Sample records for a226v mutant chikungunya

  1. Appearance of E1: A226V mutant Chikungunya virus in Coastal Karnataka, India during 2008 outbreak

    PubMed Central

    Santhosh, SR; Dash, Paban Kumar; Parida, Manmohan; Khan, Mohasin; Rao, Putcha VL

    2009-01-01

    Chikungunya has resurged in the form of unprecedented explosive epidemic in 2006 after a long gap in India affecting 1.39 million of persons. The disease continued for the next two consecutive years affecting 59,535 and 64,548 persons during 2007 and 2008 respectively. The 2008 outbreak being the second largest among these three years the information regarding the etiology and the mutations involved are useful for further control measures. Among the 2008 outbreaks the Coastal Karnataka accounts for the 46,510 persons. An in-depth investigation of Chikungunya epidemic of Coastal Karnataka, India, 2008 by serology, virus isolation, RT-PCR and genome sequencing revealed the presence and continued circulation of A226V mutant Chikungunya virus. The appearance of this mutant virus was found to be associated with higher prevalence of vector Aedes albopictus and the geographical proximity of coastal Karnataka with the adjoining Kerala state. This is the first report regarding the appearance of this mutation in Karnataka state of India. The present study identified the presence and association of A226V mutant virus with Chikungunya outbreak in India during 2008. PMID:19857273

  2. Vector competence of Italian Aedes albopictus populations for the chikungunya virus (E1-226V).

    PubMed

    Severini, Francesco; Boccolini, Daniela; Fortuna, Claudia; Di Luca, Marco; Toma, Luciano; Amendola, Antonello; Benedetti, Eleonora; Minelli, Giada; Romi, Roberto; Venturi, Giulietta; Rezza, Giovanni; Remoli, Maria Elena

    2018-04-01

    Chikungunya virus (CHIKV) is an emerging arbovirus, belonging to the Togaviridae family, Alphavirus genus, transmitted by Aedes spp. mosquitoes. Since 2007, two different CHIKV strains (E1-226A and E1-226V) have been responsible for outbreaks in European countries, including Italy, sustained by Ae. albopictus mosquitoes. In this study, we assessed the susceptibility to the CHIKV E1-226V, strain responsible for the Italian 2007 outbreak, of eight Ae. albopictus populations collected in Northern, Central, Southern, and Island Italy, by experimental infections. Vector competence was evaluated by estimating infection, dissemination, and transmission rates (IR, DR, TR), through detection of the virus in the bodies, legs plus wings, and saliva, respectively. Additionally, vertical transmission was evaluated by the detection of the virus in the offspring. The results of our study demonstrated that the Italian populations of Ae. albopictus tested were susceptible to CHIKV infection, and can disseminate the virus outside the midgut barrier with high values of IR and DR. Viral infectious RNA was detected in the saliva of three populations from Central, Southern, and Island Italy, also tested for TR and population transmission rate (PTR) values. No progeny of the first and second gonotrophic cycle were positive for CHIKV. This study strongly confirms the role of Ae. albopictus as a potential CHIKV vector in Italy. This may represent a threat, especially considering both the high density of this species, which is widespread throughout the country, and the increasing number of cases of imported arboviruses.

  3. Entomologic and Virologic Investigation of Chikungunya, Singapore

    PubMed Central

    Tan, Li-Kiang; Tan, Cheong-Huat; Tan, Sharon S.Y.; Hapuarachchi, Hapuarachchige C.; Pok, Kwoon-Yong; Lai, Yee-Ling; Lam-Phua, Sai-Gek; Bucht, Göran; Lin, Raymond T.P.; Leo, Yee-Sin; Tan, Boon-Hian; Han, Hwi-Kwang; Ooi, Peng-Lim S; James, Lyn; Khoo, Seow-Poh

    2009-01-01

    Local transmission of chikungunya, a debilitating mosquito-borne viral disease, was first reported in Singapore in January 2008. After 3 months of absence, locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak that resulted in a total of 231 cases by September 2008. The circulating viruses were related to East, Central, and South African genotypes that emerged in the Indian Ocean region in 2005. The first local outbreak was due to a wild-type virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where Aedes aegypti mosquitoes were the primary vector. Strains isolated during subsequent outbreaks showed alanine to valine substitution (A226V) and largely spread in areas predominated by Ae. albopictus mosquitoes. These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas. PMID:19751586

  4. Entomologic and virologic investigation of Chikungunya, Singapore.

    PubMed

    Ng, Lee-Ching; Tan, Li-Kiang; Tan, Cheong-Huat; Tan, Sharon S Y; Hapuarachchi, Hapuarachchige C; Pok, Kwoon-Yong; Lai, Yee-Ling; Lam-Phua, Sai-Gek; Bucht, Göran; Lin, Raymond T P; Leo, Yee-Sin; Tan, Boon-Hian; Han, Hwi-Kwang; Ooi, Peng-Lim S; James, Lyn; Khoo, Seow-Poh

    2009-08-01

    Local transmission of chikungunya, a debilitating mosquito-borne viral disease, was first reported in Singapore in January 2008. After 3 months of absence, locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak that resulted in a total of 231 cases by September 2008. The circulating viruses were related to East, Central, and South African genotypes that emerged in the Indian Ocean region in 2005. The first local outbreak was due to a wild-type virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where Aedes aegypti mosquitoes were the primary vector. Strains isolated during subsequent outbreaks showed alanine to valine substitution (A226V) and largely spread in areas predominated by Ae. albopictus mosquitoes. These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas.

  5. Detection of a chikungunya outbreak in Central Italy, August to September 2017.

    PubMed

    Venturi, Giulietta; Di Luca, Marco; Fortuna, Claudia; Remoli, Maria Elena; Riccardo, Flavia; Severini, Francesco; Toma, Luciano; Del Manso, Martina; Benedetti, Eleonora; Caporali, Maria Grazia; Amendola, Antonello; Fiorentini, Cristiano; De Liberato, Claudio; Giammattei, Roberto; Romi, Roberto; Pezzotti, Patrizio; Rezza, Giovanni; Rizzo, Caterina

    2017-09-01

    An autochthonous chikungunya outbreak is ongoing near Anzio, a coastal town in the province of Rome. The virus isolated from one patient and mosquitoes lacks the A226V mutation and belongs to an East Central South African strain. As of 20 September, 86 cases are laboratory-confirmed. The outbreak proximity to the capital, its late summer occurrence, and diagnostic delays, are favouring transmission. Vector control, enhanced surveillance and restricted blood donations are being implemented in affected areas.

  6. Chikungunya: a bending reality.

    PubMed

    Her, Zhisheng; Kam, Yiu-Wing; Lin, Raymond T P; Ng, Lisa F P

    2009-12-01

    Chikungunya fever is an acute illness caused by the arbovirus Chikungunya virus. The virus is transmitted primarily in a sylvatic cycle involving the Aedes mosquitoes. Since 2005, a Chikungunya fever outbreak of unprecedented magnitude occurred on several Indian Ocean islands. Since then, the disease has spread to many parts of the world due to imported cases among travellers returning from epidemic areas. Chikungunya virus causes a wide spectrum of illness including fever, a characteristic rash, disabling joint symptoms which can sometimes become severe that lasts months. This review summarises on this history of Chikungunya fever, host specificity, the characteristics of Chikungunya virus, clinical features of disease and current control measures. It focuses on how the re-emergence of an old changed the outlook of managing arboviral diseases in the present social and public health context.

  7. Chikungunya Myeloradiculopathy: A Rare Complication

    PubMed Central

    Krishnan, Mohana; Rahul; Krishnamoorthy

    2012-01-01

    Chikungunya, an alpha virus belonging to the family of Togaviridae is transmitted to humans by the bite of Aedes aegypti mosquito and presents with fever, headache, rash, and severe arthralgia. Chikungunya virus is not known to be neurotropic, but cases of meningoencephalitis have been reported during outbreaks. The clinical, laboratory and neuroimaging findings of a 56-year-old man who initially developed Chikungunya fever with arthralagia and later on lead to Chikungunya myeloradiculopathy, a relatively unknown and rare complication of the infection has been presented. PMID:23326078

  8. Structural characterization of V57D and V57P mutants of human cystatin C, an amyloidogenic protein

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

    Orlikowska, Marta; Szymańska, Aneta; Borek, Dominika

    2013-04-01

    Val57 point mutants of human cystatin C, which were designed to assess the influence of changes in the properties of the L1 loop on the dimerization propensity, were structurally characterized. Wild-type human cystatin C (hCC wt) is a low-molecular-mass protein (120 amino-acid residues, 13 343 Da) that is found in all nucleated cells. Physiologically, it functions as a potent regulator of cysteine protease activity. While the biologically active hCC wt is a monomeric protein, all crystallization efforts to date have resulted in a three-dimensional domain-swapped dimeric structure. In the recently published structure of a mutated hCC, the monomeric fold wasmore » preserved by a stabilization of the conformationally constrained loop L1 caused by a single amino-acid substitution: Val57Asn. Additional hCC mutants were obtained in order to elucidate the relationship between the stability of the L1 loop and the propensity of human cystatin C to dimerize. In one mutant Val57 was substituted by an aspartic acid residue, which is favoured in β-turns, and in the second mutant proline, a residue known for broadening turns, was substituted for the same Val57. Here, 2.26 and 3.0 Å resolution crystal structures of the V57D andV57P mutants of hCC are reported and their dimeric architecture is discussed in terms of the stabilization and destabilization effects of the introduced mutations.« less

  9. First Report of the East-Central South African Genotype of Chikungunya Virus in Rio de Janeiro, Brazil.

    PubMed

    Souza, Thiara Manuele Alves; Azeredo, Elzinandes Leal; Badolato-Corrêa, Jessica; Damasco, Paulo Vieira; Santos, Carla; Petitinga-Paiva, Fabienne; Nunes, Priscila Conrado Guerra; Barbosa, Luciana Santos; Cipitelli, Márcio Costa; Chouin-Carneiro, Thais; Faria, Nieli Rodrigues Costa; Nogueira, Rita Maria Ribeiro; de Bruycker-Nogueira, Fernanda; Dos Santos, Flavia Barreto

    2017-02-14

    Chikungunya virus (CHIKV) is an arbovirus that causes an acute febrile syndrome with a severe and debilitating arthralgia. In Brazil, the Asian and East-Central South African (ECSA) genotypes are circulating in the north and northeast of the country, respectively. In 2015, the first autochthonous cases in Rio de Janeiro, Brazil were reported but until now the circulating strains have not been characterized. Therefore, we aimed here to perform the molecular characterization and phylogenetic analysis of CHIKV strains circulating in the 2016 outbreak occurred in the municipality of Rio de Janeiro. The cases analyzed in this study were collected at a private Hospital, from April 2016 to May 2016, during the chikungunya outbreak in Rio de Janeiro, Brazil. All cases were submitted to the Real Time RT-PCR for CHIKV genome detection and to anti-CHIKV IgM ELISA. Chikungunya infection was laboratorially confirmed by at least one diagnostic method and, randomly selected positive cases (n=10), were partially sequenced (CHIKV E1 gene) and analyzed. The results showed that all the samples grouped in ECSA genotype branch and the molecular characterization of the fragment did not reveal the A226V mutation in the Rio de Janeiro strains analyzed, but a K211T amino acid substitution was observed for the first time in all samples and a V156A substitution in two of ten samples. Phylogenetic analysis and molecular characterization reveals the circulation of the ECSA genotype of CHIKV in the city of Rio de Janeiro, Brazil and two amino acids substitutions (K211T and V156A) exclusive to the CHIKV strains obtained during the 2016 epidemic, were reported.

  10. First Report of the East-Central South African Genotype of Chikungunya Virus in Rio de Janeiro, Brazil

    PubMed Central

    Souza, Thiara Manuele Alves; Azeredo, Elzinandes Leal; Badolato-Corrêa, Jessica; Damasco, Paulo Vieira; Santos, Carla; Petitinga-Paiva, Fabienne; Nunes, Priscila Conrado Guerra; Barbosa, Luciana Santos; Cipitelli, Márcio Costa; Chouin-Carneiro, Thais; Faria, Nieli Rodrigues Costa; Nogueira, Rita Maria Ribeiro; de Bruycker-Nogueira, Fernanda; dos Santos, Flavia Barreto

    2017-01-01

    Background: Chikungunya virus (CHIKV) is an arbovirus that causes an acute febrile syndrome with a severe and debilitating arthralgia. In Brazil, the Asian and East-Central South African (ECSA) genotypes are circulating in the north and northeast of the country, respectively. In 2015, the first autochthonous cases in Rio de Janeiro, Brazil were reported but until now the circulating strains have not been characterized. Therefore, we aimed here to perform the molecular characterization and phylogenetic analysis of CHIKV strains circulating in the 2016 outbreak occurred in the municipality of Rio de Janeiro. Methods: The cases analyzed in this study were collected at a private Hospital, from April 2016 to May 2016, during the chikungunya outbreak in Rio de Janeiro, Brazil. All cases were submitted to the Real Time RT-PCR for CHIKV genome detection and to anti-CHIKV IgM ELISA. Chikungunya infection was laboratorially confirmed by at least one diagnostic method and, randomly selected positive cases (n=10), were partially sequenced (CHIKV E1 gene) and analyzed. Results: The results showed that all the samples grouped in ECSA genotype branch and the molecular characterization of the fragment did not reveal the A226V mutation in the Rio de Janeiro strains analyzed, but a K211T amino acid substitution was observed for the first time in all samples and a V156A substitution in two of ten samples. Conclusions: Phylogenetic analysis and molecular characterization reveals the circulation of the ECSA genotype of CHIKV in the city of Rio de Janeiro, Brazil and two amino acids substitutions (K211T and V156A) exclusive to the CHIKV strains obtained during the 2016 epidemic, were reported. PMID:28286701

  11. Long-Lasting Immune Protection and Other Epidemiological Findings after Chikungunya Emergence in a Cambodian Rural Community, April 2012

    PubMed Central

    Duong, Veasna; Baisley, Kathy; Nguon, Kunthy; Chan, Siam; Huy, Rekol; Ly, Sovann; Sorn, Sopheak; Som, Leakhann; Buchy, Philippe; Tarantola, Arnaud

    2016-01-01

    The East/Central/South African genotype of Chikungunya virus with the E1-A226V mutation emerged in 2011 in Cambodia and spread in 2012. An outbreak of 190 cases was documented in Trapeang Roka, a rural village. We surveyed 425 village residents within 3–4 weeks after the outbreak, and determined the sensitivity and specificity of case definitions and factors associated with infection by CHIKV. Self-reported clinical presentation consisted mostly of fever, rash and arthralgia. The presence of all three clinical signs or symptoms was identified as the most sensitive (67%) and specific (84%) self-reported diagnostic clinical indicator compared to biological confirmation by MAC-ELISA or RT-PCR used as a reference. Having an indoor occupation was associated with lower odds of infection compared with people who remained at home (adjOR 0.32, 95%CI 0.12–0.82). In contrast with findings from outbreaks in other settings, persons aged above 40 years were less at risk of CHIKV infection, likely reflecting immune protection acquired when Chikungunya circulated in Cambodia before the Khmer Rouge regime in 1975. In view of the very particular history of Cambodia, our epidemiological data from Trapeang Roka are the first to support the persistence of CHIKV antibodies over a period of 40 years. PMID:26752630

  12. Engineering of a glycosidase Family 7 cellobiohydrolase to more alkaline pH optimum: the pH behaviour of Trichoderma reesei Cel7A and its E223S/ A224H/L225V/T226A/D262G mutant.

    PubMed Central

    Becker, D; Braet, C; Brumer , H; Claeyssens, M; Divne, C; Fagerström, B R; Harris, M; Jones, T A; Kleywegt, G J; Koivula, A; Mahdi, S; Piens, K; Sinnott, M L; Ståhlberg, J; Teeri, T T; Underwood, M; Wohlfahrt, G

    2001-01-01

    The crystal structures of Family 7 glycohydrolases suggest that a histidine residue near the acid/base catalyst could account for the higher pH optimum of the Humicola insolens endoglucanase Cel7B, than the corresponding Trichoderma reesei enzymes. Modelling studies indicated that introduction of histidine at the homologous position in T. reesei Cel7A (Ala(224)) required additional changes to accommodate the bulkier histidine side chain. X-ray crystallography of the catalytic domain of the E223S/A224H/L225V/T226A/D262G mutant reveals that major differences from the wild-type are confined to the mutations themselves. The introduced histidine residue is in plane with its counterpart in H. insolens Cel7B, but is 1.0 A (=0.1 nm) closer to the acid/base Glu(217) residue, with a 3.1 A contact between N(epsilon2) and O(epsilon1). The pH variation of k(cat)/K(m) for 3,4-dinitrophenyl lactoside hydrolysis was accurately bell-shaped for both wild-type and mutant, with pK(1) shifting from 2.22+/-0.03 in the wild-type to 3.19+/-0.03 in the mutant, and pK(2) shifting from 5.99+/-0.02 to 6.78+/-0.02. With this poor substrate, the ionizations probably represent those of the free enzyme. The relative k(cat) for 2-chloro-4-nitrophenyl lactoside showed similar behaviour. The shift in the mutant pH optimum was associated with lower k(cat)/K(m) values for both lactosides and cellobiosides, and a marginally lower stability. However, k(cat) values for cellobiosides are higher for the mutant. This we attribute to reduced non-productive binding in the +1 and +2 subsites; inhibition by cellobiose is certainly relieved in the mutant. The weaker binding of cellobiose is due to the loss of two water-mediated hydrogen bonds. PMID:11336632

  13. [Chikungunya fever - A new global threat].

    PubMed

    Montero, Antonio

    2015-08-07

    The recent onset of epidemics caused by viruses such as Ebola, Marburg, Nipah, Lassa, coronavirus, West-Nile encephalitis, Saint Louis encephalitis, human immunodeficiency virus, dengue, yellow fever and Venezuelan hemorrhagic fever alerts about the risk these agents represent for the global health. Chikungunya virus represents a new threat. Surged from remote African regions, this virus has become endemic in the Indic ocean basin, the Indian subcontinent and the southeast of Asia, causing serious epidemics in Africa, Indic Ocean Islands, Asia and Europe. Due to their epidemiological and biological features and the global presence of their vectors, chikungunya represents a serious menace and could become endemic in the Americas. Although chikungunya infection has a low mortality rate, its high attack ratio may collapse the health system during epidemics affecting a sensitive population. In this paper, we review the clinical and epidemiological features of chikungunya fever as well as the risk of its introduction into the Americas. We remark the importance of the epidemiological control and mosquitoes fighting in order to prevent this disease from being introduced into the Americas. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  14. Precise Determination of the Intensity of 226Ra Alpha Decay to the 186 keV Excited State

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

    S.P. LaMont; R.J. Gehrke; S.E. Glover

    There is a significant discrepancy in the reported values for the emission probability of the 186 keV gamma-ray resulting from the alpha decay of 226 Ra to 186 keV excited state of 222 Rn. Published values fall in the range of 3.28 to 3.59 gamma-rays per 100 alpha-decays. An interesting observation is that the lower value, 3.28, is based on measuring the 186 keV gamma-ray intensity relative to the 226 Ra alpha-branch to the 186 keV level. The higher values, which are close to 3.59, are based on measuring the gamma-ray intensity from mass standards of 226 Ra that aremore » traceable to the mass standards prepared by HÓNIGSCHMID in the early 1930''s. This discrepancy was resolved in this work by carefully measuring the 226 Ra alpha-branch intensities, then applying the theoretical E2 multipolarity internal conversion coefficient of 0.692±0.007 to calculate the 186 keV gamma-ray emission probability. The measured value for the alpha branch to the 186 keV excited state was (6.16±0.03)%, which gives a 186 keV gamma-ray emission probability of (3.64±0.04)%. This value is in excellent agreement with the most recently reported 186 keV gamma-ray emission probabilities determined using 226 Ra mass standards.« less

  15. Treatment of chikungunya musculoskeletal disorders: a systematic review.

    PubMed

    Guaraldo, Lusiele; Wakimoto, Mayumi Duarte; Ferreira, Heloisa; Bressan, Clarisse; Calvet, Guilherme Amaral; Pinheiro, Geraldo Castelar; Siqueira, Andre Machado; Brasil, Patrícia

    2018-04-01

    Chikungunya virus is amongst the fastest expanding vector transmissible diseases in recent years and has been causing massive epidemics in Africa, Asia, Latin America and the Caribbean. Despite human infection by this virus being first described in the 1950s, there is a lack of adequate therapeutic evaluations to guide evidence-based recommendations. The current guidelines rely heavily in specialists' opinion and experience instead of using higher rated evidence. Areas covered: A systematic review of the literature was performed- not restricted to clinical trials - reporting the therapeutic response against this infection with the intent to gather the best evidence of the treatment options against musculoskeletal disorders following chikungunya fever. The 15 studies included in the analysis were categorized considering the initiation of treatment during the acute, subacute and chronic phase. Expert commentary: This review demonstrates the complexity of chikungunya fever and difficulty of therapeutic management. This review found no current evidence-based treatment recommendations for the musculoskeletal disorders following chikungunya fever. To provide an optimal treatment that prevents perpetuation or progression of chikungunya infection to a potentially destructive and permanent condition without causing more harm is an aim that must be pursued by researchers and health professionals working with this disease.

  16. Epidemiology of Chikungunya in the Americas

    PubMed Central

    Yactayo, Sergio; Staples, J. Erin; Millot, Véronique; Cibrelus, Laurence; Ramon-Pardo, Pilar

    2016-01-01

    Chikungunya virus (CHIKV) emerged in the Americas in late 2013 to cause substantial acute and chronic morbidity. About 1.1 million cases of chikungunya were reported within a year, including severe cases and deaths. The burden of chikungunya is unclear owing to inadequate disease surveillance and underdiagnosis. Virus evolution, globalization, and climate change may further CHIKV spread. No approved vaccine or antiviral therapeutics exist. Early detection and appropriate management could reduce the burden of severe atypical and chronic arthritic disease. Improved surveillance and risk assessment are needed to mitigate the impact of chikungunya. PMID:27920170

  17. Pharmacokinetic properties of radiolabeled mutant Interleukin-2v: a PET imaging study.

    PubMed

    Hartimath, Siddesh V; Manuelli, Valeria; Zijlma, Rolf; Signore, Alberto; Nayak, Tapan K; Freimoser-Grundschober, Anne; Klein, Christian; Dierckx, Rudi A J O; de Vries, Erik F J

    2018-01-23

    Interleukin-2 (IL2) is a cytokine that can stimulate cytotoxic immune cells to attack infected and malignant cells. Unfortunately, IL2 can also cause serious immune-related toxicity. Recently, a mutant of IL2 (IL2v) with abolished CD25 binding, increased plasma half-life and less toxicity was engineered. Unlike wild-type IL2 (wt-IL2), mutant IL2v does not bind to the α-subunit (CD25) of the high affinity IL2αβγ receptor, but only to its β and γ subunit. Here, we investigated the biological properties of IL2v and compared with the wt-IL2 using fluorine-18 and PET. [ 18 F]FB-IL2v binds specifically to IL2 receptors (IL2R) on activated human peripheral blood monocytes (hPBMCs) and is cleared mainly by the kidneys (Balb/c mice). [ 18 F]FB-IL2v PET studies in SCID mice injected with hPBMCs revealed high uptake in the implant (0.85 ± 0.15 SUV), which was significantly reduced after pretreatment with wt-IL2 or mutant IL2v (SUV 0.26 ± 0.1 and 0.46 ± 0.1, p < 0.01). Compartment modeling and Logan graphical analysis in wistar rats inoculated with hPBMCs indicated that the binding of [ 18 F]FB-IL2v to IL2R was reversible. The volume of distribution (V T ) and the non-displaceable binding potential (BP nd ) of mutant [ 18 F]FB-IL2v in the implant were approximately 3 times lower than those of wild-type [ 18 F]FB-IL2 ( p < 0.01). Pretreatment with wt-IL2 significantly reduced the V T and BPnd of mutant [ 18 F]FB-IL2v in the implant ( p < 0.001). This demonstrates that wild-type [ 18 F]FB-IL2 binds stronger to IL2R and has faster kinetics than [18F]FB-IL2v, which makes it less suitable as a therapeutic drug. [ 18 F]FB-IL2v, on the other hand, seems to have better properties for use as a therapeutic drug.

  18. Epidemiology of Chikungunya in the Americas.

    PubMed

    Yactayo, Sergio; Staples, J Erin; Millot, Véronique; Cibrelus, Laurence; Ramon-Pardo, Pilar

    2016-12-15

    Chikungunya virus (CHIKV) emerged in the Americas in late 2013 to cause substantial acute and chronic morbidity. About 1.1 million cases of chikungunya were reported within a year, including severe cases and deaths. The burden of chikungunya is unclear owing to inadequate disease surveillance and underdiagnosis. Virus evolution, globalization, and climate change may further CHIKV spread. No approved vaccine or antiviral therapeutics exist. Early detection and appropriate management could reduce the burden of severe atypical and chronic arthritic disease. Improved surveillance and risk assessment are needed to mitigate the impact of chikungunya. © 2016 World Health Organization; licensee Oxford Journals.

  19. Pharmacokinetic properties of radiolabeled mutant Interleukin-2v: a PET imaging study

    PubMed Central

    Hartimath, Siddesh V.; Manuelli, Valeria; Zijlma, Rolf; Signore, Alberto; Nayak, Tapan K.; Freimoser-Grundschober, Anne; Klein, Christian; Dierckx, Rudi A.J.O.; de Vries, Erik F.J.

    2018-01-01

    Interleukin-2 (IL2) is a cytokine that can stimulate cytotoxic immune cells to attack infected and malignant cells. Unfortunately, IL2 can also cause serious immune-related toxicity. Recently, a mutant of IL2 (IL2v) with abolished CD25 binding, increased plasma half-life and less toxicity was engineered. Unlike wild-type IL2 (wt-IL2), mutant IL2v does not bind to the α-subunit (CD25) of the high affinity IL2αβγ receptor, but only to its β and γ subunit. Here, we investigated the biological properties of IL2v and compared with the wt-IL2 using fluorine-18 and PET. [18F]FB-IL2v binds specifically to IL2 receptors (IL2R) on activated human peripheral blood monocytes (hPBMCs) and is cleared mainly by the kidneys (Balb/c mice). [18F]FB-IL2v PET studies in SCID mice injected with hPBMCs revealed high uptake in the implant (0.85 ± 0.15 SUV), which was significantly reduced after pretreatment with wt-IL2 or mutant IL2v (SUV 0.26 ± 0.1 and 0.46 ± 0.1, p < 0.01). Compartment modeling and Logan graphical analysis in wistar rats inoculated with hPBMCs indicated that the binding of [18F]FB-IL2v to IL2R was reversible. The volume of distribution (VT) and the non-displaceable binding potential (BPnd) of mutant [18F]FB-IL2v in the implant were approximately 3 times lower than those of wild-type [18F]FB-IL2 (p < 0.01). Pretreatment with wt-IL2 significantly reduced the VT and BPnd of mutant [18F]FB-IL2v in the implant (p < 0.001). This demonstrates that wild-type [18F]FB-IL2 binds stronger to IL2R and has faster kinetics than [18F]FB-IL2v, which makes it less suitable as a therapeutic drug. [18F]FB-IL2v, on the other hand, seems to have better properties for use as a therapeutic drug. PMID:29467958

  20. Clinical Spectrum of Chikungunya in Pakistan.

    PubMed

    Naqvi, Syeda; Bashir, Shehroz; Rupareliya, Chintan; Shams, Abdullah; Giyanwani, Pirthvi Raj; Ali, Zeeshan; Qamar, Faiza; Kumar, Vijesh; Talib, Vikash

    2017-07-06

    Background Chikungunya fever is a pandemic disease caused by an arthropod-borne chikungunya virus (CHIKV). The virus spreads through mosquitoes. This mosquito induced viral illness is clinically suspected on symptoms from fever and severe polyarthralgia. The recent outbreak of chikungunya was reported in November 2016 in the metropolitan city Karachi, Pakistan. We emphasis on the awareness of the etiology and vector control to prevent serious consequences. Method A total number of 1275 patients were included in this cross-sectional study. These patients were enrolled based on clinical findings described by Centers for Disease Control and Prevention (CDC). Our exclusion criteria were patients with missing data or having co-infection with dengue or malaria. The patients were tested for chikungunya antibodies, malaria, and dengue. The patients were followed for three months. Results Out of 1275 consenting patients from the emergency department, 564 tested positive for chikungunya antibodies and out of these 564 patients 365 had co-infection of dengue and malaria. So based on exclusion criteria, 199 patients had isolated chikungunya infection and were studied for the frequency of clinical symptoms. The most common finding was joint pain and fever on presentation and joint pain was the only chronic finding which persisted. Conclusion Our study demonstrated the frequency of clinical findings in chikungunya infection. It also signifies the importance of testing for antibodies because it helped in excluding patients with false positive clinical findings and differentiating co-infection with malaria and dengue. It also gauged patient's view about the cause of this disease.

  1. Clinical Spectrum of Chikungunya in Pakistan

    PubMed Central

    Bashir, Shehroz; Rupareliya, Chintan; Shams, Abdullah; Giyanwani, Pirthvi Raj; Ali, Zeeshan; Qamar, Faiza; Kumar, Vijesh; Talib, Vikash

    2017-01-01

    Background Chikungunya fever is a pandemic disease caused by an arthropod-borne chikungunya virus (CHIKV). The virus spreads through mosquitoes. This mosquito induced viral illness is clinically suspected on symptoms from fever and severe polyarthralgia. The recent outbreak of chikungunya was reported in November 2016 in the metropolitan city Karachi, Pakistan. We emphasis on the awareness of the etiology and vector control to prevent serious consequences. Method A total number of 1275 patients were included in this cross-sectional study. These patients were enrolled based on clinical findings described by Centers for Disease Control and Prevention (CDC). Our exclusion criteria were patients with missing data or having co-infection with dengue or malaria. The patients were tested for chikungunya antibodies, malaria, and dengue. The patients were followed for three months. Results Out of 1275 consenting patients from the emergency department, 564 tested positive for chikungunya antibodies and out of these 564 patients 365 had co-infection of dengue and malaria. So based on exclusion criteria, 199 patients had isolated chikungunya infection and were studied for the frequency of clinical symptoms. The most common finding was joint pain and fever on presentation and joint pain was the only chronic finding which persisted. Conclusion Our study demonstrated the frequency of clinical findings in chikungunya infection. It also signifies the importance of testing for antibodies because it helped in excluding patients with false positive clinical findings and differentiating co-infection with malaria and dengue. It also gauged patient's view about the cause of this disease.  PMID:28924518

  2. Chikungunya virus

    MedlinePlus

    ... months or longer. The disease can lead to death in frail older adults. Treatment There is no ... and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Chikungunya Browse the Encyclopedia A. ...

  3. Surveillance for Chikungunya and Dengue During the First Year of Chikungunya Virus Circulation in Puerto Rico

    PubMed Central

    Sharp, Tyler M.; Ryff, Kyle R.; Alvarado, Luisa; Shieh, Wun-Ju; Zaki, Sherif R.; Margolis, Harold S.; Rivera-Garcia, Brenda

    2016-01-01

    After chikungunya virus (CHIKV) transmission was detected in Puerto Rico in May 2014, multiple surveillance systems were used to describe epidemiologic trends and CHIKV-associated disease. Of 28 327 cases reported via passive surveillance, 6472 were tested for evidence of CHIKV infection, and results for 4399 (68%) were positive. Of 250 participants in household cluster investigations, 70 (28%) had evidence of recent CHIKV infection. Enhanced surveillance for chikungunya at 2 hospitals identified 1566 patients who tested positive for CHIKV, of whom 10.9% were hospitalized. Enhanced surveillance for fatal cases enabled identification of 31 cases in which CHIKV was detected in blood or tissue specimens. All surveillance systems detected a peak incidence of chikungunya in September 2014 and continued circulation in 2015. Concomitant surveillance for dengue demonstrated low incidence, which had decreased before CHIKV was introduced. Multifaceted chikungunya surveillance in Puerto Rico resolved gaps in traditional passive surveillance and enabled a holistic description of the spectrum of disease associated with CHIKV infection. PMID:27920177

  4. Chikungunya

    MedlinePlus

    ... way to prevent chikungunya infection is to avoid mosquito bites: Use insect repellent Wear clothes that cover your arms, legs, and feet Stay in places that have air conditioning or that use window and door screens Centers for Disease Control and Prevention

  5. A complex adenovirus vaccine against chikungunya virus provides complete protection against viraemia and arthritis

    PubMed Central

    Wang, Danher; Suhrbier, Andreas; Penn-Nicholson, Adam; Woraratanadharm, Jan; Gardner, Joy; Luo, Min; Le, Thuy T.; Anraku, Itaru; Sakalian, Michael; Einfeld, David; Dong, John Y.

    2011-01-01

    Chikungunya virus, a mosquito-borne alphavirus, recently caused the largest epidemic ever seen for this virus. Chikungunya disease primarily manifests as a painful and debilitating arthralgia/arthritis, and no effective drug or vaccine is currently available. Here we describe a recombinant chikungunya virus vaccine comprising a non-replicating complex adenovirus vector encoding the structural polyprotein cassette of chikungunya virus. A single immunisation with this vaccine consistently induced high titres of anti-chikungunya virus antibodies that neutralised both an old Asian isolate and a Réunion Island isolate from the recent epidemic. The vaccine also completely protected mice against viraemia and arthritic disease caused by both virus isolates. PMID:21320541

  6. Historical inability to control Aedes aegypti as a main contributor of fast dispersal of chikungunya outbreaks in Latin America.

    PubMed

    Fernández-Salas, Ildefonso; Danis-Lozano, Rogelio; Casas-Martínez, Mauricio; Ulloa, Armando; Bond, J Guillermo; Marina, Carlos F; Lopez-Ordóñez, Teresa; Elizondo-Quiroga, Armando; Torres-Monzón, Jorge A; Díaz-González, Esteban E

    2015-12-01

    The arrival of chikungunya fever (CHIKF) in Latin American countries has been expected to trigger epidemics and challenge health systems. Historically considered as dengue-endemic countries, abundant Aedes aegypti populations make this region highly vulnerable to chikungunya virus (CHIKV) circulation. This review describes the current dengue and CHIKF epidemiological situations, as well as the role of uncontrolled Ae. aegypti and Aedes albopictus vectors in spreading the emerging CHIKV. Comments are included relating to the vector competence of both species and failures of surveillance and vector control measures. Dengue endemicity is a reflection of these abundant and persistent Aedes populations that are now spreading CHIKV in the Americas. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World." Copyright © 2015 Elsevier B.V. All rights reserved.

  7. A Mathematical Model Of Dengue-Chikungunya Co-Infection In A Closed Population

    NASA Astrophysics Data System (ADS)

    Aldila, Dipo; Ria Agustin, Maya

    2018-03-01

    Dengue disease has been a major health problem in many tropical and sub-tropical countries since the early 1900s. On the other hand, according to a 2017 WHO fact sheet, Chikungunya was detected in the first outbreak in 1952 in Tanzania and has continued increasing until now in many tropical and sub-tropical countries. Both these diseases are vector-borne diseases which are spread by the same mosquito, i.e. the female Aedes aegypti. According to the WHO report, there is a great possibility that humans and mosquitos might be infected by dengue and chikungunya at the same time. Here in this article, a mathematical model approach will be used to understand the spread of dengue and chikungunya in a closed population. A model is developed as a nine-dimensional deterministic ordinary differential equation. Equilibrium points and their local stability are analyzed analytically and numerically. We find that the basic reproduction number, the endemic indicator, is given by the maximum of three different basic reproduction numbers of a complete system, i.e. basic reproduction numbers for dengue, chikungunya and for co-infection between dengue and chikungunya. We find that the basic reproduction number for the co-infection sub-system dominates other basic reproduction numbers whenever it is larger than one. Some numerical simulations are provided to confirm these analytical results.

  8. Reemergence of Endemic Chikungunya, Malaysia

    PubMed Central

    Sam, I-Ching; Wong, Pooi-Fong; Hooi, Poh-Sim; Roslan, Nuruliza

    2007-01-01

    Chikungunya virus infection recently reemerged in Malaysia after 7 years of nondetection. Genomic sequences of recovered isolates were highly similar to those of Malaysian isolates from the 1998 outbreak. The reemergence of the infection is not part of the epidemics in other Indian Ocean countries but raises the possibility that chikungunya virus is endemic in Malaysia. PMID:17370532

  9. Chikungunya Virus: What You Need to Know

    MedlinePlus

    ... Aedes species mosquito bites. Aedes mosquitoes also spread dengue and Zika viruses. ŠŠ A risk to anyone traveling ... to look for chikungunya or similar diseases, like dengue or Zika. Chikungunya is preventable, but not treatable Š Š ...

  10. Chikungunya Virus

    MedlinePlus

    ... Information For Health Care Providers Fact Sheets and Posters Chikungunya Nowcast for the Americas Get Email Updates ... Providers Nowcast for the Americas Fact Sheets and Posters Resources Vector Surveillance and Control File Formats Help: ...

  11. Two Chikungunya isolates from the outbreak of La Reunion (Indian Ocean) exhibit different patterns of infection in the mosquito, Aedes albopictus.

    PubMed

    Vazeille, Marie; Moutailler, Sara; Coudrier, Daniel; Rousseaux, Claudine; Khun, Huot; Huerre, Michel; Thiria, Julien; Dehecq, Jean-Sébastien; Fontenille, Didier; Schuffenecker, Isabelle; Despres, Philippe; Failloux, Anna-Bella

    2007-11-14

    A Chikungunya (CHIK) outbreak hit La Réunion Island in 2005-2006. The implicated vector was Aedes albopictus. Here, we present the first study on the susceptibility of Ae. albopictus populations to sympatric CHIKV isolates from La Réunion Island and compare it to other virus/vector combinations. We orally infected 8 Ae. albopictus collections from La Réunion and 3 from Mayotte collected in March 2006 with two Chikungunya virus (CHIKV) from La Réunion: (i) strain 05.115 collected in June 2005 with an Alanine at the position 226 of the glycoprotein E1 and (ii) strain 06.21 collected in November 2005 with a substitution A226V. Two other CHIKV isolates and four additional mosquito strains/species were also tested. The viral titer of the infectious blood-meal was 10(7) plaque forming units (pfu)/mL. Dissemination rates were assessed by immunofluorescent staining on head squashes of surviving females 14 days after infection. Rates were at least two times higher with CHIKV 06.21 compared to CHIKV 05.115. In addition, 10 individuals were analyzed every day by quantitative RT-PCR. Viral RNA was quantified on (i) whole females and (ii) midguts and salivary glands of infected females. When comparing profiles, CHIKV 06.21 produced nearly 2 log more viral RNA copies than CHIKV 05.115. Furthermore, females infected with CHIKV 05.115 could be divided in two categories: weakly susceptible or strongly susceptible, comparable to those infected by CHIKV 06.21. Histological analysis detected the presence of CHIKV in salivary glands two days after infection. In addition, Ae. albopictus from La Réunion was as efficient vector as Ae. aegypti and Ae. albopictus from Vietnam when infected with the CHIKV 06.21. Our findings support the hypothesis that the CHIK outbreak in La Réunion Island was due to a highly competent vector Ae. albopictus which allowed an efficient replication and dissemination of CHIKV 06.21.

  12. Two Chikungunya Isolates from the Outbreak of La Reunion (Indian Ocean) Exhibit Different Patterns of Infection in the Mosquito, Aedes albopictus

    PubMed Central

    Vazeille, Marie; Moutailler, Sara; Coudrier, Daniel; Rousseaux, Claudine; Khun, Huot; Huerre, Michel; Thiria, Julien; Dehecq, Jean-Sébastien; Fontenille, Didier; Schuffenecker, Isabelle; Despres, Philippe; Failloux, Anna-Bella

    2007-01-01

    Background A Chikungunya (CHIK) outbreak hit La Réunion Island in 2005–2006. The implicated vector was Aedes albopictus. Here, we present the first study on the susceptibility of Ae. albopictus populations to sympatric CHIKV isolates from La Réunion Island and compare it to other virus/vector combinations. Methodology and Findings We orally infected 8 Ae. albopictus collections from La Réunion and 3 from Mayotte collected in March 2006 with two Chikungunya virus (CHIKV) from La Réunion: (i) strain 05.115 collected in June 2005 with an Alanine at the position 226 of the glycoprotein E1 and (ii) strain 06.21 collected in November 2005 with a substitution A226V. Two other CHIKV isolates and four additional mosquito strains/species were also tested. The viral titer of the infectious blood-meal was 107 plaque forming units (pfu)/mL. Dissemination rates were assessed by immunofluorescent staining on head squashes of surviving females 14 days after infection. Rates were at least two times higher with CHIKV 06.21 compared to CHIKV 05.115. In addition, 10 individuals were analyzed every day by quantitative RT-PCR. Viral RNA was quantified on (i) whole females and (ii) midguts and salivary glands of infected females. When comparing profiles, CHIKV 06.21 produced nearly 2 log more viral RNA copies than CHIKV 05.115. Furthermore, females infected with CHIKV 05.115 could be divided in two categories: weakly susceptible or strongly susceptible, comparable to those infected by CHIKV 06.21. Histological analysis detected the presence of CHIKV in salivary glands two days after infection. In addition, Ae. albopictus from La Réunion was as efficient vector as Ae. aegypti and Ae. albopictus from Vietnam when infected with the CHIKV 06.21. Conclusions Our findings support the hypothesis that the CHIK outbreak in La Réunion Island was due to a highly competent vector Ae. albopictus which allowed an efficient replication and dissemination of CHIKV 06.21. PMID:18000540

  13. Surveillance for Chikungunya and Dengue During the First Year of Chikungunya Virus Circulation in Puerto Rico.

    PubMed

    Sharp, Tyler M; Ryff, Kyle R; Alvarado, Luisa; Shieh, Wun-Ju; Zaki, Sherif R; Margolis, Harold S; Rivera-Garcia, Brenda

    2016-12-15

    After chikungunya virus (CHIKV) transmission was detected in Puerto Rico in May 2014, multiple surveillance systems were used to describe epidemiologic trends and CHIKV-associated disease. Of 28 327 cases reported via passive surveillance, 6472 were tested for evidence of CHIKV infection, and results for 4399 (68%) were positive. Of 250 participants in household cluster investigations, 70 (28%) had evidence of recent CHIKV infection. Enhanced surveillance for chikungunya at 2 hospitals identified 1566 patients who tested positive for CHIKV, of whom 10.9% were hospitalized. Enhanced surveillance for fatal cases enabled identification of 31 cases in which CHIKV was detected in blood or tissue specimens. All surveillance systems detected a peak incidence of chikungunya in September 2014 and continued circulation in 2015. Concomitant surveillance for dengue demonstrated low incidence, which had decreased before CHIKV was introduced. Multifaceted chikungunya surveillance in Puerto Rico resolved gaps in traditional passive surveillance and enabled a holistic description of the spectrum of disease associated with CHIKV infection. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. An app for climate-based Chikungunya risk monitoring and mapping

    NASA Astrophysics Data System (ADS)

    Soebiyanto, R. P.; Rama, X.; Jepsen, R.; Bijoria, S.; Linthicum, K. J.; Anyamba, A.

    2017-12-01

    There is an increasing concern for reemergence and spread of chikungunya in the last 10 years in Africa, the Indian Ocean, and Asia, and range expansion that now reaches the Caribbean, South America and threatens North America. The outbreak of Chikungunya in 2013 and its spread throughout the Americas has so far resulted in more than 1.7 million suspected cases. This has demonstrated the importance of readiness in assessing potential risk of the emergence of vector-borne diseases. Climate and ecological conditions are now recognized as major contributors to the emergence and re-emergence of various vector-borne diseases including Chikungunya. Variations and persistence of extreme climate conditions provide suitable environment for the increase of certain disease vector populations, which then further amplify vector-borne disease transmission. This highlights the importance of climate anomaly information in assessing regions at risk for Chikungunya. In order to address such issue, we are developing a climate-based app, CHIKRISK, which will help decision makers to answer three critical questions: (i) Where has Chikungunya activity occurred; (ii) Where it is occurring now; (iii) Which regions are currently at risk for Chikungunya. We first develop a database of historical Chikungunya outbreak locations compiled from publicly available information. These records are used to map where Chikungunya activity has occurred over time. We leverage on various satellite-based climate data records - such as rainfall, land surface and near surface temperature to characterize evolving conditions prior to and during Chikungunya activity. Chikungunya outbreak data, climate and ancillary (i.e. population and elevation) data are used to develop analytics capability that will produce risk maps. The CHIKRISK app has the capability to visualize historical Chikungunya activity locations, climate anomaly conditions and Chikungunya risk maps. Currently, the focus of the development is on the

  15. [The chikungunya epidemic in the Caribbean: implications for travellers and physicians].

    PubMed

    Cleton, Natalie B; Reusken, Chantal B E M; van Gorp, Eric C M

    2014-01-01

    In 2013, the first autochthonous cases of the chikungunya virus (CHIKV) were reported on the Caribbean island of Saint Martin. The chikungunya virus has since become endemic in the Caribbean due to autochthonous transmission. In the presence of fever and joint symptoms in any traveller returning from the Caribbean, CHIKV should be considered. Although symptoms resemble those of dengue fever, the course of chikungunya is milder. Chikungunya much more commonly causes chronic joint pain. Laboratory tests for the chikungunya virus may give false positive results due to cross reactions with closely related viruses, so taking a full disease and travel history from the patient is necessary in order to interpret these test results correctly. There is no specific treatment for the chikungunya virus. A correct diagnosis can prevent unnecessary additional tests and unjustified treatment. The chikungunya virus can be prevented by the use of insect-repelling substances, nets and air-conditioning.

  16. Case Series: Chikungunya and Dengue at a Forward Operating Location

    DTIC Science & Technology

    2015-05-01

    Journal Article 3. DATES COVERED (From – To) November 2014 – January 2015 4. TITLE AND SUBTITLE Case Series: Chikungunya and Dengue at a Forward...series and discusses the significance of this disease in the Americas and diagnostic challenges when other arboviruses such as dengue are present. 15...SUBJECT TERMS Chikungunya, dengue , mosquitoes 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT SAR 18. NUMBER OF PAGES 3

  17. Preventing dengue and chikungunya fever among international travelers.

    PubMed

    Tither, Pauline Herold

    2014-11-01

    To describe the vulnerability of U.S. travelers in tropical and subtropical regions of the world to dengue and chikungunya fever, to provide practical recommendations to avoid these mosquito-borne diseases, and to offer a communication tool as an aid for pretravel health consultations. Medical, epidemiological, and entomological research articles and reviews, and reports from government agencies. Dengue and chikungunya fever have growing public health impact around the world. International travelers return to the United States infected with these diseases. Mosquito bite avoidance is the only way to prevent dengue and chikungunya fever. Informed travelers have many options for simple and practical measures to lessen the risk of mosquito bites. A message map can be used as a communication tool for pretravel counseling on the prevention of dengue and chikungunya fever within the time frame of an office visit. In a pretravel health consultation, a nurse practitioner can promote travelers' health and prevent dengue, chikungunya fever, and other mosquito-borne diseases by counseling on the risk of these diseases and giving practical recommendations for prevention using a message map. ©2014 American Association of Nurse Practitioners.

  18. BRAF Inhibitors for BRAF V600E Mutant Colorectal Cancers: Literature Survey and Case Report

    PubMed Central

    Can, Mehmet Fatih; Ozerhan, Ismail Hakki; Yagci, Gokhan; Zeybek, Nazif; Kavakli, Kutan; Gurkok, Sedat; Gozubuyuk, Alper; Genc, Onur; Erdem, Gokhan; Ozet, Ahmet; Gerek, Mustafa; Peker, Yusuf

    2018-01-01

    The main method of fighting against colon cancer is targeted treatment. BRAF inhibitors, which are accepted as standard treatment for V600E mutant malign melanomas, are the newest approach for targeted treatment of V600E mutant colorectal cancers. In this case report, we share our experience about the use of BRAF inhibitor vemurafenib on a V600E mutant metastatic right colon adenocarcinoma patient. A 59-year-old male with only lung multiple metastatic V600E mutant right colon cancer presented to our clinic. The patient was evaluated and FOLFOX + bevacizumab treatment was initiated, which was then continued with vemurafenib. A remarkable response was achieved with vemurafenib treatment in which the drug resistance occurred approximately in the sixth month. Even though the patient benefited majorly from vemurafenib, he died on the 20th month of the diagnosis. The expected overall survival for metastatic V600E mutant colon adenocarcinoma patients is 4.7 months. BRAF inhibitors provide new treatment alternatives for V600E mutant colorectal cancers, with prolonged overall survival. BRAF inhibitors in combination with MEK inhibitors are reported as feasible treatment to overcome BRAF inhibitor drug resistance on which phase studies are still in progress. To conclude, BRAF inhibitors alone or in combination with other drugs provide a chance for curing BRAF V600E mutant colorectal cancer patients. PMID:29850361

  19. Mapping recent chikungunya activity in the Americas

    USDA-ARS?s Scientific Manuscript database

    To better understand chikungunya activity in the America we mapped recent chikungunya activity in the Americas. This activity is needed to better understand that the relationships between climatic factors and disease outbreak patters are critical to the design and constructing of predictive models....

  20. Dengue and Chikungunya Vector Control Pocket Guide

    USDA-ARS?s Scientific Manuscript database

    This technical guide consolidates information and procedures for surveillance and control of mosquitoes that transmit dengue and chikungunya viruses. The guide focuses on mosquitoes that transmit dengue but also makes reference to chikungunya and yellow fever because the pathogens that cause these ...

  1. Chikungunya infection presenting as mild encephalitis with a reversible lesion in the splenium: a case report.

    PubMed

    Nagpal, Kadam; Agarwal, Puneet; Kumar, Amit; Reddi, Rajashekhar

    2017-06-01

    Chikungunya fever is an Aedes mosquito-transmitted infection caused by chikungunya virus, an RNA virus in the family Togaviridae. The disease is characteristically manifested as fever, arthralgia, and/or rash. Various neurological manifestations like meningoencephalitis, myelitis, and myeloneuropathy have been mentioned in various reports. We present a rare case of chikungunya fever presenting with mild encephalitis with a reversible lesion of the splenium (MERS), which showed complete clinical and radiological recovery.

