracellular calcium showed that calcium within the early endosome was required for virus fusion and infection. Calcium triggered the reversible insertion of E1 into the target membrane at neutral pH, but E1 homotrimer formation and fusion required a low pH. Thus, RuV E1, unlike other known class II fusion proteins, has distinct triggers for membrane insertion and fusion protein refolding mediated, respectively, by endosomal calcium and low pH. Rubella virus causes a mild disease of childhood, but infection of pregnant women frequently results in miscarriage or severe birth defects. In spite of an effective vaccine, RuV disease remains a serious problem in many developing countries. RuV infection of host cells involves endocytic uptake and low pH-triggered membrane fusion and is unusual in its requirement for calcium binding by the membrane

  7. Calcium-Dependent Rubella Virus Fusion Occurs in Early Endosomes

    PubMed Central

    Dubé, Mathieu; Etienne, Loïc; Fels, Maximilian

    2016-01-01

    ABSTRACT The E1 membrane protein of rubella virus (RuV) is a class II membrane fusion protein structurally related to the fusion proteins of the alphaviruses, flaviviruses, and phleboviruses. Virus entry is mediated by a low pH-dependent fusion reaction through E1's insertion into the cell membrane and refolding to a stable homotrimer. Unlike the other described class II proteins, RuV E1 contains 2 fusion loops, which complex a metal ion between them by interactions with residues N88 and D136. Insertion of the E1 protein into the target membrane, fusion, and infection require calcium and are blocked by alanine substitution of N88 or D136. Here we addressed the requirements of E1 for calcium binding and the intracellular location of the calcium requirement during virus entry. Our results demonstrated that N88 and D136 are optimally configured to support RuV fusion and are strongly selected for during the virus life cycle. While E1 has some similarities with cellular proteins that bind calcium and anionic lipids, RuV binding to the membrane was independent of anionic lipids. Virus fusion occurred within early endosomes, and chelation of intracellular calcium showed that calcium within the early endosome was required for virus fusion and infection. Calcium triggered the reversible insertion of E1 into the target membrane at neutral pH, but E1 homotrimer formation and fusion required a low pH. Thus, RuV E1, unlike other known class II fusion proteins, has distinct triggers for membrane insertion and fusion protein refolding mediated, respectively, by endosomal calcium and low pH. IMPORTANCE Rubella virus causes a mild disease of childhood, but infection of pregnant women frequently results in miscarriage or severe birth defects. In spite of an effective vaccine, RuV disease remains a serious problem in many developing countries. RuV infection of host cells involves endocytic uptake and low pH-triggered membrane fusion and is unusual in its requirement for calcium

  8. Lack of association between ectoparasite intensities and rabies virus neutralizing antibody seroprevalence in wild big brown bats (Eptesicus fuscus), Fort Collins, Colorado

    USGS Publications Warehouse

    Pearce, R.D.; O'Shea, T.J.; Shankar, V.; Rupprecht, C.E.

    2007-01-01

    Recently, bat ectoparasites have been demonstrated to harbor pathogens of potential importance to humans. We evaluated antirabies antibody seroprevalence and the presence of ectoparasites in big brown bats (Eptesicus fuscus) sampled in 2002 and 2003 in Colorado to investigate if an association existed between ectoparasite intensity and exposure to rabies virus (RV). We used logistic regression and Akaike's Information Criteria adjusted for sample size (AICc) in a post-hoc analysis to investigate the relative importance of three ectoparasite species, as well as bat colony size, year sampled, age class, colony size, and year interaction on the presence of rabies virus neutralizing antibodies (VNA) in serum of wild E. fuscus. We obtained serum samples and ectoparasite counts from big brown bats simultaneously in 2002 and 2003. Although the presence of ectoparasites (Steatonyssus occidentalis and Spinturnix bakeri) were important in elucidating VNA seroprevalence, their intensities were higher in seronegative bats than in seropositive bats, and the presence of a third ectoparasite (Cimex pilosellus) was inconsequential. Colony size and year sampled were the most important variables in these AICc models. These findings suggest that these ectoparasites do not enhance exposure of big brown bats to RV. ?? 2007 Mary Ann Liebert, Inc.

  9. Comparison of immune responses of brown-headed cowbird and related blackbirds to west Nile and other mosquito-borne encephalitis viruses.

    PubMed

    Reisen, William K; Hahn, D Caldwell

    2007-07-01

    The rapid geographic spread of West Nile virus (family Flaviviridae, genus Flavivirus, WNV) across the United States has stimulated interest in comparative host infection studies to delineate competent avian hosts critical for viral amplification. We compared the host competence of four taxonomically related blackbird species (Icteridae) after experimental infection with WNV and with two endemic, mosquito-borne encephalitis viruses, western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), and St. Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV). We predicted differences in disease resistance among the blackbird species based on differences in life history, because they differ in geographic range and life history traits that include mating and breeding systems. Differences were observed among the response of these hosts to all three viruses. Red-winged Blackbirds were more susceptible to SLEV than Brewer's Blackbirds, whereas Brewer's Blackbirds were more susceptible to WEEV than Red-winged Blackbirds. In response to WNV infection, cowbirds showed the lowest mean viremias, cleared their infections faster, and showed lower antibody levels than concurrently infected species. Brown-headed Cowbirds also exhibited significantly lower viremia responses after infection with SLEV and WEEV as well as coinfection with WEEV and WNV than concurrently infected icterids. We concluded that cowbirds may be more resistant to infection to both native and introduced viruses because they experience heightened exposure to a variety of pathogens of parenting birds during the course of their parasitic life style.

  10. Comparison of immune responses of brown-headed cowbird and related blackbirds to West Nile and other mosquito-borne encephalitis viruses

    USGS Publications Warehouse

    Reisen, W.K.; Hahn, D.C.

    2007-01-01

    The rapid geographic spread of West Nile virus (family Flaviviridae, genus Flavivirus, WNV) across the United States has stimulated interest in comparative host infection studies to delineate competent avian hosts critical for viral amplification. We compared the host competence of four taxonomically related blackbird species (Icteridae) after experimental infection with WNV and with two endemic, mosquito-borne encephalitis viruses, western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), and St, Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV). We predicted differences in disease resistance among the blackbird species based on differences in life history, because they differ in geographic range and life history traits that include mating and breeding systems. Differences were observed among the response of these hosts to all three viruses, Red-winged Blackbirds were more susceptible to SLEV than Brewer's Blackbirds, whereas Brewer's Blackbirds were more susceptible to WEEV than Red-winged Blackbirds. In response to WNV infection, cowbirds showed the lowest mean viremias, cleared their infections faster, and showed lower antibody levels than concurrently infected species. Brown-headed Cowbirds also exhibited significantly lower viremia responses after infection with SLEV and WEEV as well as coinfection with WEEV and WNV than concurrently infected icterids. We concluded that cowbirds may be more resistant to infection to both native and introduced viruses because they experience heightened exposure to a variety of pathogens of parenting birds during the course of their parasitic life style.

  11. Molecular and cellular effects of chemicals disrupting steroidogenesis during early ovarian development of brown trout (Salmo trutta fario).

    PubMed

    a Marca Pereira, M L; Eppler, E; Thorpe, K L; Wheeler, J R; Burkhardt-Holm, P

    2014-02-01

    A range of chemicals found in the aquatic environment have the potential to influence endocrine function and affect sexual development by mimicking or antagonizing the effects of hormones, or by altering the synthesis and metabolism of hormones. The aim of this study was to evaluate whether the effects of chemicals interfering with sex hormone synthesis may affect the regulation of early ovarian development via the modulation of sex steroid and insulin-like growth factor (IGF) systems. To this end, ex vivo ovary cultures of juvenile brown trout (Salmo trutta fario) were exposed for 2 days to either 1,4,6-androstatriene-3,17-dione (ATD, a specific aromatase inhibitor), prochloraz (an imidazole fungicide), or tributyltin (TBT, a persistent organic pollutant). Further, juvenile female brown trout were exposed in vivo for 2 days to prochloraz or TBT. The ex vivo and in vivo ovarian gene expression of the aromatase (CYP19), responsible for estrogen production, and of IGF1 and 2 were compared. Moreover, 17β-estradiol (E2) and testosterone (T) production from ex vivo ovary cultures was assessed. Ex vivo exposure to ATD inhibited ovarian E2 synthesis, while T levels accumulated. However, ATD did not affect ex vivo expression of cyp19, igf1, or igf2. Ex vivo exposure to prochloraz inhibited ovarian E2 production, but did not affect T levels. Further prochloraz up-regulated igf1 expression in both ex vivo and in vivo exposures. TBT exposure did not modify ex vivo synthesis of either E2 or T. However, in vivo exposure to TBT down-regulated igf2 expression. The results indicate that ovarian inhibition of E2 production in juvenile brown trout might not directly affect cyp19 and igf gene expression. Thus, we suggest that the test chemicals may interfere with both sex steroid and IGF systems in an independent manner, and based on published literature, potentially lead to endocrine dysfunction and altered sexual development. Copyright © 2011 Wiley Periodicals, Inc., A Wiley

  12. Comparative Proteomic Analysis of Susceptible and Resistant Rice Plants during Early Infestation by Small Brown Planthopper

    PubMed Central

    Dong, Yan; Fang, Xianping; Yang, Yong; Xue, Gang-Ping; Chen, Xian; Zhang, Weilin; Wang, Xuming; Yu, Chulang; Zhou, Jie; Mei, Qiong; Fang, Wang; Yan, Chengqi; Chen, Jianping

    2017-01-01

    The small brown planthopper (Laodelphax striatellus Fallén, Homoptera, Delphacidae-SBPH) is one of the major destructive pests of rice (Oryza sativa L.). Understanding on how rice responds to SBPH infestation will contribute to developing strategies for SBPH control. However, the response of rice plant to SBPH is poorly understood. In this study, two contrasting rice genotypes, Pf9279-4 (SBPH-resistant) and 02428 (SBPH-susceptible), were used for comparative analysis of protein profiles in the leaf sheath of rice plants in responses to SBPH infestation. One hundred and thirty-two protein spots that were differentially expressed between the resistant and susceptible rice lines were identified with significant intensity differences (≥2-fold, P < 0.05) at 0, 6, and 12 h after SBPH infestation. Protein expression profile analysis in the leaf sheath of SBPH-resistant and SBPH-susceptible rice lines after SBPH infestation showed that proteins induced by SBPH feeding were involved mainly in stress response, photosynthesis, protein metabolic process, carbohydrate metabolic process, energy metabolism, cell wall-related proteins, amino acid metabolism and transcriptional regulation. Gene expression analysis of 24 differentially expressed proteins (DEPs) showed that more than 50% DEPs were positively correlated with their mRNA levels. Analysis of some physiological indexes mainly involved in the removal of oxygen reactive species showed that the levels of superoxide dismutase (SOD) and glutathione (GSH) were considerably higher in Pf9279-4 than 02428 during SBPH infestation. The catalase (CAT) activity and hydroxyl radical inhibition were lower in Pf9279-4 than 02428. Analysis of enzyme activities indicates that Pf9279-4 rice plants defend against SBPH through the activation of the pathway of the salicylic acid (SA)-dependent systemic acquired resistance. In conclusion, this study provides some insights into the molecular networks involved on cellular and physiological

  13. Spillover Events of Infection of Brown Hares (Lepus europaeus) with Rabbit Haemorrhagic Disease Type 2 Virus (RHDV2) Caused Sporadic Cases of an European Brown Hare Syndrome-Like Disease in Italy and Spain.

    PubMed

    Velarde, R; Cavadini, P; Neimanis, A; Cabezón, O; Chiari, M; Gaffuri, A; Lavín, S; Grilli, G; Gavier-Widén, D; Lavazza, A; Capucci, L

    2017-12-01

    Rabbit haemorrhagic disease virus (RHDV) is a lagovirus that can cause fatal hepatitis (rabbit haemorrhagic disease, RHD) with mortality of 80-90% in farmed and wild rabbits. Since 1986, RHDV has caused outbreaks in rabbits (Oryctolagus cuniculus) in Europe, but never in European brown hares (Lepus europaeus, EBH). In 2010, a new RHDV-related virus, called RHDV2, emerged in Europe, causing extended epidemics because it largely overcame the immunity to RHDV present in most rabbit populations. RHDV2 also was identified in Cape hare (Lepus capensis subsp. mediterraneus) and in Italian hare (Lepus corsicanus). Here, we describe two distinct incidents of RHDV2 infection in EBH that occurred in Italy (2012) and Spain (2014). The two RHDV2 strains caused macroscopic and microscopic lesions similar to European brown hare syndrome (EBHS) in hares, and they were genetically related to other RHDV2 strains in Europe. EBHs are common in Europe, often sharing habitat with rabbits. They likely have been exposed to high levels of RHDV2 during outbreaks in rabbits in recent years, yet only two incidents of RHDV2 in EBHs have been found in Italy and Spain, suggesting that EBHs are not a primary host. Instead, they may act as spillover hosts in situations when infection pressure is high and barriers between rabbits and hares are limited, resulting in occasional infections causing EBHS-like lesions. The serological survey of stocked hare sera taken from Italian and Spanish hare populations provided an understanding of naturally occurring RHDV2 infection in the field confirming its sporadic occurrence in EBH. Our findings increase the knowledge on distribution, host range and epidemiology of RHDV2. © 2016 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

  14. Early physiological abnormalities after simian immunodeficiency virus infection.

    PubMed

    Horn, T F; Huitron-Resendiz, S; Weed, M R; Henriksen, S J; Fox, H S

    1998-12-08

    Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction.

  15. Early physiological abnormalities after simian immunodeficiency virus infection

    PubMed Central

    Horn, Thomas F. W.; Huitron-Resendiz, Salvador; Weed, Michael R.; Henriksen, Steven J.; Fox, Howard S.

    1998-01-01

    Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction. PMID:9844017

  16. Early Detection of Epstein-Barr Virus Related Disease.

    ClinicalTrials.gov

    2018-05-22

    Post-transplant Lymphoproliferative Disorder; Mononucleosis; Epstein-Barr Virus Infections; Epstein-Barr Virus Related Malignancy; Epstein-Barr Viraemia; Epstein-Barr Virus-Related Hodgkin Lymphoma; Epstein-Barr Virus-Related Non-Hodgkin Lymphoma; Hemophagocytic Lymphohistiocytoses; Hemophagocytosis

  17. Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters

    PubMed Central

    Baseler, Laura; Scott, Dana P.; Saturday, Greg; Horne, Eva; Rosenke, Rebecca; Thomas, Tina; Meade-White, Kimberly; Haddock, Elaine; Feldmann, Heinz

    2016-01-01

    Background Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B). Methodology/Principal Findings Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi. Conclusions/Significance Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central

  18. Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters.

    PubMed

    Baseler, Laura; Scott, Dana P; Saturday, Greg; Horne, Eva; Rosenke, Rebecca; Thomas, Tina; Meade-White, Kimberly; Haddock, Elaine; Feldmann, Heinz; de Wit, Emmie

    2016-11-01

    Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B). Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi. Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.

  19. Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.

    PubMed

    Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

    2016-08-03

    Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance.

  20. Characterizing early embryonic development of Brown Tsaiya Ducks (Anas platyrhynchos) in comparison with Taiwan Country Chicken (Gallus gallus domestics)

    PubMed Central

    Lumsangkul, Chompunut; Fan, Yang-Kwang; Chang, Shen-Chang; Ju, Jyh-Cherng

    2018-01-01

    Avian embryos are among the most convenient and the primary representatives for the study of classical embryology. It is well-known that the hatching time of duck embryos is approximately one week longer than that of chicken embryos. However, the key features associated with the slower embryonic development in ducks have not been adequately described. This study aimed to characterize the pattern and the speed of early embryogenesis in Brown Tsaiya Ducks (BTD) compared with those in Taiwan Country Chicken (TCC) by using growth parameters including embryonic crown-tail length (ECTL), primitive streak formation, somitogenesis, and other development-related parameters, during the first 72 h of incubation. Three hundred and sixty eggs from BTD and TCC, respectively, were incubated at 37.2°C, and were then dissected hourly to evaluate their developmental stages. We found that morphological changes of TCC embryos shared a major similarity with that of the Hamburger and Hamilton staging system during early chick embryogenesis. The initial primitive streak in TCC emerged between 6 and 7 h post-incubation, but its emergence was delayed until 10 to 13 h post-incubation in BTD. Similarly, the limb primordia (wing and limb buds) were observed at 51 h post-incubation in TCC embryos compared to 64 h post-incubation in BTD embryos. The allantois first appeared around 65 to 68 h in TCC embryos, but it was not observed in BTD embryos. At the 72 h post-incubation, 40 somites were clearly formed in TCC embryos while only 32 somites in BTD embryos. Overall, the BTD embryos developed approximately 16 h slower than the chicken embryo during the first 72 h of development. To our best knowledge, this is the first study to describe two distinct developmental time courses between TCC and BTD, which would facilitate future embryogenesis-related studies of the two important avian species in Taiwan. PMID:29742160

  1. Local Adaptation at the Transcriptome Level in Brown Trout: Evidence from Early Life History Temperature Genomic Reaction Norms

    PubMed Central

    Meier, Kristian; Hansen, Michael Møller; Normandeau, Eric; Mensberg, Karen-Lise D.; Frydenberg, Jane; Larsen, Peter Foged; Bekkevold, Dorte; Bernatchez, Louis

    2014-01-01

    Local adaptation and its underlying molecular basis has long been a key focus in evolutionary biology. There has recently been increased interest in the evolutionary role of plasticity and the molecular mechanisms underlying local adaptation. Using transcriptome analysis, we assessed differences in gene expression profiles for three brown trout (Salmo trutta) populations, one resident and two anadromous, experiencing different temperature regimes in the wild. The study was based on an F2 generation raised in a common garden setting. A previous study of the F1 generation revealed different reaction norms and significantly higher QST than FST among populations for two early life-history traits. In the present study we investigated if genomic reaction norm patterns were also present at the transcriptome level. Eggs from the three populations were incubated at two temperatures (5 and 8 degrees C) representing conditions encountered in the local environments. Global gene expression for fry at the stage of first feeding was analysed using a 32k cDNA microarray. The results revealed differences in gene expression between populations and temperatures and population × temperature interactions, the latter indicating locally adapted reaction norms. Moreover, the reaction norms paralleled those observed previously at early life-history traits. We identified 90 cDNA clones among the genes with an interaction effect that were differently expressed between the ecologically divergent populations. These included genes involved in immune- and stress response. We observed less plasticity in the resident as compared to the anadromous populations, possibly reflecting that the degree of environmental heterogeneity encountered by individuals throughout their life cycle will select for variable level of phenotypic plasticity at the transcriptome level. Our study demonstrates the usefulness of transcriptome approaches to identify genes with different temperature reaction norms. The

  2. Brown Syndrome

    MedlinePlus

    ... Does Brown syndrome cause eye problems besides abnormal eye movements? In the more severely affected cases of Brown ... acquired and congenital cases. In congenital cases, the eye movement problem is usually constant and unlikely to resolve ...

  3. Studies of angiospermous woods in Australian brown coal by nuclear magnetic resonance and analytical pyrolysis: new insight into early coalification

    USGS Publications Warehouse

    Hatcher, P.G.; Wilson, M.A.; Vassalo, M.; Lerch, H. E.

    1990-01-01

    Many Tertiary coals contain abundant fossilized remains of angiosperms that often dominated some ancient peat-swamp environments; modern analogs of which can be found in tropical and subtropical regions of the world. Comparisons of angiospermous woods from Australian brown coal with similar woods buried in modern peat swamps of Indonesia have provided some new insights into coalification reactions. These comparisons were made by using solid-state 13C nuclear magnetic resonance (NMR) techniques and pyrolysis-gas chromatography-mass spectrometry (py-gc-ms), two modern techniques especially suited for detailed structural evaluation of the complex macromolecules in coal. From these studies, we conclude that the earliest transformation (peatification) of organic matter in angiospermous wood is the degradation of cellulosic components. The efficiency of removal of cellulosic components in the wood varies considerably in peat, which results in variable levels of cellulose in peatified wood. However, the net trend is towards eventual removal of the cellulose. The angiospermous lignin that becomes enriched in wood as a result of cellulose degradation also is modified by coalifications reactions; this modification, however, does not involve degradation and removal. Rather, the early coalification process transforms the lignin phenols (guaiacyl and syringyl) to eventually yield the aromatic structures typically found in brown coal. One such transformation, which is determined from the NMR data, involves the cleavage of aryl ether bonds that link guaiacyl and syringyl units in lignin and leads to the formation of free lignin phenols. Another transformation, which is also determined from the NMR data, involves the loss of methoxyl groups, probably via demethylation, to produce catechol-like structures. Coincident with ether-cleavage and demethylation, the aromatic rings derived from lignin phenols become more carbon-substituted and cross-linked, as determined by dipolar

  4. Characterization of Founder Viruses in Very Early SIV Rectal Transmission

    PubMed Central

    Yuan, Zhe; Ma, Fangrui; Demers, Andrew J.; Wang, Dong; Xu, Jianqing; Lewis, Mark G.; Li, Qingsheng

    2016-01-01

    A better understanding of HIV-1 transmission is critical for developing preventative strategies. To that end, we analyzed 524 full-length env sequences of SIVmac251 at 6 and 10 days post intrarectal infection of rhesus macaques. There was no tissue compartmentalization of founder viruses across plasma, rectal and distal lymphatic tissues for most animals; however one animal has evidence of virus tissue compartmentalization. Despite identical viral inoculums, founder viruses were animal-specific, primarily derived from rare variants in the inoculum, and have a founder virus signature that can distinguish dominant founder variants from minor founder or untransmitted variants in the inoculum. Importantly, the sequences of post-transmission defective viruses were phylogenetically associated with competent viral variants in the inoculum and were mainly converted from competent viral variants by frameshift rather than APOBEC mediated mutations, suggesting the converting the transmitted viruses into defective viruses through frameshift mutation is an important component of rectal transmission bottleneck. PMID:28027479

  5. Analytical and computational modeling of early penetration of non-enveloped icosahedral viruses into cells.

    PubMed

    Katzengold, Rona; Zaharov, Evgeniya; Gefen, Amit

    2016-07-27

    As obligate intracellular parasites, all viruses penetrate target cells to initiate replication and infection. This study introduces two approaches for evaluating the contact loads applied to a cell during early penetration of non-enveloped icosahedral viruses. The first approach is analytical modeling which is based on Hertz's theory for the contact of two elastic bodies; here we model the virus capsid as a triangle and the cell as an order-of-magnitude larger sphere. The second approach is finite element modeling, where we simulate three types of viruses: adeno-, papilloma- and polio- viruses, each interacting with a cell section. We find that the peak contact pressures and forces generated at the initial virus-cell contact depend on the virus geometry - that is both size and shape. With respect to shape, we show that the icosahedral virus shape induces greater peak pressures compared to a spherical virus shape. With respect to size, it is shown that the larger the virus is the greater are the contact loads in the attacked cell. Utilization of our modeling can be substantially useful not only for basic science studies, but also in other, more applied fields, such as in the field of gene therapy, or in `phage' virus studies.

  6. A Sample of Very Young Field L Dwarfs and Implications for the Brown Dwarf "Lithium Test" at Early Ages

    NASA Astrophysics Data System (ADS)

    Kirkpatrick, J. Davy; Cruz, Kelle L.; Barman, Travis S.; Burgasser, Adam J.; Looper, Dagny L.; Tinney, C. G.; Gelino, Christopher R.; Lowrance, Patrick J.; Liebert, James; Carpenter, John M.; Hillenbrand, Lynne A.; Stauffer, John R.

    2008-12-01

    Using a large sample of optical spectra of late-type dwarfs, we identify a subset of late-M through L field dwarfs that, because of the presence of low-gravity features in their spectra, are believed to be unusually young. From a combined sample of 303 field L dwarfs, we find observationally that 7.6% +/- 1.6% are younger than 100 Myr. This percentage is in agreement with theoretical predictions once observing biases are taken into account. We find that these young L dwarfs tend to fall in the southern hemisphere (decl . < 0°) and may be previously unrecognized, low-mass members of nearby, young associations like Tucana-Horologium, TW Hydrae, β Pictoris, and AB Doradus. We use a homogeneously observed sample of ~150 optical spectra to examine lithium strength as a function of L/T spectral type and further corroborate the trends noted by Kirkpatrick and coworkers. We use our low-gravity spectra to investigate lithium strength as a function of age. The data weakly suggest that for early- to mid-L dwarfs the line strength reaches a maximum for a few × 100 Myr, whereas for much older (few Gyr) and much younger (<100 Myr) L dwarfs the line is weaker or undetectable. We show that a weakening of lithium at lower gravities is predicted by model atmosphere calculations, an effect partially corroborated by existing observational data. Larger samples containing L dwarfs of well-determined ages are needed to further test this empirically. If verified, this result would reinforce the caveat first cited by Kirkpatrick and coworkers that the lithium test should be used with caution when attempting to confirm the substellar nature of the youngest brown dwarfs. Most of the spectroscopic data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous

  7. Identification, cloning, and expression analysis of three putative Lymantria dispar nuclear polyhedrosis virus immediate early genes

    Treesearch

    James M. Slavicek; Nancy Hayes-Plazolles

    1991-01-01

    Viral immediate early gene products are usually regulatory proteins that control expression of other viral genes at the transcriptional level or are proteins that are part of the viral DNA replication complex. The identification and functional characterization of the immediate early gene products of Lymantria dispar nuclear polyhedrosis virus (LdNPV...

  8. Early-season avian deaths from West Nile virus as warnings of human infection

    USGS Publications Warehouse

    Guptill, S.C.; Julian, K.G.; Campbell, G.L.; Price, S.D.; Marfin, A.A.

    2003-01-01

    An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds.

  9. Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring.

    PubMed

    Almeida, Mariana M; Dias-Rocha, Camilla P; Souza, André S; Muros, Mariana F; Mendonca, Leonardo S; Pazos-Moura, Carmen C; Trevenzoli, Isis H

    2017-11-01

    Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS's components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.

  10. Variability in Seroprevalence of Rabies Virus Neutralizing Antibodies and Associated Factors in a Colorado Population of Big Brown Bats (Eptesicus fuscus)

    PubMed Central

    O’Shea, Thomas J.; Bowen, Richard A.; Stanley, Thomas R.; Shankar, Vidya; Rupprecht, Charles E.

    2014-01-01

    In 2001–2005 we sampled permanently marked big brown bats (Eptesicus fuscus) at summer roosts in buildings at Fort Collins, Colorado, for rabies virus neutralizing antibodies (RVNA). Seroprevalence was higher in adult females (17.9%, n = 2,332) than males (9.4%, n = 128; P = 0.007) or volant juveniles (10.2%, n = 738; P<0.0001). Seroprevalence was lowest in a drought year with local insecticide use and highest in the year with normal conditions, suggesting that environmental stress may suppress RVNA production in big brown bats. Seroprevalence also increased with age of bat, and varied from 6.2 to 26.7% among adult females at five roosts sampled each year for five years. Seroprevalence of adult females at 17 other roosts sampled for 1 to 4 years ranged from 0.0 to 47.1%. Using logistic regression, the only ranking model in our candidate set of explanatory variables for serological status at first sampling included year, day of season, and a year by day of season interaction that varied with relative drought conditions. The presence or absence of antibodies in individual bats showed temporal variability. Year alone provided the best model to explain the likelihood of adult female bats showing a transition to seronegative from a previously seropositive state. Day of the season was the only competitive model to explain the likelihood of a transition from seronegative to seropositive, which increased as the season progressed. We found no rabies viral RNA in oropharyngeal secretions of 261 seropositive bats or in organs of 13 euthanized seropositive bats. Survival of seropositive and seronegative bats did not differ. The presence of RVNA in serum of bats should not be interpreted as evidence for ongoing rabies infection. PMID:24465996

  11. Variability in seroprevalence of rabies virus neutralizing antibodies and associated factors in a Colorado population of big brown bats (Eptesicus fuscus)

    USGS Publications Warehouse

    O’Shea, Thomas J.; Bowen, Richard A.; Stanley, Thomas R.; Shankar, Vidya; Rupprecht, Charles E.

    2014-01-01

    In 2001–2005 we sampled permanently marked big brown bats (Eptesicus fuscus) at summer roosts in buildings at Fort Collins, Colorado, for rabies virus neutralizing antibodies (RVNA). Seroprevalence was higher in adult females (17.9%, n = 2,332) than males (9.4%, n = 128; P = 0.007) or volant juveniles (10.2%, n = 738; P<0.0001). Seroprevalence was lowest in a drought year with local insecticide use and highest in the year with normal conditions, suggesting that environmental stress may suppress RVNA production in big brown bats. Seroprevalence also increased with age of bat, and varied from 6.2 to 26.7% among adult females at five roosts sampled each year for five years. Seroprevalence of adult females at 17 other roosts sampled for 1 to 4 years ranged from 0.0 to 47.1%. Using logistic regression, the only ranking model in our candidate set of explanatory variables for serological status at first sampling included year, day of season, and a year by day of season interaction that varied with relative drought conditions. The presence or absence of antibodies in individual bats showed temporal variability. Year alone provided the best model to explain the likelihood of adult female bats showing a transition to seronegative from a previously seropositive state. Day of the season was the only competitive model to explain the likelihood of a transition from seronegative to seropositive, which increased as the season progressed. We found no rabies viral RNA in oropharyngeal secretions of 261 seropositive bats or in organs of 13 euthanized seropositive bats. Survival of seropositive and seronegative bats did not differ. The presence of RVNA in serum of bats should not be interpreted as evidence for ongoing rabies infection.

  12. An Early Tobacco Mosaic Virus-Induced Oxidative Burst in Tobacco Indicates Extracellular Perception of the Virus Coat Protein1

    PubMed Central

    Allan, Andrew C.; Lapidot, Moshe; Culver, James N.; Fluhr, Robert

    2001-01-01

    Induction of reactive oxygen species (ROS) was observed within seconds of the addition of exogenous tobacco mosaic virus (TMV) to the outside of tobacco (Nicotiana tabacum cv Samsun NN, EN, or nn) epidermal cells. Cell death was correlated with ROS production. Infectivity of the TMV virus was not a prerequisite for this elicitation and isolated coat protein (CP) subunits could also elicit the fast oxidative burst. The rapid induction of ROS was prevented by both inhibitors of plant signal transduction and inhibitors of NAD(P)H oxidases, suggesting activation of a multi-step signal transduction pathway. Induction of intracellular ROS by TMV was detected in TMV-resistant and -susceptible tobacco cultivars isogenic for the N allele. The burst was also detected with strains of virus that either elicit (ToMV) or fail to elicit (TMV U1) N′ gene-mediated responses. Hence, early ROS generation is independent or upstream of known genetic systems in tobacco that can mediate hypersensitive responses. Analysis of other viruses and TMV CP mutants showed marked differences in their ability to induce ROS showing specificity of the response. Thus, initial TMV-plant cell interactions that lead to early ROS induction occur outside the plasma membrane in an event requiring specific CP epitopes. PMID:11351074

  13. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    NASA Astrophysics Data System (ADS)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  14. Serological evidence of hepatitis E virus infection in zoo animals and identification of a rodent-borne strain in a Syrian brown bear.

    PubMed

    Spahr, Carina; Ryll, René; Knauf-Witzens, Tobias; Vahlenkamp, Thomas W; Ulrich, Rainer G; Johne, Reimar

    2017-12-01

    Hepatitis E virus (HEV) is the causative agent of hepatitis E, an emerging infectious disease of humans. HEV infections have also been described in various animal species. Whereas domestic pigs and wild boars are well-known animal reservoirs for HEV, the knowledge on natural HEV infection in zoo animals is scarce so far. Here, we analysed 244 sera from 66 mammal species derived from three zoos in Germany using a commercial double antigen sandwich ELISA. HEV-specific antibodies were detected in 16 animal species, with the highest detection rates in suids (33.3%) and carnivores (27.0%). However, RNA of the human pathogenic HEV genotypes 1-4 was not detected in the serum samples from suids or carnivores. Using a broad spectrum RT-PCR, a ratHEV-related sequence was identified in a sample of a female Syrian brown bear (Ursus arctos syriacus). Subsequent serum samples within a period of five years confirmed a HEV seroconversion in this animal. No symptoms of hepatitis were recorded. In a follow-up investigation at the same location, closely related ratHEV sequences were identified in free-living Norway rats (Rattus norvegicus), whereas feeder rats (Rattus norvegicus forma domestica) were negative for HEV-specific antibodies and RNA. Therefore, a spillover infection of ratHEV from free-living Norway rats is most likely. The results indicate that a wide range of zoo animals can be naturally infected with HEV or HEV-related viruses. Their distinct role as possible reservoir animals for HEV and sources of HEV infection for humans and other animals remains to be investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Apple Browning.

    ERIC Educational Resources Information Center

    Chemecology, 1992

    1992-01-01

    Describes an activity in which students investigate the effects of selected natural and synthetic substances on the rate of apple browning. Includes background information for the teacher, a list of necessary materials, and student instructions. (KR)

  16. An Evaluation of Molybdenum Toxicity to the Oligochaete, Tubifex tubifex, and Early-Life Stages of Brown Trout, Salmo trutta.

    PubMed

    Lucas, Brett T; Quinteros, Claudio; Burnett-Seidel, Charlene; Elphick, James R

    2017-06-01

    Limited data are available describing the aquatic toxicity of molybdenum in freshwater environments, making it difficult to assess the aquatic risk to freshwater organisms. In order to increase available information on the aquatic toxicity of molybdenum, a 96-h LC50 test with the oligochaete Tubifex tubifex and an 85-day development test using brown trout, Salmo trutta, were conducted. The T. tubifex test resulted in an LC50 value of 2782 mg/L. No adverse effects were observed on brown trout survival or length in the concentrations tested, however an IC10 value for growth (wet weight) was determined to be 202 mg/L. Whole body fish tissue concentrations for molybdenum increased in all treatment concentrations tested, although bioconcentration factors decreased at greater exposure concentrations, and ranged from 0.13 at an exposure concentration of 20 mg/L to 0.04 at an exposure of 1247 mg/L. A body burden of 26.0 mg/kg was associated with reduced wet weight.

  17. Is the gut the major source of virus in early simian immunodeficiency virus infection?

    PubMed

    Lay, Matthew D H; Petravic, Janka; Gordon, Shari N; Engram, Jessica; Silvestri, Guido; Davenport, Miles P

    2009-08-01

    The acute phases of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection are characterized by rapid and profound depletion of CD4+ T cells from the guts of infected individuals. The large number of CD4+ T cells in the gut (a large fraction of which are activated and express the HIV/SIV coreceptor CCR5), the high level of infection of these cells, and the temporal coincidence of this CD4+ T-cell depletion with the peak of virus in plasma in acute infection suggest that the intestinal mucosa may be the major source of virus driving the peak viral load. Here, we used data on CD4+ T-cell proportions in the lamina propria of the rectums of SIV-infected rhesus macaques (which progress to AIDS) and sooty mangabeys (which do not progress) to show that in both species, the depletion of CD4+ T cells from this mucosal site and its maximum loss rate are often observed several days before the peak in viral load, with few CD4+ T cells remaining in the rectum by the time of peak viral load. In contrast, the maximum loss rate of CD4+ T cells from bronchoalveolar lavage specimens and lymph nodes coincides with the peak in virus. Analysis of the kinetics of depletion suggests that, in both rhesus macaques and sooty mangabeys, CD4+ T cells in the intestinal mucosa are a highly susceptible population for infection but not a major source of plasma virus in acute SIV infection.

  18. Is the Gut the Major Source of Virus in Early Simian Immunodeficiency Virus Infection? ▿

    PubMed Central

    Lay, Matthew D. H.; Petravic, Janka; Gordon, Shari N.; Engram, Jessica; Silvestri, Guido; Davenport, Miles P.

    2009-01-01

    The acute phases of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection are characterized by rapid and profound depletion of CD4+ T cells from the guts of infected individuals. The large number of CD4+ T cells in the gut (a large fraction of which are activated and express the HIV/SIV coreceptor CCR5), the high level of infection of these cells, and the temporal coincidence of this CD4+ T-cell depletion with the peak of virus in plasma in acute infection suggest that the intestinal mucosa may be the major source of virus driving the peak viral load. Here, we used data on CD4+ T-cell proportions in the lamina propria of the rectums of SIV-infected rhesus macaques (which progress to AIDS) and sooty mangabeys (which do not progress) to show that in both species, the depletion of CD4+ T cells from this mucosal site and its maximum loss rate are often observed several days before the peak in viral load, with few CD4+ T cells remaining in the rectum by the time of peak viral load. In contrast, the maximum loss rate of CD4+ T cells from bronchoalveolar lavage specimens and lymph nodes coincides with the peak in virus. Analysis of the kinetics of depletion suggests that, in both rhesus macaques and sooty mangabeys, CD4+ T cells in the intestinal mucosa are a highly susceptible population for infection but not a major source of plasma virus in acute SIV infection. PMID:19458001

  19. Zika virus in the Americas: Early epidemiological and genetic findings.

    PubMed

    Faria, Nuno Rodrigues; Azevedo, Raimunda do Socorro da Silva; Kraemer, Moritz U G; Souza, Renato; Cunha, Mariana Sequetin; Hill, Sarah C; Thézé, Julien; Bonsall, Michael B; Bowden, Thomas A; Rissanen, Ilona; Rocco, Iray Maria; Nogueira, Juliana Silva; Maeda, Adriana Yurika; Vasami, Fernanda Giseli da Silva; Macedo, Fernando Luiz de Lima; Suzuki, Akemi; Rodrigues, Sueli Guerreiro; Cruz, Ana Cecilia Ribeiro; Nunes, Bruno Tardeli; Medeiros, Daniele Barbosa de Almeida; Rodrigues, Daniela Sueli Guerreiro; Queiroz, Alice Louize Nunes; da Silva, Eliana Vieira Pinto; Henriques, Daniele Freitas; da Rosa, Elisabeth Salbe Travassos; de Oliveira, Consuelo Silva; Martins, Livia Caricio; Vasconcelos, Helena Baldez; Casseb, Livia Medeiros Neves; Simith, Darlene de Brito; Messina, Jane P; Abade, Leandro; Lourenço, José; Alcantara, Luiz Carlos Junior; de Lima, Maricélia Maia; Giovanetti, Marta; Hay, Simon I; de Oliveira, Rodrigo Santos; Lemos, Poliana da Silva; de Oliveira, Layanna Freitas; de Lima, Clayton Pereira Silva; da Silva, Sandro Patroca; de Vasconcelos, Janaina Mota; Franco, Luciano; Cardoso, Jedson Ferreira; Vianez-Júnior, João Lídio da Silva Gonçalves; Mir, Daiana; Bello, Gonzalo; Delatorre, Edson; Khan, Kamran; Creatore, Marisa; Coelho, Giovanini Evelim; de Oliveira, Wanderson Kleber; Tesh, Robert; Pybus, Oliver G; Nunes, Marcio R T; Vasconcelos, Pedro F C

    2016-04-15

    Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas. Copyright © 2016, American Association for the Advancement of Science.

  20. Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

    PubMed

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2017-03-01

    Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

  1. Massively parallel pyrosequencing-based transcriptome analyses of small brown planthopper (Laodelphax striatellus), a vector insect transmitting rice stripe virus (RSV)

    PubMed Central

    2010-01-01

    Background The small brown planthopper (Laodelphax striatellus) is an important agricultural pest that not only damages rice plants by sap-sucking, but also acts as a vector that transmits rice stripe virus (RSV), which can cause even more serious yield loss. Despite being a model organism for studying entomology, population biology, plant protection, molecular interactions among plants, viruses and insects, only a few genomic sequences are available for this species. To investigate its transcriptome and determine the differences between viruliferous and naïve L. striatellus, we employed 454-FLX high-throughput pyrosequencing to generate EST databases of this insect. Results We obtained 201,281 and 218,681 high-quality reads from viruliferous and naïve L. striatellus, respectively, with an average read length as 230 bp. These reads were assembled into contigs and two EST databases were generated. When all reads were combined, 16,885 contigs and 24,607 singletons (a total of 41,492 unigenes) were obtained, which represents a transcriptome of the insect. BlastX search against the NCBI-NR database revealed that only 6,873 (16.6%) of these unigenes have significant matches. Comparison of the distribution of GO classification among viruliferous, naïve, and combined EST databases indicated that these libraries are broadly representative of the L. striatellus transcriptomes. Functionally diverse transcripts from RSV, endosymbiotic bacteria Wolbachia and yeast-like symbiotes were identified, which reflects the possible lifestyles of these microbial symbionts that live in the cells of the host insect. Comparative genomic analysis revealed that L. striatellus encodes similar innate immunity regulatory systems as other insects, such as RNA interference, JAK/STAT and partial Imd cascades, which might be involved in defense against viral infection. In addition, we determined the differences in gene expression between vector and naïve samples, which generated a list of

  2. A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

    PubMed

    Fukuoka, Takuya; Nakazato, Yoshihiko; Miyake, Akifumi; Tamura, Naotoshi; Araki, Nobuo; Yamamoto, Toshimasa

    2017-06-01

    A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery. Copyright © 2017. Published by Elsevier B.V.

  3. Brown recluse spider (image)

    MedlinePlus

    ... The brown recluse is brown with a characteristic dark violin-shaped marking on its head. It is ... brown recluse wanders indoors they will go to dark closets, shoes, or attics. The brown recluse is ...

  4. Nigericin is a potent inhibitor of the early stage of vaccinia virus replication.

    PubMed

    Myskiw, Chad; Piper, Jessica; Huzarewich, Rhiannon; Booth, Tim F; Cao, Jingxin; He, Runtao

    2010-12-01

    Poxviruses remain a significant public health concern due to their potential use as bioterrorist agents and the spread of animal borne poxviruses, such as monkeypox virus, to humans. Thus, the identification of small molecule inhibitors of poxvirus replication is warranted. Vaccinia virus is the prototypic member of the Orthopoxvirus genus, which also includes variola and monkeypox virus. In this study, we demonstrate that the carboxylic ionophore nigericin is a potent inhibitor of vaccinia virus replication in several human cell lines. In HeLa cells, we found that the 50% inhibitory concentration of nigericin against vaccinia virus was 7.9 nM, with a selectivity index of 1038. We present data demonstrating that nigericin targets vaccinia virus replication at a post-entry stage. While nigericin moderately inhibits both early vaccinia gene transcription and translation, viral DNA replication and intermediate and late gene expression are severely compromised in the presence of nigericin. Our results demonstrate that nigericin has the potential to be further developed into an effective antiviral to treat poxvirus infections. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  5. Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection.

    PubMed

    Caballero, Ignacio S; Yen, Judy Y; Hensley, Lisa E; Honko, Anna N; Goff, Arthur J; Connor, John H

    2014-11-06

    Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever. Their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. Current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. Using the transcriptional response of the host during infection can lead to earlier diagnoses compared to those of traditional methods. In this study, we use RNA sequencing to obtain a high-resolution view of the in vivo transcriptional dynamics of peripheral blood mononuclear cells (PBMCs) throughout both types of infection. We report a subset of host mRNAs, including heat-shock proteins like HSPA1B, immunoglobulins like IGJ, and cell adhesion molecules like SIGLEC1, whose differences in expression are strong enough to distinguish Lassa infection from Marburg infection in non-human primates. We have validated these infection-specific expression differences by using microarrays on a larger set of samples, and by quantifying the expression of individual genes using RT-PCR. These results suggest that host transcriptional signatures are correlated with specific viral infections, and that they can be used to identify highly pathogenic viruses during the early stages of disease, before standard detection methods become effective.

  6. Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

    PubMed Central

    Jayasooriya, Shamanthi; de Silva, Thushan I.; Njie-jobe, Jainaba; Sanyang, Chilel; Leese, Alison M.; Bell, Andrew I.; McAulay, Karen A.; Yanchun, Peng; Long, Heather M.; Dong, Tao; Whittle, Hilton C.; Rickinson, Alan B.; Rowland-Jones, Sarah L.; Hislop, Andrew D.; Flanagan, Katie L.

    2015-01-01

    Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14–18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms. PMID:25816224

  7. Origins and early development of the concept that brown adipose tissue thermogenesis is linked to energy balance and obesity.

    PubMed

    Trayhurn, Paul

    2017-03-01

    Brown adipose tissue (BAT) was identified as a thermogenic organ in 1961, and in 1978 shown to be the major site of thermoregulatory non-shivering thermogenesis in rats acclimated to the cold. Investigations in the mid-late 1970s established the uncoupling of oxidative phosphorylation through a proton conductance pathway across the mitochondrial inner membrane as the mechanism for heat production in BAT, this being regulated by UCP1 which was first discovered as a 32,000 M r cold-inducible protein. These developments came when those concerned with nutritional energetics were proposing that thermogenesis is a significant factor in energy balance and the aetiology of obesity. A link with BAT was first demonstrated in obese ob/ob mice, which were shown to have decreased thermogenic activity in the tissue, and in rats exhibiting diet-induced thermogenesis (DIT) during overfeeding on a cafeteria diet where an activation of brown fat was evident. These pioneering observations led to extensive studies on BAT in different animal models of obesity, both genetic (particularly ob/ob and db/db mice, fa/fa rats) and experimentally-induced. In each case, indices of BAT activity and capacity (mitochondrial content, GDP binding, amount of UCP1) indicated that the tissue plays a role in DIT and that obesity is characterised by reduced thermogenesis. Links between BAT and whole-body energetics were also made in physiological situations such as lactation and fasting. Studies in the 1980s also provided clear evidence for the presence of BAT in adult humans, particularly through the detection of UCP1, and its activation in patients with phaeochromocytoma. Interest in BAT in energetics and obesity waned by the 1990s; the current major renewal of interest has undoubtedly been contingent on the pioneering developments that emerged some 40 years ago. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  8. Strong Effects of Temperature on the Early Life Stages of a Cold Stenothermal Fish Species, Brown Trout (Salmo trutta L.).

    PubMed

    Réalis-Doyelle, Emilie; Pasquet, Alain; De Charleroy, Daniel; Fontaine, Pascal; Teletchea, Fabrice

    2016-01-01

    Temperature is the main abiotic factor that influences the life cycle of poikilotherms. The present study investigated the thermal tolerance and phenotypic plasticity of several parameters (development time, morphometric measures, bioenergetics) for both embryos and fry of a cold stenothermal fish species, brown trout (Salmo trutta L.) in order to allow for a holistic evaluation of the potential effects of temperature. Five temperatures (4°C, 6°C, 8°C, 10°C, and 12°C) were tested, and the effects of temperature were analyzed at three stages: hatching, emergence, and first food intake. A mean of 5,440 (S.E. ± 573) eggs, coming from seven females and seven males (seven families) captured close to Linkebeek (Belgium), were used for each temperature. Maximum survival of well-formed fry at first food intake and better use of energy budget were found at 6°C and 8°C, temperatures at which the possible contribution to the next generation should therefore be greatest. At 12°C, the experimental population fell dramatically (0.9% survival rate for well-formed fry at first food intake), and fry had almost no yolk sac at first food intake. The present results on survival at 12°C are in accordance with predictions of a sharp decrease in brown trout numbers in France over the coming decades according to climate change projections (1°C to 5°C temperature rise by 2100 for France). At 10°C, there was also a lower survival rate (55.4% at first food intake). At 4°C, the survival rate was high (76.4% at first food intake), but the deformity rate was much higher (22% at first food intake) than at 6°C, 8°C, and 10°C. The energetic budget showed that at the two extreme temperatures (4°C and 12°C) there was less energy left in the yolk sac at first food intake, suggesting a limited ability to survive starvation.

  9. Strong Effects of Temperature on the Early Life Stages of a Cold Stenothermal Fish Species, Brown Trout (Salmo trutta L.)

    PubMed Central

    Réalis-Doyelle, Emilie; Pasquet, Alain; De Charleroy, Daniel; Fontaine, Pascal; Teletchea, Fabrice

    2016-01-01

    Temperature is the main abiotic factor that influences the life cycle of poikilotherms. The present study investigated the thermal tolerance and phenotypic plasticity of several parameters (development time, morphometric measures, bioenergetics) for both embryos and fry of a cold stenothermal fish species, brown trout (Salmo trutta L.) in order to allow for a holistic evaluation of the potential effects of temperature. Five temperatures (4°C, 6°C, 8°C, 10°C, and 12°C) were tested, and the effects of temperature were analyzed at three stages: hatching, emergence, and first food intake. A mean of 5,440 (S.E. ± 573) eggs, coming from seven females and seven males (seven families) captured close to Linkebeek (Belgium), were used for each temperature. Maximum survival of well-formed fry at first food intake and better use of energy budget were found at 6°C and 8°C, temperatures at which the possible contribution to the next generation should therefore be greatest. At 12°C, the experimental population fell dramatically (0.9% survival rate for well-formed fry at first food intake), and fry had almost no yolk sac at first food intake. The present results on survival at 12°C are in accordance with predictions of a sharp decrease in brown trout numbers in France over the coming decades according to climate change projections (1°C to 5°C temperature rise by 2100 for France). At 10°C, there was also a lower survival rate (55.4% at first food intake). At 4°C, the survival rate was high (76.4% at first food intake), but the deformity rate was much higher (22% at first food intake) than at 6°C, 8°C, and 10°C. The energetic budget showed that at the two extreme temperatures (4°C and 12°C) there was less energy left in the yolk sac at first food intake, suggesting a limited ability to survive starvation. PMID:27170996

  10. Autonomic dysfunction with early respiratory syncytial virus-related infection.

    PubMed

    Stock, Claire; Teyssier, Georges; Pichot, Vincent; Goffaux, Philippe; Barthelemy, Jean-Claude; Patural, Hugues

    2010-08-25

    Apparent life-threatening events (ALTE) and/or prolonged apnoea have been well-documented during respiratory syncytial virus (RSV) infection in infants less than 2 months of age but fundamental mechanisms remain unclear. The possibility of a central origin for the development of severe cardiac and respiratory events encouraged us, to explore the autonomic nervous system (ANS) profile of infected infants, since ANS activity may contribute to the constellation of symptoms observed during severe forms of RSV bronchiolitis. Eight infants (2 preterm and 6 full-term) less than 2 months of age and presenting with severe and apnoeic forms of RSV infection were evaluated using non-invasive electrophysiological monitoring obtained simultaneously for approximately 2 consecutive hours, including a quiet sleep period. Eight control subjects, paired for gestational and postnatal age, were also evaluated. ANS status was monitored using electrocardiogram recordings and quantified through a frequency-domain analysis of heart rate variability (HRV). This included sympathetic (VLF and LF) and parasympathetic (HF) indices as well as a measure of baroreflex sensitivity (BRS) obtained using non-invasive continuous arterial pressure. Regardless of gestational and postnatal age, heart rate variability components (Ptot, VLF, LF, and HF) and baroreflex components (alpha LF, alpha HF and sBR) were found to be significantly lower in the RSV-infected group than in the control group (p<0.05). RSV infection in neonates is associated with profound central autonomic dysfunction. The potentially fatal consequence stresses the importance of maintaining prolonged cardiopulmonary monitoring. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Effective surveillance for early classical swine fever virus detection will utilize both virus and antibody detection capabilities.

    PubMed

    Panyasing, Yaowalak; Kedkovid, Roongtham; Thanawongnuwech, Roongroje; Kittawornrat, Apisit; Ji, Ju; Giménez-Lirola, Luis; Zimmerman, Jeffrey

    2018-03-01

    Early recognition and rapid elimination of infected animals is key to controlling incursions of classical swine fever virus (CSFV). In this study, the diagnostic characteristics of 10 CSFV assays were evaluated using individual serum (n = 601) and/or oral fluid (n = 1417) samples collected from -14 to 28 days post inoculation (DPI). Serum samples were assayed by virus isolation (VI), 2 commercial antigen-capture enzyme-linked immunosorbent assays (ELISA), virus neutralization (VN), and 3 antibody ELISAs. Both serum and oral fluid samples were tested with 3 commercial real-time reverse transcription-polymerase chain reaction (rRT-PCR) assays. One or more serum samples was positive by VI from DPIs 3 to 21 and by antigen-capture ELISAs from DPIs 6 to 17. VN-positive serum samples were observed at DPIs ≥ 7 and by antibody ELISAs at DPIs ≥ 10. CSFV RNA was detected in serum samples from DPIs 2 to 28 and in oral fluid samples from DPIs 4 to 28. Significant differences in assay performance were detected, but most importantly, no single combination of sample and assay was able to dependably identify CSFV-inoculated pigs throughout the 4-week course of the study. The results show that effective surveillance for CSFV, especially low virulence strains, will require the use of PCR-based assays for the detection of early infections (<14 days) and antibody-based assays, thereafter. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Evidence of the presence of the Zika virus in Mexico since early 2015.

    PubMed

    Díaz-Quiñonez, José Alberto; López-Martínez, Irma; Torres-Longoria, Belem; Vázquez-Pichardo, Mauricio; Cruz-Ramírez, Edith; Ramírez-González, José Ernesto; Ruiz-Matus, Cuitláhuac; Kuri-Morales, Pablo

    2016-12-01

    To assess the possible circulation of Zika virus (ZIKV) prior to the first documented case in Mexico, we reanalyzed the stored samples from the states of Veracruz and Yucatán, which were originally collected to test for dengue (DENV) and chikungunya (CHIKV) but were negative for these viruses despite the symptomatology. The samples were originally collected between the 30 and 46 epidemiological weeks (EW) when the ZIKV was not yet declared as a Public Health Emergency of International Concern (PHEIC). From the total 4016 negative samples, a total of one hundred samples, 50 from Veracruz (CHIK - DENV - ) and 50 from Yucatán (4 CHIK - DENV - and 46 CHIK - or DENV - ), were tested for Zika virus by using RT-PCR. Results showed that in Veracruz and Yucatán, 20 % (10/50) and 70 % (35/50) were, respectively, ZIKV positive, indicating unequivocally the presence of ZIKV at least since July 2015. We also tested non-confirmed suspect measles cases from early 2015 for ZIKV by RT-PCR. Remarkably in 11 Mexican states, 86 % (18/21) were positive with the earlier symptoms onset as early as May 2015. Finally, RT-PCR analyses on RNA extracted from Aedes aegypti mosquitoes captured from January to March 2015 showed the presence of ZIKV, strongly suggesting that the vector was already carrying the virus at the start of 2015.

  13. Influence of surface flattening on biodiversity of terrestrial arthropods during early stages of brown coal spoil heap restoration.

    PubMed

    Moradi, Jabbar; Potocký, Pavel; Kočárek, Petr; Bartuška, Martin; Tajovský, Karel; Tichánek, Filip; Frouz, Jan; Tropek, Robert

    2018-08-15

    Heterogeneity of environmental conditions is the crucial factor supporting biodiversity in various habitats, including post-mining sites. The effects of micro-topographic heterogeneity on biodiversity and conservation potential of arthropod communities in post-industrial habitats had not been studied before now. At one of the largest European brown coal spoil heaps, we sampled eight groups of terrestrial arthropods with different life strategies (moths, spiders, ground beetles, ants, orthopteroids, centipedes, millipedes, and woodlice), in successionally young plots (5-18 y), with a heterogeneous wavy surface after heaping, and compared the communities with plots flattened by dozing. A combination of the standardized quantitative sampling, using two different methods, and a paired design of the plot selection enabled a robust analysis. Altogether, we recorded 380 species of the focal arthropods, 15 of them nationally threatened. We revealed the importance of the micro-topographic heterogeneity for the formation of the biodiversity of arthropods in their secondary refuges. The communities with higher biodiversity and conservation value were detected in the plots with heterogeneous surfaces; exceptions were ground beetles and millipedes. The surface flattening, often the first step of technical reclamation projects, thus suppress biodiversity of most terrestrial arthropods during the restoration of post-mining sites. Since the communities of both surface types differed, the proportional presence on both surfaces could be more efficient in supporting the local biodiversity. We suggest reducing the surface dozing for the cases with other concerns only, to achieve a proportional representation of both surface types. Such a combination of different restoration approaches would, thus, efficiently support high biodiversity of groups with various needs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection

    PubMed Central

    Lee, Chia Min; Weight, Alisha K.; Haldar, Jayanta; Wang, Ling; Klibanov, Alexander M.; Chen, Jianzhu

    2012-01-01

    Covalently conjugating multiple copies of the drug zanamivir (ZA; the active ingredient in Relenza) via a flexible linker to poly-l-glutamine (PGN) enhances the anti-influenza virus activity by orders of magnitude. In this study, we investigated the mechanisms of this phenomenon. Like ZA itself, the PGN-attached drug (PGN-ZA) binds specifically to viral neuraminidase and inhibits both its enzymatic activity and the release of newly synthesized virions from infected cells. Unlike monomeric ZA, however, PGN-ZA also synergistically inhibits early stages of influenza virus infection, thus contributing to the markedly increased antiviral potency. This inhibition is not caused by a direct virucidal effect, aggregation of viruses, or inhibition of viral attachment to target cells and the subsequent endocytosis; rather, it is a result of interference with intracellular trafficking of the endocytosed viruses and the subsequent virus-endosome fusion. These findings both rationalize the great anti-influenza potency of PGN-ZA and reveal that attaching ZA to a polymeric chain confers a unique mechanism of antiviral action potentially useful for minimizing drug resistance. PMID:23185023

  15. EPISODIC ACCRETION AT EARLY STAGES OF EVOLUTION OF LOW-MASS STARS AND BROWN DWARFS: A SOLUTION FOR THE OBSERVED LUMINOSITY SPREAD IN H-R DIAGRAMS?

    SciTech Connect

    Baraffe, I.; Chabrier, G.; Gallardo, J.

    2009-09-01

    We present evolutionary models for young low-mass stars and brown dwarfs taking into account episodic phases of accretion at early stages of the evolution, a scenario supported by recent large surveys of embedded protostars. An evolution including short episodes of vigorous accretion followed by longer quiescent phases can explain the observed luminosity spread in H-R diagrams of star-forming regions at ages of a few Myr, for objects ranging from a few Jupiter masses to a few tenths of a solar mass. The gravitational contraction of these accreting objects strongly departs from the standard Hayashi track at constant T{sub eff}. Themore » best agreement with the observed luminosity scatter is obtained if most of the accretion shock energy is radiated away. The obtained luminosity spread at 1 Myr in the H-R diagram is equivalent to what can be misinterpreted as an {approx}10 Myr age spread for non-accreting objects. We also predict a significant spread in radius at a given T{sub eff}, as suggested by recent observations. These calculations bear important consequences for our understanding of star formation and early stages of evolution and on the determination of the initial mass function for young ({<=} a few Myr) clusters. Our results also show that the concept of a stellar birthline for low-mass objects has no valid support.« less

  16. Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses

    PubMed Central

    Sun, Xiangjie; Zeng, Hui; Kumar, Amrita; Belser, Jessica A.; Maines, Taronna R.

    2016-01-01

    ABSTRACT A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. IMPORTANCE Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary

  17. Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses.

    PubMed

    Sun, Xiangjie; Zeng, Hui; Kumar, Amrita; Belser, Jessica A; Maines, Taronna R; Tumpey, Terrence M

    2016-12-15

    A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage

  18. The use of early summer mosquito surveillance to predict late summer West Nile virus activity

    USGS Publications Warehouse

    Ginsberg, Howard S.; Rochlin, Ilia; Campbell, Scott R.

    2010-01-01

    Utility of early-season mosquito surveillance to predict West Nile virus activity in late summer was assessed in Suffolk County, NY. Dry ice-baited CDC miniature light traps paired with gravid traps were set weekly. Maximum-likelihood estimates of WNV positivity, minimum infection rates, and % positive pools were generally well correlated. However, positivity in gravid traps was not correlated with positivity in CDC light traps. The best early-season predictors of WNV activity in late summer (estimated using maximum-likelihood estimates of Culex positivity in August and September) were early date of first positive pool, low numbers of mosquitoes in July, and low numbers of mosquito species in July. These results suggest that early-season entomological samples can be used to predict WNV activity later in the summer, when most human cases are acquired. Additional research is needed to establish which surveillance variables are most predictive and to characterize the reliability of the predictions.

  19. Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication

    PubMed Central

    2014-01-01

    an early point in infection, probably by rendering the virus non-infectious. They also suggest that future studies using S. nigra extract to treat or prevent IBV or other coronaviruses are warranted. PMID:24433341

  20. Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro.

    PubMed

    Zhao, Fu-Rong; Xie, Yin-Li; Liu, Ze-Zhong; Shao, Jun-Jun; Li, Shi-Fang; Zhang, Yong-Guang; Chang, Hui-Yun

    2017-11-01

    Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV-A71 virus. In this study, our findings were the first to demonstrate that LiCl inhibition of the FMDV replication. In this study, BHK-21 cell was dose-dependent with LiCl at various stages of FMDV. Virus titration assay was calculated by the 50% tissue culture infected dose (TCID 50 ) with the Reed and Muench method. The cytotoxicity assay of LiCl was performed by the CCK8 kit. The expression level of viral mRNA was measured by RT-qPCR. The results revealed LiCl can inhibit FMDV replication, but it cannot affect FMDV attachment stage and entry stage in the course of FMDV life cycle. Further studies confirmed that the LiCl affect the replication stage of FMDV, especially the early stages of FMDV replication. So LiCl has potential as an effective anti-FMDV drug. Therefore, LiCl may be an effective drug for the control of FMDV. Based on that, the mechanism of the antiviral effect of LiCl on FMDV infection is need to in-depth research in vivo. © 2017 Wiley Periodicals, Inc.

  1. Identification of Unequally Represented Founder Viruses Among Tissues in Very Early SIV Rectal Transmission

    PubMed Central

    Chen, Jian; Ren, Yanqin; Daharsh, Lance; Liu, Lu; Kang, Guobin; Li, Qingsheng; Wei, Qiang; Wan, Yanmin; Xu, Jianqing

    2018-01-01

    Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission. We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 104 TCID50) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses was unequally represented in different tissues. This cluster of rare T/F viruses phylogenetically related to the non-dominant SIV variants in the inoculum and was not detected in any rectum tissues, but could be identified in the descending colon, jejunum, spleen, or plasma. In 2 out of 6 macaques, identical SIVmac251 variants belonging to this cluster were detected simultaneously in descending colon/jejunum and the inoculum. We also demonstrated that the average CG dinucleotide frequency of these rare T/F viruses found in tissues, as well as non-dominant variants in the inoculum, was significantly higher than the dominant T/F viruses in tissues and the inoculum. Collectively, these findings suggest that descending colon/jejunum might be more susceptible than rectum to SIV in the very early phase of infection. And host CG suppression, which was previously shown to inhibit HIV replication in vitro, may also contribute to the bottleneck selection during in vivo transmission. PMID:29651274

  2. M Gene Reassortment in H9N2 Influenza Virus Promotes Early Infection and Replication: Contribution to Rising Virus Prevalence in Chickens in China.