  2. Chikungunya, climate change, and human rights.

    PubMed

    Meason, Braden; Paterson, Ryan

    2014-06-14

    Chikungunya is a re-emerging arbovirus that causes significant morbidity and some mortality. Global climate change leading to warmer temperatures and changes in rainfall patterns allow mosquito vectors to thrive at altitudes and at locations where they previously have not, ultimately leading to a spread of mosquito-borne diseases. While mutations to the chikungunya virus are responsible for some portion of the re-emergence, chikungunya epidemiology is closely tied with weather patterns in Southeast Asia. Extrapolation of this regional pattern, combined with known climate factors impacting the spread of malaria and dengue, summate to a dark picture of climate change and the spread of this disease from south Asia and Africa into Europe and North America. This review describes chikungunya and collates current data regarding its spread in which climate change plays an important part. We also examine human rights obligations of States and others to protect against this disease. Copyright © 2014 Meason, Paterson. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

  3. Chikungunya: Its History in Africa and Asia and Its Spread to New Regions in 2013-2014.

    PubMed

    Zeller, Herve; Van Bortel, Wim; Sudre, Bertrand

    2016-12-15

    Chikungunya virus (CHIKV) is transmitted by Aedes aegypti and Aedes albopictus mosquitoes and causes febrile illness with severe arthralgia in humans. There are 3 circulating CHIKV genotypes, Asia, East/Central/South Africa, and West Africa. CHIKV was first reported in 1953 in Tanzania, and up until the early 2000s, a few outbreaks and sporadic cases of CHIKV were mainly reported in Africa and Asia. However, from 2004 to 2005, a large epidemic spanned from Kenya over to the southwestern Indian Ocean region, India, and Southeast Asia. Identified in 2005, the E1 glycoprotein A226V mutation of the East/Central/South Africa genotype conferred enhanced transmission by the A. albopictus mosquito and has been implicated in CHIKV's further spread in the last decade. In 2013, the Asian CHIKV genotype emerged in the Caribbean and quickly took the Americas by storm. This review will discuss the history of CHIKV as well as its expanding geographic distribution. © 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. Cloning, preparation and preliminary crystallographic studies of penicillin V acylase autoproteolytic processing mutants

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

    Chandra, P. Manish; Brannigan, James A., E-mail: jab@ysbl.york.ac.uk; Prabhune, Asmita

    The production, crystallization and characterization of three inactive mutants of penicillin V acylase from B. sphaericus in their respective precursor and processed forms are reported. The space groups are different for the native enzyme and the mutants. The crystallization of three catalytically inactive mutants of penicillin V acylase (PVA) from Bacillus sphaericus in precursor and processed forms is reported. The mutant proteins crystallize in different primitive monoclinic space groups that are distinct from the crystal forms for the native enzyme. Directed mutants and clone constructs were designed to study the post-translational autoproteolytic processing of PVA. The catalytically inactive mutants willmore » provide three-dimensional structures of precursor PVA forms, plus open a route to the study of enzyme–substrate complexes for this industrially important enzyme.« less

  5. Inflammation of the external ear in acute chikungunya infection: Experience from the outbreak in Johor Bahru, Malaysia, 2008.

    PubMed

    Javelle, Emilie; Tiong, Tee Hua; Leparc-Goffart, Isabelle; Savini, Hélène; Simon, Fabrice

    2014-04-01

    The re-emerging invalidating chikungunya disease has recently extended to temperate areas. Other alphaviruses can also present with febrile arthalgias. Dengue virus transmitted by the same species of mosquitoes may cocirculate, leading to dual infections and concurrent epidemics. Although these diseases share similar clinical features, their prognoses considerably differ. Prominent and prolonged articular disorders are more consistent with chikungunya virus, whereas haemorrhages make the gravity of dengue infection. Specific symptoms are required, especially when diagnostic tests are not available or performable at a large scale. Indeed, early clinical suspicion of a vector-borne disease is crucial to isolate the first cases in the course of an outbreak, and discrimination between arboviruses help to optimal management of patients. No specific chikungunya clinical sign has been yet reported. We highlight here the high prevalence (about 25%) of acute ear redness in infected people during the 2008 chikungunya outbreak in Jahor Bahru in Malaysia. Nine consenting patients are more precisely described. Ear chondritis could be sensitive diagnostic criterion of the acute stage of chikungunya, every physician - even in occidental non endemic areas - should be aware of. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Seroprevalence of Chikungunya Virus in a Rural Community in Brazil.

    PubMed

    Cunha, Rivaldo V; Trinta, Karen S; Montalbano, Camila A; Sucupira, Michel V F; de Lima, Maricelia M; Marques, Erenilde; Romanholi, Izilyanne H; Croda, Julio

    2017-01-01

    The emergence of the Chikungunya virus (CHIKV) is currently expanding. In 2015, 38,332 cases of Chikungunya were reported to the Brazilian epidemiological surveillance system. Eighteen months after notification of the first case in the city of Feira de Santana, we conducted the first serosurvey to define the magnitude of transmission in a rural community in Brazil. The serosurvey was conducted in a random sample of 450 residences in the Chapada district, located 100 kilometers from Feira de Santana. We administered questionnaires and tested 120 sera from Chapada district residents for CHIKV IgM- and IgG-specific antibodies. An individual with CHIKV infection was defined as any person with CHIKV IgM or IgG antibodies detected in the serum. One Hundred cases of Chikungunya were reported after prolonged rainfall, which reinforced the relationship between the rainfall index and CHIKV transmission. Eighteen months after the start of the outbreak, we identified a seroprevalence of 20% (95% CI, 15.4-35%). CHIKV IgG- and IgM-specific antibodies were detected in 22/120 (18.3%) and 6/120 (5.0%) individuals, respectively. Among seropositive patients, 13/24 (54.2%) reported fever and joint pain over the previous two years (p<0.01). The rate of symptomatic CHIKV infection was 40.7%. We identified a moderate seroprevalence of Chikungunya in the Chapada district, and in half of the confirmed CHIKV infections, patients reported arthralgia and fever over the previous two years.

  7. Altered agonist sensitivity of a mutant v2 receptor suggests a novel therapeutic strategy for nephrogenic diabetes insipidus.

    PubMed

    Erdélyi, László Sándor; Balla, András; Patócs, Attila; Tóth, Miklós; Várnai, Péter; Hunyady, László

    2014-05-01

    Loss-of-function mutations of the type 2 vasopressin receptor (V2R) in kidney can lead to nephrogenic diabetes insipidus (NDI). We studied a previously described, but uncharacterized, mutation of the V2R (N321K missense mutation) of a patient with NDI. The properties of the mutant receptor were evaluated. We constructed a highly sensitive Epac-based bioluminescence resonance energy transfer biosensor to perform real-time cAMP measurements after agonist stimulation of transiently transfected HEK293 cells with V2Rs. β-Arrestin binding of the activated receptors was examined with luciferase-tagged β-arrestin and mVenus-tagged V2Rs using the bioluminescence resonance energy transfer technique. Cell surface expression levels of hemagglutinin-tagged receptors were determined with flow cytometry using anti-hemagglutinin-Alexa 488 antibodies. Cellular localization examinations were implemented with fluorescent tagged receptors visualized with confocal laser scanning microscopy. The effect of various vasopressin analogs on the type 1 vasopressin receptor (V1R) was tested on mouse arteries by wire myography. The N321K mutant V2R showed normal cell surface expression, but the potency of arginine vasopressin for cAMP generation was low, whereas the clinically used desmopressin was not efficient. The β-arrestin binding and internalization properties of the mutant receptor were also different than those for the wild type. The function of the mutant receptor can be rescued with administration of the V2R agonist Val(4)-desmopressin, which had no detectable side effects on V1R in the effective cAMP generating concentrations. Based on these findings we propose a therapeutic strategy for patients with NDI carrying the N321K mutation, as our in vivo experiments suggest that Val(4)-desmopressin could rescue the function of the N321K-V2R without significant side effects on the V1R.

  8. Detection of chikungunya virus in saliva and urine.

    PubMed

    Musso, Didier; Teissier, Anita; Rouault, Eline; Teururai, Sylviane; de Pina, Jean-Jacques; Nhan, Tu-Xuan

    2016-06-16

    Saliva and urine have been used for arthropod-borne viruses molecular detection but not yet for chikungunya virus (CHIKV). We investigated the use of saliva and urine for molecular detection of CHIKV during the French Polynesian outbreak. During the French Polynesian chikungunya outbreak (2014-2015), we collected the same day blood and saliva samples from 60 patients with probable chikungunya (47 during the 1st week post symptoms onset and 13 after), urine was available for 39 of them. All samples were tested using a CHIKV reverse-transcription PCR. Forty eight patients had confirmed chikungunya. For confirmed chikungunya presenting during the 1st week post symptoms onset, CHIKV RNA was detected from 86.1 % (31/36) of blood, 58.3 % (21/36) of saliva and 8.3 % (2/24) of urine. Detection rate of CHIKV RNA was significantly higher in blood compared to saliva. For confirmed chikungunya presenting after the 1st week post symptoms onset, CHIKV RNA was detected from 8.3 % (1/12) of blood, 8.3 % (1/12) of saliva and 0 % (0/8) of urine. In contrast to Zika virus (ZIKV), saliva did not increased the detection rate of CHIKV RNA during the 1st week post symptoms onset. In contrast to ZIKV, dengue virus and West Nile virus, urine did not enlarged the window of detection of CHIKV RNA after the 1st week post symptoms onset. Saliva can be used for molecular detection of CHIKV during the 1st week post symptoms onset only if blood is impossible to collect but with a lower sensitivity compared to blood.

  9. Chikungunya Arthritis Mechanisms in the Americas (CAMA): A cross sectional analysis of chikungunya arthritis patients 22 months post-infection demonstrates a lack of viral persistence in synovial fluid

    DTIC Science & Technology

    2017-06-30

    Chikungunya Arthritis Mechanisms in the Americas (CAMA): 1 A cross-sectional analysis of chikungunya arthritis patients 22-months post -infection...school or less level of education (94%). CHIKV arthritis 58 patients (Median 22-months (IQR 21-23) post -CHIKV infection) had moderate disease...rheumatoid arthritis are being tested in this patient population. However, such therapeutics could be 76 dangerous if active virus is still present

  10. A nonhuman primate model of chikungunya disease

    PubMed Central

    Higgs, Stephen; Ziegler, Sarah A.

    2010-01-01

    Chikungunya disease is a severely debilitating, mosquito-borne, viral illness that has reached epidemic proportions in Africa, Asia, and the islands of the Indian Ocean. A mutation enhancing the ability of the chikungunya virus (CHIKV) to infect and be transmitted by Aedes albopictus has increased the geographical range at risk for infection due to the continuing global spread of this mosquito. Research into disease pathogenesis, vaccine development, and therapeutic design has been hindered by the lack of appropriate animal models of this disease. The meticulous study reported in this issue of the JCI by Labadie et al. is one of the first reports describing CHIKV infection of adult immunocompetent nonhuman primates. Using traditional and modern molecular and immunological approaches, the authors demonstrate that macaques infected with CHIKV are a good model of human CHIKV infection and also show that persistent arthralgia in humans may be caused by persistent CHIKV infection of macrophages. PMID:20179348

  11. The neurological complications of chikungunya virus: A systematic review

    PubMed Central

    Gerardin, Patrick; de Brito, Carlos Alexandre Antunes; Soares, Cristiane Nascimento; Ferreira, Maria Lucia Brito

    2018-01-01

    Summary We performed a systematic review on the neurological complications of chikungunya virus. Such complications are being reported increasingly, owing primarily to the scale of recent epidemics but also to a growing understanding of the virus' neurovirulence. We performed a thorough literature search using PubMed and Scopus databases, summating the data on all published reports of neurological disease associated with chikungunya virus. We appraised the data for each major condition in adults, children, and neonates, as well as evaluating the latest evidence on disease pathogenesis and management strategies. The review provides a comprehensive summary for clinicians, public health officials, and researchers tackling the challenges associated with this important emerging pathogen. PMID:29671914

  12. Seroprevalence of Chikungunya Virus in a Rural Community in Brazil

    PubMed Central

    Cunha, Rivaldo V.; Trinta, Karen S.; Montalbano, Camila A.; Sucupira, Michel V. F.; de Lima, Maricelia M.; Marques, Erenilde; Romanholi, Izilyanne H.

    2017-01-01

    Background The emergence of the Chikungunya virus (CHIKV) is currently expanding. In 2015, 38,332 cases of Chikungunya were reported to the Brazilian epidemiological surveillance system. Eighteen months after notification of the first case in the city of Feira de Santana, we conducted the first serosurvey to define the magnitude of transmission in a rural community in Brazil. Methodology/Main findings The serosurvey was conducted in a random sample of 450 residences in the Chapada district, located 100 kilometers from Feira de Santana. We administered questionnaires and tested 120 sera from Chapada district residents for CHIKV IgM- and IgG-specific antibodies. An individual with CHIKV infection was defined as any person with CHIKV IgM or IgG antibodies detected in the serum. One Hundred cases of Chikungunya were reported after prolonged rainfall, which reinforced the relationship between the rainfall index and CHIKV transmission. Eighteen months after the start of the outbreak, we identified a seroprevalence of 20% (95% CI, 15.4–35%). CHIKV IgG- and IgM-specific antibodies were detected in 22/120 (18.3%) and 6/120 (5.0%) individuals, respectively. Among seropositive patients, 13/24 (54.2%) reported fever and joint pain over the previous two years (p<0.01). The rate of symptomatic CHIKV infection was 40.7%. Conclusions/Significance We identified a moderate seroprevalence of Chikungunya in the Chapada district, and in half of the confirmed CHIKV infections, patients reported arthralgia and fever over the previous two years. PMID:28107342

  13. Chikungunya Arthritis: Implications of Acute and Chronic Inflammation Mechanisms on Disease Management.

    PubMed

    Zaid, Ali; Gérardin, Patrick; Taylor, Adam; Mostafavi, Helen; Malvy, Denis; Mahalingam, Suresh

    2018-04-01

    In the past decade, arboviruses-arthropod-borne viruses-have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus, an arbovirus that belongs to the alphavirus genus, is a reemerging arthritogenic virus that has caused explosive outbreaks since 2006, notably on Réunion Island, and more recently in the Caribbean, South America, India, and Southeast Asia. The severity of arthritic disease caused by chikungunya virus has prompted public health authorities in affected countries to develop specific guidelines to tackle this pathogen. Chikungunya virus disease manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, during which patients may experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of chikungunya virus pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of chikungunya virus to date. In addition, the review explores the practical aspects of treatment and management of both acute and chronic chikungunya virus based on clinical experience during chikungunya virus outbreaks. Finally, recent findings on potential therapeutic solutions-from antiviral agents to immunomodulators-are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a reemerging arboviral disease of significant public health concern, and insight into future therapeutic approaches to better address the treatment and management of chikungunya virus. © 2017, American College of Rheumatology.

  14. The Global Virus Network: Challenging chikungunya

    PubMed Central

    McSweegan, Edward; Weaver, Scott C.; Lecuit, Marc; Frieman, Matthew; Morrison, Thomas E.; Hrynkow, Sharon

    2016-01-01

    The recent spread of chikungunya virus to the Western Hemisphere, together with the ongoing Ebola epidemic in West Africa, have highlighted the importance of international collaboration in the detection and management of disease outbreaks. In response to this need, the Global Virus Network (GVN) was formed in 2011. The GVN is a coalition of leading medical virologists in 34 affiliated laboratories in 24 countries, who collaborate to share their resources and expertise. The GVN supports research, promotes training for young scientists, serves as a technical resource for governments, businesses and international organizations, facilitates international scientific cooperation, and advocates for funding and evidence-based public policies. In response to the spread of chikungunya, the GVN formed a task force to identify research gaps and opportunities, including models of infection and disease, candidate vaccines and antivirals, epidemiology and vector control measures. Its members also serve as authoritative sources of information for the public, press, and policy-makers. This article forms part of a symposium in Antiviral Research on “Chikungunya discovers the New World”. PMID:26071007

  15. Reappearance of chikungunya, formerly called dengue, in the Americas.

    PubMed

    Halstead, Scott B

    2015-04-01

    After an absence of ≈200 years, chikungunya returned to the American tropics in 2013. The virus is maintained in a complex African zoonotic cycle but escapes into an urban cycle at 40- to 50-year intervals, causing global pandemics. In 1823, classical chikungunya, a viral exanthem in humans, occurred on Zanzibar, and in 1827, it arrived in the Caribbean and spread to North and South America. In Zanzibar, the disease was known as kidenga pepo, Swahili for a sudden cramp-like seizure caused by an evil spirit; in Cuba, it was known as dengue, a Spanish homonym of denga. During the eighteenth century, dengue (present-day chikungunya) was distinguished from breakbone fever (present-day dengue), another febrile exanthem. In the twentieth century, experiments resulted in the recovery and naming of present-day dengue viruses. In 1952, chikungunya virus was recovered during an outbreak in Tanzania, but by then, the virus had lost its original name to present-day dengue viruses.

  16. Chikungunya Virus Arthritis in Adult Wild-Type Mice▿ †

    PubMed Central

    Gardner, Joy; Anraku, Itaru; Le, Thuy T.; Larcher, Thibaut; Major, Lee; Roques, Pierre; Schroder, Wayne A.; Higgs, Stephen; Suhrbier, Andreas

    2010-01-01

    Chikungunya virus is a mosquito-borne arthrogenic alphavirus that has recently reemerged to produce the largest epidemic ever documented for this virus. Here we describe a new adult wild-type mouse model of chikungunya virus arthritis, which recapitulates the self-limiting arthritis, tenosynovitis, and myositis seen in humans. Rheumatic disease was associated with a prolific infiltrate of monocytes, macrophages, and NK cells and the production of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ). Infection with a virus isolate from the recent Reunion Island epidemic induced significantly more mononuclear infiltrates, proinflammatory mediators, and foot swelling than did an Asian isolate from the 1960s. Primary mouse macrophages were shown to be productively infected with chikungunya virus; however, the depletion of macrophages ameliorated rheumatic disease and prolonged the viremia. Only 1 μg of an unadjuvanted, inactivated, whole-virus vaccine derived from the Asian isolate completely protected against viremia and arthritis induced by the Reunion Island isolate, illustrating that protection is not strain specific and that low levels of immunity are sufficient to mediate protection. IFN-α treatment was able to prevent arthritis only if given before infection, suggesting that IFN-α is not a viable therapy. Prior infection with Ross River virus, a related arthrogenic alphavirus, and anti-Ross River virus antibodies protected mice against chikungunya virus disease, suggesting that individuals previously exposed to Ross River virus should be protected from chikungunya virus disease. This new mouse model of chikungunya virus disease thus provides insights into pathogenesis and a simple and convenient system to test potential new interventions. PMID:20519386

  17. Altered Agonist Sensitivity of a Mutant V2 Receptor Suggests a Novel Therapeutic Strategy for Nephrogenic Diabetes Insipidus

    PubMed Central

    Erdélyi, László Sándor; Balla, András; Patócs, Attila; Tóth, Miklós; Várnai, Péter

    2014-01-01

    Loss-of-function mutations of the type 2 vasopressin receptor (V2R) in kidney can lead to nephrogenic diabetes insipidus (NDI). We studied a previously described, but uncharacterized, mutation of the V2R (N321K missense mutation) of a patient with NDI. The properties of the mutant receptor were evaluated. We constructed a highly sensitive Epac-based bioluminescence resonance energy transfer biosensor to perform real-time cAMP measurements after agonist stimulation of transiently transfected HEK293 cells with V2Rs. β-Arrestin binding of the activated receptors was examined with luciferase-tagged β-arrestin and mVenus-tagged V2Rs using the bioluminescence resonance energy transfer technique. Cell surface expression levels of hemagglutinin-tagged receptors were determined with flow cytometry using anti-hemagglutinin-Alexa 488 antibodies. Cellular localization examinations were implemented with fluorescent tagged receptors visualized with confocal laser scanning microscopy. The effect of various vasopressin analogs on the type 1 vasopressin receptor (V1R) was tested on mouse arteries by wire myography. The N321K mutant V2R showed normal cell surface expression, but the potency of arginine vasopressin for cAMP generation was low, whereas the clinically used desmopressin was not efficient. The β-arrestin binding and internalization properties of the mutant receptor were also different than those for the wild type. The function of the mutant receptor can be rescued with administration of the V2R agonist Val4-desmopressin, which had no detectable side effects on V1R in the effective cAMP generating concentrations. Based on these findings we propose a therapeutic strategy for patients with NDI carrying the N321K mutation, as our in vivo experiments suggest that Val4-desmopressin could rescue the function of the N321K-V2R without significant side effects on the V1R. PMID:24628417

  18. Imported Chikungunya Virus Strains, Taiwan, 2006–2014

    PubMed Central

    Yang, Cheng-Fen; Su, Chien-Ling; Hsu, Tung-Chien; Chang, Shu-Fen; Lin, Chien-Chou

    2016-01-01

    We identified 78 imported chikungunya cases in Taiwan during 2006–2014. Sixty-six (84.6%) cases were initially suspected to be dengue, which indicates the necessity for laboratory diagnostics in differentiation between dengue and chikungunya. Results also emphasize the need for active surveillance of febrile illness at points of entry. PMID:27767908

  19. Molecular and Clinical Characterization of Chikungunya Virus Infections in Southeast Mexico.

    PubMed

    Galán-Huerta, Kame A; Martínez-Landeros, Erik; Delgado-Gallegos, Juan L; Caballero-Sosa, Sandra; Malo-García, Iliana R; Fernández-Salas, Ildefonso; Ramos-Jiménez, Javier; Rivas-Estilla, Ana M

    2018-05-09

    Chikungunya fever is an arthropod-borne infection caused by Chikungunya virus (CHIKV). Even though clinical features of Chikungunya fever in the Mexican population have been described before, there is no detailed information. The aim of this study was to perform a full description of the clinical features in confirmed Chikungunya-infected patients and describe the molecular epidemiology of CHIKV. We evaluated febrile patients who sought medical assistance in Tapachula, Chiapas, Mexico, from June through July 2015. Infection was confirmed with molecular and serological methods. Viruses were isolated and the E1 gene was sequenced. Phylogeny reconstruction was inferred using maximum-likelihood and maximum clade credibility approaches. We studied 52 patients with confirmed CHIKV infection. They were more likely to have wrist, metacarpophalangeal, and knee arthralgia. Two combinations of clinical features were obtained to differentiate between Chikungunya fever and acute undifferentiated febrile illness. We obtained 10 CHIKV E1 sequences that grouped with the Asian lineage. Seven strains diverged from the formerly reported. Patients infected with the divergent CHIKV strains showed a broader spectrum of clinical manifestations. We defined the complete clinical features of Chikungunya fever in patients from Southeastern Mexico. Our results demonstrate co-circulation of different CHIKV strains in the state of Chiapas.

  20. Molecular and Clinical Characterization of Chikungunya Virus Infections in Southeast Mexico

    PubMed Central

    Martínez-Landeros, Erik; Delgado-Gallegos, Juan L.; Caballero-Sosa, Sandra; Malo-García, Iliana R.

    2018-01-01

    Chikungunya fever is an arthropod-borne infection caused by Chikungunya virus (CHIKV). Even though clinical features of Chikungunya fever in the Mexican population have been described before, there is no detailed information. The aim of this study was to perform a full description of the clinical features in confirmed Chikungunya-infected patients and describe the molecular epidemiology of CHIKV. We evaluated febrile patients who sought medical assistance in Tapachula, Chiapas, Mexico, from June through July 2015. Infection was confirmed with molecular and serological methods. Viruses were isolated and the E1 gene was sequenced. Phylogeny reconstruction was inferred using maximum-likelihood and maximum clade credibility approaches. We studied 52 patients with confirmed CHIKV infection. They were more likely to have wrist, metacarpophalangeal, and knee arthralgia. Two combinations of clinical features were obtained to differentiate between Chikungunya fever and acute undifferentiated febrile illness. We obtained 10 CHIKV E1 sequences that grouped with the Asian lineage. Seven strains diverged from the formerly reported. Patients infected with the divergent CHIKV strains showed a broader spectrum of clinical manifestations. We defined the complete clinical features of Chikungunya fever in patients from Southeastern Mexico. Our results demonstrate co-circulation of different CHIKV strains in the state of Chiapas. PMID:29747416

  1. Preparedness for Threat of Chikungunya in the Pacific

    PubMed Central

    Hoy, Damian; Horwood, Paul F.; Ropa, Berry; Hancock, Thane; Guillaumot, Laurent; Rickart, Keith; Frison, Pascal; Pavlin, Boris; Souares, Yvan

    2014-01-01

    Chikungunya virus (CHIKV) caused significant outbreaks of illness during 2005–2007 in the Indian Ocean region. Chikungunya outbreaks have also occurred in the Pacific region, including in Papua New Guinea in 2012; New Caledonia in April 2013; and Yap State, Federated States of Micronesia, in August 2013. CHIKV is a threat in the Pacific, and the risk for further spread is high, given several similarities between the Pacific and Indian Ocean chikungunya outbreaks. Island health care systems have difficulties coping with high caseloads, which highlights the need for early multidisciplinary preparedness. The Pacific Public Health Surveillance Network has developed several strategies focusing on surveillance, case management, vector control, laboratory confirmation, and communication. The management of this CHIKV threat will likely have broad implications for global public health. PMID:25062306

  2. Discovery of a highly selective KIT kinase primary V559D mutant inhibitor for gastrointestinal stromal tumors (GISTs).

    PubMed

    Yu, Kailin; Liu, Xuesong; Jiang, Zongru; Hu, Chen; Zou, Fengming; Chen, Cheng; Ge, Juan; Wu, Jiaxin; Liu, Xiaochuan; Wang, Aoli; Wang, Wenliang; Wang, Wenchao; Qi, Ziping; Wang, Beilei; Wang, Li; Yan, Hezhong; Wang, Jiaoxue; Ren, Tao; Tang, Jun; Liu, Qingsong; Liu, Jing

    2017-12-19

    KIT kinase V559D mutation is the most prevalent primary gain-of-function mutation in Gastrointestinal Stromal Tumors (GISTs). Here we reported a highly selective KIT V559D inhibitor CHMFL-KIT-031, which displayed about 10-20 fold selectivity over KIT wt in the biochemical assay (IC 50 : 28 nM over 168 nM; Kd: 266 nM versus 6640 nM) and in cell (EC 50 : 176 nM versus 2000 nM for pY703) examination. It also displayed 15∼400-fold selectivity over other primary mutants such as L576P and secondary mutants including T670I, V654A (ATP binding pocket) as well as N822K and D816V (activation loop). In addition, it exhibited a selectivity S score (1) of 0.01 among 468 kinases/mutants in the KINOMEScan ™ assay. CHMFL-KIT-031 showed potent inhibitory efficacy for KIT V559D mediated signaling pathways in cell and anti-tumor activity in vivo (Tumor Growth Inhibition: 68.5%). Its superior selectivity would make it a good pharmacological tool for further dissection of KIT V559D mediated pathology in the GISTs.

  3. Discovery of a highly selective KIT kinase primary V559D mutant inhibitor for gastrointestinal stromal tumors (GISTs)

    PubMed Central

    Yu, Kailin; Liu, Xuesong; Jiang, Zongru; Hu, Chen; Zou, Fengming; Chen, Cheng; Ge, Juan; Wu, Jiaxin; Liu, Xiaochuan; Wang, Aoli; Wang, Wenliang; Wang, Wenchao; Qi, Ziping; Wang, Beilei; Wang, Li; Yan, Hezhong; Wang, Jiaoxue; Ren, Tao; Tang, Jun; Liu, Qingsong; Liu, Jing

    2017-01-01

    KIT kinase V559D mutation is the most prevalent primary gain-of-function mutation in Gastrointestinal Stromal Tumors (GISTs). Here we reported a highly selective KIT V559D inhibitor CHMFL-KIT-031, which displayed about 10-20 fold selectivity over KIT wt in the biochemical assay (IC50: 28 nM over 168 nM; Kd: 266 nM versus 6640 nM) and in cell (EC50: 176 nM versus 2000 nM for pY703) examination. It also displayed 15∼400-fold selectivity over other primary mutants such as L576P and secondary mutants including T670I, V654A (ATP binding pocket) as well as N822K and D816V (activation loop). In addition, it exhibited a selectivity S score (1) of 0.01 among 468 kinases/mutants in the KINOMEScan™ assay. CHMFL-KIT-031 showed potent inhibitory efficacy for KIT V559D mediated signaling pathways in cell and anti-tumor activity in vivo (Tumor Growth Inhibition: 68.5%). Its superior selectivity would make it a good pharmacological tool for further dissection of KIT V559D mediated pathology in the GISTs. PMID:29340041

  4. Cloning, preparation and preliminary crystallographic studies of penicillin V acylase autoproteolytic processing mutants

    PubMed Central

    Chandra, P. Manish; Brannigan, James A.; Prabhune, Asmita; Pundle, Archana; Turkenburg, Johan P.; Dodson, G. Guy; Suresh, C. G.

    2005-01-01

    The crystallization of three catalytically inactive mutants of penicillin V acylase (PVA) from Bacillus sphaericus in precursor and processed forms is reported. The mutant proteins crystallize in different primitive monoclinic space groups that are distinct from the crystal forms for the native enzyme. Directed mutants and clone constructs were designed to study the post-translational autoproteolytic processing of PVA. The catalytically inactive mutants will provide three-dimensional structures of precursor PVA forms, plus open a route to the study of enzyme–substrate complexes for this industrially important enzyme. PMID:16508111

  5. Structure of the G225P/G226P mutant of mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) ternary complex: implications for the binding of inhibitor and substrate.

    PubMed

    Dhagat, Urmi; Endo, Satoshi; Mamiya, Hiroaki; Hara, Akira; El-Kabbani, Ossama

    2009-03-01

    3(17)alpha-Hydroxysteroid dehydrogenase (AKR1C21) is a unique member of the aldo-keto reductase (AKR) superfamily owing to its ability to reduce 17-ketosteroids to 17alpha-hydroxysteroids, as opposed to other members of the AKR family, which can only produce 17beta-hydroxysteroids. In this paper, the crystal structure of a double mutant (G225P/G226P) of AKR1C21 in complex with the coenzyme NADP(+) and the inhibitor hexoestrol refined at 2.1 A resolution is presented. Kinetic analysis and molecular-modelling studies of 17alpha- and 17beta-hydroxysteroid substrates in the active site of AKR1C21 suggested that Gly225 and Gly226 play an important role in determining the substrate stereospecificity of the enzyme. Additionally, the G225P/G226P mutation of the enzyme reduced the affinity (K(m)) for both 3alpha- and 17alpha-hydroxysteroid substrates by up to 160-fold, indicating that these residues are critical for the binding of substrates.

  6. Chikungunya in the region of the Americas. A challenge for rheumatologists and health care systems.

    PubMed

    Pineda, Carlos; Muñoz-Louis, Roberto; Caballero-Uribe, Carlo V; Viasus, Diego

    2016-10-01

    At the end of 2013, the Pan American Health Organization issued an epidemiological alert due to the detection of the first local cases of Chikungunya in the Americas. By August 2015, autochthonous transmissions were detected in 33 countries and territories of the Americas. Latin America has reported nearly one million cases; only Colombia has issued a report of >200,000 cases during the first 4 months of 2015. In some Latin American and Caribbean countries, Chikungunya becomes a major public health problem. The disease commonly exhibits a self-limited course of arthritis, usually lasting for a few days or that may be prolonged to weeks; however, in 10-60 % of cases, joint pain may become chronic and persist for up to 3-5 years. Human-caused environmental changes, such as climate change, the globalization of international exchange, and disordered urban growth, are some factors that aid in its emergence and dissemination. Outbreaks of Chikungunya comprise a challenge for health care systems and rheumatologists because of the high attack rate on the population and the anticipated development of post-Chikungunya chronic rheumatism. This review emphasizes the rheumatologic clinical manifestations reported in the American continent and highlights the challenges that health care systems face in the absence of an effective vaccine and specific treatment to fight Chikungunya.

  7. New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates

    NASA Astrophysics Data System (ADS)

    Li, Guangyue; Yao, Peiyuan; Cong, Peiqian; Ren, Jie; Wang, Lei; Feng, Jinhui; Lau, Peter C. K.; Wu, Qiaqing; Zhu, Dunming

    2016-05-01

    To further expand the substrate range of the cyclohexylamine oxidase (CHAO) from Brevibacterium oxydans, a library of diverse mutants was created and assayed toward a group of structurally diverse substrates. Among them, mutants T198A and M226A exhibited enhanced activity relative to wt CHAO for most (S)-enantiomers of primary amines and some secondary amines. While mutants T198I, L199I, L199F, M226I and M226T were more active than wt CHAO toward the primary amines, mutants T198F, L199T, Y321A, Y321T, Y321I and Y321F enhanced the enzyme activity toward the secondary amines. In particular, mutant Y321I displayed an enhanced catalytic efficiency toward 1-(4-methoxybenzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydroisoquinoline (13). Whereas a double mutant, Y321I/M226T, acted on (S)-N-(prop-2-yn-1-yl)-2, 3-dihydro-1H-inden-1-amine [(S)-8]. Since (R)-8 is an irreversible inhibitor of monoamine oxidase and (S)-13 is an intermediate of dextromethorphan, a cough suppressant drug, deracemizations of 8 and 13 were carried out with crude enzyme extracts of the respective mutants. This resulted in 51% and 78% isolated yields of (R)-8 and (S)-13, respectively, each with high enantiomeric excess (93% and 99% ee). The results demonstrated the application potential of the evolved CHAO mutants in drug synthesis requiring chiral secondary amines.

  8. New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates

    PubMed Central

    Li, Guangyue; Yao, Peiyuan; Cong, Peiqian; Ren, Jie; Wang, Lei; Feng, Jinhui; Lau, Peter C.K.; Wu, Qiaqing; Zhu, Dunming

    2016-01-01

    To further expand the substrate range of the cyclohexylamine oxidase (CHAO) from Brevibacterium oxydans, a library of diverse mutants was created and assayed toward a group of structurally diverse substrates. Among them, mutants T198A and M226A exhibited enhanced activity relative to wt CHAO for most (S)-enantiomers of primary amines and some secondary amines. While mutants T198I, L199I, L199F, M226I and M226T were more active than wt CHAO toward the primary amines, mutants T198F, L199T, Y321A, Y321T, Y321I and Y321F enhanced the enzyme activity toward the secondary amines. In particular, mutant Y321I displayed an enhanced catalytic efficiency toward 1-(4-methoxybenzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydroisoquinoline (13). Whereas a double mutant, Y321I/M226T, acted on (S)-N-(prop-2-yn-1-yl)-2, 3-dihydro-1H-inden-1-amine [(S)-8]. Since (R)-8 is an irreversible inhibitor of monoamine oxidase and (S)-13 is an intermediate of dextromethorphan, a cough suppressant drug, deracemizations of 8 and 13 were carried out with crude enzyme extracts of the respective mutants. This resulted in 51% and 78% isolated yields of (R)-8 and (S)-13, respectively, each with high enantiomeric excess (93% and 99% ee). The results demonstrated the application potential of the evolved CHAO mutants in drug synthesis requiring chiral secondary amines. PMID:27138090

  9. Spatial and temporal distribution of chikungunya activity in the Americas

    USDA-ARS?s Scientific Manuscript database

    To better understand chikungunya activity in the America we mapped recent chikungunya activity in the Americas. This activity is needed to better understand that the relationships between climatic factors and disease outbreak patters are critical to the design and constructing of predictive models....

  10. A sensitive epitope-blocking ELISA for the detection of Chikungunya virus-specific antibodies in patients.

    PubMed

    Goh, Lucas Y H; Kam, Yiu-Wing; Metz, Stefan W; Hobson-Peters, Jody; Prow, Natalie A; McCarthy, Suzi; Smith, David W; Pijlman, Gorben P; Ng, Lisa F P; Hall, Roy A

    2015-09-15

    Chikungunya fever (CHIKF) has re-emerged as an arboviral disease that mimics clinical symptoms of other diseases such as dengue, malaria, as well as other alphavirus-related illnesses leading to problems with definitive diagnosis of the infection. Herein we describe the development and evaluation of a sensitive epitope-blocking ELISA (EB-ELISA) capable of specifically detecting anti-chikungunya virus (CHIKV) antibodies in clinical samples. The assay uses a monoclonal antibody (mAb) that binds an epitope on the E2 protein of CHIKV and does not exhibit cross-reactivity to other related alphaviruses. We also demonstrated the use of recombinant CHIK virus-like particles (VLPs) as a safe alternative antigen to infectious virions in the assay. Based on testing of 60 serum samples from patients in the acute or convalescent phase of CHIKV infection, the EB-ELISA provided us with 100% sensitivity, and exhibited 98.5% specificity when Ross River virus (RRV)- or Barmah Forest virus (BFV)-immune serum samples were included. This assay meets the public health demands of a rapid, robust, sensitive and specific, yet simple assay for specifically diagnosing CHIK-infections in humans. Copyright © 2015. Published by Elsevier B.V.

  11. IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity

    PubMed Central

    Sun, Yong-Jiang; Kwek, Dyan J. C.; Lim, Poh-Lian; Dimatatac, Frederico; Ng, Lee-Ching; Ooi, Eng-Eong; Choo, Khar-Heng; Her, Zhisheng; Kourilsky, Philippe; Leo, Yee-Sin

    2009-01-01

    Background Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity. Methods and Findings Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity. Conclusions This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease. PMID:19156204

  12. Chikungunya Virus–Vector Interactions

    PubMed Central

    Coffey, Lark L.; Failloux, Anna-Bella; Weaver, Scott C.

    2014-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. Since 2004, CHIKV has emerged in Africa, Indian Ocean islands, Asia, Europe, and the Americas, causing millions of human infections. Central to understanding CHIKV emergence is knowledge of the natural ecology of transmission and vector infection dynamics. This review presents current understanding of CHIKV infection dynamics in mosquito vectors and its relationship to human disease emergence. The following topics are reviewed: CHIKV infection and vector life history traits including transmission cycles, genetic origins, distribution, emergence and spread, dispersal, vector competence, vector immunity and microbial interactions, and co-infection by CHIKV and other arboviruses. The genetics of vector susceptibility and host range changes, population heterogeneity and selection for the fittest viral genomes, dual host cycling and its impact on CHIKV adaptation, viral bottlenecks and intrahost diversity, and adaptive constraints on CHIKV evolution are also discussed. The potential for CHIKV re-emergence and expansion into new areas and prospects for prevention via vector control are also briefly reviewed. PMID:25421891

  13. Asian genotype of Chikungunya virus circulating in Venezuela during 2014.

    PubMed

    Camacho, Daría; Reyes, Jesús; Negredo, Ana; Hernández, Lourdes; Sánchez-Seco, María; Comach, Guillermo

    2017-10-01

    Chikungunya virus emerged on Saint-Martin Island in the Caribbean in late 2013. Since then in July of 2104 Venezuela reported autochthonous cases. This study reports the first phylogenetic characterization of CHIKV autochthonous cases in Venezuela, 2014. The phylogenetic analysis showed that the CHIKV circulating in Venezuela (Aragua state) belong to the Asian genotype (Caribbean clade) and it is related to viruses that circulated in the same year in the Caribbean. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Summary results of the 2014-2015 DARPA Chikungunya challenge

    DOE PAGES

    Del Valle, Sara Y.; McMahon, Benjamin Hamilton; Asher, Jason; ...

    2018-05-30

    Here, emerging pathogens such as Zika, chikungunya, Ebola, and dengue viruses are serious threats to national and global health security. Accurate forecasts of emerging epidemics and their severity are critical to minimizing subsequent mortality, morbidity, and economic loss. The recent introduction of chikungunya and Zika virus to the Americas underscores the need for better methods for disease surveillance and forecasting.

  15. Summary results of the 2014-2015 DARPA Chikungunya challenge

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

    Del Valle, Sara Y.; McMahon, Benjamin Hamilton; Asher, Jason

    Here, emerging pathogens such as Zika, chikungunya, Ebola, and dengue viruses are serious threats to national and global health security. Accurate forecasts of emerging epidemics and their severity are critical to minimizing subsequent mortality, morbidity, and economic loss. The recent introduction of chikungunya and Zika virus to the Americas underscores the need for better methods for disease surveillance and forecasting.

  16. An app for climate-based Chikungunya risk monitoring and mapping

    USDA-ARS?s Scientific Manuscript database

    There is an increasing concern for reemergence and spread of chikungunya in the last 10 years in Africa, the Indian Ocean, and Asia, and range expansion that now reaches the Caribbean, South America and threatens North America. The outbreak of Chikungunya in 2013 and its spread throughout the Americ...

  17. Antiviral Perspectives for Chikungunya Virus

    PubMed Central

    Cherian, Sarah

    2014-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne pathogen that has a major health impact in humans and causes acute febrile illness in humans accompanied by joint pains and, in many cases, persistent arthralgia lasting for weeks to years. CHIKV reemerged in 2005-2006 in several parts of the Indian Ocean islands and India after a gap of 32 years, causing millions of cases. The re-emergence of CHIKV has also resulted in numerous outbreaks in several countries in the eastern hemisphere, with a threat to further expand in the near future. However, there is no vaccine against CHIKV infection licensed for human use, and therapy for CHIKV infection is still mainly limited to supportive care as antiviral agents are yet in different stages of testing or development. In this review we explore the different perspectives for chikungunya treatment and the effectiveness of these treatment regimens and discuss the scope for future directions. PMID:24955364

  18. Homeopathic drug therapy. Homeopathy in Chikungunya Fever and Post-Chikungunya Chronic Arthritis: an observational study.

    PubMed

    Wadhwani, Gyandas G

    2013-07-01

    To observe the effect of homeopathic therapy in Chikungunya Fever (CF) and in Post-Chikungunya Chronic Arthritis (PCCA) in a primary health care setting. A prospective observational study was conducted at Delhi Government Homeopathic Dispensary, Aali Village, New Delhi, India, for a period of 6 months, from 1st October 2010 to 31st March 2011. 126 patients (75 CF, 51 PCCA) were enrolled based on predefined inclusion criteria. A single homeopathic medicine was prescribed for each patient after case taking with the help of Materia Medica and/or Repertory. Results were evaluated on the basis of visual analogue scale and symptom scores. Complete recovery was seen in 84.5% CF cases in a mean time of 6.8 days. 90% cases of PCCA recovered completely in a mean time of 32.5 days. Homeopathic therapy may be effective in CF and PCCA. A randomized controlled trial should be considered. Copyright © 2013 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  19. Radium-226 transfer factor from soils to crops and its simple estimation method using uranium and barium concentrations.

    PubMed

    Tagami, Keiko; Uchida, Shigeo

    2009-09-01

    Radium-226 ((226)Ra) should be assessed to determine the safety of geological disposal of high-level radioactive and transuranic wastes. Among the environmental transfer parameters that have been used in mathematical models for the environmental safety assessment, soil-to-plant transfer factor (F(v)) is of importance; it is defined as the plant/soil concentration ratio. Reported F(v) data for (226)Ra are still limited due to the low concentration of (226)Ra in plants in the natural environment. In this study, we collected F(v) of (226)Ra (F(v)-Ra) for crops and then applied a statistical approach to estimate F(v)-Ra instead of directly measuring the radionuclide. We found high correlations between (226)Ra and U concentrations in soils (because (226)Ra is a progeny in the (238)U series), and between (226)Ra and Ba concentrations in plants (because they are chemically similar in plant uptake). Using U in soil and Ba in plant values, we could estimate F(v)-Ra with good accuracy; the difference between estimated and measured F(v)-Ra values was a factor of 1.2 on average for crops. The method could estimate F(v)-Ra for the soil-to-plant systems where (226)Ra and Ba concentrations in soil are within the normal range, e.g. 8-100 Bq kg(-1)-dry for (226)Ra and 84-960 mg kg(-1)-dry for Ba.

  20. Antiviral activity of silymarin against chikungunya virus

    PubMed Central

    Lani, Rafidah; Hassandarvish, Pouya; Chiam, Chun Wei; Moghaddam, Ehsan; Chu, Justin Jang Hann; Rausalu, Kai; Merits, Andres; Higgs, Stephen; Vanlandingham, Dana; Abu Bakar, Sazaly; Zandi, Keivan

    2015-01-01

    The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection. PMID:26078201

  1. Prevalence of Malaria, Dengue, and Chikungunya Significantly Associated with Mosquito Breeding Sites

    PubMed Central

    Islam, Mohammad Nazrul; ZulKifle, Mohammad; Sherwani, Arish Mohammad Khan; Ghosh, Susanta Kumar; Tiwari, Satyanarayan

    2011-01-01

    Objectives: To observe the prevalence of malaria, dengue, and chikungunya and their association with mosquito breeding sites. Methods: The study was observational and analytical. A total of 162 houses and 670 subjects were observed during the study period. One hundred forty-two febrile patients were eligible for the study. After obtaining informed consent from all febrile patients, 140 blood samples were collected to diagnose malaria, dengue, and chikungunya. Larval samples were collected by the standard protocol that follows. Correlation of data was performed by Pearson correlation test. Results: Forty-seven blood samples were found positive: 33 for chikungunya, 3 for dengue, and 11 for malaria. Fifty-one out of 224 larval samples were found positive. Out of the 51 positive samples, 37 were positive for Aedes, 12 were positive for Anopheles, and two were positive for Culex larvae. Interpretation and Conclusion: Mosquito-borne fevers, especially malaria, dengue, and chikungunya, have shown a significant relationship with mosquito breeding sites. PMID:23610486

  2. A smartphone-based diagnostic platform for rapid detection of Zika, chikungunya, and dengue viruses

    PubMed Central

    Priye, Aashish; Bird, Sara W.; Light, Yooli K.; Ball, Cameron S.; Negrete, Oscar A.; Meagher, Robert J.

    2017-01-01

    Current multiplexed diagnostics for Zika, dengue, and chikungunya viruses are situated outside the intersection of affordability, high performance, and suitability for use at the point-of-care in resource-limited settings. Consequently, insufficient diagnostic capabilities are a key limitation facing current Zika outbreak management strategies. Here we demonstrate highly sensitive and specific detection of Zika, chikungunya, and dengue viruses by coupling reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with our recently developed quenching of unincorporated amplification signal reporters (QUASR) technique. We conduct reactions in a simple, inexpensive and portable “LAMP box” supplemented with a consumer class smartphone. The entire assembly can be powered by a 5 V USB source such as a USB power bank or solar panel. Our smartphone employs a novel algorithm utilizing chromaticity to analyze fluorescence signals, which improves the discrimination of positive/negative signals by 5-fold when compared to detection with traditional RGB intensity sensors or the naked eye. The ability to detect ZIKV directly from crude human sample matrices (blood, urine, and saliva) demonstrates our device’s utility for widespread clinical deployment. Together, these advances enable our system to host the key components necessary to expand the use of nucleic acid amplification-based detection assays towards point-of-care settings where they are needed most. PMID:28317856

  3. A smartphone-based diagnostic platform for rapid detection of Zika, chikungunya, and dengue viruses

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

    Priye, Aashish; Bird, Sara W.; Light, Yooli K.

    Current multiplexed diagnostics for Zika, dengue, and chikungunya viruses are situated outside the intersection of affordability, high performance, and suitability for use at the point-of-care in resource-limited settings. Consequently, insufficient diagnostic capabilities are a key limitation facing current Zika outbreak management strategies. We demonstrate highly sensitive and specific detection of Zika, chikungunya, and dengue viruses by coupling reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with our recently developed quenching of unincorporated amplification signal reporters (QUASR) technique. We conduct reactions in a simple, inexpensive and portable “LAMP box” supplemented with a consumer class smartphone. The entire assembly can be powered by a 5more » V USB source such as a USB power bank or solar panel. The smartphone employs a novel algorithm utilizing chromaticity to analyze fluorescence signals, which improves the discrimination of positive/negative signals by 5-fold when compared to detection with traditional RGB intensity sensors or the naked eye. The ability to detect ZIKV directly from crude human sample matrices (blood, urine, and saliva) demonstrates our device’s utility for widespread clinical deployment. Altogether, these advances enable our system to host the key components necessary to expand the use of nucleic acid amplification-based detection assays towards point-of-care settings where they are needed most.« less

  4. A smartphone-based diagnostic platform for rapid detection of Zika, chikungunya, and dengue viruses

    DOE PAGES

    Priye, Aashish; Bird, Sara W.; Light, Yooli K.; ...

    2017-03-20

    Current multiplexed diagnostics for Zika, dengue, and chikungunya viruses are situated outside the intersection of affordability, high performance, and suitability for use at the point-of-care in resource-limited settings. Consequently, insufficient diagnostic capabilities are a key limitation facing current Zika outbreak management strategies. We demonstrate highly sensitive and specific detection of Zika, chikungunya, and dengue viruses by coupling reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with our recently developed quenching of unincorporated amplification signal reporters (QUASR) technique. We conduct reactions in a simple, inexpensive and portable “LAMP box” supplemented with a consumer class smartphone. The entire assembly can be powered by a 5more » V USB source such as a USB power bank or solar panel. The smartphone employs a novel algorithm utilizing chromaticity to analyze fluorescence signals, which improves the discrimination of positive/negative signals by 5-fold when compared to detection with traditional RGB intensity sensors or the naked eye. The ability to detect ZIKV directly from crude human sample matrices (blood, urine, and saliva) demonstrates our device’s utility for widespread clinical deployment. Altogether, these advances enable our system to host the key components necessary to expand the use of nucleic acid amplification-based detection assays towards point-of-care settings where they are needed most.« less

  5. Characterization of Reemerging Chikungunya Virus

    PubMed Central

    Sourisseau, Marion; Schilte, Clémentine; Casartelli, Nicoletta; Trouillet, Céline; Guivel-Benhassine, Florence; Rudnicka, Dominika; Sol-Foulon, Nathalie; Roux, Karin Le; Prevost, Marie-Christine; Fsihi, Hafida; Frenkiel, Marie-Pascale; Blanchet, Fabien; Afonso, Philippe V; Ceccaldi, Pierre-Emmanuel; Ozden, Simona; Gessain, Antoine; Schuffenecker, Isabelle; Verhasselt, Bruno; Zamborlini, Alessia; Saïb, Ali; Rey, Felix A; Arenzana-Seisdedos, Fernando; Desprès, Philippe; Michault, Alain; Albert, Matthew L; Schwartz, Olivier

    2007-01-01

    An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host. PMID:17604450

  6. Functional analysis of potassium channels in Kv7.2 G271V mutant causing early onset familial epilepsy.

    PubMed

    Wang, Juanjuan; Li, Yuan; Hui, Zhiyan; Cao, Min; Shi, Ruiming; Zhang, Wei; Geng, Limeng; Zhou, Xihui

    2015-08-07

    Kv7 (KCNQ) channels underlying a class of voltage-gated K+ current are best known for regulating neuronal excitability. The first glycine (G) residue in the pore helix of Kv7.2 (KCNQ2) subunit is highly conserved among different classes of Kv7 channel family. A missense mutation causing the replacement of the corresponding G residues with a valine (p.G271V) in Kv7.2 was found in a large, four-generation pedigree. Here, we set out to examine the molecular pathomechanism of G271V mutants using patch clamp technology combined with biochemical and immunocytochemical techniques in transiently transfected human embryonic kidney (HEK) 293 cells. The expression of Kv7.2 protein had the same intensity for both wild type (WT) and G271V. In transfected HEK cells, G271V mutants induced large depolarizing shifts of the conductance-voltage relationships and marked slowing of current activation kinetics compared to WT. In addition, G271V mutants abolished currents in homomeric channels, and resulted in about 50% reduction of current in Kv7.2/G271V/Kv7.3 heteromultimeric condition, indicating a more severe functional defect. To test for G271V mutant channel expression in surface membrane, we performed fluorescence confocal microscopy imaging, which revealed no differences between the mutant and WT, suggesting that G271V channels fail to open in response to depolarization even though they are present in the membrane. Furthermore, pharmacologic intervention experiments revealed that upon specific incubation of transfected HEK 293 cells expressing G271V heteromultimeric channels in presence of Kv7 channel enhancer retigabine (ezogabine), the potassium currents increased significantly, suggesting the potential of retigabine as gene-specific therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. An agent-based model driven by tropical rainfall to understand the spatio-temporal heterogeneity of a chikungunya outbreak.

    PubMed

    Dommar, Carlos J; Lowe, Rachel; Robinson, Marguerite; Rodó, Xavier

    2014-01-01

    Vector-borne diseases, such as dengue, malaria and chikungunya, are increasing across their traditional ranges and continuing to infiltrate new, previously unaffected, regions. The spatio-temporal evolution of these diseases is determined by the interaction of the host and vector, which is strongly dependent on social structures and mobility patterns. We develop an agent-based model (ABM), in which each individual is explicitly represented and vector populations are linked to precipitation estimates in a tropical setting. The model is implemented on both scale-free and regular networks. The spatio-temporal transmission of chikungunya is analysed and the presence of asymptomatic silent spreaders within the population is investigated in the context of implementing travel restrictions during an outbreak. Preventing the movement of symptomatic individuals is found to be an insufficient mechanism to halt the spread of the disease, which can be readily carried to neighbouring nodes via sub-clinical individuals. Furthermore, the impact of topology structure vs. precipitation levels is assessed and precipitation is found to be the dominant factor driving spatio-temporal transmission. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Identification of Yeast V-ATPase Mutants by Western Blots Analysis of Whole Cell Lysates

    NASA Astrophysics Data System (ADS)

    Parra-Belky, Karlett

    2002-11-01

    A biochemistry laboratory was designed for an undergraduate course to help students better understand the link between molecular engineering and biochemistry. Students identified unknown yeast strains with high specificity using SDS-PAGE and Western blot analysis of whole cell lysates. This problem-solving exercise is a common application of biochemistry in biotechnology research. Three different strains were used: a wild-type and two mutants for the proton pump vacuolar ATPase (V-ATPase). V-ATPases are multisubunit enzymes and the mutants used were deletion mutants; each lacked one structural gene of the complex. After three, three-hour labs, mutant strains were easily identified by the students and distinguished from wild-type cells analyzing the pattern of SDS-PAGE distribution of proteins. Identifying different subunits of one multimeric protein allowed for discussion of the structure and function of this metabolic enzyme, which captured the interest of the students. The experiment can be adapted to other multimeric protein complexes and shows improvement of the described methodology over previous reports, perhaps because the problem and its solution are representative of the type of techniques currently used in research labs.

  9. Differential calcium sensitivity in NaV 1.5 mixed syndrome mutants.

    PubMed

    Abdelsayed, Mena; Baruteau, Alban-Elouen; Gibbs, Karen; Sanatani, Shubhayan; Krahn, Andrew D; Probst, Vincent; Ruben, Peter C

    2017-09-15

    SCN5a mutations may express gain-of-function (Long QT Syndrome-3), loss-of-function (Brugada Syndrome 1) or both (mixed syndromes), depending on the mutation and environmental triggers. One such trigger may be an increase in cytosolic calcium, accompanying exercise. Many mixed syndromes mutants, including ∆KPQ, E1784K, 1795insD and Q1909R, are found in calcium-sensitive regions. Elevated cytosolic calcium attenuates gain-of-function properties in ∆KPQ, 1795insD and Q1909R, but not in E1784K. By contrast, elevated cytosolic calcium further exacerbates gain-of-function in E1784K by destabilizing slow inactivation. Action potential modelling, using a modified O'Hara Rudy model, suggests that elevated heart rate rescues action potential duration in ∆KPQ, 1795insD and Q1909R, but not in E1784K. Action potential simulations suggest that E1784K carriers have an increased intracellular sodium-to-calcium ratio under bradycardia and tachycardia conditions. Elevated cytosolic calcium, which is common during high heart rates, ameliorates or exacerbates the mixed syndrome phenotype depending on the genetic signature. Inherited arrhythmias may arise from mutations in the gene for SCN5a, which encodes the cardiac voltage-gated sodium channel, Na V 1.5. Mutants in Na V 1.5 result in Brugada Syndrome (BrS1), Long-QT Syndrome (LQT3) or mixed syndromes (an overlap of BrS1/LQT3). Exercise is a potential arrhythmogenic trigger in mixed syndromes. We aimed to determine the effects of elevated cytosolic calcium, which is common during exercise, in mixed syndrome Na V 1.5 mutants. We used whole-cell patch clamp to assess the biophysical properties of Na V 1.5 wild-type (WT), ∆KPQ, E1784K, 1795insD and Q1909R mutants in human embryonic kidney 293 cells transiently transfected with the Na V 1.5 α subunit (WT or mutants), β1 subunit and enhanced green fluorescent protein. Voltage-dependence and kinetics were measured at cytosolic calcium levels of approximately 0, 500 and 2500

  10. Comparison of Activity Determination of Radium 226 in FUSRAP Soil using Various Energy Lines - 12299

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

    Tucker, Brian; Donakowski, Jough; Hays, David

    2012-07-01

    Gamma spectroscopy is used at the Formerly Utilized Sites Remedial Action Program (FUSRAP) Maywood Superfund Site as the primary radioanalytical tool for quantization of activities of the radionuclides of concern in site soil. When selecting energy lines in gamma spectroscopy, a number of factors are considered including assumptions concerning secondary equilibrium, interferences, and the strength of the lines. The case of the Maywood radionuclide of concern radium-226 (Ra-226) is considered in this paper. At the FUSRAP Maywood Superfund Site, one of the daughters produced from radioactive decay of Ra-226, lead-214 (Pb- 214), is used to quantitate Ra-226. Another Ra-226 daughter,more » bismuth-214 (Bi-214), also may be used to quantitate Ra-226. In this paper, a comparison of Ra-226 to Pb-214 activities and Ra-226 to Bi-214 activities, obtained using gamma spectrometry for a large number of soil samples, was performed. The Pb-214, Bi-214, and Ra-226 activities were quantitated using the 352 kilo electron volt (keV), 609 keV, and 186 keV lines, respectively. The comparisons were made after correcting the Ra-226 activities by a factor of 0.571 and both ignoring and accounting for the contribution of a U-235 interfering line to the Ra-226 line. For the Pb-214 and Bi-214 activities, a mean in-growth factor was employed. The gamma spectrometer was calibrated for efficiency and energy using a mixed gamma standard and an energy range of 59 keV to 1830 keV. The authors expect other sites with Ra-226 contamination in soil may benefit from the discussions and points in this paper. Proper use of correction factors and comparison of the data from three different gamma-emitting radionuclides revealed agreement with expectations and provided confidence that using such correction factors generates quality data. The results indicate that if contamination is low level and due to NORM, the Ra-226 can be measured directly if corrected to subtract the contribution from U-235. If

  11. Analysis of recombinant H7N9 wild-type and mutant viruses in pigs shows that the Q226L mutation in HA is important for transmission.

    PubMed

    Liu, Qinfang; Zhou, Bin; Ma, Wenjun; Bawa, Bhupinder; Ma, Jingjiao; Wang, Wei; Lang, Yuekun; Lyoo, Young; Halpin, Rebecca A; Lin, Xudong; Stockwell, Timothy B; Webby, Richard; Wentworth, David E; Richt, Juergen A

    2014-07-01

    The fact that there have been more than 300 human infections with a novel avian H7N9 virus in China indicates that this emerging strain has pandemic potential. Furthermore, many of the H7N9 viruses circulating in animal reservoirs contain putative mammalian signatures in the HA and PB2 genes that are believed to be important in the adaptation of other avian strains to humans. To date, the definitive roles of these mammalian-signature substitutions in transmission and pathogenesis of H7N9 viruses remain unclear. To address this we analyzed the biological characteristics, pathogenicity, and transmissibility of A/Anhui/1/2013 (H7N9) virus and variants in vitro and in vivo using a synthetically created wild-type virus (rAnhui-WT) and two mutants (rAnhui-HA-226Q and rAnhui-PB2-627E). All three viruses replicated in lungs of intratracheally inoculated pigs, yet nasal shedding was limited. The rAnhui-WT and rAnhui-PB2-627E viruses were transmitted to contact animals. In contrast, the rAnhui-HA-226Q virus was not transmitted to sentinel pigs. Deep sequencing of viruses from the lungs of infected pigs identified substitutions arising in the viral population (e.g., PB2-T271A, PB2-D701N, HA-V195I, and PB2-E627K reversion) that may enhance viral replication in pigs. Collectively, the results demonstrate that critical mutations (i.e., HA-Q226L) enable the H7N9 viruses to be transmitted in a mammalian host and suggest that the myriad H7N9 genotypes circulating in avian species in China and closely related strains (e.g., H7N7) have the potential for further adaptation to human or other mammalian hosts (e.g., pigs), leading to strains capable of sustained human-to-human transmission. Importance: The genomes of the zoonotic avian H7N9 viruses emerging in China have mutations in critical genes (PB2-E627K and HA-Q226L) that may be important in their pandemic potential. This study shows that (i) HA-226L of zoonotic H7N9 strains is critical for binding the α-2,6-linked receptor and

  12. The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series

    PubMed Central

    da Silva, Marcus Tulius Texeira; Rosala-Hallas, Anna; Jardim, Marcia Rodrigues; Burnside, Girvan; Pamplona, Luciana; Bhojak, Maneesh; Manohar, Radhika; da Silva, Gabriel Amorelli Medeiros; Adriano, Marcus Vinicius; Brasil, Patricia; Nogueira, Rita Maria Ribeiro; Dos Santos, Carolina Cardoso; Turtle, Lance; de Sequeira, Patricia Carvalho; Brown, David W.; Griffiths, Michael J.; de Filippis, Ana Maria Bispo

    2018-01-01

    Background During 2015–16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barré syndrome (GBS) in adults but other neurological associations are uncertain. Chikungunya virus has caused outbreaks in Brazil since 2014 but associated neurological disease has rarely been reported here. We investigated adults with acute neurological disorders for Zika, chikungunya and dengue, another arbovirus circulating in Brazil. Methods We studied adults who had developed a new neurological condition following suspected Zika virus infection between 1st November 2015 and 1st June 2016. Cerebrospinal fluid (CSF), serum, and urine were tested for evidence of Zika, chikungunya, and dengue viruses. Results Of 35 patients studied, 22 had evidence of recent arboviral infection. Twelve had positive PCR or IgM for Zika, five of whom also had evidence for chikungunya, three for dengue, and one for all three viruses. Five of them presented with GBS; seven had presentations other than GBS, including meningoencephalitis, myelitis, radiculitis or combinations of these syndromes. Additionally, ten patients positive for chikungunya virus, two of whom also had evidence for dengue virus, presented with a similar range of neurological conditions. Conclusions Zika virus is associated with a wide range of neurological manifestations, including central nervous system disease. Chikungunya virus appears to have an equally important association with neurological disease in Brazil, and many patients had dual infection. To understand fully the burden of Zika we must look beyond GBS, and also investigate for other co-circulating arboviruses, particularly chikungunya. PMID:29432457

  13. Immunosurveillance and therapy of multiple myeloma are CD226 dependent

    PubMed Central

    Guillerey, Camille; Ferrari de Andrade, Lucas; Vuckovic, Slavica; Miles, Kim; Ngiow, Shin Foong; Yong, Michelle C.R.; Teng, Michele W.L.; Colonna, Marco; Ritchie, David S.; Chesi, Martha; Bergsagel, P. Leif; Hill, Geoffrey R.; Smyth, Mark J.; Martinet, Ludovic

    2015-01-01

    Multiple myeloma (MM) is an age-dependent hematological malignancy. Evaluation of immune interactions that drive MM relies on in vitro experiments that do not reflect the complex cellular stroma involved in MM pathogenesis. Here we used Vk*MYC transgenic mice, which spontaneously develop MM, and demonstrated that the immune system plays a critical role in the control of MM progression and the response to treatment. We monitored Vk*MYC mice that had been crossed with Cd226 mutant mice over a period of 3 years and found that CD226 limits spontaneous MM development. The CD226-dependent anti-myeloma immune response against transplanted Vk*MYC MM cells was mediated both by NK and CD8+ T cells through perforin and IFN-γ pathways. Moreover, CD226 expression was required for optimal antimyeloma efficacy of cyclophosphamide (CTX) and bortezomib (Btz), which are both standardly used to manage MM in patients. Activation of costimulatory receptor CD137 with mAb (4-1BB) exerted strong antimyeloma activity, while inhibition of coinhibitory receptors PD-1 and CTLA-4 had no effect. Taken together, the results of this study provide in vivo evidence that CD226 is important for MM immunosurveillance and indicate that specific immune components should be targeted for optimal MM treatment efficacy. As progressive immunosuppression associates with MM development, strategies aimed to increase immune functions may have important therapeutic implications in MM. PMID:25893601

  14. [First case of chikungunya fever in Hermosillo, Sonora, Mexico].

    PubMed

    Martínez-Medina, Miguel Ángel; Cañedo-Dorame, Ismael Antonio

    2017-01-01

    The Chikungunya is an arbovirus first described during a 1952 outbreak of febrile exantematic disease in southern Tanganyika (now Tanzania). It is a virus within the alphavirus genus of the Togaviridae family, it is usually transmitted to humans by Aedes mosquitoes. Typically, the disease manifests as acute onset of fever and joint pains. This study describes the clinical characteristics the first imported case infected with chikungunya fever (CHIK) in Hermosillo, Sonora, Mexico. We report the case of a 30 years old man seen in our emergency department due to fever, polyarthralgia, rash and headache. This patient has been in Tapachula, Chiapas, a jungle area in southern México, and he returned from a 45 days trip before the onset his symptoms. The chikungunya viral infection (CHIK) was diagnosed by RT-PCR procedure. Paracetamol therapy was administered and his clinical course was self-limited. We concluded that with the increase of mosquito´s habitat by global warming and frequent traveling, CHIK reemerged and showed global distribution recently. This disease must be suspected in patients with compatible clinical symptoms returning from epidemic/endemic areas. CHIK must be diagnosed on the basis of clinical, epidemiological and laboratory criteria.

  15. Chikungunya: Information for the General Public

    MedlinePlus

    ... air conditioning or window/door screens o Use mosquito repellents on exposed skin o Wear long-sleeved shirts and long pants o Wear permethrin-treated clothing o Empty ... you are sick with chikungunya, avoiding mosquito bites will help prevent further spread of the ...

  16. Evidence for natural vertical transmission of chikungunya viruses in field populations of Aedes aegypti in Delhi and Haryana states in India-a preliminary report.

    PubMed

    Jain, Jaspreet; Kushwah, Raja Babu S; Singh, Shashi S; Sharma, Anil; Adak, Tridibes; Singh, Om P; Bhatnagar, Raj Kamal; Subbarao, Sarala K; Sunil, Sujatha

    2016-10-01

    Aedes aegypti and Aedes albopictus are principal vectors for the transmission of chikungunya virus (CHIKV). India is a hub for both dengue and chikungunya infections and there are several reports of co-infection of dengue and chikungunya virus in the clinical scenario. The present pilot entomological survey was conducted to evaluate vertical transmission of CHIKV in Aedes field populations. Aedes immature (larvae and pupae) collection was done in 2012, over a period of six months from selected sites in Delhi and Haryana, India. The immatures collected were reared for adult emergence and species identification was done. A. aegypti male and female mosquitoes were separated and pooled collection spot-wise, RNA extracted and RT PCR performed to test for the presence of CHIKV in the pools. Container index (CI) and minimum infection rate (MIR) were estimated. From study areas that tested positive for CHIKV, adult collections were made and females upon feeding on uninfected blood in laboratory were allowed to lay eggs. The progeny that emerged from these field-collected mothers were tested for CHIKV presence. Our pilot survey showed the existence of A. aegypti population even during peak summer season in a few foci which eventually helped the mosquitoes to tide over adverse environmental conditions and with the start of rainfall, the population exploded within a short period of time. Immatures collected from field and progeny of adults collected from the field were CHIKV positive demonstrating the presence of vertical transmission of chikungunya virus in field population of A. aegypti. The present study further demonstrates the importance of identifying permanent breeding sites for proper Aedes species control. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Entomological study of chikungunya infections in the State of Kelantan, Malaysia

    PubMed Central

    Rozilawati, H.; Faudzi, A.Y.; Rahidah, A.A. Siti; Azlina, A.H. Nor; Abdullah, A.G.; Amal, N.M.; Mansor, H. Wan; Hani, H.; Apandi, Y.; Noor, Faezah; Norziyana; Nazni, W.A.; Zairi, J.; Lee, H.L.

    2011-01-01

    Background & objectives: Chikungunya infection has become a public health threat in Malaysia since the 2008 nationwide outbreaks. Aedes albopictus Skuse has been identified as the chikungunya vector in Johor State during the outbreaks. In 2009, several outbreaks had been reported in the State of Kelantan. Entomological studies were conducted in Kelantan in four districts, namely Jeli, Tumpat, Pasir Mas and Tanah Merah to identify the vector responsible for the virus transmission. Methods: CHIKV cases records were obtained from State Health Department, Kelantan and localities involved were identified. Larva survey was conducted to collect the immature mosquito stages. Modified aspirators were used to collect the adult mosquitoes. All samples on dry ice were transferred to laboratory and the presence of the virus was detected using reverse transcriptase PCR. Results: A total of 1,245 mosquito larvae were collected during larval survey and 2,019 adult mosquitoes were collected using aspirator. From these collections, 640 mosquito pools were tested for the presence of CHIKV by RT-PCR but none found positive. Ae. albopictus was the most abundant mosquito collected, followed by Culex sp., Armigeres sp. and Anopheles sp. A total of 2, 814 artificial containers were inspected during the study. Interpretation & conclusions: Since none of the mosquito samples was found to be positive for chikungunya virus, the vector(s) of chikungunya virus in these localities could not be identified. PMID:21727669

  18. Chikungunya virus: is this the next emerging disease threat to the americas?

    PubMed

    Girimont, Trina M

    2014-12-01

    Chikungunya fever is a mosquito-borne infection for which no cure or vaccine is available. It made its first appearance in the Americas in December 2013. Seven months later, two locally acquired cases of the disease emerged in the United States. The emergence of chikungunya fever cases in the Americas emphasizes the need for sustained vector control, clear public health information, and disease awareness and surveillance. Copyright 2014, SLACK Incorporated.

  19. Emergence of chikungunya seropositivity in healthy Malaysian adults residing in outbreak-free locations: Chikungunya seroprevalence results from the Malaysian Cohort

    PubMed Central

    2013-01-01

    Background In 1998, Malaysia experienced its first chikungunya virus (CHIKV) outbreak in the suburban areas followed by another two in 2006 (rural areas) and 2008 (urban areas), respectively. Nevertheless, there is still a lack of documented data regarding the magnitude of CHIKV exposure in the Malaysian population. The aim of this study was to determine the extent of chikungunya virus infection in healthy Malaysian adults residing in outbreak-free locations. Methods A cross sectional study of chikungunya (CHIK) seroprevalence was carried out in 2009 amongst The Malaysian Cohort participants living in four states (Kuala Lumpur, Selangor, Pahang and Negeri Sembilan). A total of 945 participants were randomly identified for the study. Potential risk factors for CHIK infection were determined via questionnaires, and IgG antibodies against CHIK were detected by an enzyme-linked immunosorbent assay. Logistic regression identified risk factors associated with CHIK seropositivity, while geographical information system was used for visual and spatial analysis. Results From the 945 serum samples tested, 5.9% was positive for CHIK IgG. Being male, Malay, rural occupancy and Negeri Sembilan residency were identified as univariate predictors for CHIK seropositivity, while multivariate analysis identified being male and rural occupancy as risk factors. Conclusions This study provided evidence that CHIK is slowly emerging in Malaysia. Although the current baseline seroprevalence is low in this country, increasing number of CHIK cases reported to the Malaysia Ministry of Health imply the possibility of CHIK virus becoming endemic in Malaysia. PMID:23379541

  20. Compensatory Internalization of Pma1 in V-ATPase Mutants in Saccharomyces cerevisiae Requires Calcium- and Glucose-Sensitive Phosphatases.

    PubMed

    Velivela, Swetha Devi; Kane, Patricia M

    2018-02-01

    Loss of V-ATPase activity in organelles, whether through V-ATPase inhibition or V-ATPase ( vma ) mutations, triggers a compensatory downregulation of the essential plasma membrane proton pump Pma1 in Saccharomyces cerevisiae We have previously determined that the α-arrestin Rim8 and ubiquitin ligase Rsp5 are essential for Pma1 ubiquination and endocytosis in response to loss of V-ATPase activity. Here, we show that Pma1 endocytosis in V-ATPase mutants does not require Rim101 pathway components upstream and downstream of Rim8, indicating that Rim8 is acting independently in Pma1 internalization. We find that two phosphatases, the calcium-responsive phosphatase calcineurin and the glucose-sensitive phosphatase Glc7 (PP1), and one of the Glc7 regulatory subunits Reg1, exhibit negative synthetic genetic interactions with vma mutants, and demonstrate that both phosphatases are essential for ubiquitination and endocytic downregulation of Pma1 in these mutants. Although both acute and chronic loss of V-ATPase activity trigger the internalization of ∼50% of surface Pma1, a comparable reduction in Pma1 expression in a pma1-007 mutant neither compensates for loss of V-ATPase activity nor stops further Pma1 endocytosis. The results indicate that the cell surface level of Pma1 is not directly sensed and that internalized Pma1 may play a role in compensating for loss of V-ATPase-dependent acidification. Taken together, these results provide new insights into cross talk between two major proton pumps central to cellular pH control. Copyright © 2018 by the Genetics Society of America.

  1. Increase in cases of Guillain-Barré syndrome during a Chikungunya outbreak, French Polynesia, 2014 to 2015.

    PubMed

    Oehler, Erwan; Fournier, Emmanuel; Leparc-Goffart, Isabelle; Larre, Philippe; Cubizolle, Stéphanie; Sookhareea, Chantal; Lastère, Stéphane; Ghawche, Frédéric

    2015-01-01

    During the recent chikungunya fever outbreak in French Polynesia in October 2014 to March 2015, we observed an abnormally high number of patients with neurological deficit. Clinical presentation and complementary exams were suggestive of Guillain-Barré syndrome (GBS) for nine patients. All nine had a recent dengue-like syndrome and tested positive for chikungunya virus (CHIKV) in serology or RT-PCR. GBS incidence was increased four- to nine-fold during this period, suggesting a link to CHIKV infection.

  2. Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase

    NASA Astrophysics Data System (ADS)

    Sangeetha, Balasubramanian; Muthukumaran, Rajagopalan; Amutha, Ramaswamy

    2015-04-01

    The C-terminal domain (CTD) of HIV-1 integrase is a five stranded β-barrel resembling an SH3 fold. Mutational studies on isolated CTD and full-length IN have reported V260E mutant as either homo-dimerization defective or affecting the stability and folding of CTD. In this study, molecular dynamics simulation techniques were used to unveil the effect of V260E mutation on isolated CTD monomer and dimer. Both monomeric and dimeric forms of wild type and V260E mutant are highly stable during the simulated period. However, the stabilizing π-stacking interaction between Trp243 and Trp243' at the dimer interface is highly disturbed in CTD-V260E (>6 Å apart). The loss in entropy for dimerization is -30 and -25 kcal/mol for CTD-wt and CTD-V260E respectively signifying a weak hydrophobic interaction and its perturbation in CTD-V260E. The mutant Glu260 exhibits strong attraction/repulsion with all the basic/acidic residues of CTD. In addition to this, the dynamics of CTD-wild type and V260E monomers at 498 K was analyzed to elucidate the effect of V260E mutation on CTD folding. Increase in SASA and reduction in the number of contacts in CTD-V260E during simulation highlights the instability caused by the mutation. In general, V260E mutation affects both multimerization and protein folding with a pronounced effect on protein folding rather than multimerization. This study emphasizes the importance of the hydrophobic nature and SH3 fold of CTD in proper functioning of HIV integrase and perturbing this nature would be a rational approach toward designing more selective and potent allosteric anti-HIV inhibitors.

  3. Dynamics of Chikungunya Virus Cell Entry Unraveled by Single-Virus Tracking in Living Cells.

    PubMed

    Hoornweg, Tabitha E; van Duijl-Richter, Mareike K S; Ayala Nuñez, Nilda V; Albulescu, Irina C; van Hemert, Martijn J; Smit, Jolanda M

    2016-05-01

    Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne human pathogen causing major outbreaks in Africa, Asia, and the Americas. The cell entry pathway hijacked by CHIKV to infect a cell has been studied previously using inhibitory compounds. There has been some debate on the mechanism by which CHIKV enters the cell: several studies suggest that CHIKV enters via clathrin-mediated endocytosis, while others show that it enters independently of clathrin. Here we applied live-cell microscopy and monitored the cell entry behavior of single CHIKV particles in living cells transfected with fluorescent marker proteins. This approach allowed us to obtain detailed insight into the dynamic events that occur during CHIKV entry. We observed that almost all particles fused within 20 min after addition to the cells. Of the particles that fused, the vast majority first colocalized with clathrin. The average time from initial colocalization with clathrin to the moment of membrane fusion was 1.7 min, highlighting the rapidity of the cell entry process of CHIKV. Furthermore, these results show that the virus spends a relatively long time searching for a receptor. Membrane fusion was observed predominantly from within Rab5-positive endosomes and often occurred within 40 s after delivery to endosomes. Furthermore, we confirmed that a valine at position 226 of the E1 protein enhances the cholesterol-dependent membrane fusion properties of CHIKV. To conclude, our work confirms that CHIKV enters cells via clathrin-mediated endocytosis and shows that fusion occurs from within acidic early endosomes. Since its reemergence in 2004, chikungunya virus (CHIKV) has spread rapidly around the world, leading to millions of infections. CHIKV often causes chikungunya fever, a self-limiting febrile illness with severe arthralgia. Currently, no vaccine or specific antiviral treatment against CHIKV is available. A potential antiviral strategy is to interfere with the cell entry process of the

  4. [Dengue, Zika and Chikungunya].

    PubMed

    Kantor, Isabel N

    2016-01-01

    Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation.

  5. Knowledge and practice regarding dengue and chikungunya: a cross-sectional study among Healthcare workers and community in Northern Tanzania.

    PubMed

    Kajeguka, Debora C; Desrochers, Rachelle E; Mwangi, Rose; Mgabo, Maseke R; Alifrangis, Michael; Kavishe, Reginald A; Mosha, Franklin W; Kulkarni, Manisha A

    2017-05-01

    To investigate knowledge and prevention practices regarding dengue and chikungunya amongst community members, as well as knowledge, treatment and diagnostic practices among healthcare workers. We conducted a cross-sectional survey with 125 community members and 125 healthcare workers from 13 health facilities in six villages in the Hai district of Tanzania. A knowledge score was generated based on participant responses to a structured questionnaire, with a score of 40 or higher (of 80 and 50 total scores for community members and healthcare workers, respectively) indicating good knowledge. We conducted qualitative survey (n = 40) to further assess knowledge and practice regarding dengue and chikungunya fever. 15.2% (n = 19) of community members had good knowledge regarding dengue, whereas 53.6%, (n = 67) of healthcare workers did. 20.3% (n = 16) of participants from lowland areas and 6.5% (n = 3) from highland areas had good knowledge of dengue (χ 2 = 4.25, P = 0.03). Only 2.4% (n = 3) of all participants had a good knowledge score for chikungunya. In the qualitative study, community members expressed uncertainty about dengue and chikungunya. Some healthcare workers thought that they were new diseases. There is insufficient knowledge regarding dengue and chikungunya fever among community members and healthcare workers. Health promotion activities on these diseases based on Ecological Health Mode components to increase knowledge and improve preventive practices should be developed. © 2017 John Wiley & Sons Ltd.

  6. Combined BRAF and HSP90 inhibition in patients with unresectable BRAF V600E mutant melanoma.

    PubMed

    Eroglu, Zeynep; Chen, Yian Ann; Gibney, Geoffrey T; Weber, Jeffrey S; Kudchadkar, Ragini R; Khushalani, Nikhil I; Markowitz, Joseph; Brohl, Andrew S; Tetteh, Leticia F; Ramadan, Howida; Arnone, Gina; Li, Jiannong; Zhao, Xiuhua; Sharma, Ritin; Darville, Lancia N F; Fang, Bin; Smalley, Inna; Messina, Jane L; Koomen, John M; Sondak, Vernon K; Smalley, Keiran S M

    2018-04-19

    BRAF inhibitors are clinically active in patients with advanced BRAF V600 -mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAF V600 -mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose. Correlative proteomic studies were performed to confirm HSP inhibitor activity. Objective responses were observed in 15/20 evaluable patients (75%; 95% CI: 51-91%), with 3 complete and 12 partial responses. Median progression-free and overall survival were 9.2 months (95% CI: 3.8-not reached) and 34.6 months (6.2-not reached), respectively. The most common grade 3/4 toxicities were skin toxicities such as rash (n=4, 19%) and cutaneous squamous cell carcinomas (n=3, 14%), along with diarrhea (n=3, 14%). Pharmacodynamic analysis of patients' PBMCs showed increased day 8 HSP70 expression compared to baseline in the three cohorts with XL888 doses ≥45 mg. Diverse effects of vemurafenib-XL888 upon intratumoral HSP-client protein expression were noted, with the expression of multiple proteins (including ERBB3 and BAD) modulated on therapy. XL888 in combination with vemurafenib has clinical activity in patients with advanced BRAF V600 -mutant melanoma, with a tolerable side-effect profile. HSP90 inhibitors warrant further evaluation in combination with current standard-of-care BRAF plus MEK inhibitors in BRAF V600 -mutant melanoma. Copyright ©2018, American Association for Cancer Research.

  7. Genetic divergence of Chikungunya viruses in India (1963-2006) with special reference to the 2005-2006 explosive epidemic.

    PubMed

    Arankalle, Vidya A; Shrivastava, Shubham; Cherian, Sarah; Gunjikar, Rashmi S; Walimbe, Atul M; Jadhav, Santosh M; Sudeep, A B; Mishra, Akhilesh C

    2007-07-01

    Re-emergence of Chikungunya (CHIK), caused by CHIK virus, was recorded in India during 2005-2006 after a gap of 32 years, causing 1.3 million cases in 13 states. Several islands of the Indian Ocean reported similar outbreaks in the same period. These outbreaks were attributed to the African genotype of CHIK virus. To examine relatedness of the Indian isolates (IND-06) with Reunion Island isolates (RU), full-genome sequences of five CHIK virus isolates representative of different Indian states were determined. In addition, an isolate obtained from mosquitoes in the year 2000 (Yawat-2000), identified as being of the African genotype, and two older strains isolated in 1963 and 1973 (of the Asian genotype), were sequenced. The IND-06 isolates shared 99.9 % nucleotide identity with RU isolates, confirming involvement of the same strain in these outbreaks. The IND-06 isolates shared 98.2 % identity with the Yawat-2000 isolate. Of two crucial substitutions reported for RU isolates in the E1 region, M269V was noted in the Yawat-2000 and IND-06 isolates, whereas D284E was seen only in the IND-06 isolates. The A226V shift observed with the progression of the epidemic in Reunion Island, probably associated with adaptation to the mosquito vector, was absent in all of the Indian isolates. Three unique substitutions were noted in the IND-06 isolates: two (T128K and T376M) in the Nsp1 region and one (P23S) in the capsid protein. The two Asian strains showed 99.4 % nucleotide identity to each other, indicating relative stability of the virus. No evidence of recombination of the Asian and African genotypes, or of positive selection was observed. The results may help in understanding the association, if any, of the unique mutations with the explosive nature of the CHIK outbreak.

  8. A change in structural integrity of c-Kit mutant D816V causes constitutive signaling.

    PubMed

    Raghav, Pawan Kumar; Singh, Ajay Kumar; Gangenahalli, Gurudutta

    2018-03-01

    Several signaling pathways, ligands, and genes that regulate proliferative and self-renewal properties of the Hematopoietic Stem Cells (HSCs) have been studied meticulously. One of the signaling pathways that play a crucial role in the process of hematopoiesis is the Stem Cell Factor (SCF) mediated c-Kit pathway. The c-Kit is a Receptor Tyrosine Kinase (RTK), which is expressed in the cells including HSCs. It undergoes dimerization upon binding with its cognate ligand SCF. As a result, phosphorylation of the Juxtamembrane (JM) domain of c-Kit takes place at Tyr568 and Tyr570 residues. These phosphorylated residues become the docking sites for protein tyrosine phosphatases (PTPs) namely SHP-1 and SHP-2, which in turn cause dephosphorylation and negative regulation of the downstream signaling responsible for the cell proliferation. Interestingly, it has been reported that the mutation of c-Kit at D816V makes it independent of SCF stimulation and SHP-1/SHP-2 inhibition, thereby, causing its constitutive activation. The present study was commenced to elucidate the structural behavior of this mutation in the JM and A-loop region of c-Kit using Molecular Dynamics (MD) simulations of the wild-type and mutant c-Kit in unphosphorylated and phosphorylated states. The energy difference computed between the wild type and mutant (D816V) c-Kit, and protein-protein docking and complex analysis revealed the impact of this single residue mutation on the integrity dynamics of c-Kit that makes it independent of SHP-1/SHP-2 negative regulation. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

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

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Denguemore » and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.« less

  10. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    NASA Astrophysics Data System (ADS)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-12-01

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  11. CHIKRisk: Global monitoring & mapping of chikungunya risk

    USDA-ARS?s Scientific Manuscript database

    The 2013 Chikungunya outbreak in the Americas demonstrated the importance of readiness in assessing potential risk of the emergence of vector-borne diseases. More thatn 1.7 million suspected cases occurred and the disease spread to 33 countries and territories in 8 months. Climate and ecological con...

  12. A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis

    PubMed Central

    Wu, Fenfen; Mi, Wentao; Burns, Dennis K.; Fu, Yu; Gray, Hillery F.; Struyk, Arie F.; Cannon, Stephen C.

    2011-01-01

    Hypokalemic periodic paralysis (HypoPP) is an ion channelopathy of skeletal muscle characterized by attacks of muscle weakness associated with low serum K+. HypoPP results from a transient failure of muscle fiber excitability. Mutations in the genes encoding a calcium channel (CaV1.1) and a sodium channel (NaV1.4) have been identified in HypoPP families. Mutations of NaV1.4 give rise to a heterogeneous group of muscle disorders, with gain-of-function defects causing myotonia or hyperkalemic periodic paralysis. To address the question of specificity for the allele encoding the NaV1.4-R669H variant as a cause of HypoPP and to produce a model system in which to characterize functional defects of the mutant channel and susceptibility to paralysis, we generated knockin mice carrying the ortholog of the gene encoding the NaV1.4-R669H variant (referred to herein as R669H mice). Homozygous R669H mice had a robust HypoPP phenotype, with transient loss of muscle excitability and weakness in low-K+ challenge, insensitivity to high-K+ challenge, dominant inheritance, and absence of myotonia. Recovery was sensitive to the Na+/K+-ATPase pump inhibitor ouabain. Affected fibers had an anomalous inward current at hyperpolarized potentials, consistent with the proposal that a leaky gating pore in R669H channels triggers attacks, whereas a reduction in the amplitude of action potentials implies additional loss-of-function changes for the mutant NaV1.4 channels. PMID:21881211

  13. The Chikungunya Epidemic on La Réunion Island in 2005–2006: A Cost-of-Illness Study

    PubMed Central

    Soumahoro, Man-Koumba; Boelle, Pierre-Yves; Gaüzere, Bernard-Alex; Atsou, Kokuvi; Pelat, Camille; Lambert, Bruno; La Ruche, Guy; Gastellu-Etchegorry, Marc; Renault, Philippe; Sarazin, Marianne; Yazdanpanah, Yazdan; Flahault, Antoine; Malvy, Denis; Hanslik, Thomas

    2011-01-01

    Background This study was conducted to assess the impact of chikungunya on health costs during the epidemic that occurred on La Réunion in 2005–2006. Methodology/Principal Findings From data collected from health agencies, the additional costs incurred by chikungunya in terms of consultations, drug consumption and absence from work were determined by a comparison with the expected costs outside the epidemic period. The cost of hospitalization was estimated from data provided by the national hospitalization database for short-term care by considering all hospital stays in which the ICD-10 code A92.0 appeared. A cost-of-illness study was conducted from the perspective of the third-party payer. Direct medical costs per outpatient and inpatient case were evaluated. The costs were estimated in Euros at 2006 values. Additional reimbursements for consultations with general practitioners and drugs were estimated as €12.4 million (range: €7.7 million–€17.1 million) and €5 million (€1.9 million–€8.1 million), respectively, while the cost of hospitalization for chikungunya was estimated to be €8.5 million (€5.8 million–€8.7 million). Productivity costs were estimated as €17.4 million (€6 million–€28.9 million). The medical cost of the chikungunya epidemic was estimated as €43.9 million, 60% due to direct medical costs and 40% to indirect costs (€26.5 million and €17.4 million, respectively). The direct medical cost was assessed as €90 for each outpatient and €2,000 for each inpatient. Conclusions/Significance The medical management of chikungunya during the epidemic on La Réunion Island was associated with an important economic burden. The estimated cost of the reported disease can be used to evaluate the cost/efficacy and cost/benefit ratios for prevention and control programmes of emerging arboviruses. PMID:21695162

  14. Waiting for chikungunya fever in Argentina: spatio-temporal risk maps

    PubMed Central

    Carbajo, Aníbal E; Vezzani, Darío

    2015-01-01

    Chikungunya virus (CHIKV) transmission has been detected in America in 2013 and recently reached south up to Bolivia, Brazil and Paraguay, bordering countries of Argentina. The presence of the mosquito Aedes aegypti in half of the country together with the regional context drove us to make a rapid assessment of transmission risk. Temperature thresholds for vector breeding and for virus transmission, together with adult activity from the literature, were mapped on a monthly basis to estimate risk. Transmission of chikungunya by Ae. aegypti in the world was seen at monthly mean temperatures from 21-34ºC, with the majority occurring between 26-28ºC. In Argentina temperatures above 21ºC are observed since September in the northeast, expanding south until January and retreating back to the northeast in April. The maximum area under risk encompasses more than half the country and around 32 million inhabitants. Vector adult activity was registered where monthly means temperatures exceeded 13ºC, in the northeast all over the year and in the northern half from September-May. The models herein proposed show that conditions for transmission are already present. Considering the regional context and the historic inability to control dengue in the region, chikungunya fever illness seems unavoidable. PMID:25946252

  15. Observation of a Neutral Structure near the D D¯* Mass Threshold in e+e-→(D D¯ *)0π0 at √{s }=4.226 and 4.257 GeV

    NASA Astrophysics Data System (ADS)

    Ablikim, M.; Achasov, M. N.; Ai, X. C.; Albayrak, O.; Albrecht, M.; Ambrose, D. J.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Ferroli, R. Baldini; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, H. Y.; Chen, J. C.; Chen, M. L.; Chen, S. Chen; Chen, S. J.; Chen, X.; Chen, X. R.; Chen, Y. B.; Cheng, H. P.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Duan, P. F.; Fan, J. Z.; Fang, J.; Fang, S. S.; Fang, X.; Fang, Y.; Fava, L.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. L.; Gao, X. Y.; Gao, Y.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, R. P.; Guo, Y.; Guo, Y. P.; Haddadi, Z.; Hafner, A.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, X. Q.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, J. F.; Hu, T.; Hu, Y.; Huang, G. M.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, Y.; Hussain, T.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, L. W.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Kiese, P.; Kliemt, R.; Kloss, B.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kühn, W.; Kupsc, A.; Lange, J. S.; Lara, M.; Larin, P.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, H. J.; Li, J. C.; Li, Jin; Li, K.; Li, K.; Li, Lei; Li, P. R.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. M.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, J. J.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B. J.; Liu, C. X.; Liu, D.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. H.; Liu, H. H.; Liu, H. M.; Liu, J.; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqing; Loehner, H.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, M. M.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Maas, F. E.; Maggiora, M.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Messchendorp, J. G.; Min, J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales, C. Morales; Moriya, K.; Muchnoi, N. Yu.; Muramatsu, H.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pan, Y.; Patteri, P.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Poling, R.; Prasad, V.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, L. Q.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Ripka, M.; Rong, G.; Rosner, Ch.; Ruan, X. D.; Sarantsev, A.; Savrié, M.; Schoenning, K.; Schumann, S.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Shi, M.; Song, W. M.; Song, X. Y.; Sosio, S.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. H.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tapan, I.; Thorndike, E. H.; Tiemens, M.; Ullrich, M.; Uman, I.; Varner, G. S.; Wang, B.; Wang, D.; Wang, D. Y.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, S. G.; Wang, W.; Wang, W. P.; Wang, X. F.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Wang, Z. Y.; Weber, T.; Wei, D. H.; Wei, J. B.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, L. J.; Wu, Z.; Xia, L.; Xia, L. G.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, J. J.; Xu, L.; Xu, Q. J.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y.; Yang, Y. X.; Ye, M.; Ye, M. H.; Yin, J. H.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zeng, Z.; Zhang, B. X.; Zhang, B. Y.; Zhang, C.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. N.; Zhang, Y. H.; Zhang, Y. T.; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, Q. W.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zotti, L.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

    2015-11-01

    A neutral structure in the D D¯* system around the D D¯* mass threshold is observed with a statistical significance greater than 10 σ in the processes e+e-→D+D*-π0+c . c . and e+e-→D0D¯ *0π0+c . c . at √{s }=4.226 and 4.257 GeV in the BESIII experiment. The structure is denoted as Zc(3885 )0. Assuming the presence of a resonance, its pole mass and width are determined to be [3885. 7-5.7+4.3 (stat )±8.4 (syst )] MeV /c2 and [3 5-12+11(stat )±15 (syst )] MeV , respectively. The Born cross sections are measured to be σ [e+e-→Zc(3885 )0π0,Zc(3885 )0→D D¯ *]=[77 ±13 (stat )±17 (syst )] pb at 4.226 GeV and [47 ±9 (stat )±10 (syst )] pb at 4.257 GeV. The ratio of decay rates B [Zc(3885 )0→D+D*-+c .c .] /B [Zc(3885 )0→D0D¯ *0+c .c .] is determined to be 0.96 ±0.18 (stat )±0.12 (syst ) , consistent with no isospin violation in the process, Zc(3885 )0→D D¯*.

  16. Chikungunya fever: CNS infection and pathologies of a re-emerging arbovirus.

    PubMed

    Das, Trina; Jaffar-Bandjee, Marie Christine; Hoarau, Jean Jacques; Krejbich Trotot, Pascale; Denizot, Melanie; Lee-Pat-Yuen, Ghislaine; Sahoo, Renubala; Guiraud, Pascale; Ramful, Duksha; Robin, Stephanie; Alessandri, Jean Luc; Gauzere, Bernard Alex; Gasque, Philippe

    2010-06-01

    Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes an acute symptomatic illness with fever, skin rash, and incapacitating arthralgia, which can evolve into chronic rheumatoid arthritis in elderly patients. This is a tropical disease originally described in central/east Africa in the 1960s, but its 2004 re-emergence in Africa and rapid spread in lands in and around the Indian Ocean (Reunion island, India, Malaysia) as well as Europe (Italy) led to almost 6 million cases worldwide. The risk of importation and spreading diseases with long-term sequelae is even greater today given the global distribution of the vectors (including in the Americas), increased tourism and the apparent capacity of CHIKV to produce high levels of viremia (10(9)-10(12) virus/ml of blood) and new mutants. CHIKV-associated neuropathology was described early in the 1960s, but it is the unprecedented incidence rate in Indian Ocean areas with efficient clinical facilities that allowed a better description of cases with severe encephalitis, meningoencephalitis, peripheral neuropathies and deaths among newborns (mother-to-child infection), infants and elderly patients. Death rates following CHIKV infection were estimated at 1:1000 cases in la Reunion's outbreak. These clinical observations have been corroborated by experimental infection in several mouse models, leading to CNS pathologies. We further describe in this review the capacity of CHIKV to infect neurons and glial cells, delineate the fundamental innate (intrinsic) immune defence mechanisms to protect from infection and argue about the possible mechanisms involved in the encephalopathy. (c) 2010 Elsevier Ltd. All rights reserved.

  17. Cold-sensitive mutants G680V and G691C of Dictyostelium myosin II confer dramatically different biochemical defects.

    PubMed

    Patterson, B; Ruppel, K M; Wu, Y; Spudich, J A

    1997-10-31

    Cold-sensitive myosin mutants represent powerful tools for dissecting discrete deficiencies in myosin function. Biochemical characterization of two such mutants, G680V and G691C, has allowed us to identify separate facets of myosin motor function perturbed by each alteration. Compared with wild type, the G680V myosin exhibits a substantially enhanced affinity for several nucleotides, decreased ATPase activity, and overoccupancy or creation of a novel strongly actin-binding state. The properties of the novel strong binding state are consistent with a partial arrest or pausing at the onset of the mechanical stroke. The G691C mutant, on the other hand, exhibits an elevated basal ATPase indicative of premature phosphate release. By releasing phosphate without a requirement for actin binding, the G691C can bypass the part of the cycle involving the mechanical stroke. The two mutants, despite having alterations in glycine residues separated by only 11 residues, have dramatically different consequences on the mechanochemical cycle.

  18. Clinical Features and Neurologic Complications of Children Hospitalized With Chikungunya Virus in Honduras.

    PubMed

    Samra, José A; Hagood, Nancy L; Summer, Andrea; Medina, Marco T; Holden, Kenton R

    2017-07-01

    The first case of Chikungunya virus in Honduras was identified in 2014. The virus has spread widely across Honduras via the Aedes aegypti mosquito, leading to an outbreak of Chikungunya virus (CHIKV) in 2015 that significantly impacted children. A retrospective chart review of 235 children diagnosed with CHIKV and admitted to the National Autonomous University of Honduras Hospital Escuela (Hospital Escuela) in Tegucigalpa, Honduras, was accomplished with patients who were assessed for clinical features and neurologic complications. Of 235 children admitted to Hospital Escuela with CHIKV, the majority had symptoms of fever, generalized erythematous rash, and irritability. Fourteen percent had clinical arthritis. Ten percent of patients had seizures. Six percent had meningoencephalitis. There were 2 childhood deaths during the course of this study, one from meningoencephalitis and another from myocarditis. Chikungunya virus can cause severe complications in children, the majority of which impact the central nervous system.

  19. Acquired auditory neuropathy spectrum disorder after an attack of chikungunya: case study.

    PubMed

    Prabhu, Prashanth

    2016-01-01

    Auditory neuropathy spectrum disorder (ANSD) is a retrocochlear disorder in which the cochlear functioning is normal but the transmission in the auditory neural pathway is affected. The present study reports of a 14-year-old teenager with acquired ANSD after an attack of chikungunya. He reported symptoms of difficulty in understanding speech, tinnitus and vertigo when exposed to loud sounds. The audiological characteristics suggested auditory neuropathy spectrum disorder with raising audiogram configuration. The results of tinnitus evaluation showed low-pitched tinnitus and it was persistent causing significant handicap to him based on self report tinnitus handicap questionnaire results. The results of depression, anxiety and stress scale also suggested symptoms of mild depression and anxiety. Chikungunya virus is suspected to be neurotropic in nature which can damage auditory nerve cells and may have caused ANSD. The result also shows presence of tullio's phenomenon and absence of cervical vestibular evoked myogenic potentials suggesting damage to the vestibular neuronal system. The possible pathophysiology of chikungunya virus causing ANSD and vestibular symptoms needs to be explored further in future studies.

  20. A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs

    PubMed Central

    Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F.; Lecuit, Marc

    2016-01-01

    Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents. PMID:27177310

  1. A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

    PubMed

    Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F; Lecuit, Marc

    2016-05-12

    Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents.

  2. Molecular Characterization of Chikungunya Virus, Philippines, 2011-2013.

    PubMed

    Sy, Ava Kristy; Saito-Obata, Mariko; Medado, Inez Andrea; Tohma, Kentaro; Dapat, Clyde; Segubre-Mercado, Edelwisa; Tandoc, Amado; Lupisan, Socorro; Oshitani, Hitoshi

    2016-05-01

    During 2011-2013, a nationwide outbreak of chikungunya virus infection occurred in the Philippines. The Asian genotype was identified as the predominant genotype; sporadic cases of the East/Central/South African genotype were detected in Mindanao. Further monitoring is needed to define the transmission pattern of this virus in the Philippines.