    PubMed

    Pu, Juan; Sun, Honglei; Qu, Yi; Wang, Chenxi; Gao, Weihua; Zhu, Junda; Sun, Yipeng; Bi, Yuhai; Huang, Yinhua; Chang, Kin-Chow; Cui, Jie; Liu, Jinhua

    2017-04-15

    Segment reassortment and base mutagenesis of influenza A viruses are the primary routes to the rapid evolution of high-fitness virus genotypes. We recently described a predominant G57 genotype of avian H9N2 viruses that caused countrywide outbreaks in chickens in China during 2010 to 2013, which led to the zoonotic emergence of H7N9 viruses. One of the key features of the G57 genotype is the replacement of the earlier A/chicken/Beijing/1/1994 (BJ/94)-like M gene with the A/quail/Hong Kong/G1/1997 (G1)-like M gene of quail origin. We report here the functional significance of the G1-like M gene in H9N2 viruses in conferring increased infection severity and infectivity in primary chicken embryonic fibroblasts and chickens. H9N2 virus housing the G1-like M gene, in place of the BJ/94-like M gene, showed an early surge in viral mRNA and viral RNA (vRNA) transcription that was associated with enhanced viral protein production and with an early elevated release of progeny virus comprising largely spherical rather than filamentous virions. Importantly, H9N2 virus with the G1-like M gene conferred extrapulmonary virus spread in chickens. Five highly represented signature amino acid residues (37A, 95K, 224N, and 242N in the M1 protein and 21G in the M2 protein) encoded by the prevalent G1-like M gene were demonstrated to be prime contributors to enhanced infectivity. Therefore, the genetic evolution of the M gene in H9N2 virus increases reproductive virus fitness, indicating its contribution to the rising virus prevalence in chickens in China. IMPORTANCE We recently described the circulation of a dominant genotype (genotype G57) of H9N2 viruses in countrywide outbreaks in chickens in China, which was responsible, through reassortment, for the emergence of H7N9 viruses that cause severe human infections. A key feature of the genotype G57 H9N2 virus is the presence of the quail-origin G1-like M gene, which had replaced the earlier BJ/94-like M gene. We found that H9N2 virus

  3. M Gene Reassortment in H9N2 Influenza Virus Promotes Early Infection and Replication: Contribution to Rising Virus Prevalence in Chickens in China

    PubMed Central

    Pu, Juan; Sun, Honglei; Qu, Yi; Wang, Chenxi; Gao, Weihua; Zhu, Junda; Sun, Yipeng; Bi, Yuhai; Huang, Yinhua; Chang, Kin-Chow

    2017-01-01

    ABSTRACT Segment reassortment and base mutagenesis of influenza A viruses are the primary routes to the rapid evolution of high-fitness virus genotypes. We recently described a predominant G57 genotype of avian H9N2 viruses that caused countrywide outbreaks in chickens in China during 2010 to 2013, which led to the zoonotic emergence of H7N9 viruses. One of the key features of the G57 genotype is the replacement of the earlier A/chicken/Beijing/1/1994 (BJ/94)-like M gene with the A/quail/Hong Kong/G1/1997 (G1)-like M gene of quail origin. We report here the functional significance of the G1-like M gene in H9N2 viruses in conferring increased infection severity and infectivity in primary chicken embryonic fibroblasts and chickens. H9N2 virus housing the G1-like M gene, in place of the BJ/94-like M gene, showed an early surge in viral mRNA and viral RNA (vRNA) transcription that was associated with enhanced viral protein production and with an early elevated release of progeny virus comprising largely spherical rather than filamentous virions. Importantly, H9N2 virus with the G1-like M gene conferred extrapulmonary virus spread in chickens. Five highly represented signature amino acid residues (37A, 95K, 224N, and 242N in the M1 protein and 21G in the M2 protein) encoded by the prevalent G1-like M gene were demonstrated to be prime contributors to enhanced infectivity. Therefore, the genetic evolution of the M gene in H9N2 virus increases reproductive virus fitness, indicating its contribution to the rising virus prevalence in chickens in China. IMPORTANCE We recently described the circulation of a dominant genotype (genotype G57) of H9N2 viruses in countrywide outbreaks in chickens in China, which was responsible, through reassortment, for the emergence of H7N9 viruses that cause severe human infections. A key feature of the genotype G57 H9N2 virus is the presence of the quail-origin G1-like M gene, which had replaced the earlier BJ/94-like M gene. We found that H9N

  4. Macrophages and cytokines in the early defence against herpes simplex virus

    PubMed Central

    Ellermann-Eriksen, Svend

    2005-01-01

    Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone

  5. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.

    PubMed

    Keele, Brandon F; Giorgi, Elena E; Salazar-Gonzalez, Jesus F; Decker, Julie M; Pham, Kimmy T; Salazar, Maria G; Sun, Chuanxi; Grayson, Truman; Wang, Shuyi; Li, Hui; Wei, Xiping; Jiang, Chunlai; Kirchherr, Jennifer L; Gao, Feng; Anderson, Jeffery A; Ping, Li-Hua; Swanstrom, Ronald; Tomaras, Georgia D; Blattner, William A; Goepfert, Paul A; Kilby, J Michael; Saag, Michael S; Delwart, Eric L; Busch, Michael P; Cohen, Myron S; Montefiori, David C; Haynes, Barton F; Gaschen, Brian; Athreya, Gayathri S; Lee, Ha Y; Wood, Natasha; Seoighe, Cathal; Perelson, Alan S; Bhattacharya, Tanmoy; Korber, Bette T; Hahn, Beatrice H; Shaw, George M

    2008-05-27

    The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.

  6. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection

    PubMed Central

    Keele, Brandon F.; Giorgi, Elena E.; Salazar-Gonzalez, Jesus F.; Decker, Julie M.; Pham, Kimmy T.; Salazar, Maria G.; Sun, Chuanxi; Grayson, Truman; Wang, Shuyi; Li, Hui; Wei, Xiping; Jiang, Chunlai; Kirchherr, Jennifer L.; Gao, Feng; Anderson, Jeffery A.; Ping, Li-Hua; Swanstrom, Ronald; Tomaras, Georgia D.; Blattner, William A.; Goepfert, Paul A.; Kilby, J. Michael; Saag, Michael S.; Delwart, Eric L.; Busch, Michael P.; Cohen, Myron S.; Montefiori, David C.; Haynes, Barton F.; Gaschen, Brian; Athreya, Gayathri S.; Lee, Ha Y.; Wood, Natasha; Seoighe, Cathal; Perelson, Alan S.; Bhattacharya, Tanmoy; Korber, Bette T.; Hahn, Beatrice H.; Shaw, George M.

    2008-01-01

    The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense. PMID:18490657

  7. Diverse mechanisms evolved by DNA viruses to inhibit early host defenses

    PubMed Central

    Sheng, Xinlei; Song, Bokai; Cristea, Ileana M.

    2016-01-01

    In mammalian cells, early defenses against infection by pathogens are mounted through a complex network of signaling pathways shepherded by immune-modulatory pattern-recognition receptors. As obligate parasites, the survival of viruses is dependent upon the evolutionary acquisition of mechanisms that tactfully dismantle and subvert the cellular intrinsic and innate immune responses. Here, we review the diverse mechanisms by which viruses that accommodate DNA genomes are able to circumvent activation of cellular immunity. We start by discussing viral manipulation of host defense protein levels by either transcriptional regulation or protein degradation. We next review viral strategies used to repurpose or inhibit these cellular immune factors by molecular hijacking or by regulating their post-translational modification status. Additionally, we explore the infection-induced temporal modulation of apoptosis to facilitate viral replication and spread. Lastly, the co-evolution of viruses with their hosts is highlighted by the acquisition of elegant mechanisms for suppressing host defenses via viral mimicry of host factors. In closing, we present a perspective on how characterizing these viral evasion tactics both broadens the understanding of virus-host interactions and reveals essential functions of the immune system at the molecular level. This knowledge is critical in understanding the sources of viral pathogenesis, as well as for the design of antiviral therapeutics and autoimmunity treatments. PMID:27650455

  8. Prunus necrotic ringspot virus Early Invasion and Its Effects on Apricot Pollen Grain Performance.

    PubMed

    Amari, Khalid; Burgos, Lorenzo; Pallas, Vicente; Sanchez-Pina, María Amelia

    2007-08-01

    ABSTRACT The route of infection and the pattern of distribution of Prunus necrotic ringspot virus (PNRSV) in apricot pollen were studied. PNRSV was detected both within and on the surface of infected pollen grains. The virus invaded pollen during its early developmental stages, being detected in pollen mother cells. It was distributed uniformly within the cytoplasm of uni- and bicellular pollen grains and infected the generative cell. In mature pollen grains, characterized by their triangular shape, the virus was located mainly at the apertures, suggesting that PNRSV distribution follows the same pattern as the cellular components required for pollen tube germination and cell wall tube synthesis. PNRSV also was localized inside pollen tubes, especially in the growth zone. In vitro experiments demonstrated that infection with PNRSV decreases the germination percentage of pollen grains by more than half and delays the growth of pollen tubes by approximately 24 h. However, although PNRSV infection affected apricot pollen grain performance during germination, the presence of the virus did not completely prevent fertilization, because the infected apricot pollen tubes, once germinated, were able to reach the apricot embryo sacs, which, in the climatic conditions of southeastern Spain, mature later than in other climates. Thus, infected pollen still could play an important role in the vertical transmission of PNRSV in apricot.

  9. The African swine fever virus virion membrane protein pE248R is required for virus infectivity and an early postentry event.

    PubMed

    Rodríguez, Irene; Nogal, María L; Redrejo-Rodríguez, Modesto; Bustos, María J; Salas, María L

    2009-12-01

    The African swine fever virus (ASFV) protein pE248R, encoded by the gene E248R, is a late structural component of the virus particle. The protein contains intramolecular disulfide bonds and has been previously identified as a substrate of the ASFV-encoded redox system. Its amino acid sequence contains a putative myristoylation site and a hydrophobic transmembrane region near its carboxy terminus. We show here that the protein pE248R is myristoylated during infection and associates with the membrane fraction in infected cells, behaving as an integral membrane protein. Furthermore, the protein localizes at the inner envelope of the virus particles in the cytoplasmic factories. The function of the protein pE248R in ASFV replication was investigated by using a recombinant virus that inducibly expresses the gene E248R. Under repressive conditions, the ASFV polyproteins pp220 and pp62 are normally processed and virus particles with morphology indistinguishable from that of those produced in a wild-type infection or under permissive conditions are generated. Moreover, the mutant virus particles can exit the cell as does the parental virus. However, the infectivity of the pE248R-deficient virions was reduced at least 100-fold. An investigation of the defect of the mutant virus indicated that neither virus binding nor internalization was affected by the absence of the protein pE248R, but a cytopathic effect was not induced and early and late gene expression was impaired, indicating that the protein is required for some early postentry event.

  10. The African Swine Fever Virus Virion Membrane Protein pE248R Is Required for Virus Infectivity and an Early Postentry Event ▿

    PubMed Central

    Rodríguez, Irene; Nogal, María L.; Redrejo-Rodríguez, Modesto; Bustos, María J.; Salas, María L.

    2009-01-01

    The African swine fever virus (ASFV) protein pE248R, encoded by the gene E248R, is a late structural component of the virus particle. The protein contains intramolecular disulfide bonds and has been previously identified as a substrate of the ASFV-encoded redox system. Its amino acid sequence contains a putative myristoylation site and a hydrophobic transmembrane region near its carboxy terminus. We show here that the protein pE248R is myristoylated during infection and associates with the membrane fraction in infected cells, behaving as an integral membrane protein. Furthermore, the protein localizes at the inner envelope of the virus particles in the cytoplasmic factories. The function of the protein pE248R in ASFV replication was investigated by using a recombinant virus that inducibly expresses the gene E248R. Under repressive conditions, the ASFV polyproteins pp220 and pp62 are normally processed and virus particles with morphology indistinguishable from that of those produced in a wild-type infection or under permissive conditions are generated. Moreover, the mutant virus particles can exit the cell as does the parental virus. However, the infectivity of the pE248R-deficient virions was reduced at least 100-fold. An investigation of the defect of the mutant virus indicated that neither virus binding nor internalization was affected by the absence of the protein pE248R, but a cytopathic effect was not induced and early and late gene expression was impaired, indicating that the protein is required for some early postentry event. PMID:19793823

  11. Studies of angiospermous wood in Australian brown coal by nuclear magnetic resonance and analytical pyrolysis: new insights into the early coalification process

    USGS Publications Warehouse

    Hatcher, P.G.; Wilson, M.A.; Vassallo, A.M.; Lerch, H. E.

    1989-01-01

    Many Tertiary coals contain abundant fossilized remains of angiosperms, which commonly dominated the ancient peat-swamp environments; modern analogs of such swamps can be found in tropical and subtropical regions of the world. Comparisons of angiospermous wood from Australian brown coal with similar wood buried in modern peat swamps of Indonesia have provided some new insights into coalification reactions. These comparisons were made by using solid-state 13C nuclear magnetic resonance (NMR) techniques and pyrolsis-gas chromatography-mass spectrometry (py-gc-ms). These two modern techniques are especially suited for detailed structural evaluation of the complex macromolecules in coal. The earliest transformation (peatification) of organic matter in angiospermous wood is the degradation and removal of cellulosic components and the concomitant selective preservation of lignin-derived components. The angiospermous lignin that becomes enriched in wood as a result of cellulose degradation also is modified by coalification reactions; this modification, however, does not involve degradation and removal of the lignin. Rather, the early coalification process transforms the lignin phenols (guiacyl and syringyl) to eventually yield the aromatic structures typically found in brown coal. One such transformation, which is determined from NMR data, involves the cleavage of aryl-ether bonds that link guaiacyl and syringyl units in lignin, and this transformation leads to the formation of free lignin phenols. Another transformation, which is also determined from the NMR data, involves the loss of methoxyl groups, probably via demethylation, to produce catechol-like structures. Coincident with ether-cleavage and demethylation, the aromatic rings derived from lignin phenols become more carbon-substituted and cross linked, as determined by dipolar-dephasing NMR studies. This cross linking is probably responsible for preventing the lignin phenols, which are freed from the lignin

  12. Diverse host feeding on nesting birds may limit early-season West Nile virus amplification.

    PubMed

    Egizi, Andrea M; Farajollahi, Ary; Fonseca, Dina M

    2014-06-01

    Arboviral activity tracks vector availability, which in temperate regions means that transmission ceases during the winter and must be restarted each spring. In the northeastern United States, Culex restuans Theobald resumes its activity earlier than Culex pipiens L. and is thought to be important in restarting West Nile virus (WNV) transmission. Its role in WNV amplification, however, is unclear, because viral levels commonly remain low until the rise of Cx. pipiens later in the season. Because a vector's feeding habits can reveal key information about disease transmission, we identified early-season (April-June) blood meals from Cx. restuans collected throughout New Jersey, and compared them to published datasets from later in the season and also from other parts of the country. We found significantly higher avian diversity, including poor WNV hosts, and fewer blood meals derived from American Robins (17% versus over 40% found in later season). Critically, we identified blood meals from significantly more female than male birds in species where females are the incubating sex, suggesting that Cx. restuans is able to feed on such a wide variety of hosts in early spring because incubating birds are easy targets. Because WNV amplification depends on virus consistently reaching competent hosts, our results indicate that Cx. restuans is unlikely to be an amplifying vector of WNV in the early season. As the season progresses, however, changes in the availability of nesting birds may make it just as capable as Cx. pipiens, although at somewhat lower abundance as the summer progresses.

  13. Visualization of early influenza A virus trafficking in human dendritic cells using STED microscopy.

    PubMed

    Baharom, Faezzah; Thomas, Oliver S; Lepzien, Rico; Mellman, Ira; Chalouni, Cécile; Smed-Sörensen, Anna

    2017-01-01

    Influenza A viruses (IAV) primarily target respiratory epithelial cells, but can also replicate in immune cells, including human dendritic cells (DCs). Super-resolution microscopy provides a novel method of visualizing viral trafficking by overcoming the resolution limit imposed by conventional light microscopy, without the laborious sample preparation of electron microscopy. Using three-color Stimulated Emission Depletion (STED) microscopy, we visualized input IAV nucleoprotein (NP), early and late endosomal compartments (EEA1 and LAMP1 respectively), and HLA-DR (DC membrane/cytosol) by immunofluorescence in human DCs. Surface bound IAV were internalized within 5 min of infection. The association of virus particles with early endosomes peaked at 5 min when 50% of NP+ signals were also EEA1+. Peak association with late endosomes occurred at 15 min when 60% of NP+ signals were LAMP1+. At 30 min of infection, the majority of NP signals were in the nucleus. Our findings illustrate that early IAV trafficking in human DCs proceeds via the classical endocytic pathway.

  14. Brown dwarfs in young stellar clusters

    NASA Technical Reports Server (NTRS)

    Stringfellow, Guy S.

    1991-01-01

    The present calculations of the early evolution of brown dwarfs and very low mass stars (LMSs) yield isochrones spanning 0.01-0.2 solar masses for ages in the 1 to 300 million year range. Since the brown dwarfs remain sharply segregated in T(eff) from LMSs for ages of less than 100 million years, it follows that for coeval populations of known age, a domain exists in the H-R diagram in which only brown dwarfs exist. These theoretical results are compared with recent observations of the Pleiades brown dwarf candidates, using two new sets of color-T(eff) transformations. Both sets yield consistent interpretations.

  15. The neutralizing role of IgM during early Chikungunya virus infection

    PubMed Central

    Chua, Chong-Long; Chiam, Chun-Wei; Chan, Yoke-Fun

    2017-01-01

    The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays. PMID:28182795

  16. Evaluation of the novel respiratory virus surveillance program: Pediatric Early Warning Sentinel Surveillance (PEWSS).

    PubMed

    Armour, Patricia A; Nguyen, Linh M; Lutman, Michelle L; Middaugh, John P

    2013-01-01

    Infections caused by respiratory viruses are associated with recurrent epidemics and widespread morbidity and mortality. Routine surveillance of these pathogens is necessary to determine virus activity, monitor for changes in circulating strains, and plan for public health preparedness. The Southern Nevada Health District in Las Vegas, Nevada, recruited five pediatric medical practices to serve as sentinel sites for the Pediatric Early Warning Sentinel Surveillance (PEWSS) program. Sentinel staff collected specimens throughout the year from ill children who met the influenza-like illness case definition and submitted specimens to the Southern Nevada Public Health Laboratory for molecular testing for influenza and six non-influenza viruses. Laboratory results were analyzed and reported to the medical and general communities in weekly bulletins year-round. PEWSS data were also used to establish viral respiratory seasonal baselines and in influenza vaccination campaigns. The surveillance program was evaluated using the Centers for Disease Control and Prevention's (CDC's) Updated Guidelines for Evaluating Public Health Surveillance Systems. PEWSS met three of six program usefulness criteria and seven of nine surveillance system attributes, which exceeded the CDC Guidelines evaluation criteria for a useful and complete public health surveillance program. We found that PEWSS is a useful and complete public health surveillance system that is simple, flexible, accessible, and stable.

  17. Evaluation of the Novel Respiratory Virus Surveillance Program: Pediatric Early Warning Sentinel Surveillance (PEWSS)

    PubMed Central

    Nguyen, Linh M.; Lutman, Michelle L.; Middaugh, John P.

    2013-01-01

    Objectives Infections caused by respiratory viruses are associated with recurrent epidemics and widespread morbidity and mortality. Routine surveillance of these pathogens is necessary to determine virus activity, monitor for changes in circulating strains, and plan for public health preparedness. The Southern Nevada Health District in Las Vegas, Nevada, recruited five pediatric medical practices to serve as sentinel sites for the Pediatric Early Warning Sentinel Surveillance (PEWSS) program. Methods Sentinel staff collected specimens throughout the year from ill children who met the influenza-like illness case definition and submitted specimens to the Southern Nevada Public Health Laboratory for molecular testing for influenza and six non-influenza viruses. Results Laboratory results were analyzed and reported to the medical and general communities in weekly bulletins year-round. PEWSS data were also used to establish viral respiratory seasonal baselines and in influenza vaccination campaigns. The surveillance program was evaluated using the Centers for Disease Control and Prevention's (CDC's) Updated Guidelines for Evaluating Public Health Surveillance Systems. PEWSS met three of six program usefulness criteria and seven of nine surveillance system attributes, which exceeded the CDC Guidelines evaluation criteria for a useful and complete public health surveillance program. Conclusion We found that PEWSS is a useful and complete public health surveillance system that is simple, flexible, accessible, and stable. PMID:23997308

  18. Artificial receptors in serologic tests for the early diagnosis of dengue virus infection.

    PubMed

    Tai, Dar-Fu; Lin, Chung-Yin; Wu, Tzong-Zeng; Huang, Jyh-Hsiung; Shu, Pei-Yun

    2006-08-01

    Because of the range and nonspecificity of clinical presentations of dengue virus infections, we felt there was a need to create diagnostic tests. We used artificial receptors for the virus to develop serologic assays to detect dengue virus infection. We coated a quartz crystal microbalance (QCM) with molecularly imprinted polymers specific for nonstructural protein 1 of flavivirus. These artificial receptors were specifically created on a QCM chip by polymerization of monomers and were cross-linked in the presence of the epitope site of nonstructural protein 1. We tested serum samples from patients with confirmed cases of dengue reported to the Center for Disease Control in Taipei. Samples were diluted 100-fold; no other sample pretreatment was used. The QCM response was compared with results of monoclonal ELISA. QCM signals were >15 Hz in 18 of 21 (86%) of dengue samples and in 0 of 16 control samples. The correlation (r2) of the QCM response and the ELISA result was 0.73. Within-run and run-to-run imprecisions (CV) were 4%-28% and 10%-32%, respectively. The described assay offers a serologic technique for diagnosis of early viremia. The results illustrate the potential of well-organized polymers on the highly sensitive sensor system for diagnostic and biotechnological applications.

  19. Pomerelle Russet: An early maturing potato variety with high yield of U.S. No.1 tubers suitable for fresh market and early processing and resistance to Potato mop top virus and corky ringspot

    USDA-ARS?s Scientific Manuscript database

    Pomerelle Russet is an early maturing fresh potato variety, which produces moderately high early-season yields of oblong-long tubers with brown-russet skin. It is notable for its very attractive, smooth tubers and resistances to internal and external defects with a high percentage of U.S. No. 1 tube...

  20. Cassava Brown Streak Virus (Potyviridae) Encodes a Putative Maf/HAM1 Pyrophosphatase Implicated in Reduction of Mutations and a P1 Proteinase That Suppresses RNA Silencing but Contains No HC-Pro ▿

    PubMed Central

    Mbanzibwa, Deusdedith R.; Tian, Yanping; Mukasa, Settumba B.; Valkonen, Jari P. T.

    2009-01-01

    The complete positive-sense single-stranded RNA genome of Cassava brown streak virus (CBSV; genus Ipomovirus; Potyviridae) was found to consist of 9,069 nucleotides and predicted to produce a polyprotein of 2,902 amino acids. It was lacking helper-component proteinase but contained a single P1 serine proteinase that strongly suppressed RNA silencing. Besides the exceptional structure of the 5′-proximal part of the genome, CBSV also contained a Maf/HAM1-like sequence (678 nucleotides, 226 amino acids) recombined between the replicase and coat protein domains in the 3′-proximal part of the genome, which is highly conserved in Potyviridae. HAM1 was flanked by consensus proteolytic cleavage sites for ipomovirus NIaPro cysteine proteinase. Homology of CBSV HAM1 with cellular Maf/HAM1 pyrophosphatases suggests that it may intercept noncanonical nucleoside triphosphates to reduce mutagenesis of viral RNA. PMID:19386713

  1. Apoptosis induced in an early step of African swine fever virus entry into vero cells does not require virus replication.

    PubMed

    Carrascosa, Angel L; Bustos, María J; Nogal, María L; González de Buitrago, Gonzalo; Revilla, Yolanda

    2002-03-15

    Permissive Vero cells develop apoptosis, as characterized by DNA fragmentation, caspases activation, cytosolic release of mitochondrial cytochrome c, and flow cytometric analysis of DNA content, upon infection with African swine fever virus (ASFV). To determine the step in virus replication that triggers apoptosis, we used UV-inactivated virus, inhibitors of protein and nucleic acid synthesis, and lysosomotropic drugs that block virus uncoating. ASFV-induced apoptosis was accompanied by caspase-3 activation, which was detected even in the presence of either cytosine arabinoside or cycloheximide, indicating that viral DNA replication and protein synthesis were not required to activate the apoptotic process. The activation of caspase-3 was released from chloroquine inhibition 2 h after virus absorption, while the infection with UV-inactivated ASFV did not induce the activation of the caspase cascade. We conclude that ASFV induces apoptosis in the infected cell by an intracellular pathway probably triggered during the process of virus uncoating.

  2. Nucleotide sequence of a cluster of early and late genes in a conserved segment of the vaccinia virus genome.

    PubMed Central

    Plucienniczak, A; Schroeder, E; Zettlmeissl, G; Streeck, R E

    1985-01-01

    The nucleotide sequence of a 7.6 kb vaccinia DNA segment from a genomic region conserved among different orthopox virus has been determined. This segment contains a tight cluster of 12 partly overlapping open reading frames most of which can be correlated with previously identified early and late proteins and mRNAs. Regulatory signals used by vaccinia virus have been studied. Presumptive promoter regions are rich in A, T and carry the consensus sequences TATA and AATAA spaced at 20-24 base pairs. Tandem repeats of a CTATTC consensus sequence are proposed to be involved in the termination of early transcription. PMID:2987815

  3. MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain.

    PubMed

    Kip, E; Staal, J; Verstrepen, L; Tima, H G; Terryn, S; Romano, M; Lemeire, K; Suin, V; Hamouda, A; Kalai, M; Beyaert, R; Van Gucht, S

    2018-04-15

    MALT1 is involved in the activation of immune responses, as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. Although MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus, Evelyn-Rotnycki-Abelseth (ERA) virus, and observed increased susceptibility with ERA virus in MALT1 -/- mice. Indeed, after intranasal infection with ERA virus, wild-type mice developed mild transient clinical signs with recovery at 35 days postinoculation (dpi). Interestingly, MALT1 -/- mice developed severe disease requiring euthanasia at around 17 dpi. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1 -/- mice at 10 dpi compared to MALT1 +/+ infected mice. At 17 dpi, however, the level of inflammatory cell activation was comparable to that observed in MALT1 +/+ mice. Moreover, MALT1 -/- mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain. IMPORTANCE Rabies virus is a neurotropic virus which can infect any mammal. Annually, 59,000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular

  4. Isolation and characterization of a Chinese strain of Tembusu virus from Hy-Line Brown layers with acute egg-drop syndrome in Fujian, China.

    PubMed

    Chen, Shilong; Wang, Shao; Li, Zhaolong; Lin, Fengqiang; Cheng, Xiaoxia; Zhu, Xiaoli; Wang, Jingxiang; Chen, Shaoying; Huang, Meiqing; Zheng, Min

    2014-05-01

    Tembusu virus (TMUV) has been a causative agent of an acute egg-drop syndrome found in Chinese duck populations since at least 2010. In this paper, we report the characterization of a TMUV-like flavivirus (named CJD05) isolated from naturally infected egg-laying fowl. The virus was identified and then isolated from hens suffering from severe egg drop and fever in Fujian Province, China. The virus replicated well in MDEF and CEF cells, and its cytopathogenic effect (CPE) was apparent. Hemagglutinating activity (HA) was negative for this virus using erythrocytes from both chickens and pigeons. Viral particles were enveloped and approximately 45 nm in diameter, as observed by electron microscopy. Phylogenetic analysis of the full-length nucleotide sequence of CJD05 indicated that this virus is closely related to the duck-origin TMUV, belonging to Ntaya group of flavivirus. Most importantly, pathogenicity studies showed that CJD05 is highly virulent in 1-day-old chicks, 1-day-old Muscovy ducks, egg-laying chickens and shelducks. Our research highlights the increase in epidemic disease caused by avian TMUV, and subsequent outbreaks are becoming more complicated to treat. The pathogenic mechanisms of the virus are still not fully understood, further research is needed.

  5. An Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat.

    PubMed Central

    Kenney, S; Kamine, J; Markovitz, D; Fenrick, R; Pagano, J

    1988-01-01

    Acquired immunodeficiency syndrome patients are frequently coinfected with Epstein-Barr virus (EBV). In this report, we demonstrate that an EBV immediate-early gene product, BamHI MLF1, stimulates expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the human immunodeficiency virus (HIV) promoter. The HIV promoter sequences necessary for trans-activation by EBV do not include the tat-responsive sequences. In addition, in contrast to the other herpesvirus trans-activators previously studied, the EBV BamHI MLF1 gene product appears to function in part by a posttranscriptional mechanism, since it increases pHIV-CAT protein activity more than it increases HIV-CAT mRNA. This ability of an EBV gene product to activate HIV gene expression may have biologic consequences in persons coinfected with both viruses. Images PMID:2830625

  6. An Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat.

    PubMed

    Kenney, S; Kamine, J; Markovitz, D; Fenrick, R; Pagano, J

    1988-03-01

    Acquired immunodeficiency syndrome patients are frequently coinfected with Epstein-Barr virus (EBV). In this report, we demonstrate that an EBV immediate-early gene product, BamHI MLF1, stimulates expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the human immunodeficiency virus (HIV) promoter. The HIV promoter sequences necessary for trans-activation by EBV do not include the tat-responsive sequences. In addition, in contrast to the other herpesvirus trans-activators previously studied, the EBV BamHI MLF1 gene product appears to function in part by a posttranscriptional mechanism, since it increases pHIV-CAT protein activity more than it increases HIV-CAT mRNA. This ability of an EBV gene product to activate HIV gene expression may have biologic consequences in persons coinfected with both viruses.

  7. Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat

    SciTech Connect

    Kenney, S.; Kamine, J.; Markovitz, D.

    Acquired immunodeficiency syndrome patients are frequently coinfected with Epstein-Barr virus (EBV). In this report, the authors demonstrate that an EBV immediate-early gene product, BamHI MLF1, stimulates expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the human immunodeficiency virus (HIV) promoter. The HIV promoter sequences necessary for trans-activation by EBV do not include the tat-responsive sequences. In addition, in contrast to the other herpesvirus trans-activators previously studied, the EBV BamHI MLF1 gene product appears to function in part by a posttranscriptional mechanism, since it increases pHIV-CAT protein activity more than it increases HIV-CAT mRNA. This ability of an EBVmore » gene product to activate HIV gene expression may have biologic consequences in persons coinfected with both viruses.« less

  8. Early Antibody Response Contributes to the Virus Eradication and Clinical Recovery of H7N9 Influenza Infection.

    PubMed

    Liu, Xi; Yang, Zheng; Yuan, Jing; Liao, Jian; Duan, Lian; Wang, Wenfei; Zhang, Fuping; Chen, Xinchun; Zhou, Boping

    2017-09-01

    A new type of highly pathogenic avian influenza virus, H7N9, has been a great threat to public health since its 2013 outbreak. The humoral immune response plays a critical role in protection from the influenza virus, but its role and kinetics in H7N9-infected patients remain to be determined. In this study, we performed a retrospective investigation of the antibody response in plasma samples from 37 cases of hospitalized patients and analysed the relationship between the antibody response and the clinical outcomes. Our results showed that the HA7-binding antibody was generated earlier than the neutralizing antibody. Higher titer of HA7-binding antibody during the first 14 days after disease onset were associated with a shorter virus-positive continuation period, which is an important risk predictor ( P <0.05). Additionally, the titers of HA7-binding antibody were consistently and significantly lower in patients who died than those who recovered from the severe disease. Unexpectedly, no correlation between the titer of neutralizing antibody and the resulting clinical outcomes was found, suggesting that a neutralizing antibody-independent mechanism also contributed to virus control. In summary, our data suggests that an early antibody response against H7N9 influenza virus contributes to the eradication of the virus. A higher, early HA7-binding antibody response is associated with better clinical outcomes in H7N9 patients. © 2017 by the Association of Clinical Scientists, Inc.

  9. Are Sunflower chlorotic mottle virus infection symptoms modulated by early increases in leaf sugar concentration?

    PubMed

    Rodríguez, Marianela; Taleisnik, Edith; Lenardon, Sergio; Lascano, Ramiro

    2010-09-15

    Symptom development in a susceptible sunflower line inoculated with Sunflower chlorotic mottle virus (SuCMoV) was followed in the second pair of leaves at different post-inoculation times: before symptom expression (BS), at early (ES) and late (LS) symptom expression. Sugar and starch increases and photoinhibition were observed as early effects BS, and were maintained or enhanced later on, however, chlorophyll loss was detected only at LS. Photoinhibition correlated with a drastic decrease in D1 protein level. The progress of infection was accompanied by decreasing levels of apoplastic reactive oxygen species (ROS). In infected leaves, higher antioxidant enzyme activities (superoxide dismutase, SOD; ascorbate peroxidase, APX; glutathione reductase, GR) were observed from BS. The purpose of this work was to evaluate whether the early increases in carbohydrate accumulation may participate in SuCMoV symptom expression. Similar effects on photoinhibition, apoplastic ROS generation and antioxidant activity were generated when healthy leaves were treated with sugars. These results suggest that photoinhibitory processes and lower apoplastic superoxide levels induced by SuCMoV infection may be modulated by sugar increases. Copyright 2010 Elsevier GmbH. All rights reserved.

  10. A model for early onset of protection against lethal challenge with highly pathogenic H5N1 influenza virus.

    PubMed

    Röhrs, Susanne; Kalthoff, Donata; Beer, Martin

    2014-05-07

    Highly pathogenic avian influenza viruses of subtype H5N1 sporadically cause severe disease in humans and involve the risk of inducing a pandemic by gaining the ability for human-to-human transmission. In naïve poultry, primarily gallinaceous birds, the virus induces fatal disease and the used inactivated vaccines occasionally are unable to provide efficient and early onset of protection. Therefore, optimized vaccines must be developed and evaluated in model systems. In our study, we tested a novel H5 neuraminidase-deleted influenza A virus variant to analyze the induction of a very early onset of immunity. Ferrets, mice and chickens were each immunized with a single vaccine dose seven, three and one day before lethal challenge infection, respectively. Sound protection was conferred in 100% of animals immunized seven days prior to challenge infection. In these animals, no clinical signs were observed, and no challenge virus RNA was detected by real-time RT-PCR analyses of swabs, nasal washings, and organ samples. Moreover, the attenuated modified-live virus variant protected all chickens, mice, and ferrets as early as three days after vaccination against severe clinical signs. Chickens and ferrets developed hemagglutinin-specific antibodies after seven days, but no neuraminidase-specific antibodies, making this kind of neuraminidase-negative strain suitable for the DIVA ("differentiating vaccinated from infected animals") strategy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Impairment of Human Immunodeficiency Virus Type-1 Integrase SUMOylation Correlates with an Early Replication Defect*

    PubMed Central

    Zamborlini, Alessia; Coiffic, Audrey; Beauclair, Guillaume; Delelis, Olivier; Paris, Joris; Koh, Yashuiro; Magne, Fabian; Giron, Marie-Lou; Tobaly-Tapiero, Joelle; Deprez, Eric; Emiliani, Stephane; Engelman, Alan; de Thé, Hugues; Saïb, Ali

    2011-01-01

    HIV-1 integrase (IN) orchestrates the integration of the reverse transcribed viral cDNA into the host cell genome and participates also in other steps of HIV-1 replication. Cellular and viral factors assist IN in performing its multiple functions, and post-translational modifications contribute to modulate its activities. Here, we show that HIV-1 IN is modified by SUMO proteins and that phylogenetically conserved SUMOylation consensus motifs represent major SUMO acceptor sites. Viruses harboring SUMOylation site IN mutants displayed a replication defect that was mapped during the early stages of infection, before integration but after reverse transcription. Because SUMOylation-defective IN mutants retained WT catalytic activity, we hypothesize that SUMOylation might regulate the affinity of IN for co-factors, contributing to efficient HIV-1 replication. PMID:21454548

  12. Ancient DNA identification of early 20th century simian T-cell leukemia virus type 1.

    PubMed

    Calvignac, Sébastien; Terme, Jean-Michel; Hensley, Shannon M; Jalinot, Pierre; Greenwood, Alex D; Hänni, Catherine

    2008-06-01

    The molecular identification of proviruses from ancient tissues (and particularly from bones) remains a contentious issue. It can be expected that the copy number of proviruses will be low, which magnifies the risk of contamination with retroviruses from exogenous sources. To assess the feasibility of paleoretrovirological studies, we attempted to identify proviruses from early 20th century bones of museum specimens while following a strict ancient DNA methodology. Simian T-cell leukemia virus type 1 sequences were successfully obtained and authenticated from a Chlorocebus pygerythrus specimen. This represents the first clear evidence that it will be possible to use museum specimens to better characterize simian and human T-tropic retrovirus genetic diversity and analyze their origin and evolution, in greater detail.

  13. Biophysical Properties of Frog Virus and Its Deoxyribonucleic Acid: Fate of Radioactive Virus in the Early Stage of Infection 1

    PubMed Central

    Smith, William R.; McAuslan, Brian R.

    1969-01-01

    Frog virus (FV-3) was banded by isopycnic centrifugation in cesium chloride, sucrose, or potassium tartrate. Two bands of infectivity were regularly found at positions in cesium chloride corresponding to densities of 1.26 and 1.30 g/cm3, respectively. Deoxyribonucleic acid from either band had the following characteristics: double-stranded; a Tm of 76.3 C in 0.1 SSC (0.015 m NaCl plus 0.015 m sodium citrate) and a buoyant density of 1.720 g/cm3 in cesium chloride, corresponding to a guanine plus cytosine content of 56 to 58% and a molecular weight of 130 × 106 daltons, determined by velocity sedimentation. These data, together with electron micrographs of sections of cells infected with material from either band suggest that two types of infectious frog virus particles exists, rather than a second virus in the frog virus stocks. The composition of frog virus was determined. It was found that highly purified preparations of frog virus were composed of 55.8% protein, 30.1% deoxyribonucleic acid, and 14.2% lipid. The kinetics of adsorption and uncoating of FV-3 was studied with radioactive virus. Uncoating is comparatively rapid and in contrast to poxvirus is unaffected by inhibitors of protein synthesis. Images PMID:4980848

  14. Pathophysiology of infectious hematopoietic necrosis virus disease in rainbow trout (Salmo gairdneri): early changes in blood and aspects of the immune Response after Injection of IHN Virus

    USGS Publications Warehouse

    Amend, Donald F.; Smith, Lynnwood

    1974-01-01

    Juvenile rainbow trout (Salmo gairdneri) were injected with infectious hematopoietic necrosis (IHN) virus and various hematological and blood chemical changes were monitored over 9 days. The packed cell volume, hemoglobin, red blood cell count, and plasma bicarbonate were significantly depressed by day 4. Plasma chloride, calcium, phosphorus, total protein, and blood cell types did not change during the 9 days. Furthermore, plasma  LDH isozyme was significantly increased by the fourth day, and fish infected with infectious pancreatic necrosis virus, Vibrio anguillarum, Aeromonas salmonicida, and redmouth bacterium did not show specific LDH isozyme alterations. Acid-base alterations occurred at 10 C but not at 18 C. The acid-base imbalance and elevation of the  LDH isozyme were consistently associated with the early development of the disease.The immune response after injection of IHN virus was determined and protection from disease was tested by passive immunization. Actively immunized fish developed IHN-neutralizing antibodies within 54 days after injection of virus, and the antibodies were protective when juvenile fish were passively immunized and experimentally challenged with IHN virus.

  15. Photodynamic therapy of virus-associated precancer and early stages cancer of cervix uteri.

    PubMed

    Trushina, O I; Novikova, E G; Sokolov, V V; Filonenko, E V; Chissov, V I; Vorozhtsov, G N

    2008-12-01

    We have analyzed the results of photodynamic therapy using light-sensitizing agent "Photogem" in 72 patients - 56 women with pre-cancerous lesions of cervix and 16 women with early cervical cancer (group 1); Photosens in 47 patients - 35 women with pre-cancerous lesions (CIN III), 12 women with non-invasive cervical cancer (carcinoma in situ) (group 2); and Alasens in 22 patients - 8 women with virus-associated pre-cancerous lesions (high-grade CIN III), 14 with virus-associated early cervical cancer (carcinoma in situ, cervical cancer 1A1) (group 3). The results were as follows: group 1 - complete regression of CIN III and non-invasive cervical cancer (carcinoma in situ) was achieved in 50 (89.2%) and 11 (68.8%) cases, significant regression was achieved in 2 cases (3.6%) and in 2 cases (12.5%), stabilization was achieved in 2 cases (3.6%) and in 2 cases (12.5%), progression was achieved in 2 cases (3.6%) and in 1 case (6.2%) accordingly. In the group of patients after PDT using Photosens complete regression of CIN III and non-invasive cervical cancer (carcinoma in situ) was achieved in 33 cases (94.2%) and in 10 cases (83.4%) cases, significant regression was achieved in 1 case (2.9%) and in 1 case (8.3%), stabilization was achieved in 1 cases (2.9%) and in 1 cases (8.3%). In the group of women after surgical treatment anti-viral efficacy was assessed. It s necessary to note that not a single relapse was observed. Anti-viral effect was registered in 49 (90.4%) cases The longest HPV-free period that we observed was 5 years. 12 women with CIN III and 4 women with carcinoma in situ became pregnant.

  16. West nile virus infections suppress early viral RNA synthesis and avoid inducing the cell stress granule response.

    PubMed

    Courtney, S C; Scherbik, S V; Stockman, B M; Brinton, M A

    2012-04-01

    West Nile virus (WNV) recently became endemic in the United States and is a significant cause of human morbidity and mortality. Natural WNV strain infections do not induce stress granules (SGs), while W956IC (a lineage 2/1 chimeric WNV infectious clone) virus infections produce high levels of early viral RNA and efficiently induce SGs through protein kinase R (PKR) activation. Additional WNV chimeric viruses made by replacing one or more W956IC genes with the lineage 1 Eg101 equivalent in the W956IC backbone were analyzed. The Eg-NS4b+5, Eg-NS1+3+4a, and Eg-NS1+4b+5 chimeras produced low levels of viral RNA at early times of infection and inefficiently induced SGs, suggesting the possibility that interactions between viral nonstructural proteins and/or between viral nonstructural proteins and cell proteins are involved in suppressing early viral RNA synthesis and membrane remodeling during natural WNV strain infections. Detection of exposed viral double-stranded RNA (dsRNA) in W956IC-infected cells suggested that the enhanced early viral RNA synthesis surpassed the available virus-induced membrane protection and allowed viral dsRNA to activate PKR.

  17. Early detection of foot-and-mouth disease virus from infected cattle using a dry filter air sampling system

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is a highly contagious livestock disease of high economic impact. Early detection of FMD virus (FMDV) is fundamental for rapid outbreak control. Air sampling collection has been demonstrated as a useful technique for detection of FMDV RNA in infected animals, related to ...

  18. Brown Dwarf Comparison

    NASA Image and Video Library

    2009-11-17

    NASA Wide-field Infrared Survey Explorer will uncover many failed stars, or brown dwarfs, in infrared light. This diagram shows a brown dwarf in relation to Earth, Jupiter, a low-mass star and the sun.

  19. Significance of brown dwarfs

    NASA Technical Reports Server (NTRS)

    Black, D. C.

    1986-01-01

    The significance of brown dwarfs for resolving some major problems in astronomy is discussed. The importance of brown dwarfs for models of star formation by fragmentation of molecular clouds and for obtaining independent measurements of the ages of stars in binary systems is addressed. The relationship of brown dwarfs to planets is considered.

  20. Hepatitis C Virus Reveals a Novel Early Control in Acute Immune Response

    PubMed Central

    Arnaud, Noëlla; Dabo, Stéphanie; Akazawa, Daisuke; Fukasawa, Masayoshi; Shinkai-Ouchi, Fumiko; Hugon, Jacques; Wakita, Takaji; Meurs, Eliane F.

    2011-01-01

    Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity. Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25, its interaction with the mitochondria-bound MAVS protein, recruitment of TRAF3, IRF3- and NF-κB-kinases and transcription of Interferon (IFN). In addition, IRF3 alone induces some of the Interferon-Stimulated Genes (ISGs), referred to as early ISGs. Infection of hepatocytes with Hepatitis C virus (HCV) results in poor production of IFN despite recognition of the viral RNA by RIG-I but can lead to induction of early ISGs. HCV was shown to inhibit IFN production by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2α-kinase containing dsRNA-binding domains (DRBD). Here, we have identified a third mode of control of IFN induction by HCV. Using HCVcc and the Huh7.25.CD81 cells, we found that HCV controls RIG-I ubiquitination through the di-ubiquitine-like protein ISG15, one of the early ISGs. A transcriptome analysis performed on Huh7.25.CD81 cells silenced or not for PKR and infected with JFH1 revealed that HCV infection leads to induction of 49 PKR-dependent genes, including ISG15 and several early ISGs. Silencing experiments revealed that this novel PKR-dependent pathway involves MAVS, TRAF3 and IRF3 but not RIG-I, and that it does not induce IFN. Use of PKR inhibitors showed that this pathway requires the DRBD but not the kinase activity of PKR. We then demonstrated that PKR interacts with HCV RNA and MAVS prior to RIG-I. In conclusion, HCV recruits PKR early in infection as a sensor to trigger induction of several IRF3-dependent genes. Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response. PMID:22022264

  1. Raman spectroscopy based investigation of molecular changes associated with an early stage of dengue virus infection

    NASA Astrophysics Data System (ADS)

    Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan

    2017-04-01

    Raman spectroscopy based investigations of the molecular changes associated with an early stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775-875 cm-1, lectins at 1003, 1238, 1340, 1449 and 1672 cm-1, DNA in the region 1040-1140 cm-1 and alpha and beta structures of proteins in the region 933-967 cm-1 have been identified in the regression vector for their role in an early stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.

  2. Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

    PubMed Central

    McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.

    2011-01-01

    Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection. PMID:21912520

  3. Robust Lys63-Linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection

    PubMed Central

    Jiang, Jingwen; Fan, Wenhui; Zheng, Weinan; Yu, Meng; Chen, Can; Sun, Lei; Bi, Yuhai; Ding, Chan; Gao, George F.

    2016-01-01

    ABSTRACT Influenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and proinflammatory factors can be induced by influenza B virus rather than influenza A virus infection in alveolar epithelial (A549) cells during early infection. This response is mainly dependent on the retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway. Infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25 and that this interaction blocks the inhibitory effect of the NS1-B C-terminal effector domain (TED) on RIG-I ubiquitination. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins. IMPORTANCE Influenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response to influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are

  4. Robust Lys63-Linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection.

    PubMed

    Jiang, Jingwen; Li, Jing; Fan, Wenhui; Zheng, Weinan; Yu, Meng; Chen, Can; Sun, Lei; Bi, Yuhai; Ding, Chan; Gao, George F; Liu, Wenjun

    2016-07-15

    Influenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and proinflammatory factors can be induced by influenza B virus rather than influenza A virus infection in alveolar epithelial (A549) cells during early infection. This response is mainly dependent on the retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway. Infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25 and that this interaction blocks the inhibitory effect of the NS1-B C-terminal effector domain (TED) on RIG-I ubiquitination. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins. Influenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response to influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are induced by virus

  5. Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections

    PubMed Central

    Iversen, Patrick L.; Warren, Travis K.; Wells, Jay B.; Garza, Nicole L.; Mourich, Dan V.; Welch, Lisa S.; Panchal, Rekha G.; Bavari, Sina

    2012-01-01

    There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates. PMID:23202506

  6. Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections.

    PubMed

    Iversen, Patrick L; Warren, Travis K; Wells, Jay B; Garza, Nicole L; Mourich, Dan V; Welch, Lisa S; Panchal, Rekha G; Bavari, Sina

    2012-11-06

    There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.

  7. [Human brown adipose tissue].

    PubMed

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  8. Microcephaly and Zika virus: Neuroradiological aspects, clinical findings and a proposed framework for early evaluation of child development.

    PubMed

    Cicuto Ferreira Rocha, Nelci Adriana; de Campos, Ana Carolina; Cicuto Ferreira Rocha, Fellipe; Pereira Dos Santos Silva, Fernanda

    2017-11-01

    As the recent outbreak of microcephaly cases caused by Zika virus has been declared a global health emergency, providing assessment guidelines for multidisciplinary teams providing early developmental screening and stimulation to infants with microcephaly is much needed. Thus, the aim of this manuscript is to provide an overview on what is known about neuroradiological aspects and clinical findings in infants with microcephaly caused by Zika virus and to propose a framework for early evaluation of child development. The keywords "Zika virus" and "microcephaly" were searched in PubMed database for articles published from incept to May 2017. These texts were reviewed, and the ones addressing neuroradiological and clinical findings in infants were selected. Recommendations for early assessment were made based on the International Classification of Functionality Disability and Health (ICF) model. The database search yielded 599 publications and 36 were selected. The studies detected microcephaly with diffuse brain malformations and calcifications, ventriculomegaly, optic nerve hypoplasia, macular atrophy, cataracts, impaired visual and hearing function, arthrogryposis, spasticity, hyperreflexia, irritability, tremors, and seizures, but very little is known about early development. Early assessments were described based on the ICF domains (Body Function and Structures, Activities and Participation and Contextual factors). Studies published showed abnormal brain, optic, neurologic and orthopedic findings, but very little is known about other aspects of functioning in infants with microcephaly caused by Zika virus. The biopsychosocial model based on the ICF paradigm provides an adequate framework to describe the condition of the infant with microcephaly receiving rehabilitative efforts to minimize disability. Efforts towards early identification of developmental delays should be taken within the first six months of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Analysis of early dengue virus infection in mice as modulated by Aedes aegypti probing.

    PubMed

    McCracken, M K; Christofferson, R C; Chisenhall, D M; Mores, C N

    2014-02-01

    Dengue virus (DENV), the etiologic agent of dengue fever, is transmitted during probing of human skin by infected-mosquito bite. The expectorated viral inoculum also contains an assortment of mosquito salivary proteins that have been shown to modulate host hemostasis and innate immune responses. To examine the potential role of mosquito probing in DENV establishment within the vertebrate host, we inoculated mice intradermally with DENV serotype 2 strain 1232 at sites where Aedes aegypti had or had not probed immediately prior. We assayed these sites 3 h postinoculation with transcript arrays for the Toll-like receptor (TLR), RIG-I-like receptor, and NOD-like receptor signaling pathways of the innate immune system. We then chose TLR7, transcription factor p65 (RelA), gamma interferon (IFN-γ), and IFN-γ-inducible protein 10 (IP-10) from the arrays for further investigation and assayed these transcripts at 10 min, 3 h, and 6 h postinoculation. The transcripts for TLR7, RelA, IFN-γ, and IP-10 were significantly downregulated between 2- and 3-fold in the group subjected to mosquito probing relative to the virus-only inoculation group at 3 h postinoculation. A reduction in these transcripts could indicate reduced DENV recognition and antigen presentation and diminished inhibition of viral replication and spread. Further, mosquito probing resulted in viremia titers significantly higher than those in mice that did not receive probing. A. aegypti probing has a significant effect on the innate immune response to DENV infection and generates an early immune environment more permissive to the establishment of infection.

  10. Rab7 Associates with Early Endosomes to Mediate Sorting and Transport of Semliki Forest Virus to Late Endosomes

    PubMed Central

    Vonderheit, Andreas

    2005-01-01

    Semliki forest virus (SFV) is internalized by clathrin-mediated endocytosis, and transported via early endosomes to late endosomes and lysosomes. The intracellular pathway taken by individual fluorescently labeled SFV particles was followed using immunofluorescence in untransfected cells, and by video-enhanced, triple-color fluorescence microscopy in live cells transfected with GFP- and RFP-tagged Rab5, Rab7, Rab4, and Arf1. The viruses progressed from Rab5-positive early endosomes to a population of early endosomes (about 10% of total) that contained both Rab5 and Rab7. SFV were sequestered in the Rab7 domains, and they were sorted away from the early endosomes when these domains detached as separate transport carriers devoid of Rab5, Rab4, EEA1, Arf1, and transferrin. The process was independent of Arf1 and the acidic pH in early endosomes. Nocodazole treatment showed that the release of transport carriers was assisted by microtubules. Expression of constitutively inactive Rab7T22N resulted in accumulation of SFV in early endosomes. We concluded that Rab7 is recruited to early endosomes, where it forms distinct domains that mediate cargo sorting as well as the formation of late-endosome-targeted transport vesicles. PMID:15954801

  11. Early Evidence for Zika Virus Circulation among Aedes aegypti Mosquitoes, Rio de Janeiro, Brazil

    PubMed Central

    Ayllón, Tania; Campos, Renata de Mendonça; Brasil, Patrícia; Morone, Fernanda Cristina; Câmara, Daniel Cardoso Portela; Meira, Guilherme Louzada Silva; Tannich, Egbert; Yamamoto, Kristie Aimi; Carvalho, Marilia Sá; Pedro, Renata Saraiva; Cadar, Daniel; Ferreira, Davis Fernandes; Honório, Nildimar Alves

    2017-01-01

    During 2014–2016, we conducted mosquito-based Zika virus surveillance in Rio de Janeiro, Brazil. Results suggest that Zika virus was probably introduced into the area during May–November 2013 via multiple in-country sources. Furthermore, our results strengthen the hypothesis that Zika virus in the Americas originated in Brazil during October 2012–May 2013. PMID:28628464

  12. Distinct Lineage of Vesiculovirus from Big Brown Bats, United States

    PubMed Central

    Driscoll, Cindy; Carlos, Maria Paz; Prioleau, Algernon; Schmieder, Robert; Dwivedi, Bhakti; Wong, Jakk; Cha, Yunhee; Head, Steven; Breitbart, Mya; Delwart, Eric

    2013-01-01

    We identified a novel rhabdovirus, American bat vesiculovirus, from postmortem tissue samples from 120 rabies-negative big brown bats with a history of human contact. Five percent of the tested bats were infected with this virus. The extent of zoonotic exposure and possible health effects in humans from this virus are unknown. PMID:24274823

  13. Severity of Disease in Humanized Mice Infected With Ebola Virus or Reston Virus Is Associated With Magnitude of Early Viral Replication in Liver.

    PubMed

    Spengler, Jessica R; Saturday, Greg; Lavender, Kerry J; Martellaro, Cynthia; Keck, James G; Nichol, Stuart T; Spiropoulou, Christina F; Feldmann, Heinz; Prescott, Joseph

    2017-12-27

    Both Ebola virus (EBOV) and Reston virus (RESTV) cause disease in nonhuman primates, yet only EBOV causes disease in humans. To investigate differences in viral pathogenicity, humanized mice (hu-NSG-SGM3) were inoculated with EBOV or RESTV. Consistent with differences in disease in human infection, pronounced weight loss and markers of hepatic damage and disease were observed exclusively in EBOV-infected mice. These abnormalities were associated with significantly higher EBOV replication in the liver but not in the spleen, suggesting that in this model, efficiency of viral replication in select tissues early in infection may contribute to differences in viral pathogenicity. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  14. Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?

    PubMed

    Burbelo, Peter D; Price, Richard W; Hagberg, Lars; Hatano, Hiroyu; Spudich, Serena; Deeks, Steven G; Gisslén, Magnus

    2018-03-13

    Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) likely persists in the central nervous system (CNS) in treated individuals. We examined anti-HIV antibodies in cerebrospinal fluid (CSF) and blood as markers of persistence. Human immunodeficiency virus antibodies were measured in paired CSF and serum before and after long-term treatment of chronic (n = 10) and early infection (n = 12), along with untreated early infection (n = 10). Treatment of chronic infection resulted in small reductions of anti-HIV antibodies in CSF and serum despite >10 years of suppressive ART. In untreated early infection, anti-HIV antibodies emerged in blood by day 30, whereas CSF antibodies reached similar levels 2 weeks later. Compared with long-term treatment of chronic infection, early ART initiation reduced CSF antibodies by 43-fold (P > .0001) and blood antibodies by 7-fold (P = .0003). Two individuals receiving pre-exposure prophylaxis and then ART early after infection failed to develop antibodies in CSF or blood, whereas CSF antibodies were markedly reduced in the Berlin patient. To the extent that differential CSF and blood antibodies indicate HIV persistence, these data suggest a relative delay in establishment of the CNS compared with the systemic HIV reservoir that provides an opportunity for early treatment to have a greater impact on the magnitude of long-term CNS infection.

  15. Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?

    PubMed Central

    Burbelo, Peter D; Price, Richard W; Hagberg, Lars; Hatano, Hiroyu; Spudich, Serena; Deeks, Steven G; Gisslén, Magnus

    2018-01-01

    Abstract Background Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) likely persists in the central nervous system (CNS) in treated individuals. We examined anti-HIV antibodies in cerebrospinal fluid (CSF) and blood as markers of persistence. Methods Human immunodeficiency virus antibodies were measured in paired CSF and serum before and after long-term treatment of chronic (n = 10) and early infection (n = 12), along with untreated early infection (n = 10). Results Treatment of chronic infection resulted in small reductions of anti-HIV antibodies in CSF and serum despite >10 years of suppressive ART. In untreated early infection, anti-HIV antibodies emerged in blood by day 30, whereas CSF antibodies reached similar levels 2 weeks later. Compared with long-term treatment of chronic infection, early ART initiation reduced CSF antibodies by 43-fold (P > .0001) and blood antibodies by 7-fold (P = .0003). Two individuals receiving pre-exposure prophylaxis and then ART early after infection failed to develop antibodies in CSF or blood, whereas CSF antibodies were markedly reduced in the Berlin patient. Conclusions To the extent that differential CSF and blood antibodies indicate HIV persistence, these data suggest a relative delay in establishment of the CNS compared with the systemic HIV reservoir that provides an opportunity for early treatment to have a greater impact on the magnitude of long-term CNS infection. PMID:29401308

  16. Early development and life cycle of Contracaecum multipapillatum s.l. from a brown pelican Pelecanus occidentalis in the Gulf of California, Mexico.

    PubMed

    Valles-Vega, Isabel; Molina-Fernández, Dolores; Benítez, Rocío; Hernández-Trujillo, Sergio; Adroher, Francisco Javier

    2017-08-09

    The initial developmental stages of Contracaecum multipapillatum (von Drasche, 1882) Lucker, 1941 sensu lato were studied using eggs obtained from the uteri of female nematodes (genetically identified) found in a brown pelican Pelecanus occidentalis from Bahía de La Paz (Gulf of California, Mexico). Optical microscopy revealed a smooth or slightly rough surface to the eggs. Egg dimensions were approximately 53 × 43 µm, although after the larvae had developed inside, egg size increased to 66 × 55 µm. Hatching and survival of the larvae were greater at 15°C than at 24°C, and increased salinity resulted in a slight increase in hatching but seemed to reduce survival at 24°C, but not at 15°C. The recently hatched larvae measured 261 × 16 µm within their sheath. When placed in culture medium, the larvae grew within their sheath, and a small percentage (~2%) exsheathed completely (314 × 19 µm). The larvae continued to grow and develop once they had exsheathed, attaining mean dimensions of 333 × 22 µm. Although they did not moult during culture, optical microscopy revealed a morphology typical of third-stage larvae. Finally, the genetic identity between the larval parasites collected from mullet Mugil curema and adult female parasites collected from the brown pelican suggests a life cycle of C. multipapillatum in which the mullet are involved as intermediate/paratenic hosts and the brown pelicans as final hosts in the geographical area of Bahía de La Paz.

  17. Early Warning System for West Nile Virus Risk Areas, California, USA

    PubMed Central

    Ahearn, Sean C.; McConchie, Alan; Glaser, Carol; Jean, Cynthia; Barker, Chris; Park, Bborie; Padgett, Kerry; Parker, Erin; Aquino, Ervic; Kramer, Vicki

    2011-01-01

    The Dynamic Continuous-Area Space-Time (DYCAST) system is a biologically based spatiotemporal model that uses public reports of dead birds to identify areas at high risk for West Nile virus (WNV) transmission to humans. In 2005, during a statewide epidemic of WNV (880 cases), the California Department of Public Health prospectively implemented DYCAST over 32,517 km2 in California. Daily risk maps were made available online and used by local agencies to target public education campaigns, surveillance, and mosquito control. DYCAST had 80.8% sensitivity and 90.6% specificity for predicting human cases, and κ analysis indicated moderate strength of chance-adjusted agreement for >4 weeks. High-risk grid cells (populations) were identified an average of 37.2 days before onset of human illness; relative risk for disease was >39× higher than for low-risk cells. Although prediction rates declined in subsequent years, results indicate DYCAST was a timely and effective early warning system during the severe 2005 epidemic. PMID:21801622

  18. Acute and chronic neurological consequences of early-life Zika virus infection in mice.

    PubMed

    Nem de Oliveira Souza, Isis; Frost, Paula S; França, Julia V; Nascimento-Viana, Jéssica B; Neris, Rômulo L S; Freitas, Leandro; Pinheiro, Daniel J L L; Nogueira, Clara O; Neves, Gilda; Chimelli, Leila; De Felice, Fernanda G; Cavalheiro, Ésper A; Ferreira, Sergio T; Assunção-Miranda, Iranaia; Figueiredo, Claudia P; Da Poian, Andrea T; Clarke, Julia R

    2018-06-06

    Although congenital Zika virus (ZIKV) exposure has been associated with microcephaly and other neurodevelopmental disorders, long-term consequences of perinatal infection are largely unknown. We evaluated short- and long-term neuropathological and behavioral consequences of neonatal ZIKV infection in mice. ZIKV showed brain tropism, causing postnatal-onset microcephaly and several behavioral deficits in adulthood. During the acute phase of infection, mice developed frequent seizures, which were reduced by tumor necrosis factor-α (TNF-α) inhibition. During adulthood, ZIKV replication persisted in neonatally infected mice, and the animals showed increased susceptibility to chemically induced seizures, neurodegeneration, and brain calcifications. Altogether, the results show that neonatal ZIKV infection has long-term neuropathological and behavioral complications in mice and suggest that early inhibition of TNF-α-mediated neuroinflammation might be an effective therapeutic strategy to prevent the development of chronic neurological abnormalities. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  19. Single-Genome Sequencing of Hepatitis C Virus in Donor-Recipient Pairs Distinguishes Modes and Models of Virus Transmission and Early Diversification.