  3. Modelling the effects of global climate change on Chikungunya transmission in the 21st century.

    PubMed

    Tjaden, Nils B; Suk, Jonathan E; Fischer, Dominik; Thomas, Stephanie M; Beierkuhnlein, Carl; Semenza, Jan C

    2017-06-19

    The arrival and rapid spread of the mosquito-borne viral disease Chikungunya across the Americas is one of the most significant public health developments of recent years, preceding and mirroring the subsequent spread of Zika. Globalization in trade and travel can lead to the importation of these viruses, but climatic conditions strongly affect the efficiency of transmission in local settings. In order to direct preparedness for future outbreaks, it is necessary to anticipate global regions that could become suitable for Chikungunya transmission. Here, we present global correlative niche models for autochthonous Chikungunya transmission. These models were used as the basis for projections under the representative concentration pathway (RCP) 4.5 and 8.5 climate change scenarios. In a further step, hazard maps, which account for population densities, were produced. The baseline models successfully delineate current areas of active Chikungunya transmission. Projections under the RCP 4.5 and 8.5 scenarios suggest the likelihood of expansion of transmission-suitable areas in many parts of the world, including China, sub-Saharan Africa, South America, the United States and continental Europe. The models presented here can be used to inform public health preparedness planning in a highly interconnected world.

  4. Health-related impact on quality of life and coping strategies for chikungunya: A qualitative study in Curaçao

    PubMed Central

    Grobusch, Martin P.; Tami, Adriana; Gerstenbluth, Izzy; Bailey, Ajay

    2017-01-01

    Introduction Chikungunya is an emerging public health problem in tropical and subtropical regions, due to ongoing transmission and its incapacitating acute disease phase, and chronic sequelae. The disease is responsible for a major impact on Health Related Quality of Life (HRQoL), which may last several years. To our knowledge, this study is the first qualitative examination of HRQoL and coping strategies of chikungunya-infected individuals. Methods Qualitative research methods consisted of 20 in-depth interviews and seven Focus Group Discussions (FGDs), n = 50. Analysis was based on the principles of the grounded theory. Results Different impacts on HRQoL were reported. The physical and emotional domains of the HRQoL were mainly affected by chikungunya, while social and individual financial consequences were limited. Individual financial impact was limited through the universal health care program of Curaçao. Long-term lingering musculoskeletal and other manifestations caused significant pain and limited mobility. Hence, participants experienced dependency, impairment of normal daily life activities, moodiness, hopelessness, a change of identity, and insecurity about their future. The unpredictable nature and consequences of chikungunya gave rise to various coping strategies. Problem-focused coping styles led to higher uptake of medical care and were linked to more negative impact of HRQoL, whereas emotional coping strategies focusing on acceptance of the situation were linked to less uptake of medical care and more positive impact on HRQoL. Conclusions This study provides an in-depth understanding of acute and long-term HRQoL impact of chikungunya. The results can better inform health promotion policies and interventions. Messages to the public should focus on promoting healthy and efficient coping strategies, in order to prevent additional stress in affected individuals. PMID:28991920

  5. Curcumin and Boswellia serrata gum resin extract inhibit chikungunya and vesicular stomatitis virus infections in vitro.

    PubMed

    von Rhein, Christine; Weidner, Tatjana; Henß, Lisa; Martin, Judith; Weber, Christopher; Sliva, Katja; Schnierle, Barbara S

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes chikungunya fever and has infected millions of people mainly in developing countries. The associated disease is characterized by rash, high fever, and severe arthritis that can persist for years. CHIKV has adapted to Aedes albopictus, which also inhabits temperate regions including Europe and the United States of America. CHIKV has recently caused large outbreaks in Latin America. No treatment or licensed CHIKV vaccine exists. Traditional medicines are known to have anti-viral effects; therefore, we examined whether curcumin or Boswellia serrata gum resin extract have antiviral activity against CHIKV. Both compounds blocked entry of CHIKV Env-pseudotyped lentiviral vectors and inhibited CHIKV infection in vitro. In addition, vesicular stomatitis virus vector particles and viral infections were also inhibited to the same extent, indicating a broad antiviral activity. Although the bioavailability of these compounds is rather poor, they might be used as a lead structure to develop more effective antiviral drugs or might be used topically to prevent CHIKV spread in the skin after mosquito bites. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Ce-Fe-modified zeolite-rich tuff to remove Ba(2+)-like (226)Ra(2+) in presence of As(V) and F(-) from aqueous media as pollutants of drinking water.

    PubMed

    Olguín, María Teresa; Deng, Shuguang

    2016-01-25

    The sorption behavior of the Ba(2+)-like (226)Ra(2+) in the presence of H2AsO4(-)/HAsO4(2-) and F(-) from aqueous media using Ce-Fe-modified zeolite-rich tuff was investigated in this work. The Na-modified zeolite-rich tuff was also considered for comparison purposes. The zeolite-rich tuff collected from Wyoming (US) was in contact with NaCl and CeCl3-FeCl3 solutions to obtain the Na- and Ce-Fe-modified zeolite-rich tuffs (ZUSNa and ZUSCeFe). These zeolites were characterized by scanning electron microscopy and X-ray diffraction. The BET-specific surface and the points of zero charge were determined as well as the content of Na, Ce and Fe by neutron activation analysis. The textural characteristics and the point of zero charge were changed by the presence of Ce and Fe species in the zeolitic network. A linear model described the Ba(2+)-like (226)Ra(2+) sorption isotherms and the distribution coefficients (Kd) varied with respect to the metallic species present in the zeolitic material. The As(V) oxianionic chemical species and F(-) affected this parameter when the Ba(2+)-like (226)Ra(2+)-As(V)-F(-) solutions were in contact with ZUSCeFe. The H2AsO4(-)/HAsO4(2-) and F(-) were adsorbed by ZUSCeFe in the same amount, independent of the concentration of Ba(2+)-like (226)Ra(2+) in the initial solution. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Association of human leukocyte antigen class II allele and haplotypes in chikungunya viral infection in a western Indian population.

    PubMed

    Thanapati, Subrat; Hande, Aparna; Das, Rumki; Gurav, Yogesh; Tripathy, Anuradha S

    2014-05-01

    Genes coding for human leukocyte antigen (HLA) class II molecules are polymorphic and have been shown to influence susceptibility to viral diseases. One hundred patients with acute chikungunya with and without viral load and 250 chikungunya negative controls from western India were studied for the distribution of HLA class II alleles by PCR with sequence-specific primer (SSP) method. Frequency of DRB1*11 allele group (patients vs controls: p=0.002, Pc=0.036, OR=0.21) and haplotype DRB1*11/DQB1*03 (patients vs controls: p=0.007, OR=0.15) were significantly low, while haplotype DRB1*04/DQB1*03 (patients vs controls: p=0.042, OR=1.94) was significantly high in the patient population. HLA DQB1*04 allele was found only in the patient group with viral load (n=17), suggesting possible involvement of the same with chikungunya virus (CHIKV) replication. Association of HLA-DRB1*11 and the emergence of DRB1*11/DQB1*03 & DRB1*04/DQB1*03 as resistant and susceptible haplotypes towards CHIKV infection is being reported for the first time. Our results suggest that genetic susceptibility and/or resistance to chikungunya infection may be modulated by HLA class II alleles.

  8. ⁵¹V NMR Crystallography of Vanadium Chloroperoxidase and Its Directed Evolution P395D/L241V/T343A Mutant: Protonation Environments of the Active Site.

    PubMed

    Gupta, Rupal; Hou, Guangjin; Renirie, Rokus; Wever, Ron; Polenova, Tatyana

    2015-04-29

    Vanadium-dependent haloperoxidases (VHPOs) perform two-electron oxidation of halides using hydrogen peroxide. Their mechanism, including the factors determining the substrate specificity and the pH-dependence of the catalytic rates, is poorly understood. The vanadate cofactor in the active site of VHPOs contains "spectroscopically silent" V(V), which does not change oxidation state during the reaction. We employed an NMR crystallography approach based on (51)V magic angle spinning NMR spectroscopy and Density Functional Theory, to gain insights into the structure and coordination environment of the cofactor in the resting state of vanadium-dependent chloroperoxidases (VCPO). The cofactor environments in the wild-type VCPO and its P395D/L241V/T343A mutant exhibiting 5-100-fold improved catalytic activity are examined at various pH values. Optimal sensitivity attained due to the fast MAS probe technologies enabled the assignment of the location and number of protons on the vanadate as a function of pH. The vanadate cofactor changes its protonation from quadruply protonated at pH 6.3 to triply protonated at pH 7.3 to doubly protonated at pH 8.3. In contrast, in the mutant, the vanadate protonation is the same at pH 5.0 and 8.3, and the cofactor is doubly protonated. This methodology to identify the distinct protonation environments of the cofactor, which are also pH-dependent, could help explain the different reactivities of the wild-type and mutant VCPO and their pH-dependence. This study demonstrates that (51)V-based NMR crystallography can be used to derive the detailed coordination environments of vanadium centers in large biological molecules.

  9. 12 CFR 226.16 - Advertising.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Advertising. 226.16 Section 226.16 Banks and... LENDING (REGULATION Z) Open-End Credit § 226.16 Advertising. (a) Actually available terms. If an... accordance with § 226.5a do not constitute advertising terms for purposes of the requirements of this section...

  10. Enzymatic analysis of a thermostabilized mutant of an Escherichia coli hygromycin B phosphotransferase.

    PubMed

    Nakamura, Akira; Takakura, Yasuaki; Sugimoto, Naohisa; Takaya, Naoki; Shiraki, Kentaro; Hoshino, Takayuki

    2008-09-01

    An Escherichia coli hygromycin B phosphotransferase (HPH) and its thermostabilized mutant protein, HPH5, containing five amino acid substitutions, D20G, A118V, S225P, Q226L, and T246A (Nakamura et al., J. Biosci. Bioeng., 100, 158-163 (2005)), obtained by an in vivo directed evolution procedure in Thermus thermophilus, were produced and purified from E. coli recombinants, and enzymatic comparisons were performed. The optimum temperatures for enzyme activity were 50 and 55 degrees C for HPH and HPH5 respectively, but the thermal stability of the enzyme activity and the temperature for protein denaturation of HPH5 increased, from 36 and 37.2 degrees C of HPH to 53 and 58.8 degrees C respectively. Specific activities and steady-state kinetics measured at 25 degrees C showed only slight differences between the two enzymes. From these results we concluded that HPH5 was thermostabilized at the protein level, and that the mutations introduced did not affect its enzyme activity, at least under the assay conditions.

  11. 22 CFR 226.10 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Purpose. 226.10 Section 226.10 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Pre-award Requirements § 226.10 Purpose. Sections 226.11 through 226.17 prescribe forms and...

  12. 22 CFR 226.70 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Purpose. 226.70 Section 226.70 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS After-the-Award Requirements § 226.70 Purpose. Sections 226.71 through 226.73 contain closeout...

  13. Sequential Chikungunya and Zika Virus Infections in a Traveler from Honduras.

    PubMed

    Norman, Francesca F; Chamorro, Sandra; Vázquez, Ana; Sánchez-Seco, María-Paz; Pérez-Molina, José-Antonio; Monge-Maillo, Begoña; Vivancos, María-Jesús; Rodríguez-Dominguez, Mario; Galán, Juan-Carlos; de Ory, Fernando; López-Vélez, Rogelio

    2016-11-02

    Zika virus (ZIKV) and chikungunya virus (CHIKV) are currently circulating in overlapping areas in the American continents and may both be transmitted by Aedes spp. mosquitoes. The first documented case, to the authors' knowledge, of sequential CHIKV and ZIKV infections diagnosed in a nonendemic area in a returning traveler is reported. The implications for heightened clinical surveillance for these infections and specific patient recommendations are emphasized. © The American Society of Tropical Medicine and Hygiene.

  14. Rheumatic manifestations associated with Chikungunya virus infection: A study of 307 patients with 32-month follow-up (RHUMATOCHIK study).

    PubMed

    Bouquillard, Eric; Fianu, Adrian; Bangil, Marianne; Charlette, Nathalie; Ribéra, Anne; Michault, Alain; Favier, François; Simon, Fabrice; Flipo, René-Marc

    2018-03-01

    In the wake of the Chikungunya epidemic which struck Reunion Island in 2005 and 2006, we conducted a prospective, multicentre study (RHUMATOCHIK) whose main objective was analyse the characteristics and progression of rheumatic manifestations in patients with post-Chikungunya joint pain. A cohort of 307 consecutively included patients underwent rheumatological examinations for pain secondary to Chikungunya virus infection. The long-term evaluation was conducted by telephone survey 1 and 2 years after the onset of the viral infection. At inclusion, mean age was 54 years (24-87) and 83.1% of the patients were female. Chronic joint pain was associated with synovitis in 64.2% of the patients, affecting primarily the wrists, the proximal interphalangeal joints of the fingers, and the ankles. Attempts to detect the viral genome in joint fluid (10 patients) and synovial tissue (6 patients) using the RT-PCR technique were repeatedly unsuccessful. With a mean follow-up of 32 months, joint pain persisted in 83.1% of the patients. Functional impairment, however, was moderate, with a HAQ score of 0.44±0.5. Chikungunya virus infection is frequently the cause of joint manifestations that can persist for several months, or even several years. In some cases, the clinical symptoms closely resemble those usually associated with rheumatoid arthritis. Further studies are necessary to improve the therapeutic management of these patients. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  15. Switch II Mutants Reveal Coupling between the Nucleotide- and Actin-Binding Regions in Myosin V

    PubMed Central

    Trivedi, Darshan V.; David, Charles; Jacobs, Donald J.; Yengo, Christopher M.

    2012-01-01

    Conserved active-site elements in myosins and other P-loop NTPases play critical roles in nucleotide binding and hydrolysis; however, the mechanisms of allosteric communication among these mechanoenzymes remain unresolved. In this work we introduced the E442A mutation, which abrogates a salt-bridge between switch I and switch II, and the G440A mutation, which abolishes a main-chain hydrogen bond associated with the interaction of switch II with the γ phosphate of ATP, into myosin V. We used fluorescence resonance energy transfer between mant-labeled nucleotides or IAEDANS-labeled actin and FlAsH-labeled myosin V to examine the conformation of the nucleotide- and actin-binding regions, respectively. We demonstrate that in the absence of actin, both the G440A and E442A mutants bind ATP with similar affinity and result in only minor alterations in the conformation of the nucleotide-binding pocket (NBP). In the presence of ADP and actin, both switch II mutants disrupt the formation of a closed NBP actomyosin.ADP state. The G440A mutant also prevents ATP-induced opening of the actin-binding cleft. Our results indicate that the switch II region is critical for stabilizing the closed NBP conformation in the presence of actin, and is essential for communication between the active site and actin-binding region. PMID:22713570

  16. Dengue and Chikungunya fever among viral diseases in outpatient febrile children in Kilosa district hospital, Tanzania.

    PubMed

    Chipwaza, Beatrice; Mugasa, Joseph P; Selemani, Majige; Amuri, Mbaraka; Mosha, Fausta; Ngatunga, Steve D; Gwakisa, Paul S

    2014-11-01

    Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria. A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2-13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used. A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35-3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus. Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended.

  17. LcrV Mutants That Abolish Yersinia Type III Injectisome Function

    PubMed Central

    Ligtenberg, Katherine Given; Miller, Nathan C.; Mitchell, Anthony; Plano, Gregory V.

    2013-01-01

    LcrV, the type III needle cap protein of pathogenic Yersinia, has been proposed to function as a tether between YscF, the needle protein, and YopB-YopD to constitute the injectisome, a conduit for the translocation of effector proteins into host cells. Further, insertion of LcrV-capped needles from a calcium-rich environment into host cells may trigger the low-calcium signal for effector translocation. Here, we used a genetic approach to test the hypothesis that the needle cap responds to the low-calcium signal by promoting injectisome assembly. Growth restriction of Yersinia pestis in the absence of calcium (low-calcium response [LCR+] phenotype) was exploited to isolate dominant negative lcrV alleles with missense mutations in its amber stop codon (lcrV*327). The addition of at least four amino acids or the eight-residue Strep tag to the C terminus was sufficient to generate an LCR− phenotype, with variant LcrV capping type III needles that cannot assemble the YopD injectisome component. The C-terminal Strep tag appears buried within the cap structure, blocking effector transport even in Y. pestis yscF variants that are otherwise calcium blind, a constitutive type III secretion phenotype. Thus, LcrV*327 mutants arrest the needle cap in a state in which it cannot respond to the low-calcium signal with either injectisome assembly or the activation of type III secretion. Insertion of the Strep tag at other positions of LcrV produced variants with wild-type LCR+, LCR−, or dominant negative LCR− phenotypes, thereby allowing us to identify discrete sites within LcrV as essential for its attributes as a secretion substrate, needle cap, and injectisome assembly factor. PMID:23222719

  18. Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

    NASA Astrophysics Data System (ADS)

    Shrinet, Jatin; Shastri, Jayanthi S.; Gaind, Rajni; Bhavesh, Neel Sarovar; Sunil, Sujatha

    2016-11-01

    Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as co-infections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management.

  19. Globalization of Chikungunya Virus: Threat to the U.S.

    USDA-ARS?s Scientific Manuscript database

    In August, 2004, Kenyan health authorities and partners identified chikungunya virus as the cause of the febrile epidemic in a coastal island city. The virus is transmitted by Aedes mosquitoes in tropical Africa and Asia; the fever is rarely fatal but can incapacitate for weeks. Control was delayed,...

  20. Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels

    PubMed Central

    Watase, Kei; Barrett, Curtis F.; Miyazaki, Taisuke; Ishiguro, Taro; Ishikawa, Kinya; Hu, Yuanxin; Unno, Toshinori; Sun, Yaling; Kasai, Sayumi; Watanabe, Masahiko; Gomez, Christopher M.; Mizusawa, Hidehiro; Tsien, Richard W.; Zoghbi, Huda Y.

    2008-01-01

    Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disorder caused by CAG repeat expansions within the voltage-gated calcium (CaV) 2.1 channel gene. It remains controversial whether the mutation exerts neurotoxicity by changing the function of CaV2.1 channel or through a gain-of-function mechanism associated with accumulation of the expanded polyglutamine protein. We generated three strains of knockin (KI) mice carrying normal, expanded, or hyperexpanded CAG repeat tracts in the Cacna1a locus. The mice expressing hyperexpanded polyglutamine (Sca684Q) developed progressive motor impairment and aggregation of mutant CaV2.1 channels. Electrophysiological analysis of cerebellar Purkinje cells revealed similar Ca2+ channel current density among the three KI models. Neither voltage sensitivity of activation nor inactivation was altered in the Sca684Q neurons, suggesting that expanded CAG repeat per se does not affect the intrinsic electrophysiological properties of the channels. The pathogenesis of SCA6 is apparently linked to an age-dependent process accompanied by accumulation of mutant CaV2.1 channels. PMID:18687887

  1. Development of in-house serological methods for diagnosis and surveillance of chikungunya.

    PubMed

    Galo, Saira Saborío; González, Karla; Téllez, Yolanda; García, Nadezna; Pérez, Leonel; Gresh, Lionel; Harris, Eva; Balmaseda, Ángel

    2017-08-21

    To develop and evaluate serological methods for chikungunya diagnosis and research in Nicaragua. Two IgM ELISA capture systems (MAC-ELISA) for diagnosis of acute chikungunya virus (CHIKV) infections, and two Inhibition ELISA Methods (IEM) to measure total antibodies against CHIKV were developed using monoclonal antibodies (mAbs) and hyperimmune serum at the National Virology Laboratory of Nicaragua in 2014-2015. The sensitivity, specificity, predictive values, and agreement of the MAC-ELISAs were obtained by comparing the results of 198 samples (116 positive; 82 negative) with the Centers for Disease Control and Prevention's IgM ELISA (Atlanta, Georgia, United States; CDC-MAC-ELISA). For clinical evaluation of the four serological techniques, 260 paired acute and convalescent phase serum samples of suspected chikungunya cases were used. All four assays were standardized by determining the optimal concentrations of the different reagents. Processing times were substantially reduced compared to the CDC-MAC-ELISA. For the MAC-ELISA systems, a sensitivity of 96.6% and 97.4%, and a specificity of 98.8% and 91.5% were obtained using mAb and hyperimmune serum, respectively, compared with the CDC method. Clinical evaluation of the four serological techniques versus the CDC real-time RT-PCR assay resulted in a sensitivity of 95.7% and a specificity of 88.8%-95.9%. Two MAC-ELISA and two IEM systems were standardized, demonstrating very good quality for chikungunya diagnosis and research demands. This will achieve more efficient epidemiological surveillance in Nicaragua, the first country in Central America to produce its own reagents for serological diagnosis of CHIKV. The methods evaluated here can be applied in other countries and will contribute to sustainable diagnostic systems to combat the disease.

  2. Development of in-house serological methods for diagnosis and surveillance of chikungunya

    PubMed Central

    Galo, Saira Saborío; González, Karla; Téllez, Yolanda; García, Nadezna; Pérez, Leonel; Gresh, Lionel; Harris, Eva; Balmaseda, Ángel

    2017-01-01

    Objective To develop and evaluate serological methods for chikungunya diagnosis and research in Nicaragua. Methods Two IgM ELISA capture systems (MAC-ELISA) for diagnosis of acute chikungunya virus (CHIKV) infections, and two Inhibition ELISA Methods (IEM) to measure total antibodies against CHIKV were developed using monoclonal antibodies (mAbs) and hyperimmune serum at the National Virology Laboratory of Nicaragua in 2014–2015. The sensitivity, specificity, predictive values, and agreement of the MAC-ELISAs were obtained by comparing the results of 198 samples (116 positive; 82 negative) with the Centers for Disease Control and Prevention’s IgM ELISA (Atlanta, Georgia, United States; CDC-MAC-ELISA). For clinical evaluation of the four serological techniques, 260 paired acute and convalescent phase serum samples of suspected chikungunya cases were used. Results All four assays were standardized by determining the optimal concentrations of the different reagents. Processing times were substantially reduced compared to the CDC-MAC-ELISA. For the MAC-ELISA systems, a sensitivity of 96.6% and 97.4%, and a specificity of 98.8% and 91.5% were obtained using mAb and hyperimmune serum, respectively, compared with the CDC method. Clinical evaluation of the four serological techniques versus the CDC real-time RT-PCR assay resulted in a sensitivity of 95.7% and a specificity of 88.8%–95.9%. Conclusion Two MAC-ELISA and two IEM systems were standardized, demonstrating very good quality for chikungunya diagnosis and research demands. This will achieve more efficient epidemiological surveillance in Nicaragua, the first country in Central America to produce its own reagents for serological diagnosis of CHIKV. The methods evaluated here can be applied in other countries and will contribute to sustainable diagnostic systems to combat the disease. PMID:28902269

  3. Laboratory-confirmed dengue fever and chikungunya fever cases at the Narita Airport Quarantine Station in 2013.

    PubMed

    Furuichi, Mieko; Makie, Toshio; Honma, Yasuko; Isoda, Takayoshi; Miyake, Satoru

    2015-01-01

    Fourteen patients were laboratory-confirmed cases of imported infectious diseases at the Narita Airport Quarantine Station in 2013. Blood tests were performed on 283 subjects suspected of having imported infectious diseases. Of these, 11 were diagnosed as having dengue fever (dengue) and 3 as having chikungunya fever (chikungunya) using real-time RT-PCR. The possible countries from which dengue virus infections were contracted were Thailand, Laos, Sri Lanka, and some other countries in Southeast Asia and South Asia. The 3 chikungunya cases were also diagnosed in individuals that returned from Southeast Asia. Most of the patients with dengue had a fever of over 38℃. The other symptoms were generalized fatigue, dull headache, pain behind the eyes, arthralgia, and digestive symptoms. Four of the patients were unaware of any mosquito bites. The information obtained from the confirmed cases showed that it is important to consider both the destination to which individuals travelled and the clinical symptoms, regardless of whether the subjects were aware of mosquito bites. The detection rate of chikungunya at the Quarantine Station was higher than that of dengue in all reported cases in Japan.

  4. Domestic and Environmental Factors of Chikungunya-affected Families in Thiruvananthapuram (Rural) District of Kerala, India

    PubMed Central

    Anish, TS; Vijayakumar, K; Leela, Itty Amma KR

    2011-01-01

    Background: The world is experiencing a pandemic of chikungunya which has swept across Indian Ocean and the Indian subcontinent. Kerala the southernmost state of India was affected by the chikungunya epidemic twice, first in 2006 and then in 2007. Kerala has got geography and climate which are highly favorable for the breeding of Aedes albopictus, the suspected vector. Aim: The aim of the study was to highlight the various domestic and environmental factors of the families affected by chikungunya in 2007 in Thiruvananthapuram district (rural) of Kerala. Settings and design:This is a cross-sectional survey conducted in Thiruvananthapuram (rural) district during November 2007. Settings and design: This is a cross-sectional survey conducted in Thiruvananthapuram (rural) district during November 2007 Materials and Methods: Samples were selected from field area under three Primary Health Centers.These areas represent the three terrains of the district namely the highland, midland, and lowland. The sample size was estimated to be 134 houses from each study area.The field area of health workers was selected as clusters and six subcenters from each primary health center were randomly selected (lot method). Results and Conclusions: The proportion of population affected by chikungunya fever is 39.9% (38.9-40.9%). The investigators observed water holding containers in the peri-domestic area of 95.6% of the houses. According to regression (binary logistic) analysis, the area of residence [adjusted odds ratio (OR) = 8.01 (6.06-14.60)], residing in a non-remote area [adjusted OR=0.25 (0.16-0.38)], perceived mosquito menace [adjusted OR=3.07 (2.31-4.64)], and containers/tires outside the house [adjusted OR=5.61 (2.74-27.58)] were the independent predictors of the occurrence of chikungunya in households. PMID:21572606

  5. Analysis of the V2 Vasopressin Receptor (V2R) Mutations Causing Partial Nephrogenic Diabetes Insipidus Highlights a Sustainable Signaling by a Non-peptide V2R Agonist*

    PubMed Central

    Makita, Noriko; Sato, Tomohiko; Yajima-Shoji, Yuki; Sato, Junichiro; Manaka, Katsunori; Eda-Hashimoto, Makiko; Ootaki, Masanori; Matsumoto, Naoki; Nangaku, Masaomi; Iiri, Taroh

    2016-01-01

    Disease-causing mutations in G protein-coupled receptor (GPCR) genes, including the V2 vasopressin receptor (V2R) gene, often cause misfolded receptors, leading to a defect in plasma membrane trafficking. A novel V2R mutation, T273M, identified in a boy with partial nephrogenic diabetes insipidus (NDI), shows intracellular localization and partial defects similar to the two mutants we described previously (10). Although non-peptide V2R antagonists have been shown to rescue the membrane localization of V2R mutants, their level of functional rescue is weak. Interestingly, it has been reported that a non-peptide agonist, OPC51803, activates misfolded V2R mutants intracellularly without degradation, thus potentially serving as a therapeutic agent against NDI (14). In our current experiments, however, a peptide antagonist blocked arginine vasopressin (AVP)- or OPC51803-stimulated cAMP accumulation both in COS-7 and MDCK cells, suggesting that OPC51803 mainly stimulates cell surface V2R mutants. In addition, our analyses revealed that OPC51803 works not only as a non-peptide agonist that causes activation/β-arrestin-dependent desensitization of V2R mutants expressed at the plasma membrane but also as a pharmacochaperone that promotes the endoplasmic reticulum-retained mutant maturation and trafficking to the plasma membrane. The ratio of the pharmacochaperone effect to the desensitization effect likely correlates negatively with the residual function of the tested mutants, suggesting that OPC5 has a more favorable effect on the V2R mutants with a less residual function. We speculated that the canceling of the desensitization effect of OPC51803 by the pharmacochaperone effect after long-term treatment may produce sustainable signaling, and thus pharmacochaperone agonists such as OPC51803 may serve as promising therapeutics for NDI caused by misfolded V2R mutants. PMID:27601473

  6. Chikungunya Virus Infection of Aedes Mosquitoes.

    PubMed

    Wong, Hui Vern; Chan, Yoke Fun; Sam, I-Ching; Sulaiman, Wan Yusof Wan; Vythilingam, Indra

    2016-01-01

    In vivo infection of mosquitoes is an important method to study and characterize arthropod-borne viruses. Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is transmitted primarily by Aedes mosquitoes. In this chapter, we describe a protocol for infection of CHIKV in two species of Aedes mosquitoes, Aedes aegypti and Aedes albopictus, together with the isolation of CHIKV in different parts of the infected mosquito such as midgut, legs, wings, salivary gland, head, and saliva. This allows the study of viral infection, replication and dissemination within the mosquito vector.

  7. Characterization of a Thermo-Inducible Chlorophyll-Deficient Mutant in Barley.

    PubMed

    Wang, Rong; Yang, Fei; Zhang, Xiao-Qi; Wu, Dianxin; Tan, Cong; Westcott, Sharon; Broughton, Sue; Li, Chengdao; Zhang, Wenying; Xu, Yanhao

    2017-01-01

    Leaf color is an important trait for not only controlling crop yield but also monitoring plant status under temperature stress. In this study, a thermo-inducible chlorophyll-deficient mutant, named V-V-Y, was identified from a gamma-radiated population of the barley variety Vlamingh. The leaves of the mutant were green under normal growing temperature but turned yellowish under high temperature in the glasshouse experiment. The ratio of chlorophyll a and chlorophyll b in the mutant declined much faster in the first 7-9 days under heat treatment. The leaves of V-V-Y turned yellowish but took longer to senesce under heat stress in the field experiment. Genetic analysis indicated that a single nuclear gene controlled the mutant trait. The mutant gene ( vvy ) was mapped to the long arm of chromosome 4H between SNP markers 1_0269 and 1_1531 with a genetic distance of 2.2 cM and a physical interval of 9.85 Mb. A QTL for grain yield was mapped to the same interval and explained 10.4% of the yield variation with a LOD score of 4. This QTL is coincident with the vvy gene interval that is responsible for the thermo-inducible chlorophyll-deficient trait. Fine mapping, based on the barley reference genome sequence, further narrowed the vvy gene to a physical interval of 0.428 Mb with 11 annotated genes. This is the first report of fine mapping a thermo-inducible chlorophyll-deficient gene in barley.

  8. Chikungunya virus infections among travellers returning to Spain, 2008 to 2014

    PubMed Central

    Fernandez-Garcia, Maria Dolores; Bangert, Mathieu; de Ory, Fernando; Potente, Arantxa; Hernandez, Lourdes; Lasala, Fatima; Herrero, Laura; Molero, Francisca; Negredo, Anabel; Vázquez, Ana; Minguito, Teodora; Balfagón, Pilar; de la Fuente, Jesus; Puente, Sabino; Ramírez de Arellano, Eva; Lago, Mar; Martinez, Miguel; Gascón, Joaquim; Norman, Francesca; Lopez-Velez, Rogelio; Sulleiro, Elena; Pou, Diana; Serre, Nuria; Roblas, Ricardo Fernández; Tenorio, Antonio; Franco, Leticia; Sanchez-Seco, Maria Paz

    2016-01-01

    Since the first documented autochthonous transmission of chikungunya virus in the Caribbean island of Saint Martin in 2013, the infection has been reported within the Caribbean region as well as North, Central and South America. The risk of autochthonous transmission of chikungunya virus becoming established in Spain may be elevated due to the large numbers of travellers returning to Spain from countries affected by the 2013 epidemic in the Caribbean and South America, as well as the existence of the Aedes albopictus vector in certain parts of Spain. We retrospectively analysed the laboratory diagnostic database of the National Centre for Microbiology, Institute of Health Carlos III (CNM-ISCIII) from 2008 to 2014. During the study period, 264 confirmed cases, of 1,371 suspected cases, were diagnosed at the CNM-ISCIII. In 2014 alone, there were 234 confirmed cases. The highest number of confirmed cases were reported from the Dominican Republic (n = 136), Venezuela (n = 30) and Haiti (n = 11). Six cases were viraemic in areas of Spain where the vector is present. This report highlights the need for integrated active case and vector surveillance in Spain and other parts of Europe where chikungunya virus may be introduced by returning travellers. PMID:27631156

  9. Chikungunya virus infections among travellers returning to Spain, 2008 to 2014.

    PubMed

    Fernandez-Garcia, Maria Dolores; Bangert, Mathieu; de Ory, Fernando; Potente, Arantxa; Hernandez, Lourdes; Lasala, Fatima; Herrero, Laura; Molero, Francisca; Negredo, Anabel; Vázquez, Ana; Minguito, Teodora; Balfagón, Pilar; de la Fuente, Jesus; Puente, Sabino; Ramírez de Arellano, Eva; Lago, Mar; Martinez, Miguel; Gascón, Joaquim; Norman, Francesca; Lopez-Velez, Rogelio; Sulleiro, Elena; Pou, Diana; Serre, Nuria; Roblas, Ricardo Fernández; Tenorio, Antonio; Franco, Leticia; Sanchez-Seco, Maria Paz

    2016-09-08

    Since the first documented autochthonous transmission of chikungunya virus in the Caribbean island of Saint Martin in 2013, the infection has been reported within the Caribbean region as well as North, Central and South America. The risk of autochthonous transmission of chikungunya virus becoming established in Spain may be elevated due to the large numbers of travellers returning to Spain from countries affected by the 2013 epidemic in the Caribbean and South America, as well as the existence of the Aedes albopictus vector in certain parts of Spain. We retrospectively analysed the laboratory diagnostic database of the National Centre for Microbiology, Institute of Health Carlos III (CNM-ISCIII) from 2008 to 2014. During the study period, 264 confirmed cases, of 1,371 suspected cases, were diagnosed at the CNM-ISCIII. In 2014 alone, there were 234 confirmed cases. The highest number of confirmed cases were reported from the Dominican Republic (n = 136), Venezuela (n = 30) and Haiti (n = 11). Six cases were viraemic in areas of Spain where the vector is present. This report highlights the need for integrated active case and vector surveillance in Spain and other parts of Europe where chikungunya virus may be introduced by returning travellers. This article is copyright of The Authors, 2016.

  10. [Confirmed Dengue, Chikungunya and Zika Cases during the Period 2014 to 2016 in Barcelona, Spain].

    PubMed

    González, Roser; Camprubí, Esteve; Fernández, Lidia; Millet, Joan Pau; Peracho, Víctor; Gorrindo, Pilar; Avellanés, Ingrid; Romero, Arancha; Caylà, Joan A

    2017-03-07

    Arbovirus infections are a group of diseases whose incidence is increasing and that entail an important problem for public health. The aim of this study was to describe detected cases of arbovirosis in Barcelona, and surveillance and control actions performed in order to reduce the risk of transmission. Descriptive cross-sectional study of confirmed dengue, chikungunya and Zika cases in Barcelona during 2014-2016 (1st trimester). Suspected cases detected in the city were notified to the Epidemiology Department of the Barcelona Public Health Agency, where an epidemiological survey is undertaken and, if appropriate, Urban Pests Surveillance and Control Department is contacted. They perform an entomological inspection and implement control and monitoring actions. We collected sociodemographical, epidemiological, clinical and entomological variables. In 2014, 50 chikungunya and 20 dengue cases were detected; 25 entomological inspections were carried out in residences and 38 in the street. In 2015, 47 chikungunya, 51 dengue and 2 Zika cases were detected; 27 inspections were carried out in residences and 80 in the street. In 2016, 17 chikungunya, 52 dengue and 48 Zika cases were detected; 50 inspections were carried out in residences and 103 in the street. No autochtonous case was detected. We observed an increasing incidence of arbovirosis cases during the 3-year study period. There was a progressive intensification of vector surveillance and control actions (inspections, sample collection…).

  11. BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors.

    PubMed

    Roque, Ashley; Odia, Yazmin

    2017-04-01

    We present a patient with BRAF-V600E mutant papillary craniopharyngioma successfully treated with combination BRAF (dabrafenib 150 mg twice daily) and MEK (trametinib 2 mg daily) inhibitors after her unresectable tumor proved refractory to radiation. Serial brain MRIs and PET revealed marked tumor reduction with gradual neurological improvement and permanent panhypopituitarism.

  12. Zika, chikungunya and dengue: the causes and threats of new and re-emerging arboviral diseases.

    PubMed

    Paixão, Enny S; Teixeira, Maria Gloria; Rodrigues, Laura C

    2018-01-01

    The recent emergence and re-emergence of viral infections transmitted by vectors-Zika, chikungunya, dengue, Japanese encephalitis, West Nile, yellow fever and others-is a cause for international concern. Using as examples Zika, chikungunya and dengue, we summarise current knowledge on characteristics of the viruses and their transmission, clinical features, laboratory diagnosis, burden, history, possible causes of the spread and the expectation for future epidemics. Arboviruses are transmitted by mosquitoes, are of difficult diagnosis, can have surprising clinical complications and cause severe burden. The current situation is complex, because there is no vaccine for Zika and chikungunya and no specific treatment for the three arboviruses. Vector control is the only comprehensive solution available now and this remains a challenge because up to now this has not been very effective. Until we develop new technologies of control mosquito populations, the globalised and urbanised world we live in will remain vulnerable to the threat of successive arbovirus epidemics.

  13. Zika, chikungunya and dengue: the causes and threats of new and re-emerging arboviral diseases

    PubMed Central

    Paixão, Enny S.; Teixeira, Maria Gloria; Rodrigues, Laura C

    2018-01-01

    The recent emergence and re-emergence of viral infections transmitted by vectors—Zika, chikungunya, dengue, Japanese encephalitis, West Nile, yellow fever and others—is a cause for international concern. Using as examples Zika, chikungunya and dengue, we summarise current knowledge on characteristics of the viruses and their transmission, clinical features, laboratory diagnosis, burden, history, possible causes of the spread and the expectation for future epidemics. Arboviruses are transmitted by mosquitoes, are of difficult diagnosis, can have surprising clinical complications and cause severe burden. The current situation is complex, because there is no vaccine for Zika and chikungunya and no specific treatment for the three arboviruses. Vector control is the only comprehensive solution available now and this remains a challenge because up to now this has not been very effective. Until we develop new technologies of control mosquito populations, the globalised and urbanised world we live in will remain vulnerable to the threat of successive arbovirus epidemics. PMID:29435366

  14. Reptiles and Amphibians as Potential Reservoir Hosts of Chikungunya Virus.

    PubMed

    Bosco-Lauth, Angela M; Hartwig, Airn E; Bowen, Richard A

    2018-03-01

    Chikungunya virus is an emerging arbovirus of significant human-health concern. Little is known about its sylvatic cycle, including whether ectothermic vertebrates are permissive to infection. In this study, individuals from ten species of reptiles and amphibians were inoculated with chikungunya virus and samples of blood were tested to characterize viremia and seroconversion. Viremia was not detected in cane toads, house geckos, or American alligators, but most of the green iguanas, red-eared sliders, ball and Burmese pythons, leopard frogs, Texas toads, and garter snakes developed viremia. Peak virus titers in serum of up to 4.5, 4.7, and 5.1 log 10 plaque-forming units per milliliter were observed for garter snakes, ball pythons, and Texas toads, respectively. These results add to those of other studies that have suggested a possible role for ectothermic vertebrates in the ecology of arbovirus maintenance and transmission in nature.

  15. Anti-chikungunya activity of luteolin and apigenin rich fraction from Cynodon dactylon.

    PubMed

    Murali, Krishnan Saravana; Sivasubramanian, Srinivasan; Vincent, Savariar; Murugan, Shanmugaraj Bala; Giridaran, Bupesh; Dinesh, Sundaram; Gunasekaran, Palani; Krishnasamy, Kaveri; Sathishkumar, Ramalingam

    2015-05-01

    To obtain luteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon (L.) (C. dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells. The ethanolic extract of C. dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus (CHIKV) fraction. Reverse phase-HPLC and GC-MS studies were carried out to identify the major phytochemicals in the fraction using phytochemical standards. Cytotoxicity and the potential of the fraction against CHIKV were evaluated in vitro using Vero cells. Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) after treating the viral infected Vero cells with the fraction. Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids, luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction of C. dactylon. The fraction was found to exhibit potent viral inhibitory activity (about 98%) at the concentration of 50 µg/mL as observed by reduction in cytopathic effect, and the cytotoxic concentration of the fraction was found to be 250 µg/mL. RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells. Luteolin and apigenin rich ethanolic fraction from C. dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  16. Help Control Mosquitoes that Spread Dengue, Chikungunya, and Zika Viruses

    MedlinePlus

    Help Control Mosquitoes that Spread Dengue, Chikungunya, and Zika Viruses B Z Z Z Z . Aside from being itchy ... for your information only. The Centers for Disease Control and Prevention and the U.S. Department of Health ...

  17. Pan-RAF and MEK vertical inhibition enhances therapeutic response in non-V600 BRAF mutant cells.

    PubMed

    Molnár, Eszter; Rittler, Dominika; Baranyi, Marcell; Grusch, Michael; Berger, Walter; Döme, Balázs; Tóvári, József; Aigner, Clemens; Tímár, József; Garay, Tamás; Hegedűs, Balázs

    2018-05-08

    Currently, there are no available targeted therapy options for non-V600 BRAF mutated tumors. The aim of this study was to investigate the effects of RAF and MEK concurrent inhibition on tumor growth, migration, signaling and apoptosis induction in preclinical models of non-V600 BRAF mutant tumor cell lines. Six BRAF mutated human tumor cell lines CRL5885 (G466 V), WM3629 (D594G), WM3670 (G469E), MDAMB231 (G464 V), CRL5922 (L597 V) and A375 (V600E as control) were investigated. Pan-RAF inhibitor (sorafenib or AZ628) and MEK inhibitor (selumetinib) or their combination were used in in vitro viability, video microscopy, immunoblot, cell cycle and TUNEL assays. The in vivo effects of the drugs were assessed in an orthotopic NSG mouse breast cancer model. All cell lines showed a significant growth inhibition with synergism in the sorafenib/AZ628 and selumetinib combination. Combination treatment resulted in higher Erk1/2 inhibition and in increased induction of apoptosis when compared to single agent treatments. However, single selumetinib treatment could cause adverse therapeutic effects, like increased cell migration in certain cells, selumetinib and sorafenib combination treatment lowered migratory capacity in all the cell lines. Importantly, combination resulted in significantly increased tumor growth inhibition in orthotropic xenografts of MDAMB231 cells when compared to sorafenib - but not to selumetinib - treatment. Our data suggests that combined blocking of RAF and MEK may achieve increased therapeutic response in non-V600 BRAF mutant tumors.

  18. Molecular Characterization of Chikungunya Virus, Philippines, 2011–2013

    PubMed Central

    Sy, Ava Kristy; Saito-Obata, Mariko; Medado, Inez Andrea; Tohma, Kentaro; Dapat, Clyde; Segubre-Mercado, Edelwisa; Tandoc, Amado; Lupisan, Socorro

    2016-01-01

    During 2011–2013, a nationwide outbreak of chikungunya virus infection occurred in the Philippines. The Asian genotype was identified as the predominant genotype; sporadic cases of the East/Central/South African genotype were detected in Mindanao. Further monitoring is needed to define the transmission pattern of this virus in the Philippines. PMID:27088593

  19. 22 CFR 226.62 - Enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Enforcement. 226.62 Section 226.62 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Suspension, Termination and Enforcement § 226.62 Enforcement. (a) Remedies...

  20. 7 CFR 226.3 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 4 2011-01-01 2011-01-01 false Administration. 226.3 Section 226.3 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM General § 226.3 Administration. (a) Within...

  1. 22 CFR 226.90 - Disputes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Disputes. 226.90 Section 226.90 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Miscellaneous § 226.90 Disputes. (a) Any dispute under or relating to a grant or agreement shall...

  2. Partial complementation of the UV sensitivity of E. coli and yeast excision repair mutants by the cloned denV gene of bacteriophage T4.

    PubMed

    Chenevert, J M; Naumovski, L; Schultz, R A; Friedberg, E C

    1986-04-01

    The denV gene of bacteriophage T4 was reconstituted from two overlapping DNA fragments cloned in M13 vectors. The coding region of the intact gene was tailored into a series of plasmid vectors containing different promoters suitable for expression of the gene in E. coli and in yeast. Induction of the TAC promoter with IPTG resulted in overexpression of the gene, which was lethal to E. coli. Expression of the TACdenV gene in the absence of IPTG, or the use of the yeast GAL1 or ADH promoters resulted in partial complementation of the UV sensitivity of uvrA, uvrB, uvrC and recA mutants of E. coli and rad1, rad2, rad3, rad4 and rad10 mutants of S. cerevisiae. The extent of denV-mediated reactivation of excision-defective mutants was approximately equal to that of photoreactivation of such strains. Excision proficient E. coli cells transformed with a plasmid containing the denV gene were slightly more resistant to ultraviolet (UV) radiation than control cells without the denV gene. On the other hand, excision proficient yeast cells were slightly more sensitive to killing by UV radiation following transformation with a plasmid containing the denV gene. This effect was more pronounced in yeast mutants of the RAD52 epistasis group.

  3. Analysis of the V2 Vasopressin Receptor (V2R) Mutations Causing Partial Nephrogenic Diabetes Insipidus Highlights a Sustainable Signaling by a Non-peptide V2R Agonist.

    PubMed

    Makita, Noriko; Sato, Tomohiko; Yajima-Shoji, Yuki; Sato, Junichiro; Manaka, Katsunori; Eda-Hashimoto, Makiko; Ootaki, Masanori; Matsumoto, Naoki; Nangaku, Masaomi; Iiri, Taroh

    2016-10-21

    Disease-causing mutations in G protein-coupled receptor (GPCR) genes, including the V2 vasopressin receptor (V2R) gene, often cause misfolded receptors, leading to a defect in plasma membrane trafficking. A novel V2R mutation, T273M, identified in a boy with partial nephrogenic diabetes insipidus (NDI), shows intracellular localization and partial defects similar to the two mutants we described previously (10). Although non-peptide V2R antagonists have been shown to rescue the membrane localization of V2R mutants, their level of functional rescue is weak. Interestingly, it has been reported that a non-peptide agonist, OPC51803, activates misfolded V2R mutants intracellularly without degradation, thus potentially serving as a therapeutic agent against NDI (14). In our current experiments, however, a peptide antagonist blocked arginine vasopressin (AVP)- or OPC51803-stimulated cAMP accumulation both in COS-7 and MDCK cells, suggesting that OPC51803 mainly stimulates cell surface V2R mutants. In addition, our analyses revealed that OPC51803 works not only as a non-peptide agonist that causes activation/β-arrestin-dependent desensitization of V2R mutants expressed at the plasma membrane but also as a pharmacochaperone that promotes the endoplasmic reticulum-retained mutant maturation and trafficking to the plasma membrane. The ratio of the pharmacochaperone effect to the desensitization effect likely correlates negatively with the residual function of the tested mutants, suggesting that OPC5 has a more favorable effect on the V2R mutants with a less residual function. We speculated that the canceling of the desensitization effect of OPC51803 by the pharmacochaperone effect after long-term treatment may produce sustainable signaling, and thus pharmacochaperone agonists such as OPC51803 may serve as promising therapeutics for NDI caused by misfolded V2R mutants. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Multidisciplinary Prospective Study of Mother-to-Child Chikungunya Virus Infections on the Island of La Réunion

    PubMed Central

    Gérardin, Patrick; Barau, Georges; Michault, Alain; Bintner, Marc; Randrianaivo, Hanitra; Choker, Ghassan; Lenglet, Yann; Touret, Yasmina; Bouveret, Anne; Grivard, Philippe; Roux, Karin Le; Blanc, Séverine; Schuffenecker, Isabelle; Couderc, Thérèse; Arenzana-Seisdedos, Fernando; Lecuit, Marc; Robillard, Pierre-Yves

    2008-01-01

    Background An outbreak of chikungunya virus affected over one-third of the population of La Réunion Island between March 2005 and December 2006. In June 2005, we identified the first case of mother-to-child chikungunya virus transmission at the Groupe Hospitalier Sud-Réunion level-3 maternity department. The goal of this prospective study was to characterize the epidemiological, clinical, biological, and radiological features and outcomes of all the cases of vertically transmitted chikungunya infections recorded at our institution during this outbreak. Methods and Findings Over 22 mo, 7,504 women delivered 7,629 viable neonates; 678 (9.0%) of these parturient women were infected (positive RT-PCR or IgM serology) during antepartum, and 61 (0.8%) in pre- or intrapartum. With the exception of three early fetal deaths, vertical transmission was exclusively observed in near-term deliveries (median duration of gestation: 38 wk, range 35–40 wk) in the context of intrapartum viremia (19 cases of vertical transmission out of 39 women with intrapartum viremia, prevalence rate 0.25%, vertical transmission rate 48.7%). Cesarean section had no protective effect on transmission. All infected neonates were asymptomatic at birth, and median onset of neonatal disease was 4 d (range 3–7 d). Pain, prostration, and fever were present in 100% of cases and thrombocytopenia in 89%. Severe illness was observed in ten cases (52.6%) and mainly consisted of encephalopathy (n = 9; 90%). These nine children had pathologic MRI findings (brain swelling, n = 9; cerebral hemorrhages, n = 2), and four evolved towards persistent disabilities. Conclusions Mother-to-child chikungunya virus transmission is frequent in the context of intrapartum maternal viremia, and often leads to severe neonatal infection. Chikungunya represents a substantial risk for neonates born to viremic parturients that should be taken into account by clinicians and public health authorities in the event of a chikungunya

  5. Rapid determination of 226Ra in emergency urine samples

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

    Maxwell, Sherrod L.; Culligan, Brian K.; Hutchison, Jay B.

    2014-02-27

    A new method has been developed at the Savannah River National Laboratory (SRNL) that can be used for the rapid determination of 226Ra in emergency urine samples following a radiological incident. If a radiological dispersive device event or a nuclear accident occurs, there will be an urgent need for rapid analyses of radionuclides in urine samples to ensure the safety of the public. Large numbers of urine samples will have to be analyzed very quickly. This new SRNL method was applied to 100 mL urine aliquots, however this method can be applied to smaller or larger sample aliquots as needed.more » The method was optimized for rapid turnaround times; urine samples may be prepared for counting in <3 h. A rapid calcium phosphate precipitation method was used to pre-concentrate 226Ra from the urine sample matrix, followed by removal of calcium by cation exchange separation. A stacked elution method using DGA Resin was used to purify the 226Ra during the cation exchange elution step. This approach combines the cation resin elution step with the simultaneous purification of 226Ra with DGA Resin, saving time. 133Ba was used instead of 225Ra as tracer to allow immediate counting; however, 225Ra can still be used as an option. The rapid purification of 226Ra to remove interferences using DGA Resin was compared with a slightly longer Ln Resin approach. A final barium sulfate micro-precipitation step was used with isopropanol present to reduce solubility; producing alpha spectrometry sources with peaks typically <40 keV FWHM (full width half max). This new rapid method is fast, has very high tracer yield (>90 %), and removes interferences effectively. The sample preparation method can also be adapted to ICP-MS measurement of 226Ra, with rapid removal of isobaric interferences.« less

  6. 7 CFR 226.3 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Administration. 226.3 Section 226.3 Agriculture... CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM General § 226.3 Administration. (a) Within the Department, FNS shall act on behalf of the Department in the administration of the Program. (b...

  7. 7 CFR 226.3 - Administration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 4 2013-01-01 2013-01-01 false Administration. 226.3 Section 226.3 Agriculture... CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM General § 226.3 Administration. (a) Within the Department, FNS shall act on behalf of the Department in the administration of the Program. (b...

  8. 7 CFR 226.3 - Administration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 4 2012-01-01 2012-01-01 false Administration. 226.3 Section 226.3 Agriculture... CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM General § 226.3 Administration. (a) Within the Department, FNS shall act on behalf of the Department in the administration of the Program. (b...

  9. 7 CFR 226.3 - Administration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Administration. 226.3 Section 226.3 Agriculture... CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM General § 226.3 Administration. (a) Within the Department, FNS shall act on behalf of the Department in the administration of the Program. (b...

  10. Existence of c-Kit negative cells with ultrastructural features of interstitial cells of Cajal in the subserosal layer of the W/W(v) mutant mouse colon.

    PubMed

    Tamada, Hiromi; Kiyama, Hiroshi

    2015-01-01

    Interstitial cells of Cajal (ICC) are mesenchymal cells that are distributed along the gastrointestinal tract and function as pacemaker cells or intermediary cells between nerves and smooth muscle cells. ICC express a receptor tyrosine kinase c-Kit, which is an established marker for ICC. The c-kit gene is allelic with the murine white-spotting locus (W), and some ICC subsets were reported to be missing in heterozygous mutant W/W(v) mice carrying W and W(v) mutated alleles. In this study, the characterization of interstitial cells in the subserosal layer of W/W(v) mice was analyzed by immunohistochemistry and electron microscopy. In the proximal and distal colon of W/W(v) mutant mice, no c-Kit-positive cells were detected in the subserosal layer by immunohistochemistry. By electron microscopy, the interstitial cells, which were characterized by the existence of caveolae, abundant mitochondria and gap junctions, were observed in the W/W(v) mutant colon. The morphological characteristics were comparable to those of the multipolar c-Kit positive ICC seen in the subserosa of proximal and distal colon of wild-type mice. Fibroblasts were also located in the same layers, but the morphology of the fibroblasts was distinguishable from that of ICC in wild type mice or of ICC-like cells in W/W(v) mutant mice. Collectively, it is concluded that c-Kit-negative interstitial cells showing a typical ICC ultrastructure exist in the proximal and distal colon of W/W(v) mutant mice.

  11. Specific Silencing of L392V PSEN1 Mutant Allele by RNA Interference

    PubMed Central

    Sierant, Malgorzata; Paduszynska, Alina; Kazmierczak-Baranska, Julia; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Sochacka, Elzbieta; Nawrot, Barbara

    2011-01-01

    RNA interference (RNAi) technology provides a powerful molecular tool to reduce an expression of selected genes in eukaryotic cells. Short interfering RNAs (siRNAs) are the effector molecules that trigger RNAi. Here, we describe siRNAs that discriminate between the wild type and mutant (1174 C→G) alleles of human Presenilin1 gene (PSEN1). This mutation, resulting in L392V PSEN1 variant, contributes to early onset familial Alzheimer's disease. Using the dual fluorescence assay, flow cytometry and fluorescent microscopy we identified positions 8th–11th, within the central part of the antisense strand, as the most sensitive to mismatches. 2-Thiouridine chemical modification introduced at the 3′-end of the antisense strand improved the allele discrimination, but wobble base pairing adjacent to the mutation site abolished the siRNA activity. Our data indicate that siRNAs can be designed to discriminate between the wild type and mutant alleles of genes that differ by just a single nucleotide. PMID:21559198

  12. Autochthonous Chikungunya Transmission and Extreme Climate Events in Southern France.

    PubMed

    Roiz, David; Boussès, Philippe; Simard, Frédéric; Paupy, Christophe; Fontenille, Didier

    2015-06-01

    Extreme precipitation events are increasing as a result of ongoing global warming, but controversy surrounds the relationship between flooding and mosquito-borne diseases. A common view among the scientific community and public health officers is that heavy rainfalls have a flushing effect on breeding sites, which negatively affects vector populations, thereby diminishing disease transmission. During 2014 in Montpellier, France, there were at least 11 autochthonous cases of chikungunya caused by the invasive tiger mosquito Aedes albopictus in the vicinity of an imported case. We show that an extreme rainfall event increased and extended the abundance of the disease vector Ae. albopictus, hence the period of autochthonous transmission of chikungunya. We report results from close monitoring of the adult and egg population of the chikungunya vector Ae. albopictus through weekly sampling over the entire mosquito breeding season, which revealed an unexpected pattern. Statistical analysis of the seasonal dynamics of female abundance in relation to climatic factors showed that these relationships changed after the heavy rainfall event. Before the inundations, accumulated temperatures are the most important variable predicting Ae. albopictus seasonal dynamics. However, after the inundations, accumulated rainfall over the 4 weeks prior to capture predicts the seasonal dynamics of this species and extension of the transmission period. Our empirical data suggests that heavy rainfall events did increase the risk of arbovirus transmission in Southern France in 2014 by favouring a rapid rise in abundance of vector mosquitoes. Further studies should now confirm these results in different ecological contexts, so that the impact of global change and extreme climatic events on mosquito population dynamics and the risk of disease transmission can be adequately understood.

  13. 12 CFR 226.16 - Advertising.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 3 2012-01-01 2012-01-01 false Advertising. 226.16 Section 226.16 Banks and... LENDING (REGULATION Z) Open-End Credit § 226.16 Advertising. (a) Actually available terms. If an... only the periodic payment amount advertised. The disclosure of the total of payments and the time...

  14. 12 CFR 226.16 - Advertising.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 3 2013-01-01 2013-01-01 false Advertising. 226.16 Section 226.16 Banks and...) TRUTH IN LENDING (REGULATION Z) Open-End Credit § 226.16 Advertising. (a) Actually available terms. If... only the periodic payment amount advertised. The disclosure of the total of payments and the time...

  15. 12 CFR 226.16 - Advertising.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 3 2014-01-01 2014-01-01 false Advertising. 226.16 Section 226.16 Banks and...) TRUTH IN LENDING (REGULATION Z) Open-End Credit § 226.16 Advertising. (a) Actually available terms. If... only the periodic payment amount advertised. The disclosure of the total of payments and the time...

  16. 12 CFR 226.16 - Advertising.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Advertising. 226.16 Section 226.16 Banks and... LENDING (REGULATION Z) Open-End Credit § 226.16 Advertising. (a) Actually available terms. If an... only the periodic payment amount advertised. The disclosure of the total of payments and the time...

  17. 12 CFR 226.24 - Advertising.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Advertising. 226.24 Section 226.24 Banks and... LENDING (REGULATION Z) Closed-End Credit § 226.24 Advertising. (a) Actually available terms. If an... than one simple annual rate of interest will apply over the term of the advertised loan, the...

  18. 12 CFR 226.24 - Advertising.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 3 2012-01-01 2012-01-01 false Advertising. 226.24 Section 226.24 Banks and... LENDING (REGULATION Z) Closed-End Credit § 226.24 Advertising. (a) Actually available terms. If an... than one simple annual rate of interest will apply over the term of the advertised loan, the...

  19. Relative risk estimation of Chikungunya disease in Malaysia: An analysis based on Poisson-gamma model

    NASA Astrophysics Data System (ADS)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2015-05-01

    Disease mapping is a method to display the geographical distribution of disease occurrence, which generally involves the usage and interpretation of a map to show the incidence of certain diseases. Relative risk (RR) estimation is one of the most important issues in disease mapping. This paper begins by providing a brief overview of Chikungunya disease. This is followed by a review of the classical model used in disease mapping, based on the standardized morbidity ratio (SMR), which we then apply to our Chikungunya data. We then fit an extension of the classical model, which we refer to as a Poisson-Gamma model, when prior distributions for the relative risks are assumed known. Both results are displayed and compared using maps and we reveal a smoother map with fewer extremes values of estimated relative risk. The extensions of this paper will consider other methods that are relevant to overcome the drawbacks of the existing methods, in order to inform and direct government strategy for monitoring and controlling Chikungunya disease.

  20. 7 CFR 226.19a - Adult day care center provisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 4 2013-01-01 2013-01-01 false Adult day care center provisions. 226.19a Section 226..., DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Operational Provisions § 226.19a Adult day care center provisions. (a) Adult day care centers may participate in the Program...

  1. 7 CFR 226.19a - Adult day care center provisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 4 2012-01-01 2012-01-01 false Adult day care center provisions. 226.19a Section 226..., DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Operational Provisions § 226.19a Adult day care center provisions. (a) Adult day care centers may participate in the Program...

  2. 7 CFR 226.19a - Adult day care center provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Adult day care center provisions. 226.19a Section 226..., DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Operational Provisions § 226.19a Adult day care center provisions. (a) Adult day care centers may participate in the Program...

  3. Estimating and mapping the incidence of dengue and chikungunya in Honduras during 2015 using Geographic Information Systems (GIS).

    PubMed

    Zambrano, Lysien I; Sierra, Manuel; Lara, Bredy; Rodríguez-Núñez, Iván; Medina, Marco T; Lozada-Riascos, Carlos O; Rodríguez-Morales, Alfonso J

    Geographical information systems (GIS) use for development of epidemiological maps in dengue has been extensively used, however not in other emerging arboviral diseases, nor in Central America. Surveillance cases data (2015) were used to estimate annual incidence rates of dengue and chikungunya (cases/100,000 pop) to develop the first maps in the departments and municipalities of Honduras. The GIS software used was Kosmo Desktop 3.0RC1 ® . Four thematic maps were developed according departments, municipalities, diseases incidence rates. A total of 19,289 cases of dengue and 85,386 of chikungunya were reported (median, 726 cases/week for dengue and 1460 for chikungunya). Highest peaks were observed at weeks 25th and 27th, respectively. There was association between progression by weeks (p<0.0001). The cumulated crude national rate was estimated in 224.9 cases/100,000 pop for dengue and 995.6 for chikungunya. The incidence rates ratio between chikungunya and dengue is 4.42 (ranging in municipalities from 0.0 up to 893.0 [San Vicente Centenario]). Burden of both arboviral diseases is concentrated in capital Central District (>37%, both). Use of GIS-based epidemiological maps allow to guide decisions-taking for prevention and control of diseases that still represents significant issues in the region and the country, but also in emerging conditions. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  4. 12 CFR 226.24 - Advertising.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 3 2014-01-01 2014-01-01 false Advertising. 226.24 Section 226.24 Banks and...) TRUTH IN LENDING (REGULATION Z) Closed-End Credit § 226.24 Advertising. (a) Actually available terms. If... than one simple annual rate of interest will apply over the term of the advertised loan, the...

  5. 12 CFR 226.24 - Advertising.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 3 2013-01-01 2013-01-01 false Advertising. 226.24 Section 226.24 Banks and...) TRUTH IN LENDING (REGULATION Z) Closed-End Credit § 226.24 Advertising. (a) Actually available terms. If... than one simple annual rate of interest will apply over the term of the advertised loan, the...

  6. 21 CFR 556.226 - Enrofloxacin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enrofloxacin. 556.226 Section 556.226 Food and... Residues of New Animal Drugs § 556.226 Enrofloxacin. (a) Acceptable daily intake (ADI). The ADI for total residues of enrofloxacin is 3 micrograms per kilogram of body weight per day. (b) Tolerances. The...

  7. Overexpression of ATP-Binding Cassette Transporter ABCG2 as a Potential Mechanism of Acquired Resistance to Vemurafenib in BRAF(V600E) Mutant Cancer Cells

    PubMed Central

    Wu, Chung-Pu; Sim, Hong-May; Huang, Yang-Hui; Liu, Yen-Chen; Hsiao, Sung-Han; Cheng, Hsing-Wen; Li, Yan-Qing; Ambudkar, Suresh V.; Hsu, Sheng-Chieh

    2012-01-01

    Melanoma is the most serious type of skin cancer with a high potential for metastasis and very low survival rates. The discovery of constitutive activation of the BRAF kinase caused by activating BRAF(V600E) kinase mutation in most melanoma patients led to the discovery of the first potent BRAF(V600E) signaling inhibitor, vemurafenib. Vemurafenib was effective in treating advanced melanoma patients and was proposed for the treatment of other BRAF(V600E) mutant cancers as well. Unfortunately, the success of vemurafenib was hampered by the rapid development of acquired resistance in different types of BRAF(V600E) mutant cancer cells. It becomes important to identify and evaluate all of the potential mechanisms of cellular resistance to vemurafenib. In this study, we characterized the interactions of vemurafenib with three major ATP-binding cassette (ABC) transporters, ABCB1, ABCC1 and ABCG2. We found that vemurafenib stimulated the ATPase activity and potently inhibited drug efflux mediated by ABCB1 and ABCG2. Vemurafenib also restored drug sensitivity in ABCG2-overexpressing cells. Moreover, we revealed that in the presence of functional ABCG2, BRAF kinase inhibition by vemurafenib is reduced in BRAF(V600E) mutant A375 cells. Taken together, our findings indicate that ABCG2 confers resistance to vemurafenib in A375 cells, suggesting involvement of this transporter in acquired resistance to vemurafenib. Thus, combination chemotherapy targeting multiple pathways could be an effective therapeutic strategy to overcome acquired resistance to vemurafenib for cancers harboring the BRAF(V600E) mutation. PMID:23153455

  8. Co-infections with Chikungunya and Dengue Viruses, Guatemala, 2015.

    PubMed

    Edwards, Thomas; Signor, Leticia Del Carmen Castillo; Williams, Christopher; Donis, Evelin; Cuevas, Luis E; Adams, Emily R

    2016-11-01

    We screened serum samples referred to the national reference laboratory in Guatemala that were positive for chikungunya or dengue viruses in June 2015. Co-infection with both viruses was detected by reverse transcription PCR in 46 (32%) of 144 samples. Specimens should be tested for both arboviruses to detect co-infections.

  9. 27 CFR 41.226 - Change in control of a corporation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... corporation. 41.226 Section 41.226 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Ownership and Control § 41.226 Change in control of a corporation. Where the issuance, sale, or transfer of the stock of a corporation operating as an importer of tobacco products results in a change in the...

  10. Mosquito Exposure and Chikungunya and Dengue Infection Among Travelers During the Chikungunya Outbreak in the Americas

    PubMed Central

    Lindholm, David A.; Myers, Todd; Widjaja, Susana; Grant, Edward M.; Telu, Kalyani; Lalani, Tahaniyat; Fraser, Jamie; Fairchok, Mary; Ganesan, Anuradha; Johnson, Mark D.; Kunz, Anjali; Tribble, David R.; Yun, Heather C.

    2017-01-01

    Travelers are at risk for arbovirus infection. We prospectively enrolled 267 Department of Defense beneficiaries traveling to chikungunya-outbreak regions in the Americas between December 2013 and May 2015 and assessed travel characteristics and serologic exposure to chikungunya virus (CHIKV) and dengue virus (DENV). Ten ill-returning travelers were also assessed retrospectively. Self-reported mosquito exposure was common (64% of 198 evaluable travelers saw mosquitoes; 53% of 201 reported ≥ 1 bite). Increased exposure was associated with active-duty travelers (odds ratio [OR] = 2.6 [1.3–5.4] for seeing mosquitoes) or travelers visiting friends and relatives (VFR) (OR = 3.5 [1.0–10.0] for high-intensity bite exposure). Arbovirus infection was defined as seroconversion on plaque reduction neutralization testing (PRNT) of pre- and posttravel sera. For ill subjects enrolled posttravel, infection was defined by a positive convalescent PRNT and/or a positive reverse transcription polymerase chain reaction for CHIKV or DENV. We identified seven cases of arbovirus infection: four with CHIKV, five with DENV, and two with both. The composite attack rate for CHIKV and DENV infection was 3.7% of 108 evaluable, immunologically naïve, prospectively assessed travelers; there was serologic and/or polymerase chain reaction evidence of arbovirus infection in three of four evaluable (three of 10 total) ill-returning travelers. We identified both symptomatic and asymptomatic cases. Military purpose of travel and VFR travel accounted for five of seven cases. Pretravel counseling is important and should target higher risk groups. Given a shared vector between CHIKV, DENV, and Zika virus (ZIKV), this study can also help guide counseling for travelers to ZIKV-outbreak regions. PMID:28115671

  11. A comparison of compliance rates with anti-vectorial protective measures during travel to regions with dengue or chikungunya activity, and regions endemic for Plasmodium falciparum malaria

    PubMed Central

    Lalani, Tahaniyat; Yun, Heather; Tribble, David; Ganesan, Anuradha; Kunz, Anjali; Fairchok, Mary; Schnaubelt, Elizabeth; Fraser, Jamie; Mitra, Indrani; Kronmann, Karl C.; Burgess, Timothy; Deiss, Robert G.; Riddle, Mark S.; Johnson, Mark D.

    2016-01-01

    Background. There is limited information on compliance rates with anti-vectorial protective measures (AVPMs) during travel to countries with risk of dengue and chikungunya. We evaluated differences in mosquito exposures, and factors associated with AVPM compliance in travellers going to countries where the principal mosquito-borne infectious disease threat is falciparum malaria and those where risk of dengue or chikungunya predominates. Methods. Department of Defence beneficiaries with planned travel to regions where the predominant mosquito-borne infection is falciparum malaria, and those with predominantly dengue or chikungunya risk, were included. Regions were divided into three groups: ‘high-risk falciparum malaria’, ‘low-risk falciparum malaria’ and ‘chikungunya/dengue risk’. Demographics, trip characteristics, arthropod exposure and AVPM compliance were captured using pre- and post-travel surveys. Skin repellent compliance was defined as self-reported use, categorized as ‘often/every day’. A logistic regression model was used to estimate factors associated with AVPM compliance. Results. 183 (9%), 185 (9%) and 149 (7%) travelled to high and low falciparum malaria risk regions, and chikungunya/dengue risk regions, respectively. Overall, 53% (95% CI: 48–57%) and 16% (95% CI: 12–19%) were compliant with repellent use on skin and clothing, respectively. Daytime bites were reported more frequently in chikungunya/dengue risk regions than high malaria risk regions (37% vs. 10%), while night time bites were frequently in high malaria risk regions (53% vs 20%; P < 0.001). Compliance with skin repellents was associated with female gender [RR: 1.54 (95% CI: 1.05–2.28)], observing mosquitoes during travel [RR: 2.77 (95% CI: 1.76–4.36)] and travel during the rainy season [RR: 2.45 (95% CI: 1.66–3.71)]). Conclusions. Poor AVPM compliance was observed in the overall cohort. Compliance with skin repellent use was associated with female gender

  12. Chikungunya: an emerging viral infection with varied clinical presentations in Bangladesh: Reports of seven cases.

    PubMed

    Rahim, Muhammad Abdur; Uddin, Khwaja Nazim

    2017-08-15

    Chikungunya is an emerging and rapidly spreading viral infection in many parts of the world including Bangladesh. It shares many epidemiological and clinical characteristics with dengue. So, a sound knowledge is required for its detection and differentiation from dengue, specially in endemic regions. We present seven confirmed cases of chikungunya having different clinical presentations occurring among middle aged males and females from different socio-economic background in Dhaka city, the capital of Bangladesh. All patients had fever and aches and pains. Less common features were rash, diarrhea, vomiting and altered liver biochemistry. Dengue was excluded in six patients. Paracetamol remained the mainstay of treatment during febrile periods, but over 50% of the patients had prolonged joint symptoms requiring non-steroidal anti-inflammatory drugs. In spite of being a self-limiting disease, chikungunya may have different presentations and a protracted clinical course. During the febrile episode, exclusion of dengue is equally important. Physicians should be aware of the condition and public health initiatives are necessary to break the disease transmission.

  13. 32 CFR 226.3 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false [Reserved] 226.3 Section 226.3 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS SHELTER FOR THE HOMELESS § 226.3 [Reserved] ...

  14. Economic Costs of Chikungunya Virus in Colombia.

    PubMed

    Alvis-Zakzuk, Nelson J; Díaz-Jiménez, Diana; Castillo-Rodríguez, Liliana; Castañeda-Orjuela, Carlos; Paternina-Caicedo, Ángel; Pinzón-Redondo, Hernando; Carrasquilla-Sotomayor, María; Alvis-Guzmán, Nelson; De La Hoz-Restrepo, Fernando

    2018-04-05

    The aim of the present study was to estimate the economic impact of chikungunya virus (CHIKV) infection in Colombia from a societal perspective. We conducted a retrospective, bottom-up cost-of-illness study in clinically confirmed cases during the first chikungunya (CHIK) outbreak in Colombia in 2014. Direct and indirect costs were estimated per patient. Economic costs were calculated by the addition of direct costs (direct medical costs and out-of-pocket heath expenditures) and indirect cost as a result of loss of productivity. A total of 126 patients (67 children and 59 adults) with CHIK were included. The median of the direct medical cost in children was US$257.9 (interquartile range [IQR] 121.7-563.8), and US$66.6 (IQR 26.5-317.3) for adults. The productivity loss median expenditures reached US$81.3 (IQR 72.2-203.2) per adult patient. The median economic cost in adults as a result of CHIK was US$152.9 (IQR 101.0-539.6), of which 53.2% was a result of indirect costs. Out-of-pocket expenditures comprised 3.3% of all economic costs. Our study can help health decision makers to properly assess the burden of disease caused by CHIK in Colombia, an endemic tropical country. We recommend to strength the health information systems and to continue investing in public health measures to prevent CHIK. Copyright © 2018. Published by Elsevier Inc.

  15. Dengue, chikungunya … and the missing entity - Zika fever: A new emerging threat.

    PubMed

    Tilak, Rina; Ray, Sougat; Tilak, V W; Mukherji, Sandip

    2016-04-01

    Zika virus (ZIKV), a relative newcomer from the flavivirus group that includes dengue, Japanese encepahalitis and yellow fever, is one of the emerging pathogens that is fast transcending geographical boundaries. It is a vector-borne disease transmitted by the same Aedes aegypti and Aedes albopictus, which cause dengue and chikungunya. In addition to the vector-mediated transmission of Zika fever, probable human-to-human transmission through exchange of body fluids, including sexual and perinatal transmission and through blood transfusion, makes containment of this new entity more challenging. Moreover, a high index of suspicion by an astute physician is necessary for diagnosis of Zika fever in view of the similarity of symptoms with dengue and chikungunya, especially in areas, where these two diseases are already endemic. Zika, till recently, has had minimal impact, but its true potential is unfolding with increasing detection of congenital malformities, Guillain-Barré syndrome and other neurological and autoimmune syndromes in patients with recent history of ZIKV infection, or when mothers get infected with Zika during first or second trimester of pregnancy. The association, however, needs to be established, nonetheless it is important that we keep a close vigil on this emerging vector borne disease - the 'ZIKA' fever.

  16. 22 CFR 226.43 - Competition.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Competition. 226.43 Section 226.43 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.43 Competition. All procurement transactions...

  17. Perceived morbidity and community burden after a Chikungunya outbreak: the TELECHIK survey, a population-based cohort study

    PubMed Central

    2011-01-01

    Background Persistent disabilities are key manifestations of Chikungunya virus (CHIKV) infection, especially incapacitating polyarthralgia and fatigue. So far, little is known about their impact on health status. The present study aimed at describing the burden of CHIKV prolonged or late-onset symptoms on the self-perceived health of La Réunion islanders. Methods At 18 months after an outbreak of Chikungunya virus, we implemented the TELECHIK survey; a retrospective cohort study conducted on a random sample of the representative SEROCHIK population-based survey. A total of 1,094 subjects sampled for CHIKV-specific IgG antibodies in the setting of La Réunion island in the Indian Ocean, between August 2006 and October 2006, were interviewed about current symptoms divided into musculoskeletal/rheumatic, fatigue, cerebral, sensorineural, digestive and dermatological categories. Results At the time of interview, 43% of seropositive (CHIK+) subjects reported musculoskeletal pain (vs 17% of seronegative (CHIK-) subjects, P < 0.001), 54% fatigue (vs 46%, P = 0.04), 75% cerebral disorders (vs 57%, P < 0.001), 49% sensorineural impairments (vs 37%, P = 0.001), 18% digestive complaints (vs 15%, P = 0.21), and 36% skin involvement (vs 34%, P = 0.20) on average 2 years after infection (range: 15-34 months). After controlling for confounders such as age, gender, body mass index or major comorbidities in different Poisson regression models, 33% of joint pains were attributable to CHIKV, 10% of cerebral disorders and 7.5% of sensorineural impairments, while Chikungunya did not enhance fatigue states, digestive and skin disorders. Conclusions On average, 2 years after infection 43% to 75% of infected people reported prolonged or late-onset symptoms highly attributable to CHIKV. These manifestations carry a significant burden in the community in the fields of rheumatology, neurology and sensorineural health. PMID:21235760

  18. 46 CFR 169.226 - Periodic inspection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Periodic inspection. 169.226 Section 169.226 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Inspection and Certification Reinspection § 169.226 Periodic inspection. (a) Your vessel must undergo a...

  19. 46 CFR 169.226 - Periodic inspection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Periodic inspection. 169.226 Section 169.226 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Inspection and Certification Reinspection § 169.226 Periodic inspection. (a) Your vessel must undergo a...

  20. Evidence for chikungunya and dengue transmission in Quelimane, Mozambique: Results from an investigation of a potential outbreak of chikungunya virus

    PubMed Central

    Ali, Sadia; Chelene, Imelda; Monteiro, Vanessa Onofre; Guiliche, Onélia; Muianga, Argentina Felisbela; Mula, Flora; António, Virgílio; Chongo, Inocêncio; Falk, Kerstin; Paploski, Igor A.; Reis, Mitermayer G.; Kitron, Uriel; Kümmerer, Beate M.

    2018-01-01

    Background In January 2016, health authorities from Zambézia province, Mozambique reported the detection of some patients presenting with fever, arthralgia, and a positive result for chikungunya in an IgM-based Rapid Diagnostic Test (RDT). We initiated a study to investigate a potential chikungunya outbreak in the city of Quelimane. Methods/Principal findings From February to June 2016, we conducted a cross-sectional study enrolling febrile patients attending five outpatient health units in Quelimane. Serum from each patient was tested for CHIKV and DENV, using IgM and IgG ELISA and qRT-PCR. Patients were also tested for malaria by RDT. Entomological surveys were performed around patients’ households, and we calculated the proportion of positive ovitraps and the egg density per trap. A total of 163 patients were recruited, of which 99 (60.7%) were female. The median age was 28 years. IgM and IgG anti-CHIKV antibodies were identified in 17 (10.4%) and 103 (63.2%) patients, respectively. Plaque reduction neutralization assay confirmed the presence of anti-CHIKV antibodies in a subset of 11 tested patients with positive IgG results. IgM anti-DENV antibodies were found in 1 (0.9%) of 104 tested patients. Malaria was diagnosed in 35 (21.5%) patients, 2 of whom were also IgM-positive for CHIKV. Older age and lower education level were independently associated with the prevalence of IgG anti-CHIKV antibodies. Immature forms of Aedes aegypti were collected in 16 (20.3%) of 79 surveyed households. We also found that 25.0% (16/64) of the traps were positive, with an average of 90.8 eggs per pallet. Conclusions Our investigation demonstrated that no CHIKV outbreak was ongoing in Quelimane; rather, endemic transmission of the virus has been ongoing. Aedes aegypti mosquitoes are abundant, but dengue cases occurred only sporadically. Further population-based cohort studies are needed to improve our understanding of aspects related to the dynamics of arboviral transmission in

  1. Chikungunya Virus: Pathophysiology, Mechanism, and Modeling

    PubMed Central

    Ganesan, Vaishnavi K.; Reid, St Patrick

    2017-01-01

    Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, is recurring in epidemic waves. In the past decade and a half, the disease has resurged in several countries around the globe, with outbreaks becoming increasingly severe. Though CHIKV was first isolated in 1952, there remain significant gaps in knowledge of CHIKV biology, pathogenesis, transmission, and mechanism. Diagnosis is largely simplified and based on symptoms, while treatment is supportive rather than curative. Here we present an overview of the disease, the challenges that lie ahead for future research, and what directions current studies are headed towards, with emphasis on improvement of current animal models and potential use of 3D models. PMID:29194359

  2. 22 CFR 226.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Deviations. 226.4 Section 226.4 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS General § 226.4 Deviations. The Office of Management and Budget (OMB) may grant exceptions for...

  3. Chikungunya virus infection.

    PubMed

    Sam, I-C; AbuBakar, S

    2006-06-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which causes epidemic fever, rash and polyarthralgia in Africa and Asia. Two outbreaks have been reported in Malaysia, in Klang, Selangor (1998) and Bagan Panchor, Perak (2006). It is not known if the outbreaks were caused by the recent introduction of CHIKV, or if the virus was already circulating in Malaysia. Seroprevalence studies from the 1960s suggested previous disease activity in certain parts of the country. In Asia, CHIKV is thought to be transmitted by the same mosquitoes as dengue, Aedes aegypti and Ae. albopictus. Due to similarities in clinical presentation with dengue, limited awareness, and a lack of laboratory diagnostic capability, CHIKV is probably often underdiagnosed or misdiagnosed as dengue. Treatment is supportive. The prognosis is generally good, although some patients experience chronic arthritis. With no vaccine or antiviral available, prevention and control depends on surveillance, early identification of outbreaks, and vector control. CHIKV should be borne in mind in sporadic cases, and in patients epidemiologically linked to ongoing local or international outbreaks or endemic areas.

  4. Observation of a Neutral Structure near the DD[over ¯]^{*} Mass Threshold in e^{+}e^{-}→(DD[over ¯]^{*})^{0}π^{0} at sqrt[s]=4.226 and 4.257 GeV.

    PubMed

    Ablikim, M; Achasov, M N; Ai, X C; Albayrak, O; Albrecht, M; Ambrose, D J; Amoroso, A; An, F F; An, Q; Bai, J Z; Ferroli, R Baldini; Ban, Y; Bennett, D W; Bennett, J V; Bertani, M; Bettoni, D; Bian, J M; Bianchi, F; Boger, E; Boyko, I; Briere, R A; Cai, H; Cai, X; Cakir, O; Calcaterra, A; Cao, G F; Cetin, S A; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, H Y; Chen, J C; Chen, M L; Chen, S Chen; Chen, S J; Chen, X; Chen, X R; Chen, Y B; Cheng, H P; Chu, X K; Cibinetto, G; Dai, H L; Dai, J P; Dbeyssi, A; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; De Mori, F; Ding, Y; Dong, C; Dong, J; Dong, L Y; Dong, M Y; Du, S X; Duan, P F; Fan, J Z; Fang, J; Fang, S S; Fang, X; Fang, Y; Fava, L; Feldbauer, F; Felici, G; Feng, C Q; Fioravanti, E; Fritsch, M; Fu, C D; Gao, Q; Gao, X L; Gao, X Y; Gao, Y; Gao, Z; Garzia, I; Goetzen, K; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, R P; Guo, Y; Guo, Y P; Haddadi, Z; Hafner, A; Han, S; Hao, X Q; Harris, F A; He, K L; He, X Q; Held, T; Heng, Y K; Hou, Z L; Hu, C; Hu, H M; Hu, J F; Hu, T; Hu, Y; Huang, G M; Huang, G S; Huang, J S; Huang, X T; Huang, Y; Hussain, T; Ji, Q; Ji, Q P; Ji, X B; Ji, X L; Jiang, L W; Jiang, X S; Jiang, X Y; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Johansson, T; Julin, A; Kalantar-Nayestanaki, N; Kang, X L; Kang, X S; Kavatsyuk, M; Ke, B C; Kiese, P; Kliemt, R; Kloss, B; Kolcu, O B; Kopf, B; Kornicer, M; Kühn, W; Kupsc, A; Lange, J S; Lara, M; Larin, P; Leng, C; Li, C; Li, Cheng; Li, D M; Li, F; Li, F Y; Li, G; Li, H B; Li, H J; Li, J C; Li, Jin; Li, K; Li, K; Li, Lei; Li, P R; Li, T; Li, W D; Li, W G; Li, X L; Li, X M; Li, X N; Li, X Q; Li, Z B; Liang, H; Liang, J J; Liang, Y F; Liang, Y T; Liao, G R; Lin, D X; Liu, B J; Liu, C X; Liu, D; Liu, F H; Liu, Fang; Liu, Feng; Liu, H B; Liu, H H; Liu, H H; Liu, H M; Liu, J; Liu, J B; Liu, J P; Liu, J Y; Liu, K; Liu, K Y; Liu, L D; Liu, P L; Liu, Q; Liu, S B; Liu, X; Liu, Y B; Liu, Z A; Liu, Zhiqing; Loehner, H; Lou, X C; Lu, H J; Lu, J G; Lu, Y; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lyu, X R; Ma, F C; Ma, H L; Ma, L L; Ma, M M; Ma, Q M; Ma, T; Ma, X N; Ma, X Y; Maas, F E; Maggiora, M; Mao, Y J; Mao, Z P; Marcello, S; Messchendorp, J G; Min, J; Mitchell, R E; Mo, X H; Mo, Y J; Morales, C Morales; Moriya, K; Muchnoi, N Yu; Muramatsu, H; Nefedov, Y; Nerling, F; Nikolaev, I B; Ning, Z; Nisar, S; Niu, S L; Niu, X Y; Olsen, S L; Ouyang, Q; Pacetti, S; Pan, Y; Patteri, P; Pelizaeus, M; Peng, H P; Peters, K; Pettersson, J; Ping, J L; Ping, R G; Poling, R; Prasad, V; Qi, M; Qian, S; Qiao, C F; Qin, L Q; Qin, N; Qin, X S; Qin, Z H; Qiu, J F; Rashid, K H; Redmer, C F; Ripka, M; Rong, G; Rosner, Ch; Ruan, X D; Sarantsev, A; Savrié, M; Schoenning, K; Schumann, S; Shan, W; Shao, M; Shen, C P; Shen, P X; Shen, X Y; Sheng, H Y; Shi, M; Song, W M; Song, X Y; Sosio, S; Spataro, S; Sun, G X; Sun, J F; Sun, S S; Sun, X H; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, I; Thorndike, E H; Tiemens, M; Ullrich, M; Uman, I; Varner, G S; Wang, B; Wang, D; Wang, D Y; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, S G; Wang, W; Wang, W P; Wang, X F; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z H; Wang, Z Y; Wang, Z Y; Weber, T; Wei, D H; Wei, J B; Weidenkaff, P; Wen, S P; Wiedner, U; Wolke, M; Wu, L H; Wu, L J; Wu, Z; Xia, L; Xia, L G; Xia, Y; Xiao, D; Xiao, H; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, J J; Xu, L; Xu, Q J; Xu, X P; Yan, L; Yan, W B; Yan, W C; Yan, Y H; Yang, H J; Yang, H X; Yang, L; Yang, Y; Yang, Y X; Ye, M; Ye, M H; Yin, J H; Yu, B X; Yu, C X; Yu, J S; Yuan, C Z; Yuan, W L; Yuan, Y; Yuncu, A; Zafar, A A; Zallo, A; Zeng, Y; Zeng, Z; Zhang, B X; Zhang, B Y; Zhang, C; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J; Zhang, J J; Zhang, J L; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, K; Zhang, L; Zhang, X Y; Zhang, Y; Zhang, Y N; Zhang, Y H; Zhang, Y T; Zhang, Yu; Zhang, Z H; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, J W; Zhao, J Y; Zhao, J Z; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, Q W; Zhao, S J; Zhao, T C; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, W J; Zheng, Y H; Zhong, B; Zhou, L; Zhou, X; Zhou, X K; Zhou, X R; Zhou, X Y; Zhu, K; Zhu, K J; Zhu, S; Zhu, S H; Zhu, X L; Zhu, Y C; Zhu, Y S; Zhu, Z A; Zhuang, J; Zotti, L; Zou, B S; Zou, J H

    2015-11-27

    A neutral structure in the DD[over ¯]^{*} system around the DD[over ¯]^{*} mass threshold is observed with a statistical significance greater than 10σ in the processes e^{+}e^{-}→D^{+}D^{*-}π^{0}+c.c. and e^{+}e^{-}→D^{0}D[over ¯]^{*0}π^{0}+c.c. at sqrt[s]=4.226 and 4.257 GeV in the BESIII experiment. The structure is denoted as Z_{c}(3885)^{0}. Assuming the presence of a resonance, its pole mass and width are determined to be [3885.7_{-5.7}^{+4.3}(stat)±8.4(syst)]  MeV/c^{2} and [35_{-12}^{+11}(stat)±15(syst)]  MeV, respectively. The Born cross sections are measured to be σ[e^{+}e^{-}→Z_{c}(3885)^{0}π^{0},Z_{c}(3885)^{0}→DD[over ¯]^{*}]=[77±13(stat)±17(syst)]  pb at 4.226 GeV and [47±9(stat)±10(syst)]  pb at 4.257 GeV. The ratio of decay rates B[Z_{c}(3885)^{0}→D^{+}D^{*-}+c.c.]/B[Z_{c}(3885)^{0}→D^{0}D[over ¯]^{*0}+c.c.] is determined to be 0.96±0.18(stat)±0.12(syst), consistent with no isospin violation in the process, Z_{c}(3885)^{0}→DD[over ¯]^{*}.

  5. Assessing the threat of chikungunya virus emergence in Australia.

    PubMed

    Viennet, Elvina; Knope, Katrina; Faddy, Helen M; Williams, Craig R; Harley, David

    2013-06-30

    Chikungunya virus (CHIKV) is a major threat to Australia given the distribution of competent vectors, and the large number of travellers returning from endemic regions. We describe current knowledge of CHIKV importations into Australia, and quantify reported viraemic cases, with the aim of facilitating the formulation of public health policy and ensuring maintenance of blood safety. Cases reported to the National Notifiable Disease Surveillance System (NNDSS) from 2002 to 2012 were analysed by place, month of acquisition, and place of residence. Rates of chikungunya importation were estimated based on reported cases and on the numbers of short-term movements. Between 2002 and 2012, there were 168 cases of chikungunya virus (CHIKV) imported into Australia. Victoria and New South Wales had the largest number of notifications. The main sources were Indonesia, India and Malaysia. The number of cases increased from 2008 to reach a peak in 2010 (n=64; 40%). Although Indonesia accounted for the majority of CHIKV notifications in Australia, travel from India had the highest CHIKV importation rate (number of imported cases per 100,000 travellers). The Australian population is increasingly at risk from CHIKV. Arrivals from endemic countries have increased concurrently with vector incursions via imported goods, as well as via local movement from the Torres Strait to North Queensland ports. An outbreak of CHIKV could have a significant impact on health, the safety of the blood supply and on tourism. Case and vector surveillance as well as population health responses are crucial for minimising any potential impact of CHIKV establishment in Australia. This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General

  6. 22 CFR 226.47 - Contract administration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Contract administration. 226.47 Section 226.47 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.47 Contract administration. A...

  7. A method for the generation of ectromelia virus (ECTV) recombinants: in vivo analysis of ECTV vCD30 deletion mutants.

    PubMed

    Alejo, Ali; Saraiva, Margarida; Ruiz-Argüello, Maria Begoña; Viejo-Borbolla, Abel; de Marco, Mar Fernández; Salguero, Francisco Javier; Alcami, Antonio

    2009-01-01

    Ectromelia virus (ECTV) is the causative agent of mousepox, a lethal disease of mice with similarities to human smallpox. Mousepox progression involves replication at the initial site of infection, usually the skin, followed by a rapid spread to the secondary replicative organs, spleen and liver, and finally a dissemination to the skin, where the typical rash associated with this and other orthopoxviral induced diseases appears. Case fatality rate is genetically determined and reaches up to 100% in susceptible mice strains. Like other poxviruses, ECTV encodes a number of proteins with immunomodulatory potential, whose role in mousepox progression remains largely undescribed. Amongst these is a secreted homologue of the cellular tumour necrosis factor receptor superfamily member CD30 which has been proposed to modulate a Th1 immune response in vivo. To evaluate the contribution of viral CD30 (vCD30) to virus pathogenesis in the infected host, we have adapted a novel transient dominant method for the selection of recombinant ECTVs. Using this method, we have generated an ECTV vCD30 deletion mutant, its corresponding revertant control virus as well as a virus encoding the extracellular domain of murine CD30. These viruses contain no exogenous marker DNA sequences in their genomes, as opposed to other ECTVs reported up to date. We show that the vCD30 is expressed as a secreted disulfide linked trimer and that the absence of vCD30 does not impair mousepox induced fatality in vivo. Replacement of vCD30 by a secreted version of mouse CD30 caused limited attenuation of ECTV. The recombinant viruses generated may be of use in the study of the role of the cellular CD30-CD30L interaction in the development of the immune response. The method developed might be useful for the construction of ECTV mutants for the study of additional genes.

  8. 32 CFR 226.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Purpose. 226.1 Section 226.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS SHELTER FOR THE HOMELESS § 226.1 Purpose. This part implements 10 U.S.C. 2556 by establishing DoD policy...

  9. 22 CFR 226.71 - Closeout procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Closeout procedures. 226.71 Section 226.71 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS After-the-Award Requirements § 226.71 Closeout procedures. (a) Recipients shall...

  10. A comparison of compliance rates with anti-vectorial protective measures during travel to regions with dengue or chikungunya activity, and regions endemic for Plasmodium falciparum malaria.

    PubMed

    Lalani, Tahaniyat; Yun, Heather; Tribble, David; Ganesan, Anuradha; Kunz, Anjali; Fairchok, Mary; Schnaubelt, Elizabeth; Fraser, Jamie; Mitra, Indrani; Kronmann, Karl C; Burgess, Timothy; Deiss, Robert G; Riddle, Mark S; Johnson, Mark D

    2016-05-01

    There is limited information on compliance rates with anti-vectorial protective measures (AVPMs) during travel to countries with risk of dengue and chikungunya. We evaluated differences in mosquito exposures, and factors associated with AVPM compliance in travellers going to countries where the principal mosquito-borne infectious disease threat is falciparum malaria and those where risk of dengue or chikungunya predominates. Department of Defence beneficiaries with planned travel to regions where the predominant mosquito-borne infection is falciparum malaria, and those with predominantly dengue or chikungunya risk, were included. Regions were divided into three groups: 'high-risk falciparum malaria', 'low-risk falciparum malaria' and 'chikungunya/dengue risk'. Demographics, trip characteristics, arthropod exposure and AVPM compliance were captured using pre- and post-travel surveys. Skin repellent compliance was defined as self-reported use, categorized as 'often/every day'. A logistic regression model was used to estimate factors associated with AVPM compliance. 183 (9%), 185 (9%) and 149 (7%) travelled to high and low falciparum malaria risk regions, and chikungunya/dengue risk regions, respectively. Overall, 53% (95% CI: 48-57%) and 16% (95% CI: 12-19%) were compliant with repellent use on skin and clothing, respectively. Daytime bites were reported more frequently in chikungunya/dengue risk regions than high malaria risk regions (37% vs. 10%), while night time bites were frequently in high malaria risk regions (53% vs 20%; P < 0.001). Compliance with skin repellents was associated with female gender [RR: 1.54 (95% CI: 1.05-2.28)], observing mosquitoes during travel [RR: 2.77 (95% CI: 1.76-4.36)] and travel during the rainy season [RR: 2.45 (95% CI: 1.66-3.71)]). Poor AVPM compliance was observed in the overall cohort. Compliance with skin repellent use was associated with female gender, observing mosquitoes and travelling during the rainy season, and was not

  11. 22 CFR Appendix A to Part 226 - Contract Provisions

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-GOVERNMENTAL ORGANIZATIONS Pt. 226, App. A Appendix A to Part 226—Contract Provisions All contracts, awarded by a recipient including small purchases, shall contain the following provisions as applicable: 1... not apply to the purchases of supplies or materials or articles ordinarily available on the open...

  12. 22 CFR 226.32 - Real property.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Real property. 226.32 Section 226.32 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Property Standards § 226.32 Real property. (a) Unless the agreement...

  13. 21 CFR 226.58 - Laboratory controls.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Laboratory controls. 226.58 Section 226.58 Food...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Product Quality Control § 226.58 Laboratory controls. Laboratory controls shall include the establishment of adequate specifications and test...

  14. 21 CFR 226.58 - Laboratory controls.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Laboratory controls. 226.58 Section 226.58 Food...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Product Quality Control § 226.58 Laboratory controls. Laboratory controls shall include the establishment of adequate specifications and test...

  15. 21 CFR 226.58 - Laboratory controls.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Laboratory controls. 226.58 Section 226.58 Food...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Product Quality Control § 226.58 Laboratory controls. Laboratory controls shall include the establishment of adequate specifications and test...

  16. [Atypical mucocutaneous manifestations in neonates and infants with chikungunya fever in the municipalities of Cúcuta, Los Patios and Villa del Rosario, Norte de Santander, Colombia, 2014].

    PubMed

    Muñoz, Claudia Marcela; Castillo, José Orlando; Salas, Daniela; Valderrama, Milena Alexandra; Rangel, Claudia Teresa; Vargas, Heiddy Patricia; Silva, Diana Carolina

    2016-09-01

    Atypical clinical manifestations have been observed in newborns and infants suffering from fever caused by the chikungunya virus. Objective: To describe the cases of fever caused by the chikungunya virus in newborns and infants with atypical mucocutaneous lesions. Materials and methods: We reviewed the clinical records, as well as lab tests and histopathological results, of newborns and infants diagnosed with Chikungunya virus and atypical mucocutaneous lesions in three regional hospitals. Results: Out of 18 suspected cases of chikungunya virus in newborns and infants, 11 were positive and presented atypical mucocutaneous manifestations. Six of the eleven confirmed cases corresponded to children under five months of age. The most common symptoms were fever, skin rash, irritability, and diarrhea. Three of the patients were infected with both dengue and chikungunya viruses. The ulcers occurred in the scalp, abdomen, genital and perianal region. We report mucocutaneous manifestations in newborns and infants diagnosed with fever caused by the chikungunya virus in Colombia. The rapid development of ulcers is most likely due to the immune response to the virus. Special attention should be given to pregnant women presenting symptoms of chikungunya virus infection prior to delivery, and their offspring should be followed-up in order to monitor possible complications.

  17. 22 CFR Appendix A to Part 226 - Contract Provisions

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Pt. 226, App. A Appendix A to Part 226—Contract Provisions All contracts, awarded by... Organizations and Small Business Firms Under Government Grants, Contracts and Cooperative Agreements,” and any...

  18. 22 CFR 226.32 - Real property.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Real property. 226.32 Section 226.32 Foreign... ORGANIZATIONS Post-award Requirements Property Standards § 226.32 Real property. (a) Unless the agreement provides otherwise, title to real property shall vest in the recipient subject to the condition that the...

  19. 22 CFR 226.32 - Real property.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Real property. 226.32 Section 226.32 Foreign... ORGANIZATIONS Post-award Requirements Property Standards § 226.32 Real property. (a) Unless the agreement provides otherwise, title to real property shall vest in the recipient subject to the condition that the...

  20. 22 CFR 226.32 - Real property.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Real property. 226.32 Section 226.32 Foreign... ORGANIZATIONS Post-award Requirements Property Standards § 226.32 Real property. (a) Unless the agreement provides otherwise, title to real property shall vest in the recipient subject to the condition that the...

  1. 22 CFR 226.32 - Real property.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Real property. 226.32 Section 226.32 Foreign... ORGANIZATIONS Post-award Requirements Property Standards § 226.32 Real property. (a) Unless the agreement provides otherwise, title to real property shall vest in the recipient subject to the condition that the...

  2. 21 CFR 226.115 - Complaint files.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Complaint files. 226.115 Section 226.115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Records and Reports § 226.115 Complaint...

  3. 22 CFR 226.52 - Financial reporting.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Financial reporting. 226.52 Section 226.52...-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Reports and Records § 226.52 Financial reporting. USAID requires recipients to use the Standard Form 425 or Standard Form 425a, Federal Financial Report, or such...

  4. Ra-226 bioaccumulation and growth indices in fish.

    PubMed

    Shi, Xiaopei; Smith, Richard; Seymour, Colin; Mothersill, Carmel

    2017-06-01

    To determine the accumulated activity of Ra-226 in fathead minnows fed with environmentally relevant levels of Ra-226 for 5 months in water at 20 °C, and to evaluate the influence of this level of Ra-226 on the growth of fathead minnows. Fathead minnows were fed with fish food containing 10-10,000 mBq/g Ra-226 for 5 months. At the end of the experiment, the fish were sacrificed, flash frozen in liquid nitrogen and kept at -20 °C. Longitudinal sections of 40 μm thickness were cut at the middle of the fish body using a cryostat. The activity of Ra-226 in each section was determined using autoradiography with a nuclear track detector CR-39. According to the weight and the width of the fish, the activity of Ra-226 in the whole fish body could be estimated. In addition, the length and the weight of the fish were measured and the condition factor was calculated to evaluate the growth and fitness of the fish. There is a positive but non-linear relationship between the accumulated activity of Ra-226 in fish body and the concentration of Ra-226 in fish food. The highest activity of Ra-226 accumulated in fish body was found from fish fed with 10,000 mBq/g Ra-226 food. This was calculated as 256.4 ± 49.1 mBq/g, p < 0.05, and the calculated dose rate was 6.2 ± 1.2 mGy/y. For fish fed with food containing lower concentration of Ra-226 (up to 1000 mBq/g), the bioaccumulation of Ra-226 in the body saturated. The Ra-226 concentration factor (CF) for fish was inversely proportional to the Ra-226 activity in food, and the highest CF value was 2.489, obtained from the lowest dietary Ra-226 activity (10 mBq/g). In addition, condition factors (K) of fish in all Ra-226-treated groups were significantly lower than those of the controls. The results show that the bioaccumulation of Ra-226 in fish is not simply related to the dietary Ra-226 activity, and has a saturation value when the dietary activity is low. In addition, the environmental level of Ra-226 in the fish

  5. Imported Chikungunya fever case in Greece in June 2014 and public health response

    PubMed Central

    Pervanidou, Danai; Papadopoulou, Elpida; Kavatha, Dimitra; Baka, Agoritsa; Koliopoulos, George; Badieritakis, Evangelos; Michaelakis, Antonios; Gavana, Elpida; Patsoula, Eleni; Tsimpos, Ioannis; Gioksari, Thalia; Kyriazopoulou, Evdoxia; Vakali, Annita; Pavli, Androula; Maltezou, Helena C.; Georgakopoulou, Theano; Hadjichristodoulou, Christos; Kremastinou, Jenny; Papa, Anna

    2016-01-01

    We report about the first imported case of Chikungunya fever in Greece in a Greek traveler returning from the Dominican Republic and the associated public health response. We investigated the case and performed focused epidemiological and entomological investigation in all areas the patient visited during the infectious period, to identify the targeted interventions needed. Entomological investigation revealed the occurrence of the competent vector Aedes albopictus (Diptera: Culicidae) in the environment surrounding the hospital where the patient was admitted and in her workplace. All captured mosquitoes tested negative for Chikungunya virus. We further conducted clinical and laboratory examination of the patient’s co-travelers, gave advice on appropriate personal preventive measures against mosquito bites to the patient and co-travelers and on vector control, and raised awareness among health professionals throughout Greece. The risk of introduction and local transmission of Chikungunya and other arboviruses in Greece and other European countries is present, as the competent vector exists in many parts of Europe. Public health professionals, travel medicine specialists and clinicians should maintain awareness regarding this possibility of importation of arbovirus cases in order to provide the appropriate advice, seek the prompt diagnosis, and implement appropriate interventions. Mobilization of various stakeholders will lead to enhanced epidemiological and entomological surveillance that will allow for improved risk assessment in each area. PMID:27159571

  6. 20 CFR 226.16 - Supplemental annuity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Supplemental annuity. 226.16 Section 226.16... EMPLOYEE, SPOUSE, AND DIVORCED SPOUSE ANNUITIES Computing an Employee Annuity § 226.16 Supplemental annuity. A supplemental annuity is payable in addition to tiers I and II and the vested dual benefit to an...