    PubMed

    Li, Hui; Stoddard, Mark B; Wang, Shuyi; Giorgi, Elena E; Blair, Lily M; Learn, Gerald H; Hahn, Beatrice H; Alter, Harvey J; Busch, Michael P; Fierer, Daniel S; Ribeiro, Ruy M; Perelson, Alan S; Bhattacharya, Tanmoy; Shaw, George M

    2016-01-01

    Despite the recent development of highly effective anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and development of an effective vaccine. A precise molecular identification of transmitted/founder (T/F) HCV genomes that lead to productive clinical infection could play a critical role in vaccine research, as it has for HIV-1. However, the replication schema of these two RNA viruses differ substantially, as do viral responses to innate and adaptive host defenses. These differences raise questions as to the certainty of T/F HCV genome inferences, particularly in cases where multiple closely related sequence lineages have been observed. To clarify these issues and distinguish between competing models of early HCV diversification, we examined seven cases of acute HCV infection in humans and chimpanzees, including three examples of virus transmission between linked donors and recipients. Using single-genome sequencing (SGS) of plasma vRNA, we found that inferred T/F sequences in recipients were identical to viral sequences in their respective donors. Early in infection, HCV genomes generally evolved according to a simple model of random evolution where the coalescent corresponded to the T/F sequence. Closely related sequence lineages could be explained by high multiplicity infection from a donor whose viral sequences had undergone a pretransmission bottleneck due to treatment, immune selection, or recent infection. These findings validate SGS, together with mathematical modeling and phylogenetic analysis, as a novel strategy to infer T/F HCV genome sequences. Despite the recent development of highly effective, interferon-sparing anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and the development of an effective

  20. Bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit.

    PubMed Central

    Lusky, M; Berg, L; Weiher, H; Botchan, M

    1983-01-01

    Bovine papilloma virus (BPV) contains a cis-acting DNA element which can enhance transcription of distal promoters. Utilizing both direct and indirect transient transfection assays, we showed that a 59-base-pair DNA sequence from the BPV genome could activate the simian virus 40 promoter from distances exceeding 2.5 kilobases and in an orientation-independent manner. In contrast to the promoter 5'-proximal localization of other known viral activators, this element was located immediately 3' to the early polyadenylation signal in the BPV genome. Deletion of these sequences from the BPV genome inactivated the transforming ability of BPV recombinant plasmids. Orientation-independent reinsertion of this 59-base-pair sequence, or alternatively of activator DNA sequences from simian virus 40 or polyoma virus, restored the transforming activity of the BPV recombinant plasmids. Furthermore, the stable transformation frequency of the herpes simplex virus type 1 thymidine kinase gene was enhanced when linked to restriction fragments of BPV DNA which included the defined activator element. This enhancement was orientation independent with respect to the thymidine kinase promoter. The enhancement also appeared to be unrelated to the establishment of the recombinant plasmids as episomes, since in transformed cells these sequences are found linked to high-molecular-weight DNA. We propose that the enhancement of stable transformation frequencies and the activation of transcription units are in this case alternate manifestations of the same biochemical events. Images PMID:6308425

  1. Early Disseminated Lyme Disease Causing False-Positive Serology for Primary Epstein-Barr Virus Infection: Report of 2 Cases.

    PubMed

    Pavletic, Adriana J; Marques, Adriana R

    2017-07-15

    False-positive serology for Lyme disease was reported in patients with acute infectious mononucleosis. Here we describe 2 patients with early disseminated Lyme disease who were misdiagnosed with infectious mononucleosis based on false-positive tests for primary Epstein-Barr virus infection. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Human cytomegalovirus and Herpes Simplex type I virus can engage RNA polymerase I for transcription of immediate early genes

    PubMed Central

    Kostopoulou, Ourania N.; Wilhelmi, Vanessa; Raiss, Sina; Ananthaseshan, Sharan; Lindström, Mikael S.; Bartek, Jiri; Söderberg-Naucler, Cecilia

    2017-01-01

    Human cytomegalovirus (HCMV) utilizes RNA polymerase II to transcribe viral genes and produce viral mRNAs. It can specifically target the nucleolus to facilitate viral transcription and translation. As RNA polymerase I (Pol I)-mediated transcription is active in the nucleolus, we investigated the role of Pol I, along with relative contributions of the human Pol II and Pol III, to early phases of viral transcription in HCMV infected cells, compared with Herpes Simplex Virus-1 (HSV-1) and Murine cytomegalovirus (MCMV). Inhibition of Pol I with siRNA or the Pol I inhibitors CX-5461 or Actinomycin D (5nM) resulted in significantly decreased IE and pp65 mRNA and protein levels in human fibroblasts at early times post infection. This initially delayed replication was compensated for later during the replication process, at which stage it didn’t significantly affect virus production. Pol I inhibition also reduced HSV-1 ICP0 and gB transcripts, suggesting that some herpesviruses engage Pol I for their early transcription. In contrast, inhibition of Pol I failed to affect MCMV transcription. Collectively, our results contribute to better understanding of the functional interplay between RNA Pol I-mediated nucleolar events and the Herpes viruses, particularly HCMV whose pathogenic impact ranges from congenital malformations and potentially deadly infections among immunosuppressed patients, up to HCMV’s emerging oncomodulatory role in human tumors. PMID:29228551

  3. Early Detection of Dengue Virus by Use of Reverse Transcription-Recombinase Polymerase Amplification

    PubMed Central

    Teoh, Boon-Teong; Sam, Sing-Sin; Tan, Kim-Kee; Danlami, Mohammed Bashar; Shu, Meng-Hooi; Johari, Jefree; Hooi, Poh-Sim; Brooks, David; Piepenburg, Olaf; Nentwich, Oliver; Wilder-Smith, Annelies; Franco, Leticia; Tenorio, Antonio

    2015-01-01

    A method for the rapid diagnosis of early dengue virus (DENV) infection is highly needed. Here, a prototype reverse transcription-recombinase polymerase amplification (RT-RPA) assay was developed. The assay detected DENV RNA in <20 min without the need for thermocycling amplification. The assay enabled the detection of as few as 10 copies of DENV RNA. The designed RT-RPA primers and exo probe detected the DENV genome of at least 12 genotypes of DENV circulating globally without cross-reacting with other arboviruses. We assessed the diagnostic performance of the RT-RPA assay for the detection of DENV RNA in 203 serum samples of patients with clinically suspected dengue. The sera were simultaneously tested for DENV using a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay, quantitative RT-PCR (qRT-PCR), and IgM- and IgG-capture enzyme-linked immunosorbent assays (ELISA). Acute DENV infection was confirmed in 130 samples and 61 of the samples (46.9%) were classified as viremic with qRT-PCR. The RT-RPA assay showed good concordance (κ of ≥0.723) with the RT-LAMP and qRT-PCR assays in detecting the dengue viremic samples. When used in combination with ELISA, both the RT-RPA and RT-LAMP assays increased the detection of acute DENV infection to ≥95.7% (≥45/47) in samples obtained within 5 days of illness. The results from the study suggest that the RT-RPA assay is the most rapid molecular diagnostic tool available for the detection of DENV. Hence, it is possible to use the RT-RPA assay in a laboratory to complement routine serology testing for dengue. PMID:25568438

  4. Early Immune Responses in Rainbow Trout Liver upon Viral Hemorrhagic Septicemia Virus (VHSV) Infection

    PubMed Central

    Castro, Rosario; Abós, Beatriz; Pignatelli, Jaime; von Gersdorff Jørgensen, Louise; González Granja, Aitor; Buchmann, Kurt; Tafalla, Carolina

    2014-01-01

    Among the essential metabolic functions of the liver, in mammals, a role as mediator of systemic and local innate immunity has also been reported. Although the presence of an important leukocyte population in mammalian liver is well documented, the characterization of leukocyte populations in the teleost liver has been only scarcely addressed. In the current work, we have confirmed the presence of IgM+, IgD+, IgT+, CD8α+, CD3+ cells, and cells expressing major histocompatibility complex (MHC-II) in rainbow trout (Oncorhynchus mykiss) liver by flow cytometry and/or immunohistochemistry analysis. Additionally, the effect of viral hemorrhagic septicemia virus (VHSV) on the liver immune response was assessed. First, we studied the effect of viral intraperitoneal injection on the transcription of a wide selection of immune genes at days 1, 2 and 5 post-infection. These included a group of leukocyte markers genes, pattern recognition receptors (PRRs), chemokines, chemokine receptor genes, and other genes involved in the early immune response and in acute phase reaction. Our results indicate that T lymphocytes play a key role in the initial response to VHSV in the liver, since CD3, CD8, CD4, perforin, Mx and interferon (IFN) transcription levels were up-regulated in response to VHSV. Consequently, flow cytometry analysis of CD8α+ cells in liver and spleen at day 5 post-infection revealed a decrease in the number of CD8α+ cells in the spleen and an increased population in the liver. No differences were found however in the percentages of B lymphocyte (IgM+ or IgD+) populations. In addition, a strong up-regulation in the transcription levels of several PRRs and chemokines was observed from the second day of infection, indicating an important role of these factors in the response of the liver to viral infections. PMID:25338079

  5. Detection of autoimmunity in early primary Epstein-Barr virus infection by Western blot analysis.

    PubMed

    Mascia, M T; Sandri, G; Guerzoni, C; Roncaglia, R; Mantovani, G; Ferri, C

    2008-01-01

    The Epstein-Barr virus (EBV) represents a potentially important factor in the pathogenesis of certain autoimmune disorders such as systemic lupus erythematosus (SLE), and Sjögren's syndrome, probably through a molecular mimicry mechanism. Several studies have focused on the relationship between previous EBV infection and clinically overt connective tissue diseases (CTDs), while the aim of this study was to investigate the immunological alterations during the early phase of primary acute EBV infection by means of ENA Western blotting (WB) analysis. This technique is able to detect a wide spectrum of anti-ENA autoantibodies, potentially directed against diverse epitopes of the same antigen. Sera from 54 subjects (F/M=24/30, mean age 17+/-6 SD years) with primary acute EBV infection were analysed using indirect immunofluorescence (IF) on Hep-2 cells for ANA, and both ELISA and WB for ENA. Only 8 ANA+ and no ENA+ were found by means of IF and ELISA techniques, respectively; however, one or more ENA autoantibodies were detected in 24/54 (44%) sera using WB. The autoantibodies were no longer present at the second evaluation. Subjects with immunological alterations had not developed any significant clinical manifestations at a 5-year follow-up. This study demonstrated the appearance of autoantibody production in a high proportion of individuals with primary acute EBV infection; interestingly, the observed serological subsets are quite similar to clinical SLE clusters. Moreover, the absence of immunological disorders during the follow-up reinforces the role of multiple genetic and/or environmental co-factors in the pathogenesis of CTDs.

  6. Herpes zoster could be an early manifestation of undiagnosed human immunodeficiency virus infection.

    PubMed

    Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu; Chen, Wen-Chi

    2016-05-01

    No formal epidemiological research based on systematic analysis has focused on the relationship between herpes zoster and immunodeficiency virus (HIV) infection in Taiwan. Our aim was to explore whether herpes zoster is an early manifestation of undiagnosed human HIV infection in Taiwan. This was a retrospective cohort study using the database of the Taiwan National Health Insurance Program. A total of 35,892 individuals aged ≤ 84 years with newly diagnosed herpes zoster from 1998 to 2010 were assigned to the herpes zoster group, whereas 143,568 sex-matched and age-matched, randomly selected individuals without herpes zoster served as the non-herpes zoster group. The incidence of HIV diagnosis at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence interval (CI) for risk of HIV diagnosis associated with herpes zoster and other comorbidities including drug dependence and venereal diseases. The overall incidence of HIV diagnosis was 4.19-fold greater in the herpes zoster group than that in the non-herpes zoster group (3.33 per 10,000 person-years vs. 0.80 per 10,000 person-years, 95% CI 4.04-4.35). The multivariable Cox proportional hazards regression analysis revealed that the adjusted hazard ratio of HIV diagnosis was 4.37 (95% CI 3.10-6.15) for individuals with herpes zoster and without comorbidities, as compared with individuals without herpes zoster and without comorbidities. Herpes zoster is associated with HIV diagnosis. Patients who have risk behaviors of HIV infection should receive regular surveillance for undiagnosed HIV infection when they present with herpes zoster. Copyright © 2015. Published by Elsevier B.V.

  7. Initial characterization of 17 viruses harboring mutant forms of the immediate-early gene of equine herpesvirus 1.

    PubMed

    Buczynski, Kimberly A; Kim, Seong K; O'Callaghan, Dennis J

    2005-10-01

    The sole immediate-early (IE) gene of equine herpesvirus 1 (EHV-1) encodes a major regulatory protein of 1487 amino acids (aa) capable of modulating gene expression from both early and late promoters and also of trans-repressing its own promoter. Using a specially designed recombination system and a library of IE linker-insertion, deletion, point, and nonsense mutant constructs that encode forms of the IE protein (IEP) harboring mutations within all five regions, 17 mutant viruses were generated and characterized. Ribonuclease protection analyses revealed that all 17 mutants synthesize the IE mRNA in RK-13 cells, whereas those that failed to replicate on non-complementing RK-13 cells displayed a defect in the transcription of either an important early gene (EICP0) and/or an essential late gene (glycoprotein D). Western blot analyses showed that the IEP was synthesized and detectable in cells infected with each mutant virus, including those mutants that failed to replicate on non-complementing RK-13 cells. Eleven of the 17 mutants were capable of growth on non-complementing RK-13 cells, whereas mutant viruses with deletions within the serine-rich tract (SRT), nucleus localization signal (NLS), or DNA-binding domain (DBD) were capable of growth only on the IEP-producing cell line (IE13.1). Lastly, temperature shift experiments revealed that mutant viruses containing deletions within the C-terminus (KyAn1029 and KyAn1411) or within the SRT (KyADeltaSRT2) of the IEP exhibited a temperature-sensitive phenotype in that these viruses, in contrast to the parent KyA, failed to replicate at 39 degrees C. Overall, these results indicate that the C-terminus of the IEP is not essential for IEP function in cell culture, but this region contains elements that enhance the function(s) of the IEP. The initial characterization of these 17 EHV-1 mutants has shown that sequences totaling at least 43% of the IEP are not essential for virus replication in cell culture.

  8. [Preclinical study of AV0012 early stage inhibitor of hepatitis C virus infection: I. In vitro ADME and pharmacokinetics].

    PubMed

    Ivashchenko, A V; Iamanushkin, P M; Mit'kin, O D; Ezhova, E V; Korzinov, O M; Shevkun, N A; Koriakova, A G; Karapetian, R N; Bychko, V V; Ivashchenko, A A; Agrba, V Z; Lapin, B A; Orlov, S V

    2014-01-01

    In vitro immunohistochemical investigations on the human hepatoma cell line (Huh7) infected with hepatitis C virus (HCV) strain JFH-1 showed that AV0012 compound blocks the early stages of viral infection. AV0012 also blocked viral infection spread in tissue culture through the secreted virus and through tight cell-to-cell contact. AV0012 is a specific inhibitor of HCV but not of related pestivirus, flaviviruses and other RNA-containing viruses such as bovine diarrhea (BVDV), Venezuelan equine encephalitis (strain TC-83), dengue type 2 (New Guinea), yellow fever (strain 17D), west Nile fever, parainfluenza (type 3) virus, RSV (strain A2), and Rhinovirus (type 2 strain HGP). It is established that human serum does not significantly affect the antiviral activity of AV0012 in vitro. The drug combination studies with AV0012 and interferon alpha 2a in vitro showed that the two inhibitors act additively, which makes possible the use of this combination in clinical tests. AV0012 is highly soluble and stable in aqueous solutions and murine blood plasma, has limited metabolic stability, low binding to human plasma proteins, high permeability through biological membranes, and only interacts with isoenzymes 2D6 and 3A4 of human cytochrome P450. In animal pharmacokinetic studies, AV0012 was rapidly absorbed into the blood stream upon oral administration, showed sufficiently long half-elimination times, and had high oral bioavailability that reached 92% in monkeys. Further preclinical development of AV0012 is in progress.

  9. Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.

    PubMed

    Li, Hui; Stoddard, Mark B; Wang, Shuyi; Blair, Lily M; Giorgi, Elena E; Parrish, Erica H; Learn, Gerald H; Hraber, Peter; Goepfert, Paul A; Saag, Michael S; Denny, Thomas N; Haynes, Barton F; Hahn, Beatrice H; Ribeiro, Ruy M; Perelson, Alan S; Korber, Bette T; Bhattacharya, Tanmoy; Shaw, George M

    2012-01-01

    A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures.

  10. Elucidation of Hepatitis C Virus Transmission and Early Diversification by Single Genome Sequencing

    PubMed Central

    Li, Hui; Stoddard, Mark B.; Wang, Shuyi; Blair, Lily M.; Giorgi, Elena E.; Parrish, Erica H.; Learn, Gerald H.; Hraber, Peter; Goepfert, Paul A.; Saag, Michael S.; Denny, Thomas N.; Haynes, Barton F.; Hahn, Beatrice H.; Ribeiro, Ruy M.; Perelson, Alan S.; Korber, Bette T.; Bhattacharya, Tanmoy; Shaw, George M.

    2012-01-01

    A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures. PMID:22927816

  11. Development of artificial bait for brown treesnake suppression

    USDA-ARS?s Scientific Manuscript database

    The brown treesnake (Boiga irregularis) was accidentally introduced to Guam in the late 1940s or early 1950s, probably from the Solomon Islands. A native of Australia, Papua New Guinea, and the Solomon Islands, the brown treesnake (BTS) continues to threaten the economy and ecology of Guam and is c...

  12. Protease-deficient herpes simplex virus protects mice from lethal herpesvirus infection.

    PubMed Central

    Hippenmeyer, P J; Rankin, A M; Luckow, V A; Neises, G R

    1997-01-01

    Null mutants and attenuated mutants of herpes simplex virus (HSV) have been shown to induce immunity against challenge from wild-type virus. Null viruses with a defect in late gene products would be expected to express more viral genes than viruses with defects in essential early gene products and thus induce a better immune response. Herpesviruses encode a late gene product (serine protease) that is autocatalytic and cleaves the capsid assembly protein during viral replication. To determine whether a virus with a mutation in this gene could induce immunity, we constructed a recombinant virus containing the gusA reporter gene in the protease domain of the HSV type 1 UL26 open reading frame (ORF). Consistent with previous results (M. Gao, L. Matusick-Kumar, W. Hurlburt, S. F. DiTusa, W. W. Newcomb, J. C. Brown, P. J. McCann, I. Deckman, and R. J. Colonno, J. Virol. 68:3702-3712, 1994), recombinant virus could be isolated only from helper cell lines expressing the product of the UL26 ORF. Mice inoculated with the recombinant virus were unaffected by doses of virus that were lethal to mice infected with wild-type virus. Mice which were previously inoculated with the recombinant virus were also protected by a subsequent challenge with wild-type virus in a dose-dependent manner. These results indicate that recombinant viruses lacking the protease gene are avirulent but render protection from subsequent challenge. PMID:8995617

  13. 7 CFR 29.3505 - Brown colors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Type 95) § 29.3505 Brown colors. A group of colors ranging from a light brown to a dark brown. These... standards, the colors are expressed as light brown (L), medium brown (F), reddish brown (R), and dark brown... 7 Agriculture 2 2013-01-01 2013-01-01 false Brown colors. 29.3505 Section 29.3505 Agriculture...

  14. 7 CFR 29.3505 - Brown colors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Type 95) § 29.3505 Brown colors. A group of colors ranging from a light brown to a dark brown. These... standards, the colors are expressed as light brown (L), medium brown (F), reddish brown (R), and dark brown... 7 Agriculture 2 2012-01-01 2012-01-01 false Brown colors. 29.3505 Section 29.3505 Agriculture...

  15. 7 CFR 29.3505 - Brown colors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Type 95) § 29.3505 Brown colors. A group of colors ranging from a light brown to a dark brown. These... standards, the colors are expressed as light brown (L), medium brown (F), reddish brown (R), and dark brown... 7 Agriculture 2 2014-01-01 2014-01-01 false Brown colors. 29.3505 Section 29.3505 Agriculture...

  16. 7 CFR 29.3505 - Brown colors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Type 95) § 29.3505 Brown colors. A group of colors ranging from a light brown to a dark brown. These... standards, the colors are expressed as light brown (L), medium brown (F), reddish brown (R), and dark brown... 7 Agriculture 2 2011-01-01 2011-01-01 false Brown colors. 29.3505 Section 29.3505 Agriculture...

  17. Mink predation on brown trout in a Black Hills stream

    USGS Publications Warehouse

    Davis, Jacob L.; Wilhite, Jerry W.; Chipps, Steven R.

    2016-01-01

    In the early 2000’s, declines in the brown trout (Salmo trutta) fishery in Rapid Creek, South Dakota, caused concern for anglers and fisheries managers. We conducted a radio telemetry study in 2010 and 2011 to identify predation mortality associated with mink, using hatchery-reared (2010) or wild (2011) brown trout. Estimated predation rates by mink (Mustela vison) on radio-tagged brown trout were 30% for hatchery fish and 32% for wild fish. Size frequency analysis revealed that the size distribution of brown trout lost to predation was similar to that of other, radio-tagged brown trout. In both years, a higher proportion of predation mortality (83–92%) occurred during spring, consistent with seasonal fish consumption by mink. Predation by mink appeared to be a significant source of brown trout mortality in our study.

  18. Properties of a herpes simplex virus multiple immediate-early gene-deleted recombinant as a vaccine vector

    SciTech Connect

    Watanabe, Daisuke; Brockman, Mark A.; Ndung'u, Thumbi

    2007-01-20

    Herpes simplex virus (HSV) recombinants induce durable immune responses in rhesus macaques and mice and have induced partial protection in rhesus macaques against mucosal challenge with virulent simian immunodeficiency virus (SIV). In this study, we evaluated the properties of a new generation HSV vaccine vector, an HSV-1 multiple immediate-early (IE) gene deletion mutant virus, d106, which contains deletions in the ICP4, ICP27, ICP22, and ICP47 genes. Because several of the HSV IE genes have been implicated in immune evasion, inactivation of the genes encoding these proteins was expected to result in enhanced immunogenicity. The d106 virus expresses few HSV genemore » products and shows minimal cytopathic effect in cultured cells. When d106 was inoculated into mice, viral DNA accumulated at high levels in draining lymph nodes, consistent with an ability to transduce dendritic cells and activate their maturation and movement to lymph nodes. A d106 recombinant expressing Escherichia coli {beta}-galactosidase induced durable {beta}-gal-specific IgG and CD8{sup +} T cell responses in naive and HSV-immune mice. Finally, d106-based recombinants have been constructed that express simian immunodeficiency virus (SIV) gag, env, or a rev-tat-nef fusion protein for several days in cultured cells. Thus, d106 shows many of the properties desirable in a vaccine vector: limited expression of HSV gene products and cytopathogenicity, high level expression of transgenes, ability to induce durable immune responses, and an ability to transduce dendritic cells and induce their maturation and migration to lymph nodes.« less

  19. Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection.

    PubMed

    Price, Alexander M; Dai, Joanne; Bazot, Quentin; Patel, Luv; Nikitin, Pavel A; Djavadian, Reza; Winter, Peter S; Salinas, Cristina A; Barry, Ashley Perkins; Wood, Kris C; Johannsen, Eric C; Letai, Anthony; Allday, Martin J; Luftig, Micah A

    2017-04-20

    Latent Epstein-Barr virus (EBV) infection is causally linked to several human cancers. EBV expresses viral oncogenes that promote cell growth and inhibit the apoptotic response to uncontrolled proliferation. The EBV oncoprotein LMP1 constitutively activates NFκB and is critical for survival of EBV-immortalized B cells. However, during early infection EBV induces rapid B cell proliferation with low levels of LMP1 and little apoptosis. Therefore, we sought to define the mechanism of survival in the absence of LMP1/NFκB early after infection. We used BH3 profiling to query mitochondrial regulation of apoptosis and defined a transition from uninfected B cells (BCL-2) to early-infected (MCL-1/BCL-2) and immortalized cells (BFL-1). This dynamic change in B cell survival mechanisms is unique to virus-infected cells and relies on regulation of MCL-1 mitochondrial localization and BFL-1 transcription by the viral EBNA3A protein. This study defines a new role for EBNA3A in the suppression of apoptosis with implications for EBV lymphomagenesis.

  20. Mutational analysis of varicella-zoster virus (VZV) immediate early protein (IE62) subdomains and their importance in viral replication

    SciTech Connect

    Khalil, Mohamed I., E-mail: mkhalil2@stanford.edu; Department of Molecular Biology, National Research Centre, El-Buhouth St., Cairo; Che, Xibing

    VZV IE62 is an essential, immediate-early, tegument protein and consists of five domains. We generated recombinant viruses carrying mutations in the first three IE62 domains and tested their influence on VZV replication kinetics. The mutations in domain I did not affect replication kinetics while domain II mutations, disrupting the DNA binding and dimerization domain (DBD), were lethal for VZV replication. Mutations in domain III of the nuclear localization signal (NLS) and the two phosphorylation sites S686A/S722A resulted in slower growth in early and late infection respectively and were associated with IE62 accumulation in the cytoplasm and nucleus respectively. This studymore » mapped the functional domains of IE62 in context of viral infection, indicating that DNA binding and dimerization domain is essential for VZV replication. In addition, the correct localization of IE62, whether nuclear or cytoplasmic, at different points in the viral life cycle, is important for normal progression of VZV replication. - Highlights: • Mutation of IE62 domain I did not affect VZV replication in melanoma cells. • IE62 domain II and III are important for VZV replication in melanoma cells. • Mutations of IE62 domain II (DBD) were lethal for virus replication. • Mutations of IE62 NLS and phosphorylation sites inhibited VZV replication. • NLS and S686A/S722A mutations altered localization of IE62 during early and late infection.« less

  1. Brown-Vialetto-Van Laere syndrome.

    PubMed

    Francis, D A; Ponsford, J R; Wiles, C M; Thomas, P K; Duchen, L W

    1993-02-01

    The clinical and pathological findings of a male with the Brown-Vialetto-Van Laere syndrome are described. This rare and fatal affection of the nervous system involves mainly the brain stem with the prominent and early manifestation of sensorineural deafness. Increased awareness and documentation of this disorder has added information on the mode of inheritance.

  2. Civil Rights Law and the Brown Decision.

    ERIC Educational Resources Information Center

    Greenberg, Jack

    The Brown decision of 1954 was the product of a planned program of litigation begun in the late 1920s and the early 1930s by a group of Black lawyers. Their work would not have succeeded if the ethos of the United States had not been changing simultaneously. The growth of a climate more conducive to civil rights is reflected in the presidential…

  3. The Scientific Attack on Brown v. Board of Education, 1954-1964

    ERIC Educational Resources Information Center

    Jackson, John P.

    2004-01-01

    Psychologists' work was cited in the Supreme Court case of Brown v. Board of Education (1954). One criticism of the citation was that psychology could be used to overturn the Brown decision and return the country to segregation. A historical examination of such an attempt to overturn Brown in the early 1960s on the basis of new psychological…

  4. After Brown U.'s Report on Slavery, Silence (So Far)

    ERIC Educational Resources Information Center

    Bartlett, Thomas

    2006-01-01

    This article, discusses Brown University's slavery report, a 106-page narrative examination of the early connections between Brown University and slavery, that has been greeted--so far--with silence. The report, done at the behest of Ruth J. Simmons, Brown's president and herself a descendant of slaves, is an unsparing look at a shameful side of…

  5. Cyclooxygenase activity is important for efficient replication of mouse hepatitis virus at an early stage of infection

    PubMed Central

    Raaben, Matthijs; Einerhand, Alexandra WC; Taminiau, Lucas JA; van Houdt, Michel; Bouma, Janneke; Raatgeep, Rolien H; Büller, Hans A; de Haan, Cornelis AM; Rossen, John WA

    2007-01-01

    Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy. PMID:17555580

  6. Corticosteroid therapy in Epstein-Barr virus infection. Effect on lymphocyte class, subset, and response to early antigen.

    PubMed

    Brandfonbrener, A; Epstein, A; Wu, S; Phair, J

    1986-02-01

    Corticosteroid treatment of impending upper airway obstruction due to Epstein-Barr virus (EBV) infectious mononucleosis did not alter the pattern of lymphocyte changes induced by this viral infection during the first two weeks following administration of prednisone. By 12 weeks, 11 treated students had significantly fewer lymphocytes, including B, total T, helper, and T-suppressor cell numbers, than 11 untreated EBV-infected students, and values were closer to those noted in uninfected controls. Corticosteroid therapy did not alter the serologic response to early antigens of EBV. Fever and lymphadenopathy resolved somewhat more quickly in treated students.

  7. Brown-Sequard Syndrome

    MedlinePlus

    ... infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. × Definition Brown-Sequard syndrome (BSS) is a rare ... infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. View Full Definition Treatment Generally treatment for individuals ...

  8. Brown adipose tissue

    PubMed Central

    Townsend, Kristy; Tseng, Yu-Hua

    2012-01-01

    Obesity is currently a global pandemic, and is associated with increased mortality and co-morbidities including many metabolic diseases. Obesity is characterized by an increase in adipose mass due to increased energy intake, decreased energy expenditure, or both. While white adipose tissue is specialized for energy storage, brown adipose tissue has a high concentration of mitochondria and uniquely expresses uncoupling protein 1, enabling it to be specialized for energy expenditure and thermogenesis. Although brown fat was once considered only necessary in babies, recent morphological and imaging studies have provided evidence that, contrary to prior belief, this tissue is present and active in adult humans. In recent years, the topic of brown adipose tissue has been reinvigorated with many new studies regarding brown adipose tissue differentiation, function and therapeutic promise. This review summarizes the recent advances, discusses the emerging questions and offers perspective on the potential therapeutic applications targeting this tissue. PMID:23700507

  9. Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication.

    PubMed

    Abdul Ahmad, Siti Aisyah; Palanisamy, Uma D; Tejo, Bimo A; Chew, Miaw Fang; Tham, Hong Wai; Syed Hassan, Sharifah

    2017-11-21

    The rapid rise and spread in dengue cases, together with the unavailability of safe vaccines and effective antiviral drugs, warrant the need to discover and develop novel anti-dengue treatments. In this study the antiviral activity of geraniin, extracted from the rind of Nephelium lappaceum, against dengue virus type-2 (DENV-2) was investigated. Geraniin was prepared from Nephelium lappaceum rind by reverse phase C-18 column chromatography. Cytotoxicity of geraniin towards Vero cells was evaluated using MTT assay while IC 50 value was determined by plaque reduction assay. The mode-of-action of geraniin was characterized using the virucidal, attachment, penetration and the time-of-addition assays'. Docking experiments with geraniin molecule and the DENV envelope (E) protein was also performed. Finally, recombinant E Domain III (rE-DIII) protein was produced to physiologically test the binding of geraniin to DENV-2 E-DIII protein, through ELISA competitive binding assay. Cytotoxicity assay confirmed that geraniin was not toxic to Vero cells, even at the highest concentration tested. The compound exhibited DENV-2 plaque formation inhibition, with an IC 50 of 1.75 μM. We further revealed that geraniin reduced viral infectivity and inhibited DENV-2 from attaching to the cells but had little effect on its penetration. Geraniin was observed to be most effective when added at the early stage of DENV-2 infection. Docking experiments showed that geraniin binds to DENV E protein, specifically at the DIII region, while the ELISA competitive binding assay confirmed geraniin's interaction with rE-DIII with high affinity. Geraniin from the rind of Nephelium lappaceum has antiviral activity against DENV-2. It is postulated that the compound inhibits viral attachment by binding to the E-DIII protein and interferes with the initial cell-virus interaction. Our results demonstrate that geraniin has the potential to be developed into an effective antiviral treatment, particularly for

  10. Hibernoma formation in transgenic mice and isolation of a brown adipocyte cell line expressing the uncoupling protein gene.

    PubMed Central

    Ross, S R; Choy, L; Graves, R A; Fox, N; Solevjeva, V; Klaus, S; Ricquier, D; Spiegelman, B M

    1992-01-01

    Transgenic mice were produced containing the adipocyte-specific regulatory region from the adipocyte P2 (aP2) gene linked to the simian virus 40 transforming genes. Most of the transgenic mice developed brown fat tumors (hibernomas) in their interscapular brown adipose tissue. Hibernoma formation was noticeable in some of the mice as early as 1 day after birth and most of the mice developed very large tumors by 1 month of age. All of the tumor tissue expressed the brown fat-specific uncoupling protein (UCP) gene as well as the aP2 gene. Several of the tumors have been used to establish cultured cell lines and at least one of these lines can be induced to differentiate into brown adipocytes. The cultured adipocytes express mRNA for UCP upon stimulation with N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate, norepinephrine, isoproterenol or D7114, a beta 3 adrenergic agonist. Thus, regulation of the key thermogenic gene UCP can now be studied in an established cell line. Images PMID:1323843

  11. Characterization of influenza A(H1N1)pdm09 viruses isolated from Nepalese and Indian outbreak patients in early 2015.

    PubMed

    Nakamura, Kazuya; Shirakura, Masayuki; Fujisaki, Seiichiro; Kishida, Noriko; Burke, David F; Smith, Derek J; Kuwahara, Tomoko; Takashita, Emi; Takayama, Ikuyo; Nakauchi, Mina; Chadha, Mandeep; Potdar, Varsha; Bhushan, Arvind; Upadhyay, Bishnu Prasad; Shakya, Geeta; Odagiri, Takato; Kageyama, Tsutomu; Watanabe, Shinji

    2017-09-01

    We characterized influenza A(H1N1)pdm09 isolates from large-scale outbreaks that occurred in Nepal and India in early 2015. Although no specific viral features, which may have caused the outbreaks, were identified, an S84N substitution in hemagglutinin was frequently observed. Chronological phylogenetic analysis revealed that these Nepalese and Indian viruses possessing the S84N substitution constitute potential ancestors of the novel genetic subclade 6B.1 virus that spread globally in the following (2015/16) influenza season. Thus, active surveillance of circulating influenza viruses in the Southern Asia region, including Nepal and India, would be beneficial for detecting novel variant viruses prior to their worldwide spread. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  12. Early diagnosis of a Mexican variant of Papaya meleira virus (PMeV-Mx) by RT-PCR.

    PubMed

    Zamudio-Moreno, E; Ramirez-Prado, J H; Moreno-Valenzuela, O A; Lopez-Ochoa, L A

    2015-02-06

    Papaya meleira disease was identified in Brazil in the 1980s. The disease is caused by a double-stranded RNA virus known as Papaya meleira virus (PMeV), which has also been recently reported in Mexico. However, previously reported PMeV primers failed to diagnose the Mexican form of the disease. A genomic approach was used to identify sequences of the Mexican virus isolate, referred here to as PMeV-Mx, to develop a diagnostic method. A mini cDNA library was generated using total RNA from the latex of fruits; this RNA was also sequenced using the Illumina platform. Sequences corresponding to the previously reported 669-base pair sequence for PMeV from Brazil (PMeV-Br) were identified within the PMeV-Mx genome, exhibiting 79-92% identity with PMeV-Br. In addition, a new sequence of 1154-base pairs encoding a putative RNA-dependent RNA polymerase was identified in PMeV-Mx. Primers designed against this sequence detected both virus isolates, 2 amplicons of 173 and 491 base pairs from PMeV-Br and PMeV-Mx, and shared 100 and 98% identity, respectively. PMeV-Mx was found in the latex of fruits, in seedlings, and in the leaves, flowers, petioles, and seeds of mature plants. PMeV-Mx was more abundant in the latex of fruits than in the leaves. The limit of detection of the CB38/CB39 primer pair was 1 fg and 1 pg using total RNA extracted from the latex of fruits and from seedlings, respectively. A sensitive and early diagnosis protocol was developed; this method will enable the certification of seeds and seedlings prior to transplantation to the field.

  13. Development of a quantitative NS1-capture enzyme-linked immunosorbent assay for early detection of yellow fever virus infection.

    PubMed

    Ricciardi-Jorge, Taissa; Bordignon, Juliano; Koishi, Andrea; Zanluca, Camila; Mosimann, Ana Luiza; Duarte Dos Santos, Claudia Nunes

    2017-11-24

    Yellow fever is an arboviral disease that causes thousands of deaths every year in Africa and the Americas. However, few commercial diagnostic kits are available. Non-structural protein 1 (NS1) is an early marker of several flavivirus infections and is widely used to diagnose dengue virus (DENV) infection. Nonetheless, little is known about the dynamics of Yellow fever virus (YFV) NS1 expression and secretion, to encourage its use in diagnosis. To tackle this issue, we developed a quantitative NS1-capture ELISA specific for YFV using a monoclonal antibody and recombinant NS1 protein. This test was used to quantify NS1 in mosquito and human cell line cultures infected with vaccine and wild YFV strains. Our results showed that NS1 was detectable in the culture supernatants of both cell lines; however, a higher concentration was maintained as cell-associated rather than secreted into the extracellular milieu. A panel of 73 human samples was used to demonstrate the suitability of YFV NS1 as a diagnostic tool, resulting in 80% sensitivity, 100% specificity, a 100% positive predictive value and a 95.5% negative predictive value compared with RT-PCR. Overall, the developed NS1-capture ELISA showed potential as a promising assay for the detection of early YF infection.

  14. Infants with Congenital Zika Virus Infection: A New Challenge for Early Intervention Professionals

    ERIC Educational Resources Information Center

    Porter, Sallie; Mimm, Nancy

    2017-01-01

    Zika virus infection-associated microcephaly has generated public health and media concern. Unsettling images emerging from Brazil of infants with abnormally small heads have raised concern among women of childbearing age, international travelers, government officials, and health care professionals. The World Health Organization declared the most…

  15. Identification and characterization of an early gene in the Lymantria dispar multinucleocapsid nuclear polyhedrosis virus

    Treesearch

    David S. Bischoff; James M. Slavicek

    1995-01-01

    The Lymantria dispar multinucleocapsid nuclear polyhedrosis virus (LdMNPV) gene encoding G22 was cloned and sequenced. The G22 gene codes for a 191 amino acid protein with a predicted Mr of 22000. Expression of G22 in a rabbit reticulocyte system generated a protein with an M...

  16. Brown Dwarf Microlensing (Illustration)

    NASA Image and Video Library

    2016-11-10

    This illustration depicts a newly discovered brown dwarf, an object that weighs in somewhere between our solar system's most massive planet (Jupiter) and the least-massive-known star. This brown dwarf, dubbed OGLE-2015-BLG-1319, interests astronomers because it may fall in the "desert" of brown dwarfs. Scientists have found that, for stars roughly the mass of our sun, less than 1 percent have a brown dwarf orbiting within 3 AU (1 AU is the distance between Earth and the sun). This brown dwarf was discovered when it and its star passed between Earth and a much more distant star in our galaxy. This created a microlensing event, where the gravity of the system amplified the light of the background star over the course of several weeks. This microlensing was observed by ground-based telescopes looking for these uncommon events, and was the first to be seen by two space-based telescopes: NASA's Spitzer and Swift missions. http://photojournal.jpl.nasa.gov/catalog/PIA21076

  17. Clinical Laboratory Values as Early Indicators of Ebola Virus Infection in Nonhuman Primates.

    PubMed

    Reisler, Ronald B; Yu, Chenggang; Donofrio, Michael J; Warren, Travis K; Wells, Jay B; Stuthman, Kelly S; Garza, Nicole L; Vantongeren, Sean A; Donnelly, Ginger C; Kane, Christopher D; Kortepeter, Mark G; Bavari, Sina; Cardile, Anthony P

    2017-08-01

    The Ebola virus (EBOV) outbreak in West Africa during 2013-2016 demonstrated the need to improve Ebola virus disease (EVD) diagnostics and standards of care. This retrospective study compared laboratory values and clinical features of 3 nonhuman primate models of lethal EVD to assess associations with improved survival time. In addition, the study identified laboratory values useful as predictors of survival, surrogates for EBOV viral loads, and triggers for initiation of therapeutic interventions in these nonhuman primate models. Furthermore, the data support that, in nonhuman primates, the Makona strain of EBOV may be less virulent than the Kikwit strain of EBOV. The applicability of these findings as potential diagnostic and management tools for EVD in humans warrants further investigation.

  18. Early dissemination of foot-and-mouth disease virus through sheep marketing in February 2001.

    PubMed

    Mansley, L M; Dunlop, P J; Whiteside, S M; Smith, R G H

    2003-07-12

    The results of epidemiological investigations suggest that livestock on up to 79 premises, spread widely throughout the British Isles, may have been exposed to infection by foot-and-mouth disease (FMD) virus by the movement of infected sheep before the first case of the disease was confirmed at an abattoir in Essex on February 20, 2001. A further 36 premises may have been infected by this route before the national livestock movement ban was imposed on February 23.

  19. Genome Sequences of Akhmeta Virus, an Early Divergent Old World Orthopoxvirus.

    PubMed

    Gao, Jinxin; Gigante, Crystal; Khmaladze, Ekaterine; Liu, Pengbo; Tang, Shiyuyun; Wilkins, Kimberly; Zhao, Kun; Davidson, Whitni; Nakazawa, Yoshinori; Maghlakelidze, Giorgi; Geleishvili, Marika; Kokhreidze, Maka; Carroll, Darin S; Emerson, Ginny; Li, Yu

    2018-05-12

    Annotated whole genome sequences of three isolates of the Akhmeta virus (AKMV), a novel species of orthopoxvirus (OPXV), isolated from the Akhmeta and Vani regions of the country Georgia, are presented and discussed. The AKMV genome is similar in genomic content and structure to that of the cowpox virus (CPXV), but a lower sequence identity was found between AKMV and Old World OPXVs than between other known species of Old World OPXVs. Phylogenetic analysis showed that AKMV diverged prior to other Old World OPXV. AKMV isolates formed a monophyletic clade in the OPXV phylogeny, yet the sequence variability between AKMV isolates was higher than between the monkeypox virus strains in the Congo basin and West Africa. An AKMV isolate from Vani contained approximately six kb sequence in the left terminal region that shared a higher similarity with CPXV than with other AKMV isolates, whereas the rest of the genome was most similar to AKMV, suggesting recombination between AKMV and CPXV in a region containing several host range and virulence genes.

  20. A scanning electron microscopy study of early development in vitro of Contracaecum multipapillatum s.l. (Nematoda: Anisakidae) from a brown pelican (Pelecanus occidentalis) from the Gulf of California, Mexico.

    PubMed

    Molina-Fernández, Dolores; Valles-Vega, Isabel; Hernández-Trujillo, Sergio; Adroher, Francisco Javier; Benítez, Rocío

    2017-10-01

    Eggs obtained from the uteri of female nematodes, genetically identified as Contracaecum multipapillatum s.l., found in a brown pelican (Pelecanus occidentalis) from Bahía de La Paz, Gulf of California, Mexico, were used to study the early developmental stages of this anisakid by scanning electron microscopy (SEM). Egg dimensions were approximately 54 × 45 μm measured by SEM. Observation of the eggs revealed an outer surface of fibrous appearance. The newly hatched larvae were ensheathed and highly motile. Observation with SEM showed that the sheaths of the larvae were striated and revealed an excretory pore and a cleft near the anterior end of the sheath, presumably to facilitate the opening of the sheath for the emergence of the larva. The hatched larvae were placed in nutritive culture medium, where they grew within their sheath, some exsheathing completely 2 weeks later. The surface patterns of the sheath and the cuticle of the exsheathed larvae were clearly different. Although they did not moult during culture, SEM revealed a morphology typical of third-stage larvae of Contracaecum from fish, as previously observed by optical microscopy. Thus, we suggest that newly hatched larvae from eggs of C. multipapillatum are third larval stage but with sheath of the second larval stage, as occuring in other anisakids.

  1. CDR Brown on middeck

    NASA Image and Video Library

    1999-12-20

    S103-E-5007 (20 December 1999) --- Astronaut Curtis L. Brown, mission commander, retrieves supplies from a mid deck stowage locker onboard the Space Shuttle Discovery. He and six other astronauts will spend a great deal of time later in the week performing a variety of service tasks on the Hubble Space Telescope (HST). As commander of the mission, Brown will remain inside Discovery while several of the other crew members will perform service tasks on HST. The photo was taken with an electronic still camera (ESC) at 16:12:27 GMT, Dec. 20, 1999.

  2. Prenatal Exposure to Respiratory Syncytial Virus Alters Postnatal Immunity and Airway Smooth Muscle Contractility during Early-Life Reinfections

    PubMed Central

    Harford, Terri J.; Agrawal, Vandana; Yen-Lieberman, Belinda; Rezaee, Fariba; Piedimonte, Giovanni

    2017-01-01

    Maternal viral infections can have pathological effects on the developing fetus which last long after birth. Recently, maternal-fetal transmission of respiratory syncytial virus (RSV) was shown to cause postnatal airway hyperreactivity (AHR) during primary early-life reinfection; however, the influence of prenatal exposure to RSV on offspring airway immunity and smooth muscle contractility during recurrent postnatal reinfections remains unknown. Therefore, we sought to determine whether maternal RSV infection impairs specific aspects of cell-mediated offspring immunity during early-life reinfections and the mechanisms leading to AHR. Red fluorescent protein-expressing recombinant RSV (rrRSV) was inoculated into pregnant rat dams at midterm, followed by primary and secondary postnatal rrRSV inoculations of their offspring at early-life time points. Pups and weanlings were tested for specific lower airway leukocyte populations by flow cytometry; serum cytokine/chemokine concentrations by multiplex ELISA and neurotrophins concentrations by standard ELISA; and ex vivo lower airway smooth muscle (ASM) contraction by physiological tissue bath. Pups born to RSV-infected mothers displayed elevated total CD3+ T cells largely lacking CD4+ and CD8+ surface expression after both primary and secondary postnatal rrRSV infection. Cytokine/chemokine analyses revealed reduced IFN-γ, IL-2, IL-12, IL-17A, IL-18, and TNF-α, as well as elevated nerve growth factor (NGF) expression. Prenatal exposure to RSV also increased ASM reactivity and contractility during early-life rrRSV infection compared to non-exposed controls. We conclude that maternal RSV infection can predispose offspring to postnatal lower airways dysfunction by altering immunity development, NGF signaling, and ASM contraction during early-life RSV reinfections. PMID:28178290

  3. Differences in Early Cytokine Production Are Associated With Development of a Greater Number of Symptoms Following West Nile Virus Infection.

    PubMed

    Hoffman, Kevin W; Sachs, David; Bardina, Susana V; Michlmayr, Daniela; Rodriguez, Carlos A; Sum, Janet; Foster, Gregory A; Krysztof, David; Stramer, Susan L; Lim, Jean K

    2016-08-15

    West Nile virus (WNV) is an emerging cause of meningitis and encephalitis in the United States. Although severe neuroinvasive disease and death can occur in rare instances, the majority of infected individuals remain asymptomatic or present with a range of clinical manifestations associated with West Nile fever. To better understand the interindividual variability associated with the majority of WNV infections, we evaluated the association of cytokine/chemokine production and outcome of infection among 115 WNV-positive US blood donors identified in 2008-2011. All subjects self-reported symptoms as having occurred during the 2 weeks following blood donation, using a standardized questionnaire. We discovered that, prior to seroconversion, an early potent, largely type I interferon-mediated response correlated with development of a greater number of symptoms in WNV-infected individuals. Interestingly, individuals who developed fewer symptoms had not only a more modest type I interferon response initially, but also a protracted cytokine response after seroconversion, marked by the production of monocyte and T-cell-associated chemokines. Collectively, our data suggest that, although an early type I interferon response appears to be crucial to control WNV infection, successful immunity may require a modest early response that is maintained during the course of infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. Early detection of West Nile virus in France: quantitative assessment of syndromic surveillance system using nervous signs in horses.

    PubMed

    Faverjon, C; Vial, F; Andersson, M G; Lecollinet, S; Leblond, A

    2017-04-01

    West Nile virus (WNV) is a growing public health concern in Europe and there is a need to develop more efficient early detection systems. Nervous signs in horses are considered to be an early indicator of WNV and, using them in a syndromic surveillance system, might be relevant. In our study, we assessed whether or not data collected by the passive French surveillance system for the surveillance of equine diseases can be used routinely for the detection of WNV. We tested several pre-processing methods and detection algorithms based on regression. We evaluated system performances using simulated and authentic data and compared them to those of the surveillance system currently in place. Our results show that the current detection algorithm provided similar performances to those tested using simulated and real data. However, regression models can be easily and better adapted to surveillance objectives. The detection performances obtained were compatible with the early detection of WNV outbreaks in France (i.e. sensitivity 98%, specificity >94%, timeliness 2·5 weeks and around four false alarms per year) but further work is needed to determine the most suitable alarm threshold for WNV surveillance in France using cost-efficiency analysis.

  5. Ebola Virus Disease: Rapid Diagnosis and Timely Case Reporting are Critical to the Early Response for Outbreak Control

    PubMed Central

    Stamm, Lola V.

    2015-01-01

    Ebola virus disease (EVD) is a life-threatening zoonosis caused by infection with the Ebola virus. Since the first reported EVD outbreak in the Democratic Republic of the Congo, several small outbreaks have been reported in central Africa with about 2,400 cases occurring between 1976 and 2013. The 2013–2015 EVD outbreak in west Africa is the first documented outbreak in this region and the largest ever with over 27,000 cases and more than 11,000 deaths. Although EVD transmission rates have recently decreased in west Africa, this crisis continues to threaten global health and security, particularly since infected travelers could spread EVD to other resource-limited areas of the world. Because vaccines and drugs are not yet licensed for EVD, outbreak control is dependent on the use of non-pharmaceutical interventions (e.g., infection control practices, isolation of EVD cases, contact tracing with follow-up and quarantine, sanitary burial, health education). However, delays in diagnosing and reporting EVD cases in less accessible rural areas continue to hamper control efforts. New advances in rapid diagnostics for identifying presumptive EVD cases and in mobile-based technologies for communicating critical health-related information should facilitate deployment of an early response to prevent the amplification of sporadic EVD cases into large-scale outbreaks. PMID:26175026

  6. Early Increases in Superantigen-Specific Foxp3+ Regulatory T Cells during Mouse Mammary Tumor Virus Infection▿ †

    PubMed Central

    Cabrera, Gabriel; Burzyn, Dalia; Mundiñano, Juliana; Courreges, M. Cecilia; Camicia, Gabriela; Lorenzo, Daniela; Costa, Héctor; Ross, Susan R.; Nepomnaschy, Irene; Piazzon, Isabel

    2008-01-01

    Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. Here, we show in a natural model of MMTV infection that the virus causes early and progressive increases in superantigen (SAg)-specific Foxp3+ regulatory T cells (Treg) in Peyer's patches (PP). These increases were shown to be dependent on the presence of dendritic cells. CD4+ CD25+ T cells from the PP of infected mice preferentially suppress the proliferative response of T cells to SAg-expressing antigen-presenting cells ex vivo. We investigated the influence of the depletion of CD25+ cells at different stages of the infection. When CD25+ cells were depleted before MMTV infection, an increase in the number of PP SAg-cognate Foxp3− T cells was found at day 6 of infection. Since the SAg response is associated with viral amplification, the possibility exists that Treg cells attenuate the increase in viral load at the beginning of the infection. In contrast, depletion of CD25+ cells once the initial SAg response has developed caused a lower viral load, suggesting that at later stages Treg cells may favor viral persistence. Thus, our results indicated that Treg cells play an important and complex role during MMTV infection. PMID:18495774

  7. Thirty Years After Brown.

    ERIC Educational Resources Information Center

    Hochschild, Jennifer L.

    Although many school districts and classrooms have desegregated since the 1954 Brown decision, desegregation is neither complete nor uniform. Moreover, racial isolation is growing in some regions and cities, and new forms of separation are arising within desegregated schools. New desegregation strategies and policies are needed, but these will be…

  8. "Brown's" Far Reaching Impact

    ERIC Educational Resources Information Center

    Chinn, Philip C.

    2004-01-01

    Although the 1954 "Brown v. Board of Education" U.S. Supreme Court decision changed the face of American education forever, few individuals at that time could have fully realized its far-reaching implications. Certainly, the National Association for the Advancement of Colored People Legal Director Thurgood Marshall in his arguments was…

  9. Large Brown Oval

    NASA Image and Video Library

    1996-01-29

    This large brown oval, photographed on Mar. 2, 1979 by NASA Voyager 1. Features of this sort are not rare on Jupiter and have an average lifetime of one to two years. Above the feature is the pale orange North Temperate Belt. http://photojournal.jpl.nasa.gov/catalog/PIA00015

  10. Brown on middeck

    NASA Image and Video Library

    1998-10-30

    STS095-E-5054 (30 Oct. 1998) --- Astronaut Curtis L. Brown, STS-95 commander, has a handful of vials as he checks a notebook during Flight Day two activity onboard the Space Shuttle Discovery. The photo was taken with an electronic still camera at 10:42:49 GMT, Oct. 30.

  11. Brown enters transfer tunnel

    NASA Image and Video Library

    1998-11-01

    STS095-E-5160 (1 Nov. 1998) --- Astronaut Curtis L. Brown Jr., STS-95 commander, floats through airlock hatchway during Flight Day three activity. The photo was taken with an electronic still camera (ESC) at 01:39:20 GMT, Nov. 1.

  12. maxwell brown | NREL

    Science.gov Websites

    Research Interests Optimization and modeling techniques Economic impacts of energy sector transformation . Transportation Research Record. Caron, J, S Cohen, J Reilly, M Brown. 2018. Exploring the Impacts of a National : Economic and GHG Impacts of a National Low Carbon Fuel Standard. Transportation Research Record: Journal of

  13. Kate Brown | NREL

    Science.gov Websites

    -7721 Research Interests Kate Brown received her Ph.D. from the Massachusetts Institute of Technology in 2008. While at the National Renewable Energy Laboratory, her research has focused on the synthesis and ] hydrogenase complexes and implications for photochemical H2 generation," Journal of the American Chemical

  14. Host-cell interaction of attenuated and wild-type strains of yellow fever virus can be differentiated at early stages of hepatocyte infection.

    PubMed

    Lefeuvre, Anabelle; Contamin, Hugues; Decelle, Thierry; Fournier, Christophe; Lang, Jean; Deubel, Vincent; Marianneau, Philippe

    2006-05-01

    Yellow fever (YF) virus is currently found in tropical Africa and South America, and is responsible for a febrile to severe illness characterized by organ failure and shock. The attenuated YF 17D strain, used in YF vaccine, was derived from the wild-type strain Asibi. Although studies have been done on genetic markers of YF virulence, differentiation of the two strains in terms of host-cell interaction during infection remains elusive. As YF wild-type strains are hepatotropic, we chose a hepatic cell line (HepG2) to study YF virus-host cell interaction. HepG2 cells rapidly produced high titres of infectious viral particles for 17D and Asibi YF strains. However, HepG2 cells were more susceptible to the attenuated 17D virus infection, and only this virus strain induced early apoptosis in these cells. Molecular markers specific for the 17D virus were identified by microarray analysis and confirmed by quantitative RT-PCR analysis. As early as 1h postinfection, three genes, (IEX-1, IRF-1, DEC-1) all implicated in apoptosis pathways, were upregulated. Later in infection (48 h) two other genes (HSP70-1A and 1B), expressed in cases of cellular stress, were highly upregulated in 17D-infected HepG2 cells. The early specific upregulation of these cellular genes in HepG2 cells may be considered markers of the 17D virus. This study on the YF attenuated strain gives a new approach to the analysis of the factors involved in virus attenuation.

  15. The Challenge of Teaching "Brown"

    ERIC Educational Resources Information Center

    Waite, Cally L.

    2004-01-01

    This paper examines the issues on whether Brown really desegregate school. Study shows that many cases of large number of segregated schools still exist today. This was the complexity of addressing this issue that makes teaching Brown a challenge. The 1954 Supreme Court decision--Brown v. Board of Education was the basis of their study for the…

  16. Early events in herpes simplex virus lifecycle with implications for an infection of lifetime.

    PubMed

    Salameh, Sarah; Sheth, Urmi; Shukla, Deepak

    2012-01-01

    Affecting a large percentage of human population herpes simplex virus (HSV) types -1 and -2 mainly cause oral, ocular, and genital diseases. Infection begins with viral entry into a host cell, which may be preceded by viral "surfing" along filopodia. Viral glycoproteins then bind to one or more of several cell surface receptors, such as herpesvirus entry mediator (HVEM), nectin-1, 3-O sulfated heparan sulfate (3-OS HS), paired immunoglobulin-like receptor α, and non-muscle myosin-IIA. At least five viral envelope glycoproteins participate in entry and these include gB, gC, gD and gH-gL. Post-entry, these glycoproteins may also facilitate cell-to-cell spread of the virus, which helps in the evasion of physical barriers as well as several components of the innate and adaptive immune responses. The spread may be facilitated by membrane fusion, movement across tight junctions, transfer across neuronal synapses, or the recruitment of actin-containing structures. This review summarizes some of the recent advances in our understanding of HSV entry and cell-to-cell spread.

  17. Early Detection of Foot-And-Mouth Disease Virus from Infected Cattle Using A Dry Filter Air Sampling System.

    PubMed

    Pacheco, J M; Brito, B; Hartwig, E; Smoliga, G R; Perez, A; Arzt, J; Rodriguez, L L

    2017-04-01

    Foot-and-mouth disease (FMD) is a highly contagious livestock disease of high economic impact. Early detection of FMD virus (FMDV) is fundamental for rapid outbreak control. Air sampling collection has been demonstrated as a useful technique for detection of FMDV RNA in infected animals, related to the aerogenous nature of the virus. In the current study, air from rooms housing individual (n = 17) or two groups (n = 4) of cattle experimentally infected with FDMV A24 Cruzeiro of different virulence levels was sampled to assess the feasibility of applying air sampling as a non-invasive, screening tool to identify sources of FMDV infection. Detection of FMDV RNA in air was compared with first detection of clinical signs and FMDV RNA levels in serum and oral fluid. FMDV RNA was detected in room air samples 1-3 days prior (seven animals) or on the same day (four animals) as the appearance of clinical signs in 11 of 12 individually housed cattle. Only in one case clinical signs preceded detection in air samples by one day. Overall, viral RNA in oral fluid or serum preceded detection in air samples by 1-2 days. Six individually housed animals inoculated with attenuated strains did not show clinical signs, but virus was detected in air in one of these cases 3 days prior to first detection in oral fluid. In groups of four cattle housed together, air detection always preceded appearance of clinical signs by 1-2 days and coincided more often with viral shedding in oral fluid than virus in blood. These data confirm that air sampling is an effective non-invasive screening method for detecting FMDV infection in confined to enclosed spaces (e.g. auction barns, milking parlours). This technology could be a useful tool as part of a surveillance strategy during FMD prevention, control or eradication efforts. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  18. 7 CFR 29.2254 - Brown colors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Brown colors. 29.2254 Section 29.2254 Agriculture... colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to... expressed as light brown (L), medium brown (F), and dark brown (D). ...

  19. 7 CFR 29.2254 - Brown colors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Brown colors. 29.2254 Section 29.2254 Agriculture... colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to... expressed as light brown (L), medium brown (F), and dark brown (D). ...

  20. 7 CFR 29.2254 - Brown colors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Brown colors. 29.2254 Section 29.2254 Agriculture... colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to... expressed as light brown (L), medium brown (F), and dark brown (D). ...

  1. 7 CFR 29.2254 - Brown colors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Brown colors. 29.2254 Section 29.2254 Agriculture... colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to... expressed as light brown (L), medium brown (F), and dark brown (D). ...

  2. Recombinant modified vaccinia virus Ankara generating excess early double-stranded RNA transiently activates protein kinase R and triggers enhanced innate immune responses.

    PubMed

    Wolferstätter, Michael; Schweneker, Marc; Späth, Michaela; Lukassen, Susanne; Klingenberg, Marieken; Brinkmann, Kay; Wielert, Ursula; Lauterbach, Henning; Hochrein, Hubertus; Chaplin, Paul; Suter, Mark; Hausmann, Jürgen

    2014-12-01

    Double-stranded RNA (dsRNA) is an important molecular pattern associated with viral infection and is detected by various extra- and intracellular recognition molecules. Poxviruses have evolved to avoid producing dsRNA early in infection but generate significant amounts of dsRNA late in infection due to convergent transcription of late genes. Protein kinase R (PKR) is activated by dsRNA and triggers major cellular defenses against viral infection, including protein synthesis shutdown, apoptosis, and type I interferon (IFN-I) production. The poxviral E3 protein binds and sequesters viral dsRNA and is a major antagonist of the PKR pathway. We found that the highly replication-restricted modified vaccinia virus Ankara (MVA) engineered to produce excess amounts of dsRNA early in infection showed enhanced induction of IFN-β in murine and human cells in the presence of an intact E3L gene. IFN-β induction required a minimum overlap length of 300 bp between early complementary transcripts and was strongly PKR dependent. Excess early dsRNA produced by MVA activated PKR early but transiently in murine cells and induced enhanced systemic levels of IFN-α, IFN-γ, and other cytokines and chemokines in mice in a largely PKR-dependent manner. Replication-competent chorioallantois vaccinia virus Ankara (CVA) generating excess early dsRNA also enhanced IFN-I production and was apathogenic in mice even at very high doses but showed no in vitro host range defect. Thus, genetically adjuvanting MVA and CVA to generate excess early dsRNA is an effective method to enhance innate immune stimulation by orthopoxvirus vectors and to attenuate replicating vaccinia virus in vivo. Efficient cellular sensing of pathogen-specific components, including double-stranded RNA (dsRNA), is an important prerequisite of an effective antiviral immune response. The prototype poxvirus vaccinia virus (VACV) and its derivative modified vaccinia virus Ankara (MVA) produce dsRNA as a by-product of viral

  3. Early function of the Abutilon mosaic virus AC2 gene as a replication brake.

    PubMed

    Krenz, Björn; Deuschle, Kathrin; Deigner, Tobias; Unseld, Sigrid; Kepp, Gabi; Wege, Christina; Kleinow, Tatjana; Jeske, Holger

    2015-04-01

    The C2/AC2 genes of monopartite/bipartite geminiviruses of the genera Begomovirus and Curtovirus encode important pathogenicity factors with multiple functions described so far. A novel function of Abutilon mosaic virus (AbMV) AC2 as a replication brake is described, utilizing transgenic plants with dimeric inserts of DNA B or with a reporter construct to express green fluorescent protein (GFP). Their replicational release upon AbMV superinfection or the individual and combined expression of epitope-tagged AbMV AC1, AC2, and AC3 was studied. In addition, the effects were compared in the presence and in the absence of an unrelated tombusvirus suppressor of silencing (P19). The results show that AC2 suppresses replication reproducibly in all assays and that AC3 counteracts this effect. Examination of the topoisomer distribution of supercoiled DNA, which indicates changes in the viral minichromosome structure, did not support any influence of AC2 on transcriptional gene silencing and DNA methylation. The geminiviral AC2 protein has been detected here for the first time in plants. The experiments revealed an extremely low level of AC2, which was slightly increased if constructs with an intron and a hemagglutinin (HA) tag in addition to P19 expression were used. AbMV AC2 properties are discussed with reference to those of other geminiviruses with respect to charge, modification, and size in order to delimit possible reasons for the different behaviors. The (A)C2 genes encode a key pathogenicity factor of begomoviruses and curtoviruses in the plant virus family Geminiviridae. This factor has been implicated in the resistance breaking observed in agricultural cotton production. AC2 is a multifunctional protein involved in transcriptional control, gene silencing, and regulation of basal biosynthesis. Here, a new function of Abutilon mosaic virus AC2 in replication control is added as a feature of this protein in viral multiplication, providing a novel finding on

  4. Early Spatial and Temporal Events of Human T-Lymphotropic Virus Type 1 Spread following Blood-Borne Transmission in a Rabbit Model of Infection ▿

    PubMed Central

    Haynes, Rashade A. H.; Zimmerman, Bevin; Millward, Laurie; Ware, Evan; Premanandan, Christopher; Yu, Lianbo; Phipps, Andrew J.; Lairmore, Michael D.