  7. 42 CFR 137.226 - How does a Self-Governance Tribe request a waiver?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false How does a Self-Governance Tribe request a waiver? 137.226 Section 137.226 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 137.226 How does a Self-Governance Tribe request a waiver? A Self-Governance Tribe may request a...

  8. 42 CFR 137.226 - How does a Self-Governance Tribe request a waiver?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false How does a Self-Governance Tribe request a waiver? 137.226 Section 137.226 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 137.226 How does a Self-Governance Tribe request a waiver? A Self-Governance Tribe may request a...

  9. 42 CFR 137.226 - How does a Self-Governance Tribe request a waiver?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false How does a Self-Governance Tribe request a waiver? 137.226 Section 137.226 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 137.226 How does a Self-Governance Tribe request a waiver? A Self-Governance Tribe may request a...

  10. 12 CFR Appendix A to Part 226 - Effect on State Laws

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Effect on State Laws A Appendix A to Part 226... TRUTH IN LENDING (REGULATION Z) Pt. 226, App. A Appendix A to Part 226—Effect on State Laws Request for Determination A request for a determination that a State law is inconsistent or that a State law is...

  11. 12 CFR Appendix A to Part 226 - Effect on State Laws

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 3 2013-01-01 2013-01-01 false Effect on State Laws A Appendix A to Part 226... (CONTINUED) TRUTH IN LENDING (REGULATION Z) Pt. 226, App. A Appendix A to Part 226—Effect on State Laws Request for Determination A request for a determination that a State law is inconsistent or that a State...

  12. 29 CFR 553.226 - Training time.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Training time. 553.226 Section 553.226 Labor Regulations... Enforcement Employees of Public Agencies Tour of Duty and Compensable Hours of Work Rules § 553.226 Training time. (a) The general rules for determining the compensability of training time under the FLSA are set...

  13. 12 CFR 226.4 - Finance charge.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 3 2013-01-01 2013-01-01 false Finance charge. 226.4 Section 226.4 Banks and...) TRUTH IN LENDING (REGULATION Z) General § 226.4 Finance charge. (a) Definition. The finance charge is... transaction. (1) Charges by third parties. The finance charge includes fees and amounts charged by someone...

  14. 12 CFR 226.4 - Finance charge.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 3 2014-01-01 2014-01-01 false Finance charge. 226.4 Section 226.4 Banks and...) TRUTH IN LENDING (REGULATION Z) General § 226.4 Finance charge. (a) Definition. The finance charge is... transaction. (1) Charges by third parties. The finance charge includes fees and amounts charged by someone...

  15. 12 CFR 226.4 - Finance charge.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Finance charge. 226.4 Section 226.4 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM TRUTH IN LENDING (REGULATION Z) General § 226.4 Finance charge. (a) Definition. The finance charge is the cost of consumer credit as a dollar amount. It...

  16. 12 CFR 226.4 - Finance charge.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 3 2012-01-01 2012-01-01 false Finance charge. 226.4 Section 226.4 Banks and... LENDING (REGULATION Z) General § 226.4 Finance charge. (a) Definition. The finance charge is the cost of...) Charges by third parties. The finance charge includes fees and amounts charged by someone other than the...

  17. Surveillance of deaths caused by arboviruses in Brazil: from dengue to chikungunya

    PubMed Central

    Cavalcanti, Luciano Pamplona de Góes; Freitas, André Ricardo Ribas; Brasil, Patrícia; da Cunha, Rivaldo Venâncio

    2017-01-01

    Did death occur DUE TO dengue, or in a patient WITH dengue virus infection? It seems a matter of semantics, but in fact, it underscores how challenging it is to distinguish whether the disease contributed to death, or was itself the underlying cause of death. Can a death be attributed to chikungunya virus, when some deaths occur after the acute phase? Did the virus decompensate the underlying diseases, leading to death? Did prolonged hospitalisation lead to infection, resulting in the patient’s progression to death? Were there iatrogenic complications during patient care? The dengue question, for which there has not yet been a definitive response, resurfaces prominently under the chikungunya surveillance scenario. We are facing an epidemic of a disease that seems to be more lethal than previously thought. The major challenge ahead is to investigate deaths suspected of occurring due to arbovirus infections and to understand the role of each infection in the unfavourable outcome. PMID:28767985

  18. First Report of Aedes aegypti Transmission of Chikungunya Virus in the Americas

    PubMed Central

    Díaz-González, Esteban E.; Kautz, Tiffany F.; Dorantes-Delgado, Alicia; Malo-García, Iliana R.; Laguna-Aguilar, Maricela; Langsjoen, Rose M.; Chen, Rubing; Auguste, Dawn I.; Sánchez-Casas, Rosa M.; Danis-Lozano, Rogelio; Weaver, Scott C.; Fernández-Salas, Ildefonso

    2015-01-01

    During a chikungunya fever outbreak in late 2014 in Chiapas, Mexico, entomovirological surveillance was performed to incriminate the vector(s). In neighborhoods, 75 households with suspected cases were sampled for mosquitoes, of which 80% (60) harbored Aedes aegypti and 2.7% (2) Aedes albopictus. A total of 1,170 Ae. aegypti and three Ae. albopictus was collected and 81 pools were generated. Although none of the Ae. albopictus pools were chikungunya virus (CHIKV)–positive, 18 Ae. aegypti pools (22.8%) contained CHIKV, yielding an infection rate of 32.3/1,000 mosquitoes. A lack of herd immunity in conjunction with high mosquito populations, poor vector control services in this region, and targeted collections in locations of human cases may explain the high infection rate in this vector. Consistent with predictions from experimental studies, Ae. aegypti appears to be the principal vector of CHIKV in southern Mexico, while the role of Ae. albopictus remains unknown. PMID:26416113

  19. Detection of Wolbachia in Aedes albopictus and Their Effects on Chikungunya Virus

    PubMed Central

    Ahmad, Noor Afizah; Vythilingam, Indra; Lim, Yvonne A. L.; Zabari, Nur Zatil Aqmar M.; Lee, Han Lim

    2017-01-01

    Wolbachia-based vector control strategies have been proposed as a means to augment the currently existing measures for controlling dengue and chikungunya vectors. Prior to utilizing Wolbachia as a novel vector control strategy, it is crucial to understand the Wolbachia–mosquito interactions. In this study, field surveys were conducted to screen for the infection status of Wolbachia in field-collected Aedes albopictus. The effects of Wolbachia in its native host toward the replication and dissemination of chikungunya virus (CHIKV) was also studied. The prevalence of Wolbachia-infected field-collected Ae. albopictus was estimated to be 98.6% (N = 142) for females and 95.1% (N = 102) for males in the population studied. The Ae. albopictus were naturally infected with both wAlbA and wAlbB strains. We also found that the native Wolbachia has no impact on CHIKV infection and minimal effect on CHIKV dissemination to secondary organs. PMID:27920393

  20. First Report of Aedes aegypti Transmission of Chikungunya Virus in the Americas.

    PubMed

    Díaz-González, Esteban E; Kautz, Tiffany F; Dorantes-Delgado, Alicia; Malo-García, Iliana R; Laguna-Aguilar, Maricela; Langsjoen, Rose M; Chen, Rubing; Auguste, Dawn I; Sánchez-Casas, Rosa M; Danis-Lozano, Rogelio; Weaver, Scott C; Fernández-Salas, Ildefonso

    2015-12-01

    During a chikungunya fever outbreak in late 2014 in Chiapas, Mexico, entomovirological surveillance was performed to incriminate the vector(s). In neighborhoods, 75 households with suspected cases were sampled for mosquitoes, of which 80% (60) harbored Aedes aegypti and 2.7% (2) Aedes albopictus. A total of 1,170 Ae. aegypti and three Ae. albopictus was collected and 81 pools were generated. Although none of the Ae. albopictus pools were chikungunya virus (CHIKV)-positive, 18 Ae. aegypti pools (22.8%) contained CHIKV, yielding an infection rate of 32.3/1,000 mosquitoes. A lack of herd immunity in conjunction with high mosquito populations, poor vector control services in this region, and targeted collections in locations of human cases may explain the high infection rate in this vector. Consistent with predictions from experimental studies, Ae. aegypti appears to be the principal vector of CHIKV in southern Mexico, while the role of Ae. albopictus remains unknown. © The American Society of Tropical Medicine and Hygiene.

  1. Chikungunya virus emergence in the Lao PDR, 2012–2013

    PubMed Central

    Somlor, Somphavanh; Vongpayloth, Khamsing; Diancourt, Laure; Buchy, Philippe; Duong, Veasna; Phonekeo, Darouny; Ketmayoon, Pakapak; Vongphrachanh, Phengta; Brey, Paul T.; Grandadam, Marc

    2017-01-01

    In May 2012, the first authenticated cases of active chikungunya virus infection were detected in Champasak Province, Southern Laos. Analysis of series of human samples and mosquito specimens collected during the outbreak and over the year that followed the emergence enabled the drawing up of a map of the progression of CHIKV and the establishment of a full genetic characterization of the virus. PMID:29284012

  2. Identification of infection by Chikungunya, Zika, and Dengue in an area of the Peruvian coast. Molecular diagnosis and clinical characteristics.

    PubMed

    Sánchez-Carbonel, José; Tantaléan-Yépez, Derek; Aguilar-Luis, Miguel Angel; Silva-Caso, Wilmer; Weilg, Pablo; Vásquez-Achaya, Fernando; Costa, Luis; Martins-Luna, Johanna; Sandoval, Isabel; Del Valle-Mendoza, Juana

    2018-03-14

    To assess the presence of Dengue, Chikungunya, and Zika in serum samples of patients with acute febrile illness in Piura, Peru and describe the most common clinical features. Dengue was the most common arbovirus detected in 170/496 (34.3%), followed by Zika in 39/496 (7.9%) and Chikungunya in 23/496 (4.6%). Among the 170 samples positive for Dengue, serotype 2 was the most predominant type present in 97/170 (57.1%) of samples, followed by the serotype 3 in 9/170 (5.3%). Headaches, muscle pain, and joint pain were the most common symptoms associated with fever in patients with Dengue and Zika. No symptoms predominance was observed in patients with Chikungunya.Dengue is considered the most frequent arbovirus in Peru and the number of cases has increased dramatically in the last 5 years. However, it is not the only arbovirus that circulates along the northern coast of Peru. It has also been determined the presence of Zika and Chikungunya in our population, which may suggest the circulation of other arboviruses that have not been detected.

  3. 22 CFR 226.41 - Recipient responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recipient responsibilities. 226.41 Section 226.41 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.41 Recipient...

  4. Mutant calreticulin-expressing cells induce monocyte hyperreactivity through a paracrine mechanism

    PubMed Central

    Garbati, Michael R.; Welgan, Catherine A.; Landefeld, Sally H.; Newell, Laura F.; Agarwal, Anupriya; Dunlap, Jennifer B.; Chourasia, Tapan K.; Lee, Hyunjung; Elferich, Johannes; Traer, Elie; Rattray, Rogan; Cascio, Michael J.; Press, Richard D.; Bagby, Grover C.; Tyner, Jeffrey W.; Druker, Brian J.; Dao, Kim-Hien T.

    2016-01-01

    Mutations in the calreticulin gene (CALR) were recently identified in approximately 70–80% of patients with JAK2-V617F-negative essential thrombocytosis and primary myelofibrosis. All frameshift mutations generate a recurring novel C-terminus. Here we provide evidence that mutant calreticulin does not accumulate efficiently in cells and is abnormally enriched in the nucleus and extracellular space compared to wildtype calreticulin. The main determinant of these findings is the loss of the calcium-binding and KDEL domains. Expression of type I mutant CALR in Ba/F3 cells confers minimal IL-3-independent growth. Interestingly, expression of type I and type II mutant CALR in a non-hematopoietic cell line does not directly activate JAK/STAT signaling compared to JAK2-V617F expression. These results led us to investigate paracrine mechanisms of JAK/STAT activation. Here we show that conditioned media from cells expressing type I mutant CALR exaggerate cytokine production from normal monocytes with or without treatment with a toll-like receptor agonist. These effects are not dependent on the novel C-terminus. These studies offer novel insights into the mechanism of JAK/STAT activation in patients with JAK2-V617F-negative essential thrombocytosis and primary myelofibrosis. PMID:26573090

  5. 22 CFR 226.46 - Procurement records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Procurement records. 226.46 Section 226.46 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.46 Procurement records...

  6. 22 CFR 226.48 - Contract provisions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Contract provisions. 226.48 Section 226.48 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.48 Contract provisions. The...

  7. 21 CFR 226.1 - Current good manufacturing practice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Current good manufacturing practice. 226.1 Section...) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES General Provisions § 226.1 Current good manufacturing practice. (a) The criteria in §§ 226.10 through 226.115, inclusive...

  8. 22 CFR 226.52 - Financial reporting.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Financial reporting. 226.52 Section 226.52 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Reports and Records § 226.52 Financial reporting. USAID...

  9. 30 CFR 22.6 - General requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false General requirements. 22.6 Section 22.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.6 General requirements. Methane detectors approved under...

  10. 30 CFR 22.6 - General requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false General requirements. 22.6 Section 22.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.6 General requirements. Methane detectors approved under...

  11. 30 CFR 22.6 - General requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false General requirements. 22.6 Section 22.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.6 General requirements. Methane detectors approved under...

  12. 30 CFR 22.6 - General requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false General requirements. 22.6 Section 22.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.6 General requirements. Methane detectors approved under...

  13. 30 CFR 22.6 - General requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false General requirements. 22.6 Section 22.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.6 General requirements. Methane detectors approved under...

  14. 31 CFR 226.6 - Financial reports.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Financial reports. 226.6 Section 226..., DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE RECOGNITION OF INSURANCE COVERING TREASURY TAX AND LOAN DEPOSITARIES § 226.6 Financial reports. Financial reports of Insurance Organizations shall be...

  15. Community context and sub-neighborhood scale detail to explain dengue, chikungunya and Zika patterns in Cali, Colombia.

    PubMed

    Krystosik, Amy R; Curtis, Andrew; Buritica, Paola; Ajayakumar, Jayakrishnan; Squires, Robert; Dávalos, Diana; Pacheco, Robinson; Bhatta, Madhav P; James, Mark A

    2017-01-01

    Cali, Colombia has experienced chikungunya and Zika outbreaks and hypoendemic dengue. Studies have explained Cali's dengue patterns but lack the sub-neighborhood-scale detail investigated here. Spatial-video geonarratives (SVG) with Ministry of Health officials and Community Health Workers were collected in hotspots, providing perspective on perceptions of why dengue, chikungunya and Zika hotspots exist, impediments to control, and social outcomes. Using spatial video and Google Street View, sub-neighborhood features possibly contributing to incidence were mapped to create risk surfaces, later compared with dengue, chikungunya and Zika case data. SVG captured insights in 24 neighborhoods. Trash and water risks in Calipso were mapped using SVG results. Perceived risk factors included proximity to standing water, canals, poverty, invasions, localized violence and military migration. These risks overlapped case density maps and identified areas that are suitable for transmission but are possibly underreporting to the surveillance system. Resulting risk maps with local context could be leveraged to increase vector-control efficiency- targeting key areas of environmental risk.

  16. Co-circulation of Dengue and Chikungunya Viruses, Al Hudaydah, Yemen, 2012

    PubMed Central

    El-Sawaf, Gamal; Faggioni, Giovanni; Vescio, Fenicia; Al Ameri, Ranya; De Santis, Riccardo; Helaly, Ghada; Pomponi, Alice; Metwally, Dalia; Fantini, Massimo; Qadi, Hussein; Ciccozzi, Massimo; Lista, Florigio

    2014-01-01

    We investigated 400 cases of dengue-like illness in persons hospitalized during an outbreak in Al Hudaydah, Yemen, in 2012. Overall, 116 dengue and 49 chikungunya cases were diagnosed. Dengue virus type 2 was the predominant serotype. The co-circulation of these viruses indicates that mosquitoborne infections represent a public health threat in Yemen. PMID:25061762

  17. 34 CFR 303.226 - Fiscal control.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false Fiscal control. 303.226 Section 303.226 Education... DISABILITIES State Application and Assurances Assurances § 303.226 Fiscal control. The State must ensure that fiscal control and fund accounting procedures will be adopted as necessary to ensure proper disbursement...

  18. 34 CFR 300.226 - Early intervening services.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true Early intervening services. 300.226 Section 300.226... CHILDREN WITH DISABILITIES Local Educational Agency Eligibility § 300.226 Early intervening services. (a... coordinated, early intervening services, which may include interagency financing structures, for students in...

  19. A novel DANP-coupled hairpin RT-PCR for rapid detection of Chikungunya virus.

    PubMed

    Chen, Huixin; Takei, Fumie; Koay, Evelyn Siew-Chuan; Nakatani, Kazuhiko; Chu, Justin Jang Hann

    2013-03-01

    Chikungunya has re-emerged as an important arboviral infection of global health significance. Because of lack of a vaccine and effective treatment, rapid diagnosis plays an important role in early clinical management of patients. In this study, we have developed a novel molecular diagnostic platform that ensures a rapid and cost-effective one-step RT-PCR assay, with high sensitivity and specificity, for the early detection of the Chikungunya virus (CHIKV). It uses 2,7-diamino-1,8-naphthyridine derivative (DANP)-labeled cytosine-bulge hairpin primers to amplify the nsP2 region of the CHIKV genome, followed by measurement of the fluorescence emitted from DANP-primer complexes after PCRs. The detection limit of our assay was 0.01 plaque-forming units per reaction of CHIKV. Furthermore, the HP-nsP2 primers were highly specific in detecting CHIKV, without any cross-reactivity with the panel of RNA viruses validated in this study. The feasibility of the DANP-coupled hairpin RT-PCR for clinical diagnosis was evaluated using clinical serum samples from CHIKV-infected patients, and the specificity and sensitivity were 100% (95% CI, 80.0% to 100%) and 95.5% (95% CI, 75.1% to 99.8%), respectively. These findings confirmed its potential as a point-of-care clinical molecular diagnostic assay for CHIKV in acute-phase patient serum samples. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  20. Comparative evaluation of the diagnostic potential of recombinant envelope proteins and native cell culture purified viral antigens of Chikungunya virus.

    PubMed

    Khan, Mohsin; Dhanwani, Rekha; Kumar, Jyoti S; Rao, P V Lakshmana; Parida, Manmohan

    2014-07-01

    Despite the fact that Chikungunya resurgence is associated with epidemic of unprecedented magnitude, there are challenges in the field of its clinical diagnosis. However, serological tests in an ELISA format provide a rapid tool for the diagnosis of Chikungunya infection. Indeed, ELISAs based on recombinant proteins hold a great promise as these methods are cost effective and are free from the risk of handling biohazardous material. In this study, the performance of recombinant CHIKV antigens was compared in various ELISA formats for the diagnosis of Chikungunya. Two recombinant antigens derived from the envelope proteins of Chikungunya virus were prepared and evaluated by comparing their competence for detecting circulating antibodies in serum samples of patients infected with CHIKV using MAC-ELISA and indirect IgM-ELISA. The efficacy of the recombinant antigens was also compared with the native antigen. The indirect antibody capture IgM microplate ELISA revealed ≥90% concordance with the native antigen in detecting the CHIKV specific IgM antibodies whereas the recombinant antigen based MAC-ELISA showed 100% specificity. The recombinant antigens used in this study were effective and reliable targets for the diagnosis of CHIKV infection and also provide an alternative for native antigen use which is potentially biohazardous. © 2013 Wiley Periodicals, Inc.

  1. Leidos Biomed Supports Clinical Trials for Vaccine Against Mosquito-borne Chikungunya | FNLCR Staging

    Cancer.gov

    An experimental vaccine for mosquito-borne chikungunya is being tested at sites in the Caribbean as part of a phase II clinical trial being managed by the Frederick National Lab. No vaccine or treatment currently exists for the viral disease, which c

  2. 31 CFR 226.7 - Effective date.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Effective date. 226.7 Section 226.7 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... LOAN DEPOSITARIES § 226.7 Effective date. The provisions of this part become effective November 2, 1978...

  3. 25 CFR 226.46 - Information collection.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Information collection. 226.46 Section 226.46 Indians... LANDS FOR OIL AND GAS MINING Appeals and Notices § 226.46 Information collection. The Office of Management and Budget has determined that the information collection requirements contained in this part need...

  4. 25 CFR 226.36 - Control devices.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Control devices. 226.36 Section 226.36 Indians BUREAU OF... AND GAS MINING Requirements of Lessees § 226.36 Control devices. In drilling operations in fields... operations to maintain proper control of subsurface strata. [55 FR 33116, Aug. 14, 1990] ...

  5. 25 CFR 226.36 - Control devices.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Control devices. 226.36 Section 226.36 Indians BUREAU OF... AND GAS MINING Requirements of Lessees § 226.36 Control devices. In drilling operations in fields... operations to maintain proper control of subsurface strata. [55 FR 33116, Aug. 14, 1990] ...

  6. 25 CFR 226.36 - Control devices.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Control devices. 226.36 Section 226.36 Indians BUREAU OF... AND GAS MINING Requirements of Lessees § 226.36 Control devices. In drilling operations in fields... operations to maintain proper control of subsurface strata. [55 FR 33116, Aug. 14, 1990] ...

  7. 21 CFR 226.20 - Buildings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Buildings. 226.20 Section 226.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Construction and Maintenance of...

  8. The quantitative structure-insecticidal activity relationships from plant derived compounds against chikungunya and zika Aedes aegypti (Diptera:Culicidae) vector.

    PubMed

    Saavedra, Laura M; Romanelli, Gustavo P; Rozo, Ciro E; Duchowicz, Pablo R

    2018-01-01

    The insecticidal activity of a series of 62 plant derived molecules against the chikungunya, dengue and zika vector, the Aedes aegypti (Diptera:Culicidae) mosquito, is subjected to a Quantitative Structure-Activity Relationships (QSAR) analysis. The Replacement Method (RM) variable subset selection technique based on Multivariable Linear Regression (MLR) proves to be successful for exploring 4885 molecular descriptors calculated with Dragon 6. The predictive capability of the obtained models is confirmed through an external test set of compounds, Leave-One-Out (LOO) cross-validation and Y-Randomization. The present study constitutes a first necessary computational step for designing less toxic insecticides. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 22 CFR 226.11 - Pre-award policies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Pre-award policies. 226.11 Section 226.11 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Pre-award Requirements § 226.11 Pre-award policies. (a) Use of grants and...

  10. 25 CFR 226.22 - Prohibition of pollution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Prohibition of pollution. 226.22 Section 226.22 Indians... LANDS FOR OIL AND GAS MINING Operations § 226.22 Prohibition of pollution. (a) All operators... holes) in a manner that will prevent pollution and the migration of oil, gas, salt water or other...

  11. Plant expression systems, a budding way to confront chikungunya and Zika in developing countries?

    PubMed Central

    Cardona-Ospina, Jaime A.; Sepúlveda-Arias, Juan C.; Mancilla, L.; Gutierrez-López, Luis G.

    2016-01-01

    Plant expression systems could be used as biofactories of heterologous proteins that have the potential to be used with biopharmaceutical aims and vaccine design. This technology is scalable, safe and cost-effective and it has been previously proposed as an option for vaccine and protein pharmaceutical development in developing countries. Here we present a proposal of how plant expression systems could be used to address Zika and chikungunya outbreaks through development of vaccines and rapid diagnostic kits. PMID:27781090

  12. 20 CFR 226.33 - Spouse regular annuity rate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Spouse regular annuity rate. 226.33 Section... COMPUTING EMPLOYEE, SPOUSE, AND DIVORCED SPOUSE ANNUITIES Computing a Spouse or Divorced Spouse Annuity § 226.33 Spouse regular annuity rate. The final tier I and tier II rates, from §§ 226.30 and 226.32, are...

  13. 25 CFR 226.33 - Line drilling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Line drilling. 226.33 Section 226.33 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.33 Line drilling. Lessee shall not drill within 300 feet...

  14. 25 CFR 226.33 - Line drilling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Line drilling. 226.33 Section 226.33 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.33 Line drilling. Lessee shall not drill within 300 feet...

  15. 25 CFR 226.33 - Line drilling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Line drilling. 226.33 Section 226.33 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.33 Line drilling. Lessee shall not drill within 300 feet...

  16. 25 CFR 226.33 - Line drilling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Line drilling. 226.33 Section 226.33 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.33 Line drilling. Lessee shall not drill within 300 feet...

  17. 25 CFR 226.33 - Line drilling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Line drilling. 226.33 Section 226.33 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.33 Line drilling. Lessee shall not drill within 300 feet...

  18. 49 CFR 195.226 - Welding: Arc burns.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Welding: Arc burns. 195.226 Section 195.226 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... PIPELINE Construction § 195.226 Welding: Arc burns. (a) Each arc burn must be repaired. (b) An arc burn may...

  19. 49 CFR 195.226 - Welding: Arc burns.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Welding: Arc burns. 195.226 Section 195.226 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... PIPELINE Construction § 195.226 Welding: Arc burns. (a) Each arc burn must be repaired. (b) An arc burn may...

  20. 49 CFR 195.226 - Welding: Arc burns.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Welding: Arc burns. 195.226 Section 195.226 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... PIPELINE Construction § 195.226 Welding: Arc burns. (a) Each arc burn must be repaired. (b) An arc burn may...

  1. 49 CFR 195.226 - Welding: Arc burns.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Welding: Arc burns. 195.226 Section 195.226 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... PIPELINE Construction § 195.226 Welding: Arc burns. (a) Each arc burn must be repaired. (b) An arc burn may...

  2. 49 CFR 195.226 - Welding: Arc burns.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Welding: Arc burns. 195.226 Section 195.226 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... PIPELINE Construction § 195.226 Welding: Arc burns. (a) Each arc burn must be repaired. (b) An arc burn may...

  3. 31 CFR 800.226 - U.S. business.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false U.S. business. 800.226 Section 800.226... FOREIGN PERSONS Definitions § 800.226 U.S. business. The term U.S. business means any entity, irrespective... subsidiary is a U.S. business. Corporation A and its branch or subsidiary is each also a foreign person...

  4. 31 CFR 800.226 - U.S. business.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false U.S. business. 800.226 Section 800.226... FOREIGN PERSONS Definitions § 800.226 U.S. business. The term U.S. business means any entity, irrespective... subsidiary is a U.S. business. Corporation A and its branch or subsidiary is each also a foreign person...

  5. 31 CFR 800.226 - U.S. business.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false U.S. business. 800.226 Section 800.226... FOREIGN PERSONS Definitions § 800.226 U.S. business. The term U.S. business means any entity, irrespective... subsidiary is a U.S. business. Corporation A and its branch or subsidiary is each also a foreign person...

  6. 21 CFR 226.10 - Personnel.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Personnel. 226.10 Section 226.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL.... The key personnel and any consultants involved in the manufacture and control of the Type A medicated...

  7. 21 CFR 226.10 - Personnel.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Personnel. 226.10 Section 226.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL.... The key personnel and any consultants involved in the manufacture and control of the Type A medicated...

  8. 21 CFR 226.10 - Personnel.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Personnel. 226.10 Section 226.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL.... The key personnel and any consultants involved in the manufacture and control of the Type A medicated...

  9. 21 CFR 226.10 - Personnel.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Personnel. 226.10 Section 226.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL.... The key personnel and any consultants involved in the manufacture and control of the Type A medicated...

  10. 21 CFR 226.10 - Personnel.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Personnel. 226.10 Section 226.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL.... The key personnel and any consultants involved in the manufacture and control of the Type A medicated...

  11. A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action.

    PubMed

    McInerney, E M; Ince, B A; Shapiro, D J; Katzenellenbogen, B S

    1996-12-01

    We have characterized a human estrogen receptor (ER) mutant, V364E, which has a single amino acid substitution in its hormone-binding domain. This ER mutant is fully active or even superactive at saturating levels of estradiol (10(-8) M E2) yet has the capacity to act as a strong dominant negative inhibitor of the wild type ER. In transient transfection assays using ER-negative Chinese hamster ovary (CHO) cells and two different estrogen response element (ERE)-containing promoter reporter genes, V364E treated with 10(-8) M E2 exhibited approximately 250% and 100% of the activity of the wild type ER with these two promoter contexts, respectively. Despite the high activity of V364E when present alone in cells, coexpression of both V364E and wild type ER causes a significant decrease in overall ER-mediated transcriptional activity. On the TATA promoter, where V364E was more inhibitory, estrogen-stimulated activity was reduced by approximately 50% at a 1:1 ratio of mutant to wild type ER expression vector, and at a 10:1 ratio, 75% of ER activity was inhibited. V364E was expressed at lower levels than wild type ER and has a approximately 40-fold lower affinity for E2 compared with wild type ER. In promoter interference assays, V364E exhibited a strict dependence upon E2 for binding to an ERE. Surprisingly, even when V364E was unable to bind to ERE DNA (i.e. either at low E2 concentration or by mutation of its DNA-binding domain), this mutant retained full dominant negative activity. This highly active ER mutant is, thus, able to repress ER-mediated transcription when the mutant and wild type ER are present together in cells, even without DNA binding. Since competition for ERE binding and the formation of inactive heterodimers cannot fully account for the dominant negative activity of V364E, it is probable that altered interactions with proteins important in ER-mediated transcription play a key role in the repression of transcription by V364E. The properties and probable

  12. 22 CFR 22.6 - Refund of fees.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Refund of fees. 22.6 Section 22.6 Foreign... FOREIGN SERVICE § 22.6 Refund of fees. (a) Fees which have been collected for deposit in the Treasury are refundable: (1) As specifically authorized by law (See 22 U.S.C. 214a concerning passport fees erroneously...

  13. 22 CFR 22.6 - Refund of fees.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Refund of fees. 22.6 Section 22.6 Foreign... FOREIGN SERVICE § 22.6 Refund of fees. (a) Fees which have been collected for deposit in the Treasury are refundable: (1) As specifically authorized by law (See 22 U.S.C. 214a concerning passport fees erroneously...

  14. 22 CFR 22.6 - Refund of fees.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Refund of fees. 22.6 Section 22.6 Foreign... FOREIGN SERVICE § 22.6 Refund of fees. (a) Fees which have been collected for deposit in the Treasury are refundable: (1) As specifically authorized by law (See 22 U.S.C. 214a concerning passport fees erroneously...

  15. 22 CFR 22.6 - Refund of fees.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Refund of fees. 22.6 Section 22.6 Foreign... FOREIGN SERVICE § 22.6 Refund of fees. (a) Fees which have been collected for deposit in the Treasury are refundable: (1) As specifically authorized by law (See 22 U.S.C. 214a concerning passport fees erroneously...

  16. 22 CFR 22.6 - Refund of fees.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Refund of fees. 22.6 Section 22.6 Foreign... FOREIGN SERVICE § 22.6 Refund of fees. (a) Fees which have been collected for deposit in the Treasury are refundable: (1) As specifically authorized by law (See 22 U.S.C. 214a concerning passport fees erroneously...

  17. 12 CFR 226.27 - Language of disclosures.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Language of disclosures. 226.27 Section 226.27... TRUTH IN LENDING (REGULATION Z) Miscellaneous § 226.27 Language of disclosures. Disclosures required by this regulation may be made in a language other than English, provided that the disclosures are made...

  18. First report of naturally infected Aedes aegypti with chikungunya virus genotype ECSA in the Americas.

    PubMed

    Costa-da-Silva, André Luis; Ioshino, Rafaella Sayuri; Petersen, Vivian; Lima, Antonio Fernando; Cunha, Marielton Dos Passos; Wiley, Michael R; Ladner, Jason T; Prieto, Karla; Palacios, Gustavo; Costa, Danuza Duarte; Suesdek, Lincoln; Zanotto, Paolo Marinho de Andrade; Capurro, Margareth Lara

    2017-06-01

    The worldwide expansion of new emergent arboviruses such as Chikungunya and Zika reinforces the importance in understanding the role of mosquito species in spreading these pathogens in affected regions. This knowledge is essential for developing effective programs based on species specificity to avoid the establishment of endemic transmission cycles sustained by the identified local vectors. Although the first autochthonous transmission of Chikungunya virus was described in 2014 in the north of Brazil, the main outbreaks were reported in 2015 and 2016 in the northeast of Brazil. During 5 days of February 2016, we collected mosquitoes in homes of 6 neighborhoods of Aracaju city, the capital of Sergipe state. Four mosquito species were identified but Culex quinquefasciatus and Aedes aegypti were the most abundant. Field-caught mosquitoes were tested for Chikungunya (CHIKV), Zika (ZIKV) and Dengue viruses (DENV) by qRT-PCR and one CHIKV-infected Ae. aegypti female was detected. The complete sequence of CHIKV genome was obtained from this sample and phylogenetic analysis revealed that this isolate belongs to the East-Central-South-African (ECSA) genotype. Our study describes the first identification of a naturally CHIKV-infected Ae. aegypti in Brazil and the first report of a CHIKV from ECSA genotype identified in this species in the Americas. These findings support the notion of Ae. aegypti being a vector involved in CHIKV outbreaks in northeast of Brazil.

  19. 12 CFR 226.10 - Payments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Payments. 226.10 Section 226.10 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM TRUTH IN...) Specifying one particular address for receiving payments, such as a post office box. (3) In-person payments...

  20. 12 CFR 226.17 - General disclosure requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... identity under § 226.18(a). For private education loan disclosures made in compliance with § 226.47, the... applicable provisions of the Electronic Signatures in Global and National Commerce Act (E-Sign Act) (15 U.S.C...) must be separate from the other disclosures under § 226.18, except for private education loan...

  1. 21 CFR 226.42 - Components.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-contamination from manufacturing operations. ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Components. 226.42 Section 226.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL...

  2. 27 CFR 41.226 - Change in control of a corporation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Change in control of a corporation. 41.226 Section 41.226 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS...

  3. 27 CFR 41.226 - Change in control of a corporation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Change in control of a corporation. 41.226 Section 41.226 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS...

  4. 25 CFR 226.2 - Sale of leases.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Sale of leases. 226.2 Section 226.2 Indians BUREAU OF... AND GAS MINING Leasing Procedure, Rental and Royalty § 226.2 Sale of leases. (a) Written application... sale of oil leases, gas leases, and oil and gas leases to the highest responsible bidder on specific...

  5. 25 CFR 226.2 - Sale of leases.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Sale of leases. 226.2 Section 226.2 Indians BUREAU OF... AND GAS MINING Leasing Procedure, Rental and Royalty § 226.2 Sale of leases. (a) Written application... sale of oil leases, gas leases, and oil and gas leases to the highest responsible bidder on specific...

  6. Emerging Causes of Arbovirus Encephalitis in North America: Powassan, Chikungunya, and Zika Viruses.

    PubMed

    Doughty, Christopher T; Yawetz, Sigal; Lyons, Jennifer

    2017-02-01

    Arboviruses are arthropod-borne viruses transmitted by the bite of mosquitoes, ticks, or other arthropods. Arboviruses are a common and an increasing cause of human illness in North America. Powassan virus, Chikungunya virus, and Zika virus are arboviruses that have all recently emerged as increasing causes of neurologic illness. Powassan virus almost exclusively causes encephalitis, but cases are rare, sporadic, and restricted to portions of North America and Russia. Chikungunya virus has spread widely across the world, causing millions of infections. Encephalitis is a rare manifestation of illness but is more common and severe in neonates and older adults. Zika virus has recently spread through much of the Americas and has been associated mostly with microcephaly and other congenital neurologic complications. Encephalitis occurring in infected adults has also been recently reported. This review will discuss the neuropathogenesis of these viruses, their transmission and geographic distribution, the spectrum of their neurologic manifestations, and the appropriate method of diagnosis.

  7. Single-Reaction Multiplex Reverse Transcription PCR for Detection of Zika, Chikungunya, and Dengue Viruses

    PubMed Central

    Waggoner, Jesse J.; Gresh, Lionel; Mohamed-Hadley, Alisha; Ballesteros, Gabriela; Davila, Maria Jose Vargas; Tellez, Yolanda; Sahoo, Malaya K.; Balmaseda, Angel; Harris, Eva

    2016-01-01

    Clinical manifestations of Zika virus, chikungunya virus, and dengue virus infections can be similar. To improve virus detection, streamline molecular workflow, and decrease test costs, we developed and evaluated a multiplex real-time reverse transcription PCR for these viruses. PMID:27184629

  8. Public reaction to Chikungunya outbreaks in Italy-Insights from an extensive novel data streams-based structural equation modeling analysis.

    PubMed

    Mahroum, Naim; Adawi, Mohammad; Sharif, Kassem; Waknin, Roy; Mahagna, Hussein; Bisharat, Bishara; Mahamid, Mahmud; Abu-Much, Arsalan; Amital, Howard; Luigi Bragazzi, Nicola; Watad, Abdulla

    2018-01-01

    The recent outbreak of Chikungunya virus in Italy represents a serious public health concern, which is attracting media coverage and generating public interest in terms of Internet searches and social media interactions. Here, we sought to assess the Chikungunya-related digital behavior and the interplay between epidemiological figures and novel data streams traffic. Reaction to the recent outbreak was analyzed in terms of Google Trends, Google News and Twitter traffic, Wikipedia visits and edits, and PubMed articles, exploiting structural modelling equations. A total of 233,678 page-views and 150 edits on the Italian Wikipedia page, 3,702 tweets, 149 scholarly articles, and 3,073 news articles were retrieved. The relationship between overall Chikungunya cases, as well as autochthonous cases, and tweets production was found to be fully mediated by Chikungunya-related web searches. However, in the allochthonous/imported cases model, tweet production was not found to be significantly mediated by epidemiological figures, with web searches still significantly mediating tweet production. Inconsistent relationships were detected in mediation models involving Wikipedia usage as a mediator variable. Similarly, the effect between news consumption and tweets production was suppressed by the Wikipedia usage. A further inconsistent mediation was found in the case of the effect between Wikipedia usage and tweets production, with web searches as a mediator variable. When adjusting for the Internet penetration index, similar findings could be obtained, with the important exception that in the adjusted model the relationship between GN and Twitter was found to be partially mediated by Wikipedia usage. Furthermore, the link between Wikipedia usage and PubMed/MEDLINE was fully mediated by GN, differently from what was found in the unadjusted model. In conclusion-a significant public reaction to the current Chikungunya outbreak was documented. Health authorities should be aware of

  9. Public reaction to Chikungunya outbreaks in Italy—Insights from an extensive novel data streams-based structural equation modeling analysis

    PubMed Central

    Sharif, Kassem; Waknin, Roy; Mahagna, Hussein; Bisharat, Bishara; Mahamid, Mahmud; Abu-Much, Arsalan; Amital, Howard; Luigi Bragazzi, Nicola

    2018-01-01

    The recent outbreak of Chikungunya virus in Italy represents a serious public health concern, which is attracting media coverage and generating public interest in terms of Internet searches and social media interactions. Here, we sought to assess the Chikungunya-related digital behavior and the interplay between epidemiological figures and novel data streams traffic. Reaction to the recent outbreak was analyzed in terms of Google Trends, Google News and Twitter traffic, Wikipedia visits and edits, and PubMed articles, exploiting structural modelling equations. A total of 233,678 page-views and 150 edits on the Italian Wikipedia page, 3,702 tweets, 149 scholarly articles, and 3,073 news articles were retrieved. The relationship between overall Chikungunya cases, as well as autochthonous cases, and tweets production was found to be fully mediated by Chikungunya-related web searches. However, in the allochthonous/imported cases model, tweet production was not found to be significantly mediated by epidemiological figures, with web searches still significantly mediating tweet production. Inconsistent relationships were detected in mediation models involving Wikipedia usage as a mediator variable. Similarly, the effect between news consumption and tweets production was suppressed by the Wikipedia usage. A further inconsistent mediation was found in the case of the effect between Wikipedia usage and tweets production, with web searches as a mediator variable. When adjusting for the Internet penetration index, similar findings could be obtained, with the important exception that in the adjusted model the relationship between GN and Twitter was found to be partially mediated by Wikipedia usage. Furthermore, the link between Wikipedia usage and PubMed/MEDLINE was fully mediated by GN, differently from what was found in the unadjusted model. In conclusion—a significant public reaction to the current Chikungunya outbreak was documented. Health authorities should be aware of

  10. Next generation sequencing of DNA-launched Chikungunya vaccine virus

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

    Hidajat, Rachmat; Nickols, Brian; Forrester, Naomi

    Chikungunya virus (CHIKV) represents a pandemic threat with no approved vaccine available. Recently, we described a novel vaccination strategy based on iDNA® infectious clone designed to launch a live-attenuated CHIKV vaccine from plasmid DNA in vitro or in vivo. As a proof of concept, we prepared iDNA plasmid pCHIKV-7 encoding the full-length cDNA of the 181/25 vaccine. The DNA-launched CHIKV-7 virus was prepared and compared to the 181/25 virus. Illumina HiSeq2000 sequencing revealed that with the exception of the 3′ untranslated region, CHIKV-7 viral RNA consistently showed a lower frequency of single-nucleotide polymorphisms than the 181/25 RNA including at themore » E2-12 and E2-82 residues previously identified as attenuating mutations. In the CHIKV-7, frequencies of reversions at E2-12 and E2-82 were 0.064% and 0.086%, while in the 181/25, frequencies were 0.179% and 0.133%, respectively. We conclude that the DNA-launched virus has a reduced probability of reversion mutations, thereby enhancing vaccine safety. - Highlights: • Chikungunya virus (CHIKV) is an emerging pandemic threat. • In vivo DNA-launched attenuated CHIKV is a novel vaccine technology. • DNA-launched virus was sequenced using HiSeq2000 and compared to the 181/25 virus. • DNA-launched virus has lower frequency of SNPs at E2-12 and E2-82 attenuation loci.« less

  11. Community context and sub-neighborhood scale detail to explain dengue, chikungunya and Zika patterns in Cali, Colombia

    PubMed Central

    Curtis, Andrew; Buritica, Paola; Ajayakumar, Jayakrishnan; Squires, Robert; Dávalos, Diana; Pacheco, Robinson; Bhatta, Madhav P.; James, Mark A.

    2017-01-01

    Background Cali, Colombia has experienced chikungunya and Zika outbreaks and hypoendemic dengue. Studies have explained Cali’s dengue patterns but lack the sub-neighborhood-scale detail investigated here. Methods Spatial-video geonarratives (SVG) with Ministry of Health officials and Community Health Workers were collected in hotspots, providing perspective on perceptions of why dengue, chikungunya and Zika hotspots exist, impediments to control, and social outcomes. Using spatial video and Google Street View, sub-neighborhood features possibly contributing to incidence were mapped to create risk surfaces, later compared with dengue, chikungunya and Zika case data. Results SVG captured insights in 24 neighborhoods. Trash and water risks in Calipso were mapped using SVG results. Perceived risk factors included proximity to standing water, canals, poverty, invasions, localized violence and military migration. These risks overlapped case density maps and identified areas that are suitable for transmission but are possibly underreporting to the surveillance system. Conclusion Resulting risk maps with local context could be leveraged to increase vector-control efficiency- targeting key areas of environmental risk. PMID:28767730

  12. 22 CFR 226.17 - Certifications and representations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certifications and representations. 226.17 Section 226.17 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Pre-award Requirements § 226.17 Certifications and...

  13. 22 CFR 226.1003 - Air transportation. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Air transportation. [Reserved] 226.1003 Section 226.1003 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1003 Air transportation...

  14. 22 CFR 226.1003 - Air transportation. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Air transportation. [Reserved] 226.1003 Section 226.1003 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1003 Air transportation...

  15. 22 CFR 226.1003 - Air transportation. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Air transportation. [Reserved] 226.1003 Section 226.1003 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1003 Air transportation...

  16. Evaluation of chikungunya virus infection in children from India during 2009-2010: A cross sectional observational study.

    PubMed

    Raghavendhar, B Siva; Ray, Pratima; Ratagiri, Vinod H; Sharma, B S; Kabra, Sushil K; Lodha, Rakesh

    2016-06-01

    Chikungunya virus, a small (about 60-70 nm diameter), spherical, enveloped, positive, single stranded RNA virus is transmitted by Aedes mosquitoes. After a short period of incubation (3-5 days) symptoms like fever with joint pains and others start appearing. After a gap of 20 years, this virus re-emerged during 2006-2008 in India causing a major outbreak of CHIKV in India. This study was conducted subsequent to the major outbreak in order to evaluate the proportion of chikungunya virus infection in children with suggestive symptoms at three geographical locations of India. Lineage of circulating strains and changes in the E1 structural polypeptide were also determined. Blood samples were collected (in Sodium citrate vacutainer tubes) during 1st June 2009 to 31st May 2010 from children (age 0 ≤ 18 years) suspected to have chikungunya infection, that is, those who presented with sudden onset of fever and/or joint pain, myalgia, and headache from three regions of India, All India Institute of Medical Sciences (AIIMS) in New Delhi, Karnataka Institute of Medical Sciences (KIMS) in Hubli and Sawai Mansingh Medical College (SMS) in Jaipur. Detection of CHIKV antibodies in all acute-phase patient plasma samples was done by IgM ELISA and for samples within ≤5 days of fever, a one-step RT-PCR was carried out on a block thermo-cycler targeting 294 bp region of E1 gene that codes for the viral envelope protein. Comparison of nucleotide and amino acid sequences from few positive samples of two regions was done with African S-27 reference strain using BioEdit. A phylogenetic tree was constructed using MEGA 6 by using the Maximum Likelihood method based on the Kimura 2-parameter model. Out of the 723 acute phase samples tested from three geographical locations of India, Chikungunya virus infection was detected in 249/723 (34.44%) subjects by either IgM Elisa (180/723) or RT-PCR (69/412). RT-PCR was employed in samples collected from children with ≤5 days of fever. Maximum

  17. A Conducting State with Properties of a Slow Inactivated State in a Shaker K+ Channel Mutant

    PubMed Central

    Olcese, Riccardo; Sigg, Daniel; Latorre, Ramon; Bezanilla, Francisco; Stefani, Enrico

    2001-01-01

    In Shaker K+ channel, the amino terminus deletion Δ6-46 removes fast inactivation (N-type) unmasking a slow inactivation process. In Shaker Δ6-46 (Sh-IR) background, two additional mutations (T449V-I470C) remove slow inactivation, producing a noninactivating channel. However, despite the fact that Sh-IR-T449V-I470C mutant channels remain conductive, prolonged depolarizations (1 min, 0 mV) produce a shift of the QV curve by about −30 mV, suggesting that the channels still undergo the conformational changes typical of slow inactivation. For depolarizations longer than 50 ms, the tail currents measured during repolarization to −90 mV display a slow component that increases in amplitude as the duration of the depolarizing pulse increases. We found that the slow development of the QV shift had a counterpart in the amplitude of the slow component of the ionic tail current that is not present in Sh-IR. During long depolarizations, the time course of both the increase in the slow component of the tail current and the change in voltage dependence of the charge movement could be well fitted by exponential functions with identical time constant of 459 ms. Single channel recordings revealed that after prolonged depolarizations, the channels remain conductive for long periods after membrane repolarization. Nonstationary autocovariance analysis performed on macroscopic current in the T449V-I470C mutant confirmed that a novel open state appears with increasing prepulse depolarization time. These observations suggest that in the mutant studied, a new open state becomes progressively populated during long depolarizations (>50 ms). An appealing interpretation of these results is that the new open state of the mutant channel corresponds to a slow inactivated state of Sh-IR that became conductive. PMID:11158167

  18. Dual MAPK inhibition is an effective therapeutic strategy for a subset of class II BRAF mutant melanoma.

    PubMed

    Dankner, Matthew; Lajoie, Mathieu; Moldoveanu, Dan; Nguyen, Tan-Trieu; Savage, Paul; Rajkumar, Shivshankari; Huang, Xiu; Lvova, Maria; Protopopov, Alexei; Vuzman, Dana; Hogg, David; Park, Morag; Guiot, Marie-Christine; Petrecca, Kevin; Mihalcioiu, Catalin; Watson, Ian R; Siegel, Peter M; Rose, April A N

    2018-06-14

    Dual MAPK pathway inhibition (dMAPKi) with BRAF and MEK inhibitors improves survival in BRAF V600E/K mutant melanoma, but the efficacy of dMAPKi in non-V600 BRAF mutant tumors is poorly understood. We sought to characterize the responsiveness of class II (enhanced kinase activity, dimerization dependent) BRAF mutant melanoma to dMAPKi. Tumors from patients with BRAF WT, V600E (class I) and L597S (class II) metastatic melanoma were used to generate patient-derived-xenografts (PDX). We assembled a panel of melanoma cell lines with class IIa (activation segment) or IIb (p-loop) mutations and compared these to wild-type or V600E/K BRAF mutant cells. Cell lines and PDXs were treated with BRAFi (vemurafenib, dabrafenib, encorafenib, LY3009120), MEKi (cobimetinib, trametinib, binimetinib) or the combination. We identified two patients with BRAF L597S metastatic melanoma who were treated with dMAPKi. BRAFi impaired MAPK signalling and cell growth in class I and II BRAF mutant cells. dMAPKi was more effective than either single MAPKi at inhibiting cell growth in all class II BRAF mutant cells tested. dMAPKi caused tumor regression in two melanoma PDXs with class II BRAF mutations, and prolonged survival of mice with class II BRAF mutant melanoma brain metastases. Two patients with BRAF L597S mutant melanoma clinically responded to dMAPKi. Class II BRAF mutant melanoma are growth inhibited by dMAPKi. Responses to dMAPKi have been observed in two patients with class II BRAF mutant melanoma. This data provides rationale for clinical investigation of dMAPKi in patients with class II BRAF mutant metastatic melanoma. Copyright ©2018, American Association for Cancer Research.