    2010-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia/lymphoma (ATL) and is associated with a variety of lymphocyte-mediated disorders. HTLV-1 transmission occurs by transmission of infected cells via breast-feeding by infected mothers, sexual intercourse, and contaminated blood products. The route of exposure and early virus replication events are believed to be key determinants of virus-associated spread, antiviral immune responses, and ultimately disease outcomes. The lack of knowledge of early events of HTLV-1 spread following blood-borne transmission of the virus in vivo hinders a more complete understanding of the immunopathogenesis of HTLV-1 infections. Herein, we have used an established animal model of HTLV-1 infection to study early spatial and temporal events of the viral infection. Twelve-week-old rabbits were injected intravenously with cell-associated HTLV-1 (ACH-transformed R49). Blood and tissues were collected at defined intervals throughout the study to test the early spread of the infection. Antibody and hematologic responses were monitored throughout the infection. HTLV-1 intracellular Tax and soluble p19 matrix were tested from ex vivo cultured lymphocytes. Proviral copy numbers were measured by real-time PCR from blood and tissue mononuclear leukocytes. Our data indicate that intravenous infection with cell-associated HTLV-1 targets lymphocytes located in both primary lymphoid and gut-associated lymphoid compartments. A transient lymphocytosis that correlated with peak virus detection parameters was observed by 1 week postinfection before returning to baseline levels. Our data support emerging evidence that HTLV-1 promotes lymphocyte proliferation preceding early viral spread in lymphoid compartments to establish and maintain persistent infection. PMID:20219918

  5. Serologic markers in early stages of African horse sickness virus infection.

    PubMed

    Martínez-Torrecuadrada, J L; Díaz-Laviada, M; Roy, P; Sánchez, C; Vela, C; Sánchez-Vizcaíno, J M; Casal, J I

    1997-02-01

    Fifteen horses were experimentally infected with African horse sickness virus (AHSV) serotype 4. To learn more about the time course of production and specificity of AHSV-specific antibodies, sera were analyzed by immunoblot analysis. Only animals that survived for more than 9 days were able to develop a humoral immune response detectable by immunoblotting. The earliest serological markers corresponded mainly to VP5, VP6, and NS2 and to a lesser extent to VP3, NS1, and NS3. Neutralizing antibodies to VP2 were not detected by immunoblotting, suggesting that they are mostly conformation dependent. VP7-specific antibodies were detected later in infection. These results make NS2 and VP6 the most attractive candidates for the rapid diagnosis of the infection.

  6. Serologic markers in early stages of African horse sickness virus infection.

    PubMed Central

    Martínez-Torrecuadrada, J L; Díaz-Laviada, M; Roy, P; Sánchez, C; Vela, C; Sánchez-Vizcaíno, J M; Casal, J I

    1997-01-01

    Fifteen horses were experimentally infected with African horse sickness virus (AHSV) serotype 4. To learn more about the time course of production and specificity of AHSV-specific antibodies, sera were analyzed by immunoblot analysis. Only animals that survived for more than 9 days were able to develop a humoral immune response detectable by immunoblotting. The earliest serological markers corresponded mainly to VP5, VP6, and NS2 and to a lesser extent to VP3, NS1, and NS3. Neutralizing antibodies to VP2 were not detected by immunoblotting, suggesting that they are mostly conformation dependent. VP7-specific antibodies were detected later in infection. These results make NS2 and VP6 the most attractive candidates for the rapid diagnosis of the infection. PMID:9003637

  7. The dark side of browning.

    PubMed

    Tamucci, Kirstin A; Namwanje, Maria; Fan, Lihong; Qiang, Li

    2018-02-01

    The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.

  8. Early intranuclear replication of African swine fever virus genome modifies the landscape of the host cell nucleus.

    PubMed

    Simões, Margarida; Martins, Carlos; Ferreira, Fernando

    2015-12-02

    Although African swine fever virus (ASFV) replicates in viral cytoplasmic factories, the presence of viral DNA within the host cell nucleus has been previously reported to be essential for productive infection. Herein, we described, for the first time, the intranuclear distribution patterns of viral DNA replication events, preceding those that occur in the cytoplasmic compartment. Using BrdU pulse-labelling experiments, newly synthesized ASFV genomes were exclusively detected inside the host cell nucleus at the early phase of infection, both in swine monocyte-derived macrophages (MDMs) and Vero cells. From 8hpi onwards, BrdU labelling was only observed in ASFV cytoplasmic factories. Our results also show that ASFV specifically activates the Ataxia Telangiectasia Mutated Rad-3 related (ATR) pathway in ASFV-infected swine MDMs from the early phase of infection, most probably because ASFV genome is recognized as foreign DNA. Morphological changes of promyelocytic leukaemia nuclear bodies (PML-NBs), nuclear speckles and Cajal bodies were also found in ASFV-infected swine MDMs, strongly suggesting the viral modulation of cellular antiviral responses and cellular transcription, respectively. As described for other viral infections, the nuclear reorganization that takes place during ASFV infection may also provide an environment that favours its intranuclear replication events. Altogether, our results contribute for a better understanding of ASFV replication strategies, starting with an essential intranuclear DNA replication phase which induces host nucleus changes towards a successful viral infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Early Epstein-Barr Virus Genomic Diversity and Convergence toward the B95.8 Genome in Primary Infection.

    PubMed

    Weiss, Eric R; Lamers, Susanna L; Henderson, Jennifer L; Melnikov, Alexandre; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa; Nusbaum, Chad; Luzuriaga, Katherine

    2018-01-15

    Over 90% of the world's population is persistently infected with Epstein-Barr virus. While EBV does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (AIM) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. At present, very few primary, circulating EBV genomes have been sequenced directly from infected individuals. While low levels of diversity and low viral evolution rates have been predicted for double-stranded DNA (dsDNA) viruses, recent studies have demonstrated appreciable diversity in common dsDNA pathogens (e.g., cytomegalovirus). Here, we report 40 full-length EBV genome sequences obtained from matched oral wash and B cell fractions from a cohort of 10 AIM patients. Both intra- and interpatient diversity were observed across the length of the entire viral genome. Diversity was most pronounced in viral genes required for establishing latent infection and persistence, with appreciable levels of diversity also detected in structural genes, including envelope glycoproteins. Interestingly, intrapatient diversity declined significantly over time ( P < 0.01), and this was particularly evident on comparison of viral genomes sequenced from B cell fractions in early primary infection and convalescence ( P < 0.001). B cell-associated viral genomes were observed to converge, becoming nearly identical to the B95.8 reference genome over time (Spearman rank-order correlation test; r = -0.5589, P = 0.0264). The reduction in diversity was most marked in the EBV latency genes. In summary, our data suggest independent convergence of diverse viral genome sequences toward a reference-like strain within a relatively short period following primary EBV infection. IMPORTANCE Identification of viral proteins with low variability and high immunogenicity is important for the development of a protective vaccine. Knowledge of genome diversity within circulating viral

  10. Viral reprogramming of the Daxx histone H3.3 chaperone during early Epstein-Barr virus infection.

    PubMed

    Tsai, Kevin; Chan, Lilian; Gibeault, Rebecca; Conn, Kristen; Dheekollu, Jayaraju; Domsic, John; Marmorstein, Ronen; Schang, Luis M; Lieberman, Paul M

    2014-12-01

    Host chromatin assembly can function as a barrier to viral infection. Epstein-Barr virus (EBV) establishes latent infection as chromatin-assembled episomes in which all but a few viral genes are transcriptionally silent. The factors that control chromatin assembly and guide transcription regulation during the establishment of latency are not well understood. Here, we demonstrate that the EBV tegument protein BNRF1 binds the histone H3.3 chaperone Daxx to modulate histone mobility and chromatin assembly on the EBV genome during the early stages of primary infection. We demonstrate that BNRF1 substitutes for the repressive cochaperone ATRX to form a ternary complex of BNRF1-Daxx-H3.3-H4, using coimmunoprecipitation and size-exclusion chromatography with highly purified components. FRAP (fluorescence recovery after photobleaching) assays were used to demonstrate that BNRF1 promotes global mobilization of cellular histone H3.3. Mutation of putative nucleotide binding motifs on BNRF1 attenuates the displacement of ATRX from Daxx. We also show by immunofluorescence combined with fluorescence in situ hybridization that BNRF1 is important for the dissociation of ATRX and Daxx from nuclear bodies during de novo infection of primary B lymphocytes. Virion-delivered BNRF1 suppresses Daxx-ATRX-mediated H3.3 loading on viral chromatin as measured by chromatin immunoprecipitation assays and enhances viral gene expression during early infection. We propose that EBV tegument protein BNRF1 replaces ATRX to reprogram Daxx-mediated H3.3 loading, in turn generating chromatin suitable for latent gene expression. Epstein-Barr Virus (EBV) is a human herpesvirus that efficiently establishes latent infection in primary B lymphocytes. Cellular chromatin assembly plays an important role in regulating the establishment of EBV latency. We show that the EBV tegument protein BNRF1 functions to regulate chromatin assembly on the viral genome during early infection. BNRF1 alters the host cellular

  11. Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

    SciTech Connect

    Nomura, Fumio, E-mail: fnomura@faculty.chiba-u.jp; Sogawa, Kazuyuki; Noda, Kenta

    Highlights: Black-Right-Pointing-Pointer Overexpression of Ku86 in human liver cancer was shown by immunohistochemistry. Black-Right-Pointing-Pointer Serum anti-Ku86 was significantly elevated in early hepatocellular carcinoma. Black-Right-Pointing-Pointer Anti-Ku86 may be more sensitive than the conventional markers for early detection. Black-Right-Pointing-Pointer Serum anti-Ku86 significantly decreased after surgical resection of liver tumors. Black-Right-Pointing-Pointer Elevation of serum anti-Ku86 in other non-liver solid tumors was minimal. -- Abstract: Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is one of the most common cancers worldwide and the third most common cause of cancer-related death. Imaging studies including ultrasound and computed tomography are recommended for early detectionmore » of HCC, but they are operator dependent, costly and involve radiation. Therefore, there is a need for simple and sensitive serum markers for the early detection of hepatocellular carcinoma (HCC). In our recent proteomic studies, a number of proteins overexpressed in HCC tissues were identified. We thought if the serum autoantibodies to these overexpressed proteins were detectable in HCC patients. Of these proteins, we focused on Ku86, a nuclear protein involved in multiple biological processes and aimed to assess the diagnostic value of serum anti-Ku86 in the early detection of HCC. Serum samples were obtained prior to treatment from 58 consecutive patients with early or relatively early hepatitis C virus (HCV)-related HCC and 137 patients with HCV-related liver cirrhosis without evidence of HCC. Enzyme immunoassays were used to measure serum levels of autoantibodies. Serum levels of anti-Ku86 antibodies were significantly elevated in HCC patients compared to those in liver cirrhosis patients (0.41 {+-} 0.28 vs. 0.18 {+-} 0.08 Abs at 450 nm, P < 0001). Setting the cut-off level to give 90% specificity, anti-Ku86 was positive in 60

  12. Brown Dwarf Microlensing Diagram

    NASA Image and Video Library

    2016-11-10

    For the first time, two space-based telescopes have teamed up with ground-based observatories to observe a microlensing event, a magnification of the light of a distant star due to the gravitational effects of an unseen object in the foreground. In this case, the cause of the microlensing event was a brown dwarf, dubbed OGLE-2015-BLG-1319, orbiting a star. In terms of mass, brown dwarfs fall somewhere between the size of the largest planets and the smallest stars. Curiously, scientists have found that, for stars roughly the mass of our sun, less than 1 percent have a brown dwarf orbiting within 3 AU (1 AU is the distance between Earth and the sun). This newly discovered brown dwarf may fall in that distance range. This microlensing event was observed by ground-based telescopes looking for these uncommon events, and subsequently seen by NASA's Spitzer and Swift space telescopes. As the diagram shows, Spitzer and Swift offer additional vantage points for viewing this chance alignment. While Swift orbits close to Earth, and saw (blue diamonds) essentially the same change in light that the ground-based telescopes measured (grey markers), Spitzer's location much farther away from Earth gave it a very different perspective on the event (red circles). In particular, Spitzer's vantage point resulted in a time lag in the microlensing event it observed, compared to what was seen by Swift and the ground-based telescope. This offset allowed astronomers to determine the distance to OGLE-2015-BLG-1319 as well as its mass: around 30-65 times that of Jupiter. http://photojournal.jpl.nasa.gov/catalog/PIA21077

  13. Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis

    PubMed Central

    Biswas, Hope H.; Ortega, Oscar; Gordon, Aubree; Standish, Katherine; Balmaseda, Angel; Kuan, Guillermina; Harris, Eva

    2012-01-01

    Background Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. Methods Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2–14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. Results One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. Conclusions Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management. PMID:22413033

  14. Induction of Epstein-Barr Virus Oncoprotein LMP1 by Transcription Factors AP-2 and Early B Cell Factor

    PubMed Central

    Noda, Chieko; Narita, Yohei; Watanabe, Takahiro; Yoshida, Masahiro; Ashio, Keiji; Sato, Yoshitaka; Goshima, Fumi; Kanda, Teru; Yoshiyama, Hironori; Tsurumi, Tatsuya; Kimura, Hiroshi

    2016-01-01

    ABSTRACT Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter. IMPORTANCE Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is crucial for B cell transformation and oncogenesis of other EBV-related malignancies, such as nasopharyngeal carcinoma and T/NK lymphoma. Its expression is largely dependent on the cell type or condition, and some transcription factors have been implicated in its regulation. However, these previous reports evaluated the significance of specific factors mostly by reporter assay. In this study, we prepared point-mutated EBV at the binding sites of such transcription factors and confirmed the importance of AP-2, EBF, PU.1, and POU domain factors. Our results will provide insight into the transcriptional regulation of the major oncogene LMP1. PMID:26819314

  15. Novel graphene-based biosensor for early detection of Zika virus infection.

    PubMed

    Afsahi, Savannah; Lerner, Mitchell B; Goldstein, Jason M; Lee, Joo; Tang, Xiaoling; Bagarozzi, Dennis A; Pan, Deng; Locascio, Lauren; Walker, Amy; Barron, Francie; Goldsmith, Brett R

    2018-02-15

    We have developed a cost-effective and portable graphene-enabled biosensor to detect Zika virus with a highly specific immobilized monoclonal antibody. Field Effect Biosensing (FEB) with monoclonal antibodies covalently linked to graphene enables real-time, quantitative detection of native Zika viral (ZIKV) antigens. The percent change in capacitance in response to doses of antigen (ZIKV NS1) coincides with levels of clinical significance with detection of antigen in buffer at concentrations as low as 450pM. Potential diagnostic applications were demonstrated by measuring Zika antigen in a simulated human serum. Selectivity was validated using Japanese Encephalitis NS1, a homologous and potentially cross-reactive viral antigen. Further, the graphene platform can simultaneously provide the advanced quantitative data of nonclinical biophysical kinetics tools, making it adaptable to both clinical research and possible diagnostic applications. The speed, sensitivity, and selectivity of this first-of-its-kind graphene-enabled Zika biosensor make it an ideal candidate for development as a medical diagnostic test. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection.

    PubMed

    Price, Alexander M; Messinger, Joshua E; Luftig, Micah A

    2018-01-15

    Recent evidence has shown that the Epstein-Barr virus (EBV) oncogene LMP1 is not expressed at high levels early after EBV infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased 50-fold between 7 days postinfection and the LCL state. Metabolic labeling of nascent transcribed mRNA indicated that this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to that in infected B cells early after infection. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc both in LCLs and early after primary B cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B cell infection directly repress LMP1 transcription. IMPORTANCE EBV is a highly successful pathogen that latently infects more than 90% of adults worldwide and is also causally associated with a number of B cell malignancies. During the latent life cycle, EBV expresses a set of viral oncoproteins and noncoding RNAs with the potential to promote cancer. Critical among these is the viral latent membrane protein LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here we show that transcription of the LMP1 gene can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV oncogenes will allow us

  17. Early Outbreak of 2009 Influenza A (H1N1) in Mexico Prior to Identification of pH1N1 Virus

    PubMed Central

    Hsieh, Ying-Hen; Ma, Stefan; Velasco Hernandez, Jorge X.; Lee, Vernon J.; Lim, Wei Yen

    2011-01-01

    Background In the aftermath of the global spread of 2009 influenza A (pH1N1) virus, still very little is known of the early stages of the outbreak in Mexico during the early months of the year, before the virus was identified. Methodology/Main Findings We fit a simple mathematical model, the Richards model, to the number of excess laboratory-confirmed influenza cases in Mexico and Mexico City during the first 15 weeks in 2009 over the average influenza case number of the previous five baseline years of 2004-2008 during the same period to ascertain the turning point (or the peak incidence) of a wave of early influenza infections, and to estimate the transmissibility of the virus during these early months in terms of its basic reproduction number. The results indicate that there may have been an early epidemic in Mexico City as well as in all of Mexico during February/March. Based on excess influenza cases, the estimated basic reproduction number R0 for the early outbreak was 1.59 (0.55 to 2.62) for Mexico City during weeks 5–9, and 1.25 (0.76, 1.74) for all of Mexico during weeks 5–14. Conclusions We established the existence of an early epidemic in Mexico City and in all of Mexico during February/March utilizing the routine influenza surveillance data, although the location of seeding is unknown. Moreover, estimates of R0 as well as the time of peak incidence (the turning point) for Mexico City and all of Mexico indicate that the early epidemic in Mexico City in February/March had been more transmissible (larger R0) and peaked earlier than the rest of the country. Our conclusion lends support to the possibility that the virus could have already spread to other continents prior to the identification of the virus and the reporting of lab-confirmed pH1N1 cases in North America in April. PMID:21909366

  18. Salivary pH and buffering capacity in early and late human immunodeficiency virus infection.

    PubMed

    Hegde, Mithra N; Malhotra, Amit; Hegde, Nidarsh D

    2013-11-01

    Human immunodeficiency virus (HIV) causes severe immunosuppression due to progressive decrease in the CD4 T lymphocyte cells during the course of the disease and this affects all the body systems including glandular secretions. A number of lesions affecting the salivary glands have been noted in HIV infection. The objective of this study was to evaluate the salivary pH and the buffering capacity in HIV positive individuals and comparing it with the HIV negative healthy individuals. The study was carried out on 200 HIV positive subjects aged 20-40 years, divided into two groups on the basis of CD4 count and 100 HIV negative healthy individuals as control group. Both unstimulated and stimulated saliva were collected and the pH and buffering capacity ascertained using the saliva check kit. (GC Asia Dental Pvt. Ltd., Singapore, 508724). All the three groups were compared using the ANOVA and it was found there was highly significant decrease in pH and buffering capacity with increase in immunosuppression. The intergroup comparison was carried out using the Tukey honestly significant difference (HSD) and the Chi square test. Group 1; CD4 count <200 and Group 2, CD4 count >200 showed a significant decrease in unstimulated salivary flow, stimulated salivary flow, and pH in comparison to HIV negative individuals; however, change in buffering capacity in Group 2 was not significant. There is a decrease in pH and buffering capacity in HIV infected patients. This decrease may be one of the factors responsible for increased caries in HIV infected population.

  19. Surveillance of dengue fever virus: a review of epidemiological models and early warning systems.

    PubMed

    Racloz, Vanessa; Ramsey, Rebecca; Tong, Shilu; Hu, Wenbiao

    2012-01-01

    Dengue fever affects over a 100 million people annually hence is one of the world's most important vector-borne diseases. The transmission area of this disease continues to expand due to many direct and indirect factors linked to urban sprawl, increased travel and global warming. Current preventative measures include mosquito control programs, yet due to the complex nature of the disease and the increased importation risk along with the lack of efficient prophylactic measures, successful disease control and elimination is not realistic in the foreseeable future. Epidemiological models attempt to predict future outbreaks using information on the risk factors of the disease. Through a systematic literature review, this paper aims at analyzing the different modeling methods and their outputs in terms of acting as an early warning system. We found that many previous studies have not sufficiently accounted for the spatio-temporal features of the disease in the modeling process. Yet with advances in technology, the ability to incorporate such information as well as the socio-environmental aspect allowed for its use as an early warning system, albeit limited geographically to a local scale.

  20. Interleukin-10 production at the early stage of infection with foot-and-mouth disease virus related to the likelihood of persistent infection in cattle.

    PubMed

    Zhang, Zhidong; Doel, Claudia; Bashiruddin, John B

    2015-11-19

    The factors leading to persistent infection of foot-and-mouth disease (FMD) virus in ruminants are not well defined. This paper provides evidence of the presence of interleukin-10 (IL-10) early in the course of infection (1-4 days) as a factor in the development of persistence of FMD virus in cattle. Results showed that serum IL-10 in carrier cattle infected with FMD virus type O (n = 4) was detected and peaked at 1 or 2 days post infection and rapidly declined thereafter. In contract, serum IL-10 levels in non-carrier cattle (n = 21) were very low or undetectable during the same period.

  1. Hyperactive immune cells (T cells) may be responsible for acute lung injury in influenza virus infections: a need for early immune-modulators for severe cases.

    PubMed

    Lee, Kyung-Yil; Rhim, Jung-Woo; Kang, Jin-Han

    2011-01-01

    It has been believed that acute lung injury in influenza virus infections is caused by a virus-induced cytopathy; viruses that have multiplied in the upper respiratory tract spread to lung tissues along the lower respiratory tract. However, some experimental and clinical studies have suggested that the pathogenesis of acute lung injury in influenza virus infections is associated with excessive host response including a cell-mediated immune reaction. During the pandemic H1N1 2009 influenza A virus infections in Korea, we experienced a dramatic effect of immune-modulators (corticosteroids) on the patients with severe pneumonia who had significant respiratory distress at presentation and those who showed rapidly progressive pneumonia during oseltamivir treatment. We also found that the pneumonia patients treated with corticosteroids showed the lowest lymphocyte differential and that the severity of pneumonia was associated with the lymphocyte count at presentation. From our findings and previous experimental and clinical studies, we postulated that hyperactive immune cells (T cells) may be involved in the acute lung injury of influenza virus infections, using a hypothesis of 'protein homeostasis system'; the inducers of the cell-mediated immune response are initially produced at the primary immune sites by the innate immune system. These substances reach the lung cells, the main target organ, via the systemic circulation, and possibly the cells of other organs, including myocytes or central nerve system cells, leading to extrapulmonary symptoms (e.g., myalgia and rhabdomyolysis, and encephalopathy). To control these substances that may be possibly toxic to host cells, the adaptive immune reaction may be operated by immune cells, mainly lymphocytes. Hyperimmune reaction of immune cells produces higher levels of cytokines which may be associated with acute lung injury, and may be controlled by early use of immune-modulators. Early initiation and proper dosage of immune

  2. On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles

    PubMed Central

    Carvalho, Carlos A.M.; Silva, Jerson L.; Oliveira, Andréa C.

    2017-01-01

    Mayaro virus (MAYV) is an emergent sylvatic alphavirus in South America, related to sporadic outbreaks of a chikungunya-like human febrile illness accompanied by severe arthralgia. Despite its high potential for urban emergence, MAYV is still an obscure virus with scarce information about its infection cycle, including the corresponding early events. Even for prototypical alphaviruses, the cell entry mechanism still has some rough edges to trim: although clathrin-mediated endocytosis is quoted as the putative route, alternative paths as distinct as direct virus genome injection through the cell plasma membrane seems to be possible. Our aim was to clarify crucial details on the entry route exploited by MAYV to gain access into the host cell. Tracking the virus since its first contact with the surface of Vero cells by fluorescence microscopy, we show that its entry occurs by a fast endocytic process and relies on fusion with acidic endosomal compartments. Moreover, blocking clathrin-mediated endocytosis or depleting cholesterol from the cell membrane leads to a strong inhibition of viral infection, as assessed by plaque assays. Following this clue, we found that early endosomes and caveolae-derived vesicles are both implicated as target membranes for MAYV fusion. Our findings unravel the very first events that culminate in a productive infection by MAYV and shed light on potential targets for a rational antiviral therapy, besides providing a better comprehension of the entry routes exploited by alphaviruses to get into the cell. PMID:28462045

  3. Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment.

    PubMed

    Grant, Robert M; Smith, Dawn K

    2015-12-01

    Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers.

  4. Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment

    PubMed Central

    Grant, Robert M.; Smith, Dawn K.

    2015-01-01

    Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers. PMID:26512356

  5. Exome capture sequencing reveals new insights into hepatitis B virus-induced hepatocellular carcinoma at the early stage of tumorigenesis.

    PubMed

    Chen, Yong; Wang, Lijuan; Xu, Hexiang; Liu, Xingxiang; Zhao, Yingren

    2013-10-01

    Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the third primary cause of cancer-related mortality worldwide. The molecular mechanisms underlying the initiation and formation of HCC remain obscure. In the present study, we performed exome sequencing using tumor and normal tissues from 3 hepatitis B virus (HBV)-positive BCLC stage A HCC patients. Bioinformatic analysis was performed to find candidate protein-altering somatic mutations. Eighty damaging mutations were validated and 59 genes were reported to be mutated in HBV-related HCCs for the first time here. Further analysis using whole genome sequencing (WGS) data of 88 HBV-related HCC patients from the European Genome-phenome Archive database showed that mutations in 33 of the 59 genes were also detected in other samples. Variants of two newly found genes, ZNF717 and PARP4, were detected in more than 10% of the WGS samples. Several other genes, such as FLNA and CNTN2, are also noteworthy. Thus, the exome sequencing analysis of three BCLC stage A patients provides new insights into the molecular events governing the early steps of HBV-induced HCC tumorigenesis.

  6. Loss of Robustness and Addiction to IGF1 during Early Keratinocyte Transformation by Human Papilloma Virus 16

    PubMed Central

    Geiger, Tamar; Levitzki, Alexander

    2007-01-01

    Infection of keratinocytes with high risk human Papilloma virus causes immortalization, and when followed by further mutations, leads to cervical cancer and other anogenital tumors. Here we monitor the progressive loss of robustness in an in vitro model of the early stages of transformation that comprises normal keratinocytes and progressive passages of HPV16 immortalized cells. As transformation progresses, the cells acquire higher proliferation rates and gain the ability to grow in soft agar. Concurrently, the cells lose robustness, becoming more sensitive to serum starvation and DNA damage by Cisplatin. Loss of robustness in the course of transformation correlates with significant reductions in the activities of the anti-apoptotic proteins PKB/Akt, Erk, Jnk and p38 both under normal growth conditions and upon stress. In parallel, loss of robustness is manifested by the shrinkage of the number of growth factors that can rescue starving cells from apoptosis, with the emergence of dependence solely on IGF1. Treatment with IGF1 activates PKB/Akt and Jnk and through them inhibits p53, rescuing the cells from starvation. We conclude that transformation in this model induces higher susceptibility of cells to stress due to reduced anti-apoptotic signaling and hyper-activation of p53 upon stress. PMID:17622350

  7. Forced Complementation between Subgenomic RNAs: Does Human Immunodeficiency Type 1 Virus Reverse Transcription Occur in Viral Core, Cytoplasm, or Early Endosome?

    PubMed Central

    Han, Weining; Li, Yuejin; Bagaya, Bernard S.; Tian, Meijuan; Chamanian, Mastooreh; Zhu, Chuanwu; Shen, Jie; Gao, Yong

    2016-01-01

    Although the process of reverse transcription is well elucidated, it remains unclear if viral core disruption provides a more cellular or viral milieu for HIV-1 reverse transcription. We have devised a method to require mixing of viral cores or core constituents to produce infectious progeny virus by a bipartite subgenomic RNA (sgRNA) system, in which HIV-1 cplt_R/U5/gag/Δpol and nfl sgRNAs are complementary to each other and when together can complete viral reverse transcription. Only the heterodiploid virus containing both the nfl and cplt_R/U5/gag/Δpol sgRNAs can complete reverse transcription and propagate infectious virus upon de novo infection. Dual exposure of U87.CD4.CXCR4 cells with high titers of the homodimeric nfl and cplt_R/U5/gag/Δpol virus particles did not result in productive virus infection. On the other hand, in early endosomes, the HIV-1 sgRNAs released from viral cores can retain function and complete the reverse transcription and result in productive infection. These findings confirm the assumptions that, in natural infection, HIV-1 cores, and likely other retrovirus cores, remain largely intact and do not mix/fuse in the cytoplasm during the reverse transcription process, and circulating cytoplasmic HIV-1 sgRNA (produced through transfection) could not help the complementary sgRNA in the viral core to complement the reverse transcription process. PMID:27239643

  8. Chronic restraint stress during early Theiler’s virus infection exacerbates the subsequent demyelinating disease in SJL mice: II. CNS disease severity

    PubMed Central

    Young, Erin E.; Sieve, Amy N.; Vichaya, Elisabeth G.; Carcoba, Luis M.; Young, Colin R.; Ambrus, Andrew; Storts, Ralph; Welsh, C. Jane R.; Meagher, Mary W.

    2010-01-01

    Theiler’s murine encephalomyelitis virus (TMEV) infection is a well-characterized model of multiple sclerosis (MS). Previous research has shown that chronic restraint stress (RS) during early TMEV infection exacerbates behavioral signs of disease. The present data suggest RS-induced increases in CNS inflammation, demyelination, and axonal degeneration may underlie this exacerbation. In addition, we report that males exhibit greater CNS inflammation and higher numbers of demyelinating lesions while females show greater susceptibility to RS-induced exacerbation. These findings indicate RS during early TMEV infection increases CNS lesion formation during the late phase and suggest the effects of RS are sex-dependent. PMID:20167380

  9. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    PubMed

    Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C

    2014-12-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  10. Inhibition of browning in foodstuffs

    NASA Technical Reports Server (NTRS)

    Rosenthal, N. A.

    1969-01-01

    Addition of water-soluble sulfur-containing compounds, thio compounds or potential thio compounds, to a mixture of carbohydrates, and either proteins, peptides, or amino acids can retard or completely eliminate the browning process. Determining factor is dependent upon the concentration of the anti-browning agent in the aqueous media.

  11. Biological characteristics of genetic variants of Urabe AM9 mumps vaccine virus.

    PubMed

    Wright, K E; Dimock, K; Brown, E G

    2000-03-01

    The Urabe AM9 mumps vaccine is composed of a mixture of variants distinguishable by a difference at nucleotide (nt) 1081 of the hemagglutinin-neuraminidase (HN) gene (Brown, E.G., Dimock, K., Wright, K.E., 1996. The Urabe AM9 mumps vaccine is a mixture of viruses differing at amino acid (aa) 335 of the hemagglutinin-neuraminidase gene with one form associated with disease. J. Infect. Dis. 174, 619-622.). Further genetic and biological variation was detected in plaque purified viruses from the Urabe AM9 vaccine by examining the HN gene sequence, plaque morphology, cytopathic effects and growth in Vero cells, and temperature sensitivity (ts). Infection of Vero cells with plaque purified viruses with a G at nt 1081 of the HN gene produced large, clear plaques, caused significant CPE early after infection but yielded lower titres of virus than other purified viruses. None of these viruses were ts. In contrast, half of the plaque purified viruses with an A at nt 1081 were sensitive to a temperature of 39.5 degrees C. These viruses produced small plaques, caused significant CPE and grew to low titres. Two ts viruses possessed a unique aa substitution at aa 468 of HN. The remaining A(1081) viruses were not ts, produced large plaques but little CPE, and grew to titres 10-fold higher than the G(1081) viruses. Isolates of Urabe AM9 associated with post-vaccination illness were similar to these non-ts A(1081) viruses, but could be further sub-divided into two groups on the basis of a difference at aa 464 of HN. The post-vaccination isolates may represent insufficiently attenuated components of the vaccine, while the G(1081) and ts subset of A(1081) viruses may be more fully attenuated.

  12. Molecular phylogeography of the brown bear (Ursus arctos) in Northeastern Asia based on analyses of complete mitochondrial DNA sequences.

    PubMed

    Hirata, Daisuke; Mano, Tsutomu; Abramov, Alexei V; Baryshnikov, Gennady F; Kosintsev, Pavel A; Vorobiev, Alexandr A; Raichev, Evgeny G; Tsunoda, Hiroshi; Kaneko, Yayoi; Murata, Koichi; Fukui, Daisuke; Masuda, Ryuichi

    2013-07-01

    To further elucidate the migration history of the brown bears (Ursus arctos) on Hokkaido Island, Japan, we analyzed the complete mitochondrial DNA (mtDNA) sequences of 35 brown bears from Hokkaido, the southern Kuril Islands (Etorofu and Kunashiri), Sakhalin Island, and the Eurasian Continent (continental Russia, Bulgaria, and Tibet), and those of four polar bears. Based on these sequences, we reconstructed the maternal phylogeny of the brown bear and estimated divergence times to investigate the timing of brown bear migrations, especially in northeastern Eurasia. Our gene tree showed the mtDNA haplotypes of all 73 brown and polar bears to be divided into eight divergent lineages. The brown bear on Hokkaido was divided into three lineages (central, eastern, and southern). The Sakhalin brown bear grouped with eastern European and western Alaskan brown bears. Etorofu and Kunashiri brown bears were closely related to eastern Hokkaido brown bears and could have diverged from the eastern Hokkaido lineage after formation of the channel between Hokkaido and the southern Kuril Islands. Tibetan brown bears diverged early in the eastern lineage. Southern Hokkaido brown bears were closely related to North American brown bears.

  13. Early Math.

    ERIC Educational Resources Information Center

    Van Nuys, Ute Elisabeth

    1986-01-01

    Presents reviews of the following mathematics software designed to teach young children counting, number recognition, visual discrimination, matching, addition, and subtraction skills; Stickybear Numbers, Learning with Leeper, Getting Ready to Read and Add, Counting Parade, Early Games for Young Children, Charlie Brown's 1,2,3's, Let's Go Fishing,…

  14. Gamma-interferon exerts a critical early restriction on replication and dissemination of yellow fever virus vaccine strain 17D-204.

    PubMed

    Lam, L K Metthew; Watson, Alan M; Ryman, Kate D; Klimstra, William B

    2018-01-01

    Live attenuated viruses are historically among the most effective viral vaccines. Development of a safe vaccine requires the virus to be less virulent, a phenotype that is historically arrived by empirical evaluation often leaving the mechanisms of attenuation unknown. The yellow fever virus 17D live attenuated vaccine strain has been developed as a delivery vector for heterologous antigens; however, the mechanisms of attenuation remain elusive. The successful and safe progress of 17D as a vaccine vector and the development of live attenuated vaccines (LAVs) to related flaviviruses requires an understanding of the molecular mechanisms leading to attenuation. Using subcutaneous infection of interferon-deficient mouse models of wild type yellow fever virus (WT YFV) pathogenesis and 17D-mediated immunity, we found that, in the absence of type I IFN (IFN-α/β), type II interferon (IFN-γ) restricted 17D replication, but not that of WT YFV, by 1-2 days post-infection. In this context, IFN-γ responses protected 17D-infected animals from mortality, largely restricted the virus to lymphoid organs, and eliminated viscerotropic disease signs such as steatosis in the liver and inflammatory cell infiltration into the spleen. However, WT YFV caused a disseminated infection, gross liver pathology, and rapid death of the animals. In vitro, IFN-γ treatment of myeloid cells suppressed the replication of 17D significantly more than that of WT YFV, suggesting a direct differential effect on 17D virus replication. Together these data indicate that an important mechanism of 17D attenuation in vivo is increased sensitivity to IFN-γ stimulated responses elicited early after infection.

  15. An environmental DNA marker for detecting nonnative brown trout (Salmo trutta)

    Treesearch

    K. J. Carim; T. M. Wilcox; M. Anderson; D. Lawrence; Michael Young; Kevin McKelvey; Michael Schwartz

    2016-01-01

    Brown trout (Salmo trutta) are widely introduced in western North America where their presence has led to declines of several native species. To assist conservation efforts aimed at early detection and eradication of this species, we developed a quantitative PCR marker to detect the presence of brown trout DNA in environmental samples. The marker strongly...

  16. Atmospheres of Brown Dwarfs

    NASA Astrophysics Data System (ADS)

    Seay, Christopher; Wang, Ruoyan; Fortney, Jonathan

    2018-01-01

    We construct a grid of brown dwarf model atmospheres spanning a wide range of atmospheric metallicity (0.3x ≤ met ≤ 100x), C/O ratios (0.25x ≤ C/O ≤ 2.5x), and cloud properties, encompassing atmospheres of effective temperatures 200 ≤ Teff ≤ 2400 K and gravities 2.5 ≤ log g ≤ 5.5. We produce the expected temperature-pressure profiles and emergent spectra from an atmosphere in radiative-convective equilibrium. We can then compare our predicted spectra to observations and retrieval results to aid in their predictions and influence future missions and telescopic observations. In our poster we briefly describe our modeling methodology and present our progress on model grid construction, spanning solar and subsolar C/O and metallicity.

  17. Early exposure to interleukin-21 limits rapidly generated anti-Epstein-Barr virus T-cell line differentiation.

    PubMed

    Orio, Julie; Carli, Cédric; Janelle, Valérie; Giroux, Martin; Taillefer, Julie; Goupil, Mathieu; Richaud, Manon; Roy, Denis-Claude; Delisle, Jean-Sébastien

    2015-04-01

    The adoptive transfer of ex vivo-expanded Epstein-Barr virus (EBV)-specific T-cell lines is an attractive strategy to treat EBV-related neoplasms. Current evidence suggests that for adoptive immunotherapy in general, clinical responses are superior if the transferred cells have not reached a late or terminal effector differentiation phenotype before infusion. The cytokine interleukin (IL)-21 has shown great promise at limiting late T-cell differentiation in vitro, but this remains to be demonstrated in anti-viral T-cell lines. We adapted a clinically validated protocol to rapidly generate EBV-specific T-cell lines in 12 to 14 days and tested whether the addition of IL-21 at the initiation of the culture would affect T-cell expansion and differentiation. We generated clinical-scale EBV-restricted T-cell line expansion with balanced T-cell subset ratios. The addition of IL-21 at the beginning of the culture decreased both T-cell expansion and effector memory T-cell accumulation, with a relative increase in less-differentiated T cells. Within CD4 T-cell subsets, exogenous IL-21 was notably associated with the cell surface expression of CD27 and high KLF2 transcript levels, further arguing for a role of IL-21 in the control of late T-cell differentiation. Our results show that IL-21 has profound effects on T-cell differentiation in a rapid T-cell line generation protocol and as such should be further explored as a novel approach to program anti-viral T cells with features associated with early differentiation and optimal therapeutic efficacy. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  18. Successful Vaccination Induces Multifunctional Memory T-Cell Precursors Associated with Early Control of Hepatitis C Virus

    PubMed Central

    Park, Su-Hyung; Shin, Eui-Cheol; Capone, Stefania; Caggiari, Laura; De Re, Valli; Nicosia, Alfredo; Folgori, Antonella; Rehermann, Barbara

    2012-01-01

    Background & Aims T cells are an important component for development of a vaccine against hepatitis C virus (HCV), but little is known about the features of successful vaccine-induced T cells. Methods We compared the phenotype, function, and kinetics of vaccine-induced and infection-induced T cells in chimpanzees with HCV infection using multicolor flow cytometry and real-time PCR. Results In chimpanzees successfully vaccinated with recombinant adenovirus and DNA against HCV NS3-NS5, HCV-specific T cells appeared earlier, maintained better functionality, and persisted at higher frequencies, for a longer time after HCV-challenge, than those of mock-vaccinated chimpanzees. Vaccine-induced T cells displayed higher levels of CD127, a marker of memory precursors, and lower levels of programmed death (PD)-1 than infection-induced T cells. Vaccine-induced, but not infection-induced T cells, were multifunctional; their ability to secrete interferon-γ and tumor necrosis factor-α correlated with early expression of CD127 but not PD-1. Based on a comparison of vaccine-induced and infection-induced T cells from the same chimpanzee, the CD127+ memory precursor phenotype was induced by the vaccine itself, rather than by low viremia. In contrast, PD-1 induction correlated with viremia, and levels of intrahepatic PD-1, PD-L1, and 2,5-OAS-1 mRNAs correlated with peak titers of HCV. Conclusions Compared with infection, vaccination induced HCV-specific CD127+ T cells with high functionality that persisted at higher levels for a longer time. Control of viremia prevented upregulation of PD-1 on T cells, and induction of PD-1, PD-L1, and 2,5-OAS-1 in the liver. Early development of a memory T-cell phenotype and, via control of viremia, attenuation of the inhibitory PD1–PD-L1 pathway might be necessary components of successful vaccine-induced protection against HCV. PMID:22705008

  19. The early protective thymus-independent antibody response to foot-and-mouth disease virus is mediated by splenic CD9+ B lymphocytes.

    PubMed

    Ostrowski, Matias; Vermeulen, Monica; Zabal, Osvaldo; Zamorano, Patricia I; Sadir, Ana M; Geffner, Jorge R; Lopez, Osvaldo J

    2007-09-01

    Infection of mice with cytopathic foot-and-mouth disease virus (FMDV) induces a rapid and specific thymus-independent (TI) neutralizing antibody response that promptly clears the virus. Herein, it is shown that FMDV-infected dendritic cells (DCs) directly stimulate splenic innate-like CD9(+) B lymphocytes to rapidly (3 days) produce neutralizing anti-FMDV immunoglobulin M antibodies without T-lymphocyte collaboration. In contrast, neither follicular (CD9(-)) B lymphocytes from the spleen nor B lymphocytes from lymph nodes efficiently respond to stimulation with FMDV-infected DCs. The production of these protective neutralizing antibodies is dependent on DC-derived interleukin-6 (IL-6) and on CD9(+) cell-derived IL-10 secretion. In comparison, DCs loaded with UV-inactivated FMDV are significantly less efficient in directly stimulating B lymphocytes to secrete TI antibodies. A critical role of the spleen in the early production of anti-FMDV antibodies in infected mice was also demonstrated in vivo. Indeed, either splenectomy or functional disruption of the marginal zone of the spleen delays and reduces the magnitude of the TI anti-FMDV antibody response in infected mice. Together, these results indicate that in addition to virus localization, the FMDV-mediated modulation of DC functionality is a key parameter that collaborates in the induction of a rapid and protective TI antibody response against this virus.

  20. Indomethacin Enhances Brown Fat Activity.

    PubMed

    Hao, Lei; Kearns, Jamie; Scott, Sheyenne; Wu, Dayong; Kodani, Sean D; Morisseau, Christophe; Hammock, Bruce D; Sun, Xiaocun; Zhao, Ling; Wang, Shu

    2018-06-01

    Indomethacin, a nonsteroidal anti-inflammatory drug, has been shown to induce white adipocyte differentiation; however, its roles in brown adipocyte differentiation and activation in brown adipose tissue (BAT) and obesity are unknown. To address this issue, we treated mouse brown preadipocytes with different doses of indomethacin, and delivered indomethacin to interscapular BAT (iBAT) of obese mice using implanted osmotic pumps. Indomethacin dose dependently increased brown preadipocyte differentiation and upregulated both mRNA and protein expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor (PPAR) γ coactivator 1-alpha. The mechanistic study showed that indomethacin significantly activated the reporter driven by the PPAR response element, indicating that indomethacin may work as a PPAR γ agonist in this cell line. Consistently, indomethacin significantly decreased iBAT mass and fasting blood glucose levels in high-fat diet-induced obesity (DIO) mice. Histologic analysis showed that brown adipocytes of indomethacin-treated mice contained smaller lipid droplets compared with control mice, suggesting that indomethacin alleviated the whitening of BAT induced by the high-fat diet. Moreover, indomethacin significantly increased UCP1 mRNA expression in iBAT. Taken together, this study indicates that indomethacin can promote mouse brown adipocyte differentiation, and might increase brown fat and glucose oxidation capacity in DIO mice. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Accumulation of Herpes Simplex Virus Type 1 Early and Leaky-Late Proteins Correlates with Apoptosis Prevention in Infected Human HEp-2 Cells

    PubMed Central

    Aubert, Martine; Rice, Stephen A.; Blaho, John A.

    2001-01-01

    We previously reported that a recombinant ICP27-null virus stimulated, but did not prevent, apoptosis in human HEp-2 cells during infection (M. Aubert and J. A. Blaho, J. Virol. 73:2803–2813, 1999). In the present study, we used a panel of 15 recombinant ICP27 mutant viruses to determine which features of herpes simplex virus type 1 (HSV-1) replication are required for the apoptosis-inhibitory activity. Each virus was defined experimentally as either apoptotic, partially apoptotic, or nonapoptotic based on infected HEp-2 cell morphologies, percentages of infected cells with condensed chromatin, and patterns of specific cellular death factor processing. Viruses d27-1, d1-5, d1-2, M11, M15, M16, n504R, n406R, n263R, and n59R are apoptotic or partially apoptotic in HEp-2 cells and severely defective for growth in Vero cells. Viruses d2-3, d3-4, d4-5, d5-6, and d6-7 are nonapoptotic, demonstrating that ICP27 contains a large amino-terminal region, including its RGG box RNA binding domain, which is not essential for apoptosis prevention. Accumulations of viral TK, VP16, and gD but not gC, ICP22, or ICP4 proteins correlated with prevention of apoptosis during the replication of these viruses. Of the nonapoptotic viruses, d4-5 did not produce gC, indicating that accumulation of true late gene products is not necessary for the prevention process. Analyses of viral DNA synthesis in HEp-2 cells indicated that apoptosis prevention by HSV-1 requires that the infection proceeds to the stage in which viral DNA replication takes place. Infections performed in the presence of the drug phosphonoacetic acid confirmed that the process of viral DNA synthesis and the accumulation of true late (γ2) proteins are not required for apoptosis prevention. Based on our results, we conclude that the accumulation of HSV-1 early (β) and leaky-late (γ1) proteins correlates with the prevention of apoptosis in infected HEp-2 cells. PMID:11134315

  2. Sequential detection of different antigens induced by Epstein-Barr virus and herpes simplex virus in the same Western blot by using dual antibody probes.

    PubMed

    Lin, J C; Pagano, J S

    1986-08-01

    A dual antibody probing technique that permitted a color-coded identification of polypeptides representing different classes of Epstein-Barr virus (EBV) antigens as well as differentiation of the polypeptides induced by different herpesviruses in the same Western blot was developed. When the nitrocellulose sheet was probed first with monoclonal antibody against EBV early antigen diffuse component (EA-D) and then stained with 4-chloro-1-naphthol, four polypeptides specific for EA-D were identified by purple bands. Subsequently, the same nitrocellulose sheet was reprobed with human serum containing antibodies against EBV early antigen, viral capsid antigen, and nuclear antigen and stained with 3,3'-diaminobenzidine. Several brown bands corresponding to early, viral capsid, and nuclear antigen polypeptides were detected. The dual antibody probing technique was used in an analysis to differentiate polypeptides resulting from either EBV or herpes simplex virus infection, either in cells infected by individual virus or in a cell line dually infected by both viruses. On the basis of different colored bands in different lanes of the same gel, 20 polypeptides with molecular weights ranging from 31,000 to 165,000 were identified as herpes simplex virus-specific proteins. These results suggested that the dual antibody probing technique may be applicable in clinical diagnosis for detecting antigens and antibodies derived from different pathogens.

  3. Rabies virus co-localizes with early (Rab5) and late (Rab7) endosomal proteins in neuronal and SH-SY5Y cells.

    PubMed

    Ahmad, Waqas; Li, Yingying; Guo, Yidi; Wang, Xinyu; Duan, Ming; Guan, Zhenhong; Liu, Zengshan; Zhang, Maolin

    2017-06-01

    Rabies virus (RABV) is a highly neurotropic virus that follows clathrin-mediated endocytosis and pH-dependent pathway for trafficking and invasion into endothelial cells. Early (Rab5, EEA1) and late (Rab7, LAMP1) endosomal proteins play critical roles in endosomal sorting, maturity and targeting various molecular cargoes, but their precise functions in the early stage of RABV neuronal infection remain elusive. In this study, the relationship between enigmatic entry of RABV with these endosomal proteins into neuronal and SH-SY5Y cells was investigated. Immunofluorescence, TCID 50 titers, electron microscopy and western blotting were carried out to determine the molecular interaction of the nucleoprotein (N) of RABV with early or late endosomal proteins in these cell lines. The expression of N was also determined by down-regulating Rab5 and Rab7 in both cell lines through RNA interference. The results were indicative that N proficiently colocalized with Rab5/EEA1 and Rab7/LAMP1 in both cell lines at 24 and 48 h post-infection, while N titers significantly decreased in early infection of RABV. Down-regulation of Rab5 and Rab7 did not inhibit N expression, but it prevented productive infection via blocking the normal trafficking of RABV in a low pH environment. Ultrathin sections of cells studied by electron microscope also verified the close association of RABV with Rab5 and Rab7 in neurons. From the data it was concluded that primary entry of RABV strongly correlates with the kinetics of Rab-proteins present on early and late vesicles, which provides helpful clues to explain the early events of RABV in nerve cells.

  4. 7 CFR 29.2504 - Brown colors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Brown colors. 29.2504 Section 29.2504 Agriculture...-Cured Tobacco (u.s. Types 22, 23, and Foreign Type 96) § 29.2504 Brown colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to medium saturation and from very...

  5. 7 CFR 29.2504 - Brown colors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Brown colors. 29.2504 Section 29.2504 Agriculture...-Cured Tobacco (u.s. Types 22, 23, and Foreign Type 96) § 29.2504 Brown colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to medium saturation and from very...

  6. 7 CFR 29.2504 - Brown colors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Brown colors. 29.2504 Section 29.2504 Agriculture...-Cured Tobacco (u.s. Types 22, 23, and Foreign Type 96) § 29.2504 Brown colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to medium saturation and from very...

  7. 7 CFR 29.2504 - Brown colors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Brown colors. 29.2504 Section 29.2504 Agriculture...-Cured Tobacco (u.s. Types 22, 23, and Foreign Type 96) § 29.2504 Brown colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to medium saturation and from very...

  8. 7 CFR 29.3505 - Brown colors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Brown colors. 29.3505 Section 29.3505 Agriculture... Type 95) § 29.3505 Brown colors. A group of colors ranging from a light brown to a dark brown. These colors vary from medium to low saturation and from medium to very low brillance. As used in these...

  9. 7 CFR 29.2504 - Brown colors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Brown colors. 29.2504 Section 29.2504 Agriculture...-Cured Tobacco (u.s. Types 22, 23, and Foreign Type 96) § 29.2504 Brown colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to medium saturation and from very...

  10. Brown Dwarf Weather (Artist's Concept)

    NASA Image and Video Library

    2017-08-17

    This artist's concept animation shows a brown dwarf with bands of clouds, thought to resemble those seen on Neptune and the other outer planets in the solar system. By using NASA's Spitzer Space Telescope, astronomers have found that the varying glow of brown dwarfs over time can be explained by bands of patchy clouds rotating at different speeds. Videos are available at https://photojournal.jpl.nasa.gov/catalog/PIA21752

  11. Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection.

    PubMed

    Rossenkhan, Raabya; MacLeod, Iain J; Brumme, Zabrina L; Magaret, Craig A; Sebunya, Theresa K; Musonda, Rosemary; Gashe, Berhanu A; Edlefsen, Paul T; Novitsky, Vlad; Essex, M

    Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission.

  12. Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

    PubMed Central

    Rossenkhan, Raabya; MacLeod, Iain J.; Brumme, Zabrina L.; Magaret, Craig A.; Sebunya, Theresa K.; Musonda, Rosemary; Gashe, Berhanu A.; Edlefsen, Paul T.; Novitsky, Vlad

    2016-01-01

    Abstract Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission. PMID:27349335

  13. Early detection of a two-long-terminal-repeat junction molecule in the cytoplasm of recombinant murine leukemia virus-infected cells.

    PubMed

    Serhan, Fatima; Penaud, Magalie; Petit, Caroline; Leste-Lasserre, Thierry; Trajcevski, Stéphane; Klatzmann, David; Duisit, Ghislaine; Sonigo, Pierre; Moullier, Philippe

    2004-06-01

    We showed that a U5-U3 junction was reproducibly detected by a PCR assay as early as 1 to 2 h postinfection with a DNase-treated murine leukemia virus (MLV)-containing supernatant in aphidicolin-arrested NIH 3T3 cells, as well as in nonarrested cells. Such detection is azidothymidine sensitive and corresponded to neosynthesized products of the reverse transcriptase. This observation was confirmed in two additional human cell lines, TE671 and ARPE-19. Using cell fractionation combined with careful controls, we found that a two-long-terminal-repeat (two-LTR) junction molecule was detectable in the cytoplasm as early as 2 h post virus entry. Altogether, our data indicated that the neosynthesized retroviral DNA led to the early formation of structures including true two-LTR junctions in the cytoplasm of MLV-infected cells. Thus, the classical assumption that two-LTR circles are a mitosis-dependent dead-end product accumulating in the nucleus must be reconsidered. MLV-derived products containing a two-LTR junction can no longer be used as an exclusive surrogate for the preintegration complex nuclear translocation event.

  14. Tomato chocolàte virus: a new plant virus infecting tomato and a proposed member of the genus Torradovirus.

    PubMed

    Verbeek, Martin; Dullemans, Annette; van den Heuvel, Hans; Maris, Paul; van der Vlugt, René

    2010-05-01

    A new virus was isolated from a tomato plant from Guatemala showing necrotic spots on the bases of the leaves and chocolate-brown patches on the fruits. Structural and molecular analysis showed the virus to be clearly related to but distinct from the recently described Tomato torrado virus (ToTV) and Tomato marchitez virus (ToMarV), both members of the genus Torradovirus. The name tomato chocolàte virus is proposed for this new torradovirus.

  15. Characterization of the Mysteriously Cool Brown Dwarf HD 4113

    NASA Astrophysics Data System (ADS)

    Ednie, Michaela; Follette, Katherine; Ward-Duong, Kimberly

    2018-01-01

    Characterizing the physical properties of brown dwarfs is necessary to expand and improve our understanding of low mass companions, including exoplanets. Systems with both close radial velocity companions and distant directly imaged companions are particularly powerful in understanding planet formation mechanisms. Early in 2017, members of the SPHERE team discovered a companion brown dwarf in the HD 4113 system, which also contains a known RV planet. Atmospheric model fits to the Y and J-band spectra and H2/H3 photometry of the brown dwarf suggested it is unusually cool. We obtained new Magellan data in the Z and K’ bands in mid-2017. This data will help us to complete a more detailed atmospheric and astrometric characterization of this unusually cool companion. Broader wavelength coverage will help in accurate spectral typing and estimations of luminosity, temperature, surface gravity, radius, and composition. Additionally, a second astrometric epoch will help constrain the architecture of the system.

  16. Impact of virus strain characteristics on early detection of highly pathogenic avian influenza infection in commercial table-egg layer flocks and implications for outbreak control.

    PubMed

    Weaver, J Todd; Malladi, Sasidhar; Goldsmith, Timothy J; Hueston, Will; Hennessey, Morgan; Lee, Brendan; Voss, Shauna; Funk, Janel; Der, Christina; Bjork, Kathe E; Clouse, Timothy L; Halvorson, David A

    2012-12-01

    Early detection of highly pathogenic avian influenza (HPAI) infection in commercial poultry flocks is a critical component of outbreak control. Reducing the time to detect HPAI infection can reduce the risk of disease transmission to other flocks. The timeliness of different types of detection triggers could be dependent on clinical signs that are first observed in a flock, signs that might vary due to HPAI virus strain characteristics. We developed a stochastic disease transmission model to evaluate how transmission characteristics of various HPAI strains might effect the relative importance of increased mortality, drop in egg production, or daily real-time reverse transcriptase (RRT)-PCR testing, toward detecting HPAI infection in a commercial table-egg layer flock. On average, daily RRT-PCR testing resulted in the shortest time to detection (from 3.5 to 6.1 days) depending on the HPAI virus strain and was less variable over a range of transmission parameters compared with other triggers evaluated. Our results indicate that a trigger to detect a drop in egg production would be useful for HPAI virus strains with long infectious periods (6-8 days) and including an egg-drop detection trigger in emergency response plans would lead to earlier and consistent reporting in some cases. We discuss implications for outbreak control and risk of HPAI spread attributed to different HPAI strain characteristics where an increase in mortality or a drop in egg production or both would be among the first clinical signs observed in an infected flock.

  17. Application of syndromic surveillance on routinely collected cattle reproduction and milk production data for the early detection of outbreaks of Bluetongue and Schmallenberg viruses.

    PubMed

    Veldhuis, Anouk; Brouwer-Middelesch, Henriëtte; Marceau, Alexis; Madouasse, Aurélien; Van der Stede, Yves; Fourichon, Christine; Welby, Sarah; Wever, Paul; van Schaik, Gerdien

    2016-02-01

    This study aimed to evaluate the use of routinely collected reproductive and milk production data for the early detection of emerging vector-borne diseases in cattle in the Netherlands and the Flanders region of Belgium (i.e., the northern part of Belgium). Prospective space-time cluster analyses on residuals from a model on milk production were carried out to detect clusters of reduced milk yield. A CUSUM algorithm was used to detect temporal aberrations in model residuals of reproductive performance models on two indicators of gestation length. The Bluetongue serotype-8 (BTV-8) epidemics of 2006 and 2007 and the Schmallenberg virus (SBV) epidemic of 2011 were used as case studies to evaluate the sensitivity and timeliness of these methods. The methods investigated in this study did not result in a more timely detection of BTV-8 and SBV in the Netherlands and BTV-8 in Belgium given the surveillance systems in place when these viruses emerged. This could be due to (i) the large geographical units used in the analyses (country, region and province level), and (ii) the high level of sensitivity of the surveillance systems in place when these viruses emerged. Nevertheless, it might be worthwhile to use a syndromic surveillance system based on non-specific animal health data in real-time alongside regular surveillance, to increase the sense of urgency and to provide valuable quantitative information for decision makers in the initial phase of an emerging disease outbreak. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

    PubMed

    Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

    2014-05-01

    Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

  19. Hepatitis B virus DNA integration occurs early in the viral life cycle in an in vitro infection model via NTCP-dependent uptake of enveloped virus particles.

    PubMed

    Tu, Thomas; Budzinska, Magdalena A; Vondran, Florian W R; Shackel, Nicholas A; Urban, Stephan

    2018-02-07

    Chronic infection by the Hepatitis B Virus (HBV) is the major contributor to liver disease worldwide. Though HBV replicates via a nuclear episomal DNA (cccDNA), integration of HBV DNA into the host cell genome is regularly observed in the liver of infected patients. While reported as a pro-oncogenic alteration, the mechanism(s) and timing of HBV DNA integration are not well-understood, chiefly due to the lack of in vitro infection models that have detectable integration events. Here, we have established an in vitro system in which integration can be reliably detected following HBV infection. We measured HBV DNA integration using inverse nested PCR in primary human hepatocytes, HepaRG-NTCP, HepG2-NTCP, and Huh7-NTCP cells after HBV infection. Integration was detected in all cell types at a rate of >1 per 10000 cells, with the most consistent detection in Huh7-NTCP cells. Integration rate remained stable between 3 and 9 days post-infection. HBV DNA integration was efficiently blocked by treatment with 200nM of the HBV entry inhibitor Myrcludex B, but not with 10μM Tenofovir, 100U Interferon alpha, or 1μM of the capsid assembly inhibitor GLS4. This suggests integration of HBV DNA occurs immediately after infection of hepatocytes and is likely independent of de novo HBV replication in this model. Site analysis revealed that HBV DNA integrations were distributed over the entire human genome. Further, integrated HBV DNA sequences were consistent with double-stranded linear HBV DNA being the major precursor. Thus, we have established an in vitro system to interrogate the mechanisms of HBV DNA integration. Importance Hepatitis B Virus (HBV) is a common blood-borne pathogen and, following a chronic infection, can cause liver cancer and liver cirrhosis. Integration of HBV DNA into the host genome occurs in all known members of the hepadnaviridae family, despite this form not being necessary for viral replication. HBV DNA integration has been reported to drive liver cancer

  20. Phylogenetic Tracings of Proteome Size Support the Gradual Accretion of Protein Structural Domains and the Early Origin of Viruses from Primordial Cells

    PubMed Central

    Nasir, Arshan; Kim, Kyung Mo; Caetano-Anollés, Gustavo

    2017-01-01

    Untangling the origin and evolution of viruses remains a challenging proposition. We recently studied the global distribution of protein domain structures in thousands of completely sequenced viral and cellular proteomes with comparative genomics, phylogenomics, and multidimensional scaling methods. A tree of life describing the evolution of proteomes revealed viruses emerging from the base of the tree as a fourth supergroup of life. A tree of domains indicated an early origin of modern viral lineages from ancient cells that co-existed with the cellular ancestors. However, it was recently argued that the rooting of our trees and the basal placement of viruses was artifactually induced by small genome (proteome) size. Here we show that these claims arise from misunderstanding and misinterpretations of cladistic methodology. Trees are reconstructed unrooted, and thus, their topologies cannot be distorted a posteriori by the rooting methodology. Tracing proteome size in trees and multidimensional views of evolutionary relationships as well as tests of leaf stability and exclusion/inclusion of taxa demonstrated that the smallest proteomes were neither attracted toward the root nor caused any topological distortions of the trees. Simulations confirmed that taxa clustering patterns were independent of proteome size and were determined by the presence of known evolutionary relatives in data matrices, highlighting the need for broader taxon sampling in phylogeny reconstruction. Instead, phylogenetic tracings of proteome size revealed a slowdown in innovation of the structural domain vocabulary and four regimes of allometric scaling that reflected a Heaps law. These regimes explained increasing economies of scale in the evolutionary growth and accretion of kernel proteome repertoires of viruses and cellular organisms that resemble growth of human languages with limited vocabulary sizes. Results reconcile dynamic and static views of domain frequency distributions that are

  1. Expression kinetics of key genes in the early innate immune response to Great Lakes viral hemorrhagic septicemia virus IVb infection in yellow perch (Perca flavescens)

    USGS Publications Warehouse

    Olson, Wendy; Emmenegger, Eveline; Glenn, Jolene; Simchick, Crystal; Winton, Jim; Goetz, Frederick

    2013-01-01

    The recently discovered strain of viral hemorrhagic septicemia virus, VHSV-IVb, represents an example of the introduction of an extremely pathogenic rhabdovirus capable of infecting a wide variety of new fish species in a new host-environment. The goal of the present study was to delineate the expression kinetics of key genes in the innate immune response relative to the very early stages of VHSV-IVb infection using the yellow perch (Perca flavescens) as a model. Administration of VHSV-IVb by IP-injection into juvenile yellow perch resulted in 84% cumulative mortality, indicating their high susceptibility to this disease. In fish sampled in the very early stages of infection, a significant up-regulation of Mx gene expression in the liver, as well as IL-1β and SAA activation in the head kidney, spleen, and liver was directly correlated to viral load. The potential down-regulation of Mx in the hematopoietic tissues, head kidney and spleen, may represent a strategy utilized by the virus to increase replication.