  19. 22 CFR 226.61 - Suspension and termination.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Suspension and termination. 226.61 Section 226.61 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Suspension, Termination and Enforcement § 226...

  20. 22 CFR 226.37 - Property trust relationship.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Property trust relationship. 226.37 Section 226.37 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Property Standards § 226.37 Property trust...

  1. External quality assessment of dengue and chikungunya diagnostics in the Asia Pacific region, 2015

    PubMed Central

    Soh, Li Ting; Squires, Raynal C; Tan, Li Kiang; Pok, Kwoon Yong; Yang, HuiTing; Liew, Christina; Shah, Aparna Singh; Aaskov, John; Abubakar, Sazaly; Hasabe, Futoshi; Ng, Lee Ching

    2016-01-01

    Objective To conduct an external quality assessment (EQA) of dengue and chikungunya diagnostics among national-level public health laboratories in the Asia Pacific region following the first round of EQA for dengue diagnostics in 2013. Methods Twenty-four national-level public health laboratories performed routine diagnostic assays on a proficiency testing panel consisting of two modules. Module A contained serum samples spiked with cultured dengue virus (DENV) or chikungunya virus (CHIKV) for the detection of nucleic acid and DENV non-structural protein 1 (NS1) antigen. Module B contained human serum samples for the detection of anti-DENV antibodies. Results Among 20 laboratories testing Module A, 17 (85%) correctly detected DENV RNA by reverse transcription polymerase chain reaction (RT–PCR), 18 (90%) correctly determined serotype and 19 (95%) correctly identified CHIKV by RT–PCR. Ten of 15 (66.7%) laboratories performing NS1 antigen assays obtained the correct results. In Module B, 18/23 (78.3%) and 20/20 (100%) of laboratories correctly detected anti-DENV IgM and IgG, respectively. Detection of acute/recent DENV infection by both molecular (RT–PCR) and serological methods (IgM) was available in 19/24 (79.2%) participating laboratories. Discussion Accurate laboratory testing is a critical component of dengue and chikungunya surveillance and control. This second round of EQA reveals good proficiency in molecular and serological diagnostics of these diseases in the Asia Pacific region. Further comprehensive diagnostic testing, including testing for Zika virus, should comprise future iterations of the EQA. PMID:27508088

  2. 7 CFR 226.21 - Food service management companies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Food service management companies. 226.21 Section 226... § 226.21 Food service management companies. (a) Any institution may contract with a food service management company. An institution which contracts with a food service management company shall remain...

  3. 21 CFR 226.20 - Buildings.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Buildings. 226.20 Section 226.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL... insecticides, fungicides, rodenticides, or other pesticides or their components unless such materials are...

  4. Using Remote Sensing, Weather, and Demographic Data to Create Risk Maps for Zika, Dengue, and Chikungunya in Brazil

    NASA Astrophysics Data System (ADS)

    Manore, C.; Conrad, J.; Del Valle, S.; Ziemann, A.; Fairchild, G.; Generous, E. N.

    2017-12-01

    Mosquito-borne diseases such as Zika, dengue, and chikungunya viruses have dynamics coupled to weather, ecology, human infrastructure, socio-economic demographics, and behavior. We use time-varying remote sensing and weather data, along with demographics and ecozones to predict risk through time for Zika, dengue, and chikungunya outbreaks in Brazil. We use distributed lag methods to quantify the lag between outbreaks and weather. Our statistical model indicates that the relationships between the variables are complex, but that quantifying risk is possible with the right data at appropriate spatio-temporal scales.

  5. 50 CFR 226.101 - Purpose and scope.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Purpose and scope. 226.101 Section 226.101 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT § 226.101 Purpose and scope...

  6. 50 CFR 226.101 - Purpose and scope.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Purpose and scope. 226.101 Section 226.101 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT § 226.101 Purpose and scope. The...

  7. Dynamics of translocation and substrate binding in individual complexes formed with active site mutants of {phi}29 DNA polymerase.

    PubMed

    Dahl, Joseph M; Wang, Hongyun; Lázaro, José M; Salas, Margarita; Lieberman, Kate R

    2014-03-07

    The Φ29 DNA polymerase (DNAP) is a processive B-family replicative DNAP. Fluctuations between the pre-translocation and post-translocation states can be quantified from ionic current traces, when individual Φ29 DNAP-DNA complexes are held atop a nanopore in an electric field. Based upon crystal structures of the Φ29 DNAP-DNA binary complex and the Φ29 DNAP-DNA-dNTP ternary complex, residues Tyr-226 and Tyr-390 in the polymerase active site were implicated in the structural basis of translocation. Here, we have examined the dynamics of translocation and substrate binding in complexes formed with the Y226F and Y390F mutants. The Y226F mutation diminished the forward and reverse rates of translocation, increased the affinity for dNTP in the post-translocation state by decreasing the dNTP dissociation rate, and increased the affinity for pyrophosphate in the pre-translocation state. The Y390F mutation significantly decreased the affinity for dNTP in the post-translocation state by decreasing the association rate ∼2-fold and increasing the dissociation rate ∼10-fold, implicating this as a mechanism by which this mutation impedes DNA synthesis. The Y390F dissociation rate increase is suppressed when complexes are examined in the presence of Mn(2+) rather than Mg(2+). The same effects of the Y226F or Y390F mutations were observed in the background of the D12A/D66A mutations, located in the exonuclease active site, ∼30 Å from the polymerase active site. Although translocation rates were unaffected in the D12A/D66A mutant, these exonuclease site mutations caused a decrease in the dNTP dissociation rate, suggesting that they perturb Φ29 DNAP interdomain architecture.

  8. Construction and symbiotic competence of a luxA-deletion mutant of Vibrio fischeri.

    PubMed

    Visick, K G; Ruby, E G

    1996-10-10

    Bioluminescence by the squid Euprymna scolopes requires colonization of its light organ by the symbiotic luminous bacterium Vibrio fischeri. Investigation of the genetic determinants underlying bacterial symbiotic competence in this system has necessitated the continuing establishment and application of molecular genetic techniques in V. fischeri. We developed a procedure for the introduction of plasmid DNA into V. fischeri by electroporation, and isolated a mutant strain that overcame the apparent restriction barrier between V. fischeri and Escherichia coli. Using the technique of electroporation in combination with that of gene replacement, we constructed a non-luminous strain of V. fischeri (delta luxA::erm). In addition, we used the transducing phage rp-1 for the first time to transfer a chromosomal antibiotic resistance marker to another strain of V. fischeri. The luxA mutant was able to colonize E. scolopes as quickly and to the same extent as wild type. This result suggested that, at least during the initial stages of colonization, luminescence per se is not an essential factor for the symbiotic infection.

  9. 22 CFR 226.14 - Special award conditions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Special award conditions. 226.14 Section 226.14 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Pre-award Requirements § 226.14 Special award conditions. If an applicant or...

  10. 22 CFR 226.13 - Debarment and suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Debarment and suspension. 226.13 Section 226.13 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Pre-award Requirements § 226.13 Debarment and suspension. USAID and recipients shall...

  11. 7 CFR 226.5 - Donation of commodities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 4 2012-01-01 2012-01-01 false Donation of commodities. 226.5 Section 226.5 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Assistance to States § 226.5 Donation...

  12. 7 CFR 226.5 - Donation of commodities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Donation of commodities. 226.5 Section 226.5 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Assistance to States § 226.5 Donation...

  13. 7 CFR 226.5 - Donation of commodities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 4 2013-01-01 2013-01-01 false Donation of commodities. 226.5 Section 226.5 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Assistance to States § 226.5 Donation...

  14. 20 CFR 226.51 - Maximum monthly amount.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Maximum monthly amount. 226.51 Section 226.51... EMPLOYEE, SPOUSE, AND DIVORCED SPOUSE ANNUITIES Railroad Retirement Family Maximum § 226.51 Maximum monthly amount. The railroad retirement family maximum is equal to an employee's “final average monthly...

  15. Zika virus displacement by a chikungunya outbreak in Recife, Brazil.

    PubMed

    Magalhaes, Tereza; Braga, Cynthia; Cordeiro, Marli T; Oliveira, Andre L S; Castanha, Priscila M S; Maciel, Ana Paula R; Amancio, Nathalia M L; Gouveia, Pollyanne N; Peixoto-da-Silva, Valter J; Peixoto, Thaciana F L; Britto, Helena; Lima, Priscilla V; Lima, Andreza R S; Rosenberger, Kerstin D; Jaenisch, Thomas; Marques, Ernesto T A

    2017-11-01

    Several arboviruses, including dengue virus (DENV), Zika virus (ZIKV) and chikungunya virus (CHIKV), transmitted by Aedes mosquitoes, circulate in northeast Brazil. Diseases caused by these viruses are of great public health relevance, however, their epidemiological features in areas where the three viruses co-circulate are scarce. Here, we present analyses of molecular and serological diagnostics in a prospective study of acute febrile patients recruited from May 2015 to May 2016 in Recife, Brazil. Two hundred sixty-three acute febrile patients with symptoms suggestive of an arboviral disease who attended an urgent heath care clinic in the Recife Metropolitan Region in northeast Brazil were enrolled. Acute and convalescent blood samples were collected and tested using molecular and serological assays for infection with DENV, ZIKV and CHIKV. Quantitative real-time reverse-transcriptase polymerase chain reactions (qRTPCR) performed on acute phase sera detected no patients positive for DENV, but 26 (9.9%) positive for ZIKV and 132 (50.2%) positive for CHIKV. There were a few suspected and only one confirmed dengue case. Specific serological assays for ZIKV and CHIKV confirmed the qRTPCR data. Analyses of DENV IgM and IgG ELISAs in the context of qRTPCR results suggested high levels of cross reactive antibodies in ZIKV-positive samples. Results from neutralization assays highly corroborated those from qRTPCR and ZIKV ELISA, indicating very few positive DENV cases. ZIKV infections were temporally clustered in the first months of the study and started to decrease concomitantly with an increase in CHIKV infections in August 2015. The proportion of CHIKV infections increased significantly in September 2015 and remained high until the end of the study period, with an average of 84.7% of recruited patients being diagnosed from August 2015 to May 2016. ZIKV infections exhibited a female bias and the cases were spread over the study site, while CHIKV cases had a male bias and

  16. First report of naturally infected Aedes aegypti with chikungunya virus genotype ECSA in the Americas

    PubMed Central

    Costa-da-Silva, André Luis; Ioshino, Rafaella Sayuri; Petersen, Vivian; Lima, Antonio Fernando; Cunha, Marielton dos Passos; Wiley, Michael R.; Ladner, Jason T.; Prieto, Karla; Palacios, Gustavo; Costa, Danuza Duarte; Suesdek, Lincoln; Zanotto, Paolo Marinho de Andrade

    2017-01-01

    Background The worldwide expansion of new emergent arboviruses such as Chikungunya and Zika reinforces the importance in understanding the role of mosquito species in spreading these pathogens in affected regions. This knowledge is essential for developing effective programs based on species specificity to avoid the establishment of endemic transmission cycles sustained by the identified local vectors. Although the first autochthonous transmission of Chikungunya virus was described in 2014 in the north of Brazil, the main outbreaks were reported in 2015 and 2016 in the northeast of Brazil. Methodology/Principal findings During 5 days of February 2016, we collected mosquitoes in homes of 6 neighborhoods of Aracaju city, the capital of Sergipe state. Four mosquito species were identified but Culex quinquefasciatus and Aedes aegypti were the most abundant. Field-caught mosquitoes were tested for Chikungunya (CHIKV), Zika (ZIKV) and Dengue viruses (DENV) by qRT-PCR and one CHIKV-infected Ae. aegypti female was detected. The complete sequence of CHIKV genome was obtained from this sample and phylogenetic analysis revealed that this isolate belongs to the East-Central-South-African (ECSA) genotype. Conclusions Our study describes the first identification of a naturally CHIKV-infected Ae. aegypti in Brazil and the first report of a CHIKV from ECSA genotype identified in this species in the Americas. These findings support the notion of Ae. aegypti being a vector involved in CHIKV outbreaks in northeast of Brazil. PMID:28614394

  17. 22 CFR 226.15 - Metric system of measurement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Metric system of measurement. 226.15 Section 226.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Pre-award Requirements § 226.15 Metric system of measurement. (a...

  18. Identification of Dengue and Chikungunya Cases Among Suspected Cases of Yellow Fever in the Democratic Republic of the Congo.

    PubMed

    Makiala-Mandanda, Sheila; Ahuka-Mundeke, Steve; Abbate, Jessica L; Pukuta-Simbu, Elisabeth; Nsio-Mbeta, Justus; Berthet, Nicolas; Leroy, Eric Maurice; Becquart, Pierre; Muyembe-Tamfum, Jean-Jacques

    2018-05-16

    For more than 95% of acute febrile jaundice cases identified through surveillance for yellow fever, a reemerging arthropod-borne viral disease, no etiological exploration is ever done. The aim of this study was to test for other arthropod-borne viruses that can induce the same symptoms in patients enrolled in the yellow fever surveillance in the Democratic Republic of the Congo (DRC). Of 652 patients included in the surveillance of yellow fever in DRC from January 2003 to January 2012, 453 patients that tested negative for yellow fever virus (YFV) immunoglobulin M (IgM) antibodies were selected for the study. Real-time polymerase chain reaction was performed for the detection of dengue, West Nile, Chikungunya, O'nyong-nyong, Rift Valley fever, Zika, and YFV. The average age of patients was 22.1 years. We reported 16 cases (3.5%; confidence interval [CI]: 0.8-5.2) of dengue (serotypes 1 and 2) and 2 cases (0.4%; CI: 0.0-1.0) of Chikungunya. Three patients were co-infected with the two serotypes of dengue virus. Three cases of dengue were found in early July 2010 from the city of Titule (Oriental province) during a laboratory-confirmed outbreak of yellow fever, suggesting simultaneous circulation of dengue and yellow fever viruses. This study showed that dengue and Chikungunya viruses are potential causes of acute febrile jaundice in the DRC and highlights the need to consider dengue and Chikungunya diagnosis in the integrated disease surveillance and response program in the DRC. A prospective study is necessary to establish the epidemiology of these diseases.

  19. Clinical characterization of acute and convalescent illness of confirmed chikungunya cases from Chiapas, S. Mexico: A cross sectional study.

    PubMed

    Danis-Lozano, Rogelio; Díaz-González, Esteban Eduardo; Trujillo-Murillo, Karina Del Carmen; Caballero-Sosa, Sandra; Sepúlveda-Delgado, Jesús; Malo-García, Iliana Rosalía; Canseco-Ávila, Luis Miguel; Salgado-Corsantes, Luis Manuel; Domínguez-Arrevillaga, Sergio; Torres-Zapata, Raúl; Gómez-Cruz, Omar; Fernández-Salas, Ildefonso

    2017-01-01

    The emerging chikungunya virus (CHIKV), is an arbovirus causing intense outbreaks in North America. The situation in Mexico is alarming, and CHIKV threatens to spread further throughout North America. Clinical and biological features of CHIKF outbreaks in Mexico have not been well described; thus, we conducted a cross sectional study of a CHIKV outbreak in Chiapas, Southern Mexico to further characterize these features. We collected blood samples from patients suspected of having chikungunya fever (CHIKF) who presented to Clinical Hospital ISSSTE Dr. Roberto Nettel in Tapachula, Chiapas, Mexico. In addition to the clinical examination, real-time polymerase chain reaction (PCR) standardized for the Asian Chikungunya lineage and/or enzyme-linked immunosorbent assay for immunoglobulin M (IgM) were used to confirm CHIKV diagnosis. Of a total of 850 patients who presented with probably CHIKV at Hospital "Dr. Roberto Nettel", 112 probable CHIKF cases were enrolled in this study from November 2014- June 2015, of which 95 patients (84.8%) were CHIKV positive and 17 were negative (15.2%). Of these 95 CHIKV positive patients, 62 were positive by real-time reverse transcriptase PCR (+qRT-PCR); and 33 were seropositive to +IgM with a negative qRT-PCR. The most frequent symptoms reported were fever (100%), headache (82.3%), polyarthralgia (72.1%), and exanthem (82.3%). Biological abnormalities observed during CHIKV infection were lymphopenia (41.1%), leukopenia (51.6%), elevated transaminases (30.5%-46.3%) and high LDH (46.3%) and CRP (60.0%). Clinical and biological data obtained from this study is providing more useful information for benchmarking purposes with outbreaks from different parts of the world and would be helpful for better patient care and treatment.

  20. 25 CFR 226.8 - Corporation and corporate information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Corporation and corporate information. 226.8 Section 226.8... RESERVATION LANDS FOR OIL AND GAS MINING Leasing Procedure, Rental and Royalty § 226.8 Corporation and corporate information. (a) If the applicant for a lease is a corporation, it shall file evidence of...

  1. 25 CFR 226.8 - Corporation and corporate information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Corporation and corporate information. 226.8 Section 226... RESERVATION LANDS FOR OIL AND GAS MINING Leasing Procedure, Rental and Royalty § 226.8 Corporation and corporate information. (a) If the applicant for a lease is a corporation, it shall file evidence of...

  2. 25 CFR 226.8 - Corporation and corporate information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Corporation and corporate information. 226.8 Section 226... RESERVATION LANDS FOR OIL AND GAS MINING Leasing Procedure, Rental and Royalty § 226.8 Corporation and corporate information. (a) If the applicant for a lease is a corporation, it shall file evidence of...

  3. 25 CFR 226.8 - Corporation and corporate information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Corporation and corporate information. 226.8 Section 226... RESERVATION LANDS FOR OIL AND GAS MINING Leasing Procedure, Rental and Royalty § 226.8 Corporation and corporate information. (a) If the applicant for a lease is a corporation, it shall file evidence of...

  4. 25 CFR 226.8 - Corporation and corporate information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Corporation and corporate information. 226.8 Section 226... RESERVATION LANDS FOR OIL AND GAS MINING Leasing Procedure, Rental and Royalty § 226.8 Corporation and corporate information. (a) If the applicant for a lease is a corporation, it shall file evidence of...

  5. 9 CFR 354.226 - Lighting and ventilation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Lighting and ventilation. 354.226 Section 354.226 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Facilities § 354.226 Lighting and ventilation. There shall be ample light, either natural or artificial or...

  6. 42 CFR 457.226 - Fiscal policies and accountability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Fiscal policies and accountability. 457.226 Section 457.226 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Claims; Reduction of Federal Medical Payments § 457.226 Fiscal policies and accountability. A State plan...

  7. 22 CFR 226.73 - Collection of amounts due.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Collection of amounts due. 226.73 Section 226.73 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS After-the-Award Requirements § 226.73 Collection of amounts due. (a...

  8. Surveillance for West Nile, Dengue, and Chikungunya Virus Infections, Veneto Region, Italy, 2010

    PubMed Central

    Barzon, Luisa; Capelli, Gioia; Angheben, Andrea; Pacenti, Monia; Napoletano, Giuseppina; Piovesan, Cinzia; Montarsi, Fabrizio; Martini, Simone; Rigoli, Roberto; Cattelan, Anna M.; Rinaldi, Roberto; Conforto, Mario; Russo, Francesca; Palù, Giorgio; Bisoffi, Zeno

    2012-01-01

    In 2010, in Veneto Region, Italy, surveillance of summer fevers was conducted to promptly identify autochthonous cases of West Nile fever and increase detection of imported dengue and chikungunya in travelers. Surveillance highlighted the need to modify case definitions, train physicians, and when a case is identified, implement vector control measures PMID:22469230

  9. 22 CFR 226.31 - Insurance coverage.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Insurance coverage. 226.31 Section 226.31 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON... shall, at a minimum, provide the equivalent insurance coverage for real property and equipment acquired...

  10. 22 CFR 226.31 - Insurance coverage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Insurance coverage. 226.31 Section 226.31 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON... shall, at a minimum, provide the equivalent insurance coverage for real property and equipment acquired...

  11. 22 CFR 226.31 - Insurance coverage.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Insurance coverage. 226.31 Section 226.31 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON... shall, at a minimum, provide the equivalent insurance coverage for real property and equipment acquired...

  12. 22 CFR 226.31 - Insurance coverage.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Insurance coverage. 226.31 Section 226.31 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON... shall, at a minimum, provide the equivalent insurance coverage for real property and equipment acquired...

  13. 22 CFR 226.31 - Insurance coverage.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Insurance coverage. 226.31 Section 226.31 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON... shall, at a minimum, provide the equivalent insurance coverage for real property and equipment acquired...

  14. Development of low level 226Ra analysis for live fish using gamma-ray spectrometry

    NASA Astrophysics Data System (ADS)

    Chandani, Z.; Prestwich, W. V.; Byun, S. H.

    2017-06-01

    A low level 226Ra analysis method for live fish was developed using a 4π NaI(Tl) gamma-ray spectrometer. In order to find out the best algorithm for accomplishing the lowest detection limit, the gamma-ray spectrum from a 226Ra point was collected and nine different methods were attempted for spectral analysis. The lowest detection limit of 0.99 Bq for an hour counting occurred when the spectrum was integrated in the energy region of 50-2520 keV. To extend 226Ra analysis to live fish, a Monte Carlo simulation model with a cylindrical fish in a water container was built using the MCNP code. From simulation results, the spatial distribution of the efficiency and the efficiency correction factor for the live fish model were determined. The MCNP model will be able to be conveniently modified when a different fish or container geometry is employed as fish grow up in real experiments.

  15. 7 CFR 226.17 - Child care center provisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 4 2013-01-01 2013-01-01 false Child care center provisions. 226.17 Section 226.17... AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Operational Provisions § 226.17 Child care center provisions. (a) Child care centers may participate in the Program either as independent...

  16. 7 CFR 226.17 - Child care center provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Child care center provisions. 226.17 Section 226.17... AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Operational Provisions § 226.17 Child care center provisions. (a) Child care centers may participate in the Program either as independent...

  17. 7 CFR 226.17 - Child care center provisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 4 2012-01-01 2012-01-01 false Child care center provisions. 226.17 Section 226.17... AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Operational Provisions § 226.17 Child care center provisions. (a) Child care centers may participate in the Program either as independent...

  18. Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology.

    PubMed

    Jones, Jennifer E; Long, Kristin M; Whitmore, Alan C; Sanders, Wes; Thurlow, Lance R; Brown, Julia A; Morrison, Clayton R; Vincent, Heather; Peck, Kayla M; Browning, Christian; Moorman, Nathaniel; Lim, Jean K; Heise, Mark T

    2017-11-14

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene. However, CHIKV strains that encode an arginine codon in place of the opal stop codon have been described, and deep-sequencing analysis of a CHIKV isolate from the Caribbean identified both arginine and opal variants within this strain. Therefore, we hypothesized that the introduction of the arginine mutation in place of the opal termination codon may influence CHIKV virulence. We tested this by introducing the arginine mutation into a well-characterized infectious clone of a CHIKV strain from Sri Lanka and designated this virus Opal524R. This mutation did not impair viral replication kinetics in vitro or in vivo Despite this, the Opal524R virus induced significantly less swelling, inflammation, and damage within the feet and ankles of infected mice. Further, we observed delayed induction of proinflammatory cytokines and chemokines, as well as reduced CD4 + T cell and NK cell recruitment compared to those in the parental strain. Therefore, the opal termination codon plays an important role in CHIKV pathogenesis, independently of effects on viral replication. IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes significant outbreaks of viral arthralgia. Studies with CHIKV and other alphaviruses demonstrated that the opal termination codon within nsP3 is highly conserved. However, some strains of CHIKV and other alphaviruses contain mutations in the opal termination codon. These mutations alter the virulence

  19. Climate change effects on Chikungunya transmission in Europe: geospatial analysis of vector's climatic suitability and virus' temperature requirements.

    PubMed

    Fischer, Dominik; Thomas, Stephanie M; Suk, Jonathan E; Sudre, Bertrand; Hess, Andrea; Tjaden, Nils B; Beierkuhnlein, Carl; Semenza, Jan C

    2013-11-12

    Chikungunya was, from the European perspective, considered to be a travel-related tropical mosquito-borne disease prior to the first European outbreak in Northern Italy in 2007. This was followed by cases of autochthonous transmission reported in South-eastern France in 2010. Both events occurred after the introduction, establishment and expansion of the Chikungunya-competent and highly invasive disease vector Aedes albopictus (Asian tiger mosquito) in Europe. In order to assess whether these outbreaks are indicative of the beginning of a trend or one-off events, there is a need to further examine the factors driving the potential transmission of Chikungunya in Europe. The climatic suitability, both now and in the future, is an essential starting point for such an analysis. The climatic suitability for Chikungunya outbreaks was determined by using bioclimatic factors that influence, both vector and, pathogen. Climatic suitability for the European distribution of the vector Aedes albopictus was based upon previous correlative environmental niche models. Climatic risk classes were derived by combining climatic suitability for the vector with known temperature requirements for pathogen transmission, obtained from outbreak regions. In addition, the longest potential intra-annual season for Chikungunya transmission was estimated for regions with expected vector occurrences.In order to analyse spatio-temporal trends for risk exposure and season of transmission in Europe, climate change impacts are projected for three time-frames (2011-2040, 2041-2070 and 2071-2100) and two climate scenarios (A1B and B1) from the Intergovernmental Panel on Climate Change (IPCC). These climatic projections are based on regional climate model COSMO-CLM, which builds on the global model ECHAM5. European areas with current and future climatic suitability of Chikungunya transmission are identified. An increase in risk is projected for Western Europe (e.g. France and Benelux-States) in the

  20. 22 CFR 226.24 - Program income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Financial and Program Management § 226.24 Program income. (a) Recipients... organizations may not apply paragraph (b)(1) of this section, in accordance with § 226.82 of this part. (e...

  1. 20 CFR 226.61 - Use of military service.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Use of military service. 226.61 Section 226... § 226.61 Use of military service. (a) Claim for use of military service. An employee is deemed to have filed a claim for the use of military service and earnings as service and compensation under the...

  2. 12 CFR 226.28 - Effect on State laws.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 3 2013-01-01 2013-01-01 false Effect on State laws. 226.28 Section 226.28... (CONTINUED) TRUTH IN LENDING (REGULATION Z) Miscellaneous § 226.28 Effect on State laws. (a) Inconsistent disclosure requirements. (1) Except as provided in paragraph (d) of this section, State law requirements that...

  3. 12 CFR 226.28 - Effect on State laws.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Effect on State laws. 226.28 Section 226.28... TRUTH IN LENDING (REGULATION Z) Miscellaneous § 226.28 Effect on State laws. (a) Inconsistent disclosure requirements. (1) Except as provided in paragraph (d) of this section, State law requirements that are...

  4. 12 CFR 226.28 - Effect on State laws.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Effect on State laws. 226.28 Section 226.28... TRUTH IN LENDING (REGULATION Z) Miscellaneous § 226.28 Effect on State laws. (a) Inconsistent disclosure...), or chapter 3 (Credit Advertising) of the act and the implementing provisions of this regulation are...

  5. Spread of Chikungunya Virus East/Central/South African Genotype in Northeast Brazil.

    PubMed

    Charlys da Costa, Antonio; Thézé, Julien; Komninakis, Shirley Cavalcante Vasconcelos; Sanz-Duro, Rodrigo Lopes; Felinto, Marta Rejane Lemos; Moura, Lúcia Cristina Corrêa; Barroso, Ivoneide Moreira de Oliveira; Santos, Lucineide Eliziario Correia; Nunes, Mardjane Alves de Lemos; Moura, Adriana Avila; Lourenço, José; Deng, Xutao; Delwart, Eric L; Guimarães, Maria Raquel Dos Anjos Silva; Pybus, Oliver G; Sabino, Ester C; Faria, Nuno R

    2017-10-01

    We investigated an outbreak of exanthematous illness in Maceió by using molecular surveillance; 76% of samples tested positive for chikungunya virus. Genetic analysis of 23 newly generated genomes identified the East/Central/South African genotype, suggesting that this lineage has persisted since mid-2014 in Brazil and may spread in the Americas and beyond.

  6. 25 CFR 226.41 - Accidents to be reported.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Accidents to be reported. 226.41 Section 226.41 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.41 Accidents to be reported. Lessee shall make a complete report to the Superintendent of all accidents, fires, or acts of theft and vandalism...

  7. 25 CFR 226.41 - Accidents to be reported.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Accidents to be reported. 226.41 Section 226.41 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.41 Accidents to be reported. Lessee shall make a complete report to the Superintendent of all accidents, fires, or acts of theft and vandalism...

  8. 25 CFR 226.32 - Well records and reports.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Well records and reports. 226.32 Section 226.32 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.32 Well records and reports. (a) Lessee shall..., plugging, or abandonment of all wells. These records shall show all the formations penetrated, the content...

  9. 25 CFR 226.32 - Well records and reports.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Well records and reports. 226.32 Section 226.32 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.32 Well records and reports. (a) Lessee shall..., plugging, or abandonment of all wells. These records shall show all the formations penetrated, the content...

  10. 25 CFR 226.32 - Well records and reports.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Well records and reports. 226.32 Section 226.32 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.32 Well records and reports. (a) Lessee shall..., plugging, or abandonment of all wells. These records shall show all the formations penetrated, the content...

  11. Induction of diphtheria toxin-resistant mutants in human cells by ultraviolet light

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

    Rocchi, P.; Ferreri, A.M.; Capucci, A.

    1981-01-01

    Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line EUE at a very low frequency (less than 8 x 10(-6)). U.v.-induced mutation has been quantitatively measured: treatment of cells with u.v. light increased the frequencies of diphtheria toxin resistant (DTr) mutants up to 1000-fold. The maximum recovery of DTr mutants was observed after a short expression period, for all u.v. doses tested, and was followed by a decrease in mutation frequency on subsequent passages.

  12. Induction of diphtheria toxin-resistant mutants in human cells by ultraviolet light

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

    Rocchi, P.; Ferreri, A.M.; Capucci, A.

    1981-01-01

    Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line EUE at a very low frequency (< 8 x 10/sup -6/). U.v.-induced mutation has been quantitatively measured: treatment of cells with u.v. light increased the frequencies of diphtheria toxin resistant (DTsup(r)) mutants up to 1000-fold. The maximum recovery of DTsup(r) mutants was observed after a short expression period, for all u.v. doses tested, and was followed by a decrease in mutation frequency on subsequent passages.

  13. 25 CFR 226.26 - Determining cost of well.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Determining cost of well. 226.26 Section 226.26 Indians... LANDS FOR OIL AND GAS MINING Operations § 226.26 Determining cost of well. The term “cost of drilling” as applied where one lessee takes over a well drilled by another, shall include all reasonable, usual...

  14. 25 CFR 226.26 - Determining cost of well.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Determining cost of well. 226.26 Section 226.26 Indians... LANDS FOR OIL AND GAS MINING Operations § 226.26 Determining cost of well. The term “cost of drilling” as applied where one lessee takes over a well drilled by another, shall include all reasonable, usual...

  15. 25 CFR 226.26 - Determining cost of well.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Determining cost of well. 226.26 Section 226.26 Indians... LANDS FOR OIL AND GAS MINING Operations § 226.26 Determining cost of well. The term “cost of drilling” as applied where one lessee takes over a well drilled by another, shall include all reasonable, usual...

  16. Chikungunya in the Americas: Recommendations and Conclusions.

    PubMed

    Graham, Barney S; Repik, Patricia M; Yactayo, Sergio

    2016-12-15

    Discovered in 1953, chikungunya virus (CHIKV) circulated in Africa and Southeast Asia, with periodic outbreaks, for many years. Highly efficient transmission following a genetic mutation of the virus in 2005 caused its global spread. Associated with significant morbidity, CHIKV creates a large public health burden, and despite various efforts, there are currently no licensed vaccines nor specific treatments. To garner a better understanding of the virus, identify gaps in knowledge, and guide the development of more-effective interventions, the World Health Organization and National Institute of Allergy and Infectious Diseases assembled global experts for discussion and review. Herein described are the outcomes. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  17. Clinical characterization of acute and convalescent illness of confirmed chikungunya cases from Chiapas, S. Mexico: A cross sectional study

    PubMed Central

    Trujillo-Murillo, Karina del Carmen; Caballero-Sosa, Sandra; Sepúlveda-Delgado, Jesús; Malo-García, Iliana Rosalía; Canseco-Ávila, Luis Miguel; Salgado-Corsantes, Luis Manuel; Domínguez-Arrevillaga, Sergio; Torres-Zapata, Raúl; Gómez-Cruz, Omar; Fernández-Salas, Ildefonso

    2017-01-01

    Background The emerging chikungunya virus (CHIKV), is an arbovirus causing intense outbreaks in North America. The situation in Mexico is alarming, and CHIKV threatens to spread further throughout North America. Clinical and biological features of CHIKF outbreaks in Mexico have not been well described; thus, we conducted a cross sectional study of a CHIKV outbreak in Chiapas, Southern Mexico to further characterize these features. Methodology/Principal findings We collected blood samples from patients suspected of having chikungunya fever (CHIKF) who presented to Clinical Hospital ISSSTE Dr. Roberto Nettel in Tapachula, Chiapas, Mexico. In addition to the clinical examination, real-time polymerase chain reaction (PCR) standardized for the Asian Chikungunya lineage and/or enzyme-linked immunosorbent assay for immunoglobulin M (IgM) were used to confirm CHIKV diagnosis. Of a total of 850 patients who presented with probably CHIKV at Hospital “Dr. Roberto Nettel”, 112 probable CHIKF cases were enrolled in this study from November 2014- June 2015, of which 95 patients (84.8%) were CHIKV positive and 17 were negative (15.2%). Of these 95 CHIKV positive patients, 62 were positive by real-time reverse transcriptase PCR (+qRT-PCR); and 33 were seropositive to +IgM with a negative qRT-PCR. The most frequent symptoms reported were fever (100%), headache (82.3%), polyarthralgia (72.1%), and exanthem (82.3%). Biological abnormalities observed during CHIKV infection were lymphopenia (41.1%), leukopenia (51.6%), elevated transaminases (30.5%-46.3%) and high LDH (46.3%) and CRP (60.0%). Conclusion Clinical and biological data obtained from this study is providing more useful information for benchmarking purposes with outbreaks from different parts of the world and would be helpful for better patient care and treatment. PMID:29065182

  18. A garage sale bargain: A leaking 2.2 GBq Ra-226 source, Phase II - Internal dose assessment

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

    Toohey, R.E.; Goans, R.E.

    1996-06-01

    The Radiation Emergency Assistance Center and Training Site (REAC/TS) at the Oak Ridge Institute for Science and Education (ORISE) in Oak Ridge was asked by the Department of Energy to assist the Tennessee Division of Radiological Health in assessing the potential health consequences of this incident. The purchaser of the radium source and his wife visited the REAMS facility on 8 May 1995, approximately 50 d after the purchase. Medical histories were taken and physical exams were performed by the REAC/TS physician, and blood samples were collected for complete blood counts (CBC), differentials, chemistry panels, and cytogenetic testing. The clinicalmore » results were normal, and a chromosome analysis of cultured peripheral lymphocytes showed no aberrations (rings or dicentrics) above background levels found in unexposed controls. A whole-body count was performed on the purchaser in the ORISE facility, but his wife declined because of discomfort with the enclosed space within the shield. In the energy band from 1.61 to 1.87 MeV, bracketing the 1.76-MeV peak from {sup 214}Bi, the subject had a net count rate of 0. 1 5 {+-} 0.04, counts per second, corresponding to a {sup 214}Bi body content of 400 {+-} 100 Bq. With the assumption that the {sup 222}Rn retention fraction was 0.37, this figure corresponded to a {sup 226}Ra content of 1.1 {+-} 0.3 kBq. With the further assumption that the primary intake route was Inhalation of 1.0-micron AMAD particles of class W {sup 226}Ra, the intake was computed to be 13 {+-} 3 kBq. The annual limit of intake by inhalation for class W {sup 226}Ra is based on the stochastic limit and is 20 kBq; therefore, the committed effective dose equivalent for this subject was 30 {+-} 7 mSv. A separate whole-body count of the subject`s wife was performed with an unshielded detector at the REAC/TS facility, with negative results.« less

  19. Ocular manifestations of emerging arboviruses: Dengue fever, Chikungunya, Zika virus, West Nile virus, and yellow fever.

    PubMed

    Merle, H; Donnio, A; Jean-Charles, A; Guyomarch, J; Hage, R; Najioullah, F; Césaire, R; Cabié, A

    2018-06-18

    Arboviruses are viral diseases transmitted by mosquitoes and tick bites. They are a major cause of morbidity and sometimes mortality. Their expansion is constant and due in part to climate change and globalization. Mostly found in tropical regions, arboviruses are sometimes the source of epidemics in Europe. Recently, the Chikungunya virus and the Zika virus were responsible for very large epidemics impacting populations that had never been in contact with those viruses. There are currently no effective antiviral treatments or vaccines. Ocular manifestations due to those infections are thus more frequent and increasingly better described. They are sometimes, as with Zika, complicated by a congenital ocular syndrome. The goal of this review is to describe the ophthalmological manifestations of Dengue fever, Chikungunya virus, Zika virus, West Nile virus, and yellow fever. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. 29 CFR 553.226 - Training time.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Training time. 553.226 Section 553.226 Labor Regulations... time. (a) The general rules for determining the compensability of training time under the FLSA are set forth in §§ 785.27 through 785.32 of this title. (b) While time spent in attending training required by...

  1. 29 CFR 553.226 - Training time.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Training time. 553.226 Section 553.226 Labor Regulations... time. (a) The general rules for determining the compensability of training time under the FLSA are set forth in §§ 785.27 through 785.32 of this title. (b) While time spent in attending training required by...

  2. 29 CFR 553.226 - Training time.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Training time. 553.226 Section 553.226 Labor Regulations... time. (a) The general rules for determining the compensability of training time under the FLSA are set forth in §§ 785.27 through 785.32 of this title. (b) While time spent in attending training required by...

  3. Estimating Drivers of Autochthonous Transmission of Chikungunya Virus in its Invasion of the Americas

    PubMed Central

    Perkins, T. Alex; Metcalf, C. Jessica E.; Grenfell, Bryan T.; Tatem, Andrew J.

    2015-01-01

    Background Chikungunya is an emerging arbovirus that has caused explosive outbreaks in Africa and Asia for decades and invaded the Americas just over a year ago. During this ongoing invasion, it has spread to 45 countries where it has been transmitted autochthonously, infecting nearly 1.3 million people in total. Methods Here, we made use of weekly, country-level case reports to infer relationships between transmission and two putative climatic drivers: temperature and precipitation averaged across each country on a monthly basis. To do so, we used a TSIR model that enabled us to infer a parametric relationship between climatic drivers and transmission potential, and we applied a new method for incorporating a probabilistic description of the serial interval distribution into the TSIR framework. Results We found significant relationships between transmission and linear and quadratic terms for temperature and precipitation and a linear term for log incidence during the previous pathogen generation. The lattermost suggests that case numbers three to four weeks ago are largely predictive of current case numbers. This effect is quite nonlinear at the country level, however, due to an estimated mixing parameter of 0.74. Relationships between transmission and the climatic variables that we estimated were biologically plausible and in line with expectations. Conclusions Our analysis suggests that autochthonous transmission of Chikungunya in the Americas can be correlated successfully with putative climatic drivers, even at the coarse scale of countries and using long-term average climate data. Overall, this provides a preliminary suggestion that successfully forecasting the future trajectory of a Chikungunya outbreak and the receptivity of virgin areas may be possible. Our results also provide tentative estimates of timeframes and areas of greatest risk, and our extension of the TSIR model provides a novel tool for modeling vector-borne disease transmission. PMID:25737803

  4. 22 CFR 226.40 - Purpose of procurement standards.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Purpose of procurement standards. 226.40 Section 226.40 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.40 Purpose...

  5. 22 CFR 226.49 - USAID-Specific procurement requirements

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false USAID-Specific procurement requirements 226.49 Section 226.49 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.49 USAID...

  6. 22 CFR 226.1002 - Local cost financing. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Local cost financing. [Reserved] 226.1002 Section 226.1002 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1002 Local cost financing...

  7. 22 CFR 226.1002 - Local cost financing. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Local cost financing. [Reserved] 226.1002 Section 226.1002 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1002 Local cost financing...

  8. [Lessons learned in the control of Aedes aegypti to address dengue and the emergency of chikungunya in Iquitos, Peru].

    PubMed

    Vilcarromero, Stalin; Casanova, Wilma; Ampuero, Julia S; Ramal-Asayag, Cesar; Siles, Crystyan; Díaz, Gloria; Durand, Salomón; Celis-Salinas, Juan C; Astete, Helvio; Rojas, Percy; Vásquez-La Torre, Gabriela; Marín, Johan; Bazán, Isabel; Alegre, Yuri; Morrison, Amy C; Rodriguez-Ferrucci, Hugo

    2015-01-01

    Dengue has affected Iquitos since 1990 causing outbreaks of major impact on public health and for this reason great efforts have been made for its temporal control. Currently, with the expansion of the chikungunya virus in the Americas and the threat of the emergence of the virus in Iquitos, we reflect on lessons learned by way of the activities undertaken in the area of vector control; epidemiological surveillance, diagnosis and clinical management during periods of outbreaks of dengue, in a way that will allow us to better face the threat of an outbreak of chikungunya virus in the largest city in the Peruvian Amazon.

  9. 48 CFR 226.370-3 - Policy.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Policy. 226.370-3 Section 226.370-3 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities...

  10. 48 CFR 226.370-3 - Policy.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Policy. 226.370-3 Section 226.370-3 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities...

  11. 48 CFR 226.370-3 - Policy.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Policy. 226.370-3 Section 226.370-3 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities...

  12. 48 CFR 226.370-3 - Policy.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Policy. 226.370-3 Section 226.370-3 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities...

  13. Radium-226 dose to a boy from playing on mill tailings

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

    Mays, C.W.; Lucas, H.F.; Lloyd, R.D.

    Two boys born in September 1949 played on uranium mill tailings from about ages 8 to 12. One of these boys was diagnosed as having leukemia at age 15.5. The 226Ra body burden of the survivor was measured at age 38. The whole-body 226Ra content measured by counting in vivo was 0 {plus minus} 17 Bq and independently by Rn breath analysis as 4.3 {plus minus} 2.1 Bq. At the same time, a control subject with no known exposure to 226Ra, matched in age, height, and weight, was also measured. The whole-body content was estimated as 4 {plus minus} 15more » Bq and independently by Rn breath analysis as 5.5 {plus minus} 3.7 Bq. The body burden of the control subject was not significantly different from that of the exposed person. The radiation dose to the marrow-free skeleton assuming a constant 226Ra:Ca ratio since birth was 0.49 and 1.33 mGy at ages 14 and 38, respectively. The radiation dose to the marrow-free skeleton assuming 226Ra intake only between ages 8 to 12 was 1.4 and 2.8 mGy at ages 14 and 38, respectively. The best estimate is the mean of these two estimates: 0.9 and 2.1 mGy at ages 14 and 38, respectively. The alpha-particle dose to the red marrow from 226Ra and its decay products was 0.05 mGy at age 14 and 0.10 mGy at age 38. Since no excess was found for the radium dial painters whose doses were much higher, the induction of leukemia by doses of this magnitude would seem quite unlikely.« less

  14. 22 CFR 226.30 - Purpose of property standards.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Purpose of property standards. 226.30 Section 226.30 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Property Standards § 226.30 Purpose of...

  15. 48 CFR 226.370-2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities and Minority Institutions 226.370-2 Definitions. Definitions of HBCUs and MIs are in the clause at 252.226-7000, Notice of Historically Black College or University and Minority Institution Set-Aside. ...

  16. 48 CFR 226.370-2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities and Minority Institutions 226.370-2 Definitions. Definitions of HBCUs and MIs are in the clause at 252.226-7000, Notice of Historically Black College or University and Minority Institution Set-Aside. ...

  17. 48 CFR 226.370-2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities and Minority Institutions 226.370-2 Definitions. Definitions of HBCUs and MIs are in the clause at 252.226-7000, Notice of Historically Black College or University and Minority Institution Set-Aside. ...

  18. 48 CFR 226.370-2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities and Minority Institutions 226.370-2 Definitions. Definitions of HBCUs and MIs are in the clause at 252.226-7000, Notice of Historically Black College or University and Minority Institution Set-Aside. ...

  19. 48 CFR 226.370-2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities and Minority Institutions 226.370-2 Definitions. Definitions of HBCUs and MIs are in the clause at 252.226-7000, Notice of Historically Black College or University and Minority Institution Set-Aside. ...

  20. 22 CFR 226.45 - Cost and price analysis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Cost and price analysis. 226.45 Section 226.45 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.45 Cost and price analysis. Some...

  1. Radium 226,228

    Integrated Risk Information System (IRIS)

    Integrated Risk Information System ( IRIS ) Chemical Assessment Summary U.S . Environmental Protection Agency National Center for Environmental Assessment Radium 226,228 ; CASRN 7440 - 14 - 4 , Human health assessment information on a chemical substance is included in the IRIS database only after a

  2. A Mutant Connexin50 with Enhanced Hemichannel Function Leads to Cell Death

    PubMed Central

    Minogue, Peter J.; Tong, Jun-Jie; Arora, Anita; Russell-Eggitt, Isabelle; Hunt, David M.; Moore, Anthony T.; Ebihara, Lisa; Beyer, Eric C.; Berthoud, Viviana M.

    2009-01-01

    PURPOSE To determine the consequences of expression of a novel connexin50 (CX50) mutant identified in a child with congenital total cataracts. METHODS The GJA8 gene was directly sequenced. Formation of functional channels was assessed by two-microelectrode voltage-clamp. Connexin protein levels and distribution were assessed by immunoblotting and immunofluorescence. The proportion of apoptotic cells was determined by flow cytometry. RESULTS Direct sequencing of the GJA8 gene identified a 137 G>T transition that resulted in the replacement of glycine by valine at position 46 of the coding region of CX50 (CX50G46V). Both CX50 and CX50G46V induced gap junctional currents in pairs of Xenopus oocytes. In single Xenopus oocytes, CX50G46V induced connexin hemichannel currents that were activated by removal of external calcium; their magnitudes were much higher than those in oocytes injected with similar amounts of CX50 cRNA. When expressed in HeLa cells under the control of an inducible promoter, both CX50 and CX50G46V formed gap junctional plaques. Induction of CX50G46V expression led to a decrease in cell number and an increase in the proportion of apoptotic cells. CX50G46V-induced cell death was prevented by high concentrations of extracellular calcium ions. CONCLUSIONS Unlike previously characterized CX50 mutants that exhibit impaired trafficking and/or lack of function, CX50G46V traffics properly to the plasma membrane and forms functional hemichannels and gap junction channels; however, it causes cell death even when expressed at minute levels. The biochemical results indirectly suggest a potential novel mechanism by which connexin mutants could lead to cataracts: cytotoxicity due to enhanced hemichannel function. PMID:19684000

  3. 22 CFR 226.3 - Effect on other issuances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Effect on other issuances. 226.3 Section 226.3 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS General § 226.3 Effect on other issuances. For awards subject to this part, all...

  4. Immunological Study of the O-Antigens of Streptomycin-Dependent Mutants of Salmonella

    DTIC Science & Technology

    1974-10-23

    AD/A-O00 361 IMMUNOLOGICAL STUDY OF THE O-ANTIGENS OF STREPTOMYCIN-DEPENDENT MUTANTS OF SALMONELLA L. S. Edvabnaya, et al Foreign Technology Division...U. S. Air Force SREPORT TITLE IMMUNOLOGICAL STUDY OF THE 0-ANTIGENS OF STREPTOMYCIN-DEPENDENT MUTANTS OF SALMONELLA 4 DCESCRIPTIVIE NOTES (?T’pe of...THE O-ANTIGENS OF STREPTOMYCIN-DEPENDENT MUTANTS OF SALMONELLA By: L. S. Yedvabnaya, Ye. S. Stanislavskiy, and V. V. Sergeyev Englihs pages: 10 Source

  5. 22 CFR 226.45 - Cost and price analysis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Cost and price analysis. 226.45 Section 226.45...-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.45 Cost and price analysis. Some form of cost or price analysis shall be made and documented in the procurement files in connection with...

  6. 25 CFR 226.35 - Formations to be protected.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Formations to be protected. 226.35 Section 226.35 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.35 Formations to be protected. Lessee shall...

  7. 25 CFR 226.35 - Formations to be protected.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Formations to be protected. 226.35 Section 226.35 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.35 Formations to be protected. Lessee shall...

  8. 25 CFR 226.35 - Formations to be protected.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Formations to be protected. 226.35 Section 226.35 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.35 Formations to be protected. Lessee shall...

  9. 25 CFR 226.35 - Formations to be protected.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Formations to be protected. 226.35 Section 226.35 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.35 Formations to be protected. Lessee shall...

  10. 25 CFR 226.35 - Formations to be protected.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Formations to be protected. 226.35 Section 226.35 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.35 Formations to be protected. Lessee shall...

  11. 25 CFR 226.38 - Measuring and storing oil.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Measuring and storing oil. 226.38 Section 226.38 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.38 Measuring and storing oil. All production.... Facilities suitable for containing and measuring accurately all crude oil produced from the wells shall be...

  12. 25 CFR 226.38 - Measuring and storing oil.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Measuring and storing oil. 226.38 Section 226.38 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.38 Measuring and storing oil. All production.... Facilities suitable for containing and measuring accurately all crude oil produced from the wells shall be...