  2. Identifying the Target Cell in Primary Simian Immunodeficiency Virus (SIV) Infection: Highly Activated Memory CD4+ T Cells Are Rapidly Eliminated in Early SIV Infection In Vivo

    PubMed Central

    Veazey, Ronald S.; Tham, Irene C.; Mansfield, Keith G.; DeMaria, MaryAnn; Forand, Amy E.; Shvetz, Daniel E.; Chalifoux, Laura V.; Sehgal, Prabhat K.; Lackner, Andrew A.

    2000-01-01

    It has recently been shown that rapid and profound CD4+ T-cell depletion occurs almost exclusively within the intestinal tract of simian immunodeficiency virus (SIV)-infected macaques within days of infection. Here we demonstrate (by three- and four-color flow cytometry) that this depletion is specific to a definable subset of CD4+ T cells, namely, those having both a highly and/or acutely activated (CD69+ CD38+ HLA-DR+) and memory (CD45RA− Leu8−) phenotype. Moreover, we demonstrate that this subset of helper T cells is found primarily within the intestinal lamina propria. Viral tropism for this particular cell type (which has been previously suggested by various studies in vitro) could explain why profound CD4+ T-cell depletion occurs in the intestine and not in peripheral lymphoid tissues in early SIV infection. Furthermore, we demonstrate that an acute loss of this specific subset of activated memory CD4+ T cells may also be detected in peripheral blood and lymph nodes in early SIV infection. However, since this particular cell type is present in such small numbers in circulation, its loss does not significantly affect total CD4+ T cell counts. This finding suggests that SIV and, presumably, human immunodeficiency virus specifically infect, replicate in, and eliminate definable subsets of CD4+ T cells in vivo. PMID:10590091

  3. Early response to the emergence of influenza A(H7N9) virus in humans in China: the central role of prompt information sharing and public communication.

    PubMed

    Vong, Sirenda; O'Leary, Michael; Feng, Zijian

    2014-04-01

    In 2003, China's handling of the early stages of the epidemic of severe acute respiratory syndrome (SARS) was heavily criticized and generally considered to be suboptimal. Following the SARS outbreak, China made huge investments to improve surveillance, emergency preparedness and response capacity and strengthen public health institutions. In 2013, the return on these investments was evaluated by investigating China's early response to the emergence of avian influenza A(H7N9) virus in humans. Clusters of human infection with a novel influenza virus were detected in China - by national surveillance of pneumonia of unknown etiology - on 26 February 2013. On 31 March 2013, China notified the World Health Organization (WHO) of the first recorded human infections with A(H7N9) virus. Poultry markets - which were rapidly identified as a major source of transmission of A(H7N9) to humans - were closed down in the affected areas. Surveillance in humans and poultry was heightened and technical guidelines were quickly updated and disseminated. The health authorities collaborated with WHO in risk assessments and risk communication. New cases were reported promptly and publicly. The relevant infrastructures, surveillance systems and response capacity need to be strengthened in preparation for future emergencies caused by emerging or existing disease threats. Results of risk assessments and other data should be released promptly and publicly and such release should not jeopardize future publication of the data in scientific journals. Coordination between public health and veterinary services would be stronger during an emergency if these services had already undertaken joint preparedness planning.

  4. Understanding the early dynamics of the 2014 porcine epidemic diarrhea virus (PEDV) outbreak in Ontario using the incidence decay and exponential adjustment (IDEA) model.

    PubMed

    Greer, Amy L; Spence, Kelsey; Gardner, Emma

    2017-01-05

    The United States swine industry was first confronted with porcine epidemic diarrhea virus (PEDV) in 2013. In young pigs, the virus is highly pathogenic and the associated morbidity and mortality has a significant negative impact on the swine industry. We have applied the IDEA model to better understand the 2014 PEDV outbreak in Ontario, Canada. Using our simple, 2-parameter IDEA model, we have evaluated the early epidemic dynamics of PEDV on Ontario swine farms. We estimated the best-fit R 0 and control parameter (d) for the between farm transmission component of the outbreak by fitting the model to publically available cumulative incidence data. We used maximum likelihood to compare model fit estimates for different combinations of the R 0 and d parameters. Using our initial findings from the iterative fitting procedure, we projected the time course of the epidemic using only a subset of the early epidemic data. The IDEA model projections showed excellent agreement with the observed data based on a 7-day generation time estimate. The best-fit estimate for R 0 was 1.87 (95% CI: 1.52 - 2.34) and for the control parameter (d) was 0.059 (95% CI: 0.022 - 0.117). Using data from the first three generations of the outbreak, our iterative fitting procedure suggests that R 0 and d had stabilized sufficiently to project the time course of the outbreak with reasonable accuracy. The emergence and spread of PEDV represents an important agricultural emergency. The virus presents a significant ongoing threat to the Canadian swine industry. Developing an understanding of the important epidemiological characteristics and disease transmission dynamics of a novel pathogen such as PEDV is critical for helping to guide the implementation of effective, efficient, and economically feasible disease control and prevention strategies that are able to help decrease the impact of an outbreak.

  5. Impact of Early Detection of Respiratory Viruses by Multiplex PCR Assay on Clinical Outcomes in Adult Patients

    PubMed Central

    Schuetz, Audrey N.; Jenkins, Stephen G.; Calfee, David P.; Walsh, Thomas J.; Wells, Martin T.; Hollenberg, James P.; Glesby, Marshall J.

    2016-01-01

    Rapid and definitive diagnosis of viral respiratory infections is imperative in patient triage and management. We compared the outcomes for adult patients with positive tests for respiratory viruses at a tertiary care center across two consecutive influenza seasons (winters of 2010-2011 and 2012). Infections were diagnosed by conventional methods in the first season and by multiplex PCR (FilmArray) in the second season. FilmArray decreased the time to diagnosis of influenza compared to conventional methods (median turnaround times of 1.7 h versus 7.7 h, respectively; P = 0.015); FilmArray also decreased the time to diagnosis of non-influenza viruses (1.5 h versus 13.5 h, respectively; P < 0.0001). Multivariate logistic regression found that a diagnosis of influenza by FilmArray was associated with significantly lower odds ratios (ORs) for admission (P = 0.046), length of stay (P = 0.040), duration of antimicrobial use (P = 0.032), and number of chest radiographs (P = 0.005), when controlling for potential confounders. We conclude that the rapid turnaround time, multiplex nature of the test (allowing simultaneous detection of an array of viruses), and superior sensitivity of FilmArray may improve the evaluation and management of patients suspected of having respiratory virus infections. PMID:27225406

  6. Early warning of West Nile virus mosquito vector: climate and land use models successfully explain phenology and abundance of Culex pipiens mosquitoes in north-western Italy.

    PubMed

    Rosà, Roberto; Marini, Giovanni; Bolzoni, Luca; Neteler, Markus; Metz, Markus; Delucchi, Luca; Chadwick, Elizabeth A; Balbo, Luca; Mosca, Andrea; Giacobini, Mario; Bertolotti, Luigi; Rizzoli, Annapaola

    2014-06-12

    West Nile Virus (WNV) is an emerging global health threat. Transmission risk is strongly related to the abundance of mosquito vectors, typically Culex pipiens in Europe. Early-warning predictors of mosquito population dynamics would therefore help guide entomological surveillance and thereby facilitate early warnings of transmission risk. We analysed an 11-year time series (2001 to 2011) of Cx. pipiens mosquito captures from the Piedmont region of north-western Italy to determine the principal drivers of mosquito population dynamics. Linear mixed models were implemented to examine the relationship between Cx. pipiens population dynamics and environmental predictors including temperature, precipitation, Normalized Difference Water Index (NDWI) and the proximity of mosquito traps to urban areas and rice fields. Warm temperatures early in the year were associated with an earlier start to the mosquito season and increased season length, and later in the year, with decreased abundance. Early precipitation delayed the start and shortened the length of the mosquito season, but increased total abundance. Conversely, precipitation later in the year was associated with a longer season. Finally, higher NDWI early in the year was associated with an earlier start to the season and increased season length, but was not associated with abundance. Proximity to rice fields predicted higher total abundance when included in some models, but was not a significant predictor of phenology. Proximity to urban areas was not a significant predictor in any of our models. Predicted variations in start of the season and season length ranged from one to three weeks, across the measured range of variables. Predicted mosquito abundance was highly variable, with numbers in excess of 1000 per trap per year when late season temperatures were low (average 21°C) to only 150 when late season temperatures were high (average 30°C). Climate data collected early in the year, in conjunction with local land

  7. Brown Dwarf Weather (Artist's Concept)

    NASA Image and Video Library

    2017-06-06

    This artist's concept shows what the weather might look like on cool star-like bodies known as brown dwarfs. These giant balls of gas start out life like stars, but lack the mass to sustain nuclear fusion at their cores, and instead, fade and cool with time. Observations from NASA's Spitzer Space Telescope suggest that most brown dwarfs are roiling with one or more planet-size storms akin to Jupiter's "Great Red Spot." https://photojournal.jpl.nasa.gov/catalog/PIA21475

  8. Geographic distribution: Boiga irregularis (Brown treesnake)

    USGS Publications Warehouse

    Knox, Adam; Holldorf, Elden; Reed, Robert N.; Igisomar, Sylvan; Gotte, Steve W.

    2015-01-01

    Rota: Rota Seaport (14.136502°N, 145.135351°E; WGS84). 3 September 2014. Shelwyn Taisacan, Robert Ulloa. Verified by G. Zug. USNM 581745. Snake (42 g, 810 mm SVL, 1020 mm total length) captured in a mouse-baited trap hung on the fence perimeter of the Rota Seaport. Because the Northern Marianas Islands are historically snake-free, these traps are used around ports and airports for early detection of snakes that may stow away in vessels or aircraft from Guam (60 km to the south), possibly evading quarantine detections. Necropsy revealed no prey items in stomach or gas- trointestinal tract. Dissection at USNM confirmed the snake was female. To our knowledge, this is the first incursion of a live Boiga irregularis on Rota. Brown Treesnakes previously observed on the island (N = 3) arrived in cargo already dead. The USGS Brown Treesnake Rapid Response Team mobilized 4 September–20 Oc- tober 2014 to search the focal and surrounding areas for evidence of a possible incipient population; no additional snakes were found during this search effort.

  9. Immediate-Early Transactivator Rta of Epstein-Barr Virus (EBV) Shows Multiple Epitopes Recognized by EBV-Specific Cytotoxic T Lymphocytes

    PubMed Central

    Pepperl, Sandra; Benninger-Döring, Gerlinde; Modrow, Susanne; Wolf, Hans; Jilg, Wolfgang

    1998-01-01

    We analyzed the immediate-early transactivator Rta of Epstein-Barr virus (EBV) for its role as a target for specific cytotoxic T lymphocytes (CTL). Panels of overlapping peptides covering the entire amino acid sequence of Rta were synthesized and used to induce and analyze specific CTL responses in EBV-positive donors. Using peptide-pulsed target cells, we found nine different CTL epitopes that are distributed over the entire protein sequence. One epitope restricted by HLA-A24 could be mapped to the decameric sequence DYCNVLNKEF between amino acid positions 28 and 37 of the Rta protein. A second epitope could be assigned to the same region of Rta (residues 25 to 39) and was shown to be restricted by HLA-B18. Another, minimal epitope could be mapped to the nonameric sequence ATIGTAMYK between amino acid positions 134 and 142; this peptide was restricted by HLA-A11. Another four epitopes were proven to be restricted by HLA-A2, -A3, -B61, and -Cw4 and were located between Rta residues 225 and 239, 145 and 159, 529 and 543, and 393 and 407, respectively. For two other epitopes, only the location within the Rta protein is known so far (residues 121 to 135 and 441 to 455); their exact HLA restriction patterns have not yet been identified. Using target cells infected with recombinant vaccinia virus containing the gene for Rta, we showed that six of eight Rta-specific CTL lines recognized the corresponding peptides also after endogenous processing. These data suggest that Rta comprises an important target for EBV-specific cellular cytotoxicity. Together with recent findings of other immediate-early and early proteins also acting as CTL targets, they reveal the role of proteins of the lytic cycle in the immune recognition of EBV-infected cells. PMID:9765404

  10. Pathobiology of Clade 2.3.4.4 H5Nx High-Pathogenicity Avian Influenza Virus Infections in Minor Gallinaceous Poultry Supports Early Backyard Flock Introductions in the Western United States in 2014-2015

    PubMed Central

    Bertran, Kateri; Lee, Dong-Hun; Pantin-Jackwood, Mary J.; Spackman, Erica; Balzli, Charles; Suarez, David L.

    2017-01-01

    ABSTRACT In 2014 and 2015, the United States experienced an unprecedented outbreak of Eurasian clade 2.3.4.4 H5 highly pathogenic avian influenza (HPAI) virus. Initial cases affected mainly wild birds and mixed backyard poultry species, while later outbreaks affected mostly commercial chickens and turkeys. The pathogenesis, transmission, and intrahost evolutionary dynamics of initial Eurasian H5N8 and reassortant H5N2 clade 2.3.4.4 HPAI viruses in the United States were investigated in minor gallinaceous poultry species (i.e., species for which the U.S. commercial industries are small), namely, Japanese quail, bobwhite quail, pearl guinea fowl, chukar partridges, and ring-necked pheasants. Low mean bird infectious doses (<2 to 3.7 log10) support direct introduction and infection of these species as observed in mixed backyard poultry during the early outbreaks. Pathobiological features and systemic virus replication in all species tested were consistent with HPAI virus infection. Sustained virus shedding with transmission to contact-exposed birds, alongside long incubation periods, may enable unrecognized dissemination and adaptation to other gallinaceous species, such as chickens and turkeys. Genome sequencing of excreted viruses revealed numerous low-frequency polymorphisms and 20 consensus-level substitutions in all genes and species, but especially in Japanese quail and pearl guinea fowl and in internal proteins PB1 and PB2. This genomic flexibility after only one passage indicates that influenza viruses can continue to evolve in galliform species, increasing their opportunity to adapt to other species. Our findings suggest that these gallinaceous poultry are permissive for infection and sustainable transmissibility with the 2014 initial wild bird-adapted clade 2.3.4.4 virus, with potential acquisition of mutations leading to host range adaptation. IMPORTANCE The outbreak of clade 2.3.4.4 H5 highly pathogenic avian influenza (HPAI) virus that occurred in the

  11. Brown at 50: Keeping Promises

    ERIC Educational Resources Information Center

    Wu, Frank H.

    2004-01-01

    The story of Brown is compelling. Blacks and Whites alike understood that the Jim Crow system of "separate but equal" was a convenient fiction. There was no actual effort to ensure that Whites and Blacks were provided the same services. Invariably, the White schools had higher funding, better buildings, newer supplies and so on. Indeed,…

  12. The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting.

    PubMed

    Elattar, Sawsan; Dimri, Manali; Satyanarayana, Ande

    2018-03-23

    Cachexia is a complex tissue-wasting syndrome characterized by inflammation, hypermetabolism, increased energy expenditure, and anorexia. Browning of white adipose tissue (WAT) is one of the significant factors that contribute to energy wasting in cachexia. By utilizing a cell implantation model, we demonstrate here that the lipid mobilizing factor zinc-α 2 -glycoprotein (ZAG) induces WAT browning in mice. Increased circulating levels of ZAG not only induced lipolysis in adipose tissues but also caused robust browning in WAT. Stimulating WAT progenitors with ZAG recombinant protein or expression of ZAG in mouse embryonic fibroblasts (MEFs) strongly enhanced brown-like differentiation. At the molecular level, ZAG stimulated peroxisome proliferator-activated receptor γ (PPARγ) and early B cell factor 2 expression and promoted their recruitment to the PR/SET domain 16 (Prdm16) promoter, leading to enhanced expression of Prdm16, which determines brown cell fate. In brown adipose tissue, ZAG stimulated the expression of PPARγ and PPARγ coactivator 1α and promoted recruitment of PPARγ to the uncoupling protein 1 (Ucp1) promoter, leading to increased expression of Ucp1. Overall, our results reveal a novel function of ZAG in WAT browning and highlight the targeting of ZAG as a potential therapeutic application in humans with cachexia.-Elattar, S., Dimri, M., Satyanarayana, A. The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting.

  13. Activation of TRPV2 negatively regulates the differentiation of mouse brown adipocytes.

    PubMed

    Sun, Wuping; Uchida, Kunitoshi; Takahashi, Nobuyuki; Iwata, Yuko; Wakabayashi, Shigeo; Goto, Tsuyoshi; Kawada, Teruo; Tominaga, Makoto

    2016-09-01

    Transient receptor potential vanilloid 2 (TRPV2) acts as a Ca(2+)-permeable non-selective cation channel that has been reported to be sensitive to temperature, mechanical force, and some chemicals. We recently showed that TRPV2 is critical for maintenance of the thermogenic function of brown adipose tissue in mice. However, the involvement of TRPV2 in the differentiation of brown adipocytes remains unexplored. We found that the expression of TRPV2 was dramatically increased during the differentiation of brown adipocytes. Non-selective TRPV2 agonists (2-aminoethoxydiphenyl borate and lysophosphatidylcholine) inhibited the differentiation of brown adipocytes in a dose-dependent manner during the early stage of differentiation of brown adipocytes. The inhibition was rescued by a TRPV2-selective antagonist, SKF96365 (SKF). Mechanical force, which activates TRPV2, also inhibited the differentiation of brown adipocytes in a strength-dependent manner, and the effect was reversed by SKF. In addition, the inhibition of adipocyte differentiation by either TRPV2 ligand or mechanical stimulation was significantly smaller in the cells from TRPV2KO mice. Moreover, calcineurin inhibitors, cyclosporine A and FK506, partially reversed TRPV2 activation-induced inhibition of brown adipocyte differentiation. Thus, we conclude that TRPV2 might be involved in the modulation of brown adipocyte differentiation partially via a calcineurin pathway.

  14. 21 CFR 184.1120 - Brown algae.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Brown algae. 184.1120 Section 184.1120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1120 Brown algae. (a) Brown algae are seaweeds of the species Analipus...

  15. 21 CFR 184.1120 - Brown algae.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Brown algae. 184.1120 Section 184.1120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1120 Brown algae. (a) Brown algae are seaweeds of the species Analipus...

  16. 21 CFR 184.1120 - Brown algae.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Brown algae. 184.1120 Section 184.1120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD....1120 Brown algae. (a) Brown algae are seaweeds of the species Analipus japonicus, Eisenia bicyclis...

  17. 21 CFR 184.1120 - Brown algae.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Brown algae. 184.1120 Section 184.1120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1120 Brown algae. (a) Brown algae are seaweeds of the species Analipus...

  18. 21 CFR 184.1120 - Brown algae.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Brown algae. 184.1120 Section 184.1120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1120 Brown algae. (a) Brown algae are seaweeds of the species Analipus...

  19. Brown Dwarf Companion Frequencies and Dynamical Interactions

    NASA Astrophysics Data System (ADS)

    Sterzik, Michael F.; Durisen, Richard H.

    2003-06-01

    Numerical simulations are used to explore how gravitational interactions within young multiple star systems may determine the binary properties of brown dwarfs. We compare different scenarios for cluster formation and decay and find that brown dwarf binaries, although possible, generally have a low frequency. We also discuss the frequencies of brown dwarf companions to normal stars expected from these models.

  20. 7 CFR 29.2254 - Brown colors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Brown colors. 29.2254 Section 29.2254 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... colors. A group of colors ranging from a reddish brown to yellowish brown. These colors vary from low to...

  1. The brown dwarf kinematics project

    NASA Astrophysics Data System (ADS)

    Faherty, Jackie K.

    2010-10-01

    Brown dwarfs are a recent addition to the plethora of objects studied in Astronomy. With theoretical masses between 13 and 75 MJupiter , they lack sustained stable Hydrogen burning so they never join the stellar main sequence. They have physical properties similar to both planets and low-mass stars so studies of their population inform on both. The distances and kinematics of brown dwarfs provide key statistical constraints on their ages, moving group membership, absolute brightnesses, evolutionary trends, and multiplicity. Yet, until my thesis, fundamental measurements of parallax and proper motion were made for only a relatively small fraction of the known population. To address this deficiency, I initiated the Brown Dwarf Kinematics (BDKP). Over the past four years I have re-imaged the majority of spectroscopically confirmed field brown dwarfs (or ultracool dwarfs---UCDs) and created the largest proper motion catalog for ultracool dwarfs to date. Using new astrometric information I examined population characteristics such as ages calculated from velocity dispersions and correlations between kinematics and colors. Using proper motions, I identified several new wide co-moving companions and investigated binding energy (and hence formation) limitations as well as the frequency of hierarchical companions. Concurrently over the past four years I have been conducting a parallax survey of 84 UCDs including those showing spectral signatures of youth, metal-poor brown dwarfs, and those within 20 pc of the Sun. Using absolute magnitude relations in J,H, and K, I identified overluminous binary candidates and investigated known flux-reversal binaries. Using current evolutionary models, I compared the MK vs J-K color magnitude diagram to model predictions and found that the low-surface gravity dwarfs are significantly red-ward and underluminous of predictions and a handful of late-type T dwarfs may require thicker clouds to account for their scatter.

  2. Antigenic Detection of Human Strain of Influenza Virus A (H3N2) in Swine Populations at Three Locations in Nigeria and Ghana during the Dry Early Months of 2014.

    PubMed

    Adeola, O A; Olugasa, B O; Emikpe, B O

    2016-03-01

    Since the first detection of human H3N2 influenza virus in Taiwanese pigs in 1970, infection of pigs with wholly human viruses has been known to occur in other parts of the world. These viruses, referred to as human-like H3N2 viruses, have been known to cause clinical and subclinical infections of swine populations. Due to the paucity and complete unavailability of information on transmission of influenza viruses from other species, especially humans, to swine in Nigeria and Ghana, respectively, this study was designed to investigate the presence and prevalence of a human strain of influenza A (H3N2) in swine populations at three locations in two cities within these two West African countries in January and February, 2014. Using stratified random technique, nasal swab specimens were collected from seventy-five (75) pigs at two locations in Ibadan, Nigeria and from fifty (50) pigs in Kumasi, Ghana. These specimens were tested directly by a sensitive Quantitative Solid Phase Antigen-detection Sandwich ELISA using anti-A/Brisbane/10/2007 haemagglutinin monoclonal antibody. Influenza virus A/Brisbane/10/2007 (H3N2) was detected among pigs at the three study locations, with an aggregate prevalence of 4.0% for the two locations in Ibadan, Nigeria and also 4.0% for Kumasi, Ghana. Transmission of influenza viruses from other species to swine portends serious sinister prospects for genetic reassortment and evolvement of novel viruses. We therefore recommend that further studies should be carried out to investigate the presence of other circulating human and avian influenza viruses in swine populations in West Africa and also determine the extent of genetic reassortment of strains circulating among these pigs. This would provide an early warning system for detection of novel influenza viruses, which could have pandemic potentials. © 2015 Blackwell Verlag GmbH.

  3. Investigation of airborne foot-and-mouth disease virus transmission during low-wind conditions in the early phase of the UK 2001 epidemic

    NASA Astrophysics Data System (ADS)

    Mikkelsen, T.; Alexandersen, S.; Astrup, P.; Champion, H. J.; Donaldson, A. I.; Dunkerley, F. N.; Gloster, J.; Sørensen, J. H.; Thykier-Nielsen, S.

    2003-11-01

    Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed domesticated and wild animals. The highly contagious nature of FMD is a reflection of the wide range of host species, the enormous quantities of virus liberated by infected animals, the range of excretions and secretions which can be infectious, the stability of the virus in the environment, the multiplicity of routes of infection and the very small doses of the virus that can initiate infection. One of the mechanisms of spread is the carriage of droplets and droplet nuclei exhaled in the breath of infected animals. Such spread can be rapid and extensive, and it is known in certain circumstances to have transmitted disease over a distance of several hundred kilometres. During the 2001 FMD epidemic in the United Kingdom (UK), atmospheric dispersion models were applied in real time in order to assess the potential for atmospheric dispersion of the disease. The operational value of such modelling is primarily to identify premises which may have been exposed so that the human resources for surveillance and disease control purposes are employed most effectively.

    The paper describes the combined modelling techniques and presents the results obtained of detailed analyses performed during the early stages of the UK 2001 epidemic. This paper investigates the potential for disease spread in relation to two outbreaks (Burnside Farm, Heddon-on-the-Wall and Prestwick Hall Farm, Ponteland, Northumberland). A separate paper (Gloster et al., 2002) provides a more detailed analysis of the airborne disease transmission in the vicinity of Burnside Farm.

    The combined results are consistent with airborne transmission of disease to livestock in the Heddon-on-the-Wall area. Local topography may have played a significant role in influencing the pattern of disease spread.

  4. Investigation of airborne foot-and-mouth disease virus transmission during low-wind conditions in the early phase of the UK 2001 epidemic

    NASA Astrophysics Data System (ADS)

    Mikkelsen, T.; Alexandersen, S.; Astrup, P.; Champion, H. J.; Donaldson, A. I.; Dunkerley, F. N.; Gloster, J.; Sørensen, J. H.; Thykier-Nielsen, S.

    2003-02-01

    Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed domesticated and wild animals. The highly contagious nature of FMD is a reflection of the wide range of host species, the enormous quantities of virus liberated by infected animals, the range of excretions and secretions which can be infectious, the stability of the virus in the environment, the multiplicity of routes of infection and the very small doses of the virus that can initiate infection. One of the mechanisms of spread is the carriage of droplets and droplet nuclei exhaled in the breath of infected animals. Such spread can be rapid and extensive, and it is known in certain circumstances to have transmitted disease over a distance of several hundred kilometres. During the 2001 FMD epidemic in the United Kingdom (UK), atmospheric dispersion models were applied in real time in order to assess the potential for atmospheric dispersion of the disease. The operational value of such modelling is primarily to identify premises which may have been exposed so that the human resources for surveillance and disease control purposes are employed most effectively. The paper describes the combined modelling techniques and presents the results obtained of detailed analyses performed during the early stages of the UK 2001 epidemic. This paper investigates the potential for disease spread in relation to two outbreaks (Burnside Farm, Heddon-on-the-Wall and Prestwick Hall Farm, Ponteland, Northumberland). A separate paper (Gloster et al., 2002) provides a more detailed analysis of the airborne disease transmission in the vicinity of Burnside Farm. The combined results are consistent with airborne transmission of disease to livestock in the Heddon-on-the Wall area. Local topography may have played a significant role in influencing the pattern of disease spread.

  5. CTCF Occupation of the Herpes Simplex Virus 1 Genome Is Disrupted at Early Times Postreactivation in a Transcription-Dependent Manner

    PubMed Central

    Ertel, Monica K.; Cammarata, Amy L.; Hron, Rebecca J.

    2012-01-01

    In herpes simplex virus 1 (HSV-1), binding clusters enriched in CTCF during latency have been previously identified. We hypothesized that CTCF binding to CTCF clusters in HSV-1 would be disrupted in a reactivation event. To investigate, CTCF occupation of three CTCF binding clusters in HSV-1 was analyzed following sodium butyrate (NaB)- and explant-induced reactivation in the mouse. Our data show that the CTCF domains positioned within the HSV-1 genome, specifically around the latency-associated transcript (LAT) and ICP0 and ICP4 regions of the genome, lose CTCF occupancy following the application of reactivation stimuli in wild-type virus. We also found that CTCF binding clusters upstream of the ICP0 and ICP4 promoters both function as classical insulators capable of acting as enhancer blockers of the LAT enhancer. Finally, our results suggest that CTCF occupation of domains in HSV-1 may be differentially regulated both during latency and at early times following reactivation by the presence of lytic transcripts and further implicate epigenetic regulation of HSV-1 as a critical component of the latency-reactivation transition. PMID:22973047

  6. Induction of immune response in macaque monkeys infected with simian-human immunodeficiency virus having the TNF-{alpha} gene at an early stage of infection

    SciTech Connect

    Shimizu, Yuya; Miyazaki, Yasuyuki; Ibuki, Kentaro

    2005-12-20

    TNF-{alpha} has been implicated in the pathogenesis of, and the immune response against, HIV-1 infection. To clarify the roles of TNF-{alpha} against HIV-1-related virus infection in an SHIV-macaque model, we genetically engineered an SHIV to express the TNF-{alpha} gene (SHIV-TNF) and characterized the virus's properties in vivo. After the acute viremic stage, the plasma viral loads declined earlier in the SHIV-TNF-inoculated monkeys than in the parental SHIV (SHIV-NI)-inoculated monkeys. SHIV-TNF induced cell death in the lymph nodes without depletion of circulating CD4{sup +} T cells. SHIV-TNF provided some immunity in monkeys by increasing the production of the chemokine RANTES andmore » by inducing an antigen-specific proliferation of lymphocytes. The monkeys immunized with SHIV-TNF were partly protected against a pathogenic SHIV (SHIV-C2/1) challenge. These findings suggest that TNF-{alpha} contributes to the induction of an effective immune response against HIV-1 rather than to the progression of disease at the early stage of infection.« less

  7. The Early Gulf of Mexico as a Subaerial Basin Below Sea Level (SABSEL) Basin. Evidence from Stratigraphy and Facies of Luanne salt, Norphlet sandstone and Smackover Brown Dense Formations.

    NASA Astrophysics Data System (ADS)

    Cassidy, M. M.

    2016-12-01

    Many workers recognize that large salt deposits form in post-rift sag basins which were subaerial and susceptible to rapid flooding from adjacent oceansl. I have termed these basins "subaerial basins below sea level" or "SABSEL" basins. A key marker of SABSEL basins are terrestrial sediments immediately overlain by deepwater sediments with no transition. Desert deposits -including Aeolian dunes- are preserved in the adiabatically heated depression. Dunes are not eroded by transgressing seas but are drowned by rising water as in a bath tub. They maintain their shape. Deepwater marine black shales or limestones drape the dunes. The Southern North sea is an example. Above the original marine shale over the dunes are evaporites. Winds descending into the basin were heated by adiabatic compression providing the very hot air need to allow survival of potassium salts. A similar situation was probably active during the Messinian salinity crisis in the Mediterranean basin, and the opening of the South Atlantic. In the Gulf of Mexico (GOM) a desert is on the Louann salt. Here the sea invaded the lows first to deposit the salt overlying tilted fault blocks of the opening basin, as in the Afar Triangle of Africa. In the GOM entry to the west fed in sea water, then closed. The Norphlet desert formed. Streams carried sands to the basin to be spread by winds where they willed, not limited to sand entry areas. Upon deposition their original weight depressed the salt. Seismic shows depressions in the salt but the dunes are high at the top Norphlet, forming distinctive small "eyes" at the top salt. The 600 foot dunes are draped by deep water dolomitic finely laminated organic rich black/ brown shale, the Brown Dense Facies of the Smackover formation. The lack of reworking of the dunes found by detailed seismic is distinctive of deposition in a SABSEL basin. The overlap of terrestrial sediments by deep water deposition is good evidence of sudden flooding. In summary this vertical

  8. Inhibition of Nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry.

    PubMed

    Porotto, Matteo; Rockx, Barry; Yokoyama, Christine C; Talekar, Aparna; Devito, Ilaria; Palermo, Laura M; Liu, Jie; Cortese, Riccardo; Lu, Min; Feldmann, Heinz; Pessi, Antonello; Moscona, Anne

    2010-10-28

    In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.

  9. Inhibition of Nipah Virus Infectin In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry

    SciTech Connect

    M Porotto; B Rockx; C Yokoyama

    2011-12-31

    In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viralmore » and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.« less

  10. The first cases of 2009 pandemic influenza A (H1N1) virus infection in the United States: a serologic investigation demonstrating early transmission

    PubMed Central

    Fry, Alicia M.; Hancock, Kathy; Patel, Minal; Gladden, Matthew; Doshi, Saumil; Blau, Dianna M.; Sugerman, David; Veguilla, Vic; Lu, Xiuhua; Noland, Heather; Bai, Yaohui; Maroufi, Azarnoush; Kao, Annie; Kriner, Paula; Lopez, Karla; Ginsberg, Michele; Jain, Seema; Olsen, Sonja J.; Katz, Jacqueline M.

    2012-01-01

    Please cite this paper as: Fry et al. (2012) The first cases of 2009 pandemic influenza A (H1N1) virus infection in the United States: a serologic investigation demonstrating early transmission. Influenza and Other Respiratory Viruses 6(3), e48–e53. Background  The first two laboratory‐confirmed cases of 2009 pandemic influenza A (H1N1) virus (H1N1pdm09) infection were detected in San Diego (SD) and Imperial County (IC) in southern California, April 2009. Objectives  To describe H1N1pdm09 infections and transmission early in the 2009 H1N1 pandemic. Patients/Methods  We identified index case‐patients from SD and IC with polymerase chain reaction (PCR)‐confirmed H1N1pdm09 infections and investigated close contacts for a subset of case‐patients from April 17–May 6, 2009. Acute and convalescent serum was collected. Serologic evidence for H1N1pdm09 infection was determined by microneutralization and hemagglutination inhibition assays. Results  Among 75 close contacts of seven index case‐patients, three reported illness onset prior to patient A or B, including two patient B contacts and a third with no links to patient A or B. Among the 69 close contacts with serum collected >14 days after the onset of index case symptoms, 23 (33%) were seropositive for H1N1pdm09, and 8 (35%) had no fever, cough, or sore throat. Among 15 household contacts, 8 (53%) were seropositive for H1N1pdm09. The proportion of contacts seropositive for H1N1pdm09 was highest in persons aged 5–24 years (50%) and lowest in persons aged ≥50 years (13%) (P = 0·07). Conclusions  By the end of April 2009, before H1N1pdm09 was circulating widely in the community, a third of persons with close contact to confirmed H1N1pdm09 cases had H1N1pdm09 infection in SD and IC. Three unrelated clusters during March 21–30 suggest that transmission of H1N1pdm09 had begun earlier in southern California. PMID:22353441

  11. A novel double recognition enzyme-linked immunosorbent assay based on the nucleocapsid protein for early detection of European porcine reproductive and respiratory syndrome virus infection.

    PubMed

    Venteo, A; Rebollo, B; Sarraseca, J; Rodriguez, M J; Sanz, A

    2012-04-01

    Precise and rapid detection of porcine reproductive respiratory syndrome virus (PRRSV) infection in swine farms is critical. Improvement of control procedures, such as testing incoming gilt and surveillance of seronegative herds requires more rapid and sensitive methods. However, standard serological techniques detect mainly IgG antibodies. A double recognition enzyme-linked immunosorbent assay (DR-ELISA) was developed for detection of antibodies specific to European PRRSV. This new assay can recognize both IgM and IgG antibodies to PRSSV which might be useful for detecting in routine surveillance assays pigs that are in the very early stages of infection and missed by conventional assays detecting only IgG antibodies. DR-ELISA is based on the double recognition of antigen by antibody. In this study, the recombinant nucleocapsid protein (N) of PRRSV was used both as the coating and the enzyme-conjugated antigen. To evaluate the sensitivity of the assay at early stages of the infection, sera from 69 pigs infected with PRRSV were collected during successive days post infection (pi) and tested. While standard methods showed low sensitivity rates before day 14 pi, DR-ELISA detected 88.4% seropositive samples at day 7 showing greater sensitivity at early stages of the infection. Further studies were carried out to assess the efficiency of the new assay, and the results showed DR-ELISA to be a sensitive and accurate method for early diagnosis of EU-PRRSV infection. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Plum Pox Virus 6K1 Protein Is Required for Viral Replication and Targets the Viral Replication Complex at the Early Stage of Infection.

    PubMed

    Cui, Hongguang; Wang, Aiming

    2016-05-15

    The potyviral RNA genome encodes two polyproteins that are proteolytically processed by three viral protease domains into 11 mature proteins. Extensive molecular studies have identified functions for the majority of the viral proteins. For example, 6K2, one of the two smallest potyviral proteins, is an integral membrane protein and induces the endoplasmic reticulum (ER)-originated replication vesicles that target the chloroplast for robust viral replication. However, the functional role of 6K1, the other smallest protein, remains uncharacterized. In this study, we developed a series of recombinant full-length viral cDNA clones derived from a Canadian Plum pox virus (PPV) isolate. We found that deletion of any of the short motifs of 6K1 (each of which ranged from 5 to 13 amino acids), most of the 6K1 sequence (but with the conserved sequence of the cleavage sites being retained), or all of the 6K1 sequence in the PPV infectious clone abolished viral replication. The trans expression of 6K1 or the cis expression of a dislocated 6K1 failed to rescue the loss-of-replication phenotype, suggesting the temporal and spatial requirement of 6K1 for viral replication. Disruption of the N- or C-terminal cleavage site of 6K1, which prevented the release of 6K1 from the polyprotein, either partially or completely inhibited viral replication, suggesting the functional importance of the mature 6K1. We further found that green fluorescent protein-tagged 6K1 formed punctate inclusions at the viral early infection stage and colocalized with chloroplast-bound viral replicase elements 6K2 and NIb. Taken together, our results suggest that 6K1 is required for viral replication and is an important viral element of the viral replication complex at the early infection stage. Potyviruses account for more than 30% of known plant viruses and consist of many agriculturally important viruses. The genomes of potyviruses encode two polyproteins that are proteolytically processed into 11 mature

  13. Plum Pox Virus 6K1 Protein Is Required for Viral Replication and Targets the Viral Replication Complex at the Early Stage of Infection

    PubMed Central

    Cui, Hongguang

    2016-01-01

    ABSTRACT The potyviral RNA genome encodes two polyproteins that are proteolytically processed by three viral protease domains into 11 mature proteins. Extensive molecular studies have identified functions for the majority of the viral proteins. For example, 6K2, one of the two smallest potyviral proteins, is an integral membrane protein and induces the endoplasmic reticulum (ER)-originated replication vesicles that target the chloroplast for robust viral replication. However, the functional role of 6K1, the other smallest protein, remains uncharacterized. In this study, we developed a series of recombinant full-length viral cDNA clones derived from a Canadian Plum pox virus (PPV) isolate. We found that deletion of any of the short motifs of 6K1 (each of which ranged from 5 to 13 amino acids), most of the 6K1 sequence (but with the conserved sequence of the cleavage sites being retained), or all of the 6K1 sequence in the PPV infectious clone abolished viral replication. The trans expression of 6K1 or the cis expression of a dislocated 6K1 failed to rescue the loss-of-replication phenotype, suggesting the temporal and spatial requirement of 6K1 for viral replication. Disruption of the N- or C-terminal cleavage site of 6K1, which prevented the release of 6K1 from the polyprotein, either partially or completely inhibited viral replication, suggesting the functional importance of the mature 6K1. We further found that green fluorescent protein-tagged 6K1 formed punctate inclusions at the viral early infection stage and colocalized with chloroplast-bound viral replicase elements 6K2 and NIb. Taken together, our results suggest that 6K1 is required for viral replication and is an important viral element of the viral replication complex at the early infection stage. IMPORTANCE Potyviruses account for more than 30% of known plant viruses and consist of many agriculturally important viruses. The genomes of potyviruses encode two polyproteins that are proteolytically

  14. Brown continues crusade against earmarking

    NASA Astrophysics Data System (ADS)

    Leath, Audrey T.

    House Science Committee Chairman George Brown (D-Calif.), a crusader against earmarking of academic research and facilities, continues his efforts to raise the subject's visibility with a new report that was released on August 9."Academic Earmarks: An Interim Report by the Chairman of the Committee on Science, Space, and Technology" includes preliminary results of a survey of about fifty institutions receiving recent earmarks and offers a trio of recommendations to help stem the flood of unauthorized projects.

  15. Brown continues crusade against earmarking

    NASA Astrophysics Data System (ADS)

    Leath, Audrey T.

    House Science Committee Chairman George Brown (D-Calif.), a crusader against earmarking of academic research and facilities, continues his efforts to raise the subject's visibility with a new report that was released on August 9.“Academic Earmarks: An Interim Report by the Chairman of the Committee on Science, Space, and Technology” includes preliminary results of a survey of about fifty institutions receiving recent earmarks and offers a trio of recommendations to help stem the flood of unauthorized projects.

  16. Brown Dwarf HIP 79124 B

    NASA Image and Video Library

    2017-01-30

    This image shows brown dwarf HIP 79124 B, located 23 times as far from its host star as Earth is from the sun. The vortex coronagraph, an instrument at the W.M. Keck Observatory, was used to suppress light from the much brighter host star, allowing its dim companion to be imaged for the first time. http://photojournal.jpl.nasa.gov/catalog/PIA21417

  17. Irradiation for quarantine control of the invasive light brown apple moth, Epiphyas

    USDA-ARS?s Scientific Manuscript database

    The effects of irradiation on egg, larval, and pupal development, and adult reproduction in light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae), were examined. Eggs, neonates, early instars, late instars, early pupae and late pupae were irradiated at target doses of 60, ...

  18. Drought increases cowpea (Vigna unguiculata [L.] Walp.) susceptibility to cowpea severe mosaic virus (CPSMV) at early stage of infection.

    PubMed

    Silva, Rodolpho G G; Vasconcelos, Ilka M; Martins, Thiago F; Varela, Anna L N; Souza, Pedro F N; Lobo, Ana K M; Silva, Fredy D A; Silveira, Joaquim A G; Oliveira, Jose T A

    2016-12-01

    The physiological and biochemical responses of a drought tolerant, virus-susceptible cowpea genotype exposed to drought stress (D), infected by Cowpea severe mosaic virus (CPSMV) (V), and to these two combined stresses (DV), at 2 and 6 days post viral inoculation (DPI), were evaluated. Gas exchange parameters (net photosynthesis, transpiration rate, stomatal conductance, and internal CO 2 partial pressure) were reduced in D and DV at 2 and 6 DPI compared to control plants (C). Photosynthesis was reduced by stomatal and biochemical limitations. Water use efficiency increased at 2 DPI in D, DV, and V, but at 6 DPI only in D and DV compared to C. Photochemical parameters (effective quantum efficiency of photosystem II and electron transport rate) decreased in D and DV compared to C, especially at 6 DPI. The potential quantum efficiency of photosystem II did not change, indicating reversible photoinhibition of photosystem II. In DV, catalase decreased at 2 and 6 DPI, ascorbate peroxidase increased at 2 DPI, but decreased at 6 DPI. Hydrogen peroxide increased at 2 and 6 DPI. Peroxidase increased at 6 DPI and chitinase at 2 and 6 DPI. β-1,3-glucanase decreased in DV at 6 DPI compared to V. Drought increased cowpea susceptibility to CPSMV at 2 DPI, as verified by RT-PCR. However, at 6 DPI, the cowpea plants overcome this effect. Likewise, CPSMV increased the negative effects of drought at 2 DPI, but not at 6 DPI. It was concluded that the responses to combined stresses are not additive and cannot be extrapolated from the study of individual stresses. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Surveillance plan for the early detection of H5N1 highly pathogenic avian influenza virus in migratory birds in the United States: surveillance year 2009

    USGS Publications Warehouse

    Brand, Christopher J.

    2009-01-01

    Executive Summary: This Surveillance Plan (Plan) describes plans for conducting surveillance of wild birds in the United States and its Territories and Freely-Associated States to provide for early detection of the introduction of the H5N1 Highly Pathogenic Avian Influenza (HPAI) subtype of the influenza A virus by migratory birds during the 2009 surveillance year, spanning the period of April 1, 2009 - March 31, 2010. The Plan represents a continuation of surveillance efforts begun in 2006 under the Interagency Strategic Plan for the Early Detection of H5N1 Highly Pathogenic Avian Influenza in Wild Migratory Birds (U.S. Department of Agriculture and U.S. Department of the Interior, 2006). The Plan sets forth sampling plans by: region, target species or species groups to be sampled, locations of sampling, sample sizes, and sampling approaches and methods. This Plan will be reviewed annually and modified as appropriate for subsequent surveillance years based on evaluation of information from previous years of surveillance, changing patterns and threats of H5N1 HPAI, and changes in funding availability for avian influenza surveillance. Specific sampling strategies will be developed accordingly within each of six regions, defined here as Alaska, Hawaiian/Pacific Islands, Lower Pacific Flyway (Washington, Oregon, California, Idaho, Nevada, Arizona), Central Flyway, Mississippi Flyway, and Atlantic Flyway.

  20. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.

    PubMed

    Marchandeau, Stéphane; Pontier, Dominique; Guitton, Jean-Sébastien; Letty, Jérôme; Fouchet, David; Aubineau, Jacky; Berger, Francis; Léonard, Yves; Roobrouck, Alain; Gelfi, Jacqueline; Peralta, Brigitte; Bertagnoli, Stéphane

    2014-03-04

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.

  1. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations

    PubMed Central

    2014-01-01

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen. PMID:24589193

  2. Chemical Decontamination at Browns Ferry Unit 1

    SciTech Connect

    Hartwig, Ed; Reid, Richard

    2003-09-01

    In May, 2002, the Tennessee Valley Authority's (TVA) Board of Directors approved the recovery and restart of Unit 1 at Browns Ferry Nuclear Station. As an initial step in the site characterization and restart feasibility review, a majority of the primary reactor circuit was chemically decontaminated. Close cooperation between TVA and vendor personnel resulted in project completion ahead of schedule with outstanding results. The final average decontamination factors were excellent, and the final dose rates were very low, with contact readings on most points between one and three mRem/hr. In addition to allowing TVA to do a complete and thoroughmore » job of determining the feasibility of the Unit 1 restart, the decontamination effort will greatly reduce personnel exposure during plant recovery, both whole body exposure to gamma radiation and airborne exposure during pipe replacement efforts. The implementation of lessons learned from previous decontamination work performed at Browns Ferry, as well as decontamination efforts at other plants aided greatly in the success. Specific items of note are: (1) The initial leak check of the temporary decontamination system should include ancillary systems such as the spent resin system, as well as the main circulation loop. This could save time and dose exposure if leaks are discovered before the use of such systems is required. (2) Due to the quick turnaround time from the award of contract, a vendor representative was onsite early in the project to help with engineering efforts and procedures. This aided greatly in completing preparations for the decontamination. (3) The work was performed under a single maintenance activity. This resulted in great craft and plant support. (4) The constant coverage by the site's decontamination flush directors provided timely plant support and interface. (5) The FPC system isolation and back flushing to prevent residual chemicals from being left in the FPC system should have been addressed

  3. [AVIAN RECOMBINANT VIRUS H5N1 INFLUENZA (A/VIETNAM/1203/04) AND ITS ESCAPE-MUTANT m13(13) INDUCE EARLY SIGNALING REACTIONS OF THE IMMUNITY IN HUMAN LYMPHOCYTES].

    PubMed

    Sokolova, T M; Poloskov, V V; Shuvalov, A N; Rudneva, I A; Ershov, F I

    2016-01-01

    The innate immune receptors TLR4, TLR7, TLR8, and RIG1 recognized the structures of the influenza viruses in human lymphocytes and were activated by the recombinant avian influenza virus A/Vietnam/1203/04 and its escape-mutant m13(13) during early period of interaction. The stimulated levels are not connected with viral reproduction. Donor cells with the low constitutive immune receptors gene expression levels showed higher stimulation. Inflammation virus effects resulted in. increasing production of TNF-alpha and IFN-gamma by lymphocytes. Signaling gene reactions of the parent and mutant viruses endosomal as well as cytoplasmic receptors are very similar. The mutant virus A/Vietnam/1203/04 (HA S145F), stimulated an increase in the transcription level of the membrane receptor gene TLR4 and a decrease in the level of activation of TNF-alpha gene. Further studies of natural influenza virus isolates are necessary to estimate the role of HA antigenic changes on immune reactions in humans.

  4. The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection

    PubMed Central

    Ibekwe, Titus S.; Nwegbu, Maxwell M.; Asogun, Daniel; Adomeh, Donatus I.; Okokhere, Peter O.

    2012-01-01

    Background: Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. Patients and Methods: A prospective case–control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Results: Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. Conclusion: The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF “rapid screening kit” since RT-PCR is unavailable in most centers. In the interim, “high clinical index of suspicion,” irrespective of IgM status, requires urgent referral to confirmatory centers. PMID:23661877

  5. The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection.

    PubMed

    Ibekwe, Titus S; Nwegbu, Maxwell M; Asogun, Daniel; Adomeh, Donatus I; Okokhere, Peter O

    2012-10-01

    Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. A prospective case-control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF "rapid screening kit" since RT-PCR is unavailable in most centers. In the interim, "high clinical index of suspicion," irrespective of IgM status, requires urgent referral to confirmatory centers.

  6. The Assessment of African Swine Fever Virus Risk to Belgium Early 2014, using the Quick and Semiquantitative Pandora Screening Protocol.

    PubMed

    Roelandt, S; Van der Stede, Y; D'hondt, B; Koenen, F

    2017-02-01

    A risk assessment was organized during the early EU ASF outbreaks of early 2014 (February-April) and performed in cooperation with 15 Belgian and European experts on ASFV and its epidemiology in pigs/wild boar. African swine fever (ASF) is considered as one of the most dangerous infectious pig diseases, causing many outbreaks. Since the end of 2013 - early 2014, several outbreaks within the European Union (Lithuania, Poland, Estonia and Latvia) were reported to OIE, which prompted several risk assessments by (inter)national bodies and scientists. In this study, the open source, semiquantitative Pandora risk assessment tool was used for a quick overall screening of the risk posed by ASF to Belgium early 2014. A set of integrated risk scores was calculated within the Pandora framework. Experts scored the questions and uncertainty levels in the Pandora modules individually, after which the calculations were performed and averaged scores were used within pre-defined risk scales to define and visualize the ASF risk to Belgium. Emergence risk was considered low (Pandora score 0.29), while disease consequences were deemed high (0.93); the resulting multiplicative overall risk of ASFV for Belgium was low (0.27). The Belgian experts tended to give lower risk scores than the European experts, especially for entry risk and trade/public opinion consequences. These risk scores are further interpreted with a due consideration of the qualitative data in the expert remarks and of other ASF risk assessments. The results are similar to more extensive and elaborate risk assessment models/procedures which may require more time and resources. The Pandora tool allows sequential updates to monitor (rates of) increasing risk and provides information for risk managers to organize targeted control. © 2015 Blackwell Verlag GmbH.

  7. Arctic Tundra Greening and Browning at Circumpolar and Regional Scales

    NASA Astrophysics Data System (ADS)

    Epstein, H. E.; Bhatt, U. S.; Walker, D. A.; Raynolds, M. K.; Yang, X.

    2017-12-01

    Remote sensing data have historically been used to assess the dynamics of arctic tundra vegetation. Until recently the scientific literature has largely described the "greening" of the Arctic; from a remote sensing perspective, an increase in the Normalized Difference Vegetation Index (NDVI), or a similar satellite-based vegetation index. Vegetation increases have been heterogeneous throughout the Arctic, and were reported to be up to 25% in certain areas over a 30-year timespan. However, more recently, arctic tundra vegetation dynamics have gotten more complex, with observations of more widespread tundra "browning" being reported. We used a combination of remote sensing data, including the Global Inventory Monitoring and Modeling System (GIMMS), as well as higher spatial resolution Landsat data, to evaluate the spatio-temporal patterns of arctic tundra vegetation dynamics (greening and browning) at circumpolar and regional scales over the past 3-4 decades. At the circumpolar scale, we focus on the spatial heterogeneity (by tundra subzone and continent) of tundra browning over the past 5-15 years, followed by a more recent recovery (greening since 2015). Landsat time series allow us to evaluate the landscape-scale heterogeneity of tundra greening and browning for northern Alaska and the Yamal Peninsula in northwestern Siberia, Russia. Multi-dataset analyses reveal that tundra greening and browning (i.e. increases or decreases in the NDVI respectively) are generated by different sets of processes. Tundra greening is largely a result of either climate warming, lengthening of the growing season, or responses to disturbances, such as fires, landslides, and freeze-thaw processes. Browning on the other hand tends to be more event-driven, such as the shorter-term decline in vegetation due to fire, insect defoliation, consumption by larger herbivores, or extreme weather events (e.g. winter warming or early summer frost damage). Browning can also be caused by local or

  8. Does human immunodeficiency virus status affect early wound healing in open surgically stabilised tibial fractures?: A prospective study.

    PubMed

    Howard, N E; Phaff, M; Aird, J; Wicks, L; Rollinson, P

    2013-12-01

    We compared early post-operative rates of wound infection in HIV-positive and -negative patients presenting with open tibial fractures managed with surgical fixation. The wounds of 84 patients (85 fractures), 28 of whom were HIV positive and 56 were HIV negative, were assessed for signs of infection using the ASEPIS wound score. There were 19 women and 65 men with a mean age of 34.8 years. A total of 57 fractures (17 HIV-positive, 40 HIV-negative) treated with external fixation were also assessed using the Checkett score for pin-site infection. The remaining 28 fractures were treated with internal fixation. No significant difference in early post-operative wound infection between the two groups of patients was found (10.7% (n = 3) vs 19.6% (n = 11); relative risk (RR) 0.55 (95% confidence interval (CI) 0.17 to 1.8); p = 0.32). There was also no significant difference in pin-site infection rates (17.6% (n = 3) vs 12.5% (n = 5); RR 1.62 (95% CI 0.44 to 6.07); p = 0.47). The study does not support the hypothesis that HIV significantly increases the rate of early wound or pin-site infection in open tibial fractures. We would therefore suggest that a patient's HIV status should not alter the management of open tibial fractures in patients who have a CD4 count > 350 cells/μl.

  9. Development of leafhopper cell culture to trace the early infection process of a nucleorhabdovirus, rice yellow stunt virus, in insect vector cells.

    PubMed

    Wang, Haitao; Wang, Juan; Xie, Yunjie; Fu, Zhijun; Wei, Taiyun; Zhang, Xiao-Feng

    2018-04-20

    In China, the rice pathogen Rice yellow stunt virus (RYSV), a member of the genus Nucleorhabdovirus in the family Rhabdoviridae, was a severe threat to rice production during the1960s and1970s. Fundamental aspects of the biology of this virus such as protein localization and formation of the RYSV viroplasm during infection of insect vector cells are largely unexplored. The specific role(s) of the structural proteins nucleoprotein (N) and phosphoprotein (P) in the assembly of the viroplasm during RYSV infection in insect vector is also unclear. In present study, we used continuous leafhopper cell culture, immunocytochemical techniques, and transmission electron microscopy to investigate the subcellular distributions of N and P during RYSV infection. Both GST pull-down assay and yeast two-hybrid assay were used to assess the in vitro interaction of N and P. The dsRNA interference assay was performed to study the functional roles of N and P in the assembly of RYSV viroplasm. Here we demonstrated that N and P colocalized in the nucleus of RYSV-infected Nephotettix cincticeps cell and formed viroplasm-like structures (VpLSs). The transiently expressed N and P are sufficient to form VpLSs in the Sf9 cells. In addition, the interactions of N/P, N/N and P/P were confirmed in vitro. More interestingly, the accumulation of RYSV was significantly reduced when the transcription of N gene or P gene was knocked down by dsRNA treatment. In summary, our results suggest that N and P are the main viral factors responsible for the formation of viroplasm in RYSV-infected insect cells. Early during RYSV infection in the insect vector, N and P interacted with each other in the nucleus to form viroplasm-like structures, which are essential for the infection of RYSV.

  10. Early postnatal virus inoculation into the scala media achieved extensive expression of exogenous green fluorescent protein in the inner ear and preserved auditory brainstem response thresholds.

    PubMed

    Wang, Yunfeng; Sun, Yu; Chang, Qing; Ahmad, Shoeb; Zhou, Binfei; Kim, Yeunjung; Li, Huawei; Lin, Xi

    2013-01-01

    Gene transfer into the inner ear is a promising approach for treating sensorineural hearing loss. The special electrochemical environment of the scala media raises a formidable challenge for effective gene delivery at the same time as keeping normal cochlear function intact. The present study aimed to define a suitable strategy for preserving hearing after viral inoculation directly into the scala media performed at various postnatal developmental stages. We assessed transgene expression of green fluorescent protein (GFP) mediated by various types of adeno-associated virus (AAV) and lentivirus (LV) in the mouse cochlea. Auditory brainstem responses were measured 30 days after inoculation to assess effects on hearing. Patterns of GFP expression confirmed extensive exogenous gene expression in various types of cells lining the endolymphatic space. The use of different viral vectors and promoters resulted in specific cellular GFP expression patterns. AAV2/1 with cytomegalovirus promoter apparently gave the best results for GFP expression in the supporting cells. Histological examination showed normal cochlear morphology and no hair cell loss after either AAV or LV injections. We found that hearing thresholds were not significantly changed when the injections were performed in mice younger than postnatal day 5, regardless of the type of virus tested. Viral inoculation and expression in the inner ear for the restoration of hearing must not damage cochlear function. Using normal hearing mice as a model, we have achieved this necessary step, which is required for the treatment of many types of congenital deafness that require early intervention. Copyright © 2013 John Wiley & Sons, Ltd.

  11. Control of brown and beige fat development

    PubMed Central

    Wang, Wenshan; Seale, Patrick

    2017-01-01

    Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight. Brown adipocytes develop in discrete and relatively homogenous depots of brown adipose tissue, whereas beige adipocytes are induced to develop in white adipose tissue in response to certain stimuli — notably, exposure to cold. Fate-mapping analyses have identified progenitor populations that give rise to brown and beige fat cells and revealed unanticipated cell-lineage relationships between vascular smooth muscle and beige adipocytes, and between brown fat and skeletal muscle cells. Additionally, non-adipocyte cells in adipose tissue, including neurons, blood vessel-associated cells and immune cells play crucial roles in regulating the differentiation and function of brown and beige fat. PMID:27552974

  12. Sexually transmitted diseases, human immunodeficiency virus, and pregnancy prevention. Combined contraceptive practices among urban African-American early adolescents.

    PubMed

    Stanton, B F; Li, X; Galbraith, J; Feigelman, S; Kaljee, L

    1996-01-01

    To evaluate the success of efforts to educate youth not only to use prescription contraceptives to avoid pregnancy, but also to use condoms to avoid sexually transmitted diseases, including infection with the human immunodeficiency virus. Longitudinal study of 383 African-American youth aged 9 to 15 years enrolled in a randomized, controlled trial of an acquired immunodeficiency syndrome (AIDS) risk reduction intervention. Data about contraceptive practices were obtained at baseline and 6, 12, and 18 months later using a culturally and developmentally appropriate risk assessment tool administered with "talking" computers (Macintosh, Apple Computer Inc, Cupertino, Calif). Approximately three fourths of sexually active youth used some form of contraception in each 6-month round, with almost half of the youth using combinations of contraceptives. Among all youth at baseline and among control youth throughout the study, more than half used condoms and more than two thirds who used oral contraceptives also used condoms. Receipt of an AIDS education intervention was associated with use of more effective contraceptive practices (eg, condoms and another prescription or nonprescription method of birth control). After receiving the intervention, more than 80% of the youth who used oral contraceptives also used condoms. Contraceptive practices showed considerable stability. Knowledge about AIDS was positively associated with use of more effective contraceptive methods. Many youth are using condoms and prescription birth control simultaneously, and these use rates can be increased through AIDS education interventions.

  13. Cowpox Virus Transmission from Rats to Monkeys, the Netherlands

    PubMed Central

    Martina, Byron E.E.; van Doornum, Gerard; Dorrestein, Gerry M.; Niesters, Hubert G.M.; Stittelaar, Koert J.; Wolters, Marno A.B.I.; van Bolhuis, Hester G.H.

    2006-01-01

    We report an outbreak of cowpox virus among monkeys at a sanctuary for exotic animals. Serologic analysis and polymerase chain reaction were performed on blood and swab samples from different rodent species trapped at the sanctuary during the outbreak. Sequence comparison and serologic results showed that brown rats (Rattus norvegicus) transmitted the virus to monkeys. PMID:16707063

  14. Enzymatic browning reactions in apple and apple products.

    PubMed

    Nicolas, J J; Richard-Forget, F C; Goupy, P M; Amiot, M J; Aubert, S Y

    1994-01-01

    This review examines the parameters of enzymatic browning in apple and apple products that is, phenolic compounds, polyphenoloxidases, and other factors (ascorbic acid and peroxidases), both qualitatively and quantitatively. Then the relationships between intensity of browning and the browning parameters are discussed, including a paragraph on the methods used for browning evaluation. Finally, the different methods for the control of browning are presented.

  15. Exploiting biological activities of brown seaweed Ecklonia cava for potential industrial applications: a review.

    PubMed

    Wijesinghe, W A J P; Jeon, You-Jin

    2012-03-01

    Seaweeds are rich in vitamins, minerals, dietary fibres, proteins, polysaccharides and various functional polyphenols. Many researchers have focused on brown algae as a potential source of bioactive materials in the past few decades. Ecklonia cava is a brown seaweed that is abundant in the subtidal regions of Jeju Island in the Republic of Korea. This seaweed attracted extensive interest due to its multiple biological activities. E. cava has been identified as a potential producer of wide spectrum of natural substances such as carotenoids, fucoidans and phlorotannins showing different biological activities in vital industrial applications including pharmaceutical, nutraceutical, cosmeceutical and functional food. This review focuses on biological activities of the brown seaweed E. cava based on latest research results, including antioxidant, anticoagulative, antimicrobial, antihuman immunodeficiency virus, anti-inflammatory, immunomodulatory, antimutagenic, antitumour and anticancer effects. The facts summarized here may provide novel insights into the functions of E. cava and its derivatives and potentially enable their use as functional ingredients in potential industrial applications.

  16. Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.

    PubMed

    Murata, Miki; Matsuzaki, Koichi; Yoshida, Katsunori; Sekimoto, Go; Tahashi, Yoshiya; Mori, Shigeo; Uemura, Yoshiko; Sakaida, Noriko; Fujisawa, Junichi; Seki, Toshihito; Kobayashi, Kazuki; Yokote, Koutaro; Koike, Kazuhiko; Okazaki, Kazuichi

    2009-04-01

    Hepatitis B virus X (HBx) protein is suspected to participate in oncogenesis during chronic hepatitis B progression. Transforming growth factor beta (TGF-beta) signaling involves both tumor suppression and oncogenesis. TGF-beta activates TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Reversible shifting of Smad3-mediated signaling between tumor suppression and oncogenesis in HBx-expressing hepatocytes indicated that TbetaRI-dependent pSmad3C transmitted a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promoted cell growth. We used immunostaining, immunoblotting, and in vitro kinase assay to compare pSmad3L- and pSmad3C-mediated signaling in biopsy specimens representing chronic hepatitis, cirrhosis, or hepatocellular carcinoma (HCC) from 90 patients chronically infected with hepatitis B virus (HBV) with signaling in liver specimens from HBx transgenic mice. In proportion to plasma HBV DNA levels, early chronic hepatitis B specimens showed prominence of pSmad3L in hepatocytic nuclei. HBx-activated JNK/pSmad3L/c-Myc oncogenic pathway was enhanced, while the TbetaRI/pSmad3C/p21(WAF1) tumor-suppressive pathway was impaired as human and mouse HBx-associated hepatocarcinogenesis progressed. Of 28 patients with chronic hepatitis B who showed strong oncogenic pSmad3L signaling, six developed HCC within 12 years; only one of 32 patients showing little pSmad3L developed HCC. In contrast, seven of 30 patients with little Smad3C phosphorylation developed HCC, while no patient who retained hepatocytic tumor-suppressive pSmad3C developed HCC within 12 years. HBx shifts hepatocytic TGF-beta signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway in early carcinogenic process. Hepatocytic pSmad3L and pSmad3C assessment in HBV-infected liver specimens should prove

  17. Comparison of protoporphyrin IX content and related gene expression in the tissues of chickens laying brown-shelled eggs.

    PubMed

    Li, Guangqi; Chen, Sirui; Duan, Zhongyi; Qu, Lujiang; Xu, Guiyun; Yang, Ning

    2013-12-01

    Protoporphyrin IX (PpIX), an immediate precursor of heme, is the main pigment resulting in the brown coloration of eggshell. The brownness and uniformity of the eggshell are important marketing considerations. In this study, 9 chickens laying darker brown shelled eggs and 9 chickens laying lighter brown shelled eggs were selected from 464 individually caged layers in a Rhode Island Red pureline. The PpIX contents were measured with a Microplate Reader at the wavelength of 412 nm and were compared in different tissues of the 2 groups. Although no significant difference in serum, bile, and excreta was found between the 2 groups, PpIX content in the shell gland and eggshell of the darker group was higher than in those of the lighter group, suggesting that PpIX was synthesized in the shell gland. We further determined the expression levels of 8 genes encoding enzymes involved in the heme synthesis and transport in the liver and shell gland at 6 h postoviposition by quantitative PCR. The results showed that expression of aminolevulinic acid synthase-1 (ALAS1) was higher in the liver of hens laying darker brown shelled eggs, whereas in the shell gland the expression levels of ALAS1, coproporphyrinogen oxidase (CPOX), ATP-binding cassette family members ABCB7 and ABCG2, and receptor for feline leukemia virus, subgroup C (FLVCR) were significantly higher in the hens laying darker brown shelled eggs. Our results demonstrated that hens laying darker brown shelled eggs could deposit more PpIX onto the eggshell and the brownness of the eggshell was dependent on the total quantity of PpIX in the eggshell. More heme was synthesized in the liver and shell gland of hens laying darker brown shelled eggs than those of hens laying lighter brown shelled eggs. High expression level of ABCG2 might facilitate the accumulation of PpIX in the shell gland.

  18. Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination

    PubMed Central

    Brooks, Jill M.; Long, Heather M.; Tierney, Rose J.; Shannon-Lowe, Claire; Leese, Alison M.; Fitzpatrick, Martin; Taylor, Graham S.; Rickinson, Alan B.

    2016-01-01

    Epstein-Barr virus, a B-lymphotropic herpesvirus, is the cause of infectious mononucleosis, has strong aetiologic links with several malignancies and has been implicated in certain autoimmune diseases. Efforts to develop a prophylactic vaccine to prevent or reduce EBV-associated disease have, to date, focused on the induction of neutralising antibody responses. However, such vaccines might be further improved by inducing T cell responses capable of recognising and killing recently-infected B cells. In that context, EBNA2, EBNA-LP and BHRF1 are the first viral antigens expressed during the initial stage of B cell growth transformation, yet have been poorly characterised as CD8+ T cell targets. Here we describe CD8+ T cell responses against each of these three “first wave” proteins, identifying target epitopes and HLA restricting alleles. While EBNA-LP and BHRF1 each contained one strong CD8 epitope, epitopes within EBNA2 induced immunodominant responses through several less common HLA class I alleles (e.g. B*3801 and B*5501), as well as subdominant responses through common class I alleles (e.g. B7 and C*0304). Importantly, such EBNA2-specific CD8+ T cells recognised B cells within the first day post-infection, prior to CD8+ T cells against well-characterised latent target antigens such as EBNA3B or LMP2, and effectively inhibited outgrowth of EBV-transformed B cell lines. We infer that “first wave” antigens of the growth-transforming infection, especially EBNA2, constitute potential CD8+ T cell immunogens for inclusion in prophylactic EBV vaccine design. PMID:27096949

  19. Acyclovir-resistant herpes simplex virus 1 infection early after allogeneic hematopoietic stem cell transplantation with T-cell depletion.

    PubMed

    Akahoshi, Yu; Kanda, Junya; Ohno, Ayumu; Komiya, Yusuke; Gomyo, Ayumi; Hayakawa, Jin; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Shiraki, Kimiyasu; Kanda, Yoshinobu

    2017-07-01

    We previously reported that oral low-dose acyclovir (200 mg/day) for the prevention of herpes simplex virus (HSV) infections after allogenic hematopoietic stem cell transplantation (HSCT) is effective without the emergence of acyclovir-resistant HSV infections. However, HSV infections are of significant concern because the number of allogeneic HSCT with T-cell depletion, which is a risk factor of the emergence of drug-resistant HSV infections, has been increasing. We experienced a 25-year-old female who received allogenic HSCT from an unrelated donor with 1-antigen mismatch using anti-thymocyte globulin. Despite acyclovir prophylaxis (200 mg/day), she developed the right palatal ulcer that was positive for HSV-1 specific antigen by fluorescent antibody on day 20 and developed new hypoglossal and tongue ulcers on day 33. Replacement of acyclovir with foscarnet improved her ulcers. We isolated 2 acyclovir-resistant and foscarnet-sensitive strains from the right palatal and hypoglossal ulcers, which had the same frame shift mutation in the thymidine kinase genes. The rate of proliferation of the isolate from the hypoglossal ulcer was faster than that from the right palatal ulcer in the plaque reduction assay. HSV strains that acquired acyclovir-resistant mutations at the right palatal ulcer with larger plaque might spread to the hypoglossal ulcer as the secondary site of infection because of better growth property. Second-line antiviral agents should be considered when we suspect treatment failure of HSV infection, especially in HSCT with T-cell depletion. Further studies are required whether low-dose acyclovir prophylaxis leads to the emergence of virological resistance. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  20. [Viruses in water].

    PubMed

    Zvizdić, Sukrija; Rodinis-Pejić, Ines; Avdić-Kamberović, Fadila; Mujkić, Anesa; Hamzić, Sadeta; Puvacić, Sandra; Tandir, Salih; Kudumović, Mensura

    2005-01-01

    The article elaborates the significance of water, which is necessary for the maintenance of an organism and specifies its daily needs in human beings. Reference data on the early isolations of viruses from sewage water and modern understanding on the occurring virus species are listed. The article considers virus survival in sewage and flowing water and other fresh and marine water systems as well as marine silt or fruit. Finally, we give here an overview of basic features of individual virus kinds that are potential water contaminants.

  1. 50 Years after Brown v. the Board of Education: An Interview with Cheryl Brown Henderson

    ERIC Educational Resources Information Center

    Carriuolo, Nancy E.

    2004-01-01

    This spring marks the 50th anniversary (May 17, 1954-2004) of the Supreme Courts' decision to outlaw segregation by ruling unanimously in favor of the plaintiffs in Brown v. the Board of Education. Of course, segregation never really ended, as will be explained in this interview with Cheryl Brown Henderson, daughter of Oliver Brown, the 10th of…

  2. The brain and brown fat

    PubMed Central

    Gonzalez, Francisco; Fernø, Johan; Diéguez, Carlos; Rahmouni, Kamal; Nogueiras, Rubén

    2015-01-01

    Brown adipose tissue (BAT) is a specialized organ responsible for thermogenesis, a process required for maintaining body temperature. BAT is regulated by the sympathetic nervous system (SNS), which activates lipolysis and mitochondrial uncoupling in brown adipocytes. For many years, BAT was considered to be important only in small mammals and newborn humans, but recent data have shown that BAT is also functional in adult humans. On the basis of this evidence, extensive research has been focused on BAT function, where new molecules, such as irisin and bone morphogenetic proteins, particularly BMP7 and BMP8B, as well as novel central factors and new regulatory mechanisms, such as orexins and the canonical ventomedial nucleus of the hypothalamus (VMH) AMP- activated protein kinase (AMPK)–SNS–BAT axis, have been discovered and emerged as potential drug targets to combat obesity. In this review we provide an overview of the complex central regulation of BAT and how different neuronal cell populations co-ordinately work to maintain energy homeostasis. PMID:24915455

  3. Early diagnosis and follow-up of chronic active Epstein-Barr-virus-associated cardiovascular complications with cardiovascular magnetic resonance imaging: A case report.

    PubMed

    Jiang, Shu; Li, Xiao; Cao, Jian; Wu, Di; Kong, Lingyan; Lin, Lu; Jin, Zhengyu; An, Jing; Wang, Yining

    2016-08-01

    Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is characterized as chronic or recurrent mononucleosis-like symptoms and elevated EBV deoxyribonucleic acid (EBV-DNA) copies. Cardiovascular complications have high morbidity and mortality. The treatment regimen for CAEBV has not been established yet, resulting in poor prognoses. Herein, we present a case of cardiovascular magnetic resonance imaging (CMRI) evaluation with a series of sequences for CAEBV-associated cardiovascular involvement, which has never been reported. A 16-year-old female (body weight, 55 kg) developed a persistent fever and a positive EBV-DNA level of 28,000 copies/mL. Computed tomography angiography (CTA) showed aneurysms involving the aorta and its major branches, as well as multiple aneurysms and stenoses of the coronary arteries. CMRI of the coronary arteries depicted the dilution and stenosis of the arterial lumen as well as the thickening of the arterial wall. Late gadolinium enhancement (LGE) showed subendocardial and transmural delayed enhancement of the left ventricle, suggesting myocardial infarction.CAEBV and associated cardiovascular complications were diagnosed. After treatment with Medrol and Leflunomide, the clinical manifestation and serological parameters reversed to normal. However, the EBV-DNA level increased again to 13,900 copies/mL 2 months later. A follow-up with aorta CTA showed that the arterial walls of the bilateral common iliac artery aneurysms were thicker with new-onset mural thrombi. The aorta CTA also showed new-onset occlusion of the right coronary artery, but a follow-up of CMRI at the same day did not find new-onset delayed enhancement lesion. This case reminds clinicians of the vital importance of early diagnosis and close follow-up of CAEBV-associated cardiovascular complications. With cine imaging, coronary artery imaging, LGE imaging, and other novel techniques, CMRI can effectively and comprehensively reveal the early and dynamic changes, and

  4. The B-Cell Specific Transcription Factor, Oct-2, Promotes Epstein-Barr Virus Latency by Inhibiting the Viral Immediate-Early Protein, BZLF1

    PubMed Central

    Robinson, Amanda R.; Kwek, Swee Sen; Kenney, Shannon C.

    2012-01-01

    The Epstein-Barr virus (EBV) latent-lytic switch is mediated by the BZLF1 immediate-early protein. EBV is normally latent in memory B cells, but cellular factors which promote viral latency specifically in B cells have not been identified. In this report, we demonstrate that the B-cell specific transcription factor, Oct-2, inhibits the function of the viral immediate-early protein, BZLF1, and prevents lytic viral reactivation. Co-transfected Oct-2 reduces the ability of BZLF1 to activate lytic gene expression in two different latently infected nasopharyngeal carcinoma cell lines. Furthermore, Oct-2 inhibits BZLF1 activation of lytic EBV promoters in reporter gene assays, and attenuates BZLF1 binding to lytic viral promoters in vivo. Oct-2 interacts directly with BZLF1, and this interaction requires the DNA-binding/dimerization domain of BZLF1 and the POU domain of Oct-2. An Oct-2 mutant (Δ262–302) deficient for interaction with BZLF1 is unable to inhibit BZLF1-mediated lytic reactivation. However, an Oct-2 mutant defective for DNA-binding (Q221A) retains the ability to inhibit BZLF1 transcriptional effects and DNA-binding. Importantly, shRNA-mediated knockdown of endogenous Oct-2 expression in several EBV-positive Burkitt lymphoma and lymphoblastoid cell lines increases the level of lytic EBV gene expression, while decreasing EBNA1 expression. Moreover, treatments which induce EBV lytic reactivation, such as anti-IgG cross-linking and chemical inducers, also decrease the level of Oct-2 protein expression at the transcriptional level. We conclude that Oct-2 potentiates establishment of EBV latency in B cells. PMID:22346751

  5. Prediction of Early BK Virus Infection in Kidney Transplant Recipients by the Number of Cells With Intranuclear Inclusion Bodies (Decoy Cells)

    PubMed Central

    Yamada, Yoshiteru; Tsuchiya, Tomohiro; Inagaki, Isao; Seishima, Mitsuru; Deguchi, Takashi

    2018-01-01

    Background BK virus (BKV) is the cause of nephropathy. Because BKV nephropathy can progress to graft loss, early diagnosis of BKV infection is very important. In this study, we aimed to investigate the utility of quantifying cells with intranuclear inclusion bodies (decoy cells) in urinary sediment for the screening and monitoring of BKV infection in renal transplant recipients at our hospital. Methods This was a retrospective single-center study. Urine sediment examination was performed at each outpatient visit, and the number of decoy cells was measured in the whole microscopic field. Patients (n = 41) were divided into the BK viremia group (blood positive for BKV DNA by polymerase chain reaction [PCR]) and non-BK viremia group (blood negative for BKV DNA by PCR), and the decoy cell count in urinary sediments was examined. Results The maximum decoy cell count was significantly higher (P = 0.04) in the BK viremia group than in the non-BK viremia group. In the receiver operating characteristic curve for the maximum decoy cells, the cutoff value was 507 cells. The area under the receiver operating characteristic curve was 0.8774 (95% confidence interval, 0.7739-0.9810). The number of decoy cells at the time of appearance in the BK viremia group was not significantly different from that in the non-BK viremia group. However, the BK viremia group showed an increasing trend, whereas the non-BK viremia group showed a decreasing trend, in the number of decoy cells. There was a positive correlation between the number of decoy cells and the data from the urine BKV-DNA PCR quantification (correlation coefficient [r] = 0.74). Conclusions Measurement of decoy cells in urinary sediments may predict early BKV infection, and if performed quickly, it may be useful for screening and continuous monitoring of BKV infection in renal transplant recipients. PMID:29464201

  6. CP7_E2alf oral vaccination confers partial protection against early classical swine fever virus challenge and interferes with pathogeny-related cytokine responses

    PubMed Central

    2013-01-01

    The conventional C-strain vaccine induces early protection against classical swine fever (CSF), but infected animals cannot be distinguished from vaccinated animals. The CP7_E2alf marker vaccine, a pestivirus chimera, could be a suitable substitute for C-strain vaccine to control CSF outbreaks. In this study, single oral applications of CP7_E2alf and C-strain vaccines were compared for their efficacy to induce protection against a CSF virus (CSFV) challenge with the moderately virulent Bas-Rhin isolate, in pigs as early as two days post-immunization. This work emphasizes the powerful potential of CP7_E2alf vaccine administered orally by a rapid onset of partial protection similar to that induced by the C-strain vaccine. Furthermore, our results revealed that both vaccinations attenuated the effects induced by CSFV on production of the pig major acute phase protein (PigMAP), IFN-α, IL-12, IL-10, and TGF-β1 cytokines. By this interference, several cytokines that may play a role in the pathogeny induced by moderately virulent CSFV strains were revealed. New hypotheses concerning the role of each of these cytokines in CSFV pathogeny are discussed. Our results also show that oral vaccination with either vaccine (CP7_E2alf or C-strain) enhanced CSFV–specific IgG2 production, compared to infection alone. Interestingly, despite the similar antibody profiles displayed by both vaccines post-challenge, the production of CSFV-specific IgG1 and neutralizing antibodies without challenge was lower with CP7_E2alf vaccination than with C-strain vaccination, suggesting a slight difference in the balance of adaptive immune responses between these vaccines. PMID:23398967

  7. Reactivation of Latent Tuberculosis in Cynomolgus Macaques Infected with SIV Is Associated with Early Peripheral T Cell Depletion and Not Virus Load

    PubMed Central

    Klein, Edwin; Janssen, Chris; Phuah, Jiayao; Sturgeon, Timothy J.; Montelaro, Ronald C.; Lin, Philana Ling; Flynn, JoAnne L.

    2010-01-01

    HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb) infection are at significantly greater risk of reactivation tuberculosis (TB) than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV). Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks) had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection. PMID:20224771

  8. APOBEC3H haplotypes and HIV-1 pro-viral vif DNA sequence diversity in early untreated human immunodeficiency virus-1 infection.

    PubMed

    Gourraud, P A; Karaouni, A; Woo, J M; Schmidt, T; Oksenberg, J R; Hecht, F M; Liegler, T J; Barbour, J D

    2011-03-01

    We examined single nucleotide polymorphisms (SNP) in the APOBEC3 locus on chromosome 22, paired with population sequences of pro-viral human immunodeficiency virus-1 (HIV-1) vif from peripheral blood mononuclear cells, from 96 recently HIV-1-infected treatment-naive adults. We found evidence for the existence of an APOBEC3H linkage disequilibrium (LD) block associated with variation in GA → AA, or APOBEC3F/H signature, sequence changes in pro-viral HIV-1 vif sequence (top 10 significant SNPs with a significant p = 4.8 × 10(-3)). We identified a common five position risk haplotype distal to APOBEC3H (A3Hrh). These markers were in high LD (D' = 1; r(2) = 0.98) to a previously described A3H "RED" haplotype containing a variant (E121) with enhanced susceptibility to HIV-1 Vif. This association was confirmed by a haplotype analysis. Homozygote carriers of the A3Hrh had lower GA->AA (A3F/H) sequence editing upon pro-viral HIV-1 vif sequence (p = 0.01), and lower HIV-1 RNA levels over time during early, untreated HIV-1 infection, (p = 0.015 mixed effects model). This effect may be due to enhanced susceptibility of A3H forms to HIV-1 Vif mediated viral suppression of sequence editing activity, slowing viral diversification and escape from immune responses. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  9. Sera DNA Methylation of CDH1, DNMT3b and ESR1 Promoters as Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Hepatocellular Carcinoma.

    PubMed

    Dou, Cheng-Yun; Fan, Yu-Chen; Cao, Chuang-Jie; Yang, Yang; Wang, Kai

    2016-04-01

    DNA methylation mainly affects tumor suppressor genes in the development of hepatocellular carcinoma (HCC). However, sera methylation of specific genes in hepatitis B virus (HBV)-related HCC remains unknown. The purpose of this study was to identify methylation frequencies of sera E-cadherin (CDH1), DNA methyltransferase 3b (DNMT3b) and estrogen receptor 1 (ESR1) promoter in HBV-related HCC and analyze the associated clinical significance. Methylation-specific PCR was used to determine the frequencies of DNA methylation for CDH1, DNMT3b and ESR1 genes in sera from 183 patients with HCC, 47 liver cirrhosis (LC), 126 chronic hepatitis B (CHB), and 50 normal controls (NCs). Significantly higher frequencies of methylation of CDH1, DNMT3b and ESR1 were found in HBV-related HCC compared with LC, CHB and NCs. Nodule numbers, tumor size and the presence of liver cirrhosis were significantly associated with gene methylation status in HBV-related HCC. Moreover, HBV may have a strong and enhanced effect on the concurrent methylation of CDH1, DNMT3b and ESR1 in HBV-related HCC. More importantly, combined methylation as a biomarker displayed significantly higher diagnostic value than AFP to discriminate HCC from CHB and LC. Aberrant sera DNA methylation of CDH1, DNMT3b and ESR1 gene promoters could be a biomarker in the early diagnosis of HBV-related HCC.

  10. Common Host-Derived Chemicals Increase Catches of Disease-Transmitting Mosquitoes and Can Improve Early Warning Systems for Rift Valley Fever Virus

    PubMed Central

    Tchouassi, David P.; Sang, Rosemary; Sole, Catherine L.; Bastos, Armanda D. S.; Teal, Peter E. A.; Borgemeister, Christian; Torto, Baldwyn

    2013-01-01

    Rift Valley fever (RVF), a mosquito-borne zoonosis, is a major public health and veterinary problem in sub-Saharan Africa. Surveillance to monitor mosquito populations during the inter-epidemic period (IEP) and viral activity in these vectors is critical to informing public health decisions for early warning and control of the disease. Using a combination of field bioassays, electrophysiological and chemical analyses we demonstrated that skin-derived aldehydes (heptanal, octanal, nonanal, decanal) common to RVF virus (RVFV) hosts including sheep, cow, donkey, goat and human serve as potent attractants for RVFV mosquito vectors. Furthermore, a blend formulated from the four aldehydes and combined with CO2-baited CDC trap without a light bulb doubled to tripled trap captures compared to control traps baited with CO2 alone. Our results reveal that (a) because of the commonality of the host chemical signature required for attraction, the host-vector interaction appears to favor the mosquito vector allowing it to find and opportunistically feed on a wide range of mammalian hosts of the disease, and (b) the sensitivity, specificity and superiority of this trapping system offers the potential for its wider use in surveillance programs for RVFV mosquito vectors especially during the IEP. PMID:23326620

  11. Legal Aspects of the Brown Decision.

    ERIC Educational Resources Information Center

    Carter, Robert L.

    In Brown v. Board of Education of Topeka, Kansas, the Supreme Court outlawed segregation in the nation's public schools. This decision has not eliminated racial segregation, but it fundamentally altered the psychological pattern of race relations in the United States. Brown concerned a form of racial discrimination that has virtually vanished from…

  12. Calcifying Sorting and Segregating: "Brown" at 60

    ERIC Educational Resources Information Center

    Graff, Cristina Santamaria; Kozleski, Elizabeth

    2014-01-01

    The 2007 "Parents Involved in Community Schools v. Seattle School District No. 1". Supreme Court 5:4 decision suggests that the Court is divided in its interpretation of "Brown" and its intent in addressing racial segregation. Although "Brown" intended equal educational opportunities through desegregation practices,…

  13. Thyroid hormones induce browning of white fat

    PubMed Central

    Martínez-Sánchez, Noelia; Moreno-Navarrete, José M; Contreras, Cristina; Rial-Pensado, Eva; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos

    2016-01-01

    The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism. However, the possible central effects of THs on the browning of white fat remain unclear. Here, we show that 3,3′,5,5′ tetraiodothyroxyne (T4)-induced hyperthyroidism promotes a marked browning of WAT. Of note, central or VMH-specific administration of 3,3′,5-triiodothyronine (T3) recapitulates that effect. The specific genetic activation of hypothalamic AMPK in the VMH reversed the central effect of T3 on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T4. Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance. PMID:27913573

  14. On Browne's Solution for Oblique Procrustes Rotation

    ERIC Educational Resources Information Center

    Cramer, Elliot M.

    1974-01-01

    A form of Browne's (1967) solution of finding a least squares fit to a specified factor structure is given which does not involve solution of an eigenvalue problem. It suggests the possible existence of a singularity, and a simple modification of Browne's computational procedure is proposed. (Author/RC)

  15. Speaking Personally--With John Seely Brown

    ERIC Educational Resources Information Center

    American Journal of Distance Education, 2008

    2008-01-01

    This article presents an interview with John Seely Brown, a visiting scholar at the University of Southern California and a former chief scientist of Xerox Corporation and director of its Palo Alto Research Center (PARC)--a position he held for nearly two decades. While head of PARC, Brown expanded the role of corporate research to include such…

  16. Thyroid hormones induce browning of white fat.

    PubMed

    Martínez-Sánchez, Noelia; Moreno-Navarrete, José M; Contreras, Cristina; Rial-Pensado, Eva; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos; Fernández-Real, José-Manuel; López, Miguel

    2017-02-01

    The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism. However, the possible central effects of THs on the browning of white fat remain unclear. Here, we show that 3,3',5,5' tetraiodothyroxyne (T 4 )-induced hyperthyroidism promotes a marked browning of WAT. Of note, central or VMH-specific administration of 3,3',5-triiodothyronine (T 3 ) recapitulates that effect. The specific genetic activation of hypothalamic AMPK in the VMH reversed the central effect of T 3 on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T 4 Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance. © 2017 The authors.

  17. Some Aspects of Enzymatic Browning in Apples

    ERIC Educational Resources Information Center

    Liffen, C. L.; Cleeve, H. N.

    1975-01-01

    Describes material modified from the Nuffield advanced chemistry course to make it meaningful and relevant to pupils in the middle school. Discusses a series of simple experiments on apple browning and summarizes the browning process and its control. (Author/GS)

  18. Collecting Brown Dwarfs in the Night Sky

    NASA Image and Video Library

    2010-11-09

    The green dot in the middle of this image might look like an emerald amidst glittering diamonds, but is a dim star belonging to a class called brown dwarfs; it is the first ultra-cool brown dwarf discovered by NASA Wide-field Infrared Survey Explorer.

  19. Brown-Spot Needle Blight of Pines

    Treesearch

    W.R. Phelps; A.G. Kais; T.H. Nicholls

    1978-01-01

    Brown-spot needle blight, caused by Scirrhia acicola (Dearn.) Siggers, delays growth and causes mortality of longleaf pine (Pinus palustris Mill.). Brown spot reduces total annual growth of southern pines by more than 16 million cubic feet (0.453 million cubic meters) of timber. Damage is most severe on longleaf seedlings in the grass stage; i.e., those that have not...

  20. HARPERS FERRY, A PLAY ABOUT JOHN BROWN.

    ERIC Educational Resources Information Center

    STAVIS, BARRIE

    THIS PLAY IS A DRAMATIC RENDERING OF JOHN BROWN'S ATTACK ON THE ARMORY AT HARPERS FERRY AND HIS SUBSEQUENT TRIAL FOR TREASON. ALTHOUGH IT ADHERES TO THE FACTS OF HISTORY, THEY ARE NOT TREATED REALISTICALLY. "HARPERS FERRY" PORTRAYS BROWN AS POSSESSING A PURE IDEALISM UNTAINTED IN THE SLIGHTEST DEGREE BY MATERIALISM OR SELF-SEEKING, WHICH…

  1. "Brown" and Black-White Achievement

    ERIC Educational Resources Information Center

    Armor, David J.

    2006-01-01

    "Brown v. Board of Education" only presumed to eliminate the "de jure" apartheid that existed in 1954. It was never intended to resolve the "de facto" gap in minority achievement that still faces education policymakers today. Sociologist David J. Armor goes beyond "Brown" to identify a set of definite risk…

  2. A novel antivirally active fucan sulfate derived from an edible brown alga, Sargassum horneri.

    PubMed

    Preeprame, S; Hayashi, K; Lee, J B; Sankawa, U; Hayashi, T

    2001-04-01

    A novel fucan sulfate (Hor-1) was isolated from the hot water extract of an edible brown alga, Sargassum horneri (Turner) C. Agardh. The fucan sulfate was revealed to have sugar linkage types, sulfate content and uronic acid content different from those of sodium hornan (Na-HOR), another fucan sulfate isolated from this alga. However, it exhibited inhibitory activity against replication of herpes simplex virus type 1 with similar potency to Na-HOR.

  3. Characterization of the central neural projections to brown, white, and beige adipose tissue.

    PubMed

    Wiedmann, Nicole M; Stefanidis, Aneta; Oldfield, Brian J

    2017-11-01

    The functional recruitment of classic brown adipose tissue (BAT) and inducible brown-like or beige fat is, to a large extent, dependent on intact sympathetic neural input. Whereas the central neural circuits directed specifically to BAT or white adipose tissue (WAT) are well established, there is only a developing insight into the nature of neural inputs common to both fat types. Moreover, there is no clear view of the specific central and peripheral innervation of the browned component of WAT: beige fat. The objective of the present study is to examine the neural input to both BAT and WAT in the same animal and, by exposing different cohorts of rats to either thermoneutral or cold conditions, define changes in central neural organization that will ensure that beige fat is appropriately recruited and modulated after browning of inguinal WAT (iWAT). At thermoneutrality, injection of the neurotropic (pseudorabies) viruses into BAT and WAT demonstrates that there are dedicated axonal projections, as well as collateral axonal branches of command neurons projecting to both types of fat. After cold exposure, central neural circuits directed to iWAT showed evidence of reorganization with a greater representation of command neurons projecting to both brown and beiged WAT in hypothalamic (paraventricular nucleus and lateral hypothalamus) and brainstem (raphe pallidus and locus coeruleus) sites. This shift was driven by a greater number of supraspinal neurons projecting to iWAT under cold conditions. These data provide evidence for a reorganization of the nervous system at the level of neural connectivity following browning of WAT.-Wiedmann, N. M., Stefanidis, A., Oldfield, B. J. Characterization of the central neural projections to brown, white, and beige adipose tissue. © FASEB.

  4. Weather and Rotation on Young Brown Dwarfs

    NASA Astrophysics Data System (ADS)

    Vos, Johanna; Biller, Beth; Allers, Katelyn; Manjavacas, Elena; Liu, Michael; Best, William; Metchev, Stanimir; Buenzli, Esther; Bonavita, Mariangela; Eriksson, Simon; Dupuy, Trent; Kopytova, Taisiya; Brandner, Wolfgang; Henning, Thomas; Bonnefoy, Mickael; Crossfield, Ian; Schlieder, Joshua; Homeier, Derek; Janson, Markus; Radigan, Jacqueline

    2018-05-01

    As part of a large, ground-based survey for weather patterns on exoplanet analogues, we have detected J-band variability in 5 young exoplanet analogues. We have already carried out followup Spitzer monitoring of two objects and here we propose Spitzer 3.6um and 4.5um monitoring of three early-mid-L detections in our survey. The proposed observations will enable us to assess the role of gravity in the variability properties of these young objects by providing a full measure of mid-IR amplitude across the full L spectral sequence for low-gravity objects. The proposed observations will also allow us to measure the rotational periods of our three targets. This will provide vital information on the angular momentum of young brown dwarfs, while enabling us to correct for geometric effects when considering the variability properties of our targets. This study will act as a necessary pathfinder for future variability studies of free-floating and companion exoplanets with JWST.

  5. Dietary fat overload reprograms brown fat mitochondria.

    PubMed

    Lettieri Barbato, Daniele; Tatulli, Giuseppe; Vegliante, Rolando; Cannata, Stefano M; Bernardini, Sergio; Ciriolo, Maria R; Aquilano, Katia

    2015-01-01

    Chronic nutrient overload accelerates the onset of several aging-related diseases reducing life expectancy. Although the mechanisms by which overnutrition affects metabolic processes in many tissues are known, its role on BAT physiology is still unclear. Herein, we investigated the mitochondrial responses in BAT of female mice exposed to high fat diet (HFD) at different steps of life. Although adult mice showed an unchanged mitochondrial amount, both respiration and OxPHOS subunits were strongly affected. Differently, offspring pups exposed to HFD during pregnancy and lactation displayed reduced mitochondrial mass but high oxidative efficiency that, however, resulted in increased bioenergetics state of BAT rather than augmented uncoupling respiration. Interestingly, the metabolic responses triggered by HFD were accompanied by changes in mitochondrial dynamics characterized by decreased content of the fragmentation marker Drp1 both in mothers and offspring pups. HFD-induced inactivation of the FoxO1 transcription factor seemed to be the up-stream modulator of Drp1 levels in brown fat cells. Furthermore, HFD offspring pups weaned with normal diet only partially reverted the mitochondrial dysfunctions caused by HFD. Finally these mice failed in activating the thermogenic program upon cold exposure. Collectively our findings suggest that maternal dietary fat overload irreversibly commits BAT unresponsiveness to physiological stimuli such as cool temperature and this dysfunction in the early stage of life might negatively modulate health and lifespan.

  6. Elizabeth Brown (1830-1899), solar astronomer

    NASA Astrophysics Data System (ADS)

    Creese, M.

    1998-08-01

    Were it not for the fact that she was a woman, Elizabeth Brown might well be thought of as a fairly typical nineteenth-century British amateur astronomer. She has a place, although a relatively modest one, in the distinguished group of people who, with their own fortunes, carried out much of the astronomical research being done in the country at a time before extensive government support was forthcoming for the work.1 Her career in fact follows a pattern common to several of the nineteenth-century men astronomers in that her full productive period came only after she was freed from her primary responsibilities; she did not have to amass the necessary financial resources as did many of the men,2 but she had the time-consuming responsibility, not unusual for a Victorian woman, of caring for a parent through a lengthy old age. Only after her father died at the age of ninety-one, did Elizabeth, then in her early fifties, begin her sixteen years of remarkable public activity in astronomy.

  7. Early viral replication and induced or constitutive immunity in rainbow trout families with differential resistance to Infectious hematopoietic necrosis virus (IHNV)

    USGS Publications Warehouse

    Purcell, M.K.; LaPatra, S.E.; Woodson, J.C.; Kurath, G.; Winton, J.R.

    2010-01-01

    The main objective of this study was to assess correlates of innate resistance in rainbow trout full-sibling families that differ in susceptibility to Infectious hematopoietic necrosis virus (IHNV). As part of a commercial breeding program, full-sibling families were challenged with IHNV by waterborne exposure at the 1 g size to determine susceptibility to IHNV. Progeny from select families (N = 7 families) that varied in susceptibility (ranging from 32 to 90% cumulative percent mortality (CPM)) were challenged again at the 10 g size by intra-peritoneal injection and overall mortality, early viral replication and immune responses were evaluated. Mortality challenges included 20–40 fish per family while viral replication and immune response studies included 6 fish per family at each time point (24, 48 and 72 h post-infection (hpi)). CPM at the 1 g size was significantly correlated with CPM at the 10 g size, indicating that inherent resistance was a stable trait irrespective of size. In the larger fish, viral load was measured by quantitative reverse-transcriptase PCR in the anterior kidney and was a significant predictor of family disease outcome at 48 hpi. Type I interferon (IFN) transcript levels were significantly correlated with an individual's viral load at 48 and 72 hpi, while type II IFN gene expression was significantly correlated with an individual's viral load at 24 and 48 hpi. Mean family type I but not type II IFN gene expression was weakly associated with susceptibility at 72 hpi. There was no association between mean family susceptibility and the constitutive expression of a range of innate immune genes (e.g. type I and II IFN pathway genes, cytokine and viral recognition receptor genes). The majority of survivors from the challenge had detectable serum neutralizing antibody titers but no trend was observed among families. This result suggests that even the most resistant families experienced sufficient levels of viral replication to trigger specific

  8. Serum MicroRNAs as Potential Biomarkers for Early Diagnosis of Hepatitis C Virus-Related Hepatocellular Carcinoma in Egyptian Patients

    PubMed Central

    Motawi, Tarek K.; Shaker, Olfat G.; El-Maraghy, Shohda A.; Senousy, Mahmoud A.

    2015-01-01

    Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV)-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis

  9. BZLF1, an Epstein-Barr virus immediate-early protein, induces p65 nuclear translocation while inhibiting p65 transcriptional function

    SciTech Connect

    Morrison, Thomas E.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Kenney, Shannon C.

    We have previously demonstrated that the Epstein-Barr virus immediate-early BZLF1 protein interacts with, and is inhibited by, the NF-{kappa}B family member p65. However, the effects of BZLF1 on NF-{kappa}B activity have not been intensively studied. Here we show that BZLF1 inhibits p65-dependent gene expression. BZLF1 inhibited the ability of IL-1, as well as transfected p65, to activate the expression of two different NF-{kappa}B-responsive genes, ICAM-1 and I{kappa}B-{alpha}. BZLF1 also reduced the constitutive level of I{kappa}B-{alpha} protein in HeLa and A549 cells, and increased the amount of nuclear NF-{kappa}B to a similar extent as tumor necrosis factor-alpha (TNF-{alpha}) treatment. In spitemore » of this BZLF1-associated increase in the nuclear form of NF-{kappa}B, BZLF1 did not induce binding of NF-{kappa}B to NF-{kappa}B responsive promoters (as determined by chromatin immunoprecipitation assay) in vivo, although TNF-{alpha} treatment induced NF-{kappa}B binding as expected. Overexpression of p65 dramatically inhibited the lytic replication cycle of EBV in 293-EBV cells, confirming that NF-{kappa}B also inhibits BZLF1 transcriptional function. Our results are consistent with a model in which BZLF1 inhibits the transcriptional function of p65, resulting in decreased transcription of I{kappa}B-{alpha}, decreased expression of I{kappa}B-{alpha} protein, and subsequent translocation of NF-{kappa}B to the nucleus. This nuclear translocation of NF-{kappa}B may promote viral latency by negatively regulating BZLF1 transcriptional activity. In situations where p65 activity is limiting in comparison to BZLF1, the ability of BZLF1 to inhibit p65 transcriptional function may protect the virus from the host immune system during the lytic form of infection.« less

  10. The initial antibody response to HIV-1: induction of ineffective early B cell responses against GP41 by the transmitted/founder virus

    SciTech Connect

    Chavez, Leslie L; Perelson, Alan

    2008-01-01

    A window of opportunity for immune responses to extinguish HIV -1 exists from the moment of transmission through establishment of the latent pool of HIV -I-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus) but, to date, this period has been logistically difficult to analyze. Studies in non-human primates challenged with chimeric simianhuman immunodeficiency virus have shown that neutralizing antibodies, when present at the time of infection, can prevent virus infection.

  11. Could brown bears (Ursus arctos) have survived in Ireland during the Last Glacial Maximum?

    PubMed

    Leonard, Saoirse A; Risley, Claire L; Turvey, Samuel T

    2013-08-23

    Brown bears are recorded from Ireland during both the Late Pleistocene and early-mid Holocene. Although most of the Irish landmass was covered by an ice sheet during the Last Glacial Maximum (LGM), Irish brown bears are known to have hybridized with polar bears during the Late Pleistocene, and it is suggested that the Irish brown bear population did not become extinct but instead persisted in situ through the LGM in a southwestern ice-free refugium. We use historical population modelling to demonstrate that brown bears are highly unlikely to have survived through the LGM in Ireland under any combination of life-history parameters shown by living bear populations, but instead would have rapidly become extinct following advance of the British-Irish ice sheet, and probably recolonized Ireland during the end-Pleistocene Woodgrange Interstadial from a closely related nearby source population. The time available for brown bear-polar bear hybridization was therefore restricted to narrow periods at the beginning or end of the LGM. Brown bears would have been extremely vulnerable to extinction in Quaternary habitat refugia and required areas substantially larger than southwestern Ireland to survive adverse glacial conditions.

  12. Respiratory syncytial virus (RSV) entry is inhibited by serine protease inhibitor AEBSF when present during an early stage of infection.

    PubMed

    Van der Gucht, Winke; Leemans, Annelies; De Schryver, Marjorie; Heykers, Annick; Caljon, Guy; Maes, Louis; Cos, Paul; Delputte, Peter L

    2017-08-17

    Host proteases have been shown to play important roles in many viral activities such as entry, uncoating, viral protein production and disease induction. Therefore, these cellular proteases are putative targets for the development of antivirals that inhibit their activity. Host proteases have been described to play essential roles in Ebola, HCV, HIV and influenza, such that specific protease inhibitors are able to reduce infection. RSV utilizes a host protease in its replication cycle but its potential as antiviral target is unknown. Therefore, we evaluated the effect of protease inhibitors on RSV infection. To measure the sensitivity of RSV infection to protease inhibitors, cells were infected with RSV and incubated for 18 h in the presence or absence of the inhibitors. Cells were fixed, stained and studied using fluorescence microscopy. Several protease inhibitors, representing different classes of proteases (AEBSF, Pepstatin A, E-64, TPCK, PMSF and aprotinin), were tested for inhibitory effects on an RSV A2 infection of HEp-2 cells. Different treatment durations, ranging from 1 h prior to inoculation and continuing for 18 h during the assay, were evaluated. Of all the inhibitors tested, AEBSF and TPCK significantly decreased RSV infection. To ascertain that the observed effect of AEBSF was not a specific feature related to HEp-2 cells, A549 and BEAS-2B cells were also used. Similar to HEp-2, an almost complete block in the number of RSV infected cells after 18 h of incubation was observed and the effect was dose-dependent. To gain insight into the mechanism of this inhibition, AEBSF treatment was applied during different phases of an infection cycle (pre-, peri- and post-inoculation treatment). The results from these experiments indicate that AEBSF is mainly active during the early entry phase of RSV. The inhibitory effect was also observed with other RSV isolates A1998/3-2 and A2000/3-4, suggesting that this is a general feature of RSV. RSV infection can be

  13. Risk of herpes simplex virus type 2 acquisition increases over early adulthood: evidence from a cohort study.

    PubMed

    Dickson, N; van Roode, T; Herbison, P; Taylor, J; Cunningham, A; Paul, C

    2007-04-01

    DESIGN/ SETTING: A cohort study of 1037 people born in Dunedin, New Zealand, in 1972 or 1973. At assessment at age 32 years, 884 participants (432 women and 452 men; 87.1% of the surviving cohort) provided both sera and information on sexual behaviour. The proportion of participants with antibodies to HSV-2 infection at ages 26 and 32 years was measured, and the incidence rates from first coitus to age 26 years and from age 26 to 32 years calculated, adjusting for the number of sexual partners and same-sex contact in these age periods. At age 32 years, 14.6% of men and 22.5% of women had antibodies to HSV-2. The incidence rates for men and women from first coitus to age 26 years were, respectively, 6.5 and 14.3 per 1000 person-years. The incidence rates for men and women from age 26-32 years, respectively, were 14.3 and 15.8 per 1000 person-years. When adjusted for sexual behaviour, the incidence rate ratio, comparing the older with the younger age periods, was 2.9 (95% confidence interval (CI) 1.7 to 4.9) for men and 2.0 (1.2 to 3.4) for women. The adjusted incidence rate ratio when comparing women to men from first coitus to age 26 years was 2.5 (1.6 to 4.0), and from age 26-32 years was 1.3 (0.78 to 2.2). A test for interaction indicated that men and women had different patterns of incidence over time (p = 0.039). In the general population, the risk of acquiring HSV-2 infection seems to increase with age at least to the early 30s, and differences in risk of acquisition for women compared with men become less with age. Health promotion and treatment to control HSV-2 infection should be aimed at all ages, not just at the young.

  14. NTT Observations Indicate that Brown Dwarfs Form Like Stars

    NASA Astrophysics Data System (ADS)

    2001-06-01

    candidates detected via the NTT observations are also identified with optical "proplyds" , the famous dusty disks first imaged in 1994 by the Hubble Space Telescope (HST) at optical wavelengths, cf. the corresponding HST Press Release and images [4]. Dusty disks The presence of such hot and dusty disks around these objects is a clear sign of their extreme youth - this in turn confirms both their membership in the young cluster and their nature as bona-fide substellar objects . Thus, the Trapezium Cluster contains the largest population (approximately 100) of Brown Dwarfs yet known. Indeed, only about 80 freely floating Brown Dwarfs have so far been positively identified outside this cluster. " Brown Dwarfs are considerably easier to detect and study when they are young, because they are ten times larger and thousands of times brighter during their early youth than during their middle age " says Elizabeth Lada from the University of Florida and a member of the team. Her colleague August Muench explains that " even at their brightest, however, most Brown Dwarfs are still 100 or more times intrinsically fainter than our Sun, explaining why astronomers have great difficulties in detecting such objects ". A common origin of normal stars and Brown Dwarfs " The high incidence of disks around both young stars and Brown Dwarfs in this cluster strongly suggests that both stars and Brown Dwarfs trace their origin to a common physical process and that Brown Dwarfs are more similar in nature to stars than to planets " says Charles Lada from the Smithsonian Astrophysical Observatory. Moreover, as is the case for stars, the disks that surround Brown Dwarfs may be capable of forming systems of planets. According to João Alves from ESO, " it is entirely possible that the Milky Way Galaxy contains numerous planetary systems that orbit cold and dark, failed stars. Whether these disks can indeed form planetary systems, however, still remains to be determined ". Even if Brown Dwarfs do have

  15. Spatial and temporal movement dynamics of brook Salvelinus fontinalis and brown trout Salmo trutta

    USGS Publications Warehouse

    Davis, L.A.; Wagner, Tyler; Barton, Meredith L.

    2015-01-01

    Native eastern brook trout Salvelinus fontinalis and naturalized brown trout Salmo trutta occur sympatrically in many streams across the brook trout’s native range in the eastern United States. Understanding within- among-species variability in movement, including correlates of movement, has implications for management and conservation. We radio tracked 55 brook trout and 45 brown trout in five streams in a north-central Pennsylvania, USA watershed to quantify the movement of brook trout and brown trout during the fall and early winter to (1) evaluate the late-summer, early winter movement patterns of brook trout and brown trout, (2) determine correlates of movement and if movement patterns varied between brook trout and brown trout, and (3) evaluate genetic diversity of brook trout within and among study streams, and relate findings to telemetry-based observations of movement. Average total movement was greater for brown trout (mean ± SD = 2,924 ± 4,187 m) than for brook trout (mean ± SD = 1,769 ± 2,194 m). Although there was a large amount of among-fish variability in the movement of both species, the majority of movement coincided with the onset of the spawning season, and a threshold effect was detected between stream flow and movement: where movement increased abruptly for both species during positive flow events. Microsatellite analysis of brook trout revealed consistent findings to those found using radio-tracking, indicating a moderate to high degree of gene flow among brook trout populations. Seasonal movement patterns and the potential for relatively large movements of brook and brown trout highlight the importance of considering stream connectivity when restoring and protecting fish populations and their habitats.

  16. Type specificity of complement-fixing antibody against herpes simplex virus type 2 AG-4 early antigen in patients with asymptomatic infection.

    PubMed Central

    Sherlock, C H; Ashley, R L; Shurtleff, M L; Mack, K D; Corey, L

    1986-01-01

    We evaluated the type specificity of complement-fixing (CF) antibody against the AG-4 early antigen of herpes simplex virus (HSV) type 2 (HSV-2) by comparing a commercial AG-4 CF kit (Simplex-2; Gene Link Australia, Inc., Princeton, N.J.) with quantal microneutralization (MN) and absorption-Western blotting in testing sera from patients with and without a history of genital herpes. Sera characterized as HSV type 1 (HSV-1) or HSV-2 positive or negative by MN were selected and tested by CF, and those with discordant results were further analyzed for specific antibodies by absorption with HSV-1 or HSV-2 antigen and Western blotting with heterologous HSV proteins. A total of 34 of 42 (81%) sera HSV-2 positive by MN, 19 of 43 (44%) sera HSV-1 positive by MN, and 0 of 19 sera negative by MN were positive by CF. Absorption-Western blotting showed that 12 of 18 (67%) sera HSV-1 positive by MN but positive by CF had no HSV-2-specific antibody and that all 7 sera HSV-2 positive by MN but negative by CF had HSV-2-specific antibody. When MN and absorption-Western blotting data were combined to analyze patients with no history of genital herpes, 7 of 19 (37%) with no HSV-2-specific antibody were positive by CF, and 7 of 27 (26%) with HSV-2-specific antibody were negative by CF. The positive and negative predictive values for the CF test were 78 and 75%, respectively, in this group. The presence of antibody to the HSV AG-4 antigen does not discriminate sufficiently between HSV-1- and HSV-2-infected patients to be of value in predicting HSV-2 infection in the absence of symptomatic disease. Images PMID:3023439

  17. Latency of Epstein-Barr virus is stabilized by antisense-mediated control of the viral immediate-early gene BZLF-1.

    PubMed

    Prang, N; Wolf, H; Schwarzmann, F

    1999-12-01

    The ability of the Epstein-Barr virus (EBV) to avoid lytic replication and to establish a latent infection in B-lymphocytes is fundamental for its lifelong persistence and the pathogenesis of various EBV-associated diseases. The viral immediate-early gene BZLF-1 plays a key role for the induction of lytic replication and its activity is strictly regulated on different levels of gene expression. Recently, it was demonstrated that BZLF-1 is also controlled by a posttranscriptional mechanism. Transient synthesis of a mutated competitor RNA saturated this mechanism and caused both expression of the BZLF-1 protein and the induction of lytic viral replication. Using short overlapping fragments of the competitor, it is shown that this control acts on the unspliced primary transcript. RT-PCR demonstrated unspliced BZLF-1 RNA in latently infected B-lymphocytes in the absence of BZLF-1 protein. Due to the complementarity of the gene BZLF-1 and the latency-associated gene EBNA-1 on the opposite strand of the genome, we propose an antisense-mediated mechanism. RNase protection assays demonstrated transcripts in antisense orientation to the BZLF-1 transcript during latency, which comprise a comparable constellation to other herpesviruses. A combined RNAse protection/RT-PCR assay detected the double-stranded hybrid RNA, consisting of the unspliced BZLF-1 transcript and a noncoding intron of the EBNA-1 gene. Binding of BZLF-1 transcripts is suggested to be an important backup control mechanism in addition to transcriptional regulation, stabilizing latency and preventing inappropriate lytic viral replication in vivo. Copyright 1999 Wiley-Liss, Inc.

  18. Effectiveness and safety of ombitasvir, paritaprevir, ritonavir ± dasabuvir ± ribavirin: An early access programme for Spanish patients with genotype 1/4 chronic hepatitis C virus infection.

    PubMed

    Perelló, C; Carrión, J A; Ruiz-Antorán, B; Crespo, J; Turnes, J; Llaneras, J; Lens, S; Delgado, M; García-Samaniego, J; García-Paredes, F; Fernández, I; Morillas, R M; Rincón, D; Porres, J C; Prieto, M; Lázaro Ríos, M; Fernández-Rodríguez, C; Hermo, J A; Rodríguez, M; Herrero, J I; Ruiz, P; Fernández, J R; Macías, M; Pascasio, J M; Moreno, J M; Serra, M Á; Arenas, J; Real, Y; Jorquera, F; Calleja, J L

    2017-03-01

    Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naïve and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation. © 2016 John Wiley & Sons Ltd.

  19. Evaluation of four bed bug traps for surveillances of brown dog ticks (Acari: Ixodidae)

    USDA-ARS?s Scientific Manuscript database

    The brown dog tick can be a serious residential pest due to its unique ability, among ticks, to complete its lifecycle indoors. A single engorged and fertilized female tick can oviposit around 4,000 eggs, allowing indoor establishment to be rapid and easy to miss in early-stage infestations. Acari...

  20. A Mistaken Account of the Age-Crime Curve: Response to Males and Brown (2013)

    ERIC Educational Resources Information Center

    Shulman, Elizabeth P.; Steinberg, Laurence; Piquero, Alex R.

    2014-01-01

    The present article responds to Males and Brown's "Teenagers' High Arrest Rates: Features of Young Age or Youth Poverty?" which claims that the widely observed pattern of crime rates peaking in late adolescence or early adulthood is an artifact of age differences in poverty. We note that the authors' interpretation of their aggregated…

  1. Early diagnosis and follow-up of chronic active Epstein–Barr-virus-associated cardiovascular complications with cardiovascular magnetic resonance imaging

    PubMed Central

    Jiang, Shu; Li, Xiao; Cao, Jian; Wu, Di; Kong, Lingyan; Lin, Lu; Jin, Zhengyu; An, Jing; Wang, Yining

    2016-01-01

    Abstract Introduction: Chronic active Epstein–Barr virus (EBV) infection (CAEBV) is characterized as chronic or recurrent mononucleosis-like symptoms and elevated EBV deoxyribonucleic acid (EBV-DNA) copies. Cardiovascular complications have high morbidity and mortality. The treatment regimen for CAEBV has not been established yet, resulting in poor prognoses. Herein, we present a case of cardiovascular magnetic resonance imaging (CMRI) evaluation with a series of sequences for CAEBV-associated cardiovascular involvement, which has never been reported. Case presentation: A 16-year-old female (body weight, 55 kg) developed a persistent fever and a positive EBV-DNA level of 28,000 copies/mL. Computed tomography angiography (CTA) showed aneurysms involving the aorta and its major branches, as well as multiple aneurysms and stenoses of the coronary arteries. CMRI of the coronary arteries depicted the dilution and stenosis of the arterial lumen as well as the thickening of the arterial wall. Late gadolinium enhancement (LGE) showed subendocardial and transmural delayed enhancement of the left ventricle, suggesting myocardial infarction. CAEBV and associated cardiovascular complications were diagnosed. After treatment with Medrol and Leflunomide, the clinical manifestation and serological parameters reversed to normal. However, the EBV-DNA level increased again to 13,900 copies/mL 2 months later. A follow-up with aorta CTA showed that the arterial walls of the bilateral common iliac artery aneurysms were thicker with new-onset mural thrombi. The aorta CTA also showed new-onset occlusion of the right coronary artery, but a follow-up of CMRI at the same day did not find new-onset delayed enhancement lesion. Conclusion: This case reminds clinicians of the vital importance of early diagnosis and close follow-up of CAEBV-associated cardiovascular complications. With cine imaging, coronary artery imaging, LGE imaging, and other novel techniques, CMRI can effectively and

  2. Sequence analysis of Epstein-Barr virus (EBV) early genes BARF1 and BHRF1 in NK/T cell lymphoma from Northern China.

    PubMed

    Sun, Lingling; Che, Kui; Zhao, Zhenzhen; Liu, Song; Xing, Xiaoming; Luo, Bing

    2015-09-04

    NK/T cell lymphoma is an aggressive lymphoma almost always associated with EBV. BamHI-A rightward open reading frame 1 (BARF1) and BamHI-H rightward open reading frame 1 (BHRF1) are two EBV early genes, which may be involved in the oncogenicity of EBV. It has been found that V29A strains, a BARF1 mutant subtype, showed higher prevalence in NPC, which may suggest the association between this variation and nasopharyngeal carcinoma (NPC). To characterize the sequence variation patterns of the Epstein-Barr virus (EBV) early genes and to elucidate their association with NK/T cell lymphoma, we analyzed the sequences of BARF1 and BHRF1 in EBV-positive NK/T cell lymphoma samples from Northern China. In situ hybridization (ISH) performed for EBV-encoded small RNA1 (EBER1) with specific digoxigenin-labeled probes was used to select the EBV positive lymphoma samples. Nested-polymerase chain reaction (nested-PCR) and DNA sequence analysis technique were used to obtain the sequences of BARF1 and BHRF1. The polymorphisms of these two genes were classified according to the signature changes and compared with the known corresponding EBV gene variation data. Two major subtypes of BARF1 gene, designated as B95-8 and V29A subtype, were identified. B95-8 subtype was the dominant subtype. The V29A subtype had one consistent amino acid change at amino acid residue 29 (V → A). Compared with B95-8, AA change at 88 (L → V) of BHRF1 was found in the majority of the isolates, and AA79 (V → L) mutation in a few isolates. Functional domains of BARF1 and BHRF1 were highly conserved. The distributions of BARF1 and BHRF1 subtypes had no significant differences among different EBV-associated malignancies and healthy donors. The sequences of BARF1 and BHRF1 are highly conserved which may contribute to maintain the biological function of these two genes. There is no evidence that particular EBV substrains of BARF1 or BHRF1 is region-restricted or disease-specific.

  3. De novo assembly of Sockeye salmon kidney transcriptomes reveal a limited early response to piscine reovirus with or without infectious hematopoietic necrosis virus superinfection.

    PubMed

    Polinski, Mark P; Bradshaw, Julia C; Inkpen, Sabrina M; Richard, Jon; Fritsvold, Camilla; Poppe, Trygve T; Rise, Matthew L; Garver, Kyle A; Johnson, Stewart C

    2016-11-02

    Piscine reovirus (PRV) has been associated with the serious disease known as Heart and Skeletal Muscle Inflammation (HSMI) in cultured Atlantic salmon Salmo salar in Norway. PRV is also prevalent in wild and farmed salmon without overt disease manifestations, suggesting multifactorial triggers or PRV variant-specific factors are required to initiate disease. In this study, we explore the head kidney transcriptome of Sockeye salmon Oncorhynchus nerka during early PRV infection to identify host responses in the absence of disease in hopes of elucidating mechanisms by which PRV may directly alter host functions and contribute to the development of a disease state. We further investigate the role of PRV as a coinfecting agent following superinfection with infectious hematopoietic necrosis virus (IHNV) - a highly pathogenic rhabdovirus endemic to the west coast of North America. Challenge of Sockeye salmon with PRV resulted in high quantities of viral transcripts to become present in the blood and kidney of infected fish without manifestations of disease. De novo transcriptome assembly of over 2.3 billion paired RNA-seq reads from the head kidneys of 36 fish identified more than 320,000 putative unigenes, of which less than 20 were suggested to be differentially expressed in response to PRV at either 2 or 3 weeks post challenge by DESeq2 and edgeR analysis. Of these, only one, Ependymin, was confirmed to be differentially expressed by qPCR in an expanded sample set. In contrast, IHNV induced substantial transcriptional changes (differential expression of > 20,000 unigenes) which included transcripts involved in antiviral and inflammatory response pathways. Prior infection with PRV had no significant effect on host responses to superinfecting IHNV, nor did host responses initiated by IHNV exposure influence increasing PRV loads. PRV does not substantially alter the head kidney transcriptome of Sockeye salmon during early (2 to 3 week) infection and dissemination in

  4. Browning boreal forests of western North America

    NASA Astrophysics Data System (ADS)

    Verbyla, David

    2011-12-01

    The GIMMS NDVI dataset has been widely used to document a 'browning trend' in North American boreal forests (Goetz et al 2005, Bunn et al 2007, Beck and Goetz 2011). However, there has been speculation (Alcaraz-Segura et al 2010) that this trend may be an artifact due to processing algorithms rather than an actual decline in vegetation activity. This conclusion was based primarily on the fact that GIMMS NDVI did not capture NDVI recovery within most burned areas in boreal Canada, while another dataset consistently showed post-fire increasing NDVI. I believe that the results of Alcaraz-Segura et al (2010) were due simply to different pixel sizes of the two datasets (64 km2 versus 1 km2 pixels). Similar results have been obtained from tundra areas greening in Alaska, with the results simply due to these pixel size differences (Stow et al 2007). Furthermore, recent studies have documented boreal browning trends based on NDVI from other sensors. Beck and Goetz (2011) have shown the boreal browning trend derived from a different sensor (MODIS) to be very similar to the boreal browning trend derived from the GIMMS NDVI dataset for the circumpolar boreal region. Parent and Verbyla (2010) found similar declining NDVI patterns based on NDVI from Landsat sensors and GIMMS NDVI in boreal Alaska. Zhang et al (2008) found a similar 'browning trend' in boreal North America based on a production efficiency model using an integrated AVHRR and MODIS dataset. The declining NDVI trend in areas of boreal North America is consistent with tree-ring studies (D'Arrigo et al 2004, McGuire et al 2010, Beck et al 2011). The decline in tree growth may be due to temperature-induced drought stress (Barber et al 2000) caused by higher evaporative demands in a warming climate (Lloyd and Fastie 2002). In a circumpolar boreal study, Lloyd and Bunn (2007) found that a negative relationship between temperature and tree-ring growth occurred more frequently in warmer parts of species' ranges

  5. Early transduction produces highly functional chimeric antigen receptor-modified virus-specific T-cells with central memory markers: a Production Assistant for Cell Therapy (PACT) translational application.

    PubMed

    Sun, Jiali; Huye, Leslie E; Lapteva, Natalia; Mamonkin, Maksim; Hiregange, Manasa; Ballard, Brandon; Dakhova, Olga; Raghavan, Darshana; Durett, April G; Perna, Serena K; Omer, Bilal; Rollins, Lisa A; Leen, Ann M; Vera, Juan F; Dotti, Gianpietro; Gee, Adrian P; Brenner, Malcolm K; Myers, Douglas G; Rooney, Cliona M

    2015-01-01

    Virus-specific T-cells (VSTs) proliferate exponentially after adoptive transfer into hematopoietic stem cell transplant (HSCT) recipients, eliminate virus infections, then persist and provide long-term protection from viral disease. If VSTs behaved similarly when modified with tumor-specific chimeric antigen receptors (CARs), they should have potent anti-tumor activity. This theory was evaluated by Cruz et al. in a previous clinical trial with CD19.CAR-modified VSTs, but there was little apparent expansion of these cells in patients. In that study, VSTs were gene-modified on day 19 of culture and we hypothesized that by this time, sufficient T-cell differentiation may have occurred to limit the subsequent proliferative capacity of the transduced T-cells. To facilitate the clinical testing of this hypothesis in a project supported by the NHLBI-PACT mechanism, we developed and optimized a good manufacturing practices (GMP) compliant method for the early transduction of VSTs directed to Epstein-Barr virus (EBV), Adenovirus (AdV) and cytomegalovirus (CMV) using a CAR directed to the tumor-associated antigen disialoganglioside (GD2). Ad-CMVpp65-transduced EBV-LCLs effectively stimulated VSTs directed to all three viruses (triVSTs). Transduction efficiency on day three was increased in the presence of cytokines and high-speed centrifugation of retroviral supernatant onto retronectin-coated plates, so that under optimal conditions up to 88% of tetramer-positive VSTs expressed the GD2.CAR. The average transduction efficiency of early-and late transduced VSTs was 55 ± 4% and 22 ± 5% respectively, and early-transduced VSTs maintained higher frequencies of T cells with central memory or intermediate memory phenotypes. Early-transduced VSTs also had higher proliferative capacity and produced higher levels of TH1 cytokines IL-2, TNF-α, IFN-γ, MIP-1α, MIP-1β and other cytokines in vitro. We developed a rapid and GMP compliant method for the early transduction of

  6. Storage stability of flour-blasted brown rice

    USDA-ARS?s Scientific Manuscript database

    Brown rice was blasted with rice flour rather than sand in a sand blaster to make microscopic nicks and cuts so that water can easily penetrate into the brown rice endosperm and cook the rice in a shorter time. The flour-blasted American Basmati brown rice, long grain brown rice, and parboiled long...

  7. The IFITMs Inhibit Zika Virus Replication.

    PubMed

    Savidis, George; Perreira, Jill M; Portmann, Jocelyn M; Meraner, Paul; Guo, Zhiru; Green, Sharone; Brass, Abraham L

    2016-06-14

    Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses. Copyright © 2016. Published by Elsevier Inc.

  8. Browning phenomenon of medieval stained glass windows.

    PubMed

    Ferrand, Jessica; Rossano, Stéphanie; Loisel, Claudine; Trcera, Nicolas; van Hullebusch, Eric D; Bousta, Faisl; Pallot-Frossard, Isabelle

    2015-04-07

    In this work, three pieces of historical on-site glass windows dated from the 13th to 16th century and one archeological sample (8th century) showing Mn-rich brown spots at their surface or subsurface have been characterized by optical microscopy and Scanning Electron Microscopy coupled with Energy Dispersive X-ray spectroscopy. The oxidation state of Mn as well as the Mn environment in the alteration phase have been characterized by X-ray absorption spectroscopy at the Mn K-edge. Results show that the oxidation state of Mn and therefore the nature of the alteration phase varies according to the sample considered and is correlated with the extent of the brown alteration. The larger the brown areas the more oxidized the Mn. However, by contrast with literature, the samples presenting the more extended brown areas are not similar to pyrolusite and contain Mn mainly under a (+III) oxidation state.