  13. 25 CFR 226.38 - Measuring and storing oil.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Measuring and storing oil. 226.38 Section 226.38 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.38 Measuring and storing oil. All production.... Facilities suitable for containing and measuring accurately all crude oil produced from the wells shall be...

  14. 25 CFR 226.38 - Measuring and storing oil.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Measuring and storing oil. 226.38 Section 226.38 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.38 Measuring and storing oil. All production.... Facilities suitable for containing and measuring accurately all crude oil produced from the wells shall be...

  15. 25 CFR 226.38 - Measuring and storing oil.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Measuring and storing oil. 226.38 Section 226.38 Indians... LANDS FOR OIL AND GAS MINING Requirements of Lessees § 226.38 Measuring and storing oil. All production.... Facilities suitable for containing and measuring accurately all crude oil produced from the wells shall be...

  16. 7 CFR 226.1 - General purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false General purpose and scope. 226.1 Section 226.1 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM General § 226.1 General purpose and scope. This part announces the...

  17. 25 CFR 226.9 - Rental and drilling obligations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Rental and drilling obligations. 226.9 Section 226.9... RESERVATION LANDS FOR OIL AND GAS MINING Leasing Procedure, Rental and Royalty § 226.9 Rental and drilling... in the lease terms, or 12 months from the date the Superintendent consents to drilling on any...

  18. 25 CFR 226.9 - Rental and drilling obligations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Rental and drilling obligations. 226.9 Section 226.9... RESERVATION LANDS FOR OIL AND GAS MINING Leasing Procedure, Rental and Royalty § 226.9 Rental and drilling... in the lease terms, or 12 months from the date the Superintendent consents to drilling on any...

  19. 25 CFR 226.9 - Rental and drilling obligations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Rental and drilling obligations. 226.9 Section 226.9... RESERVATION LANDS FOR OIL AND GAS MINING Leasing Procedure, Rental and Royalty § 226.9 Rental and drilling... in the lease terms, or 12 months from the date the Superintendent consents to drilling on any...

  20. [Situational panorama of Mexico against the chikungunya virus pandemic].

    PubMed

    Martínez-Sánchez, Abisai; Martínez-Ramos, Ericay Berenice; Chávez-Angeles, Manuel Gerardo

    2015-01-01

    Recent outbreaks of emerging diseases emphasize the vulnerability of health systems, as is the case of chikungunya fever. The wide geographical incidence of the virus in the last years requires alerting systems for the prevention, diagnosis, control and eradication of the disease. Given the ecological, epidemiological and socio-economic characteristic of Mexico, this disease affects directly or indirectly the health of the population and development of agricultural, livestock, industrial, fishing, oil and tourism activities in the country. Due to this situation it is essential to make a brief analysis on the main clinical data, epidemiological and preventive measures with which our country counts with to confront the situation.

  1. Simultaneous detection of Zika, Chikungunya and Dengue viruses by a multiplex real-time RT-PCR assay.

    PubMed

    Pabbaraju, Kanti; Wong, Sallene; Gill, Kara; Fonseca, Kevin; Tipples, Graham A; Tellier, Raymond

    2016-10-01

    In the recent past, arboviruses such as Chikungunya (CHIKV) and Zika (ZIKV) have increased their area of endemicity and presented as an emerging global public health threat. To design an assay for the simultaneous detection of ZIKV, CHIKV and Dengue (DENV) 1-4 from patients with symptoms of arboviral infection. This would be advantageous because of the similar clinical presentation typically encountered with these viruses and their co-circulation in endemic areas. In this study we have developed and validated a triplex real time reverse transcription PCR assay using hydrolysis probes targeting the non-structural 5 (NS5) region of ZIKV, non-structural protein 4 (nsP4) from CHIKV and 3' untranslated region (3'UTR) of DENV 1-4. The 95% LOD by the triplex assay was 15 copies/reaction for DENV-1 and less than 10 copies/reaction for all other viruses. The triplex assay was 100% specific and did not amplify any of the other viruses tested. The assay was reproducible and adaptable to testing different specimen types including serum, plasma, urine, placental tissue, brain tissue and amniotic fluid. This assay can be easily implemented for diagnostic testing of patient samples, even in a high throughput laboratory. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Toxicity of injected radium-226 in immature dogs

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

    Muggenburg, B.A.; Hahn, F.F.; Griffith, W.C.

    1995-12-01

    This study was conducted to determine the toxicity of injected {sup 226}Ra in immature dogs and to compare the results with those from studies of injected {sup 226}Ra in young adult dogs. An historic objective of these studies, initiated at the University of Utah and continued at ITRI, was to compare the results in dogs to the population of dial painters who ingested {sup 226}Ra as young adults. Age at the time of exposure is considered to be an important factor in dosimetry and risk of developing radiation-induced disease, particularly bone cancer. In summary, dogs injected with {sup 226}Ra whenmore » immature had increased occurrences of bone tumors in a dose-related fashion.« less

  3. 25 CFR 226.24 - Lessee's use of water.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Lessee's use of water. 226.24 Section 226.24 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Operations § 226.24 Lessee's use of water. Lessee or his contractor may, with the approval of the Superintendent, use water...

  4. 12 CFR 226.9 - Subsequent disclosure requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... information: (i) The disclosures contained in § 226.5a(b) (1) through (7) that would apply if the account were... increased as a penalty for one or more events specified in the account agreement, such as making a late... account. The notice shall contain the following information: (i) The disclosures contained in § 226.5a(b...

  5. Chromosome instability of HPRT-mutant subclones induced by ionising radiation of various LET.

    PubMed

    Govorun, R D; Koshlan, I V; Koshlan, N A; Krasavin, E A; Shmakova, N L

    2002-01-01

    The induction of HPRT-mutations and survival of Chinese hamster cells (line B11ii-FAF28, clone 431) were studied after irradiation by 4He and 12C-ions of various LET (20-360 keV/micrometers), produced by the U-200 heavy ion accelerator. The RBE increases with LET up to the maximum at 100-200 keV/micrometers and then decreases. Cytogenetic analysis was performed on the HPRT-mutant subclones selected from unirradiated Chinese hamster V-79 cells and from HPRT-mutant subclones that arose after exposure to gamma-rays, 1 GeV protons and 14N-ions (LET-77 keV/micrometers), produced by the synchrophasotron and the U-400M heavy ion accelerator. Slow growing mutant subclones were observed. The cytogenetic properties of individual clones were highly heterogeneous and chromosome instability was observed in both spontaneous and radiation-induced mutants. Chromosome instability was highest among spontaneous mutants and decreased with increasing LET. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  6. 21 CFR 226.80 - Packaging and labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...

  7. 21 CFR 226.80 - Packaging and labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...

  8. 21 CFR 226.80 - Packaging and labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...

  9. 21 CFR 226.80 - Packaging and labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...

  10. 21 CFR 226.80 - Packaging and labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...

  11. Characterization of Three Vasopressin Receptor 2 Variants: An Apparent Polymorphism (V266A) and Two Loss-of-Function Mutations (R181C and M311V)

    PubMed Central

    Armstrong, Stephen P.; Seeber, Ruth M.; Ayoub, Mohammed Akli; Feldman, Brian J.; Pfleger, Kevin D. G.

    2013-01-01

    Arginine vasopressin (AVP) is released from the posterior pituitary and controls water homeostasis. AVP binding to vasopressin V2 receptors (V2Rs) located on kidney collecting duct epithelial cells triggers activation of Gs proteins, leading to increased cAMP levels, trafficking of aquaporin-2 water channels, and consequent increased water permeability and antidiuresis. Typically, loss-of-function V2R mutations cause nephrogenic diabetes insipidus (NDI), whereas gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Here we provide further characterization of two mutant V2Rs, R181C and M311V, reported to cause complete and partial NDI respectively, together with a V266A variant, in a patient diagnosed with NSIAD. Our data in HEK293FT cells revealed that for cAMP accumulation, AVP was about 500- or 30-fold less potent at the R181C and M311V mutants than at the wild-type receptor respectively (and about 4000- and 60-fold in COS7 cells respectively). However, in contrast to wild type V2R, the R181C mutant failed to increase inositol phosphate production, while with the M311V mutant, AVP exhibited only partial agonism in addition to a 37-fold potency decrease. Similar responses were detected in a BRET assay for β-arrestin recruitment, with the R181C receptor unresponsive to AVP, and partial agonism with a 23-fold decrease in potency observed with M311V in both HEK293FT and COS7 cells. Notably, the V266A V2R appeared functionally identical to the wild-type receptor in all assays tested, including cAMP and inositol phosphate accumulation, β-arrestin interaction, and in a BRET assay of receptor ubiquitination. Each receptor was expressed at comparable levels. Hence, the M311V V2R retains greater activity than the R181C mutant, consistent with the milder phenotype of NDI associated with this mutant. Notably, the R181C mutant appears to be a Gs protein-biased receptor incapable of signaling to inositol phosphate or recruiting

  12. Characterization of three vasopressin receptor 2 variants: an apparent polymorphism (V266A) and two loss-of-function mutations (R181C and M311V).

    PubMed

    Armstrong, Stephen P; Seeber, Ruth M; Ayoub, Mohammed Akli; Feldman, Brian J; Pfleger, Kevin D G

    2013-01-01

    Arginine vasopressin (AVP) is released from the posterior pituitary and controls water homeostasis. AVP binding to vasopressin V2 receptors (V2Rs) located on kidney collecting duct epithelial cells triggers activation of Gs proteins, leading to increased cAMP levels, trafficking of aquaporin-2 water channels, and consequent increased water permeability and antidiuresis. Typically, loss-of-function V2R mutations cause nephrogenic diabetes insipidus (NDI), whereas gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Here we provide further characterization of two mutant V2Rs, R181C and M311V, reported to cause complete and partial NDI respectively, together with a V266A variant, in a patient diagnosed with NSIAD. Our data in HEK293FT cells revealed that for cAMP accumulation, AVP was about 500- or 30-fold less potent at the R181C and M311V mutants than at the wild-type receptor respectively (and about 4000- and 60-fold in COS7 cells respectively). However, in contrast to wild type V2R, the R181C mutant failed to increase inositol phosphate production, while with the M311V mutant, AVP exhibited only partial agonism in addition to a 37-fold potency decrease. Similar responses were detected in a BRET assay for β-arrestin recruitment, with the R181C receptor unresponsive to AVP, and partial agonism with a 23-fold decrease in potency observed with M311V in both HEK293FT and COS7 cells. Notably, the V266A V2R appeared functionally identical to the wild-type receptor in all assays tested, including cAMP and inositol phosphate accumulation, β-arrestin interaction, and in a BRET assay of receptor ubiquitination. Each receptor was expressed at comparable levels. Hence, the M311V V2R retains greater activity than the R181C mutant, consistent with the milder phenotype of NDI associated with this mutant. Notably, the R181C mutant appears to be a Gs protein-biased receptor incapable of signaling to inositol phosphate or recruiting

  13. JAK2V617F-mutant megakaryocytes contribute to hematopoietic stem/progenitor cell expansion in a model of murine myeloproliferation

    PubMed Central

    Zhan, H; Ma, Y; Lin, CHS; Kaushansky, K

    2016-01-01

    The myeloproliferative neoplasms (MPNs) are characterized by hematopoietic stem/progenitor cell (HSPC) expansion and overproduction of mature blood cells. The JAK2V617F mutation is present in hematopoietic cells in a majority of patients with MPNs, but the mechanism(s) responsible for MPN stem cell expansion remain incomplete. One hallmark feature of the marrow in patients with MPNs is megakaryocyte (MK) hyperplasia. We report here that mice bearing a human JAK2V617F gene restricted exclusively to the MK lineage develop many of the features of a MPN. Specifically, these mice exhibit thrombocytosis, splenomegaly, increased numbers of marrow and splenic hematopoietic progenitors and a substantial expansion of HSPCs. In addition, wild-type mice transplanted with cells from JAK2V617F-bearing MK marrow develop a myeloproliferative syndrome with thrombocytosis and erythrocytosis as well as pan-hematopoietic progenitor and stem cell expansion. As marrow histology in this murine model of myeloproliferation reveals a preferentially perivascular localization of JAK2V617F-mutant MKs and an increased marrow sinusoid vascular density, it adds to accumulating data that MKs are an important component of the marrow HSPC niche, and that MK expansion might indirectly contribute to the critical role of the thrombopoietin/c-Mpl signaling pathway in HSPC maintenance and expansion. PMID:27133820

  14. Crystallization of a non-B and a B mutant HIV protease.

    PubMed

    Sanches, Mario; Martins, Nádia Helena; Calazans, Alexandre; Brindeiro, Rodrigo de Moraes; Tanuri, Amilcar; Antunes, Octavio Augusto Ceva; Polikarpov, Igor

    2004-09-01

    HIV polymorphism is responsible for the selection of variant viruses resistant to inhibitors used in AIDS treatment. Knowledge of the mechanism of resistance of those viruses is determinant to the development of new inhibitors able to stop, or at least slow down, the disease's progress caused by new mutations. In this paper, the crystallization and preliminary crystallographic structure solution for two multi-resistant 99 amino acid HIV proteases, both isolated from Brazilian patients failing intensive anti-AIDS therapy are presented, viz. the subtype B mutant, with mutations Q7K, S37N, R41K, K45R, I54V, L63P, A71V, V82A and L90M, and the subtype F (wild type), naturally carrying mutations Q7K, I15V, E35D, M36I, S37N, R41K, R57K, D60E, Q61N, I62V, L63S, I64L and L89M, with respect to the B consensus sequence. Both proteins crystallized as a complex with the inhibitor TL-3 in space group P6(1)22. X-ray diffraction data were collected from these crystals to resolutions of 2.1 and 2.6 A for the subtype B mutant and subtype F wild type, respectively, and the enzyme structures were solved by molecular replacement. The crystals of subtype F HIV protease are, to the best of the authors' knowledge, the first protein crystals obtained for a non-B HIV protease.

  15. 31 CFR 800.226 - U.S. business.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false U.S. business. 800.226 Section 800... TAKEOVERS BY FOREIGN PERSONS Definitions § 800.226 U.S. business. The term U.S. business means any entity... organized under the laws of a foreign state and is wholly owned and controlled by a foreign national. It...

  16. Transformation by HrasG12V is Consistently Associated with Mutant Allele Copy Gains and is Reversed by Farnesyl Transferase Inhibition

    PubMed Central

    Chen, Xu; Makarewicz, Jacek M.; Knauf, Jeffrey A.; Johnson, Linda K.; Fagin, James A.

    2014-01-01

    RAS-driven malignancies remain a major therapeutic challenge. The two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) model of mouse skin carcinogenesis has been used to study mechanisms of epithelial tumor development by oncogenic Hras. We used mice with a HrasG12V knock-in allele to elucidate the early events after Hras activation, and to evaluate the therapeutic effectiveness of farnesyltransferase (FTI) inhibition. Treatment of Caggs-Cre/FR-HrasG12V mice with TPA alone was sufficient to trigger papilloma development with shorter latency and a ~10-fold greater tumor burden than DMBA/TPA-treated WT controls. HrasG12V allele copy number was increased in all papillomas induced by TPA. DMBA/TPA treatment of HrasG12V knock-in mice induced an even greater incidence of papillomas, which either harbored HrasG12V amplification, or developed a HrasQ61L mutation in the second allele. Laser-capture microdissection of normal skin, hyperplastic skin and papillomas showed that amplification occurred only at the papilloma stage. HRAS mutant allelic imbalance was also observed in human cancer cell lines, consistent with a requirement for augmented oncogenic HRAS signaling for tumor development. The FTI SCH66336 blocks HRAS farnesylation and delocalizes it from the plasma membrane. NRAS and KRAS are not affected as they are alternatively prenylated. When tested in lines harboring HRAS, NRAS or KRAS mutations, SCH66336 delocalized, inhibited signaling and preferentially inhibited growth only of HRAS-mutant lines. Treatment with SCH66336 also induced near-complete regression of papillomas of TPA-treated HrasG12V knock-in mice. These data suggest that farnesyl transferase inhibitors should be reevaluated as targeted agents for human HRAS-driven cancers, such as those of bladder, thyroid and other epithelial lineages. PMID:24240680

  17. Understanding the evolution and spread of chikungunya virus in the Americas using complete genome sequences.

    PubMed

    Sahadeo, N S D; Allicock, O M; De Salazar, P M; Auguste, A J; Widen, S; Olowokure, B; Gutierrez, C; Valadere, A M; Polson-Edwards, K; Weaver, S C; Carrington, C V F

    2017-01-01

    Local transmission of chikungunya virus (CHIKV) was first detected in the Americas in December 2013, after which it spread rapidly throughout the Caribbean islands and American mainland, causing a major chikungunya fever epidemic. Previous phylogenetic analysis of CHIKV from a limited number of countries in the Americas suggests that an Asian genotype strain was responsible, except in Brazil where both Asian and East/Central/South African (ECSA) lineage strains were detected. In this study, we sequenced thirty-three complete CHIKV genomes from viruses isolated in 2014 from fourteen Caribbean islands, the Bahamas and two mainland countries in the Americas. Phylogenetic analyses confirmed that they all belonged to the Asian genotype and clustered together with other Caribbean and mainland sequences isolated during the American outbreak, forming an 'Asian/American' lineage defined by two amino acid substitutions, E2 V368A and 6K L20M, and divided into two well-supported clades. This lineage is estimated to be evolving at a mean rate of 5 × 10 -4 substitutions per site per year (95% higher probability density, 2.9-7.9 × 10 -4 ) and to have arisen from an ancestor introduced to the Caribbean (most likely from Oceania) in about March 2013, 9 months prior to the first report of CHIKV in the Americas. Estimation of evolutionary rates for individual gene regions and selection analyses indicate that (in contrast to the Indian Ocean Lineage that emerged from the ECSA genotype followed by adaptive evolution and with a significantly higher substitution rate) the evolutionary dynamics of the Asian/American lineage are very similar to the rest of the Asian genotype and natural selection does not appear to have played a major role in its emergence. However, several codon sites with evidence of positive selection were identified within the non-structural regions of Asian genotype sequences outside of the Asian/American lineage.

  18. Coelenterazine-v ligated to Ca2+-triggered coelenterazine-binding protein is a stable and efficient substrate of the red-shifted mutant of Renilla muelleri luciferase.

    PubMed

    Stepanyuk, Galina A; Unch, James; Malikova, Natalia P; Markova, Svetlana V; Lee, John; Vysotski, Eugene S

    2010-10-01

    It has been shown that the coelenterazine analog, coelenterazine-v, is an efficient substrate for a reaction catalyzed by Renilla luciferase. The resulting bioluminescence emission maximum is shifted to a longer wavelength up to 40 nm, which allows the use of some "yellow" Renilla luciferase mutants for in vivo imaging. However, the utility of coelenterazine-v in small-animal imaging has been hampered by its instability in solution and in biological tissues. To overcome this drawback, we ligated coelenterazine-v to Ca(2+)-triggered coelenterazine-binding protein from Renilla muelleri, which apparently functions in the organism for stabilizing and protecting coelenterazine from oxidation. The coelenterazine-v bound within coelenterazine-binding protein has revealed a greater long-term stability at both 4 and 37 °C. In addition, the coelenterazine-binding protein ligated by coelenterazine-v yields twice the total light over free coelenterazine-v as a substrate for the red-shifted R. muelleri luciferase. These findings suggest the possibility for effective application of coelenterazine-v in various in vitro assays.

  19. 22 CFR 226.72 - Subsequent adjustments and continuing responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Subsequent adjustments and continuing responsibilities. 226.72 Section 226.72 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS After-the-Award Requirements § 226.72 Subsequent...

  20. 50 CFR 226.209 - Critical habitat for hawksbill turtle.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Critical habitat for hawksbill turtle. 226.209 Section 226.209 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT § 226.209...

  1. 50 CFR 226.209 - Critical habitat for hawksbill turtle.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Critical habitat for hawksbill turtle. 226.209 Section 226.209 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT § 226.209...

  2. 50 CFR 226.208 - Critical habitat for green turtle.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Critical habitat for green turtle. 226.208 Section 226.208 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT § 226.208...

  3. 50 CFR 226.207 - Critical habitat for leatherback turtle.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Critical habitat for leatherback turtle. 226.207 Section 226.207 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT § 226.207...

  4. First 226Ra- 210Pb dating of a young speleothem

    NASA Astrophysics Data System (ADS)

    Condomines, M.; Rihs, S.

    2006-10-01

    Whereas the method based on the decrease of excess 210Pb has already been used to date young (< 120 yr) speleothems (e.g. [M. Baskaran, T. M. Iliffe, Age determination of recent cave deposits using excess 210Pb — A new technique, Geophys. Res. Lett. 20 (1993) 603-606.]), this paper presents the first dating of a speleothem through the 226Ra- 210Pb method. Dating of a young hydrothermal stalagmite from the Mt Cornadore cave (St Nectaire, French Massif Central) was made possible by the high 226Ra and negligible 210Pb contents of such carbonates, formed by precipitation from CO 2-rich thermal waters. ( 210Pb/ 226Ra) ratios regularly increase with depth along the axis of the 33 cm long stalagmite. The age-depth relationship can be interpreted by two main phases of growth, with high but variable axial growth rates of 5.3 mm/yr from 1909 to 1967, and 2.6 mm/yr from 1967 to 1989 (alternatively, the oldest phase can be subdivided in three episodes with growth rates varying from 2 to 7 mm/yr). Thin-section examination reveals the presence of numerous laminae, indicating infra-annual variations. We suggest that this fine layered structure might reflect short-term fluctuations in drip waters, possibly induced by near-surface mixing between thermal and ground waters, and ultimately linked to the pluviometry. A detailed examination of this laminated structure combined with 226Ra- 210Pb dating could thus provide a high-resolution record of local paleohydrological fluctuations.

  5. The cataract-associated V41M mutant of human γS-crystallin shows specific structural changes that directly enhance local surface hydrophobicity

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

    Bharat, Somireddy Venkata; Shekhtman, Alexander; Pande, Jayanti, E-mail: jpande@albany.edu

    2014-01-03

    Highlights: •We present NMR analysis of V41M, a cataract-causing mutant of human γS-crystallin. •Mutation alters strand–strand interactions throughout the N-terminal domain. •Mutation directly affects Trp46 due to key Met41-S–Trp46-pi interactions. •We identify the basis of the surface hydrophobicity increase and residues involved. -- Abstract: The major crystallins expressed in the human lens are γS-, γC- and γD-crystallins. Several mutations in γS-crystallin are associated with hereditary cataracts, one of which involves the substitution of a highly conserved Valine at position 41 to Methionine. According to a recent report, the mutant protein, V41M, shows lower stability and increased surface hydrophobicity compared tomore » the wild-type, and a propensity for self-aggregation. Here we address the structural differences between the two proteins, with residue-level specificity using NMR spectroscopy. Based on the structural model of the mutant protein, our results clearly show that the mutation creates a major local perturbation almost at the junction of the first and second “Greek-key” motifs in the N-terminal domain. A larger section of the second motif (residues 44–86) appears to be mainly affected. Based on the sizeable chemical shift of the imino proton of the indole side-chain of Trp46 in V41M, we suggest that the sulphur atom of Met41 is involved in an S–π interaction with Trp46. This interaction would bring the last β-strand of the first “Greek-key” motif closer to the first β-strand of the second motif. This appears to lead to a domino effect, towards both the N- and C-terminal ends, even as it decays off substantially beyond the domain interface. During this process discreet hydrophobic surface patches are created, as revealed by ANS-binding. Such changes would not affect the secondary structure or cause a major change in the tertiary structure, but can lead to self-aggregation or aberrant binding interactions of the

  6. 48 CFR 226.370-9 - Solicitation provision and contract clause.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Black Colleges and Universities and Minority Institutions 226.370-9 Solicitation provision and contract clause. (a) Use the clause at 252.226-7000, Notice of Historically Black College or University and... provision at FAR 52.226-2, Historically Black College or University and Minority Institution Representation...

  7. 48 CFR 226.370-9 - Solicitation provision and contract clause.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Black Colleges and Universities and Minority Institutions 226.370-9 Solicitation provision and contract clause. (a) Use the clause at 252.226-7000, Notice of Historically Black College or University and... provision at FAR 52.226-2, Historically Black College or University and Minority Institution Representation...

  8. 48 CFR 226.370-9 - Solicitation provision and contract clause.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Black Colleges and Universities and Minority Institutions 226.370-9 Solicitation provision and contract clause. (a) Use the clause at 252.226-7000, Notice of Historically Black College or University and... provision at FAR 52.226-2, Historically Black College or University and Minority Institution Representation...

  9. 48 CFR 226.370-9 - Solicitation provision and contract clause.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Black Colleges and Universities and Minority Institutions 226.370-9 Solicitation provision and contract clause. (a) Use the clause at 252.226-7000, Notice of Historically Black College or University and... provision at FAR 52.226-2, Historically Black College or University and Minority Institution Representation...

  10. 48 CFR 226.370-9 - Solicitation provision and contract clause.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Black Colleges and Universities and Minority Institutions 226.370-9 Solicitation provision and contract clause. (a) Use the clause at 252.226-7000, Notice of Historically Black College or University and... provision at FAR 52.226-2, Historically Black College or University and Minority Institution Representation...

  11. 22 CFR 226.51 - Monitoring and reporting program performance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Monitoring and reporting program performance. 226.51 Section 226.51 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Reports and Records § 226.51...

  12. 22 CFR 226.28 - Period of availability of funds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Period of availability of funds. 226.28 Section 226.28 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Financial and Program Management § 226.28...

  13. 22 CFR 226.16 - Resource Conservation and Recovery Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Resource Conservation and Recovery Act. 226.16 Section 226.16 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Pre-award Requirements § 226.16 Resource Conservation and...

  14. 22 CFR 226.1004 - Ocean shipment of goods. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Ocean shipment of goods. [Reserved] 226.1004 Section 226.1004 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1004 Ocean shipment of...

  15. 22 CFR 226.1004 - Ocean shipment of goods. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Ocean shipment of goods. [Reserved] 226.1004 Section 226.1004 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1004 Ocean shipment of...

  16. 22 CFR 226.1004 - Ocean shipment of goods. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Ocean shipment of goods. [Reserved] 226.1004 Section 226.1004 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1004 Ocean shipment of...

  17. 22 CFR 226.1004 - Ocean shipment of goods. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Ocean shipment of goods. [Reserved] 226.1004 Section 226.1004 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1004 Ocean shipment of...

  18. 22 CFR 226.1004 - Ocean shipment of goods. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Ocean shipment of goods. [Reserved] 226.1004 Section 226.1004 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS USAID-Specific Requirements § 226.1004 Ocean shipment of...

  19. 9 CFR 2.26 - Acknowledgment of regulations and standards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

  20. 9 CFR 2.26 - Acknowledgment of regulations and standards.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

  1. 9 CFR 2.26 - Acknowledgment of regulations and standards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

  2. 9 CFR 2.26 - Acknowledgment of regulations and standards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

  3. 9 CFR 2.26 - Acknowledgment of regulations and standards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Acknowledgment of regulations and standards. 2.26 Section 2.26 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Registration § 2.26 Acknowledgment of regulations and...

  4. 48 CFR 752.226-2 - Subcontracting with disadvantaged enterprises.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... management and daily business are controlled by one or more such individuals. (2) Owned by socially and... disadvantaged enterprises. 752.226-2 Section 752.226-2 Federal Acquisition Regulations System AGENCY FOR... Clauses 752.226-2 Subcontracting with disadvantaged enterprises. As prescribed in 726.7007, insert the...

  5. Molecular characterization of chikungunya virus from Andhra Pradesh, India & phylogenetic relationship with Central African isolates.

    PubMed

    M Naresh Kumar, C V; Anthony Johnson, A M; R Sai Gopal, D V

    2007-12-01

    Chikungunya virus has caused numerous large outbreaks in India. Suspected blood samples from the epidemic were collected and characterized for the identification of the responsible causative from Rayalaseema region of Andhra Pradesh. RT-PCR was used for screening of suspected blood samples. Primers were designed to amplify partial E1 gene and the amplified fragment was cloned and sequenced. The sequence was analyzed and compared with other geographical isolates to find the phylogenetic relationship. The sequence was submitted to the Gen bank DNA database (accession DQ888620). Comparative nucleotide homology analysis of the AP Ra-CTR isolate with the other isolates revealed 94.7+/-3.6 per cent of homology of CHIKAPRa-CTR with other isolates of Chikungunya virus at nucleotide level and 96.8+/-3.2 per cent of homology at amino acid level. The current epidemic was caused by the Central African genotype of CHIKV, grouped in Central Africa cluster in phylogenetic trees generated based on nucleotide and amino acid sequences.

  6. 22 CFR 226.50 - Purpose of reports and records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Purpose of reports and records. 226.50 Section 226.50 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Reports and Records § 226.50 Purpose of...

  7. 50 CFR 226.208 - Critical habitat for green turtle.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Critical habitat for green turtle. 226.208 Section 226.208 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT § 226.208 Critical habitat for...

  8. Differential effects of hydroxyurea and INC424 on mutant allele burden and myeloproliferative phenotype in a JAK2-V617F polycythemia vera mouse model.

    PubMed

    Kubovcakova, Lucia; Lundberg, Pontus; Grisouard, Jean; Hao-Shen, Hui; Romanet, Vincent; Andraos, Rita; Murakami, Masato; Dirnhofer, Stephan; Wagner, Kay-Uwe; Radimerski, Thomas; Skoda, Radek C

    2013-02-14

    To establish a preclinical animal model for testing drugs with potential effects on myeloproliferative neoplasms (MPNs), we first performed a detailed phenotypic characterization of Cre-inducible transgenic JAK2-V617F mice. Deleting the conditional mouse Jak2-knockout alleles increased erythropoiesis and accentuated the polycythemia vera phenotype, but did not alter platelet or granulocyte levels. In a transplantation assay, JAK2-V617F(+) BM cells had an advantage over wild-type competitor cells. Using this competitive repopulation assay, we compared the effects of INC424 (ruxolitinib), a dual Jak1/Jak2 inhibitor, and hydroxyurea (HU). HU led to weight loss, but did not reduce spleen weight. The hematologic parameters were lowered and a slight decrease of the mutant allele burden was noted. INC424 had little effect on body weight, but strongly decreased spleen size and rapidly normalized RBC and neutrophil parameters. No significant decrease in the mutant allele burden was observed. INC424 reduced the phospho-Stat5 levels, whereas HU strongly increased phospho-Stat5, most likely because of the elevated erythropoietin levels in response to the HU-induced anemia. This compensatory increase in JAK/STAT signaling may counteract the beneficial effects of cytoreduction at higher doses of HU and represents an adverse effect that should be avoided.

  9. 7 CFR 226.24 - Property management requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Property management requirements. 226.24 Section 226.24 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS CHILD AND ADULT CARE FOOD PROGRAM Food Service Equipment...

  10. 50 CFR 226.203 - Critical habitat for northern right whales.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Critical habitat for northern right whales. 226.203 Section 226.203 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL... § 226.203 Critical habitat for northern right whales. (a) Great South Channel. The area bounded by 41°40...

  11. 50 CFR 226.203 - Critical habitat for northern right whales.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Critical habitat for northern right whales. 226.203 Section 226.203 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL... § 226.203 Critical habitat for northern right whales. (a) Great South Channel. The area bounded by 41°40...

  12. 50 CFR 226.203 - Critical habitat for northern right whales.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Critical habitat for northern right whales. 226.203 Section 226.203 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL... § 226.203 Critical habitat for northern right whales. (a) Great South Channel. The area bounded by 41°40...

  13. Mutants of the pentose-fermenting yeast Pachysolen tannophilus tolerant to hardwood spent sulfite liquor and acetic acid.

    PubMed

    Harner, Nicole K; Bajwa, Paramjit K; Habash, Marc B; Trevors, Jack T; Austin, Glen D; Lee, Hung

    2014-01-01

    A strain development program was initiated to improve the tolerance of the pentose-fermenting yeast Pachysolen tannophilus to inhibitors in lignocellulosic hydrolysates. Several rounds of UV mutagenesis followed by screening were used to select for mutants of P. tannophilus NRRL Y2460 with improved tolerance to hardwood spent sulfite liquor (HW SSL) and acetic acid in separate selection lines. The wild type (WT) strain grew in 50 % (v/v) HW SSL while third round HW SSL mutants (designated UHW301, UHW302 and UHW303) grew in 60 % (v/v) HW SSL, with two of these isolates (UHW302 and UHW303) being viable and growing, respectively, in 70 % (v/v) HW SSL. In defined liquid media containing acetic acid, the WT strain grew in 0.70 % (w/v) acetic acid, while third round acetic acid mutants (designated UAA301, UAA302 and UAA303) grew in 0.80 % (w/v) acetic acid, with one isolate (UAA302) growing in 0.90 % (w/v) acetic acid. Cross-tolerance of HW SSL-tolerant mutants to acetic acid and vice versa was observed with UHW303 able to grow in 0.90 % (w/v) acetic acid and UAA302 growing in 60 % (v/v) HW SSL. The UV-induced mutants retained the ability to ferment glucose and xylose to ethanol in defined media. These mutants of P. tannophilus are of considerable interest for bioconversion of the sugars in lignocellulosic hydrolysates to ethanol.

  14. 12 CFR Supplement I to Part 226 - Official Staff Interpretations

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM TRUTH IN LENDING (REGULATION Z) Pt. 226, Supp. I Supplement I to Part 226—Official Staff... interpretation issued by a duly authorized official or employee of the Federal Reserve System. 2. Procedure for...

  15. 22 CFR 226.37 - Property trust relationship.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Property trust relationship. 226.37 Section 226.37 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S... relationship. Real property, equipment, intangible property and debt instruments that are acquired or improved...

  16. 40 CFR 98.226 - Data reporting requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... reporting year that missing data procedures were followed to measure nitric acid production (months). (m) If... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Data reporting requirements. 98.226... (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Nitric Acid Production § 98.226 Data reporting requirements...

  17. 40 CFR 98.226 - Data reporting requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...). (l) Number of times in the reporting year that missing data procedures were followed to measure... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Data reporting requirements. 98.226... (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Nitric Acid Production § 98.226 Data reporting requirements...

  18. 40 CFR 98.226 - Data reporting requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...). (l) Number of times in the reporting year that missing data procedures were followed to measure... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Data reporting requirements. 98.226... (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Nitric Acid Production § 98.226 Data reporting requirements...

  19. A Yersinia pestis YscN ATPase mutant functions as a live attenuated vaccine against bubonic plague in mice.

    PubMed

    Bozue, Joel; Cote, Christopher K; Webster, Wendy; Bassett, Anthony; Tobery, Steven; Little, Stephen; Swietnicki, Wieslaw

    2012-07-01

    Yersinia pestis is the causative agent responsible for bubonic and pneumonic plague. The bacterium uses the pLcr plasmid-encoded type III secretion system to deliver virulence factors into host cells. Delivery requires ATP hydrolysis by the YscN ATPase encoded by the yscN gene also on pLcr. A yscN mutant was constructed in the fully virulent CO92 strain containing a nonpolar, in-frame internal deletion within the gene. We demonstrate that CO92 with a yscN mutation was not able to secrete the LcrV protein (V-Antigen) and attenuated in a subcutaneous model of plague demonstrating that the YscN ATPase was essential for virulence. However, if the yscN mutant was complemented with a functional yscN gene in trans, virulence was restored. To evaluate the mutant as a live vaccine, Swiss-Webster mice were vaccinated twice with the ΔyscN mutant at varying doses and were protected against bubonic plague in a dose-dependent manner. Antibodies to F1 capsule but not to LcrV were detected in sera from the vaccinated mice. These preliminary results suggest a proof-of-concept for an attenuated, genetically engineered, live vaccine effective against bubonic plague. Published 2012. This article is a US Government work and is in the public domain in the USA.

  20. Mosquito Cellular Factors and Functions in Mediating the Infectious entry of Chikungunya Virus

    PubMed Central

    Lee, Regina Ching Hua; Hapuarachchi, Hapuarachchige Chanditha; Chen, Karen Caiyun; Hussain, Khairunnisa' Mohamed; Chen, Huixin; Low, Swee Ling; Ng, Lee Ching; Lin, Raymond; Ng, Mary Mah-Lee; Chu, Justin Jang Hann

    2013-01-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus responsible for recent epidemics in the Asia Pacific regions. A customized gene expression microarray of 18,760 transcripts known to target Aedes mosquito genome was used to identify host genes that are differentially regulated during the infectious entry process of CHIKV infection on C6/36 mosquito cells. Several genes such as epsin I (EPN1), epidermal growth factor receptor pathway substrate 15 (EPS15) and Huntingtin interacting protein I (HIP1) were identified to be differentially expressed during CHIKV infection and known to be involved in clathrin-mediated endocytosis (CME). Transmission electron microscopy analyses further revealed the presence of CHIKV particles within invaginations of the plasma membrane, resembling clathrin-coated pits. Characterization of vesicles involved in the endocytic trafficking processes of CHIKV revealed the translocation of the virus particles to the early endosomes and subsequently to the late endosomes and lysosomes. Treatment with receptor-mediated endocytosis inhibitor, monodansylcadaverine and clathrin-associated drug inhibitors, chlorpromazine and dynasore inhibited CHIKV entry, whereas no inhibition was observed with caveolin-related drug inhibitors. Inhibition of CHIKV entry upon treatment with low-endosomal pH inhibitors indicated that low pH is essential for viral entry processes. CHIKV entry by clathrin-mediated endocytosis was validated via overexpression of a dominant-negative mutant of Eps15, in which infectious entry was reduced, while siRNA-based knockdown of genes associated with CME, low endosomal pH and RAB trafficking proteins exhibited significant levels of CHIKV inhibition. This study revealed, for the first time, that the infectious entry of CHIKV into mosquito cells is mediated by the clathrin-dependent endocytic pathway. PMID:23409203

  1. A fixed-time diffusion analysis method determines that the three cheV genes of Helicobacter pylori differentially affect motility

    PubMed Central

    Lowenthal, Andrew C.; Simon, Christopher; Fair, Amber S.; Mehmood, Khalid; Terry, Karianne; Anastasia, Stephanie; Ottemann, Karen M.

    2009-01-01

    Helicobacter pylori is a chemotactic bacterium that has three CheV proteins in its predicted chemotaxis signal transduction system. CheV proteins contain both CheW- and response-regulator-like domains. To determine the function of these proteins, we developed a fixed-time diffusion method that would quantify bacterial direction change without needing to define particular behaviours, to deal with the many behaviours that swimming H. pylori exhibit. We then analysed mutants that had each cheV gene deleted individually and found that the behaviour of each mutant differed substantially from wild-type and the other mutants. cheV1 and cheV2 mutants displayed smooth swimming behaviour, consistent with decreased cellular CheY-P, similar to a cheW mutant. In contrast, the cheV3 mutation had the opposite effect and the mutant cells appeared to change direction frequently. Additional analysis showed that the cheV mutants displayed aberrant behaviour as compared to the wild-type in the soft-agar chemotaxis assay. The soft-agar assay phenotype was less extreme compared to that seen in the fixed-time diffusion model, suggesting that the cheV mutants are able to partially compensate for their defects under some conditions. Each cheV mutant furthermore had defects in mouse colonization that ranged from severe to modest, consistent with a role in chemotaxis. These studies thus show that the H. pylori CheV proteins each differently affect swimming behaviour. PMID:19332820

  2. 40 CFR 98.226 - Data reporting requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... pressure). (l) Number of times in the reporting year that missing data procedures were followed to measure... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Data reporting requirements. 98.226... (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Nitric Acid Production § 98.226 Data reporting requirements...

  3. A Polarized Cell Model for Chikungunya Virus Infection: Entry and Egress of Virus Occurs at the Apical Domain of Polarized Cells

    PubMed Central

    Lim, Pei Jin; Chu, Justin Jang Hann

    2014-01-01

    Chikungunya virus (CHIKV) has resulted in several outbreaks in the past six decades. The clinical symptoms of Chikungunya infection include fever, skin rash, arthralgia, and an increasing incidence of encephalitis. The re-emergence of CHIKV with more severe pathogenesis highlights its potential threat on our human health. In this study, polarized HBMEC, polarized Vero C1008 and non-polarized Vero cells grown on cell culture inserts were infected with CHIKV apically or basolaterally. Plaque assays, viral binding assays and immunofluorescence assays demonstrated apical entry and release of CHIKV in polarized HBMEC and Vero C1008. Drug treatment studies were performed to elucidate both host cell and viral factors involved in the sorting and release of CHIKV at the apical domain of polarized cells. Disruption of host cell myosin II, microtubule and microfilament networks did not disrupt the polarized release of CHIKV. However, treatment with tunicamycin resulted in a bi-directional release of CHIKV, suggesting that N-glycans of CHIKV envelope glycoproteins could serve as apical sorting signals. PMID:24587455

  4. Behavior of 226Ra in the Mississippi River mixing zone

    NASA Astrophysics Data System (ADS)

    Moore, Daniel G.; Scott, Martha R.

    1986-12-01

    The behavior of 226Ra in the Mississippi River mixing zone is strongly nonconservative and includes desorption similar to that reported for the Hudson, Pee Dee, and Amazon rivers. However, dissolved and desorbed 226Ra concentrations in the Mississippi are 2 to 5 times greater than in the other rivers at the same salinity. Radium concentrations vary inversely with the water discharge rate. The 226Ra desorption maximum occurs at a salinity of 5.0, much lower than the 18 to 28 salinity values for the maxima of the other three rivers. High concentrations of dissolved 226Ra (up to 82 dpm per 100 L) and the low salinity values for the desorption maximum in the Mississippi River result from three major factors. Suspended sediments include a large fraction of montmorillonite, which gives the sediment a high cation exchange capacity, 0.54 meq/g. The average suspended sediment load is large, about 510 mg/L, and contains 1.9 dpm/g desorbable 226Ra. The dissolved 226Ra river water end-member (9.6 dpm per 100 L) is higher than in surface seawater. The annual contribution of 226Ra to the ocean from the Mississippi River is 3.7 × 1014 dpm/yr, based on data from three cruises. Evidence of flux of 226Ra from estuarine and shelf sediments is common in vertical profile sampling of the deltaic waters but is not reflected in calculations made with an "apparent" river water Ra value extrapolated to zero salinity.

  5. Risk assessment of human exposure to Ra-226 in oil produced water from the Bakken Shale.

    PubMed

    Torres, Luisa; Yadav, Om Prakash; Khan, Eakalak

    2018-06-01

    Unconventional oil production in North Dakota (ND) and other states in the United States uses large amounts of water for hydraulic fracturing to stimulate oil flow. Most of the water used returns to the surface as produced water (PW) containing different constituents. Some of these contents are total dissolved solids and radionuclides. The most predominant radionuclide in PW is radium-226 (Ra-226) of which level depends on several factors including the content of certain cations. A multivariate regression model was developed to predict Ra-226 in PW from the Bakken Shale based on the levels of barium, strontium, and calcium. The simulated Ra-226 activity concentration in PW was 535 pCi/L supporting extremely limited actual data based on three PW samples from the Bakken (527, 816, and 1210 pCi/L). The simulated activity concentration was further analyzed by studying its impact in the event of a PW spill reaching a surface water body that provides drinking water, irrigation water for crops, and recreational fishing. Using food transfer factors found in the literature, the final annual effective dose rate for an adult in ND was estimated. The global average annual effective dose rate via food and drinking water is 0.30 mSv, while the predicted dose rate in this study was 0.49 mSv indicating that there is potential risk to human health in ND due to Ra-226 in PW spills. This predicted dose rate is considered the best case scenario as it is based on the simulated Ra-226 activity concentration in PW of 535 pCi/L which is close to the low end actual activity concentration of 527 pCi/L. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. 20 CFR 226.31 - Reduction for public pension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Reduction for public pension. 226.31 Section... § 226.31 Reduction for public pension. (a) The tier I annuity component of a spouse/divorced spouse... in receipt of a public pension. (b) When reduction is required. Unless the spouse or divorced spouse...

  7. Mutants of the lactose carrier of Escherichia coli which show altered sugar recognition plus a severe defect in sugar accumulation.

    PubMed

    Varela, M F; Wilson, T H; Rodon-Rivera, V; Shepherd, S; Dehne, T A; Rector, A C

    2000-04-01

    Lactose and melibiose are actively accumulated by the wild-type Escherichia coli lactose carrier, which is an integral membrane protein energized by the proton motive force. Mutants of the E. coli lactose carrier were isolated by their ability to grow on minimal plates with succinate plus IPTG in the presence of the toxic lactose analog beta-thio-o-nitrophenylgalactoside (TONPG). TONPG-resistant mutants were streaked on melibiose MacConkey indicator plates, and red clones were picked. These melibiose positive mutants were then streaked on lactose MacConkey plates, and white clones were picked. Transport assays indicated that the mutants had altered sugar recognition and a defect in sugar accumulation. The mutants had a poor apparent K(m) for both lactose and melibiose in transport. One mutant had almost no ability to take up lactose, but melibiose downhill transport was 58% (V(max)) of normal. All of the mutants accumulated methyl-alpha-d-galactopyranoside (TMG) to only 8% or less of normal, and two failed to accumulate. Immunoblot analysis of the mutant lactose carrier proteins indicated that loss of sugar transport activity was not due to loss of expression in the membrane. Nucleotide sequencing of the lacY gene from the mutants revealed changes in the following amino acids of the lactose carrier: M23I, W151L, G257D, A295D and G377V. Two of the mutants (G257D and G377V) are novel in that they represent the first amino acids in periplasmic loops to be implicated with changes in sugar recognition. We conclude that the amino acids M23, W151, G257, A295 and G377 of the E. coli lactose carrier play either a direct or an indirect role in sugar recognition and accumulation.

  8. 7 CFR 226.16 - Sponsoring organization provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ....16 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE... regulations. In addition to the information required in §§ 226.6(b) and 226.6(f), the application must include... applying for initial participation on or after June 20, 2000, if required by State law, regulation, or...

  9. 7 CFR 226.16 - Sponsoring organization provisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ....16 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE... regulations. In addition to the information required in §§ 226.6(b) and 226.6(f), the application must include... applying for initial participation on or after June 20, 2000, if required by State law, regulation, or...

  10. 7 CFR 226.16 - Sponsoring organization provisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....16 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE... regulations. In addition to the information required in §§ 226.6(b) and 226.6(f), the application must include... applying for initial participation on or after June 20, 2000, if required by State law, regulation, or...

  11. Current status, challenges and perspectives in the development of vaccines against yellow fever, dengue, Zika and chikungunya viruses.

    PubMed

    Silva, José V J; Lopes, Thaísa R R; Oliveira-Filho, Edmilson F de; Oliveira, Renato A S; Durães-Carvalho, Ricardo; Gil, Laura H V G

    2018-06-01

    Emerging and re-emerging viral infections transmitted by insect vectors (arthopode-borne viruses, arbovirus) are a serious threat to global public health. Among them, yellow fever (YFV), dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses are particularly important in tropical and subtropical regions. Although vector control is one of the most used prophylactic measures against arboviruses, it often faces obstacles, such as vector diversity, uncontrolled urbanization and increasing resistance to insecticides. In this context, vaccines may be the best control strategy for arboviral diseases. Here, we provide a general overview about licensed vaccines and the most advanced vaccine candidates against YFV, DENV, CHIKV and ZIKV. In particular, we highlight vaccine difficulties, the current status of the most advanced strategies and discuss how the molecular characteristics of each virus can influence the choice of the different vaccine formulations. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. 20 CFR 226.12 - Employee vested dual benefit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Employee vested dual benefit. 226.12 Section 226.12 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... vested dual benefit. (a) General. An employee vested dual benefit is payable, in addition to tiers I and...

  13. 20 CFR 226.12 - Employee vested dual benefit.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Employee vested dual benefit. 226.12 Section 226.12 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... vested dual benefit. (a) General. An employee vested dual benefit is payable, in addition to tiers I and...

  14. 20 CFR 226.12 - Employee vested dual benefit.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Employee vested dual benefit. 226.12 Section 226.12 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... vested dual benefit. (a) General. An employee vested dual benefit is payable, in addition to tiers I and...

  15. 21 CFR 226.40 - Production and control procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Production and control procedures. 226.40 Section 226.40 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Product Quality Control...

  16. 48 CFR 226.370-6 - Eligibility for award.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... defined in the clause at 252.226-7000, Notice of Historically Black College or University and Minority..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities and Minority Institutions 226.370-6 Eligibility for award. (a) To be eligible for award as an HBCU...

  17. 48 CFR 226.370-6 - Eligibility for award.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... defined in the clause at 252.226-7000, Notice of Historically Black College or University and Minority..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities and Minority Institutions 226.370-6 Eligibility for award. (a) To be eligible for award as an HBCU...

  18. 48 CFR 226.370-6 - Eligibility for award.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... defined in the clause at 252.226-7000, Notice of Historically Black College or University and Minority..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities and Minority Institutions 226.370-6 Eligibility for award. (a) To be eligible for award as an HBCU...

  19. 48 CFR 226.370-6 - Eligibility for award.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... defined in the clause at 252.226-7000, Notice of Historically Black College or University and Minority..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS OTHER SOCIOECONOMIC PROGRAMS Historically Black Colleges and Universities and Minority Institutions 226.370-6 Eligibility for award. (a) To be eligible for award as an HBCU...

  20. Rapid method to determine 226Ra in steel samples

    DOE PAGES

    Maxwell, Sherrod L.; Culligan, Brian; Hutchison, Jay B.; ...

    2017-09-22

    The rapid measurement of 226Ra in steel samples is very important in the event of a radiological emergency. 226Ra (T 1/2 = 1600 y) is a natural radionuclide present in the environment and a highly toxic alpha-emitter. Due to its long life and tendency to concentrate in bones, 226Ra ingestion or inhalation can lead to significant committed dose to individuals. A new method for the determination of 226Ra in steel samples has been developed at the Savannah River Environmental Laboratory. The new method employs a rugged acid digestion method that includes hydrofluoric acid, followed by a single precipitation step tomore » rapidly preconcentrate the radium and remove most of the dissolved steel sample matrix. Radium is then separated using a combination of cation exchange and extraction chromatography, and 226Ra is measured by alpha spectrometry. This approach has a sample preparation time of ~ 8 h for steel samples, has a very high tracer yield (> 88%), and removes interferences effectively. A 133Ba yield tracer is used so that samples can be counted immediately following the separation method, avoiding lengthy ingrowth times that are required in other methods.« less