  9. Anatomy of Brown Dwarf Atmosphere Artist Concept

    NASA Image and Video Library

    2013-01-08

    This artist illustration shows the atmosphere of a brown dwarf called 2MASSJ22282889-431026, which was observed simultaneously by NASA Spitzer and Hubble space telescopes. The results were unexpected, revealing offset layers of material.

  10. A Trio of Brown Dwarfs Artist Concept

    NASA Image and Video Library

    2011-08-23

    This artist conception based on data from NASA Wide-field Infrared Survey Explorer illustrates what brown dwarfs of different types might look like to a hypothetical interstellar traveler who has flown a spaceship to each one.

  11. Control of enzymatic browning in potato (Solanum tuberosum L.) by sense and antisense RNA from tomato polyphenol oxidase.

    PubMed

    Coetzer, C; Corsini, D; Love, S; Pavek, J; Tumer, N

    2001-02-01

    Polyphenol oxidase (PPO) activity of Russet Burbank potato was inhibited by sense and antisense PPO RNAs expressed from a tomato PPO cDNA under the control of the 35S promoter from the cauliflower mosaic virus. Transgenic Russet Burbank potato plants from 37 different lines were grown in the field. PPO activity and the level of enzymatic browning were measured in the tubers harvested from the field. Of the tubers from 28 transgenic lines that were sampled, tubers from 5 lines exhibited reduced browning. The level of PPO activity correlated with the reduction in enzymatic browning in these lines. These results indicate that expression of tomato PPO RNA in sense or antisense orientation inhibits PPO activity and enzymatic browning in the major commercial potato cultivar. Expression of tomato PPO RNA in sense orientation led to the greatest decrease in PPO activity and enzymatic browning, possibly due to cosuppression. These results suggest that expression of closely related heterologous genes can be used to prevent enzymatic browning in a wide variety of food crops without the application of various food additives.

  12. Cassava virus diseases: biology, epidemiology, and management.

    PubMed

    Legg, James P; Lava Kumar, P; Makeshkumar, T; Tripathi, Leena; Ferguson, Morag; Kanju, Edward; Ntawuruhunga, Pheneas; Cuellar, Wilmer

    2015-01-01

    Cassava (Manihot esculenta Crantz.) is the most important vegetatively propagated food staple in Africa and a prominent industrial crop in Latin America and Asia. Its vegetative propagation through stem cuttings has many advantages, but deleteriously it means that pathogens are passed from one generation to the next and can easily accumulate, threatening cassava production. Cassava-growing continents are characterized by specific suites of viruses that affect cassava and pose particular threats. Of major concern, causing large and increasing economic impact in Africa and Asia are the cassava mosaic geminiviruses that cause cassava mosaic disease in Africa and Asia and cassava brown streak viruses causing cassava brown streak disease in Africa. Latin America, the center of origin and domestication of the crop, hosts a diverse set of virus species, of which the most economically important give rise to cassava frog skin disease syndrome. Here, we review current knowledge on the biology, epidemiology, and control of the most economically important groups of viruses in relation to both farming and cultural practices. Components of virus control strategies examined include: diagnostics and surveillance, prevention and control of infection using phytosanitation, and control of disease through the breeding and promotion of varieties that inhibit virus replication and/or movement. We highlight areas that need further research attention and conclude by examining the likely future global outlook for virus disease management in cassava. © 2015 Elsevier Inc. All rights reserved.

  13. Polarization of Young Brown Dwarfs

    NASA Astrophysics Data System (ADS)

    Manjavacas, Elena; Miles-Páez, Paulo A.; Zapatero-Osorio, Maria Rosa; Goldman, Bertrand; Buenzli, Esther; Henning, Thomas; Pallé, Enric

    2016-08-01

    Linear polarization due to scattering processes can be used as a probe of the existence of atmospheric condensates in ultracool dwarfs. Models predict that the observed linear polarization increases with the degree of oblateness, which is inverse to the surface gravity.We aimed to measure optical linear polarization from a sample of six young brown dwarfs, with spectral types between M6 to L2, and cataloged previously as objects with low gravity using spectroscopy. These targets are believed to have dusty atmospheres as a consequence of their low gravity, therefore linearly polarized light is expected from these objects.Linear polarimetric data were collected in I and R-band using CAFOS at the 2.2m telescope in Calar Alto Observatory.We obtained results of linear polarization in the I-band compatible with non polarization for all the objects, and similar results for the polarization degree in the R-band for all objects with the exception of 2M0422. For this object we find a linear polarization degree of 0.81+-0.18%. 2M0422 is 10 deg to the south of the Taurus star-forming region, thus, we suspect that its polarization is caused by the dust in the cloud in which 2M0422 might be embedded.

  14. BRIC - Brown with canisters on middeck

    NASA Image and Video Library

    1998-11-02

    STS095-E-5166 (2 Nov. 1998) --- Astronaut Curtis L. Brown Jr. (left), STS-95 commander, and U.S. Sen. John H. Glenn Jr., payload specialist, are seen on the middeck of the Space Shuttle Discovery during Flight Day three activity. Brown has retrieved an experiment from a stowage locker and Glenn works out on the ergometer device. The photo was taken with an electronic still camera (ESC) at 05:55:42 GMT, Nov. 2.

  15. What Brown saw and you can too

    NASA Astrophysics Data System (ADS)

    Pearle, Philip; Collett, Brian; Bart, Kenneth; Bilderback, David; Newman, Dara; Samuels, Scott

    2010-12-01

    A discussion of Robert Brown's original observations of particles ejected by pollen of the plant Clarkia pulchella undergoing what is now called Brownian motion is given. We consider the nature of those particles and how he misinterpreted the Airy disk of the smallest particles to be universal organic building blocks. Relevant qualitative and quantitative investigations with a modern microscope and with a "homemade" single lens microscope similar to Brown's are presented.

  16. How Long? Cosby, Brown and Racial Progress

    ERIC Educational Resources Information Center

    Malveaux, Julianne

    2004-01-01

    Bill Cosby ruffled feathers, raised eyebrows and said a mouthful when, at a Howard University black-tie celebration of the 50th anniversary of Brown v. Board of Education, he launched into a rift about "the lower economic people" not holding up their end of the bargain in the wake of Brown. "We can't blame White people," Cosby said, for an array…

  17. Interim reliability evaluation program, Browns Ferry 1

    SciTech Connect

    Mays, S.E.; Poloski, J.P.; Sullivan, W.H.

    1981-01-01

    Probabilistic risk analysis techniques, i.e., event tree and fault tree analysis, were utilized to provide a risk assessment of the Browns Ferry Nuclear Plant Unit 1. Browns Ferry 1 is a General Electric boiling water reactor of the BWR 4 product line with a Mark 1 (drywell and torus) containment. Within the guidelines of the IREP Procedure and Schedule Guide, dominant accident sequences that contribute to public health and safety risks were identified and grouped according to release categories.

  18. Accelerated detection of brown-rot decay : comparison of soil block test, chemical analysis, mechanical properties, and immunodetection

    Treesearch

    C. A. Clausen; S. N. Kartal

    2003-01-01

    Early detection of wood decay is critical because decay fungi can cause rapid structural failure. The objective of this study was to compare the sensitivity of different methods purported to detect brown-rot decay in the early stages of development. The immunodiagnostic wood decay (IWD)test, soil block test/cake pan test, mechanical property tests, and chemical...

  19. The Unevenly Distributed Nearest Brown Dwarfs

    NASA Astrophysics Data System (ADS)

    Bihain, Gabriel; Scholz, Ralf-Dieter

    2016-08-01

    To address the questions of how many brown dwarfs there are in the Milky Way, how do these objects relate to star formation, and whether the brown dwarf formation rate was different in the past, the star-to-brown dwarf number ratio can be considered. While main sequence stars are well known components of the solar neighborhood, lower mass, substellar objects increasingly add to the census of the nearest objects. The sky projection of the known objects at <6.5 pc shows that stars present a uniform distribution and brown dwarfs a non-uniform distribution, with about four times more brown dwarfs behind than ahead of the Sun relative to the direction of rotation of the Galaxy. Assuming that substellar objects distribute uniformly, their observed configuration has a probability of 0.1 %. The helio- and geocentricity of the configuration suggests that it probably results from an observational bias, which if compensated for by future discoveries, would bring the star-to-brown dwarf ratio in agreement with the average ratio found in star forming regions.

  20. Large Outbreaks of Ciguatera after Consumption of Brown Marbled Grouper

    PubMed Central

    Chan, Thomas Y. K.

    2014-01-01

    Brown marbled grouper (Epinephelus fuscoguttatus) is an apex predator from coral reefs of the Indo-Pacific region. All five published case series of ciguatera after consumption of brown marbled grouper were reviewed to characterize the types, severity and chronicity of ciguatera symptoms associated with its consumption. Three of these case series were from large outbreaks affecting over 100–200 subjects who had eaten this reef fish served at banquets. Affected subjects generally developed a combination of gastrointestinal, neurological and, less commonly, cardiovascular symptoms. Gastrointestinal symptoms occurred early and generally subsided in 1–2 days. Some neurological symptoms (e.g., paresthesia of four limbs) could last for weeks or months. Sinus bradycardia and hypotension occurred early, but could be severe and prolonged, necessitating the timely use of intravenous fluids, atropine and dopamine. Other cardiovascular and neurological features included atrial ectopics, ventricular ectopics, dyspnea, chest tightness, PR interval >0.2 s, ST segment changes, polymyositis and coma. Concomitant alcohol consumption was associated with a much higher risk of developing bradycardia, hypotension and altered skin sensation. The public should realize that consumption of the high-risk fish (especially the ciguatoxin-rich parts and together with alcohol use) and repeated ciguatoxin exposures will result in more severe and chronic illness. PMID:25019942

  1. Large outbreaks of ciguatera after consumption of brown marbled grouper.

    PubMed

    Chan, Thomas Y K

    2014-07-11

    Brown marbled grouper (Epinephelus fuscoguttatus) is an apex predator from coral reefs of the Indo-Pacific region. All five published case series of ciguatera after consumption of brown marbled grouper were reviewed to characterize the types, severity and chronicity of ciguatera symptoms associated with its consumption. Three of these case series were from large outbreaks affecting over 100-200 subjects who had eaten this reef fish served at banquets. Affected subjects generally developed a combination of gastrointestinal, neurological and, less commonly, cardiovascular symptoms. Gastrointestinal symptoms occurred early and generally subsided in 1-2 days. Some neurological symptoms (e.g., paresthesia of four limbs) could last for weeks or months. Sinus bradycardia and hypotension occurred early, but could be severe and prolonged, necessitating the timely use of intravenous fluids, atropine and dopamine. Other cardiovascular and neurological features included atrial ectopics, ventricular ectopics, dyspnea, chest tightness, PR interval >0.2 s, ST segment changes, polymyositis and coma. Concomitant alcohol consumption was associated with a much higher risk of developing bradycardia, hypotension and altered skin sensation. The public should realize that consumption of the high-risk fish (especially the ciguatoxin-rich parts and together with alcohol use) and repeated ciguatoxin exposures will result in more severe and chronic illness.

  2. ECHO virus

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001340.htm ECHO virus To use the sharing features on this page, please enable JavaScript. Enteric cytopathic human orphan (ECHO) viruses are a group of viruses that can lead ...

  3. Discovery of Nearest Known Brown Dwarf

    NASA Astrophysics Data System (ADS)

    2003-01-01

    near-infrared (0.9-2.5 µm) spectrum of Epsilon Indi B, obtained on November 16-17, 2002, with the SOFI multi-mode instrument on the ESO 3.5-m New Technology Telescope (NTT) at the La Silla Observatory (Chile) The total integration time is 360 sec. Regions of strong absorption in the Earth's atmosphere have been removed for clarity. The locations of prominent molecular absorption bands from water (H2O), methane (CH4) and carbon monoxide (CO) in the atmosphere of Epsilon Indi B are indicated. Also labelled are some spectral lines from potassium (KI, at 1.25 and 1.52 µm) and sodium (NaI, at 2.33 µm) atoms. From these data, the spectral type of Epsilon Indi B is determined as T2.5V, corresponding to an effective temperature of 'just' 1000 ± 60 °C. Within days of its discovery in the database, the astronomers managed to secure an infrared spectrum of Epsilon Indi B using the SOFI instrument on the ESO 3.5-m New Technology Telescope (NTT) at the La Silla Observatory (Chile). The spectrum showed the broad absorption features due to methane and water steam in its upper atmosphere, indicating a temperature of 'only' 1000 °C. Ordinary stars are never this cool - Epsilon Indi B was confirmed as a brown dwarf. Brown dwarfs are thought to form in much the same way as stars, by the gravitational collapse of clumps of cold gas and dust in dense molecular clouds. However, for reasons not yet entirely clear, some clumps end up with masses less than about 7.5% of that of our Sun, or 75 times the mass of planet Jupiter. Below that boundary, there is not enough pressure in the core to initiate nuclear hydrogen fusion, the long-lasting and stable source of power for ordinary stars like the Sun. Except for a brief early phase where some deuterium is burned, these low-mass objects simply continue to cool and fade slowly away while releasing the heat left-over from their birth. Theoretical discussions of such objects began some 40 years ago. They were first named 'black dwarfs' and

  4. R5 human immunodeficiency virus type 1 with efficient DC-SIGN use is not selected for early after birth in vertically infected children.

    PubMed

    Borggren, Marie; Navér, Lars; Casper, Charlotte; Ehrnst, Anneka; Jansson, Marianne

    2013-04-01

    The binding of human immunodeficiency virus (HIV) to C-type lectin receptors may result in either enhanced trans-infection of T-cells or virus degradation. We have investigated the efficacy of HIV-1 utilization of DC-SIGN, a C-type lectin receptor, in the setting of intrauterine or intrapartum mother-to-child transmission (MTCT). Viruses isolated from HIV-1-infected mothers at delivery and from their vertically infected children both shortly after birth and later during the progression of the disease were analysed for their use of DC-SIGN, binding and ability to trans-infect. DC-SIGN use of a child's earlier virus isolate tended to be reduced as compared with that of the corresponding maternal isolate. Furthermore, the children's later isolate displayed enhanced DC-SIGN utilization compared with that of the corresponding earlier virus. These results were also supported in head-to-head competition assays and suggest that HIV-1 variants displaying efficient DC-SIGN use are not selected for during intrauterine or intrapartum MTCT. However, viruses with increased DC-SIGN use may evolve later in paediatric HIV-1 infections.

  5. Effect of Maillard browning reaction on protein utilization and plasma amino acid response by rainbow trout (Salmo gairdneri).

    PubMed

    Plakas, S M; Lee, T C; Wolke, R E; Meade, T L

    1985-12-01

    The effect of the Maillard browning reaction in the diet of rainbow trout (Salmo gairdneri) on growth and amino acid availability was investigated. Chemical and enzymatic hydrolysis methods were applied for the detection of the losses of amino acids in a model protein browning system. Arginine and lysine exhibited the greatest losses in the mixture of fish protein isolate and glucose stored for 40 d at 37 degrees C. The apparent digestibility and absorption of individual amino acids, particularly lysine, was lower in trout fed browned protein than in those fed the control protein. Plasma lysine levels were significantly depressed, while the plasma levels of glucose and most other amino acids were elevated in relation to the loss in nutritive value of dietary protein after browning. The early Maillard reaction derivative of lysine, epsilon-deoxy-fructosyl-lysine, was recovered from browned protein (by using the in vitro enzymatic hydrolysis procedure) and from the plasma of trout fed browned protein. Analysis of plasma free amino acids provided an indication of lysine bioavailability and identified lysine as the first-limiting amino acid in the diets containing browned protein.

  6. On the relationship between boreal forest browning and tree mortality: insights from Alaska

    NASA Astrophysics Data System (ADS)

    Rogers, B. M.; Goetz, S. J.

    2015-12-01

    Long-term satellite measurements of vegetation productivity in high-latitude environments have revealed profound and widespread responses to climate warming. Although warmer and longer summers are causing the Arctic to "green", many regions of boreal forest are showing the opposite response, particularly since the mid 1990s. This "browning" phenomenon was generally unexpected at the time of discovery, is not captured by global models, and may have profound consequences for the boreal biome. A number of studies have linked satellite-based browning trends to tree productivity through tree rings. However, our understanding of the environmental controls and ecosystem consequences of browning remains remarkably limited. Here we examine to what extent browning patterns are related to a fundamental demographic process: tree mortality. We focus on a long-term inventory database in Alaska to characterize mortality events and trends from 1994 to 2014. These patterns were related to vegetation productivity indices from MODIS and the AVHRR-based GIMMS3g data set. We explore three central hypotheses: (1) mortality events are likely to be preceded by 5-10 year browning trends ("press stress"), (2) mortality events are likely to be preceded by distinct pulses of low productivity ("pulse stress"), and (3) long-term trends in mortality are related to long-term browning. Within our study region, which encompasses eastern Alaskan from the Pacific coastal mountains up through the interior, we find strong evidence for the first two hypotheses. The third is weakly supported, which may be a consequence of the episodic nature of mortality in the region. However, preliminary analyses in the southern Canadian boreal reveal a markedly stronger relationship between long-term mortality and browning. Taken together, our study suggests a robust correlation between satellite-based metrics of productivity and forest demography; one that has consequences for forest composition, carbon stocks, and

  7. Measles Virus Defective Interfering RNAs Are Generated Frequently and Early in the Absence of C Protein and Can Be Destabilized by Adenosine Deaminase Acting on RNA-1-Like Hypermutations.

    PubMed

    Pfaller, Christian K; Mastorakos, George M; Matchett, William E; Ma, Xiao; Samuel, Charles E; Cattaneo, Roberto

    2015-08-01

    Defective interfering RNAs (DI-RNAs) of the viral genome can form during infections of negative-strand RNA viruses and outgrow full-length viral genomes, thereby modulating the severity and duration of infection. Here we document the frequent de novo generation of copy-back DI-RNAs from independent rescue events both for a vaccine measles virus (vac2) and for a wild-type measles virus (IC323) as early as passage 1 after virus rescue. Moreover, vaccine and wild-type C-protein-deficient (C-protein-knockout [CKO]) measles viruses generated about 10 times more DI-RNAs than parental virus, suggesting that C enhances the processivity of the viral polymerase. We obtained the nucleotide sequences of 65 individual DI-RNAs, identified breakpoints and reinitiation sites, and predicted their structural features. Several DI-RNAs possessed clusters of A-to-G or U-to-C transitions. Sequences flanking these mutation sites were characteristic of those favored by adenosine deaminase acting on RNA-1 (ADAR1), which catalyzes in double-stranded RNA the C-6 deamination of adenosine to produce inosine, which is recognized as guanosine, a process known as A-to-I RNA editing. In individual DI-RNAs the transitions were of the same type and occurred on both sides of the breakpoint. These patterns of mutations suggest that ADAR1 edits unencapsidated DI-RNAs that form double-strand RNA structures. Encapsidated DI-RNAs were incorporated into virus particles, which reduced the infectivity of virus stocks. The CKO phenotype was dominant: DI-RNAs derived from vac2 with a CKO suppressed the replication of vac2, as shown by coinfections of interferon-incompetent lymphatic cells with viruses expressing different fluorescent reporter proteins. In contrast, coinfection with a C-protein-expressing virus did not counteract the suppressive phenotype of DI-RNAs. Recombinant measles viruses (MVs) are in clinical trials as cancer therapeutics and as vectored vaccines for HIV-AIDS and other infectious

  8. Measles Virus Defective Interfering RNAs Are Generated Frequently and Early in the Absence of C Protein and Can Be Destabilized by Adenosine Deaminase Acting on RNA-1-Like Hypermutations

    PubMed Central

    Pfaller, Christian K.; Mastorakos, George M.; Matchett, William E.; Ma, Xiao; Samuel, Charles E.

    2015-01-01

    ABSTRACT Defective interfering RNAs (DI-RNAs) of the viral genome can form during infections of negative-strand RNA viruses and outgrow full-length viral genomes, thereby modulating the severity and duration of infection. Here we document the frequent de novo generation of copy-back DI-RNAs from independent rescue events both for a vaccine measles virus (vac2) and for a wild-type measles virus (IC323) as early as passage 1 after virus rescue. Moreover, vaccine and wild-type C-protein-deficient (C-protein-knockout [CKO]) measles viruses generated about 10 times more DI-RNAs than parental virus, suggesting that C enhances the processivity of the viral polymerase. We obtained the nucleotide sequences of 65 individual DI-RNAs, identified breakpoints and reinitiation sites, and predicted their structural features. Several DI-RNAs possessed clusters of A-to-G or U-to-C transitions. Sequences flanking these mutation sites were characteristic of those favored by adenosine deaminase acting on RNA-1 (ADAR1), which catalyzes in double-stranded RNA the C-6 deamination of adenosine to produce inosine, which is recognized as guanosine, a process known as A-to-I RNA editing. In individual DI-RNAs the transitions were of the same type and occurred on both sides of the breakpoint. These patterns of mutations suggest that ADAR1 edits unencapsidated DI-RNAs that form double-strand RNA structures. Encapsidated DI-RNAs were incorporated into virus particles, which reduced the infectivity of virus stocks. The CKO phenotype was dominant: DI-RNAs derived from vac2 with a CKO suppressed the replication of vac2, as shown by coinfections of interferon-incompetent lymphatic cells with viruses expressing different fluorescent reporter proteins. In contrast, coinfection with a C-protein-expressing virus did not counteract the suppressive phenotype of DI-RNAs. IMPORTANCE Recombinant measles viruses (MVs) are in clinical trials as cancer therapeutics and as vectored vaccines for HIV-AIDS and

  9. 'This excellent observer ...': the correspondence between Charles Darwin and James Crichton-Browne, 1869-75.

    PubMed

    Pearn, Alison M

    2010-06-01

    Between May 1869 and December 1875, Charles Darwin exchanged more than 40 letters with James Crichton-Browne, superintendent of the West Riding Pauper Lunatic Asylum, Wakefield, Yorkshire. This paper charts their relationship within the context of Darwin's wider research networks and methods; it analyses the contribution that Crichton-Browne made to the writing of Expression, arguing that the information he provided materially affected Darwin's thesis, and that it was partly the need to assimilate this that led Darwin to publish Expression separately from Descent. The letters help to reconstruct Crichton-Browne's early research interests, and document Darwin's little-explored role as a patron. Both men are revealed within a collaborative scientific network, with each of them at various times a beneficiary or a promoter.

  10. Effects of Peach Cultivar on Enzymatic Browning Following Cell Damage from High-Pressure Processing.

    PubMed

    Techakanon, Chukwan; Gradziel, Thomas M; Barrett, Diane M

    2016-10-12

    Peach cultivars contribute to unique product characteristics and may affect the degree of browning after high-pressure processing (HPP). Nine peach cultivars were subjected to HPP at 0, 100, and 400 MPa for 10 min. Proton nuclear magnetic resonance ( 1 H NMR) relaxometry, light microscopy, color, polyphenol oxidase (PPO) activity, and total phenols were evaluated. The development of enzymatic browning during refrigerated storage occurred because of damage during HPP that triggered loss of cell integrity, allowing substrates to interact with enzymes. Increasing pressure levels resulted in greater damage, as determined by shifts in transverse relaxation time (T 2 ) and by light micrographs. Discoloration was triggered by membrane decompartmentalization but limited by PPO activity, which was found to correlate to cultivar harvest time (early, mid, and late season). Outcomes from the microstructure, 1 H NMR ,and PPO activity evaluation were an effective means of determining membrane decompartmentalization and allowed for prediction of browning scenarios.

  11. Susceptibility of North American big brown bats (Eptesicus fuscus) to infection with European bat lyssavirus type 1.

    PubMed

    Franka, R; Johnson, N; Müller, T; Vos, A; Neubert, L; Freuling, C; Rupprecht, C E; Fooks, A R

    2008-08-01

    The aim of this study was to determine the susceptibility of insectivorous bats (using the big brown bat as a model) to infection with European bat lyssavirus type 1a (EBLV-1a), to assess the dynamics of host immune responses and to evaluate the opportunity for horizontal viral transmission within colonies. Two isolates of EBLV-1a, originating from Slovakia (EBLV-1aSK) and Germany (EBLV-1aGE), were tested. Four different routes of inoculation were used with isolate EBLV-1aSK [10(4.8) mouse intracerebral median lethal dose (MICLD(50)) in 50 mul]: intramuscular (i.m.) in the deltoid area or masseter region, per os (p.o.) and intradermal (i.d.) scratches. Isolate EBLV-1aGE (10(3.2) and 10(2.2) MICLD(50) in 20 mul) was inoculated via the intranasal (i.n.), i.m. (low- and high-dose groups, into pectoral muscles); p.o. and intracerebral (i.c.) routes. None of the bats infected by the i.n., p.o. or i.d. route with either virus isolate developed disease during the experiments (91 or 120 days, respectively). Incubation periods were 9-12 days for i.c.-inoculated bats (66 % mortality), 12-33 days for bats inoculated i.m. with the higher dose (23-50 % mortality) and 21-58 days in bats inoculated i.m. with the lower dose of virus (57 % mortality). Virus or viral RNA in bat saliva was detected occasionally, as early as 37 days before death. All i.d.-inoculated and the majority of i.m.-inoculated bats seroconverted within 7-10 days of inoculation. These observations suggest that exposure of bats to varying doses of EBLV-1 from rabid conspecifics via natural (i.d.) routes could lead to an abortive infection and serve as a natural mode of immunization resulting in the presence of virus-neutralizing antibodies in free-ranging bats.

  12. Imprints of dynamical interactions on brown dwarf pairing statistics and kinematics

    NASA Astrophysics Data System (ADS)

    Sterzik, M. F.; Durisen, R. H.

    2003-03-01

    We present statistically robust predictions of brown dwarf properties arising from dynamical interactions during their early evolution in small clusters. Our conclusions are based on numerical calculations of the internal cluster dynamics as well as on Monte-Carlo models. Accounting for recent observational constraints on the sub-stellar mass function and initial properties in fragmenting star forming clumps, we derive multiplicity fractions, mass ratios, separation distributions, and velocity dispersions. We compare them with observations of brown dwarfs in the field and in young clusters. Observed brown dwarf companion fractions around 15 +/- 7% for very low-mass stars as reported recently by Close et al. (\\cite{CSFB03}) are consistent with certain dynamical decay models. A significantly smaller mean separation distribution for brown dwarf binaries than for binaries of late-type stars can be explained by similar specific energy at the time of cluster formation for all cluster masses. Due to their higher velocity dispersions, brown-dwarfs and low-mass single stars will undergo time-dependent spatial segregation from higher-mass stars and multiple systems. This will cause mass functions and binary statistics in star forming regions to vary with the age of the region and the volume sampled.

  13. Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population

    PubMed Central

    Chahal, Harinder S.; Marseille, Elliot A.; Tice, Jeffrey A.; Pearson, Steve D.; Ollendorf, Daniel A.; Fox, Rena K.; Kahn, James G.

    2016-01-01

    IMPORTANCE Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown. OBJECTIVE To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis. DESIGN, SETTING, AND PARTICIPANTS This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015. INTERVENTIONS Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment. MAIN OUTCOMES AND MEASURES Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs. RESULTS We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28 899, for an ICER of $39 475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19 833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81 165 per QALY gained

  14. Magnetic resonance imaging in congenital Brown syndrome.

    PubMed

    Kim, Jae Hyoung; Hwang, Jeong-Min

    2015-08-01

    Our aim was to elucidate the etiology of Brown syndrome by evaluating the trochlea position, morphologic characteristics of the extraocular muscles including superior oblique muscle/tendon complex, and the presence of the cranial nerves (CN) III, IV, and VI using magnetic resonance imaging (MRI) in eight patients with unilateral congenital Brown syndrome and one patient with bilateral congenital Brown syndrome. Nine consecutive patients diagnosed with congenital Brown syndrome had a comprehensive ocular examination and MRI for the CN III, CN VI, and the extraocular muscles. Five of the nine patients underwent additional high resolution MRI for CN IV. The distance from the annulus of Zinn to the trochlea was measured. Normal sized CN III, IV, and VI, as well as all extraocular muscles, could be identified bilaterally in all patients with available MRI. The distance from the annulus of Zinn to the trochlea was the same in both eyes. The findings for our patients, particularly in those who underwent additional high resolution MRI, did not provide evidence of a lack of CN IV as a cause of Brown syndrome.

  15. Foodborne viruses

    USDA-ARS?s Scientific Manuscript database

    Testing for human pathogenic viruses in foods represents a formidable task requiring the extraction, concentration, and assay of a host of viruses from a wide range of food matrices. The enteric viruses, particularly genogroup I and II (GI and GII) noroviruses and hepatitis A virus, are the princip...

  16. Detection of avian H7N9 influenza A viruses at the Yangtze Delta Region of China during early H7N9 outbreaks

    PubMed Central

    Li, Yin; Huang, Xin-mei; Zhao, Dong-min; Liu, Yu-zhuo; He, Kong-wang; Liu, Yao-xing; Chen, Chang-hai; Long, Li-Ping; Xu, Yifei; Xie, Xing-xing; Han, Kai-kai; Liu, Xiao-yan; Yang, Jing; Zhang, You-Fa; Fan, Feng; Webby, Richard; Wan, Xiu-Feng

    2016-01-01

    SUMMARY Since the first H7N9 human case in Shanghai, February 19, 2013, the emerging avian-origin H7N9 influenza A virus has become an epizootic virus in China, posing a potential pandemic threat to public health. From April 2 to April 28, 2013, 422 oral-pharyngeal and cloacal swabs were collected from birds and environmental surfaces at five live poultry markets (LPMs) and 13 backyard poultry farms (BPFs) across three cities, Wuxi, Suzhou, and Nanjing, in the Yangtze Delta Region. A total of 22 isolates were recovered, and 6 were subtyped as H7N9, 9 as H9N2, 4 as H7N9/H9N2, and 3 un-subtyped influenza A viruses. Genomic sequences showed that the HA and NA genes of the H7N9 viruses were similar to those of the H7N9 human isolates as well as other avian origin H7N9 isolates in the region but the PB1, PA, NP, and MP genes of the sequenced viruses were, however, more diverse. Among the four H7N9/H9N2 mixed infections, three were from LPM whereas the other one from the ducks at one BPF, which were H7N9 negative in serological analyses. A survey of the bird trading records of the LPMs and BPFs indicates that trading was a likely route for virus transmission across these regions. Our results suggested that a better biosecurity and more effective vaccination should be implemented in backyard farms besides biosecurity management in LPMs. PMID:27309047

  17. Detection of Avian H7N9 Influenza A Viruses in the Yangtze Delta Region of China During Early H7N9 Outbreaks.

    PubMed

    Li, Yin; Huang, Xin-Mei; Zhao, Dong-Min; Liu, Yu-Zhuo; He, Kong-Wang; Liu, Yao-Xing; Chen, Chang-Hai; Long, Li-Ping; Xu, Yifei; Xie, Xing-Xing; Han, Kai-Kai; Liu, Xiao-Yan; Yang, Jing; Zhang, You-Fa; Fan, Feng; Webby, Richard; Wan, Xiu-Feng

    2016-05-01

    Since the first H7N9 human case in Shanghai, February 19, 2013, the emerging avian-origin H7N9 influenza A virus has become an epizootic virus in China, posing a potential pandemic threat to public health. From April 2 to April 28, 2013, some 422 oral-pharyngeal and cloacal swabs were collected from birds and environmental surfaces at five live poultry markets (LPMs) and 13 backyard poultry farms (BPFs) across three cities, Wuxi, Suzhou, and Nanjing, in the Yangtze Delta region. In total 22 isolates were recovered, and six were subtyped as H7N9, nine as H9N2, four as H7N9/H9N2, and three unsubtyped influenza A viruses. Genomic sequences showed that the HA and NA genes of the H7N9 viruses were similar to those of the H7N9 human isolates, as well as other avian-origin H7N9 isolates in the region, but the PB1, PA, NP, and MP genes of the sequenced viruses were more diverse. Among the four H7N9/H9N2 mixed infections, three were from LPM, whereas the other one was from the ducks at one BPF, which were H7N9 negative in serologic analyses. A survey of the bird trading records of the LPMs and BPFs indicates that trading was a likely route for virus transmission across these regions. Our results suggested that better biosecurity and more effective vaccination should be implemented in backyard farms, in addition to biosecurity management in LPMs.

  18. a Faint and Lonely Brown Dwarf in the Solar Vicinity

    NASA Astrophysics Data System (ADS)

    1997-04-01

    as a hydrogen line in emission. However, when the colour of this mysterious object was measured in different wavebands, it was found to be very red and quite similar to that of one of the two known Brown Dwarfs in double star systems. The presence of the lithium line in the spectrum is also an indication that it might be of that type. The astronomer now decided to give the new object the name KELU-1 ; this word means `red' in the language of the Mapuche people, the ancient population in the central part of Chile. Its visual magnitude is 22.3, i.e. more than 3 million times fainter than what can be seen with the unaided eye. In early April, additional infrared observations with the UKIRT (UK Infrared Telescope) on Mauna Kea (Hawaii) by Sandra K. Leggett (Joint Astrophysical Centre, Hilo, Hawaii, USA) confirmed the Brown Dwarf nature of KELU-1, in particular through the unambiguous detection of Methane (CH 4 ) bands in its spectrum. The nature of Brown Dwarfs Brown Dwarfs are first of all characterised by their low mass. When a body of such a small mass is formed in an interstellar cloud and subsequently begins to contract, its temperature at the centre will rise, but it will never reach a level that is sufficient to ignite the nuclear burning of hydrogen to helium, the process that it is main source of energy in the Sun and most other stars. The Brown Dwarf will just continue to contract, more and more slowly, and it will eventually fade from view. This is also the reason that some astronomers consider Brown Dwarfs in the Milky Way and other galaxies as an important component of the `dark matter' whose presence is infered from other indirect measurements but has never been directly observed. It is assumed that the mass limit that separates nuclear-burning stars and slowly contracting Brown Dwarfs is at about 90 times the mass of the giant planet Jupiter, or 8 percent of that of the Sun. KELU-1: a great opportunity for Brown Dwarf studies Assuming that KELU-1 is

  19. Brown adipogenesis of mouse embryonic stem cells in alginate microstrands

    NASA Astrophysics Data System (ADS)

    Unser, Andrea Mannarino

    The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders. Employing pluripotent stem cells, with an emphasis on directed differentiation, may overcome many issues currently associated with primary fat cell cultures. However, brown adipocytes are difficult to transplant in vivo due to the instability of fat, in terms of necrosis and neovascularization, once injected. Thus, 3D cell culture systems that have the potential to mimic adipogenic microenvironments are needed, not only to advance brown fat implantation, but also to better understand the role of brown adipocytes in treating obesity. To address this need, we created 3D "Brown-Fat-in-Microstrands" by microfluidic synthesis of alginate hydrogel microstrands that encapsulated cells and directly induced cell differentiation into brown adipocytes, using mouse embryonic stem cells (ESCs) as a model of pluripotent stem cells and brown preadipocytes as a positive control. The effect of hydrogel formation parameters on brown adipogenesis was studied, leading to the establishment of "Brown-Fat-in-Microstrands". Brown adipocyte differentiation within microstrands was confirmed by lipid droplet accumulation, immunocytochemistry and qPCR analysis of gene expression of brown adipocyte marker uncoupling protein 1 (UCP1) in addition to adipocyte marker expression. Compared to a 2D approach, 3D differentiated "Brown-Fat-in-Microstrands" exhibited higher level of brown adipocyte marker expression. The functional analysis of "Brown-Fat-in-Microstrands" was attempted by measuring the mitochondrial activity of ESC-differentiated brown adipocytes in 3D using Seahorse XF24 3 Extracellular Flux Analyzer. The ability to create "Brown-Fat-in-Microstrands" from pluripotent stem cells opens up a new arena to understanding brown adipogenesis and its implications in obesity and metabolic disorders.

  20. Active hematite concretion formation in modern acid saline lake sediments, Lake Brown, Western Australia

    NASA Astrophysics Data System (ADS)

    Bowen, Brenda Beitler; Benison, K. C.; Oboh-Ikuenobe, F. E.; Story, S.; Mormile, M. R.

    2008-04-01

    Concretions can provide valuable records of diagenesis and fluid-sediment interactions, however, reconstruction of ancient concretion-forming conditions can be difficult. Observation of modern hematite concretion growth in a natural sedimentary setting provides a rare glimpse of conditions at the time of formation. Spheroidal hematite-cemented concretions are actively precipitating in shallow subsurface sediments at Lake Brown in Western Australia. Lake Brown is a hypersaline (total dissolved solids up to 23%) and acidic (pH ˜ 4) ephemeral lake. The concretion host sediments were deposited between ˜ 1 and 3 ka, based on dating of stratigraphically higher and lower beds. These age constraints indicate that the diagenetic concretions formed < 3 ka, and field observations suggest that some are currently forming. These modern concretions from Lake Brown provide an example of very early diagenetic formation in acid and saline conditions that may be analogous to past conditions on Mars. Previously, the hematite concretions in the Burns formation on Mars have been interpreted as late stage diagenetic products, requiring long geologic time scales and multiple fluid flow events to form. In contrast, the Lake Brown concretions support the possibility of similar syndepositional to very early diagenetic concretion precipitation on Mars.

  1. Benchmarking Brown Dwarf Models With a Non-irradiated Transiting Brown Dwarf in Praesepe

    NASA Astrophysics Data System (ADS)

    Beatty, Thomas; Marley, Mark; Line, Michael; Gizis, John

    2018-05-01

    We wish to use 9.4 hours of Spitzer time to observe two eclipses, one each at 3.6um and 4.5um, of the transiting brown dwarf AD 3116b. AD 3116b is a 54.2+/-4.3 MJ, 1.08+/-0.07 RJ object on a 1.98 day orbit about a 3200K M-dwarf. Uniquely, AD 3116 and its host star are both members of Praesepe, a 690+/-60 Myr old open cluster. AD 3116b is thus one of two transiting brown dwarfs for which we have a robust isochronal age that is not dependent upon brown dwarf evolutionary models, and the youngest brown dwarf for which this is the case. Importantly, the flux AD 3116b receives from its host star is only 0.7% of its predicted internal luminosity (Saumon & Marley 2008). This makes AD 3116b the first known transiting brown dwarf that simultaneously has a well-defined age, and that receives a negligible amount of external irradiation, and a unique laboratory to test radius and luminosity predictions from brown dwarf evolutionary models. Our goal is to measure the emission from the brown dwarf. AD 3116b should have large, 25 mmag, eclipse depths in the Spitzer bandpasses, and we expect to measure them with a precision of +/-0.50 mmag at 3.6um and +/-0.54 mmag at 4.5um. This will allow us to make measure AD 3116b?s internal effective temperature to +/-40K. We will also use the upcoming Gaia DR2 parallaxes to measure AD 3116b's absolute IRAC magnitudes and color, and hence determine the cloud properties of the atmosphere. As the only known brown dwarf with an independently measured mass, radius, and age, Spitzer measurements of AD 3116b's luminosity and clouds will provide a critical benchmark for brown dwarf observation and theory.

  2. Long-term results of silicone expander for moderate and severe Brown syndrome (Brown syndrome "plus").

    PubMed

    Stager, D R; Parks, M M; Stager, D R; Pesheva, M

    1999-12-01

    The treatment of Brown syndrome has been undergoing an evolution toward more effective procedures with fewer operative interventions. Dr Kenneth Wright has introduced a procedure of superior oblique muscle tenotomy with a silicone expander to reduce the incidence of overcorrection. There was a retrospective study of 20 eyes of 19 consecutive patients with moderate or severe Brown syndrome (Brown syndrome "plus"). Follow-up ranged from 12 to 72 months. The expander, which varies 6 to 10 mm in length, was placed in all patients in the tenotomized superior oblique muscle tendon 5 mm nasal to the nasal border of the superior rectus muscle using 7-0 or 8-0 Prolene suture without violating the inner layer of the intermuscular septum. The intermuscular septum was closed over the silicone expander. One hundred percent of patients had resolution of the down shoot in adduction and some or full ability to elevate the eye in adduction. Twenty percent of patients required reoperation (12.5% using 5-8 mm expanders) for overcorrection. Restriction of downgaze was not seen postoperatively. Patients often show an undercorrection 1 to 6 months postoperatively and improve or occasionally overcorrect at 1 to 2 years postoperatively. One patient with a 10-mm expander extruded the implant. Placement of a 5- to 8-mm silicone expander in the tenotomized superior oblique muscle tendon is an effective means of correcting Brown syndrome with a low rate of reoperation. Initial undercorrection should not discourage the surgeon because improvement may continue for up to 3 years. The goal of treatment should be to convert a moderate or severe Brown syndrome (Brown syndrome plus) to a mild Brown syndrome ("true" Brown syndrome). This technique reduces the need for either simultaneous or subsequent inferior oblique muscle weakening and represents an advance in the treatment of Brown syndrome.

  3. Multiplicity Among Young Brown Dwarfs and Very Low Mass Stars

    NASA Astrophysics Data System (ADS)

    Ahmic, Mirza; Jayawardhana, R.; Brandeker, A.; Scholz, A.; van Kerkwijk, M. H.; Delgado-Donate, E.; Froebrich, D.

    2007-05-01

    Characterizing multiplicity in the very low mass (VLM) domain is a topic of much current interest and fundamental importance. Here we report on a near-infrared adaptive optics imaging survey of 28 young brown dwarfs and VLM stars, 26 of which are in the Chamaeleon I star-forming region, using the ESO Very Large Telescope. Our findings in Cha I -- the low multiplicity frequency of 8%, the preference for equal mass pairs, and the lack of wide binaries -- are strikingly similar to what has previously been reported for VLM objects in the field and in open clusters. Thus, we argue that there is no significant evolution of multiplicity with age among brown dwarfs and VLM stars between a few Myr to several Gyr. Instead, the observations to date suggest that VLM objects are either less likely to be born in wide multiple systems than solar mass stars or such systems are disrupted very early (within the first couple of Myr). Our results also imply that systems like 2MASSW J1207334-393254 and Oph 162225-240515, with planetary mass companions at wide separations, are rare. This research was supported by an NSERC grant, University of Toronto research funds and the Ontario Graduate Scholarship.

  4. The role of the whitefly, Bemisia tabaci (Gennadius), and farmer practices in the spread of cassava brown streak ipomoviruses.

    PubMed

    Maruthi, Midatharahally N; Jeremiah, Simon C; Mohammed, Ibrahim U; Legg, James P

    2017-12-01

    Cassava brown streak disease (CBSD) is arguably the most dangerous current threat to cassava, which is Africa's most important food security crop. CBSD is caused by two RNA viruses: Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). The roles of the whitefly Bemisia tabaci (Gennadius) and farmer practices in the spread of CBSD were investigated in a set of field and laboratory experiments. The virus was acquired and transmitted by B. tabaci within a short time (5-10 min each for virus acquisition and inoculation), and was retained for up to 48 hr. Highest virus transmission (60%) was achieved using 20-25 suspected viruliferous whiteflies per plant that were given acquisition and inoculation periods of 24 and 48 hr, respectively. Experiments mimicking the agronomic practices of cassava leaf picking or the use of contaminated tools for making cassava stem cuttings did not show the transmission of CBSV or UCBSV. Screenhouse and field experiments in Tanzania showed that the spread of CBSD next to spreader rows was high, and that the rate of spread decreased with increasing distance from the source of inoculum. The disease spread in the field up to a maximum of 17 m in a cropping season. These results collectively confirm that CBSV and UCBSV are transmitted by B. tabaci semipersistently, but for only short distances in the field. This implies that spread over longer distances is due to movements of infected stem cuttings used for planting material. These findings have important implications for developing appropriate management strategies for CBSD.

  5. Glycoprotein from street rabies virus BD06 induces early and robust immune responses when expressed from a non-replicative adenovirus recombinant.

    PubMed

    Wang, Shuchao; Sun, Chenglong; Zhang, Shoufeng; Zhang, Xiaozhuo; Liu, Ye; Wang, Ying; Zhang, Fei; Wu, Xianfu; Hu, Rongliang

    2015-09-01

    The rabies virus (RABV) glycoprotein (G) is responsible for inducing neutralizing antibodies against rabies virus. Development of recombinant vaccines using the G genes from attenuated strains rather than street viruses is a regular practice. In contrast to this scenario, we generated three human adenovirus type 5 recombinants using the G genes from the vaccine strains SRV9 and Flury-LEP, and the street RABV strain BD06 (nrAd5-SRV9-G, nrAd5-Flury-LEP-G, and nrAd5-BD06-G). These recombinants were non-replicative, but could grow up to ~10(8) TCID50/ml in helper HEK293AD cells. Expression of the G protein was verified by immunostaining, quantitative PCR and cytometry. Animal experiments revealed that immunization with nrAd5-BD06-G can induce a higher seroconversion rate, a higher neutralizing antibody level, and a longer survival time after rabies virus challenge in mice when compared with the other two recombinants. Moreover, the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly higher in mice immunized with nrAd5-BD06-G, which might also contribute to the increased protection. These results show that the use of street RABV G for non-replicative systems may be an alternative for developing effective recombinant rabies vaccines.

  6. PA-X protein contributes to virulence of triple-reassortant H1N2 influenza virus by suppressing early immune responses in swine.

    PubMed

    Xu, Guanlong; Zhang, Xuxiao; Liu, Qinfang; Bing, Guoxia; Hu, Zhe; Sun, Honglei; Xiong, Xin; Jiang, Ming; He, Qiming; Wang, Yu; Pu, Juan; Guo, Xin; Yang, Hanchun; Liu, Jinhua; Sun, Yipeng

    2017-08-01

    Previous studies have identified a functional role of PA-X for influenza viruses in mice and avian species; however, its role in swine remains unknown. Toward this, we constructed PA-X deficient virus (Sw-FS) in the background of a Triple-reassortment (TR) H1N2 swine influenza virus (SIV) to assess the impact of PA-X in viral virulence in pigs. Expression of PA-X in TR H1N2 SIV enhanced viral replication and host protein synthesis shutoff, and inhibited the mRNA levels of type I IFNs and proinflammatory cytokines in porcine cells. A delay of proinflammatory responses was observed in lungs of pigs infected by wild type SIV (Sw-WT) compared to Sw-FS. Furthermore, Sw-WT virus replicated and transmitted more efficiently than Sw-FS in pigs. These results highlight the importance of PA-X in the moderation of virulence and immune responses of TR SIV in swine, which indicated that PA-X is a pro-virulence factor in TR SIV in pigs. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Early detection and visualization of human adenovirus serotype 5-viral vectors carrying foot-and-mouth disease virus or luciferase transgenes in cell lines and bovine tissues

    USDA-ARS?s Scientific Manuscript database

    Recombinant replication-defective human adenovirus type 5 (Ad5) vaccines containing capsid-coding regions from foot-and-mouth disease virus (FMDV) have been demonstrated to induce effective immune responses and provide homologous protective immunity against FMDV in cattle. However, basic mechanisms ...

  8. Marek’s Disease Virus influences the core gut microbiome of the chicken during the early and late phases of viral replication

    USDA-ARS?s Scientific Manuscript database

    Marek’s disease (MD) is an important neoplastic disease of chickens caused by the Marek’s disease virus (MDV), an oncogenic alphaherpesvirus. In this study, dysbiosis induced by MDV on the core gut flora of chicken was assessed using next generation sequence (NGS) analysis. Total fecal and cecum-der...

  9. 1. OVERALL VIEW OF BROWN DUCK LAKE, LOOKING SOUTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. OVERALL VIEW OF BROWN DUCK LAKE, LOOKING SOUTHWEST - High Mountain Dams in Upalco Unit, Brown Duck Lake Dam, Ashley National Forest, 4.4 miles North of Miners Gulch Campground, Mountain Home, Duchesne County, UT

  10. 2. OVERALL VIEW OF BROWN DUCK LAKE, LOOKING WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. OVERALL VIEW OF BROWN DUCK LAKE, LOOKING WEST - High Mountain Dams in Upalco Unit, Brown Duck Lake Dam, Ashley National Forest, 4.4 miles North of Miners Gulch Campground, Mountain Home, Duchesne County, UT

  11. DDE in brown and white fat of hibernating bats

    USGS Publications Warehouse

    Clark, D.R.; Krynitsky, A.J.

    1983-01-01

    Samples of brown and white fat from hibernating bats (big brown bat, Eptesicus fuscus; little brown bat, Myotis lucifugus; and eastern pipistrelle, Pipistrellus subflavus) collected in western Maryland, USA, were analysed to determine lipid and DDE content. Amounts of brown fat, expressed as percentages of total bat weight, were the same for all three species. Lipid content of brown fat was significantly less than that of white fat. Lipids of brown fat contained significantly higher (28%) concentrations of DDE than did lipids of white fat. In our mixed-species sample of 14 bats, concentrations of DDE increased exponentially in both brown and white fat as white fat reserves declined. Brown fat facilitates arousal from hibernation by producing heat through rapid metabolism of triglycerides. The question is raised whether organochlorine residues, such as DDE, may be concentrated and then liberated in lethal amounts by the processes of hibernation and arousal.

  12. Use of Brown Algae to Demonstrate Natural Products Techniques.

    ERIC Educational Resources Information Center

    Porter, Lee A.

    1985-01-01

    Background information is provided on the natural products found in marine organisms in general and the brown algae in particular. Also provided are the procedures needed to isolate D-mannitol (a primary metabolite) and cholesterol from brown algae. (JN)

  13. Cucurbit chlorotic yellows virus

    USDA-ARS?s Scientific Manuscript database

    Cucurbit chlorotic yellows virus (CCYV) emerged as a threat to cucurbit production in Japan during the early 2000s and has since spread to China and Taiwan, as well as to the Middle East, and parts of Africa. CCYV (genus Crinivirus, family Closteroviridae) causes chlorotic mottle symptoms, intervein...

  14. Cucumber mosaic virus

    USDA-ARS?s Scientific Manuscript database

    Cucumber mosaic virus (CMV) has been reported on red raspberry in Chile, Scotland and the Soviet Union and in Chile on blackberry. Its occurrence in Rubus is rare and seems to cause little damage. Except for one early, unconfirmed report, CMV has not been reported on Rubus in North America. This vir...

  15. Human immunodeficiency virus.

    PubMed

    Skinner, Anita

    2016-11-23

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article discussed the importance of human immunodeficiency virus (HIV) testing and diagnosing the condition as early as possible, so that antiretroviral treatment can be initiated and patient outcomes improved.

  16. Rabies in a captive colony of big brown bats (Eptesicus fuscus)

    USGS Publications Warehouse

    Shankar, V.; Bowen, R.A.; Davis, A.D.; Rupprecht, C.E.; O'Shea, T.J.

    2004-01-01

    Our research has focused on the ecology of commensal populations of big brown bats (Eptesicus fuscus) in Fort Collins, Colorado (USA), in relation to rabies virus (RV) transmission. We captured 35 big brown bats (Eptesicus fuscus) in late summer 2001 and held them captive for 4.8 mo. The bats were initially placed in an indoor cage for 1 mo then segregated into groups of two to six per cage. Two of the bats succumbed to rabies virus (RV) within the first month of capture. Despite group housing, all of the remaining bats were healthy over the course of the investigation; none developed rabies, although one of the rabid bats was observed to bite her cage mates. Reverse transcription–polymerase chain reaction (RT-PCR) and Taqman® real-time PCR analysis of the RNA derived from the brain tissue, salivary glands, and oral swab samples confirmed RV infection in the dead bats. Rabies virus was also isolated from the brain tissue upon passage in mouse neuroblastoma cells. Nucleotide sequence analysis of the RV nucleoprotein (N) gene showed 100% identity with the N gene sequence of a 1985 E. fuscus isolate from El Paso County, Colorado. Bat sera obtained six times throughout the study were assayed for RV neutralizing antibodies using the rapid fluorescent focus inhibition test. The RV neutralizing activity in the serum was associated with the IgG component, which was purified by binding to protein G Sepharose. Five bats were RV seropositive prior to their capture and maintained titers throughout captivity. Two adult bats seroconverted during captivity. Two volant juvenile bats had detectable RV antibody titers at the first serum collection but were negative thereafter. Four seronegative bats responded to a RV vaccine administration with high titers of RV antibodies. A serologic survey of big brown bats in the roost from which one of the captive rabid bats had originated showed a significant rise in seroprevalence during 2002.

  17. Two key temporally distinguishable molecular and cellular components of white adipose tissue browning during cold acclimation.

    PubMed

    Jankovic, Aleksandra; Golic, Igor; Markelic, Milica; Stancic, Ana; Otasevic, Vesna; Buzadzic, Biljana; Korac, Aleksandra; Korac, Bato

    2015-08-01

    White to brown adipose tissue conversion and thermogenesis can be ignited by different conditions or agents and its sustainability over the long term is still unclear. Browning of rat retroperitoneal white adipose tissue (rpWAT) during cold acclimation involves two temporally apparent components: (1) a predominant non-selective browning of most adipocytes and an initial sharp but transient induction of uncoupling protein 1, peroxisome proliferator-activated receptor (PPAR) coactivator-1α, PPARγ and PPARα expression, and (2) the subsistence of relatively few thermogenically competent adipocytes after 45 days of cold acclimation. The different behaviours of two rpWAT beige/brown adipocyte subsets control temporal aspects of the browning process, and thus regulation of both components may influence body weight and the potential successfulness of anti-obesity therapies. Conversion of white into brown adipose tissue may have important implications in obesity resistance and treatment. Several browning agents or conditions ignite thermogenesis in white adipose tissue (WAT). To reveal the capacity of WAT to function in a brownish/burning mode over the long term, we investigated the progression of the rat retroperitoneal WAT (rpWAT) browning during 45 days of cold acclimation. During the early stages of cold acclimation, the majority of rpWAT adipocytes underwent multilocularization and thermogenic-profile induction, as demonstrated by the presence of a multitude of uncoupling protein 1 (UCP1)-immunopositive paucilocular adipocytes containing peroxisome proliferator-activated receptor (PPAR) coactivator-1α (PGC-1α) and PR domain-containing 16 (PRDM16) in their nuclei. After 45 days, all adipocytes remained PRDM16 immunopositive, but only a few multilocular adipocytes rich in mitochondria remained UCP1/PGC-1α immunopositive. Molecular evidence showed that thermogenic recruitment of rpWAT occurred following cold exposure, but returned to starting levels after cold

  18. Efficient transmission of cassava brown streak disease viral pathogens by chip bud grafting.

    PubMed

    Wagaba, Henry; Beyene, Getu; Trembley, Cynthia; Alicai, Titus; Fauquet, Claude M; Taylor, Nigel J

    2013-12-06

    Techniques to study plant viral diseases under controlled growth conditions are required to fully understand their biology and investigate host resistance. Cassava brown streak disease (CBSD) presents a major threat to cassava production in East Africa. No infectious clones of the causal viruses, Cassava brown streak virus (CBSV) or Ugandan cassava brown streak virus (UCBSV) are available, and mechanical transmission to cassava is not effective. An improved method for transmission of the viruses, both singly and as co-infections has been developed using bud grafts. Axillary buds from CBSD symptomatic plants infected with virulent isolates of CBSV and UCBSV were excised and grafted onto 6-8 week old greenhouse-grown, disease-free cassava plants of cultivars Ebwanateraka, TME204 and 60444. Plants were assessed visually for development of CBSD symptoms and by RT-PCR for presence of the viruses in leaf and storage root tissues. Across replicated experiments, 70-100% of plants inoculated with CBSV developed CBSD leaf and stem symptoms 2-6 weeks after bud grafting. Infected plants showed typical, severe necrotic lesions in storage roots at harvest 12-14 weeks after graft inoculation. Sequential grafting of buds from plants infected with UCBSV followed 10-14 days later by buds carrying CBSV, onto the same test plant, resulted in 100% of the rootstocks becoming co-infected with both pathogens. This dual transmission rate was greater than that achieved by simultaneous grafting with UCBSV and CBSV (67%), or when grafting first with CBSV followed by UCBSV (17%). The bud grafting method described presents an improved tool for screening cassava germplasm for resistance to CBSD causal viruses, and for studying pathogenicity of this important disease. Bud grafting provides new opportunities compared to previously reported top and side grafting systems. Test plants can be inoculated as young, uniform plants of a size easily handled in a small greenhouse or large growth chamber and

  19. Nonhealing Wounds Caused by Brown Spider Bites: Application of Hyperbaric Oxygen Therapy.

    PubMed

    Hadanny, Amir; Fishlev, Gregory; Bechor, Yair; Meir, Oshra; Efrati, Shai

    2016-12-01

    Bites by Loxosceles spiders (also known as recluse spiders or brown spiders) can cause necrotic ulcerations of various sizes and dimensions. The current standard of care for brown spider bites includes analgesics, ice, compression, elevation, antihistamines, and surgical debridement. Hyperbaric oxygen therapy (HBOT) in the treatment of brown spider bites has been administered in the early stage of ulceration, or 2 to 6 days after the bite. Unfortunately, the diagnosis of spider bite-related ulcers is often delayed and weeks or months may elapse before HBOT is considered. To evaluate the effect of HBOT on nonhealing wounds caused by brown spider bites in the late, chronic, nonhealing stage. Analysis of 3 patients with brown spider-bite healing wounds treated at The Sagol Center for Hyperbaric Medicine and Research in Israel. Patients presented 2 to 3 months after failure of other therapies including topical dressings, antibiotics, and corticosteroids. All patients were treated with daily 2 ATA (atmospheres absolute) with 100% oxygen HBOT sessions. All 3 patients were previously healthy without any chronic disease. Their ages were 30, 42, and 73 years. They were treated once daily for 13, 17, and 31 sessions, respectively. The wounds of all 3 patients healed, and there was no need for additional surgical intervention. There were no significant adverse events in any of the patients. Microvascular injury related to brown spider bites may culminate in ischemic nonhealing wounds even in a relatively young, healthy population. Hyperbaric oxygen therapy should be considered as a valuable therapeutic tool even months after the bite.

  20. Prevalence of Tumors in Brown Bullhead from Three Lakes in Southeastern Massachusetts, 2002

    USGS Publications Warehouse

    Baumann, Paul C.; LeBlanc, Denis R.; Blazer, Vicki; Meier, John R.; Hurley, Stephen T.; Kiryu, Yasu

    2008-01-01

    The Massachusetts Military Reservation (MMR) has been a military base on western Cape Cod since the early 1900s. Contaminated surface water and ground water from the MMR have discharged into several kettle lakes on or near the base. To discover whether the prevalences of tumors and other lesions in brown bullhead (Ameiurus nebulosus) in these lakes, particularly Ashumet Pond, were elevated above normal, the U.S. Geological Survey (USGS), assisted by the U.S. Environmental Protection Agency (USEPA) and the Massachusetts Division of Fisheries and Wildlife (MADFW), conducted a study in 2002 of brown bullhead in Ashumet Pond and in two reference lakes, Santuit Pond (on Cape Cod) and Great Herring Pond (on the mainland of Massachusetts). Brown bullhead from Great Herring Pond had few external raised lesions (2.8 percent), a low prevalence of liver neoplasms (5 percent), and little genetic damage to their red blood cell nuclei. Brown bullhead from Ashumet Pond had a high prevalence of raised lesions (62.1 percent), which included histopathologically verified papillomas and squamous carcinoma; an elevated incidence of liver neoplasms (16.7 percent); and an elevated level of genetic damage to their red blood cell nuclei. Because red blood cells in fish have a lifespan of about 100 days, these results indicate an ongoing exposure to genotoxins in Ashumet Pond. Brown bullhead from Santuit Pond also had elevated prevalences of raised lesions (48.3 percent) and liver neoplasms (15 percent), although the prevalences of large and multiple lesions were significantly lower than those in fish from Ashumet Pond. These differences may indicate differing causes of pathology in the two lakes. The high prevalence of melanistic lesions on brown bullhead from Ashumet Pond, combined with the tumor pathology and genetic damage, implicates chemical carcinogens as one of the causal factors in that lake.

  1. Rapamycin negatively impacts insulin signaling, glucose uptake and uncoupling protein-1 in brown adipocytes.

    PubMed

    García-Casarrubios, Ester; de Moura, Carlos; Arroba, Ana I; Pescador, Nuria; Calderon-Dominguez, María; Garcia, Laura; Herrero, Laura; Serra, Dolors; Cadenas, Susana; Reis, Flavio; Carvalho, Eugenia; Obregon, Maria Jesus; Valverde, Ángela M

    2016-12-01

    New onset diabetes after transplantation (NODAT) is a metabolic disorder that affects 40% of patients on immunosuppressive agent (IA) treatment, such as rapamycin (also known as sirolimus). IAs negatively modulate insulin action in peripheral tissues including skeletal muscle, liver and white fat. However, the effects of IAs on insulin sensitivity and thermogenesis in brown adipose tissue (BAT) have not been investigated. We have analyzed the impact of rapamycin on insulin signaling, thermogenic gene-expression and mitochondrial respiration in BAT. Treatment of brown adipocytes with rapamycin for 16h significantly decreased insulin receptor substrate 1 (IRS1) protein expression and insulin-mediated protein kinase B (Akt) phosphorylation. Consequently, both insulin-induced glucose transporter 4 (GLUT4) translocation to the plasma membrane and glucose uptake were decreased. Early activation of the N-terminal Janus activated kinase (JNK) was also observed, thereby increasing IRS1 Ser 307 phosphorylation. These effects of rapamycin on insulin signaling in brown adipocytes were partly prevented by a JNK inhibitor. In vivo treatment of rats with rapamycin for three weeks abolished insulin-mediated Akt phosphorylation in BAT. Rapamycin also inhibited norepinephrine (NE)-induced lipolysis, the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and uncoupling protein (UCP)-1 in brown adipocytes. Importantly, basal mitochondrial respiration, proton leak and maximal respiratory capacity were significantly decreased in brown adipocytes treated with rapamycin. In conclusion, we demonstrate, for the first time the important role of brown adipocytes as target cells of rapamycin, suggesting that insulin resistance in BAT might play a major role in NODAT development. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Do You Mean Us, Mr Brown?

    ERIC Educational Resources Information Center

    Harriman, Jenny

    2007-01-01

    This summer Chris Wardley, Chair of Access to Community Education (ACE), a small charity run by and for disabled people in Torbay, wrote to Gordon Brown. She asked him whether his mission to "fulfil the potential and realise the talents of all people" was based solely on economic goals or whether everyone, including disabled people,…

  3. The browning of Alaska's boreal forest

    Treesearch

    Mary Beth Parent; David Verbyla

    2010-01-01

    We used twelve Landsat scenes from the 1980s-2009 and regional 2000-2009 MODIS data to examine the long-term trend in the normalized difference vegetation index (NDVI) within unburned areas of the Alaskan boreal forest. Our analysis shows that there has been a declining trend in NDVI in this region, with the strongest "browning trend" occurring in eastern...

  4. Nixon's "Southern Strategy" and Forces against Brown

    ERIC Educational Resources Information Center

    Brown, Frank

    2004-01-01

    Richard M. Nixon, the United States President in 1968 gave birth to the modern reform movement through public vouchers and other educational reform measures under his "Southern Strategy" that was designed to gain the votes of individuals who oppose school desegregation. The political activities in school desegregation after Brown by the…

  5. Black-Brown Relations and Stereotypes.

    ERIC Educational Resources Information Center

    Mindiola, Tatcho Jr.; Niemann, Yolanda Flores; Rodriguez, Nestor

    This book analyzes how African and Hispanic Americans perceive and interact with one another, highlighting black-brown relations in Houston, Texas, one of the largest cities with a majority ethnic population and one in which Hispanic Americans outnumber African Americans. Using results from several sociological studies, the book examines: how each…

  6. Black-Brown Relations: Are Alliances Possible?

    ERIC Educational Resources Information Center

    Klor de Alva, J. Jorge; West, Cornel

    1997-01-01

    Dialogue between Cornel West and Jorge Klor de Alva explores the question of black-brown alliances, those between African Americans and Hispanic Americans. If minority groups can put aside the difference of skin color and join to combat economic and social racism, they can have far-reaching and meaningful impacts on society. (SLD)

  7. Brown and the Distribution of School Resources.

    ERIC Educational Resources Information Center

    Berg, William M.; Colton, David L.

    1982-01-01

    The case of Brown v Topeka has had important consequences affecting the availability and allocation of funds for public schooling. Research to more accurately identify and explain these financial effects will be hampered by such problems as lack of standardized accounting systems, distortions of desegregation costs, and ambiguities of policy.…

  8. Phospholipids of New Zealand Edible Brown Algae.

    PubMed

    Vyssotski, Mikhail; Lagutin, Kirill; MacKenzie, Andrew; Mitchell, Kevin; Scott, Dawn

    2017-07-01

    Edible brown algae have attracted interest as a source of beneficial allenic carotenoid fucoxanthin, and glyco- and phospholipids enriched in polyunsaturated fatty acids. Unlike green algae, brown algae contain no or little phosphatidylserine, possessing an unusual aminophospholipid, phosphatidyl-O-[N-(2-hydroxyethyl) glycine], PHEG, instead. When our routinely used technique of 31 P-NMR analysis of phospholipids was applied to the samples of edible New Zealand brown algae, a number of signals corresponding to unidentified phosphorus-containing compounds were observed in total lipids. NI (negative ion) ESI QToF MS spectra confirmed the presence of more familiar phospholipids, and also suggested the presence of PHEG or its isomers. The structure of PHEG was confirmed by comparison with a synthetic standard. An unusual MS fragmentation pattern that was also observed prompted us to synthesise a number of possible candidates, and was found to follow that of phosphatidylhydroxyethyl methylcarbamate, likely an extraction artefact. An unexpected outcome was the finding of ceramidephosphoinositol that has not been reported previously as occurring in brown algae. An uncommon arsenic-containing phospholipid has also been observed and quantified, and its TLC behaviour studied, along with that of the newly synthesised lipids.

  9. Browns in Anger: The Overlooked Minority.

    ERIC Educational Resources Information Center

    Lara-Braud, Jorge

    This speech advocates that Mexican-Americans must undergo a process of radicalization to attempt to transfer anger from deeds to words. This minority is losing faith in speech as a means of redress, but corrective measures should come through dialogue and not collision. Few Mixican Americans designated themselves "browns" a year ago--but it is now…

  10. Parallax measurements of six brown dwarfs.

    NASA Astrophysics Data System (ADS)

    Manjavacas, E.; Goldman, B.; Reffert, S.; Henning, T.

    Accurate parallax measurements allow us to determine physical properties of brown dwarfs, and help us to constrain evolutionary and atmospheric models and reveal unresolved binaries. We measured absolute trigonometric parallaxes and proper motions of six cool brown dwarfs using background galaxies to establish an absolute reference frame. The brown dwarfs in our sample have spectral types between T2.5 and T7.5. The observations were taken in the J-band with the Omega2000 camera at the 3.5 m telescope at CAHA during a time period of 27 months. We obtained absolute parallaxes for our 6 brown dwarfs with a precision between 3 and 6 mas. We compared our results with the study by \\cite{Dupuy} and with the evolutionary models of \\cite{Allard}. For four of the six targets we found a good agreement in luminosity among objects of similar spectral types. The object 2MASS J11061197+2754225 is more than 1 mag overluminous in all bands pointing to binarity or higher order multiplicity. Based on observations taken with Omega-2000 at the 3.5 m telescope at the Centro Astronómico Hispano Alemán (CAHA) at Calar Alto, operated by the Max Planck Institut für Astronomie and the Instituto de Astrofísica de Andalucía (CSIC).

  11. PHYSIOLOGICAL ACTIVITY OF THE BROWN ADIPOSE TISSUE.

    DTIC Science & Technology

    Studies were performed to clarify the influence of various factors which might be involved in vascular regulation. Topical application of lidocain ...and treatment with reserpine effectively blocked, while denervation of brown fat, syrosingopine and atropine were ineffective to prevent the blood flow

  12. Brown on aft flight deck with microphone

    NASA Image and Video Library

    1998-10-31

    STS095-E-5177 (31 Oct. 1998) --- On Discovery's aft flight deck, astronaut Curtis L. Brown Jr., STS-95 commander, checks over notes with ground controllers in Houston. The photo was taken with an electronic still camera (ESC) at 00:41:51 GMT, Oct. 31.

  13. Glen and Brown on aft flight deck

    NASA Image and Video Library

    1998-10-31

    STS095-E-5180 (31 Oct. 1998) --- Astronaut Curtis L. Brown Jr. (left), STS-95 commander, stands by on Discovery's aft flight deck as U.S. Sen. John H. Glenn Jr., payload specialist, talks with ground controllers in Houston. The photo was taken with an electronic still camera (ESC) at 00:48:48 GMT, Oct. 31.

  14. Brown on middeck with drink packet

    NASA Image and Video Library

    1998-10-31

    STS095-E-5125 (31 Oct. 1998) --- Astronaut Curtis L. Brown Jr., STS-95 commander, has just added water to a snack at Discovery's galley on the middeck. The photo was taken with an electronic still camera (ESC) at 9:52:32, Oct. 31.

  15. BRIC - Brown with canisters on middeck

    NASA Image and Video Library

    1998-11-02

    STS095-E-5171 (2 Nov. 1998) --- Astronaut Curtis L. Brown, STS-95 commander, during Flight Day 3 activity aboard the Space Shuttle Discovery. The photo was taken with an electronic still camera (ESC) at 05:57:03 GMT, Nov. 2.

  16. BRIC - Brown works with middeck experiment

    NASA Image and Video Library

    1997-08-12

    S85-E-5058 (12 August 1997) --- Astronaut Curtis L. Brown, Jr., commander, performs operations with an experiment called Biological Research in Canisters (BRIC) operations on the mid-deck of the Space Shuttle Discovery during flight day six. The photograph was taken with the Electronic Still Camera (ESC).

  17. Reading Second. Brown Letters on Education

    ERIC Educational Resources Information Center

    Whitehurst, Grover

    2009-01-01

    Former President George W. Bush finished his tenure without having won congressional renewal of his No Child Left Behind (NCLB) policy. With President Barack Obama now at the helm, NCLB is up for debate. Brown Center Director Grover "Russ" Whitehurst examines Reading First, a key component of NCLB, that aims to ensure that all children…

  18. Brown Dwarfs: Discovery and Detailed Studies

    NASA Technical Reports Server (NTRS)

    Kulkarni, Shrinivas R.

    2001-01-01

    We obtained the optical and IR spectra of Gliese 229B and identified Cs, I, and CO features - as expected in theoretical models. Our optical IR spectrum showed that most of the refractory metals have condensed out of the atmosphere and the presence of Cs, I and CO shows evidence for disequilibrium chemistry. We reported orbital evidence for Gliese 229B. The HST measured optical magnitudes provide additional evidence for the absence of dust in the atmosphere of this cool object. The luminosity of brown dwarfs depend on their masses and ages and in order to interpret the results of the survey we have carried out an extensive Monte Carlo analysis. Our conclusion is that warm brown dwarfs are rare, as companions in the orbital period range beyond approximately 30 - 50 AU. The Palomer survey poses no constraint for brown dwarfs in planetary orbits similar to those of the outer planets. We have just started a program of imaging nearby stars with the newly commissioned AO system at Palomar and Keck and have already found a brown dwarf candidate.

  19. Doppler Imaging of Exoplanets and Brown Dwarfs

    NASA Astrophysics Data System (ADS)

    Crossfield, I.; Biller, B.; Schlieder, J.; Deacon, N.; Bonnefoy, M.; Homeier, D.; Allard, F.; Buenzli, E.; Henning, T.; Brandner, W.; Goldman, Bertr; Kopytova, T.

    2014-03-01

    Doppler Imaging produces 2D global maps. When applied to cool planets or more massive brown dwarfs, it can map atmospheric features and track global weather patterns. The first substellar map, of the 2pc-distant brown dwarf Luhman 16B (Crossfeld et al. 2014), revealed patchy regions of thin & thick clouds. Here, I investigate the feasibility of future Doppler Imaging of additional objects. Searching the literature, I find that all 3 of P, v sin i, and variability are published for 22 brown dwarfs. At least one datum exists for 333 targets. The sample is very incomplete below ~L5; we need more surveys to find the best targets for Doppler Imaging! I estimate limiting magnitudes for Doppler Imaging with various hi-resolution near-infrared spectrographs. Only a handful of objects - at the M/L and L/T transitions - can be mapped with current tools. Large telescopes such as TMT and GMT will allow Doppler Imaging of many dozens of brown dwarfs and the brightest exoplanets. More targets beyond type L5 likely remain to be found. Future observations will let us probe the global atmospheric dynamics of many diverse objects.

  20. Trustworthy-Looking Face Meets Brown Eyes

    PubMed Central

    Kleisner, Karel; Priplatova, Lenka; Frost, Peter; Flegr, Jaroslav

    2013-01-01

    We tested whether eye color influences perception of trustworthiness. Facial photographs of 40 female and 40 male students were rated for perceived trustworthiness. Eye color had a significant effect, the brown-eyed faces being perceived as more trustworthy than the blue-eyed ones. Geometric morphometrics, however, revealed significant correlations between eye color and face shape. Thus, face shape likewise had a significant effect on perceived trustworthiness but only for male faces, the effect for female faces not being significant. To determine whether perception of trustworthiness was being influenced primarily by eye color or by face shape, we recolored the eyes on the same male facial photos and repeated the test procedure. Eye color now had no effect on perceived trustworthiness. We concluded that although the brown-eyed faces were perceived as more trustworthy than the blue-eyed ones, it was not brown eye color per se that caused the stronger perception of trustworthiness but rather the facial features associated with brown eyes. PMID:23326406

  1. Brown marmorated stink bug detections in Mississippi

    USDA-ARS?s Scientific Manuscript database

    The brown marmorated stink bug (BMSB), Halyomorpha halys, was first detected in the U.S. in Pennsylvania in 1998. This pest is now well-established in the northeast and has been detected in more than 25 states, including Oregon. These non-native stink bugs look much like many of our native stink b...

  2. Ron Brown Scholar Program. Evaluation Summary

    ERIC Educational Resources Information Center

    Broton, Katie; Mueller, Dan

    2009-01-01

    The Ron Brown Scholar Program aims to be a major force in producing this nation's next generation of leaders by providing academic scholarships, service opportunities, and leadership experiences to exemplary young African Americans. The program is highly selective, with several hundred applicants per scholarship awarded. Students are selected…

  3. Old Business: From Brown to Now.

    ERIC Educational Resources Information Center

    Clark, Kenneth B.

    1978-01-01

    During the past ten years, subtle White northern liberal racism, White backlash, and Black separatism have seriously threatened the gains of the civil rights movement that were triggered by the "Brown" decision. Fortunately, this negative tide is now being reversed. (Author/IRT)

  4. 49 CFR 173.216 - Asbestos, blue, brown or white.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Asbestos, blue, brown or white. 173.216 Section... Class 7 § 173.216 Asbestos, blue, brown or white. (a) Asbestos, blue, brown or white, includes each of the following hydrated mineral silicates: chrysolite, crocidolite, amosite, anthophyllite asbestos...

  5. 49 CFR 173.216 - Asbestos, blue, brown or white.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Asbestos, blue, brown or white. 173.216 Section... Class 7 § 173.216 Asbestos, blue, brown or white. (a) Asbestos, blue, brown or white, includes each of the following hydrated mineral silicates: chrysolite, crocidolite, amosite, anthophyllite asbestos...

  6. 49 CFR 173.216 - Asbestos, blue, brown or white.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Asbestos, blue, brown or white. 173.216 Section... Class 7 § 173.216 Asbestos, blue, brown or white. (a) Asbestos, blue, brown or white, includes each of the following hydrated mineral silicates: chrysolite, crocidolite, amosite, anthophyllite asbestos...

  7. 49 CFR 173.216 - Asbestos, blue, brown or white.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Asbestos, blue, brown or white. 173.216 Section... Class 7 § 173.216 Asbestos, blue, brown or white. (a) Asbestos, blue, brown or white, includes each of the following hydrated mineral silicates: chrysolite, crocidolite, amosite, anthophyllite asbestos...

  8. 49 CFR 173.216 - Asbestos, blue, brown or white.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Asbestos, blue, brown or white. 173.216 Section... Class 7 § 173.216 Asbestos, blue, brown or white. (a) Asbestos, blue, brown or white, includes each of the following hydrated mineral silicates: chrysolite, crocidolite, amosite, anthophyllite asbestos...

  9. African American Principals and the Legacy of "Brown"

    ERIC Educational Resources Information Center

    Tillman, Linda C.

    2004-01-01

    The 1954 "Brown v. Board of Education" decision is significant with respect to African Americans in the principalship for several reasons. First, teachers, principals, and parents were the most important influences in the education of Black children in the pre-"Brown" era of schooling. Thus, discussions about the "Brown" decision and the education…

  10. 40 CFR 721.10532 - Tar, brown coal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tar, brown coal. 721.10532 Section 721... Tar, brown coal. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as tar, brown coal (PMN P-12-167, CAS No. 101316-83-0) is subject to...

  11. 40 CFR 721.10532 - Tar, brown coal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Tar, brown coal. 721.10532 Section 721... Tar, brown coal. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as tar, brown coal (PMN P-12-167, CAS No. 101316-83-0) is subject to...

  12. Dyslexics at Brown. A Student Perspective. Third Edition.

    ERIC Educational Resources Information Center

    Cain, Carol; And Others

    An account of what it means to be a dyslexic student in higher education, put together by a group of Brown students who are dyslexic, is presented in an attempt to make the Brown community aware of dyslexia, its symptoms, and some study strategies for coping with it. Some of the resources that Brown offers its student body are listed. Nine…

  13. Iodothyronine 5'-deiodinase activity and thyroid hormone content in brown adipose tissue during the breeding cycle of the rat.

    PubMed Central

    Viñas, O; Giralt, M; Obregón, M J; Iglesias, R; Villarroya, F; Mampel, T

    1988-01-01

    Brown adipose tissue iodothyronine 5'-deiodinase activity is significantly lower in 17-day pregnant rats compared with virgin controls and remains low during late pregnancy and lactation. It fully recovers with abrupt weaning, but only partially with spontaneous weaning. Even though this profile of changes is remarkably in step with the known pattern of modifications in brown fat thermogenesis during the breeding cycle, the lowered iodothyronine 5'-deiodinase activity appearing between days 15 and 17 of pregnancy occurs earlier than the reduction in brown adipose tissue thermogenesis. Brown fat 3,3',5-tri-iodothyronine content is also reduced in late pregnant, early and mid-lactating rats, most probably as a consequence of the lowered 5'-deiodination of thyroxine in situ. Acute insulin treatment increases brown fat iodothyronine 5'-deiodinase activity in virgin animals as well as in late-pregnant and lactating rats, despite the lowered basal enzyme activity levels in the latter groups. Thus an impaired response to insulin in brown fat does not appear to be a factor leading to the lowered iodothyronine 5'-deiodinase activity during late pregnancy and lactation. PMID:3060112

  14. Fall and winter survival of brook trout and brown trout in a north-central Pennsylvania watershed

    USGS Publications Warehouse

    Sweka, John A.; Davis, Lori A.; Wagner, Tyler

    2017-01-01

    Stream-dwelling salmonids that spawn in the fall generally experience their lowest survival during the fall and winter due to behavioral changes associated with spawning and energetic deficiencies during this time of year. We used data from Brook Trout Salvelinus fontinalis and Brown Trout Salmo trutta implanted with radio transmitters in tributaries of the Hunts Run watershed of north-central Pennsylvania to estimate survival from the fall into the winter seasons (September 2012–February 2013). We examined the effects that individual-level covariates (trout species, size, and movement rates) and stream-level covariates (individual stream and cumulative drainage area of a stream) have on survival. Brook Trout experienced significantly lower survival than Brown Trout, especially in the early fall during their peak spawning period. Besides a significant species effect, none of the other covariates examined influenced survival for either species. A difference in life history between these species, with Brook Trout having a shorter life expectancy than Brown Trout, is likely the primary reason for the lower survival of Brook Trout. However, Brook Trout also spawn earlier in the fall than Brown Trout and low flows during Brook Trout spawning may have resulted in a greater risk of predation for Brook Trout compared with Brown Trout, thereby also contributing to the observed differences in survival between these species. Our estimates of survival can aid parameterization of future population models for Brook Trout and Brown Trout through the spawning season and into winter.

  15. A Panchromatic View of Brown Dwarf Aurorae

    SciTech Connect

    Pineda, J. Sebastian; Hallinan, Gregg; Kao, Melodie M.

    Stellar coronal activity has been shown to persist into the low-mass star regime, down to late M-dwarf spectral types. However, there is now an accumulation of evidence suggesting that at the end of the main sequence, there is a transition in the nature of the magnetic activity from chromospheric and coronal to planet-like and auroral, from local impulsive heating via flares and MHD wave dissipation to energy dissipation from strong large-scale magnetospheric current systems. We examine this transition and the prevalence of auroral activity in brown dwarfs through a compilation of multiwavelength surveys of magnetic activity, including radio, X-ray, andmore » optical. We compile the results of those surveys and place their conclusions in the context of auroral emission as a consequence of large-scale magnetospheric current systems that accelerate energetic electron beams and drive the particles to impact the cool atmospheric gas. We explore the different manifestations of auroral phenomena, like H α , in brown dwarf atmospheres and define their distinguishing characteristics. We conclude that large-amplitude photometric variability in the near-infrared is most likely a consequence of clouds in brown dwarf atmospheres, but that auroral activity may be responsible for long-lived stable surface features. We report a connection between auroral H α emission and quiescent radio emission in electron cyclotron maser instability pulsing brown dwarfs, suggesting a potential underlying physical connection between quiescent and auroral emissions. We also discuss the electrodynamic engines powering brown dwarf aurorae and the possible role of satellites around these systems both to power the aurorae and seed the magnetosphere with plasma.« less

  16. RADIAL VELOCITY VARIABILITY OF FIELD BROWN DWARFS

    SciTech Connect

    Prato, L.; Mace, G. N.; Rice, E. L.

    2015-07-20

    We present paper six of the NIRSPEC Brown Dwarf Spectroscopic Survey, an analysis of multi-epoch, high-resolution (R ∼ 20,000) spectra of 25 field dwarf systems (3 late-type M dwarfs, 16 L dwarfs, and 6 T dwarfs) taken with the NIRSPEC infrared spectrograph at the W. M. Keck Observatory. With a radial velocity (RV) precision of ∼2 km s{sup −1}, we are sensitive to brown dwarf companions in orbits with periods of a few years or less given a mass ratio of 0.5 or greater. We do not detect any spectroscopic binary brown dwarfs in the sample. Given our target properties,more » and the frequency and cadence of observations, we use a Monte Carlo simulation to determine the detection probability of our sample. Even with a null detection result, our 1σ upper limit for very low mass binary frequency is 18%. Our targets included seven known, wide brown dwarf binary systems. No significant RV variability was measured in our multi-epoch observations of these systems, even for those pairs for which our data spanned a significant fraction of the orbital period. Specialized techniques are required to reach the high precisions sensitive to motion in orbits of very low-mass systems. For eight objects, including six T dwarfs, we present the first published high-resolution spectra, many with high signal to noise, that will provide valuable comparison data for models of brown dwarf atmospheres.« less

  17. A Panchromatic View of Brown Dwarf Aurorae

    NASA Astrophysics Data System (ADS)

    Pineda, J. Sebastian; Hallinan, Gregg; Kao, Melodie M.

    2017-09-01

    Stellar coronal activity has been shown to persist into the low-mass star regime, down to late M-dwarf spectral types. However, there is now an accumulation of evidence suggesting that at the end of the main sequence, there is a transition in the nature of the magnetic activity from chromospheric and coronal to planet-like and auroral, from local impulsive heating via flares and MHD wave dissipation to energy dissipation from strong large-scale magnetospheric current systems. We examine this transition and the prevalence of auroral activity in brown dwarfs through a compilation of multiwavelength surveys of magnetic activity, including radio, X-ray, and optical. We compile the results of those surveys and place their conclusions in the context of auroral emission as a consequence of large-scale magnetospheric current systems that accelerate energetic electron beams and drive the particles to impact the cool atmospheric gas. We explore the different manifestations of auroral phenomena, like Hα, in brown dwarf atmospheres and define their distinguishing characteristics. We conclude that large-amplitude photometric variability in the near-infrared is most likely a consequence of clouds in brown dwarf atmospheres, but that auroral activity may be responsible for long-lived stable surface features. We report a connection between auroral Hα emission and quiescent radio emission in electron cyclotron maser instability pulsing brown dwarfs, suggesting a potential underlying physical connection between quiescent and auroral emissions. We also discuss the electrodynamic engines powering brown dwarf aurorae and the possible role of satellites around these systems both to power the aurorae and seed the magnetosphere with plasma.

  18. Zika Virus

    MedlinePlus

    Zika is a virus that is spread mostly by mosquitoes. A pregnant mother can pass it to ... through blood transfusions. There have been outbreaks of Zika virus in the United States, Africa, Southeast Asia, ...

  19. Factors controlling the early stages of viral haemorrhagic septicaemia epizootics: Low exposure levels, virus amplification and fish-to-fish transmission

    USGS Publications Warehouse

    Hershberger, P.K.; Gregg, J.L.; Grady, C.A.; Hart, L.M.; Roon, S.R.; Winton, J.R.

    2011-01-01

    Viral haemorrhagic septicaemia virus, Genogroup IVa (VHSV), was highly infectious to Pacific herring, Clupea pallasii (Valenciennes), even at exposure doses occurring below the threshold of sensitivity for a standard viral plaque assay; however, further progression of the disease to a population-level epizootic required viral amplification and effective fish-to-fish transmission. Among groups of herring injected with VHSV, the prevalence of infection was dose-dependent, ranging from 100%, 75% and 38% after exposure to 19, 0.7 and 0.07 plaque-forming units (PFU)/fish, respectively. Among Pacific herring exposed to waterborne VHSV (140PFUmL-1), the prevalence of infection, geometric mean viral tissue titre and cumulative mortality were greater among cohabitated herring than among cohorts that were held in individual aquaria, where fish-to-fish transmission was prevented. Fish-to-fish transmission among cohabitated herring probably occurred via exposure to shed virus which peaked at 680PFUmL-1; shed virus was not detected in the tank water from any isolated individuals. The results provide insights into mechanisms that initiate epizootic cascades in populations of wild herring and have implications for the design of VHSV surveys in wild fish populations. ?? Published 2011. This article is a US Government work and is in the public domain in the USA.

  20. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

    PubMed Central

    Messaoudi, Ilhem; Amarasinghe, Gaya K.; Basler, Christopher F.

    2016-01-01

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people. The Ebola virus epidemic in West Africa, which was first recognized in early 2014, highlights the threat posed by these deadly viruses. Filovirus disease is characterized by uncontrolled virus replication and the activation of damaging host pathways. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon (IFN) response, which allows high levels of replication. Here we review the mechanisms deployed by filoviruses to block host innate immunity and discuss aspects of virus replication that promote disease. PMID:26439085

  2. Wnt inhibition enhances browning of mouse primary white adipocytes.

    PubMed

    Lo, Kinyui Alice; Ng, Pei Yi; Kabiri, Zahra; Virshup, David; Sun, Lei

    2016-01-01

    The global epidemic in obesity and metabolic syndrome requires novel approaches to tackle. White adipose tissue, traditionally seen as a passive energy-storage organ, can be induced to take on certain characteristics of brown fat in a process called browning. The "browned" white adipose tissue, or beige fat, is a potential anti-obesity target. Various signaling pathways can enhance browning. Wnt is a key regulator of adipocyte biology, but its role in browning has not been explored. In this study, we found that in primary mouse adipocytes derived from the inguinal depot, Wnt inhibition by both chemical and genetic methods significantly enhanced browning. The effect of Wnt inhibition on browning most likely targets the beige precursor cells in selected adipose depots.

  3. A Very Cool Pair of Brown Dwarfs

    NASA Astrophysics Data System (ADS)

    2011-03-01

    Observations with the European Southern Observatory's Very Large Telescope, along with two other telescopes, have shown that there is a new candidate for the coldest known star: a brown dwarf in a double system with about the same temperature as a freshly made cup of tea - hot in human terms, but extraordinarily cold for the surface of a star. This object is cool enough to begin crossing the blurred line dividing small cold stars from big hot planets. Brown dwarfs are essentially failed stars: they lack enough mass for gravity to trigger the nuclear reactions that make stars shine. The newly discovered brown dwarf, identified as CFBDSIR 1458+10B, is the dimmer member of a binary brown dwarf system located just 75 light-years from Earth [1]. The powerful X-shooter spectrograph on ESO's Very Large Telescope (VLT) was used to show that the composite object was very cool by brown dwarf standards. "We were very excited to see that this object had such a low temperature, but we couldn't have guessed that it would turn out to be a double system and have an even more interesting, even colder component," said Philippe Delorme of the Institut de planétologie et d'astrophysique de Grenoble (CNRS/Université Joseph Fourier), a co-author of the paper. CFBDSIR 1458+10 is the coolest brown dwarf binary found to date. The dimmer of the two dwarfs has now been found to have a temperature of about 100 degrees Celsius - the boiling point of water, and not much different from the temperature inside a sauna [2]. "At such temperatures we expect the brown dwarf to have properties that are different from previously known brown dwarfs and much closer to those of giant exoplanets - it could even have water clouds in its atmosphere," said Michael Liu of the University of Hawaii's Institute for Astronomy, who is lead author of the paper describing this new work. "In fact, once we start taking images of gas-giant planets around Sun-like stars in the near future, I expect that many of them

  4. [Cancer cachexia and white adipose tissue browning].

    PubMed

    Zhang, S T; Yang, H M

    2016-08-01

    Cancer cachexia occurs in a majority of advanced cancer patients. These patients with impaired physical function are unable to tolerance cancer treatment well and have a significantly reduced survival rate. Currently, there is no effective clinical treatment available for cancer cachexia, therefore, it is necessary to clarify the molecular mechanisms of cancer cachexia, moreover, new therapeutic targets for cancer cachexia treatment are urgently needed. Very recent studies suggest that, during cancer cachexia, white adipose tissue undergo a 'browning' process, resulting in increased lipid mobilization and energy expenditure, which may be necessary for the occurrence of cancer cachexia. In this article, we summarize the definition and characteristics of cancer cachexia and adipose tissue 'browning', then, we discuss the new study directions presented in latest research.

  5. Brown CA et al 2016 Dataset

    EPA Pesticide Factsheets

    This dataset contains the research described in the following publication:Brown, C.A., D. Sharp, and T. Mochon Collura. 2016. Effect of Climate Change on Water Temperature and Attainment of Water Temperature Criteria in the Yaquina Estuary, Oregon (USA). Estuarine, Coastal and Shelf Science. 169:136-146, doi: 10.1016/j.ecss.2015.11.006.This dataset is associated with the following publication:Brown , C., D. Sharp, and T. MochonCollura. Effect of Climate Change on Water Temperature and Attainment of Water Temperature Criteria in the Yaquina Estuary, Oregon (USA). ESTUARINE, COASTAL AND SHELF SCIENCE. Elsevier Science Ltd, New York, NY, USA, 169: 136-146, (2016).

  6. Recommendations related to Browns Ferry Fire

    SciTech Connect

    Not Available

    1976-02-01

    Based on its review of the events transpiring before, during and after the Browns Ferry fire, the Review Group concludes that the probability of disruptive fires of the magnitude of the Browns Ferry event is small, and that there is no need to restrict operation of nuclear power plants for public safety. However, it is clear that much can and should be done to reduce even further the likelihood of disabling fires and to improve assurance of rapid extinguishment of fires that occur. Consideration should be given also to features that would increase further the ability of nuclear facilities tomore » withstand large fires without loss of important functions should such fires occur. The Review Group believes that improvements, especially in the areas of fire prevention and fire control, can and should be made in most existing facilities.« less

  7. The Interaction of Risk Network Structures and Virus Natural History in the Non-spreading of HIV Among People Who Inject Drugs in the Early Stages of the Epidemic.

    PubMed

    Dombrowski, Kirk; Khan, Bilal; Habecker, Patrick; Hagan, Holly; Friedman, Samuel R; Saad, Mohamed

    2017-04-01

    This article explores how social network dynamics may have reduced the spread of HIV-1 infection among people who inject drugs during the early years of the epidemic. Stochastic, discrete event, agent-based simulations are used to test whether a "firewall effect" can arise out of self-organizing processes at the actor level, and whether such an effect can account for stable HIV prevalence rates below population saturation. Repeated simulation experiments show that, in the presence of recurring, acute, and highly infectious outbreaks, micro-network structures combine with the HIV virus's natural history to reduce the spread of the disease. These results indicate that network factors likely played a significant role in the prevention of HIV infection within injection risk networks during periods of peak prevalence. They also suggest that social forces that disturb network connections may diminish the natural firewall effect and result in higher rates of HIV.

  8. Youngest Brown Dwarf Yet in a Multiple Stellar System

    NASA Astrophysics Data System (ADS)

    2000-07-01

    to an atmospheric temperature of "only" ~2200 °C (2500 K). For comparison, that of the Sun is ~ 6000 °C. The hydrogen (H-alpha) emission line indicates strong activity in the upper atmospheric layers (the chromosphere), as normally found in young stars and young Brown Dwarfs. Moreover, the comparatively weak sodium (Na) absorption line shows that this object must be relatively large for its low mass, and that it is still in the early stage of contraction. These are clear signs of young age and fully consistent with TWA-5 B being a bona-fide companion to the young star TWA-5 A . In fact, the possibility that an object as cold as TWA-5 B is located within 2 arcsec from TWA-5 A by chance is less than 10 -8. The motion of TWA-5 B ESO PR Photo 17d/00 ESO PR Photo 17d/00 [Preview - JPEG: 400 x 463 pix - 64k] [Normal - JPEG: 800 x 925 pix - 140k] Caption : The diagramme shows the relative positions of TWA-5 A and TWA-5 B , as measured on the sky by the HST in 1998 (points 1 and 2) and the VLT in 2000 (3 and 4). The ellipses indicate the measurement uncertainties. It is obvious that the two objects move in nearly the same direction and with the same speed. This greatly strengthens the conclusion that they are physically connected in the same multiple stellar system. When comparing the HST positional observations from 1998 and those with the VLT in 2000 ( PR Photo 17d/00 ), it is obvious that TWA-5 A and TWA-5 B move with very nearly the same speed and in the same direction on the sky. There is therefore no doubt that the two objects are physically connected within a stellar multiple system. At the distance of about 180 light-years, the angular separation (2 arcsec) corresponds to a projected distance of 110 AU (about 2.75 times the mean distance between the Sun and the outermost planet in the solar system, Pluto). From this and the mass of TWA-5 A , it is possible to conclude that one full orbit of TWA-5 B around TWA-5 A will last about 900 years. Mass, temperature and age

  9. Finding Brown's peony a sweet attraction

    Treesearch

    Nan. Vance

    2012-01-01

    I first encountered Brown’s peony (Paeonia brownie) with its verdant, lavender-tinged leaves and elegantly nodding maroon flowers growing among bitterbrush and bunchgrass on the eastern flank of the Oregon Cascades. My first thought was “What is a plant like you doing in a place like this?” It would be natural to visualize this native wild peony as...

  10. Browning boreal forests of western North America

    Treesearch

    David Verbyla

    2011-01-01

    The GIMMS NDVI dataset has been widely used to document a “browning trend” in North American boreal forests (Goetz et al. 2005, Bunn et al. 2007, Beck and Goetz 2011). However, there has been speculation (Alcaraz-Segura et al. 2010) that this trend may be an artifact due to processing algorithms rather than an actual decline in vegetation activity. This conclusion was...

  11. Molecular selectivity of brown carbon chromophores.

    PubMed

    Laskin, Julia; Laskin, Alexander; Nizkorodov, Sergey A; Roach, Patrick; Eckert, Peter; Gilles, Mary K; Wang, Bingbing; Lee, Hyun Ji Julie; Hu, Qichi

    2014-10-21

    Complementary methods of high-resolution mass spectrometry and microspectroscopy were utilized for molecular analysis of secondary organic aerosol (SOA) generated from ozonolysis of two structural monoterpene isomers: D-limonene SOA (LSOA) and α-pinene SOA (PSOA). The LSOA compounds readily formed adducts with Na(+) under electrospray ionization conditions, with only a small fraction of compounds detected in the protonated form. In contrast, a significant fraction of PSOA compounds appeared in the protonated form because of their increased molecular rigidity. Laboratory simulated aging of LSOA and PSOA, through conversion of carbonyls into imines mediated by NH3 vapors in humid air, resulted in selective browning of the LSOA sample, while the PSOA sample remained white. Comparative analysis of the reaction products in the aged LSOA and PSOA samples provided insights into chemistry relevant to formation of brown carbon chromophores. A significant fraction of carbonyl-imine conversion products with identical molecular formulas was detected in both samples. This reflects the high level of similarity in the molecular composition of these two closely related SOA materials. Several highly conjugated products were detected exclusively in the brown LSOA sample and were identified as potential chromophores responsible for the observed color change. The majority of the unique products in the aged LSOA sample with the highest number of double bonds contain two nitrogen atoms. We conclude that chromophores characteristic of the carbonyl-imine chemistry in LSOA are highly conjugated oligomers of secondary imines (Schiff bases) present at relatively low concentrations. Formation of this type of conjugated compounds in PSOA is hindered by the structural rigidity of the α-pinene oxidation products. Our results suggest that the overall light-absorbing properties of SOA may be determined by trace amounts of strong brown carbon chromophores.

  12. New White Dwarf-Brown Dwarf Binaries

    NASA Astrophysics Data System (ADS)

    Casewell, S. L.; Geier, S.; Lodieu, N.

    2017-03-01

    We present follow-up spectroscopy to 12 candidate white dwarf-brown dwarf binaries. We have confirmed that 8 objects do indeed have a white dwarf primary (7 DA, 1 DB) and two are hot subdwarfs. We have determined the Teff and log g for the white dwarfs and subdwarfs, and when combining these values with a model spectrum and the photometry, we have 3 probable white dwarf-substellar binaries with spectral types between M6 and L6.

  13. Parallaxes for the Coldest Brown Dwarfs

    NASA Astrophysics Data System (ADS)

    Dupuy, Trent; Kraus, Adam; Liu, Michael

    2014-12-01

    Understanding extremely cool atmospheres is a major goal of both brown dwarf and exoplanet studies. The WISE all-sky survey has uncovered the coolest brown dwarfs to date including the first unambiguous Y dwarfs. These discoveries are spectroscopically estimated to have temperatures of ~300-500 K and masses of ~5-20 Mjup, overlapping discoveries from radial velocity exoplanet surveys. However, direct distances are needed to determine model-independent temperatures and to test the observed properties against theoretical models in this new physical frontier. From our Cycle 8 program, we have successfully measured the first robust parallaxes for these extremely low-luminosity objects using Spitzer [3.6]-band astrometry, made possible with our improved distortion solution for IRAC. Our results, comprising less than half the currently known late-T/Y census, have uncovered a number of puzzles. Perhaps the most intriguing is the possibility that the observed near-IR spectral types and spectral energy distributions do not follow a simple correspondence with temperature, in contrast to all other (hotter) substellar and stellar objects. We propose here to obtain definitive parallaxes and temperatures to the ~2 dozen known coldest brown dwarfs. For our Cycle 8 sample, these new data will double the time baseline, leading to major improvements over our preliminary results. We will also double the total sample with parallaxes for more recent discoveries. Altogether, our work will establish the temperature scale as a function of spectral type, delineate the cooling (and intrinsic scatter) through the T/Y transition, and enable strong test of theoretical models for these coldest brown dwarfs, which are ~100x fainter than previously known objects at near-IR wavelengths.

  14. Powerful Auroras Found at Brown Dwarf

    NASA Image and Video Library

    2017-12-08

    This artist's concept shows an auroral display on a brown dwarf. If you could see an aurora on a brown dwarf, it would be a million times brighter than an aurora on Earth. Credits: Chuck Carter and Gregg Hallinan/Caltech --- Mysterious objects called brown dwarfs are sometimes called "failed stars." They are too small to fuse hydrogen in their cores, the way most stars do, but also too large to be classified as planets. But a new study in the journal Nature suggests they succeed in creating powerful auroral displays, similar to the kind seen around the magnetic poles on Earth. "This is a whole new manifestation of magnetic activity for that kind of object," said Leon Harding, a technologist at NASA's Jet Propulsion Laboratory, Pasadena, California, and co-author on the study. On Earth, auroras are created when charged particles from the solar wind enter our planet's magnetosphere, a region where Earth's magnetic field accelerates and sends them toward the poles. There, they collide with atoms of gas in the atmosphere, resulting in a brilliant display of colors in the sky. Read more: www.nasa.gov/jpl/powerful-auroras-found-at-brown-dwarf NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  15. Evaluation of CMV/human herpes virus-6 positivity in bronchoalveolar lavage fluids as early detection of acute GVHD following BMT: evidence of a significant relationship.

    PubMed

    Takemoto, Y; Takatsuka, H; Wada, H; Mori, A; Saheki, K; Okada, M; Tamura, S; Fujimori, Y; Okamoto, T; Kakishita, E; Kanamaru, A

    2000-07-01

    We evaluated the relationship between CMV and human herpes virus-6 (HHV-6) reactivation and the incidence of grades 2 to 4 acute GVHD post BMT. Bronchoalveolar lavage fluid (BALF) samples extracted from 54 BMT recipients on post-BMT day 35 were analyzed by PCR for detection of CMV DNA, HHV-6 DNA and CMV plus HHV-6 DNA. CMV DNA was detected in 26 patients and 13 (50%) developed grades 2 to 4 acute GVHD. Of the 28 who were CMV negative, only six (21.4%) developed grades 2 to 4 acute GVHD. HHV-6 was detected in 18 patients, and 11 (61.1%) developed grades 2 to 4 acute GVHD. Of the 36 who were HHV-6 negative, only eight (22.2%) developed grades 2 to 4 acute GVHD. CMV and HHV-6 were detected in 13 patients, and eight (61.5%) developed grades 2 to 4 acute GVHD. Of the 23 who were negative for both CMV and HHV-6, only three (13%) developed grades 2 to 4 acute GVHD. In all experiments, the difference between the groups was significant (P<0.05, P<0.05 and P<0.01, respectively). We conclude that herpes virus infection, in particular CMV concurrent with HHV-6 reactivation, is predictive of moderate to severe acute GVHD.

  16. Quasispecies evolution of the prototypical genotype 1 porcine reproductive and respiratory syndrome virus early during in vivo infection is rapid and tissue specific.

    PubMed

    Lu, Zen H; Wang, Xinglong; Wilson, Alison D; Dorey-Robinson, Daniel L W; Archibald, Alan L; Ait-Ali, Tahar; Frossard, Jean-Pierre

    2017-08-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a major infectious threat to the pig industry worldwide. Increasing evidence suggests that microevolution within a quasispecies population can give rise to high sequence heterogeneity in PRRSV; potentially impacting the pathogenicity of the virus. Here, we report on micro-evolutionary events taking place within the viral quasispecies population in lung and lymph node 3 days post infection (dpi) following experimental in vivo infection with the prototypical Lelystad PRRSV (LV). Sequence analysis revealed 16 high frequency single nucleotide variants (SNV) or differences from the reference LV genome which are assumed to be representative of the consensus inoculum genome. Additionally, 49 other low frequency SNVs were also found in the inoculum population. At 3 dpi, a total of 9 and 10 SNVs of varying frequencies could already be detected in the LV population infecting the lung and lymph nodes, respectively. Interestingly, of these, three and four novel SNVs emerged independently in the two respective tissues when compared to the inoculum. The remaining variants, though already present at lower frequencies in the inoculum, were positively selected and their frequency increased within the quasispecies population. Hence, we were able to determine directly from tissues infected with PRRSV the repertoire of genetic variants within the viral quasispecies population. Our data also suggest that microevolution of these variants is rapid and some may be tissue-specific.

  17. UCP1 in adipose tissues: two steps to full browning.

    PubMed

    Kalinovich, Anastasia V; de Jong, Jasper M A; Cannon, Barbara; Nedergaard, Jan

    2017-03-01

    The possibility that brown adipose tissue thermogenesis can be recruited in order to combat the development of obesity has led to a high interest in the identification of "browning agents", i.e. agents that increase the amount and activity of UCP1 in brown and brite/beige adipose tissues. However, functional analysis of the browning process yields confusingly different results when the analysis is performed in one of two alternative steps. Thus, in one of the steps, using cold acclimation as a potent model browning agent, we find that if the browning process is followed in mice initially housed at 21 °C (the most common procedure), there is only weak molecular evidence for increases in UCP1 gene expression or UCP1 protein abundance in classical brown adipose tissue; however, in brite/beige adipose depots, there are large increases, apparently associating functional browning with events only in the brite/beige tissues. Contrastingly, in another step, if the process is followed starting with mice initially housed at 30 °C (thermoneutrality for mice, thus similar to normal human conditions), large increases in UCP1 gene expression and UCP1 protein abundance are observed in the classical brown adipose tissue depots; there is then practically no observable UCP1 gene expression in brite/beige tissues. This apparent conundrum can be resolved when it is realized that the classical brown adipose tissue at 21 °C is already essentially fully differentiated and thus expands extensively through proliferation upon further browning induction, rather than by further enhancing cellular differentiation. When the limiting factor for thermogenesis, i.e. the total amount of UCP1 protein per depot, is analyzed, classical brown adipose tissue is by far the predominant site for the browning process, irrespective of which of the two steps is analyzed. There are to date no published data demonstrating that alternative browning agents would selectively promote brite/beige tissues

  18. The development of academic anesthesiology at the Roswell Park Memorial Institute: James O. Elam, MD, and Elwyn S. Brown, MD.

    PubMed

    Peppriell, J E; Bacon, D R; Lema, M J; Ament, R; Yearley, C K

    1991-04-01

    In the early 1950s, Drs. James Elam and Elwyn Brown were recruited to establish the department of anesthesiology at the Roswell Park Memorial Institute. With substantial financial support from both the New York State coffers and the Institute's director, Dr. George Moore, Elam and Brown were able to create a department of anesthesiology renowned for clinical excellence and basic science research. Their work on carbon dioxide elimination led to a redesigning of the soda lime canisters that is still in clinical use. By popularizing mouth-to-mouth rescue breathing, these two anesthesiologists changed the manner in which emergency aid was given and won international acclaim.

  19. Influence of selected factors on browning of Camembert cheese.

    PubMed

    Carreira, Alexandra; Dillinger, Klaus; Eliskases-Lechner, Frieda; Loureiro, Virgílio; Ginzinger, Wolfgang; Rohm, Harald

    2002-05-01

    Experimental Camembert cheeses were made to investigate the effects on browning of the following factors: inoculation with Yarrowia lipolytica, the use of Penicillium candidum strains with different proteolytic activity, the addition of tyrosine, and the addition of Mn2+ thus leading to 16 different variants of cheese. Two physical colour parameters were used to describe browning, depending on the location in the cheeses: a whiteness index for the outside browning (mould mycelium), and a brownness index for the inside browning (surface of the cheese body). Mn2+ promoted a significant increase of browning at both locations, whereas Yar. lipolytica had the opposite effect. Outside browning was significantly more intense when using the Pen. candidum strain with higher proteolytic activity. A significant interaction was found between Yar. lipolytica and Pen. candidum. The yeast had no effect in combination with a low proteolytic strain of Pen. candidum, but significantly reduced proteolysis and browning in combination with a high proteolytic strain of Pen. candidum. We further confirmed that both strains of Pen. candidum were able to produce brown pigments from tyrosine and thus both are presumably responsible for the browning activity in this type of cheese.

  20. Cannabidiol promotes browning in 3T3-L1 adipocytes.

    PubMed

    Parray, Hilal Ahmad; Yun, Jong Won

    2016-05-01

    Recruitment of the brown-like phenotype in white adipocytes (browning) and activation of existing brown adipocytes are currently being investigated as a means to combat obesity. Thus, a wide variety of dietary agents that contribute to browning of white adipocytes have been identified. The present study was designed to investigate the effects of cannabidiol (CBD), a major nonpsychotropic phytocannabinoid of Cannabis sativa, on induction of browning in 3T3-L1 adipocytes. CBD enhanced expression of a core set of brown fat-specific marker genes (Ucp1, Cited1, Tmem26, Prdm16, Cidea, Tbx1, Fgf21, and Pgc-1α) and proteins (UCP1, PRDM16, and PGC-1α). Increased expression of UCP1 and other brown fat-specific markers contributed to the browning of 3T3-L1 adipocytes possibly via activation of PPARγ and PI3K. In addition, CBD increased protein expression levels of CPT1, ACSL, SIRT1, and PLIN while down-regulating JNK2, SREBP1, and LPL. These data suggest possible roles for CBD in browning of white adipocytes, augmentation of lipolysis, thermogenesis, and reduction of lipogenesis. In conclusion, the current data suggest that CBD plays dual modulatory roles in the form of inducing the brown-like phenotype as well as promoting lipid metabolism. Thus, CBD may be explored as a potentially promising therapeutic agent for the prevention of obesity.

  1. Parallax measurements of cool brown dwarfs

    NASA Astrophysics Data System (ADS)

    Manjavacas, E.; Goldman, B.; Reffert, S.; Henning, T.

    2013-12-01

    Context. Accurate parallax measurements allow us to determine physical properties of brown dwarfs and help us constrain evolutionary and atmospheric models, break age-mass degeneracy, and reveal unresolved binaries. Aims: We measured absolute trigonometric parallaxes and proper motions of six cool brown dwarfs using background galaxies to establish an absolute reference frame. We derive the absolute J-band magnitude. The six T brown dwarfs in our sample have spectral types between T2.5 and T8 and magnitudes between 13.9 and 18.0 in the Two Micron All Sky Survey (2MASS) with photometric distances below 25 pc. Methods: The observations were taken in the J-band with the Omega-2000 camera on the 3.5 m telescope at Calar Alto during a time period of 27 months between March 2011 and June 2013. The number of epochs varied between 11 and 12 depending on the object. The reduction of the astrometric measurements was carried out with respect to the field stars. The relative parallax and proper motions were transformed into absolute measurements using the background galaxies in our fields. Results: We obtained absolute parallaxes for our six brown dwarfs with a precision between 3 and 6 mas. We compared our results in a color-magnitude diagram with other brown dwarfs with determined parallax and with the BT-Settl 2012 atmospheric models. For four of the six targets, we found a good agreement in luminosity with objects of similar spectral types. We obtained an improved accuracy in the parallaxes and proper motions in comparison to previous works. The object 2MASS J11061197+2754225 is more than 1 mag overluminous in all bands, which point to binarity or high order multiplicity. Based on observations taken with Omega-2000 at the 3.5 m telescope at the Centro Astronómico Hispano Alemán (CAHA) at Calar Alto, operated by the Max Planck Institut für Astronomie and the Instituto de Astrofísica de Andalucía (CSIC).Appendix A is available in electronic form at http://www.aanda.org

  2. The pathogenic role of virus-specific antibody-secreting cells in the central nervous system of rats with different susceptibility to coronavirus-induced demyelinating encephalitis.

    PubMed Central

    Schwender, S; Imrich, H; Dörries, R

    1991-01-01

    The humoral immune response in the central nervous system (CNS) of susceptible Lewis (LE) rats and resistant Brown Norway (BN) rats was analysed after intracerebral infection with the murine coronavirus JHM (MHV4). The subclinical course of the infection in BN rats was characterized by an early rise of neutralizing antibodies in the cerebrospinal fluid (CSF) 7 days post-infection. At this time in LE rats, neutralizing antibodies were not detectable in the CSF and the animals developed neurological signs of infection. Subsequently, LE rats recovered from disease. This process was accompanied by increasing titres of virus-neutralizing antibodies. Within the CNS parenchyma of both rat strains, equivalent numbers of IgM-secreting cells were detected. However, in BN rats, virus-specific IgG secreting cells appeared earlier and in higher numbers. Moreover, based on the size of zones of antibody secreted by single cells in the Spot-ELISA assay, it appeared that cells from BN rats secreted IgG antibody of higher affinity. These data suggest that early maturation of antiviral antibody responses in the resistant BN rat probably restricts the spread of viral infection to small foci within the CNS, resulting in a subclinical level of primary demyelination. In contrast, the absence of neutralizing antibodies in the susceptible LE rats favours spread of the virus throughout the CNS, resulting finally in severe neurological disease. Images Figure 1 Figure 2 Figure 3 PMID:1663078

  3. Multiplicity among Young Brown Dwarfs and Very Low Mass Stars

    NASA Astrophysics Data System (ADS)

    Ahmic, Mirza; Jayawardhana, Ray; Brandeker, Alexis; Scholz, Alexander; van Kerkwijk, Marten H.; Delgado-Donate, Eduardo; Froebrich, Dirk

    2007-12-01

    We report on a near-infrared adaptive optics imaging survey of 31 young brown dwarfs and very low mass (VLM) stars, 28 of which are in the Chamaeleon I star-forming region, using the ESO Very Large Telescope. We resolve the suspected 0.16'' (~26 AU) binary Cha Hα 2 and present two new binaries, Hn 13 and CHXR 15, with separations of 0.13'' (~20 AU) and 0.30'' (~50 AU), respectively; the latter is one of the widest VLM systems known. We find a binary frequency of 11+9-6%, thus confirming the trend for a lower binary frequency with decreasing mass. By combining our work with previous surveys, we arrive at the largest sample of young VLM objects (72) with high angular resolution imaging to date. Its multiplicity fraction is in statistical agreement with that for VLM objects in the field. Furthermore, we note that many field stellar binaries with lower binding energies and/or wider cross sections have survived dynamical evolution and that statistical models suggest tidal disruption by passing stars is unlikely to affect the binary properties of our systems. Thus, we argue that there is no significant evolution of multiplicity with age among brown dwarfs and VLM stars in OB and T associations between a few megayears to several gigayears. Instead, the observations so far suggest that VLM objects are either less likely to be born in fragile multiple systems than solar-mass stars or such systems are disrupted very early. We dedicate this paper to the memory of our coauthor, Eduardo Delgado-Donate, who died in a hiking accident in Tenerife earlier this year.

  4. Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface.

    PubMed

    Weisblum, Yiska; Oiknine-Djian, Esther; Vorontsov, Olesya M; Haimov-Kochman, Ronit; Zakay-Rones, Zichria; Meir, Karen; Shveiky, David; Elgavish, Sharona; Nevo, Yuval; Roseman, Moshe; Bronstein, Michal; Stockheim, David; From, Ido; Eisenberg, Iris; Lewkowicz, Aya A; Yagel, Simcha; Panet, Amos; Wolf, Dana G

    2017-02-15

    Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions. In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn

  5. A Universal Spin–Mass Relation for Brown Dwarfs and Planets

    NASA Astrophysics Data System (ADS)

    Scholz, Aleks; Moore, Keavin; Jayawardhana, Ray; Aigrain, Suzanne; Peterson, Dawn; Stelzer, Beate

    2018-06-01

    While brown dwarfs show similarities to stars early in their lives, their spin evolutions are much more akin to those of planets. We have used light curves from the K2 mission to measure new rotation periods for 18 young brown dwarfs in the Taurus star-forming region. Our sample spans masses from 0.02 to 0.08 M ⊙ and has been characterized extensively in the past. To search for periods, we utilize three different methods (autocorrelation, periodogram, Gaussian processes). The median period for brown dwarfs with disks is twice as long as for those without (3.1 versus 1.6 days), a signature of rotational braking by the disk, albeit with small numbers. With an overall median period of 1.9 days, brown dwarfs in Taurus rotate slower than their counterparts in somewhat older (3–10 Myr) star-forming regions, consistent with spin-up of the latter due to contraction and angular momentum conservation, a clear sign that disk braking overall is inefficient and/or temporary in this mass domain. We confirm the presence of a linear increase of the typical rotation period as a function of mass in the substellar regime. The rotational velocities, when calculated forward to the age of the solar system, assuming angular momentum conservation, fit the known spin–mass relation for solar system planets and extra-solar planetary-mass objects. This spin–mass trend holds over six orders of magnitude in mass, including objects from several different formation paths. Our result implies that brown dwarfs by and large retain their primordial angular momentum through the first few Myr of their evolution.

  6. Brown dwarf photospheres are patchy: A Hubble space telescope near-infrared spectroscopic survey finds frequent low-level variability

    SciTech Connect

    Buenzli, Esther; Apai, Dániel; Radigan, Jacqueline

    2014-02-20

    Condensate clouds strongly impact the spectra of brown dwarfs and exoplanets. Recent discoveries of variable L/T transition dwarfs argued for patchy clouds in at least some ultracool atmospheres. This study aims to measure the frequency and level of spectral variability in brown dwarfs and to search for correlations with spectral type. We used Hubble Space Telescope/Wide Field Camera 3 to obtain spectroscopic time series for 22 brown dwarfs of spectral types ranging from L5 to T6 at 1.1-1.7 μm for ≈40 minutes per object. Using Bayesian analysis, we find six brown dwarfs with confident (p > 95%) variability in themore » relative flux in at least one wavelength region at sub-percent precision, and five brown dwarfs with tentative (p > 68%) variability. We derive a minimum variability fraction f{sub min}=27{sub −7}{sup +11}% over all covered spectral types. The fraction of variables is equal within errors for mid-L, late-L, and mid-T spectral types; for early-T dwarfs we do not find any confident variable but the sample is too small to derive meaningful limits. For some objects, the variability occurs primarily in the flux peak in the J or H band, others are variable throughout the spectrum or only in specific absorption regions. Four sources may have broadband peak-to-peak amplitudes exceeding 1%. Our measurements are not sensitive to very long periods, inclinations near pole-on and rotationally symmetric heterogeneity. The detection statistics are consistent with most brown dwarf photospheres being patchy. While multiple-percent near-infrared variability may be rare and confined to the L/T transition, low-level heterogeneities are a frequent characteristic of brown dwarf atmospheres.« less

  7. A Foxtail mosaic virus Vector for Virus-Induced Gene Silencing in Maize.

    PubMed

    Mei, Yu; Zhang, Chunquan; Kernodle, Bliss M; Hill, John H; Whitham, Steven A

    2016-06-01

    Plant viruses have been widely used as vectors for foreign gene expression and virus-induced gene silencing (VIGS). A limited number of viruses have been developed into viral vectors for the purposes of gene expression or VIGS in monocotyledonous plants, and among these, the tripartite viruses Brome mosaic virus and Cucumber mosaic virus have been shown to induce VIGS in maize (Zea mays). We describe here a new DNA-based VIGS system derived from Foxtail mosaic virus (FoMV), a monopartite virus that is able to establish systemic infection and silencing of endogenous maize genes homologous to gene fragments inserted into the FoMV genome. To demonstrate VIGS applications of this FoMV vector system, four genes, phytoene desaturase (functions in carotenoid biosynthesis), lesion mimic22 (encodes a key enzyme of the porphyrin pathway), iojap (functions in plastid development), and brown midrib3 (caffeic acid O-methyltransferase), were silenced and characterized in the sweet corn line Golden × Bantam. Furthermore, we demonstrate that the FoMV infectious clone establishes systemic infection in maize inbred lines, sorghum (Sorghum bicolor), and green foxtail (Setaria viridis), indicating the potential wide applications of this viral vector system for functional genomics studies in maize and other monocots. © 2016 American Society of Plant Biologists. All Rights Reserved.

  8. A Foxtail mosaic virus Vector for Virus-Induced Gene Silencing in Maize1[OPEN

    PubMed Central

    Mei, Yu; Kernodle, Bliss M.; Hill, John H.

    2016-01-01

    Plant viruses have been widely used as vectors for foreign gene expression and virus-induced gene silencing (VIGS). A limited number of viruses have been developed into viral vectors for the purposes of gene expression or VIGS in monocotyledonous plants, and among these, the tripartite viruses Brome mosaic virus and Cucumber mosaic virus have been shown to induce VIGS in maize (Zea mays). We describe here a new DNA-based VIGS system derived from Foxtail mosaic virus (FoMV), a monopartite virus that is able to establish systemic infection and silencing of endogenous maize genes homologous to gene fragments inserted into the FoMV genome. To demonstrate VIGS applications of this FoMV vector system, four genes, phytoene desaturase (functions in carotenoid biosynthesis), lesion mimic22 (encodes a key enzyme of the porphyrin pathway), iojap (functions in plastid development), and brown midrib3 (caffeic acid O-methyltransferase), were silenced and characterized in the sweet corn line Golden × Bantam. Furthermore, we demonstrate that the FoMV infectious clone establishes systemic infection in maize inbred lines, sorghum (Sorghum bicolor), and green foxtail (Setaria viridis), indicating the potential wide applications of this viral vector system for functional genomics studies in maize and other monocots. PMID:27208311

  9. Nonmuscle myosin heavy chain IIA is a critical factor contributing to the efficiency of early infection of severe fever with thrombocytopenia syndrome virus.

    PubMed

    Sun, Yinyan; Qi, Yonghe; Liu, Chenxuan; Gao, Wenqing; Chen, Pan; Fu, Liran; Peng, Bo; Wang, Haimin; Jing, Zhiyi; Zhong, Guocai; Li, Wenhui

    2014-01-01

    Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus in the Bunyaviridae family. Most patients infected by SFTSV present with fever and thrombocytopenia, and up to 30% die due to multiple-organ dysfunction. The mechanisms by which SFTSV enters multiple cell types are unknown. SFTSV contains two species of envelope glycoproteins, Gn (44.2 kDa) and Gc (56 kDa), both of which are encoded by the M segment and are cleaved from a precursor polypeptide (about 116 kDa) in the endoplasmic reticulum (ER). Gn fused with an immunoglobulin Fc tag at its C terminus (Gn-Fc) bound to multiple cells susceptible to the infection of SFTSV and blocked viral infection of human umbilical vein endothelial cells (HUVECs). Immunoprecipitation assays following mass spectrometry analysis showed that Gn binds to nonmuscle myosin heavy chain IIA (NMMHC-IIA), a cellular protein with surface expression in multiple cell types. Small interfering RNA (siRNA) knockdown of NMMHC-IIA, but not the closely related NMMHC-IIB or NMMHC-IIC, reduced SFTSV infection, and NMMHC-IIA specific antibody blocked infection by SFTSV but not other control viruses. Overexpression of NMMHC-IIA in HeLa cells, which show limited susceptivity to SFTSV, markedly enhanced SFTSV infection of the cells. These results show that NMMHC-IIA is critical for the cellular entry of SFTSV. As NMMHC-IIA is essential for the normal functions of platelets and human vascular endothelial cells, it is conceivable that NMMHC-IIA directly contributes to the pathogenesis of SFTSV and may be a useful target for antiviral interventions against the viral infection.

  10. Absence of Association between Cord Specific Antibody Levels and Severe Respiratory Syncytial Virus (RSV) Disease in Early Infants: A Case Control Study from Coastal Kenya.

    PubMed

    Nyiro, Joyce Uchi; Sande, Charles Jumba; Mutunga, Martin; Kiyuka, Patience Kerubo; Munywoki, Patrick Kioo; Scott, John Anthony G; Nokes, David James

    2016-01-01

    The target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development. A case control study nested in a birth cohort (2002-07) was conducted in Kilifi, Kenya; where 30 hospitalised cases of RSV-associated severe disease were matched to 60 controls. Participants had a cord blood and 2 subsequent 3-monthly blood samples assayed for RSV-specific neutralising antibody by the plaque reduction neutralisation test (PRNT). Two sample paired t test and conditional logistic regression were used in analyses of log2PRNT titres. The mean RSV log2PRNT titre at birth for cases and controls were not significantly different (P = 0.4) and remained so on age-stratification. Cord blood PRNT titres showed considerable overlap between cases and controls. The odds of RSV disease decreased with increase in log2PRNT cord blood titre. There was a 30% reduction in RSV disease per unit increase in log2PRNT titre (<3months age group) but not significant (P = 0.3). From this study, there is no strong evidence of protection by maternal RSV specific antibodies from severe RSV disease. Cord antibody levels show wide variation with considerable overlap between cases and controls. It is likely that, there are additional factors to specific PRNT antibody levels which determine susceptibility to severe RSV disease. In addition, higher levels of neutralizing antibody beyond the normal range may be required for protection; which it is hoped can be achieved by a maternal RSV vaccine.

  11. White Adipose Tissue Browning: A Double-edged Sword.

    PubMed

    Abdullahi, Abdikarim; Jeschke, Marc G

    2016-08-01

    The study of white adipose tissue (WAT) 'browning' has become a 'hot topic' in various acute and chronic metabolic conditions, based on the idea that WAT browning might be able to facilitate weight loss and improve metabolic health. However, this view cannot be translated into all areas of medicine. Recent studies identified effects of browning associated with adverse outcomes, and as more studies are being conducted, a very different picture has emerged about WAT browning and its detrimental effect in acute and chronic hypermetabolic conditions. Therefore, the notion that browning is supposedly beneficial may be inadequate. In this review we analyze how and why browning in chronic hypermetabolic associated diseases can be detrimental and lead to adverse outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. CHLORELLA VIRUSES

    PubMed Central

    Yamada, Takashi; Onimatsu, Hideki; Van Etten, James L.

    2007-01-01

    Chlorella viruses or chloroviruses are large, icosahedral, plaque‐forming, double‐stranded‐DNA—co